ΤΕΥΧΟΣ 19 ΣΕΠΤΕΜΒΡΙΟΣ 2008 - ΑΘΗΡΟΣΚΛΗΡΩΣΗ

∆ƒπª∏¡π∞π√ ¶∂ƒπ√¢π∫√ §π¶π¢πø¡

2 17 18 23

∆∂ÀÃ√™ 19 ñ ™∂¶∆∂ªµƒπ√™ 2008

¶·Ú¿ÁÔÓÙ˜ ∫ÈÓ‰‡ÓÔ˘ ∫ÏÈÓÈΤ˜ ªÂϤÙ˜ ¶·ıÔÊ˘ÛÈÔÏÔÁ›·

¶ÚÔÎÏÈÓÈ΋ ŒÚ¢ӷ

¶ÚÔÙÂÈÓfiÌÂÓË µÈ‚ÏÈÔÁÚ·Ê›·

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À‡ı˘ÓÔ˜ ™‡ÓÙ·Í˘ HÏ›·˜ XÂÈÌÒÓ·˜ K·Ú‰ÈÔÏfiÁÔ˜ YÔÙ¤Ú·Ú¯Ô˜ Â.·.

¶∞ƒ∞°√¡∆∂™ ∫π¡¢À¡√À ÷ÌËÏ‹ HDL ÃÔÏËÛÙÂÚfiÏË Î·È Ë ∞ÓÙÈÌÂÙÒÈÛ‹ Ù˘

2

ƒ›˙Ô˜ ÃÚ‹ÛÙÔ˜, ∂ÈÛÙËÌÔÓÈÎfi˜ ™˘ÓÂÚÁ¿Ù˘ ÙÔ˘ ∂Í. π·ÙÚ›Ԣ ¢È·Ù·Ú·¯ÒÓ ÙÔ˘ ªÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ §Èȉ›ˆÓ ∂ÏÈÛ¿Ê ªˆ˘Û‹˜, ∫·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜, ∆Ô̤·˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ

¢È·ÁÓˆÛÙÈ΋ ¶ÚÔÛ¤Ï·ÛË Î·È ∞ÓÙÈÌÂÙÒÈÛË ∞ÛıÂÓÒÓ Ì ÀÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· ¢ÈÔÈÎËÙÈÎfi ™˘Ì‚Ô‡ÏÈÔ ∂ÏÏËÓÈ΋˜ ∂Ù·ÈÚ›·˜ ∞ıËÚÔÛÎÏ‹ÚˆÛ˘ °ÂÓÔ‚¤Ê· KÔÏÔ‚Ô‡ ¶Úfi‰ÚÔ˜ ªˆ˘Û‹˜ ∂ÏÈÛ¿Ê ∞ÓÙÈÚfi‰ÚÔ˜ HÏ›·˜ XÂÈÌÒÓ·˜ °ÂÓÈÎfi˜ °Ú·ÌÌ·Ù¤·˜ ¢ËÌÔÛı¤Ó˘ ¶·Ó·ÁȈٿÎÔ˜ ∂ȉÈÎfi˜ °Ú·ÌÌ·Ù¤·˜ ∂ϤÓË ªÈÏÈ·ÓÔ‡ ∆·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˜ ∆ÛÂϤ˘ ª¤ÏÔ˜

5

∞ÁÁÔ˘Ú›‰Ë˜ ÕÚ˘-¢ËÌ‹ÙÚÈÔ˜, ∂ÈÛÙËÌÔÓÈÎfi˜ ™˘ÓÂÚÁ¿Ù˘ ÙÔ˘ ∂Í. π·ÙÚ›Ԣ ÙˆÓ ¢È·Ù·Ú·¯ÒÓ ÙÔ˘ ªÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ §Èȉ›ˆÓ ÙÔ˘ ¶·ÓÂÈÛÙËÌÈ·ÎÔ‡ °ÂÓÈÎÔ‡ ¡ÔÛÔÎÔÌ›Ԣ πˆ·ÓÓ›ÓˆÓ ∂ÏÈÛ¿Ê ªˆ˘Û‹˜, ∫·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜, ∆Ô̤·˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ

ªË ™ÙÂÚÔÂȉ‹ ∞ÓÙÈÊÏÂÁÌÔÓÒ‰Ë º¿Ú̷η Î·È ∫·Ú‰È·ÁÁÂÈ·Îfi˜ ∫›Ó‰˘ÓÔ˜

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º. ∞ÔÛÙfiÏÔ˘ ∂ÈÌÂÏ‹ÙÚÈ· µ' Ù˘ µ' ¶·ıÔÏÔÁÈ΋˜ ∫ÏÈÓÈ΋˜ ÙÔ˘ ¶·ÓÂÈÛÙËÌÈ·ÎÔ‡ °ÂÓÈÎÔ‡ ¡ÔÛÔÎÔÌ›Ԣ πˆ·ÓÓ›ÓˆÓ ∂. §˘ÌÂÚfiÔ˘ÏÔ˜ §¤ÎÙÔÚ·˜ ¶·ıÔÏÔÁ›·˜, π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ ª. ∂ÏÈÛ¿Ê ∫·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ

∫§π¡π∫∂™ ª∂§∂∆∂™ ªÂϤÙË CORONA (COntrolled ROsuvastatin in MultinatioNAl Trial in Heart Failure)

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ƒÔÛÔ˘‚·ÛÙ·Ù›ÓË Û ËÏÈÎȈ̤ÓÔ˘˜ ·ÛıÂÓ›˜ ÌÂ Û˘ÛÙÔÏÈ΋ ηډȷ΋ ·ÓÂ¿ÚÎÂÈ· Kjekshus J, Apetrei E, Barrios V, Böhm M, Cleland JG, Cornel JH, Dunselman P, Fonseca C, Goudev A, Grande P, Gullestad L, Hjalmarson A, Hradec J, Jànosi A, Kamensky G, Komajda M, Korewicki J, Kuusi T, Mach F, Mareev V, McMurray JJ, Ranjith N, Schaufelberger M, Vanhaecke J, van Veldhuisen DJ, Waagstein F, Wedel H, Wikstrand J; CORONA Group.

N Engl J Med. 2007 Nov 29;357(22):2248-61.

¶∞£√ºÀ™π√§√°π∞ ¢ÔÌ‹ Î·È §ÂÈÙÔ˘ÚÁ›· ÙˆÓ À„ËÏ‹˜ ¶˘ÎÓfiÙËÙ·˜ §ÈÔÚˆÙÂ˚ÓÒÓ ÛÙÔ ªÂÙ·‚ÔÏÈÎfi ™‡Ó‰ÚÔÌÔ

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∫ˆÓÛÙ·ÓÙ›ÓÔ˜ §·Áfi˜, ∂ÈÛÙËÌÔÓÈÎfi˜ Û˘ÓÂÚÁ¿Ù˘ ÙÔ˘ π·ÙÚ›Ԣ ¢È·Ù·Ú·¯ÒÓ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ §Èȉ›ˆÓ, ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô πˆ·ÓÓ›ÓˆÓ ªˆ˘Û‹˜ ∂ÏÈÛ¿Ê, ∫·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜, ∆Ô̤·˜ ¶·ıÔÏÔÁ›·˜, π·ÙÚÈ΋ ™¯ÔÏ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ

¶ƒ√∫§π¡π∫∏ ∂ƒ∂À¡∞ ∆›ÙÏÔÈ ∞˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ŒÓ·ÓÙÈ ¢È·ÊfiÚˆÓ ªÔÚÊÒÓ √ÍÂȉˆÌ¤Ó˘ LDL Û ∞ÛıÂÓ›˜ Ì √͇ ™ÙÂÊ·ÓÈ·›Ô ™‡Ó‰ÚÔÌÔ. ∏ ∂›‰Ú·ÛË Ù˘ ∞ÙÔÚ‚·ÛÙ·Ù›Ó˘ ∞. ¶··ı·Ó·Û›Ô˘, π. °Ô˘‰¤‚ÂÓÔ˜, ∞. ∆ÛÂϤ˘1 ∫·Ú‰ÈÔÏÔÁÈ΋ ∫ÏÈÓÈ΋, π·ÙÚÈ΋ ™¯ÔÏ‹, ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô πˆ·ÓÓ›ÓˆÓ 1 ∂ÚÁ·ÛÙ‹ÚÈÔ µÈÔ¯ËÌ›·˜, ∆Ì‹Ì· ÃËÌ›·˜, ¶·ÓÂÈÛÙ‹ÌÈÔ πˆ·ÓÓ›ÓˆÓ

23

¶POTEINOMENH BIB§IO°PAºIA

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ÔڈȷıËÚˆÁfiÓÔ ÏÈ ÓÙ · È· Ú ‡ Î Ó ÛË Ù˘ ÙÂÏ› ÙË ÙËÚÂ›Ù·È ·‡ÍË ÓË (HDL) ·Ô · Ú Â˝ Ù ·  ˆ Ú )  C Ô  L ÏÈ D ÏÔ‡Ó ÙÔ ÓfiÙËÙ·˜ ÙÂÚfiÏ˘ (H HDL-C ÚÔη ∏ ˘„ËÏ‹˜ ˘Î ˜ ˜ HDL ¯ÔÏËÛ Ë Ë Ù Ù Ó Ë ˆ Û ¤‰ ˆ È › Ì ÙˆÓ Â ÈÛÌ¤ÓˆÓ ¿ı 1% 2-3%. ªÂ›ˆÛË ¯ÔÚ‹ÁËÛË ÔÚ Ù½ÓË. °È· Î ¿ Ë Ù , · · Î Ù Ë ˜ Ù · Ù Èfi Ë Ú Ù Ë fi ‹˜ ıÓËÙ ·˘ÍË̤ӷ È΋ ‰Ú·Û٠ηډȷÁÁÂÈ·Î Ù·Ú·¯¤˜. Δ· ˆÌ¤ÓË ÛˆÌ·Ù È· ÂÈ ‰ Ì Ë ¤˜ Î , È· ›· ‰ Î Ú ÓÈ ·¯˘Û· ·‡ÍËÛË Ù˘ ‰È¿ÊÔÚ˜ ÁÔ È· È Á · ˜ Î ÂÈ ˜ Û Ë Î¿ÓÈÛÌ·, Ë ¿ Ù ‚ ‹ ‚ ÂÌ ‰È· L-C. ¶·Ú ۷ί·Ú҉˘ Ó ·ÒÏÂÈ· ·Ùو̤ÓË HD ÂÏ Â Ì Ê·Ú̿ΈÓ, Ô È ‰È·ÙÚÔÊ‹, ÙË · ‹ ÓÙ Ô ÈÓ ›˙ È ÂÙ ˘Á ¯ Ó Û Ë ‹ Ù ˜ Â›ÛË È΋ ¿ÛÎËÛË, Ô‡ ηıËÌÂÚÈÓ Ù Ì · ı Ì · ˆ ‚ Û ˘ ÙÚÈÁÏ˘ÎÂÚ›‰È· ‹ ›Ô ÈÎ Ú Ù ÂÙ Î Ù· ·ÓÒ˜ ÙË Ì Ì‚¿ÓÔ˘Ó ÙËÓ ËÁËıÔ‡Ó Ê¿Ú ·ıÒ˜ Î·È Èı Ú Î Ô ¯ , ˜ Ô Ó· Ù HDL-C ÂÚÈÏ· · Ó Ì ‡ Û Ô Ú Ó› · ÂÙ¿, ÌÔ ›· È·ÎÔ‹ ÙÔ˘ Î ‰ÂÓ Â›Ó·È ·ÚÎ ÚÈÁÏ˘ÎÂÚȉ·ÈÌ Ù ¿ ÂÚ ˘Ù · ˘ ‚¿ÚÔ˘˜, ÙË ‰ · ∏ Ú . ¤Ù Ì Â˜ · Ô. È ÛÙ·Ù›Ó ·ÏÎÔfiÏ. ∞Ó Ù ÂÊ·ÓÈ·›· ÓfiÛ Ú¿Ù˜ Î·È Ô Ù Û ÈÌ Ê Ë È ÈÌ Î·Ù·Ó¿ÏˆÛË Ô Ò Ú ,  ͇ Â Ô ›˙ÂÙ·È Ì ˆÓ ÙÔ ÓÈÎÔÙÈÓÈÎfi ÊÔÚ¤˜ Û˘Û¯ÂÙ È ÙË Ì›ˆÛË Ù · Î ¤˜ Ó ÏÏ Ì·Î·, fiˆ˜ Ô ›ˆ  ȉ ˘ Ù Ô ·  Ì LDL Ûˆ Û Ӌ ‰È·Ù·Ú·¯‹ Ú·ÙËÚÔ‡ÓÙ·È ÈÎÚÒÓ ˘ÎÓÒÓ Ì ·  ›· Ó¿ Â›Ó·È Ì›· Û˘¯ ˘Û Ô ˘¯ Ú Û · ˘  Ô ËÓ Ù·Ú·¯¤˜  ›˙ÂÙ·È Ì ÙËÓ ÈÓ‰‡ÓÔ˘ ÁÈ· Ù Î ·‚ÔÏÈΤ˜ ‰È· Â٠˜ Ì ÓÙ ∂›Û˘ Û˘Û¯ÂÙ Ô Ô ‡ Á ‰ ¿ È Ú Ô · ÙËÙÔ˘˜  Ì¿ÙˆÓ. ∞˘Ù¤˜ ˜ ÁÈ· ÙËÓ Â›ÂÏÔ‡Ó ·ÓÂÍ¿Ú ›Â Ù Á Ô Ë  ‰ · Ô HDL2 ˘ÔÎÏ·Û ˜ ›· › ÈÌ Ê · · Û ¿Ú¯Ô˘Ó ËÛË ÂÚÙÚÈÁÏ˘ÎÂÚȉ ∞Ó Î·È ‰ÂÓ ˘ Ù¿Ù·È ¯ÔÚ‹Á ÈÛ ˘. Ô ˘Ó Û ·ÛıÂÓ›˜ Ì ˘ Û Ófi Ó, ˜ ›ˆ ›· ȉ · ÈÁÏ˘ÎÂÚ ÙÔ˘ ÈÌ˘ ÛÙÂÊ·ÓÈ ›‰· ÙˆÓ ÙÚ È· ÙË Ì›ˆÛË Â Á l · Ù ÂÌÊ¿ÓÈÛË ÚÒ /d g È· m Á 0 Ó 0 ˆ ·fi 10 ›ˆÓ ÚÈÌ¤ÓˆÓ ÛÙfi¯ ÎÂÚȉ›ˆÓ ¿Óˆ · ÙÚÈÁÏ˘ÎÂÚȉ Ï˘ ‰ ÈÁ › Ú Ù¢ÍË Û˘ÁÎÂÎ Ù Â · · ‰ ÂÚ › Ù ÈË Ì ÌÈÎÚfi ¿ÙÔÌ· Ì Â ÏË, Û˘ÓÈÛٿٷ ™Â ·ÛıÂÓ›˜ fi . ÂÚ ˜ Ù · ÊÈÌÚ·ÙÒÓ ÛÂ Û È‰ ÏË ›Ù Ô Ù ¯ · L Ú Ì ڿ ÙËÓ LD ¿ÓÈÛ˘ ·ÁÎ ·Î¿ ÂÂÈÛfi‰È· Ô˜ fiÛÔÓ ·ÊÔ ¯ ÂÈ fi Á Ù ÎÈÓ‰‡ÓÔ˘ ÂÌÊ Á Û · Ô Ó ‡ › ÏÔ ı · ¯ Ús ÚÔÎ fiÙ·Ó ÂÈÙ¢ ·‡ÍËÛË Ù˘ · ›ˆÓ. Δ· NSAID + · ȉ Ì ÂÚ (200 mg/dl), ÂÛ Î ¤Ï Ï˘ Ù Ô ÈÁ  Ú · Ù ÙÔ˘ ¡· , Ì È¤‰ˆÓ ÙˆÓ ∫·Ù·ÎÚ·ÙÔ‡Ó Î·ÏÔ‡Ó ‚Ï¿‚Ë Ô . Ú ˜  Ì›ˆÛË ÙˆÓ Â ‡ Ô Ó Ì Ô Û Ï¤ ÓÈ · È ¯  Ì‚Ô˘ ¿ÚÎÂÈ·. ∂ ¤ÌÌÂÛÔ˘˜ ÌË ËÌ·ÙÈÛÌfi ıÚfi ¯ ·Ú‰È·Î‹ ·ÓÂ Û Î ¿ÌÂÛÔ˘˜ Î·È ‹ Ô Ù ÈÎ Û Ù Ë Ú ˘Ó Ô Ô Ê ·Ú‰›Úԉȷı¤Ù Û˘ Î·È Û˘Ì Ô˘ÚÁ›·, ÂÓÒ ÁÌ· ÙÔ˘ Ì˘ÔÎ · ÈÙ ÙËÚȷ΋˜ ›Â Ú ÏÂ Ê ˘Û ¤Ì ‰ È · ‹ Î Î · ÂÈÛfi‰ÈÔ ÚÔ·È ÂÓ‰ÔıËÏÈ Ó·È Ë ÚÒÙË fi ηډȷÎfi Â › ÈÎ A ÂÓ‰ÔıËÏ›Ô˘ Î ÈÌ N · O ¯ R Û O C (È ∏ ÈÔ ı¿Ó·ÙÔ). ÌÂϤÙË Îfi ÂÂÈÛfi‰ Î·È ·ÈÊÓ›‰ÈÔ ·ÎÔ ÎÏÈÓÈ΋ Ì ÈÔ Î·È Û ·ÁÁÂÈ· Ú ‰ ¿ fi Ê Û fi ÂÈ Î Â ÓÈ Ô fi ÏÔ‡Ë Ì ÂÈÎ ÂÁÎÂÊ·ÏÈÎ · Ù˘ ·Ú·ÎÔ Ë, ÂÏÂÁ¯fiÌÂÓ ÂÈ ¤Ó Î Ô˘, ·ÁÁÂÈ·Îfi Ì Ú ÈË È¿ Ô ‰  Ë ÈÔ Ù · ¿ ˘¯ ηÚÂÈ·. ∫·Ù ÂÓÙÚÈ΋, ٠ȷ΋ ·ÓÂ¿ÚÎ Ô Û‡ÓÔÏÔ ÙˆÓ ‰ Ù Ú ÔÙÈ΋ ÔÏ˘Î Û · ¿ Î Ú Ó Ô Ë Ê Ù Û È· ‰ Ó ÏÈÎÒÓ. ËÚ‹ıËΠˆÓ ÛÙ·ÙÈÓÒ ·ÎÒÓ ÂÁÎÂÊ· ˜) ‰ÂÓ ·Ú·Ù ÂÈ Ù˘ ‰Ú¿Û˘ Ù Á Ó Á ‹ Ì · È ,8 · 2 Î 3 Ó · ËÓ ·‡ÊÚ·ÁÌ¿Ùˆ Ë ‰È¿ÚÎÂÈ È‰·ÈÌ›·, Ì ٠ Ó·ÙËÊfiÚˆÓ ÂÌ ıËÛ˘ (‰È¿ÌÂÛ · ÏÈ ı ˘Û Ë ‰ Ì ÓÔ Ó fi ˆ Á Ù ˜ ÂÌÓ ·ıËÚÔ ı·Ó¿ÙˆÓ, ›˙ÂÙ·È ·fi ÙË L ¯ÔÏËÛÙÂÚfiÏË Ú D ‰È·ÁÁÂÈ·ÎÒÓ Ë H Ù Î ∏ · . Ú ˜ · ¯ ÏË fi Ô ¯ÔÏËÛÙÂÚ ÛË ÙÔ˘ fi ™‡Ó‰ÚÔÌ ˆÛË Ù˘ HDL È ÙËÓ ÂΉ‹Ïˆ › ΔÔ ªÂÙ·‚ÔÏÈÎ · Ì Î Ë Ù Ó‹ È Ô · Ì Î Á Ó ÏÂ Ï˘ÎÂÚȉ›ˆ (oxLDL) ÁÂÈ ÙËÓ Ê ÔÚˆÙ½Ó˘ ËÙ· Î·È Â¿ ÍËÛË ÙˆÓ ÙÚÈÁ Ù ÏÈ fi ˜ ÈÎ · Á Ù Ë ˘Ú Ù Ô Ófi ÈÙ ÌËÏ‹˜ ˘Î ÏÔÁÈ΋ Ï ·fi Ô͇ ÌÔÚÊ‹ Ù˘ ¯· ˆÛ˘. ªÂÙ¿ Ê·Ó›˙ÂÈ ·ıÔ Ú Ë Ï‹ ¤Ó Î Ì Û ˆ Ô Ú È‰ Ë Í ı Ô · Ó ¤Ó·ÓÙÈ ÂÈ· Ù˘ ÛÙÚ˜. ∏ Ô·ÓÙÈۈ̿و ÔÍÂȉˆÙÈÎÔ‡ ÛÙËÓ ·ıÔÁ¤Ó ˘Ù · ÏÔ Ó fi ˆ Ú Ù Ó fi ˆ ÈÎ ÛËÌ·ÓÙ Ó ÂÈ¤‰ ‹ÍË Ù˘ ÓÈÛÌÔ‡ ÛÙË Ú ·È ·‡ÍËÛË Ùˆ ‰È·‰Ú·Ì·Ù›˙ÂÈ · Ù Á › Ú Ú Ô Ë Ù ˘ · Ô Ú Ù · Ë  Û Ù·ÙȇӉÚÔÌÔ, ˆ˜ ·¿ÓÙË ‰Ú·ÛÙÈÎÒÓ Û˘Û ÛÙÂÊ·ÓÈ·›Ô Û ÈÔ DL, Èı·ÓÒ˜ ‚ L ˜ ›· Ë Ú Ô ¤Ó Ê Ì ˆ ÏÔ È‰ ÛÙËÓ Î˘Î ÙËÓ ·ÊÒÓ ÔÍ ÂÏ¢ı¤ÚˆÛ˘ ˜ ·Ó·ÛÙ¤ÏÏÂÈ fiÏˆÓ ÙˆÓ ÌÔÚ  ‡ · Ô ˜ ˘Ù Ë · Ù ˜ È Â› · Î ÂÓ ¤ÂÈ Ó· ˜ Ͽη˜ ÛÙÔ˘˜ ·Ûı ËÌ·Û›· ı· Ú ·ıËڈ̷ÙÈ΋ Û Ú‚·ÛÙ·Ù›Ó˘ Ô ‹ Ù Î · ÓÈ Ë ÏÈ Û Î Ë Á Ë ‹ Ú ÌÂÛË ¯Ô ˜ ÔÔ›·˜ ÎÒÓ Ù˘. ∏ ¿ ÌÈ· ‰Ú¿ÛË ÙË , Ë ÈÛ Ú Î fi  · ÔÏÔÁÈ΋ ˜. ÈÌÒÓ·˜  à ڷ¿Óˆ ·ÓÔÛ ˜ ÎÏÈÓÈΤ˜ ÌÂϤ٠· ˜ › Ë Ï Û · ∏ Ù ¤Î ˜  ÌÂÁ¿ÏË ·Ô‰Âȯı› Û ˜

˘ T˘ ™‡ÓÙ·Í

ÓÙ·ÍË Y‡ı˘ÓÔ˜ ™‡

™∂¶Δ∂ªμƒπ√™ 2008

÷ÌËÏ‹ HDL ÃÔÏËÛÙÂÚfiÏË Î·È Ë ∞ÓÙÈÌÂÙÒÈÛ‹ Ù˘ ÃÚ‹ÛÙÔ˜ ƒ›˙Ô˜, ∂ÈÛÙËÌÔÓÈÎfi˜ ™˘ÓÂÚÁ¿Ù˘ ÙÔ˘ ∂Í. π·ÙÚ›Ԣ ¢È·Ù·Ú·¯ÒÓ ÙÔ˘ ªÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ §Èȉ›ˆÓ ªˆ˘Û‹˜ ∂ÏÈÛ¿Ê, ∫·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜, ΔÔ̤·˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ

