Δƒπª∏¡π∞π√ ¶∂ƒπ√¢π∫√ §π¶π¢πø¡
2 11 20 36 40
¶·Ú¿ÁÔÓÙ˜ ∫ÈÓ‰‡ÓÔ˘ ¶·ıÔÊ˘ÛÈÔÏÔÁ›·
£Âڷ›· - º¿Ú̷η ¢È·ÙÚÔÊ‹
Δ∂ÀÃ√™ 17 ñ ª∞ƒΔπ√™ 2008
¶ÚÔÙÂÈÓfiÌÂÓË μÈ‚ÏÈÔÁÚ·Ê›·
À‡ı˘ÓÔ˜ ™‡ÓÙ·Í˘ HÏ›·˜ XÂÈÌÒÓ·˜ K·Ú‰ÈÔÏfiÁÔ˜ YÔÙ¤Ú·Ú¯Ô˜ Â.·.
¶∞ƒ∞°√¡Δ∂™ ∫π¡¢À¡√À ΔÔ ªÂÙ·‚ÔÏÈÎfi ™‡Ó‰ÚÔÌÔ: ¢È¿ÁÓˆÛË Î·È ∫·Ú‰È·ÁÁÂÈ·Îfi˜ ∫›Ó‰˘ÓÔ˜ ™‡Á¯ÚÔÓ˜ £ÂˆÚ‹ÛÂȘ ¢Ú. ∞. ªÂÏȉÒÓ˘ ¶·ıÔÏfiÁÔ˜ - ¢È·‚ËÙÔÏfiÁÔ˜
2
∞Û‡ÌÌÂÙÚË ¢ÈÌÂı˘Ï·ÚÁÈÓ›ÓË: ŒÓ·˜ ¡¤Ô˜ ¢Â›ÎÙ˘ ∫ÈÓ‰‡ÓÔ˘ °ÂÒÚÁÈÔ˜ ¶. ∫˘ÚȷΛ‰Ë˜, ∞Ó·ÏËÚˆÙ‹˜ ¢È¢ı˘ÓÙ‹˜ μ’ ¶·ıÔÏÔÁÈÎÔ‡ ΔÌ‹Ì·ÙÔ˜ °¡£ «Ô ÕÁÈÔ˜ ¢ËÌ‹ÙÚÈÔ˜», £ÂÛÛ·ÏÔÓ›ÎË
6
¶A£√ºÀ™π√§√°π∞ ¢ÈÔÈÎËÙÈÎfi ™˘Ì‚Ô‡ÏÈÔ ∂ÏÏËÓÈ΋˜ ∂Ù·ÈÚ›·˜ ∞ıËÚÔÛÎÏ‹ÚˆÛ˘ °ÂÓÔ‚¤Ê· KÔÏÔ‚Ô‡ ¶Úfi‰ÚÔ˜ ªˆ˘Û‹˜ ∂ÏÈÛ¿Ê ∞ÓÙÈÚfi‰ÚÔ˜ HÏ›·˜ XÂÈÌÒÓ·˜ °ÂÓÈÎfi˜ °Ú·ÌÌ·Ù¤·˜ ¢ËÌÔÛı¤Ó˘ ¶·Ó·ÁȈٿÎÔ˜ ∂ȉÈÎfi˜ °Ú·ÌÌ·Ù¤·˜ ∂ϤÓË ªÈÏÈ·ÓÔ‡ Δ·Ì›·˜ μ·Û›Ï˘ Õı˘ÚÔ˜ ª¤ÏÔ˜ ª·ÓÒÏ˘ °·ÓˆÙ¿Î˘ ª¤ÏÔ˜ ∞ÛÙ¤ÚÈÔ˜ ∫·Ú·ÁÈ¿ÓÓ˘ ª¤ÏÔ˜ μ·Û›Ï˘ ¡ÈÎÔÏ¿Ô˘ ª¤ÏÔ˜ ÃÚ‹ÛÙÔ˜ ¶›ÙÛ·‚Ô˜ ª¤ÏÔ˜ ∞ϤͷӉÚÔ˜ ΔÛÂϤ˘ ª¤ÏÔ˜
ªÔÚÈ·ÎÔ› ªË¯·ÓÈÛÌÔ› ∞ıËÚÔÛÎÏ‹ÚˆÛ˘. √ ƒfiÏÔ˜ ÙˆÓ ΔÂÏÈÎÒÓ ¶ÚÔ˚fiÓÙˆÓ ¶ÚÔËÁ̤Ó˘ °Ï˘ÎÔ˙˘Ï›ˆÛ˘ (AGEs) ¢ÈÛÏÈ¿Ó μ·ÏÂÓÙ›Ó·, MD, Msc, ÀÔ„‹ÊÈ· ¢È‰¿ÎÙˆÚ π·ÙÚÈ΋˜ ∞¶£ °È·ÓÓfiÁÏÔ˘ °ÂÒÚÁÈÔ˜, ∫·ıËÁËÙ‹˜ ∫·Ú‰ÈÔÏÔÁ›·˜, ∞’ ∫·Ú‰ÈÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌÈ·ÎÔ‡ °ÂÓÈÎÔ‡ ¡ÔÛÔÎÔÌ›Ԣ ∞Ã∂¶∞
11
ªÔÓÔÁÔÓÈΤ˜ ÀÂÚ¯ÔÏËÛÙÂÚÔÏ·È̛˜. °ÂÓÂÙÈÎfi Àfi‚·ıÚÔ. πˆ¿ÓÓ˘ ™Îԇ̷˜, ∞Ó·ÏËÚˆÙ‹˜ ¢È¢ı˘ÓÙ‹˜, ∫·Ú‰ÈÔÏfiÁÔ˜, ÃÚ‹ÛÙÔ˜ ¶›ÙÛ·‚Ô˜, ∞Ó·ÏËÚˆÙ‹˜ ∫·ıËÁËÙ‹˜ ∫·Ú‰ÈÔÏÔÁ›·˜, ∞’ ¶·ÓÂÈÛÙËÌȷ΋ ∫·Ú‰ÈÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ
16
£EPA¶EIA — ºAPMAKA ¶ÚfiˆÚË ¢È·ÎÔ‹ Ù˘ ÀÔÏÈȉ·ÈÌÈ΋˜ º·Ú̷΢ÙÈ΋˜ ∞ÁˆÁ‹˜ : ∞›ÙÈ· Î·È ∞ÔÙÂϤÛÌ·Ù· μ. Õı˘ÚÔ˜, ∞. ∫·Î·Ê‹Î·, ∂. ¶·ÁÎÔ˘Ú¤ÏÈ·˜, ∫. Δ˙ÈfiÌ·ÏÔ˜, ¶. ∞Ó·ÁÓˆÛÙ‹˜, π. °È·‚·Ó›‰Ë˜, Ã. ∫Ô˘Ì·Ú¿˜, ∞. ∫·Ú·ÁÈ¿ÓÓ˘. μ’ ¶ÚÔ·È‰Â˘ÙÈ΋ ¶·ıÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ∞ÚÈÛÙÔÙ¤ÏÂÈÔ ¶·ÓÂÈÛÙ‹ÌÈÔ £ÂÛÛ·ÏÔӛ΢, °¶¡ «π¶¶√∫ƒ∞Δ∂π√»
20
ªË ∫·Ú‰È·Î¤˜ ∂Á¯ÂÈÚ‹ÛÂȘ Û ∞ÛıÂÓ›˜ Ì πÛÙÔÚÈÎfi ∞ÁÁÂÈÔÏ·ÛÙÈ΋˜ ÙˆÓ ™ÙÂÊ·ÓÈ·›ˆÓ ∞ÚÙËÚÈÒÓ °ÂÒÚÁÈÔ˜ ªÔÌfiÙ˘: ∞Ó·Ï ¢È¢ı˘ÓÙ‹˜ ∞ÈÌÔ‰˘Ó·ÌÈÎÔ‡ ∂ÚÁ·ÛÙËÚ›Ô˘ ¡ÔÛÔÎÔÌ›Ԣ ¶··ÁˆÚÁ›Ô˘ £ÂÛÛ·ÏÔÓ›ÎË °È¿ÓÓ˘ °Ô˘‰¤‚ÂÓÔ˜: ∫·ıËÁËÙ‹˜ ∫·Ú‰ÈÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ πˆ·ÓÓ›ÓˆÓ
22
∏ ∞Ó·ÈÌ›· ˆ˜ £Âڷ¢ÙÈÎfi˜ ™Ùfi¯Ô˜ ÛÙËÓ ∫·Ú‰È·Î‹ ∞Ó¿ÚÎÂÈ·. ∫ÏÈÓÈΤ˜ ªÂϤÙ˜ ÁÈ· ÙË ÃÚ‹ÛË ∂Ú˘ıÚÔÔÈËÙ›Ó˘ Î·È ™È‰ËÚÔıÂڷ›·˜. ∂˘ÛÙ¿ıÈÔ˜ ¶·ÁÎÔ˘Ú¤ÏÈ·˜, ÷ڿϷÌÔ˜ ∫Ô˘Ì·Ú¿˜, ÕÓÓ· ∫·Î·Ê‹Î·, ¶·Ú·Û΢‹ ∑ÒÚÔ˘, μ·Û›ÏÂÈÔ˜ Õı˘ÚÔ˜, ∞ÛÙ¤ÚÈÔ˜ ∫·Ú·ÁÈ¿ÓÓ˘. μ' ¶ÚÔ·È‰Â˘ÙÈ΋ ¶·ıÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ∞¶£, πÔÎÚ¿ÙÂÈÔ ¡ÔÛÔÎÔÌ›Ô, £ÂÛÛ·ÏÔÓ›ÎË.
25
∏ ∂›‰Ú·ÛË Ù˘ ∞ÛÈÚ›Ó˘, Ù˘ ¶·Ú·ÎÂÙ·ÌfiÏ˘ Î·È ÙˆÓ ªË-ÛÙÂÚÔÂȉÒÓ ∞ÓÙÈÊÏÂÁÌÔÓˆ‰ÒÓ º·ÚÌ¿ÎˆÓ ÛÙËÓ ∞ÚÙËÚȷ΋ ¶›ÂÛË. ÃÚ‹ÛÙÔ˜ ƒ›˙Ô˜, ∂ÈÛÙËÌÔÓÈÎfi˜ ™˘ÓÂÚÁ¿Ù˘ ÙÔ˘ ∂Í. π·ÙÚ›Ԣ ¢È·Ù·Ú·¯ÒÓ ÙÔ˘ ªÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ §Èȉ›ˆÓ ªˆ˘Û‹˜ ∂ÏÈÛ¿Ê, ∫·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜,
29
√È ∞ÓÂÈı‡ÌËÙ˜ ∂Ó¤ÚÁÂȘ Ù˘ ™ÈÌÔ˘ÙÚ·Ì›Ó˘ ª. ºÏˆÚÂÓÙ›Ó, ∂ÈÛÙËÌÔÓÈÎfi˜ ™˘ÓÂÚÁ¿Ù˘ ÙÔ˘ π·ÙÚ›Ԣ §Èȉ›ˆÓ ∂. §˘ÌÂÚfiÔ˘ÏÔ˜, §¤ÎÙÔÚ·˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ ª. ∂ÏÈÛ¿Ê, ∫·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ
32
¢π∞Δƒ√º∏ ∫·Ù·Ó¿ÏˆÛË ∫·Ê¤ Î·È ∫·Ú‰È·ÁÁÂÈ·Îfi˜ ∫›Ó‰˘ÓÔ˜ ÃÚÈÛÙ›Ó·-ª·Ú›· ∫·ÛÙÔÚ›ÓË, ¢È·ÈÙÔÏfiÁÔ˜-¢È·ÙÚÔÊÔÏfiÁÔ˜, ¢ËÌÔÛı¤Ó˘ μ. ¶·Ó·ÁȈٿÎÔ˜, §¤ÎÙÔÚ·˜ μÈÔÛÙ·ÙÈÛÙÈ΋˜ & ∂ȉËÌÈÔÏÔÁ›·˜ ÃÚ‹ÛÙÔ˜ ¶›ÙÛ·‚Ô˜, ∞Ó. ∫·ıËÁËÙ‹˜ ∫·Ú‰ÈÔÏÔÁ›·˜
36
¶POTEINOMENH BIB§IO°PAºIA
40
ÔÚ›‚Ô˘˜ ηı ‹ Ê Â È · Î ·È‰È¿ ÈÌÂfiÌÔ˘ Û ‡ÌÌÂÙÚË ‰ Ú Û ‰ · Ó ˘ ∏ Û . Ë ‡ Ù Ô È·‚‹ ÓÔ‚ÔÏÈÎ ÁÈ· ÙÔÓ ‰ ÙÔ˘ ÌÂÙ· ÛË ÙÔ˘ ÌÔ Â Ë ˜ ı Û Ó Ë ˆ ‡ Û Ó Û ˆ ¿ Ó Á Ë Á Ú Ù ¿ È· ‰È ÁÁÂÈÙ¤ÏÏÂÈ fiÛÌÈ· √ Ô˘ ·Ó·Û Δ· ÎÚÈÙ‹Ú Ù¿ ηډȷ ÙËÓ ¶·ÁÎ Â Ô Î fi È Ú Ú · · fi Ì Â · Û Ù ˜ Ëı› ÂÓ›˜ ÔÁÂÓ¤ ÚfiÛÊ· ¯Ô˘Ó ÌÂÙÚ È ¤Ó· ÂÓ‰ ·˜ Û ·Ûı ÛıËÎ·Ó ¤ Ù · Ë A ›Ó Ù M  fi D Ì ) A È A Û M · Ë ÓÔ˘˜ Ë (AD ›Â‰ ˘ ıÓ ·Ó·‰˘fiÌ . À„ËÏ¿  ˜ ·˘ÍËÌ¤Ó ı˘Ï·ÚÁÈÓ›Ó ) ˜ Ë √ ˘ Ù ¡ Ô ( ›Î Ù Â ˘ ‰ ‹ Ô È Ù ˜ · Â˚ÓÒÓ Ì¤ÓÔ˘ Ô˘ ·˙Ò ·È Â›Ó ÙˆÓ ÚˆÙ Ó·ÁÓˆÚÈÛ ÍÂȉ›Ô˘ Ù Û‹Ì·Ù· Î · Ô Ë Ó Û ˜ ˘ ¿ ›ˆ Ô Î Ï È Ù ˘ Ï ˙ Ô ÂÙ·‚ ÁÏ˘ÎÔ ÎÔ˙˘Ù· ·fi ·Î¿ Î·È Ì Ì¤Ó˘ ÁÏ˘ -ÂÓ˙˘ÌÈ΋ ·ÓÂÍ¿ÚÙË Á Ë Ë , Ì Ô Ô Ú Û ∏ fi . Ó Ó ˘ ˆ ÓÈ·›· · Ô˘ÛÈÒÓ, ˜ ÎÈÓ‰‡ÓÔ Ó ÚÔ˚fiÓÙ ‰ Â Ò ¿ Ù Î Ì Ó È Ô Ô Ï Ì ÛÙÂÊ·  Á ‹ Ù ¿ Ó Ú Â fi · ·ÙÈÛÌ Ó ÂÙÂÚÔÁ ÂÈ·ÎÔ‡˜ ÛÙÔÓ Û¯ËÌ ‰È·‚ËÙÈÎÒ Es), Ì›· È G Ó Â A ˆ Á ηډȷÁÁ Ù ‹ Ï Ë · s Ù t Û · ÚfiÎÏË Produc Èȉ›ˆÓ Î ˆÓ ‰È·Êfi È· ÙËÓ Ù Á ion End t ˜ È a Ô · Î·È ÙˆÓ Ï Ï c Ù Â fi y Ó l Ú ‡ G Î·È Ô Î·È Â˘ı dvanced ÚË ·ÓÙÈÌ ȉ·ÈÌÈÒÓ È Â ÎÏ‹ÚˆÛË Ï Ù Û Û ‡ Ô Ï›ˆÛ˘ (A Ï ˘ Ú ‰ · Ë Î Ó ı ˆ Ó · ˜ ϤÙË Ù Û ÛÙË ËÚ› ÙËÓ ÈÌÂÙÒÈÛË ÓÂÙÈ΋ Ì ٠ÒÓ ‚Ô‹ıË Â Ó ¯ Á · · Ô˘ Û˘ÓÙ Ú ∏ ˜ · ‹ . Ù Î Ó · È È Ò ÔÈËÙ ÙˆÓ ‰ ˆÓ Ó ÂÈÏÔÎ ÌË ÈηÓÔ fiÏ˄˘ Ù È· ·˘ÙÒÓ ˜ Ú Â Ë Ó Ù ¤ ·ÁÁÂÈ·ÎÒ Á ˜ ˜ ‡ Ô Â › ı Ô Ù Ó · È ÚÔÁÂ Ó·È ÈΤ˜ · Ó ÛÙËÓ Î·È ‰Â˘Ù ÙÈÓÒÓ. ∂› ˜ ÛËÌ·ÓÙ ˜ È · ‡ Ù Ù Ô ÚˆÓ ÌÔÚ›ˆ Û Ó fi Â Ó Á · ˆ Ô Ù Ù Úˆ ‹ ÎÔ‹ ˘˜. ªÈ· ÙËÓ ·ÁˆÁ fiˆÚË ‰È· ·›ÛÈ· Ù˘ Ú Ó Ï ˘ Ô ÙÒÈÛË ÙÔ È · ›˙ · Ù ¯ Î Û Â Ó · ˘ È Ó· Û fi ·Ó·›Ù ȉ·ÈÌ›·˜ ·ÛıÂÓ›˜ ˜ ÌÂÙ¿ · Ó Â›Ó·È Ë ˜ ‰ ˆ ˘ ¿ Ù Ù˘ ‰˘ÛÏÈ Ô Ì ¿ Ù Ô Ì ‰ Ë Ó ‚ ˘ Û Â Ô Ô 1-2 Â›Û ¤ÂÈ·ÎÒÓ Ó Â¤Ì‚·ÛË t ÌÂ Û˘Ó È·ÙÚÒÓ Ó· n ‹ e Ó Î Î·Ú‰È·ÁÁ t ˆ · s È Ù ‰ Ó ˘ Ú fi Ô · Ù ˆÛ˘  ÌË Î Ù˘ ÙˆÓ ıÂÚ· ÓÔ ıÚfiÌ‚ ¤ÎÙˆÛË ÏÏÔÓÙ·È Û ˘ ¿ ‰ Ó Î·ı‹ÎÔÓ ‚ Ë ›Ó Ô Ù Î ˘  fi Ì Ï ˘ ˘ Ó ˘„Ë ÛÌfi ÂÓ›˜ Ô ‰È·ÙÚ¤¯Ô˘ ÔÚÚ‡ıÌÈÛ ÛÂ Û˘Ó‰˘· · t · ÙÔ˘˜. ∞Ûı È n › · Ì e È Î t · s Ó ˜ Ë ·  .∏ ˜. ∏ ›‰Ú·Û ÛÙÈ΋ Ì ÂˆÊÂÏ‹˜ ÂÚÈÙÒÛÂÈ Ô ·ÏÏËÏ ˜ Ï ·ÁÁÂÈÔÏ· Ò Î ˜ Ó ‡ ¤ · Î Û ı È È Ô Ì Ï ‡ Â›Ó·È Î·È Ó· Ê· ÙÔ ÛÙȘ ÓÈÛ˘ ∞À ÔÔÈËÙ›ÓË ¿ ËÁ› Û ¤ Ú ‰ Ê ÂÈ· ı¿Ó· ı Ô Ì ˘ Â Ú ˜ Â Ô ·  › Ó ˘ Ì Á Ú¤Ó Î›Ó‰ ÏÂÈÙÔ˘Ú Ú·Â›· ÂÓ¤¯ÂÈ ÙÔ ËÁÔÚ›·˜ È·˜. ∏ ı ٠ÓÂÊÚÈ΋˜ ·  · Ì Î Î Ë Ú Ù ˜ ¿ Û Ë Ù ¿ Â È Ó ·˘Ù‹˜ ÎÈÓÓÈÎfi ‰ ·Î‹˜ · Ê¿Ú̷η Á¿ÏÔ ¯ÚÔ Èı·ÓÔ‡˜  Ù˘ Î·Ú‰È Â ˜ Ì Ì ˘ · Ô ˜ È Ù ‹ Á Á  ˆ º Ì ›·˜, ÚÈÛË È·˜ ·Á Ì ª™∞ ·¯˘Û·ÚÎ Ë Û ۇÁÎ ·ÎÚÔ¯ÚfiÓ Ï ıÂڷ›· ˜ Ì ¤ Ë Ê Ù Ë Ô Û ¿ Ë · Ù Á Ó · ‹  ·ÎÔ Î ˘Ï¿ÌÂÓfiÌ ÙË ¯ÔÚ Ï¤˜ Ê¿ÚÌ Ë Ù· ·Ó· È Ì ÂÈÊ · „ · ÚÈÓ ·fi Ê Î fi Û ˘ · · Ì È ¿ fi · Ù Î Ù Â · ·ÚÎ ¯‹ ‹ Ì‚¿ÓÔÓ Â›Ó·È ¤Ó· ÚË ÚÔÛÔ Ë ÂÈ Ó· Ï·  ›Ó ›Ù ÛÔ. Ì · È · ‰ Ú È Ù ˘ Â È Ì ÈÌÔ ·ÙÚÈ΋ Ófi · È Û ¯ ›Ù ˘  ∏ „ Á . Ë ˜ ‹ Ú ˘ Ô ‹ Ô ‰‡Ó ÂÈ Ó· ¯ ·Ú‰È·Î ̈˜ Ú¤ ΛÌÂÓË Î fi Ô ˘ ›Ô Ô Â Ì Ô ÙÔ ÃÂÈÌÒÓ·˜ ·ÛıÂÓ›˜ ˜  · Û › Ï · ∏ Ú Â ›Ù ÍÂȘ, ȉȷ
Ù·ÍË Ó ‡ ™ ˜ Ë T
˜
Ù·Í˘ Ó ‡ ™ ˜ Ô Ó ˘ Y‡ı
ª∞ƒΔπ√™ 2008
ΔÔ ªÂÙ·‚ÔÏÈÎfi ™‡Ó‰ÚÔÌÔ: ¢È¿ÁÓˆÛË Î·È ∫·Ú‰È·ÁÁÂÈ·Îfi˜ ∫›Ó‰˘ÓÔ˜ ™‡Á¯ÚÔÓ˜ £ÂˆÚ‹ÛÂȘ ¢Ú. ∞. ªÂÏȉÒÓ˘ ¶·ıÔÏfiÁÔ˜ - ¢È·‚ËÙÔÏfiÁÔ˜ À‡ı˘ÓÔ˜ ¢È·‚ËÙÔÏÔÁÈÎÔ‡ ∫¤ÓÙÚÔ˘ Δ˙·Ó›Ԣ ¡ÔÛÔÎÔÌ›Ԣ ¶ÂÈÚ·È¿ ΔÔ ÌÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ (ª™) Â›Ó·È ¤Ó· ·˙Ï ÌÂÙ·‚ÔÏÈÎÒÓ ‰È·Ù·Ú·¯ÒÓ Ô˘ Ô‰ËÁÔ‡Ó ·Ó·fiÊ¢ÎÙ· ÛÙËÓ ·ıËڈ̿وÛË Î·È ÛÙËÓ Î·Ú‰È·ÁÁÂȷ΋ ÓfiÛÔ. μ·ÛÈΤ˜ „ËÊ›‰Â˜ ·˘ÙÔ‡ ÙÔ˘ ·˙Ï Â›Ó·È Ë ·¯˘Û·ÚΛ· (΢ڛˆ˜ Ë ÎÂÓÙÚÈÎÔ‡ Ù‡Ô˘), Ë ‰˘ÛÏÈȉ·ÈÌ›·, Ë ˘¤ÚÙ·ÛË Î·È Ô Û·Î¯·Ú҉˘ ‰È·‚‹Ù˘. ∫ÔÈÓfi˜ ·Ú·ÓÔÌ·ÛÙ‹˜ ÙˆÓ ‰È·Ù·Ú·¯ÒÓ ·˘ÙÒÓ Â›Ó·È Ë ·ÚÔ˘Û›· ·ÓÙ›ÛÙ·Û˘ ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ÈÛÙÒÓ (Î·È Î˘Ú›ˆ˜ ÙÔ˘ Ì˘˚ÎÔ‡ ÈÛÙÔ‡) ÛÙËÓ ‰Ú¿ÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘.1 ∏ ÈÓÛÔ˘ÏÈÓÔ·ÓÙ›ÛÙ·ÛË ·˘Ù‹ ‰ÂÓ Â›Ó·È ÌÂÓ ÓfiÛÔ˜, Â›Ó·È fï˜ ÎÂÓÙÚÈ΋ ÌÂÙ·‚ÔÏÈ΋ ‰È·Ù·Ú·¯‹ Ô˘ ·˘Í¿ÓÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ÙˆÓ ‰È·Ù·Ú·¯ÒÓ Ô˘ Û˘Ó·ÔÙÂÏÔ‡Ó ÙÔ ÌÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ, ÂÓÒ Û˘Ó‰¤ÂÙ·È ·ÈÙÈÔÏÔÁÈο Ì ÙȘ ‰È·Ù·Ú·¯¤˜ ·˘Ù¤˜. ™‹ÌÂÚ·, ÂÎÙfi˜ ÙˆÓ ‚·ÛÈÎÒÓ Û˘ÓÈÛÙˆÛÒÓ ÙÔ˘ ª.™. ·Ó·Ê¤ÚÂÙ·È Î·È ÌÈ· ÛÂÈÚ¿ ¿ÏÏˆÓ ‰È·Ù·Ú·¯ÒÓ, ÔÈ Ôԛ˜ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙÔ ª.™.: ∏ ˘ÂÚÔ˘Úȯ·ÈÌ›·, ÙÔ ÏÈ҉˜ ‹·Ú, Ë ˘ÓÈ΋ ¿ÓÔÈ·, ÙÔ Û‡Ó‰ÚÔÌÔ ÔÏ˘Î˘ÛÙÈÎÒÓ ˆÔıËÎÒÓ, Ë ·˘ÍË̤ÓË ËÎÙÈÎfiÙËÙ· ÙÔ˘ ·›Ì·ÙÔ˜ ÎÏ. √È ‰È·Ù·Ú·¯¤˜ ·˘Ù¤˜ ‰ÂÓ ÔÚÈÔıÂÙÔ‡Ó ‚‚·›ˆ˜ ÙÔ ª.™., ÂÓ ÙÔ‡ÙÔȘ fï˜ Û˘Ó‰¤ÔÓÙ·È Ì ·˘Ùfi, ÂÍ ·ÈÙ›·˜ Ù˘ ÎÔÈÓ‹˜ ÌÂÙ·‚ÔÏÈ΋˜ ÙÔ˘˜ ·Ó·ÊÔÚ¿˜ Ô˘ Â›Ó·È Ë ÈÓÛÔ˘ÏÈÓÔ·ÓÙ›ÛÙ·ÛË. ΔÔ ª.™. ÂÎÊÚ¿˙ÂÙ·È, ÂÌÊ·Ó›˙ÂÙ·È fiÙ·Ó ÁÂÓÂÙÈÎÒ˜ ÂÈÚÚ‹ ¿ÙÔÌ· ·ÔÎÙÔ‡Ó ˘ÂÚ‚ÔÏÈÎfi ‚¿ÚÔ˜. ∫·Ù' ·˘Ùfi ÙÔÓ ÙÚfiÔ, ·Ú¿ÁÔÓÙ˜ fiˆ˜ ·Óı˘ÁÈÂÈÓ‹ ‰È·ÙÚÔÊ‹ Î·È ÌÂȈ̤ÓË ¤ˆ˜ ·Ó‡·ÚÎÙË ÛˆÌ·ÙÈ΋ ‰Ú·ÛÙËÚÈfiÙËÙ· ‰È·ÌÔÚÊÒÓÔ˘Ó ¤Ó· 'ÙÔÍÈÎfi' ÂÚÈ‚¿ÏÏÔÓ Ô˘ Ú·Á‰·›· ·˘Í¿ÓÂÈ ÙËÓ Û˘¯ÓfiÙËÙ· ÂÌÊ¿ÓÈÛ˘ ÙÔ˘ ÌÂÙ·‚ÔÏÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘.
2
ΔÔ 25% ÙÔ˘ ÏËı˘ÛÌÔ‡ ÛÙËÓ ∞ÌÂÚÈ΋ ‹‰Ë ÂÎÙÈÌ¿Ù·È fiÙÈ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÌÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ. ¶·ÚfiÌÔÈ· Ê·›ÓÂÙ·È fiÙÈ Â›Ó·È Ù· ‰Â‰Ô̤ӷ ÁÈ· ÙÔÓ ÂÈÔÏ·ÛÌfi ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ Î·È ÛÙÔÓ ÂÏÏËÓÈÎfi ÏËı˘ÛÌfi (23-25%, ªÂϤÙ˜ Õı˘ÚÔ˘ Î·È Û˘Ó. Î·È ¶›ÙÛ·‚Ô˘ Î·È Û˘Ó.). ™ÙÔ Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË ‰Â, Ô ÂÈÔÏ·ÛÌfi˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘ Êı¿ÓÂÈ ÙÔ 92%. À¿Ú¯Ô˘Ó ‰È¿ÊÔÚ˜ ÚÔÙ¿ÛÂȘ ÙÂÎÌËÚ›ˆÛ˘ ÙÔ˘ ÌÂÙ·‚ÔÏÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘ ·fi ÌÂÁ¿ÏÔ˘˜ ÔÚÁ·ÓÈÛÌÔ‡˜: WHO (¶·ÁÎfiÛÌÈÔ˜ √ÚÁ·ÓÈÛÌfi˜ ÀÁ›·˜) , NCEP ATP III (∞ÌÂÚÈοÓÈÎË ∂ÈÙÚÔ‹ ∂ȉÈÎÒÓ), IDF (¶·ÁÎfiÛÌÈ· √ÚÁ¿ÓˆÛË ÁÈ· ÙÔÓ ¢È·‚‹ÙË), NCEP-R (∞ÌÂÚÈηÓÈ΋ ∫·Ú‰ÈÔÏÔÁÈ΋ ∂Ù·ÈÚ›· Î·È NHLBI).2 ∏ ÎÏÈÓÈ΋ Ù·ÍÈÓfiÌËÛË ÙÔ˘ ª.™. Ô˘ ¤¯ÂÈ ÚÔÙ·ı› ·fi ∞ÌÂÚÈηÓÈ΋ ÂÈÙÚÔ‹ ÂȉÈÎÒÓ (NCEP) ÚÔ 6ÂÙ›·˜ ÈÛ¯‡ÂÈ ¤ÎÙÔÙ (·Ó·ıˆÚË̤ÓË Â› ̤ÚÔ˘˜ ÙÔ 2005 Û·Ó NCEP-R)3 (¶›Ó·Î·˜ 1) ΢ڛˆ˜ ÁÈ·Ù› ÂÈÙÚ¤ÂÈ ÙÔÓ Â‡ÎÔÏÔ ÚÔÛ‰ÈÔÚÈÛÌfi ÛÙËÓ ÎÏÈÓÈ΋ Ú¿ÍË ÙÔ˘ ª.™. ¶¿ÓÙˆ˜ ÚfiÛÊ·Ù· ÔÈ ‰È¿ÊÔÚ˜ Ù·ÍÈÓÔÌ‹ÛÂȘ Û˘Ó‰¤ÔÓÙ·È Î·È Ì ‰È·ÊÔÚÂÙÈΤ˜ ÚÔ-
ÛÂÁÁ›ÛÂȘ Û¯ÂÙÈο Ì ÙÔÓ ÌÂÙ·‚ÔÏÈÎfi «˘ÚÔ‰ÔÙËÙ‹» ÙÔ˘ ª.™. ∏ ÚÔÛ¤ÁÁÈÛË ÙÔ˘ WHO Ô˘ÛÈ·ÛÙÈο ıˆÚ› ÙËÓ ÈÓÛÔ˘ÏÈÓÔ·ÓÙ›ÛÙ·ÛË ÚˆÙ·Ú¯ÈÎfi ·›ÙÈÔ Ô˘ Ô‰ËÁ› Û ÏÈfiÏ˘ÛË Î·È ÏÈÔÙÔÍÈÎfiÙËÙ·. ∏ ÚÔÛ¤ÁÁÈÛË ÙÔ˘ NCEP ıˆÚ› ÙËÓ ÎÔÈÏȷ΋ ·¯˘Û·ÚΛ· ·ÊÂÙËÚȷ΋ ·ÈÙ›· ÙÔ˘ ª.™., ηıÒ˜ ÙÔ ÌÂÁ¿ÏÔ ÎÔÈÏÈ·Îfi ·ÙÙ·ÚÔ ÂÎÎÚ›ÓÂÈ Î˘ÙÔΛÓ˜ Î·È Î˘Ú›ˆ˜ ÙËÓ ÚˆÙ½ÓË TNFa Ô˘ Âȉڿ ÛÙÔÓ ˘Ô‰Ô¯¤· Ù˘ ÈÓÛÔ˘Ï›Ó˘ Î·È Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ‰ËÌÈÔ˘ÚÁ›· ÈÓÛÔ˘ÏÈÓÔ·ÓÙ›ÛÙ·Û˘. ∂ÈÚfiÛıÂÙ·, Ë ·˘ÍË̤ÓË ·ÂÏ¢ı¤ÚˆÛË ÏÈ·ÚÒÓ ÔͤˆÓ (FFA) › ÎÔÈÏȷ΋˜ ·¯˘Û·ÚΛ·˜ Ô‰ËÁ› ·ÊÂÓfi˜ ÌÂÓ Û ·˘ÍË̤ÓË Û‡ÓıÂÛË ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ, Û ·˘ÍË̤ÓË Û‡ÓıÂÛË ÂȉÈÎÒÓ ·ıËÚÔÌ·ÙˆÁfiÓˆÓ ÌÔÚ›ˆÓ (ÌÈÎÚ¤˜ ˘ÎÓ¤˜ LDL) Î·È Û Ì›ˆÛË Ù˘ ÚÔÛٷ٢ÙÈ΋˜ ¯ÔÏËÛÙÂÚ›Ó˘ (∏DL). √È ‰‡Ô ·˘Ù¤˜ ÚÔÛÂÁÁ›ÛÂȘ ηٷϋÁÔ˘Ó Î·È ÛÙËÓ ‰ËÌÈÔ˘ÚÁ›· ‰‡Ô ÔÓÙÔÙ‹ÙˆÓ Ô˘ ·ÌÊfiÙÂÚ˜ ¢ԉÒÓÔ˘Ó ÙËÓ ·ıËڈ̷ÙÈ΋ ‰È·‰Èηۛ·. ΔÔÓ ‰È·‚‹ÙË Ì ÌÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ Î·È ÙÔ ÌÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ ¯ˆÚ›˜ ‰È·‚‹ÙË. ∏ IDF (¶·ÁÎfiÛÌÈ· √ÚÁ¿ÓˆÛË
¶›Ó·Î·˜ 1. ∫ÚÈÙ‹ÚÈ· ÁÈ· ÙË ‰È¿ÁÓˆÛË ÙÔ˘ ªÂÙ·‚ÔÏÈÎÔ‡ ™˘Ó‰ÚfiÌÔ˘ Statement AHA - NHLBI KÚÈÙ‹ÚÈ· (3 ·fi Ù· 5 Û˘ÓÈÛÙÔ‡Ó ÌÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ) 1. A˘ÍË̤ÓË ÂÚ›ÌÂÙÚÔ˜ ̤Û˘
>102 cm (¿Ó‰Ú˜) >88 (Á˘Ó·›Î˜)
2. A˘ÍË̤ӷ ÙÚÈÁÏ˘ÎÂÚ›‰È·
>150 mg/dl ‹ Ï‹„Ë ·ÁˆÁ‹˜ ÁÈ· TG
3. MÂȈ̤ÓË HDL
<40 mg/dl (¿Ó‰Ú˜) <50 mg/dl (Á˘Ó·›Î˜) ‹ Ï‹„Ë ·ÁˆÁ‹˜ ÁÈ· HDL
4. A˘ÍË̤ÓË AÚÙËÚȷ΋ ›ÂÛË
>130/85 mmHg ‹ Ï‹„Ë ·ÓÙȸ/΋˜ ·ÁˆÁ‹˜
5. A˘ÍË̤ÓÔ Û¿Î¯·ÚÔ ÓËÛÙ›·˜
> 100 mg/dl ‹ Ï‹„Ë ˘ÔÁÏ˘Î·ÈÌÈ΋˜ ·ÁˆÁ‹˜ Circulation 2005;112:2735-52
¶∞ƒ∞°√¡Δ∂™ ∫π¡¢À¡√À ¶›Ó·Î·˜ 2. √ÚÈÛÌfi˜ ÌÂÙ·‚ÔÏÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘ Û ·È‰È¿ Î·È ÂÊ‹‚Ô˘˜ (IDF* 2007).
MÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ ÛÙ· ·È‰È¿ Î·È ÙÔ˘˜ ÂÊ‹‚Ô˘˜ (¶ÚÔÛ‰ÈÔÚÈÛÌfi˜ IDF* 2007) HÏÈ˘ 6 - 10 ÂÙÒÓ
HÏÈ˘ 10 - 16 ÂÙÒÓ
HÏÈ˘ > 16 ÂÙÒÓ
¶·¯˘Û·ÚΛ· = ÂÚ›ÌÂÙÚÔ˜ ̤Û˘ > 90˘ ÂηÙÔÛÙÈ·›·˜ ı¤Û˘
¶·¯˘Û·ÚΛ· = ¶ÂÚ›ÌÂÙÚÔ˜ ̤Û˘ > 90˘ ÂηÙÔÛÙÈ·›·˜ ı¤Û˘
¶·¯˘Û·ÚΛ·: ¶ÂÚ›ÌÂÙÚÔ˜ ̤Û˘ > 94 cm ÁÈ· ·ÁfiÚÈ· Î·È 80 cm ÁÈ· ÎÔÚ›ÙÛÈ·
MÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ ‰ÂÓ ‰È·ÁÈÁÓÒÛÎÂÙ·È.
¶·ÚÔ˘Û›· 2 ·ÎfiÌË ÎÚÈÙËÚ›ˆÓ
¶·ÚÔ˘Û›· 2 ·ÎfiÌË ÎÚÈÙ‹ÚÈ·
ñ ™¿Î¯·ÚÔ ÓËÛÙ›·˜ > 100 mg% ‹ ÁÓˆÛÙfi˜ ™¢II
ñ ™¿Î¯·Ú· ÓËÛÙ›·˜ > 100 mg% ‹ ÁÓˆÛÙfi˜ ™¢II
¶ÚfiÛıÂÙ˜ ÂÍÂÙ¿ÛÂȘ Â¿Ó ˘¿Ú¯ÂÈ ÔÈÎÔÁÂÓÈ·Îfi ÈÛÙÔÚÈÎfi
ñ ™˘ÛÙ. A.¶. > 130 ‹ ¢È·ÛÙ. A.¶. >85
ñ ™˘ÛÙ. A.¶. > 130 ‹ ¢È·ÛÙ. A.¶. >85 ‹ ÁÓˆÛÙ‹ ˘¤ÚÙ·ÛË ˘fi ·ÁˆÁ‹
ñ MÂÙ·‚ÔÏÈÎÔ‡ ™˘Ó‰ÚfiÌÔ˘
ñ HDL < 40 mg
EÊ›ÛÙ·Ù·È ÚÔÛÔ¯‹ ÁÈ· Ì›ˆÛË ‚¿ÚÔ˘˜.
ñ TÚÈÁÏ˘Î. NËÛÙ›·˜ > 150 mg%
ñ ¢˘ÛÏÈȉ·ÈÌ›·˜
ñ TÚÈÁÏ˘Î > 150 mg% ‹ Ï‹„Ë ˘ÔÏÈ/΢ ·ÁˆÁ‹˜ ñ HDL < 40 ÁÈ· ·ÁfiÚÈ· ‹ < 50 ÁÈ· ÎÔÚ›ÙÛÈ· ‹ Ï‹„Ë ÂȉÈ΋˜ ˘ÔÏÈ/΢ ·ÁˆÁ‹˜
ñ K·Ú‰È·ÁÁÂȷ΋˜ ÓfiÛÔ˘ ñ Y¤ÚÙ·Û˘ ñ ¶·¯˘Û·ÚΛ·˜ Zimmet et al: Lancet 2007;369:2059-2061
ÁÈ· ÙÔÓ ‰È·‚‹ÙË) ÚfiÛÊ·Ù· ·Ó¤Ù˘Í ¤Ó· Ó¤Ô Ï·›ÛÈÔ ÚÔÛ‰ÈÔÚÈÛÌÔ‡ ÙÔ˘ ÌÂÙ·‚ÔÏÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘ ÛÙ· ·È‰È¿ Î·È ÛÙÔ˘˜ ÂÊ‹‚Ô˘˜. ™‡Ìʈӷ Ì ·˘ÙfiÓ: ñ Δ· ·È‰È¿ ËÏÈΛ·˜ οو ÙˆÓ 6 ÂÙÒÓ ÂÍ·ÈÚÔ‡ÓÙ·È ·fi ÙÔÓ ÔÚÈÛÌfi ·˘Ùfi ÂÂȉ‹ ˘Ê›ÛÙ·ÓÙ·È ÂÓȯڿ ÛÙÔȯ›· ÁÈ· ÙËÓ ÎÏÈÓÈ΋ ·˘Ù‹ ÔÌ¿‰·. ñ °È· Ù· ·È‰È¿ ËÏÈΛ·˜ 6 - 10 ÂÙÒÓ Â›Û˘ ‰ÂÓ Ù›ıÂÙ·È ‰È¿ÁÓˆÛË ÌÂÙ·‚ÔÏÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘. ŸÌˆ˜ ÂÊÈÛÙ¿Ù·È È‰È·›ÙÂÚË ÚÔÛÔ¯‹ ÛÙ· ·È‰È¿ Ì ÎÔÈÏȷ΋ ·¯˘Û·ÚΛ· (ÂÚ›ÌÂÙÚÔ˜ ̤Û˘ >90˘ ÂηÙÔÛÙÈ·›·˜ ı¤Û˘), ÛÙ· ÔÔ›· Ú¤ÂÈ Ó· ‰Ôı› ÈÛ¯˘Úfi Ì‹Ó˘Ì· ÁÈ· Ì›ˆÛË ÙÔ˘ ‚¿ÚÔ˘˜ ÙÔ˘. ∂›Û˘ ÚfiÛıÂÙ˜ ÌÂÙÚ‹ÛÂȘ Ú¤ÂÈ Ó· Á›ÓÔ˘Ó Â¿Ó ˘¿Ú¯ÂÈ ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi ÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ Î·È Î·Ú‰È·ÁÁÂȷ΋˜ ÓfiÛÔ˘ (¶›Ó·Î·˜ 2) ñ ™ÙÔ˘˜ ÂÊ‹‚Ô˘˜ 10 - 16 ÂÙÒÓ ‰È·ÁÈÁÓÒÛÎÂÙ·È ÌÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ Â¿Ó ˘¿Ú¯ÂÈ ÎÔÈÏȷ΋ ·¯˘Û·ÚΛ· (ÂÚ›ÌÂÙÚÔ˜ ̤Û˘ >90˘ ÂηÙÔÛÙÈ·›·˜ ı¤Û˘) Î·È ·ÚÔ˘Û›· ‰‡Ô ÙÔ˘Ï¿¯ÈÛÙÔÓ ÂÈϤÔÓ ÎÚÈÙËÚ›ˆÓ - ÎÏÈÓÈÎÒÓ ÛÙÔȯ›ˆÓ (¶›Ó·Î·˜ 2) . ñ ™ÙȘ ÌÂÙÂÊË‚ÈΤ˜ ËÏÈ˘ >16 ÂÙÒÓ ÁÈ· ÙË ‰È¿ÁÓˆÛË ÙÔ˘ ÌÂÙ·‚ÔÏÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È Ù· ÎÚÈÙ‹ÚÈ· ÙÔ˘ IDF Ô˘ ÈÛ¯‡Ô˘Ó ÁÈ· ÙËÓ ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ÛÙÔ˘˜ ÂÓ‹ÏÈΘ (¶›Ó·Î·˜ 2).
∫·Ú‰È·ÁÁÂÈ·Îfi˜ ΛӉ˘ÓÔ˜ Î·È ªÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ ∂ÓÒ ÛÙÔ ·ÚÂÏıfiÓ ‹Ù·Ó ‰Â‰Ô̤ÓÔ˜, ·ıÔÊ˘ÛÈÔÏÔÁÈο ÚÔÛ‰ÈÔÚÈṲ̂ÓÔ˜ (™¯‹Ì· 1) Î·È ÂȉËÌÈÔÏÔÁÈο ÙÂÎÌËÚȈ̤ÓÔ˜ Ô ·˘ÍË̤ÓÔ˜ ηډȷÁÁÂÈ·Îfi˜ ΛӉ˘ÓÔ˜ › ÌÂÙ·‚ÔÏÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘, Û‹ÌÂÚ· ¤¯Ô˘Ó ·Ó·Ù˘¯ı› ÌÈ· ÛÂÈÚ¿ ·fi ÂÚˆÙ‹Ì·Ù· Ô˘ ·Ó·˙ËÙÔ‡Ó ‚È‚ÏÈÔÁÚ·ÊÈο ÙÂÎÌËÚȈ̤ÓË Û·Ê‹ ·¿ÓÙËÛË. ñ ∂›Ó·È ·˘ÍË̤ÓÔ˜ Ô Î·Ú‰È·ÁÁÂÈ·Îfi˜ ΛӉ˘ÓÔ˜ (∫.∫) › ª.™.; ∂Í·ÎÔÏÔ˘ı› Ó· Â›Ó·È ·˘ÍË̤ÓÔ˜ ·ÊÔ‡ Á›ÓÂÈ ÚÔÛ·ÚÌÔÁ‹ ÛÙȘ › ̤ÚÔ˘˜ Û˘ÓÈÛÙÒÛ˜ ÙÔ˘; ñ ¢È·ÊÔÚÔÔÈÂ›Ù·È Ô Î›Ó‰˘ÓÔ˜ ·Ó¿ÏÔÁ· Ì ÙËÓ Î·ÙËÁÔÚÈÔÔ›ËÛË ÙÔ˘ ª.™ ‹ ·Ó¿ÏÔÁ· Ì ÙÔÓ Û˘Ó‰˘·ÛÌfi ÙˆÓ ·Ú·ÁfiÓÙˆÓ Ô˘ ÚÔÛ‰ÈÔÚ›˙ÂÈ ÙÔ ª.™;
(HR=1,21 p<0,0001) ·ÏÏ¿ Î·È Î·Ú‰È·ÁÁÂȷ΋˜ ıÓËÛÈÌfiÙËÙ·˜ (HR=1,51 p<0,0001). ™ÙËÓ ÌÂϤÙË ARIC6 (12.000 ¿ÙÔÌ· Ì 11 ¤ÙË ·Ú·ÎÔÏÔ‡ıËÛË) ÙÔ ª.™. Û˘Ó‰ÂfiÙ·Ó Ì ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘ ȉȷ›ÙÂÚ· ÛÙȘ Á˘Ó·›Î˜ (HR=2,5 ÁÈ· Á˘Ó·›Î˜ Ì ª.™ Î·È HR=1,51, ÁÈ· ¿Ó‰Ú˜ Ì ª.™) fiˆ˜ ›Û˘ Î·È ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ∞∂∂ (HR=1,9 ÁÈ· Á˘Ó·›Î˜ Î·È 1,5 ÁÈ· ¿Ó‰Ú˜). ∞ÏÏ¿ Î·È Û ÂȉÈΤ˜ ÌÂÙ·‚ÔÏÈΤ˜ ηٷÛÙ¿ÛÂȘ Ë ·ÚÔ˘Û›· ª.™ Û˘Ó‰¤ÂÙ·È Ì ·˘ÍË̤ÓÔ ∫.∫. ™ÙËÓ WOSCOPS7 (ÚˆÙÔÁÂÓ‹˜ ÌÂϤÙË Û ·ÛıÂÓ›˜ Ì ˘ÂÚÏÈȉ·ÈÌ›·) Ë ÔÌ¿‰· ÙÔ˘ ª.™ ›¯Â HR=3,1.
ñ ¶ÚÔÛı¤ÙÂÈ ÙÔ ª.™. ÚÔÁÓˆÛÙÈ΋ ÛËÌ·Û›· ÛÙ· ÎÏ·ÛÈο ÚÔÁÓˆÛÙÈο Û˘ÛÙ‹Ì·Ù· ÁÈ· ÙËÓ Î·Ú‰È·ÁÁÂȷ΋ ÓfiÛÔ;
™ÙËÓ ÌÂϤÙË PIUMA8 (·ÛıÂÓ›˜ Ì ˘¤ÚÙ·ÛË) Ë ·ÚÔ˘Û›· ÙÔ˘ ª.™ ÙÚÈÏ·Û›·˙ ÙÔÓ Û¯ÂÙÈÎfi ΛӉ˘ÓÔ ÁÈ· ∫.¡. ™ÙËÓ ÌÂϤÙË RICOAMI9 (·ÛıÂÓ›˜ Ì √∂ª) ÙÔ ª.™. Û˘Óԉ¢fiÙ·Ó Ì O.R=2,13 ÁÈ· ηډȷ΋ ·Ó¿ÚÎÂÈ· Î·È ÙÚÈÏ¿ÛÈÔ Î›Ó‰˘ÓÔ ÁÈ· ı·Ó·ÙËÊfiÚÔ ÂÂÈÛfi‰ÈÔ.
∞fi ÙËÓ ‚È‚ÏÈÔÁÚ·Ê›· ÙÂÎÌËÚÈÒÓÂÙ·È ÁÂÓÈο fiÙÈ ÙÔ ª.™. Û˘Óԉ‡ÂÙ·È Ì ·˘ÍË̤ÓÔ Î·Ú‰È·ÁÁÂÈ·Îfi ΛӉ˘ÓÔ. ™ÙËÓ ÌÂϤÙË KUOPIO4 ÙÔ ª. ™. Û˘Ó‰ÂfiÙ·Ó Ì ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ıÓËÛÈÌfiÙËÙ·˜ (RR=2,43) Î·È ÛÙÂÊ·ÓÈ·›·˜ ıÓËÛÈÌfiÙËÙ·˜ (RR=3,77). ™ÙËÓ ÁÓˆÛÙ‹ MRFIT5 ÌÂϤÙË Ë ·ÚÔ˘Û›· ÙÔ˘ ª.™. Û˘Ó‰ÂfiÙ·Ó Ì ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÔÏÈ΋˜ ıÓËÛÈÌfiÙËÙ·˜
™ÙËÓ NHANES10 ÌÂϤÙË (6200 ¿ÙÔÌ· Ì 13,5 ¤ÙË ·Ú·ÎÔÏÔ‡ıËÛË) ÙÔ ª.™ (¯ˆÚ›˜ ‰È·‚‹ÙË) Û˘Ó‰ÂfiÙ·Ó Ì ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ Î·Ú‰È·ÁÁÂȷ΋˜ ıÓËÛÈÌfiÙËÙ·˜ (HR=1,17 p<0,0001) ·ÏÏ¿ fi¯È ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÔÏÈ΋˜ ıÓËÛÈÌfiÙËÙ·˜ (HR=1,17 p<0,11). ™ÙËÓ ›‰È· ÌÂϤÙË fï˜ ÙÔ ª.™ (Ì ‰È·‚ËÙÈÎÔ‡˜) Û˘Ó‰ÂfiÙ·Ó Ì ȉȷ›ÙÂÚ· ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ Î·Ú-
3
ª∞ƒΔπ√™ 2008
‰È·ÁÁÂȷ΋˜ ıÓËÛÈÌfiÙËÙ·˜ (HR = 2,42 p<0,0001) ·ÏÏ¿ Î·È ÔÏÈ΋˜ ıÓËÛÈÌfiÙËÙ·˜ (HR = 1,97 p<0,0001). Δ· ›‰È· ‰Â‰Ô̤ӷ ÚÔÛ‰ÈÔÚ›˙Ô˘Ó Î·È 2 ÚfiÛÊ·Ù˜ ÌÂÙ··Ó·Ï‡ÛÂȘ. ∏ ÌÂÙ··Ó¿Ï˘ÛË ÙÔ˘ FORD11 (2005) ¤‰ÂÈÍ fiÙÈ ÙÔ ª.™ Û˘Ó‰¤ÂÙ·È Ì ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ∫.¡ HR=1,58 Ô˘ Á›ÓÂÙ·È È‰È·›ÙÂÚ· ·˘ÍË̤ÓÔ˜ fiÙ·Ó ÛÙËÓ ÌÂÙ··Ó¿Ï˘ÛË Û˘ÌÂÚÈÂÏ‹ÊıËÛ·Ó Î·È ÔÈ ÌÂϤÙ˜ Ô˘ ÂÚÈÂÏ¿Ì‚·Ó·Ó Î·È ‰È·‚ËÙÈÎÔ‡˜ ·ÛıÂÓ›˜ (HR = 2,12). ™Â ÌÂÙ··Ó¿Ï˘ÛË 37 ÌÂÏÂÙÒÓ - 17.200 ·ÙfiÌˆÓ (Gami et al 2007)12 Ë ·Ó·ÏÔÁ›· ÎÈÓ‰‡ÓÔ˘ ÁÈ· ™.¡ ‹Ù·Ó 1,74 Î·È ·Ú¤ÌÂÈÓ ÛËÌ·ÓÙÈ΋ (1,54) ÌÂÙ¿ ÚÔÛ·ÚÌÔÁ‹ ÁÈ· Ù· Û˘ÛÙ·ÙÈο ÙÔ˘ ª.™. ™˘ÌÂÚ·ÛÌ·ÙÈο ˆ˜ ÚÔ˜ ÙÔ ÚÒÙÔ ÂÚÒÙËÌ·: √ ΛӉ˘ÓÔ˜ ∫. ¡ Â›Ó·È ·˘ÍË̤ÓÔ˜ ÛÙÔ ª.™. ∏ ·ÚÔ˘Û›· ÙÔ˘ ‰È·‚‹ÙË ÛÙ· ÚÔÛ‰ÈÔÚ›˙ÔÓÙ· ÎÚÈÙ‹ÚÈ· ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ·˘Í¿ÓÂÈ ÛËÌ·ÓÙÈο ÙÔÓ Î›Ó‰˘ÓÔ, ÂÓÒ Ë ÚÔÛ·ÚÌÔÁ‹ ÚÔ˜ ÙȘ ·Ú·Ì¤ÙÚÔ˘˜ ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ÙÔÓ ÌÂÈÒÓÂÈ È‰È·›ÙÂÚ· ¯ˆÚ›˜ fï˜ Ó· ÙÔÓ ÂÍ·Ï›ÊÂÈ. ∞Ó·ÊÔÚÈο Ì ÙÔ ‰Â‡ÙÂÚÔ ÂÚÒÙËÌ·: √ ·˘ÍË̤ÓÔ˜ ηډȷÁÁÂÈ·Îfi˜ ΛӉ˘ÓÔ˜ ÙÔ˘ ª.™ ‰ÂÓ Ê·›ÓÂÙ·È Ó· ˘Ê›ÛÙ·Ù·È fiÙ·Ó Ë Î·ÙËÁÔÚÈÔÔ›ËÛË ÙÔ˘ ª.™ Á›ÓÂÙ·È ‚¿ÛÂÈ
ÙˆÓ ÎÚÈÙËÚ›ˆÓ ÙÔ˘ IDF (ÌÂϤÙ˜ Õı˘ÚÔ˘ Î·È Û˘ÓÂÚÁ·ÙÒÓ, Peter et al).13,14 º·›ÓÂÙ·È Â›Û˘ fiÙÈ Ô Î·Ú‰È·ÁÁÂÈ·Îfi˜ ΛӉ˘ÓÔ˜ ÙÔ˘ ª.™ ‰È·ÊÔÚÔÔÈÂ›Ù·È ·Ó¿ÏÔÁ· Ì ÙÔÓ Û˘Ó‰˘·ÛÌfi ·Ú·ÁfiÓÙˆÓ Ô˘ ÚÔÛ‰ÈÔÚ›˙ÂÈ ÙÔ ª.™. ™Â ÏËı˘ÛÌȷ΋ ÌÂϤÙË 40.000 ·ÙfiÌˆÓ Ì ‰È¿ÚÎÂÈ· ·Ú·ÎÔÏÔ‡ıËÛ˘ 4 ¯ÚfiÓÈ· (Guize et al 2007)15 Ô ÈÛ¯˘ÚfiÙÂÚÔ˜ Û˘Ó‰˘·ÛÌfi˜ ª.™ Ì ·Ó·ÏÔÁ›· ÎÈÓ‰‡ÓÔ˘ (HR) = 4.3 ‹Ù·Ó Ô Û˘Ó‰˘·ÛÌfi˜ ÎÔÈÏȷ΋˜ ·¯˘Û·ÚΛ·˜, ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜ Î·È ‰È·‚‹ÙË. ™Ù· ¿ÙÔÌ· Ì ‰È·‚‹ÙË ÌÂϤÙË ÌÂÁ¿Ï˘ ‰È¿ÚÎÂÈ·˜ ·Ú·ÎÔÏÔ‡ıËÛ˘ (10 ¯ÚfiÓÈ·, ¶ÚˆÙÔ„¿ÏÙ˘ 2007)16 ¤‰ÂÈÍ fiÙÈ Ô Û˘Ó‰˘·ÛÌfi˜ ‰È·‚‹ÙÔ˘ - ˘¤ÚÙ·Û˘ Î·È ¯·ÌËÏ‹˜ HDL Â›Ó·È Ô Ï¤ÔÓ ÈÛ¯˘Ú¿ Û˘Û¯ÂÙÈ˙fiÌÂÓÔ˜ Ì ∫.¡ (HR=1,79) ÂÓÒ ˘¿Ú¯Ô˘Ó Î·È Û˘Ó‰˘·ÛÌÔ› ª.™ Ô˘ ‰ÂÓ Û¯ÂÙ›˙ÔÓÙ·È ÛËÌ·ÓÙÈο Ì ÙÔÓ ∫.∫. ™˘ÌÂÚ·ÛÌ·ÙÈο ˆ˜ ÚÔ˜ ÙÔ ‰Â‡ÙÂÚÔ ÂÚÒÙËÌ·: √ ·˘ÍË̤ÓÔ˜ ΛӉ˘ÓÔ˜ ∫.¡ Ê·›ÓÂÙ·È Ó· ÂÍ·ÚÙ¿Ù·È Î·È ·fi Ù· ÎÚÈÙ‹ÚÈ· ÚÔÛ‰ÈÔÚÈÛÌÔ‡ ÙÔ˘ ª.™, Ì ÙÔ ª.™ ηٿ IDF Ó· ÌË Û˘Óԉ‡ÂÙ·È ¿ÓÙ· Ì ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ∫.¡. À¿Ú¯ÂÈ Â›Û˘ ‰È·‚¿ıÌÈÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ∫.¡ ·Ó¿ÏÔÁ· Ì ÙÔ Â›‰Ô˜ ÙˆÓ ÎÚÈÙËÚ›ˆÓ Ô˘ ÂÚÈÏ·Ì-
™¯‹Ì· 1. ªÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ Î·È ·ıËÚÔÌ¿ÙˆÛË
°ÂÓÂÙÈο ·›ÙÈ·
ΔÔÍÈÎfiÙËÙ· ÁÏ˘Îfi˙˘
™¢ Ù‡Ô˘ ππ
÷ÌËÏfi ‚¿ÚÔ˜ Á¤ÓÓËÛ˘
¶·¯˘Û·ÚΛ· Î·È ¤ÏÏÂÈ„Ë Ê˘ÛÈ΋˜ ¿ÛÎËÛ˘ ∏ÏÈΛ·
º¿Ú̷η §ÈÔ·ÙÚÔÊ›·
π¡™√À§π¡√∞¡Δπ™Δ∞™∏ ª∂Δ∞μ√§π∫√ ™À¡¢ƒ√ª√
À¤ÚÙ·ÛË
¢˘ÛÏÈȉ·ÈÌ›·
¶ÚÔËÎÙÈ΋ º¿ÛË
ÃÚfiÓÈ· ¯·ÌËÏÔ‡ ‚·ıÌÔ‡ ÊÏÂÁÌÔÓ‹
∂Ó‰Ôı˘Ïȷ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·
∫ÔÈÏȷ΋ ·¯˘Û·ÚΛ·
∫∞ƒ¢π√/ª∞∫ƒ√∞°°∂π√¶∞£∏Δπ∫∏ ¡√™√™ Standl E. et al. Eur. Heart J. 2005; 7:D10-13
4
‚¿ÓÔÓÙ·È ÛÙËÓ ÙÚÈ¿‰· Ô˘ ÔÚ›˙ÂÈ ÙÔ ª.™. ∏ ·ÚÔ˘Û›· ‰È·‚‹ÙË Î·È ÎÔÈÏȷ΋˜ ·¯˘Û·ÚΛ·˜ ÛÙËÓ ÙÚÈ¿‰· ÚÔÛ‰›‰Ô˘Ó ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘. ŸÛÔÓ ·ÊÔÚ¿ ÙÔÓ ÚÔ‚ÏËÌ·ÙÈÛÌfi Â¿Ó ÙÔ ª.™ ÚÔÛı¤ÙÂÈ ÚÔÁÓˆÛÙÈ΋ ·Í›· ÛÙ· ˘¿Ú¯ÔÓÙ· ÌÔÓ٤Ϸ ηډȷÁÁÂÈ·ÎÔ‡ ÎÈÓ‰‡ÓÔ˘ fiˆ˜ ÙÔ Framingham risc model Ù· ÂÚ¢ÓËÙÈο ‰Â‰Ô̤ӷ Â›Ó·È Û·Ê‹: ΔÔ ª.™ ‰ÂÓ ÚÔÛı¤ÙÂÈ ÚÔÁÓˆÛÙÈ΋ ·Í›· ÛÙÔ Framingham score fiˆ˜ Ê¿ÓËΠ۠·Ó·Ï‡ÛÂȘ Ì c-statistic Î·È ROC η̇Ϙ (Johan Sundström et al, 2006)17. ¶ÚfiÛÊ·ÙË Â›Û˘ ·Ó¿Ï˘ÛË ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ Ù˘ UKPDS ¤‰ÂÈÍ fiÙÈ Ë ·ÚÔ˘Û›· ÙÔ˘ ª.™ ‰ÂÓ ÙÚÔÔÔÈ› ÙËÓ Î·Ì‡ÏË ÙÔ˘ 10ÂÙÔ‡˜ ηډȷÁÁÂÈ·ÎÔ‡ ÎÈÓ‰‡ÓÔ˘ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ‰È·‚‹ÙË.18 ™˘ÌÂÚ·ÛÌ·ÙÈο ˆ˜ ÚÔ˜ ÙÔ ÙÚ›ÙÔ ÂÚÒÙËÌ·: ΔÔ ª.™ ‰ÂÓ ·˘Í¿ÓÂÈ ÙËÓ ÚÔÁÓˆÛÙÈ΋ ÈηÓfiÙËÙ· ÙˆÓ ˘·Ú¯fiÓÙˆÓ ÌÔÓÙ¤ÏˆÓ ÚÔÛ‰ÈÔÚÈÛÌÔ‡ ÙÔ˘ ∫.∫. ΔÔ ÂӉȷʤÚÔÓ ¿ÓÙˆ˜ ÛÙÔÈ¯Â›Ô Û ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ Â›Ó·È fiÙÈ Ë ·ÚÔ˘Û›· ÈÓÛÔ˘ÏÈÓÔ·ÓÙ›ÛÙ·Û˘ ‰ÈÏ·ÛÈ¿˙ÂÈ ÙÔÓ Î·Ú‰È·ÁÁÂÈ·Îfi ΛӉ˘ÓÔ ÙÔ˘ ª.™ (ÌÂϤÙË Framingham offspring study 2007)19. ª‹ˆ˜ ÙÂÏÈο Ë ·Ôχو˜ ÂӉȷʤÚÔ˘Û· ηٿÛÙ·ÛË ÁÈ· ÙËÓ Î·Ú‰È·ÁÁÂȷ΋ ÓfiÛÔ Â›Ó·È Ë ÈÓÛÔ˘ÏÈÓÔ·ÓÙ›ÛÙ·ÛË Î·È fi¯È ÙÔ Ô‡Ùˆ˜ ‹ ¿Ïψ˜ ·Û·Ê¤˜ Î·È Ì ÔÏÏ¿ ·ÓÙÈÊ·ÙÈο ÛÙÔȯ›· ª.™; ª‹ˆ˜ ÙÂÏÈο Ô Reaven Ô ÁÂÓÓ‹ÙÔÚ·˜ Î·È Ûη·Ó¤·˜ ÙÔ 1988 ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ÈÓÛÔ˘ÏÈÓÔ·ÓÙ›ÛÙ·Û˘ (Ô˘ ·ÚÁfiÙÂÚ· ÌÂÙÂÍÂÏ›¯ıËΠ۠ÌÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ) ÚˆÙÔÔÚ› Í·Ó¿ ÌÂÙ¿ 20ÂÙ›· ·Ó·Ê¤ÚÔÓÙ·˜ ÚfiÛÊ·Ù· fiÙÈ20: «∏ ¤ÌÊ·ÛË Ú¤ÂÈ Ó· ‰Ôı› ÛÙËÓ ÂÈÏÔÁ‹ ÙÔ˘ ηٿÏÏËÏÔ˘ ıÂڷ¢ÙÈÎÔ‡ Û¯‹Ì·ÙÔ˜ ÁÈ· ÙËÓ Ì›ˆÛË ÙÔ˘ ηډȷÁÁÂÈ·ÎÔ‡ ÎÈÓ‰‡ÓÔ˘ Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ÈÓÛÔ˘ÏÈÓÔ·ÓÙ›ÛÙ·ÛË ·ÓÂÍ¿ÚÙËÙ· ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ÎÚÈÙËÚ›ˆÓ ÁÈ· ª.™ ηٿ NCEP - ATP III Ô˘ ÈηÓÔÔÈÔ‡ÓÙ·È;»
¶∞ƒ∞°√¡Δ∂™ ∫π¡¢À¡√À μÈ‚ÏÈÔÁÚ·Ê›·
1.
2.
3.
4.
5.
6.
7.
£. ∞ÏÂÍ·Ó‰Ú›‰Ë˜. ∞ÓÙ›ÛÙ·ÛË ÛÙËÓ ÈÓÛÔ˘Ï›ÓË: ªÔÚÈ·ÎÔ› Ì˯·ÓÈÛÌÔ›, ۷ί·Ú҉˘ ‰È·‚‹Ù˘, ÌÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ, ·ıËÚˆÛÎÏ‹Ú˘ÓÛË. ÛÙÔ ∞. ªÂÏȉÒÓ˘ «∫·Ú‰ÈÔÌÂÙ·‚ÔÏÈÎfi˜ ∫›Ó‰˘ÓÔ˜», ÛÂÏ. 759 795, ∂Ή. π. ¶·ÚÈÛÈ¿ÓÔ˘, (2007) ∂. §˘ÌÂÚfiÔ˘ÏÔ˜ - ª. ∂ÏÈÛ¿Ê. ªÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ. ¢È·ÁÓˆÛÙÈο ÎÚÈÙ‹ÚÈ· - ıÂڷ¢ÙÈΤ˜ ·ÚÂÌ‚¿ÛÂȘ ÛÙÔ ∞. ªÂÏȉÒÓ˘ «∫·Ú‰ÈÔÌÂÙ·‚ÔÏÈÎfi˜ ∫›Ó‰˘ÓÔ˜», ÛÂÏ. 795 - 831, ∂Ή. π. ¶·ÚÈÛÈ¿ÓÔ˘,(2007) Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, and Costa F. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005;112:2735-2752 Lakka H-M, Laaksonen DA, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT. The Metabolic Syndrome and Total and Cardiovascular Disease Mortality in Middle-aged Men JAMA 2002;288:2709 - 2716.
8.
Schillaci G, Pirro M, Vaudo G, Gemelli F, Marchesi S, Porcellati C, Mannarino E. Prognostic value of the metabolic syndrome in essential hypertension. J Am Coll Cardiol 2004;43:1817-1822.
9.
ZellerM, Steg PG, Ravisy J, Laurent Y, Janin-Manificat L, L'Huillier I, Beer J-C, Oudot A, Rioufol G, Makki H, Farnier M, Rochette L, Vergès B, Cottin Y, for the Observatoire des Infarctus de Côte-d'Or Survey Working Group Prevalence and Impact of Metabolic Syndrome on Hospital Outcomes in Acute Myocardial Infarction. Arch Intern Med 2005;165:1192-1198.
10. Malik S, Wong ND, Franklin SS, Kamath TV, L'Italien GJ, Pio JR, Williams GR. Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation 2002;110:1245-1250. 11. Ford ES. Risks for All-Cause Mortality, Cardiovascular Disease, and Diabetes Associated With the Metabolic Syndrome: A summary of the evidence. Diabetes Care 2005;28:1769-1778.
Eberly LE, Prineas R, Cohen GD, Vazquez G, Zhi X, Neaton JD, KullerLH for the Multiple Risk Factor Intervention Trial Research Group. Metabolic Syndrome: Risk factor distribution and 18-year mortality in the Multiple Risk Factor Intervention Trial. Diabetes Care 2006;29:123-130.
12. Gami AS, Witt BJ, Howard DE, Erwin PJ, Gami LA, Somers VK, Montori VM. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and metaanalysis of longitudinal studies. J. Am. Coll. Cardiol. 2007;49:403-414.
McNeill AM, Rosamond WD, Girman CJ, Golden SH, Schmidt MI, East SH, Ballantyne SM, Heiss G. The Metabolic Syndrome and 11-Year Risk of Incident Cardiovascular Disease in the Atherosclerosis Risk in Communities Study. Diabetes Care 2005;28:385-390.
13. Athyros VG, Ganotakis ES, Bathianaki M, Monedas I, Goudevenos IA, Papageorgiou AA, Papathanasiou A, Kakafika AI, Mikhailidis DP, Elisaf M; MetS-Greece Collaborative Group. Awareness, treatment and control of the metabolic syndrome and its components: a multicentre Greek study. Hellenic J. Cardiol. 2005; 46:380-386.
Sattar N, Gaw A, Scherbakova O, Ford I, O'Reilly DSTJ, Haffner SM, Isles C, Macfarlane PW, Packard CJ, Cobbe SM, Shepherd J. Metabolic Syndrome With and Without C-Reactive Protein as a Predictor of Coronary Heart Disease and Diabetes in the West of Scotland Coronary Prevention Study. Circulation 2003;108:414 - 419.
14. Tong PC, Kong AP, So W-Y, Yang X, Ho C-S, Ma RC, Ozaki R,Chow C-C, Lam CW, Chan JCN, Cockram CS. The Usefulness of the International Diabetes Federation and the National Cholesterol Education Program's Adult Treatment Panel III Definitions of the Metabolic
Syndrome in Predicting Coronary Heart Disease in Subjects With Type 2 Diabetes. Diabetes Care 2007;30:12061211. 15. Guize L, Thomas F, Pannier B, Bean K, Jego B, Benetos A. All-Cause Mortality Associated With Specific Combinations of the Metabolic Syndrome According to Recent Definitions Diabetes Care 2007;30:2381-2387. 16. Protopsaltis I, Nikolopoulos G, Dimoua E, Brestas P, Kokkoris S, Korantzopoulos P, Melidonis A. Metabolic syndrome and its components as predictors of allcause mortality and coronary heart disease in type 2 diabetic patients. Atherosclerosis 2007;195:189-194. 17. Sundström J, Vallhagen E, Risérus U, Byberg L, Zethelius B, Berne C, Lind L, Ingelsson E. Risk Associated With the Metabolic Syndrome Versus the Sum of Its Individual Components Diabetes Care 2006;29:1673-1674. 18. Cull CA, Jensen CC, Retnakaran R, Holman RR. Impact of the Metabolic Syndrome on Macrovascular and Microvascular Outcomes in Type 2 Diabetes Mellitus: United Kingdom Prospective Diabetes Study. Circulation 2007;116: 2119 - 2126. 19. Meigs JB, Rutter MK, Sullivan LM, Fox CS, D'Agostino PB,Sr Wilson BWF, (Framingham offspring study). Impact of Insulin Resistance on Risk of Type 2 Diabetes and Cardiovascular Disease in People With Metabolic Syndrome. Diabetes Care 2007;30:1219-1225. 20. Reaven GM. Insulin Resistance, Cardiovascular Disease and the Metabolic Syndrome: How well do the emperor's clothes fit? Diabetes Care 2004;27:10111012. 21. Zimmet P, Alberti G, Kaufman F et al: The Metabolic syndrome in children and adolescents. Lancet 2007;369: 2059 2061.
5
ª∞ƒΔπ√™ 2008
∞Û‡ÌÌÂÙÚË ¢ÈÌÂı˘Ï·ÚÁÈÓ›ÓË: ŒÓ·˜ ¡¤Ô˜ ¢Â›ÎÙ˘ ∫ÈÓ‰‡ÓÔ˘ °ÂÒÚÁÈÔ˜ ¶. ∫˘ÚȷΛ‰Ë˜, ∞Ó·ÏËÚˆÙ‹˜ ¢È¢ı˘ÓÙ‹˜ μ’ ¶·ıÔÏÔÁÈÎÔ‡ ΔÌ‹Ì·ÙÔ˜ °¡£ «Ô ÕÁÈÔ˜ ¢ËÌ‹ÙÚÈÔ˜», £ÂÛÛ·ÏÔÓ›ÎË
∂ÈÛ·ÁˆÁ‹ ∏ ·Û‡ÌÌÂÙÚË ‰ÈÌÂı˘Ï·ÚÁÈÓ›ÓË (ADMA) Â›Ó·È ¤Ó· ÂÓ‰ÔÁÂÓ¤˜ ÌfiÚÈÔ ÙÔ ÔÔ›Ô ÌÔÚ› Ó· ·ÓȯÓ¢ı› ÛÙÔ ·›Ì· Î·È Ù· Ô‡Ú· ÙÔ˘ ·ÓıÚÒÔ˘. ΔÔ 1992, ÔÈ P. Vallance Î·È Û˘Ó1 ·fi ÙÔ §ÔÓ‰›ÓÔ ‹Ù·Ó ÔÈ ÚÒÙÔÈ Ô˘ ÂÚȤÁÚ·„·Ó Ô˘Û›Â˜ Ô˘ ‰ÚÔ˘Ó Û·Ó ·Ó·ÛÙÔÏ›˜ Ù˘ Û‡ÓıÂÛ˘ ÙÔ˘ ÌÔÓÔÍÂȉ›Ô˘ ÙÔ˘ ·˙ÒÙÔ˘ (¡√), ¤¯Ô˘Ó ‰ÔÌÈ΋ ÔÌÔÈfiÙËÙ· Ì ÙËÓ L-·ÚÁÈÓ›ÓË, ·ÏÏ¿ ‰È·Ê¤ÚÔ˘Ó ·fi ·˘Ù‹Ó ÛÙÔ fiÙÈ ÂÚȤ¯Ô˘Ó Ì›· ‹ ‰‡Ô ÌÂı˘ÏÔÌ¿‰Â˜. ΔÔ ¡√ Â›Ó·È ¤Ó·˜ ·fi ÙÔ˘˜ ÌÂÁ·Ï‡ÙÂÚÔ˘˜ ÌÂÛÔÏ·‚ËÙ¤˜ Ô˘ ·ÂÏ¢ıÂÚÒÓÔÓÙ·È ·fi Ù· ˘ÁÈ‹ ÂÓ‰ÔıËÏȷο ·ÙÙ·Ú· Î·È Û¯ËÌ·Ù›˙ÂÙ·È ·fi ÙËÓ L-·ÚÁÈÓ›ÓË Ì¤Ûˆ ÙÔ˘ ÂÓ˙‡ÌÔ˘ ¡√-Û˘ÓıÂÙ¿ÛË.2 ∏ ADMA ÚÔηÏ› Ì›· ÛËÌ·ÓÙÈ΋ Î·È ‰ÔÛÔ-ÂÍ·ÚÙÒÌÂÓË ·Ó·ÛÙÔÏ‹ Ù˘ ·Ú·ÁˆÁ‹˜ ¡√ ·fi ·ÓıÚÒÈÓ· ·ÙÙ·Ú· in vitro.3 ∞ÓÙ›ıÂÙ· Ì ÙËÓ ADMA, Ë Û˘ÌÌÂÙÚÈ΋ ‰ÈÌÂı˘Ï·ÚÁÈÓ›ÓË (SDMA) ‰ÂÓ ¤¯ÂÈ Î·Ì›· ›‰Ú·ÛË ÛÙËÓ ·Ú·ÁˆÁ‹
ÙÔ˘ ¡√. √È ‰‡Ô ·ÚÈÔÈ ·Ú¿ÁÔÓÙ˜ Ô˘ ÂϤÁ¯Ô˘Ó Ù· ›‰· ADMA Â›Ó·È Ë ÓÂÊÚÈ΋ οı·ÚÛË Î·È Ô Ë·ÙÈÎfi˜ ÌÂÙ·‚ÔÏÈÛÌfi˜. ∏ ADMA ˘‰ÚÔχÂÙ·È ÂÓ‰Ô΢ÙÙ¿ÚÈ· ·fi ÙËÓ ‰ÈÌÂı˘Ï·ÚÁÈÓÈ΋ ‰ÈÌÂı˘Ï·ÌÈÓÔ¸‰ÚÔÏ¿ÛË (DDAH) Û ÎÈÙÚÔ˘Ï›ÓË Î·È ‰ÈÌÂı˘Ï·Ì›ÓË.
™‡ÓıÂÛË √È ‰ÈÌÂı˘Ï·ÚÁÈÓ›Ó˜ Û¯ËÌ·Ù›˙ÔÓÙ·È Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÚˆÙÂfiÏ˘Û˘ ÙˆÓ ÌÂı˘ÏÈˆÌ¤ÓˆÓ ÚˆÙÂ˚ÓÒÓ. √È ÌÂı˘ÏÈΤ˜ ÔÌ¿‰Â˜ Ô˘ ÂÚȤ¯ÔÓÙ·È ÛÙȘ ‰ÈÌÂı˘Ï·ÚÁÈÓ›Ó˜ ÚÔ¤Ú¯ÔÓÙ·È ·fi ÙËÓ ·ÓÙ·¯Ô‡ ·ÚÔ‡Û· ‰fiÙÚÈ· ÌÂı˘ÏÈÎÒÓ ÔÌ¿‰ˆÓ, ÙËÓ S-·‰ÂÓÔÛ˘ÏÌÂıÂÈÔÓ›ÓË, ¤Ó· ÂӉȿÌÂÛÔ ÚÔ˚fiÓ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ Ù˘ ÔÌÔ΢ÛÙ½Ó˘. ∞˘Ùfi ·Ô‰ÂÈÎÓ‡ÂÙ·È ÂÈÚ·Ì·ÙÈο, fiÙ·Ó Î·ÏÏȤÚÁÂȘ ·ÓıÚÒÈÓˆÓ ÂÓ‰ÔıËÏÈ·ÎÒÓ Î˘ÙÙ¿ÚˆÓ Âˆ¿˙ÔÓÙ·È Ì ڷ‰ÈÔÛÂÛËÌ·Ṳ̂ÓË S[14C]-·‰ÂÓÔÛ˘ÏÌÂıÂÈÔÓ›ÓË, ÔfiÙ ̤ÚÔ˜ Ù˘ Ú·‰ÈÂÓ¤ÚÁÂÈ·˜ ·ÓȯÓ‡ÂÙ·È ÛÙË ÓÂÔÛ˘ÓÙÂı›۷
∞ÚÁÈÓ›ÓË Î·È ADMA ÛÙË Û‡ÓıÂÛË ÙÔ˘ ÌÔÓÔÍÂȉ›Ô˘ ÙÔ˘ ·˙ÒÙÔ˘ CO2-
H 3N +
CO2-
H 3N +
CH
CH
CH2
CH2
CH2
CH2
NH N 2H +
NH
C
N 2H + CH2
N(CH3)2
∞ÚÁÈÓ›ÓË
ADMA
¡√-Û˘ÓıÂÙ¿ÛË ¡√
6
C
ADMA.4 ΔÔ Â‡ÚËÌ· ·˘Ùfi ÌÔÚ› Ó· ÂÍËÁ‹ÛÂÈ ÁÈ·Ù› Ë ÔÌÔ΢ÛÙ½ÓË ÂÏ·ÙÙÒÓÂÈ ÙËÓ ÂÓ‰ÔıËÏȷ΋ ÏÂÈÙÔ˘ÚÁ›·.
¶·ıÔÊ˘ÛÈÔÏÔÁÈÎfi˜ ÚfiÏÔ˜ √È ·Ú·‰ÔÛÈ·ÎÔ› ηډȷÁÁÂÈ·ÎÔ› ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘, fiˆ˜ Ë ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌ›·, Ë ˘¤ÚÙ·ÛË, ÙÔ Î¿ÓÈÛÌ· Î·È Ô Û·Î¯·Ú҉˘ ‰È·‚‹Ù˘ ÌÔÚÔ‡Ó Ó· ÂÍËÁ‹ÛÔ˘Ó Ì¤¯ÚÈ ÙÔ 80% ÙˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ Û˘Ì‚¿ÓÙˆÓ Ô˘ ·Ú·ÙËÚÔ‡ÓÙ·È ÛÙȘ ∏¶∞ Î·È ÛÙË ¢˘ÙÈ΋ ∂˘ÚÒË. ™Â οÔȘ ÔÌ¿‰Â˜ ·ÛıÂÓÒÓ Ì ˘ÂÚ‚ÔÏÈο ˘„ËÏ¿ ÔÛÔÛÙ¿ ÛÙÂÊ·ÓÈ·›ˆÓ Û˘Ì‚·Ì¿ÙˆÓ, fiˆ˜ ÔÈ ·ÛıÂÓ›˜ Û ·ÈÌ·ÙÔοı·ÚÛË, ¤Ó· ·ÎfiÌË ÌÂÁ·Ï‡ÙÂÚÔ ÔÛÔÛÙfi ηډȷÁÁÂÈ·ÎÒÓ Û˘Ì‚·Ì¿ÙˆÓ ·Ú·Ì¤ÓÂÈ ·ÓÂÍ‹ÁËÙÔ ·fi ÙÔ˘˜ ·Ú·‰ÔÛÈ·ÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘.5 À¿Ú¯Ô˘Ó ÔÏ˘¿ÚÈıÌ· ÂÈÚ·Ì·ÙÈο ‰Â‰Ô̤ӷ Ô˘ ‰Â›¯ÓÔ˘Ó fiÙÈ ÙÔ ·ÁÁÂÈ·Îfi ÂÓ‰Ôı‹ÏÈÔ ·›˙ÂÈ ¤Ó·Ó ÎÂÓÙÚÈÎfi ÚfiÏÔ ÛÙË ‰È·Ù‹ÚËÛË ÙÔ˘ Ê˘ÛÈÔÏÔÁÈÎÔ‡ ·ÁÁÂÈ·ÎÔ‡ ÙfiÓÔ˘ Î·È Ù˘ ·ÁÁÂȷ΋˜ ‰ÔÌ‹˜.6 ΔÔ ·ÂÏ¢ıÂÚÔ‡ÌÂÓÔ ¡√ ·fi Ù· ˘ÁÈ‹ ÂÓ‰ÔıËÏȷο ·ÙÙ·Ú· ·ÚÔ˘ÛÈ¿˙ÂÈ ÈÛ¯˘Ú‹ ·ÁÁÂÈԉȷÛÙ·ÏÙÈ΋ ‰Ú¿ÛË. ∂›Û˘ ‰Ú· Û·Ó ÂÓ‰ÔÁÂÓ‹˜ ·Ó·ÛÙÔϤ·˜ Ù˘ Û˘ÁÎfiÏÏËÛ˘ ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ. ∂› ϤÔÓ ·Ó·ÛÙ¤ÏÏÂÈ ÙËÓ ÚÔÛÎfiÏÏËÛË ÙˆÓ ÌÔÓÔ΢ÙÙ¿ÚˆÓ Î·È ÙˆÓ Ï¢ÎÔ΢ÙÙ¿ÚˆÓ ÛÙÔ ˘ÁȤ˜ ·ÁÁÂÈ·Îfi ÂÓ‰Ôı‹ÏÈÔ, οÙÈ Ô˘ ·Ó ‰È·Ù·Ú·¯ı›, ÚÔηÏ› ÙËÓ ÌÂÙ·Ó¿ÛÙ¢ÛË ÙˆÓ ÊÏÂÁÌÔÓˆ‰ÒÓ Î˘ÙÙ¿ÚˆÓ ÛÙÔ ·ÁÁÂÈ·Îfi ÙÔ›¯ˆÌ· Û ı¤ÛÂȘ fiÔ˘ ·ÚÁfiÙÂÚ· ‰ËÌÈÔ˘ÚÁÔ‡ÓÙ·È Ï¿Î˜. ∞ÎfiÌË ·Ó·ÛÙ¤ÏÏÂÈ ÙÔÓ ÔÏÏ·Ï·ÛÈ·ÛÌfi ÙˆÓ ·ÁÁÂÈ·ÎÒÓ Ï›ˆÓ Ì˘˚ÎÒÓ Î˘ÙÙ¿ÚˆÓ (ÙÂÚ¿ÛÙÈ·˜ ÛËÌ·Û›·˜ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ·ӷÛÙ¤ÓˆÛ˘ ÌÂÙ¿ ·fi ·ÁÁÂÈÔÏ·ÛÙÈ΋). ∂Ï·ÙÙÒÓÂÈ ÙËÓ ·Ú·ÁˆÁ‹ ÙˆÓ ÂχıÂÚˆÓ ÚÈ˙ÒÓ (√2), Ô˘ ÂÓ¤¯ÔÓÙ·È ÛÙȘ ÊÏÂÁÌÔÓÒ‰ÂȘ Î·È Î˘ÙÙ·ÚÔÙÔÍÈΤ˜ ‰È·‰Èηۛ˜ Î·È ·Ó·ÛÙ¤Ï-
¶∞ƒ∞°√¡Δ∂™ ∫π¡¢À¡√À ÏÂÈ ÙËÓ ÔÍ›‰ˆÛË Ù˘ LDL. ªÂÙ¿ Ù· ·ÓˆÙ¤Úˆ Á›ÓÂÙ·È ·ÓÙÈÏËÙfi˜ Ô ÚfiÏÔ˜ Ù˘ ADMA.
¡ÔÛ‹Ì·Ù· Ì ˘„ËÏ¿ ›‰· ADMA À„ËÏ¿ ›‰· ADMA ¤¯Ô˘Ó ÌÂÙÚËı› Û ·ÚÎÂÙ¿ ηډȷÁÁÂȷο Î·È ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù· (¶›Ó·Î·˜ 1).
ÃÚfiÓÈ· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· ∏ ÚÒÙË ÔÌ¿‰· ·ÛıÂÓÒÓ ÛÙËÓ ÔÔ›· ¢ڤıËÛ·Ó ·˘ÍË̤ӷ ›‰· ADMA ‹Ù·Ó ÂΛÓË Ì ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ·, Î·È ‚¤‚·È· ˘‹ÚÍ ÂȂ‚·›ˆÛË Û ÔÏ˘¿ÚÈı̘ ÌÂϤÙ˜. Δ· ·˘ÍË̤ӷ ›‰· ADMA Û˘Ì‚¿ÏÏÔ˘Ó ÛÙËÓ ÂÓ‰ÔıËÏȷ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· Ô˘ ˘¿Ú¯ÂÈ Û ·˘Ù‹Ó ÙËÓ ÓfiÛÔ Î·È ÌÔÚ› Ó· Â›Ó·È ÂÓ Ì¤ÚÂÈ ˘Â‡ı˘Ó· ÁÈ· ÙËÓ Ôχ ˘„ËÏ‹ ηډȷÁÁÂȷ΋ ÓÔÛËÚfiÙËÙ· Î·È ıÓËÛÈÌfiÙËÙ· ÛÙË ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ·.7 Δ· ·˘ÍË̤ӷ ›‰· ADMA Û ·ÛıÂÓ›˜ Ì ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘ ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· ÔÊ›ÏÔÓÙ·È ÂÓ Ì¤ÚÂÈ ÛÙËÓ ·Ó·Ú΋ ·ÔÌ¿ÎÚ˘ÓÛË ÙÔ˘˜ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ·ÈÌ·ÙÔοı·ÚÛ˘.8 √ ÚÔÛ‰ÈÔÚÈÛÌfi˜ ÙˆÓ ÂȤ‰ˆÓ Ì·˜ ÂÈÙÚ¤ÂÈ Ó· ÂÍ¿ÁÔ˘Ì ¯Ú‹ÛÈÌ· Û˘ÌÂÚ¿ÛÌ·Ù· ÁÈ· ÙËÓ ÚfiÁÓˆÛË ·˘ÙÒÓ ÙˆÓ ·ÛıÂÓÒÓ. ™Â ÌÈ· ÚÔÔÙÈ΋ ÌÂϤÙË 224 ·ÈÌÔηı·ÈÚfiÌÂÓˆÓ ·ÛıÂÓÒÓ, ·ÛıÂÓ›˜ ÙˆÓ ÔÔ›ˆÓ Ù· ›‰· ADMA ·Ú¯Èο ‹Ù·Ó ÛÙÔ ˘„ËÏfiÙÂÚÔ ÙÂÙ·ÚÙËÌfiÚÈÔ Â›¯·Ó ÙËÓ ˘„ËÏfiÙÂÚË ÔÏÈ΋ ıÓËÛÈÌfiÙËÙ· Î·È ÙÔ ˘„ËÏfiÙÂÚÔ ÔÛÔÛÙfi ÌÂÈ˙fiÓˆÓ Î·Ú‰È·ÁÁÂÈ·¶›Ó·Î·˜ 1. ¡ÔÛ‹Ì·Ù· ÛÙ· ÔÔ›· ·Ú·ÙËÚÔ‡ÓÙ·È ˘„ËÏ¿ ›‰· ADMA. ÃÚfiÓÈ· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· À¤ÚÙ·ÛË ¶ÚÔÂÎÏ·Ì„›· ¶Ó¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË ™ÙÂÊ·ÓÈ·›· ÓfiÛÔ˜ ¶ÂÚÈÊÂÚÈ΋ ·ÚÙËÚȷ΋ ÓfiÛÔ˜ ∞ÁÁÂÈ·Îfi ÂÁÎÂÊ·ÏÈÎfi ÂÂÈÛfi‰ÈÔ ÀÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌ›· ÀÂÚÔÌÔ΢ÛÙÂ˚Ó·ÈÌ›· ™˘ÌÊÔÚËÙÈ΋ ηډȷ΋ ·Ó¿ÚÎÂÈ· ÀÂÚı˘ÚÂÔÂȉÈÛÌfi˜ ™·Î¯·Ú҉˘ ‰È·‚‹Ù˘ ™Ù˘ÙÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·
ÎÒÓ Û˘Ì‚·Ì¿ÙˆÓ ηٿ ÙË ‰È¿ÚÎÂÈ· ·Ú·ÎÔÏÔ‡ıËÛ˘ 3 ÂÙÒÓ.9 ¶·Ú¿ Ù· ·˘ÍË̤ӷ ›‰· ADMA Û ·ÛıÂÓ›˜ Ì ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· Û ۇÁÎÚÈÛË Ì ÂΛӷ ÙˆÓ ˘ÁÈÒÓ ·ÙfïÓ, Ë ÔÛÔÙÈÎÔÔ›ËÛË ÙˆÓ ÂȤ‰ˆÓ Ì·˜ ÂÈÙÚ¤ÂÈ ÙËÓ ÂÚ·ÈÙ¤Úˆ ‰È·ÊÔÚÔÔ›ËÛË Û ·ÛıÂÓ›˜ Ì ˘„ËÏfi ‹ ¯·ÌËÏfi ηډȷÁÁÂÈ·Îfi ΛӉ˘ÓÔ, Î·È ÙËÓ ·Ó¿ÏÔÁË ıÂڷ¢ÙÈ΋ ÚÔÛ¤ÁÁÈÛË. ∂ÎÛÂÛËÌ·Ṳ̂ÓË ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ Ù˘ ADMA ·Ú·ÙËÚ‹ıËÎ·Ó Î·È Û ·ÛıÂÓ›˜ Ì ·Ú¯fiÌÂÓË ÚˆÙÔ·ı‹ ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ·.10
À¤ÚÙ·ÛË ™Â ·ÛıÂÓ›˜ Ì ڈÙÔ·ı‹ ˘¤ÚÙ·ÛË Ù· ›‰· ADMA ‚Ú¤ıËÎ·Ó ‰ÈÏ¿ÛÈ· ·fi ÂΛӷ ÙˆÓ ÓÔÚÌÔÙ·ÛÈÎÒÓ ·ÙfïÓ. ∂›Û˘, Ë ·¤ÎÎÚÈÛË ÛÙ· Ô‡Ú· ÙˆÓ ÌÂÙ·‚ÔÏÈÙÒÓ ÙÔ˘ ¡√ , ‚Ú¤ıËΠÂÏ·Ùو̤ÓË Û ˘ÂÚÙ·ÛÈÎÔ‡˜ ·ÛıÂÓ›˜.11 ¶ÂÈÚ·Ì·ÙÈΤ˜ ÌÂϤÙ˜ ¤¯Ô˘Ó ·Ô‰Â›ÍÂÈ fiÙÈ Ë ÂÓ‰·ÚÙËÚȷ΋ ¤Á¯˘ÛË ADMA ÚÔηÏ› ÙÔÈ΋ ·ÁÁÂÈÔÛ‡Û·ÛË ÛÙËÓ ·ÓÙ›ÛÙÔÈ¯Ë ÂÚÈÔ¯‹.12 ∂›Û˘ ÂÓ‰ÔÊϤ‚È· ¤Á¯˘ÛË ADMA Û ‰fiÛÂȘ Ô˘ ‰ËÌÈÔ˘ÚÁÔ‡Ó Î˘ÎÏÔÊÔÚÔ‡ÓÙ· ›‰· ÂÚ›Ô˘ 2 Ìmol/l, ÚÔηÏ› ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË Ù˘ ÔÏÈ΋˜ ÂÚÈÊÂÚÈ΋˜ ·ÓÙ›ÛÙ·Û˘.13 ™Â ÓÔÚÌÔÙ·ÛÈΤ˜ ÌÂÙÂÌÌËÓÔ·˘ÛȷΤ˜ Á˘Ó·›Î˜, Ë ·Ó·ÛÙÔÏ‹ ÙÔ˘ ¡√ Â›Ó·È ¤Ó·˜ Ì˯·ÓÈÛÌfi˜ ·‡ÍËÛ˘ Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘ ηٿ ÙË ‰È¿ÚÎÂÈ· ÊfiÚÙÈÛ˘ Ì ·Ï¿ÙÈ.14 À¿Ú¯Ô˘Ó ‰È·ÊÔÚÂÙÈο ÚfiÙ˘· Û ÌÂÙ·ÌfiÛ¯Â˘ÛË Î·Ú‰È¿˜ Î·È Û ¿ÙÔÌ· Ì ڈÙÔ·ı‹ ˘¤ÚÙ·ÛË. ¶ÔÏÏÔ› ·ÛıÂÓ›˜ Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË Î·Ú‰È¿˜ ·Ó·Ù‡ÛÛÔ˘Ó ˘¤ÚÙ·ÛË, ¯·Ú·ÎÙËÚÈ˙fiÌÂÓË ·fi ·˘ÍË̤Ó˜ ÂÚÈÊÂÚÈΤ˜ ·ÓÙÈÛÙ¿ÛÂȘ Î·È ÂÓ‰ÔıËÏȷ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·. ∫·È, ÂÓÒ Ë ADMA Ù›ÓÂÈ Ó· ·˘Í¿ÓÂÙ·È ÛÙËÓ ÚˆÙÔ·ı‹ ˘¤ÚÙ·ÛË, Â›Ó·È ÛËÌ·ÓÙÈο ÂÏ·Ùو̤ÓË Û ·ÛıÂÓ›˜ Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË Î·Ú‰È¿˜.15 ∞˘ÍË̤ӷ ›‰· ADMA ·Ó·Ê¤ÚıËÎ·Ó Â›Û˘ ÛÙËÓ ·È‰È΋ ˘¤ÚÙ·ÛË Î·È ÛÙËÓ ˘¤ÚÙ·ÛË Ù˘ ·ËÛ˘.16,17
¶ÚÔÂÎÏ·Ì„›· ™‹ÌÂÚ· ÈÛÙ‡ÂÙ·È fiÙÈ Ë ÚÔÂÎÏ·Ì„›· Â›Ó·È Â·ÎfiÏÔ˘ıÔ Ù˘, ÂÍ·ÚÙÒÌÂÓ˘ ·fi ÙÔ ÂÓ‰Ôı‹ÏÈÔ,
‰È·Ù·Ú·¯‹˜ Ù˘ ÚÔ‹˜ ÙÔ˘ ·›Ì·ÙÔ˜ ÛÙË Ì‹ÙÚ· Î·È ÛÙË Û˘ÛÙËÌ·ÙÈ΋ ÌËÙÚÈ΋ ΢ÎÏÔÊÔÚ›·. ∞˘ÙÔ› ÔÈ Ì˯·ÓÈÛÌÔ› ÂÚÌËÓÂ‡Ô˘Ó Ù· ÙÚ›· ÌÂÁ¿Ï· Û˘ÌÙÒÌ·Ù· Ù˘ ÚÔÂÎÏ·Ì„›·˜, ÙËÓ ˘¤ÚÙ·ÛË, ÙËÓ ÚˆÙÂïÓÔ˘Ú›· Î·È ÙÔ Ô›‰ËÌ·, fiˆ˜ Î·È ÙÔÓ Î›Ó‰˘ÓÔ Î·ı˘ÛÙ¤ÚËÛ˘ ·Ó¿Ù˘Í˘ ÙÔ˘ ÂÌ‚Ú‡Ô˘. ∞˘ÍË̤ӷ ›‰· ADMA ÚÔËÁ‹ıËÎ·Ó Ù˘ ·Ó¿Ù˘Í˘ ÎÏÈÓÈÎÒÓ ÛËÌ›ˆÓ ÚÔÂÎÏ·Ì„›·˜.18 ∂›Û˘ ·˘ÍË̤Ó˜ Û˘ÁÎÂÓÙÚÒÛÂȘ ADMA ·ÓȯÓ‡ıËÎ·Ó Û ¤ÁÎ˘Â˜ Á˘Ó·›Î˜ Ô˘ ·ÎÔÏÔ‡ıˆ˜ ·Ó¤Ù˘Í·Ó ÚÔÂÎÏ·Ì„›·.19
™ÙÂÊ·ÓÈ·›· ÓfiÛÔ˜ ™Â ÌÈ· ºÈÏ·Ó‰È΋ ÌÂϤÙË, ¿Ó‰Ú˜ ÎÏÈÓÈο ˘ÁÈ›˜, ÌË Î·ÓÈÛÙ¤˜, ÙˆÓ ÔÔ›ˆÓ Ù· ›‰· ADMA ‹Ù·Ó ÛÙÔ ˘„ËÏfiÙÂÚÔ ÙÂÙ·ÚÙËÌfiÚÈÔ ·ÚÔ˘Û›·Û·Ó ÌÈ· ÛËÌ·ÓÙÈ΋, ۯ‰fiÓ ÙÂÙÚ·Ï¿ÛÈ· ·‡ÍËÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ·Ó¿Ù˘Í˘ ÌÂÈ˙fiÓˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ Û˘Ì‚·Ì¿ÙˆÓ Û˘ÁÎÚÈÓfiÌÂÓÔÈ Ì ÂΛÓÔ˘˜ ÙÔ˘ ¯·ÌËÏfiÙÂÚÔ˘ ÙÂÙ·ÚÙËÌfiÚÈÔ˘.20 ™ÙË ÌÂÁ¿ÏË ÔÏ˘ÎÂÓÙÚÈ΋ °ÂÚÌ·ÓÈ΋ ÌÂϤÙË CARDIAC (Coronary Artery Risk Determination evaluating the Influence of ADMA Concentration), ÌÂÏÂÙ‹ıËÎ·Ó 800 ¿ÙÔÌ· ËÏÈΛ·˜ ·fi 25 ̤¯ÚÈ 85 ÂÙÒÓ, ÙÔ 75% ÙˆÓ ÔÔ›ˆÓ ‹Ù·Ó ¿Ó‰Ú˜. √È ÌÈÛÔ› ‹Ù·Ó Ì ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ (ÛÙ·ıÂÚ‹ ÛÙËı¿Á¯Ë ‹ ÈÛÙÔÚÈÎfi ÂÌÊÚ¿ÁÌ·ÙÔ˜ ÙÔ˘ Ì˘Ôηډ›Ô˘) Î·È ÔÈ ¿ÏÏÔÈ ÌÈÛÔ› Ì¿ÚÙ˘Ú˜ Ì ηډȷÁÁÂÈ·ÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ¯ˆÚ›˜ ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ. Δ· ›‰· ADMA ‹Ù·Ó 20% ˘„ËÏfiÙÂÚ· Û ·ÛıÂÓ›˜ Ì ηډȷÁÁÂȷΤ˜ ÓfiÛÔ˘˜ Î·È ¤‰ÂÈÍ·Ó Ù¿ÛË ·‡ÍËÛ˘ Ì ÙËÓ ·ÚÔ˘Û›· ·Ú·‰ÔÛÈ·ÎÒÓ ·Ú·ÁfiÓÙˆÓ ÎÈÓ‰‡ÓÔ˘. √ ΛӉ˘ÓÔ˜ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘ ‹Ù·Ó 2.35 ÊÔÚ¤˜ ˘„ËÏfiÙÂÚÔ˜ ÁÈ· οı ·‡ÍËÛË Ù˘ ADMA ηٿ 1 Ìmol/l. ™Â ÙÈ̤˜ ADMA ¿Óˆ ·fi 1.751 Ìmol/l, Ô Î›Ó‰˘ÓÔ˜ ηډȷÁÁÂȷ΋˜ ÓfiÛÔ˘ ‹Ù·Ó 6-7 ÊÔÚ¤˜ ˘„ËÏfiÙÂÚÔ˜.21 ™ÙË ÌÂϤÙË ÙˆÓ Nijveldt Î·È Û˘Ó ÂϤÁ¯ıËÎ·Ó 52 ‚·ÚÈ¿ ¿ÚÚˆÛÙÔÈ, Ì ÔÏÏ·Ï‹ ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ·, ·fi ¯ÂÈÚÔ˘ÚÁÈ΋ ÌÔÓ¿‰· ÂÓÙ·ÙÈ΋˜ ıÂڷ›·˜. ∏ ıÓËÛÈÌfiÙËÙ· Û ·˘Ù‹Ó ÙËÓ ÔÌ¿‰· ‹Ù·Ó 40%. Δ· ›‰· ADMA ‹Ù·Ó ÛËÌ·ÓÙÈο ˘„ËÏfiÙÂÚ· Û ·˘ÙÔ‡˜ ÙÔ˘˜ ·ÛıÂÓ›˜ Û˘ÁÎÚÈÓfiÌÂÓ· ÌÂ
7
ª∞ƒΔπ√™ 2008
ÂΛӷ Ù˘ ÔÌ¿‰·˜ ÂϤÁ¯Ô˘. ∏ ADMA Ê¿ÓËΠӷ Â›Ó·È Ô ÈÛ¯˘ÚfiÙÂÚÔ˜ ·ÓÂÍ¿ÚÙËÙÔ˜ ·Ú¿ÁÔÓÙ·˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙÔÓ ı¿Ó·ÙÔ Ù¤ÙÔÈˆÓ ·ÛıÂÓÒÓ. ™ÙÔ ˘„ËÏfiÙÂÚÔ ÙÂÙ·ÚÙËÌfiÚÈÔ ÙˆÓ ÂȤ‰ˆÓ ADMA (1.05 Ìmol/l) ˘‹ÚÍ 17.2 ÊÔÚ¤˜ ˘„ËÏfiÙÂÚÔ˜ ΛӉ˘ÓÔ˜ ı·Ó¿ÙÔ˘ Î·È Ô Î›Ó‰˘ÓÔ˜ ·˘Í‹ıËΠηٿ 32 ÊÔÚ¤˜ Û ·‡ÍËÛË Î·Ù¿ 1 Ìmol/l ÙˆÓ ÂȤ‰ˆÓ ADMA.22 ™ÙËÓ ÚÔÔÙÈ΋ ÌÂϤÙË ÙˆÓ Lu Î·È Û˘Ó ·Ú·ÎÔÏÔ˘ı‹ıËÎ·Ó 153 ·ÛıÂÓ›˜ (133 ¿Ó‰Ú˜ Î·È 20 Á˘Ó·›Î˜, Ì ̤ÛË ËÏÈΛ· 71±8 ¤ÙË) Ì ÛÙ·ıÂÚ‹ ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ Ô˘ ˘¤ÛÙËÛ·Ó ‰È·‰ÂÚÌÈΤ˜ ÛÙÂÊ·ÓÈ·›Â˜ ·ÚÂÌ‚¿ÛÂȘ. √È ·ÛıÂÓ›˜ ¯ˆÚ›ÛÙËÎ·Ó Û ÙÚÂȘ ÈÛ¿ÚÈı̘ ÔÌ¿‰Â˜, Ù· ›‰· ADMA ÙˆÓ ÔÔ›ˆÓ ‹Ù·Ó ·ÓÙ›ÛÙÔȯ·: <0.50 Ìmol/l, 0.50-0.62 Ìmol/l Î·È >0.62 Ìmol/l. ™ÙËÓ ÚÒÙË ÔÌ¿‰· Û˘Ó¤‚ËÛ·Ó ÌfiÓÔ 6 ηډȷÁÁÂȷο Û˘Ì‚¿Ì·Ù·, ÂÓÒ ÛÙȘ ¿ÏϘ 17 Î·È 28 ·ÓÙ›ÛÙÔȯ·.23 ™ÙË ÌÂϤÙË ÙˆÓ Schnabel Î·È Û˘Ó ÂϤÁ¯ıËÎ·Ó 1908 ·ÛıÂÓ›˜ Ì ÛÙ·ıÂÚ‹ ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ, ÂȂ‚·ÈˆÌ¤ÓË Ì ÛÙÂÊ·ÓÈ·ÈÔÁÚ·Ê›· ( 79.1% ¿Ó‰Ú˜, Ì ̤ÛË ËÏÈΛ· 61±9 ¤ÙË). ∏ ̤ÛË ÙÈÌ‹ ÙˆÓ ÂȤ‰ˆÓ ADMA ‹Ù·Ó 0.63 Ìmol/l, ÙÔ˘ ¯·ÌËÏfiÙÂÚÔ˘ ÙÂÙ·ÚÙËÌÔÚ›Ô˘ 0.53 Ìmol/l Î·È ÙÔ˘ ˘„ËÏfiÙÂÚÔ˘ 0.74 Ìmol/l. ™ÙÔ ˘„ËÏfiÙÂÚÔ ÙÂÙ·ÚÙËÌfiÚÈÔ ˘‹ÚÍ ÌÈ·, ηٿ 2.48 ÊÔÚ¤˜, ·‡ÍËÛË ÙÔ˘ ηډȷÁÁÂÈ·ÎÔ‡ ÎÈÓ‰‡ÓÔ˘, ·ÔηχÙÔÓÙ·˜ fiÙÈ Ù· ›‰· ADMA Â›Ó·È ¤Ó·˜ ·fi ÙÔ˘˜ ÈÛ¯˘ÚfiÙÂÚÔ˘˜ ‰Â›ÎÙ˜ ÎÈÓ‰‡ÓÔ˘ ÙˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ Û˘Ì‚·Ì¿ÙˆÓ Û ·ÛıÂÓ›˜ Ì ÛÙ·ıÂÚ‹ ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ.24
¶ÂÚÈÊÂÚÈ΋ ·ÚÙËÚȷ΋ ÓfiÛÔ˜ ™Â ·ÛıÂÓ›˜ Ì ÂÚÈÊÂÚÈ΋ ·ÚÙËÚȷ΋ ÓfiÛÔ Ù· ›‰· ADMA Â›Ó·È ·˘ÍË̤ӷ Î·È ÂÍ·ÚÙÒÌÂÓ· ·fi ÙÔ ÎÏÈÓÈÎfi ÛÙ¿‰ÈÔ Ù˘ ÓfiÛÔ˘. ™˘ÁÎÚÈÓfiÌÂÓÔÈ Ì ̿ÚÙ˘Ú˜ Ù˘ ›‰È·˜ ËÏÈΛ·˜, ÔÈ ·ÛıÂÓ›˜ Ì ‰È·ÏÂ›Ô˘Û· ¯ˆÏfiÙËÙ· (LericheFontaine ÛÙ¿‰ÈÔ ππ) ›¯·Ó ÌÈ· ‰ÈÏ¿ÛÈ· ·‡ÍËÛË, ÂΛÓÔÈ Ì ˘ÔÏÂÈfiÌÂÓÔ ¿ÏÁÔ˜ (Leriche-Fontaine ÛÙ¿‰ÈÔ πππ) ›¯·Ó ÌÈ· ÙÚÈÏ¿ÛÈ· ·‡ÍËÛË, Î·È ·ÛıÂÓ›˜ Ì ÂÚÈÊÂÚÈ΋ Ó¤ÎÚˆÛË Î·È Á¿ÁÁÚ·ÈÓ· (LericheFontaine ÛÙ¿‰ÈÔ πV) ›¯·Ó ÌÈ· 3.5Ï¿ÛÈ· ·‡ÍËÛË ÙˆÓ Î˘ÎÏÔÊÔ-
8
ÚÔ‡ÓÙˆÓ ÂȤ‰ˆÓ ADMA.25 ∏ ·Ó·ÊÂÚı›۷ ÛÙ·‰ÈÔ-ÂÍ·ÚÙÒÌÂÓË ÂÏ¿ÙÙˆÛË ÙÔ˘ ÌÂÙ·‚ÔÏ›ÙË ÙÔ˘ ¡√ ÛÙ· Ô‡Ú·, fiˆ˜ Î·È Ù· ÎÏÈÓÈο Û˘ÌÙÒÌ·Ù· Ù˘ ‰È·ÏÂ›Ô˘Û·˜ ¯ˆÏfiÙËÙ·˜, ·Ó·ÛÙÚ¤ÊÔÓÙ·È Ì ÙË ¯ÔÚ‹ÁËÛË L-·ÚÁÈÓ›Ó˘.26 √È Mittermayer Î·È Û˘Ó ÌÂϤÙËÛ·Ó ÙË Û¯¤ÛË ÌÂٷ͇ ÙˆÓ ÂȤ‰ˆÓ ADMA Î·È ÙˆÓ ÌÂÈ˙fiÓˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ Û˘Ì‚·Ì¿ÙˆÓ (√∂ª, PTCA, ·ÔÚÙÔÛÙÂÊ·ÓÈ·›· ·Ú¿Î·Ì„Ë, ∞∂∂, ·ӷÁÁ›ˆÛË Î·ÚˆÙ›‰ˆÓ, ı¿Ó·ÙÔ˜) Û ·ÛıÂÓ›˜ Ì ÚÔ¯ˆÚË̤ÓË ÂÚÈÊÂÚÈ΋ ·ÚÙËÚȷ΋ ÓfiÛÔ (496 ·ÛıÂÓ›˜, 56% ¿Ó‰Ú˜, Ì ̤ÛË ËÏÈΛ· 70 ¤ÙË). ∫·Ù·ÁÚ¿ÊËÎ·Ó Û˘Ì‚¿Ì·Ù· Û 141 ·ÛıÂÓ›˜. ™Â ÂΛÓÔ˘˜ Ì ÙÔ ˘„ËÏfiÙÂÚÔ ÙÂÙ·ÚÙËÌfiÚÈÔ (0.64 Ìmol/l) ÂȤ‰ˆÓ ADMA ˘‹ÚÍ 65% ÌÂÁ·Ï‡ÙÂÚÔ˜ Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜ ·Ó¿Ù˘Í˘ ÌÂÏÏÔÓÙÈÎÒÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ Û˘Ì‚·Ì¿ÙˆÓ ·fi ÂΛÓÔ˘˜ ÙÔ˘ ¯·ÌËÏfiÙÂÚÔ˘ ÙÂÙ·ÚÙËÌÔÚ›Ô˘ (<0.48 Ìmol/l).27
¢È·Ù·Ú·¯¤˜ ÏÈȉ›ˆÓ ¶·Ú·ÙËÚ‹ıËΠÂÚ›Ô˘ ‰ÈÏ¿ÛÈ· ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ ADMA Û ÎÏÈÓÈο ·Û˘Ìو̷ÙÈο ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌÈο ¿ÙÔÌ·. ™ËÌ·ÓÙÈÎfi ÛÙÔÈ¯Â›Ô ‹Ù·Ó Ë ·Ô˘Û›· ¤Î‰ËÏ˘ ηډȷÁÁÂȷ΋˜ ÓfiÛÔ˘, οÙÈ Ô˘ ˘Ô‰ËÏÒÓÂÈ fiÙÈ Ë ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ ADMA Û˘Ì‚·›ÓÂÈ ÚÒÈÌ· ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ·ıÔÁ¤ÓÂÈ·˜ Ù˘ ·ıËÚÔÛÎÏ‹ÚˆÛ˘ Î·È ›Ûˆ˜ Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ÂͤÏÈÍË Ù˘.28 √È ÛÙ·Ù›Ó˜, ÂÎÙfi˜ ·fi ÙËÓ ÂÏ¿ÙÙˆÛË Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘, ·˘Í¿ÓÔ˘Ó Ù· ›‰· ÙÔ˘ ¡√ Î·È ¤¯Ô˘Ó ÌÈ· ¿ÌÂÛË Â›‰Ú·ÛË ÛÙËÓ ·ÈÌ¿ÙˆÛË Ù˘ ηډȿ˜. Δ· ·˘ÍË̤ӷ ›‰· ADMA Ê·›ÓÂÙ·È Ó· ÙÚÔÔÔÈÔ‡Ó ·˘Ù‹ ÙËÓ ‰Ú¿ÛË Î·È Ó· ‰ËÌÈÔ˘ÚÁÔ‡Ó ÚÔ‚Ï‹Ì·Ù· ÛÙËÓ ·ÓÙ·fiÎÚÈÛË ÙˆÓ ·ÛıÂÓÒÓ Ô˘ Ï·Ì‚¿ÓÔ˘Ó ÛÙ·Ù›Ó˜.29,30 √È ÔÍÂȉˆÌ¤Ó˜ LDL ‰ÈÂÁ›ÚÔ˘Ó ÙËÓ ¤ÎÊÚ·ÛË ÙˆÓ ÂÓ˙‡ÌˆÓ (ÚˆÙÂ˚ÓÈΤ˜ ·ÚÁÈÓÈÓÔ ¡-ÌÂı˘ÏÙÚ·ÓÛÊÂÚ¿Û˜) Ô˘ ‰ËÌÈÔ˘ÚÁÔ‡Ó ÙËÓ ADMA.31 ∂›Û˘, Ë ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· Ô‰ËÁ› ÛÙËÓ ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ ADMA Î·È ÌÔÚ› ̤ۈ ·˘ÙÔ‡ ÙÔ˘ Ì˯·ÓÈÛÌÔ‡ Ó· ÚÔηϤÛÂÈ ÂÓ‰ÔıËÏȷ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·.32
ÀÂÚÔÌÔ΢ÛÙÂ˚Ó·ÈÌ›· ™Â ¿ÙÔÌ· Ì ˘ÂÚÔÌÔ΢ÛÙÂ˚Ó·ÈÌ›· ·Ú·ÙËÚ‹ıËÎ·Ó ÛËÌ·ÓÙÈο ·˘ÍË̤ӷ ›‰· ADMA.33 ∫¿ÔȘ ÌÂϤÙ˜ ÂÍ¤Ù·Û·Ó Ù· Û¯ÂÙÈο ÔʤÏË ·fi ÙËÓ ÂÏ¿ÙÙˆÛË ÙˆÓ ÂȤ‰ˆÓ Ù˘ ÔÌÔ΢ÛÙ½Ó˘ ¤Ó·ÓÙÈ Ù˘ ‰È¤ÁÂÚÛ˘ ÙÔ˘ ¡√. ∞ÛıÂÓ›˜ Ô˘ ›¯·Ó ÂÚÈÊÂÚÈ΋ ·ÔÊÚ·ÎÙÈ΋ ·ÚÙËÚȷ΋ ÓfiÛÔ Ì ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌ›· Î·È ˘ÂÚÔÌÔ΢ÛÙÂ˚Ó·ÈÌ›· ‰ÂÓ ·ÚÔ˘Û›·Û·Ó ηÌÈ¿ ‚ÂÏÙ›ˆÛË ÛÙËÓ ÂÓ‰ÔıËÏÈÔ-ÂÍ·ÚÙÒÌÂÓË ·ÁÁÂÈԉȷÛÙÔÏ‹ Ì ÙËÓ ¯ÔÚ‹ÁËÛË ‚ÈÙ·ÌÈÓÒÓ ÙÔ˘ Û˘ÌϤÁÌ·ÙÔ˜ μ (μ12 200 mcg, B6 20 mg/ËÌÂÚËÛ›ˆ˜) Î·È Ê˘ÏÏÈÎÔ‡ ÔͤԘ (10 mg). H ¯ÔÚ‹ÁËÛË L-·ÚÁÈÓ›Ó˘ ·fi ÙÔ˘ ÛÙfiÌ·ÙÔ˜ (24g/ËÌÂÚ.) ‚ÂÏÙ›ˆÛ ÛËÌ·ÓÙÈο ÙËÓ ÂÓ‰ÔıËÏȷ΋ ÏÂÈÙÔ˘ÚÁ›·.34 ™ÙË ÌÂϤÙË HOPE-2 (Heart Outcomes Prevention Evaluation) Ë ¯ÔÚ‹ÁËÛË Ê˘ÏÏÈÎÔ‡ ÔͤԘ Î·È ‚ÈÙ·ÌÈÓÒÓ μ6 Î·È μ12 ‰ÂÓ ÂÏ¿ÙÙˆÛ ÙÔÓ Î›Ó‰˘ÓÔ ÙˆÓ ÌÂÈ˙fiÓˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ Û˘Ì‚·Ì¿ÙˆÓ Û ·ÛıÂÓ›˜ Ì ηډȷÁÁÂȷ΋ ÓfiÛÔ.35 ∂›Û˘ ÛÙË ÌÂϤÙË ÙˆÓ Kaare HB Î·È Û˘Ó, Ë ¯ÔÚ‹ÁËÛË ÙˆÓ ‚ÈÙ·ÌÈÓÒÓ μ6 Î·È μ12 fi¯È ÌfiÓÔÓ ‰ÂÓ ÂÏ¿ÙÙˆÛ ÙÔÓ Î›Ó‰˘ÓÔ ˘ÔÙÚÔÈ¿˙Ô˘Û·˜ ηډȷÁÁÂȷ΋˜ ÓfiÛÔ˘ ÌÂÙ¿ ·fi Ô͇ ¤ÌÊÚ·ÁÌ· ÙÔ˘ Ì˘Ôηډ›Ô˘, ·ÏÏ¿ ı· ÌÔÚÔ‡Û ӷ Â›Ó·È Î·È ÂÈ‚Ï·‚‹˜.36
™·Î¯·Ú҉˘ ‰È·‚‹Ù˘ ∏ ADMA ›Ûˆ˜ ·›˙ÂÈ ¤Ó· ÛËÌ·ÓÙÈÎfi ÚfiÏÔ Û·Ó ‰Â›ÎÙ˘ ÎÈÓ‰‡ÓÔ˘ ÛÙËÓ ·ıÔÁ¤ÓÂÈ· ÙÔ˘ ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË Î·È ÙˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ ÂÈÏÔÎÒÓ ÙÔ˘. ∞ӷʤÚıËΠ·fi ‰È¿ÊÔÚÔ˘˜ ÂÚ¢ÓËÙ¤˜, fiÙÈ ·ÛıÂÓ›˜ Ì ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË Ù‡Ô˘ 2 ¤¯Ô˘Ó ÛËÌ·ÓÙÈο ·˘ÍË̤ӷ ›‰· ADMA37-39 ∞ÎfiÌË Î·È ¤Ó· Ôχ ÏÈ·Úfi Á‡̷ ÌÔÚ› ·Ì¤Ûˆ˜ Ó· ·˘Í‹ÛÂÈ ÙËÓ ADMA Û ·ÛıÂÓ›˜ Ì ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË Ù‡Ô˘ 2. ΔÔ ÔÍÂȉˆÙÈÎfi stress ÚÔηÏ› ·ÔÚÚ‡ıÌÈÛË ÙÔ˘ ÂÓ˙‡ÌÔ˘ Ô˘ ·‰Ú·ÓÔÔÈ› ÙËÓ ADMA.40 ™˘˙ËÙÈ¤Ù·È Â›Û˘ fiÙÈ ÙÔ ÌÂÙ·ÙÚÂÙÈÎfi ¤Ó˙˘ÌÔ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘ ÂÌϤÎÂÙ·È ÛÙÔÓ Ì˯·ÓÈÛÌfi ·‡ÍËÛ˘ ÙÔ˘ ·Ó·ÛÙÔϤ· Ù˘ Û˘ÓıÂÙ¿Û˘ ÙÔ˘ ÂÓ‰ÔÁÂÓÔ‡˜ ¡√ Û ·ÛıÂÓ›˜ Ì ۷ί·-
¶∞ƒ∞°√¡Δ∂™ ∫π¡¢À¡√À ÚÒ‰Ë ‰È·‚‹ÙË Ù‡Ô˘ 2.41 √È ·ª∂∞ ÂÏ·ÙÙÒÓÔ˘Ó Ù· ›‰· ADMA Î·È Ë ‰Ú¿ÛË ·˘Ù‹ Â›Ó·È ·ÓÂÍ¿ÚÙËÙË ·fi ÙËÓ ·ÚÙËÚȷ΋ ›ÂÛË. ∞ÛıÂÓ›˜ Ì ‰È·Ù·Ú·Á̤ÓË ·ÓÔ¯‹ ÁÏ˘Îfi˙˘ ¤¯Ô˘Ó ÛËÌ·ÓÙÈο ·˘ÍË̤ӷ ›‰· ADMA ÚÈÓ ·ÎfiÌË ·fi ÙËÓ ÂΉ‹ÏˆÛË ÙÔ˘ ÎÏÈÓÈο ¤Î‰ËÏÔ˘ ‰È·‚‹ÙË.38 º·Ú̷΢ÙÈ΋ ·ÔηٿÛÙ·ÛË Ù˘ ¢·ÈÛıËÛ›·˜ Ù˘ ÈÓÛÔ˘Ï›Ó˘ Ì ÚÔÛÈÁÏÈÙ·˙fiÓË Ô‰ËÁ› Û ÂÏ¿ÙÙˆÛË ÙˆÓ ÂȤ‰ˆÓ ADMA,38 οÙÈ Ô˘ Û˘Ì‚·›ÓÂÈ Î·È Ì ÙËÓ ÌÂÙÊÔÚÌ›ÓË.42 ∞˘ÍË̤ӷ ›‰· ADMA ·Ú·ÙËÚ‹ıËÎ·Ó Î·È Û ¢ÁÏ˘Î·ÈÌÈΤ˜ Á˘Ó·›Î˜ Ì ÚÔËÁËı¤ÓÙ· ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË Î‡ËÛ˘. ∏ ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ ADMA ‹Ù·Ó ·ÓÂÍ¿ÚÙËÙË ·fi ¿ÏÏÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ‹ ‰Â›ÎÙ˜ ÁÈ· ‰È·‚‹ÙË ‹ ηډȷÁÁÂȷο Û˘Ì‚¿Ì·Ù·.43
™Ù˘ÙÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ™Â ÔÏÏÔ‡˜ ·ÛıÂÓ›˜ Ì ÛÙ˘ÙÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙÔ ÌÔÓÔ¿ÙÈ L·ÚÁÈÓ›Ó˘ -NO - cGMP Â›Ó·È ‰È·Ù·Ú·Á̤ÓÔ.44 ΔÔ ‚ÈÔ¯ËÌÈÎfi Úfi‚ÏËÌ· Û˘Ó‹ıˆ˜ ÚÔηÏÂ›Ù·È ·fi Ù·˘Ùfi¯ÚÔÓË Î·Ú‰È·ÁÁÂȷ΋ ÓfiÛÔ
‹ ÙËÓ ·ÚÔ˘Û›· ηډȷÁÁÂÈ·ÎÒÓ ·Ú·ÁfiÓÙˆÓ ÎÈÓ‰‡ÓÔ˘. Δ· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ¤ÁÈÓ·Ó ·ÚÎÂÙ¤˜ ÌÂϤÙ˜ Ô˘ ·¤‰ÂÈÍ·Ó fiÙÈ Ë ÛÙ˘ÙÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÌÔÚ› Ó· ·ÔηٷÛÙ·ı› Ì ÙËÓ ¯ÔÚ‹ÁËÛË L-·ÚÁÈÓ›Ó˘.45,46 ∞ÛıÂÓ›˜ Ì ÛÙ˘ÙÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· Î·È Ù·˘Ùfi¯ÚÔÓË Î·Ú‰È·ÁÁÂȷ΋ ÓfiÛÔ ‹ ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË ‰ÂÓ ¤¯Ô˘Ó ÌfiÓÔÓ ·˘ÍË̤ӷ ›‰· ADMA ·ÏÏ¿ Î·È ÂÏ·Ùو̤ӷ ›‰· L·ÚÁÈÓ›Ó˘. ∞ÓÙ›ıÂÙ· Û ·ÛıÂÓ›˜ Ì ÛÙ˘ÙÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙÚ·˘Ì·ÙÈ΋˜ ·ÈÙÈÔÏÔÁ›·˜ ‰ÂÓ ˘‹ÚÍ·Ó ·˘ÍË̤ӷ ›‰· ADMA Û ۇÁÎÚÈÛË Ì ÙÔ˘˜ ˘ÁÈ›˜ Ì¿ÚÙ˘Ú˜.
ÕÏϘ ηٷÛÙ¿ÛÂȘ ∞˘ÍË̤ӷ ›‰· ADMA ·Ú·ÙËÚ‹ıËÎ·Ó Û ηÓÈÛÙ¤˜ Î·È ·¯‡Û·ÚÎÔ˘˜47·ÏÏ¿ Î·È Û ·ÛıÂÓ›˜ Ì ˘ÂÚı˘ÚÂÔÂȉÈÛÌfi,48 Û˘ÌÊÔÚËÙÈ΋ ηډȷ΋ ·Ó¿ÚÎÂÈ·,49 ȉÈÔ·ı‹ Ó¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË50 Î·È ·ÁÁÂȷο ÂÁÎÂÊ·ÏÈο ÂÂÈÛfi‰È·.51 ∏ ADMA ›Ûˆ˜ ·›˙ÂÈ Î¿ÔÈÔ ÚfiÏÔ ÛÙËÓ ÂÌ‚Ú˘Ô-Ï·ÎÔ˘ÓÙȷ΋ ΢ÎÏÔÊÔÚ›· Î·È ÛÙËÓ Î˘ÎÏÔÊÔÚÈ΋ ÚÔÛ·ÚÌÔÁ‹ ÙÔ˘ ÓÂÔÁ¤ÓÓËÙÔ˘.52 ™ÙȘ ·ÚÂÌ‚¿ÛÂȘ ÁÈ· ÙËÓ ÂÏ¿ÙÙˆÛË ÙˆÓ ÂȤ‰ˆÓ ADMA ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È Ë ÂÓÙ·ÙÈÎÔÔ›ËÛË
Ù˘ ¿ÛÎËÛ˘, Ë ÂÏ¿ÙÙˆÛË ÙÔ˘ ÔÍÂȉˆÙÈÎÔ‡ stress, Ë ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ ·ÓÙÈÔÍÂȉˆÙÈÎÒÓ Î·È Ë ÓÔÚÌ·ÏÔÔ›ËÛË ÙˆÓ ÙÈÌÒÓ ÙÔ˘ Ê˘ÏÏÈÎÔ‡ ÔͤԘ. ™Â ÌÂϤÙË ÁÈ· ÙË Ú·ÌÈÚ›ÏË Î·È ÙËÓ ‚·ÏÛ·ÚÙ¿ÓË Ê¿ÓËΠfiÙÈ Î·È Ù· ‰‡Ô Ê¿Ú̷η Â›Ó·È ÂÍ ›ÛÔ˘ ·ÔÙÂÏÂÛÌ·ÙÈο ÛÙË Ì›ˆÛË ÙˆÓ ·˘ÍËÌ¤ÓˆÓ ÂȤ‰ˆÓ ADMA Î·È ÛÙË ‚ÂÏÙ›ˆÛË Ù˘ ÂÓ‰ÔıËÏȷ΋˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ Û ·ÛıÂÓ›˜ Ì ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ·.53 ∂›Â‰· ADMA ·Ó¢ڛÛÎÔÓÙ·È Î·È ÙÔÈο ÛÙȘ ÛÙÂÊ·ÓÈ·›Â˜ ‚Ï¿‚˜, οÙÈ Ô˘ ˘Ô‰ËÏÒÓÂÈ fiÙÈ ·ÂÏ¢ıÂÚÒÓÔÓÙ·È ÛÙËÓ ·ıËڈ̷ÙÈ΋ Ͽη. ∏ ÙÔÈ΋ Û˘ÛÛÒÚ¢ÛË ADMA ›Ûˆ˜ Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ÂÓ‰ÔıËÏȷ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ˘„ËÏÔ‡ ‚·ıÌÔ‡ ÛÙÂÊ·ÓÈ·›Â˜ ‚Ï¿‚˜.54 ™˘ÌÂÚ·ÛÌ·ÙÈο ÔÈ Û˘ÁÎÂÓÙÚÒÛÂȘ Ù˘ ADMA Â›Ó·È ‰Â›ÎÙ˘ fiÏˆÓ ÙˆÓ ·ÈÙÈÒÓ ıÓËÛÈÌfiÙËÙ·˜ ·ÏÏ¿ Î·È Ù˘ ηډȷÁÁÂȷ΋˜ ıÓËÛÈÌfiÙËÙ·˜ Û ·ÛıÂÓ›˜ Ì ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ ·ÓÂÍ¿ÚÙËÙ· ·fi ÙÔ˘˜ ·Ó·ÁÓˆÚÈṲ̂ÓÔ˘˜ ‹ ÙÔ˘˜ ·Ó·‰˘fiÌÂÓÔ˘˜ ηډȷÁÁÂÈ·ÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘.55
μÈ‚ÏÈÔÁÚ·Ê›· 1.
Vallance P, Leone A, Calver A et al. Endogenous dimethyl-arginine as an inhibitor of nitric oxide synthesis. J. Cardiovasc Pharmacol 1992; 20 (Suppl. 12): S60- S62.
2.
Böger RH, Bode-Böger SM, Frolich JC. The L- arginine- nitric oxide pathway: Role in atherosclerosis and therapeutic implications. Atherosclerosis 1996; 127:1-11.
3.
4.
Vallance P, Leone A, Calver A et al. Accumulation of an endogenous inhibitor of NO synthesis in chronic renal failure. Lancet 1992; 339:572-575. Böger RH, Sydow K, Borlak J et al. LDL cholesterol upregulates synthesis of asymmetric dimethylarginine (ADMA) in human endothelial cells. Involvement of S-adenosylmethionine-dependent methyltranferases. Circ Res 2000; 87:99105.
5.
Zoccali C. Cardiovascular risk in uraemic patients: is it fully explained by classical risk factors? Nephrol Dial Tranplant 2000; 15:454-456.
6.
Vane JR, Anggard EE, Botting RM. Regulatory functions of vascular endothelium. N Engl J Med 1990; 323:27-36.
7.
8.
Böger RH, Zoccali C. ADMA. A novel risk factor that explains excess cardiovascular event rate in patients with endstage renal disease. Atherosclerosis Suppl. 2003; 4:23-28. Kielstein JT, Böger RH, Bode-Böger SM et al. Asymmetric dimethylarginine plasma concentrations differ in patients with end-stage renal disease: Relation to treatment method and atherosclerotic disease. J Am Soc Nephrol 1999; 10:594-600.
9.
Zoccali C, Bode-Böger SM, Mallamaci F et al. Asymmetric dimethylarginine (ADMA): An endogenous inhibitor of nitric oxide synthase predicts mortality in end-stage renal disease (ESRD). Lancet 2001; 358: 2113-17.
10. Kielstein JT, Böger RH, Bode-Böger SM et al. Marked increase of asymmetric dimethylarginine in patients with incipient primary chronic renal disease. J Am Soc Nephrol 2002;13(1): 170-176. 11. Surdacki A, Nowicki M, Sandmann J et al. Reduced urinary excretion of nitric oxide metabolites and increased plasma levels of of Cardiovasc Pharmacol 1999; 33:652-658. 12. Calver A, Collier J, Leone A et al. Effect of local intra-arterial asymmetric dimethylarginine(ADMA) on the forearm arteriolar bed of healthy volunteers. J Hum Hypertens 1993; 7:193-194.
9
ª∞ƒΔπ√™ 2008
13. Achan V, Broadhead M, Malaki M, et al. Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethyl aminohydrolase. Arterioscler Thromb Vasc Biol 2003; 23:1455-59. 14. Scuteri A, St_linger MC, Cooke JP et al. Nitric oxide inhibition as a mechanism for blood pressure increase during salt loading in normotensive post menopausal women. J Hypertens 2003;21(7):1339-46. 15. Holm T, Aucrust P, Aagaard E et al. Hypertension in relation to nitric oxide, asymmetric dimethylarginine and inflammation: different patterns in heart transplant recipients and individuals with essential hypertension. Transplantation 2002; 74(10): 1395-400. 16. Böger RH. Asymmetric dimethylarginine (ADMA) and cardiovascular disease: insights from prospective clinical trials. Vasc Med 2005;10 (Suppl 1):S19-S25. 17. Böger RH. Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, explains the ''L- arginine paradox'' and acts as a novel cardiovascular risk factor.J Nutr 2004; 134(Suppl 10): 2842S2847S, discussion 2853S. 18. Petterson A, Hedner T, Milsom I. Increased circulating concentrations of asymmetric dimethylarginine(ADMA), an endogenous inhibitor of nitric oxide synthesis, in preeclampsia. Acta Obstet Gynecol Scand 1998;77:808-813. 19. Savvidou MD, Hingorani AD, Tsikas D et al. Endothelial dysfunction and raised plasma concentrations of asymmetric dimethylarginine in pregnant women who subsequently develop preeclampsia. Lancet 2003;361:1511-517. 20. Valkonen VP, Paiva H, Salonen JT et al. Risk of acute coronary eventsand serum concentration of asymmetric dimethylarginine. Lancet 2001; 358: 2127-28. 21. Lenzen H, Tsikas D, Böger RH. Asymmetric dimethylarginine (ADMA) and the risk for coronary heart disease: the multicenter CARDIAC study. Eur J Clin Pharmacol 2006;62 (Suppl 13):45-49. 22. Nijveldt RJ, Teerlink T, Van der Hoven B et al. Asymmetric dimethylarginine (ADMA) in critically ill patients: high plasma ADMA concentration is an independent risk factor of ICU mortality. Clin Nutr 2003;22:23-30. 23. Lu TM, Ding YA, Lin SJ et al. Plasma levels of asymmetric dimethylarginine and adverse cardiovascular events after percutaneous coronary intervention. Eur Heart J 2003;24:1912-19. 24. Schnabel R, Blankeberg S, Lubos E et al. Asymmetric dimethylarginine (ADMA) and the risk of cardiovascular events and death in patients with coronary artery disease: results from AtheroGene Study. Circ Res 2005;97:e53-e59.
10
27. Mittermayer F, Krzyzanowska K, Exner M et al. Asymmetric dimethylarginine predicts major adverse cardiovascular events in patients with advanced peripheral artery disease. Arterioscler Thromb Vasc Biol 2006;26:2536-40. 28. Böger RH, Bode-Böger SM, Szuba A et al. Asymmetric dimethylarginine: a novel risk factor for endothelial dysfunction. Its role in hypercholesterolemia. Circulation 1998;98:1842-47. 29. Janatuinen T, Laakso J, Laaksonen R et al. Plasma asymmetric dimethylarginine modifies the effect of pravastatin on myocardial blood flow in young adults. Vasc Med 2003;8:185-89. 30. Eid HM, Eritsland J, Larsen J et al. Increased levels of asymmetric dimethylarginine in populations at risk for atherosclerotic disease. Effects of pravastatin. Atherosclerosis 2003;166(2):279-84. 31. Böger RH, Sydow K, Borlak J et al. LDLcholesterol upregulates synthesis of asymmetric dimethylarginine in human endothelial cells: involvement of S-adenosylmethionine-dependent methyltranserases. Circ Res 2000;87(2);99-105. 32. Lundman P, Eriksson MJ, Stuhlinger M et al. Mild-to-moderate hypertrigyceridemia in young men is associated with endothelial dysfunction and increased plasma concentration of asymmetric dimethylarginine. J Am Coll Cardiol 2001;38:111-16 33. Dayal S, Lentz SR. ADMA and hyperomocysteinemia. Vasc M ed 2005;10 (Suppl 1):S27-S33. 34. Sydow K, Schwedhelm E, Atakawa N et al. ADMA and oxidative stress are responsible for endothelial dysfunction in hyperomocysteinemia: effects of L-arginine and B vitamins. Cardivasc Res 2003; 57(1):244-52.
42. Asagami T, Abbasi F, St_linger M et al. Metformin treatment lowers asymmetric dimethylarginine concentrations in patients with type 2 diabetes. Metabolism 2002;51:843-846. 43. Mittermayer F, Mayer BX, Meyer A et al. Circulating concentrations of assymetrical dimethyl-L-arginine are increased in women with previous gestational diabetes. Diabetologia 2002; 45(10): 1372-78. 44. Maas R, Schwedhelm E, Albsmeier J et al. The pathophysiology of erectile dysfunction related to endothelial dysfunction and mediators of vascular function. Vasc Med 2002; 7:213-225. 45. Zorgniotti AW, Lizza EF. Effect of large doses of nitric oxide precursor, Larginine, on erectile dysfunction. Int J Impot Res 1994;6:33-35. 46. Chen J, Wollman Y, Chernichovsky T et al. Effect of oral administration of highdose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of double-blind, randomized, placebocontrolled study. Brit J Urol Int 1999;83:269-73. 47. Eid HM, Arnesen H, Hjerkinn EM et al. Relationship between obesity, smoking, and the endogenous inhibitor of nitric oxide synthase, dimethylarginine. Metabolism 2004;53:1574-79. 48. Hermenegildo C, Medina P, Peiro M et al. Plasma concentration of asymmetric, an endogenous inhibitor of nitric oxide synthase, is elevated in hyperthyroid patients. J Clin Endocrinol Metab 2002;87:5636-40. 49. Usui M, Matsuoka H, Miyazaki H et al. Increased endogenous inhibitor of nitric oxide synthase in patients with congestive heart failure. Life Sci 1998;62:2425-30.
35. Lonn E, Yusuf S, Arnold MJO et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006;354:1567-77.
50. Kielstein JT, Bode-Böger SM, Hesse G et al. Asymmetric dimethylarginine in idiopathic pulmonary arterial hypertension. Arterioscler Thromb Vasc Biol 2005; 25:1414-18.
36. Kaare HB, Njolstad I, Ueland PM et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006;354:157888.
51. Wanby P, Teerlink T, Brudin L et al. Asymmetric dimethylarginine (ADMA) as a risk marker for stroke and TIA in a Swedish population. Atherosclerosis 2006;185:271-277.
37. Fard A, Tuck CH, Donis JA et al. Acute elevations of plasma asymmetric dimethylarginine and impaired endothelial function in response to high-fat meal in patients with type 2 diabetes. Arterioscler Thromb Vasc Biol 2000;20”2039-44.
52. Vida G, Sulyok E, Ertl T et al. Plasma asymmetric dimethylarginine concentration during the perinatal period. Neonatology 2007;92:8-13.
38. St_linger M, Abbasi F, Chu JW et al. Relationship between insulin resistance and an endogenous inhibitor of nitric oxide synthase. J Am Med Assoc 2002;287:1420-26. 39. Sydow K, Mondon CE, Cooke JP. Insulin resistance: potential role of an endogenous inhibitor of nitric oxide synthase ADMA. Vasc Med 2005;10(Suppl 1):S35S43.
25. Böger RH, Bode-Böger SM, Thiele W et al. Biochemical evidence of impaired nitric oxide synthesis in patients with peripheral occlusive disease. Circulation 1997;95:2068-74.
40. Lin KY, Ito A, Asagami T et al. Impaired nitric oxide synthase pathway in diabetes mellitus. Role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation2002;106:987-992.
26. Böger RH, Bode-Böger SM, Thiele W et al. Restoring vascular NO formation by Larginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease. J Am Coll Cardiol 1998;32:1336-44.
41. Ito A, Egashira K, Narisighe T et al. Angiotensin-converting enzyme activity is involved in the mechanism of increased nitric oxide synthase inhibitor in patients with type 2 diabetes. Circ J 2002;66:811815.
53. Yilmaz M, Saglam M, Sonmez A et al. Improoving proteinuria, endothelial functions and asymmetric dimethylarginine levels in chronic kidney disease: Ramipril versus Valsartan. Blood Pur 2007;25:327-335. 54. Joyal D, Leya F, Obada Al Chekakie M et al. Presence of asymmetric dimethylarginine gradients across high-grade lesions in patients with coronary artery disease. Coronary Art Dis 2007;18(6): 471-475. 55. Meinitzer A, Seelhorst U, Wellnitz B et al. Asymmetrical dimethylarginine independently predicts total and cardiovascular mortality in individuals with angiographic coronary artery disease (the Ludwigshafen risk and cardiovascular health study). Clin Chem 2007;53 (20:273-283.