∂ÈÛ·ÁˆÁ‹ ∏ ˘„ËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙ½ÓË (HDL) ·ÔÙÂÏ› ÙËÓ Î‡ÚÈ· ·ÓÙÈ·ıËÚˆÁfiÓÔ ÏÈÔÚˆÙ½ÓË. ¶Ú¿ÁÌ·ÙÈ, Ë HDL ‰È·‰Ú·Ì·Ù›˙ÂÈ Î·ıÔÚÈÛÙÈÎfi ÚfiÏÔ ÛÙÔ Ì˯·ÓÈÛÌfi Ù˘ ·Ó¿ÛÙÚÔÊ˘ ÌÂÙ·ÊÔÚ¿˜ ¯ÔÏËÛÙÂÚfiÏ˘, ‰ËÏ·‰‹ ÛÙË ÌÂÙ·ÊÔÚ¿ Ù˘ ÂÚ›ÛÛÂÈ·˜ ¯ÔÏËÛÙÂÚfiÏ˘ ·fi Ù· ÂÚÈÊÂÚÈο ·ÙÙ·Ú· ÛÙÔ ‹·Ú. ∂ÈÚfiÛıÂÙ·, Ë HDL ¤¯ÂÈ ·ÓÙÈÔÍÂȉˆÙÈΤ˜ Î·È ·ÓÙÈıÚÔÌ‚ˆÙÈΤ˜ ‰Ú¿ÛÂȘ, ÂÓÒ ·ÛΛ ¢ÓÔ˚΋ Â›‰Ú·ÛË ÛÙË ÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ÂÓ‰ÔıËÏÈ·ÎÒÓ Î˘ÙÙ¿ÚˆÓ [1]. ªÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ ÁÈ· οı ηٿ 1% ·‡ÍËÛË Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘ (HDL-C) ·Ú·ÙËÚÂ›Ù·È Ì›ˆÛË Ù˘ ηډȷÁÁÂȷ΋˜ ıÓËÙfiÙËÙ·˜ ηٿ 2-3% [2]. Δ· ¯·ÌËÏ¿ Â›‰· Ù˘ HDL-C (οو ·fi 40 mg/dl) ·ÔÙÂÏÔ‡Ó ·ÓÂÍ¿ÚÙËÙÔ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË Î·Ú‰È·ÁÁÂȷ΋˜ ÓfiÛÔ˘ [3]. ¶ÔÏϤ˜ ηٷÛÙ¿ÛÂȘ ¤¯Ô˘Ó Û˘Û¯ÂÙÈÛı› Ì Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ Ù˘ HDL-C, fiˆ˜ ÙÔ Î¿ÓÈÛÌ·, Ë ·¯˘Û·ÚΛ·, Ë ÌÂȈ̤ÓË ÛˆÌ·ÙÈ΋ ‰Ú·ÛÙËÚÈfiÙËÙ·, Ë ¯ÔÚ‹ÁËÛË Ê·ÚÌ¿ÎˆÓ (.¯. ‚-·ÔÎÏÂÈÛÙÒÓ, ıÂÈ·˙ȉÈÎÒÓ ‰ÈÔ˘ÚËÙÈÎÒÓ), ηıÒ˜ Î·È Ô Û·Î¯·Ú҉˘ ‰È·‚‹Ù˘. Δ· ·˘ÍË̤ӷ ÙÚÈÁÏ˘ÎÂÚ›‰È· Â›Û˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÂÏ·Ùو̤ÓË HDL-C. ∏ ÚˆÙ½ÓË Ô˘ ÌÂٷʤÚÂÈ ÂÛÙ¤Ú˜ ¯ÔÏËÛÙÂÚfiÏ˘ (CETP) ·ÓÙ·ÏÏ¿ÛÂÈ Ù· ÙÚÈÁÏ˘ÎÂÚ›‰È· ÙˆÓ Ôχ ¯·ÌËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙÂ˚ÓÒÓ (VLDL) Ì ÂÛÙ¤Ú˜ ¯ÔÏËÛÙÂÚfiÏ˘ ÙˆÓ HDL. ™Â ÂÚÈÙÒÛÂȘ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜ ·˘Ù‹ Ë ·ÓÙ·ÏÏ·Á‹ ÏÈȉ›ˆÓ ÂÈÙ·¯‡ÓÂÙ·È Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·Ú·ÁˆÁ‹ ÏÔ‡ÛÈˆÓ Û ÙÚÈÁÏ˘ÎÂÚ›‰È· HDL ۈ̷Ùȉ›ˆÓ. ∏ Ë·ÙÈ΋ ÏÈ¿ÛË ˘‰ÚÔχÂÈ Ù· ÙÚÈÁÏ˘ÎÂÚ›‰È· ÙˆÓ HDL ۈ̷Ùȉ›ˆÓ Ì ·ÔÙ¤ÏÂÛÌ· ÙÔ Û¯ËÌ·ÙÈÛÌfi ÌÈÎÚÒÓ Î·È ˘ÎÓÒÓ HDL ۈ̷Ùȉ›ˆÓ. ∞˘Ù¿ Ù· ۈ̷ٛ‰È· ·Ô‰ÂÛÌÂ‡Ô˘Ó Â‡-

2

ÎÔÏ· ÙËÓ ·ÔÏÈÔÚˆÙ½ÓË ∞-π (Apo A-I), Ë ÔÔ›· Û ÂχıÂÚË ÌÔÚÊ‹ ·ÔÌ·ÎÚ‡ÓÂÙ·È ·fi ÙËÓ Î˘ÎÏÔÊÔÚ›· ‰È·Ì¤ÛÔ˘ ÙˆÓ ÓÂÊÚÒÓ, Ì ÙÂÏÈÎfi ·ÔÙ¤ÏÂÛÌ· ÙË Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ Ù˘ HDLC. ∂ÈϤÔÓ, Ë CETP ·ÓÙ·ÏÏ¿ÛÂÈ ÙÚÈÁÏ˘ÎÂÚ›‰È· ÙˆÓ VLDL Ì ÂÛÙ¤Ú˜ ¯ÔÏËÛÙÂÚfiÏ˘ ÙˆÓ ¯·ÌËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙÂ˚ÓÒÓ (LDL) Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·Ú·ÁˆÁ‹ ·ıËÚÔÁfiÓˆÓ ÌÈÎÚÒÓ ˘ÎÓÒÓ LDL ۈ̷Ùȉ›ˆÓ.

¶·ÚÂÌ‚¿ÛÂȘ ÁÈ· ÙËÓ ·‡ÍËÛË Ù˘ HDL-C A) ÀÁÈÂÈÓԉȷÈÙËÙÈΤ˜ ·ÚÂÌ‚¿ÛÂȘ i) ÕÛÎËÛË ∏ Ù·ÎÙÈ΋ ·ÂÚfi‚È· ¿ÛÎËÛË ÌÔÚ› Ó· ‚ÔËı‹ÛÂÈ ÛÙËÓ ·‡ÍËÛË ÙˆÓ ÂÈ¤‰ˆÓ Ù˘ HDL-C ηٿ 3-9% [4]. ∏ Û˘¯ÓfiÙËÙ· Ù˘ ¿ÛÎËÛ˘ Ê·›ÓÂÙ·È fiÙÈ ‰È·‰Ú·Ì·Ù›˙ÂÈ ÛËÌ·ÓÙÈÎfiÙÂÚÔ ÚfiÏÔ ·fi fiÙÈ Ë ¤ÓÙ·Û‹ Ù˘. ŒÙÛÈ Ë Û˘ÛÙËÌ·ÙÈ΋ ̤ÙÚÈ·˜ ¤ÓÙ·Û˘ ·ÂÚfi‚È· ¿ÛÎËÛË 5 ÊÔÚ¤˜ ÙËÓ Â‚‰ÔÌ¿‰· ÁÈ· 30 ÏÂÙ¿ ÙËÓ Ë̤ڷ Â›Ó·È ÈÔ ·ÔÙÂÏÂÛÌ·ÙÈ΋ ·fi ÙËÓ ¤ÓÙÔÓË ¿ÛÎËÛË 3 ÊÔÚ¤˜ ÙËÓ Â‚‰ÔÌ¿‰· ÁÈ· 60 ÏÂÙ¿ [4]. ™ÙËÓ ÂÚ›ÙˆÛË Ù˘ ۈ̷ÙÈ΋˜ ¿ÛÎËÛ˘ Ù· Â›‰· Ù˘ HDL-C ·˘Í¿ÓÔÓÙ·È ÛÙ·‰È·Î¿.

Θ Ô˘ ÚÔηÏÔ‡Ó ·‡ÍËÛË ÙÔ˘ ÁÏ˘Î·ÈÌÈÎÔ‡ ÊÔÚÙ›Ô˘ (.¯. ·Ù¿Ù˜, Ï¢Îfi „ˆÌ›) ÌÂÈÒÓÔ˘Ó Ù· Â›‰· Ù˘ HDL-C [7]. ™Ù· Ï·›ÛÈ· ÌÈ·˜ ÈÛÔÚÚÔË̤Ó˘ ‰È·ÙÚÔÊ‹˜, Ë ·ÒÏÂÈ· ‚¿ÚÔ˘˜ ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·ÎfiÌË ÌÂÁ·Ï‡ÙÂÚË ·‡ÍËÛË Ù˘ HDL-C. Δ· Â˘Ú‹Ì·Ù· ÌÈ·˜ ÌÂÙ¿-·Ó¿Ï˘Û˘ ¤‰ÂÈÍ·Ó fiÙÈ Î·Ù¿ ÙËÓ ÚÔÛ¿ıÂÈ· ·ÒÏÂÈ·˜ ‚¿ÚÔ˘˜ Ù· Â›‰· Ù˘ HDL-C ÌÂÈÒÓÔÓÙ·È Î·Ù¿ 0.27 mg/dl ÁÈ· οı ÎÈÏfi Ì›ˆÛ˘ ÙÔ˘ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜ [8]. øÛÙfiÛÔ, ÌÂÙ¿ ÙË ÛÙ·ıÂÚÔÔ›ËÛË ÙÔ˘ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜ ·Ú·ÙËÚÂ›Ù·È ·‡ÍËÛË Ù˘ HDL-C ηٿ 0.35 mg/dl ÁÈ· οı ÎÈÏfi Ì›ˆÛ˘ ÙÔ˘ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜. ∂Ô̤ӈ˜ Ë Ú‡ıÌÈÛË ÙÔ˘ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜ Â›Ó·È ¤Ó·˜ ·ÔÙÂÏÂÛÌ·ÙÈÎfi˜ ÙÚfiÔ˜ ÁÈ· ÙËÓ ·‡ÍËÛË ÙˆÓ ÂÈ¤‰ˆÓ Ù˘ HDL-C Û ˘¤Ú‚·Ú· ¿ÙÔÌ·. iii) ¢È·ÎÔ‹ ÙÔ˘ ηÓ›ÛÌ·ÙÔ˜ ªÈ· ·fi ÙȘ ÔÏϤ˜ ‚Ï·ÙÈΤ˜ Û˘Ó¤ÂȘ ÙÔ˘ ηÓ›ÛÌ·ÙÔ˜ Â›Ó·È Î·È Ë Ì›ˆÛË Ù˘ HDL-C. ¶Ú¿ÁÌ·ÙÈ, Ë ‰È·ÎÔ‹ ÙÔ˘ ηÓ›ÛÌ·ÙÔ˜ ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·‡ÍËÛË ÙˆÓ ÂÈ¤‰ˆÓ Ù˘ HDLC ηٿ 7-12% [9]. ∞˘Ù‹ Ë ÌÂÙ·‚ÔÏ‹ Â›Ó·È ÈÔ ÂÌÊ·Ó‹˜ ÛÙȘ Á˘Ó·›Î˜, ηıÒ˜ Î·È Û ¿ÙÔÌ· Ì ·˘ÍË̤ӷ Â›‰· HDL-C (>47 mg/dl) [9].

ii) ¢È·ÙÚÔÊ‹ Î·È ·ÒÏÂÈ· ‚¿ÚÔ˘˜

iv) ∞ÏÎÔfiÏ

∏ Ùˆ¯‹ Û ÏÈ·Ú¿ ‰›·ÈÙ· Û˘Óԉ‡ÂÙ·È ·fi Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ Ù˘ HDL-C [5]. øÛÙfiÛÔ, Ù· ÔʤÏË ÌÈ·˜ Ù¤ÙÔÈ·˜ ‰›·ÈÙ·˜ ·fi ÙË Ì›ˆÛË Ù˘ LDL-C ·ÓÙÈÛÙ·ıÌ›˙Ô˘Ó ÙË ‰˘ÛÌÂÓ‹ Â›‰Ú·ÛË Ù˘ ·fi ÙËÓ ÂÏ¿ÙÙˆÛË Ù˘ HDL-C. ¶Ú¤ÂÈ Ó· ·Ó·ÊÂÚı› fiÙÈ ÏËı˘ÛÌÔ› ÛÙÔ˘˜ ÔÔ›Ô˘˜ Ù· ˆ-3 ÔÏ˘·ÎfiÚÂÛÙ· ÏÈ·Ú¿ Ôͤ· η٤¯Ô˘Ó ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙË ‰È·ÙÚÔÊ‹ ¤¯Ô˘Ó ·˘ÍË̤ӷ Â›‰· HDL-C [6]. ∂ÈÚfiÛıÂÙ·, ÙÚÔʤ˜ ÏÔ‡ÛȘ Û ˘‰·Ù¿ÓıÚ·-

∏ ηٷӿψÛË ÌÈÎÚ‹˜ ÔÛfiÙËÙ·˜ ·ÏÎÔfiÏ Î·ıËÌÂÚÈÓ¿ ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·‡ÍËÛË ÙˆÓ ÂÈ¤‰ˆÓ Ù˘ HDL-C. Δ· ·ÔÙÂϤÛÌ·Ù· ÌÈ·˜ ÌÂÙ¿-·Ó¿Ï˘Û˘ ¤‰ÂÈÍ·Ó fiÙÈ Ë Î·Ù·Ó¿ÏˆÛË 30 gr ·ÏÎÔfiÏ ÙËÓ Ë̤ڷ Ô‰ËÁ› Û ·‡ÍËÛË Ù˘ HDL-C ηٿ 8.3% ·ÓÂÍ¿ÚÙËÙ· ·fi ÙÔ Â›‰Ô˜ ÙÔ˘ ÔÙÔ‡ [10]. øÛÙfiÛÔ, Ú¤ÂÈ Ó· Ï·Ì‚¿ÓÔÓÙ·È ˘fi„Ë ÔÈ È‰È·ÈÙÂÚfiÙËÙ˜ ÙÔ˘ οı ·ÙfiÌÔ˘ ÚÈÓ ÙËÓ ˘ÈÔı¤ÙËÛË Ù˘ ηıËÌÂÚÈÓ‹˜ ηٷӿψÛ˘ ÌÈÎÚÒÓ ÔÛÔًوÓ

¶∞ƒ∞°√¡Δ∂™ ∫π¡¢À¡√À ·ÏÎÔfiÏ. ŒÙÛÈ Û ¿ÙÔÌ· Ì ‰È·Ù·Ú·¯¤˜ Ù˘ Ë·ÙÈ΋˜ ‚ÈÔÏÔÁ›·˜, ˘„ËÏ¿ Â›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ, ηıÒ˜ Î·È Û ¿ÙÔÌ· ÂÈÚÚÂ‹ Û ÂıÈÛÌfi Ù· ÔʤÏË ·fi ÙËÓ ·‡ÍËÛË Ù˘ HDL-C Ú¤ÂÈ Ó· ÛÙ·ıÌ›˙ÔÓÙ·È Ì ÙÔ˘˜ ÎÈÓ‰‡ÓÔ˘˜ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙË Û˘Ó¯È˙fiÌÂÓË Î·Ù·Ó¿ÏˆÛË ·ÏÎÔÔÏÔ‡¯ˆÓ ÔÙÒÓ.

B) º·Ú̷΢ÙÈΤ˜ ·ÚÂÌ‚¿ÛÂȘ i) ¡ÈÎÔÙÈÓÈÎfi Ô͇ ΔÔ ÓÈÎÔÙÈÓÈÎfi Ô͇ ·ÔÙÂÏ› ÙËÓ ÈÔ ·ÔÙÂÏÂÛÌ·ÙÈ΋ Ê·Ú̷΢ÙÈ΋ ·Ú¤Ì‚·ÛË ÁÈ· ÙËÓ ·‡ÍËÛË Ù˘ HDL-C. ŒÓ·˜ ·fi ÙÔ˘˜ Ì˯·ÓÈÛÌÔ‡˜ ‰Ú¿Û˘ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ Â›Ó·È Ë ·Ó·ÛÙÔÏ‹ Ù˘ Ë·ÙÈ΋˜ ÚfiÛÏ˄˘ Ù˘ Apo A-I, Ô˘ ·ÔÙÂÏ› ‚·ÛÈÎfi Û˘ÛÙ·ÙÈÎfi Ù˘ HDL [11], Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·‡ÍËÛË ÙˆÓ ÂÈ¤‰ˆÓ Ù˘ HDL-C ÛÙÔ Ï¿ÛÌ· ηٿ 20-35% [12]. ∂ÈÚfiÛıÂÙ·, ÌÈÎÚ¤˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ Ë ¯ÔÚ‹ÁËÛË ÓÈÎÔÙÈÓÈÎÔ‡ ÔͤԘ Û¯ÂÙ›˙ÂÙ·È Ì ÂÈ‚Ú¿‰˘ÓÛË Ù˘ ÂͤÏÈ͢ Ù˘ ·ıËÚÔÛÎÏ‹ÚˆÛ˘ Î·È Ì›ˆÛË ÙˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ Û˘Ì‚·Ì¿ÙˆÓ [13]. øÛÙfiÛÔ, Ë Â˘ÂÚÁÂÙÈ΋ Â›‰Ú·ÛË ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ ÂÚÈÔÚ›˙ÂÙ·È ·fi ÙȘ ·ÚÂÓ¤ÚÁÂȤ˜ ÙÔ˘ Ô˘ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ¤Í·„Ë, ‰˘Û„›·, ηıÒ˜ Î·È ÌÈÎÚ‹ ·‡ÍËÛË ÙˆÓ ÂÈ¤‰ˆÓ Ù˘ ÁÏ˘Îfi˙˘ Î·È ÙÔ˘ Ô˘ÚÈÎÔ‡ ÔͤԘ. ii) ºÈÌÚ¿Ù˜ √È ÊÈÌÚ¿Ù˜ Â›Ó·È Ê¿Ú̷η Ô˘ ÂÏ·ÙÙÒÓÔ˘Ó Ù· ÙÚÈÁÏ˘ÎÂÚ›‰È· [14] Î·È ÂÈϤÔÓ ·˘Í¿ÓÔ˘Ó ÙËÓ HDL-C Û ÔÛÔÛÙfi 10-25% [15, 16]. √È ÊÈÌÚ¿Ù˜ ÂÓÂÚÁÔÔÈÔ‡Ó ÙÔ˘˜ PPAR· ˘ÚËÓÈÎÔ‡˜ ˘ԉԯ›˜ Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·‡ÍËÛË Ù˘ HDL-C Î·È ÙˆÓ 2 ·ÚÈˆÓ Û˘ÛÙ·ÙÈÎÒÓ Ù˘, ‰ËÏ·‰‹ Ù˘ Apo ∞-π Î·È Ù˘ Apo ∞-ππ [17]. ŒÙÛÈ, Û ÌÈ· ÌÂϤÙË ·ÙfiÌˆÓ Ì ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ, LDL-C≤140 mg/dl Î·È ¯·ÌËÏ‹ HDL-C Ë ¯ÔÚ‹ÁËÛË ÁÂÌÊÈ‚ÚÔ˙›Ï˘ ›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·‡ÍËÛË Ù˘ HDL-C ηٿ 6% (p<0.001 ¤Ó·ÓÙÈ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘) [18] Î·È ÙË Ì›ˆÛË Î·Ù¿ 22% (p<0.001) ÙˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ Û˘Ì‚·Ì¿ÙˆÓ. ™ÙË Û˘Ó¤¯ÂÈ·, ‰ÈÂÚ¢ӋıËÎÂ Ë Û˘Û¯¤ÙÈÛË ÙÔ˘ ÔʤÏÔ˘˜ fiÛÔÓ ·ÊÔÚ¿ ÙË Ì›ˆÛË ÙˆÓ Û˘Ì‚·Ì¿ÙˆÓ Ì ÙȘ ÌÂÙ·‚ÔϤ˜ ÙˆÓ ÏÈȉ·ÈÌÈÎÒÓ ·Ú·Ì¤ÙÚˆÓ. ªfiÓÔ Ë

·‡ÍËÛË Ù˘ HDL-C Û˘Û¯ÂÙ›˙ÔÓÙ·Ó Ì ÙË Ì›ˆÛË ÙˆÓ Û˘Ì‚·Ì¿ÙˆÓ ·Ú¿ ÙË Û˘Ó˘¿Ú¯Ô˘Û· ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ (-31%; p<0.001) [19]. iii) ™Ù·Ù›Ó˜ √È ÛÙ·Ù›Ó˜ ¤Ú·Ó Ù˘ ÌÂÁ¿Ï˘ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ¿˜ ÙÔ˘˜ fiÛÔÓ ·ÊÔÚ¿ ÙË Ì›ˆÛË Ù˘ LDL-C ¤¯Ô˘Ó ÙËÓ ÈηÓfiÙËÙ· Ó· ·˘Í¿ÓÔ˘Ó Û ÌÈÎÚfiÙÂÚÔ ‚·ıÌfi ÙËÓ HDL-C ηٿ 2-15% [20, 21]. ∞˘Ù‹ Ë È‰ÈfiÙËÙ¿ ÙÔ˘˜ ÔÊ›ÏÂÙ·È Û ·‡ÍËÛË Ù˘ ·Ú·ÁˆÁ‹˜ Ù˘ Apo ∞-π. ŒÙÛÈ, Ô Û˘Ó‰˘·ÛÌfi˜ ÛÙ·ÙÈÓÒÓ Ì ÓÈÎÔÙÈÓÈÎfi Ô͇ ÌÔÚ› Ó· ·ÔÙÂϤÛÂÈ ÌÈ· ÂÏ΢ÛÙÈ΋ ÂÈÏÔÁ‹ ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ÌÈÎÙÒÓ ‰˘ÛÏÈȉ·ÈÌÈÒÓ Ì ٷ˘Ùfi¯ÚÔÓË Ì›ˆÛË Ù˘ LDL-C Î·È ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË Ù˘ HDL-C. ™Â ÌÈ· ÌÂϤÙË ÛÙËÓ ÔÔ›· ¯ÔÚËÁ‹ıËΠÛÈÌ‚·ÛÙ·Ù›ÓË (20-40 mg/ Ë̤ڷ) Ì ÓÈÎÔÙÈÓÈÎfi Ô͇ (2-4 gr/Ë̤ڷ) Û ¿ÙÔÌ· Ì ηډȷÁÁÂȷ΋ ÓfiÛÔ, ¯·ÌËÏ‹ HDL-C Î·È Ê˘ÛÈÔÏÔÁÈ΋ LDL-C ·Ú·ÙËÚ‹ıËΠ·‡ÍËÛË Ù˘ HDL-C ηٿ 26% [22]. ™ÙË ÌÂϤÙË ·˘Ù‹, ÔÈ ÛÙÂÓÒÛÂȘ ÛÙ· ÛÙÂÊ·ÓÈ·›· ·ÁÁ›· ·Ú¤ÌÂÈÓ·Ó ÛÙ¿ÛÈ̘ ÛÙËÓ ÔÌ¿‰· ÙÔ˘ Û˘Ó‰˘·ÛÌÔ‡ (+0.4%), ÂÓÒ ·˘Í‹ıËÎ·Ó ÛÙËÓ ÔÌ¿‰· ÙÔ˘ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ (+3.9%; p<0.001 ¤Ó·ÓÙÈ Ù˘ ÔÌ¿‰·˜ ÙÔ˘ Û˘Ó‰˘·ÛÌÔ‡). iv) ÕÏÏ· Ê¿Ú̷η ∏ ¯ÔÚ‹ÁËÛË ·Ó·Û˘Ó‰˘·Ṳ̂Ó˘ Apo ∞-π ªÈÏ¿ÓÔ ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÂÈÙ¿¯˘ÓÛË ÙÔ˘ Ì˯·ÓÈÛÌÔ‡ Ù˘ ·Ó¿ÛÙÚÔÊ˘ ÌÂÙ·ÊÔÚ¿˜ ¯ÔÏËÛÙÂÚfiÏ˘. ™Â ÌÈ· ÌÂϤÙË 47 ·ÛıÂÓÒÓ Ô˘ ÂÏ¿Ì‚·Ó·Ó 5 ‚‰ÔÌ·‰È·›Â˜ ÂÁ¯‡ÛÂȘ Ù˘ Apo ∞-π ªÈÏ¿ÓÔ (15-45 mg/kg) ·Ú·ÙËÚ‹ıËΠ‹È· ˘ÔÛÙÚÔÊ‹ (0.81%; p=0.02 ¤Ó·ÓÙÈ Ù˘ ·Ú¯È΋˜ ÙÈÌ‹˜) Ù˘ ÛÙÂÊ·ÓÈ·›·˜ ·ıËÚÔÛÎÏ‹ÚˆÛ˘, fiˆ˜ ·˘Ù‹ ÂÎÙÈÌ‹ıËΠ̠ÂÓ‰ÔÛÙÂÊ·ÓÈ·›Ô ˘¤ÚË¯Ô [23]. √È ÁÏÈÙ·˙fiÓ˜ Î·È È‰È·›ÙÂÚ· Ë ÈÔÁÏÈÙ·˙fiÓË ·˘Í¿ÓÔ˘Ó Ù· Â›‰· Ù˘ HDL-C ηٿ 14-19% [24]. ∏ ·‡ÍËÛË ·˘Ù‹ Ê·›ÓÂÙ·È fiÙÈ Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ È‰ÈfiÙËÙ· ÙˆÓ Ê·ÚÌ¿ÎˆÓ Ó· ÂÓÂÚÁÔÔÈÔ‡Ó Û οÔÈÔ ‚·ıÌfi Î·È ÙÔ˘˜ PPAR· ˘ԉԯ›˜. ΔÔ rimonabant, ¤Ó·˜ ·Ó·ÛÙÔϤ·˜ ÙˆÓ ÂÓ‰ÔηÓÓ·‚ÈÓÔÂȉÒÓ ˘Ô‰Ô¯¤ˆÓ, ÚÔηÏ› ÂÏ¿ÙÙˆÛË ÙÔ˘

ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜ Î·È ·˘Í¿ÓÂÈ ÛËÌ·ÓÙÈο Ù· Â›‰· Ù˘ HDLC ηٿ 10% Û ۇÁÎÚÈÛË Ì ÙÔ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ [25]. ∞˘Ù‹ Ë ·‡ÍËÛË ÙˆÓ ÂÈ¤‰ˆÓ Ù˘ HDL-C Â›Ó·È ÌÂÁ·Ï‡ÙÂÚË ·fi ÙËÓ ·Ó·ÌÂÓfiÌÂÓË ·fi ÙËÓ ·ÒÏÂÈ· ÙÔ˘ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜ [26]. ∂ÈÚfiÛıÂÙ·, ÙÔ rimonabant ÌÂÈÒÓÂÈ ÛËÌ·ÓÙÈο Ù· Â›‰· ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ [25]. ŒÓ· ¿ÏÏÔ Ê¿ÚÌ·ÎÔ Ì ÛËÌ·ÓÙÈ΋ ÈηÓfiÙËÙ· ·‡ÍËÛ˘ Ù˘ HDLC (+72%) Â›Ó·È ÙÔ torcetrapib Ô˘ ·Ó·ÛÙ¤ÏÏÂÈ ÙËÓ CETP. ŸÌˆ˜, ·Ú¿ ÙË ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË Ù˘ HDL-C, Ë ¯ÔÚ‹ÁËÛË ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ ‰ÂÓ Û˘Óԉ‡ÂÙ·È ·fi ÙËÓ ·Ó·ÌÂÓfiÌÂÓË Â˘ÂÚÁÂÙÈ΋ Â›‰Ú·ÛË Û ÎÏÈÓÈÎfi Â›‰Ô. ∞ÓÙ›ıÂÙ·, ÙÔ torcetrapib Û˘Û¯ÂÙ›ÛÙËΠ̠·‡ÍËÛË Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘ Î·È ÙˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ Û˘Ì‚·Ì¿ÙˆÓ, ηıÒ˜ Î·È ÙˆÓ ı·Ó¿ÙˆÓ ·fi ÔÔÈ·‰‹ÔÙ ·ÈÙ›· [27]. øÛÙfiÛÔ, ‰ÂÓ Â›Ó·È ÍÂηı·ÚÈṲ̂ÓÔ Â¿Ó Ë ‰˘ÛÌÂÓ‹˜ Â›‰Ú·ÛË ÙÔ˘ torcetrapib ÔÊ›ÏÂÙ·È ÛÙÔ Ì˯·ÓÈÛÌfi ‰Ú¿Û˘ ÙÔ˘ ‹ Â›Ó·È ·ÔÎÏÂÈÛÙÈÎfi ¯·Ú·ÎÙËÚÈÛÙÈÎfi ÙÔ˘ Û˘ÁÎÂÎÚÈ̤ÓÔ˘ Ê·ÚÌ¿ÎÔ˘ [28]. ™˘ÌÂÚ¿ÛÌ·Ù· ∏ HDL-C ‰È·‰Ú·Ì·Ù›˙ÂÈ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙË ÌÂÙ·ÊÔÚ¿ ¯ÔÏËÛÙÂÚfiÏ˘ ·fi Ù· ·ÙÙ·Ú· ÛÙÔ ‹·Ú Î·È Ë Ì›ˆÛ‹ Ù˘ ·ÔÙÂÏ› ·ÓÂÍ¿ÚÙËÙÔ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË Î·Ú‰È·ÁÁÂȷ΋˜ ÓfiÛÔ˘. øÛÙfiÛÔ, Ë ∂ıÓÈ΋ (ÙˆÓ ∏.¶.∞.) ∂ÈÙÚÔ‹ ÁÈ· ÙË ÃÔÏËÛÙÂÚfiÏË (NCEP) ‰ÂÓ ÚÔÙ›ÓÂÈ Û˘ÁÎÂÎÚÈ̤ÓÔ˘˜ ÛÙfi¯Ô˘˜ ÁÈ· ÙËÓ HDL-C [3]. H LDL-C ·ÔÙÂÏ› ÙÔÓ Î‡ÚÈÔ ÛÙfi¯Ô Ù˘ ˘ÔÏÈȉ·ÈÌÈ΋˜ ·ÁˆÁ‹˜. ∞ÊÔ‡ ÂÈÙ¢¯ı› Ô ÛÙfi¯Ô˜ fiÛÔÓ ·Ó·ÊÔÚ¿ ÙËÓ LDL-C Î·È ÂÊfiÛÔÓ Û˘Ó˘¿Ú¯Ô˘Ó ¯·ÌËÏ¿ Â›‰· HDL-C Û˘ÓÈÛÙ¿Ù·È Ë ˘ÈÔı¤ÙËÛË ·ÚÂÌ‚¿ÛÂˆÓ Ì ÛÙfi¯Ô ÙËÓ ·‡ÍËÛË Ù˘ HDL-C. ∞˘Ù¤˜ ÔÈ ·ÚÂÌ‚¿ÛÂȘ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÙËÓ Ù·ÎÙÈ΋ ۈ̷ÙÈ΋ ¿ÛÎËÛË, ÙËÓ ˘ÁÈÂÈÓ‹ ‰È·ÙÚÔÊ‹ Î·È ÙËÓ ·ÒÏÂÈ· ‚¿ÚÔ˘˜. ∂ÈÚfiÛıÂÙ·, Ë ‰È·ÎÔ‹ ÙÔ˘ ηÓ›ÛÌ·ÙÔ˜, ηıÒ˜ Î·È Ë ÌÂÙÚ›Ô˘ ‚·ıÌÔ‡ ηıËÌÂÚÈÓ‹ ηٷӿψÛË ·ÏÎÔfiÏ Û˘Ì‚¿ÏÔ˘Ó Â›Û˘ ÛÙËÓ ·‡ÍËÛË Ù˘ HDL-C. ∞Ó Ù· ̤ÙÚ· ·˘Ù¿ ‰ÂÓ Â›Ó·È ·ÚÎÂÙ¿ ÁÈ· ÙË ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË Ù˘ HDL-C ÌÔÚÔ‡Ó Ó· ¯ÔÚË-

3

™∂¶Δ∂ªμƒπ√™ 2008

ÁËıÔ‡Ó Ê¿Ú̷η, fiˆ˜ ÙÔ ÓÈÎÔÙÈÓÈÎfi Ô͇, ÔÈ ÊÈÌÚ¿Ù˜ Î·È ÔÈ ÛÙ·Ù›Ó˜, ȉȷ›ÙÂÚ· Û ¿ÙÔÌ· Ì ·˘ÍË̤ÓÔ Î·Ú‰È·ÁÁÂÈ·Îfi ΛӉ˘ÓÔ, fiˆ˜ Û ·ÛıÂÓ›˜ Ì ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ ‹ ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË. øÛÙfiÛÔ, Ú¤ÂÈ Ó· ·Ó·ÊÂÚı› fiÙÈ ÌÂÁ·Ï‡ÙÂÚË ÛËÌ·Û›· ¤¯ÂÈ Ë ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ· ÙˆÓ HDL ۈ̷Ùȉ›ˆÓ Î·È ÏÈÁfiÙÂÚÔ Ë Û˘ÁΤÓÙÚˆÛË Ù˘ HDL-C ÛÙÔÓ ÔÚfi. ¶Ú¿ÁÌ·ÙÈ, Ù· ·˘ÍË̤-

Ó· Â›‰· Ù˘ HDL-C Û ¿ÙÔÌ· Ì ÌÂÙ·ÏÏ¿ÍÂȘ Ù˘ CETP ‰ÂÓ Û˘Û¯ÂÙ›˙ÔÓÙ·È Ì ÌÂȈ̤ÓÔ Î·Ú‰È·ÁÁÂÈ·Îfi ΛӉ˘ÓÔ [29]. ∂ÈϤÔÓ, ÌÂȈ̤ӷ Â›‰· HDL-C Û ¿ÙÔÌ· Ì ÌÂÙ·ÏÏ¿ÍÂȘ ÙÔ˘ ÁÔÓȉ›Ô˘ Ù˘ Apo A-I ‰ÂÓ ·˘Í¿ÓÔ˘Ó ÙÔÓ Î›Ó‰˘ÓÔ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË Î·Ú‰È·ÁÁÂÈ·ÎÒÓ ÓÔÛËÌ¿ÙˆÓ [30]. ∂›Û˘, ¿ÙÔÌ· Ì ÙË ÌÂÙ¿ÏÏ·ÍË Apo A-I ªÈÏ¿ÓÔ ‰ÂÓ ¤¯Ô˘Ó ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË

·ıËڈ̿وÛ˘ ·Ú¿ Ù· ¯·ÌËÏ¿ Â›‰· Ù˘ HDL-C [31]. ∂Ô̤ӈ˜, Ô ‚·ÛÈÎfi˜ ÛÙfi¯Ô˜ ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ‰˘ÛÏÈȉ·ÈÌ›·˜ Â›Ó·È Ë Ì›ˆÛË Ù˘ LDL-C Î·È ÂÊfiÛÔÓ ·˘Ùfi˜ Ô ÛÙfi¯Ô˜ ÂÈÙ¢¯ı› Ú¤ÂÈ Ó· ÂȯÂÈÚÂ›Ù·È Ë ·‡ÍËÛË Ù˘ HDL-C ΢ڛˆ˜ Ì ˘ÁÈÂÈÓԉȷÈÙËÙÈο ̤ÙÚ·.

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Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001; 345: 1583-92.

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26. Van Gaal LF, Rissanen AM, Scheen AJ, et al. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study.

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27. Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007; 357: 2109-22.

28. Tall AR, Yvan-Charvet L, and Wang N. The failure of torcetrapib: was it the molecule or the mechanism? Arterioscler Thromb Vasc Biol 2007; 27: 257-60.

29. Zhong S, Sharp DS, Grove JS, et al.

Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels. J Clin Invest 1996; 97: 2917-23.

30. Frikke-Schmidt R, Nordestgaard BG, Stene MC, et al. Association of loss-offunction mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease. JAMA 2008; 299: 2524-32.

31. Chiesa G and Sirtori CR. Apolipoprotein A-I(Milano): current perspectives.

Curr Opin Lipidol 2003; 14: 159-63.

μÈ‚ÏÈÔÁÚ·Ê›· 1.

Florentin M, Liberopoulos EN, Wierzbicki AS, et al. Multiple actions of highdensity lipoprotein. Curr Opin Cardiol 2008; 23: 370-8.

2. Gordon DJ, Probstfield JL, Garrison RJ, et al. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies.

Circulation 1989; 79: 8-15.

3. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002; 106: 3143421.

4. King AC, Haskell WL, Young DR, et al.

Long-term effects of varying intensities and formats of physical activity on participation rates, fitness, and lipoproteins in men and women aged 50 to 65 years. Circulation 1995; 91: 2596-604.

5. Meksawan K, Pendergast DR, Leddy JJ, et al. Effect of low and high fat diets on nutrient intakes and selected cardiovascular risk factors in sedentary men and women. J Am Coll Nutr 2004; 23: 131-40.

6. Gerasimova E, Perova N, Ozerova I, et al. The effect of dietary n-3 polyunsaturated fatty acids on HDL cholesterol in Chukot residents vs muscovites.

Lipids 1991; 26: 261-5.

7. Slyper A, Jurva J, Pleuss J, et al.

Influence of glycemic load on HDL cholesterol in youth. Am J Clin Nutr 2005; 81: 376-9.

8. Dattilo AM and Kris-Etherton PM. Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr 1992; 56: 320-8.

9. Maeda K, Noguchi Y, and Fukui T. The effects of cessation from cigarette smoking on the lipid and lipoprotein profiles: a meta-analysis. Prev Med 2003; 37: 283-90.

10. Rimm EB, Williams P, Fosher K, et al.

Moderate alcohol intake and lower risk of coronary heart disease: metaanalysis of effects on lipids and haemostatic factors. BMJ 1999; 319: 1523-8.

11. Piepho RW. The pharmacokinetics and pharmacodynamics of agents proven to raise high-density lipoprotein cholesterol. Am J Cardiol 2000; 86: 35L-40L.

4

¶∞ƒ∞°√¡Δ∂™ ∫π¡¢À¡√À

¢È·ÁÓˆÛÙÈ΋ ¶ÚÔÛ¤Ï·ÛË Î·È ∞ÓÙÈÌÂÙÒÈÛË ∞ÛıÂÓÒÓ Ì ÀÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· ÕÚ˘-¢ËÌ‹ÙÚÈÔ˜ ∞ÁÁÔ˘Ú›‰Ë˜, ∂ÈÛÙËÌÔÓÈÎfi˜ ™˘ÓÂÚÁ¿Ù˘ ÙÔ˘ ∂Í. π·ÙÚ›Ԣ ÙˆÓ ¢È·Ù·Ú·¯ÒÓ ÙÔ˘ ªÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ §Èȉ›ˆÓ ÙÔ˘ ¶·ÓÂÈÛÙËÌÈ·ÎÔ‡ °ÂÓÈÎÔ‡ ¡ÔÛÔÎÔÌ›Ԣ πˆ·ÓÓ›ÓˆÓ ªˆ˘Û‹˜ ∂ÏÈÛ¿Ê, ∫·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜, ΔÔ̤·˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ ΔÔ̤·˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ

¶·ÚÔ˘Û›·ÛË ÂÚÈÛÙ·ÙÈÎÔ‡ ÕÓ‰Ú·˜ 45 ÂÙÒÓ Û ¤ÏÂÁ¯Ô ÚÔ˘Ù›Ó·˜ ÂÌÊ¿ÓÈÛ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·. √ ·ÛıÂÓ‹˜ ‰ÂÓ Î¿ÓÈ˙Â, ·ÎÔÏÔ˘ıÔ‡Û ۈÛÙ‹ ‰È·ÙÚÔÊ‹, ηٷӿψÓ ¤Ó· ÔÙfi ·ÏÎÔfiÏ ÙËÓ Â‚‰ÔÌ¿‰· Î·È ·ÛÎÔ‡ÓÙ·Ó Ù·ÎÙÈο. ¢ÂÓ ¤·ÈÚÓ ʿÚ̷η, Ô ·Ù¤Ú·˜ ÙÔ˘ ¤ı·Ó Û ËÏÈΛ· 55 ÂÙÒÓ Û ÙÚÔ¯·›Ô ·Ù‡¯ËÌ·, ÂÓÒ Ë ÌËÙ¤Ú· ÙÔ˘ ‹Ù·Ó 67 ÂÙÒÓ ¯ˆÚ›˜ ÚÔ‚Ï‹Ì·Ù· ˘Á›·˜, fiˆ˜ Î·È ÔÈ ‰‡Ô ÌÂÁ·Ï‡ÙÂÚÔÈ ·‰ÂÏÊÔ› ÙÔ˘. ∏ ·ÚÙËÚȷ΋ ÙÔ˘ ›ÂÛË ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈ΋, Ô ‰Â›ÎÙ˘ Ì¿˙·˜ ÛÒÌ·ÙÔ˜ 28 kg/mg2 Î·È Ë ÂÚ›ÌÂÙÚÔ˜ ̤Û˘ 96 cm. ∞fi Ù· ÂÚÁ·ÛÙËÚȷο Â˘Ú‹Ì·Ù·, Ù· Â›‰· ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÓËÛÙ›·˜ ‹Ù·Ó 400 mg/dl, Ù˘ ÔÏÈ΋˜ ¯ÔÏËÛÙÂÚfiÏ˘ 230 mg/dl, Ù˘ LDL ¯ÔÏËÛÙÂÚfiÏ˘ 120 mg/dl Î·È Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘ 30 mg/dl, ÂÓÒ Ù· Â›‰· Ù˘ ÁÏ˘Îfi˙˘ ÓËÛÙ›·˜ 90 mg/dl. ¢ÂÓ ˘‹Ú¯·Ó ‰È·Ù·Ú·¯¤˜ Ù˘ ı˘ÚÂÔÂȉÈ΋˜ Î·È Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜.

¢È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ·ÛıÂÓÒÓ Ì ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· ∏ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· Â›Ó·È Ì›· Û˘¯Ó‹ ‰È·Ù·Ú·¯‹ Ô˘ ÔÏϤ˜ ÊÔÚ¤˜ Û˘Û¯ÂÙ›˙ÂÙ·È Ì ÚÒÈÌË ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ.1-4 ∂›Û˘ Û˘Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ·ÚÔ˘Û›· ÌÈÎÚÒÓ ˘ÎÓÒÓ LDL ۈ̷Ùȉ›ˆÓ Î·È ÙË Ì›ˆÛË ÙˆÓ HDL2 ˘ÔÎÏ·ÛÌ¿ÙˆÓ. ∞˘Ù¤˜ ÔÈ ‰‡Ô ÌÂÙ·‚ÔÏÈΤ˜ ‰È·Ù·Ú·¯¤˜ Ô˘ Û˘¯Ó¿ ·Ú·ÙËÚÔ‡ÓÙ·È Û ·ÛıÂÓ›˜ Ì ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· ·ÔÙÂÏÔ‡Ó ·ÓÂÍ¿ÚÙËÙÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ÚÒÈÌ˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘.5 ∞ÛıÂÓ›˜ Ì ˘„ËÏ¿ Â›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Â›Ó·È Èı·Ófi Ó· ÂÌÊ·Ó›˙Ô˘Ó ÁÂÓÂÙÈΤ˜ ‰È·Ù·Ú·-

¯¤˜ Ô˘ Û˘Û¯ÂÙ›˙ÔÓÙ·È Ì ÚÒÈÌË ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ. ∞˘Ù¤˜ ÔÈ ‰È·Ù·Ú·¯¤˜ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÙËÓ ÔÈÎÔÁÂÓ‹ ÌÂÈÎÙ‹ ˘ÂÚÏÈȉ·ÈÌ›·, ÙËÓ ˘ÔÏÂÈÌÌ·ÙÈ΋ (residual) ‰˘ÛÏÈȉ·ÈÌ›· ·ÛıÂÓÒÓ Ì ڢıÌÈṲ̂ÓÔ Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË Ù‡Ô˘ 2 (™¢2) Î·È ÙËÓ ÔÈÎÔÁÂÓ‹ ˘Ô·ÏÊ·ÏÈÔÚˆÙÂ˚Ó·ÈÌ›·. ∞˘Ù¤˜ ÔÈ ‰È·Ù·Ú·¯¤˜ ·Ú·ÙËÚÔ‡ÓÙ·È Û˘¯Ó¿ Û ·ÛıÂÓ›˜ Ô˘ ÏËÚÔ‡Ó Ù· ÎÚÈÙ‹ÚÈ· ÁÈ· ÙË ‰È¿ÁÓˆÛË ÙÔ˘ ÌÂÙ·‚ÔÏÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘.6 ∏ Â›ÙˆÛË Ù˘ ÔÈÎÔÁÂÓÔ‡˜ ÌÂÈÎÙ‹˜ ˘ÂÚÏÈȉ·ÈÌ›·˜1 3 4 Î·È Ù˘ ÔÈÎÔÁÂÓÔ‡˜ ˘Ô·ÏÊ·ÏÈÔÚˆÙÂ˚Ó·ÈÌ›·˜3 7 Â›Ó·È ÂÚ›Ô˘ 1% ÛÙÔ ÁÂÓÈÎfi ÏËı˘ÛÌfi, ÂÓÒ Ô ™¢2 ·ÓȯÓ‡ÂÙ·È ÙÔ˘Ï¿¯ÈÛÙÔÓ ÛÙÔ 5% ÙÔ˘ ÁÂÓÈÎÔ‡ ÏËı˘ÛÌÔ‡. ÀÔÏÔÁ›˙ÂÙ·È fiÙÈ ¿Óˆ

·fi ÙÔ 50% ÙˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ Û˘Ì‚·Ì¿ÙˆÓ Û¯ÂÙ›˙ÂÙ·È Ì ·˘Ù¤˜ ÙȘ ÙÚÂȘ ÌÂÙ·‚ÔÏÈΤ˜ ‰È·Ù·Ú·¯¤˜.8 ∏ ‰È¿ÁÓˆÛË ÙˆÓ ·Ú·¿Óˆ ‰È·Ù·Ú·¯ÒÓ ··ÈÙ› ÂÈıÂÙÈ΋ ·Ú¤Ì‚·ÛË Ì ÛÎÔfi ÙË Ì›ˆÛË ÙÔ˘ ηډȷÁÁÂÈ·ÎÔ‡ ÎÈÓ‰‡ÓÔ˘. ∞ÓÙ›ıÂÙ· ÌÈ· ¿ÏÏË ÎÏËÚÔÓÔÌÈ΋ ÌÔÚÊ‹ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜, Ë ÌÔÓÔÁÂÓ‹˜ ÔÈÎÔÁÂÓ‹˜ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·, Ô˘ ·Ú·ÙËÚÂ›Ù·È Â›Û˘ ÛÙÔ 1% ÙÔ˘ ÁÂÓÈÎÔ‡ ÏËı˘ÛÌÔ‡, ‰ÂÓ Ê·›ÓÂÙ·È Ó· Û¯ÂÙ›˙ÂÙ·È Ì ÚÒÈÌË ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ.2 8 9 ¶Ú¤ÂÈ ÏÔÈfiÓ Û οı ÂÚ›ÙˆÛË Ó· Á›ÓÂÙ·È ÛˆÛÙ‹ ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ÙˆÓ ·Ú·¿Óˆ ‰È·Ù·Ú·¯ÒÓ ¤ÙÛÈ ÒÛÙ ӷ ÂÈϤÁÂÙ·È Ë Î·Ù¿ÏÏËÏË ıÂÚ·¢ÙÈ΋ ·ÁˆÁ‹.

¶›Ó·Î·˜ 1: ∂›‰Ú·ÛË Ê·ÚÌ¿ÎˆÓ ÛÙ· Â›‰· ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Î·È Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ º¿Ú̷η

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5

™∂¶Δ∂ªμƒπ√™ 2008

∏ ·¯˘Û·ÚΛ·, Î·È ÈÔ Û˘ÁÎÂÎÚÈ̤ӷ Ë ÛÏ·¯ÓÈ΋ ·¯˘Û·ÚΛ·, Û¯ÂÙ›˙ÂÙ·È Ì ·‡ÍËÛË ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Î·È Ì Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘. √ Û˘Ó‰˘·ÛÌfi˜ Ù˘ ÛÏ·¯ÓÈ΋˜ ·¯˘Û·ÚΛ·˜ Ì ÙËÓ ·ÓÙ›ÛÙ·ÛË ÛÙË ‰Ú¿ÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘ Èı·Ó¿ ÌÔÚ› Ó· ÂÍËÁ‹ÛÂÈ ÙȘ ÔÛÔÙÈΤ˜ Î·È ÔÈÔÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙˆÓ ÏÈÔÚˆÙÂ˚ÓÒÓ Ô˘ ·Ú·ÙËÚÔ‡ÓÙ·È ÛÙË ‰˘ÛÏÈȉ·ÈÌ›· Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ÙÔÓ ™¢2,10 ÛÙËÓ ÔÈÎÔÁÂÓ‹ ÌÂÈÎÙ‹ ˘ÂÚÏÈȉ·ÈÌ›· Î·È ÛÙËÓ ÔÈÎÔÁÂÓ‹ ˘Ô·ÏÊ·ÏÈÔÚˆÙÂ˚Ó·ÈÌ›·. ¡ÔÛ‹Ì·Ù· Ô˘ ÚÔηÏÔ‡Ó ‰Â˘ÙÂÚÔ·ı‹ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· Â›Ó·È Ô ¯ˆÚ›˜ ıÂÚ·›· ‹ Ô ÌË Ú˘ıÌÈṲ̂ÓÔ˜ ™¢2, Ë ıÂÚ·›· ÌÂ Û˘ÁÎÂÎÚÈ̤ӷ Ê¿Ú̷η (¶›Ó·Î·˜ 1) Î·È Ë Î·Ù·Ó¿ÏˆÛË ·ÏÎÔfiÏ. ÕÏÏ· Û¿ÓÈ· ·›ÙÈ· ‰Â˘ÙÂÚÔ·ıÔ‡˜ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜ ·ÔÙÂÏÔ‡Ó Ô ˘Ôı˘ÚÂÔÂȉÈÛÌfi˜, Ë ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘ ÓÂÊÚÈ΋ ·ÓÂ¿ÚÎÂÈ·, ÙÔ ÓÂÊÚˆÛÈÎfi Û‡Ó‰ÚÔÌÔ Î·È Ë Ïԛ̈ÍË ·fi ÙÔÓ Èfi Ù˘ Â›ÎÙËÙ˘ ·ÓÔÛÔ·ÓÂ¿ÚÎÂÈ·˜. ∞ÛıÂÓ›˜ Ì Â›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ¿Óˆ ·fi 2000 mg/dl ηٿ ηÓfiÓ· ÂÌÊ·Ó›˙Ô˘Ó Û˘Ó‰˘·ÛÌfi ‰Â˘ÙÂÚÔ·ıÔ‡˜ Î·È ÔÈÎÔÁÂÓÔ‡˜ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜.