¶∞£√ºÀ™π√§√°π∞
ªÔÚÈ·ÎÔ› ªË¯·ÓÈÛÌÔ› ∞ıËÚÔÛÎÏ‹ÚˆÛ˘. √ ƒfiÏÔ˜ ÙˆÓ ΔÂÏÈÎÒÓ ¶ÚÔ˚fiÓÙˆÓ ¶ÚÔËÁ̤Ó˘ °Ï˘ÎÔ˙˘Ï›ˆÛ˘ (AGEs) ¢ÈÛÏÈ¿Ó μ·ÏÂÓÙ›Ó·, MD, Msc, ÀÔ„‹ÊÈ· ¢È‰¿ÎÙˆÚ π·ÙÚÈ΋˜ ∞¶£ °È·ÓÓfiÁÏÔ˘ °ÂÒÚÁÈÔ˜, ∫·ıËÁËÙ‹˜ ∫·Ú‰ÈÔÏÔÁ›·˜, ∞’ ∫·Ú‰ÈÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌÈ·ÎÔ‡ °ÂÓÈÎÔ‡ ¡ÔÛÔÎÔÌ›Ԣ ∞Ã∂¶∞
1. ÀÂÚÁÏ˘Î·ÈÌ›· Î·È ·ıËÚÔÛÎÏ‹ÚˆÛË √ ۷ί·Ú҉˘ ‰È·‚‹Ù˘ (™¢) ·ÔÙÂÏ› ¤Ó·Ó ·fi ÙÔ˘˜ ÛËÌ·ÓÙÈÎfiÙÂÚÔ˘˜ Î·È ·ÓÂÍ¿ÚÙËÙÔ˘˜ ·Ú¿ÁÔÓÙ˜ ηډȷÁÁÂÈ·ÎÔ‡ ÎÈÓ‰‡ÓÔ˘.1 ∏ ÛÙÂÓ‹ Û¯¤ÛË Ô˘ ˘Ê›ÛÙ·Ù·È ÌÂٷ͇ ÁÏ˘Î·ÈÌ›·˜ Î·È ‰È·‚ËÙÈÎÒÓ ÂÈÏÔÎÒÓ, fiˆ˜ Ë ÌÈÎÚÔ·ÁÁÂÈÔ¿ıÂÈ· Î·È Ë Ì·ÎÚÔ·ÁÁÂȷ΋ ÓfiÛÔ˜, ¤¯ÂÈ ÂȂ‚·Èˆı› ·fi ÌÂÁ¿Ï˜ ÚÔÔÙÈΤ˜ Ù˘¯·ÈÔÔÈË̤Ó˜ ÎÏÈÓÈΤ˜ ÌÂϤÙ˜.2,3 ∏ ·Ú·ÙÂٷ̤ÓË ¤ÎıÂÛË Û ˘„ËϤ˜ Û˘ÁÎÂÓÙÚÒÛÂȘ ÁÏ˘Îfi˙˘ ÚÔηÏ› ÌÈ· ÛÂÈÚ¿ ·ıÔÏÔÁÈÎÒÓ ÌÂÙ·‚ÔÏÒÓ Û ΢ÙÙ·ÚÈÎfi ›‰Ô, Ô˘ ¤¯Ô˘Ó ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ¤Ó·ÚÍË, ‰È·Ù‹ÚËÛË Î·È ÂÈÙ¿¯˘ÓÛË Ù˘ ·ıËÚÔÛÎÏËÚˆÙÈ΋˜ ‰È·‰Èηۛ·˜. ∞Ó Î·È ÔÈ ÂÚÈÛÛfiÙÂÚ˜ ‚È‚ÏÈÔÁÚ·ÊÈΤ˜ ·Ó·ÊÔÚ¤˜ Ô˘ Û˘Ó‰¤Ô˘Ó ÙËÓ ˘ÂÚÁÏ˘Î·ÈÌ›· Ì ÙËÓ ·ıËÚÔÛÎÏ‹ÚˆÛË ·ÊÔÚÔ‡Ó ÙÔÓ ™¢, Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ‰›ÓÂÙ·È È‰È·›ÙÂÚË ¤ÌÊ·ÛË ÛÙËÓ ‚Ï·ÙÈ΋ ›‰Ú·ÛË Ù˘ ÁÏ˘Îfi˙˘ ·ÎfiÌË Î·È Â› ·Ô˘Û›·˜ ™¢. ™‡Ìʈӷ Ì ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ÔÈ ·˘ÍË̤ÓË
Û˘ÁΤÓÙÚˆÛË ÁÏ˘Îfi˙˘ ÓËÛÙ›·˜ Û ÌË ‰È·‚ËÙÈÎÔ‡˜ Û˘Û¯ÂÙ›˙ÂÙ·È Ì ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ Î·Ú‰È·ÁÁÂȷ΋˜ ÓÔÛËÚfiÙËÙ·˜.4,5 ∞fi ÙËÓ Û˘ÛÙËÌ·ÙÈ΋ ·Ó·ÛÎfiËÛË Ù˘ ‰ÈÂıÓÔ‡˜ ‚È‚ÏÈÔÁÚ·Ê›·˜ ÚÔ·ÙÂÈ fiÙÈ ˘¿Ú¯Ô˘Ó Ù¤ÛÛÂÚȘ ·ÚÈÔÈ Ì˯·ÓÈÛÌÔ›, ÛÙ· Ï·›ÛÈ· ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ Ù˘ ÁÏ˘Îfi˙˘, Ô˘ ¢ı‡ÓÔÓÙ·È ÁÈ· ÙËÓ ÂÈÙ·¯˘ÓfiÌÂÓË ·ıËÚÔÛÎÏ‹ÚˆÛË Û ™¢: ·) Ë ·˘ÍË̤ÓË ‰Ú·ÛÙËÚÈfiÙËÙ· Ù˘ Ô‰Ô‡ Ù˘ ÛÔÚ‚ÈÙfiÏ˘,6 ‚) Ë ÌË-ÂÓ˙˘ÌÈ΋ ÁÏ˘ÎÔ˙˘Ï›ˆÛË ÙˆÓ ÚˆÙÂ˚ÓÒÓ Î·È ÙˆÓ ÏÈȉ›ˆÓ, Ô˘ ηٷϋÁÂÈ ÛÙÔÓ Û¯ËÌ·ÙÈÛÌfi ÙˆÓ ÙÂÏÈÎÒÓ ÚÔ˚fiÓÙˆÓ ÚÔËÁ̤Ó˘ ÁÏ˘ÎÔ˙˘Ï›ˆÛ˘ (Advanced Glycation End ProductsAGEs),7 Á) Ë ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ ÈÛÔÌÔÚÊÒÓ Ù˘ ÚˆÙÂ˚ÓÈ΋˜ ÎÈÓ¿Û˘ C (Protein Kinase C, PKC)8 Î·È ‰) Ë ·˘ÍË̤ÓË ÚÔ‹ ÛÙÔ ÌÔÓÔ¿ÙÈ Ù˘ ÂÍÔ˙·Ì›Ó˘.9 ™‡Ìʈӷ Ì ÙËÓ ÂÓÔÔÈË̤ÓË ıˆڛ·, Ô˘ ¤¯ÂÈ ÚÔÙ·ı› ·fi ÙÔÓ Michael Brownlee, ·ÔÙ¤ÏÂÛÌ· Ù˘ ˘ÂÚÁÏ˘Î·ÈÌ›·˜ Â›Ó·È Ë ·‡ÍËÛË ÙÔ˘ ÔÍÂȉˆÙÈÎÔ‡ ÛÙÚ˜
(oxidative stress, OS), ηıÒ˜ fiÏÔÈ ÔÈ ÚÔ·Ó·ÊÂÚfiÌÂÓÔÈ Ì˯·ÓÈÛÌÔ› ηٷϋÁÔ˘Ó ÛÙËÓ ˘ÂÚ·Ú·ÁˆÁ‹ ÛÔ˘ÂÚÔÍÂȉ›Ô˘ (√2-) ·fi ÙËÓ ÌÈÙÔ¯ÔÓ‰Úȷ΋ ¿Ï˘ÛÔ ÌÂÙ·ÊÔÚ¿˜ ËÏÂÎÙÚÔÓ›ˆÓ.10 ªÔÚ› ÙÔ OS Ó· Â›Ó·È ÙÔ ÎÔÈÓfi ÛËÌÂ›Ô Î·Ù¿ÏË͢, fiÏˆÓ ÙˆÓ ÚÔηÏÔ‡ÌÂÓˆÓ ·fi ÙËÓ ˘ÂÚÁÏ˘Î·ÈÌ›· Ì˯·ÓÈÛÌÒÓ, Ù·˘Ùfi¯ÚÔÓ· fï˜ ˘Ê›ÛÙ·Ù·È Î·È ¤Ó· Û‡ÛÙËÌ· ıÂÙÈ΋˜ ·Ó·ÙÚÔÊÔ‰fiÙËÛ˘: ΔÔ OS, Ô˘ ÚÔηÏÂ›Ù·È ·fi ÙËÓ ˘ÂÚÁÏ˘Î·ÈÌ›·, ÚÔ¿ÁÂÈ ÙÔÓ Û¯ËÌ·ÙÈÛÌfi ÙˆÓ AGEs Î·È ÙËÓ ÂÓÂÚÁÔÔ›ËÛË Ù˘ ÚˆÙÂ˚ÓÈ΋˜ ÎÈÓ¿Û˘ C (PKC), ·ÏÏ¿ Î·È Ô Û¯ËÌ·ÙÈÛÌfi˜ ÙˆÓ AGEs ¿ÁÂÈ ÙÔ OS Î·È ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÌÂÙ·ÁÚ·ÊÈÎÒÓ ·Ú·ÁfiÓÙˆÓ.11 ¢ËÌÈÔ˘ÚÁÂ›Ù·È ÂÔ̤ӈ˜ ¤Ó·˜ Ê·‡ÏÔ˜ ·ÎÏÔ˜ Ô˘ Û˘ÓÙËÚ› ÙËÓ ·ıËÚÔÛÎÏ‹ÚˆÛË Î·È Â˘ı‡ÓÂÙ·È ÁÈ· ÙËÓ ÚfiÎÏËÛË ÙˆÓ ‰È·‚ËÙÈÎÒÓ ·ÁÁÂÈ·ÎÒÓ ÂÈÏÔÎÒÓ. ™ÙËÓ ÂÈÎfiÓ· Ô˘ ·ÎÔÏÔ˘ı› ·ÂÈÎÔÓ›˙ÔÓÙ·È ÔÈ Ì˯·ÓÈÛÌÔ› ̤ۈ ÙˆÓ ÔÔ›ˆÓ Ë ˘ÂÚÁÏ˘Î·ÈÌ›· Û˘Ó‰¤ÂÙ·È Ì ÙȘ ÂÈÏÔΤ˜ Ù˘ ·ıËÚÔÛÎÏ‹ÚˆÛ˘.12
¢π∞μ∏Δ∏™ À¶∂ƒ°§À∫∞πªπ∞.
¶ÚˆÙÂ˚Ó. ∫ÈÓ¿ÛË C.
°Ï˘ÎÔ˙˘Ï›ˆÛË
ªÈÙÔ¯ÔÓ‰ÚȷΤ˜ ∂ƒ√
√‰fi˜ ¶ÔÏ˘ÔÏÒÓ
√‰fi˜ ÂÍÔ˙·Ì›Ó˘
¢π∞μ∏Δπ∫∏ ªπ∫ƒ√ Î·È ª∞∫ƒ√∞°°∂π√¶∞£∂π∞
∂ÈÎfiÓ· 1. ªË¯·ÓÈÛÌÔ› ÚfiÎÏËÛ˘ ‰È·‚ËÙÈÎÒÓ ·ÁÁÂÈ·ÎÒÓ ÂÈÏÔÎÒÓ.12
11
ª∞ƒΔπ√™ 2008
ÂÎÚfiÛˆÔ ÙÔÓ Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË.15
2. μÈÔ¯ËÌ›· Ù˘ ÌË ÂÓ˙˘ÌÈ΋˜ ÁÏ˘ÎÔ˙˘Ï›ˆÛ˘ ΔÔ 1912 Ô °¿ÏÏÔ˜ ¯ËÌÈÎfi˜ Maillard ÂÚȤÁÚ·„ ÙÔ ÚÒÙÔ ÛÙ¿‰ÈÔ ÙˆÓ ·ÓÙȉڿÛÂˆÓ Ù˘ ÌË ÂÓ˙˘ÌÈ΋˜ ÁÏ˘ÎÔ˙˘Ï›ˆÛ˘ Ô˘ Â›Ó·È ÁÓˆÛÙfi Î·È ˆ˜ ·ÓÙ›‰Ú·ÛË Maillard.13 √ Maillard ·Ú·Ù‹ÚËÛ fiÙÈ fiÙ·Ó Ù· ۿί·Ú· ˘Ê›ÛÙ·ÓÙ·È ıÂÚÌÈ΋ ÂÂÍÂÚÁ·Û›· Ì ·ÌÈÓÔͤ·, Ú·ÁÌ·ÙÔÔÈÂ›Ù·È Ì›· ÌË ÂÓ˙˘ÌÈ΋ ‰È·‰Èηۛ·, Ô˘ ηٷϋÁÂÈ ÛÙËÓ ÌÂÙ·‚ÔÏ‹ ÙÔ˘ ¯ÚÒÌ·ÙÔ˜ ÙˆÓ ÙÚÔʛ̈Ó. ∞Ú¯Èο ÔÈ ·ÓÙȉڿÛÂȘ Ù˘ ÌË ÂÓ˙˘ÌÈ΋˜ ÁÏ˘ÎÔ˙˘Ï›ˆÛ˘ ··Û¯fiÏËÛ·Ó ÙÔ˘˜ ÂÈÛÙ‹ÌÔÓ˜ Ô˘ ·Û¯ÔÏÔ‡ÓÙ·Ó Ì ÙËÓ ‚ÈÔ¯ËÌ›· ÙˆÓ ÙÚÔʛ̈Ó, ηıÒ˜ ‰È·ÈÛÙÒıËΠfiÙÈ Ë Û˘ÁÎÂÎÚÈ̤ÓË ·ÓÙ›‰Ú·ÛË Û¯ÂÙ›˙ÂÙ·È Ì ÙÔ ¯ÚÒÌ·, ÙËÓ Á‡ÛË Î·È ÙËÓ ‚ÈÔÏÔÁÈ΋ ÛËÌ·Û›· ÙˆÓ ÙÚÔʛ̈Ó.14 Δ· AGEs Â›Ó·È Ì›· ÂÙÂÚÔÁÂÓ‹˜ ÔÌ¿‰· Ô˘ÛÈÒÓ, Ô˘ ÚÔ¤Ú¯ÔÓÙ·È ·fi ÙËÓ ÌË ÂÓ˙˘ÌÈ΋ ÁÏ˘ÎÔ˙˘Ï›ˆÛË ÙˆÓ ÚˆÙÂ˚ÓÒÓ, ÏÈȉ›ˆÓ Î·È ÓÔ˘ÎÏÂ˚ÎÒÓ ÔͤˆÓ. ∏ ÌË ÂÓ˙˘ÌÈ΋ ÁÏ˘ÎÔ˙˘Ï›ˆÛË ıˆÚÂ›Ù·È Ì›· ·fi ÙȘ ÈÔ Û˘¯Ó¤˜ ÌÂÙ·-ÌÂÙ·ÊÚ·ÛÙÈΤ˜ ÌÂÙ·ÙÚÔ¤˜. ™Â Ê˘ÛÈÔÏÔÁÈΤ˜ ηٷÛÙ¿ÛÂȘ ·˘ÍË̤ÓË ÌË ÂÓ˙˘ÌÈ΋ ÁÏ˘ÎÔ˙˘Ï›ˆÛË ·Ú·ÙËÚÂ›Ù·È Î·Ù¿ ÙËÓ Á‹Ú·ÓÛË, ÂÓÒ Û ·ıÔÏÔÁÈΤ˜ ηٷÛÙ¿ÛÂȘ ÙÔ Ê·ÈÓfiÌÂÓÔ Û¯ÂÙ›˙ÂÙ·È Ì ·ÚÎÂÙ¿ ÓÔÛ‹Ì·Ù·, Ì ΢ÚÈfiÙÂÚÔ
ΔÔ ÚÒÙÔ ÛÙ¿‰ÈÔ Û¯ËÌ·ÙÈÛÌÔ‡ ÙˆÓ AGEs ÂÚÈÏ·Ì‚¿ÓÂÈ ÙËÓ ·ÓÙ›‰Ú·ÛË Maillard Û‡Ìʈӷ Ì ÙËÓ ÔÔ›· ÔÈ ÂχıÂÚ˜ ·ÌÈÓÔÔÌ¿‰Â˜ Ì·ÎÚÔÌÔÚ›ˆÓ, fiˆ˜ ÚˆÙ½Ó˜, ÏÈ›‰È· Î·È ÓÔ˘ÎÏÂ˚ο Ôͤ·, ·ÓÙȉÚÔ‡Ó Ì ÙȘ ·Ï‰Â¸‰ÔÔÌ¿‰Â˜ ‹ ÎÂÙÔÓÔÔÌ¿‰Â˜ ۷ί¿ÚˆÓ, fiˆ˜ Ë ÁÏ˘Îfi˙Ë. ™˘ÁÎÂÎÚÈ̤ӷ ÁÈ· ÙȘ ÚˆÙ½Ó˜, ÙÔ ·ÌÈÓÔ͇ Ï˘Û›ÓË Â›Ó·È ÂΛÓÔ Ô˘ ·ÓÙȉڿ Ì ÙË ÁÏ˘Îfi˙Ë. ∏ ·ÓÙ›‰Ú·ÛË ·˘Ù‹ ÔÓÔÌ¿˙ÂÙ·È ÌË ÂÓ˙˘ÌÈ΋ ÁÏ˘ÎÔ˙˘Ï›ˆÛË, Ú·ÁÌ·ÙÔÔÈÂ›Ù·È Ì¤Û· Û ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· Ï›ÁˆÓ ÌfiÓÔ ˆÚÒÓ Î·È Î·Ù·Ï‹ÁÂÈ ÛÙÔ Û¯ËÌ·ÙÈÛÌfi ·ÛÙ·ıÒÓ ÁÏ˘ÎÔ˙˘ÏÈˆÌ¤ÓˆÓ ÂÓÒÛÂˆÓ Ô˘ ϤÁÔÓÙ·È ‚¿ÛÂȘ ÙÔ˘ Schiff. Δ· ·ÛÙ·ı‹ ·˘Ù¿ ÌfiÚÈ· ˘fiÎÂÈÓÙ·È Û ‰È¿ÊÔÚ˜ ÂÓ‰ÔÌÔÚȷΤ˜ ·Ó·Î·Ù·Ù¿ÍÂȘ, Ô˘ ‰È·ÚÎÔ‡Ó ÌÂÁ·Ï‡ÙÂÚÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· (‚‰ÔÌ¿‰Â˜) Î·È Î·Ù·Ï‹ÁÔ˘Ó Û ÈÔ ÛÙ·ıÂÚ¿ ÚÔ˚fiÓÙ·, Ù· ÚÔ˚fiÓÙ· Amadori, fiˆ˜ Ë ·ÈÌÔÛÊ·ÈÚ›ÓË A1c. Δ· ÚÔ˚fiÓÙ· Amadori, ¯·Ú·ÎÙËÚ›˙ÔÓÙ·È ˆ˜ ÚÒÈÌ· ÚÔ˚fiÓÙ· ÌË ÂÓ˙˘ÌÈ΋˜ ÁÏ˘ÎÔ˙˘Ï›ˆÛ˘, ˘Ê›ÛÙ·ÓÙ·È Ì›· ÛÂÈÚ¿ ·ÓÙȉڿÛˆÓ, fiˆ˜ ÛÙ·‰È·Î‹ ÌÔÚȷ΋ ·ӷ‰È¢ı¤ÙËÛË, ·Ê˘‰¿ÙˆÛË, Û˘Ì‡ÎÓˆÛË, ‰È¿Û·ÛË, ÔÍ›‰ˆÛË Î·È ÙÂÏÈο ηٷϋÁÔ˘Ó ÛÙË ‰ËÌÈÔ˘ÚÁ›· ÙˆÓ ÙÂÏÈÎÒÓ ÚÔ˚fiÓÙˆÓ ÚÔËÁ̤Ó˘ ÁÏ˘ÎÔ˙˘Ï›ˆÛ˘ (AGEs).16,17 ΔÔ
ÛÙ¿‰ÈÔ ÌÂÙ·ÙÚÔ‹˜ ÙˆÓ ÚÔ˚fiÓÙˆÓ Amadori Û AGEs Â›Ó·È ÌÈ· ÌË ·ÓÙÈÛÙÚÂÙ‹ ·ÓÙ›‰Ú·ÛË Î·È ¤¯ÂÈ ÌÂÁ¿ÏË ¯ÚÔÓÈ΋ ‰È¿ÚÎÂÈ·, ·fi Ì‹Ó˜ ¤ˆ˜ ¯ÚfiÓÈ·. °È' ·˘ÙfiÓ ÙÔÓ ÏfiÁÔ Ù· Ì·ÎÚÔÌfiÚÈ· ÛÙ· ÔÔ›· ·Ú·ÙËÚÔ‡ÓÙ·È ·˘ÙÔ‡ ÙÔ˘ ›‰Ô˘˜ ÔÈ ÌÂÙ·ÙÚÔ¤˜ Â›Ó·È ÂΛӷ Ì ÌÂÁ¿ÏÔ ¯ÚfiÓÔ ËÌ›ÛÂÈ·˜ ˙ˆ‹˜, fiˆ˜ ÙÔ ÎÔÏÏ·ÁfiÓÔ ÙÔ˘ ·ÁÁÂÈ·ÎÔ‡ ÙÔȯÒÌ·ÙÔ˜. ™ÙËÓ ÂÈÎfiÓ· Ô˘ ·ÎÔÏÔ˘ı› ·ÂÈÎÔÓ›˙ÂÙ·È Ë ¯ÚÔÓÈ΋ ÂͤÏÈÍË ÙˆÓ ·ÓÙȉڿÛÂˆÓ Ù˘ ÌË ÂÓ˙˘ÌÈ΋˜ ÁÏ˘ÎÔ˙˘Ï›ˆÛ˘ ̤¯ÚÈ ÙÔÓ ÙÂÏÈÎfi Û¯ËÌ·ÙÈÛÌfi ÙˆÓ AGEs.18,19 √È ·ÓÙȉڿÛÂȘ ÌË ÂÓ˙˘ÌÈ΋˜ ÁÏ˘ÎÔ˙˘Ï›ˆÛ˘ ‰ÂÓ ·ÊÔÚÔ‡Ó ÌfiÓÔ ÙȘ ÚˆÙ½Ó˜. ∏ ÌÂÙ·ÙÚÔ‹ ÙˆÓ ÏÈÒÓ Û AGEs ‰ËÌÈÔ˘ÚÁÂ›Ù·È Î·Ù¿ ÙËÓ ¯ËÌÈ΋ ·ÓÙ›‰Ú·ÛË ÙˆÓ ÊˆÛÊÔÏÈȉ›ˆÓ, Ô˘ ÂÚȤ¯Ô˘Ó ÛÙÔ ÌfiÚÈo ÙÔ˘˜ ÚˆÙÔÙ·Á›˜ ·Ì›Ó˜, Ì ÙË ÁÏ˘Îfi˙Ë. ªË ÂÓ˙˘ÌÈ΋ ÁÏ˘ÎÔ˙˘Ï›ˆÛË ˘Ê›ÛÙ·ÓÙ·È ÙfiÛÔ ÔÈ ÏÈÔÚˆÙ½Ó˜ ¯·ÌËÏ‹˜ ˘ÎÓfiÙËÙ·˜ (Low Density Lipoproteins, LDL), fiÛÔ Î·È ÔÈ ÏÈÔÚˆÙ½Ó˜ ˘„ËÏ‹˜ ˘ÎÓfiÙËÙ·˜ (High Density Lipoproteins, HDL), Ì ·ÔÙ¤ÏÂÛÌ· Ó· ηı›ÛÙ·ÓÙ·È ÂÚÈÛÛfiÙÂÚÔ Â˘¿ÏˆÙ˜ Û ÔÍÂȉˆÙÈ΋ ÙÚÔÔÔ›ËÛË.20,21 ∏ ÁÏ˘ÎÔ˙˘Ï›ˆÛË ÙˆÓ ÏÈȉ›ˆÓ ‰ËÌÈÔ˘ÚÁÂ›Ù·È ÛÂ Û˘Ó¿ÚÙËÛË Ì ÙË Û˘ÁΤÓÙÚˆÛË Î·È Ì ÙÔ ¯ÚfiÓÔ ¤ÎıÂÛ˘ ÛÙË ÁÏ˘Îfi˙Ë.
°Ï˘ÎÔ˙˘Ï›ˆÛË ¶ÚˆÙ½ÓË + °Ï˘Îfi˙Ë
ÚÔ˚fiÓÙ· Amadori
‚¿ÛË ÙÔ˘ Schiff
.¯. HbA1c, ºÚÔ˘ÎÙÔ˙·Ì›ÓË
°Ï˘ÎÔÍ›‰ˆÛË (Ë̤Ú˜, ‚‰ÔÌ¿‰Â˜)
¶ÚÔËÁ̤ÓË ÁÏ˘ÎÔ˙˘Ï›ˆÛË (Ì‹Ó˜, ¯ÚfiÓÈ·),
ΔÂÏÈο ÚÔ˚fiÓÙ· ÚÔËÁ̤Ó˘ ÁÏ˘ÎÔ˙˘Ï›ˆÛ˘
CML
¶ÂÓÙÔ˙ȉ›ÓË ™Ù·˘ÚÔÂȉ›˜ ‰ÂÛÌÔ›
∂ÈÎfiÓ· 3. ÃÚÔÓÈ΋ ·ÏÏËÏÔ˘¯›· ÙˆÓ ·ÓÙȉڿÛÂˆÓ Û¯ËÌ·ÙÈÛÌÔ‡ ÙˆÓ AGEs.19
12
¶∞£√ºÀ™π√§√°π∞ ªÂÙ·ÙÚÔ¤˜ Û AGEs ÌÔÚÔ‡Ó Ó· ˘ÔÛÙÔ‡Ó Î·È Ù· ÌfiÚÈ· ÙÔ˘ DNA ηٿ ÙËÓ ·ÓÙ›‰Ú·ÛË Ù˘ ÁÏ˘Îfi˙˘ Ì ÙËÓ ·ÌÈÓÔÌ¿‰· ÙˆÓ ÓÔ˘ÎÏÂÔÙȉ›ˆÓ. ∏ ÁÔ˘·Ó›ÓË Â›Ó·È Ë ‚¿ÛË ÙÔ˘ DNA Ô˘ ΢ڛˆ˜ ·ÓÙȉڿ Ì ÙË ÁÏ˘Îfi˙Ë. ∏ ÚÔËÁ̤ÓË ÁÏ˘ÎÔ˙˘Ï›ˆÛË ÙÔ˘ DNA ÌÔÚ› Ó· ÂËÚ¿ÛÂÈ ÙÔÓ ÌÂÙ·‚ÔÏÈÛÌfi ÙÔ˘, ›Ù ÚÔηÏÒÓÙ·˜ ÌÂÙ·ÏÏ¿ÍÂȘ, ›Ù ·‰Ú·ÓÔÔÈÒÓÙ·˜ ÙÔ˘˜ Ì˯·ÓÈÛÌÔ‡˜ Ù˘ ÂȉÈfiÚıˆÛ˘.22 √ ‚·ıÌfi˜ Ù˘ ÌË ÂÓ˙˘ÌÈ΋˜ ÁÏ˘ÎÔ˙˘Ï›ˆÛ˘ ηıÔÚ›˙ÂÙ·È Î˘Ú›ˆ˜ ·fi ÙËÓ Û˘ÁΤÓÙÚˆÛË Ù˘ ÁÏ˘Îfi˙˘ Î·È ·fi ÙÔ ÔÍÂȉԷӷÁˆÁÈÎfi ‰˘Ó·ÌÈÎfi Ô˘ ÂÈÎÚ·Ù› ÛÙÔ ÈÛÙÈÎfi ÌÈÎÚÔÂÚÈ‚¿ÏÏÔÓ. ™Â ηٷÛÙ¿ÛÂȘ ·˘ÍË̤ÓÔ˘ OS Ô Û¯ËÌ·ÙÈÛÌfi˜ ÙˆÓ AGEs ·˘Í¿ÓÂÙ·È ÛËÌ·ÓÙÈο.17
3. ΔÂÏÈο ÚÔ˚fiÓÙ· ÚÔËÁ̤Ó˘ ÁÏ˘ÎÔ˙˘Ï›ˆÛ˘ Î·È ·ıËÚÔÛÎÏ‹ÚˆÛË √ Û¯ËÌ·ÙÈÛÌfi˜ ÙˆÓ AGEs Â›Ó·È ¤Ó·˜ ·fi ÙÔ˘˜ ÈÔ ÛËÌ·ÓÙÈÎÔ‡˜ ÌÔÚÈ·ÎÔ‡˜ Ì˯·ÓÈÛÌÔ‡˜, Ô˘ ¢ı‡ÓÂÙ·È ÁÈ· ÙËÓ ¤Ó·ÚÍË, ÚÔ·ÁˆÁ‹ Î·È ‰È·Ù‹ÚËÛË Ù˘ ·ıËÚÔÛÎÏ‹ÚˆÛ˘. Δ· AGEs ·˘Í¿ÓÔÓÙ·È ÛÂ Ê˘ÛÈÔÏÔÁÈΤ˜ Û˘Óı‹Î˜ ηٿ ÙËÓ Á‹Ú·ÓÛË Î·È Û ·ıÔÏÔÁÈΤ˜ Û˘Óı‹Î˜ Û ‰È¿ÊÔÚ· ÓÔÛ‹Ì·Ù·, Ì ΢ÚÈfiÙÂÚÔ ÂÎÚfiÛˆÔ ÙÔÓ ™¢. ™ÙÔÓ ™¢ Ë ‰ËÌÈÔ˘ÚÁ›· ÙˆÓ AGEs Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ÚfiÎÏËÛË ÙfiÛÔ ÙˆÓ ÌÈÎÚÔ·ÁÁÂÈ·ÎÒÓ ÂÈÏÔÎÒÓ (·ÌÊÈ‚ÏËÛÙÚÔÂȉԿıÂÈ·, Ó¢ÚÔ¿ıÂÈ·, ÓÂÊÚÔ¿ıÂÈ·), fiÛÔ Î·È Ù˘ Ì·ÎÚÔ·ÁÁÂȷ΋˜ ÓfiÛÔ˘ (™¡).17 Δ· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· Ë ¤Ú¢ӷ ÂÛÙÈ¿˙ÂÙ·È ÛÙÔ ÚfiÏÔ Ô˘ ‰È·‰Ú·Ì·Ù›˙Ô˘Ó Ù· AGEs ÛÙ· Ï·›ÛÈ· Ù˘ ¢ÁÏ˘Î·ÈÌÈ΋˜ ·ıËÚÔÛÎÏ‹ÚˆÛ˘. ™‡Ìʈӷ Ì ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ÔÈ Û˘ÁÎÂÓÙÚÒÛÂȘ ÙˆÓ AGEs Û˘Û¯ÂÙ›˙ÔÓÙ·È ıÂÙÈο Ì ÙÔÓ ‚·ıÌfi Ù˘ ÛÙÂÊ·ÓÈ·›·˜ ·ıËÚÔÛÎÏ‹ÚˆÛ˘ Î·È Û ÌË ‰È·‚ËÙÈÎÔ‡˜ ·ÛıÂÓ›˜.23,24 Δ· AGEs ÂÈÙ·¯‡ÓÔ˘Ó ÙËÓ ·ıËÚÔÛÎÏ‹ÚˆÛË Ì ‰È¿ÊÔÚÔ˘˜ Ì˯·ÓÈÛÌÔ‡˜, Ô˘ Û ÁÂÓÈΤ˜ ÁÚ·Ì̤˜ ÌÔÚÔ‡Ó Ó· Ù·ÍÈÓÔÌËıÔ‡Ó Û ÌË ÂÍ·ÚÙÒÌÂÓÔ˘˜ ·fi ˘Ô‰Ô¯Â›˜ (non-receptor dependent) Î·È Û ÂÍ·ÚÙÒÌÂÓÔ˘˜ ·fi ˘Ô‰Ô¯Â›˜ (receptor-mediated).25
3.1 ªË ÂÍ·ÚÙÒÌÂÓÔÈ ·fi ˘Ô‰Ô¯Â›˜ ÌÔÚÈ·ÎÔ› Ì˯·ÓÈÛÌÔ› ∂ȉڿÛÂȘ ÙˆÓ AGEs ÛÙËÓ ÂÍˆÎ˘ÙÙ¿ÚÈ· ıÂ̤ÏÈ· Ô˘Û›· Δ· AGEs ÂËÚ¿˙Ô˘Ó ÙȘ Ê˘ÛÈÎÔ¯ËÌÈΤ˜, ÏÂÈÙÔ˘ÚÁÈΤ˜ Î·È ‰ÔÌÈΤ˜ ȉÈfiÙËÙ˜ ‰È·ÊfiÚˆÓ Û˘ÛÙ·ÙÈÎÒÓ Ù˘ ıÂ̤ÏÈ·˜ Ô˘Û›·˜. ΔÔ ÎÔÏÏ·ÁfiÓÔ, Ô˘ Â›Ó·È Ì›· ÚˆÙ½ÓË Ì ÌÂÁ¿ÏÔ ¯ÚfiÓÔ ËÌ›ÛÂÈ·˜ ˙ˆ‹˜ Î·È ·ÔÙÂÏ› ‚·ÛÈÎfi Û˘ÛÙ·ÙÈÎfi ÙÔ˘ ·ÁÁÂÈ·ÎÔ‡ ÙÔȯÒÌ·ÙÔ˜, Û˘¯Ó¿ ˘Ê›ÛÙ·Ù·È ÌË ÂÓ˙˘ÌÈ΋ ÁÏ˘ÎÔ˙˘Ï›ˆÛË. √ Û¯ËÌ·ÙÈÛÌfi˜ ÙˆÓ AGEs ÛÙÔ ÎÔÏÏ·ÁfiÓÔ Â˘ı‡ÓÂÙ·È ÁÈ· ÙËÓ ‰ËÌÈÔ˘ÚÁ›· ÙˆÓ cross-links ÌÂٷ͇ ÙˆÓ ÈÓȉ›ˆÓ ÙÔ˘ ÌÂ Û˘Ó·ÎfiÏÔ˘ıÔ ÙËÓ ÂÏ¿ÙÙˆÛË Ù˘ ¢ÂÓ‰ÔÙfiÙËÙ·˜ Î·È ÙËÓ ·‡ÍËÛË Ù˘ ·ÚÙËÚȷ΋˜ ‰˘Ûη̄›·˜. √ Û˘ÁÎÂÎÚÈ̤ÓÔ˜ Ì˯·ÓÈÛÌfi˜ Û˘Ó‰¤ÂÙ·È Ì ÙËÓ ·ıÔÊ˘ÛÈÔÏÔÁ›· Ù˘ ·ÚÙËÚȷ΋˜ ˘¤ÚÙ·Û˘ Î·È Ù˘ ‰È·ÛÙÔÏÈ΋˜ ηډȷ΋˜ ·Ó¿ÚÎÂÈ·˜, ηıÒ˜ ‰È·ÈÛÙÒıËΠ·fi ÌÂϤÙ˜ fiÙÈ Ë ¯ÔÚ‹ÁËÛË Ê·ÚÌ¿ÎˆÓ Ô˘ ‰È·ÛÔ‡Ó Ù· cross-links (AGEs cross-links breakers) ‚ÂÏÙÈÒÓÂÈ ÙËÓ ·ÚÙËÚȷ΋ ¢ÂÓ‰ÔÙfiÙËÙ·.26,27 ¢È¿ÊÔÚ˜ ÚˆÙ½Ó˜ ÙÔ˘ Ï¿ÛÌ·ÙÔ˜, fiˆ˜ Ë ·Ï‚Ô˘Ì›ÓË, Ë LDL Î·È ÔÈ ·ÓÔÛÔÛÊ·ÈÚ›Ó˜ IgG, ·Áȉ‡ÔÓÙ·È ˘ÂÓ‰ÔıËÏȷο, Û˘Ó‰¤ÔÓÙ·È Ì ٷ ÈÓ›‰È· ÙÔ˘ ÎÔÏÏ·ÁfiÓÔ˘ Ô˘ ¤¯Ô˘Ó ˘ÔÛÙ› ÁÏ˘ÎÔ˙˘Ï›ˆÛË Ì ·ÔÙ¤ÏÂÛÌ· Ó· ‰ËÌÈÔ˘ÚÁÂ›Ù·È ¿¯˘ÓÛË Ù˘ ‚·ÛÈ΋˜ ÌÂÌ‚Ú¿Ó˘ Î·È ÂÏ¿ÙÙˆÛË Ù˘ ‰È·Ì¤ÙÚÔ˘ ÙÔ˘ ·˘ÏÔ‡ ÙˆÓ ·ÁÁ›ˆÓ.28 ∏ ÁÏ˘ÎÔ˙˘Ï›ˆÛË ÙˆÓ Û˘ÛÙ·ÙÈÎÒÓ Ù˘ ÌÂÛÔ΢ÙÙ¿ÚÈ·˜ Ô˘Û›·˜, fiˆ˜ Ë Ï·ÌÈÓ›ÓË Î·È Ë ‚ÈÙÚÔÓÂÎÙ›ÓË, Ô‰ËÁ› Û ÂÏ¿ÙÙˆÛË Ù˘ ıÂÈ˚΋˜ Ë·Ú¿Ó˘, ÙÚÔÔÔ›ËÛË ÙˆÓ ÂÚÈÔ¯ÒÓ Û‡Ó‰ÂÛ˘ ÙˆÓ Î˘ÙÙ¿ÚˆÓ Ì ÙÔ ÎÔÏÏ·ÁfiÓÔ Ù‡Ô˘ IV, Ì ·ÔÙ¤ÏÂÛÌ· Ó· ÌÂÙ·‚¿ÏÏÂÙ·È Ë Û˘ÓÂÎÙÈÎfiÙËÙ· ÙˆÓ ÂÓ‰ÔıËÏÈ·ÎÒÓ Î˘ÙÙ¿ÚˆÓ Î·È Ó· ‰ÈÂÁ›ÚÂÙ·È Ë ·Ú·ÁˆÁ‹ ÂÍˆÎ˘ÙÙ¿ÚÈ·˜ ıÂ̤ÏÈ·˜ Ô˘Û›·˜. √ Û˘ÁÎÂÎÚÈ̤ÓÔ˜ Ì˯·ÓÈÛÌfi˜ ¢ı‡ÓÂÙ·È ÁÈ· ÙËÓ ÚfiÎÏËÛË Ù˘ ‰È·‚ËÙÈ΋˜ ÓÂÊÚÔ¿ıÂÈ·˜.29 Δ¤ÏÔ˜ Ù· AGEs ÚÔηÏÔ‡Ó Î·Ù¿ ¤Ó· ‰ÔÛÔÂÍ·ÚÙÒÌÂÓÔ ÙÚfiÔ Ì›ˆÛË ÙÔ˘ ÌÔÓÔÍÂȉ›Ô˘ ÙÔ˘ ·˙ÒÙÔ˘ (NO), Ì ·ÔÙ¤ÏÂÛÌ· Ó· ÌÂÙ·‚¿ÏÏÂÙ·È Ë ÂÓ‰ÔıËÏÈÔ-ÂÍ·ÚÙÒÌÂÓË ·ÁÁÂÈԉȷÛÙÔÏ‹.30
∂ȉڿÛÂȘ ÙˆÓ AGEs ÛÙ· ÏÈ›‰È· ∏ LDL Â›Ó·È ¤Ó· ·fi Ù· ÌfiÚÈ· Ô˘ Û˘¯Ó¿ ˘Ê›ÛÙ·Ù·È ÌË ÂÓ˙˘ÌÈ΋ ÁÏ˘ÎÔ˙˘Ï›ˆÛË Î·È Ì¿ÏÈÛÙ· Ë ÁÏ˘ÎÔ˙˘Ï›ˆÛË Û˘Ì‚·›ÓÂÈ ÙfiÛÔ ÛÙÔ ·ÔÚˆÙÂ˚ÓÈÎfi, fiÛÔ Î·È ÛÙÔ ÏÈȉ·ÈÌÈÎfi ÙÌ‹Ì· Ù˘.31 ∫·Ù¿ ÙËÓ Û‡ÁÎÚÈÛË ·ÙfiÌˆÓ Ì ‰È·‚‹ÙË ÌÂ Ê˘ÛÈÔÏÔÁÈο ¿ÙÔÌ· ‚Ú¤ıËΠfiÙÈ Ë ÌÂÙ·ÙÚÔ‹ ÙÔ˘ ÏÈȉ·ÈÌÈÎÔ‡ ÙÌ‹Ì·ÙÔ˜ Û AGEs Â›Ó·È ‰‡Ô ÊÔÚ¤˜ ÌÂÁ·Ï‡ÙÂÚË, ÂÓÒ Ë ÌÂÙ·ÙÚÔ‹ ÙÔ˘ ·ÔÚˆÙÂ˚ÓÈÎÔ‡ Ù¤ÛÛÂÚȘ ÊÔÚ¤˜.31 √È ·ÓÙȉڿÛÂȘ ÁÏ˘ÎÔ˙˘Ï›ˆÛ˘ ηıÈÛÙÔ‡Ó ÙÔ ÌfiÚÈÔ Ù˘ LDL ÂÈÚÚ¤˜ ÛÙËÓ ÔÍÂȉˆÙÈ΋ ÙÚÔÔÔ›ËÛË.32 √È ÁÏ˘ÎÔÍÂȉˆÌ¤Ó˜ LDL ·Ó·ÁÓˆÚ›˙ÔÓÙ·È ·fi Ì›· ÂȉÈ΋ ÔÌ¿‰· ˘Ô‰Ô¯¤ˆÓ ÙˆÓ ÌÔÓÔ΢ÙÙ¿ÚˆÓ / Ì·ÎÚÔÊ¿ÁˆÓ Ô˘ ÔÓÔÌ¿˙ÔÓÙ·È ÂÎηı·ÚÈÛÙ¤˜ (scavenger receptors). ¶·Ú·ÙËÚÂ›Ù·È ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË Ù˘ ÚfiÛÏ˄˘ Ù˘ ÔÍÂȉˆÌ¤Ó˘ LDL Î·È ·Ú¿ÏÏËÏ· ÂÏ·Ùو̤ÓË ·ÔÌ¿ÎÚ˘ÓÛË ·˘Ù‹˜ ·fi ÙËÓ ˘ÂÓ‰ÔıËÏȷ΋ ÛÙÈ‚¿‰·. Δ· Ì·ÎÚÔÊ¿Á·, Ô˘ ‚Ú›ÛÎÔÓÙ·È Ï¤ÔÓ ÛÙÔ ·ÁÁÂÈ·Îfi ÙÔ›¯ˆÌ·, ¤¯ÔÓÙ·˜ ÚÔÛÏ¿‚ÂÈ ÌÂÁ¿Ï˜ ÔÛfiÙËÙ˜ ÔÍÂȉˆÌ¤Ó˘ LDL ÌÂÙ·ÙÚ¤ÔÓÙ·È ÛÙ· ·ÊÚÒ‰Ë Î‡ÙÙ·Ú·, Ù· ÔÔ›· Û¯ËÌ·Ù›˙Ô˘Ó ÙȘ ÏÈÒ‰ÂȘ Ú·‚‰ÒÛÂȘ, Ô˘ ·ÔÙÂÏÔ‡Ó ÙȘ ÚÒÙ˜ Ì·ÎÚÔÛÎÔÈΤ˜ ÂΉËÏÒÛÂȘ Ù˘ ·ıËڈ̷ÙÈ΋˜ Ͽη˜. ∂›Û˘ ÌË ÂÓ˙˘ÌÈ΋ ÁÏ˘ÎÔ˙˘Ï›ˆÛË ˘Ê›ÛÙ·Ù·È Î·È ÙÔ ÌfiÚÈÔ Ù˘ HDL, Ì ·ÔÙ¤ÏÂÛÌ· Ó· ÂÏ·ÙÙÒÓÂÙ·È Ë ‰Ú·ÛÙÈÎfiÙËÙ· ÂÓfi˜ ÂÓ˙‡ÌÔ˘, Ù˘ ·Ú·ÔÍÔÓ¿Û˘, Ô˘ ·ÚÂÌÔ‰›˙ÂÈ ÙËÓ ÔÍ›‰ˆÛË Ù˘ LDL Î·È ÙËÓ ÚÔÛÎfiÏÏËÛË ÙˆÓ ÌÔÓÔ΢ÙÙ¿ÚˆÓ ÛÙ· ÂÓ‰ÔıËÏȷο ·ÙÙ·Ú· Ù˘ ·ÔÚÙ‹˜.21,33 ΔÔ ·ÔÙ¤ÏÂÛÌ· Ù˘ ›‰Ú·Û˘ ÙˆÓ AGEs ÛÙ· ÏÈ›‰È· Â›Ó·È Ë ·‡ÍËÛË Ù˘ ·ıËÚÔÁfiÓÔ˘ ‰Ú¿Û˘ Ù˘ LDL ηıÒ˜ Î·È Ë ÂÏ¿ÙÙˆÛË Ù˘ ÚÔÛٷ٢ÙÈ΋˜ ÈηÓfiÙËÙ·˜ Ù˘ HDL.
3. 2. ∂Í·ÚÙÒÌÂÓÔÈ ·fi ˘Ô‰Ô¯Â›˜ ÌÔÚÈ·ÎÔ› Ì˯·ÓÈÛÌÔ› Δ· AGEs ·ÏÏËÏÂȉÚÒÓÙ·˜ Ì ÂȉÈÎÔ‡˜ ˘Ô‰Ô¯Â›˜, ÙÔ˘˜ ˘Ô‰Ô¯Â›˜ ÙˆÓ ÙÂÏÈÎÒÓ ÚÔ˚fiÓÙˆÓ ÚÔËÁ̤Ó˘ ÁÏ˘ÎÔ˙˘Ï›ˆÛ˘ (Receptors of Advanced Glycosylation End products, RAGE), ÂÓÂÚÁÔÔÈÔ‡Ó Û‡ÓıÂÙÔ˘˜ ÌÔÚÈ·ÎÔ‡˜
13
ª∞ƒΔπ√™ 2008
Ì˯·ÓÈÛÌÔ‡˜ ̤ۈ ÙˆÓ ÔÔ›ˆÓ ÚÔ¿ÁÔ˘Ó ÙËÓ ·ıËÚÔÛÎÏËÚˆÙÈ΋ ‰ÈÂÚÁ·Û›·.34 √È RAGEs ‚Ú›ÛÎÔÓÙ·È ÛÙËÓ ÂÈÊ¿ÓÂÈ· ‰È·ÊfiÚˆÓ Î˘ÙÙ¿ÚˆÓ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙËÓ ·ıËÚÔÛÎÏ‹ÚˆÛË, fiˆ˜ Ù· ÌÂÁ¿Ï· ÌÔÓÔ‡ÚËÓ·, Ù· ÂÓ‰ÔıËÏȷο ·ÙÙ·Ú· Î·È Ù· Ï›· Ì˘˚ο ·ÙÙ·Ú·.35 ™Â Ê˘ÛÈÔÏÔÁÈΤ˜ Û˘Óı‹Î˜ ÔÈ Û˘ÁÎÂÓÙÚÒÛÂȘ ÙˆÓ RAGEs Â›Ó·È ¯·ÌËϤ˜, fiÙ·Ó fï˜ ·˘Í¿ÓÂÙ·È Ë Û˘ÁΤÓÙÚˆÛË ÙˆÓ AGEs, fiˆ˜ ÛÙÔÓ ™¢, ÚÔηÏÂ›Ù·È ˘ÂÚ¤ÎÊÚ·ÛË ÙÔ˘ ˘Ô‰Ô¯¤·.36 √È Park Î·È Û˘ÓÂÚÁ¿Ù˜, ¤¯ÔÓÙ·˜ ˆ˜ ÛÎÔfi ÙËÓ ‰ÈÂÚ‡ÓËÛË ÙˆÓ ÌÔÚÈ·ÎÒÓ Ì˯·ÓÈÛÌÒÓ Ù˘ ‰È·‚ËÙÈ΋˜ ·ıËÚÔÛÎÏ‹ÚˆÛ˘, ·Ó¤Ù˘Í·Ó ¤Ó· ÌÔÓÙ¤ÏÔ Û ÔÓÙ›ÎÈ· Ô˘ ›¯·Ó ηٷÛÙ› ‰È·‚ËÙÈο Î·È ·ÓÂÓÂÚÁ¿ ÁÈ· ÙÔ ÁÔÓ›‰ÈÔ Ù˘ ·ÔÏÈÔÚˆÙ½Ó˘-∂, ÛÙ· ÔÔ›· ‰ÈÂÚ‡ÓËÛ·Ó ÙËÓ Èı·Ó‹ ÂÌÏÔ΋ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ RAGE ÛÙË ‰È·‚ËÙÈ΋ ·ıËÚÔÛÎÏ‹ÚˆÛË. ÃÔÚ‹ÁËÛ·Ó ÛÙ· ÔÓÙ›ÎÈ· ¤Ó· ‰È·Ï˘Ùfi ÎÔÌÌ¿ÙÈ ÙÔ˘ ˘Ô‰Ô¯¤· RAGE, ÙÔ ÔÔ›Ô ·Ó·Ê¤ÚÂÙ·È ˆ˜ sRAGE (soluble RAGE). ΔÔ ÌfiÚÈÔ ·˘Ùfi ·ÓÙÈÚÔۈ‡ÂÈ ÙÔ ÂÍˆÎ˘ÙÙ¿ÚÈÔ ÙÌ‹Ì· ÙÔ˘ ˘Ô‰Ô¯¤· RAGE, ÛÙÔ ÔÔ›Ô ÚÔÛ‰¤ÓÔÓÙ·È Ù· AGEs. Δ· ·ÔÙÂϤÛÌ·Ù¿ ÙÔ˘˜ ‰Â›¯ÓÔ˘Ó ÙËÓ Ï‹ÚË Î·Ù·ÛÙÔÏ‹ Ù˘ ·ıËÚÔÛÎÏ‹ÚˆÛ˘ ηٿ ¤Ó· ‰ÔÛÔÂÍ·ÚÙÒÌÂÓÔ ÙÚfiÔ, ·Ô‰ÂÈÎÓ‡ÔÓÙ·˜ ¤ÙÛÈ ÙË Û˘Ì‚ÔÏ‹ ÙˆÓ RAGEs Î·È ÙˆÓ AGEs ÛÙËÓ ·Ó¿Ù˘ÍË Ù˘ ·ıËÚÔÛÎÏ‹ÚˆÛ˘.37 ∂ȉڿÛÂȘ ÙˆÓ AGEs ÛÙ· ÌÔÓÔ‡ÚËÓ· / Ê·ÁÔ·ÙÙ·Ú· ∏ ¤ÓˆÛË ÙˆÓ AGEs Ì ÙÔ˘˜ RAGE ÛÙ· ÌÔÓÔ‡ÚËÓ· / Ì·ÎÚÔÊ¿Á· ÚÔηÏ› ÙËÓ ÂÓÂÚÁÔÔ›ËÛ‹ ÙÔ˘˜ Ì ·ÎfiÏÔ˘ıÔ ÙËÓ ¤ÎÎÚÈÛË Ô˘ÛÈÒÓ, Ô˘ ‰È·‰Ú·Ì·Ù›˙Ô˘Ó ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ·ıÔÁ¤ÓÂÈ· Ù˘ ·ıËÚÔÛÎÏ‹ÚˆÛ˘. ¶ÚfiÎÂÈÙ·È ÁÈ· ·˘ÍËÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜, fiˆ˜ Ô ·˘ÍËÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ ÚÔÂÚ¯fiÌÂÓÔ˜ ·fi Ù· ·ÈÌÔÂÙ¿ÏÈ· (platelet-derived growth factor, PDGF), Ô ÈÓÛÔ˘ÏÈÓfiÌÔÚÊÔ˜ ·˘ÍËÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ (insulin-like growth factor-1, IGF1) Î·È ÚÔÊÏÂÁÌÔÓÒ‰ÂȘ ΢ÙÔΛÓ˜, fiˆ˜ Ë ÈÓÙÂÚÏ¢ΛÓË-1‚ ( IL1‚) Î·È Ô TNF-a (tumor necrosis factor-a).38 H Û‡Ó‰ÂÛË ‰È·Ï˘ÙÒÓ AGEs Ì ÙÔ˘˜ RAGE ÚÔ¿ÁÂÈ ÙËÓ Î˘ÙÙ·ÚÈ΋ ÌÂÙ·Ó¿ÛÙ¢ÛË (¯ËÌÂÈÔÙ·Í›·), Ô˘ ·ÎÔÏÔ˘ıÂ›Ù·È ·fi ‰È‹ıËÛË ÌÔÓÔ΢ÙÙ¿ÚˆÓ Ì¤Ûˆ
14
ÙÔ˘ ·Î¤Ú·ÈÔ˘ ÂÓ‰ÔıËÏ›Ô˘. ™Â ·ÓÙȉȷÛÙÔÏ‹ Ì ٷ ‰È·Ï˘Ù¿ AGEs, Ù· ·ÎÈÓËÙÔÔÈË̤ӷ (immobilized) AGEs, fiˆ˜ ·˘Ù¿ Ô˘ ‚Ú›ÛÎÔÓÙ·È ÛÙȘ ‚·ÛÈΤ˜ ÌÂÌ‚Ú¿Ó˜, ÂÚÈÔÚ›˙Ô˘Ó ÙËÓ ÌÂÙ·Ó¿ÛÙ¢ÛË ÙˆÓ ÌÔÓÔ΢ÙÙ¿ÚˆÓ, ÌÈ· ‰È·‰Èηۛ· Ô˘ Â›Ó·È ÁÓˆÛÙ‹ ˆ˜ ·fiÙ·ÍË (apoptaxis). ΔfiÛÔ Ë ¯ËÌÂÈÔÙ·Í›·, fiÛÔ Î·È Ë ·fiÙ·ÍË ·Ó·ÛÙ¤ÏÏÔÓÙ·È Ì ÙË ¯ÔÚ‹ÁËÛË ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÙˆÓ RAGE (anti-RAGE IgG) ‹ ‰È·Ï˘ÙÒÓ RAGE. ŸÙ·Ó Ù· ÌÔÓÔ·ÙÙ·Ú· ÊÙ¿ÓÔ˘Ó ÛÙÔ˘˜ ÈÛÙÔ‡˜ fiÔ˘ ˘¿Ú¯Ô˘Ó Ù· ·ÎÈÓËÙÔÔÈË̤ӷ AGEs ÂÚÈÔÚ›˙ÂÙ·È Ë ÌÂÙ·Ó¿ÛÙÂ˘Û‹ ÙÔ˘˜. ™ÙË Û˘Ó¤¯ÂÈ· ‰ÂÛ̇ÔÓÙ·È ÛÙȘ ÂÈÊ¿ÓÂȘ ÙˆÓ ÈÛÙÒÓ Ô˘ ¤¯Ô˘Ó ˘ÔÛÙ› AGE ÌÂÙ·ÙÚÔ‹ Ì ·ÎfiÏÔ˘ıÔ ÙËÓ ÂÓÂÚÁÔÔ›ËÛ‹ ÙÔ˘˜. √ ÌÔÚÈ·Îfi˜ ·˘Ùfi˜ Ì˯·ÓÈÛÌfi˜ ÚÔÛÂÏ·ÂÈ Î·È ‰È·ÙËÚ› Ù· ÌÔÓÔ·ÙÙ·Ú· ÛÙȘ ı¤ÛÂȘ ÂÓ·fiıÂÛ˘ ÙˆÓ AGEs ÛÙÔ˘˜ ÈÛÙÔ‡˜.39 ∂ȉڿÛÂȘ ÙˆÓ AGEs ÛÙ· Ï›· Ì˘˚ο ·ÙÙ·Ú· ∏ Û‡Ó‰ÂÛË ÙˆÓ AGEs Ì ÙÔ˘˜ RAGE ÙˆÓ Ï›ˆÓ Ì˘˚ÎÒÓ Î˘ÙÙ¿ÚˆÓ ÙÔ˘ ·ÁÁÂÈ·ÎÔ‡ ÙÔȯÒÌ·ÙÔ˜ ¿ÁÂÈ ÙÔÓ ÔÏÏ·Ï·ÛÈ·ÛÌfi Î·È ÙËÓ ÌÂÙ·Ó¿ÛÙÂ˘Û‹ ÙÔ˘˜ ηıÒ˜ Î·È ÙËÓ ·Ú·ÁˆÁ‹ ÊÈÌÚÔÓÂÎÙ›Ó˘. √ ÈÛÙÈÎfi˜ ·˘ÍËÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ (TGF-‚) Ê·›ÓÂÙ·È Ó· ÏÂÈÙÔ˘ÚÁ› ˆ˜ ÌÂÛÔÏ·‚ËÙ‹˜ ÛÙËÓ ·Ú·ÁfiÌÂÓË ·fi Ù· Ï›· Ì˘˚ο ·ÙÙ·Ú· ÊÈÌÚÔÓÂÎÙ›ÓË.40 ∂ȉڿÛÂȘ ÙˆÓ AGEs ÛÙ· ÂÓ‰ÔıËÏȷο ·ÙÙ·Ú· ΔÔ ÂÓ‰Ôı‹ÏÈÔ ‰È·‰Ú·Ì·Ù›˙ÂÈ ÚfiÏÔ ÎÏÂȉ› ÛÙËÓ ‰È·‰Èηۛ· Ù˘ ·ıËÚÔÛÎÏ‹ÚˆÛ˘. ∂ÎÙ›ıÂÙ·È ÛÙȘ ‚Ï·‚ÂÚ¤˜ ÂȉڿÛÂȘ ÙfiÛÔ ÙˆÓ Î˘ÎÏÔÊÔÚÔ‡ÓÙˆÓ, fiÛÔ Î·È ·˘ÙÒÓ Ô˘ ‚Ú›ÛÎÔÓÙ·È ÛÙËÓ ˘ÔΛÌÂÓË ˘ÂÓ‰ÔıËÏȷ΋ ÛÙÈ‚¿‰· AGEs. ∏ Û‡Ó‰ÂÛË ÙˆÓ AGEs Ì ÙÔ˘˜ RAGE ÙˆÓ ÂÓ‰ÔıËÏÈ·ÎÒÓ Î˘ÙÙ¿ÚˆÓ ‰È·Ù·Ú¿ÛÛÂÈ ÙËÓ ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÂÓ‰ÔıËÏÈ·ÎÔ‡ ÊÚ·ÁÌÔ‡, Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·‡ÍËÛË Ù˘ ‰È·ÂÚ·ÙfiÙËÙ·˜, ÙËÓ Â›ÛÔ‰Ô ÏÈȉ›ˆÓ ÛÙËÓ ˘ÂÓ‰ÔıËÏȷ΋ ÛÙÈ‚¿‰· ηıÒ˜ Î·È ÙË Û˘ÁÎfiÏÏËÛË ÌÔÓÔ˘Ú‹ÓˆÓ. ∏ ·‡ÍËÛË Ù˘ ·ÁÁÂȷ΋˜ ‰È·ÂÚ·ÙfiÙËÙ·˜ ¿ÁÂÙ·È ·fi Ì˯·ÓÈÛÌÔ‡˜, ÛÙÔ˘˜ ÔÔ›Ô˘˜ ÂÌϤÎÔÓÙ·È Ë ÂÓÂÚÁÔÔ›ËÛË Ù˘ PKC Î·È Ë ·Ú·ÁˆÁ‹ ÙÔ˘
·ÁÁÂÈ·ÎÔ‡ ÂÓ‰ÔıËÏÈ·ÎÔ‡ ·˘ÍËÙÈÎÔ‡ ·Ú¿ÁÔÓÙ· (VEGF).41 Δ· AGEs, fi¯È ÌfiÓÔ ·˘Í¿ÓÔ˘Ó ÙËÓ ‚·ÛÈ΋ ·ÁÁÂȷ΋ ‰È·ÂÚ·ÙfiÙËÙ·, ·ÏÏ¿ Î·È ÙËÓ Â·ÁÔ̤ÓË ·fi ÙËÓ ÈÛÙ·Ì›ÓË Î·È ÙË ‚Ú·‰˘ÎÈÓ›ÓË. ¶ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ·Ô‰ÂÈÎÓ‡Ô˘Ó fiÙÈ Ë ‰È¿Û·ÛË ÙÔ˘ Û˘ÌϤÁÌ·ÙÔ˜ ÙˆÓ Î·ÓÙ¯ÂÚÈÓÒÓ (VE-canherin complex) ÙÔ˘ ÂÓ‰ÔıËÏ›Ô˘, Ô˘ ¿ÁÂÙ·È ·fi Ù· AGEs, ‰È·Ù·Ú¿ÛÛÂÈ ÙȘ Û˘Ó‰¤ÛÂȘ ÌÂٷ͇ ÙˆÓ ÂÓ‰ÔıËÏÈ·ÎÒÓ Î˘ÙÙ¿ÚˆÓ, Ì ·ÎfiÏÔ˘ıÔ ÙËÓ ·ÔÚÚ‡ıÌÈÛË Ù˘ ‰È·ÂÚ·ÙfiÙËÙ·˜ ÙÔ˘ ÂÓ‰ÔıËÏ›Ô˘.42 ∏ ‰¤ÛÌ¢ÛË ÙˆÓ AGEs Ì ÙÔ˘˜ RAGE ÚÔηÏ› ›Û˘ ·ÒÏÂÈ· ÙˆÓ Î˘ÙÙ·ÚÈÎÒÓ ·ÓÙÈÔÍÂȉˆÙÈÎÒÓ Ì˯·ÓÈÛÌÒÓ (ÁÏÔ˘Ù·ıÂÈfiÓË, ‚ÈÙ·Ì›ÓË C) Ì ·ÎfiÏÔ˘ıÔ ÙËÓ ·‡ÍËÛË ÙÔ˘ ÂÓ‰Ô΢ÙÙ¿ÚÈÔ˘ ÔÍÂȉˆÙÈÎÔ‡ stress. ΔÔ ÔÍÂȉˆÙÈÎfi stress ÛÙË Û˘Ó¤¯ÂÈ· ¿ÁÂÈ ÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ ÌÂÙ·ÁÚ·ÊÈÎÔ‡ ·Ú¿ÁÔÓÙ· NF-K‚, Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ¤ÎÊÚ·ÛË ÁÔÓȉ›ˆÓ Ô˘ Έ‰ÈÎÔÔÈÔ‡Ó ÌfiÚÈ· ÚÔÛÎfiÏÏËÛ˘, fiˆ˜ ∂-Selectin, VCAM-1, ICAM1 ηıÒ˜ Î·È ÚÔËÎÙÈÎÔ‡˜ ÈÛÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜.43 Δ· AGEs ÂÂÌ‚·›ÓÔ˘Ó Â›Û˘ ÙËÓ ÂÓ‰ÔıËÏÈÔ-ÂÍ·ÚÙÒÌÂÓË ·ÁÁÂÈԉȷÛÙÔÏ‹, ÂËÚ¿˙ÔÓÙ·˜ ÙËÓ ¤ÎÊÚ·ÛË Ô˘ÛÈÒÓ Ô˘ Ú˘ıÌ›˙Ô˘Ó ÙÔÓ ·ÁÁÂÈ·Îfi ÙfiÓÔ, fiˆ˜ ÙÔ ÌÔÓÔÍ›‰ÈÔ ÙÔ˘ ·˙ÒÙÔ˘ (NO) Î·È Ë ÂÓ‰ÔıËÏ›ÓË. ∏ Û˘ÛÛÒÚ¢ÛË ÙˆÓ AGEs ÛÙËÓ ÂÍˆÎ˘ÙÙ¿ÚÈ· ıÂ̤ÏÈ· Ô˘Û›· ÚÔηÏ› ÂÍ¿ÓÙÏËÛË ÙˆÓ ·ÔıÂÌ¿ÙˆÓ ÙÔ˘ ¡√ Î·È Ì›ˆÛË Ù˘ ÁÔÓȉȷ΋˜ ¤ÎÊÚ·Û˘ Ù˘ Û˘ÓıÂÙ¿Û˘ ÙÔ˘ ¡√, ̤ۈ ÂÏ¿ÙÙˆÛ˘ Ù˘ ʈÛÊÔÚ˘Ï›ˆÛ˘ Ù˘ ÛÂÚ›Ó˘ ÙÔ˘ ÂÓ˙‡ÌÔ˘.44 ¶ÚfiÛÊ·Ù˜ ¤Ú¢Ó˜ ·¤‰ÂÈÍ·Ó, fiÙÈ Ù· ·˘ÍË̤ӷ ›‰· ÙˆÓ AGEs Û ·ÛıÂÓ›˜ Ì ™¢ Ù‡Ô˘ 2 Û˘Û¯ÂÙ›˙ÔÓÙ·È Ì ÙËÓ ÂÓ‰ÔıËÏȷ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·, ηٿ ¤Ó·Ó ÙÚfiÔ ·ÓÂÍ¿ÚÙËÙÔ ·fi ÙÔ˘˜ ˘fiÏÔÈÔ˘˜ ηډȷÁÁÂÈ·ÎÔ‡˜ ÎÈÓ‰‡ÓÔ˘˜, ÁÂÁÔÓfi˜ Ô˘ Ê¿ÓËΠ̠ÙË ¯Ú‹ÛË ˘ÂÚ‹¯ˆÓ ˘„ËÏ‹˜ ·Ó¿Ï˘Û˘.45 ∫·Ù¿ ÙËÓ ·ÏÏËÏ›‰Ú·ÛË ÙˆÓ AGEs Ì ÙÔ˘˜ RAGE ·Ó·ÛÙ¤ÏÏÂÙ·È Ë ·Ú·ÁˆÁ‹ ÂÓfi˜ ·ÁÁÂÈԉȷÛÙ·ÏÙÈÎÔ‡ Î·È ·ÓÙÈıÚÔÌ‚ˆÙÈÎÔ‡ ·Ú¿ÁÔÓÙ·, Ù˘ ÚÔÛÙ·ÁÏ·Ó‰›Ó˘ PGI-2. ∂ÈϤÔÓ, ÚÔηÏÂ›Ù·È ˘ÂÚ¤ÎÊÚ·ÛË ÙÔ˘ ÁÔÓȉ›Ô˘ ÙÔ˘ ·Ó·ÛÙÔϤ· ÙÔ˘ ÂÓÂÚÁÔÔÈËÙ‹ ÙÔ˘ Ï·ÛÌÈÓÔÁfiÓÔ˘-1 (PAI-1) ÛÙ· ÂÓ‰ÔıËÏȷο
¶∞£√ºÀ™π√§√°π∞ ·ÙÙ·Ú· ÙˆÓ ÌÈÎÚÒÓ ·ÁÁ›ˆÓ, Ô ÔÔ›Ô˜ ·Ó·ÛÙ¤ÏÏÂÈ ÙËÓ ÈÓˆ‰fiÏ˘ÛË Î·È ÂÌϤÎÂÙ·È ÛÙË ıÚfiÌ‚ˆÛË.46 ™ÙÔ ÌÔÓÔ¿ÙÈ ÌÂÙ·ÁˆÁ‹˜ ÙÔ˘ ÌËӇ̷ÙÔ˜ Ê·›ÓÂÙ·È Ó· ÂÌϤÎÂÙ·È Î·È ÙÔ Î˘ÎÏÈÎfi AMP (c-AMP), ÙÔ ÔÔ›Ô ‰Ú· ˆ˜ ·ÁˆÓÈÛÙ‹˜ ÙÔ˘ PAI-1. Δ· AGEs ‰ÂÓ ÂËÚ¿˙Ô˘Ó ÌfiÓÔ Ù· ›‰· ÙˆÓ ·ÁÁÂÈԉȷÛÙ·ÏÙÈÎÒÓ Ô˘ÛÈÒÓ, ·ÏÏ¿ ¿ÁÔ˘Ó Ù·˘Ùfi¯ÚÔÓ· ÙËÓ ·Ú·ÁˆÁ‹ Ù˘ ·ÁÁÂÈÔÛ˘Û·ÛÙÈ΋˜ Ô˘Û›·˜, ÂÓ‰ÔıËÏ›Ó˘-1, ̤ۈ ÂÓÂÚÁÔÔ›ËÛ˘ ÙÔ˘ ˘ÚËÓÈÎÔ‡ ·Ú¿ÁÔÓÙ· Îμ (NF-kB).47
4. ™˘Ì¤Ú·ÛÌ· Δ· AGEs Â›Ó·È ÂÓÒÛÂȘ Ì ÛÔ‚·Ú¤˜ ÂÈÙÒÛÂȘ ÛÙÔÓ ·ÓıÚÒÈÓÔ ÔÚÁ·ÓÈÛÌfi. ™Â Ê˘ÛÈÔÏÔÁÈΤ˜ ηٷÛÙ¿ÛÂȘ ‰ËÌÈÔ˘ÚÁÔ‡ÓÙ·È Î·Ù¿ ÙË Á‹Ú·ÓÛË, ÂÓÒ Û ·ıÔÏÔÁÈΤ˜ ηٷÛÙ¿ÛÂȘ ÂÌÊ·Ó›˙ÔÓÙ·È Û ‰È¿ÊÔÚ· ÓÔÛ‹Ì·Ù· Î·È Î˘Ú›ˆ˜ ÛÙÔÓ ™¢. Δ· AGEs ÚÔ¿ÁÔ˘Ó ÙËÓ ·ıËÚÔÛÎÏËÚˆÙÈ΋ ‰È·‰Èηۛ· Ì ÌÔÚÈ·ÎÔ‡˜ Ì˯·ÓÈÛÌÔ‡˜, Ô˘ ¿ÏÏÔÙ ÂÍ·ÚÙÒÓÙ·È ·fi ˘Ô‰Ô¯Â›˜, Î·È ¿ÏÏÔÙ fi¯È. Ÿˆ˜ ÚÔ·ÙÂÈ ·fi ÚfiÛÊ·-
Ù˜ ÌÂϤÙ˜, Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙËÓ ·ıÔÁ¤ÓÂÈ· Ù˘ ·ıËÚÔÁ¤ÓÂÛ˘ ·ÎfiÌË Î·È Û ÌË ‰È·‚ËÙÈο ¿ÙÔÌ·. ∏ ¯ÚËÛÈÌÔÔ›ËÛË Ê·Ú̷΢ÙÈÎÒÓ Ô˘ÛÈÒÓ, Ô˘ ı· ·Ó·ÛÙ›ÏÔ˘Ó ÙÔÓ Û¯ËÌ·ÙÈÛÌfi ÙˆÓ AGEs48 ı· Ô‰ËÁ‹ÛÂÈ ÛÂ Û˘Ó·Ú·ÛÙÈΤ˜ ıÂڷ¢ÙÈΤ˜ ‰˘Ó·ÙfiÙËÙ˜ ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ ÓÔÛËÌ¿ÙˆÓ..
μÈ‚ÏÈÔÁÚ·Ê›· 1.
2.
3.
Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 1993; 16:434-444. The United Kingdom Prospective Diabetes Study Data Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837-853. The Diabetes Control and Complications Trial Data Group. The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial. Diabetes 1995;44:968983.
11. Baynes JW, Thorpe SR. Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 1999;48:1-9. 12. Gugliucci A. Glycation as the glucose link to diabetic complications. JAOA 2000; 10:621-634. 13. Maillard L. Action des acides amines sur les surces:formation des meladoidines par voie methodique. C R Hebd Seances Acad Sci 1912;154:66-68. 14. Hodge JE. Chemistry of browning reactions in model systems. J Agric Food Chem 1953;1:928-943. 15. Schleicher E, Wagner E, Nerlich A. Increased accumulation of glycoxidation product carboxymethyllysine in human tissues in diabetes and aging. J Clin Invest 1997;99:457-68.
Fisman EZ, Motro M, Tenenbaum A, et al. Impaired fasting glucose concentrations in nondiabetic patients with ischemic heart disease: a marker for a worse prognosis. Am Heart J 2001;141: 485-90.
16. Thornalley PJ, Langborg A, Minhas HS. Formation of glyoxal, methylglyoxal and 3-deoxyglucosone in the glycation of proteins by glucose. Biochem J 1999;344:106-16.