∂ÎÙ›ÌËÛË ·ÛıÂÓÒÓ Ì ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· ™Â ·ÛıÂÓ›˜ Ì ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· Ú¤ÂÈ ·Ú¯Èο Ó· ÂÈÎÂÓÙÚˆıԇ̠ÛÙËÓ ‡·ÚÍË ÔÈÎÔÁÂÓÂÈ·ÎÔ‡ ÈÛÙÔÚÈÎÔ‡ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜ ‹ ÛÙËÓ ‡·ÚÍË ·ÙÔÌÈÎÔ‡ ‹ ÔÈÎÔÁÂÓÂÈ·ÎÔ‡ ÈÛÙÔÚÈÎÔ‡ ÚÒÈÌ˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘. ∂ÈÚfiÛıÂÙ·, Ú¤ÂÈ Ó· ·Ó·ÁÓˆÚÈÛıÔ‡Ó ÂӉ¯fiÌÂÓ· ÓÔÛ‹Ì·Ù· Ô˘ Ô‰ËÁÔ‡Ó Û ·‡ÍËÛË ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ. ∏ ·ÚÔ˘Û›· ÚÒÈÌ˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘ Û ÚÒÙÔ˘ ‚·ıÌÔ‡ Û˘ÁÁÂÓ›˜ (ÁÔÓ›˜, ·È‰È¿ ‹ ·‰¤ÚÊÈ·) ‹ Î·È Û ·‰ÂÚÊÔ‡˜ ÙˆÓ ÁÔÓ¤ˆÓ ‰ËÌÈÔ˘ÚÁ› ÙËÓ ˘Ô„›· ›Ù ÔÈÎÔÁÂÓÔ‡˜ ÌÂÈÎÙ‹˜ ˘ÂÚÏÈȉ·ÈÌ›·˜ ›ÙÂ Û˘ÁÁÂÓÔ‡˜ ˘Ô·ÏÊ·ÏÈÔÚˆÙÂ˚Ó·ÈÌ›·˜ Î·È ·ÔÙÂÏ› ¤Ó‰ÂÈÍË ÁÈ· ÙË ¯ÔÚ‹ÁËÛË ıÂÚ·›·˜. ∏ ÂÌÊ¿ÓÈÛË Í·ÓıˆÌ¿ÙˆÓ Û ·ÛıÂÓ›˜ Ì ‹È· ‹ ̤ÙÚÈÔ˘ ‚·ıÌÔ‡ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· ‰ÂÓ Â›Ó·È Û˘ÓËıÈṲ̂ÓË. ™Â ·ÛıÂÓ›˜

6

¶›Ó·Î·˜ 2: ™¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ÂÌÊÚ¿ÁÌ·ÙÔ˜ ÙÔ˘ Ì˘Ôηډ›Ô˘, ÈÛ¯·ÈÌÈ΋˜ ηډȷ΋˜ ÓfiÛÔ˘ Î·È ı·Ó¿ÙÔ˘ Û ۯ¤ÛË Ì ٷ Â›‰· ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Û Á˘Ó·›Î˜ ∂›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ (mg/dl)

∞ÚÈıÌfi˜ ·ÛıÂÓÒÓ

∞ÚÈıÌfi˜ Û˘Ì‚·Ì¿ÙˆÓ

™¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜

P

ŒÌÊÚ·ÁÌ· ÙÔ˘ Ì˘Ôηډ›Ô˘ <88.5 88.5-176.1 177.0-264.6 265.5-353.0 354.0-441.6 ≥442.5 <88.5 88.5-176.1 177.0-264.6 265.5-353.0 354.0-441.6 ≥442.5 <88.5 88.5-176.1 177.0-264.6 265.5-353.0 354.0-441.6 ≥442.5

2194 109 3948 382 969 141 237 30 96 14 60 15 πÛ¯·ÈÌÈ΋ ηډȷ΋ ÓfiÛÔ˜ 2193 290 3947 878 967 289 237 66 96 23 60 21 £¿Ó·ÙÔ˜ 2210 754 3992 2076 986 623 241 164 96 64 62 50

1 1.7 2.5 2.1 2.4 5.4

<0.001

1 1.4 1.8 1.8 1.2 2.6

<0.001

1 1.3 1.6 2.2 1.9 3.3

<0.001

¶›Ó·Î·˜ 3: ™¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ÂÌÊÚ¿ÁÌ·ÙÔ˜ ÙÔ˘ Ì˘Ôηډ›Ô˘, ÈÛ¯·ÈÌÈ΋˜ ηډȷ΋˜ ÓfiÛÔ˘ Î·È ı·Ó¿ÙÔ˘ Û ۯ¤ÛË Ì ٷ Â›‰· ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Û ¿Ó‰Ú˜ ∂›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ (mg/dl)

∞ÚÈıÌfi˜ ·ÛıÂÓÒÓ

∞ÚÈıÌfi˜ Û˘Ì‚·Ì¿ÙˆÓ

™¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜

P

ŒÌÊÚ·ÁÌ· ÙÔ˘ Ì˘Ôηډ›Ô˘ <88.5 88.5-176.1 177.0-264.6 265.5-353.0 354.0-441.6 ≥442.5 <88.5 88.5-176.1 177.0-264.6 265.5-353.0 354.0-441.6 ≥442.5 <88.5 88.5-176.1 177.0-264.6 265.5-353.0 354.0-441.6 ≥442.5

882 104 2938 477 1366 270 530 133 229 54 250 64 πÛ¯·ÈÌÈ΋ ηډȷ΋ ÓfiÛÔ˜ 882 214 2935 853 1364 469 530 198 229 80 250 98 906 3026 1415 549 239 259

£¿Ó·ÙÔ˜ 470 1920 959 386 176 176

1 1.4 1.6 2.3 1.9 2.4 1 1.1 1.3 1.3 1.2 1.5 1 1.2 1.4 1.5 1.6 1.8

<0.001

<0.001

<0.001

¶∞ƒ∞°√¡Δ∂™ ∫π¡¢À¡√À Î·È ÚÒÈÌË ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ. ¶Ú¤ÂÈ ˆÛÙfiÛÔ Ó· ·Ó·ÊÂÚı› fiÙÈ Û ÌÈ· ÚfiÛÊ·ÙË ÌÂϤÙË ·Ú·ÙËÚ‹ıËΠıÂÙÈ΋ Û˘Û¯¤ÙÈÛË ÌÂٷ͇ ÙˆÓ ÌÂÙ·ÁÂ˘Ì·ÙÈÎÒÓ ÂÈ¤‰ˆÓ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Î·È Ù˘ ÂÌÊ¿ÓÈÛ˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘. ™ÙË Û˘ÁÎÂÎÚÈ̤ÓË ÌÂϤÙË, ÛÙËÓ ÔÔ›· Û˘ÌÌÂÙ›¯·Ó 7587 Á˘Ó·›Î˜ Î·È 6394 ¿Ó‰Ú˜, ÂÎÙÈÌ‹ıËÎÂ Ô Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜ ÂÌÊ¿ÓÈÛ˘ ÂÌÊÚ¿ÁÌ·ÙÔ˜ ÙÔ˘ Ì˘Ôηډ›Ô˘, ÈÛ¯·ÈÌÈ΋˜ ηډȷ΋˜ ÓfiÛÔ˘ Î·È ı·Ó¿ÙÔ˘ Û ۯ¤ÛË Ì ٷ Â›‰· ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ (¶›Ó·Î˜ 2 Î·È 3).12

Ì ·˘ÍË̤ӷ Â›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Ú¤ÂÈ Ó· ÌÂÙÚ¿Ù·È Ë ÂÚ›ÌÂÙÚÔ˜ ̤Û˘ Î·È Ó· ˘ÔÏÔÁ›˙ÂÙ·È Ô ‰Â›ÎÙ˘ Ì¿˙·˜ ÛÒÌ·ÙÔ˜. √ Û˘Ó‰˘·ÛÌfi˜ Ù˘ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜ Ì ·˘ÍË̤ÓË ÂÚ›ÌÂÙÚÔ Ì¤Û˘11 Ê·›ÓÂÙ·È fiÙÈ ·ÔÙÂÏ› ηχÙÂÚÔ ‰Â›ÎÙË Ù˘ ·ÓÙ›ÛÙ·Û˘ ÛÙË ‰Ú¿ÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘ Î·È ÈÛ¯˘ÚfiÙÂÚÔ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ÚÒÈÌ˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘ Û ۇÁÎÚÈÛË Ì ÙËÓ ·ÚÔ˘Û›· ÌÂÌÔӈ̤Ó˘ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜. ∏ ·ÚÔ˘Û›· ·˘ÍË̤Ó˘ ÂÚÈ̤ÙÚÔ˘ ̤Û˘ (¿Óˆ ·fi 102 cm ÁÈ· ÙÔ˘˜ ¿Ó‰Ú˜ Î·È ¿Óˆ ·fi 88 cm ÁÈ· ÙȘ Á˘Ó·›Î˜) ÌÔÚ› Ó· ‚ÔËı‹ÛÂÈ ÛÙË ‰È¿ÎÚÈÛË ÌÂٷ͇ Ù˘ ÔÈÎÔÁÂÓÔ‡˜ ÌÂÈÎÙ‹˜ ˘ÂÚÏÈȉ·ÈÌ›·˜ ‹ Ù˘ ÔÈÎÔÁÂÓÔ‡˜ ˘Ô·ÏÊ·ÏÈÔÚˆÙÂ˚Ó·ÈÌ›·˜ Î·È Ù˘ ÔÈÎÔÁÂÓÔ‡˜ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜, Ë ÔÔ›· ‰ÂÓ Û˘Û¯ÂÙ›˙ÂÙ·È Ì ÎÔÈÏȷ΋ ·¯˘Û·ÚΛ· Î·È Èı·Ó¿ Ì ·˘ÍË̤ÓÔ Î·Ú‰È·ÁÁÂÈ·Îfi ΛӉ˘ÓÔ.

øÛÙfiÛÔ, ‰ÂÓ Û˘ÓÈÛÙ¿Ù·È ÛÙËÓ ÎÏÈÓÈ΋ Ú¿ÍË Ë Ì¤ÙÚËÛË Î·È ÂÎÙ›ÌËÛË ÙˆÓ ÌÂÙ·ÁÂ˘Ì·ÙÈÎÒÓ ÂÈ¤‰ˆÓ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ, ηıÒ˜ ‰ÂÓ ˘¿Ú¯Ô˘Ó ·ÎfiÌË Â·Ú΋ ‰Â‰Ô̤ӷ fiÛÔÓ ·ÊÔÚ¿ ÙȘ Ê˘ÛÈÔÏÔÁÈΤ˜ ÙÈ̤˜ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÌÂÙ¿ Ù· Á‡̷ٷ, ·ÏÏ¿ Î·È ÂÍ·ÈÙ›·˜ Ù˘ ÔÈÎÈÏ›·˜ ÙˆÓ ÌÂÙ·ÁÂ˘Ì·ÙÈÎÒÓ ÙÈÌÒÓ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ, Ô˘ ηٿ ηÓfiÓ· Û˘Û¯ÂÙ›˙ÔÓÙ·È Ì ÙȘ ÙÈ̤˜ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÓËÛÙ›·˜.

™˘Ó‹ıˆ˜, Â›Ó·È ·ÚÎÂÙfi ¤Ó· Ï‹Ú˜ ÏÈȉ·ÈÌÈÎfi ÚÔÊ›Ï ÓËÛÙ›·˜ ÁÈ· ÙËÓ ÂÎÙ›ÌËÛË ·ÛıÂÓÒÓ Ì ·˘ÍË̤ӷ Â›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ

√È ·ÛıÂÓ›˜ Ì ÔÈÎÔÁÂÓ‹ ÌÂÈÎÙ‹

˘ÂÚÏÈȉ·ÈÌ›· ÌÔÚ› Ó· ¤¯Ô˘Ó ·˘ÍË̤ӷ ‹ Ê˘ÛÈÔÏÔÁÈο Â›‰· LDL ¯ÔÏËÛÙÂÚfiÏ˘. Δ· Â›‰· Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘ Â›Ó·È ÌÂȈ̤ӷ ÙfiÛÔ ÛÙËÓ ÔÈÎÔÁÂÓ‹ Û˘Ó‰˘·Ṳ̂ÓË ˘ÂÚÏÈȉ·ÈÌ›· fiÛÔ Î·È ÛÙË Û˘ÁÁÂÓ‹ ˘Ô·ÏÊ·ÏÈÔÚˆÙÂ˚Ó·ÈÌ›·. ∂ÈÚfiÛıÂÙ· Ë ·ÚÔ˘Û›· ·˘ÍËÌ¤ÓˆÓ Û˘ÁÎÂÓÙÚÒÛÂˆÓ ÌÈÎÚÒÓ, ˘ÎÓÒÓ LDL ۈ̷Ùȉ›ˆÓ ÙfiÛÔ Û ·ÛıÂÓ›˜ Ì ÔÈÎÔÁÂÓ‹ ÌÂÈÎÙ‹ ˘ÂÚÏÈȉ·ÈÌ›· fiÛÔ Î·È Û ·ÛıÂÓ›˜ Ì ÔÈÎÔÁÂÓ‹ ˘Ô·ÏÊ·ÏÈÔÚˆÙÂ˚Ó·ÈÌ›· ¤¯ÂÈ Û˘Û¯ÂÙÈÛı› Ì ÙËÓ ÂÌÊ¿ÓÈÛË ÚÒÈÌ˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘.13 ™Â ·ÛıÂÓ›˜ Ì ·˘ÍË̤ӷ Â›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Î·È ÂχıÂÚÔ ·ÙÔÌÈÎfi Î·È ÎÏËÚÔÓÔÌÈÎfi ÈÛÙÔÚÈÎfi, Ë Ì¤ÙÚËÛË Ù˘ ·ÔÏÈÔÚˆÙ½Ó˘ μ (ApoB) ÌÔÚ› Ó· ‚ÔËı‹ÛÂÈ ÛÙË ‰È¿ÎÚÈÛË ÌÂٷ͇ Ù˘ ÔÈÎÔÁÂÓÔ‡˜ ÌÂÈÎÙ‹˜ ˘ÂÚÏÈȉ·ÈÌ›·˜ Î·È Ù˘ ÔÈÎÔÁÂÓÔ‡˜ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜. ¶Ú¿ÁÌ·ÙÈ, Ù· Â›‰· Ù˘ ApoB Â›Ó·È ·˘ÍË̤ӷ (> 90Ë ı¤ÛË ÁÈ· ÙËÓ ËÏÈΛ· Î·È ÙÔ Ê‡ÏÔ) Û ·ÛıÂÓ›˜ Ì ÔÈÎÔÁÂÓ‹ ÌÂÈÎÙ‹ ˘ÂÚÏÈȉ·ÈÌ›· Î·È fi¯È Û ·ÛıÂÓ›˜ Ì ÔÈÎÔÁÂ-

∂›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ 250-1000 mg/dl ¯ˆÚ›˜ ·˘ÍË̤ӷ Â›‰· LDL ¯ÔÏËÛÙÂÚfiÏ˘

∞ÔÎÏÂÈÛÌfi˜ ‰Â˘ÙÂÚÔ·ıÔ‡˜ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜

ªÂ ÚÒÈÌË ™¡;

Ÿ¯È

¡·È

∫ÏËÚÔÓÔÌÈÎfi ÈÛÙÔÚÈÎfi ÚÒÈÌ˘ ™¡; ∞ÚÓËÙÈÎfi

£ÂÙÈÎfi

ÕÁÓˆÛÙÔ

√ÈÎÔÁÂÓ‹˜ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· ¡·È

∞˘ÍË̤ÓË Apoμ;

ªÂȈ̤ÓË ApoAI; Ÿ¯È

¡·È

¡·È √ÈÎÔÁÂÓ‹˜ ÀÔ·ÏÊ·ÏÈÔÚˆÙÂ˚Ó·ÈÌ›·;

ªfiÓÔ ·ÏÏ·Á‹ ÙÚfiÔ˘ ˙ˆ‹˜

∞ÏÏ·Á‹ ÙÚfiÔ˘ ˙ˆ‹˜ Èı·Ó¿ Ê·Ú̷΢ÙÈ΋ ·ÁˆÁ‹

¡·È

Ÿ¯È

√ÈÎÔÁÂÓ‹˜ ÌÂÈÎÙ‹ ˘ÂÚÏÈȉ·ÈÌ›·;

¡·È ¡·È

¶Èı·Ó¿ ÔÈÎÔÁÂÓ‹˜ ÌÂÈÎÙ‹ ˘ÂÚÏÈȉ·ÈÌ›· ‹ ÔÈÎÔÁÂÓ‹˜ ˘Ô·ÏÊ·ÏÈÔÚˆÙÂ˚Ó·ÈÌ›·

∞ÏÏ·Á‹ ÙÚfiÔ˘ ˙ˆ‹˜ Èı·Ó¿ Ê·Ú̷΢ÙÈ΋ ·ÁˆÁ‹

∞ÏÏ·Á‹ ÙÚfiÔ˘ ˙ˆ‹˜ Î·È Û˘Ó‰˘·Ṳ̂ÓË ˘ÔÏÈȉ·ÈÌÈ΋ ·ÁˆÁ‹

¶›Ó·Î·˜ 4: ∞ÏÁfiÚÈıÌÔ˜ ÁÈ· ÙË ‰È·ÁÓˆÛÙÈ΋ ÚÔÛ¤ÁÁÈÛË Î·È ·ÓÙÈÌÂÙÒÈÛË ·ÛıÂÓÒÓ Ì ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· (Â›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ 250-1000 mg/dl)

7

™∂¶Δ∂ªμƒπ√™ 2008

Ó‹ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·.14 ∫·È ÛÙȘ ‰‡Ô ‰È·Ù·Ú·¯¤˜ Ù· Â›‰· Ù˘ ApoB ÌÔÚÔ‡Ó Ó· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó ÁÈ· ÙÔÓ ˘ÔÏÔÁÈÛÌfi ÙÔ˘ Û˘ÓÔÏÈÎÔ‡ ·ÚÈıÌÔ‡ ÙˆÓ LDL ۈ̷Ùȉ›ˆÓ. ™‡Ìʈӷ Ì ÙȘ Ô‰ËÁ›Â˜ ÙÔ˘ NCEP (National Cholesterol Education Program) Û˘ÓÈÛÙ¿Ù·È Ë Ì¤ÙÚËÛË Ù˘ nonHDL ¯ÔÏËÛÙÂÚfiÏ˘ (non-HDL ¯ÔÏËÛÙÂÚfiÏË = TCHOL HDL ¯ÔÏËÛÙÂÚfiÏË) ·ÓÙ› ÁÈ· ÙË Ì¤ÙÚËÛË Ù˘ ApoB. ¶·ÚfiÙÈ Ë nonHDL ¯ÔÏËÛÙÂÚfiÏË ·ÔÙÂÏ› ηχÙÂÚÔ ÚÔÁÓˆÛÙÈÎfi ·Ú¿ÁÔÓÙ· ηډȷÁÁÂÈ·ÎÔ‡ ÎÈÓ‰‡ÓÔ˘ Û ۇÁÎÚÈÛË Ì ÙËÓ LDL ¯ÔÏËÛÙÂÚfiÏË,15 ·ÚÎÂÙ¤˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ Ë ApoB Â›Ó·È Î·Ï‡ÙÂÚÔ˜ ÚÔÁÓˆÛÙÈÎfi˜ ‰Â›ÎÙ˘ Û ۇÁÎÚÈÛË Ì ÙËÓ non-HDL ¯ÔÏËÛÙÂÚfiÏË.8 16 ¶Ú¤ÂÈ Ó· ·Ó·ÊÂÚı›, fiÙÈ ÙfiÛÔ Ë Ì¤ÙÚËÛË Ù˘ Û˘ÁΤÓÙÚˆÛ˘ Ù˘ ApoAI fiÛÔ Î·È Ë Ì¤ÙÚËÛË Ù˘ Û˘ÁΤÓÙÚˆÛ˘ ÙˆÓ ÌÈÎÚÒÓ ˘ÎÓÒÓ LDL ۈ̷Ùȉ›ˆÓ ‰ÂÓ ·ÔÙÂÏÔ‡Ó ÂÍÂÙ¿ÛÂȘ ÚÔ˘Ù›Ó·˜ ÛÙËÓ ÎÏÈÓÈ΋ Ú¿ÍË, ·Ó Î·È ˘¿Ú¯Ô˘Ó ‰Â‰Ô̤ӷ fiÙÈ Ô ÏfiÁÔ˜ ApoB/ ApoAI Â›Ó·È ¤Ó·˜ Ôχ ηÏfi˜ ÚÔÁÓˆÛÙÈÎfi˜ ‰Â›ÎÙ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ÚÒÈÌ˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘.17 ∞Ó Î·È Ë Ì¤ÙÚËÛË Ù˘ Lp(a) ‰ÂÓ ÌÔÚ› Ó· ‚ÔËı‹ÛÂÈ ÛÙË ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ÙˆÓ ‰È¿ÊÔÚˆÓ ÌÔÚÊÒÓ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜, ÌÔÚ› ˆÛÙfiÛÔ, ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙÔ˘˜ ¿ÏÏÔ˘˜ ·Ú¿ÁÔÓÙ˜ ηډȷÁÁÂÈ·ÎÔ‡ ÎÈÓ‰‡ÓÔ˘, Ó· Â›Ó·È ¯Ú‹ÛÈÌË ÁÈ· ÙÔÓ ÚÔÛ‰ÈÔÚÈÛÌfi ÙÔ˘ Û˘ÓÔÏÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘ ÂÌÊ¿ÓÈÛ˘ ·ıËڈ̷ÙÈ΋˜ ÓfiÛÔ˘.18 øÛÙfiÛÔ, Ë Ì¤ÙÚËÛË Ù˘ Lp(a) ‰ÂÓ ·ÔÙÂÏ› ÂͤٷÛË ÚÔ˘Ù›Ó·˜ ÛÙËÓ ÎÏÈÓÈ΋ Ú¿ÍË.

∞ÓÙÈÌÂÙÒÈÛË ·ÛıÂÓ‹ Ì ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· ªÂÙ¿ ÙÔÓ ·ÔÎÏÂÈÛÌfi Ù˘ ‰Â˘ÙÂÚÔ·ıÔ‡˜ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜, ·ÏÏ¿ Î·È ÙË ‰È·ÎÔ‹ ÙˆÓ Ê·ÚÌ¿ÎˆÓ Ô˘ ÂӉ¯fiÌÂÓ· ·˘Í¿ÓÔ˘Ó Ù· Â›‰· ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ, Ë ·ÏÏ·Á‹ ÙÔ˘ ÙÚfiÔ˘ ˙ˆ‹˜ Î·È ÂӉ¯fiÌÂÓ· Ë ÚÔÛı‹ÎË Ê·Ú̷΢ÙÈ΋˜ ·ÁˆÁ‹˜ ·ÔÙÂÏÔ‡Ó ÙȘ ηٿÏÏËϘ ıÂÚ·¢ÙÈΤ˜ ÂÈÏÔÁ¤˜ Û ·ÛıÂÓ›˜ Ì ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· Ô˘ ÂÌÊ·Ó›˙Ô˘Ó ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ÚÒÈÌ˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘ (¶›Ó·Î·˜ 4). ΔÔ ÂÚÒÙËÌ· Ô˘ ÚÔ·ÙÂÈ Â›Ó·È ·Ó Ë ıÂÚ·›·

8

Ú¤ÂÈ Ó· ·ÊÔÚ¿ ÌfiÓÔ ÛÙË Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ‹ ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ÏÈȉ·ÈÌÈÎÒÓ ‰È·Ù·Ú·¯ÒÓ Ô˘ Û˘Ó˘¿Ú¯Ô˘Ó (·˘ÍË̤ÓË LDL Î·È IDL ¯ÔÏËÛÙÂÚfiÏË Î·È ÌÂȈ̤ÓË HDL ¯ÔÏËÛÙÂÚfiÏË).6 11 19 ¶Ú¤ÂÈ Ó· ·Ó·ÊÂÚı› fiÙÈ Â›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÌÂÁ·Ï‡ÙÂÚ· ·fi 1000 mg/dl ··ÈÙÔ‡Ó ¿ÌÂÛË ıÂÚ·›· Ì ÊÈÌÚ¿Ù˜, Ì ÛÎÔfi ÙË Ì›ˆÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ·ÁÎÚ·ٛÙȉ·˜.20 ∞ÏÏ·Á‹ ÙÔ˘ ÙÚfiÔ˘ ˙ˆ‹˜ ∏ ·ÒÏÂÈ· ‚¿ÚÔ˘˜ Ô‰ËÁ› Û ̛· ‹È· ¤ˆ˜ ̤ÙÚÈ· Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ (ÂÚ›Ô˘ ηٿ 22%) Î·È Û ̛· ·‡ÍËÛË Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘ ηٿ 9% (΢ڛˆ˜ ÂÍ·ÈÙ›·˜ Ù˘ ·‡ÍËÛ˘ Ù˘ HDL2 ηٿ 43%). Δ· Â›‰· ÙˆÓ ÌÈÎÚÒÓ, ˘ÎÓÒÓ LDL ۈ̷Ùȉ›ˆÓ ÌÔÚ› Â›Û˘ Ó· ÌÂȈıÔ‡Ó ¤ˆ˜ Î·È 40% (¶›Ó·Î·˜ 5).21 ¶Ú¤ÂÈ Ó· ÂÈÛËÌ·Óı› fiÙÈ ·ÎfiÌ· Î·È Ë ÌÂÙÚ›Ô˘ ‚·ıÌÔ‡ ·ÒÏÂÈ· ‚¿ÚÔ˘˜ Ô‰ËÁ› Û Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ. ∏ ‰È·Ù‹ÚËÛË ·˘Ù‹˜ Ù˘ ·ÒÏÂÈ·˜ ‚¿ÚÔ˘˜ ÌÔÚ› Ó· ÂÈÙ¢¯ı› Ì ·ÂÚÔ‚È΋ ¿ÛÎËÛË.22-24 ∏ ·ÂÚÔ‚È΋ ¿ÛÎËÛË Ì¤ÙÚÈ·˜ ¤ÓÙ·Û˘ Î·È ·˘ÍË̤Ó˘ Û˘¯ÓfiÙËÙ·˜ (ÂÚ›Ô˘ 4 ÒÚ˜ ÙËÓ Â‚‰ÔÌ¿‰·) ¤¯ÂÈ Û˘Û¯ÂÙÈÛı› Ì ÙË ‚ÂÏÙ›ˆÛË Ù˘ ηډÈÔ·Ó·Ó¢ÛÙÈ΋˜ ÈηÓfiÙËÙ·˜.25 26 ∏ ۈ̷ÙÈ΋ ¿ÛÎËÛË ¤¯ÂÈ Â›Û˘ Û˘Û¯ÂÙÈÛı› Ì ÙË Ì›ˆÛË ÙÔ˘ ÂÓ‰ÔÎÔÈÏÈ·ÎÔ‡ Ï›Ô˘˜, Ì ÙËÓ ·‡ÍËÛË ÙˆÓ ÂÈ¤‰ˆÓ Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘ Î·È Ì ̛· ÌÈÎÚ‹ Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ.27 28

∂ÓÒ Ë Ì›ˆÛË ÙÔ˘ ‰È·ÈÙËÙÈÎÔ‡ Ï›Ô˘˜ Ô‰ËÁ› Û ·ÒÏÂÈ· ‚¿ÚÔ˘˜ (Ì Â·ÎfiÏÔ˘ıÔ ÙË Ì›ˆÛË ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ), Ë Ùˆ¯‹ Û ϛÔ˜ ‰›·ÈÙ· Ô˘ Â›Ó·È ÏÔ‡ÛÈ· Û ˘‰·Ù¿ÓıڷΘ ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û ·Ú¿ÏÏËÏË Ì›ˆÛË ÙfiÛÔ Ù˘ LDL fiÛÔ Î·È Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘.23 ŸÙ·Ó Ù· ÎÔÚÂṲ̂ӷ Ï›Ë ·ÓÙÈηı›ÛÙ·ÓÙ·È ·fi ÌÔÓÔ·ÎfiÚÂÛÙ· Ï›Ë (ÂÏ·ÈfiÏ·‰Ô), Ë Ì›ˆÛË Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘ Â›Ó·È ÌÈÎÚfiÙÂÚË ·fi ÙË Ì›ˆÛË Ô˘ ·Ú·ÙËÚÂ›Ù·È Ì ÙËÓ ·ÓÙÈηٿÛÙ·ÛË ÙˆÓ ˙ˆÈÎÒÓ ÏÈÒÓ ·fi ˘‰·Ù¿ÓıڷΘ. ŒÙÛÈ, Û˘ÓÈÛÙ¿Ù·È Ë Ì›ˆÛË ÙˆÓ ÏÔ‡ÛÈˆÓ Û ˙ˆÈο Ï›Ë ÙÚÔÊÒÓ Î·È Ë ·ÓÙÈηٿÛÙ·Û‹ ÙÔ˘˜ ÌÂ Û˘Ó‰˘·ÛÌfi ÙÚÔÊÒÓ Ô˘ Â›Ó·È ÏÔ‡ÛȘ Û ˘‰·Ù¿ÓıڷΘ, ÌÔÓÔ·ÎfiÚÂÛÙ· Ï›Ë Î·È ÔÏ˘·ÎfiÚÂÛÙ· Ï›Ë.23 ∂ÈÚfiÛıÂÙ·, ÂӉ›ÎÓ˘Ù·È Ë ·ÔÊ˘Á‹ Ù˘ ˙¿¯·Ú˘ Î·È Î˘Ú›ˆ˜ Ù˘ ÊÚÔ˘ÎÙfi˙˘, Ë ÔÔ›· ¤¯ÂÈ Û˘Û¯ÂÙÈÛı› Ì ÛËÌ·ÓÙÈ΋ ÌÂÙ·ÁÂ˘Ì·ÙÈ΋ ·‡ÍËÛË ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ.29 ∏ ÊÚÔ˘ÎÙfi˙Ë ˘¿Ú¯ÂÈ Û ÔÏÏ¿ ·ÓıÚ·ÎÔ‡¯· ÔÙ¿, ηıÒ˜ Î·È Û ÊÚÔ˘ÙÔ¯˘ÌÔ‡˜ Î·È ÔÏϤ˜ ÊÔÚ¤˜ ÚÔÛÙ›ıÂÙ·È ÛÙȘ ÙÚÔʤ˜ ˆ˜ Û˘ÓÙËÚËÙÈÎfi Î·È ÁÏ˘Î·ÓÙÈÎfi. ∏ ÚÔÛı‹ÎË ÛÙË ‰›·ÈÙ· ˆ-3 ÏÈ·ÚÒÓ ÔͤˆÓ ÌÔÚ› Ó· ÌÂÈÒÛÂÈ Ù· Â›‰· ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Î·È Û‡Ìʈӷ Ì ÔÚÈṲ̂Ó˜ ÌÂϤÙ˜ Ó· ÌÂÈÒÛÂÈ Î·È Ù· ηډȷÁÁÂȷο Û˘Ì‚¿Ì·Ù·. ™˘ÁÎÂÎÚÈ̤ӷ, Û ̛· ÌÂϤÙË, ÛÙËÓ ÔÔ›· Û˘ÁÎÚ›ıËÎÂ Ë ¯ÔÚ‹ÁËÛË ˆ-3 ÏÈ·ÚÒÓ ÔͤˆÓ (1 gr ÙËÓ Ë̤ڷ Û 2836 ·ÛıÂÓ›˜), Ë ¯ÔÚ‹ÁËÛË ‚ÈÙ·Ì›Ó˘ ∂ (300 mg ÙËÓ Ë̤ڷ Û 2830 ·ÛıÂÓ›˜), Ë Ù·˘Ùfi¯ÚÔÓË ¯ÔÚ‹ÁËÛ‹ ÙÔ˘˜ (Û 2830 ·ÛıÂÓ›˜) Î·È Ë

¶›Ó·Î·˜ 5: μ¿ÚÔ˜ ÛÒÌ·ÙÔ˜ Î·È ÏÈȉ·ÈÌÈÎfi ÚÔÊ›Ï ÚÈÓ Î·È ÌÂÙ¿ ÙËÓ ·ÒÏÂÈ· ‚¿ÚÔ˘˜ ¶ÚÈÓ ÙËÓ ·ÒÏÂÈ· ‚¿ÚÔ˘˜ (±SD) μ¿ÚÔ˜ ÛÒÌ·ÙÔ˜ (kg) √ÏÈ΋ ¯ÔÏËÛÙÂÚfiÏË (mg/dl) ΔÚÈÁÏ˘ÎÂÚ›‰È· (mg/dl) VLDL-C (mg/dl)

ªÂÙ¿ ÙËÓ ·ÒÏÂÈ· ‚¿ÚÔ˘˜ (±SD)

p

96 (11)

86 (11)

<0.001

194 (25)

189 (21)

0.18

138 (51)

107 (37)

<0.001

27.6 (10.3)

21.3 (7.2)

<0.001

LDL-C (mg/dl)

130 (24)

128 (22)

0.49

HDL-C (mg/dl)

35.9 (7.2)

39.1 (8.9)

0.006

HDL2-C (mg/dl)

6.8 (4.2)

9.7 (5.3)

<0.001

ApoAI (mg/dl)

111 (15)

114 (16)

0.18

ApoB (mg/dl)

108 (18)

100 (18)

0.004

SD:ÛÙ·ıÂÚ‹ ·fiÎÏÈÛË ΔÚÔÔÔ›ËÛË ·fi: J Clin Endocrinol Metab 2000;346:393-403

¶∞ƒ∞°√¡Δ∂™ ∫π¡¢À¡√À ¶›Ó·Î·˜ 6: º·Ú̷΢ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜ ∫·ÙËÁÔÚ›· Ê·ÚÌ¿ÎÔ˘

ªÂ›ˆÛË ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ (%)

∞ÓÙÂӉ›ÍÂȘ

¶·ÚÂÓ¤ÚÁÂȘ

ªÂ›ˆÛË ÙˆÓ ÌÈÎÚÒÓ, ˘ÎÓÒÓ LDL ۈ̷Ùȉ›ˆÓ

∞‡ÍËÛË Ù˘ HDL2 ¯ÔÏËÛÙÂÚfiÏ˘

¡ÈÎÔÙÈÓÈÎfi Ô͇ (1500-2000 mg/ËÌÂÚ.)

17-26%

ÀÂÚ¢·ÈÛıËÛ›·, Ë·ÙÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·

ŒÍ·„Ë, ÎÓËÛÌfi˜, Ó·˘Ù›·, Ë·Ù›Ùȉ·, ÂÓÂÚÁÔÔ›ËÛË ËÌÈÎÚ·Ó›·˜

¡·È

¡·È

ºÈÌÚ¿Ù˜ (ÁÂÌÊÈÌÚÔ˙›ÏË 600 mgà 2 /ËÌÂÚ., Ê·ÈÓÔÊÈÌÚ¿ÙË 145 mg/ËÌÂÚ.)

18-45%

ÀÂÚ¢·ÈÛıËÛ›·, Ë·ÙÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·, ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘ ÓÂÊÚÈ΋ ·ÓÂ¿ÚÎÂÈ·

ª˘ÔÛ›Ùȉ·, ¯ÔÏÔÏÈı›·ÛË

¡·È

Ÿ¯È

™Ù·Ù›Ó˜

5%

ÀÂÚ¢·ÈÛıËÛ›·, ÂÁ΢ÌÔÛ‡ÓË, ıËÏ·ÛÌfi˜

ª˘·ÏÁ›·, Ú·‚‰ÔÌ˘fiÏ˘ÛË, ·‰˘Ó·Ì›·

Ÿ¯È

Ÿ¯È

¡ÈÎÔÙÈÓÈÎfi Ô͇ + ÛÙ·Ù›ÓË

36%

ÿ‰È˜ Ì ٷ ·ÓÙ›ÛÙÔȯ· Ê¿Ú̷η

ÿ‰È˜ Ì ٷ ·ÓÙ›ÛÙÔȯ· Ê¿Ú̷η

¡·È

¡·È

ÌË ¯ÔÚ‹ÁËÛË ˆ-3 ÏÈ·ÚÒÓ ÔͤˆÓ ‹ ‚ÈÙ·Ì›Ó˘ ∂ (ÔÌ¿‰· ÂϤÁ¯Ô˘: 2828 ·ÛıÂÓ›˜) Û 11324 ÌÂÙÂÌÊÚ·ÁÌ·ÙÈÎÔ‡˜ ·ÛıÂÓ›˜ ·Ú·ÙËÚ‹ıËΠ̛ˆÛË ÙÔ˘ Û¯ÂÙÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË Ó¤Ô˘ ÂÌÊÚ¿ÁÌ·ÙÔ˜ ÙÔ˘ Ì˘Ôηډ›Ô˘, ·ÁÁÂÈ·ÎÔ‡ ÂÁÎÂÊ·ÏÈÎÔ‡ ÂÂÈÛÔ‰›Ô˘ Î·È ı·Ó¿ÙÔ˘ ηٿ 15% (95 % ‰È¿ÛÙËÌ· ÂÌÈÛÙÔÛ‡Ó˘ 2-26%) ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ¤·ÈÚÓ·Ó ˆ-3 ÏÈ·Ú¿ Ôͤ·.30 ∞ÓÙ›ıÂÙ· Û ÌÈ· ÌÂÙ··Ó¿Ï˘ÛË 48 Ù˘¯·ÈÔÔÈËÌ¤ÓˆÓ ÎÏÈÓÈÎÒÓ ÌÂÏÂÙÒÓ ‰ÂÓ ˘‹Ú¯Â ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ Û˘Ì‚·Ì¿ÙˆÓ [Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜: 0.87 (95% ‰È¿ÛÙËÌ· ÂÌÈÛÙÔÛ‡Ó˘: 0.73-1.03)] ‹ Ù˘ ıÓËÙfiÙËÙ·˜ [Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜: 0.95 (95% ‰È¿ÛÙËÌ· ÂÌÈÛÙÔÛ‡Ó˘: 0.82-1.12)] Û ·ÛıÂÓ›˜ Ô˘ ¤·ÈÚÓ·Ó ˆ-3 ÏÈ·Ú¿ Ôͤ· ›Ù ÛÙË ‰›·ÈÙ¿ ÙÔ˘˜ ›Ù ˆ˜ Û΢¿ÛÌ·Ù·.31 ΔÔ Î¿ÓÈÛÌ· Û˘Û¯ÂÙ›˙ÂÙ·È Ì ̛· ηٿ 10 ¯ÚfiÓÈ· ÁÚËÁÔÚfiÙÂÚË ÂÌÊ¿ÓÈÛË ÚÒÈÌ˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘. ∏ ‰È·ÎÔ‹ ÙÔ˘ ηÓ›ÛÌ·ÙÔ˜ ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙË ‚ÂÏÙ›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ ÏÈȉ›ˆÓ, ·Ú¿ ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Û ¿ÙÔÌ· Ô˘ ‰È·ÎfiÙÔ˘Ó ÙÔ Î¿ÓÈÛÌ· ·Ú·ÙËÚÂ›Ù·È ·‡ÍËÛË ÙÔ˘ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜. ∏ ηٷӿψÛË ·ÏÎÔÔÏÔ‡¯ˆÓ ÔÙÒÓ ÌÔÏÔÓfiÙÈ Û˘Û¯ÂÙ›˙ÂÙ·È Ì ÌÂȈ̤ÓÔ Î›Ó‰˘ÓÔ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ·ıËÚÔÛÎÏËÚˆÙÈ΋˜ ηډȷÁÁÂȷ΋˜ ÓfiÛÔ˘ ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û ·‡ÍËÛË Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘ Ì ΛӉ˘ÓÔ ÙËÓ ÂÌÊ¿ÓÈÛË ÂÓfi˜ ·ÈÌÔÚÚ·ÁÈÎÔ‡ ÂÁÎÂÊ·ÏÈÎÔ‡ ÂÂÈÛÔ‰›Ô˘. ∏ ̤ÙÚÈ·

Ï‹„Ë ·ÏÎÔfiÏ (2 ÔÙ¿ ÙËÓ Ë̤ڷ ÁÈ· ÙÔ˘˜ ¿ÓÙÚ˜ Î·È 1 ÔÙfi ÙËÓ Ë̤ڷ ÁÈ· ÙȘ Á˘Ó·›Î˜) ıˆÚÂ›Ù·È ·Ô‰ÂÎÙ‹ Û ¿ÙÔÌ· Ô˘ ‰ÂÓ ¤¯Ô˘Ó ÚԉȿıÂÛË ÛÙËÓ Î·Ù¿¯ÚËÛË ·ÏÎÔÔÏÔ‡¯ˆÓ ÔÙÒÓ. ∞·ÈÙÂ›Ù·È Ë ¿ÌÂÛË ‰È·ÎÔ‹ Ù˘ ηٷӿψÛ˘ ·ÏÎÔÔÏÔ‡¯ˆÓ ÔÙÒÓ Û ·ÛıÂÓ›˜ Ì ˘„ËÏ¿ Â›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ.32 33 øÛÙfiÛÔ Û ·ÛıÂÓ›˜ Ì Â›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ < 500 mg/dl ‰ÂÓ Ú¤ÂÈ Ó· ·ÔÎÏÂÈÛı› Ë Ì¤ÙÚÈ· ηٷӿψÛË ·ÏÎÔÔÏÔ‡¯ˆÓ ÔÙÒÓ.34 º·Ú̷΢ÙÈ΋ ·ÁˆÁ‹ ™Â ·ÛıÂÓ›˜ Ì ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· Ô˘ ¤¯Ô˘Ó ·ÙÔÌÈÎfi ‹ ÎÏËÚÔÓÔÌÈÎfi ÈÛÙÔÚÈÎfi ÚÒÈÌ˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘ Èı·Ó¿ ··ÈÙÂ›Ù·È Ë ¯ÔÚ‹ÁËÛË Ê·Ú̷΢ÙÈ΋˜ ·ÁˆÁ‹˜. ¶Ú¤ÂÈ Û ·˘Ù¤˜ ÙȘ ÂÚÈÙÒÛÂȘ Ó· ÚÔÙÈÌÒÓÙ·È Ê¿Ú̷η Ô˘ ÌÂÈÒÓÔ˘Ó Ù· Â›‰· ÙˆÓ ÌÈÎÚÒÓ ˘ÎÓÒÓ LDL ۈ̷Ùȉ›ˆÓ Î·È ·˘Í¿ÓÔ˘Ó Ù· Â›‰· Ù˘ HDL2 ¯ÔÏËÛÙÂÚfiÏ˘ (¶›Ó·Î·˜ 6). ™ÙÔ˘˜ ·ÛıÂÓ›˜ Ì ÚÒÈÌË ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ ‹ ÛÙ· ¿ÙÔÌ· ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ÚÒÈÌ˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘, ÔÈ ÛÙ·Ù›Ó˜ ·ÔÙÂÏÔ‡Ó ÙÔ Ê¿ÚÌ·ÎÔ ÚÒÙ˘ ÂÈÏÔÁ‹˜ ÁÈ· ÙË Ì›ˆÛË Ù˘ LDL ¯ÔÏËÛÙÂÚfiÏ˘.35 ∂Ó·ÏÏ·ÎÙÈο, ÚÔÙ›ÓÂÙ·È Ô Û˘Ó‰˘·ÛÌfi˜ ÛÙ·Ù›Ó˘ Ì ÓÈÎÔÙÈÓÈÎfi Ô͇. ΔÔ ÓÈÎÔÙÈÓÈÎfi Ô͇ ÌÂÈÒÓÂÈ Ù· Â›‰· ÙˆÓ ÌÈÎÚÒÓ ˘ÎÓÒÓ LDL ۈ̷Ùȉ›ˆÓ ηÈ

·˘Í¿ÓÂÈ Ù· Â›‰· Ù˘ HDL2 ¯ÔÏËÛÙÂÚfiÏ˘. ™Â Ì›· ÌÂϤÙË (Coronary Drug Project), Ë ıÂÚ·›· Ì ÓÈÎÔÙÈÓÈÎfi Ô͇ Û ¿Ó‰Ú˜ ·ÛıÂÓ›˜ Ì ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌ›· Î·È ÂÁηÙÂÛÙË̤ÓË ·ıËڈ̷ÙÈ΋ ÓfiÛÔ Ô‰‹ÁËÛ Û ̛· ηٿ 15% Ì›ˆÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÂÌÊ¿ÓÈÛ˘ ÂÌÊÚ¿ÁÌ·ÙÔ˜ ÙÔ˘ Ì˘Ôηډ›Ô˘36 Î·È Ì›ˆÛ ηٿ 10% ÙËÓ ÔÏÈ΋ ıÓËÙfiÙËÙ· Û 15 ¯ÚfiÓÈ·.37 ™ÙË ÌÂϤÙË ARBITER 2 (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol) Ë ÚÔÛı‹ÎË ÓÈÎÔÙÈÓÈÎÔ‡ ÔͤԘ Û ·ÛıÂÓ›˜ Ì ÂÁηÙÂÛÙË̤ÓË ·ıËÚÔÛÎÏ‹ÚˆÛË Ô˘ ¤·ÈÚÓ·Ó ‹‰Ë ÛÙ·Ù›ÓË Â›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÚfiÏË„Ë Ù˘ ÂͤÏÈ͢ Ù˘ ·ıËڈ̷ÙÈ΋˜ ÓfiÛÔ˘ ÙˆÓ Î·ÚˆÙ›‰ˆÓ (¶›Ó·Î·˜ 7).38 √ Û˘Ó‰˘·ÛÌfi˜ ÓÈÎÔÙÈÓÈÎÔ‡ ÔͤԘ Ì ¿ÏÏÔ Ê¿ÚÌ·ÎÔ Ê·›ÓÂÙ·È fiÙÈ Â›Ó·È È‰È·›ÙÂÚ· ·ÔÙÂÏÂÛÌ·ÙÈÎfi˜ fiÛÔÓ ·ÊÔÚ¿ ÙË Ì›ˆÛË Ù˘ ÂͤÏÈ͢ Ù˘ ·ıËÚÔÛÎÏ‹ÚˆÛ˘ Û ·ÛıÂÓ›˜ Ì ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·, ÔÈ ÔÔ›ÔÈ ¤¯Ô˘Ó ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÚÒÈÌ˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘. ™Â Ì›· Ù˘¯·ÈÔÔÈË̤ÓË ÌÂϤÙË, ÛÙËÓ ÔÔ›· Û˘ÌÌÂÙ›¯·Ó ·ÛıÂÓ›˜ Ì ·ıËÚÔÛÎÏ‹ÚˆÛË, ¯·ÌËÏ¿ Â›‰· HDL ¯ÔÏËÛÙÂÚfiÏ˘ Î·È ÔÚȷο ·˘ÍË̤ӷ Â›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ, Ô Û˘Ó‰˘·ÛÌfi˜ ÓÈÎÔÙÈÓÈÎÔ‡ ÔͤԘ Ì ÛÈÌ‚·ÛÙ·Ù›ÓË Â›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ˘ÔÛÙÚÔÊ‹ ÙˆÓ ·ıËڈ̷ÙÈÎÒÓ ‚Ï·‚ÒÓ ÙˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ ·ÚÙËÚÈÒÓ, ÂÓÒ Ë ıÂÚ·›· Ì ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ ‹ Ì ·ÓÙÈÔÍÂÈ-

9

™∂¶Δ∂ªμƒπ√™ 2008

¶›Ó·Î·˜ 7: ¶ÚÔÛı‹ÎË ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ ‹ ÓÈÎÔÙÈÓÈÎÔ‡ ÔͤԘ Û ·ÛıÂÓ›˜ Ô˘ ¤·ÈÚÓ·Ó ‹‰Ë ıÂÚ·›· Ì ÛÙ·Ù›ÓË (ÌÂϤÙË ARBITER 2) ∞Ú¯Èο Â›‰·

12 Ì‹Ó˜

p

∂ÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ (¡= 71)

¡ÈÎÔÙÈÓÈÎfi Ô͇ (¡= 78)

∂ÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ (¡= 71)

¡ÈÎÔÙÈÓÈÎfi Ô͇ (¡= 78)

∂ÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ

¡ÈÎÔÙÈÓÈÎfi Ô͇

TCHOL

161±29

154±27

156±24

155±38

0.06

0.92

LDL-C

91±22

87±17

86±20

85±25

0.37

0.42

HDL-C

40±7

39±7

40±9

47±16

0.61

<0.001

ΔÚÈÁÏ˘ÎÂÚȉ›·

172±104

154±82

164±83

134±87

0.07

0.009

Non-HDL-C

121±27

115±26

115±21

107±34

0.03

0.02

CIMT (mm)