Levitam EB, Song Y, Ford ES, Liu S. Is nondiabetic hyperglycemia a risk factor for cardiovascular disease? A meta-analysis of prospective studies. Arch Intern Med. 2004 Oct 25;164(19):2147-55.
17. Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med 1988;318: 1315-1321.
6.
Lee AY, Chung SS. Contributions of polyol pathway to oxidative stress in diabetic cataract. FASEB J 1999;13:23-30.
7.
Rojas A, Morales MA. Advanced glycation end endothelial functions: A link towards vascular complications in diabetes. Life Science 2004;76:715-730.
18. Ahmed N. Advanced glycation end products- role in pathology of diabetic complications. Diab Res Clin Pract 2005; 67:3-21.
8.
Koya D, King GL. Protein kinase C activation and the development of diabetic complications. Diabetes 1998;47:859-866.
4.
5.
9.
Du XL, Edelstein D, Rossetti L, Fantus IG, Goldberg H, Ziyadeh F, Wu J, Brownlee M. Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor1 expression by increasing Sp1 glycosylation. Proc Natl Acad Sci USA 2000; 97:12222-12226.
10. Brownlee M. Banting Lecture 2004. The Pathobiology of Diabetic Complications. A Unifying Mechanism. Diabetes 2005;54:1615-1625.
19. Cooper M. Importance of Advanced Glycation End Products in DiabetesAssociated Cardiovascular and Renal Disease. AJH 2004; 17:31S-38S. 20. Jenkins ∞, Best J, Richard L, Klein R, Timothy J, Lyons Δ. Lipoproteins, glycoxidation and diabetic angiopathy. Diabetes Metab Res Rev 2004;20:349-368. 21. Ferretti G, Bacchetti T, Marchionni C, Caldarelli L, Curatola G. Effect of glycation of high density lipoproteins on their physicochemical properties and on paraoxonase activity. Acta Diabetol 2001;38:163-9. 22. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001;414:813-820. 23. Kanauchi M, Tsujimoto N, Hashimoto T. Advanced glycation end products in
nondiabetic patients with coronary artery disease. Diabetes Care. 2001;24:16201623. 24. Kitauchi T, Yoshida K, Yoneda T, et al. Association between pentosidine levels and arteriosclerosis in patients receiving hemodialysis. Clin Exp Nephrol 2004; 8:48-53. 25. Basta G, Schmidt AM, De Caterina R. Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. Cardiovasc Res. 2004;63:582-592. 26. Bakris G, Bank A, Kass D, Neutel J, Preston R, Oparil S. Advanced Glycation End-Product Cross-Link Breakers. AJH 2004; 17:23S-30S. 27. Kass DA, Shapiro EP, Kawaguchi M, et al. Improved arterial compliance by a novel advanced glycation end product crosslink breaker. Circulation 2001;104: 1464- 1470. 28. Brownlee M, Vlassara H, Cerami A. Nonenzymatic glycosylation products on collagen covalently trap low-density lipoprotein. Diabetes 1985;34:938-941. 29. Makino H, Shikata K, Hironaka K, Kushiro M, Yamasaki Y, Sugimoto H, et al. Ultrastructure of nonenzymatically glycated mesangial matrix in diabetic nephropathy. Kidney Int 1995;48:517526. 30. Bucala R, Tracey KJ, Cerami A. Advanced glycosylation products quench nitric oxide and mediate defective endothelium-dependent vasodilation in experimental diabetes. J Clin Invest 1991; 87:432-438. 31. Bucala R, Mitchell R, Arnold K, Innerarity T, Vlassara H, Cerami A. Identification of the major site of apolipoprotein B modification by advanced glycosylation end products blocking uptake by the low density lipoprotein receptor. J Biol Chem 1995;270:10828-10832. 32. Bowie A, Owens D, Collins P, Johnson A, Tomkin GH. Glycosylated low density lipoprotein is more sensitive to oxidation: implications for the diabetic patient? Atherosclerosis 1993;102:63-67. 33. Ferretti G, Bacchetti T, N`egre-Salvayre A, Salvayre R, Dousset N, Curatola G. Structural modifications of HDL and
15
ª∞ƒΔπ√™ 2008
functional consequences. Atherosclerosis 2006;184:1-7. 34. Vlassara H. Receptor-mediated interactions of advanced glycosylation end products with cellular components within diabetic tissues. Diabetes 1992;41(2):5256. 35. Brett J, Schmidt AM, Yan SD, Zou YS, Weidman E, Pinsky D, Nowygrod R, Neeper M, Przysiecki C, Shaw A. Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues. Am J Pathol 1993;143:1699-1712 36. Schmidt AM, Yan SD, Wautier JL, Stern D. Activation of receptor for advanced glycation end products: a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis. Circ Res 1999;84:489-497. 37. Park L, Raman KG, Lee KJ, Lu Y, Ferran L, Chow WS, Stern D, Schmidt A M. Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts. Nat. Med. 1998;4:1025-1031. 38. Kirstein M, Brett J, Radoff S, et al. Advanced protein glycosylation induces transendothelial human monocyte chemotaxis and secretion of platelet-derived growth factor: role in vascular disease of diabetes and aging. Proc Natl Acad Sci USA 1990;87:9010- 4.
39. Schmidt AM, Yan SD, Brett J, et al. Regulation of human mononuclear phagocyte migration by cell surface-binding proteins for advanced glycation end products. J Clin Invest 1993;91:2155- 68.
44. Xu B, Chibber R, Ruggerio D, Kohner E, Ritter J, Ferro A. Impairment of vascular endothelial nitric oxide synthase activity by advanced glycation end products. FASEB J 2003;17:1289-1291.
40. Sakata N, Meng J, Takebayashi S. Effects of advanced glycation end products on the proliferation and fibronectin production of smooth muscle cells. J Atheroscler Thromb 2000;7:169-76.
45. Tan KCB, Chow WS, Ai VHG, Metz C, Bucala R, Lam KS. Advanced glycation end products and endothelial dysfunction in type 2 diabetes. Diabetes Care 2002;25:1055-1059.
41. Ido Y, Chang KC, Lejeune WS, Bjercke RJ, Reiser KM, Williamson JR, Tilton RG. Vascular dysfunction induced by AGE is mediated by VEGF via mechanisms involving reactive oxygen species, guanylate cyclase, and protein kinase C. Microcirculation 2001;8:251-263.
46. Yamagishi S, Fujimori H, Yonekyra H, Yamamoto Y, Yamamoto H. Advanced glycation end products inhibit prostacyclin production and induce plasminogen activator inhibitor-1 in human microvascular endothelial cells. Diabetologia 1998; 41:1435-1441.
42. Otero K, Mart__nez F, Beltran A, Gonza_lez D, Herrera B, Quintero G, Rojas A. Albumin-derived advanced glycation end-products trigger the disruption of the vascular endothelialcomplex in cultured human and murine endothelial cells. Biochem J 2001;359:567-574.
47. Quehenberger P, Bierhaus A, Fasching P, Muellner C, Klevesath M, Hong M, Stier G, Sattler M, Schleicher E, Speiser W, Nawroth PP. Endothelin 1 transcription is controlled by nuclear factor-nB in AGE-stimulated cultured endothelial cells. Diabetes 2000;49:1561-1570.
43. Schmidt AM, Hori O, Chen JX, Li JF, Crandall J, Zhang J, Cao R, Yan SD, Brett J, Stern D. Advanced glycation endproducts interacting with their endothelial receptor induce expression of vascular cell adhesion molecule-1 (VCAM1) in cultured human endothelial cells and in mice. A potential mechanism for the accelerated vasculopathy of diabetes. J Clin Invest 1995;96:1395-1403.
48. Geronikaki A, Gavalas A, Dislian V, Giannoglou G. Inhibition of Renin-Angiotensin System and Advanced Glycation End Products Formation: A Promising Therapeutic Approach Targeting on Cardiovascular Diseases. Cardiovasc Hematol Agents Med Chem. 2007;5 (4):249-264. .
ªÔÓÔÁÔÓÈΤ˜ ÀÂÚ¯ÔÏËÛÙÂÚÔÏ·È̛˜. °ÂÓÂÙÈÎfi Àfi‚·ıÚÔ. πˆ¿ÓÓ˘ ™Îԇ̷˜ ∫·Ú‰ÈÔÏfiÁÔ˜, ∞Ó·ÏËÚˆÙ‹˜ ¢È¢ı˘ÓÙ‹˜ ∞’ ¶·ÓÂÈÛÙËÌȷ΋˜ ∫·Ú‰ÈÔÏÔÁÈ΋˜ ∫ÏÈÓÈ΋˜, πÔÎÚ·Ù›Ԣ ¡ÔÛÔÎÔÌ›Ԣ ∞ıËÓÒÓ
ÃÚ‹ÛÙÔ˜ ¶›ÙÛ·‚Ô˜ ∫·Ú‰ÈÔÏfiÁÔ˜, ∞Ó·ÏËÚˆÙ‹˜ ∫·ıËÁËÙ‹˜ ∞’ ¶·ÓÂÈÛÙËÌȷ΋˜ ∫·Ú‰ÈÔÏÔÁÈ΋˜ ∫ÏÈÓÈ΋˜, πÔÎÚ·Ù›Ԣ ¡ÔÛÔÎÔÌ›Ԣ √È ‰˘ÛÏÈÔÚˆÙÂ˚Ó·È̛˜ ‰È·ÎÚ›ÓÔÓÙ·È Û ڈÙÔ·ı›˜ (Û˘ÁÁÂÓ›˜) Î·È Û ‰Â˘ÙÂÚÔ·ı›˜.1 √È ÚˆÙÔ·ı›˜ ‰È·ÎÚ›ÓÔÓÙ·È, Û ÌÔÓÔÁÔÓÈΤ˜, fiÙ·Ó ÙÔ ·›ÙÈÔ Ô˘ ÙȘ ÚÔηÏ› Â›Ó·È Ì›· ÎÏËÚÔÓÔÌÔ‡ÌÂÓË ‰È·Ù·Ú·¯‹, Î·È Û ÔÏ˘ÁÔÓÈΤ˜ Ë ÔÏ˘·Ú·ÁÔÓÙÈΤ˜, fiÙ·Ó ÔÊ›ÏÔÓÙ·È ÛÂ Û˘Ó‰˘·ÛÌfi ÁÂÓÂÙÈÎÒÓ Î·È ÂÚÈ‚·ÏÏÔÓÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ. √È ÌÔÓÔÁÔÓÈΤ˜, Ô˘ ·ÔÙÂÏÔ‡Ó Î·È ÙËÓ ÌÂÈÔÓfiÙËÙ·, ÎÏËÚÔÓÔÌÔ‡ÓÙ·È Ì ÙÔÓ ÂÈÎÚ·ÙÔ‡ÓÙ· ‹ ÙÔÓ ˘ÔÏÂÈfiÌÂÓÔ ¯·Ú·ÎÙ‹Ú·, ·ÎÔÏÔ˘ıÒÓÙ·˜ ÙÔ˘˜ ÓfiÌÔ˘˜ ÙÔ˘ Mendel. Δ· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ·Ú·ÙËÚÂ›Ù·È Ì›· ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË ÙˆÓ ÁÓÒÛÂˆÓ Á‡Úˆ ·fi ÙËÓ ÁÂÓÂÙÈ΋ ‚¿ÛË ÙˆÓ ‰˘ÛÏÈȉ·ÈÌÈÒÓ Î·È ÙÔ ÚfiÏÔ ‰È·ÊfiÚˆÓ ÌÔÚ›ˆÓ ÛÙËÓ ·-
16
ıÔÁ¤ÓÂÈ· ·˘ÙÒÓ ÙˆÓ ‰È·Ù·Ú·¯ÒÓ. ∏ ÁÂÓÂÙÈ΋ ·˘Ù‹ ÚÔÛ¤ÁÁÈÛË ÙˆÓ ‰˘ÛÏÈȉ·ÈÌÈÒÓ ‚Ô‹ıËÛ ÛÙËÓ ·ÔÛ·Ê‹ÓÈÛË ÙˆÓ ÌÂÙ·‚ÔÏÈÎÒÓ ‰È·Ù·Ú·¯ÒÓ ÙÔ˘˜ Î·È Û˘ÓÂÒ˜ ÛÙËÓ ÁÓÒÛË ÙÔ˘ Ì˯·ÓÈÛÌÔ‡ Ù˘ ‰˘ÛÏÈȉ·ÈÌ›·˜, Ú¿ÁÌ· Ô˘ ¤ÙÚ„ ÛÙËÓ Î·Ï‡ÙÂÚË ·ÓÙÈÌÂÙÒÈÛË ·˘ÙÒÓ ÙˆÓ ‰È·Ù·Ú·¯ÒÓ. ŸÏ· Ù· ÂÏ·Ùو̷ÙÈο ÁÔÓ›‰È· Ô˘ Â›Ó·È ÁÓˆÛÙ¿ Û‹ÌÂÚ· Î·È ·ÊÔÚÔ‡Ó ÌÔÓÔÁÔÓÈΤ˜ ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·È̛˜ ÂÌϤÎÔÓÙ·È ÛÙÔ Ì˯·ÓÈÛÌfi ÚfiÛÏ˄˘ Ù˘ LDLC ·fi ÙÔ˘˜ LDL ˘Ô‰Ô¯Â›˜ ÛÙ· Ë·ÙÔ·ÙÙ·Ú·. (∂ÈÎfiÓ· 1). ¶ÚˆÙÔfiÚÔÈ Û ·˘Ùfi ÙÔÓ ÙÔ̤· ‹Ù·Ó ÔÈ Goldstein Î·È Ô Brown2, ÔÈ ÔÔ›ÔÈ ÛÙȘ ·Ú¯¤˜ ÙÔ˘ 1970 η٤ÏËÍ·Ó ÛÙÔ Û˘Ì¤Ú·ÛÌ·, fiÙÈ Ù·
¿ÙÔÌ· Ì ÔÈÎÔÁÂÓ‹ ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌ›· (FH), ÌÈ¿ ‰˘ÛÏÈȉ·ÈÌ›· Ô˘ Ô Khachadurian3 ›¯Â ·Ó·ÁÓˆÚ›ÛÂÈ fiÙÈ ÎÏËÚÔÓÔÌÂ›Ù·È Ì ÙÔÓ ÂÈÎÚ·ÙÔ‡ÓÙ· ¯·Ú·ÎÙ‹Ú·, ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÂÏÏÂÈÌÌ·ÙÈ΋ ‰Ú·ÛÙËÚÈfiÙËÙ· ÙˆÓ LDL ˘Ô‰Ô¯¤ˆÓ Î·È Û˘ÓÂÒ˜ ÌÂȈ̤ÓÔ Î·Ù·‚ÔÏÈÛÌfi Ù˘ LDL-C. ∏ ‰È·Ù·Ú·¯‹ ·˘Ù‹ ÔÊ›ÏÂÙ·È Û ÌÂÙ¿ÏÏ·ÍË ÙÔ˘ ÁÔÓȉ›Ô˘ ÙÔ˘ ˘Â‡ı˘ÓÔ˘ ÁÈ· ÙÔ˘˜ LDL ˘Ô‰Ô¯Â›˜ (LDLR), Ô˘ ¢ڛÛÎÂÙ·È ÛÙÔ ¯ÚˆÌ·Ùfiۈ̷ 19. ∏ ÌÂÙ¿ÏÏ·ÍË ÙÔ˘ ÁÔÓȉ›Ô˘ ·˘ÙÔ‡ ¤¯ÂÈ Û·Ó ·ÔÙ¤ÏÂÛÌ· ›Ù ÙËÓ Ï‹ÚË ¤ÏÏÂÈ„Ë Ù˘ ‰Ú·ÛÙÈÎfiÙËÙ·˜ ÙˆÓ LDLR ›Ù ÌÈ¿ ˘ÔÏÂÈfiÌÂÓË ‰Ú·ÛÙÈÎfiÙËÙ· ̤¯ÚÈ ÂÚ›Ô˘ ÙÔ 25% Ù˘ Ï‹ÚÔ˘˜ ‰Ú·ÛÙÈÎfiÙËÙ·˜. √È ·ÓˆÌ·Ï›Â˜ ·˘Ù¤˜ ÂÍ·ÚÙÒÓÙ·È ·fi ÙÔÓ Ù‡Ô
¶∞£√ºÀ™π√§√°π∞ Û ¿ÓÔ‰Ô ·˘Ù‹˜ ηٿ 2 Ì 3 ÊÔÚ¤˜ ÛÙÔ Ï¿ÛÌ·. √È ÌÈÛÔ› ÂÚ›Ô˘ ·fi ·˘ÙÔ‡˜ ÙÔ˘˜ ·ÛıÂÓ›˜ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÙÂÓfiÓÙÈ· Í·ÓıÒÌ·Ù·, ÚÒÈÌÔ ÁÂÚÔÓÙfiÙÔÍÔ Î·È Í·ÓıÂÏ¿ÛÌ·Ù·. ∏ ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ˜ ÂÌÊ·Ó›˙ÂÙ·È ÙËÓ Ù¤Ù·ÚÙË ‹ ¤ÌÙË ‰ÂηÂÙ›·, 10 - 15 ¯ÚfiÓÈ· ÓˆÚ›ÙÂÚ· ·fi fiÙÈ ÛÙÔÓ ÁÂÓÈÎfi ÏËı˘ÛÌfi. ŸÛÔÓ ·ÊÔÚ¿ ÙÔ˘˜ ÔÌfi˙˘ÁÔ˘˜ FH, Î·È ÙÔ˘˜ Û‡ÓıÂÙÔ˘˜ ÂÙÂÚfi˙˘ÁÔ˘˜, ·ÚÔ˘ÛÈ¿˙Ô˘Ó ¿ÓÔ‰Ô Ù˘ LDL Ï¿ÛÌ·ÙÔ˜ ¿Óˆ ·fi 5 ÊÔÚ¤˜ Î·È ÛÔ‚·Ú‹ ·ıËÚÔÛÎÏ‹ÚˆÛË ÚÔ Ù˘ ËÏÈΛ·˜ ÙˆÓ 20 ÂÙÒÓ.
∂ÈÎfiÓ· 1. √È ˘Ô‰Ô¯Â›˜ LDL (LDLR), ·ÊÔ‡ ‰ËÌÈÔ˘ÚÁËıÔ‡Ó ÛÙÔ ÂÓ‰ÔÏ·ÛÌ·ÙÈÎfi ‰›ÎÙ˘Ô, ÌÂٷʤÚÔÓÙ·È ÛÙËÓ Î˘ÙÙ·ÚÈ΋ ÌÂÌ‚Ú¿ÓË, fiÔ˘ ‰ÂÛÌ¤Ô˘Ó ÙȘ LDL ÙÔ˘ ·›Ì·ÙÔ˜ ̤ۈ Ù˘ ÚˆÙ›Ó˘ apo B-100. H PCSK9 ÂÎÎÚ›ÓÂÙ·È ·fi Ù· Ë·ÙÔ·ÙÙ·Ú· Î·È Ô ÚfiÏÔ˜ Ù˘ Â›Ó·È Ó· ‰ÂÛ̇ÂÈ ÙÔ˘˜ LDLR ÛÙËÓ ÂÈÊ¿ÓÂÈ· ÙˆÓ Ë·ÙÔ΢ÙÙ¿ÚˆÓ. √È LDLRs, ‰ÂÛÌÂ˘Ì¤ÓÔÈ ‹ fi¯È ·fi PCSK9, ÎÈÓËÙÔÔÈÔ‡ÓÙ·È ÚÔ˜ ÙÔ˘˜ ÂÈÎ·Ï˘Ì̤ÓÔ˘˜ Ì ÎÏ·ıÚ›ÓË “Ï¿ÎÔ˘˜” Î·È ÙÂÏÈÎÒ˜ ÂÚÓ¿Ó ÛÙÔ ÂÛˆÙÂÚÈÎfi ÙÔ˘ ΢ÙÙ¿ÚÔ˘ Ì ÙËÓ ‚Ô‹ıÂÈ· ÙˆÓ LDLRAP1. ªÂÙ¿ ÙËÓ Â›ÛÔ‰Ô ÂÓ‰Ô΢ÙÙ·Ú›ˆ˜, Ù· ۈ̷ٛ‰È· LDL ‰È·¯ˆÚ›˙ÔÓÙ·È ·fi ÙÔ˘˜ LDLRs Î·È ÛÙ· Ï˘ÛÔÛÒÌ·Ù· ηٷ‚ÔÏ›˙ÔÓÙ·È Û ÂχıÂÚË ¯ÔÏËÛÙÂÚfiÏË. ¶ÔÛÔÛÙfi Ù˘ ÂχıÂÚ˘ ¯ÔÏËÛÙÂÚfiÏ˘ ηıÒ˜ Î·È ÌË ˙ˆÈΤ˜ ÛÙÂÚfiϘ Ô˘ ÂÚȤ¯ÔÓÙ·È ÛÙ· ÌfiÚÈ· LDL ·Ô‚¿ÏÏÔÓÙ·È ·fi ÙËÓ Î˘ÙÙ·ÚÈ΋ ÂÈÊ¿ÓÂÈ· ̤ۈ ÙˆÓ ÛÙÂÚÔÏÈÓÒÓ ABCG5 Î·È ABCG8. √È LDLRs ›Ù ·Ó·Î˘ÎÏÒÓÔÓÙ·È ›Ûˆ ÛÙËÓ Î˘ÙÙ·ÚÈ΋ ÌÂÌ‚Ú¿ÓË ‹ ηٷχÔÓÙ·È Ì¤Ûˆ ÙˆÓ PCSK9. ŒÙÛÈ ÔÈ Èı·ÓÔ› Ì˯·ÓÈÛÌÔ› Ô˘ ÚÔηÏÔ‡Ó ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌ›· ›ӷÈ: 1. ‚‚Ϸ̤ÓË ‰ËÌÈÔ˘ÚÁ›· ‹ ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ· ÙˆÓ LDLR. 2. ÂÏ·Ùو̷ÙÈ΋ apo B Ë ÔÔ›· Ô‰ËÁ› Û ÂËÚ·Ṳ̂ÓË Û‡Ó‰ÂÛË ÙˆÓ LDL Ì ÙÔ˘˜ LDLR. 3. ÂÏ·Ùو̷ÙÈ΋ LDLRAP1 Ô˘ ¤¯ÂÈ ·ÓÙ›ÎÙ˘Ô ÛÙËÓ Ê˘ÛÈÔÏÔÁÈ΋ ÂÓ‰Ô·وÛË ÙˆÓ LDLR. 4. ·ıÔÏÔÁÈ΋ ·‡ÍËÛË Ù˘ ‰Ú·ÛÙÈÎfiÙËÙ·˜ Ù˘ PCSK9 Ô˘ Ô‰ËÁ› Û ˘ÂÚ‚ÔÏÈÎfi ηٷ‚ÔÏÈÛÌfi ÙˆÓ LDLR. 5. ÂÏ·Ùو̷ÙÈΤ˜ ÛÙÂÚÔϛӘ Ô˘ Ô‰ËÁÔ‡Ó Û ·‡ÍËÛË Ù˘ ·ÔÚÚfiÊËÛ˘ Ê˘ÙÔÛÙÂÚÔÏÒÓ ·Ô Ù· ÂÓÙÂÚÔ·ÙÙ·Ú· Î·È ·‡ÍËÛË ÙˆÓ Ê˘ÙÔÛÙÂÚÔÏÒÓ Î·È Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ ÛÙ· Ë·ÙÔ·ÙÙ·Ú·. Ù˘ ÌÂÙ¿ÏÏ·Í˘ Î·È ÂÚÈÏ·Ì‚¿ÓÔ˘Ó: 1. ·ÓˆÌ·Ï›· ÛÙËÓ Û‡ÓıÂÛË ÙÔ˘ ˘Ô‰Ô¯¤· ÂÓ‰Ô΢ÙÙ·Ú›ˆ˜ ÛÙÔ Â›Â‰Ô ÙÔ˘ ÂÓ‰ÔÏ·ÛÌ·ÙÈÎÔ‡ ‰ÈÎÙ‡Ô˘, 2. ‰È·ÎÔ‹ Ù˘ ÌÂÙ·ÊÔÚ¿˜ ÙÔ˘ ‹‰Ë Û˘ÓÙÂıÈ̤ÓÔ˘ ˘Ô‰Ô¯¤· ÛÙËÓ Î˘ÙÙ·ÚÈ΋ ÂÈÊ¿ÓÂÈ·, 3. ÂÏÏÂÈÌÌ·ÙÈ΋ Û‡Ó‰ÂÛË ÙˆÓ ÌÔÚ›ˆÓ LDL ÛÙÔ˘˜ ˘Ô‰Ô¯Â›˜, Ô˘ ¢ڛÛÎÔÓÙ·È ‹‰Ë ÛÙËÓ Î˘ÙÙ·ÚÈ΋ ÂÈÊ¿ÓÂÈ· Î·È 4. ·‰˘Ó·Ì›· ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ó· Û˘ÛÛˆÚ‡ÛÔ˘Ó Ù· ‹‰Ë Û˘Ó‰Â‰Â̤ӷ ÌfiÚÈ· LDL Û ÂÈÎÂÎ·Ï˘Ì̤ӷ ÛÊ·ÈÚ›‰È· Î·È Ó· Ù· ÂÈÛ¿ÁÔ˘Ó ÛÙÔ ÂÛˆÙÂÚÈÎfi ÙÔ˘ ΢ÙÙ¿ÚÔ˘, ÁÈ· ÙÔÓ ÂÚ·ÈÙ¤Úˆ ηٷ‚ÔÏÈÛÌfi ÙÔ˘˜.4
¶ÚfiÎÂÈÙ·È ÁÈ· ÌÈ· ·fi ÙȘ Èfi Û˘¯Ó¤˜ ÎÏËÚÔÓÔÌÔ‡ÌÂÓ˜ ÌÂÙ·‚ÔÏÈΤ˜ ÓfiÛÔ˘˜, ÌÂ Û˘¯ÓfiÙËÙ· ÛÙÔ ÁÂÓÈÎfi ÏËı˘ÛÌfi 1:500 ÁÈ¿ ÙÔ˘˜ ÂÙÂÚfi˙˘ÁÔ˘˜ Î·È 1:1000000 ÁÈ· ÙÔ˘˜ ÔÌfi˙˘ÁÔ˘˜ ‹ ÙÔ˘˜ Û‡ÓıÂÙÔ˘˜ ÂÙÂÚfi˙˘ÁÔ˘˜ (ÂËÚ·Ṳ̂ӷ Î·È Ù· ‰‡Ô ÁÔÓ›‰È· ·ÏÏ¿ Ì ‰È·ÊÔÚÂÙÈΤ˜ ÌÂÙ·ÏÏ¿ÍÂȘ). ™Â ÚfiÛÊ·Ù˜ ÌÂϤÙ˜,5-8 ¤¯ÂÈ ‚ÚÂı› ‰È·Ù·Ú·¯‹ ÙˆÓ LDLR ÛÙÔ 5276% ÙˆÓ ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌÈÎÒÓ ·ÛıÂÓÒÓ, Ô˘ ÏËÚÔ‡Ó Ù· ÎÏÈÓÈο ÎÚÈÙ‹ÚÈ· Ù˘ ÔÈÎÔÁÂÓÔ‡˜ ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌ›·˜. √È ·ÛıÂÓ›˜ Ì ÂÙÂÚfi˙˘ÁË FH ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÌÂȈ̤ÓË Î¿ı·ÚÛË Ù˘ LDL, ÁÂÁÔÓfi˜ Ô˘ ÌÂÙ·ÊÚ¿˙ÂÙ·È
ªÈ· ¿ÏÏË ÁÔÓȉȷ΋ ‰È·Ù·Ú·¯‹, Ô˘ ¤¯ÂÈ ·ÔΈ‰ÈÎÔÔÈËı›, Â›Ó·È Ë ÔÈÎÔÁÂÓ‹˜ ÂÏ·Ùو̷ÙÈ΋ ·ÔÏÈÔÚˆÙ›ÓË μ ( FDB). ¶ÚfiÎÂÈÙ·È ÁÈ¿ ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌ›·, Ô˘ ÌÂÙ·‰›‰ÂÙ·È Ì ÙÔÓ ·˘ÙÔۈ̷ÙÈÎfi ÂÈÎÚ·ÙÔ‡ÓÙ· ¯·Ú·ÎÙ‹Ú· Î·È Ë ÁÂÓÂÙÈ΋ ‰È·Ù·Ú·¯‹ Ù˘ ÔÊ›ÏÂÙ·È Û ÌÂÙ¿ÏÏ·ÍË ÙÔ˘ ÁÔÓȉ›Ô˘ ÙÔ˘ ˘Â˘ı‡ÓÔ˘ ÁÈ· ÙËÓ apo B. º·ÈÓÔÙ˘Èο ‰ÂÓ ‰È·ÎÚ›ÓÂÙ·È ·Ô ÙËÓ ÔÈÎÔÁÂÓ‹ ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌ›· (FH). °È¿ ÙËÓ ·Ó¿‰ÂÈÍË Ù˘ ÌÂÙ¿ÏÏ·Í˘ R3500Q ˆ˜ ˘Â‡ı˘Ó˘ Ù˘ ÁÂÓÂÙÈ΋˜ ·ÈÙÈÔÏÔÁ›·˜ Ù˘, ¯ÚÂÈ¿ÛıËΠӷ ·Ú¤ÏıÔ˘Ó ÂÚ›Ô˘ 20 ¯ÚfiÓÈ· ·fi ÙËÓ ·Ó·ÁÓÒÚÈÛË Ù˘ ÂÏ·Ùو̷ÙÈ΋˜ Û‡Ó‰ÂÛ˘ Ù˘ LDL Ì ÙÔÓ ÔÌÒÓ˘ÌÔ ˘Ô‰Ô¯¤·. ¶ÚfiÛÊ·Ù·, ‚Ú¤ıËÎ·Ó ÂÈϤÔÓ ÔÎÙÒ ‹È˜ ÌÂÙ·ÏÏ¿ÍÂȘ, Ô˘ ·ÊÔÚÔ‡Ó ÙËÓ Û‡Ó‰ÂÛË Ù˘ apo B ÛÙÔÓ LDLR. ™ÙÔÓ ∂˘Úˆ·˚Îfi ¯ÒÚÔ Ë ÂÙÂÚfi˙˘ÁÔ˜ FDB ··ÓÙ¿Ù·È ÌÂ Û˘¯ÓfiÙËÙ· 1:500 - 1:7009. ∏ Û˘¯ÓfiÙËÙ· ÙˆÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ Ù˘ apo B Û ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌÈο ¿ÙÔÌ·, ·Ó¢ڛÛÎÂÙ·È Û ÔÛÔÛÙ¿ 0-11%5,7, ÔÛÔÛÙfi ÛËÌ·ÓÙÈο ÌÈÎÚfiÙÂÚÔ ·fi ·˘Ùfi ÙˆÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ ÙÔ˘ LDLR5,9,10,11. √È ·ÛıÂÓ›˜ Ì FDB, ·Ú¿ ÙËÓ ÔÌÔÈfiÙËÙ¿ ÙÔ˘˜ Ì ÙÔ˘˜ FH, ·ÚÔ˘ÛÈ¿˙Ô˘Ó Î·Ù¿ 20-25% ¯·ÌËÏfiÙÂÚ· ›‰· LDL, ·ÓÙ·ÔÎÚ›ÓÔÓÙ·È Î·Ï‡ÙÂÚ· ÛÙȘ ÛÙ·Ù›Ó˜ Î·È ·ÚÔ˘ÛÈ¿˙Ô˘Ó ¯·ÌËÏfiÙÂÚÔ ÛÙÂÊ·ÓÈ·›Ô ΛӉ˘ÓÔ13. ∏ ËÈfiÙÂÚË ·˘Ù‹ ÂÈÎfiÓ· Ù˘ FDB ÌÔÚ› Ó· ·Ô‰Ôı› ÛÙÔ fiÙÈ Ë Î¿ı·ÚÛË ÙˆÓ ˘ÔÏÂÈÌÌ¿ÙˆÓ VLDL Á›ÓÂÙ·È ·ÚfiÛÎÔÙ· ̤ۈ Ù˘ apo E ·fi ÙÔ˘˜ LDLR. ∞ÓÙ›ıÂÙ· ÛÙËÓ FH, ÂÂȉ‹ Ë ‰È·Ù·Ú·¯‹ ·ÊÔÚ¿ ÙÔ˘˜ LDLR, ÂËÚ¿˙ÂÙ·È Ë Î¿-
17
ª∞ƒΔπ√™ 2008
ı·ÚÛË ÙfiÛÔ ÙˆÓ LDL fiÛÔ Î·È ÙˆÓ ˘ÔÏÂÈÌÌ¿ÙˆÓ ÙˆÓ VLDL14. ŒÙÛÈ ÔÈ ÔÌÔ˙˘ÁfiÙ˜ ˆ˜ ÚÔ˜ ÙËÓ apo B, ·ÚÔ˘ÛÈ¿˙Ô˘Ó Â›Â‰· LDL 267 - 329 mg/dl, Ù· ÔÔ›· Â›Ó·È ·ÚfiÌÔÈ· Ì ·˘Ù¿ ÙˆÓ ÂÙÂÚÔ˙‡ÁˆÓ FH Î·È ÛËÌ·ÓÙÈο ÌÈÎÚfiÙÂÚ· ·Ô ·˘Ù¿ ÙˆÓ ÔÌÔ˙‡ÁˆÓ FH15. ¶ÚfiÛÊ·Ù· Ô Abifadel Î·È Û˘Ó.16 ·Ó·ÁÓÒÚÈÛ·Ó ¤Ó· Ó¤Ô ÁÔÓȉȷÎfi ÙfiÔ Ô˘ ·ÊÔÚ¿ ÙËÓ PCSK9 (ÙÔ ¤Ó·ÙÔ Ì¤ÏÔ˜ Ù˘ ÔÈÎÔÁÂÓ›·˜ ÙˆÓ proprotein convertase subtilisin/kexin), Ì›· ÚˆÙ¿ÛË ÛÂÚ›Ó˘, Ë ÔÔ›· ÚÔηÏÒÓÙ·˜ ÙÔÓ Î·Ù·‚ÔÏÈÛÌfi, ÂÓ‰Ô΢ÙÙ·Ú›ˆ˜, ÙˆÓ LDLR Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ÔÌÔÈfiÛÙ·ÛË Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ ÙÔ˘ ΢ÙÙ¿ÚÔ˘.16,17,18 °ÂÓÂÙÈΤ˜ ÌÂϤÙ˜ ·Ó·ÁÓÒÚÈÛ·Ó ÙËÓ PCSK9 Û·Ó ÙÔ ÙÚ›ÙÔ ÁÔÓ›‰ÈÔ ÌÂÙ¿ ·˘Ù¿ ÙˆÓ LDLR Î·È apo B, Ô˘ ÚÔηÏ› ·˘ÙÔۈ̷ÙÈ΋ ÂÈÎÚ·ÙÔ‡Û· ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌ›· (ADH). ∞Ó·ÁÓˆÚ›ÛıËΠ۠ÔÈÎÔÁ¤ÓÂȘ Ì ADH ¤Ó·˜ ·ÚÈıÌfi˜ ÌÂÙ·ÏϿ͈Ó, fiˆ˜ S127R, F216L, D374Y Î·È N175Y, Ô˘ ·˘Í¿ÓÔ˘Ó ÙËÓ ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ· Ù˘ PCSK916,19,20. ∏ ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌ›· (ADH) ·˘Ù‹, ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ·ÚfiÌÔÈ· ÂΉ‹ÏˆÛË Ì ÙËÓ FH.21 ™Â ·Ú·ÎÔÏÔ‡ıËÛË 30 ÂÙÒÓ 13 ·ÛıÂÓÒÓ Ì ÙËÓ ÌÂÙ¿ÏÏ·ÍË D374Y ·Ó·ÁÓˆÚ›ÛıËΠfiÙÈ ·˘ÙÔ›, Û ۯ¤ÛË Ì ÙËÓ ÂÙÂÚfi˙˘ÁË FH, ·ÚÔ˘Û›·˙·Ó ˘„ËÏfiÙÂÚ˜ ÙÈ̤˜ LDL-C Î·È ·˘ÍË̤ÓË Â›ÙˆÛË ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘22. ∞ÓÙ›ıÂÙ·, ¿ÙÔÌ· Ì ÌÂÙ·ÏÏ¿ÍÂȘ Ô˘ ÚÔηÏÔ‡Ó ·ÒÏÂÈ· Ù˘ ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ·˜ Ù˘ PCSK9 (À142Ã, G679X), ·ÚÔ˘ÛÈ¿˙Ô˘Ó Ì›ˆÛË 28% Ù˘ LDL-C ÙÔ˘ Ï¿ÛÌ·ÙÔ˜ Î·È Ì›ˆÛË 88% ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÂÌÊ¿ÓÈÛ˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘, fiˆ˜ ¤‰ÂÈÍ ÌÂϤÙË ·Ú·ÎÔÏÔ‡ıËÛ˘ 15 ÂÙÒÓ.23 √ ٤ٷÚÙÔ˜ ÁÔÓȉȷÎfi˜ ÙfiÔ˜ ·Ó·Ê¤ÚÂÙ·È ÛÙËÓ ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌ›· Ô˘ ÂÚȤÁÚ·„·Ó ÙÔ 1973 Ô Khachadurian Î·È Ô Uthman, fiÙ·Ó ·Ó·ÁÓÒÚÈÛ·Ó ÁÈ¿ ÚÒÙË ÊÔÚ¿ Ì›· ÔÈÎÔÁ¤ÓÂÈ· ·fi ÙÔÓ §›‚·ÓÔ Ì ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌ›· ÌÂÙ·‰È‰fiÌÂÓË Ì ·˘ÙÔۈ̷ÙÈÎfi ˘ÔÏÂÈfiÌÂÓÔ ¯·Ú·ÎÙ‹Ú·, ÎÏÈÓÈο ‰˘Û‰È¿ÎÚÈÙË ·fi ÙËÓ FH.24 OÈ Garcia Î·È Û˘Ó25 ·Ó·ÁÓÒÚÈÛ·Ó ÙÔ ˘Â‡ı˘ÓÔ ÁÔÓ›‰ÈÔ, ÙÔ ÔÔ›Ô Îˆ-
18
‰ÈÎÔÔÈ› ÌÈ¿ ÚˆÙ½ÓË ÚÔÛ·ÚÌÔÛÙ‹, ÁÓˆÛÙ‹ Î·È Û·Ó ÚˆÙ½ÓË ÚÔÛ·ÚÌÔÁ‹˜ ÙˆÓ LDLR (LDLRAP1 Ë ARH), Ë ÔÔ›· ‰ÂÛ̇ÂÈ ÙÔ˘˜ LDLR Î·È Ï·Ì‚¿ÓÂÈ Ì¤ÚÔ˜ ÛÙÔÓ Ì˯·ÓÈÛÌfi ÂÓ‰Ô·وÛ˘.26,27,28 ¶Ú¿ÁÌ·ÙÈ Ë LDLRAP1 ·ÔÙÂÏ› Ô˘ÛÈ·ÛÙÈÎfi ·Ú¿ÁÔÓÙ· ÁÈ¿ ÙËÓ ÂÓ‰Ô·وÛË ÙˆÓ LDLR, ‰ÈfiÙÈ ÚÔ¿ÁÂÈ ÙËÓ Û˘ÁΤÓÙÚˆÛË ·˘ÙÒÓ ÛÙËÓ ÂÈÊ¿ÓÂÈ· ÙÔ˘ Ë·ÙÔ΢ÙÙ¿ÚÔ˘, ̤۷ Û ϿÎÎÔ˘˜ ÂÈÛÙڈ̤ÓÔ˘˜ Ì ÎÏ·ıÚ›ÓË. ∏ ‰È·‰Èηۛ· ·˘Ù‹ ÂÈÙ˘Á¯¿ÓÂÙ·È Ì¤Ûˆ Û‡Ó‰ÂÛ˘ Ù˘ Ô˘Ú¿˜ ÙˆÓ LDLR Ì ‰ÔÌÈο Û˘ÛÙ·ÙÈο ÙÔ˘ Û¯ËÌ·ÙÈÛÌÔ‡ ÙÔ˘ ÂÈÛÙڈ̤ÓÔ˘ Ì ÎÏ·ıÚ›ÓË. ∞‰Ú·Ó›˜ ÌÂÙ·ÏÏ¿ÍÂȘ Ù˘ LDLRAP1 Ô‰ËÁÔ‡Ó Û ηٷÎÚ¿ÙËÛË ÙˆÓ LDLR ÛÙËÓ ÂÈÊ¿ÓÂÈ· ÙÔ˘ ΢ÙÙ¿ÚÔ˘ Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÛËÌ·ÓÙÈ΋ Ì›ˆÛË Ù˘ ÚfiÛÏ˄˘ ÙˆÓ LDL.29 ∞Ó Î·È Ô Ú˘ıÌfi˜ οı·ÚÛ˘ ·fi ÙËÓ Î˘ÎÏÔÊÔÚ›· ÙˆÓ LDL ‚Ú¤ıËΠfiÙÈ Â›Ó·È Û˘ÁÎÚ›ÛÈÌÔ˜ ÙfiÛÔ ÛÙËÓ ARH fiÛÔ Î·È ÛÙËÓ ÔÌfi˙˘ÁÔ FH, Ô ÌÂÙ·‚ÔÏÈÎfi˜ Î·È ÎÏÈÓÈÎfi˜ Ê·ÈÓfiÙ˘Ô˜ Ù˘ ARH Â›Ó·È ÏÈÁfiÙÂÚÔ ÛÔ‚·Úfi˜ ·fi ·˘ÙfiÓ Ù˘ ÔÌÔ˙‡ÁÔ˘ FH24,31, ‰ËÏ·‰‹ Ù· ›‰· LDL Ï¿ÛÌ·ÙÔ˜ Â›Ó·È ¯·ÌËÏfiÙÂÚ·, Ë ‰Â ÂÌÊ¿ÓÈÛË Ù˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘ ηı˘ÛÙÂÚ› ¯ÚÔÓÈο. ¶Ú¿ÁÌ·ÙÈ, ηÓ›˜ ·fi ÙÔ˘˜ ·ÛıÂÓ›˜ Ì ARH ‰ÂÓ ÂÌÊ¿ÓÈÛ ™¡ οو ÙˆÓ 20 ÂÙÒÓ.32 Δ¤ÏÔ˜ ÔÈ ·ÛıÂÓ›˜ Ì ARH ·ÓÙ·ÔÎÚ›ÓÔÓÙ·È Î·Ï‡ÙÂÚ· ÛÙ· ˘ÔÏÈȉ·ÈÌÈο Ê¿Ú̷η. ¶ÚfiÛÊ·Ù· ‰È¢ÎÚÈÓ›ÛÙËΠfiÙÈ Ô Î·ı·ÚÈÛÌfi˜ ÙˆÓ ˘ÔÏÂÈÌÌ¿ÙˆÓ ÙˆÓ VLDL, ·Ú·Ì¤ÓÂÈ ¿ıÈÎÙÔ˜ Û ARH-ÂÏÏÂÈÌÌ·ÙÈÎÔ‡˜ ÔÓÙÈÎÔ‡˜, Ú¿ÁÌ· Ô˘ ÌÔÚ› Ó· ÂÍËÁ› Ù· ¯·ÌËÏfiÙÂÚ· ›‰· LDL.33 ªÈ· ¿ÏÏË ·˘ÙÔۈ̷ÙÈ΋ ˘ÔÏÂÈfiÌÂÓË ‰È·Ù·Ú·¯‹ Â›Ó·È Ë ÛÈÙÔÛÙÂÚÔÏ·ÈÌ›· ‹ Ê˘ÙÔÛÙÂÚÔÏ·ÈÌ›·. ™ÙËÓ Î·Ù¿ÛÙ·ÛË ·˘Ù‹ ·Ú·ÙËÚÂ›Ù·È ÌÂÁ¿ÏË ·‡ÍËÛË ÙˆÓ Ê˘ÙÈÎÒÓ ÛÙÂÚÔÏÒÓ ÙÔ˘ ·›Ì·ÙÔ˜ ÂÓÒ Ê˘ÛÈÔÏÔÁÈο ÔÈ Ê˘ÙÈΤ˜ ÛÙÂÚfiϘ Û ۯ¤ÛË Ì ÙËÓ ¯ÔÏËÛÙÂÚfiÏË, Ë ÔÔ›· Â›Ó·È ˙ˆÈ΋ ÛÙÂÚfiÏË, ÂÏ¿¯ÈÛÙ· ·ÔÚÚÔÊÔ‡ÓÙ·È ·fi ÙÔ ¤ÓÙÂÚÔ.34 √È ÚÒÙÔÈ Ô˘ ÂÚȤÁÚ·„·Ó ·˘Ù‹ ÙËÓ ÎÏÈÓÈ΋ ÔÓÙfiÙËÙ· ‹Ù·Ó ÙÔ 1974 Ô Bhattacharyya Î·È Ô Connor35, ÔÈ ÔÔ›ÔÈ ·Ú·Ù‹ÚËÛ·Ó Û ‰‡Ô ·‰ÂÏʤ˜ ÙÂÓfiÓÙÈ·
Í·ÓıÒÌ·Ù· ¯ˆÚ›˜ Ó· ¤¯Ô˘Ó ˢÍË̤ӷ ›‰· ¯ÔÏËÛÙÂÚfiÏ˘ Ï¿ÛÌ·ÙÔ˜, ·ÏÏ¿ ·ÓÙ›ıÂÙ· ·ÚÔ˘Û›·˙·Ó Ôχ ˢÍË̤ӷ ›‰· Ê˘ÙÈÎÒÓ ÛÙÂÚÔÏÒÓ, ΢ڛˆ˜ ÛÈÙÔÛÙÂÚfiÏ˘. √È ·ÛıÂÓ›˜ Ì ÛÈÙÔÛÙÂÚÔÏ·ÈÌ›·, ÂÎÙfi˜ ·fi Ù· ÙÂÓfiÓÙÈ· Í·ÓıÒÌ·Ù· Î·È Ù· Í·ÓıÂÏ¿ÛÌ·Ù·, ÂÌÊ·Ó›˙Ô˘Ó Î·È ÚÒÈÌË ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ. √ ÁÔÓȉȷÎfi˜ ÙfiÔ˜ Ù˘ ÛÈÙÔÛÙÂÚÔÏ·ÈÌ›·˜ Â›Ó·È ÙÔ ¯ÚˆÌ·Ùfiۈ̷ 2p21 Î·È ·ÔÙÂÏÂ›Ù·È ·fi ‰‡Ô ÔÌfiÏÔÁ· ÁÔÓ›‰È·.36,37 ∞˘Ù¿ Ù· ÁÔÓ›‰È· Έ‰ÈÎÔÔÈÔ‡Ó ‰‡Ô ABC (ATP - binding cassette) ÌÂÙ·ÊÔÚ›˜ Ù˘ ÔÈÎÔÁÂÓ›·˜ G ÙˆÓ ÌÂÙ·ÊÔÚ¤ˆÓ, ÙÔ˘˜ ABCG5 Î·È ABCG8, ÁÓˆÛÙÔ‡˜ Î·È ˆ˜ sterolin-1 Î·È sterolin-2 ·ÓÙ›ÛÙÔȯ·. ª¤Ûˆ ·˘ÙÒÓ Á›ÓÂÙ·È Ô ‰È·Î·ÓÔÓÈÛÌfi˜ Ù˘ ÌÂÙ·ÊÔÚ¿˜ ÙˆÓ ÛÙÂÚÔÏÒÓ ÛÙÔ Ë·ÙÔ·ÙÙ·ÚÔ Î·È ÛÙÔ ÂÓÙÂÚÔ·ÙÙ·ÚÔ. √È ÌÂÙ·ÊÔÚ›˜ ABCG5 Î·È ABCG8 Ï·Ì‚¿ÓÔ˘Ó Ì¤ÚÔ˜ ÛÙËÓ ‰ËÌÈÔ˘ÚÁ›· Û˘ÌϤÁÌ·ÙÔ˜ ··Ú·›ÙËÙÔ˘ ÁÈ· ÙËÓ ·ÔÌ¿ÎÚ˘ÓÛË Ù˘ ‰È·ÈÙÈ΋˜ ¯ÔÏËÛÙÂÚfiÏ˘ Î·È ÙˆÓ Ê˘ÙÈÎÒÓ ÛÙÂÚÔÏÒÓ ·fi ÙÔ ¤ÓÙÂÚÔ Î·È ÙÔ ‹·Ú.38 ™Â ·ÛıÂÓ›˜ Ì ÛÈÙÔÛÙÂÚÔÏ·ÈÌ›· ¤¯ÂÈ ·Ó·ÁÓˆÚÈÛı› ÌÂÙ¿ÏÏ·ÍË ÙÔ˘Ï¿¯ÈÛÙÔÓ ÙÔ˘ ÂÓfi˜ ÂÎ ÙˆÓ ‰‡Ô ÁÔÓȉ›ˆÓ Ô˘ Έ‰ÈÎÔÔÈÔ‡Ó ·˘ÙÔ‡˜ ÙÔ˘˜ ‰‡Ô ÌÂÙ·ÊÔÚ›˜.36,37 √È ·ÛıÂÓ›˜ Ì ÛÈÙÔÛÙÂÚÔÏ·ÈÌ›·, ·ÓÙ›ıÂÙ· Ì ÙÔ˘˜ ÔÈÎÔÁÂÓ›˜ ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌÈÎÔ‡˜, ·ÓÙ·ÔÎÚ›ÓÔÓÙ·È Î·Ï¿ ÛÙÔÓ ÂÚÈÔÚÈÛÌfi Ù˘ ‰È·ÈÙËÙÈ΋˜ ¯ÔÏËÛÙÂÚfiÏ˘ Î·È Ê˘ÙÔÛÙÂÚfiÏ˘. ∏ ÚÔfi‰Ô˜ Ô˘ Û˘ÓÙÂϤÛıËΠٷ ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ÛÙËÓ ÁÔÓȉȷ΋ ·Ó·ÁÓÒÚÈÛË ÙˆÓ ÌÔÓÔÁÔÓÈÎÒÓ ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌÈÒÓ Â›Ó·È ¤Ú·Ó ¿Û˘ ·ÌÊÈ‚ÔÏ›·˜ ÂÓÙ˘ˆÛȷ΋. ¶·Ú·Ì¤ÓÂÈ fï˜ ¤Ó· ÔÛÔÛÙfi 17-33% ·ÛıÂÓÒÓ Ì ¯·Ú·ÎÙËÚÈÛÙÈο ÌÔÓÔÁÔÓÈÎÒÓ ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌÈÒÓ, fiˆ˜ ˘„ËÏ‹ ¯ÔÏËÛÙÂÚfiÏË, ÚÒÈÌË ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ Î·È ÙÂÓfiÓÙÈ· Í·ÓıÒÌ·Ù·39, Ô˘ ‰ÂÓ Â›Ó·È ‰˘Ó·Ùfi Ó· Ù·˘ÙÔÔÈËı› Ì ÙȘ ÁÓˆÛÙ¤˜ ÁÂÓÂÙÈΤ˜ ÌÔÓÔÁÔÓÈΤ˜ ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·È̛˜, Ú¿ÁÌ· Ô˘ ˘·ÈÓ›ÛÛÂÙ·È ÙËÓ Èı·ÓfiÙËÙ· ÂÈÚfiÛıÂÙˆÓ ÁÂÓÂÙÈÎÒÓ ÙfiˆÓ.
¶∞£√ºÀ™π√§√°π∞ μÈ‚ÏÈÔÁÚ·Ê›· 1.
Patsch W, Patsch JR, Gotto AM Jr. The hyperlipoproteinemias. Med. Clin. North America :1989; 73:859-893
2.
Goldstein JL, Brown MS. The LDL receptor locus and the genetics of familial hypercholesterolemia. Ann Rev Genet 1979;13:259-289
3.
Khachadurian AK. The inheritance of essential familial hypercholesterolemia. Am. J. Med. 1964; 37: 402-7
4.
J.Lipid Res 1984; 25: 1450 (Goldstein Brown)
5.
Fouchier SW, Kastelein JJ, Defesche JC. Update of the molecular basis of familial hypercholesterolemia in the Netherlands. Hum Mutat. 2005; 26:550-556
6.
Van Aalst-Cohen ES, Jansen AC, Tanck MW, Defesche JC, Trip MD, Lansberg PJ, Stalenhoef AF, Kastelein JJ. Diagnosing familial hypercholesterolemia : the relevance of genetic testing. Eur Heart J. 2006;27: 2240-2246
7.
Humphries SE, Whittall RA, Hubbart CS, et al .Genetic causes of familial hypercholesterolemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk. J. Med. Genet . 2006; 43: 943-949
8.
9.
Dedousis GVZ, Skoumas J, Pitsavos PC, Choumerianou DM, Genschel J, Schmidt H, Stefanadis C. Familial hypercholesterolemia clinical phenotype in Greek patients withLDL-R defective vs negative mutations . Eur J Clin Invest 2004; 34(6):402-409 Humphries SE, Talmud PS.: Hyperlipidemia associated with genetic variation in the apolipoprotein B gene. Curr. Opin. Lipidol. 1995;6:215-222
10. Vega GL, Grundy SM. In vivo evidence for reduced binding of low density lipoproteins to receptors as a cause of primary moderate hypercholesterolemia. J. Clin Invest 1986;78:1410-1414 11. Soria LF, Ludwig EH, Clarke HR, Vega GL, Grundy SM, McCarthy BJ, : Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100. Proc. Natl.Acad.Sci. USA . 1989;86:587-91 12. Soufi M, Sattler AM, Maerz W, Starke A, Herzum M, Maisch B, Schaefer JR. A new but frequent mutation of apo B-100apo B His 3543 Tyr. Atherosclerosis 2004;174:11-16 13. Fouchier SW, Defesche JC, Kastelein JJ, Sijbrands EJ. Familial defective apolipoprotein B versus familial hypercholesterolemia an assessment of risk. Semin Vasc Med 2004;4:259-264 14. Schaefer JR, Schamagl H, Baumstark MW, Schweez H, Zach LA, Seyberth H, Winkler K, Steinmetz A, Marz W. Homozygous familial defective apolipoprotein B-100 enhanced removal of apo E containing VLDLs and decreased production of LDLs. Arterio Thromb Vasc Biol 1997; 17: 348-353
15. Funke H, Rust S, Seedorf U, Brennhausen B, Chirazi A, Motti C, Assmann G. Homozygosity for FDB is associated with lower plasma cholesterol concentrations than Homozygosity for FH. Circulation 1992; 86: I-691 (Abstract) 16. Abifadel M, Varret M, Rakes JP, Allard D, Dellivers M, et al . Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 2003;34: 154-156 17. Park SW, Moon YA, Horton JD. Post transcriphional regulation of low density lipoprotein receptor protein by proprotein convertase Subtilisin/ kexin type 9a in mouse liver. J. Biol. Chem. 2004;279:50630-38. 18. Maxwell KN, Fisher EA, Breslow JL. Overexpression of PCSK9 accelerates the degradation of the LDLR in a postendoplasmic reticulum compartment. Proc Natl Acad Sci USA 2005;102:20692074 19. Timms KM, Wagner S, Samuels ME, Forben K, et al. A mutation in PCSK9 causing auyosomal-dominant hypercholesterolemia in a Utah pedigree. Hum Genet. 2004;114:349-353. 20. Leren TP. Mutations in the PCSK9 gene in Norvegian subjects with autosomal dominat hypercholesterolemia. Clin Cenet 2004;65:419-422. 21. Haddad L, Day IN, Hunt S, Williams RR, Humphries SE, Hopkins PN. Evidence for a third genetic locus causing familial hypercholesterolemia . A non LDLR, non-Apo B kindred. J Lipid Res. 1999; 40:1113-1122 22. Naumova RP, Tosi I, Patel D, Neuwirth C, Horswell SD, et al. Severe hypercholesterolemia in two British families with the D374Y mutation in the PCSK9 Gene long-term follow-up and treatment response. Arterioscler Thromb Vasc Biol. 2005;25:2654-2660 23. Cohen JC, Boerwinkle E, Mosley Jr TH , Hobbs HH. Sequence variation in PCSK9, low LDL, and protection against coronary heart disease. N, Engl J. Med. 2006;354:1264-1272 24. Khachadurian J, Hobbs H, and Brown M. Familial hypercholesterolemia in the metabolic and molecular bases of inherited disease . C Scriver, A Beauted, W Sly, D Valle, editors. McGraw-Hill. New York, New York, USA 2001;2863-2913 25. Garcia CK, et al. Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL- receptor adaptor protein. Science 2001;292:1394-1398 26. He G. Gupa S, Michaely P, Hobbs HH, Cohen JC. ARH is a modular adaptor protein that interacts with the LDL receptor ,clathrin and AP-2. J. Biol .Chem. 2002; 277: 44044-44049
28. Mishra SK, et al. Functional dissection of the AP-2 beta appendage-binding sequence with the autosomal recessive hypercholesterolemia (ARH) protein. J. Biol. Chem. 2005;280:19270-19280. 29. Garuti R, Jones C, Li WP, Michaely P, et al. The modular adaptor protein autosomal recessive hypercholesterolemia (ARH) promotes low density lipoprotein receptor clustering into clathrin - coated pits J. Biol. Chem. 2005;280:4099641004 30. Harada-Shiba M et al. Siblings with normal LDL receptor activity and severe hypercholesterolemia. Arterioscler Thromb 1992;12:1071-78. 31. Norman D. et al. Characterization of a novel cellular defect in patient with phenotypic homozygous familial hypercholesterolemia. J Clin Invest 1999;104:619-628. 32. Pisciotta L, Oliva CP, Pes GM, DiScala L, et al. Autosomal recessive hypercholesterolemia (ARH) and homozygous familial hypercholesterolemia (FH) a phenotypic comparison. Atheroscleros 2006; 188:398-405 33. Jones C, Garuti R, Michaely P, Li WP, Maeda N, Cohen JC, Vezz J, Hobbs HH. Disruption of LDL but not VLDL clearance in autosomal recessive hypercholesterolemia. J Clin Invest 2007;117:165-174 34. Gould RG , Jones RJ, LeRoy GV, Wissler RW, Tayler CB. Absorbsbility of betasitosterol in humans. Metabolism 1969; 18:652-662 35. Bhattacharayya AK, Connor WE,;Betasitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters. J Clin Invest 1974;53:103345 36. Berge KE, Tiam H, Graf GA, Yu L, Grushin NV, Schultz Z, Kwiterovich P, Shan B, Barnes R, Hobbs HH. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Sience 2000;290:1771-1775 37. Lee MH, Lu K, Hazard S, Yu H, et al. Indentig=fication of a \gene , ABC G5, important in the regulation of dieta-rycholesterol absorption. Nat. Genet. 2001; 27: 79-83 38. Hazard SE, Patel SB, : Sterolins ABC G5 and ABC G8 : regulators of whole body dietary sterols. Pflugers Arch 2007: 453;745-752 39. 1991 Risk of fatal coronary heart disease in FH. Scientific Steering Committee on behalf of the Simon Broome Register Group. BMJ 303:893-896.
27. Mishra SK, Watkins SC, Traub ,LM. The autosomal recessive hypercholesterolemia (ARH) protein interfaces directly with the clathrin - coat machinery. Proc Natl Acad Sci USA. 2002;99:16099-16104.
19
ª∞ƒΔπ√™ 2008
¶ÚfiˆÚË ¢È·ÎÔ‹ Ù˘ ÀÔÏÈȉ·ÈÌÈ΋˜ º·Ú̷΢ÙÈ΋˜ ∞ÁˆÁ‹˜ : ∞›ÙÈ· Î·È ∞ÔÙÂϤÛÌ·Ù· μ. Õı˘ÚÔ˜, ∞. ∫·Î·Ê‹Î·, ∂. ¶·ÁÎÔ˘Ú¤ÏÈ·˜, ∫. Δ˙ÈfiÌ·ÏÔ˜, ¶. ∞Ó·ÁÓˆÛÙ‹˜, π. °È·‚·Ó›‰Ë˜, Ã. ∫Ô˘Ì·Ú¿˜, ∞. ∫·Ú·ÁÈ¿ÓÓ˘. μ’ ¶ÚÔ·È‰Â˘ÙÈ΋ ¶·ıÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ∞ÚÈÛÙÔÙ¤ÏÂÈÔ ¶·ÓÂÈÛÙ‹ÌÈÔ £ÂÛÛ·ÏÔӛ΢, °¶¡ «π¶¶√∫ƒ∞Δ∂π√»
™ÙÔ ¶·ÓÂ˘Úˆ·˚Îfi ∫·Ú‰ÈÔÏÔÁÈÎfi ™˘Ó¤‰ÚÈÔ ÛÙË μȤÓÓË Ù˘ ∞˘ÛÙÚ›·˜, ÛÙȘ 2 ™Â 2007, ·Ó·ÎÔÈÓÒıËÎ·Ó Ù· ·ÔÙÂϤÛÌ·Ù· Ù˘ ¶·ÓÂ˘Úˆ·˚΋˜ ªÂϤÙ˘ EUROASPIRE III, Ë ÔÔ›· ‰ÈÂÓÂÚÁ‹ıËΠ·fi ÙÔ˘˜ ÊÔÚ›˜ Ù˘ ∂˘Úˆ·˚΋˜ ŒÓˆÛ˘ Ô˘ ··ÚÙ›˙Ô˘Ó ÙÔ European Heart Health Charter, ÌÂٷ͇ ÙˆÓ ÔÔ›ˆÓ Î·È Ë ∂˘Úˆ·˚΋ ∫·Ú‰ÈÔÏÔÁÈ΋ ∂Ù·ÈÚ›·. ∏ ÌÂϤÙË ·˘Ù‹ ·Ó·Ê¤ÚÂÙ ÛÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ·Ú·ÁfiÓÙˆÓ ÎÈÓ‰‡ÓÔ˘ Ù˘ ηډȷÁÁÂȷ΋˜ ÓfiÛÔ˘ (∫∞¡). Δ· ·ÔÙÂϤÛÌ·Ù¿ Ù˘ Û˘ÁÎÚ›ıËÎ·Ó Ì ·˘Ù¿ ÙˆÓ ÌÂÏÂÙÒÓ EUROASPIRE I & II Ô˘ ÚÔËÁ‹ıËηÓ. ™ÙË EUROASPIRE IIπ ÏÔÈfiÓ ‰È·ÈÛÙÒıËΠ·‡ÍËÛË ÛÙÔÓ ·ÚÈıÌfi ·ÛıÂÓÒÓ Ô˘ ‹Ù·Ó ·¯‡Û·ÚÎÔÈ (¢ª™>30) Û ÔÛÔÛÙfi 38% ¤Ó·ÓÙÈ 32% & 25% ÙˆÓ EUROASPIRE II & I, ·ÓÙ›ÛÙÔȯ·, ˘¤Ú‚·ÚÔÈ (¢ª™=25-30) Û ÔÛÔÛÙfi 83% ¤Ó·ÓÙÈ 80% & 77% ‹ ›¯·Ó ÎÂÓÙÚÈ΋ ·¯˘Û·ÚΛ· (55% ¤Ó·ÓÙÈ 53% & 42%). √È ‰È·‚ËÙÈÎÔ› Ù‡Ô˘ 2 ·˘Í‹ıËÎ·Ó Â›Û˘ ÛËÌ·ÓÙÈο (28% ¤Ó·ÓÙÈ 20% & 17%) Î·È Â›¯·Ó ¯ÂÈÚfiÙÂÚË Ú‡ıÌÈÛË (ÌfiÓÔ ÛÙÔ 7% ¤Ó·ÓÙÈ 25% & 25% Ú˘ıÌ›˙ÔÓÙ·Ó Ë ÁÏ˘Îfi˙Ë ÓËÛÙ›·˜) Î·È Ù¤ÏÔ˜ ÔÈ ˘ÂÚÙ·ÛÈÎÔ› ·ÛıÂÓ›˜ ‹Ù·Ó Û·ÊÒ˜ ÂÚÈÛÛfiÙÂÚÔÈ (61% ¤Ó·ÓÙÈ 58% & 58%), ÂÓÒ ÙÔ ÔÛÔÛÙfi Ú‡ıÌÈÛ˘ Ù˘ ·ÚÙËÚȷ΋˜ ˘¤ÚÙ·Û˘ ÂÏ·ÙÙÒıËΠ(39% ¤Ó·ÓÙÈ 41% & 41%). ŸÏ· ·˘Ù¿ ‰Â›¯ÓÔ˘Ó ÌÈ· Û·Ê‹ ·ÔÙ˘¯›· ÙˆÓ ÚÔÏËÙÈÎÒÓ ÛÙÚ·ÙËÁÈÎÒÓ Ô˘ ·ÎÔÏÔ˘ı‹ıËÎ·Ó ÛÙ· Ï·›ÛÈ· ‰Â˘ÙÂÚÔÁÂÓÔ‡˜ ÚfiÏ˄˘ Ù˘ ∫∞¡ ·fi ÙÔ European Heart Health Charter. ∞fi ÙȘ ıÂÙÈΤ˜ ‰È·ÈÛÙÒÛÂȘ ‹Ù·Ó fiÙÈ Ô ·ÚÈıÌfi˜ ÙˆÓ Î·ÓÈÛÙÒÓ ÂÏ·ÙÙÒıËΠ·ÏÏ¿ ÌfiÓÔ Î·-
20
Ù¿ ¤Ó· ÌÈÎÚfi ÔÛfi (18% ¤Ó·ÓÙÈ 21% & 20% ÙˆÓ EUROASPIRE II & I) Î·È fiÙÈ Ë LDL-X Ú˘ıÌ›ÛÙËÎÂ, Û‡Ìʈӷ Ì ÙȘ Ô‰ËÁ›Â˜, ÛËÌ·ÓÙÈο ÂÚÈÛÛfiÙÂÚÔ ·fi fiÙÈ ÛÙȘ ‰‡Ô ¿ÏϘ EUROASPIRE (57% ¤Ó·ÓÙÈ 29% & 8%). ∏ Ú‡ıÌÈÛË ·˘Ù‹ fï˜ ‹Ù·Ó Ôχ Ì·ÎÚÈ¿ ·fi ÙÔ Ó· ¯·Ú·ÎÙËÚÈÛÙ› ˆ˜ ÈηÓÔÔÈËÙÈ΋, ÂȉÈο Û ·ÛıÂÓ›˜ ‰Â˘ÙÂÚÔÁÂÓÔ‡˜ ÚfiÏ˄˘ (·ÔÚÙÔÛÙÂÊ·ÓÈ·›· ·Ú¿Î·Ì„Ë 28%, ·ÁÁÂÈÔÏ·ÛÙÈ΋ 50%, ¤ÌÊÚ·ÁÌ· Ì˘Ôηډ›Ô˘ 10% Î·È ÛÙËı¿Á¯Ë 12%). ªÈ· ·fi ÙȘ ÛËÌ·ÓÙÈΤ˜ ·Èٛ˜ Ù˘ ÌË ÈηÓÔÔÈËÙÈ΋˜ (·Ú¿ ÙË ‚ÂÏÙ›ˆÛË) ·ÓÙÈÌÂÙÒÈÛ˘ Ù˘ ‰˘ÛÏÈȉ·ÈÌ›·˜ ÛÙ· Ï·›ÛÈ· Ù˘ ÚˆÙÔÁÂÓÔ‡˜ Î·È ‰Â˘ÙÂÚÔÁÂÓÔ‡˜ ÚfiÏ˄˘ Ù˘ ∫∞¡ Â›Ó·È Ë ·Ó·›ÙÈ· Î·È ÚfiˆÚË ‰È·ÎÔ‹ Ù˘ ˘ÔÏÈȉ·ÈÌÈ΋˜ Ê·Ú̷΢ÙÈ΋˜ ·ÁˆÁ‹˜ (Û˘Ó‹ıˆ˜ ÛÙ·Ù›Ó˘). °È· Ó· ηٷÛÙ› ‰˘Ó·Ù‹ Ë ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ ÚÔ‚Ï‹Ì·ÙÔ˜ ·˘ÙÔ‡ Ú¤ÂÈ ÚÒÙ· Ó· ÂÓÙÔÈÛÙÔ‡Ó Ù· ·›ÙÈ· Î·È ÌÂÙ¿ Ó· ÂÓËÌÂÚˆıÔ‡Ó ÔÈ ıÂÚ¿ÔÓÙ˜ π·ÙÚÔ› Î·È ÔÈ º·ÚÌ·ÎÔÔÈÔ›, Ô˘ Ô˘ÛÈ·ÛÙÈο ı· Â›Ó·È ÔÈ Î·ÙËÁÔڛ˜ ∂ÈÛÙËÌfiÓˆÓ ÀÁ›·˜ Ô˘ ı· ‚ÔËı‹ÛÔ˘Ó ÛÙËÓ Â›Ï˘ÛË ÙÔ˘ ÚÔ‚Ï‹Ì·ÙÔ˜. 1. ∏ÏÈΛ·. ∏ Ó·ڋ ËÏÈΛ· Û¯ÂÙ›˙ÂÙ·È Ì ÂÏ·Ùو̤ӷ ÔÛÔÛÙ¿ Û˘ÌÌfiÚʈÛ˘. 2. º‡ÏÔ. √È Á˘Ó·›Î˜ ·ÈÛı¿ÓÔÓÙ·È ÏÈÁfiÙÂÚÔ Â˘¿ÏˆÙ˜ ÛÙ· ∫∞¡ Î·È ‰È·ÎfiÙÔ˘Ó ÙȘ ÛÙ·Ù›Ó˜ ÈÔ Â‡ÎÔÏ·. 3. ¶ÚˆÙÔÁÂÓ‹˜ ÚfiÏË„Ë. ∞ÛıÂÓ›˜ Ô˘ ‰ÂÓ Â›¯·Ó ¤Ó· ∫∞ ۇ̂·Ì· Ù›ÓÔ˘Ó Ó· ÌËÓ Â›ıÔÓÙ·È Â‡ÎÔÏ· ÁÈ· ÙËÓ ·Ó·ÁηÈfiÙËÙ· ÌÈ·˜ ‰È· ‚›Ô˘ ıÂڷ›·˜, ÂÊfiÛÔÓ ‰ÂÓ ¤¯Ô˘Ó η̛· ÂÓfi¯ÏËÛË Î·È ‰ÂÓ ·ÓÙÈÏ·Ì‚¿ÓÔÓÙ·È fiÓÔ, ·ÈÌÔÚÚ·Á›· ‹
¿ÏÏÔ Û‡Ìو̷ Ô˘ ı· ÙÔ˘˜ ıÔÚ˘‚Ô‡ÛÂ. 4. ∂ÌÂÈÚ›· È·ÙÚÔ‡. ∂¿Ó Ô È·ÙÚfi˜ ¤¯ÂÈ <100 ·ÛıÂÓ›˜ Ô˘ ¯ÚÂÈ¿˙ÔÓÙ·È ˘ÔÏÈȉ·ÈÌÈ΋ Ê·Ú̷΢ÙÈ΋ ·ÁˆÁ‹ ‰ÂÓ ¤¯ÂÈ Î·Ù¿ ÙÂÎÌ‹ÚÈÔ ÙËÓ ··Ú·›ÙËÙË ÂÌÂÈÚ›· ÁÈ· Ó· ÙÔ˘˜ ›ÛÂÈ Ó· ¿ÚÔ˘Ó ÌÈ· ‰È· ‚›Ô˘ ıÂڷ›·, ÂȉÈο ÛÙËÓ ÚˆÙÔÁÂÓ‹ ÚfiÏË„Ë. 5. ÃÚfiÓÔ˜ Ô˘ ‰È·ı¤ÙÂÈ Ô È·ÙÚfi˜ ÁÈ· ÙÔÓ ·ÛıÂÓ‹. ∂›Ó·È ÛËÌ·ÓÙÈÎfi ÙË ÚÒÙË Ë̤ڷ Ó· ‰È·ı¤ÛÂÈ Ì›· ÔÏfiÎÏËÚË ˆÚÔÏÔÁȷ΋ ÒÚ·. √Ùȉ‹ÔÙ ÏÈÁfiÙÂÚÔ (π∫∞ ̤ÛÔ˜ ¯ÚfiÓÔ˜ ÂͤٷÛ˘ 10 min) ¤¯ÂÈ ÂÏ¿¯ÈÛÙ˜ Èı·ÓfiÙËÙ˜ Ó· ÂÈÙ‡¯ÂÈ. 6. ∫·Ù·Ó¿ÏˆÛË ÔÈÓÔÓ‡̷ÙÔ˜. √È Ï·Ì‚¿ÓÔÓÙ˜ ÛÙ·Ù›Ó˜ ÁÓˆÚ›˙Ô˘Ó fiÙÈ ÌÔÚ› ·˘Ù¤˜ Ó· ÚÔηϤÛÔ˘Ó ·‡ÍËÛË ÙˆÓ ÙÚ·ÓÛ·ÌÈÓ·ÛÒÓ. ∂¿Ó ÏÔÈfiÓ Â›Ó·È fiÙ˜ ·ÔʇÁÔ˘Ó Ó· ·›ÚÓÔ˘Ó ÙË ÛÙ·Ù›ÓË fiÙ·Ó ÚfiÎÂÈÙ·È Ó· ηٷӷÏÒÛÔ˘Ó ÔÈÓfiÓÂ˘Ì· ÁÈ· Ó· ·ÔʇÁÔ˘Ó ÙË Û˘ÓÂÚÁÈ΋ ‰Ú¿ÛË ÛÙ·Ù›Ó˘ÔÈÓÔÓ‡̷ÙÔ˜ ÛÙÔ ‹·Ú. 7. ∫fiÛÙÔ˜ ıÂڷ›·˜. ∞˘Ùfi ÛÙËÓ ∂ÏÏ¿‰· ‰ÂÓ ·ÔÙÂÏ› Ôχ ÛËÌ·ÓÙÈ΋ ·ÈÙ›· ÌË Û˘ÌÌfiÚʈÛ˘ ÁÈ·Ù› Ë Û˘ÌÌÂÙÔ¯‹ ÙÔ˘ ·ÛıÂÓÔ‡˜ Â›Ó·È ÌfiÓÔ 10%. ™Â ·Ó·ÛÊ¿ÏÈÛÙÔ˘˜ Î·È ÂÊ' fiÛÔÓ ÙÔ ÌËÓÈ·›Ô ÎfiÛÙÔ˜ Ê·ÚÌ¿ÎˆÓ Â›Ó·È ˘„ËÏfiÙÂÚÔ ÙˆÓ 10 ˘¿Ú¯ÂÈ Úfi‚ÏËÌ·. 8. ΔÔ ÂÚÈ‚¿ÏÏÔÓ ÙÔ˘ ·ÛıÂÓÔ‡˜. ªÔÚ› Ó· ÏÂÈÙÔ˘ÚÁ‹ÛÂÈ ·ÚÓËÙÈο. À¿Ú¯ÂÈ, ÁÈ· ÏfiÁÔ˘˜ Ô˘ ‰ÂÓ Â›Ó·È ÁÓˆÛÙÔ›, ˘ÂÚ‚ÔÏÈÎfi˜ Êfi‚Ô˜ ÁÈ· ÙȘ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ ÙˆÓ ÛÙ·ÙÈÓÒÓ, ΢ڛˆ˜ ÁÈ· ÙËÓ ÙÚ·ÓÛ·ÌÈÓ·ÈÌ›· [·˘Ù‹ ÂÌÊ·Ó›˙ÂÙ·È Û ·ıÔÏÔÁÈο ›‰· (>3 Ã
£EPA¶EIA - ºAPMAKA ∞º√) ÛÙÔ 1% ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ·›ÚÓÔ˘Ó ÛÙ·Ù›Ó˜]. ∂ȉÈο ÛÙË ÂÚ›ÙˆÛË Ô˘ Ô ·ÛıÂÓ‹˜ ¤¯ÂÈ È¿ÛÂÈ ÙÔ ÛÙfi¯Ô Ù˘ LDL-X fiÏÔÈ ÙÔÓ ·ÚÔÙÚ‡ÓÔ˘Ó Ó· ‰È·Îfi„ÂÈ ÙË ÛÙ·Ù›ÓË «ÙÒÚ· Ô˘ ¤ÂÛÂ Ë ¯ÔÏËÛÙÂÚ›ÓË» Î·È «ÚÈÓ ÙÔ ¯¿È ÛÔ˘ ¯·Ï¿ÛÂÈ ÙÔ Û˘ÎÒÙÈ».