0.868±0.207

0.893±0.259

0.912±0.202

0.907±0.234

<0.001

0.23

TCHOL: ÔÏÈ΋ ¯ÔÏËÛÙÂÚfiÏË, CIMT: carotid intima-media thickness (¿¯˘ÓÛË ÙÔ˘ ÙÔȯÒÌ·ÙÔ˜ ÙˆÓ Î·ÚˆÙ›‰ˆÓ) ΔÚÔÔÔ›ËÛË ·fi: Circulation 2004;110;3512-3517 ‰ˆÙÈΤ˜ ‚Èٷ̛Ә Ô‰‹ÁËÛ Û ÂÈÙ¿¯˘ÓÛË Ù˘ ÂͤÏÈ͢ ÙˆÓ ·ıËڈ̷ÙÈÎÒÓ ‚Ï·‚ÒÓ (ÌÂϤÙË HATS).39 ™Â Ì›· ¿ÏÏË ÌÂϤÙË, ÛÙËÓ ÔÔ›· Û˘ÌÌÂÙ›¯·Ó ·ÛıÂÓ›˜ Ì ·˘ÍË̤ӷ Â›‰· apoB, Ô Û˘Ó‰˘·ÛÌfi˜ ÓÈÎÔÙÈÓÈÎÔ‡ ÔͤԘ Ì ÎÔÏÂÛÙÈfiÏË Ì›ˆÛ ÙËÓ ÂͤÏÈÍË ÙˆÓ ·ıËڈ̷ÙÈÎÒÓ ‚Ï·‚ÒÓ Û ۇÁÎÚÈÛË Ì ÙË ıÂÚ·›· Ì ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ.40 √È ÊÈÌÚ¿Ù˜ Â›Û˘ ÌÂÈÒÓÔ˘Ó Ù· Â›‰· ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ. ™Â Ì›· ÌÂϤÙË (Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial) Ë ¯ÔÚ‹ÁËÛË ÁÂÌÊÈÌÚÔ˙›Ï˘ Û ·ÛıÂÓ›˜ Ì ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ Â›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ Û˘Ì‚·Ì¿ÙˆÓ Î·È ÙˆÓ ÌË ı·Ó·ÙËÊfiÚˆÓ ÂÌÊÚ·ÁÌ¿ÙˆÓ ÙÔ˘ Ì˘Ôηډ›Ô˘. øÛÙfiÛÔ ‰ÂÓ ·Ú·ÙËÚ‹ıËΠ̛ˆÛË ÙˆÓ ı·Ó·ÙËÊfiÚˆÓ ÂÌÊÚ·ÁÌ¿ÙˆÓ ÙÔ˘ Ì˘Ôηډ›Ô˘ ‹ ÙˆÓ ı·Ó¿ÙˆÓ ·fi ÔÔÈ·‰‹ÔÙ ·ÈÙ›· Û ۇÁÎÚÈÛË Ì ÙË ¯ÔÚ‹ÁËÛË ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ (¶›Ó·Î·˜ 8).41 ¶·ÚfiÌÔÈ· ·ÔÙÂϤÛÌ·Ù· ¤‰ÂÈÍÂ Î·È Ì›· ÌÂϤÙË (World Health Organization Trial) ÛÙËÓ ÔÔ›· ¯ÔÚËÁ‹ıËΠÎÏÔÊÈÌÚ¿ÙË.42 ∞ÓÙÈÌÂÙÒÈÛË ·ÛıÂÓÒÓ Ì ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË 2 ™‡Ìʈӷ Ì ÙËÓ ∞ÌÂÚÈηÓÈ΋ ¢È·‚ËÙÔÏÔÁÈ΋ ∂Ù·ÈÚ›·43 Î·È ÙȘ Ô‰ËÁ›Â˜ Ù˘ NCEP35 Û˘ÓÈÛÙ¿Ù·È Ë ¯ÔÚ‹ÁËÛË ÛÙ·Ù›Ó˘ Ì ÛÎÔfi ÙË Ì›ˆÛË Ù˘ LDL ¯ÔÏËÛÙÂÚfiÏ˘ Û fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓ›˜ Ì ™¢2 Ì ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘. ™Â ·ÛıÂÓ›˜ Ì ™¢2, Ô Û˘Ó‰˘·ÛÌfi˜ ÛÙ·Ù›Ó˘ Ì ÊÈÌÚ¿ÙË ¯ÚËÛÈÌÔÔÈÂ›Ù·È Û˘¯Ó¿ ÁÈ· ÙËÓ

10

·ÓÙÈÌÂÙÒÈÛË Ù˘ Û˘Ó˘¿Ú¯Ô˘Û·˜ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜. ŸÌˆ˜ ÛÙË ÌÂϤÙË FIELD (Fenofibrate Intervention and Event Lowering in Diabetes Trial) Ë ¯ÔÚ‹ÁËÛË Ê·ÈÓÔÊÈÌÚ¿Ù˘ Û ·ÛıÂÓ›˜ Ì ™¢2 ›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÌÈ· ÌÈÎÚ‹ Î·È fi¯È ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ Û˘Ì‚·Ì¿ÙˆÓ Û ۇÁÎÚÈÛË Ì ÙË ¯Ú‹ÛË ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ (Ì›ˆÛË Î·Ù¿ 11%, Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜: 0.89, 95% ‰È¿ÛÙËÌ· ÂÌÈÛÙÔÛ‡Ó˘: 0.75-1.05, p=0.16).44 Œ¯ÂÈ ‰È·Ù˘ˆı› Ë ¿Ô„Ë fiÙÈ ÙÔ ÓÈÎÔÙÈÓÈÎfi Ô͇ ‰ÂÓ Ú¤ÂÈ Ó· ·ÔÙÂÏ› Ê¿ÚÌ·ÎÔ ÂÎÏÔÁ‹˜ ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜ ÛÙÔ˘˜ ‰È·‚ËÙÈÎÔ‡˜ ·ÛıÂÓ›˜ ÁÈ·Ù› ¤¯ÂÈ ‰˘ÛÌÂÓ‹ Â›‰Ú·ÛË ÛÙÔ ÁÏ˘Î·ÈÌÈÎfi ¤ÏÂÁ¯Ô. øÛÙfiÛÔ ÛÙË ÌÂϤÙË ADMIT,45 ÛÙËÓ ÔÔ›· Û˘ÌÌÂÙ›-

¯·Ó 468 ¿ÙÔÌ·, ·Ú·ÙËÚ‹ıËΠfiÙÈ Ë ¯ÔÚ‹ÁËÛË ÓÈ·Û›Ó˘ Û ·ÛıÂÓ›˜ Ì ™¢2 Â›Ó·È ·ÛÊ·Ï‹˜. ¶Ú¿ÁÌ·ÙÈ Ë ıÂÚ·›· Ì ÓÈ·Û›ÓË Û ·ÛıÂÓ›˜ Ì ‹ ¯ˆÚ›˜ ™¢2 Ô‰‹ÁËÛ Û ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘ ηٿ 28.9% Î·È 29.3% ·ÓÙ›ÛÙÔȯ·, Û Ì›ˆÛË Ù˘ LDL ¯ÔÏËÛÙÂÚfiÏ˘ ηٿ 8.3% Î·È 9% ·ÓÙ›ÛÙÔȯ· Î·È Û Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ηٿ 22.7% Î·È 28.4% ·ÓÙ›ÛÙÔȯ· (p< 0.001, ÓÈ·Û›ÓË ¤Ó·ÓÙÈ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘). ¶·Ú·ÙËÚ‹ıËΠÂ›Û˘ Ì›· ̤ÙÚÈ· ·‡ÍËÛË ÙˆÓ ÂÈ¤‰ˆÓ Ù˘ ÁÏ˘Îfi˙˘ ηٿ 5% Î·È 6.6% (p= 0.04 Î·È p< 0.001, ÓÈ·Û›ÓË ¤Ó·ÓÙÈ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘) ·ÓÙ›ÛÙÔȯ·, ÂÓÒ ‰ÂÓ ·Ú·ÙËÚ‹ıËΠη̛· ÌÂÙ·‚ÔÏ‹ ÛÙ· Â›‰· Ù˘ ÁÏ˘ÎÔ˙˘ÏȈ̤Ó˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘.39 45 46

¶›Ó·Î·˜ 8: °ÂÌÊÈÌÚÔ˙›ÏË ¤Ó·ÓÙÈ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ (ÌÂϤÙË VA-HIT) ™‡Ì‚·Ì·

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275 (21.7)

219 (17.3)

22 (7-35)

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184 (14.5)

146 (11.6)

23 (4-38)

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220 (17.4)

198 (15.7)

11 (2-38)

0.23

™¡: ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ˜ ΔÚÔÔÔ›ËÛË ·fi: New England Journal of Medicine 1999;341:410-8

¶∞ƒ∞°√¡Δ∂™ ∫π¡¢À¡√À ¶Ú·ÎÙÈΤ˜ Ô‰ËÁ›Â˜ ¢ÂÓ ˘¿Ú¯Ô˘Ó Û·Ê›˜ Ô‰ËÁ›Â˜ ÁÈ· ÙËÓ Â›Ù¢ÍË Û˘ÁÎÂÎÚÈÌ¤ÓˆÓ ÛÙfi¯ˆÓ fiÛÔÓ ·ÊÔÚ¿ Ù· Â›‰· ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ. ™˘ÓÈÛÙ¿Ù·È ˆÛÙfiÛÔ Ë ¯ÔÚ‹ÁËÛË ÊÈÌÚ·ÙÒÓ Û ¿ÙÔÌ· Ì Â›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ¿Óˆ ·fi 1000 mg/dl ÁÈ· ÙË Ì›ˆÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÂÌÊ¿ÓÈÛ˘ ·ÁÎÚ·ٛÙȉ·˜.20 ™Â ·ÛıÂÓ›˜ Ì ÌÈÎÚfiÙÂÚ· Â›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ (>200 mg/dl) fiÙ·Ó ÂÈÙ¢¯ı› Ô ÛÙfi¯Ô˜ fiÛÔÓ ·ÊÔÚ¿ ÙËÓ LDL ¯ÔÏËÛÙÂÚfiÏË, Û˘ÓÈÛÙ¿Ù·È Ë Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ, ·Ó Î·È ‰ÂÓ ˘¿Ú¯Ô˘Ó ·ÎfiÌ· Û·Ê‹ ‰Â‰Ô̤ӷ Ô˘ Ó· ˘ÔÛÙËÚ›˙Ô˘Ó ·˘Ù‹ ÙË Û‡ÛÙ·ÛË. ™˘ÌÂÚ¿ÛÌ·Ù· Î·È Û˘ÛÙ¿ÛÂȘ √ ·ÛıÂÓ‹˜ Ô˘ ÂÚÈÁÚ¿„·Ì ÛÙËÓ ·Ú¯‹ ¤¯ÂÈ ·˘ÍË̤ӷ Â›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Î·È ¯·ÌËÏ¿ Â›‰· HDL ¯ÔÏËÛÙÂÚfiÏ˘. ŸÌˆ˜ Ù· Â›‰· Ù˘ LDL ¯ÔÏËÛÙÂÚfiÏ˘ ÁÈ· ÙÔ Û˘ÁÎÂÎÚÈ̤ÓÔ ·ÛıÂÓ‹ ‚Ú›ÛÎÔÓÙ·È ÂÓÙfi˜ ÙˆÓ ıÂÚ·¢ÙÈÎÒÓ ÛÙfi¯ˆÓ. ΔfiÛÔ Ù· ·˘ÍË̤ӷ Â›‰· ÙˆÓ ÙÚÈÁÏ˘ÎÂÚÈ-

‰›ˆÓ, fiÛÔ Î·È Ù· ¯·ÌËÏ¿ Â›‰· Ù˘ HDL ‰ÂÓ Â·ÚÎÔ‡Ó ÛÙÔ Ó· ηıÔÚ›ÛÔ˘Ó Â¿Ó Ô ·ÛıÂÓ‹˜ ¤¯ÂÈ Û˘ÁÁÂÓ‹ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·, ÔÈÎÔÁÂÓ‹ ÌÂÈÎÙ‹ ˘ÂÚÏÈȉ·ÈÌ›· ‹ ÔÈÎÔÁÂÓ‹ ˘Ô·ÏÊ·ÏÈÔÚˆÙÂ˚Ó·ÈÌ›·. ¢ÂÓ Ê·›ÓÂÙ·È Ó· ˘¿Ú¯ÂÈ Î¿ÔÈÔ ˘ÔΛÌÂÓÔ ÓfiÛËÌ· Ô˘ Ó· ÌÔÚ› Ó· ÂÍËÁ‹ÛÂÈ ÙËÓ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·, ÂÓÒ ‰ÂÓ ˘¿Ú¯Ô˘Ó Â›Û˘ Î·È ¿ÏÏÔÈ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ÚÒÈÌ˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘. ΔÔ ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi ÌÔÚ› Ó· Ì·˜ ‚ÔËı‹ÛÂÈ ÛÙËÓ ÂÎÙ›ÌËÛË ·ÛıÂÓÒÓ Ì ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·. ¶Ú¤ÂÈ Ó· ·Ó·˙ËÙËıÔ‡Ó Û˘ÁÁÂÓ›˜ Ì ÂÁηÙÂÛÙË̤ÓË ·ıËÚÔÛÎÏ‹ÚˆÛË, Ë ËÏÈΛ· Ù˘ ÂÌÊ¿ÓÈÛ˘ Ù˘ ·ıËÚÔÛÎÏ‹ÚˆÛ˘, ηıÒ˜ Â›Û˘ Î·È Û ÂÚ›ÙˆÛË Ô˘ οÔÈÔ˜ Û˘ÁÁÂÓ‹˜ ¤¯ÂÈ Âı¿ÓÂÈ, Ú¤ÂÈ Ó· ·Ó·˙ËÙÂ›Ù·È Ë ËÏÈΛ· Î·È Ë ·ÈÙ›· ÙÔ˘ ı·Ó¿ÙÔ˘. ∂›Û˘, ÙÔ ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi Â›Ó·È ¯Ú‹ÛÈÌÔ ÁÈ·Ù› ÌÔÚ› Ó· ·Ôηχ„ÂÈ Î·È ¿ÏÏ· ¿ÙÔÌ· Ô˘ ¯ÚÂÈ¿˙ÔÓÙ·È ˘ÔÏÈȉ·ÈÌÈ΋ ·ÁˆÁ‹. ŒÓ· ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi ÚÒÈÌ˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘ ‚ÔËı¿ÂÈ ÛÙË ‰È¿ÁÓˆÛË Ù˘ ÔÈÎÔÁÂÓÔ‡˜ ÌÂÈÎÙ‹˜ ˘ÂÚÏÈȉ·ÈÌ›·˜ ‹ Ù˘ ÔÈÎÔÁÂÓÔ‡˜ ˘Ô-

·ÏÊ·ÏÈÔÚˆÙÂ˚Ó·ÈÌ›·˜. ŸÙ·Ó ¤Ó·˜ ·ÛıÂÓ‹˜ ¤¯ÂÈ ·ÚÎÂÙÔ‡˜ Û˘ÁÁÂÓ›˜ Ì ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·, ·ÏÏ¿ ¯ˆÚ›˜ ÎÏÈÓÈ΋ ¤Ó‰ÂÈÍË ·ıËÚÔÛÎÏ‹ÚˆÛ˘, Ë ·ÓÙÈÌÂÙÒÈÛË Ù˘ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜ ·ÏÏ¿ Î·È ÙˆÓ ¯·ÌËÏÒÓ ÂÈ¤‰ˆÓ HDL ¯ÔÏËÛÙÂÚfiÏ˘ ÌÔÚ› Ó· ÂÈÙ¢¯ı› Ì ·ÏÏ·Á‹ ÙÔ˘ ÙÚfiÔ˘ ˙ˆ‹˜, Ë ÔÔ›· ÂÚÈÏ·Ì‚¿ÓÂÈ ‰›·ÈÙ· ¯·ÌËÏ‹ Û ıÂÚÌ›‰Â˜ Î·È ˙ˆÈο Ï›Ë ÛÂ Û˘Ó‰˘·ÛÌfi Ì ۈ̷ÙÈ΋ ¿ÛÎËÛË Î·È ·ÒÏÂÈ· ‚¿ÚÔ˘˜. ∞ÛıÂÓ›˜ Ì ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· Î·È ÚÒÈÌË ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ ‹ ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛ‹ Ù˘ Ì ‚¿ÛË ÙÔ ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi Ê·›ÓÂÙ·È fiÙÈ ÂÌÊ·Ó›˙Ô˘Ó ÔÈÎÔÁÂÓ‹ ÌÂÈÎÙ‹ ˘ÂÚÏÈȉ·ÈÌ›· ‹ ÔÈÎÔÁÂÓ‹ ˘Ô·ÏÊ·ÏÈÔÚˆÙÂ˚Ó·ÈÌ›·. ™Â ·˘Ù¤˜ ÙȘ ÂÚÈÙÒÛÂȘ ¤Ú·Ó Ù˘ ·ÏÏ·Á‹˜ ÙÔ˘ ÙÚfiÔ˘ ˙ˆ‹˜ Ú¤ÂÈ Ó· Û˘˙ËÙËı› Ë ¯ÔÚ‹ÁËÛË Ê·Ú̷΢ÙÈ΋˜ ·ÁˆÁ‹˜. ∞Ó Î·È ‰ÂÓ ˘¿Ú¯Ô˘Ó Û·Ê‹ ‰Â‰Ô̤ӷ ÁÈ· ÙËÓ Î·Ù¿ÏÏËÏË ıÂÚ·›· Û ·˘Ù¤˜ ÙȘ ÂÚÈÙÒÛÂȘ, ÚÔÙ›ÓÂÙ·È Ë ¯ÔÚ‹ÁËÛË Û˘Ó‰˘·ÛÌÔ‡ ÛÙ·Ù›Ó˘ Ì ÓÈÎÔÙÈÓÈÎfi Ô͇ (‹ ÊÈÌÚ¿ÙË).

μÈ‚ÏÈÔÁÚ·Ê›·

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46. Grundy SM, Vega GL, McGovern ME, Tulloch BR, Kendall DM, Fitz-Patrick D, et al. Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2 diabetes: results of the assessment of diabetes control and evaluation of the efficacy of niaspan trial. Arch Intern Med 2002;162:156876.

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ªË ™ÙÂÚÔÂȉ‹ ∞ÓÙÈÊÏÂÁÌÔÓÒ‰Ë º¿Ú̷η Î·È ∫·Ú‰È·ÁÁÂÈ·Îfi˜ ∫›Ó‰˘ÓÔ˜ º. ∞ÔÛÙfiÏÔ˘ ∂ÈÌÂÏ‹ÙÚÈ· μ' Ù˘ μ' ¶·ıÔÏÔÁÈ΋˜ ∫ÏÈÓÈ΋˜ ÙÔ˘ ¶·ÓÂÈÛÙËÌÈ·ÎÔ‡ °ÂÓÈÎÔ‡ ¡ÔÛÔÎÔÌ›Ԣ πˆ·ÓÓ›ÓˆÓ ∂. §˘ÌÂÚfiÔ˘ÏÔ˜ §¤ÎÙÔÚ·˜ ¶·ıÔÏÔÁ›·˜, π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ ª. ∂ÏÈÛ¿Ê ∫·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ Δ· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ÔÏϤ˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó ·‡ÍËÛË ÙˆÓ ·ÁÁÂÈ·ÎÒÓ ÂÂÈÛÔ‰›ˆÓ Û ·ÛıÂÓ›˜ Ô˘ ¤·ÈÚÓ·Ó ·Ó·ÛÙÔÏ›˜ Ù˘ ΢ÎÏÔ͢ÁÂÓ¿Û˘-2 (coxibs). √È ÏËÚÔÊÔڛ˜ ÚÔ‹Úı·Ó ·fi ÙÔÓ Ù‡Ô, fiÔ˘ Â›Û˘ ‰ËÌÔÛȇÙËÎ·Ó ÚÔÛÊ˘Á¤˜ ÛÙË ‰ÈηÈÔÛ‡ÓË Î·Ù¿ Ê·Ú̷΢ÙÈÎÒÓ ÂÙ·ÈÚÈÒÓ. ™ÙËÓ ·ÌÊÈ‚ÔÏ›· ÙˆÓ ÎÏÈÓÈÎÒÓ ÁÈ·ÙÚÒÓ ·Ó Ú¤ÂÈ Ó· ¯ÔÚËÁ‹ÛÔ˘Ó ¤Ó· ÌË ÛÙÂÚÔÂȉ¤˜ ·ÓÙÈÊÏÂÁÌÔÓ҉˜ Ê¿ÚÌ·ÎÔ (NSAID) Û ¤Ó· ·ÛıÂÓ‹ ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ·ÁÁÂÈ·Îfi ÂÂÈÛfi‰ÈÔ ÚÔÛÙ¤ıËÎÂ Ë ‰˘ÛÈÛÙ›· ÙˆÓ ·ÛıÂÓÒÓ ·¤Ó·ÓÙÈ ÛÙ· ÌË ÛÙÂÚÔÂȉ‹ ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë Ê¿Ú̷η, Ù· ÔÔ›· ¯ÔÚËÁÔ‡ÓÙ·È Û˘¯Ó¿ ÛÙËÓ ÎÏÈÓÈ΋ Ú¿ÍË. √È ÌÂϤÙ˜ ۯ‰ȿÛıËÎ·Ó ÁÈ· Ó· ·Ó·‰Â›ÍÔ˘Ó ÙȘ ȉÈfiÙËÙ˜ ÙˆÓ NSAIDs (·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·, ÂÈÙÒÛÂȘ ÛÙÔ Á·ÛÙÚÂÓÙÂÚÈÎfi, ¤Ó‰ÂÈÍË ÁÈ· ÙË ÓfiÛÔ Altzheimer). ™ÙËÓ ÔÚ›· ÙˆÓ ÂÚ¢ÓÒÓ ÚԤ΢„ fiÙÈ ·˘Ù¿ Ù· Ê¿Ú̷η Û¯ÂÙ›˙ÔÓÙ·È Ì ·‡ÍËÛË ÙˆÓ ·ÁÁÂÈ·ÎÒÓ ÂÂÈÛÔ‰›ˆÓ, Ì ·ÔÙ¤ÏÂÛÌ· ÔÏϤ˜ ¤Ú¢Ó˜ Ó· ‰È·ÎÔÔ‡Ó Î·È ÔÚÈṲ̂ӷ Ê¿Ú̷η Ó· ·ÔÛ˘ÚıÔ‡Ó. ™ÙË ÌÂϤÙË APC1 ¤ÁÈÓ ۇÁÎÚÈÛË Ù˘ celecoxib Ì ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ ÁÈ· ÙËÓ ÚfiÏË„Ë ÙÔ˘ ηÚΛÓÔ˘ ÙÔ˘ ·¯¤ˆ˜ ÂÓÙ¤ÚÔ˘ Û ·ÛıÂÓ›˜ Ì ·‰Âӈ̷ÙÒ‰ÂȘ Ôχԉ˜. ∏ ÌÂϤÙË Û¯Â‰È¿ÛıËΠÁÈ· 5 ¯ÚfiÓÈ·, ·ÏÏ¿ ‰È·ÎfiËΠÛÙ· 3 ¯ÚfiÓÈ· fiÙ·Ó ‰È·ÈÛÙÒıËΠfiÙÈ ·˘Í‹ıËÎ·Ó Ù· ·ÁÁÂȷο ÂÂÈÛfi‰È· ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ¤·ÈÚÓ·Ó celecoxib. ∞‡ÍËÛË ÙˆÓ ·ÁÁÂÈ·ÎÒÓ Û˘Ì‚·Ì¿ÙˆÓ ·Ú·ÙËÚ‹ıËΠÛÙË ÌÂϤÙË VIGOR2, ÛÙËÓ ÔÔ›· Û˘ÁÎÚ›ıËÎÂ Ë rofecoxib Ì ÙË naproxen fiÛÔÓ ·ÊÔÚ¿ ÙȘ ÂÈÏÔΤ˜ ·fi ÙÔ Á·ÛÙÚÂÓÙÂÚÈÎfi Û ·ÛıÂÓ›˜ Ì ÈÛÙÔÚÈÎfi ÚÂ˘Ì·ÙÔÂȉԇ˜ ·ÚıÚ›Ùȉ·˜. ∂›Û˘ ·‡ÍËÛË ÙˆÓ ·ÁÁÂÈ·ÎÒÓ ÂÂÈÛÔ‰›ˆÓ ·Ú·ÙËÚ‹ıËΠÛÙË ÌÂϤÙË APPROVe3 ÛÙËÓ ÔÔ›· Û˘ÁÎÚ›ıËÎÂ Ë rofecocib Ì ÂÈÎÔ-

ÓÈÎfi Ê¿ÚÌ·ÎÔ ÁÈ· ÙËÓ ÚfiÏË„Ë ÙÔ˘ ηÚΛÓÔ˘ ÙÔ˘ ·¯¤ˆ˜ ÂÓÙ¤ÚÔ˘ Û ·ÛıÂÓ›˜ Ì ·‰Âӈ̷ÙÒ‰ÂȘ Ôχԉ˜. ∏ ¤Ú¢ӷ ‰È·ÎfiËÎÂ Î·È Ë ÂÙ·ÈÚ›· Merk ·¤Û˘Ú ÙË rofecocib (Vioxx). §›Á˜ ‚‰ÔÌ¿‰Â˜ ·ÚÁfiÙÂÚ· Ë Pfizer ·¤Û˘Ú ÙË valdecoxib (Valtrex). ∞ÓÙ›ıÂÙ· ·ÔÙÂϤÛÌ·Ù· ·Ú·ÙËÚ‹ıËÎ·Ó ÛÙË ÌÂϤÙË ADAPT4 (ÌÂϤÙË ÁÈ· ÙËÓ ÚfiÏË„Ë Ù˘ ÓfiÛÔ˘ ÙÔ˘ Altzheimer), Ë ÔÔ›· ¤‰ÂÈÍ fiÙÈ Ë naproxen ·‡ÍËÛ ÙÔÓ Î·Ú‰È·ÁÁÂÈ·Îfi ΛӉ˘ÓÔ Û ۇÁÎÚÈÛË Ì ÙË celecoxib. ™ÙȘ ÌÂϤÙ˜ TARGET5 Î·È MEDAL6 ÔÈ coxibs Î·È Ù· ·Ú·‰ÔÛȷο ÌË ÂÎÏÂÎÙÈο NSAIDs Ô˘ ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó ·‡ÍËÛ·Ó ÙÔÓ Î·Ú‰È·ÁÁÂÈ·Îfi ΛӉ˘ÓÔ.

Ë ÔÔ›· Â¿ÁÂÙ·È ·fi ÙȘ ΢ÙÔΛÓ˜, ·Ú¿ÁÔÓÙ·È ÚÔÛÙ·ÁÏ·Ó‰›Ó˜ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙË ÊÏÂÁÌÔÓ‹, ÙÔÓ ˘ÚÂÙfi, ÙÔÓ fiÓÔ Î·È ÙËÓ Î·ÚÎÈÓÔÁ¤ÓÂÛË 9. £ÂˆÚËÙÈο ÙÔ È‰·ÓÈÎfi ·ÓÙÈÊÏÂÁÌÔÓ҉˜ Ê¿ÚÌ·ÎÔ ·Ó·ÛÙ¤ÏÏÂÈ ÂÎÏÂÎÙÈο ÙËÓ COX-2.

ªË¯·ÓÈÛÌfi˜ ‰Ú¿Û˘ ÙˆÓ NSAIDs

Δ· NSAIDs ·ÔÙÂÏÔ‡Ó ÌÈ· ÂÙÂÚÔÁÂÓ‹ ÔÌ¿‰· Ê·ÚÌ¿ÎˆÓ Ì ‰È·ÊÔÚÂÙÈ΋ ÚԤϢÛË Î·È ‰È·ÊÔÚÂÙÈ΋ ¯ËÌÈ΋ ‰ÔÌ‹. ∞Ó·ÛÙ¤ÏÏÔ˘Ó ÙË ‰Ú¿ÛË Ù˘ COX Î·È ÙËÓ ·Ú·ÁˆÁ‹ ÙˆÓ ÚÔÛÙ·ÁÏ·Ó‰ÈÓÒÓ. Δ· NSAIDs ‰È·ÎÚ›ÓÔÓÙ·È Ì ‚¿ÛË ÙË Û¯ÂÙÈ΋ ·Ó·ÛÙÔÏ‹ Ù˘ COX ÛÙ· NSAIDs Ô˘ ·Ó·ÛÙ¤ÏÏÔ˘Ó ÂÚÈÛÛfiÙÂÚÔ ÙËÓ COX-1 Î·È Û ÂΛӷ Ô˘ ·Ó·ÛÙ¤ÏÏÔ˘Ó ÂÚÈÛÛfiÙÂÚÔ ÙËÓ COX-2 (EÈÎfiÓ· 1)11. Δ· ÌË ÂÎÏÂÎÙÈο NSAIDs ·Ó·ÛÙ¤ÏÏÔ˘Ó ÙfiÛÔ ÙËÓ COX-1 fiÛÔ Î·È ÙËÓ COX-211. ∏ ·ÛÈÚ›ÓË ·Ó·ÛÙ¤ÏÏÂÈ ÙË COX-1 ηٿ 170 ÊÔÚ¤˜ ÂÚÈÛÛfiÙÂÚÔ ·fi ÙËÓ COX-2 Ì ·ÔÙ¤ÏÂÛÌ· in vivo Ó· ·ÔÙÂÏ› ¤Ó·Ó ÂÎÏÂÎÙÈÎfi ·Ó·ÛÙÔϤ· Ù˘ COX-1 Ì ÛËÌ·ÓÙÈ΋ ·ÓÙÈ·ÈÌÔÂÙ·Ïȷ΋ ‰Ú¿ÛË10,12. OÈ coxibs Ù· ÓÂfiÙÂÚ· NSAIDs ·Ó·ÛÙ¤ÏÏÔ˘Ó ÂÎÏÂÎÙÈο ÙËÓ COX-2 Î·È ÚÔηÏÔ‡Ó ÏÈÁfiÙÂÚ˜ ·ÈÌÔÚÚ·Á›Â˜ ·fi ÙÔÓ ÂÙÈÎfi ۈϋӷ11.

∞fi ÙÔ ·Ú·¯È‰ÔÓÈÎfi Ô͇ Ì ÙË ‚Ô‹ıÂÈ· ‰È·ÊÔÚÂÙÈÎÒÓ ÂÓ˙‡ÌˆÓ ·Ú¿ÁÔÓÙ·È Ù· ÂÈÎÔÛ·ÓÔÂȉ‹. ™ËÌ·ÓÙÈÎfi˜ Â›Ó·È Ô ÚfiÏÔ˜ Ù˘ ΢ÎÏÔ͢ÁÂÓ¿Û˘ (COX), Ë ÔÔ›· ÂÌÊ·Ó›˙ÂÈ ‰‡Ô ÈÛÔ¤Ó˙˘Ì· (COX-1 Î·È COX-2). ∞fi ÙÔ ·Ú·¯È‰ÔÓÈÎfi Ô͇ Ì ÙË ‚Ô‹ıÂÈ· Ù˘ COX ·Ú¿ÁÔÓÙ·È ÔÈ ÚÔÛÙ·ÁÏ·Ó‰›Ó˜ (PGD2, PGF2a, PGE2, PGI2) Î·È Ë ıÚÔÌ‚ÔÍ¿ÓË (TxA2)7. Δ· ÈÛÔ¤Ó˙˘Ì· Ù˘ COX ¤¯Ô˘Ó ‰È·ÊÔÚÂÙÈ΋ ηٷÓÔÌ‹ ·Ó¿ÏÔÁ· Ì ÙÔÓ Ù‡Ô ÙˆÓ Î˘ÙÙ¿ÚˆÓ. ∏ COX-1 ÂÎÊÚ¿˙ÂÙ·È Û ÔÏÏÔ‡˜ Ù‡Ô˘˜ ΢ÙÙ¿ÚˆÓ Î·È Â›Ó·È Ë ÌfiÓË COX Ô˘ ‰È·ı¤ÙÔ˘Ó Ù· PLT. ∂ÈϤÔÓ Ù· ·ÙÙ·Ú· ‰È·ı¤ÙÔ˘Ó ‰È·ÊÔÚÂÙÈΤ˜ ÈÛÔÌÂÚ¿Û˜ Î·È ·Ó¿ÏÔÁ· Ì ÙÔÓ Ù‡Ô Ù˘ ÈÛÔÌÂÚ¿Û˘ ·Ú¿ÁÔ˘Ó ‰È·ÊÔÚÂÙÈΤ˜ ÚÔÛÙ·ÁÏ·Ó‰›Ó˜ ‹ TxA28. ªÂ ÙË ‚Ô‹ıÂÈ· Ù˘ COX-1 ·Ú¿ÁÔÓÙ·È ÚÔÛÙ·ÁÏ·Ó‰›Ó˜ Ô˘ Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÂ Ê˘ÛÈÔÏÔÁÈΤ˜ ÏÂÈÙÔ˘ÚÁ›Â˜. ¶Ú¿ÁÌ·ÙÈ ·˘Ù¤˜ ÔÈ ÚÔÛÙ·ÁÏ·Ó‰›Ó˜ ÚÔÛÙ·ÙÂ‡Ô˘Ó ÙÔ Á·ÛÙÚÈÎfi ‚ÏÂÓÓÔÁfiÓÔ Î·È Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙË Ê˘ÛÈÔÏÔÁÈ΋ ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›·. ªÂ ÙËÓ COX-2,

øÛÙfiÛÔ ·fi ÙÔ ·Ú·¯È‰ÔÓÈÎfi Ô͇ Ì ÙË ‚Ô‹ıÂÈ· Ù˘ COX-1 ·Ú¿ÁÂÙ·È Ë TxA2, Ë ÔÔ›· ÚÔ¿ÁÂÈ ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ PLT. ∏ ·ÛÈÚ›ÓË Û ¯·ÌËϤ˜ ‰fiÛÂȘ ·Ó·ÛÙ¤ÏÏÂÈ ÙË COX-1, ÙË ‰Ú¿ÛË Ù˘ TxA2 Î·È ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ PLT Î·È ·ÔÙÂÏ› ıÂÌÂÏÈ҉˜ Ê¿ÚÌ·ÎÔ ÁÈ· ÙËÓ ÚˆÙÔÁÂÓ‹ Î·È ÙË ‰Â˘ÙÂÚÔÁÂÓ‹ ÚfiÏË„Ë ÙˆÓ ·ÁÁÂÈ·ÎÒÓ ÂÂÈÛÔ‰›ˆÓ10.

ªË¯·ÓÈÛÌÔ› Ì ÙÔ˘˜ ÔÔ›Ô˘˜ Ù· NSAIDs ÚÔηÏÔ‡Ó ·ÁÁÂȷο ÂÂÈÛfi‰È· Δ· NSAIDs ÚÔηÏÔ‡Ó ·ÁÁÂȷο ÂÂÈÛfi‰È· Ì ¿ÌÂÛÔ˘˜ Î·È ¤ÌÌÂ-

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ºÀ™π√§√°π∫∞ Èڛ˜ £ÂÚ·›·

ÛÙÔÏ‹ Ù˘ COX-2 ·Ó·ÛÙ¤ÏÏÂÈ ÛËÌ·ÓÙÈο ÙËÓ ·Ú·ÁˆÁ‹ Ù˘ PGI2 Î·È Â˘ÓÔ› ÙÔ Û¯ËÌ·ÙÈÛÌfi ıÚfiÌ‚Ô˘ (∂ÈÎfiÓ· 2)11.

∞ӷχÛÂȘ ÌÂÏÂÙÒÓ

∞ÛÈÚ›ÓË Û ÌÈÎÚ‹ ‰fiÛË

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∂ÈÎfiÓ· 1 ™Â ·ıÔÏÔÁÈÎfi ÂÓ‰Ôı‹ÏÈÔ Ë PGI2 ·Ú¿ÁÂÙ·È Î˘Ú›ˆ˜ ·fi ÙËÓ COX-2. √È ·Ó·ÛÙÔÏ›˜ COX-2 ÂÏ·ÙÙÒÓÔ˘Ó ÙËÓ ·Ú·ÁˆÁ‹ PGI2, Ì ·ÔÙ¤ÏÂÛÌ· ÙË ‰È·Ù·Ú·¯‹ Ù˘ ÈÛÔÚÚÔ›·˜ ÌÂٷ͇ PGI2 Î·È TxA2, ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ PLT Î·È ÙÔ Û¯ËÌ·ÙÈÛÌfi ıÚfiÌ‚Ô˘.

ÛÔ˘˜ Ì˯·ÓÈÛÌÔ‡˜. ¶Ú¿ÁÌ·ÙÈ ·˘Ù¿ Ù· Ê¿Ú̷η ÚÔηÏÔ‡Ó Î·Ù·ÎÚ¿ÙËÛË ¡·+, Ì ·ÔÙ¤ÏÂÛÌ· ·‡ÍËÛË Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘ Î·È Û˘ÌÊÔÚËÙÈ΋ ηډȷ΋ ·ÓÂ¿ÚÎÂÈ· 13,14. ∂ÈϤÔÓ Ù· NSAIDs ÚÔηÏÔ‡Ó ‚Ï¿‚Ë ÙÔ˘ ÂÓ‰ÔıËÏ›Ô˘ Î·È ÂÓ‰ÔıËÏȷ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·, ÂÓÒ Úԉȷı¤ÙÔ˘Ó ÛÙÔ Û¯ËÌ·ÙÈÛÌfi ıÚfiÌ‚Ô˘ Î·È Û ·ÁÁÂÈ·Îfi ÂÂÈÛfi‰ÈÔ (ÈÛ¯·ÈÌÈÎfi ηډȷÎfi ÂÂÈÛfi‰ÈÔ Î·È ¤ÌÊÚ·ÁÌ· ÙÔ˘ Ì˘Ôηډ›Ô˘, ·ÁÁÂÈ·Îfi ÂÁÎÂÊ·ÏÈÎfi ÂÂÈÛfi‰ÈÔ Î·È ·ÈÊÓ›‰ÈÔ ı¿Ó·ÙÔ)11. ΔÔ ÂÓ‰Ôı‹ÏÈÔ ‰È·ı¤ÙÂÈ COX-1 Î·È COX-2 Î·È ·Ú¿ÁÂÈ ÚÔÛÙ·Î˘ÎÏ›ÓË (PGI2). øÛÙfiÛÔ Ù· PLT ¤¯Ô˘Ó ÌfiÓÔ COX-1 Î·È ·Ú¿ÁÔ˘Ó TxA2. ∏ PGI2 ·Ó·ÛÙ¤ÏÏÂÈ ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ PLT Î·È ÚÔηÏ› ·ÁÁÂÈԉȷÛÙÔÏ‹, ÂÓÒ ·ÓÙ›ıÂÙ· Ë TxA2 ÚÔηÏ› ·ÁÁÂÈÔÛ‡Û·ÛË

14

Î·È ÚÔ¿ÁÂÈ ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ PLT. ™Â ÂÚ›ÙˆÛË Ê˘ÛÈÔÏÔÁÈÎÔ‡ ÂÓ‰ÔıËÏ›Ô˘ Ë ÈÛÔÚÚÔ›· ÌÂٷ͇ TxA2 Î·È PGI2 Â›Ó·È ˘¤Ú Ù˘ PGI2 Ì ·ÔÙ¤ÏÂÛÌ· ÙË Ì›ˆÛË Ù˘ ÂÓÂÚÁÔÔ›ËÛ˘ ÙˆÓ PLT. ™Â ÂÚ›ÙˆÛË ·ıÔÏÔÁÈÎÔ‡ ÂÓ‰ÔıËÏ›Ô˘ ·˘Í¿ÓÂÙ·È Ë ·Ú·ÁˆÁ‹ TxA2, Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·‡ÍËÛË Ù˘ ÂÓÂÚÁÔÔ›ËÛ˘ ÙˆÓ PLT. ∏ ·‡ÍËÛË Ù˘ PGI2 Â›Ó·È ·ÓÙÈÛÙ·ıÌÈÛÙÈ΋ Î·È ‰ÂÓ Â›Ó·È ÈηӋ Ó· ·Ó·ÙÚ¤„ÂÈ ÙËÓ ·ÚÓËÙÈ΋ ÈÛÔÚÚÔ›· ˘¤Ú Ù˘ TxA211. ∏ PGI2 ÛÂ Ê˘ÛÈÔÏÔÁÈÎfi ÂÓ‰Ôı‹ÏÈÔ ·Ú¿ÁÂÙ·È Î˘Ú›ˆ˜ ‰È·Ì¤ÛÔ˘ Ù˘ COX-1, ÂÓÒ Û ·ıÔÏÔÁÈÎfi ÂÓ‰Ôı‹ÏÈÔ ‰È·Ì¤ÛÔ˘ Ù˘ COX-2. √È coxibs ÛÂ Ê˘ÛÈÔÏÔÁÈÎfi ÂÓ‰Ôı‹ÏÈÔ ‰ÂÓ ÂËÚ¿˙Ô˘Ó ÛËÌ·ÓÙÈο ÙËÓ ÈÛÔÚÚÔ›· ÌÂٷ͇ Ù˘ PGI2 Î·È Ù˘ TxA2. ∞ÓÙ›ıÂÙ· Û ·ıÔÏÔÁÈÎfi ÂÓ‰Ôı‹ÏÈÔ Ë ·Ó·-

∂ӉȷʤÚÔÓ ·ÚÔ˘ÛÈ¿˙Ô˘Ó Ù· ·ÔÙÂϤÛÌ·Ù· ÌÈ·˜ ÌÂÙ·-·Ó¿Ï˘Û˘ Ù˘¯·ÈÔÔÈËÌ¤ÓˆÓ ÌÂÏÂÙÒÓ Ô˘ ‰ËÌÔÛȇıËΠÙÔ 200615. ™ÙËÓ ·Ó¿Ï˘ÛË Û˘ÌÂÚÈÂÏ‹ÊıËÎ·Ó 138 Ù˘¯·ÈÔÔÈË̤Ó˜ ÌÂϤÙ˜ ÛÙȘ Ôԛ˜ Û˘ÌÌÂÙ›¯·Ó 145.373 ·ÛıÂÓ›˜. ™ÙȘ ÌÂϤÙ˜ ·˘Ù¤˜ Û˘ÁÎÚ›ıËÎ·Ó coxibs Ì ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ, ÌË ÂÎÏÂÎÙÈο NSAIDs ‹ naproxen. ∂ÎÙÈÌ‹ıËÎ·Ó Ù· ÛÔ‚·Ú¿ ·ÁÁÂȷο ÂÂÈÛfi‰È· (ı·Ó·ÙËÊfiÚ· Û˘Ì‚¿Ì·Ù· ‹ Û˘Ì‚¿Ì·Ù· Ô˘ ÂȂ‚·ÈÒıËÎ·Ó Û ÓÔÛÔÎÔÌ›Ô). ∂Âȉ‹ Ë ·‡ÍËÛË ÙˆÓ ·ÁÁÂÈ·ÎÒÓ ÂÂÈÛÔ‰›ˆÓ ‹Ù·Ó ÛËÌ·ÓÙÈ΋ ÌÂÙ¿ ÙÔÓ ÚÒÙÔ Ì‹Ó· ıÂÚ·›·˜ ÂÈϤ¯ıËÎ·Ó ÌÂϤÙ˜ Ì ‰È¿ÚÎÂÈ· ıÂÚ·›·˜ ÙÔ˘Ï¿¯ÈÛÙÔÓ 4 ‚‰ÔÌ¿‰ˆÓ. ™Â ¿ÏÏË ÌÂÙ··Ó¿Ï˘ÛË Ô˘ ‰ËÌÔÛȇıËΠÙÔÓ ›‰ÈÔ ¯ÚfiÓÔ Ë ‰È¿ÚÎÂÈ· ıÂÚ·›·˜ ηıÔÚ›ÛÙËΠ۠6 ‚‰ÔÌ¿‰Â˜16. ∏ naproxen ÌÂÏÂÙ‹ıËΠ¯ˆÚÈÛÙ¿ ÁÈ·Ù› ÂÎÙÈÌ‹ıËΠfiÙÈ ¤¯ÂÈ Í¯ˆÚÈÛÙfi ÚfiÏÔ15. ∏ naproxen ·Ó‹ÎÂÈ ÛÙ· NSAIDs Ô˘ ÂÌÊ·Ó›˙Ô˘Ó ÌÂÁ·Ï‡ÙÂÚË Û¯ÂÙÈ΋ ·Ó·ÛÙÔÏ‹ Ù˘ COX-1. ¶ÚÔ·ÙÂÈ ÙÔ ÂÚÒÙËÌ· ·Ó Ë naproxen Î·È Ù· NSAIDs Ì ÌÂÁ·Ï‡ÙÂÚË ·Ó·ÛÙÔÏ‹ Ù˘ COX1 ¤¯Ô˘Ó ·ÓÙÈ·ÈÌÔÂÙ·Ïȷ΋ ‰Ú¿ÛË, fiˆ˜ Ë ·ÛÈÚ›ÓË2,4,5,17,18. °È· Ó· ÂÏ·ÙÙˆı› ·ÔÙÂÏÂÛÌ·ÙÈο Ë ·Ú·ÁˆÁ‹ Ù˘ TxA2 Â›Ó·È ··Ú·›ÙËÙË Ë ·Ó·ÛÙÔÏ‹ Ù˘ COX-1 ηٿ 95%. ∏ ·ÛÈÚ›ÓË ·Ó·ÛÙ¤ÏÏÂÈ ÌË ·ÓÙÈÛÙÚÂÙ¿ ÙËÓ COX-1 ηٿ 95% Î·È ÂÏ·ÙÙÒÓÂÈ ÙËÓ ·Ú·ÁˆÁ‹ Ù˘ TxA219. Δ· NSAIDs Ô˘ ·Ó·ÛÙ¤ÏÏÔ˘Ó Î˘Ú›ˆ˜ ÙËÓ COX-1 ·Ó·ÛÙ¤ÏÏÔ˘Ó ·ÓÙÈÛÙÚÂÙ¿ ηٿ 59-95% ÙËÓ COX-120. ™ÙÔ ÚÒÙÔ Ì¤ÚÔ˜ Ù˘ ·Ó¿Ï˘Û˘ ¤ÁÈÓ ۇÁÎÚÈÛË ÙˆÓ coxibs (rofecoxib, celecoxib, etoricoxib, lumiracoxib, valdecoxib, subtotal) Ì ÙÔ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ ÁÈ· ÙÔÓ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ·ÁÁÂÈ·ÎÔ‡ ÂÂÈÛÔ‰›Ô˘, ÂÌÊÚ¿ÁÌ·ÙÔ˜ ÙÔ˘ Ì˘Ôηډ›Ô˘ (√∂ª), ·ÁÁÂÈ·ÎÔ‡ ÂÁÎÂÊ·ÏÈÎÔ‡ ÂÂÈÛÔ‰›Ô˘ (∞∂∂) Î·È ·ÁÁÂÈ·ÎÔ‡ ı·Ó¿ÙÔ˘. ¶·Ú·ÙËÚ‹ıËΠÛËÌ·ÓÙÈ΋ ·‡ÍËÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ Û˘ÓÔÏÈο ÁÈ· ·ÁÁÂȷο ÂÂÈÛfi‰È· Î·È √∂ª ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ¤·ÈÚÓ·Ó coxibs.

¶∞ƒ∞°√¡Δ∂™ ∫π¡¢À¡√À

∂ÈÎ.2 Δ· NSAIDs ·ÔÙÂÏÔ‡Ó ÌÈ· ÂÙÂÚÔÁÂÓ‹ ÔÌ¿‰· Ê·ÚÌ¿ÎˆÓ Ì ‰È·ÊÔÚÂÙÈ΋ ÚԤϢÛË Î·È ¯ËÌÈ΋ ‰ÔÌ‹. ¢È·ÎÚ›ÓÔÓÙ·È ·Ó¿ÏÔÁ· Ì ÙËÓ ÈηÓfiÙËÙ¿ ÙÔ˘˜ Ó· ·Ó·ÛÙ¤ÏÏÔ˘Ó Û¯ÂÙÈο ÂÚÈÛÛfiÙÂÚÔ ÙËÓ COX-1 ‹ ÙËÓ COX-2.

™ÙÔ ‰Â‡ÙÂÚÔ Ì¤ÚÔ˜ Ù˘ ·Ó¿Ï˘Û˘ Û˘ÁÎÚ›ıËÎ·Ó ÔÈ coxibs Ì ٷ ÌË ÂÎÏÂÎÙÈο NSAIDs ‹ ÙË naproxen. ™ÙË Û‡ÁÎÚÈÛË ÙˆÓ ÌË ÂÎÏÂÎÙÈÎÒÓ NSAIDs Ì ÙȘ coxibs ‰ÂÓ ·Ú·ÙËÚ‹ıËÎ·Ó ÛËÌ·ÓÙÈΤ˜ ‰È·ÊÔÚ¤˜ fiÛÔÓ ·ÊÔÚ¿ ÙËÓ Â›ÙˆÛË ÙˆÓ ·ÁÁÂÈ·ÎÒÓ Û˘Ì‚·Ì¿ÙˆÓ. ™ÙË Û‡ÁÎÚÈÛË ÙˆÓ coxibs Ì ÙË naproxen ·Ú·ÙËÚ‹ıËΠÛËÌ·ÓÙÈ΋ ·‡ÍËÛË Û˘ÓÔÏÈο ÙˆÓ ·ÁÁÂÈ·ÎÒÓ ÂÂÈÛÔ‰›ˆÓ Î·È ÙˆÓ √∂ª. ∂ÈϤÔÓ ‰ÂÓ ·Ú·ÙËÚ‹ıËÎ·Ó ÛËÌ·ÓÙÈΤ˜ ‰È·ÊÔÚ¤˜ fiÛÔÓ ·ÊÔÚ¿ ÙËÓ Â›ÙˆÛË ÙˆÓ ∞∂∂ Î·È ÙÔ˘ ·ÁÁÂÈ·ÎÔ‡ ı·Ó¿ÙÔ˘. ∞ÎfiÌË ¤ÁÈÓ ¤ÌÌÂÛË Û‡ÁÎÚÈÛË ÙˆÓ ÌË ÂÎÏÂÎÙÈÎÒÓ NSAIDs Ì ÙÔ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ ÁÈ· ÙËÓ ÂÎÙ›ÌËÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ·ÁÁÂÈ·Îfi ÂÂÈÛfi‰ÈÔ. ™˘ÁÎÂÎÚÈ̤ӷ ÂÎÙÈÌ‹ıËÎ·Ó Ù· ÛÙÔȯ›· Ô˘ ÚԤ΢„·Ó ·fi ÙË Û‡ÁÎÚÈÛË ÙˆÓ ÌË ÂÎÏÂÎÙÈÎÒÓ NSAIDs Ì ÙȘ coxibs Î·È ÙȘ coxibs Ì ÙÔ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ. ∏ ÌÂϤÙË ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ ¤‰ÂÈÍ fiÙÈ Ë diclofenac Î·È Ë ibuprofen ·˘Í¿ÓÔ˘Ó Ù· ·ÁÁÂȷο ÂÂÈÛfi‰È·11.