ÙË Û˘ÌÌfiÚʈÛË, ÂÎÙfi˜ Â¿Ó Â›Ó·È ¿Ú· ÔÏÏ¿, ÔfiÙ ÙËÓ ÂÏ·ÙÙÒÓÂÈ. √ ·ÛıÂÓ‹˜ ·ÓÙÈÏ·Ì‚¿ÓÂÙ·È fiÙÈ Ú¤ÂÈ Ó· ¿ÚÂÈ ÔÚÈṲ̂ӷ Ê¿Ú̷η ·ÏÏ¿ fi¯È Î·È 10 ‹ ÂÚÈÛÛfiÙÂÚ· ¯¿È· ÙËÓ Ë̤ڷ. ∂Λ Ô ·ÛıÂÓ‹˜ ·Ú¯›˙ÂÈ Ó· Îfi‚ÂÈ ¯¿È· «Î·È fiÔÈÔÓ ¿ÚÂÈ Ô ¯¿ÚÔ˜».
°È· ÙÔ˘˜ ·Ú·¿Óˆ ÏfiÁÔ˘˜ Ô Ì¤ÛÔ˜ ¯ÚfiÓÔ˜ Ï‹„˘ ÛÙ·ÙÈÓÒÓ Î·Ù' ¤ÙÔ˜ Â›Ó·È 10 Ì‹Ó˜. ∞˘Ùfi ÚÔ·ÙÂÈ ˆ˜ ̤ÛÔ˜ fiÚÔ˜ ·fi ·ÛıÂÓ›˜ Ô˘ ÙÔ ¤·ÈÚÓ·Ó Û˘Ó¤¯ÂÈ· (12 Ì‹Ó˜) Î·È ·˘ÙÒÓ Ô˘ ¤·ÈÚÓ·Ó ÛÙ·Ù›Ó˜ ÌfiÓÔ 3-4 Ì‹Ó˜.
¶fiÛÔ ÛËÌ·ÓÙÈ΋ fï˜ Â›Ó·È Ë Û˘ÌÌfiÚʈÛË ÛÙËÓ ˘ÔÏÈȉ·ÈÌÈ΋ ·ÁˆÁ‹ Î·È ÙËÓ ‰È¢ÎfiÏ˘ÓÛË ˆ˜ ÂÎ ÙÔ‡ÙÔ˘ ›Ù¢Í˘ ÙÔ˘ ıÂڷ¢ÙÈÎÔ‡ ÛÙfi¯Ô˘;
À¿Ú¯Ô˘Ó ‚¤‚·È· Î·È ÏfiÁÔÈ Ô˘ ÌÔÚ› Ó· ·˘Í‹ÛÔ˘Ó ÙË Û˘ÌÌfiÚʈÛË ‹ Ó· ‚ÔËı‹ÛÔ˘Ó ÛÙËÓ Â·Ó¤Ó·ÚÍË ÌÈ·˜ ·Ó·ÈÙ›ˆ˜ ‰È·ÎÔ›۷˜ ıÂڷ›·˜. 1. ∏ ÚÔËÁÔ‡ÌÂÓË ˘ÔÏÈȉ·ÈÌÈ΋ ·ÁˆÁ‹. ∂¿Ó ÌÂÙ¿ ÙË ‰È·ÎÔ‹ ÚÔËÁÔ‡ÌÂÓ˘ ıÂڷ›·˜ Ì ÛÙ·Ù›Ó˜ Ô ·ÛıÂÓ‹˜ ‰È·ÈÛÙÒÓÂÈ ÌÂÁ¿ÏË ·‡ÍËÛË ÙˆÓ ÏÈȉ›ˆÓ, Ô˘ ÌÂÚÈΤ˜ ÊÔÚ¤˜ Ù· ›‰¿ ÙÔ˘˜ Â›Ó·È ˘„ËÏfiÙÂÚ· ·fi Ù· ·Ú¯Èο, ›ıÂÙ·È Â‡ÎÔÏ· Ó· Í·Ó·Ú¯›ÛÂÈ ÙËÓ ˘ÔÏÈȉ·ÈÌÈ΋ Ê·Ú̷΢ÙÈ΋ ·ÁˆÁ‹. 2. ∏ ÓÔÛËÏ›· ÁÈ· ∫∞¡ ·˘Í¿ÓÂÈ ÙË Èı·ÓfiÙËÙ· ·ӤӷÚ͢. ∂¿Ó Ô ·ÛıÂÓ›˜ ÓÔÛËÏ¢Ù› ÛÙÔ ¡ÔÛÔÎÔÌÂ›Ô Ì ÂÂÈÛfi‰ÈÔ ∫∞¡ ·ÓÙÈÏ·Ì‚¿ÓÂÙ·È fiÙÈ Èı·ÓfiÓ Ë Ì›· ·fi ÙȘ ·Èٛ˜ Ô˘ Û˘Ó¤‚Ë ·˘Ùfi ‹Ù·Ó Ë ‰È·ÎÔ‹ ÙˆÓ ˘ÔÏÈȉ·ÈÌÈÎÒÓ Ê·ÚÌ¿ÎˆÓ Î·È Â›ıÂÙ·È Ó· Ù· ·Ú¯›ÛÂÈ Î·È ¿ÏÈ ÌÂÙ¿ ÙËÓ ¤ÍÔ‰Ô ·fi ÙÔ ¡ÔÛÔÎÔÌ›Ô. 3. ∏ Ï‹„Ë ¿ÏÏˆÓ Ê·ÚÌ¿ÎˆÓ ÁÈ· ÙËÓ ÚfiÏË„Ë Ù˘ ∫∞¡ ·˘Í¿Ó›
À¿Ú¯ÂÈ ÌÂϤÙË Ô˘ ÚÔ¤Ú¯ÂÙ·È ·fi ÙÔ ∫·Ó·‰¿ Î·È Ë ÔÔ›· ˘ÔÏfiÁÈÛ ÙËÓ Â›ÙˆÛË Ù˘ ÌË Û˘ÌÌfiÚʈÛ˘ Û ıÂڷ›· Ì ÛÙ·Ù›Ó˜. ∞˘Ù‹ ÂÚȤϷ‚ 1.056 ·ÛıÂÓ›˜ Î·È ÙÔ˘˜ ·Ú·ÎÔÏÔ‡ıËÛ ÁÈ· ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· ÂÓfi˜ ¤ÙÔ˘˜ ÌÂÙ¿ ·fi ¤ÌÊÚ·ÁÌ· Ì˘Ôηډ›Ô˘, ·ÛÙ·ı‹ ÛÙËı¿Á¯Ë, ÈÛ¯·ÈÌÈÎfi ·ÁÁÂÈ·Îfi ÂÁÎÂÊ·ÏÈÎfi ÂÂÈÛfi‰ÈÔ, ·ÁÁÂÈÔÏ·ÛÙÈ΋ ‹ ·ÔÚÙÔÛÙÂÊ·ÓÈ·›· ·Ú¿Î·Ì„Ë. √È ·ÛıÂÓ›˜ Ô˘ ÂÊ¿ÚÌÔ˙·Ó ÛˆÛÙ¿ ÙȘ Ô‰ËÁ›Â˜ Î·È ‰ÂÓ ‰È¤ÎÔ„·Ó ·Ó·›ÙÈ· ÙË ÛÙ·Ù›ÓË Â›¯·Ó ÙÔ ÌÈÛfi ΛӉ˘ÓÔ (-55%) Ó· ¿ıÔ˘Ó ¤Ó· ‰Â‡ÙÂÚÔ ÂÂÈÛfi‰ÈÔ (.¯. ¤ÌÊÚ·ÁÌ· ÙÔ˘ Ì˘Ôηډ›Ô˘) ·fi fiÙÈ ÔÈ ·ÛıÂÓ›˜ Ù˘ ÔÌ¿‰·˜ Ô˘ ‰È¤ÎÔ„Â ÙÔ Ê¿ÚÌ·ÎÔ (·Ó·ÏÔÁ›· ÎÈÓ‰‡ÓÔ˘ [OR] 0.45, ‰È¿ÛÙËÌ· ÂÌÈÛÙÔÛ‡Ó˘ 95% [CI] 0.20-0.99, p=0.047). ™ÙÔ˘˜ ·ÛıÂÓ›˜ οو ÙˆÓ 65 ÂÙÒÓ Ë Û¯ÂÙÈ΋ Ì›ˆÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ‰Â‡ÙÂÚÔ ¤ÌÊÚ·ÁÌ· Ì˘Ôηډ›Ô˘ ‹Ù·Ó ·ÎfiÌ· ÌÂÁ·Ï‡ÙÂÚË (-86%, OR 0.14, 95% CI 0.04-0.46, p=0.001) Î·È Û˘Óԉ‡ıËΠ·fi ÌÈ· Ù¿ÛË ÁÈ· ÌÈ· ¯·ÌËÏfiÙÂÚË Û˘¯ÓfiÙËÙ· ÂÌÊ¿ÓÈÛ˘ Ù˘ ·ÛÙ·ıÔ‡˜ ÛÙËı¿Á¯Ë˜
(-63%, OR 0.37, 95% CI 0.131.03, p=0.06). ™ÙÔȯ›· ·fi ÙË ÌÂϤÙË PRISM (Platelet Receptor Inhibition in Ischemic Syndrome Management), Ô˘ ÂÚȤϷ‚ ·ÛıÂÓ›˜ Ì Ôͤ· ÛÙÂÊ·ÓÈ·›· Û‡Ó‰ÚÔÌ·, ‰Â›¯ÓÔ˘Ó fiÙÈ Ë ÚÒÈÌË ‰È·ÎÔ‹ Ù˘ ÛÙ·Ù›Ó˘ Û¯ÂÙ›˙ÂÙ Ì 3Ï¿ÛÈ· ·‡ÍËÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÁÈ· Ó¤Ô Û‡Ì‚·Ì·, ÂÓÒ Û ·˘ÙÔ‡˜ Ô˘ ‰ÂÓ ‹Ú·Ó ηıfiÏÔ˘ ÛÙ·Ù›ÓË Ô Î›Ó‰˘ÓÔ˜ ‹Ù·Ó ηٿ 1,6 ÊÔÚ¤˜ ÌÂÁ·Ï‡ÙÂÚÔ˜. ™ÙÔȯ›· ·fi ÙË ÌÂϤÙË Global Registry of Acute Coronary Events (GRACE) Ô˘ ›Û˘ ÂÚȤϷ‚ ·ÛıÂÓ›˜ Ì Ôͤ· ÛÙÂÊ·ÓÈ·›· Û‡Ó‰ÚÔÌ·, ‰Â›¯ÓÂÈ fiÙÈ Ë ÚÒÈÌË ‰È·ÎÔ‹ Ù˘ ÛÙ·Ù›Ó˘ Û¯ÂÙ›˙ÂÙ Ì ‰ÈÏ¿ÛÈ· ¤ˆ˜ ÙÂÙÚ·Ï¿ÛÈ· ·‡ÍËÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÁÈ· Ó¤Ô Û‡Ì‚·Ì·. ∂Ô̤ӈ˜, ˘¿Ú¯ÂÈ ·fi‰ÂÈÍË fiÙÈ Ë ÂÊ·ÚÌÔÁ‹ ÙˆÓ ıÂڷ¢ÙÈÎÒÓ Ô‰ËÁÈÒÓ Î·È Ë ÌË ‰È·ÎÔ‹ Ù˘ ÛÙ·Ù›Ó˘ Ô‰ËÁ› Û ÛËÌ·ÓÙÈο ÎÏÈÓÈο ÔʤÏË ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ Û˘ÌÌÔÚÊÒÓÔÓÙ·È Ì ÙȘ Ô‰ËÁ›Â˜ ÁÈ· ıÂڷ›·. ∂›Ó·È ÏÔÈfiÓ Î˘Ú›ˆ˜ ÔÈ ÂÓ¤ÚÁÂȘ ÙˆÓ ıÂÚ·fiÓÙˆÓ È·ÙÚÒÓ Ô˘ Ô˘ÛÈ·ÛÙÈο ı· ›ÛÔ˘Ó ÙÔÓ ·ÛıÂÓ‹ Ó· Û˘Ó¯›ÛÂÈ ÙËÓ ˘ÔÏÈȉ·ÈÌÈ΋ Ê·Ú̷΢ÙÈ΋ ·ÁˆÁ‹ Ì ÛÙ·Ù›Ó˜. ∂¿Ó ÙÂÏÈο ÂÈÙ¢¯ı› ‚·ıÌfi˜ Û˘ÌÌfiÚʈÛ˘ ÛÙËÓ ˘ÔÏÈȉ·ÈÌÈ΋ ·ÁˆÁ‹ Û ‚·ıÌfi ÂÚ›Ô˘ 90% ·˘Ùfi ı· Ô‰ËÁ‹ÛÂÈ Û ηχÙÂÚË ÔÈfiÙËÙ· ÂÚ›ı·Ï„˘ ÙˆÓ ·ÛıÂÓÒÓ Î·È ı· ÂÏ·¯ÈÛÙÔÔÈ‹ÛÂÈ ÙÔ Î›Ó‰˘ÓÔ ÙÔ˘ ηډȷÁÁÂÈ·ÎÔ‡ ı·Ó¿ÙÔ˘ ‹ ÙÔ˘ ÌË ı·Ó·ÙËÊfiÚÔ˘ ηډȷÁÁÂÈ·ÎÔ‡ ÂÂÈÛÔ‰›Ô˘.
μÈ‚ÏÈÔÁÚ·Ê›· 1. Wood, AD, et al. Clinical reality of coronary prevention in Europe: A comparison of EUROASPIRE I, II and III surveys. Cardiovascular Disease Prevention - Risk Assessment and Management, ESC Congress 2007, Vienna, Austria, 2 September 2007. 2. Ellis JJ, Erickson SR, Stevenson JG, Bernstein SJ, Stiles RA, Fendrick AM. Suboptimal statin adherence and discontinuation in primary and secondary prevention populations. J Gen Intern Med 2004;19:638-645. 3. Caspard H, Chan AK, Walker AM. Compliance with a statin treatment in a usual-care setting:Retrospective databa-
se analysis over 3 years after treatment initiation in health maintenance organization enrollees with dyslipidemia. Clinical Therapeutics 2005;27: 1639-1646 4. Brookhart MA, Patrick AR, Schneeweiss S, Avorn J, Dormuth C, Shrank W, van Wijk BL, Cadarette SM, Canning CF, Solomon DH. Physician follow-up and provider continuity are associated with long-term medication adherence: a study of the dynamics of statin use. Arch Intern Med 2007;167:847-852. 5. Blackburn DF, Dobson RT, Blackburn JL, Wilson TW. Cardiovascular morbidity associated with nonadherence to statin therapy. Pharmacotherapy 2005;25:1035-1043.
6. Heeschen C, Hamm CW, Laufs U, Snapinn S, Böhm M, White HD; Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Investigators. Withdrawal of statins increases event rates in patients with acute coronary syndromes. Circulation 2002;105:1446-1452. 7. Cubeddu LX, Seamon MJ. Statin withdrawal: clinical implications and molecular mechanisms. Pharmacotherapy 2006;26:1288-1296. 8. Wald DS, Morton G, Walker K, Iosson N, Curzen NP. Long-term continuation on cardiovascular drug treatment in patients with coronary heart disease. Ann Pharmacother 2007;41:1644-1647.
21
ª∞ƒΔπ√™ 2008
ªË ∫·Ú‰È·Î¤˜ ∂Á¯ÂÈÚ‹ÛÂȘ Û ∞ÛıÂÓ›˜ Ì πÛÙÔÚÈÎfi ∞ÁÁÂÈÔÏ·ÛÙÈ΋˜ ÙˆÓ ™ÙÂÊ·ÓÈ·›ˆÓ ∞ÚÙËÚÈÒÓ °ÂÒÚÁÈÔ˜ ªÔÌfiÙ˘: ∞Ó·Ï. ¢È¢ı˘ÓÙ‹˜ ∞ÈÌÔ‰˘Ó·ÌÈÎÔ‡ ∂ÚÁ·ÛÙËÚ›Ô˘ ¡ÔÛÔÎÔÌ›Ԣ ¶··ÁˆÚÁ›Ô˘, £ÂÛÛ·ÏÔÓ›ÎË
°È¿ÓÓ˘ °Ô˘‰¤‚ÂÓÔ˜: ∫·ıËÁËÙ‹˜ ∫·Ú‰ÈÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ H ·ÁÁÂÈÔÏ·ÛÙÈ΋ ÙˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ ·ÚÙËÚÈÒÓ Â›Ó·È Ë ÈÔ Û˘¯Ó‹ ̤ıÔ‰Ô˜ ·ӷÁÁ›ˆÛ˘ ÙÔ˘ Ì˘Ôηډ›Ô˘. ™ÙȘ ∏¶∞ Á›ÓÔÓÙ·È ÂÚ›Ô˘ 1 ÂηÙÔÌ̇ÚÈÔ ·ÁÁÂÈÔÏ·ÛÙÈΤ˜ Î·È 350.000 Bypass ÙÔ ¯ÚfiÓÔ. ™ÙË ¯ÒÚ· Ì·˜ Á›ÓÔÓÙ·È ÂÚ›Ô˘ 20.000 ·ÁÁÂÈÔÏ·ÛÙÈΤ˜ Î·È 12.000 Bypass ÙÔ ¯ÚfiÓÔ. ™ÙÔ Û‡ÓÔÏÔ ÙˆÓ ÂÚÈÙÒÛÂˆÓ ·ÁÁÂÈÔÏ·ÛÙÈ΋˜ Á›ÓÂÙ·È Î·È Ù·˘Ùfi¯ÚÔÓË ÂÌʇÙ¢ÛË stent. Δ· stents ‰È·ÎÚ›ÓÔÓÙ·È Û Á˘ÌÓ¿, ÁÓˆÛÙ¿ Û·Ó BMS (μare Metal Stent) ‹ ÂÈÎ·Ï˘Ì̤ӷ Ô˘ ÂÎÏ‡Ô˘Ó Ê¿ÚÌ·ÎÔ (Ú··Ì˘Î›ÓË Î·È ·ÎÏÈٷͤÏË) ÁÓˆÛÙ¿ Û·Ó DES (Drug Eluting Stents). ™ÙË ÌÂÁ¿ÏË ÏÂÈÔÓfiÙËÙ·, ·Ó¿ÏÔÁ· Ì ÙË ¯ÒÚ· ‹ ÙÔ Î¤ÓÙÚÔ, ÂÌÊ˘Ù‡ÔÓÙ·È DES (ÙÂÏÂ˘Ù·›· Ë Û˘¯ÓfiÙËÙ· ·fi 90% ¤¯ÂÈ ÌÂȈı› ÛÙÔ 70% ). ¶·Ú¿ ÙË ÙˆÙÈ΋ Ù¿ÛË ÛÙË ¯Ú‹ÛË ÙˆÓ DES, ÙÔ Â›‰Ô˜ ÙˆÓ ·ÛıÂÓÒÓ Ô˘ Ù· ¯ÚÂÈ¿˙ÔÓÙ·È ‰ÂÓ Â›Ó·È Î·Ï¿ ‰È¢ÎÚÈÓÈṲ̂ÓÔ. ΔÂÏÂ˘Ù·›· ÙÔ ı¤Ì· Ù˘ ·ÛÊ¿ÏÂÈ·˜ Î·È ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜ ·˘ÙÒÓ ÙˆÓ ‰‡Ô Ù‡ˆÓ stent Â›Ó·È ÙÔ ÈÔ ÔÏ˘Û˘˙ËÙË̤ÓÔ ı¤Ì· ÛÙËÓ ÂÂÌ‚·ÙÈ΋ ηډÈÔÏÔÁ›·. ∂Ó‰ÂÈÎÙÈÎfi ·˘Ùo‡ ÙÔ˘ ÂӉȷʤÚÔÓÙÔ˜ Â›Ó·È ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ì¤¯ÚÈ ÙÒÚ· (¢ÂΤ̂Ú˘ 2007) ¤¯Ô˘Ó ‰ËÌÔÛÈ¢ı› ÂÚÈÛÛfiÙÂÚ˜ ·fi 40 ÌÂÙ··Ó·Ï‡ÛÂȘ Û‡ÁÎÚÈÛ˘ μªS Î·È DMS ∏ ·ӷÛÙ¤ÓˆÛË Ô˘ ·ÔÙÂÏ› ÙË Î‡ÚÈ· ÂÈÏÔ΋ ÙˆÓ BMS ÁÓˆÛÙ‹ Î·È Û·Ó «·¯›ÏÏÂÈÔ˜ Ù¤ÚÓ·» ÙˆÓ BMS - ÌÂÈÒıËΠÛËÌ·ÓÙÈο (·fi 30% ÛÙÔ 10%) Ì ÙË ¯Ú‹ÛË ÙˆÓ DES. ∞˘Ùfi fï˜ Ê·›ÓÂÙ·È Ó· ¤¯ÂÈ ¤Ó· Ù›ÌËÌ· Ô˘ Â›Ó·È Ë fi„ÈÌË ıÚfiÌ‚ˆÛË Ì¤Û· ÛÙÔ stent (™¯‹Ì· 1). H ıÚfiÌ‚ˆÛË Ì¤Û· ÛÙÔ stent ‰È·ÎÚ›ÓÂÙ·È Û ÔÍ›· (<24 ÒÚ˜), ˘ÔÍ›· (̤¯ÚÈ 30 Ë̤Ú˜), fi„ÈÌË (̤¯ÚÈ 12
22
Ì‹Ó˜) Î·È Ôχ fi„ÈÌË (ÌÂÙ¿ ÙÔ˘˜ 12 Ì‹Ó˜) (™¯‹Ì· 2). √È ıÚÔÌ‚ÒÛÂȘ ̤۷ ÛÙ· stents Û˘Ó‹ıˆ˜ Û˘Ì‚·›ÓÔ˘Ó ÙȘ ÚÒÙ˜ 30 Ë̤Ú˜ ·fi ÙÔ ¯ÚfiÓÔ ÂÌʇÙ¢Û˘. ∂ÌÂÈÚ›· ·fi ÙË ∂ÏÏ¿‰· ˘¿Ú¯ÂÈ ·fi ÌÂϤÙË Î·Ù·ÁÚ·Ê‹˜ ÛÙÔ øÓ¿ÛÂÈÔ ∫·Ú‰ÈÔ¯ÂÈÚÔ˘ÚÁÈÎfi ∫¤ÓÙÚÔ fiÔ˘, Û 530 ·ÛıÂÓ›˜ ÛÙÔ˘˜ ÔÔ›Ô˘˜ ›¯Â ÂÌÊ˘Ù¢ı› DES (Cypher), ÙÔ ÔÛÔÛÙfi ıÚÔÌ‚ÒÛÂˆÓ Î·È Non Q ÂÌÊÚ¿ÁÌ·ÙÔ˜ ÛÙȘ 30 Ë̤Ú˜ ‹Ù·Ó 6% (2). √È fi„È̘ Î·È Ôχ fi„È̘ ıÚÔÌ‚ÒÛÂȘ Â›Ó·È Î·Ù¿ ηÓfiÓ· ÚÔÓfiÌÈÔ ÙˆÓ DES. ∞ıÚÔÈÛÙÈο Û fiϘ ÙȘ Ù˘¯·ÈÔÔÈË̤Ó˜ ÌÂϤÙ˜ BMS vs DES ·Ú·ÙËÚÂ›Ù·È ÌÈ· ÌÈÎÚ‹ (ÂÚ›Ô˘ 0.5% ·fiÏ˘ÙË ·‡ÍËÛË) ÛÙËÓ Â›ÙˆÛË Ù˘ fi„ÈÌ˘ ıÚfiÌ‚ˆÛ˘ Ô˘ Á›ÓÂÙ·È ¤Î‰ËÏË ÛÙÔ˘˜ 9 Ì 12 Ì‹Ó˜ Î·È ÂÂÎÙ›ÓÂÙ·È ÛÙ· 3 Î·È 4 ¯ÚfiÓÈ·. √ Û¯ÂÙÈο ·˘Í·ÓfiÌÂÓÔ˜ ΛӉ˘ÓÔ˜ ÚÔÛÂÁÁ›˙ÂÈ ÙÔ 0.2% ÂÙËÛ›ˆ˜ (0.46% - 0.57% ÛÙ· 3 ¯ÚfiÓÈ·) Î·È Â›Ó·È ›‰ÈÔ˜ ÁÈ· ÙÔ˘˜ ‰‡Ô ·ÚÈÔ˘˜ Ù‡Ô˘˜ ÙˆÓ DES (Cypher, Taxus) (¶›Ó·Î·˜ 1) ™Ù· BMS Ë ıÚfiÌ‚ˆÛË Û˘Ì‚·›ÓÂÈ Û˘Ó‹ıˆ˜ ÙȘ ÚÒÙ˜ 2 ‚‰ÔÌ¿‰Â˜ Î·È ÂÍ·ÈÚÂÙÈο Û¿ÓÈ· ÌÂÙ¿ ÙȘ 4 ‚‰ÔÌ¿‰Â˜ (<0.1%). ¶ÚfiÛÊ·ÙË ÌÂϤÙË Î·Ù·ÁÚ·Ê‹˜ (registry) ·fi ÙË Mayo Clinic (4503 ¿ÙÔÌ· Ì BMS) ¤‰ÂÈÍ fiÙÈ Ô Î›Ó‰˘ÓÔ˜ ÁÈ· ıÚfiÌ‚ˆÛË ÛÙ· BMS Â›Ó·È 0.5% ÛÙȘ 30 Ë̤Ú˜, 0.8% ÛÙÔ ÚÒÙÔ ¯ÚfiÓÔ Î·È 2% ÛÙ· 10 ¯ÚfiÓÈ·. ¶·Ú fiÙÈ ‰ÂÓ Úfi-
ÎÂÈÙ·È ÁÈ· Û˘¯Ó‹ ÂÈÏÔ΋, fiÙ·Ó Û˘Ì‚Â›, ÛÙȘ ÌÈÛ¤˜ ÂÚ›Ô˘ ÂÚÈÙÒÛÂȘ Â›Ó·È ı·Ó·ÙËÊfiÚÔ˜ ‹ ¤¯ÂÈ Û·Ó ·ÔÙ¤ÏÂÛÌ· ÌÂÁ¿ÏÔ ¤ÌÊÚ·ÁÌ·. ∏ Û˘¯ÓfiÙËÙ· ·ӷÛÙ¤ÓˆÛ˘ ÛÙ· 10 ¯ÚfiÓÈ· ‹Ù·Ó 18% Î·È ·fi ·˘ÙÔ‡˜ ÙÔ 10% (Û˘ÓÔÏÈο 2.1%) ÂÌÊ·Ó›ÛıËÎÂ Û·Ó ¤ÌÊÚ·ÁÌ· Ì˘Ôηډ›Ô˘. ∏ Ï‹Ú˘ ÂÓ‰ÔıËÏÈÔÔ›ËÛË ÙˆÓ μªS ¯ÚÂÈ¿˙ÂÙ·È 4-6 ‚‰ÔÌ¿‰Â˜. √ ÈÔ ÛÔ˘‰·›Ô˜ ÚÔÁÓˆÛÙÈÎfi˜ ·Ú¿ÁˆÓ ÁÈ· ÔÍ›· Î·È ˘ÔÍ›· ıÚfiÌ‚ˆÛË Â›Ó·È Ë ÂÌʇÙ¢ÛË Û ڈÙÔÁÂÓ‹ ·ÁÁÂÈÔÏ·ÛÙÈ΋ ‹ Ô͇ ÛÙÂÊ·ÓÈ·›Ô Û‡Ó‰ÚÔÌÔ Î·È È‰È·›ÙÂÚ· Û ·ÛıÂÓ›˜ Ô˘ ¿Û¯Ô˘Ó ·fi ‰È·‚‹ÙË, ÓÂÊÚÈ΋ ‹ ηډȷ΋ ·Ó¿ÚÎÂÈ·. ¶ÚfiÛÊ·ÙË ÌÂÙ·-·Ó¿Ï˘ÛË 8 Ù˘¯·ÈÔÔÈËÌ¤ÓˆÓ ÌÂÏÂÙÒÓ (Û‡ÓÔÏÔ 2.786 ·ÛıÂÓÒÓ) Ì Ô͇ ¤ÌÊÚ·ÁÌ· Ì˘Ôηډ›Ô˘ ¤‰ÂÈÍ fiÙÈ Ë Û˘¯ÓfiÙËÙ· ıÚfiÌ‚ˆÛ˘ ‹Ù·Ó ›‰È· ÁÈ· ÙÔ˘˜ ‰‡Ô Ù‡Ô˘˜ stent (4). ∏ ·Ú·ÎÔÏÔ‡ıËÛË ‹Ù·Ó ·fi 12 ̤¯ÚÈ 24 Ì‹Ó˜. ∞Ó·Ï˘ÙÈο Ù· ÔÛÔÛÙ¿ ıÚfiÌ‚ˆÛ˘ ‹Ù·Ó 1.6% Î·È 2.2% ÁÈ· Ù· DES Î·È BMS ·ÓÙ›ÛÙÔȯ· (25/1474 Î·È 29/1312). ™Â 2 ÂÚÈÙÒÛÂȘ Ì DES Î·È 1 Ì BMS Ë ıÚfiÌ‚ˆÛË Û˘Ó¤‚Ë ÌÂÙ¿ ÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ. §fiÁˆ ÙÔ˘ ÌÈÎÚÔ‡ fï˜ ·ÚÈıÌÔ‡ Û˘Ì‚·Ì¿ÙˆÓ Î·È ÙÔ˘ ÌÈÎÚÔ‡ ¯ÚfiÓÔ˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ Â›Ó·È ‰‡ÛÎÔÏÔ Ó· ‚ÁÂÈ ÔÚÈÛÙÈÎfi Û˘Ì¤Ú·ÛÌ·. ΔÔ Ì‹ÎÔ˜ ÙÔ˘ stent Î·È ÚÔıÚÔÌ‚ˆÙÈΤ˜ ηٷÛÙ¿ÛÂȘ fiˆ˜ Ô ÌÂÙ·ÛÙ·ÙÈÎfi˜ ηÚΛÓÔ˜ Â›Ó·È ÌÂÚÈÎÔ›
¶›Ó·Î·˜ 1 . ™˘¯ÓfiÙËÙ· Î·È Â›‰Ô˜ ıÚÔÌ‚ÒÛÂˆÓ ÛÙ· ‰‡Ô ›‰Ë stent: Ù· Á˘ÌÓ¿ (μªS) Î·È ·˘Ù¿ Ô˘ ÂÎÏ‡Ô˘Ó Ê¿ÚÌ·ÎÔ (DES). £ÚfiÌ‚ˆÛË
YÔÍ›· (<1 Ì‹Ó·)
Ÿ„ÈÌË (1-12 Ì‹Ó˜)
¶Ôχ fi„ÈÌË (>12 Ì‹Ó˜)
Stent
BMS, DES
DES
DES
<1%
0.19%
0.2-0.5%/¯ÚfiÓÔ
™˘¯ÓfiÙËÙ·
£EPA¶EIA - ºAPMAKA ¿ÏÏÔÈ ÚԉȷıÂÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘. °È· ÙȘ fi„È̘ Î·È Ôχ fi„È̘ ıÚÔÌ‚ÒÛÂȘ Ô ÈÔ ÛËÌ·ÓÙÈÎfi˜ ·Ú¿ÁˆÓ Â›Ó·È Ë ‰È·ÎÔ‹ Ù˘ ·ÓÙÈ·ÈÌÔÂÙ·Ïȷ΋˜ ·Áˆ-
∏ ‰ÈÏ‹ ·ÓÙÈ·ÈÌÔÂÙ·Ïȷ΋ ·ÁˆÁ‹ Ì ·ÛÈÚ›ÓË Î·È ÎÏÔȉÔÁÚ¤ÏË ·ÔÙÂÏ› ÙË ÎÏ·ÛÛÈ΋ ıÂڷ›· ÚfiÏ˄˘ ıÚfiÌ‚ˆÛ˘ ÛÙÔ stent. ∂›Ó·È ¿ÁÓˆÛÙË Ë È‰·ÓÈ΋ ‰È¿Ú-
°˘ÌÓfi ÌÂÙ·ÏÏÈÎfi stent ∫·Ï˘Ì̤ӷ Ì ÂÓ‰Ôı‹ÏÈÔ ÂÏ¿ÛÌ·Ù· ∞ÚÙËÚÈ·Îfi ÙÔ›¯ˆÌ·
∂·Ó·ÛÙ¤ÓˆÛË
∫·Ï˘Ì¤Ó· Ì ʿÚÌ·ÎÔ Stents ∞ÙÂÏÒ˜ Î·Ï˘Ì̤ӷ Ì ÂÓ‰Ôı‹ÏÈÔ ÂÏ¿ÛÌ·Ù· ∞ÚÙËÚÈ·Îfi ÙÔ›¯ˆÌ·
£ÚfiÌ‚ˆÛË
∂ÈÎfiÓ· 1. ™¯ËÌ·ÙÈ΋ ·Ú¿ÛÙ·ÛË ıÚfiÌ‚ˆÛ˘ ̤۷ ÛÙÔ stent. Á‹˜ (5). ∏ ·ıÔÁ¤ÓÂÈ· Ù˘ ıÚfiÌ‚ˆÛ˘ ÛÙÔ stent ‰ÂÓ Â›Ó·È Î·Ï¿ ηٷÓÔËÙ‹. Œ¯ÂÈ Ó· οÓÂÈ Ì ¤Ó· Û˘Ó‰˘·ÛÌfi ·Ú·ÁfiÓÙˆÓ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙËÓ Â¤Ì‚·ÛË, ÙÔÓ ·ÛıÂÓ‹, ÙË ıÂڷ¢ÙÈ΋ ·ÁˆÁ‹ Î·È Ù· ¯·Ú·ÎÙËÚÈÛÙÈο Ù˘ ‚Ï¿‚˘. ªÂ Ù· DES, ‚ÈÔÏÔÁÈΤ˜ ȉÈfiÙËÙ˜ fiˆ˜ Ë ıÚÔÌ‚ÔÁ¤ÓÂÈ·, .¯. ·Ú·ÁˆÁ‹ ÈÛÙÈÎÔ‡ ·Ú¿ÁÔÓÙ· (tissue factor), ·Ó·ÛÙÔÏ‹ ÂÓ‰ÔıËÏÈÔÔ›ËÛ˘, ηı˘ÛÙÂÚË̤ÓË ÂԇψÛË ÛÙȘ ÂÚÈÔ¯¤˜ ÙˆÓ stent Î·È ·ÓÙȉڿÛÂȘ ˘ÂÚ¢·ÈÛıËÛ›·˜ ·˘Í¿ÓÔ˘Ó ÙÔÓ Î›Ó‰˘ÓÔ ¤Ú·Ó ÂΛÓÔ˘ Ô˘ ·Ú·ÙËÚÂ›Ù·È Ì ٷ μMS (6).
ÎÂÈ· Ù˘ ıÂڷ›·˜ ·ÏÏ¿ Ì ‚¿ÛË Ù· ̤¯ÚÈ ÙÒÚ· ‰Â‰Ô̤ӷ Û˘ÓÈÛÙ¿Ù·È 1 Ì‹Ó·˜ ÁÈ· Ù· μªS Î·È 1 ¯ÚfiÓÔ˜ ÁÈ· Ù· DES. £ÚfiÌ‚ˆÛË ÛÙÔ stent ÌÔÚ› Ó· Û˘Ì‚Â› Î·È fiÙ·Ó Ô ·ÛıÂÓ‹˜ ·›ÚÓÂÈ ·ÓÙÈ·ÈÌÔÂÙ·Ïȷ΋ ·ÁˆÁ‹, ÁÂÁÔÓfi˜ Ô˘ ÌÔÚ› Ó· ÛËÌ·›ÓÂÈ ·ÓÙ›ÛÙ·ÛË ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ ÛÙËÓ ·ÛÈÚ›ÓË, ÛÙËÓ ÎÏÔȉÔÁÚ¤ÏË ‹ Î·È ÛÙ· ‰‡Ô. ∏ ȉ·ÓÈ΋ ÂÚÈÂÁ¯ÂÈÚËÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË ·ÛıÂÓÒÓ Ì ÛÔ‚·Ú‹ ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ ·Ú·Ì¤ÓÂÈ ¿ÁÓˆÛÙË. H ÂÚ›ÙˆÛË fï˜ ÙÔ˘ ·ÛıÂÓÔ‡˜ Ô˘ ¤¯ÂÈ ˘Ô‚ÏËı› Û ·ÁÁÂÈÔÏ·ÛÙÈ΋ Ì ÂÌʇÙ¢ÛË stent ¤¯ÂÈ ÂÚÈϤÍÂÈ ·ÎfiÌË ÂÚÈÛÛfiÙÂÚÔ ÙËÓ ÂÚÈÂÁ¯ÂÈ-
ÚËÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË ÏfiÁˆ ÙÔ˘ ·˘ÍË̤ÓÔ˘ ÎÈÓ‰‡ÓÔ˘ ıÚfiÌ‚ˆÛ˘ ̤۷ ÛÙÔ stent. ∏ ÚÒÈÌË ‰È·ÎÔ‹ Ù˘ ·ÓÙÈ·ÈÌÔÂÙ·Ïȷ΋˜ ıÂڷ›·˜ ·˘Í¿ÓÂÈ ÛËÌ·ÓÙÈο ÙÔÓ Î›Ó‰˘ÓÔ ÁÈ· ıÚfiÌ‚ˆÛË ÛÙÔ stent. ∂›Ó·È ηϿ ÁÓˆÛÙfi fiÙÈ ÔÈ ·ÛıÂÓ›˜ Ô˘ ı· ˘Ô‚ÏËıÔ‡Ó Û ÌË Î·Ú‰È·Î‹ ÂÁ¯Â›ÚËÛË ‰È·ÙÚ¤¯Ô˘Ó ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÁÈ· ıÚfiÌ‚ˆÛË Ì¤Û· ÛÙÔ stent (7,8). √ ·ÚÈÔÈ ÏfiÁÔÈ Â›Ó·È ÌË ÂÓ‰ÔıËÏÈÔÔ›ËÛË, ηı˘ÛÙÂÚË̤ÓË ÂԇψÛË, Î·È Èı·ÓÔ› ıÚÔÌ‚ˆÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ Ô˘ ¤¯Ô˘Ó Ó· οÓÔ˘Ó Ì ÙËÓ ›‰È· ÙË Ê‡ÛË Ù˘ ÂÁ¯Â›ÚËÛ˘. ∞ÛıÂÓ›˜ Ô˘ ı· ˘Ô‚ÏËıÔ‡Ó Û ÌË Î·Ú‰È·Î‹ ¤̂·ÛË 1-2 ‚‰ÔÌ¿‰Â˜ ÌÂÙ¿ ·fi ·ÁÁÂÈÔÏ·ÛÙÈ΋ Ì stent ‰È·ÙÚ¤¯Ô˘Ó ˘„ËÏfi (̤¯ÚÈ 32% Û ÌÂÚÈΤ˜ ÌÂϤÙ˜) ΛӉ˘ÓÔ ıÚfiÌ‚ˆÛ˘ ÙÔ˘ stent ÌÂ Û˘Ó¤ÂÈ· ı¿Ó·ÙÔ ÛÙȘ ÌÈÛ¤˜ ÂÚÈÙÒÛÂȘ ·Ú¿ ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ë ·ÓÙÈ·ÈÌÔÂÙ·Ïȷ΋ ·ÁˆÁ‹ Û˘Ó¯›˙ÂÈ Î·È ÛÙËÓ ÂÚÈÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô. Œ¯ÂÈ ·Ó·ÊÂÚı› ÂÚÈÂÁ¯ÂÈÚËÙÈ΋ ıÚfiÌ‚ˆÛË Î·È 21 Ì‹Ó˜ ÌÂÙ¿ ÙËÓ ÂÌʇÙ¢ÛË DES. √ ΛӉ˘ÓÔ˜ ·fi ÙËÓ ÂÁ¯Â›ÚËÛË ¤¯ÂÈ ÂÚÈÁÚ·Ê› Û ÂÚ›Ô˘ 10 ÌÂϤÙ˜ ·Ú·Ù‹ÚËÛ˘ - ΢ڛˆ˜ ·Ó·‰ÚÔÌÈΤ˜ - ÔÈ ÂÚÈÛÛfiÙÂÚ˜ ·ÊÔÚÔ‡Ó BMS Î·È Ô Î›Ó‰˘ÓÔ˜ ÁÈ· ı¿Ó·ÙÔ Û ·˘ÙÔ‡˜ ÙÔ˘˜ ·ÛıÂÓ›˜ Î˘Ì·›ÓÂÙ·È ·fi 2.5% ̤¯ÚÈ 21.4% (7,8). ΔÔ ™¯‹Ì· 3 ‰Â›¯ÓÂÈ ¤Ó·Ó ·ÏÁfiÚÈıÌÔ ÁÈ· ÙÔÓ Î·Ù¿ÏÏËÏÔ ¯ÚfiÓÔ Ó· Á›ÓÂÈ Ë ÌË Î·Ú‰È·Î‹ ¤̂·ÛË. ∏ ÂÁ¯Â›ÚËÛË ÌÔÚ› Ó· Á›ÓÂÈ Ì ·ÛÊ¿ÏÂÈ· 6 ‚‰ÔÌ¿‰Â˜ ÌÂÙ¿ ÙËÓ ÂÌʇÙ¢ÛË BMS Î·È 1 ¯ÚfiÓÔ ÌÂÙ¿ ÙËÓ ÂÌʇÙ¢ÛË DES. ™ÙËÓ Î·ı' Ë̤ڷ Ú¿ÍË ÁÈ· Ù· BMS ·ÚÎÔ‡Ó 4 ‚‰ÔÌ¿‰Â˜ ·ÊÔ‡ ¯ÚÂÈ¿˙ÔÓÙ·È 5 Ì 10 Ë̤Ú˜ ‰È·ÎÔ‹ Ù˘ ÎÏÔȉÔÁÚ¤Ï˘ ÚÈÓ ÙËÓ ÂÁ¯Â›ÚËÛË. √È ·ÛıÂÓ›˜ Ô˘ ı· ˘Ô‚ÏËıÔ‡Ó Û ÂÁ¯Â›ÚËÛË Ì¤Û· Û' ·˘Ù¿ Ù· ¯ÚÔÓÈο ‰È·ÛÙ‹Ì·Ù· ıˆÚÔ‡ÓÙ·È ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ıÚfiÌ‚ˆÛË ÛÙÔ stent. ∏ ·Ó·ÙÔÌ›· ÙˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ - ı¤ÛË Ô˘ ¤¯ÂÈ ÂÌÊ˘Ù¢ı› ÙÔ stent fiˆ˜ ÛÙÔÌȷΤ˜ ‚Ï¿‚˜, ‰È¯·ÛÌÔ›, ÌÈÎÚ‹˜ ‰È·Ì¤ÙÚÔ˘ ·ÁÁ›·, ÔÏÏ·Ï¿ ·ÁÁ›· ‹ ÂÈÌ‹ÎÂȘ ‚Ï¿‚˜ ·˘Í¿ÓÔ˘Ó ÙÔÓ Î›Ó‰˘ÓÔ ÁÈ· ıÚfiÌ‚ˆÛË. ∏ ÂÎÙ›ÌËÛË ÙÔ˘ ·ÈÌÔÚÚ·ÁÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘, ÂÎÙfi˜ ·fi ÙËÓ ·ÒÏÂÈ· Ô˘ Û˘Ì‚·›ÓÂÈ
23
ª∞ƒΔπ√™ 2008
1 Ì‹Ó·˜
1 ¯ÚfiÓÔ˜
¶ÚÒÈÌË ≤1 Ì‹Ó·˜
√Í›· ≤1 Ë̤ڷ
Ÿ„ÈÌË 1 Ì‹Ó· - 1 ¯ÚfiÓÔ
¶Ôχ fi„ÈÌË >1 ¯ÚfiÓÔ
ÀÔÍ›· >1 Ë̤ڷ ¤ˆ˜ 1 Ì‹Ó·
≤ 1 Ë̤ڷ:
√Í›· ıÚfiÌ‚ˆÛË stent
> 1 Ë̤ڷ ¤ˆ˜ 1 Ì‹Ó·:
ÀÔÍ›· ıÚfiÌ‚ˆÛË stent
> 1 Ì‹Ó· ¤ˆ˜ 1 ¯ÚfiÓÔ:
Ÿ„ÈÌË ıÚfiÌ‚ˆÛË stent
> 1 ¯ÚfiÓÔ:
¶Ôχ fi„ÈÌË ıÚfiÌ‚ˆÛË stent
™¯‹Ì· 2. ÃÚÔÓÈÎfi Ï·›ÛÈÔ Ù˘ ıÚfiÌ‚ˆÛ˘ ÛÙÔ stent ÛÙËÓ ÂÁ¯Â›ÚËÛË Î·È ÙËÓ ·Ó¿ÁÎË ÁÈ· ÌÂÙ¿ÁÁÈÛË, Ú¤ÂÈ Ó· Ï·Ì‚¿ÓÂÈ ˘' fi„ÈÓ Î·È ÙȘ Û˘Ó¤ÂȘ Ù˘ ·ÈÌÔÚÚ·Á›·˜ fiÛÔÓ ·ÊÔÚ¿ ÙË ı¤ÛË Ô˘ ·ÈÌÔÚÚ·Á›. √È ·ÛıÂÓ›˜ ÌÂÙ¿ ·fi ÙÚÔ¯·›· ‹ ÂÁ¯ÂÈÚ‹ÛÂȘ Ô˘ ¤¯Ô˘Ó ·˘ÍË̤ÓË ·ÈÌÔÚÚ·ÁÈ΋ ‰È¿ıÂÛË (ıËÏÒÌ·Ù· ·ÛÙ˘, ÚÔÛÙ¿ÙË) Â›Ó·È ÌÂÚÈΤ˜ ·fi ÙȘ ηÙËÁÔڛ˜ fiÔ˘ ¯Ú‹˙Ô˘Ó È‰È·›ÙÂÚ˘ ÚÔÛÔ¯‹˜. ∞ÎfiÌË Î·È ÌÈÎÚ¤˜ ·ÈÌÔÚÚ·Á›Â˜ Á›ÓÔÓÙ·È ÌË ·ÓÂÎÙ¤˜ ÁÈ· ÔÊı·ÏÌÔÏÔÁÈΤ˜ ‹ ÂÓ‰ÔÎÚ¿ÓȘ ÂÂÌ‚¿ÛÂȘ. ∏ ·fiÊ·ÛË ÁÈ· ÂÁ¯Â›ÚËÛË Î·È ¯ˆÚ›˜ ‰È·ÎÔ‹ ÙˆÓ ·ÓÙÈ·ÈÌÔÂÙ·ÏÈ·ÎÒÓ Â›Ó·È ı¤Ì· ÚÔÛˆÈ΋˜
ÎÚ›Û˘. ¶¿ÓÙˆ˜ ·Ó Ú¤ÂÈ Ó· ‰È·ÎÔ› ¤Ó· ·fi Ù· ‰‡Ô ·ÓÙÈ·ÈÌÔÂÙ·Ïȷο, ·˘Ùfi Ú¤ÂÈ Ó· Â›Ó·È Ë ÎÏÔȉÔÁÚ¤ÏË. √È ·ÛıÂÓ›˜ Ì DES Ô˘ ı· ˘Ô‚ÏËıÔ‡Ó ·Ó·fiÊ¢ÎÙ· Û ÌË Î·Ú‰È·Î‹ ¤̂·ÛË ıˆÚÂ›Ù·È ÊÚfiÓÈÌÔ Ó· ÌË ‰È·ÎfiÙÔ˘Ó ÙËÓ ·ÓÙÈ·ÈÌÔÂÙ·Ïȷ΋ ·ÁˆÁ‹ Â¿Ó Â›Ó·È ¯·ÌËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ·ÈÌÔÚÚ·Á›· Î·È fiÙ·Ó ˘Ô‚¿ÏÏÔÓÙ·È Û ÌÈÎÚÔÂÂÌ‚¿ÛÂȘ (ÂÍ·ÁˆÁ‹ Ô‰fiÓÙˆÓ, ηٷÚÚ¿ÎÙ˘). ¢È·ÎÔ‹ Ù˘ ·ÛÈÚ›Ó˘ Î·È ÎÏÔȉÔÁÚ¤Ï˘ Ì Á¤Ê˘Ú· Ë·Ú›ÓË, IIb/IIIa ÛÙËÓ ÂÚÈÂÁ¯ÂÈÚËÙÈ΋
π™Δ√ƒπ∫√ ∞°°∂π√¶§∞™Δπ∫∏™
ÌÂ Ì·ÏfiÓÈ
ÌÂ BMS
ÌÂ DES
ÃÚfiÓÔ˜ (Ë̤Ú˜)
∫·ı˘ÛÙÂÚ‹ÛÙ ÙËÓ ÚÔÁÚ·ÌÌ·ÙÈṲ̂ÓË ÂÁ¯Â›ÚËÛË
¶ÚÔ¯ˆÚ‹ÛÙ ÛÙËÓ ÂÁ¯Â›ÚËÛË Ì ·ÛÈÚ›ÓË
∫·ı˘ÛÙÂÚ‹ÛÙ ÙÔ Ù·ÎÙÈÎfi ‹ ¤ÎÙ·ÎÙÔ ¯ÂÈÚÔ˘ÚÁ›Ô
¶ÚÔ¯ˆÚ‹ÛÙ ÛÙËÓ ÂÁ¯Â›ÚËÛË Ì ·ÛÈÚ›ÓË
™¯‹Ì· 3. ¶ÚÔÙÂÈÓfiÌÂÓË ÚÔÛ¤ÁÁÈÛË ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË ·ÛıÂÓÒÓ Ì ÈÛÙÔÚÈÎfi ·ÁÁÂÈÔÏ·ÛÙÈ΋˜ Ô˘ Ú¤ÂÈ Ó· ˘Ô‚ÏËıÔ‡Ó Û Â͈ηډȷ΋ ÂÁ¯Â›ÚËÛË.
24
ÂÚ›Ô‰Ô Â›Ó·È ÌÈ· ÂÓ·ÏÏ·ÎÙÈ΋ χÛË (‰ÂÓ ˘¿Ú¯Ô˘Ó fï˜ ÛÙÔȯ›· fiÙÈ ‚ÔËı¿ÂÈ) Î·È ÍÂΛÓËÌ· ÁÚ‹ÁÔÚ· (<48 ÒÚ˜) ÌÂÙÂÁ¯ÂÈÚËÙÈο Ì ‰fiÛÂȘ ÊfiÚÙÈÛ˘ ÎÏÔȉÔÁÚ¤Ï˘. ∏ ·ÓÙÈÌÂÙÒÈÛË ÂÎÏÔÁ‹˜ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ı· ·ÚÔ˘ÛÈ¿ÛÔ˘Ó ıÚfiÌ‚ˆÛË ÛÙÔ stent Â›Ó·È ÚˆÙÔÁÂÓ‹˜ ·ÁÁÂÈÔÏ·ÛÙÈ΋. £ÚÔÌ‚ÔχÛÙ ·Ó ›ÛÙ ̷ÎÚÈ¿ ·fi ΤÓÙÚÔ ·ÁÁÂÈÔÏ·ÛÙÈ΋˜ ·ÏÏ¿, ·Ó Ë ıÚfiÌ‚ˆÛË ¤¯ÂÈ Û˘Ì‚Â› ÂÚÈÂÁ¯ÂÈÚËÙÈο, Ë ıÚÔÌ‚fiÏ˘ÛË ·ÓÙÂӉ›ÎÓ˘Ù·È Î·È ¤ÙÛÈ ÌË Î·ı˘ÛÙÂÚ›ÙÂ, ÌÂÙ·ÎÈÓËı›Ù ÁÚ‹ÁÔÚ·. H ·ÓÙÈÌÂÙÒÈÛË Ù˘ Û˘Ó¯Ҙ ·˘Í·ÓfiÌÂÓ˘ Û˘¯Ó‹˜ Î·È ÔχÏÔ΢ ÔÌ¿‰·˜ ·ÛıÂÓÒÓ Ì stent ÛÙ· ÛÙÂÊ·ÓÈ·›· Ô˘ ¯ÚÂÈ¿˙ÔÓÙ·È ÌË Î·Ú‰È·Î‹ ÂÁ¯Â›ÚËÛË ··ÈÙ› ÌÈ· Û˘ÛÙËÌ·ÙÈ΋ ÚÔÛ¤ÁÁÈÛË ÁÈ· ÙËÓ fiÛÔ ÙÔ ‰˘Ó·ÙfiÓ ·ÔÊ˘Á‹ ηٷÛÙÚÔÊÈÎÒÓ ÂÈÏÔÎÒÓ. ¶ÂÚÈÁÚ¿„·Ì ÌÂÚÈΤ˜ Ô‰ËÁ›Â˜ ÁÈ· Ó· ‚ÔËı‹ÛÔ˘Ì ÛÙËÓ ·fiÊ·ÛË Ô˘ ¯ÚÂÈ¿˙ÂÙ·È Ó· ·Úı› ÚÔÙÔ‡ ·˘ÙÔ› ÔÈ ·ÛıÂÓ›˜ ÚÔÁÚ·ÌÌ·ÙÈÛıÔ‡Ó ÁÈ· ÌË Î·Ú‰È·Î‹ ÂÁ¯Â›ÚËÛË
£EPA¶EIA - ºAPMAKA μÈ‚ÏÈÔÁÚ·Ê›· 1.
Windecker S, Meier B. Late coronary stent thrombosis. Circulation 2007; 116:1952-65
2.
Voudris V, Alexopoulos E, karyofillis P, et al. Prospective native coronary artery stenosis with sirolymus eluting stents (ONASIS) registry-acute results and mid term outcomes: a single -center experience. J Invas Cardiol 2005;17:401-5
3.
Doyle μ, Rihal CS, O'Sullivan CJ, et al. Outcomes of Stent Thrombosis and Restenosis During Extended Follow-Up of Patients Treated With Bare-Metal
Coronary Stents. Circulation. 2007;116: 000-00 4.
5.
Kastrati A, Alban Dibra A, Spaulding C et al. Meta-analysis of randomized trials on drug-eluting stents vs. bare-metal stents in patients with acute myocardial infarction. European Heart Journal 2007 28, 2706-2713 Grines CL, Bonow RO, Casey DE et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents. JACC 2007;49:734-9
6.
Luscher TF, Steffel J, Eberly FR, et al. Drug eluting stents and coronary thrombosis. Biological mechanisms and clinical implications. Circulation 2007; 115:1051-82
7.
Brilakis ES, Banerjee S, Berger PB. Perioperative management of patients with coronary stents JACC 2007;49:214550
8.
Riddell JW, Chiche L, Plaud B, Hamon M. Clinician Update.Coronary Stents and Noncardiac Surgery. Circulation 2007; 116:e378-e383
∏ ∞Ó·ÈÌ›· ˆ˜ £Âڷ¢ÙÈÎfi˜ ™Ùfi¯Ô˜ ÛÙËÓ ∫·Ú‰È·Î‹ ∞Ó¿ÚÎÂÈ·. ∫ÏÈÓÈΤ˜ ªÂϤÙ˜ ÁÈ· ÙË ÃÚ‹ÛË ∂Ú˘ıÚÔÔÈËÙ›Ó˘ Î·È ™È‰ËÚÔıÂڷ›·˜. ∂˘ÛÙ¿ıÈÔ˜ ¶·ÁÎÔ˘Ú¤ÏÈ·˜, ÷ڿϷÌÔ˜ ∫Ô˘Ì·Ú¿˜, ÕÓÓ· ∫·Î·Ê‹Î·, ¶·Ú·Û΢‹ ∑ÒÚÔ˘, μ·Û›ÏÂÈÔ˜ Õı˘ÚÔ˜, ∞ÛÙ¤ÚÈÔ˜ ∫·Ú·ÁÈ¿ÓÓ˘. μ' ¶ÚÔ·È‰Â˘ÙÈ΋ ¶·ıÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ∞¶£, πÔÎÚ¿ÙÂÈÔ ¡ÔÛÔÎÔÌ›Ô, £ÂÛÛ·ÏÔÓ›ÎË.
∂ÈÛ·ÁˆÁ‹ ∂›Ó·È ÁÓˆÛÙfi fiÙÈ Ë ·Ó·ÈÌ›· ÌÔÚ› Ó· ÚÔηϤÛÂÈ Û˘Óı‹Î˜ ˘ÂÚ‰˘Ó·ÌÈ΋˜ ΢ÎÏÔÊÔÚ›·˜ Î·È Î·Ú‰È·Î‹˜ ·Ó¿ÚÎÂÈ·˜ (∫∞) ·ÎfiÌË Î·È Û ·ÛıÂÓ›˜ ¯ˆÚ›˜ ˘ÔΛÌÂÓË Î·Ú‰È·Î‹ ÓfiÛÔ[1]. ∏ ÂÈÛ·ÁˆÁ‹ ·fi ÙÔ˘˜ Silverberg Î·È Û˘Ó. ÙÔ 2002 ÙÔ˘ fiÚÔ˘ cardiorenal anemia syndrome (Û‡Ó‰ÚÔÌÔ Î·Ú‰ÈÔÓÂÊÚÈ΋˜ ·Ó·ÈÌ›·˜)[2] ÂȂ‚·›ˆÛ ÌÂÚÈΤ˜ ÌÂϤÙ˜ Ô˘ ÈÛ¯˘Ú›ÛÙËÎ·Ó Î·È ÙÔ ·ÓÙ›ıÂÙÔ: fiÙÈ ‰ËÏ·‰‹ Ë ·Ó·ÈÌ›· ‰ÂÓ ·ÔÙÂÏ› ÌfiÓÔ ÙÔ ·›ÙÈÔ ·ÏÏ¿ Î·È ÙÔ ·ÈÙÈ·Ùfi Ù˘ Û˘ÌÊÔÚËÙÈ΋˜ ∫∞. ∞ÚÎÂÙ¤˜ ÌÂϤÙ˜ Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· Û˘ÓÙ›ÓÔ˘Ó Ì¿ÏÈÛÙ· ÛÙÔ fiÙÈ Ë ·Ó·ÈÌ›· ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙËÓ ¤ÎÙˆÛË Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ Ô‰ËÁ› Û ¤Ó· Ê·‡ÏÔ Î‡ÎÏÔ ·ÏÏËÏ›‰Ú·Û˘ Î·È ·ÔÚÚ‡ıÌÈÛ˘ Ù˘ ∫∞, Ô ÔÔ›Ô˜ Â›Ó·È ‰˘Ó·Ùfi Ó· ÂÍËÁ‹ÛÂÈ ¤Ó· ÌÂÁ¿ÏÔ ÔÛÔÛÙfi Ù˘ ÓÔÛËÚfiÙËÙ·˜, ıÓËÙfiÙËÙ·˜ Î·È ÙˆÓ Û˘¯ÓÒÓ Â·ÓÂÈÛ·ÁˆÁÒÓ ÛÙ· ÓÔÛÔÎÔÌ›· ÙˆÓ ·ÛıÂÓÒÓ Ì ∫∞[3,4].
ªÂϤÙ˜ Ì ÙË ¯Ú‹ÛË ÂÚ˘ıÚÔÔÈËÙ›Ó˘ (∂ƒ√) Î·È Ûȉ‹ÚÔ˘ √È ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ Ô˘ ÂÍÂÙ¿˙Ô˘Ó ÙÔ fiÊÂÏÔ˜ ·fi ÙË ¯Ú‹ÛË ∂ƒ√ Î·È ÛȉËÚÔıÂڷ›·˜ ÛÙËÓ ∫∞ Â›Ó·È Ï›Á˜. √È ÂÚÈÛÛfiÙÂÚ˜ Â›Ó·È ·ÓÔȯ٤˜, ÌË Ù˘¯·ÈÔÔÈË̤Ó˜, ÌË ‰ÈÏ¿-Ù˘ÊϤ˜ ÌÂϤÙ˜ Ô˘ ÂÍÂÙ¿˙Ô˘Ó Û¯ÂÙÈο ‚Ú·¯˘ÚfiıÂÛÌ· (‰È¿ÚÎÂÈ· Û˘Ó‹ıˆ˜ < ¤ÙÔ˘˜) Ù· ÔʤÏË ‹ ÙȘ Û˘Ó¤ÂȘ Ù˘ ¯Ú‹Û˘ ·Ú·ÁfiÓÙˆÓ ‰ÈÂÁÂÚÙÈÎÒÓ Ù˘ ÂÚ˘ıÚÔÔ›ËÛ˘. ªÂٷ͇ ÙˆÓ ÌÂÏÂÙÒÓ Ô˘ ¯ÚËÛÈÌÔÔ›ËÛ·Ó ·ÓıÚÒÈÓË ·Ó·Û˘Ó‰˘·Ṳ̂ÓË ÂÚ˘ıÚÔÔÈËÙ›ÓË Î·È Û›‰ËÚÔ Û ·ÛıÂÓ›˜ Ì ∫∞, ˆ˜ ÌÔÓ·‰È΋ ‰ÈÏ¿ Ù˘ÊÏ‹ ÂÏÂÁ¯fiÌÂÓË ÌÂϤÙË Û˘ÁηٷϤÁÂÙ·È ·˘Ù‹ ÙˆÓ Palazzuoli Î·È Û˘Ó.[5]. ¶ÚfiÎÂÈÙ·È ÁÈ· ÌÈ· ÌÂϤÙË ÛÙËÓ ÔÔ›· Û˘ÌÌÂÙ›¯·Ó Û˘ÓÔÏÈο 40 ·ÛıÂÓ›˜ Ì ‚·ÚÈ¿ ηډȷ΋ ·Ó¿ÚÎÂÈ· Î·È ·Ó·ÈÌ›· (Hb<11g/dL), ·fi ÙÔ˘˜ ÔÔ›Ô˘˜ ÔÈ 20 Ù˘¯·ÈÔÔÈ‹ıËÎ·Ó Ó· Ï¿‚Ô˘Ó ÂÚ˘ıÚÔÔÈËÙ›ÓË ˘Ô‰ÔÚ›ˆ˜ ‰‡Ô ÊÔÚ¤˜
‚‰ÔÌ·‰È·›ˆ˜ Î·È 300 mg ÁÏ˘ÎÔÓÈÎfi Û›‰ËÚÔ Û ηıËÌÂÚÈÓ‹ ‚¿ÛË ·fi ÙÔ˘ ÛÙfiÌ·ÙÔ˜, ÂÓÒ ÔÈ ˘fiÏÔÈÔÈ ·ÂÙ¤ÏÂÛ·Ó ÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘ (¤Ï·‚·Ó ÌfiÓÔ Û›‰ËÚÔ Î·È ·ÓÙ› ÂÚ˘ıÚÔÔÈËÙ›Ó˘ Ê˘ÛÈÔÏÔÁÈÎfi ÔÚfi). ∏ ‰È¿ÚÎÂÈ· Ù˘ ÌÂϤÙ˘ ‹Ù·Ó ·Ú¯Èο 3 Ì‹Ó˜. ªÂÙ¿ ÙËÓ ÚÒÙË Ê¿ÛË Ù˘ ÌÂϤÙ˘, Ë ÔÌ¿‰· ıÂڷ›·˜ Û˘Ó¤¯ÈÛ ÙË Ê·Ú̷΢ÙÈ΋ ·ÁˆÁ‹ ÁÈ· ·ÎfiÌË 9 Ì‹Ó˜. Δ· ·ÔÙÂϤÛÌ·Ù· Ù˘ ÌÂϤÙ˘ ¤‰ÂÈÍ·Ó ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË Ù˘ Hb ·›Ì·ÙÔ˜ ÛÙËÓ ÔÌ¿‰· ÂÓÂÚÁÔ‡ ıÂڷ›·˜ ·fi 10.4 ±0.6 ÛÙ· 12.4± 0.8 g/dL (p < 0 .01), ÌÈ· ÛËÌ·ÓÙÈ΋ ‚ÂÏÙ›ˆÛË Ù˘ ÏÂÈÙÔ˘ÚÁÈ΋˜ ÎÏ¿Û˘ ηٿ ¡À∏∞ ·fi 3.5 ±0.6 ÛÙ· 2.8 ± 0.5 (p <0.05), ·‡ÍËÛË Ù˘ ‰È¿ÚÎÂÈ·˜ ·ÓÙÔ¯‹˜ ÛÙË ‰ÔÎÈÌ·Û›· ÎfiˆÛ˘ ·fi 5.8± 2.2 ÛÙ· 7.8± 2.5 min ( p < 0 .01), ÌÈ· ·‡ÍËÛË Ù˘ ‰È·Ó˘fiÌÂÓ˘ ·fiÛÙ·Û˘ ÛÙË ‰ÔÎÈÌ·Û›· 6 min ·fi 278 ± 55 ÛÙ· 356± 88 m (p < 0.01) Î·È ÌÈ· ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË ÛÙË Ì¤ÁÈÛÙË Î·Ù·Ó¿ÏˆÛË Ô͢ÁfiÓÔ˘ (VO2max) ·fi 12.8 ±2.8 ÛÙ· 15.1
25
ª∞ƒΔπ√™ 2008
±2.8 mL/kg/min (p < 0.05). ™˘Á¯ÚfiÓˆ˜ ·Ú·ÙËÚ‹ıËΠÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÛÙ· ›‰· ÙÔ˘ μ (ÂÁÎÂÊ·ÏÈÎÔ‡) Ó·ÙÚÈÔ˘ÚËÙÈÎÔ‡ ÂÙȉ›Ô˘ ·fi Ù· 568± 320 ÛÙ· 271± 120 pg/mL (p < 0 .01), ηıÒ˜ Î·È ÌÈ· ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÛÙËÓ ÎÚ·ÙÈÓ›ÓË ÔÚÔ‡ ·ÏÏ¿ Î·È ·‡ÍËÛË ÛÙËÓ ˘ÔÏÔÁÈ˙fiÌÂÓË Î¿ı·ÚÛË ÎÚ·ÙÈÓ›Ó˘. ™ÙËÓ ÔÌ¿‰· ÙÔ˘ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ η̛· ÛËÌ·ÓÙÈ΋ ÌÂÙ·‚ÔÏ‹ ‰ÂÓ ·Ú·ÙËÚ‹ıËΠ۠ηÌÈ¿ ·fi ÙȘ ·Ú·¿Óˆ ·Ú·Ì¤ÙÚÔ˘˜ ηٿ ÙËÓ ÂÚ›Ô‰Ô Ù˘ ÌÂϤÙ˘. ™ÙÔ Ù¤ÏÔ˜ ÙÔ˘ ÂÓfi˜ ¤ÙÔ˘˜ Ë ·ÈÌÔÛÊ·ÈÚ›ÓË ·Ú¤ÌÂÓ ·ÎfiÌ· ˘„ËÏ‹ ÛÙËÓ ÔÌ¿‰· ıÂڷ›·˜, ÂÓÒ Ô Ú˘ıÌfi˜ ÂÈÛ·ÁˆÁÒÓ ÛÙ· ÓÔÛÔÎÔÌ›· ‹Ù·Ó ÛÙ·ıÂÚ¿ ÌÈÎÚfiÙÂÚÔ˜. ™Â ÌÈ· ¿ÏÏË ·Ï‹ Ù˘ÊÏ‹ ÌÂϤÙË [6] 26 ·Ó·ÈÌÈÎÔ› ·ÛıÂÓ›˜ (̤ÛÔ˜ fiÚÔ˜ Hb 11gr/dL) Ì ¯ÚÔÓ›· ∫∞ ( ¡À∏∞ πππ Î·È IV) Ù˘¯·ÈÔÔÈ‹ıËÎ·Ó Ó· Ï¿‚Ô˘Ó ·ÓıÚÒÈÓË ·Ó·Û˘Ó‰˘·Ṳ̂ÓË ÂÚ˘ıÚÔÔÈËÙ›ÓË (15000 ¤ˆ˜ 30000 IU/‚‰ÔÌ¿‰·), ÁÏ˘ÎÔÓÈÎfi Û›‰ËÚÔ (325 mg) Î·È Ê˘ÏÏÈÎfi Ô͇ 1 mg ‹ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ ÁÈ· ¤Ó· ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· 3 ÌËÓÒÓ. ∏ ¯Ú‹ÛË Ù˘ ∂ƒ√ Û˘Óԉ‡ÙËΠ·fi ·‡ÍËÛË Ù˘ ÙÈÌ‹˜ Ù˘ Hb (·fi 11,0± 0,5 ÛÙ· 14,3±1,0 gr/dL), ·fi ‚ÂÏÙ›ˆÛË Ù˘ ̤ÁÈÛÙ˘ ηٷӿψÛ˘ √2 (peak VO2 ·fi 11±1,8 ÛÙ· 12,7±2,8 mL/Kg/min) (p < 0,05) ηıÒ˜ Î·È ·fi ·‡ÍËÛË Ù˘ Û˘ÓÔÏÈ΋˜ ‰È¿ÚÎÂÈ·˜ ¿ÛÎËÛ˘ ·fi Ù· 590±107 ÛÙ· 657±119 sec ÛÙËÓ ÔÌ¿‰· Ù˘ ∂ƒ√. £ÚÔÌ‚ˆÙÈο ÂÂÈÛfi‰È· ‹ ˘¤ÚÙ·ÛË ‰ÂÓ ·Ú·ÙËÚ‹ıËηÓ. ∂ÓÙ˘ˆÛÈ·Îfi ›Û˘ ÎÚ›ÓÂÙ·È ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÛÙËÓ ÔÌ¿‰· ÙÔ˘ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ fi¯È ÌfiÓÔ ‰Â ‚ÂÏÙÈÒıËÎÂ Ë Ì¤ÁÈÛÙË Î·Ù·Ó¿ÏˆÛË Ô͢ÁfiÓÔ˘ ·ÏÏ¿ ·ÓÙ›ıÂÙ· ÌÂÈÒıËΠ·fi 10,0±1,9 ÛÙ· 9,5±1,6 mL/Kg/min ¯ˆÚ›˜ ˆÛÙfiÛÔ Ë ·Ú·ÙËÚÔ‡ÌÂÓË ‰È·ÊÔÚ¿ Ó· Â›Ó·È ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋. ∞fi ÙË ÛÙÈÁÌ‹ Ô˘ ‰ÂÓ ·Ú·ÙËÚ‹ıËΠÌÂÙ·‚ÔÏ‹ ÙÔ˘ ÔÍÂȉˆÙÈÎÔ‡ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ Ì˘ÒÓ ÛÙËÓ ·Ú·¿Óˆ ÌÂϤÙË, Ë ·Ó·ÊÂÚfiÌÂÓË Â›‰Ú·ÛË ÛÙËÓ ·‡ÍËÛË ÈηÓfiÙËÙ·˜ ÚÔ˜ ¿ÛÎËÛË ·Ô‰fiıËΠÛÙËÓ Î·Ï‡ÙÂÚË Ô͢ÁfiÓˆÛË ÙˆÓ ÈÛÙÒÓ ÏfiÁˆ ·‡ÍËÛ˘ Ù˘ Hb. ™Â ·Ó¿ÏÔÁ· Û˘ÌÂÚ¿ÛÌ·Ù· η٤ÏËÍ·Ó Î·È ÔÈ 4 ·ÓÔÈÎÙ¤˜ ÌÂϤ-
26
Ù˜ ÙˆÓ Silverberg Î·È Û˘Ó[7-10]. ∫·È ÔÈ ÚÔËÁÔ‡ÌÂÓ˜ ÌÂϤÙ˜ Û˘ÁÎÏ›ÓÔ˘Ó ÛÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ë ¯Ú‹ÛË ÂÚ˘ıÚÔÔÈËÙ›Ó˘ Î·È ÂÓ‰ÔÊÏ‚›Ô˘ Ûȉ‹ÚÔ˘ ÁÈ· ÙË ‚ÂÏÙ›ˆÛË Ù˘ Hb Û ·ÛıÂÓ›˜ Ì ‚·ÚÈ¿ ∫∞ Û˘Óԉ‡ÙËΠ·fi ‚ÂÏÙ›ˆÛË ÙÔ˘ ÎÏ¿ÛÌ·ÙÔ˜ ÂÍÒıËÛ˘ ηٿ 5,5 ¤ˆ˜ 11,5% ·Ó¿ÏÔÁ· Ì ÙËÓ ‡·ÚÍË ‹ fi¯È ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË Î·ıÒ˜ Î·È ·fi ‚ÂÏÙ›ˆÛË Ù˘ ÏÂÈÙÔ˘ÚÁÈ΋˜ ÎÏ¿Û˘ ηٿ ¡À∏∞ ·fi 3,66±0,47 ÛÙÔ 2,66±0,70 (p < 0,05). ∂ÈϤÔÓ, ·Ó¿ÏÔÁ˜ ıÂÙÈΤ˜ ÌÂÙ·‚ÔϤ˜ ·Ú·ÙËÚ‹ıËÎ·Ó ÛÙË ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ·ÛıÂÓÒÓ, ÛÙËÓ ·Ó¿ÁÎË ÁÈ· ¯Ú‹ÛË ‰ÈÔ˘ÚËÙÈÎÒÓ Î·È ÂÓ‰ÔÓÔÛÔÎÔÌÂȷ΋˜ ÓÔÛËÏ›·˜. ŸÏ˜ ÔÈ ·Ú·ÙËÚÔ‡ÌÂÓ˜ ÌÂÙ·‚ÔϤ˜ ‹Ù·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜. £· Ú¤ÂÈ Ù¤ÏÔ˜ Ó· ·Ó·ÊÂÚı› Î·È Ë ÌÂϤÙË ÙˆÓ Mishra Î·È Û˘Ó[11] Ô˘ Ú·ÁÌ·ÙÔÔÈ‹ıËΠ̠ÌÈ· ÌÈÎÚ‹ ÔÌ¿‰· ·ÛıÂÓÒÓ Î·È ˆ˜ ÙÂÏÈο ÛËÌ›· ¯ÚËÛÈÌÔÔ›ËÛ ÙÔ Ú˘ıÌfi ÓÔÛÔÎÔÌÂȷ΋˜ ÓÔÛËÏ›·˜, ÙÔ Ú˘ıÌfi ÂͤÏÈ͢ Ù˘ á∞, ÙÔ ÎÏ¿ÛÌ· ÂÍÒıËÛ˘, ÙË ‰ÔÎÈÌ·Û›· ‚¿‰ÈÛ˘ 6 min Î·È ÙË Û˘ÓÔÏÈ΋ ÂÈ‚›ˆÛË Ì ıÂÙÈο ·ÔÙÂϤÛÌ·Ù· Û fiÏÔ˘˜ ÙÔ˘˜ ·Ú·¿Óˆ ‰Â›ÎÙ˜. ™Â ÌÈ· ¿ÏÏË ÌÂϤÙË ÂÓÙ¿¯ıËÎ·Ó 84 ·ÛıÂÓ›˜ Ì ¯ÚfiÓÈ· ∫∞, ·Ó·ÈÌ›· (∏b<12g/dL) Î·È Ã¡∞ (ÎÚ·ÙÈÓ›ÓË ÔÚÔ‡ >1,5 mg/dL) ÔÈ ÔÔ›ÔÈ ¤Ï·‚·Ó ÁÈ· ¤Ó· ‰È¿ÛÙËÌ· 15 ÌËÓÒÓ ÂÚ˘ıÚÔÔÈËÙ›ÓË ∞ ηıÒ˜ Î·È ÁÏ˘ÎÔÓÈÎfi Û›‰ËÚÔ ÂÓ‰ÔÊÏ‚›ˆ˜[12]. ™ÙÔ Ù¤ÏÔ˜ Ù˘ ÂÚÈfi‰Ô˘ ıÂڷ›·˜ Û ۇÁÎÚÈÛË Ì ÚÔËÁÔ‡ÌÂÓË ·ÚfiÌÔÈ· ÂÚ›Ô‰Ô, 37% ÙˆÓ ·ÛıÂÓÒÓ ÂÌÊ¿ÓÈÛ·Ó ÌÈ· Û˘ÓÔÏÈ΋ Ì›ˆÛË Ù˘ ÎÚ·ÙÈÓ›Ó˘ ÔÚÔ‡, ÂÓÒ 30% Ì›ˆÛ·Ó ÙȘ ··ÈÙÔ‡ÌÂÓ˜ ‰fiÛÂȘ ‰ÈÔ˘ÚËÙÈÎÒÓ. √ ·ÚÈıÌfi˜ ÂÈÛ·ÁˆÁÒÓ ÛÙ· ÓÔÛÔÎÔÌ›· ÌÂÈÒıËΠηٿ 43% Î·È Ô ·ÚÈıÌfi˜ ÙˆÓ ËÌÂÚÒÓ ÓÔÛËÏ›·˜ ηٿ 33%. ™Â ÌÂϤÙË Ô˘ ›Û˘ Û˘Ó¤ÎÚÈÓ ÙËÓ ÂÚ›Ô‰Ô ıÂڷ›·˜ ÙˆÓ ·ÛıÂÓÒÓ Ì ÙËÓ ÚÔËÁÔ‡ÌÂÓË ÚÔ ıÂڷ›·˜ ÂÚ›Ô‰Ô ‰È·ÈÛÙÒıËΠfiÙÈ Û ·ÛıÂÓ›˜ Ì ϋÚË ¤ÎÊÚ·ÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ηډÈÔÓÂÊÚÈ΋˜ ·Ó·ÈÌ›·˜ (¡À∏∞ πππ Î·È πV , Hb<11gr/dL Î·È ÎÚ·ÙÈÓ›ÓË ÔÚÔ‡ 2,1±1,8 mg/dL) Ë ¯ÔÚ‹ÁËÛË ÂÚ˘ıÚÔÔÈËÙ›Ó˘ Î·È Ûȉ‹ÚÔ˘ ·fi ÙÔ ÛÙfiÌ· ›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙË Ì›ˆÛË Ù˘ Ô˘Ú›·˜ ÔÚÔ‡ Î·È ÙˆÓ ËÌÂÚÒÓ ÓÔÛË-
Ï›·˜ ÛÂ Û˘Ó‰˘·ÛÌfi Ì ·‡ÍËÛË Ù˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ ÔÚÔ‡[13]. ∂ÎÙfi˜ ÙˆÓ ·Ú·¿Óˆ ÌÂÏÂÙÒÓ ÌÂ Û˘Ó‰˘·Ṳ̂ÓË ¯Ú‹ÛË ÂÚ˘ıÚÔÔÈËÙ›Ó˘ Î·È Ûȉ‹ÚÔ˘ ˘¿Ú¯Ô˘Ó Î·È ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ (ÔÌÔÏÔÁÔ˘Ì¤Óˆ˜ Ì ¯ÚËÛÈÌÔÔ›ËÛË ÌÈÎÚÔ‡ ‰Â›ÁÌ·ÙÔ˜ ·ÛıÂÓÒÓ Î·È ·Ó·Ú΋ ÛÙ·ÙÈÛÙÈ΋ ÈÛ¯‡) Ô˘ ˘ÔÛÙËÚ›˙Ô˘Ó ÙË ¯ÚËÛÈÌÔÔ›ËÛË ÌÂÌÔӈ̤Ó˘ ÛȉËÚÔıÂڷ›·˜ Û ·ÛıÂÓ›˜ Ì ∫∞ fiˆ˜ ÔÈ ÌÂϤÙ˜ ÙˆÓ Bolger AP Î·È Û˘Ó Î·È Ë ÌÂϤÙË FERRIC-HF[14,15]. ∞Í›˙ÂÈ, Ù¤ÏÔ˜, Ó· ·Ó·ÊÂÚı› Ë ‡·ÚÍË «·Ú¿ÏÂ˘ÚˆÓ» ÌÂÏÂÙÒÓ, ÔÈ Ôԛ˜ ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÏËı˘ÛÌfi Ì á∞ Î·È ·Ó·ÈÌ›· ÚÔÛ·ıÔ‡Ó Ó· ‰È¢ÎÚÈÓ›ÛÔ˘Ó ·ÔÙÂϤÛÌ·Ù· ¯Ú‹Û˘ Ù˘ ÂÚ˘ıÚÔÔÈËÙ›Ó˘ Û ۯ¤ÛË Ì ηډȷÁÁÂȷΤ˜ ·Ú·Ì¤ÙÚÔ˘˜ Î·È Î·Ú‰È·ÁÁÂȷο Û˘Ì‚¿Ì·Ù·. ªÂٷ͇ ÙˆÓ ÌÂÏÂÙÒÓ ·˘ÙÒÓ Û˘ÌÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ÔÈ ÌÂϤÙ˜ CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) Î·È CREATE (Cardiovascular Risk reduction by early Anemia treatment with Epoetin beta)[16,17] ÔÈ Ôԛ˜ Ì¿ÏÈÛÙ· η٤ÏËÍ·Ó Û ·ÓÙÈÊ·ÙÈο ·ÔÙÂϤÛÌ·Ù· fiÛÔÓ ·ÊÔÚ¿ ÛÙ· ÏÂÔÓÂÎÙ‹Ì·Ù· ¯Ú‹Û˘ Ù˘ ÂÚ˘ıÚÔÔÈËÙ›Ó˘ ÛÙËÓ ÚfiÏË„Ë Î·Ú‰È·ÁÁÂÈ·ÎÒÓ Û˘Ì‚·Ì¿ÙˆÓ ÌÂٷ͇ ·ÛıÂÓÒÓ Ì á∞. ™‡Ìʈӷ, Ì¿ÏÈÛÙ·, Ì ÙËÓ ÌÂϤÙË CHOIR Ë ÔÌ¿‰· ·ÛıÂÓÒÓ Ì XNA Î·È ˘„ËÏfiÙÂÚË ∏b ÌÂÙ¿ ·fi ¯Ú‹ÛË EƒO ÂÌÊ¿ÓÈÛ ÌÂÁ·Ï‡ÙÂÚË Â›ÙˆÛË ı·Ó¿ÙˆÓ, ÂÌÊÚ¿ÁÌ·ÙÔ˜ Ì˘Ôηډ›Ô˘ Î·È ÓÔÛÔÎÔÌÂȷ΋˜ ÓÔÛËÏ›·˜ ÁÈ· ∫∞ Î·È ·ÁÁÂȷο ÂÁÎÂÊ·ÏÈο ÂÂÈÛfi‰È· Û ۯ¤ÛË Ì ÙËÓ ÔÌ¿‰· Ì ¯·ÌËÏfiÙÂÚ· ›‰· ∏b (Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜ HR=1,34) (p=0,03). Δ· ·ÔÙÂϤÛÌ·Ù· ·˘Ù¿ ‰Â Û˘ÌʈÓÔ‡Ó Ì ٷ ·ÔÙÂϤÛÌ·Ù· Ù˘ ÌÂϤÙ˘ CREATE, ÛÙËÓ ÔÔ›· Ë ·‡ÍËÛË Ù˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ ÛÙ· ›‰· 13,0-15,0 g/dL Ì ¯Ú‹ÛË ∂ƒ√ ‰Â Û˘Óԉ‡ÙËΠ·fi ·‡ÍËÛË Ù˘ ›وÛ˘ ηډȷÁÁÂÈ·ÎÒÓ Û˘Ì‚·Ì¿ÙˆÓ, ÂÓÒ ÌfiÏȘ 13 ·ÛıÂÓ›˜ ÛÙËÓ ÔÌ¿‰· ·ÛıÂÓÒÓ Ì ˘„ËÏ‹ ·ÈÌÔÛÊ·ÈÚ›ÓË ÂÌÊ¿ÓÈÛ·Ó ÔÍ›· ∫∞ Û ·ÓÙ›ıÂÛË Ì ÙÔ˘˜ 26 ·ÛıÂÓ›˜ Ù˘ ÔÌ¿‰·˜ Ì ¯·ÌËÏ‹ Hb. ™ÎÂÙÈÎÈÛÌfi˜, ‚¤‚·È·, ÚÔηÏÂ›Ù·È Î·Ù¿ ÙËÓ ·Ó¿Ï˘ÛË ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ ÙˆÓ
£EPA¶EIA - ºAPMAKA ·Ú·¿Óˆ ÌÂÏÂÙÒÓ, ·fi ÙË ÛÙÈÁÌ‹ Ô˘ Î·È ÔÈ ‰‡Ô ·ÚÈÔÈ ÏËı˘ÛÌÔ› ÙÔ˘˜ ¿Û¯Ô˘Ó ·fi á∞ Î·È fiϘ ÙȘ ÂÈÏÔΤ˜ Ù˘ Î·È ‰ÂÓ ·ÔÙÂÏÔ‡Ó ÏËı˘ÛÌÔ‡˜ Ô˘ ΢ڛˆ˜ ¿Û¯Ô˘Ó ·fi ∫∞[18].
ªÂϤÙ˜ Ì ÙË ¯Ú‹ÛË ¢·Ú‚ÔÔÈËÙ›Ó˘ ™Â Û‡ÁÎÚÈÛË Ì ÙËÓ ÂÚ˘ıÚÔÔÈËÙ›ÓË, Ë ‰·Ú‚ÔÔÈËÙ›ÓË Ê¤ÚÂÈ ‰‡Ô ÂÚÈÛÛfiÙÂÚ˜ ı¤ÛÂȘ ˘‰·Ù·ÓıÚ¿ÎˆÓ Ô˘ Û˘Ó‰¤ÔÓÙ·È Ì ˘ÔÏ›ÌÌ·Ù· ·˙ÒÙÔ˘, ȉÈfiÙËÙ· Ô˘ ·˘Í¿ÓÂÈ Î·Ù¿ ÙÚÂȘ ÂÚ›Ô˘ ÊÔÚ¤˜ ÂÚÈÛÛfiÙÂÚÔ ÙÔ ¯ÚfiÓÔ ËÌ›ÛÂÈ·˜ ˙ˆ‹˜ Ù˘ ÛÙÔ Ï¿ÛÌ·[19]. ∞˘Ùfi ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·‡ÍËÛË ÙÔ˘ ÌÂÛԉȷÛÙ‹Ì·ÙÔ˜ ÌÂٷ͇ ÙˆÓ ¯ÔÚËÁÔ‡ÌÂÓˆÓ ‰fiÛÂˆÓ Î¿ÓÔÓÙ·˜ Ì ÙÔÓ ÙÚfiÔ ·˘Ùfi ÙË ¯Ú‹ÛË Ù˘ ‰·Ú‚ÔÔÈËÙ›Ó˘ ÈÔ ‚ÔÏÈ΋. Δ¤ÛÛÂÚȘ Û˘ÓÔÏÈο ÌÂϤÙ˜ Ì ÙË ¯Ú‹ÛË ‰·Ú‚ÔÔÈËÙ›Ó˘ ÛÙËÓ ∫∞ ¤¯Ô˘Ó Ú·ÁÌ·ÙÔÔÈËı› ̤¯ÚÈ ÛÙÈÁÌ‹˜[20-23].ŸÏ˜ ÔÈ ·Ú·¿Óˆ ÌÂϤÙ˜ Â›Ó·È Ù˘¯·ÈÔÔÈË̤Ó˜, ‰ÈÏ¿ Ù˘ÊϤ˜ Ì ÌÈÎÚfi Û¯ÂÙÈο ·ÚÈıÌfi ·ÛıÂÓÒÓ Î·È Û¯ÂÙÈο ·Ó·Ú΋ ÛÙ·ÙÈÛÙÈ΋ ÈÛ¯‡ ÚÔÎÂÈ̤ÓÔ˘ Ó· ·Ô‰Â›ÍÔ˘Ó ÙËÓ Â˘ÂÚÁÂÙÈ΋ ›‰Ú·ÛË Ù˘ ‰·Ú‚ÔÔÈËÙ›Ó˘ Û ÛËÌ·ÓÙÈΤ˜ ÎÏÈÓÈΤ˜ ·Ú·Ì¤ÙÚÔ˘˜. øÛÙfiÛÔ, ÌÈ· pooled analysis ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ ÙˆÓ ÌÂÁ·Ï‡ÙÂÚˆÓ ÌÂÏÂÙÒÓ ·Ô‰ÂÈÎÓ‡ÂÈ fiÙÈ Ë ¯Ú‹ÛË ‰·Ú‚ÔÔÈËÙ›Ó˘ Û˘Ó‰˘¿˙ÂÙ·È Ì ÌÈ· Ì›ˆÛË ÙÔ˘ Û¯ÂÙÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘ ÁÈ· Ù· Û‡ÓıÂÙ· ÙÂÏÈο ÛËÌ›· ÙˆÓ ÌÂÏÂÙÒÓ Ô˘ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ı¿Ó·ÙÔ ‹ Î·È ÓÔÛÔÎÔÌÂȷ΋ ÂÈÛ·ÁˆÁ‹ ÏfiÁˆ ∫∞ (15% Ù˘ ÔÌ¿‰·˜ ÙˆÓ ·ÛıÂÓÒÓ ˘fi ‰·Ú‚ÔÔÈËÙ›ÓË Û ۯ¤ÛË Ì ÙÔ 22% Ù˘ ÔÌ¿‰·˜ ÙÔ˘ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘, HR 0,67 95% CI 0,44-1,03, p=0,06) [18].
™˘Ì¤Ú·ÛÌ·-™˘˙‹ÙËÛË ∏ ıÂÒÚËÛË ÙˆÓ ·Ú·¿Óˆ ÌÂÏÂÙÒÓ Ô‰ËÁ› ÛÙÔ Û˘Ì¤Ú·ÛÌ· fiÙÈ
˘ÔÏ›ÔÓÙ·È ·ÎfiÌË Î·›ÚÈ· ‚‹Ì·Ù· ÛÙËÓ Î·ıȤڈÛË Ù˘ ÂÚ˘ıÚÔÔÈËÙ›Ó˘ ˆ˜ ·Ôχو˜ ÂӉ‰ÂÈÁ̤Ó˘ ıÂڷ›·˜ ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ∫∞ Î·È ÈÔ Û˘ÁÎÂÎÚÈ̤ӷ ÛÙË ıÂڷ¢ÙÈ΋ ÚÔÛ¤ÁÁÈÛË Ù˘ ÔÓÙfiÙËÙ·˜ Ô˘ ·ÎÔ‡ÂÈ ÛÙÔ fiÓÔÌ· Û‡Ó‰ÚÔÌÔ Î·Ú‰ÈÔÓÂÊÚÈ΋˜ ·Ó·ÈÌ›·˜. √È ˘¿Ú¯Ô˘Û˜ ÌÂϤÙ˜ ¯ˆÏ·›ÓÔ˘Ó ÛÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÔÈ ÂÚÈÛÛfiÙÂÚ˜ ÂÍ ·˘ÙÒÓ Â›Ó·È ÌË ‰ÈÏ¿ Ù˘ÊϤ˜ ÌÂϤÙ˜, fiÙÈ ¯ÚËÛÈÌÔÔÈÔ‡Ó ÌÈÎÚfi ·ÚÈıÌfi ·ÛıÂÓÒÓ Î·È ÂÔ̤ӈ˜ ¤¯Ô˘Ó ·Ó·Ú΋ ÛÙ·ÙÈÛÙÈ΋ ÈÛ¯‡, ÂÓÒ ÙÔ Û˘ÓÔÏÈÎfi ‰È¿ÛÙËÌ· ·Ú·ÎÔÏÔ‡ıËÛ˘ ÙˆÓ ·ÛıÂÓÒÓ Â›Ó·È È‰È·›ÙÂÚ· ÌÈÎÚfi ÁÈ· Ó· ·Ó·‰Â›ÍÂÈ Èı·Ó¿ ÔʤÏË ‹ Û˘Ó¤ÂȘ Ù˘ ·Ú·¿Óˆ ıÂڷ›·˜. ∂ÈϤÔÓ, Ë Ú·ÁÌ·ÙÔÔ›ËÛË ÌÂÙ··Ó¿Ï˘Û˘ ÙˆÓ ‹‰Ë ˘·Ú¯Ô˘ÛÒÓ ÌÂÏÂÙÒÓ ÌÔÚ› Ó· ‚ÂÏÙ›ˆÓ ÙË ÛÙ·ÙÈÛÙÈ΋ ÈÛ¯‡ ÙˆÓ Û˘ÌÂÚ·ÛÌ¿ÙˆÓ ˆÛÙfiÛÔ Ù· ·ÔÙÂϤÛÌ·Ù· Ù˘ ÌÔÚ› Ó· ·ÌÊÈÛ‚ËÙÔ‡ÓÙ·Ó ÏfiÁˆ Ù˘ ÌÂÁ¿Ï˘ ÎÏÈÓÈ΋˜ Î·È ÛÙ·ÙÈÛÙÈ΋˜ ÂÙÂÚÔÁ¤ÓÂÈ·˜ ÙˆÓ ÏËı˘ÛÌÒÓ ÙˆÓ ‰È·ÊfiÚˆÓ ÌÂÏÂÙÒÓ. ∏ ÂÙÂÚÔÁ¤ÓÂÈ· ·˘Ù‹ Â›Ó·È ·fiÚÚÔÈ· Ù˘ ‰È·ÊÔÚÂÙÈ΋˜ ËÏÈÎȷ΋˜ Û‡ÓıÂÛ˘, ÙÔ˘ ‰È·ÊÔÚÂÙÈÎÔ‡ ÛÙ·‰›Ô˘ ηٿ ¡À∏∞ ·ÏÏ¿ Î·È ¿ÏÏˆÓ ‰È·ÊÔÚÂÙÈÎÒÓ ÎÏÈÓÈÎÒÓ ·Ú·Ì¤ÙÚˆÓ Ô˘ ¯·Ú·ÎÙËÚ›˙Ô˘Ó Ù· ÂÈÏÂÁ̤ӷ ÚÔ˜ ÌÂϤÙË ‰Â›ÁÌ·Ù·. √È ÌÂÁ¿Ï˜ ÚÔÔÙÈΤ˜ ÌÂϤÙ˜ Ô˘ Ú·ÁÌ·ÙÔÔÈÔ‡ÓÙ·È Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· fiˆ˜ Ë RED-HF (·ÚÈÔ˜ ÏËı˘ÛÌfi˜ ·ÛıÂÓÒÓ Ù˘ ¿Û¯ÂÈ ·fi ∫∞)[24], ·ÏÏ¿ Î·È ¿ÏϘ ·ÚÂÌÊÂÚ›˜ fiˆ˜ Ë ÌÂϤÙË ΔR∂∞Δ[25] ‹ Î·È ÌÈÎÚfiÙÂÚ˜ ÌÂϤÙ˜ fiˆ˜ Ë πRON HF[26] ›Ûˆ˜ Ó· Ú›ÍÔ˘Ó Êˆ˜ ÛÙ· ÎÚ›ÛÈÌ· ı¤Ì·Ù· Ù˘ ·ÛÊ¿ÏÂÈ·˜ ¯Ú‹Û˘ ∂ƒ√ Î·È ÛȉËÚÔıÂڷ›·˜ ÛÙËÓ ∫∞. ∏ ·Ï‹ıÂÈ· Â›Ó·È fiÙÈ Ôχ ÂÚÈÛÛfiÙÂÚ˜ Ù˘¯·ÈÔÔÈË̤Ó˜, ‰ÈÏ¿ Ù˘ÊϤ˜, ÂÚÈÛÛfiÙÂÚÔ Ì·ÎÚÔ¯ÚfiÓȘ Î·È ÛÙ·ÙÈÛÙÈο ·ÚΛ˜ ÌÂϤÙ˜ ··ÈÙÔ‡ÓÙ·È ÚÔÎÂÈ̤ÓÔ˘ Ó· ˘¿ÚÍÔ˘Ó ·ÛÊ·Ï‹ Î·È ÂÊ·Ú-
ÌfiÛÈÌ· Û˘ÌÂÚ¿ÛÌ·Ù·. ∂ÈϤÔÓ, ˙ËÙ‹Ì·Ù· fiˆ˜ Ë ÙÈÌ‹ Ù˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ ÛÙfi¯Ô˘ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ¯Ú‹Û˘ ∂ƒ√ Î·È Ûȉ‹ÚÔ˘, Ú¤ÂÈ Ó· ηıÔÚÈÛÙÔ‡Ó ÒÛÙ ӷ ÂÈÙ¢¯ı› ÙÔ ÂÈı˘ÌËÙfi ÈÛÔ˙‡ÁÈÔ ÌÂٷ͇ ÙˆÓ ıÂÙÈÎÒÓ Î·È ·ÚÓËÙÈÎÒÓ (˘ÂÚÁÏÔÈfiÙËÙ·, ˘¤ÚÙ·ÛË) ȉÈÔÙ‹ÙˆÓ Ù˘ ∂ƒ√. ∂ÈÚfiÛıÂÙ·, ÔÏÔ¤Ó· Î·È ÂÚÈÛÛfiÙÂÚ˜ ‚ÈÔÏÔÁÈΤ˜ ‰Ú¿ÛÂȘ Ù˘ ∂ƒ√ ·Ó·ÁÓˆÚ›˙ÔÓÙ·È, ÔÈ Ôԛ˜ Ê·›ÓÂÙ·È Ó· ¤¯Ô˘Ó ‚·ÛÈ΋ ı¤ÛË ÛÙË ıÂڷ¢ÙÈ΋- ·ıÔÊ˘ÛÈÔÏÔÁÈ΋ ÚÔÛ¤ÁÁÈÛË Ù˘ ∫∞. ¶ÈÔ Û˘ÁÎÂÎÚÈ̤ӷ, ÂÎÙfi˜ ·fi ÙË ‚·ÛÈ΋ ‰ÈÂÁÂÚÙÈ΋ Ù˘ ‰Ú¿ÛË ÛÙ· ·ÈÌÔÔÈËÙÈο ·ÙÙ·Ú· ÙÔ˘ Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ, Ë ¯ÔÚ‹ÁËÛË Ù˘ ∂ƒ√ Ê·›ÓÂÙ·È Ó· ÚÔÏ·Ì‚¿ÓÂÈ ÙËÓ ·fiÙˆÛË ÙˆÓ Ì˘ÔηډȷÎÒÓ Î˘ÙÙ¿ÚˆÓ[27] Î·È Ó· ÂÚÈÔÚ›˙ÂÈ ÙËÓ ¤ÎÙ·ÛË Ù˘ Ì˘Ôηډȷ΋˜ ÈÛ¯·ÈÌ›·˜ Î·È ÙÔ ‚·ıÌfi Ù˘ ÌÂÏÏÔÓÙÈ΋˜ Ô˘ÏÔÔ›ËÛ˘[28]. ∏ ‰Ú¿ÛË ·˘Ù‹ Ù˘ ∂ƒ√ ÂÈÙ˘Á¯¿ÓÂÙ·È ·ÊÂÓfi˜ ̤ۈ Ù˘ ·ÚÔ¯‹˜ ÌÂÁ·Ï‡ÙÂÚ˘ ÔÛfiÙËÙ·˜ Ô͢ÁfiÓÔ˘ ÛÙÔÓ ›Û¯·ÈÌÔ Ì˘ÔηډȷÎfi ÈÛÙfi, ̤۷ ·fi ÙËÓ ·‡ÍËÛË Ù˘ Ì¿˙·˜ ÙˆÓ ÂÚ˘ıÚÒÓ, ·ÊÂÙ¤ÚÔ˘ ·fi ÙȘ ÓÂÔ·ÁÁÂÈÔÁÂÓÂÙÈΤ˜ Ù˘ ȉÈfiÙËÙ˜[29]. ∏ ÙÂÏÂ˘Ù·›· ·˘Ù‹ ȉÈfiÙËÙ· Ì¿ÏÈÛÙ· Â›Ó·È ÈÛÔ‰‡Ó·ÌË Ì ·˘Ù‹ Ôχ ÈÛ¯˘ÚÒÓ ·ÁÁÂÈÔÁÂÓÂÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ fiˆ˜ Ô ·ÁÁÂÈ·Îfi˜ ÂÓ‰ÔıËÏÈ·Îfi˜ ·˘ÍËÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ (VEGF) (Vascular Endothelial Growth factor) fiˆ˜ ·Ô‰Â›¯ıËΠ·fi ÂÈÚ¿Ì·Ù· in vitro [30]. Δ¤ÏÔ˜, ı· Ú¤ÂÈ Ó· ·Ó·ÊÂÚıÔ‡Ó Î·È ÔÈ ‰˘ÓËÙÈΤ˜ ·ÓÙÈÊÏÂÁÌÔÓÒ‰ÂȘ ȉÈfiÙËÙ˜ Ù˘ EPO ·fi ÙË ÛÙÈÁÌ‹ Ì¿ÏÈÛÙ· Ô˘ Ë ¯ÔÚ‹ÁËÛ‹ Ù˘ Û ˙ˆÈÎfi ÂÈÚ·Ì·ÙÈÎfi ÌÔÓÙ¤ÏÔ ÈÛ¯·ÈÌ›·˜-·ӷÈÌ¿ÙˆÛ˘ Û˘Óԉ‡ÙËΠ·fi Ì›ˆÛË ÙˆÓ ÂȤ‰ˆÓ ÊÏÂÁÌÔÓˆ‰ÒÓ ‰ÂÈÎÙÒÓ (ΔNFa, IL-6) Î·È ÌÔÚ›ˆÓ ÚÔÛÎfiÏÏËÛ˘ (ICAM-1) (intracellular adhesion molecule-1)[31].
27
ª∞ƒΔπ√™ 2008
μÈ‚ÏÈÔÁÚ·Ê›· 1.
2.
Silverberg DS, Wexler D, Iaina A. The importance of anemia and its correction in the management of severe congestive heart failure. Eur J Heart Fail 2002;4:6816 [review].
3.
Sabatine MS, Morrow DA, Giugliano RP, et al. Association of hemoglobin levels with clinical outcomes in acute coronary syndromes. Circulation 2005;111:2042-9.
4.
Harnett JD, Foley RN, Kent GM, Barre PE, Murray D, Parfrey PS. Congestive heart failure in dialysis patients: prevalence, incidence, prognosis and risk factors. Kidney Int 1995;47:884-90.
5.
Palazzuoli A, Silverberg D, Iovine F et al..Erythropoietin improves anemia exercise tolerance and renal function and reduces B-type natriuretic peptide and hospitalization in patients with heart failure and anemia. Am Heart J 2006; 152:1096.e921096.e15.)
6.
Mancini DM, Katz SD, Lang CC, LaManca J, Hudaihed A, Androne A-S. Effect of erythropoietin on exercise capacity in patients with moderate to severe chronic heart failure. Circulation 2003;107:294- 299.
7.
8.
Silverberg DS, Wexler D, Blum M, et al .The use of subcutaneous Erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function, functional cardiac class, and markedly reduces hospitalizations. J Am Coll Cardiol 2000;35:1737-1744 Silverberg DS, Wexler D, Sheps D, et al. The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study. J Am Coll Cardiol 2001;37: 1775-80.
11. Mishra TK, Mishra SK, Mohanty NK, Rath PK. Prevalence, prognostic importance and therapeutic implications of anemia in heart failure. Indian Heart J 2005;57:670-4. 12. Novak B, Sumodi V, Bynane M, Fagnilli K, Hanna MA, Hixson E. Anemia management in an outpatient heart failure center. J Cardiac Failure 2003; 9(Suppl 1):Abstract 386 13. Delgado RM, Radovancevic R, van Rossem CC, Bracey A, Radovancevic R. Effect of administration of recombinant human erythropoietin in heart failure patients. Eur Heart J 2004;25(Suppl 1): 386A 14. Bolger ∞P, Bartlett FR, Penston HS et al. Intravenous Iron Alone for the Treatment of Anemia in Patients With Chronic Heart Failure. J Am Coll Cardiol 2006;48:1225-7 15. Coletta AP, Tin L, Loh PH, Clark AL, Cleland J.Clinical trials update from the European Society of Cardiology heart failure meeting: TNT subgroup analysis, darbepoetin alfa, FERRIC-HF and KW3902. European Journal of Heart Failure 2006; 8:547-549 16. Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 2006;355:2085-98. 17. Drüeke TB, Locatelli F, Clyne N, et al. Normalization of haemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006;355:2071-84 18. Van Veldhuisen DJ, McMurray JV. Are erythropoietin stimulating proteins safe and efficacious in heart failure? Why we need an adequately powered randomised outcome trial. Editorial. European Journal of Heart Failure 2007; 9: 110-112 19. Egrie JC, Dwyer E, Browne JK, Hitz A, Lykos MA. Darbepoetin alfa has a longer circulating half-life and greater in vivo potency than recombinant human erythropoietin. Exp Hematol 2003;31:290299.
Silverberg DS,Wexler D, Blum M. The effect of correction of anaemia in diabetics and non-diabetics with severe resistant congestive heart failure and chronic renal failure by subcutaneous erythropoietin and intravenous iron. Nephrol Dial Transplant 2003;18:141-6.
20. Ghali JK, Anand I, Abraham WT, et al. Randomized, double-blind, placebo-controlled trial to assess the impact of darbepoetin alfa on exercise tolerance in anemic patients with symptomatic heart failure: results from the Studies of Anemia in Heart Failure Trial (STAMINAHeFT) (abstract). Eur Heart J 2006;27:166 [abstr suppl].
10. Silverberg DS, Wexler D, Blum M, et al. Effects of treatment with epoetin Beta on outcomes in patients with anaemia and chronic heart failure. Kidney Blood Press Res 2005;28:41-7.
21. Van Veldhuisen DJ, Dickstein K, CohenSolal A, et al. Randomized, double-blind, placebo-controlled study to evaluate the effect of two dosing-regimens of darbepoetin-alfa on hemoglobin response and
9.
28
Anand IS, Chandrashekhar Y, Ferrari R, et al. Pathogenesis of edema in chronic anemia: studies of body water and sodium, renal function, haemodynamics and plasma hormones. Br Heart J 1993;70:357 -62.
symptoms in patients with heart failure and anemia (abstract). J Am Coll Cardiol 2006;47(Suppl A):61A. 22. Cleland J GF, Sullivan JT, Ball S, et al. Once-Monthly Administration of Darbepoetin Alfa for the Treatment of Patients with Chronic Heart Failure and Anemia. A Pharmacokinetic and Pharmacodynamic Investigation. J Cardiovasc Pharmacol 2005;46:155-161 23. Ponikowski P, Anker SD, Szachniewicz J, et al. Effect of Darbepoetin Alfa on Exercise Tolerance in Anemic Patients With Symptomatic Chronic Heart Failure. J Am Coll Cardiol 2007;49:753-62 24. Young JB, Anand IS, Diaz R, et al. Reduction of events with darbepoetin alfa in Heart Failure (RED-HF) Trial (abstract). J Card Fail 2006;12(suppl 1):S77. 25. Mix TCH, Brenner RM, Cooper ME, et al. Rationale-Trial to Reduce cardiovascular events with Aranesp Therapy (TREAT): evolving the management of cardiovascular risk in patients with chronic kidney disease. Am Heart J 2005;149:408-13. 26. Beck Da Silva L, Rohde LE, Perreira Barreto AC, et al. Rationale and Design of the IRON-HF Study: A Randomized Trial to Assess the Effects of Iron Supplementation in Heart Failure Patients With Anemia. J Cardiac Fail 2007;13:14-17 27. Parsa CJ, Matsumoto A, Kim J, et al. A novel protective effect of erythropoietin in the infarcted heart. J Clin Invest 2003; 112:999-1007. 28. Namiuchi S, Kagaya Y, Ohta J, et al. High serum erythropoietin level is associated with smaller infarct size in patients with acute myocardial infarction who undergo successful primary percutaneous coronary intervention. J Am Coll Cardiol 2005; 45:1406-12. 29. Heeschen C, Aicher A, Lehmann R, et al. Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood 2003;102:1340-6. 30. Jaquet K, Krause K, Tawakol-Khodai M, Geidel S, Kuck KH. Erythropoietin and VEGF exhibit equal angiogenic potential. Microvasc Res 2002;64:326-33. 31. Liu X, XieW, Liu P, et al. Mechanism of the cardioprotection of rhEPO pretreatment on suppressing the inflammatory response in ischemia-reperfusion. Life Sci 2006;78:2255-64.
£EPA¶EIA - ºAPMAKA
∏ ∂›‰Ú·ÛË Ù˘ ∞ÛÈÚ›Ó˘, Ù˘ ¶·Ú·ÎÂÙ·ÌfiÏ˘ Î·È ÙˆÓ ªË-ÛÙÂÚÔÂȉÒÓ ∞ÓÙÈÊÏÂÁÌÔÓˆ‰ÒÓ º·ÚÌ¿ÎˆÓ ÛÙËÓ ∞ÚÙËÚȷ΋ ¶›ÂÛË. ÃÚ‹ÛÙÔ˜ ƒ›˙Ô˜, ∂ÈÛÙËÌÔÓÈÎfi˜ ™˘ÓÂÚÁ¿Ù˘ ÙÔ˘ ∂Í. π·ÙÚ›Ԣ ¢È·Ù·Ú·¯ÒÓ ÙÔ˘ ªÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ §Èȉ›ˆÓ
ªˆ˘Û‹˜ ∂ÏÈÛ¿Ê, ∫·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜, ΔÔ̤·˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ
∂ÈÛ·ÁˆÁ‹ ªÈ· ·fi ÙȘ Û˘¯ÓfiÙÂÚ· ¯ÚËÛÈÌÔÔÈÔ‡ÌÂÓ˜ ηÙËÁÔڛ˜ Ê·ÚÌ¿ÎˆÓ ÛÙËÓ ÎÏÈÓÈ΋ Ú¿ÍË Â›Ó·È Ù· ÌË ÛÙÂÚÔÂȉ‹ ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë (ª™∞º). øÛÙfiÛÔ ·˘Ù¿ Ù· Ê¿Ú̷η ÂÎÙfi˜ ·fi ÙËÓ ·Ó·ÏÁËÙÈ΋, ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë Î·È ·ÓÙÈ˘ÚÂÙÈ΋ ÙÔ˘˜ ‰Ú¿ÛË ÌÔÚÔ‡Ó Ó· ÚÔηϤÛÔ˘Ó ÌÈ· ÛÂÈÚ¿ ·ÓÂÈı‡ÌËÙˆÓ ÂÓÂÚÁÂÈÒÓ. ªÈ· ·fi ÙȘ ·ÚÂÓ¤ÚÁÂȤ˜ ÙÔ˘˜ Â›Ó·È Î·È Ë ·‡ÍËÛË Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘ (∞¶), Ë ÔÔ›· ÂËÚ¿˙ÂÙ·È ·fi ·Ú¿ÁÔÓÙ˜, fiˆ˜ Ë ‰È¿ÚÎÂÈ· Ù˘ ıÂڷ›·˜, Ë ‰Ú·ÛÙÈ΋ Ô˘Û›· ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ Ô˘ ¯ÔÚËÁÂ›Ù·È Î·È Ë Û˘Á¯ÔÚ‹ÁËÛË ·ÓÙÈ˘ÂÚÙ·ÛÈÎÒÓ Ê·Ú̿ΈÓ.
ªË¯·ÓÈÛÌÔ› Δ· ª™∞º ‰ÚÔ˘Ó ‰È·Ì¤ÛÔ˘ ÌË ÂÎÏÂÎÙÈ΋˜ ·Ó·ÛÙÔÏ‹˜ ÙÔ˘ ÂÓ˙‡ÌÔ˘ ΢ÎÏÔ͢ÁÂÓ¿ÛË (COX)[1]. ∏ ΢ÎÏÔ͢ÁÂÓ¿ÛË Î·Ù·Ï‡ÂÈ ÙȘ ¯ËÌÈΤ˜ ·ÓÙȉڿÛÂȘ Ô˘ Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙË ÌÂÙ·ÙÚÔ‹ ÙÔ˘ ·Ú·¯È‰ÔÓÈÎÔ‡ ÔͤԘ Û ÚÔÛÙ·ÓÔÂȉ‹ (ÚÔÛÙ·ÁÏ·Ó‰›Ó˜, ıÚÔÌ‚ÔÍ¿ÓÈ· Î·È ÚÔÛÙ·Î˘ÎϛӘ). À¿Ú¯Ô˘Ó 2 ÌÔÚʤ˜ ΢ÎÏÔ͢ÁÂÓ¿Û˘, Ë COX-1 Î·È Ë COX-2. ∏ COX-1, Ë ÔÔ›· ÂÓÙÔ›˙ÂÙ·È ÛÙËÓ ÏÂÈÔ„ËÊ›· ÙˆÓ ÈÛÙÒÓ, ¿ÁÔÓÙ·˜ ÙË Û‡ÓıÂÛË ÚÔÛÙ·ÁÏ·Ó‰ÈÓÒÓ, fiˆ˜ ÔÈ ÚÔÛÙ·ÁÏ·Ó‰›Ó˜ ∂2 Î·È π2, Û˘Ì‚¿ÏÂÈ Û ÌÈ· ÛÂÈÚ¿ Ê˘ÛÈÔÏÔÁÈÎÒÓ ÏÂÈÙÔ˘ÚÁÈÒÓ ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡[1]. ∏ ‰Ú¿ÛË Ù˘ Û ۯ¤ÛË Ì ÙËÓ ∞¶ ÂÚÈÏ·Ì‚¿ÓÂÈ ÙË Ú‡ıÌÈÛË ·fi ÙÔ˘˜ ÓÂÊÚÔ‡˜ Ù˘ ·¤ÎÎÚÈÛ˘ Ó·ÙÚ›Ô˘, ηıÒ˜ Î·È ÙË Ú‡ıÌÈÛË ÙÔ˘ ÈÛÔ˙˘Á›Ô˘ ÙÔ˘ ‡‰·ÙÔ˜[2,3]. ∏ ÚÔÛÙ·ÁÏ·Ó‰›ÓË ∂2, Ë ÔÔ›· ·Ú¿ÁÂÙ·È ÛÙË Ì˘ÂÏÒ‰Ë ÌÔ›Ú· ÙÔ˘ ÓÂÊÚÔ‡, ÚÔηÏ› ·ÁÁÂÈԉȷÛÙÔÏ‹, ·Ó·ÛÙ¤ÏÏÂÈ ÙËÓ Â·Ó·ÚÚfiÊËÛË Ó·ÙÚ›Ô˘ Î·È ¯ÏˆÚ›Ô˘ ·fi Ù· ÓÂÊÚÈο ÛˆÏËÓ¿ÚÈ·
Î·È ·Ó·ÛÙ¤ÏÏÂÈ ÙËÓ ‰Ú¿ÛË Ù˘ ·ÓÙȉÈÔ˘ÚËÙÈ΋˜ ÔÚÌfiÓ˘[2,3]. ∏ ÚÔÛÙ·ÁÏ·Ó‰›ÓË π2, Ë ÔÔ›· ·Ú¿ÁÂÙ·È ÛÙË ÊÏÔÈÒ‰Ë ÌÔ›Ú· ÙÔ˘ ÓÂÊÚÔ‡, ÚÔηÏ› ›Û˘ ·ÁÁÂÈԉȷÛÙÔÏ‹ Î·È ÚÔ¿ÁÂÈ ÙË Ó·ÙÚÈÔ‡ÚËÛË[2,3]. ∏ ·Ú·ÁˆÁ‹ Ù˘ COX-2 ÂÓÂÚÁÔÔÈÂ›Ù·È Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÊÏÂÁÌÔÓ‹˜ ΢ڛˆ˜ ·fi Ù· ÂÓÂÚÁÔÔÈË̤ӷ Ì·ÎÚÔÊ¿Á·, ·ÏÏ¿ Î·È ·fi ¿ÏÏ· ·ÙÙ·Ú· ÛÙÔ ÛËÌÂ›Ô Ù˘ ÊÏÂÁÌÔÓ‹˜[1,4]. ∏ COX-2, ‰È·Ì¤ÛÔ˘ Ù˘ ·Ú·ÁˆÁ‹˜ ‰È·ÊfiÚˆÓ ÚÔÛÙ·ÁÏ·Ó‰ÈÓÒÓ, ÚÔ¿ÁÂÈ ÙË ‰È·‰Èηۛ· Ù˘ ÊÏÂÁÌÔÓ‹˜. ∏ ·Ó·ÛÙÔÏ‹ Ù˘ ‰Ú·ÛÙÈÎfiÙËÙ·˜ Ù˘ COX-2 ·fi ÙË ¯ÔÚ‹ÁËÛË ª™∞º ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë ‰Ú¿ÛË ·˘ÙÒÓ ÙˆÓ Ê·Ú̿ΈÓ. ∞ÓÙ›ıÂÙ· Ë ·Ó·ÛÙÔÏ‹ Ù˘ ‰Ú·ÛÙËÚÈfiÙËÙ·˜ Ù˘ COX-1 ·fi Ù· ª™∞º ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙË ‰˘ÛÌÂÓ‹ ›‰Ú·ÛË ÙÔ˘˜ ÛÙËÓ ∞¶.
∏ ‰Ú¿ÛË ÙˆÓ ª™∞º Û ÓÔÚÌÔÙ·ÛÈο ¿ÙÔÌ· ŒÓ·˜ ÛËÌ·ÓÙÈÎfi˜ ·ÚÈıÌfi˜ ÓÔÚÌÔÙ·ÛÈÎÒÓ ·ÙfiÌˆÓ Ï·Ì‚¿ÓÂÈ ¤Ó· Ê¿ÚÌ·ÎÔ ·˘Ù‹˜ Ù˘ ηÙËÁÔÚ›·˜ ÁÈ· οÔÈÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ·. ∏ ¯ÚÔÓÈ΋ ‰È¿ÚÎÂÈ· Ï‹„˘ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ ‰È·‰Ú·Ì·Ù›˙ÂÈ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ·‡ÍËÛË Ù˘ ∞¶ Ô˘ ·Ú·ÙËÚÂ›Ù·È ÌÂÙ¿ ÙË ¯ÔÚ‹ÁËÛË ·˘ÙÒÓ ÙˆÓ Ê·Ú̿ΈÓ. ∏ Ï‹„Ë 800 mg/Ë̤ڷ È‚Ô˘ÚÔÊ·›Ó˘ ‹ placebo 3 ÊÔÚ¤˜ ÙËÓ Ë̤ڷ ÁÈ· ‚Ú·¯‡ ‰È¿ÛÙËÌ· (8 Ë̤Ú˜) Û 10 ˘ÁÈ›˜ Á˘Ó·›Î˜ ‰ÂÓ Ô‰‹ÁËÛ Û ÛËÌ·ÓÙÈ΋ ÌÂÙ·‚ÔÏ‹ Ù˘ ̤Û˘ ∞¶ Û η̛· ·fi ÙȘ 2 ÔÌ¿‰Â˜[5]. ªÈ· ÌÂÙ·-·Ó¿Ï˘ÛË ·ÍÈÔÏfiÁËÛ ÙËÓ Â›‰Ú·ÛË Ù˘ ‚Ú·¯˘¯ÚfiÓÈ·˜ ¯ÔÚ‹ÁËÛ˘ ª™∞º ÛÙËÓ ∞¶ Û 111 ÓÔÚÌÔÙ·ÛÈο ¿ÙÔÌ·[6]. ΔÔ ·ÔÙ¤ÏÂÛÌ· ‹Ù·Ó ÌÈ· ÌÈÎÚ‹ ·ÏÏ¿ ÌË ÛËÌ·ÓÙÈ΋ ·‡-
ÍËÛË Ù˘ ̤Û˘ ∞¶ ηٿ 1.2 mm Hg. ¶·ÚfiÌÔÈ· ‹Ù·Ó Î·È Ù· ·ÔÙÂϤÛÌ·Ù· ÌÈ·˜ ‰Â‡ÙÂÚ˘ ÌÂÙ··Ó¿Ï˘Û˘ fiÛÔÓ ·ÊÔÚ¿ ÙË ‚Ú·¯Â›· ¯ÔÚ‹ÁËÛË ª™∞º Û 146 ÓÔÚÌÔÙ·ÛÈο ¿ÙÔÌ·[7]. ¶Ú¿ÁÌ·ÙÈ, ·Ú·ÙËÚ‹ıËΠÌÈ· ÌÈÎÚ‹ ·‡ÍËÛË Ù˘ ∞¶, Ë ÔÔ›· ˆÛÙfiÛÔ ‰ÂÓ ‹Ù·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋. ∏ ÌÂϤÙË Nurses' Health Study I (NHS-I) ‰ÈÂÚ‡ÓËÛ ÙËÓ Â›‰Ú·ÛË Ù˘ Ì·ÎÚÔ¯ÚfiÓÈ·˜ ¯ÔÚ‹ÁËÛ˘ ª™∞º Û ÓÔÚÌÔÙ·ÛÈΤ˜ Á˘Ó·›Î˜ (ËÏÈΛ·˜ 44-69 ÂÙÒÓ)[8]. H Ï‹„Ë ª™∞º 5-14 Ë̤Ú˜ ·Ó¿ Ì‹Ó· Û˘Û¯ÂÙ›˙ÔÓÙ·Ó Ì ÙËÓ ÂÌÊ¿ÓÈÛË ·ÚÙËÚȷ΋˜ ˘¤ÚÙ·Û˘ (∞À) [¢ÈÔÚıˆÌ¤ÓÔ˜ ™¯ÂÙÈÎfi˜ ∫›Ó‰˘ÓÔ˜ (RR) 1.21; 95% ¢È¿ÛÙËÌ· ∂ÌÈÛÙÔÛ‡Ó˘ (CI) 1.121.31]. ™ÙËÓ ›‰È· ÌÂϤÙË Ë ·ÎÂÙ·ÌÈÓÔÊ·›ÓË Â›Û˘ Û˘Û¯ÂÙ›˙ÔÓÙ·Ó Ì ÙËÓ ÂÌÊ¿ÓÈÛË ∞À, ·ÊÔ‡ Ë ¯ÔÚ‹ÁËÛ‹ Ù˘ 1-4 Ë̤Ú˜ ·Ó¿ Ì‹Ó· ·‡ÍËÛ ÙÔ Û¯ÂÙÈÎfi ΛӉ˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ∞À ηٿ 7%. ∂ÈϤÔÓ ÛÙË ÌÂϤÙË NHS-I ÁÈ· fiÏ· Ù· Û΢¿ÛÌ·Ù· (·ÛÈÚ›ÓË, ·ÎÂÙ·ÌÈÓÔÊ·›ÓË Î·È ª™∞º), Ë ÂÚ·ÈÙ¤Úˆ ·‡ÍËÛË Ù˘ Û˘¯ÓfiÙËÙ·˜ ¯ÔÚ‹ÁËÛ‹˜ ÙÔ˘˜ ·Ó¿ Ì‹Ó· Û˘Û¯ÂÙ›˙ÔÓÙ·Ó Ì ÂÚ·ÈÙ¤Úˆ ·‡ÍËÛË ÙÔ˘ Û¯ÂÙÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ∞À (p<0.001). ¶·ÚfiÌÔÈ· ‹Ù·Ó Î·È Ù· ·ÔÙÂϤÛÌ·Ù· ·fi ÙË ‰ÈÂÙ‹ ·Ú·ÎÔÏÔ‡ıËÛË ÓÂÒÙÂÚˆÓ Á˘Ó·ÈÎÒÓ (ËÏÈΛ·˜ 31-50 ÂÙÒÓ) Ô˘ Û˘ÌÌÂÙ›¯·Ó ÛÙË ÌÂϤÙË Nurses' Health Study Iπ (NHS-Iπ) [9]. H ¯ÔÚ‹ÁËÛË ª™∞º 5-14 Ë̤Ú˜ ÙÔ Ì‹Ó· Û˘Û¯ÂÙ›˙ÔÓÙ·Ó Ì ·‡ÍËÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ∞À ηٿ 49% (95% CI 1.26-1.77). H ¯ÔÚ‹ÁËÛË ·ÎÂÙ·ÌÈÓÔÊ·›Ó˘ ›Û˘ Û˘Û¯ÂÙ›˙ÔÓÙ·Ó Ì ÙËÓ ÂÌÊ¿ÓÈÛË ∞À ·ÎfiÌ· Î·È Ì ¯ÔÚ‹ÁËÛ‹ Ù˘ 1-4 Ë̤Ú˜ ÙÔ Ì‹Ó· (RR 1.19; 95% CI 1.04-1.36).
29
ª∞ƒΔπ√™ 2008
ªÈ· ÌÂϤÙË Ô˘ ¯ÚËÛÈÌÔÔ›ËÛ ·ÛıÂÓ›˜ ·fi ÙËÓ NHS-I Î·È ÙËÓ NHS-II ÂȂ‚·›ˆÛ ÙË Û˘Û¯¤ÙÈÛË ¯ÔÚ‹ÁËÛ˘ ª™∞º Ì ÙËÓ ÂÌÊ¿ÓÈÛË ˘¤ÚÙ·Û˘ [10]. ¶Ú¿ÁÌ·ÙÈ, Ë ¯ÔÚ‹ÁËÛË ª™∞º Û ‰fiÛË Ô˘ ·ÓÙÈÛÙÔȯ› Û ¿Óˆ ·fi 400 mg/Ë̤ڷ È‚Ô˘ÚÔÊ·›Ó˘ ›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·‡ÍËÛË ÙÔ˘ Û¯ÂÙÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ∞À ηٿ 78% ÛÙËÓ ÔÌ¿‰· Ù˘ NHS-I Î·È Î·Ù¿ 60% ÛÙËÓ ÔÌ¿‰· Ù˘ NHS-II. ∂ÈÚfiÛıÂÙ· Ë ¯ÔÚ‹ÁËÛË ·ÎÂÙ·ÌÈÓÔÊ·›Ó˘ Û ‰fiÛË Ô˘ ·ÓÙÈÛÙÔȯ› Û ¿Óˆ ·fi 500 mg/Ë̤ڷ È‚Ô˘ÚÔÊ·›Ó˘ ›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙË ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË ÙÔ˘ Û¯ÂÙÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ∞À ÛÙËÓ ÔÌ¿‰· Ù˘ NHS-I ηٿ 93%, ÂÓÒ ‰ÈÏ·Û›·Û ÙÔÓ Î›Ó‰˘ÓÔ ÛÙËÓ ÔÌ¿‰· Ù˘ NHS-II. ∏ Û˘Û¯¤ÙÈÛË ¯ÔÚ‹ÁËÛ˘ ª™∞º Î·È ÂÌÊ¿ÓÈÛ˘ ∞À ÌÂÏÂÙ‹ıËΠ›Û˘ Û 9411 ˘ÂÚÙ·ÛÈÎÔ‡˜ ·ÛıÂÓ›˜, ÔÈ ÔÔ›ÔÈ Û˘ÁÎÚ›ıËÎ·Ó Ì 9629 ÓÔÚÌÔÙ·ÛÈο ¿ÙÔÌ·. Ì ÙÔÓ ˘ÔÏÔÁÈÛÌfi ÙÔ˘ ÔÛÔÛÙÔ‡ ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ¤Î·Ó·Ó ¯Ú‹ÛË ª™∞º 1 ¤ÙÔ˜ ÚÈÓ ·fi ÙËÓ ÂÌÊ¿ÓÈÛË Ù˘ ∞À[11]. To 41% ÙˆÓ ˘ÂÚÙ·ÛÈÎÒÓ ·ÙfiÌˆÓ Â›¯Â οÓÂÈ ¯Ú‹ÛË ª™∞º 1 ¯ÚfiÓÔ ÚÈÓ ·fi ÙËÓ ÂÌÊ¿ÓÈÛË Ù˘ ∞¶, ÂÓÒ ÙÔ ·ÓÙ›ÛÙÔÈ¯Ô ÔÛÔÛÙfi ÁÈ· Ù· ÓÔÚÌÔÙ·ÛÈο ¿ÙÔÌ· ‹Ù·Ó 26% (RR 2; 95% CI 1.89-2.14). øÛÙfiÛÔ, Ë ÌÂϤÙË PHS (Physicians' Health Study) ÛÙËÓ ÔÔ›· Û˘ÌÌÂÙ›¯·Ó ÓÔÚÌÔÙ·ÛÈÎÔ› ¿Ó‰Ú˜ (n=8229) ¤‰ÂÈÍ ÌÈ· ÌÈÎÚ‹ fi¯È fï˜ ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ Ù¿ÛË ·‡ÍËÛ˘ ÙÔ˘ Û¯ÂÙÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ∞À ÂÍ·ÈÙ›·˜ Ù˘ Ì·ÎÚÔ¯ÚfiÓÈ·˜ ¯ÔÚ‹ÁËÛ˘ ª™∞º[12].
∏ ‰Ú¿ÛË ÙˆÓ ª™∞º Û ˘ÂÚÙ·ÛÈο ¿ÙÔÌ· À¿Ú¯Ô˘Ó ÂӉ›ÍÂȘ fiÙÈ Ô ¤ÏÂÁ¯Ô˜ Ù˘ ∞À ÂËÚ¿˙ÂÙ·È ·fi ÙËÓ Ù·˘Ùfi¯ÚÔÓË ¯ÔÚ‹ÁËÛË ª™∞º. ÀÂÚÙ·ÛÈÎÔ› ·ÛıÂÓ›˜ (n=184) Ô˘ ÂÏ¿Ì‚·Ó·Ó ª™∞º Û˘ÁÎÚ›ıËÎ·Ó Ì ·ÓÙ›ÛÙÔȯ· ˘ÂÚÙ·ÛÈο ¿ÙÔÌ· (n=762) Ô˘ ‰ÂÓ ¤·ÈÚÓ·Ó ª™∞º[13]. √È ·ÛıÂÓ›˜ Ù˘ ÚÒÙ˘ ÔÌ¿‰·˜ ›¯·Ó ˘„ËÏfiÙÂÚË ∞¶ Û ۇÁÎÚÈÛË Ì ÙË ‰Â‡ÙÂÚË ÔÌ¿‰·, ¯ˆÚ›˜ fï˜ ·˘Ù‹ Ë ‰È·ÊÔÚ¿ Ó· Â›Ó·È ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋. øÛÙfiÛÔ, ÛÙËÓ
30
ÚÒÙË ÔÌ¿‰· ·ÙfiÌˆÓ ¯ÔÚËÁÔ‡ÓÙ·Ó ÌÂÁ·Ï‡ÙÂÚÔ˜ ·ÚÈıÌfi˜ ·ÓÙÈ˘ÂÚÙ·ÛÈÎÒÓ Ê·ÚÌ¿ÎˆÓ Û ۇÁÎÚÈÛË Ì ÙË ‰Â‡ÙÂÚË ÔÌ¿‰· (p=0.05), ¤Ó· ‡ÚËÌ· Ô˘ ˘Ô‰ËÏÒÓÂÈ ‰˘ÛÎÔÏfiÙÂÚË Ú‡ıÌÈÛË Ù˘ ∞¶. ¢‡Ô ÌÂÙ·-·Ó·Ï‡ÛÂȘ ÌÂϤÙËÛ·Ó ÙËÓ Â›‰Ú·ÛË ÙˆÓ ª™∞º Û ˘ÂÚÙ·ÛÈο ¿ÙÔÌ·. ™ÙËÓ ÚÒÙË ÌÂÙ·-·Ó¿Ï˘ÛË ÂÍÂÙ¿ÛıËÎÂ Ë Â›‰Ú·ÛË Ù˘ ¯ÔÚ‹ÁËÛ˘ ª™∞º Û 1213 ¿ÙÔÌ· Ì ڢıÌÈṲ̂ÓË ∞¶ (<140/89 mm∏g)[6]. ªÂÙ¿ ·fi ¤Ó· ̤ÛÔ ¯ÚfiÓÔ ·Ú·ÎÔÏÔ‡ıËÛ˘ 15 ËÌÂÚÒÓ, Ë Ì¤ÛË ∞¶ ·˘Í‹ıËΠÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ηٿ 3.2 mm Hg. ™ÙËÓ ›‰È· ÌÂÙ·-·Ó¿Ï˘ÛË Û˘ÁÎÚ›ıËÎ·Ó ‰È¿ÊÔÚ· ª™∞º fiÛÔÓ ·ÊÔÚ¿ ÙËÓ Â›‰Ú·Û‹ ÙÔ˘˜ ÛÙËÓ ∞¶. ∏ Ó·ÚÔͤÓË ·‡ÍËÛ ÙË Ì¤ÛË ∞¶ ηٿ 3.7 mmHg, Ë ÈÓ‰ÔÌÂı·Î›ÓË Î·Ù¿ 3.6 mm Hg Î·È Ë ÈÚÔÍÈοÌË Î·Ù¿ 0.5 mmHg. ∞ÓÙ›ıÂÙ· Ë ÛÔ˘ÏÈÓ‰¿ÎË Ì›ˆÛ ÙË Ì¤ÛË ∞¶ ηٿ 0.1 mmHg, Ë ·ÛÈÚ›ÓË Î·Ù¿ 1.8 mmHg Î·È ÙÔ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ Î·Ù¿ 2.6 mmHg. ¶·ÚfiÌÔÈ· ‹Ù·Ó Î·È Ù· Â˘Ú‹Ì·Ù· Ù˘ ‰Â‡ÙÂÚ˘ ÌÂÙ·-·Ó¿Ï˘Û˘, ÛÙËÓ ÔÔ›· 771 ˘ÂÚÙ·ÛÈÎÔ› ·ÛıÂÓ›˜ ¤Ï·‚·Ó οÔÈÔ ª™∞º ÁÈ· 1 ‚‰ÔÌ¿‰·[7]. ΔÔ ·ÔÙ¤ÏÂÛÌ· ‹Ù·Ó ÌÈ· ·‡ÍËÛË Ù˘ ̤Û˘ ∞¶ ηٿ 5.4 mmHg (95% CI 1.29.6). ™Â ÂÚ·ÈÙ¤Úˆ Û‡ÁÎÚÈÛË ÌÂٷ͇ ÙˆÓ ‰È·ÊfiÚˆÓ ª™∞º ÌfiÓÔ Ë ÈÚÔÍÈοÌË ÚÔοÏÂÛ ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË Ù˘ ̤Û˘ ∞¶. Δ· ˘fiÏÔÈ· ª™∞º (ÈÓ‰ÔÌÂı·Î›ÓË, È‚Ô˘ÚÔÊ·›ÓË, ‰ÈÎÏÔÊÂÓ¿ÎË, Ó·ÚÔͤÓË, ÊÏÔ˘Ú‚ÈÚÔÊ·›ÓË, ÛÔ˘ÏÈÓ‰¿ÎË Î·È ·ÛÈÚ›ÓË) ÂÌÊ¿ÓÈÛ·Ó ÌfiÓÔ Ù¿ÛË ·‡ÍËÛ˘ Ù˘ ∞¶ Ô˘ ‰ÂÓ ‹Ù·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋.
ª™∞º Î·È ·ÓÙÈ˘ÂÚÙ·ÛÈο Ê¿Ú̷η ∏ ›‰Ú·ÛË ÙˆÓ ª™∞º Û ˘ÂÚÙ·ÛÈÎÔ‡˜ ·ÛıÂÓ›˜ ÂËÚ¿˙ÂÙ·È ·fi ÙËÓ Î·ÙËÁÔÚ›· ·ÓÙÈ˘ÂÚÙ·ÛÈÎÒÓ Ê·ÚÌ¿ÎˆÓ Ô˘ Ï·Ì‚¿ÓÂÈ Ô ·ÛıÂÓ‹˜. ªÈ· ÌÂÙ·-·Ó¿Ï˘ÛË ÂÎÙ›ÌËÛ ÙËÓ Â›‰Ú·ÛË ÙˆÓ ª™∞º Û ˘ÂÚÙ·ÛÈÎÔ‡˜ ·ÛıÂÓ›˜ Ô˘ ÂÏ¿Ì‚·Ó·Ó ÌÈ· ·fi ÙÚÂȘ ηÙËÁÔڛ˜ ·ÓÙÈ˘ÂÚÙ·ÛÈÎÒÓ Ê·Ú̿ΈÓ: ‚-·ÔÎÏÂÈÛÙ¤˜, ‰ÈÔ˘ÚËÙÈο ‹ ·ÁÁÂÈԉȷÛÙ·ÏÙÈο Ê¿Ú̷η[7]. ™Â fiÏÔ˘˜ ÙÔ˘˜ Û˘Ó‰˘·ÛÌÔ‡˜ ·-
Ú·ÙËÚ‹ıËΠ·‡ÍËÛË Ù˘ ̤Û˘ ∞¶, fï˜ ÌfiÓÔ Ô Û˘Ó‰˘·ÛÌfi˜ ª™∞º Ì ‚-·ÔÎÏÂÈÛÙ¤˜ ›¯Â ·ÔÙ¤ÏÂÛÌ· ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË Ù˘ ∞¶ ηٿ 6.2 mmHg (95% CI 1-11.4). ™Â ÌÈ· ÔÌ¿‰· ˘ÂÚÙ·ÛÈÎÒÓ ·ÛıÂÓÒÓ (n=168) Ô˘ ¤·ÈÚÓ·Ó ‚ÂÚ··Ì›ÏË ÚÔÛÙ¤ıËÎÂ È‚Ô˘ÚÔÊ·›ÓË, Ó·ÚÔͤÓË ‹ placebo ÁÈ· 3 ‚‰ÔÌ¿‰Â˜[14]. ∫·È ÛÙȘ 3 ηÙËÁÔڛ˜ ‰ÂÓ ·Ú·ÙËÚ‹ıËΠÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË Ù˘ ∞¶. ªÈ· ÛÂÈÚ¿ ÌÂÏÂÙÒÓ Û˘Ó¤ÎÚÈÓ ÙËÓ Â›‰Ú·ÛË ÙˆÓ ª™∞º ÛÂ Û˘Ó‰˘·ÛÌfi Ì ·Ó·ÛÙÔÏ›˜ ÙÔ˘ ÌÂÙ·ÙÚÂÙÈÎÔ‡ ÂÓ˙‡ÌÔ˘ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘ ‹ ·ÓÙ·ÁˆÓÈÛÙ¤˜ ·Û‚ÂÛÙ›Ô˘ ÛÙ· ›‰· Ù˘ ∞¶. ™Â 18 ˘ÂÚÙ·ÛÈÎÔ‡˜ ·ÛıÂÓ›˜ ÔÈ ÔÔ›ÔÈ ÂÏ¿Ì‚·Ó·Ó ÂÓ·Ï·Ú›ÏË (20-40 mg/Ë̤ڷ) ‹ ÓÈʉțÓË (30-60 mg/Ë̤ڷ) ÚÔÛÙ¤ıËΠ·ÛÈÚ›ÓË (100 mg/Ë̤ڷ) ÁÈ· 2 ‚‰ÔÌ¿‰Â˜ Î·È ÛÙË Û˘Ó¤¯ÂÈ· Ë ·ÛÈÚ›ÓË ·ÓÙÈηٷÛÙ¿ıËΠ·fi ÈÓ‰ÔÌÂı·Î›ÓË (75 mg/Ë̤ڷ) ÁÈ· 1 ‚‰ÔÌ¿‰·[15]. ¢ÂÓ ·Ú·ÙËÚ‹ıËΠÛËÌ·ÓÙÈ΋ ÌÂÙ·‚ÔÏ‹ Ù˘ ∞¶ Û η̛· ÔÌ¿‰· ÌÂÙ¿ ÙË ¯ÔÚ‹ÁËÛË ·ÛÈÚ›Ó˘. ∞ÓÙ›ıÂÙ· Ë ÈÓ‰ÔÌÂı·Î›ÓË ·‡ÍËÛ ÛËÌ·ÓÙÈο ÙË Ì¤ÛË 24ÒÚË ∞¶ ÛÙËÓ ÔÌ¿‰· Ù˘ ÂÓ·Ï·Ú›Ï˘ (+6.8 / +4.6 mmHg ÁÈ· ÙË Û˘ÛÙÔÏÈ΋ Î·È ‰È·ÛÙÔÏÈ΋ ∞¶, ·ÓÙ›ÛÙÔȯ·), ÂÓÒ ÛÙËÓ ÔÌ¿‰· Ù˘ ÓÈʉțÓ˘ ‰ÂÓ ·Ú·ÙËÚ‹ıËΠÛËÌ·ÓÙÈ΋ ·‡ÍËÛË Ù˘ ∞¶ (+0.3 / +0.6 mmHg ÁÈ· ÙË Û˘ÛÙÔÏÈ΋ Î·È ‰È·ÛÙÔÏÈ΋ ∞¶, ·ÓÙ›ÛÙÔȯ·). ¶·ÚfiÌÔÈ· ‹Ù·Ó Î·È Ù· ·ÔÙÂϤÛÌ·Ù· ÌÈ·˜ ÌÂϤÙ˘ Û 27 ˘ÂÚÙ·ÛÈο ¿ÙÔÌ· ˘fi ·ÁˆÁ‹ Ì ÂÓ·Ï·Ú›ÏË ‹ ÊÂÏԉțÓË, ÛÙ· ÔÔ›· ÚÔÛÙ¤ıËΠÈÓ‰ÔÌÂı·Î›ÓË 100 mg ÁÈ· 4 ‚‰ÔÌ¿‰Â˜[16]. ™ËÌ·ÓÙÈ΋ ·‡ÍËÛË Ù˘ ∞¶ (+10.3 / +6.6 mmHg ÁÈ· ÙË Û˘ÛÙÔÏÈ΋ Î·È ‰È·ÛÙÔÏÈ΋ ∞¶ ·ÓÙ›ÛÙÔȯ·) ·Ú·ÙËÚ‹ıËΠÌfiÓÔ ÛÙËÓ ÔÌ¿‰· Ù˘ ÂÓ·Ï·Ú›Ï˘. À¿Ú¯Ô˘Ó ÂÔ̤ӈ˜ ÂӉ›ÍÂȘ fiÙÈ Ë ¯ÔÚ‹ÁËÛË ‰È˘‰ÚÔ˘ÚȉÈÓÒÓ Û˘Û¯ÂÙ›˙ÂÙ·È Ì ÌÈÎÚfiÙÂÚË ÌÂÙ·‚ÔÏ‹ Ù˘ ∞¶ ÌÂÙ¿ ÙË ¯ÔÚ‹ÁËÛË ª™∞º.
¢Ú¿ÛË ·Ú·ÎÂÙ·ÌfiÏ˘ ·ÛÈÚ›Ó˘ ∏ ·Ú·ÎÂÙ·ÌfiÏË Î·È Ë ·ÛÈÚ›ÓË ·ÔÙÂÏÔ‡Ó 2 ·fi Ù· Û˘¯ÓfiÙÂÚ· Ê¿Ú̷η Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È
£EPA¶EIA - ºAPMAKA ÛÙËÓ ÎÏÈÓÈ΋ Ú¿ÍË. ∞ÚÎÂÙ¤˜ ÌÂϤÙ˜ ÂÎÙ›ÌËÛ·Ó ÙËÓ Â›‰Ú·Û‹ ·˘ÙÒÓ ÙˆÓ Ê·ÚÌ¿ÎˆÓ ÛÙËÓ ∞¶. ™Â 20 ˘ÂÚÙ·ÛÈο ¿ÙÔÌ· ¯ÔÚËÁ‹ıËΠ·Ú·ÎÂÙ·ÌfiÏË (3 gr/Ë̤ڷ) ÁÈ· 4 ‚‰ÔÌ¿‰Â˜ Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·‡ÍËÛË Ù˘ ‰È·ÛÙÔÏÈ΋˜ ∞¶ ηٿ 4 mmHg ÛÙËÓ ‡ÙÈ· Î·È fiÚıÈ· ı¤ÛË (p<0.05)[17]. Δ· ‰Â‰Ô̤ӷ ÙˆÓ ÌÂÏÂÙÒÓ NHS-I Î·È NHS-II ›Û˘ ¤‰ÂÈÍ·Ó ·‡ÍËÛË Ù˘ Û˘¯ÓfiÙËÙ·˜ ÂÌÊ¿ÓÈÛ˘ ∞À Ì ÙËÓ ·‡ÍËÛË Ù˘ ‰fiÛ˘ Ù˘ ·Ú·ÎÂÙ·ÌfiÏ˘[8-10]. ∏ ¯ÔÚ‹ÁËÛË ·Ú·ÎÂÙ·ÌfiÏ˘ 1 - 4 ÊÔÚ¤˜ ÙÔÓ Ì‹Ó· Û˘Û¯ÂÙ›˙ÔÓÙ·Ó Ì ·‡ÍËÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÂÌÊ¿ÓÈÛ˘ ˘¤ÚÙ·Û˘ ηٿ 7% (RR 1.07; 95% CI 1.02-1.13) ÛÙËÓ NHS-I Î·È 19% (RR 1.19; 95% CI 1.04-1.36) ÛÙËÓ NHS-II. ∞ÓÙ›ıÂÙ· Ë ¯ÔÚ‹ÁËÛË ·ÛÈÚ›Ó˘ Û 2 ÌÂÙ·-·Ó·Ï‡ÛÂȘ Û ÓÔÚÌÔÙ·ÛÈο Î·È ˘ÂÚÙ·ÛÈο ¿ÙÔÌ· ‰ÂÓ ÂËÚ¤·Û ÛËÌ·ÓÙÈο Ù· ›‰· Ù˘ ∞¶ ÌÂÙ¿ ·fi ‰ÈfiÚıˆÛË ÁÈ· ¿ÏÏÔ˘˜ Û˘Á¯˘ÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜[6,7]. ∂ÈϤÔÓ Û ÌÂϤÙË 100 ·ÙfiÌˆÓ Ì ‹È· ˘¤ÚÙ·ÛË ¯ˆÚ›˜ ·ÁˆÁ‹ ÂϤÁ¯ıËÎÂ Ë Â›‰Ú·ÛË Ù˘ ¯ÔÚ‹ÁËÛ˘ 100 mg ·ÛÈÚ›Ó˘ ÙÔ Úˆ› Û ۇÁÎÚÈÛË Ì ϋ„Ë Ù˘ ›‰È·˜ ‰fiÛ˘ ÙÔ ‚Ú¿‰˘[18]. ∏ ÚˆÈÓ‹ ¯ÔÚ‹ÁËÛË Ù˘ ·ÛÈÚ›Ó˘ ‰ÂÓ ÂËÚ¤·Û ÛËÌ·ÓÙÈο Ù· ›‰· Ù˘ ∞¶. øÛÙfiÛÔ Ë ‚Ú·‰ÈÓ‹ ¯ÔÚ‹ÁËÛ‹ Ù˘ Û˘Û¯ÂÙ›ÛıËΠ̠ÂÏ¿ÙÙˆÛË Ù˘ ̤Û˘ ∞¶ ηٿ 6.2 / 4.2 mmHg (p<0.001), ÁÈ· ÙË Û˘ÛÙÔÏÈ΋ Î·È ‰È·ÛÙÔÏÈ΋ ›ÂÛË, ·ÓÙ›ÛÙÔȯ·. ™˘ÁÎÚ›ÛÈÌ· ·ÔÙÂϤÛÌ·Ù· ›¯·Ó Î·È ÔÈ ÌÂϤÙ˜ NHS-II Î·È PHS ÔÈ Ôԛ˜ ¤‰ÂÈÍ·Ó fiÙÈ Ë Ï‹„Ë ·ÛÈÚ›Ó˘ ÚÔοÏÂÛ ÌÈ· Ù¿ÛË ·‡ÍËÛ˘ Ù˘ ∞¶, Ë ÔÔ›· fï˜ ‰ÂÓ ‹Ù·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋[9, 12]. ™ÙË ÌÂϤÙË HOT (Hypertension Optimal Treatment Study) Û˘ÌÌÂÙ›¯·Ó ˘ÂÚÙ·ÛÈÎÔ› ·ÛıÂÓ›˜ (n=18790), ÔÈ ÔÔ›ÔÈ Ù˘¯·ÈÔÔ›Ë-
ıËÎ·Ó Û ·ÛÈÚ›ÓË (75 mg/Ë̤ڷ) ‹ placebo[19]. ªÂÙ¿ ·fi 3.8 ¤ÙË ·Ú·ÎÔÏÔ‡ıËÛ˘ Ë ∞¶ ÛÙËÓ ÔÌ¿‰· Ù˘ ·ÛÈÚ›Ó˘ ·˘Í‹ıËΠηٿ +0.6/+0.3 mmHg ÁÈ· ÙË Û˘ÛÙÔÏÈ΋ Î·È ‰È·ÛÙÔÏÈ΋ ∞¶ ·ÓÙ›ÛÙÔȯ· Û ۇÁÎÚÈÛË Ì ÙËÓ ÔÌ¿‰· ÙÔ˘ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘, ¤Ó· ‡ÚËÌ· Ô˘ ˘ÔÛËÌ·›ÓÂÈ ÙË ÌÈÎÚ‹ ·‡ÍËÛË Ù˘ ∞¶ ·fi ÙË ¯ÔÚ‹ÁËÛË Ù˘ ·ÛÈÚ›Ó˘. øÛÙfiÛÔ, ÛÙË ÌÂϤÙË NHS-I Ë Ï‹„Ë ·ÛÈÚ›Ó˘ 1-4 Ë̤Ú˜ ·Ó¿ Ì‹Ó· Û˘Û¯ÂÙ›ÛıËΠ̠·‡ÍËÛË ÙÔ˘ Û¯ÂÙÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ∞À ηٿ 8% (RR 1.08; 95% CI 1.031.15)[8].
™˘ÌÂÚ¿ÛÌ·Ù· Δ· ª™∞º ·ÔÙÂÏÔ‡Ó ÌÈ· ηÙËÁÔÚ›· Ê·ÚÌ¿ÎˆÓ Ë ÔÔ›· ¯ÚËÛÈÌÔÔÈÂ›Ù·È Û˘¯Ó¿ ÛÙËÓ ÎÏÈÓÈ΋ Ú¿ÍË. À¿Ú¯Ô˘Ó ÌÂϤÙ˜ Ô˘ Û˘Û¯ÂÙ›˙Ô˘Ó ·˘Ù¿ Ù· Ê¿Ú̷η Ì ·‡ÍËÛË Ù˘ ∞¶. ∏ ÌÂÙ·‚ÔÏ‹ Ù˘ ∞¶ ÌÂÙ¿ ÙË ¯ÔÚ‹ÁËÛË ·˘ÙÒÓ ÙˆÓ Ê·ÚÌ¿ÎˆÓ ÂËÚ¿˙ÂÙ·È ·fi ÌÈ· ÛÂÈÚ¿ ·Ú·ÁfiÓÙˆÓ, fiˆ˜ Ë ¯ÚÔÓÈ΋ ‰È¿ÚÎÂÈ· ·ÁˆÁ‹˜ Ì ª™∞º, ÙÔ Â›‰Ô˜ ÙˆÓ ª™∞º Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È Î·È ÙÔ Â›‰Ô˜ Ù˘ ·ÓÙÈ˘ÂÚÙ·ÛÈ΋˜ ıÂڷ›·˜ Ô˘ Ï·Ì‚¿ÓÂÈ Ô ·ÛıÂÓ‹˜. Δ· Â˘Ú‹Ì·Ù· ·˘Ù¿ ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ·ÎfiÌ· Î·È ÌÈÎÚ¤˜ ·˘Í‹ÛÂȘ Ù˘ ∞¶ ·˘Í¿ÓÔ˘Ó ÙÔÓ Î·Ú‰È·ÁÁÂÈ·Îfi ΛӉ˘ÓÔ Ú¤ÂÈ Ó· Ì·˜ οÓÔ˘Ó ÚÔÛÂÎÙÈÎÔ‡˜ fiÛÔÓ ·ÊÔÚ¿ ÙËÓ ÂÈÏÔÁ‹ Î·È ¯ÔÚ‹ÁËÛË ÙˆÓ ª™∞º.
ϤÔÓ Ë ·‡ÍËÛË Ù˘ ∞¶ ÂÍ·ÈÙ›·˜ Ù˘ ¯ÔÚ‹ÁËÛ˘ ª™∞º ÌÔÚ› Ó· ·ÓÙÈÌÂÙˆÈÛı› Ì ÌÈÎÚ¤˜ ·ÏÏ·Á¤˜ ÛÙÔÓ ÙÚfiÔ ˙ˆ‹˜ ÙÔ˘ ·ÛıÂÓ‹, fiˆ˜ Ô ÂÚÈÔÚÈÛÌfi˜ ÙÔ˘ Ó·ÙÚ›Ô˘, Ë ÛˆÌ·ÙÈ΋ ¿ÛÎËÛË Î·È Ë ·ÒÏÂÈ· ‚¿ÚÔ˘˜. ∂Ô̤ӈ˜ Ù· ÔʤÏË ·fi ÙË ¯ÔÚ‹ÁËÛË ÁÈ· ‚Ú·¯‡ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· ª™∞º Û ÓÔÚÌÔÙ·ÛÈο ¿ÙÔÌ· Û˘¯Ó¿ ÍÂÂÚÓÔ‡Ó Ù· ÌÂÈÔÓÂÎÙ‹Ì·Ù· Ù˘ ÌÈÎÚ‹˜ ·‡ÍËÛ˘ Ù˘ ∞¶. ™Â ÂÚÈÙÒÛÂȘ ıÂڷ›·˜ Ì ª™∞º ÁÈ· ÌÂÁ¿ÏÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· Ô Î›Ó‰˘ÓÔ˜ ÂÌÊ¿ÓÈÛ˘ ∞À ·˘Í¿ÓÂÈ Ì ÙËÓ ·‡ÍËÛË Ù˘ Û˘¯ÓfiÙËÙ·˜ ¯ÔÚ‹ÁËÛ‹˜ ÙÔ˘˜. ∂Ô̤ӈ˜ ÚÈÓ ·fi ÙË ¯ÔÚ‹ÁËÛË Ì·ÎÚÔ¯ÚfiÓÈ·˜ ·ÁˆÁ‹˜ Ì ª™∞º Ú¤ÂÈ Ó· ÏËÊıÔ‡Ó ˘fi„Ë Ù· ·Ó·ÌÂÓfiÌÂÓ· ÔʤÏË Û ۇÁÎÚÈÛË Ì ÙÔÓ Èı·Ófi ΛӉ˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ∞À. ∂ÈϤÔÓ Ë ¯ÔÚ‹ÁËÛË ÙˆÓ ª™∞º Ú¤ÂÈ Ó· Û˘Óԉ‡ÂÙ·È ·fi Ù· ··Ú·›ÙËÙ· ˘ÁÈÂÈÓԉȷÈÙËÙÈο ̤ÙÚ· ÚfiÏ˄˘ Ù˘ ∞À.
™Â ÓÔÚÌÔÙ·ÛÈο ¿ÙÔÌ· Ë ‚Ú·¯Â›·˜ ‰È¿ÚÎÂÈ·˜ (1-2 ‚‰ÔÌ¿‰Â˜) ·ÁˆÁ‹ Ì ª™∞º Ô‰ËÁ› Û ÌÈÎÚÔ‡ ‚·ıÌÔ‡ ·‡ÍËÛË Ù˘ ∞¶, ¯ˆÚ›˜ fï˜ Ó· ·˘Í¿ÓÂÈ ÛËÌ·ÓÙÈο ÙÔÓ Î›Ó‰˘ÓÔ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ∞À. ¶Ú¤ÂÈ ˆÛÙfiÛÔ Ó· ÏËÊı› ˘fi„Ë Ë Â˘ÂÚÁÂÙÈ΋ ‰Ú¿ÛË ÙˆÓ ª™∞º fiÛÔÓ ·ÊÔÚ¿ ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ fiÓÔ˘, Ô ÔÔ›Ô˜ ·ÔÙÂÏ› ·›ÙÈÔ ·‡ÍËÛ˘ Ù˘ ∞¶. ∂È-
™Â ˘ÂÚÙ·ÛÈο ¿ÙÔÌ· Ë ÌÂÙ·‚ÔÏ‹ Ù˘ ∞¶ ÂÍ·ÈÙ›·˜ ¯ÔÚ‹ÁËÛ˘ ª™∞º ÂËÚ¿˙ÂÙ·È ·fi ÙÔ Â›‰Ô˜ ÙˆÓ ª™∞º Î·È ÙÔ Â›‰Ô˜ Ù˘ ·ÓÙÈ˘ÂÚÙ·ÛÈ΋˜ ·ÁˆÁ‹˜. ŒÙÛÈ ˘¿Ú¯Ô˘Ó ÂӉ›ÍÂȘ fiÙÈ ÔÚÈṲ̂ӷ ª™∞º, fiˆ˜ Ë ÛÔ˘ÏÈÓ‰¿ÎË Î·È Ë È‚Ô˘ÚÔÊ·›ÓË, ¤¯Ô˘Ó ÌÈÎÚfiÙÂÚË Â›‰Ú·ÛË ÛÙ· ›‰· Ù˘ ∞¶. ∞ÓÙ›ıÂÙ· ª™∞º, fiˆ˜ Ë Ó·ÚÔͤÓË, Ë ÈÓ‰ÔÌÂı·Î›ÓË Î·È ÈÚÔÍÈοÌË, Ê·›ÓÂÙ·È Ó· ·˘Í¿ÓÔ˘Ó Û ÌÂÁ·Ï‡ÙÂÚÔ ‚·ıÌfi ÙËÓ ∞¶. ∏ ·Ú·ÎÂÙ·ÌfiÏË ‰ÂÓ ‰È·Ê¤ÚÂÈ ÛËÌ·ÓÙÈο ·fi Ù· ˘fiÏÔÈ· ª™∞º fiÛÔÓ ·ÊÔÚ¿ ÙËÓ ·‡ÍËÛË Ù˘ ∞¶, ÂÓÒ ·ÓÙ›ıÂÙ· Ë ·ÛÈÚ›ÓË Û˘Û¯ÂÙ›˙ÂÙ·È Ì ÌÈÎÚfiÙÂÚË ÌÂÙ·‚ÔÏ‹ Ù˘ ∞¶, ȉ›ˆ˜ fiÙ·Ó ¯ÔÚËÁÂ›Ù·È Û ÌÈÎÚ¤˜ ‰fiÛÂȘ. ∂ÈϤÔÓ ˘¿Ú¯Ô˘Ó ÂӉ›ÍÂȘ fiÙÈ ¿ÙÔÌ· Ô˘ ‚Ú›ÛÎÔÓÙ·È Û ıÂڷ›· Ì ·ÁˆÁ‹ Ì ‰È˘‰ÚÔ˘Úȉ›Ó˜ ›¯·Ó ÌÈÎÚfiÙÂÚË ·‡ÍËÛË Ù˘ ∞¶ ÌÂÙ¿ ÙË ¯ÔÚ‹ÁËÛË ª™∞º.
3.
4.
Linton MF, Fazio S. Cyclooxygenase-2 and inflammation in atherosclerosis. Curr Opin Pharmacol 2004; 4: 116-23.
5.
McKenney JM, Wright JT, Jr., Goodman RP, Cooper L, Yunker N, Lambert C. Effect of high-dose ibuprofen on 24-hour blood pressure in healthy women. Drug Intell Clin Pharm 1987; 21: 517-21.
μÈ‚ÏÈÔÁÚ·Ê›·
1.
Green GA. Understanding NSAIDs: from aspirin to COX-2. Clin Cornerstone 2001; 3: 50-60.
2.
Mulkerrin EC, Clark BA, Epstein FH. Increased salt retention and hypertension from non-steroidal agents in the elderly. QJM 1997; 90: 411-5.
Murray MD, Lazaridis EN, Brizendine E, Haag K, Becker P, Brater DC. The effect of nonsteroidal antiinflammatory drugs on electrolyte homeostasis and blood pressure in young and elderly persons with and without renal insufficiency. Am J Med Sci 1997; 314: 80-8.
31
ª∞ƒΔπ√™ 2008
6.
Pope JE, Anderson JJ, Felson DT. A meta-analysis of the effects of nonsteroidal anti-inflammatory drugs on blood pressure. Arch Intern Med 1993;153: 477-84.
12. Kurth T, Hennekens CH, Sturmer T, Sesso HD, Glynn RJ, Buring JE, et al. Analgesic use and risk of subsequent hypertension in apparently healthy men. Arch Intern Med 2005; 165: 1903-9.
7.
Johnson AG, Nguyen TV, Day RO. Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis. Ann Intern Med 1994; 121: 289-300.
8.
Dedier J, Stampfer MJ, Hankinson SE, Willett WC, Speizer FE, Curhan GC. Nonnarcotic analgesic use and the risk of hypertension in US women. Hypertension 2002; 40: 604-8; discussion 1-3.
13. Sheridan R, Montgomery AA, Fahey T. NSAID use and BP in treated hypertensives: a retrospective controlled observational study. J Hum Hypertens 2005; 19: 445-50.
9.
Curhan GC, Willett WC, Rosner B, Stampfer MJ. Frequency of analgesic use and risk of hypertension in younger women. Arch Intern Med 2002; 162:2204-8.
10. Forman JP, Stampfer MJ, Curhan GC. Non-narcotic analgesic dose and risk of incident hypertension in US women. Hypertension 2005; 46: 500-7. 11. Gurwitz JH, Avorn J, Bohn RL, Glynn RJ, Monane M, Mogun H. Initiation of antihypertensive treatment during nonsteroidal anti-inflammatory drug therapy. JAMA 1994; 272: 781-6.
14. Houston MC, Weir M, Gray J, Ginsberg D, Szeto C, Kaihlenen PM, et al. The effects of nonsteroidal anti-inflammatory drugs on blood pressures of patients with hypertension controlled by verapamil. Arch Intern Med 1995; 155: 104954. 15. Polonia J, Boaventura I, Gama G, Camoes I, Bernardo F, Andrade P, et al. Influence of non-steroidal anti inflammatory drugs on renal function and 24h ambulatory blood pressure reducing effects of enalapril and nifedipine gastrointestinal therapeutic system in hypertensive patients. J Hypertens 1995;13: 925-31.
16. Morgan T, Anderson A. Interaction of indomethacin with felodipine and enalapril. J Hypertens Suppl 1993; 11: S338-9. 17. Chalmers JP, West MJ, Wing LM, Bune AJ, Graham JR. Effects of indomethacin, sulindac, naproxen, aspirin, and paracetamol in treated hypertensive patients. Clin Exp Hypertens A 1984; 6: 1077-93. 18. Hermida RC, Ayala DE, Calvo C, Lopez JE, Fernandez JR, Mojon A, et al. Administration time-dependent effects of aspirin on blood pressure in untreated hypertensive patients. Hypertension 2003;41: 1259-67. 19. Zanchetti A, Hansson L, Leonetti G, Rahn KH, Ruilope L, Warnold I, et al. Low-dose aspirin does not interfere with the blood pressure-lowering effects of antihypertensive therapy. J Hypertens 2002; 20: 1015-22.
√È ∞ÓÂÈı‡ÌËÙ˜ ∂Ó¤ÚÁÂȘ Ù˘ ™ÈÌÔ˘ÙÚ·Ì›Ó˘ ª. ºÏˆÚÂÓÙ›Ó, ∂ÈÛÙËÌÔÓÈÎfi˜ ™˘ÓÂÚÁ¿Ù˘ ÙÔ˘ π·ÙÚ›Ԣ §Èȉ›ˆÓ ∂. §˘ÌÂÚfiÔ˘ÏÔ˜, §¤ÎÙÔÚ·˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ ª. ∂ÏÈÛ¿Ê, ∫·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ ΔÔ̤·˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ
∂ÈÛ·ÁˆÁ‹ ∏ ÛÈÌÔ˘ÙÚ·Ì›ÓË Â›Ó·È ¤Ó·˜ ÂÎÏÂÎÙÈÎfi˜ ·Ó·ÛÙÔϤ·˜ Ù˘ ·ӷÚfiÛÏ˄˘ ÌÔÓÔ·ÌÈÓÒÓ, ΢ڛˆ˜ Ù˘ ÛÂÚÔÙÔÓ›Ó˘ Î·È Ù˘ ÓÔÚ·‰ÚÂÓ·Ï›Ó˘ Î·È Ôχ ÏÈÁfiÙÂÚÔ Ù˘ ÓÙÔ·Ì›Ó˘.[1,2] ∏ ÛÈÌÔ˘ÙÚ·Ì›ÓË ÌÂÈÒÓÂÈ ÙËÓ ÚfiÛÏË„Ë ÙÚÔÊ‹˜ ÚÔηÏÒÓÙ·˜ ·›ÛıËÌ· ÎÔÚÂÛÌÔ‡,[3] ηıÒ˜ Î·È ÙËÓ ÂÏ¿ÙÙˆÛË ÙÔ˘ ÌÂÙ·‚ÔÏÈÎÔ‡ Ú˘ıÌÔ‡, Ë ÔÔ›· ·Ú·ÙËÚÂ›Ù·È Ì ÙËÓ ·ÒÏÂÈ· ‚¿ÚÔ˘˜,[4] Èı·Ó¿ ÚÔ¿ÁÔÓÙ·˜ ÙË ıÂÚÌÔÁ¤ÓÂÛË.[5] ¶ÚfiÎÂÈÙ·È ÁÈ· ¤Ó· ·ÚÎÂÙ¿ ·ÛʷϤ˜ Î·È ·ÔÙÂÏÂÛÌ·ÙÈÎfi Ê¿ÚÌ·ÎÔ ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ·¯˘Û·ÚΛ·˜. øÛÙfiÛÔ Ú¤ÂÈ Ó· ¯ÔÚËÁÂ›Ù·È Ì ȉȷ›ÙÂÚË ÚÔÛÔ¯‹ Û ·ÛıÂÓ›˜ Ì ÁÓˆÛÙ‹ ηډȷÁÁÂȷ΋ ‹ „˘¯È·ÙÚÈ΋ ÓfiÛÔ. ™Â ·˘Ù‹ ÙËÓ ·Ó·ÛÎfiËÛË ı· ·Ó·ÊÂÚıÔ‡Ó ÔÈ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ Ù˘ ÛÈÌÔ˘ÙÚ·Ì›Ó˘ Î·È ÔÈ ÚÔÊ˘Ï¿ÍÂȘ ÙȘ Ôԛ˜ ÔÊ›ÏÂÈ Ó· ·›ÚÓÂÈ Ô ÎÏÈÓÈÎfi˜ È·ÙÚfi˜ fiÙ·Ó ¯ÔÚËÁ› ÙÔ Û˘ÁÎÂÎÚÈ̤ÓÔ Ê¿ÚÌ·ÎÔ.
32
∞ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ ·fi ÙÔ Î·Ú‰È·ÁÁÂÈ·Îfi Û‡ÛÙËÌ· ∏ ·Ó·ÛÙÔÏ‹ Ù˘ ·ӷÚfiÛÏ˄˘ Ù˘ ÓÔÚ·‰ÚÂÓ·Ï›Ó˘ ·fi ÙË ÛÈÌÔ˘ÙÚ·Ì›ÓË ·Ó·Ì¤ÓÂÙ·È Ó· ÚÔηϤÛÂÈ ·‡ÍËÛË Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘ (∞¶) Î·È ÙÔ˘ ηډȷÎÔ‡ Ú˘ıÌÔ‡. ¶Ú¿ÁÌ·ÙÈ, Û ÔÚÈṲ̂Ó˜ ÌÂϤÙ˜, ÙfiÛÔ Û ˘ÂÚÙ·ÛÈο, fiÛÔ Î·È Û ¿ÙÔÌ· ÌÂ Ê˘ÛÈÔÏÔÁÈ΋ ∞¶, Ë ¯ÔÚ‹ÁËÛË Ù˘ ÛÈÌÔ˘ÙÚ·Ì›Ó˘ ›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·‡ÍËÛË Ù˘ ∞¶.[6-8] ªÈ· ÌÂÙ··Ó¿Ï˘ÛË 21 ÌÂÏÂÙÒÓ Ì ÛÈÌÔ˘ÙÚ·Ì›ÓË ¤‰ÂÈÍ ÌÈ· ‹È· ·‡ÍËÛË Ù˘ Û˘ÛÙÔÏÈ΋˜ ∞¶ ηٿ 1.6 mmHg Î·È Ù˘ ‰È·ÛÙÔÏÈ΋˜ ∞¶ ηٿ 1.8 mmHg.[9] øÛÙfiÛÔ, ·ÎfiÌ· Î·È ÌÈÎÚ‹ ·‡ÍËÛË Ù˘ ∞¶ ·˘Í¿ÓÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ÁÈ· ·ÁÁÂÈ·Îfi ÂÁÎÂÊ·ÏÈÎfi ÂÂÈÛfi‰ÈÔ Î·È ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ.[10] ¶Ú¤ÂÈ Ó· ·Ó·ÊÂÚı› fiÙÈ Ë Ù·˘Ùfi¯ÚÔÓË ¯ÔÚ‹ÁËÛË ·ÓÙÈ˘ÂÚÙ·ÛÈ΋˜ ·ÁˆÁ‹˜ (‚-·ÔÎÏÂÈÛÙ¤˜ ‹ ·Ó·ÛÙÔÏ›˜ ÙÔ˘ ÌÂÙ·ÙÚÂÙÈÎÔ‡ ÂÓ˙‡ÌÔ˘ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘ Ì ‹
¯ˆÚ›˜ ıÂÈ·˙ȉÈÎfi ‰ÈÔ˘ÚËÙÈÎfi) Ì ÛÈÌÔ˘ÙÚ·Ì›ÓË Û ·ÛıÂÓ›˜ Ì ·ÚÙËÚȷ΋ ˘¤ÚÙ·ÛË ‰ÂÓ Ê·›ÓÂÙ·È Ó· ÂÚÈÔÚ›˙ÂÈ ÙËÓ ·ÛÊ¿ÏÂÈ· Î·È ÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· Ù˘ ÛÈÌÔ˘ÙÚ·Ì›Ó˘.[11-16] √È ÌÂÙ·‚ÔϤ˜ Ù˘ ∞¶ Ô˘ ·Ú·ÙËÚÔ‡ÓÙ·È Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ¯ÔÚ‹ÁËÛ˘ Ù˘ ÛÈÌÔ˘ÙÚ·Ì›Ó˘ ÂÍ·ÚÙÒÓÙ·È ·fi ÙË Û¯¤ÛË Ô˘ ˘¿Ú¯ÂÈ ·Ó¿ÌÂÛ· ÛÙËÓ ·‡ÍËÛË Ù˘ ∞¶ ÂÍ·ÈÙ›·˜ Ù˘ ·Ó·ÛÙÔÏ‹˜ Ù˘ ·ӷÚfiÛÏ˄˘ Ù˘ ÓÔÚ·‰ÚÂÓ·Ï›Ó˘ Î·È ÙËÓ ÂӉ¯fiÌÂÓË Ì›ˆÛË Ù˘ ∞¶ Ô˘ ÚÔ·ÙÂÈ ·fi ÙËÓ ·ÒÏÂÈ· ‚¿ÚÔ˘˜. ™˘Ó‹ıˆ˜ Ë ·‡ÍËÛË Ù˘ ∞¶ ·Ú·ÙËÚÂ›Ù·È ÛÙËÓ ¤Ó·ÚÍË Ù˘ ıÂڷ›·˜ Ì ÛÈÌÔ˘ÙÚ·Ì›ÓË,[17] ÂÓÒ Ë ·ÓÂÈı‡ÌËÙË ·˘Ù‹ ÂÓ¤ÚÁÂÈ· ÌÔÚ› Ó· ÂÚÈÔÚÈÛı› Ì ÙËÓ ¿ÛÎËÛË.[14] ∏ ·ÒÏÂÈ· ‚¿ÚÔ˘˜ Ê·›ÓÂÙ·È Ó· ·ÔÙÂÏ› ÙÔÓ ÈÔ ÛËÌ·ÓÙÈÎfi ·Ú¿ÁÔÓÙ· Ô˘ ηıÔÚ›˙ÂÈ ÙÔ Î·Ú‰È·ÁÁÂÈ·Îfi ÚÔÊ›Ï ÙÔ˘ Ê·ÚÌ¿ÎÔ˘. ™˘ÁÎÂÎÚÈ̤ӷ, ¤¯ÂÈ ·Ú·ÙËÚËı› ıÂÙÈ΋ Û˘Û¯¤ÙÈÛË ÌÂٷ͇ Ù˘ Ì›ˆÛ˘ Ù˘ ∞¶ Î·È ÙÔ˘
£EPA¶EIA - ºAPMAKA ‚·ıÌÔ‡ Ì›ˆÛ˘ ÙÔ˘ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜ ÁÈ· ·ÒÏÂȘ >5% ÙÔ˘ ·Ú¯ÈÎÔ‡ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜.[17] ™Â ·ÓÙ›ıÂÛË Ì ÙȘ ÌÂÙ·‚ÔϤ˜ Ù˘ ∞¶, Ë Â›‰Ú·ÛË Ù˘ ÛÈÌÔ˘ÙÚ·Ì›Ó˘ ÛÙÔÓ Î·Ú‰È·Îfi Ú˘ıÌfi Â›Ó·È ÛÙ·ıÂÚ‹ Û fiϘ ۯ‰fiÓ ÙȘ ÌÂϤÙ˜.[11,12] ™˘ÁÎÂÎÚÈ̤ӷ, Ë ÛÈÌÔ˘ÙÚ·Ì›ÓË Û˘Û¯ÂÙ›˙ÂÙ·È Ì ·‡ÍËÛË ÙÔ˘ ηډȷÎÔ‡ Ú˘ıÌÔ‡ Û ۇÁÎÚÈÛË Ì ÙÔ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ, ·ÎfiÌ· Î·È Û ·ÛıÂÓ›˜ Ô˘ Ï·Ì‚¿ÓÔ˘Ó ‚-·ÔÎÏÂÈÛÙ‹.[12] √ ·˘ÍË̤ÓÔ˜ ηډȷÎfi˜ Ú˘ıÌfi˜, fï˜, ÌÔÚ› Ó· ÂËÚ¿ÛÂÈ ·ÚÓËÙÈο ÙË ‰ÔÌ‹ Î·È ÙË ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ηډȷÁÁÂÈ·ÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜.[18] ∞Í›˙ÂÈ Ó· ÛËÌÂȈı› fiÙÈ Ë ÛÈÌÔ˘ÙÚ·Ì›ÓË ·ÛΛ ÌÈ· ·Ú¿‰ÔÍË ‰Ú¿ÛË ÛÙËÓ ·˘ÙÔÚÚ‡ıÌÈÛË ÙÔ˘ ηډȷÁÁÂÈ·ÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜. ŒÙÛÈ ·˘Í¿ÓÂÈ ÌÂÓ ÙÔÓ Î·Ú‰È·Îfi Ú˘ıÌfi, ÂÓÒ Ù·˘Ùfi¯ÚÔÓ· ÌÂÈÒÓÂÈ ÔÚÈṲ̂ÓÔ˘˜ ‰Â›ÎÙ˜ Ô˘ Û˘Û¯ÂÙ›˙ÔÓÙ·È Ì ·˘ÍË̤ÓË ‰Ú·ÛÙËÚÈfiÙËÙ· ÙÔ˘ Û˘Ì·ıËÙÈÎÔ‡ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜.[19,20] ∏ ÛÈÌÔ˘ÙÚ·Ì›ÓË Âȉڿ ÙfiÛÔ ÛÙÔ ÎÂÓÙÚÈÎfi, fiÛÔ Î·È ÛÙÔ ÂÚÈÊÂÚÈÎfi Ó¢ÚÈÎfi Û‡ÛÙËÌ·, ·ÊÔ‡ ·Ó·ÛÙ¤ÏÏÂÈ ÙËÓ Â·Ó·ÚfiÛÏË„Ë Ù˘ ÓÔÚ·‰ÚÂÓ·Ï›Ó˘ Î·È ÛÙ· 2 Û˘ÛÙ‹Ì·Ù· Î·È ·ÛΛ ·Ú¿ÏÏËÏ· ÌÈ· ÎÂÓÙÚÈ΋ Û˘Ì·ıËÙÈÎÔÏ˘ÙÈ΋ ‰Ú¿ÛË. ∏ ÙÂÏÂ˘Ù·›· Ê·›ÓÂÙ·È fiÙÈ ÂÈÙ˘Á¯¿ÓÂÙ·È ‰È·Ì¤ÛÔ˘ ÙˆÓ ·2·‰ÚÂÓÂÚÁÈÎÒÓ ˘Ô‰Ô¯¤ˆÓ Î·È ÚÔÛÔÌÔÈ¿˙ÂÈ Ì ·˘Ù‹ Ù˘ ÎÏÔÓȉ›Ó˘.[21] ™Â ÂÚ›ÙˆÛË ˘ÂÚÂÓÂÚÁÔÔ›ËÛ˘ ÙÔ˘ Û˘Ì·ıËÙÈÎÔ‡ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ Ô˘ ·Ú·ÙËÚÂ›Ù·È ÛÙÔ˘˜ ˘ÂÚÙ·ÛÈÎÔ‡˜ ·ÛıÂÓ›˜,[22] Ê·›ÓÂÙ·È fiÙÈ ˘ÂÚÙÂÚ› Ë Û˘Ì·ıËÙÈÎÔÏ˘ÙÈ΋ ‰Ú¿ÛË Ù˘ ÛÈÌÔ˘ÙÚ·Ì›Ó˘, Ë ÔÔ›· ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙËÓ ·ÒÏÂÈ· ‚¿ÚÔ˘˜ ÌÔÚ› Ó· ÂÚÌËÓ‡ÛÂÈ ÙË Ì›ˆÛË Ù˘ ∞¶ Û ¤Ó· ÔÛÔÛÙfi ·ÛıÂÓÒÓ Ì ·ÚÙËÚȷ΋ ˘¤ÚÙ·ÛË.[23] ∏ ¯Ú‹ÛË Ù˘ ÛÈÌÔ˘ÙÚ·Ì›Ó˘ ‰ÂÓ ·ÓÙÂӉ›ÎÓ˘Ù·È Û ˘ÂÚÙ·ÛÈÎÔ‡˜ ·ÛıÂÓ›˜ Ì ηϿ Ú˘ıÌÈṲ̂ÓË ∞¶. ∞·ÈÙÂ›Ù·È fï˜ ·Ú·ÎÔÏÔ‡ıËÛË ÙˆÓ ÂȤ‰ˆÓ Ù˘ ∞¶ Î·È ÙˆÓ ÛʇÍÂˆÓ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ·ÁˆÁ‹˜. ™˘ÁÎÂÎÚÈ̤ӷ, Ë ∞¶ Î·È Ô Î·Ú‰È·Îfi˜ Ú˘ıÌfi˜ Ú¤ÂÈ Ó· ÌÂÙÚÔ‡ÓÙ·È Î¿ı 2 ‚‰ÔÌ¿‰Â˜ ÙÔ 1Ô ÙÚ›ÌË-
ÓÔ ıÂڷ›·˜, Ì›· ÊÔÚ¿ ÙÔ Ì‹Ó· ·fi ÙÔÓ 4Ô Ì¤¯ÚÈ ÙÔÓ 6Ô Ì‹Ó· Î·È ÛÙË Û˘Ó¤¯ÂÈ· οı 3 Ì‹Ó˜. ∂ÈÚfiÛıÂÙ·, Ë ·ÁˆÁ‹ Ú¤ÂÈ Ó· ‰È·ÎfiÙÂÙ·È ·Ó Û˘Ì‚Â› ÔÙȉ‹ÔÙ ·fi Ù· ·Ú·Î¿Ùˆ: 1. ·‡ÍËÛË ÙÔ˘ ηډȷÎÔ‡ Ú˘ıÌÔ‡ >10 ÛʇÍÂȘ/ÏÂÙfi ‹ Ù˘ ∞¶ (Û˘ÛÙÔÏÈ΋˜ ‹ ‰È·ÛÙÔÏÈ΋˜) >10 mmHg Û 2 Û˘Ó¯fiÌÂÓ˜ ÂÈÛΤ„ÂȘ, 2. ¿ÓÔ‰Ô˜ ÙˆÓ ÂȤ‰ˆÓ Ù˘ ∞¶>145/90 mmHg Û 2 Û˘Ó¯fiÌÂÓ˜ ÂÈÛΤ„ÂȘ Û ·ÛıÂÓ‹ Ì ڢıÌÈṲ̂ÓË ∞¶ ÚÈÓ ÙËÓ ¤Ó·ÚÍË Ù˘ ·ÁˆÁ‹˜ Ì ÛÈÌÔ˘ÙÚ·Ì›ÓË, 3. ÚÔԉ¢ÙÈ΋ ‰‡ÛÓÔÈ·, ıˆÚ·ÎÈÎfi ¿ÏÁÔ˜ ‹ Ô›‰ËÌ· ÛÙ· ÛÊ˘Ú¿. ∏ ÛÈÌÔ˘ÙÚ·Ì›ÓË ¤¯ÂÈ Û˘Û¯ÂÙÈÛı› ›Û˘ Ì ηډȷΤ˜ ·ÚÚ˘ı̛˜, ÔÈ Ôԛ˜ Û˘¯Ó¿ Û˘Óԉ‡ÔÓÙ·È Î·È ·fi ¿ÏÏ· Û˘ÌÙÒÌ·Ù· ·fi ÙÔ Î·Ú‰È·ÁÁÂÈ·Îfi Û‡ÛÙËÌ·.[24,25] ∂ÈÚfiÛıÂÙ·, ¤¯Ô˘Ó ·Ó·ÊÂÚı› 4 ÂÚÈÛÙ·ÙÈο ·Ú¿Ù·Û˘ ÙÔ˘ ‰È·ÛÙ‹Ì·ÙÔ˜ QT Û ·ÛıÂÓ›˜ Ô˘ ‹Ú·Ó ·ÁˆÁ‹ Ì ÛÈÌÔ˘ÙÚ·Ì›ÓË.[24,26] °È· ·˘Ùfi ÙÔ ÏfiÁÔ ‰ÂÓ Û˘ÓÈÛÙ¿Ù·È Ë ¯ÔÚ‹ÁËÛ‹ Ù˘ Û ¿ÙÔÌ· Ô˘ ¤¯Ô˘Ó Û‡Ó‰ÚÔÌÔ Ì·ÎÚÔ‡ QT ‹ Ô˘ Ï·Ì‚¿ÓÔ˘Ó ¿ÏÏ· Ê¿Ú̷η Ô˘ ·Ú·Ù›ÓÔ˘Ó ÙÔ ‰È¿ÛÙËÌ· QT (.¯. ÂÚ˘ıÚÔÌ˘Î›ÓË, ·ÏÔÂÚȉfiÏË, ÙÂÚÊÂÓ·‰›ÓË, ÂÓÙ·Ìȉ›ÓË, ÛÈ˙·Ú›‰Ë, ÚÔ‚Ô˘ÎfiÏË, ÈÌÔ˙›‰Ë, ·ÓÙÈ„˘¯ˆÛÈο, ·ÓÙÈηٷıÏÈÙÈο, ‰ÂÛÈÚ·Ì›ÓË, ÛÈ˙·Ú›‰Ë).[27] ∞fi Ù· ·Ú·¿Óˆ Á›ÓÂÙ·È Û·Ê¤˜ fiÙÈ Ë ÛÈÌÔ˘ÙÚ·Ì›ÓË Ú¤ÂÈ Ó· ¯ÔÚËÁÂ›Ù·È Ì ȉȷ›ÙÂÚË ÚÔÛÔ¯‹, ΢ڛˆ˜ Û ·ÛıÂÓ›˜ Ì ˘ÔΛÌÂÓË Î·Ú‰È·ÁÁÂȷ΋ ÓfiÛÔ. ∞ÓÙÂӉ›ÍÂȘ ÁÈ· ÙË ¯ÔÚ‹ÁËÛË ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ (Summary of Product Characteristics) Â›Ó·È Ë ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ˜, Ë Û˘ÌÊÔÚËÙÈ΋ ηډȷ΋ ·Ó¿ÚÎÂÈ·, Ë Ù·¯˘Î·Ú‰›·, Ë ÂÚÈÊÂÚÈ΋ ·ÔÊÚ·ÎÙÈ΋ ·ÚÙËÚÈÔ¿ıÂÈ·, ÔÈ ·ÚÚ˘ı̛˜ Î·È Ë ·ÁÁÂȷ΋ ÂÁÎÂÊ·ÏÈ΋ ÓfiÛÔ˜.[28]
¡Â˘ÚÔ„˘¯È·ÙÚÈΤ˜ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ À¿Ú¯Ô˘Ó ÛÔÚ·‰ÈΤ˜ ·Ó·ÊÔÚ¤˜ ÛÙË ‚È‚ÏÈÔÁÚ·Ê›· Ô˘ Û˘-
Û¯ÂÙ›˙Ô˘Ó ÙË ÛÈÌÔ˘ÙÚ·Ì›ÓË Ì „˘¯È·ÙÚÈΤ˜ ‰È·Ù·Ú·¯¤˜. √ Taflinski ÚÒÙÔ˜ ·Ó¤ÊÂÚ ¤Ó· „˘¯ˆÛÈÎfi ÂÂÈÛfi‰ÈÔ Û ÌÈ· 19¯ÚÔÓË ·ÛıÂÓ‹ ÂχıÂÚË „˘¯È·ÙÚÈ΋˜ ÓfiÛÔ˘ Ô˘ ÂÌÊ¿ÓÈÛ Ôͤ· ·Ú·ÓÔ˚ο Û˘ÌÙÒÌ·Ù· 3 Ì‹Ó˜ ÌÂÙ¿ ÙËÓ ¤Ó·ÚÍË ıÂڷ›·˜ Ì ÛÈÌÔ˘ÙÚ·Ì›ÓË.[29] ∏ ‰È·ÎÔ‹ Ù˘ ÛÈÌÔ˘ÙÚ·Ì›Ó˘ ·Ú¯Èο Ô‰‹ÁËÛ Û ˘Ô¯ÒÚËÛË ÙˆÓ Û˘Ìو̿وÓ, ·ÏÏ¿ ̤۷ ÛÙȘ ÂfiÌÂÓ˜ 7 Ë̤Ú˜ Ë ÓÔËÙÈ΋ ηٿÛÙ·ÛË Ù˘ ·ÛıÂÓÔ‡˜ ÂȉÂÈÓÒıËÎÂ. ∏ ¯ÔÚ‹ÁËÛË ·ÓÙÈ„˘¯ˆÛÈ΋˜ ıÂڷ›·˜ ·ӤÊÂÚ ÛÙ·‰È·Î¿ ÙËÓ ·ÛıÂÓ‹ ÛÙËÓ ·Ú¯È΋ Ù˘ ηٿÛÙ·ÛË. ¶Èı·Ó¿ Ë ÛÈÌÔ˘ÙÚ·Ì›ÓË Ó· ¿ÁÂÈ „˘¯ˆÛÈο Û˘ÌÙÒÌ·Ù· Û ¿ÙÔÌ· Ì ÚԉȿıÂÛË ÁÈ· „‡¯ˆÛË.[29] √ Binkley Î·È ÔÈ Û˘ÓÂÚÁ¿Ù˜ ÙÔ˘ ·Ó¤ÊÂÚ·Ó ÙËÓ ÂÚ›ÙˆÛË ÌÈ·˜ 62¯ÚÔÓ˘ ·ÛıÂÓÔ‡˜ Ô˘ ·ÚÔ˘Û›·Û 2 ÂÂÈÛfi‰È· ·ÓÈÎÔ‡ ̤۷ Û ‰È¿ÛÙËÌ· 10 ËÌÂÚÒÓ ·fi ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂڷ›·˜ Ì ÛÈÌÔ˘ÙÚ·Ì›ÓË.[30] ∏ ·ÛıÂÓ‹˜ ›¯Â ÁÓˆÛÙfi ÈÛÙÔÚÈÎfi ·ÚfiÌÔÈˆÓ ‰È·Ù·Ú·¯ÒÓ ·fi 25 ¤ÙË, ·ÏÏ¿ ‹Ù·Ó ÂχıÂÚË ÓfiÛÔ˘ Ì ÙËÓ ÂÍ·›ÚÂÛË 2 ÂÂÈÛÔ‰›ˆÓ ·ÓÈÎÔ‡ ÚÈÓ 30 ¯ÚfiÓÈ·. ªÂ ÙË ‰È·ÎÔ‹ Ù˘ ÛÈÌÔ˘ÙÚ·Ì›Ó˘ ‰ÂÓ ·Ú·ÙËÚ‹ıËÎ·Ó ·Ó¿ÏÔÁ· Û˘ÌÙÒÌ·Ù·, ÂÓÒ Ë Â·Ó·¯ÔÚ‹ÁËÛË ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ Ô‰‹ÁËÛ Û Ӥ· ÎÚ›ÛË ·ÓÈÎÔ‡ ̤۷ Û 3 ̤Ú˜, ηıÈÛÙÒÓÙ·˜ ¤ÙÛÈ Ôχ Èı·Ó‹ ÙËÓ ·ÈÙÈÔÏÔÁÈ΋ Û˘Û¯¤ÙÈÛË ÌÂٷ͇ ÙˆÓ ÂÂÈÛÔ‰›ˆÓ ·ÓÈÎÔ‡ Î·È Ù˘ ¯ÔÚ‹ÁËÛ˘ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘.[30] Œ¯ÂÈ Â›Û˘ ÂÚÈÁÚ·Ê› Ë ÂÚ›ÙˆÛË ÂÓfi˜ ·ÛıÂÓ‹ Ì ·Ú·ÏËÚËÙÈ΋ ‰È·Ù·Ú·¯‹ ˘fi ·ÁˆÁ‹, Ô ÔÔ›Ô˜ ÂÌÊ¿ÓÈÛ Ô͇ ·Ú·Ï‹ÚËÌ· 2 Ë̤Ú˜ ÌÂÙ¿ ÙËÓ ¤Ó·ÚÍË Ù˘ ÛÈÌÔ˘ÙÚ·Ì›Ó˘.[31] ∏ ‰È·ÎÔ‹ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ Î·È Ë ¯ÔÚ‹ÁËÛË ·ÓÙÈ„˘¯ˆÛÈ΋˜ ıÂڷ›·˜ ›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ˘Ô¯ÒÚËÛË ÙˆÓ Û˘ÌÙˆÌ¿ÙˆÓ ÙÔ˘ ·ÛıÂÓ‹, ÂÓÒ Ë Â·Ó¤Ó·ÚÍË Ù˘ ÛÈÌÔ˘ÙÚ·Ì›Ó˘ Ô‰‹ÁËÛ ÛÂ Ó¤Ô ·Ú·Ï‹ÚËÌ·. √È ÂÚ¢ÓËÙ¤˜ ‰È·Ù‡ˆÛ·Ó ÙËÓ ¿Ô„Ë fiÙÈ ··ÈÙÂ›Ù·È ÛÙÂÓ‹ ·Ú·ÎÔÏÔ‡ıËÛË ÙˆÓ ·ÛıÂÓÒÓ Ì ÁÓˆÛÙ‹ „˘¯È·ÙÚÈ΋ ‰È·Ù·Ú·¯‹ Û fiÏË ÙË ‰È¿ÚÎÂÈ· Ù˘ ·ÁˆÁ‹˜ Ì ÛÈÌÔ˘ÙÚ·Ì›ÓË.[31]
33
ª∞ƒΔπ√™ 2008
√ Cordeiro ·Ó¤ÊÂÚ ¤Ó· ˘ÔÌ·ÓÈ·Îfi/Ì·ÓÈ·Îfi ÂÂÈÛfi‰ÈÔ ¯ˆÚ›˜ „˘¯ˆÛÈο Û˘ÌÙÒÌ·Ù· Û ¤Ó· ÛÙ·ıÂÚÔÔÈË̤ÓÔ ·ÛıÂÓ‹ Ì ‰ÈÔÏÈ΋ ‰È·Ù·Ú·¯‹, Ô ÔÔ›Ô˜ ¤·ÈÚÓ ÛÈÌÔ˘ÙÚ·Ì›ÓË ÁÈ· 2 ‚‰ÔÌ¿‰Â˜.[32] ∏ ‰È·ÎÔ‹ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙËÓ Ù·˘Ùfi¯ÚÔÓË ¯ÔÚ‹ÁËÛË ·ÓÙÈ„˘¯ˆÛÈ΋˜ ·ÁˆÁ‹˜ Ô‰‹ÁËÛ Û ˘Ô¯ÒÚËÛË ÙÔ˘ ÂÂÈÛÔ‰›Ô˘ ̤۷ Û 3 ‚‰ÔÌ¿‰Â˜.[32] ∏ ¯ÔÚ‹ÁËÛË ÛÈÌÔ˘ÙÚ·Ì›Ó˘ ¤¯ÂÈ Û˘Û¯ÂÙÈÛı› ›Û˘ Î·È Ì ‰È·Ù·Ú·¯¤˜ Ù˘ ÌÓ‹Ì˘.[33] ªÈ· 39¯ÚÔÓË Á˘Ó·›Î· Ô˘ ¤·ÈÚÓ ÛÈÌÔ˘ÙÚ·Ì›ÓË ÁÈ· ¤Ó· Ì‹Ó· ÂÌÊ¿ÓÈÛ ·ÌÓËÛ›·, Ë ÔÔ›· ‚ÂÏÙÈÒıËΠ2 ‚‰ÔÌ¿‰Â˜ ÌÂÙ¿ ÙË ‰È·ÎÔ‹ Ù˘ ·ÁˆÁ‹˜ Î·È ˘Ô¯ÒÚËÛ ÙÂÏ›ˆ˜ ÌÂÙ¿ ·fi 6 ‚‰ÔÌ¿‰Â˜.[33] ∂›Û˘, Ë ‚¿ÛË ‰Â‰ÔÌ¤ÓˆÓ Ù˘ ¶·ÁÎfiÛÌÈ·˜ √ÚÁ¿ÓˆÛ˘ ÀÁ›·˜ ÂÚÈÏ·Ì‚¿ÓÂÈ 33 ·ÎfiÌ· ÂÚÈÙÒÛÂȘ ·ÌÓËÛ›·˜ Ô˘ ıˆÚÂ›Ù·È fiÙÈ ÚÔÎÏ‹ıËÎ·Ó ·fi ÙË ÛÈÌÔ˘ÙÚ·Ì›ÓË.[33] ∏ ‰È·Ù·Ú·¯‹ Ù˘ ÌÓ‹Ì˘ ÌÔÚ› Ó· ÔÊ›ÏÂÙ·È Û ÌÈ· ˘ÔΛÌÂÓË ·ÁÁÂȷ΋ ‚Ï¿‚Ë ÛÙÔÓ ÂÁΤʷÏÔ, ÂÓÒ ‰ÂÓ ·ÔÎÏ›ÂÙ·È Ë ÛÈÌÔ˘ÙÚ·Ì›ÓË Ó· Û˘Ì‚¿ÏÂÈ ¿ÌÂÛ· ÛÙËÓ ÚfiÎÏËÛË ·ÌÓËÛ›·˜.[33] ¶Ú¤ÂÈ ‚¤‚·È· Ó· ÂÈÛËÌ·Óı› fiÙÈ fiÏ· Ù· ÂÚÈÛÙ·ÙÈο ·ÌÓËÛ›·˜ ·Ó·Ê¤ÚıËÎ·Ó ÛÙÔ˘˜ ‰È¿ÊÔÚÔ˘˜ ÔÚÁ·ÓÈÛÌÔ‡˜ ÂÈÙ‹ÚËÛ˘ (postmarking surveillance) Î·È ‰ÂÓ ˘¿Ú¯Ô˘Ó ·Ó¿ÏÔÁ˜ ‰ËÌÔÛȇÛÂȘ ÛÙË ‚È‚ÏÈÔÁÚ·Ê›·.[33] ∂ÈϤÔÓ, ¤¯Ô˘Ó ηٷÁÚ·Ê› ÂÚÈÙÒÛÂȘ ηٿıÏȄ˘, ·˘ÙÔÎÙÔÓÈÎÔ‡ ȉ·ÛÌÔ‡ Î·È ·˘ÙÔÎÙÔÓ›·˜ ¯ˆÚ›˜ fï˜ Ó· ÌÔÚ› Ó· ÂȂ‚·Èˆı› Ë ·ÈÙÈÔÏÔÁÈ΋ Û˘Û¯¤ÙÈÛ‹ ÙÔ˘˜ Ì ÙË ¯ÔÚ‹ÁËÛË Ù˘ ÛÈÌÔ˘ÙÚ·Ì›Ó˘.[34] ∞Ó ÂÌÊ·ÓÈÛı› ηٿıÏÈ„Ë Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ·ÁˆÁ‹˜ Ì ÛÈÌÔ˘ÙÚ·Ì›ÓË, ··ÈÙÂ›Ù·È ÂÚ·ÈÙ¤Úˆ ‰ÈÂÚ‡ÓËÛË.[34] øÛÙfiÛÔ, Û ÌÈ· ÌÈÎÚ‹ ÌÂϤÙË Ù˘ ÔÌ¿‰·˜ Ì·˜ Ë ÛÈÌÔ˘ÙÚ·Ì›ÓË ‚ÂÏÙ›ˆÛ ÙËÓ Î·Ù·ıÏÈÙÈ΋ ‰È¿ıÂÛË, Ë ÔÔ›· ÂÎÙÈÌ‹ıËΠ̠ÙÔ Hamilton Depression Rating Scale.[35] ∏ ÂÏ¿ÙÙˆÛË ÙÔ˘ score ·˘Ù‹˜ Ù˘ Îϛ̷η˜ ˘Ô‰ËÏÒÓÂÈ ‚ÂÏÙ›ˆÛË ÙˆÓ Û˘ÌÙˆÌ¿ÙˆÓ Ù˘ ηٷıÏÈÙÈ΋˜ Û˘Ó‰ÚÔÌ‹˜. ™˘ÁÎÂÎÚÈ̤ӷ, ·Ú·ÙËÚ‹ıËΠÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙÔ˘ score Ù˘ ·Ú·¿Óˆ Îϛ̷η˜
34
Û ۇÁÎÚÈÛË, ÙfiÛÔ Ì ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ, fiÛÔ Î·È Ì ÔÚÏÈÛÙ¿ÙË.[35] ™˘ÌÂÚ·ÛÌ·ÙÈο Ê·›ÓÂÙ·È fiÙÈ ÔÈ „˘¯È·ÙÚÈΤ˜ ÂÈÏÔΤ˜ Ù˘ ÛÈÌÔ˘ÙÚ·Ì›Ó˘ Â›Ó·È Û¿ÓȘ Î·È ·Ú·ÙËÚÔ‡ÓÙ·È Î˘Ú›ˆ˜ Û ¿ÙÔÌ· Ì ÁÓˆÛÙ‹ ˘ÔΛÌÂÓË „˘¯È·ÙÚÈ΋ ‰È·Ù·Ú·¯‹. ∂Ô̤ӈ˜, Ë ¯ÔÚ‹ÁËÛË ÛÈÌÔ˘ÙÚ·Ì›Ó˘ ÛÙÔ˘˜ Û˘ÁÎÂÎÚÈ̤ÓÔ˘˜ ·ÛıÂÓ›˜ Ú¤ÂÈ Ó· Á›ÓÂÙ·È Ì ȉȷ›ÙÂÚË ÚÔÛÔ¯‹ Î·È Ì ٷ˘Ùfi¯ÚÔÓË ÛÙÂÓ‹ ·Ú·ÎÔÏÔ‡ıËÛ‹ ÙÔ˘˜.
™ÈÌÔ˘ÙÚ·Ì›ÓË Î·È Ë·ÙÔÙÔÍÈÎfiÙËÙ· ∏ ÛÈÌÔ˘ÙÚ·Ì›ÓË ‰ÂÓ ¤¯ÂÈ Û˘Û¯ÂÙÈÛı› Ì ˷ÙÔÙÔÍÈÎfiÙËÙ·. ¢È·Ù·Ú·¯¤˜ Ù˘ Ë·ÙÈ΋˜ ‚ÈÔÏÔÁ›·˜ ¤¯Ô˘Ó ·Ó·ÊÂÚı› ÛÙÔ 1.6% ÙˆÓ ·ÙfiÌˆÓ Ô˘ ‹Ú·Ó ÛÈÌÔ˘ÙÚ·Ì›ÓË ¤Ó·ÓÙÈ 0.8% ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ‹Ú·Ó ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ.[34] √È ÌÂÙ·‚ÔϤ˜ ÙˆÓ Ë·ÙÈÎÒÓ ÂÓ˙‡ÌˆÓ ‹Ù·Ó ηٿ ηÓfiÓ· ÛÔÚ·‰ÈΤ˜, Û˘¯Ó¿ ˘Ô¯ˆÚÔ‡Û·Ó Ì ÙË Û˘Ó¤¯ÈÛË Ù˘ ·ÁˆÁ‹˜ Î·È ‰ÂÓ ‹Ù·Ó ‰ÔÛÔÂÍ·ÚÙÒÌÂÓ˜.[34] À¿Ú¯ÂÈ ÌfiÓÔ ¤Ó· ÂÚÈÛÙ·ÙÈÎfi Ë·ÙÔÙÔÍÈÎfiÙËÙ·˜ ÌÂÙ¿ ·fi ıÂڷ›· Ì ÛÈÌÔ˘ÙÚ·Ì›ÓË.[36] ªÈ· Á˘Ó·›Î· ·ÚÔ˘Û›·Û ÎÓËÛÌfi, ÎfiˆÛË, ·‰˘Ó·Ì›· Î·È ÛÎÔ˘Úfi¯ÚˆÌ· Ô‡Ú· 2 ‚‰ÔÌ¿‰Â˜ ÌÂÙ¿ ÙËÓ ¤Ó·ÚÍË Ù˘ ÛÈÌÔ˘ÙÚ·Ì›Ó˘. ∏ ‚ÈÔ„›· ‹·ÙÔ˜ ·ÔÎ¿Ï˘„ ÂÈÎfiÓ· Û˘Ì‚·Ù‹ Ì ʷÚ̷΢ÙÈ΋ Ë·Ù›Ùȉ·, ÂÓÒ Ô ÂÚÁ·ÛÙËÚÈ·Îfi˜ Î·È ·ÂÈÎÔÓÈÛÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ·¤ÎÏÂÈÛ·Ó ¿ÏÏ· ·›ÙÈ· Ë·ÙÈ΋˜ ‚Ï¿‚˘. ∏ ‰È·ÎÔ‹ Ù˘ ÛÈÌÔ˘ÙÚ·Ì›Ó˘ Ô‰‹ÁËÛ Û ˘Ô¯ÒÚËÛË ÙˆÓ Û˘ÌÙˆÌ¿ÙˆÓ Î·È Â·Ó·ÊÔÚ¿ ÙˆÓ Ë·ÙÈÎÒÓ ‰ÂÈÎÙÒÓ ÛÙ· Ê˘ÛÈÔÏÔÁÈο ›‰·, ÁÂÁÔÓfi˜ Ô˘ Û˘ÓËÁÔÚ› ˘¤Ú Ù˘ ÚfiÎÏËÛ˘ Ë·ÙÈ΋˜ ‰È·Ù·Ú·¯‹˜ ·fi ÙË ÛÈÌÔ˘ÙÚ·Ì›ÓË. ¶·ÚfiÏ· ·˘Ù¿ ‰ÂÓ ÚÔÙ¿ıËΠοÔÈÔ˜ ˘ÔΛÌÂÓÔ˜ Ì˯·ÓÈÛÌfi˜ Ù˘ Ë·ÙÔÙÔÍÈÎfiÙËÙ·˜.[36] ¶Ú¤ÂÈ Ó· ÂÈÛËÌ·Óı› fiÙÈ Ë ·ÒÏÂÈ· ‚¿ÚÔ˘˜ Ô˘ ÂÈÙ˘Á¯¿ÓÂÙ·È Ì ÙË ÛÈÌÔ˘ÙÚ·Ì›ÓË ÌÔÚ› Ó· ‚ÂÏÙÈÒÛÂÈ ÙÔ˘˜ ‰Â›ÎÙ˜ Ë·ÙÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ Û ·ÛıÂÓ›˜ Ì ÌË ·ÏÎÔÔÏÈ΋ ÏÈÒ‰Ë ‰È‹ıËÛË ÙÔ˘ ‹·ÙÔ˜.[37,38]
∏ ¯ÔÚ‹ÁËÛË ÛÈÌÔ˘ÙÚ·Ì›Ó˘ ‰ÂÓ ·ÓÙÂӉ›ÎÓ˘Ù·È Ô‡Ù ··ÈÙÂ›Ù·È ÙÚÔÔÔ›ËÛË Ù˘ ‰ÔÛÔÏÔÁ›·˜ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ Û ·ÛıÂÓ›˜ Ì ‹È· ‹ ̤ÙÚÈ· Ë·ÙÈ΋ ‚Ï¿‚Ë. ∞ÓÙ›ıÂÙ· ÙÔ Ê¿ÚÌ·ÎÔ Ú¤ÂÈ Ó· ·ÔʇÁÂÙ·È Û ÂÚÈÙÒÛÂȘ ‚·ÚÈ¿˜ Ë·ÙÈ΋˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜.[34]
ÕÏϘ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ √È ÈÔ Û˘¯Ó¤˜ ·ÚÂÓ¤ÚÁÂȘ Ù˘ ÛÈÌÔ˘ÙÚ·Ì›Ó˘ Â›Ó·È Ë ÍËÚÔÛÙÔÌ›·, Ë ‰˘ÛÎÔÈÏÈfiÙËÙ·, Ë ÎÂÊ·Ï·ÏÁ›·, Ë ·¸Ó›·, Ë ·ÓÔÚÂÍ›· Î·È Ë Ó·˘Ù›·, ÔÈ ÂÚÈÛÛfiÙÂÚ˜ ·fi ÙȘ Ôԛ˜ ÌÔÚÔ‡Ó Ó· ·Ô‰ÔıÔ‡Ó ÛÙËÓ ·ÓÙȯÔÏÈÓÂÚÁÈ΋ ‰Ú¿ÛË ÙÔ˘ Ê·ÚÌ¿ÎÔ˘.[39-41] Œ¯Ô˘Ó ·Ó·ÊÂÚı› ‰È¿ÊÔÚ˜ ¿ÏϘ ·ÚÂÓ¤ÚÁÂȘ Û ÔÛÔÛÙfi ≥1% ÙÔ˘ Û˘ÓfiÏÔ˘ ÙˆÓ ·ÛıÂÓÒÓ ÛÙÔ˘˜ ÔÔ›Ô˘˜ ¯ÔÚËÁ‹ıËΠÛÈÌÔ˘ÙÚ·Ì›ÓË Û ÌÂϤÙ˜ Ô˘ ¤ÁÈÓ·Ó ÚÈÓ ÙËÓ Î˘ÎÏÔÊÔÚ›· ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ (premarketing studies), fiˆ˜ ˘ÚÂÙfi˜, ‰È¿ÚÚÔÈ·, ÌÂÙˆÚÈÛÌfi˜, Á·ÛÙÚÂÓÙÂÚ›Ùȉ·, ÂÚÈÊÂÚÈÎfi Ô›‰ËÌ·, ·ÚıÚ›Ùȉ·, Îڿ̘ ÛÙ· οو ¿ÎÚ·, ˘ÂÚÙÔÓ›·, Û‡Á¯˘ÛË, ‚ÚÔÁ¯›Ùȉ·, ‰‡ÛÓÔÈ·, ÎÓËÛÌfi˜, ·Ì‚Ï˘ˆ›·, ÔÍ›· ‰È¿ÌÂÛË ÓÂÊÚ›Ùȉ· Î·È ‰È·Ù·Ú·¯¤˜ Ù˘ ÂÌÌ‹ÓÔ˘ Ú‡Û˘. ∂Í·ÈÙ›·˜ Ù˘ ÂÌÊ¿ÓÈÛ˘ Û·ÛÌÒÓ Û ÔÚÈṲ̂ÓÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ¤Ï·‚·Ó ÛÈÌÔ˘ÙÚ·Ì›ÓË (<0.1%), Ú¤ÂÈ Ó· Á›ÓÂÙ·È ÚÔÛÂÎÙÈ΋ ¯Ú‹ÛË Ù˘ Û ·ÛıÂÓ›˜ Ì ÈÛÙÔÚÈÎfi Û·ÛÌÒÓ Î·È ‰È·ÎÔ‹ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ Û ·ÛıÂÓ›˜ Ô˘ ÂÌÊ·Ó›˙Ô˘Ó Û·ÛÌÔ‡˜.[34]
™˘ÌÂÚ¿ÛÌ·Ù· ™˘ÌÂÚ·ÛÌ·ÙÈο Ë ÛÈÌÔ˘ÙÚ·Ì›ÓË Â›Ó·È ¤Ó· ·ÚÎÂÙ¿ ·ÛʷϤ˜ Ê¿ÚÌ·ÎÔ Î·Ù¿ Ù˘ ·¯˘Û·ÚΛ·˜, ÙÔ ÔÔ›Ô fï˜ Ú¤ÂÈ Ó· ¯ÔÚËÁÂ›Ù·È Ì ȉȷ›ÙÂÚË ÚÔÛÔ¯‹ ‹ ·ÎfiÌ· Î·È Ì ÂÈÊ˘Ï¿ÍÂȘ, ȉȷ›ÙÂÚ· Û ·ÛıÂÓ›˜ Ì ˘ÔΛÌÂÓË Î·Ú‰È·Î‹ ‹ „˘¯È·ÙÚÈ΋ ÓfiÛÔ. ∂›Û˘, ÔÈ È·ÙÚÔ› ÔÊ›ÏÔ˘Ó Ó· ÙËÚÔ‡Ó Û˘ÁÎÂÎÚÈ̤Ó˜ Ô‰ËÁ›Â˜ Û ¿ÙÔÌ· Ì ·ÚÙËÚȷ΋ ˘¤ÚÙ·ÛË Ô˘ Ï·Ì‚¿ÓÔ˘Ó ÛÈÌÔ˘ÙÚ·Ì›ÓË Î·È Ó· ÚÔÛ·ÚÌfi˙Ô˘Ó ÙË ‰ÔÛÔÏÔÁ›· ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ Û ·ÛıÂÓ›˜ Ì ‚·ÚÈ¿ Ë·ÙÈ΋ ÓfiÛÔ.
£EPA¶EIA - ºAPMAKA μÈ‚ÏÈÔÁÚ·Ê›· 1.
2.
3.
Arterburn DE, Crane PK and Veenstra DL. The efficacy and safety of sibutramine for weight loss: a systematic review. Arch Intern Med 2004; 164: 9941003. Jackson HC, Bearham MC, Hutchins LJ, Mazurkiewicz SE, Needham AM and Heal DJ. Investigation of the mechanisms underlying the hypophagic effects of the 5-HT and noradrenaline reuptake inhibitor, sibutramine, in the rat. Br J Pharmacol 1997; 121: 1613-1618. McNeely W and Goa KL. Sibutramine. A review of its contribution to the management of obesity. Drugs 1998; 56: 1093-1124.
4.
Finer N. Sibutramine: its mode of action and efficacy. Int J Obes Relat Metab Disord 2002; 26 Suppl 4: S29-S33.
5.
Lean. How does sibutramine work? Int J Obes Relat Metab Disord 2001; 25 Suppl 4: S8-S11.
6.
James WP, Astrup A, Finer N, Hilsted J, Kopelman P, Rossner S et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance. Lancet 2000; 356: 2119-2125.
7.
8.
9.
McMahon FG, Fujioka K, Singh BN, Mendel CM, Rowe E, Rolston K et al. Efficacy and safety of sibutramine in obese white and African American patients with hypertension: a 1-year, double-blind, placebo-controlled, multicenter trial. Arch Intern Med 2000; 160: 2185-2191. Fujioka K, Seaton TB, Rowe E, Jelinek CA, Raskin P, Lebovitz HE et al. Weight loss with sibutramine improves glycaemic control and other metabolic parameters in obese patients with type 2 diabetes mellitus. Diabetes Obes Metab 2000; 2: 175-187. Kim SH, Lee YM, Jee SH and Nam CM. Effect of sibutramine on weight loss and blood pressure: a meta-analysis of controlled trials. Obes Res 2003; 11: 1116-1123.
10. Ohkubo T. Prognostic significance of variability in ambulatory and home blood pressure from the ohasama study. J Epidemiol 2007; 17: 109-113. 11. McMahon FG, Weinstein SP, Rowe E, Ernst KR, Johnson F and Fujioka K. Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors. J Hum Hypertens 2002; 16: 5-11. 12. Sramek JJ, Leibowitz MT, Weinstein SP, Rowe ED, Mendel CM, Levy B et al. Efficacy and safety of sibutramine for weight loss in obese patients with hypertension well controlled by betaadrenergic blocking agents: a placebocontrolled, double-blind, randomised trial. J Hum Hypertens 2002; 16: 13-19. 13. Ersoz HO, Ukinc K, Baykan M, Erem C, Durmus I, Hacihasanoglu A et al. Effect of low-dose metoprolol in combination with sibutramine therapy in normotensive obese patients: a randomized controlled study. Int J Obes Relat Metab Disord 2004; 28: 378-383.
14. Berube-Parent S, Prud'homme D, StPierre S, Doucet E and Tremblay A. Obesity treatment with a progressive clinical tri-therapy combining sibutramine and a supervised diet--exercise intervention. Int J Obes Relat Metab Disord 2001; 25: 1144-1153. 15. Fanghanel G, Cortinas L, Sanchez-Reyes L, Gomez-Santos R, Campos-Franco E and Berber A. Safety and efficacy of sibutramine in overweight Hispanic patients with hypertension. Adv Ther 2003; 20: 101-113. 16. Derosa G, Cicero AF, Murdolo G, Piccinni MN, Fogari E, Bertone G et al. Efficacy and safety comparative evaluation of orlistat and sibutramine treatment in hypertensive obese patients. Diabetes Obes Metab 2005; 7: 47-55. 17. Sharma AM. Sibutramine in overweight/obese hypertensive patients. Int J Obes Relat Metab Disord 2001; 25 Suppl 4: S20-S23. 18. Reil JC and Bohm M. The role of heart rate in the development of cardiovascular disease. Clin Res Cardiol 2007; 96: 585592. 19. Birkenfeld AL, Schroeder C, Boschmann M, Tank J, Franke G, Luft FC et al. Paradoxical effect of sibutramine on autonomic cardiovascular regulation. Circulation 2002; 106: 2459-2465. 20. Birkenfeld AL, Schroeder C, Pischon T, Tank J, Luft FC, Sharma AM et al. Paradoxical effect of sibutramine on autonomic cardiovascular regulation in obese hypertensive patients--sibutramine and blood pressure. Clin Auton Res 2005; 15: 200-206. 21. Eisenhofer G, Saigusa T, Esler MD, Cox HS, Angus JA and Dorward PK. Central sympathoinhibition and peripheral neuronal uptake blockade after desipramine in rabbits. Am J Physiol 1991; 260: R824832. 22. Grassi G, Seravalle G, Cattaneo BM, Bolla GB, Lanfranchi A, Colombo M et al. Sympathetic activation in obese normotensive subjects. Hypertension 1995; 25: 560-563. 23. Scholze J. [Sibutramine in clinical practice - a PMS-study with positive effects on blood pressure and metabolic parameters] (article in German). Dtsch Med Wochenschr 2002; 127: 606-610. 24. Coulter D. The New Zealand Intensive Medicines Monitoring Programme in proactive safety surveillance. Pharmacoepidemiol Drug Safety 2000; 9: 273-280. 25. Wooltorton E. Obesity drug sibutramine (Meridia): hypertension and cardiac arrhythmias. CMAJ 2002; 166: 13071308.
29. Taflinski T and Chojnacka J. Sibutramineassociated psychotic episode. Am J Psychiatry 2000; 157: 2057-2058. 30. Binkley K and Knowles SR. Sibutramine and panic attacks. Am J Psychiatry 2002; 159: 1793-1794. 31. Fernandez P and Peiro AM. A sibutramine-induced delusional disorder relapse. J Neuropsychiatry Clin Neurosci 2007; 19: 88-89. 32. Cordeiro Q and Vallada H. Sibutramineinduced mania episode in a bipolar patient. Int J Neuropsychopharmacol 2002; 5: 283-284. 33. Clark DW and Harrison-Woolrych M. Sibutramine may be associated with memory impairment. BMJ 2004; 329: 1316. 34. Meridia (Sibutramine Hydrochloride Monohydrate) drug description - prescription drugs and medications at RxList. Available at www.rxlist.com/cgi/ generic/sibutramine.htm. 35. Kiortsis DN, Tsouli S, Filippatos TD, Konitsiotis S and Elisaf MS. Effects of sibutramine and orlistat on mood in obese and overweight subjects: A randomised study. Nutr Metab Cardiovasc Dis 2007 Jun 12; [Epub ahead of print]. 36. Chounta A, Tsiodras S, Zouridakis S, Doumas M and Giamarellou H. Sibutramine use associated with reversible hepatotoxicity. Ann Intern Med 2005; 143: 763-764. 37. Sabuncu T, Nazligul Y, Karaoglanoglu M, Ucar E and Kilic FB. The effects of sibutramine and orlistat on the ultrasonographic findings, insulin resistance and liver enzyme levels in obese patients with non-alcoholic steatohepatitis. Rom J Gastroenterol 2003; 12: 189-192. 38. Diakou MC, Liberopoulos EN, Mikhailidis DP, Tsianos EV, Burroughs AK and Elisaf MS. Pharmacological treatment of nonalcoholic steatohepatitis: the current evidence. Scand J Gastroenterol 2007; 42: 139-147. 39. Padwal RS and Majumdar SR. Drug treatments for obesity: orlistat, sibutramine, and rimonabant. Lancet 2007; 369: 71-77. 40. Leung WY, Thomas GN, Chan JC and Tomlinson B. Weight management and current options in pharmacotherapy: orlistat and sibutramine. Clin Ther 2003; 25: 58-80. 41. Luque CA and Rey JA. Sibutramine: a serotonin-norepinephrine reuptake-inhibitor for the treatment of obesity. Ann Pharmacother 1999; 33: 968-978.
26. Harrison-Woolrych M, Clark DW, Hill GR, Rees MI and Skinner JR. QT interval prolongation associated with sibutramine treatment. Br J Clin Pharmacol 2006; 61: 464-469. 27. Escande D. Pharmacogenetics of cardiac K(+) channels. Eur J Pharmacol 2000; 410: 281-287. 28. Narkiewicz K. Sibutramine and its cardiovascular profile. Int J Obes Relat Metab Disord 2002; 26 Suppl 4: S38-S41.
35
ª∞ƒΔπ√™ 2008
∫·Ù·Ó¿ÏˆÛË ∫·Ê¤ Î·È ∫·Ú‰È·ÁÁÂÈ·Îfi˜ ∫›Ó‰˘ÓÔ˜ ÃÚÈÛÙ›Ó·-ª·Ú›· ∫·ÛÙÔÚ›ÓË, ¢È·ÈÙÔÏfiÁÔ˜-¢È·ÙÚÔÊÔÏfiÁÔ˜, ÷ÚÔÎÔ›Ԣ ¶·ÓÂÈÛÙËÌ›Ô˘ ¢ËÌÔÛı¤Ó˘ μ. ¶·Ó·ÁȈٿÎÔ˜, §¤ÎÙÔÚ·˜ μÈÔÛÙ·ÙÈÛÙÈ΋˜ & ∂ȉËÌÈÔÏÔÁ›·˜ ÷ÚÔÎÔ›Ԣ ¶·ÓÂÈÛÙËÌ›Ô˘
ÃÚ‹ÛÙÔ˜ ¶›ÙÛ·‚Ô˜, ∞Ó. ∫·ıËÁËÙ‹˜ ∫·Ú‰ÈÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ √ ηʤ˜ Â›Ó·È ¤Ó· ·fi Ù· ÈÔ ‰ËÌÔÊÈÏ‹ Î·È Ù· ÈÔ Û˘¯Ó¿ ηٷӷÏÈÛÎfiÌÂÓ· ÚÔÊ‹Ì·Ù· ‰ÈÂıÓÒ˜. §fiÁˆ Ù˘ ¢Ú›·˜ ηٷӿψۋ˜ ÙÔ˘ Û ·ÁÎfiÛÌÈÔ Â›Â‰Ô, Ë Â›‰Ú·ÛË ÙÔ˘ ηʤ ÛÙËÓ ˘Á›· ıˆÚÂ›Ù·È Ôχ ÛËÌ·ÓÙÈ΋(1). ŸÛÔÓ ·ÊÔÚ¿ ÙË ¯ËÌÈ΋ ÙÔ˘ Û‡ÛÙ·ÛË, Ô Î·Ê¤˜ ·ÔÙÂÏ› ¤Ó· Û‡ÓıÂÙÔ ¯ËÌÈÎfi Ì›ÁÌ·, Ì ÂÚÈÛÛfiÙÂÚ· ·fi ¯›ÏÈ· ‰È·ÊÔÚÂÙÈο Û˘ÛÙ·ÙÈο, Ù· ÔÔ›· ÌÔÚ› Ó· ¤¯Ô˘Ó ›Ù ¢ÂÚÁÂÙÈ΋ ›Ù ÂÈ‚Ï·‚‹ ›‰Ú·ÛË ÛÙÔÓ ÔÚÁ·ÓÈÛÌfi(2). ∏ ηʽÓË Î˘Ú›ˆ˜, ·ÏÏ¿ Î·È ÙÔ «¯ÏˆÚÔÁÂÓÈÎfi» Ô͇ (chlorogenic acid) ‚Ú›ÛÎÔÓÙ·È Û ÛËÌ·ÓÙÈΤ˜ ÔÛfiÙËÙ˜ ÛÙÔÓ Î·Ê¤(2). °È· ÙÔ˘˜ ÂÓ‹ÏÈΘ Ô˘ ηٷӷÏÒÓÔ˘Ó Ì¤ÙÚȘ ÔÛfiÙËÙ˜ ηʤ Ï›Á· Â›Ó·È ÁÓˆÛÙ¿ ÁÈ· Èı·ÓÔ‡˜ ÎÈÓ‰‡ÓÔ˘˜, ÂÓÒ ˘¿Ú¯Ô˘Ó ÂӉ›ÍÂȘ ÁÈ· Èı·Ó¿ ÔʤÏË(2). øÛÙfiÛÔ ˘¿Ú¯ÂÈ ‰˘ÛÎÔÏ›· ÛÙË ÌÂϤÙË Ù˘ ›‰Ú·Û˘ ÙÔ˘ ηʤ ÛÙËÓ ˘Á›·, ÏfiÁˆ Ù˘ ÌÂÁ¿Ï˘ ÔÈÎÈÏ›·˜ ÙˆÓ Ù‡ˆÓ ηʤ, ÙˆÓ ÙÚfiˆÓ ÚÔÂÙÔÈÌ·Û›·˜ Î·È Ù˘ ÂÚÈÂÎÙÈÎfiÙËÙ·˜ Û ηʽÓË Î¿ı ÔÈÎÈÏ›·˜(1).
¯Ô˘Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜ Û˘Û¯ÂÙ›ÛÂȘ ÌÂٷ͇ Ù˘ ˘„ËÏfiÙÂÚ˘ (> 4 ÊÏÈÙ˙¿ÓÈ· ÙË Ì¤Ú·) Î·È Ì¤ÙÚÈ·˜ (3-4 ÊÏÈÙ˙¿ÓÈ· ÙË Ì¤Ú·) ηٷӿψÛ˘ ηʤ Î·È Ù˘ ÂÌÊ¿ÓÈÛ˘ ηډȷÁÁÂȷ΋˜ ÓfiÛÔ˘, ÂÓÒ ‰ÂÓ ·Ú·ÙËÚ‹ıËÎ·Ó ÛËÌ·ÓÙÈΤ˜ Û˘Û¯ÂÙ›ÛÂȘ ÛÙ· ¿ÙÔÌ· Ô˘ ηٷӷÏÒÓÔ˘Ó Î·Ê¤ Û ÌÈÎÚ‹ ÔÛfiÙËÙ· (< 2 ÊÏÈÙ˙¿ÓÈ· ÙË Ì¤Ú·). ¶ÈÔ Û˘ÁÎÂÎÚÈ̤ӷ Ê·›ÓÂÙ·È Ó· ·Ú·ÙËÚÂ›Ù·È ÌÈ· Û¯¤ÛË Û¯‹Ì·ÙÔ˜ J ÌÂٷ͇ Ù˘ Èı·ÓfiÙËÙ·˜ ·Ó¿Ù˘Í˘ ÔͤˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ Û˘Ó‰ÚfiÌˆÓ Î·È Ù˘ ÔÛfiÙËÙ·˜ ηʤ Ô˘ ηٷӷÏÒÓÂÙ·È ËÌÂÚËÛ›ˆ˜.(3) (∂ÈÎfiÓ· 1) ∞fi ÙËÓ ¿ÏÏË ÏÂ˘Ú¿ Ë ·Ó¿Ï˘ÛË ÙˆÓ ÚÔÔÙÈÎÒÓ ÌÂÏÂÙÒÓ ‰ÂÓ ¤‰ÂÈÍÂ Û˘Û¯ÂÙ›ÛÂȘ ÌÂٷ͇ Ù˘ ηٷӿψÛ˘ ηʤ Î·È Ù˘ ÂÌÊ¿ÓÈÛ˘ ηډȷÁÁÂȷ΋˜ ÓfiÛÔ˘ (1). ∏ Ù¿ÛË ÙˆÓ ÌÂÏÂÙÒÓ ·ÛıÂÓÒÓ-
Ì·ÚÙ‡ÚˆÓ Ó· ‰Â›¯ÓÔ˘Ó ÈÔ ·˘ÍË̤ÓË Èı·ÓfiÙËÙ· ÂÌÊ¿ÓÈÛ˘ ηډȷÁÁÂÈ·ÎÒÓ ÓÔÛËÌ¿ÙˆÓ Û ۯ¤ÛË Ì ÙȘ ÚÔÔÙÈΤ˜ ÌÂϤÙ˜ ÂÍËÁÂ›Ù·È ·fi ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ë Â›‰Ú·ÛË ·fi ÙËÓ Î·Ù·Ó¿ÏˆÛË Î·Ê¤ ÛÙÔÓ ÔÚÁ·ÓÈÛÌfi Â›Ó·È ¿ÌÂÛË (4). ¶·ÚfiÏÔ Ô˘ ÔÈ ÂÚÈÛÛfiÙÂÚ˜ ÚÔÔÙÈΤ˜ ÌÂϤÙ˜ ‰ÂÓ ¤¯Ô˘Ó ‚ÚÂÈ Û¯¤ÛË ÌÂٷ͇ Ù˘ ÚfiÛÏ˄˘ ηʤ Î·È Ù˘ ÂÌÊ¿ÓÈÛ˘ ηډȷÁÁÂȷ΋˜ ÓfiÛÔ˘, Ë Î·Ù·Ó¿ÏˆÛË Î·Ê¤ Ê·›ÓÂÙ·È Ó· ·˘Í¿ÓÂÈ ÔÚÈṲ̂ÓÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÙˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ ÓÔÛËÌ¿ÙˆÓ, fiˆ˜ ÁÈ· ·Ú¿‰ÂÈÁÌ· ÙËÓ ·ÚÙËÚȷ΋ ›ÂÛË Î·È ÙËÓ ÔÌÔ΢ÛÙ½ÓË Ï¿ÛÌ·ÙÔ˜. Δ· ‰ÈÙÂÚ¤ÓÈ·, Ô˘Û›Â˜ Ô˘ ‚Ú›ÛÎÔÓÙ·È ÛÙÔÓ ·ÊÈÏÙÚ¿ÚÈÛÙÔ Î·Ê¤ Î·È Ë Î·Ê½ÓË, Ê·›ÓÂÙ·È Ó· ·˘Í¿ÓÔ˘Ó ÙÔÓ Î›Ó‰˘ÓÔ ÁÈ· ÂÌÊ¿ÓÈÛË ÛÙÂÊ·ÓÈ·›·˜ ηډȷ΋˜ ÓfiÛÔ˘ (2). ∫È ·ÎfiÌ· Ê·›ÓÂÙ·È fiÙÈ Ë ¯ÚfiÓÈ·
∏ ηʽÓË ·ÔÙÂÏ› ¤Ó· ·fi Ù· ·ÚÈ· Û˘ÛÙ·ÙÈο ÙÔ˘ ηʤ. ∞ÔÚÚÔÊ¿Ù·È ÁÚ‹ÁÔÚ· Î·È Û¯Â‰fiÓ ·ÔÎÏÂÈÛÙÈο ÛÙÔ ÛÙÔÌ¿¯È Î·È ÙÔ ÏÂÙfi ¤ÓÙÂÚÔ Î·È ÌÂٷʤÚÂÙ·È Û fiÏÔ˘˜ ÙÔ˘˜ ÈÛÙÔ‡˜ Î·È ÛÙÔÓ ÂÁΤʷÏÔ. ∏ ÚfiÛÏË„Ë Î·Ê½Ó˘ Ô‰ËÁ› Û ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ ÎÂÓÙÚÈÎÔ‡ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜, ·‡ÍËÛË Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘, ÙÔ˘ ÌÂÙ·‚ÔÏÈÎÔ‡ Ú˘ıÌÔ‡ Î·È Ù˘ ‰ÈÔ‡ÚËÛ˘(2).
¶ÚfiÛÏË„Ë Î·Ê¤
∏ ηʽÓË
∫·Ù·Ó¿ÏˆÛË Î·Ê¤ Î·È Î·Ú‰È·ÁÁÂÈ·Îfi˜ ΛӉ˘ÓÔ˜ ™‡Ìʈӷ Ì ÌÈ· ÚfiÛÊ·ÙË ÌÂÙ··Ó¿Ï˘ÛË Ë ÔÔ›· ·ÍÈÔÏfiÁËÛ 13 ÌÂϤÙ˜ ·ÛıÂÓÒÓ-Ì·ÚÙ‡ÚˆÓ Î·È 10 ÚÔÔÙÈΤ˜ ÌÂϤÙ˜, ˘¿Ú-
36
¶ÚfiÛÏË„Ë Î·Ê¤, mL/d ∂ÈÎfiÓ· 1. ∏ÌÂÚ‹ÛÈ· ηٷӿψÛË Î·Ê¤ Î·È Î·Ú‰È·ÁÁÂÈ·Îfi˜ ΛӉ˘ÓÔ˜
¢IATPOºH ηٷӿψÛË Î·Ê¤ ÂËÚ¿˙ÂÈ ·ÚÓËÙÈο ÙËÓ ÂÏ·ÛÙÈÎfiÙËÙ· Î·È ‰È·Ù·ÛÈÌfiÙËÙ· Ù˘ ·ÔÚÙ‹˜, ÛËÌ·ÓÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ Ù˘ ÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘ ηډȷÁÁÂÈ·ÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜. ª¿ÏÈÛÙ· Ú¤ÂÈ Ó· ÛËÌÂȈı› fiÙÈ ·Ú·ÙËÚÂ›Ù·È Û˘ÓÂÚÁÈÛÙÈ΋ Û¯¤ÛË ÌÂٷ͇ Ù˘ ηٷӿψÛ˘ ηʤ Î·È ÙÔ˘ ηӛÛÌ·ÙÔ˜ fiÛÔÓ ·ÊÔÚ¿ ÙËÓ ·Ú·¿Óˆ ›‰Ú·ÛË(5,6). øÛÙfiÛÔ, fiˆ˜ Ê¿ÓËÎÂ Î·È ·fi ÙȘ ÌÂϤÙ˜ ·ÛıÂÓÒÓ-Ì·ÚÙ‡ÚˆÓ, ¿ÙÔÌ· Ù· ÔÔ›· ηٷӷÏÒÓÔ˘Ó Ì¤ÙÚȘ ÔÛfiÙËÙ˜ ηʤ, ¤¯Ô˘Ó ÌÈÎÚfiÙÂÚË Èı·ÓfiÙËÙ· Ó· ÂÌÊ·Ó›ÛÔ˘Ó ÛÙÂÊ·ÓÈ·›· ηډȷ΋ ÓfiÛÔ, Èı·ÓfiÓ ÏfiÁÔ Ù˘ ·ÚÔ˘Û›·˜ ·ÓÙÈÔÍÂȉˆÙÈÎÒÓ Û˘ÛÙ·ÙÈÎÒÓ ÛÙÔ ÚfiÊËÌ·(4). Δ¤ÏÔ˜, ı· Ú¤ÂÈ Ó· ·Ó·ÊÂÚı› fiÙÈ Ë Î·Ù·Ó¿ÏˆÛË Î·Ê¤ ¯ˆÚ›˜ ηʽÓË ‰Â Ê·›ÓÂÙ·È Ó· Û¯ÂÙ›˙ÂÙ·È Ì ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ηډȷÁÁÂÈ·ÎÒÓ ÓÔÛËÌ¿ÙˆÓ, ·Ú¿ ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Â›Ó·È Ï›Á˜ Â›Ó·È ÔÈ ‰È·ı¤ÛÈ̘ ÌÂϤÙ˜ Ô˘ ÂÍÂÙ¿˙Ô˘Ó ÙËÓ ÚfiÛÏË„Ë ·˘ÙÔ‡ ÙÔ˘ ›‰Ô˘˜ ηʤ ¯ˆÚÈÛÙ¿(1).
∫·Ù·Ó¿ÏˆÛË Î·Ê¤ Î·È Û·Î¯·Ú҉˘ ‰È·‚‹Ù˘ √È ÂÚÈÛÛfiÙÂÚ˜ ÂȉËÌÈÔÏÔÁÈΤ˜ ÌÂϤÙ˜, ÚÔÔÙÈΤ˜ Î·È Û˘Á¯ÚÔÓÈΤ˜, ‰Â›¯ÓÔ˘Ó fiÙÈ Ë Î·Ù·Ó¿ÏˆÛË Î·Ê¤ Ì ‹ ¯ˆÚ›˜ ηʽÓË ÌÂÈÒÓÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ۷ί·ÚÒ‰Ô˘˜ ‰È·‚‹ÙË Ù‡Ô˘ 2(7,8) Î·È Ì¿ÏÈÛÙ· Ë Î·Ù·Ó¿ÏˆÛË Î·Ê¤ Ê·›ÓÂÙ·È Ó· Û¯ÂÙ›˙ÂÙ·È Ì ÛËÌ·ÓÙÈ΋ ‰ÔÛÔ-ÂÍ·ÚÙÒÌÂÓË Ì›ˆÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘(2). ∏ Û¯¤ÛË ÌÂٷ͇ Ù˘ Ì·ÎÚfi¯ÚÔÓ˘ ηٷӿψÛ˘ ηʤ, ηʤ ¯ˆÚ›˜ ηʽÓË Î·È ¿ÏÏˆÓ ·Ó·„˘ÎÙÈÎÒÓ Ì ηʽÓË, ·Ú·ÙËÚÂ›Ù·È ÙfiÛÔ Û ¿Ó‰Ú˜ fiÛÔ Î·È Á˘Ó·›Î˜, Ì ÙË Û˘Û¯¤ÙÈÛË Ó· Â›Ó·È ÈÛ¯˘ÚfiÙÂÚË ÛÙȘ Á˘Ó·›Î˜ ·Ú¿ ÛÙÔ˘˜ ¿Ó‰Ú˜(9). øÛÙfiÛÔ ı· Ú¤ÂÈ Ó· ÏËÊıÔ‡Ó ˘' fi„ÈÓ ÔÚÈṲ̂Ó˜ ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ ÔÈ Ôԛ˜ ‰Â›¯ÓÔ˘Ó fiÙÈ Ë ¯ÔÚ‹ÁËÛË Î·Ê½Ó˘ ¤¯ÂÈ Ù· ·ÓÙ›ıÂÙ· ·ÔÙÂϤÛÌ·Ù· fiÛÔÓ ·ÊÔÚ¿ ÙËÓ ·ÓÔ¯‹ ÁÏ˘Îfi˙˘ Î·È ÙËÓ ÈÓÛÔ˘ÏÈÓÔ¢·ÈÛıËÛ›·(2). ™˘ÁÎÂÎÚÈ̤ӷ, Ë ÚfiÛÏË„Ë Î·Ê½Ó˘ Ê·›ÓÂÙ·È Ó· Û¯ÂÙ›˙ÂÙ·È Ì ¿ÌÂÛË Ì›ˆÛË Ù˘ ÈÓÛÔ˘ÏÈÓÔ¢·ÈÛıË-
Û›·˜(9,10). ∞fi ÙËÓ ¿ÏÏË ÏÂ˘Ú¿, ¤¯ÂÈ ·Ú·ÙËÚËı› fiÙÈ ÌÂÁ·Ï‡ÙÂÚË ÚfiÛÏË„Ë Î·Ê¤ ¯ˆÚ›˜ ηʽÓË Û¯ÂÙ›˙ÂÙ·È Ì ÌÈÎÚfiÙÂÚÔ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ‰È·‚‹ÙË Ù‡Ô˘ 2, ÂÓÒ ·Ú¿ÏÏËÏ· Û¯ÂÙ›˙ÂÙ·È Î·È Ì ¯·ÌËÏfiÙÂÚ˜ Û˘ÁÎÂÓÙÚÒÛÂȘ C-ÂÙȉ›Ô˘ ÓËÛÙ›·˜(10). °È· ÙÔ ÏfiÁÔ ·˘Ùfi Ë ·ÓÙ›ÛÙÚÔÊË Û¯¤ÛË Ô˘ ·Ú·ÙËÚÂ›Ù·È ÌÂٷ͇ Ù˘ ηٷӿψÛ˘ ηʤ Î·È ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÂÌÊ¿ÓÈÛ˘ ‰È·‚‹ÙË Ù‡Ô˘ 2, ‰ÂÓ ÌÔÚ› Ó· ÂÍËÁËı› ·fi ÙË ‰Ú¿ÛË Ù˘ ηÊ½Ó˘. ∂Ô̤ӈ˜ οÔÈÔ ¿ÏÏÔ Û˘ÛÙ·ÙÈÎfi ÙÔ˘ ηʤ ÂÎÙfi˜ ·fi ÙËÓ Î·Ê½ÓË ı· Ú¤ÂÈ Ó· ·›˙ÂÈ ÚÔÛٷ٢ÙÈÎfi ÚfiÏÔ(10). ΔÔ Û˘ÛÙ·ÙÈÎfi ÙÔ˘ ηʤ ÙÔ ÔÔ›Ô Ê·›ÓÂÙ·È Ó· ÌÂÈÒÓÂÈ ÙË Û˘ÁΤÓÙÚˆÛË ÁÏ˘Îfi˙˘ Ï¿ÛÌ·ÙÔ˜ Â›Ó·È ÙÔ ¯ÏˆÚÔÁÂÓÈÎfi Ô͇(9). ∞˘Ùfi Èı·ÓÒ˜ Ó· ‰Ú· ηı˘ÛÙÂÚÒÓÙ·˜ ÙËÓ ·ÔÚÚfiÊËÛË Ù˘ ÁÏ˘Îfi˙˘ ‹ Ó· Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ÚfiÏË„Ë Î·Ù·ÛÙ¿ÛÂˆÓ fiˆ˜ Ë ÈÓÛÔ˘ÏÈÓÔ·ÓÙ›ÛÙ·ÛË Î·È Ô Û·Î¯·Ú҉˘ ‰È·‚‹Ù˘ Ù‡Ô˘ 2, ̤ۈ Ù˘ ·ÓÙÈÔÍÂȉˆÙÈ΋˜ ÙÔ˘ ÚÔÛÙ·Û›·˜(10). Δ¤ÏÔ˜, Ú¤ÂÈ Ó· ÛËÌÂȈı› fiÙÈ Â›Ó·È Èı·Ófi Ë Ì›ˆÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÂÌÊ¿ÓÈÛË Û·Î¯·ÚÒ‰Ô˘˜ ‰È·‚‹ÙË, Ó· ÔÊ›ÏÂÙ·È ÛÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ë Ì·ÎÚÔÚfiıÂÛÌË Î·Ù·Ó¿ÏˆÛË Î·Ê¤ ¤¯ÂÈ ÌÈ· ÌÈÎÚ‹ ›‰Ú·ÛË ÛÙËÓ ÂÓ›Û¯˘ÛË Ù˘ ·ÒÏÂÈ·˜ ‚¿ÚÔ˘˜. ∂›Ó·È ÁÓˆÛÙfi ÂÍ' ¿ÏÏÔ˘ fiÙÈ ·ÒÏÂÈ· ‚¿ÚÔ˘˜ Ô‰ËÁ› Û ·‡ÍËÛË Ù˘ ÈÓÛÔ˘ÏÈÓÔ¢·ÈÛıËÛ›·˜(7).
∫·Ù·Ó¿ÏˆÛË Î·Ê¤ Î·È ·ÚÙËÚȷ΋ ˘¤ÚÙ·ÛË ∏ ηٷӿψÛË Î·Ê¤ ·˘Í¿ÓÂÈ Ù· ›‰· Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘. ∏ ÈηÓfiÙËÙ· ÙÔ˘ ηʤ Ó· ·˘Í¿ÓÂÈ ÙËÓ ·ÚÙËÚȷ΋ ›ÂÛË ·Ô‰›‰ÂÙ·È ÛÙÔ ÂÚȯfiÌÂÓfi ÙÔ˘ Û ηʽÓË(11). øÛÙfiÛÔ Ê¿ÓËΠfiÙÈ Ë Â›‰Ú·ÛË Ù˘ ηÊ½Ó˘ ÛÙÔÓ ÔÚÁ·ÓÈÛÌfi Â›Ó·È ÌÈÎÚfiÙÂÚË fiÙ·Ó Î·Ù·Ó·ÏÒÓÂÙ·È Ì ÙË ÌÔÚÊ‹ ηʤ Û ۯ¤ÛË Ì ÙË ÌÔÚÊ‹ ¯·ÈÔ‡ ηÊ½Ó˘. ¶ÚÔ·ÙÂÈ ‰ËÏ·‰‹ fiÙÈ ˘¿Ú¯Ô˘Ó ¿ÏÏ· Û˘ÛÙ·ÙÈο ÙÔ˘ ηʤ, Ù· ÔÔ›· ÌÂÈÒÓÔ˘Ó ÙËÓ Â›‰Ú·ÛË Ù˘ ηÊ½Ó˘ ÛÙËÓ ·ÚÙËÚȷ΋ ›ÂÛË Û ¯ÚfiÓÈ· ηٷӿψÛË ‹ ·ÛÎÔ‡Ó ÚÔÛٷ٢ÙÈ΋ ‰Ú¿ÛË(4,12).
∫·Ù·Ó¿ÏˆÛË Î·Ê¤ Î·È ‰˘ÛÏÈȉ·È̛˜ ™‡Ìʈӷ Ì ÌÈ· ÚfiÛÊ·ÙË ÌÂÙ·-·Ó¿Ï˘ÛË ·Ú·ÙËÚÂ›Ù·È ‰ÔÛÔÂÍ·ÚÙÒÌÂÓË ·‡ÍËÛË Ù˘ ÔÏÈ΋˜ Î·È Ù˘ LDL ¯ÔÏËÛÙÂÚfiÏ˘ Û·Ó ·ÔÙ¤ÏÂÛÌ· Ù˘ ηٷӿψÛ˘ ηʤ, Ë ÔÔ›· Â›Ó·È ÌÂÁ·Ï‡ÙÂÚË ÛÙÔÓ ‚Ú·ÛÙfi ηʤ Û ۯ¤ÛË Ì ÙÔÓ Î·Ê¤ Ê›ÏÙÚÔ˘(4). ∏ ›‰Ú·ÛË ÙÔ˘ ηʤ ÛÙËÓ ·‡ÍËÛË Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ ‰ÂÓ ÔÊ›ÏÂÙ·È ÛÙËÓ Î·Ê½ÓË, ·ÏÏ¿ Û ¿ÏÏ· Û˘ÛÙ·ÙÈο Î·È Î˘Ú›ˆ˜ ÛÙ· ¤Ï·È· ÙÔ˘ ηʤ, fiˆ˜ Ë Î·ÊÂÛÙfiÏË Î·È Ë Î·Ú‚·¯fiÏË(13). √ ‚Ú·Ṳ̂ÓÔ˜ ηʤ˜, ·ÓÙ›ıÂÙ· ·fi ÙÔÓ Î·Ê¤ Ê›ÏÙÚÔ˘, Â›Ó·È ÛËÌ·ÓÙÈ΋ ËÁ‹ ηÊÂÛÙfiÏ˘ Î·È Î·Ú‚·¯fiÏ˘(2). ∏ ηÊÂÛÙfiÏË Î·È Ë Î·Ú‚·¯fiÏË Â›Ó·È ‰ÈÙÂÚ¤ÓÈ· Ì ˘ÂÚ¯ÔÏËÛÙÂÚÈÓ·ÈÌÈ΋ ‰Ú¿ÛË. ∞ÂÏ¢ıÂÚÒÓÔÓÙ·È ·fi ÙÔ˘˜ η‚Ô˘Ú‰ÈṲ̂ÓÔ˘˜ ÎfiÎÎÔ˘˜ ηʤ Ì ÙÔ ˙ÂÛÙfi ÓÂÚfi, ·ÏÏ¿ ·Áȉ‡ÔÓÙ·È ·fi ÙÔ ¯¿ÚÙÈÓÔ Ê›ÏÙÚÔ Î·Ù¿ ÙËÓ ÚÔÂÙÔÈÌ·Û›· ÙÔ˘ ηʤ. ŒÙÛÈ Ô ‚Ú·ÛÙfi˜ ηʤ˜ ·˘Í¿ÓÂÈ Ù· ›‰· ¯ÔÏËÛÙÂÚfiÏ˘ Ï¿ÛÌ·ÙÔ˜ Û ÌÂÁ·Ï‡ÙÂÚÔ ‚·ıÌfi ·fi ÙÔÓ Î·Ê¤ Ê›ÏÙÚÔ˘(2,4). √È Ô˘Û›Â˜ ·˘Ù¤˜ ·ÛÎÔ‡Ó ÙËÓ ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌÈ΋ ÙÔ˘˜ ‰Ú¿ÛË Ì¤Ûˆ ·‡ÍËÛ˘ Ù˘ Û‡ÓıÂÛ˘ Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘, ·ÚÂÌÔ‰›˙ÔÓÙ·˜ ÙËÓ ·¤ÎÎÚÈÛ‹ Ù˘ Û ¯ÔÏÈο Ôͤ· Î·È Ô˘‰¤ÙÂÚ˜ ÛÙÂÚfiϘ(13). £· Ú¤ÂÈ Ó· ·Ó·ÊÂÚı› fiÙÈ Ë ·¿ÓÙËÛË Ù˘ ÔÏÈ΋˜ Î·È Ù˘ LDL ¯ÔÏËÛÙÂÚfiÏ˘ ÛÙËÓ Î·ÊÂÛÙfiÏË Â›Ó·È ÌÂÁ·Ï‡ÙÂÚË ÛÙÔ˘˜ ¿Ó‰Ú˜ ·Ú¿ ÛÙȘ Á˘Ó·›Î˜ Î·È ·˘Ùfi ‰ÂÓ ÔÊ›ÏÂÙ·È ÛÙË ÌÂÁ·Ï‡ÙÂÚË Û˘ÓÔÏÈ΋ ‰È·ÙÚÔÊÈ΋ ÚfiÛÏË„Ë ÙˆÓ ·Ó‰ÚÒÓ, ·ÏÏ¿ Èı·ÓfiÓ ÛÙȘ ÔÚÌfiÓ˜ ÙÔ˘ ʇÏÔ˘(9).
∫·Ù·Ó¿ÏˆÛË Î·Ê¤ Î·È Â›Â‰· ÔÌÔ΢ÛÙ½Ó˘ ∏ ηٷӿψÛË Î·Ê¤ Ô‰ËÁ› Û ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ ÔÌÔ΢ÛÙ½Ó˘. ™˘ÁÎÂÎÚÈ̤ӷ, Ë Î·Ù·Ó¿ÏˆÛË ÊÈÏÙÚ·ÚÈṲ̂ÓÔ˘ ›Ù ·ÊÈÏÙÚ¿ÚÈÛÙÔ˘ ηʤ Û¯ÂÙ›˙ÂÙ·È ıÂÙÈο Î·È Ì ‰ÔÛÔÂÍ·ÚÙÒÌÂÓÔ ÙÚfiÔ Ì ٷ ›‰· ÔÌÔ΢ÛÙ½Ó˘ Ï¿ÛÌ·ÙÔ˜(4,14-16). (∂ÈÎfiÓ· 2). √ ηʤ˜ ·˘Í¿ÓÂÈ Ù· ›‰· ÔÌÔ΢ÛÙ½Ó˘ ηٿ 11% Û ۯ¤ÛË Ì ÙÔ placebo, ÂÓÒ Ë Ï‹„Ë Î·Ê½Ó˘ Ì ¯¿È ηٿ 5%. ∞˘Ùfi
37
ª∞ƒΔπ√™ 2008
¶ÚfiÛÏË„Ë Î·Ê¤, mL/d ÕÓ‰Ú˜
°˘Ó·›Î˜
∂ÈÎfiÓ· 2. ™˘Û¯¤ÙÈÛË Î·Ù·Ó¿ÏˆÛ˘ ηʤ Î·È ÔÌÔ΢ÛÙ½Ó˘ Ï¿ÛÌ·ÙÔ˜. ÛËÌ·›ÓÂÈ fiÙÈ Ë Î·Ê½ÓË Â›Ó·È ÌÂÚÈÎÒ˜ ˘Â‡ı˘ÓË ÁÈ· ÙËÓ ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ ÔÌÔ΢ÛÙ½Ó˘ ÌÂÙ¿ ÙËÓ ÚfiÛÏË„Ë Î·Ê¤, ·ÏÏ¿ Î·È fiÙÈ ˘¿Ú¯Ô˘Ó Î·È ¿ÏÏ· Û˘ÛÙ·ÙÈο ÙÔ˘ ηʤ Ô˘ ÂȉÚÔ‡Ó ÛÙËÓ ·‡ÍËÛË ·˘Ù‹(9).
∫·Ù·Ó¿ÏˆÛË Î·Ê¤ Î·È ¯ÚfiÓÈ· Û˘ÛÙËÌ·ÙÈ΋ ÊÏÂÁÌÔÓ‹ ∏ ηٷӿψÛË Î·Ê¤ ¤¯ÂÈ ·ÚÓËÙÈ΋ ›‰Ú·ÛË ÛÙÔ˘˜ ‰Â›ÎÙ˜ ÊÏÂÁÌÔÓ‹˜. ¶·Ú·ÙËÚÂ›Ù·È ıÂÙÈ΋ Û˘Û¯¤ÙÈÛË ÌÂٷ͇ Ù˘ ηٷӿψÛ˘ ηʤ Î·È ÙˆÓ ÂȤ‰ˆÓ ‰È·ÊfiÚˆÓ ‰ÂÈÎÙÒÓ ÊÏÂÁÌÔÓ‹˜ Î·È ‰È·Ù·Ú·Á̤Ó˘ ÈÓˆ‰fiÏ˘Û˘, fiˆ˜ Ë ÈÓÙÂÚÏ¢ΛÓË 6, Ë C-·ÓÙȉÚÒÛ· ÚˆÙ½ÓË Î·È Ô ·Ú¿ÁÔÓÙ·˜ Ó¤ÎÚˆÛ˘ fiÁÎˆÓ (ΔNF)-· (4,17).
∫·Ù·Ó¿ÏˆÛË Î·Ê¤ Î·È ·ÓÙÈÔÍÂȉˆÙÈ΋ ‰Ú¿ÛË ¶·Ú¿ ÙËÓ ·ÚÓËÙÈ΋ ›‰Ú·ÛË fiÛÔÓ ·ÊÔÚ¿ ÙÔ˘˜ ‰Â›ÎÙ˜ ÊÏÂÁÌÔÓ‹˜, Ë Î·Ù·Ó¿ÏˆÛË Î·Ê¤ Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ·ÓÙÈÔÍÂȉˆÙÈ΋ ÂÓ›Û¯˘ÛË ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡. ª¿ÏÈÛÙ·, ÏfiÁˆ Ù˘ ¢Ú›·˜ ηٷӿψۋ˜ ÙÔ˘ Ô Î·Ê¤˜ ·Ó·ÁÓˆÚ›˙ÂÙ·È ˆ˜ Ô Î‡ÚÈÔ˜ Û˘ÓÙÂÏÂÛÙ‹˜ Ù˘ ·ÓÙÈÔÍÂȉˆÙÈ΋˜ ÈηÓfiÙËÙ·˜ ÛÂ Û˘ÁÎÂÎÚÈ̤ÓÔ˘˜ ÏËı˘ÛÌÔ‡˜(4). ¶ÈÔ ·Ó·Ï˘ÙÈο ÔÈ ·ÓÙÈÔÍÂȉˆÙÈΤ˜ ‰Ú¿ÛÂȘ ÙÔ˘ ηʤ ·ÊÔÚÔ‡Ó ÙË Ì›ˆÛË Ù˘ Ù¿Û˘ Ù˘ LDL ÁÈ· ÔÍ›‰ˆÛË Î·È ÙËÓ
38
·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ Ù˘ ÁÏÔ˘Ù·ıÂÈfiÓ˘ ÁÈ· ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ ÂÓ‰ÔÁÂÓÔ‡˜ ·ÓÙÈÔÍÂȉˆÙÈÎÔ‡ Ì˯·ÓÈÛÌÔ‡(4). ∏ ÂͤٷÛË ÚÔÊËÌ¿ÙˆÓ Î·Ê¤ ÁÈ· ÙËÓ ·ÓÙÈÔÍÂȉˆÙÈ΋ ÙÔ˘˜ ÈηÓfiÙËÙ·, Ì ̤ÙÚËÛË Ù˘ ÈηÓfiÙËÙ·˜ ÚÔÛÙ·Û›·˜ ÙÔ˘ DNA ·fi Û˘ÛÙ‹Ì·Ù· ·Ú·ÁˆÁ‹˜ ÂÏ¢ı¤ÚˆÓ ÚÈ˙ÒÓ, ¤‰ÂÈÍ fiÙÈ Ë Î·Ê½ÓË Î·È ÔÈ ÌÂÙ·‚Ôϛ٘ Ù˘ ıÂԂڈ̛ÓË Î·È Í·Óı›ÓË, Ê·›ÓÂÙ·È Ó· ¤¯Ô˘Ó ÈÛ¯˘Ú‹ ÈηÓfiÙËÙ· ÚÔÛÙ·Û›·˜ ÙÔ˘ DNA ·fi ÙËÓ ÔÍ›‰ˆÛË(9). ŒÙÛÈ Ê·›ÓÂÙ·È fiÙÈ Ë Î·Ù·Ó¿ÏˆÛË Î·Ê¤ ÚÔÛٷهÂÈ ·fi ·Ûı¤ÓÂȘ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ·˘ÍË̤ÓÔ ÔÍÂȉˆÙÈÎfi ÛÙÚ˜(9).
∫·Ù·Ó¿ÏˆÛË Î·Ê¤ Î·È ÁÂÓÂÙÈ΋ ÚԉȿıÂÛË ¶Ú¤ÂÈ Ó· ÛËÌÂȈı› fiÙÈ Ë ÎÏËÚÔÓÔÌÈ΋ ÚԉȿıÂÛË ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË Î·Ú‰È·ÁÁÂÈ·ÎÒÓ ÓÔÛËÌ¿ÙˆÓ Ê·›ÓÂÙ·È Ó· Û¯ÂÙ›˙ÂÙ·È ÌÂ Û˘ÁÎÂÎÚÈ̤ÓÔ˘˜ ÔÏ˘ÌÔÚÊÈÛÌÔ‡˜, ÔÈ ÔÔ›ÔÈ ‰ÂÓ ·˘Í¿ÓÔ˘Ó ÙÔÓ Î›Ó‰˘ÓÔ ÁÈ· ÂÌÊ¿ÓÈÛË Î·Ú‰È·ÁÁÂÈ·ÎÒÓ ÓÔÛËÌ¿ÙˆÓ ÛÙÔ˘˜
ÂÚÈÛÛfiÙÂÚÔ˘˜ ÊÔÚ›˜, ·ÏÏ¿ ÂËÚ¿˙Ô˘Ó ÙÔÓ Î›Ó‰˘ÓÔ ÌfiÓÔ ÌÂÙ¿ ·fi ¤ÎıÂÛË ÛÂ Û˘ÁÎÂÎÚÈ̤ÓÔ˘˜ ‰È·ÙÚÔÊÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ ‹ Û ¯·Ú·ÎÙËÚÈÛÙÈο ÙÔ˘ ÙÚfiÔ˘ ˙ˆ‹˜(4). Œ¯ÂÈ Ê·Ó› fiÙÈ Ô Î·Ê¤˜ ˆ˜ ‰È·ÙÚÔÊÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ ÂËÚ¿˙ÂÈ ÙËÓ ÂÌÊ¿ÓÈÛË Î·Ú‰È·ÁÁÂÈ·ÎÒÓ ÓÔÛËÌ¿ÙˆÓ Û ¿ÙÔÌ· ÊÔÚ›˜ Û˘ÁÎÂÎÚÈ̤ÓÔ˘ ÔÏ˘ÌÔÚÊÈÛÌÔ‡. ŒÓ·˜ ÁÂÓÂÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ ÛÙÔ ÁÔÓ›‰ÈÔ 1∞2 ÙÔ˘ ΢ÙÔ¯ÚÒÌ·ÙÔ˜ ƒ 450, ÙÔ ÔÔ›Ô Â˘ı‡ÓÂÙ·È ÁÈ· ÙÔ 95% ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ Ù˘ ηÊ½Ó˘, Ê·›ÓÂÙ·È Ó· ·›˙ÂÈ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙË Û¯¤ÛË ÌÂٷ͇ Ù˘ ηٷӿψÛ˘ ηʤ Î·È Ù˘ ÂÌÊ¿ÓÈÛ˘ ÂÌÊÚ¿ÁÌ·ÙÔ˜ ÙÔ˘ Ì˘Ôηډ›Ô˘. ¢ËÏ·‰‹ ¿ÙÔÌ· Ì ·˘Ùfi ÙÔ ÁÂÓÂÙÈÎfi ·Ú¿ÁÔÓÙ· ¤¯Ô˘Ó ·ÚÁfi ÌÂÙ·‚ÔÏÈÛÌfi Ù˘ ηÊ½Ó˘ Î·È Î·Ù' ¤ÎÙ·ÛË ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ηډȷÁÁÂÈ·ÎÒÓ ÓÔÛËÌ¿ÙˆÓ(1).
™˘ÌÂÚ¿ÛÌ·Ù· º·›ÓÂÙ·È ÔÏÔ¤Ó· Î·È Î·ı·ÚfiÙÂÚ· fiÙÈ Â›‰Ú·ÛË ÛÙËÓ ˘Á›· ¤¯Ô˘Ó Î·È Ù· ¿ÏÏ· Û˘ÛÙ·ÙÈο ÙÔ˘ ηʤ, ÂÎÙfi˜ ·fi ÙËÓ Î·Ê½ÓË. øÛÙfiÛÔ Ô ÚfiÏÔ˜ ÙÔ˘˜, ηıÒ˜ Î·È Ë Ì·ÎÚÔÚfiıÂÛÌË Â›‰Ú·ÛË Ù˘ ηٷӿψÛ˘ ηʤ, ‚Ú›ÛÎÔÓÙ·È ·ÎfiÌ· ÛÙ· ÚÒÙ· ÛÙ¿‰È· Ù˘ ¤Ú¢ӷ˜, Î·È ÙÔ Â‰›Ô Â›Ó·È ·ÎfiÌ· Û¯ÂÙÈο ıÔÏfi. ŒÙÛÈ, Û‡Ìʈӷ Ì ÙËÓ ˘¿Ú¯Ô˘Û· ÁÓÒÛË, ÔÚÈṲ̂Ó˜ ÏËı˘ÛÌȷΤ˜ ÔÌ¿‰Â˜, fiˆ˜ ÔÈ ˘ÂÚÙ·ÛÈÎÔ›, Ù· ·È‰È¿, ÔÈ ¤ÊË‚ÔÈ Î·È ÔÈ ËÏÈÎȈ̤ÓÔÈ, ÔÈ ÔÔ›ÔÈ Â›Ó·È ÈÔ Â˘·›ÛıËÙÔÈ ÛÙȘ ·ÚÓËÙÈΤ˜ ÂÈÙÒÛÂȘ Ù˘ ηÊ½Ó˘, ›Ûˆ˜ ı· Ú¤ÂÈ Ó· ÚÔÛ¤¯Ô˘Ó ÂÚÈÛÛfiÙÂÚÔ ÙËÓ ÔÛfiÙËÙ· ÙÔ˘ ηʤ Ô˘ ηٷӷÏÒÓÔ˘Ó(2). ∫Ï›ÓÔÓÙ·˜ ı· Ú¤ÂÈ Ó· ÏËÊı› ˘fi„Ë ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ô Î·Ê¤˜ ‰ÂÓ Â›Ó·È ·Ï¿ ¤Ó· ÚfiÊËÌ· ÙÔ˘ ÔÔ›Ô˘ Ë Î·Ù·Ó¿ÏˆÛË ÂËÚ¿˙ÂÈ ıÂÙÈο ‹ ·ÚÓËÙÈο ÙËÓ ˘Á›·.
∂¶π¢ƒ∞™∏ ™Δ√¡ √ƒ°∞¡π™ª√ ∞¶√ Δ∏¡ ∫∞Δ∞¡∞§ø™∏ ∫∞º∂ £∂Δπ∫∏
∞ƒ¡∏Δπ∫∏
™·Î¯·Ú҉˘ ¢È·‚‹Ù˘
∞ÚÙËÚȷ΋ À¤ÚÙ·ÛË
πÓÛÔ˘ÏÈÓÔ¢·ÈÛıËÛ›·
¢˘ÛÏÈȉ·È̛˜
∞ÓÙÈÔÍÂȉˆÙÈ΋ ‰Ú¿ÛË
∂›Â‰· ÔÌÔ΢ÛÙ›Ó˘ ¢Â›ÎÙ˜ ÊÏÂÁÌÔÓ‹˜
¢IATPOºH ∞ÓÙ›ıÂÙ· Ë Î·Ù·Ó¿ÏˆÛË Î·Ê¤ ·ÔÙÂÏ› ¯·Ú·ÎÙËÚÈÛÙÈÎfi ÙÔ˘ ÙÚfiÔ˘ ˙ˆ‹˜. ∂›Ó·È Ôχ Èı·Ófi fiÙÈ Ë Î·Ù·Ó¿ÏˆÛË Î·Ê¤ Î·È Ì¿ÏÈÛÙ· Û ·˘ÍË̤ÓË ÔÛfiÙËÙ·, ¿Óˆ ·fi 4 ÊÏÈÙ˙¿ÓÈ· ÙË Ì¤Ú·, ·ÔÙÂÏ› ̤ÚÔ˜ ÂÓfi˜ ÙÚfiÔ˘ ˙ˆ‹˜ Ô˘ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ·ıËÚÔÁÂÓÂÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜, ·Ú¿ fiÙÈ Â›Ó·È ·ÈÙÈÔÏÔÁÈÎfi˜ ·Ú¿ÁÔ-
ÓÙ·˜ ·fi ÌfiÓË Ù˘. °È· ·Ú¿‰ÂÈÁÌ· ÙÔ Î¿ÓÈÛÌ· ıˆÚÂ›Ù·È Èı·Ófi˜ Û˘Á¯˘ÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜, ÌÈ· Î·È Ë Î·Ù·Ó¿ÏˆÛË Î·Ê¤ Î·È ÙÔ Î¿ÓÈÛÌ· Û˘¯Ó¿ Û¯ÂÙ›˙ÔÓÙ·È. ÕÏÏÔÈ Èı·ÓÔ› Û˘Á¯˘ÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ ÔÈ ÔÔ›ÔÈ ı· Ú¤ÂÈ Ó· Ï·Ì‚¿ÓÔÓÙ·È ˘' fi„ÈÓ Â›Ó·È Ë ËÏÈΛ·, ÙÔ Ê‡ÏÔ, Ë Î·Ù·-
ӿψÛË ·ÏÎÔfiÏ, Ô ‰Â›ÎÙ˘ Ì¿˙·˜ ÛÒÌ·ÙÔ˜, ‰È·ÙÚÔÊÈÎÔ› ·Ú¿ÁÔÓÙ˜, ÙÔ È·ÙÚÈÎfi ÈÛÙÔÚÈÎfi, Ù· ›‰· Ê˘ÛÈ΋˜ ‰Ú·ÛÙËÚÈfiÙËÙ·˜, ÛÙÔȯ›· Ù˘ ÚÔÛˆÈÎfiÙËÙ·˜, Ô ÙfiÔ˜ ‰È·ÌÔÓ‹˜ Î·È ÙÔ ÌÔÚʈÙÈÎfi ›‰Ô(4).
μÈ‚ÏÈÔÁÚ·Ê›· 8.
Panagiotakos DB, Lionis C, Zeimbekis A, Makri K, Bountziouka V, Economou M, et al. Long-term, moderate coffee consumption is associated with lower prevalence of diabetes mellitus among elderly non-tea drinkers from the Mediterranean Islands (MEDIS Study). Rev Diabet Stud 2007;4(2):105-11.
Panagiotakos DB, Pitsavos C, Chrysohoou C, Kokkinos P, Toutouzas P, Stefanadis C. The J-shaped effect of coffee consumption on the risk of developing acute coronary syndromes: the CARDIO2000 case-control study. J Nutr 2003;133(10):3228-32.
9.
Ranheim T, Halvorsen B. Coffee consumption and human health-beneficial or detrimental?--Mechanisms for effects of coffee consumption on different risk factors for cardiovascular disease and type 2 diabetes mellitus. Mol Nutr Food Res 2005;49(3):274-84.
4.
Cornelis MC, El-Sohemy A. Coffee, caffeine, and coronary heart disease. Curr Opin Lipidol 2007;18(1):13-9.
10. van Dam RM. Coffee and type 2 diabetes: from beans to beta-cells. Nutr Metab Cardiovasc Dis 2006;16(1):69-77.
5.
Vlachopoulos C, Kosmopoulou F, Panagiotakos D, Ioakeimidis N, Alexopoulos N, Pitsavos C, et al. Smoking and caffeine have a synergistic detrimental effect on aortic stiffness and wave reflections. J Am Coll Cardiol 2004;44(9):1911-7.
11. Jee SH, He J, Whelton PK, Suh I, Klag MJ. The effect of chronic coffee drinking on blood pressure: a meta-analysis of controlled clinical trials. Hypertension 1999;33(2):647-52.
1.
Sofi F, Conti AA, Gori AM, Eliana Luisi ML, Casini A, Abbate R, et al. Coffee consumption and risk of coronary heart disease: a meta-analysis. Nutr Metab Cardiovasc Dis 2007;17(3):209-23.
2.
Higdon JV, Frei B. Coffee and health: a review of recent human research. Crit Rev Food Sci Nutr 2006;46(2):101-23.
3.
6.
7.
Vlachopoulos C, Panagiotakos D, Ioakeimidis N, Dima I, Stefanadis C. Chronic coffee consumption has a detrimental effect on aortic stiffness and wave reflections. Am J Clin Nutr 2005;81(6):1307-12. Greenberg JA, Boozer CN, Geliebter A. Coffee, diabetes, and weight control. Am J Clin Nutr 2006;84(4):682-93.
12. Noordzij M, Uiterwaal CS, Arends LR, Kok FJ, Grobbee DE, Geleijnse JM. Blood pressure response to chronic intake of coffee and caffeine: a metaanalysis of randomized controlled trials. J Hypertens 2005;23(5):921-8.
14. Panagiotakos DB, Pitsavos C, Zampelas A, Zeimbekis A, Chrysohoou C, Papademetriou L, et al. The association between coffee consumption and plasma total homocysteine levels: the "ATTICA" study. Heart Vessels 2004;19(6):280-6. 15. Panagiotakos DB, Pitsavos C, Zeimbekis A, Chrysohoou C, Stefanadis C. The association between lifestyle-related factors and plasma homocysteine levels in healthy individuals from the "ATTICA" Study. Int J Cardiol 2005;98(3):471-7. 16. Chrysohoou C, Panagiotakos DB, Pitsavos C, Zeimbekis A, Zampelas A, Papademetriou L, et al. The associations between smoking, physical activity, dietary habits and plasma homocysteine levels in cardiovascular disease-free people: the 'ATTICA' study. Vasc Med 2004;9(2):117-23. 17. Zampelas A, Panagiotakos DB, Pitsavos C, Chrysohoou C, Stefanadis C. Associations between coffee consumption and inflammatory markers in healthy persons: the ATTICA study. Am J Clin Nutr 2004;80(4):862-7.
13. Jee SH, He J, Appel LJ, Whelton PK, Suh I, Klag MJ. Coffee consumption and serum lipids: a meta-analysis of randomized controlled clinical trials. Am J Epidemiol 2001;153(4):353-62.
39
ª∞ƒΔπ√™ 2008
¶ƒ√Δ∂π¡√ª∂¡∏ μπμ§π√°ƒ∞ºπ∞ 1:
Spring S, Simon R, van der Loo B, et al. High-dose atorvastatin in peripheral arterial disease (PAD): Effect on endothelial function, intima-media-thickness and local progression of PAD. An open randomized controlled pilot trial. Thromb Haemost. 2008 Jan;99(1):182-9. 2: Trenk D, Hochholzer W, Frundi D, et al. Impact of cytochrome P450 3A4-metabolized statins on the antiplatelet effect of a 600-mg loading dose clopidogrel and on clinical outcome in patients undergoing elective coronary stent placement. Thromb Haemost. 2008 Jan; 99(1):174-81. 3: Rinfret S, Behlouli H, Eisenberg MJ, et al. Class effects of statins in elderly patients with congestive heart failure: A populationbased analysis. Am Heart J. 2008 Feb;155(2):316-23. 4: Sever PS, Poulter NR, Dahlof B, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes G, Mehlsen J, Nieminen MS, O'Brien ET, Ostergren J; on behalf of the ASCOT Investigators. The Anglo-Scandinavian Cardiac Outcomes Trial lipid lowering arm: extended observations 2 years after trial closure. Eur Heart J. 2008 Jan 5; [Epub ahead of print] 5: Sdringola S, Gould KL, Zamarka LG, McLain R, Garner J. A 6 month randomized, double blind, placebo controlled, multi-center trial of high dose atorvastatin on myocardial perfusion abnormalities by positron emission tomography in coronary artery disease. Am Heart J. 2008 Feb;155(2):245-53. 6: Kishi T, Hirooka Y, Shimokawa H, Takeshita A, Sunagawa K. Atorvastatin reduces oxidative stress in the rostral ventrolateral medulla of stroke-prone spontaneously hypertensive rats. Clin Exp Hypertens. 2008 Jan;30(1):3-11. 7: Lakomkin VL, Kapel'ko VI, Lankin VZ, Konovalova GG, Kaminnyi AI. Effect of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor atorvastatin on contractility of the isolated rat heart under normal conditions and during oxidative stress. Bull Exp Biol Med. 2007 Apr;143(4):408-10. 8: Athyros VG, Liberopoulos EN, Mikhailidis DP, Papageorgiou AA, Ganotakis ES, Tziomalos K, Kakafika AI, Karagiannis A, Lambropoulos S, Elisaf M. Association of Drinking Pattern and Alcohol Beverage Type With the Prevalence of Metabolic Syndrome, Diabetes, Coronary Heart Disease, Stroke, and Peripheral Arterial Disease in a Mediterranean Cohort. Angiology 2008 Jan;58(6):689-697. 9: D'Abrosca B, Fiorentino A, Izzo A, Cefarelli G, Pascarella MT, Uzzo P, Monaco P. Phytotoxicity evaluation of five pharmaceutical pollutants detected in surface water on germination and growth of cultivated and spontaneous plants. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2008 Feb 15;43(3):285-94. 10: Kosmidou MS, Hatzitolios AI, Adamidou A, Giannopoulos S, Raikos N, Parharidis G, Milionis HJ. Effects of Atorvastatin on Red-blood Cell Na(+)/Li(+) Countertransport in Hyperlipidemic Patients With and Without Hypertension. Am J Hypertens. 2008 Jan 17; [Epub ahead of print] 11: Usher-Smith J, Ramsbottom T, Pearmain H, Kirby M. Evaluation of the clinical outcomes of switching patients from
40
12:
13:
14:
15:
16:
17:
18:
19:
20:
21:
22:
23:
24:
atorvastatin to simvastatin and losartan to candesartan in a primary care setting: 2 years on. Int J Clin Pract. 2008 Jan 14; [Epub ahead of print] 2: Karagiannis A, Mikhailidis DP, Athyros VG, Harsoulis F. Pheochromocytoma: an update on genetics and management. Endocr Relat Cancer. 2007 Dec;14(4):935956. Sanossian N, Ovbiagele B. Drug insight: translating evidence on statin therapy into clinical benefits. Nat Clin Pract Neurol. 2008 Jan;4(1):43-9. Howard PA, Barnes BJ. Potential Use of Statins to Prevent Atrial Fibrillation After Coronary Artery Bypass Surgery. Ann Pharmacother. 2008 Jan 15; [Epub ahead of print] A randomised study comparing the efficacy and safety of rosuvastatin with atorvastatin for achieving lipid goals in clinical practice in Asian patients at high risk of cardiovascular disease (DISCOVERY-Asia study). Curr Med Res Opin. 2007 Dec;23(12):3055-68. Meena AK, Ratnam DV, Chandraiah G, Ankola DD, Rao PR, Kumar MN. Oral Nanoparticulate Atorvastatin Calcium is More Efficient and Safe in Comparison to Lipicure((R)) in Treating Hyperlipidemia. Lipids. 2008 Jan 10; [Epub ahead of print] Khedr A. Stability-indicating highperformance liquid chromatographic assay of atorvastatin with fluorescence detection. J AOAC Int. 2007 NovDec;90(6):1547-53. Chaudhari BG, Patel NM, Shah PB, Patel LJ, Patel VP. Stability-indicating reversedphase liquid chromatographic method for simultaneous determination of atorvastatin and ezetimibe from their combination drug products. J AOAC Int. 2007 NovDec;90(6):1539-46. Kallem RR, Karthik A, Chakradhar L, Mullangi R, Srinivas NR. Development and validation of a highly sensitive and robust LC-MS/MS with electrospray ionization method for quantification of rosuvastatin in small volume human plasma samples and its application to a clinical study. Arzneimittelforschung. 2007;57(11):705-11. Choi DH, Shin WG, Choi JS. Drug interaction between oral atorvastatin and verapamil in healthy subjects: effects of atorvastatin on the pharmacokinetics of verapamil and norverapamil. Eur J Clin Pharmacol. 2008 Jan 12; [Epub ahead of print] Tziomalos K, Athyros VG, Mikhailidis DP. Fish oils and vascular disease prevention: an update. Curr Med Chem. 2007;14(24):2622-8. Laforest L, Moulin P, Souchet T, et al. Correlates of LDL-cholesterol goal attainment in patients under lipid lowering therapy. Atherosclerosis. 2008 Jan 10; [Epub ahead of print] Hogue JC, Lamarche B, Deshaies Y, Tremblay AJ, Bergeron J, Gagné C, Couture P. Differential effect of fenofibrate and atorvastatin on in vivo kinetics of apolipoproteins B-100 and B-48 in subjects with type 2 diabetes mellitus with marked hypertriglyceridemia. Metabolism. 2008 Feb;57(2): 246-54. Stefanadi E, Tousoulis D, Antoniades C, Katsi V, Bosinakou E, Vavuranakis E, Triantafyllou G, Marinou K, Tsioufis C, Papageorgiou N, Latsios G, Stefanadis C.
Early initiation of low-dose atorvastatin treatment after an acute ST-elevated myocardial infarction, decreases inflammatory process and prevents endothelial injury and activation. Int J Cardiol. 2008 Jan 8; [Epub ahead of print] 25: Harley CR, Gandhi SK, Anoka N, Bullano MF, McKenney JM. Understanding practice patterns and low-density lipoprotein cholesterol goal attainment implications of switching patients from simvastatin in a health plan setting. Am J Manag Care. 2007 Dec;13 Suppl 10:S27681. 26: Fox KM, Gandhi SK, Ohsfeldt RL, Davidson MH. Comparison of low-density lipoprotein cholesterol reduction after switching patients on other statins to rosuvastatin or simvastatin in a real-world clinical practice setting. Am J Manag Care. 2007 Dec;13 Suppl 10: S270-5. 27: Ferreira GA, Andrade LE, Sato EI. Comment on: Atorvastatin therapy improves endothelial-dependent vasodilation in patients with systemic lupus erythematosus: an 8 weeks controlled trial: reply. Rheumatology (Oxford). 2008 Jan 7; [Epub ahead of print] No abstract available. 28: Boodhwani M, Mieno S, Feng J, Sodha NR, Clements RT, Xu SH, Sellke FW. Atorvastatin impairs the myocardial angiogenic response to chronic ischemia in normocholesterolemic swine. J Thorac Cardiovasc Surg. 2008 Jan;135(1):117-22. 29: McLean DS, Ravid S, Blazing M, Gersh B, Shui A, Cannon CP. Effect of statin dose on incidence of atrial fibrillation: Data from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) and Aggrastat to Zocor (A to Z) trials. Am Heart J. 2008 Feb;155(2):298-302. 30: Flack JM, Victor R, Watson K, Ferdinand KC, Saunders E, Tarasenko L, Jamieson MJ, Shi H, Bruschi P. Improved Attainment of Blood Pressure and Cholesterol Goals Using Single-Pill Amlodipine/Atorvastatin in African Americans: The CAPABLE Trial. Mayo Clin Proc 2008 Jan;83(1):35-45. 31: Puccetti L, Bruni F, Pasqui AL, Pastorelli M, Ciani F, Palazzuoli A, Acampa M, Auteri A. Genetic influence in antithrombotic actions of atorvastatin in hypercholesterolaemia. Eur J Clin Invest. 2008 Jan;38(1):11-6. 32: Puccetti L, Capati E, Auteri A. Genetic modulation of anti-inflammatory effects of atorvastatin; probably a multi-gene condition. Atherosclerosis. 2007 Dec 26; [Epub ahead of print] 33: Stegmayr BG, Brännström M, Bucht S, et al; Nediat Study Group. Low-dose atorvastatin in severe chronic kidney disease patients: a randomized, controlled endpoint study. Scand J Urol Nephrol. 2005;39(6):489-97. 34: Schwertz DW, Badellino KO. High-dose statin therapy for secondary prevention of stroke: stroke prevention by aggressive reduction in cholesterol levels study review. J Cardiovasc Nurs. 2008 JanFeb;23(1):8-13. 35: Colhoun HM. Lipid goals in metabolic syndrome and diabetes. Curr Atheroscler Rep. 2007 Oct;9(4):286-95.
IATPOI KA§§ITEXNE™
IATPOI KA§§ITEXNE™
IATPOI KA§§ITEXNE™
¶›Ó·Î·˜: ¶fiÚÙ·
√£ø¡ •∂¡π∫√À¢∞∫∏™ °ÂÓÓ‹ıËΠÛÙÔÓ ∫ÔÚ˘‰·ÏÏfi ÙÔ 1947. ™Ô‡‰·Û ÛÙËÓ √‰ÔÓÙÈ·ÙÚÈ΋ ™¯ÔÏ‹ ÙÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ Î·È ·ÛΛ ÙÔ Â¿ÁÁÂÏÌ· ÙÔ˘ Ô‰ÔÓÙÈ¿ÙÚÔ˘ ·Ô ÙÔ 1976. ¶‹Ú ̷ı‹Ì·Ù· ˙ˆÁÚ·ÊÈ΋˜ ÛÙÔ Î·ÏÏÈÙ¯ÓÈÎfi ÂÚÁ·ÛÙ‹ÚÈ ÙÔ˘ ¢‹ÌÔ˘ ¡Èη›·˜. ∑ˆÁÚ·Ê›˙ÂÈ ·fi ÙÔ 1980 Î·È ¤¯ÂÈ ¿ÚÂÈ Ì¤ÚÔ˜ Û ·ÓÂÏÏ‹ÓÈ· ¤ÎıÂÛË ÂÚ·ÛÈÙ¯ÓÒÓ ˙ˆÁÚ¿ÊˆÓ ÛÙËÓ ·›ıÔ˘Û· «¶·ÚÓ·ÛÛfi˜». ∂›Û˘ ¤¯ÂÈ ÂÎı¤ÛÂÈ ¤ÚÁ· ÙÔ˘ ÛÂ Û˘Ó¤‰ÚÈ· Ù˘ ¶·ÓÂÏÏ‹ÓÈ·˜ √‰ÔÓÙÈ·ÙÚÈ΋˜ √ÌÔÛÔÓ‰›·˜.
EΉ›‰ÂÙ·È ·fi ÙȘ È·ÙÚÈΤ˜ ÂΉfiÛÂȘ “B·ÁÈÔÓ¿ÎË” Ì ¯ÔÚËÁ›· Ù˘ PFIZER HELLAS. OÈ ·fi„ÂȘ ÛÙÔ Î›ÌÂÓÔ ÂÎÊÚ¿˙Ô˘Ó ÌfiÓÔ ÙÔ˘˜ Û˘ÁÁÚ·Ê›˜ Î·È ‰ÂÓ ·ÓÙÈÚÔÛˆÂ‡Ô˘Ó ÙË ¯ÔÚËÁfi ÂÙ·ÈÚ›·.