™Â 121 ÌÂϤÙ˜ ÔÈ ·ÛıÂÓ›˜ ¤·ÈÚÓ·Ó coxibs ÁÈ· 1 ¤ÙÔ˜ ‹ ÂÚÈÛÛfiÙÂÚÔ Î·È ÛËÌÂÈÒıËÎ·Ó ÂÚÈÛÛfiÙÂÚ· ·fi Ù· 2/3 ÙˆÓ ·ÁÁÂÈ·ÎÒÓ ÂÂÈÛÔ‰›ˆÓ. ™Â 112 ÌÂϤÙ˜ Ë Ì¤ÛË ‰È¿ÚÎÂÈ· ıÂÚ·›·˜ ‹Ù·Ó 11 ‚‰ÔÌ¿‰Â˜. ∞ÎfiÌË ÂÎÙfi˜ ·fi ÙË celecoxib ‰ÂÓ ˘‹Ú¯·Ó ·ÚÎÂÙ¿ ‰Â‰Ô̤ӷ Ô˘ Ó· Û˘Û¯ÂÙ›˙Ô˘Ó ÙË ‰fiÛË ÙˆÓ Ê·ÚÌ¿ÎˆÓ Ì ÙËÓ ·‡ÍËÛË ÙˆÓ ·ÁÁÂÈ·ÎÒÓ ÂÂÈÛÔ‰›ˆÓ ÁÈ· ÙȘ ÂÚÈÛÛfiÙÂÚ˜ coxibs11. Δ· NSAIDs ·˘Í¿ÓÔ˘Ó ÙËÓ ·ÚÙËÚȷ΋ ›ÂÛË. ¶ÔÏϤ˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ ‰ÂÓ ˘¿Ú¯ÂÈ ÛËÌ·ÓÙÈ΋ ‰È·ÊÔÚ¿ ÌÂٷ͇ ÙˆÓ ÌË ÂÎÏÂÎÙÈÎÒÓ NSAIDs Î·È ÙˆÓ coxibs fiÛÔÓ ·ÊÔÚ¿ ÙËÓ ·‡ÍËÛË Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘21.

™‡Á¯ÚÔÓ˜ Ô‰ËÁ›Â˜ ¶ÚfiÛÊ·Ù· ‰ËÌÔÛȇÙËÎ·Ó Ô‰ËÁ›Â˜ ÁÈ· ÙË ¯ÔÚ‹ÁËÛË ·Ó·ÏÁËÙÈÎÒÓ Ê·ÚÌ¿ÎˆÓ Û ·ÛıÂÓ›˜ Ì ÈÛÙÔÚÈÎfi ·ÁÁÂÈ·ÎÔ‡ ÂÂÈÛÔ‰›Ô˘ ‹ Ì ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÈÛ¯·ÈÌÈ΋ ηډȷ΋ ÓfiÛÔ22. ∞Ú¯Èο Ú¤ÂÈ Ó· ‰›ÓÔÓÙ·È ·ÛÊ·Ï‹

Ê¿Ú̷η ÛÙË ¯·ÌËÏfiÙÂÚË ‰˘Ó·Ù‹ ‰fiÛË ÁÈ· ÙÔÓ ¤ÏÂÁ¯Ô ÙˆÓ Û˘Ìو̿وÓ. ∞ÛÊ·Ï‹ Ê¿Ú̷η ıˆÚÔ‡ÓÙ·È Ë ·Ú·ÎÂÙ·ÌfiÏË, Ë ·ÛÈÚ›ÓË, Ë tramadol, Î·È Ù· Ó·ÚΈÙÈο ·Ó·ÏÁËÙÈο (ÁÈ· ‚Ú·¯‡ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ·). ∂ÓÙÔ‡ÙÔȘ Ë ·ÛÈÚ›ÓË ÚÔηÏ› ·ÈÌÔÚÚ·Á›· ·fi ÙÔÓ ÂÙÈÎfi ۈϋӷ Î·È Ë ·Ú·ÎÂÙ·ÌfiÏË Ë·ÙÔÙÔÍÈÎfiÙËÙ· Û ˘„ËϤ˜ ‰fiÛÂȘ. ΔÔ ÂfiÌÂÓÔ ‚‹Ì· fiÙ·Ó ·˘Ù¿ Ù· Û¯ÂÙÈο ·ÛÊ·Ï‹ Ê¿Ú̷η ‰ÂÓ Â›Ó·È ·ÔÙÂÏÂÛÌ·ÙÈο Â›Ó·È Ë ¯ÔÚ‹ÁËÛË NSAIDs, Ù· ÔÔ›· Â›Ó·È ÈÔ ÈÛ¯˘Ú¿ ·Ó·ÏÁËÙÈο Ê¿Ú̷η, ·ÏÏ¿ Û¯ÂÙ›˙ÔÓÙ·È Ì ·˘ÍË̤ÓÔ Î·Ú‰È·ÁÁÂÈ·Îfi ΛӉ˘ÓÔ. ŸÛÔ ÌÂÁ·Ï‡ÙÂÚË Â›Ó·È Ë ·Ó·ÛÙÔÏ‹ Ù˘ COX-2, ÙfiÛÔ ÌÂÁ·Ï‡ÙÂÚÔ Â›Ó·È ÙÔ ·Ó·ÏÁËÙÈÎfi ·ÔÙ¤ÏÂÛÌ·, Ô Î›Ó‰˘ÓÔ˜ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ·ÈÌÔÚÚ·ÁÈÒÓ ·fi ÙÔ Á·ÛÙÚÂÓÙÂÚÈÎfi ÌÂÈÒÓÂÙ·È Î·È Ô Î›Ó‰˘ÓÔ˜ ÁÈ· ·ÁÁÂȷο ÂÂÈÛfi‰È· ·˘Í¿ÓÂÙ·È. º¿Ú̷η ÚÒÙ˘ ÂÈÏÔÁ‹˜ Â›Ó·È Ù· ÌË ÂÎÏÂÎÙÈο NSAIDs Ì ۯÂÙÈο ÈÔ ÈÛ¯˘Ú‹ COX-1 ‰Ú¿ÛË. √È Û˘ÁÁÚ·Ê›˜ ÚÔÙ›ÓÔ˘Ó ÙË napro-

15

™∂¶Δ∂ªμƒπ√™ 2008

xen. ∞Ó ÙÔ ·Ó·ÏÁËÙÈÎfi ·ÔÙ¤ÏÂÛÌ· ‰ÂÓ Â›Ó·È ÈηÓÔÔÈËÙÈÎfi, Ê¿Ú̷η ‰Â‡ÙÂÚ˘ ÂÈÏÔÁ‹˜ Â›Ó·È Ù· ÌË ÂÎÏÂÎÙÈο NSAIDs Ì ۯÂÙÈο ÈÔ ÈÛ¯˘Ú‹ COX-2 ‰Ú¿ÛË. ΔÚ›Ù˘ ÂÈÏÔÁ‹˜ Ê¿Ú̷η Â›Ó·È ÔÈ ÂÎÏÂÎÙÈÎÔ› ·Ó·ÛÙÔÏ›˜ Ù˘ COX-2 (coxibs). Δ· NSAIDs Ú¤ÂÈ Ó· ‰›ÓÔÓÙ·È ÌÂÙ¿ ·fi ÚÔÛÂÎÙÈ΋ ÂÎÙ›ÌËÛË ÙÔ˘ ·Ó·ÏÁËÙÈÎÔ‡ ·ÔÙÂϤÛÌ·ÙÔ˜ Î·È ÙÔ˘ ·ÁÁÂÈ·ÎÔ‡ ÎÈÓ‰‡ÓÔ˘ Û ·ÛıÂÓ›˜ ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ·ÁÁÂÈ·Îfi ÂÂÈÛfi‰ÈÔ. ∂ÈϤÔÓ Ú¤ÂÈ Ó· ¯ÔÚËÁÔ‡ÓÙ·È ÛÙË ÌÈÎÚfiÙÂÚË ‰˘Ó·Ù‹ ‰fiÛË Î·È ÁÈ· ÙÔ ÌÈÎÚfiÙÂÚÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ·. Œ¯ÂÈ È‰È·›ÙÂÚË ÛËÌ·Û›· Ë Ù·ÎÙÈ΋ ·Ú·ÎÔÏÔ‡ıËÛË ÙˆÓ ·ÛıÂÓÒÓ (̤ÙÚËÛË Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘, ÂÎÙ›ÌËÛË ÙÔ˘ ÂÚÈÊÂÚÈÎÔ‡ Ôȉ‹Ì·ÙÔ˜, Ù˘ ÓÂÊÚÈ-

΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ Î·È ·ÔÎÏÂÈÛÌfi˜ Ù˘ ·ÈÌÔÚÚ·Á›·˜ ·fi ÙÔ Á·ÛÙÚÂÓÙÂÚÈÎfi). ∂ÈϤÔÓ ÚÔÙ›ÓÂÙ·È Ë ÚÔÛı‹ÎË ·ÛÈÚ›Ó˘ Û ·ÛıÂÓ›˜ ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ·ÁÁÂÈ·Îfi ÂÂÈÛfi‰ÈÔ Ô˘ ·›ÚÓÔ˘Ó NSAIDs. ∂ÓÙÔ‡ÙÔȘ ÛËÌÂÈÒÓÂÙ·È fiÙÈ Ë ·ÛÈÚ›ÓË ‰ÂÓ ·ÔÎÏ›ÂÈ ÙËÓ ÂÌÊ¿ÓÈÛË ÂÓfi˜ ·ÁÁÂÈ·ÎÔ‡ Û˘Ì‚¿Ì·ÙÔ˜ Î·È ·˘Í¿ÓÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ·ÈÌÔÚÚ·Á›·˜ ·fi ÙÔ Á·ÛÙÚÂÓÙÂÚÈÎfi22. ¶ÚfiÛÊ·Ù· ‰ËÌÔÛȇıËΠÌÈ· ÌÂϤÙË Ô˘ ۯ‰ȿÛÙËΠÁÈ· Ó· ··ÓÙ‹ÛÂÈ ÛÙÔ ÂÚÒÙËÌ· ÔÈ· NSAIDs Â›Ó·È ÈÔ ·ÛÊ·Ï‹ ÁÈ· ÙÔ˘˜ ·ÛıÂÓ›˜ ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ·ÁÁÂÈ·Îfi ÂÂÈÛfi‰ÈÔ Ô˘ ·›ÚÓÔ˘Ó ‹‰Ë ·ÛÈÚ›ÓË. √È Û˘ÁÁÚ·Ê›˜ ÂÎÙ›ÌËÛ·Ó ÙÔÓ Î·Ú‰È·Á-

ÁÂÈ·Îfi ΛӉ˘ÓÔ Î·È ÙÔÓ Î›Ó‰˘ÓÔ ÁÈ· ·ÈÌÔÚÚ·Á›· ·fi ÙÔ Á·ÛÙÚÂÓÙÂÚÈÎfi Î·È ÚfiÙÂÈÓ·Ó ˆ˜ ηٷÏÏËÏfiÙÂÚÔ Ê¿ÚÌ·ÎÔ ÙȘ coxibs Û ۇÁÎÚÈÛË Ì ٷ ÌË ÂÎÏÂÎÙÈο NSAIDs23. ∂›Ó·È ·ÍÈÔÛËÌ›ˆÙÔ fiÙÈ Ù· ÌË ÂÎÏÂÎÙÈο NSAIDs ÂÎÙfi˜ ·fi ÙËÓ ·‡ÍËÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ·ÈÌÔÚÚ·Á›· ·fi ÙÔ Á·ÛÙÚÂÓÙÂÚÈÎfi, ·ÏÏËÏÂȉÚÔ‡Ó Ì ÙËÓ ·ÛÈÚ›ÓË. ∏ ibuprofen ·ÓÙ·ÁˆÓ›˙ÂÙ·È ÙËÓ ·ÛÈÚ›ÓË Î·È ÌÂÈÒÓÂÈ ÙËÓ ·ÓÙÈ·ÈÌÔÂÙ·Ïȷ΋ Ù˘ ‰Ú¿ÛË Î·È Ú¤ÂÈ Ó· ‰›ÓÂÙ·È 30 ÏÂÙ¿ ÌÂÙ¿ ‹ 8 ÒÚ˜ ÚÈÓ ÙËÓ ·ÛÈÚ›ÓË. ∏ ·Ú·ÎÂÙ·ÌfiÏË Î·È Ë diclofenac ‰ÂÓ ÂËÚ¿˙Ô˘Ó ÙËÓ ·ÓÙÈ·ÈÌÔÂÙ·Ïȷ΋ ‰Ú¿ÛË Ù˘ ·ÛÈÚ›Ó˘. øÛÙfiÛÔ ÁÈ· Ù· ˘fiÏÔÈ· NSAIDs ‰ÂÓ ˘¿Ú¯Ô˘Ó ·ÚÎÂÙ¿ ÛÙÔȯ›·24.

μÈ‚ÏÈÔÁÚ·Ê›· 1. Solomon SD, McMurray JJ, Pfeffer MA, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005; 352: 1071-1080.

2. Bombardier C, Laine L, Reicin A, et al.

Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis: VIGOR Study Group. N Engl J Med. 2000; 343: 1520 -1528.

3. Bresalier RS, Sandler RS, Quan H, et al.

Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005; 352: 1092-102.

4.

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6. Cannon CP, Curtis SP, Bolognese JA, Laine L; MEDAL Steering Committee.Clinical trial design and patient demographics of the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) study program: cardiovascular outcomes with etoricoxib versus diclofenac in patients with osteoarthritis and rheumatoid arthritis.

Am Heart J. 2006; 152: 237-245.

7. Antman EM, DeMets D, Loscalzo J. Cyclooxygenase inhibition and cardiovascular risk. Circulation. 2005; 112: 759-70.

8. Foegh ML, Hartmann DP, Rowles JR, Khirabadi BS, Alijani MR, Helfrich GB, Ramwell PW. Leukotrienes, thromboxane, and platelet activating factor in organ

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13. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R; Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002; 360: 1903-13.

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∫§π¡π∫∂™ ª∂§∂Δ∂™

ªÂϤÙË CORONA (COntrolled ROsuvastatin in MultinatioNAl Trial in Heart Failure) ƒÔÛÔ˘‚·ÛÙ·Ù›ÓË Û ËÏÈÎȈ̤ÓÔ˘˜ ·ÛıÂÓ›˜ ÌÂ Û˘ÛÙÔÏÈ΋ ηډȷ΋ ·ÓÂ¿ÚÎÂÈ· Kjekshus J, Apetrei E, Barrios V, Böhm M, Cleland JG, Cornel JH, Dunselman P, Fonseca C, Goudev A, Grande P, Gullestad L, Hjalmarson A, Hradec J, Jànosi A, Kamensky G, Komajda M, Korewicki J, Kuusi T, Mach F, Mareev V, McMurray JJ, Ranjith N, Schaufelberger M, Vanhaecke J, van Veldhuisen DJ, Waagstein F, Wedel H, Wikstrand J; CORONA Group.

N Engl J Med. 2007 Nov 29;357(22):2248-61. ∏ ‰Ú¿ÛË ÙˆÓ ÛÙ·ÙÈÓÒÓ ÛÙËÓ Î·Ú‰È·Î‹ ·ÓÂ¿ÚÎÂÈ· ‰ÂÓ Â›Ó·È ÁÓˆÛÙ‹, ÂÂȉ‹ Ë Î·Ú‰È·Î‹ ·ÓÂ¿ÚÎÂÈ· ‹Ù·Ó ÎÚÈÙ‹ÚÈÔ ·ÔÎÏÂÈÛÌÔ‡ ·fi ÙȘ ÌÂÁ¿Ï˜ ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ ‰Â˘ÙÂÚÔÁÂÓÔ‡˜ ÚfiÏ˄˘. ∏ ·Ó·‰ÚÔÌÈ΋ ·Ó¿Ï˘ÛË ÌÂÚÈÎÒÓ ÌÂÏÂÙÒÓ ¤‰ˆÛ ·Û·Ê‹ Î·È ·ÓÙÈÊ·ÙÈο ·ÔÙÂϤÛÌ·Ù·. ∏ ÚÒÙË ÚÔÔÙÈ΋ ÎÏÈÓÈ΋ ÌÂϤÙË Ù˘ ‰Ú¿Û˘ ÙˆÓ ÛÙ·ÙÈÓÒÓ ÛÙËÓ Î·Ú‰È·Î‹ ·ÓÂ¿ÚÎÂÈ· Â›Ó·È Ë CORONA. ¶ÚfiÎÂÈÙ·È ÁÈ· ÌÈ· ÔÏ˘ÎÂÓÙÚÈ΋, Ù˘¯·ÈÔÔÈË̤ÓË, ÂÏÂÁ¯fiÌÂÓË Ì ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ ÌÂϤÙË Ô˘ ‰ÈÂÍ‹¯ıË ÛÙËÓ ∂˘ÚÒË, ÙË ƒˆÛ›· Î·È ÙË ¡fiÙÈÔ ∞ÊÚÈ΋. ¶ÂÚȤϷ‚ 5.011 ·ÛıÂÓ›˜, ËÏÈΛ·˜ ¿Óˆ ÙˆÓ 60 ÂÙÒÓ, ÌÂ Û˘ÛÙÔÏÈ΋ ηډȷ΋ ·ÓÂ¿ÚÎÂÈ· ÈÛ¯·ÈÌÈ΋˜ ·ÈÙÈÔÏÔÁ›·˜, (ÎÏ¿ÛÌ· ÂÍÒıËÛ˘ <40%), ÏÂÈÙÔ˘ÚÁÈÎÔ‡ ÛÙ·‰›Ô˘ ηٿ ¡À∏∞ ππ (37%), πππ (62%), ‹ IV, Ô˘ ‰ÂÓ Â›¯·Ó ¤Ó‰ÂÈÍË ÛÙ·Ù›Ó˘. ∞ÔÎÏ›ÛıËÎ·Ó ·ÛıÂÓ›˜ Ì ·ÛÙ·ı‹ ÛÙËı¿Á¯Ë ‹ ÚfiÛÊ·ÙÔ ¤ÌÊÚ·ÁÌ· ÙÔ˘ Ì˘Ôηډ›Ô˘, ÌË ·ÓÙÈÚÚÔÔ‡ÌÂÓË Î·Ú‰È·Î‹ ·ÓÂ¿ÚÎÂÈ·, ÚˆÙÔ·ı›˜ ‚·Ï‚ȉÔ¿ıÂȘ Ì ‰ÈÔÚıˆÌ¤Ó˜, ˘ÂÚÙÚÔÊÈ΋ Ì˘ÔηډÈÔ¿ıÂÈ· Î·È ·ÛıÂÓ›˜ Ì Ë·ÙÈ΋ ‹ ÓÂÊÚÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·. √È ·ÛıÂÓ›˜ ηٷÓÂÌ‹ıËÎ·Ó Ù˘¯·›· Ó· Ï¿‚Ô˘Ó 10 mg ÚÔÛÔ˘‚·ÛÙ·Ù›Ó˘ ÙËÓ Ë̤ڷ ‹ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ. ¶ÚˆÙ‡ÔÓ Î·Ù·ÏËÎÙÈÎfi ÛËÌÂ›Ô ÔÚ›ÛıËΠÙÔ ¿ıÚÔÈÛÌ· ÙˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ ı·Ó¿ÙˆÓ Î·È ÙˆÓ ÌË ı·Ó·ÙËÊfiÚˆÓ ÂÌÊÚ·ÁÌ¿ÙˆÓ ÙÔ˘ Ì˘Ôηډ›Ô˘ Î·È ·ÁÁÂÈ·ÎÒÓ ÂÁÎÂÊ·ÏÈÎÒÓ. ¢Â˘ÙÂÚ‡ÔÓÙ· ηٷÏËÎÙÈο ÛËÌ›· ‹Ù·Ó: Ô ı¿Ó·ÙÔ˜ ·fi ÔÔÈ·‰‹ÔÙ ·ÈÙ›·, οı ÛÙÂÊ·ÓÈ·›Ô ÂÂÈÛfi‰ÈÔ, Ô ı¿Ó·ÙÔ˜ ·fi ηډȷÁÁÂȷο ·›ÙÈ· Î·È ÔÈ ÂÈÛ·ÁˆÁ¤˜ ÛÙ· ÓÔÛÔÎÔÌ›·. ∞ÔÙÂϤÛÌ·Ù·: ∏ ÔÌ¿‰· ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ¤Ï·‚ ÚÔÛÔ˘‚·ÛÙ·Ù›ÓË ÂÌÊ¿ÓÈÛ ÂÏ¿ÙÙˆÛË Ù˘ LDL-¯ÔÏËÛÙÂÚfiÏ˘ (‰È·ÊÔÚ¿ ÌÂٷ͇ ÙˆÓ ÔÌ¿‰ˆÓ 45%, ƒ<0,001) Î·È Ù˘ CRP (‰È·ÊÔÚ¿ ÌÂٷ͇ ÙˆÓ ÔÌ¿‰ˆÓ

¶›Ó·Î·˜ 1. ∞ÚÈıÌfi˜ ÂÈÛ·ÁˆÁÒÓ Û ÓÔÛÔÎÔÌ›·, ηٿ ·ÈÙ›· ÂÈÛ·ÁˆÁ‹˜ ∞ÈÙ›· ÂÈÛ·ÁˆÁ‹˜

Placebo, n=2497 (n)

Rosuvastatin, n=2514 (n)

∞fi οı ·ÈÙ›·

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3694

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2564

2193

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1299

1109

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37,1%, ƒ<0,001). ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ (‰È¿ÌÂÛË ‰È¿ÚÎÂÈ· 32,8 Ì‹Ó˜) ·Ú·ÙËÚ‹ıËÎ·Ó 692 ÂÚÈÙÒÛÂȘ ÚˆÙ‡ÔÓÙÔ˜ ηٷÏËÎÙÈÎÔ‡ ÛËÌ›Ԣ ÛÙËÓ ÔÌ¿‰· Ù˘ ÚÔÛÔ˘‚·ÛÙ·Ù›Ó˘ Î·È 732 ÛÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘ (HR 0,92: 95% CI 0,83 - 1,02: P = 0,12). ¢ÂÓ ˘‹ÚÍ Â›Û˘ ÛÙ·ÙÈÛÙÈÎÒ˜ ÛËÌ·ÓÙÈ΋ ‰È·ÊÔÚ¿ ÛÙÔÓ ·ÚÈıÌfi ÙˆÓ ı·Ó¿ÙˆÓ, ›Ù ·fi ÔÔÈÔ‰‹ÔÙ ·›ÙÈÔ Â›Ù ·fi ηډȷÁÁÂȷο ÓÔÛ‹Ì·Ù· Ô‡Ù ÛÙÔÓ ·ÚÈıÌfi ÙˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ ÂÂÈÛÔ‰›ˆÓ. ™ÙÔ ÌfiÓÔ ‰Â˘ÙÂÚ‡ÔÓ Î·Ù·ÏËÎÙÈÎfi ÛËÌÂ›Ô ÛÙÔ ÔÔ›Ô ·Ú·ÙËÚ‹ıËΠÛÙ·ÙÈÛÙÈÎÒ˜ ÛËÌ·ÓÙÈ΋ ‰È·ÊÔÚ¿ ÌÂٷ͇ ÙˆÓ ‰‡Ô ÔÌ¿‰ˆÓ ‹Ù·Ó Ô ·ÚÈıÌfi˜ ÙˆÓ ÂÈÛ·ÁˆÁÒÓ Û ÓÔÛÔÎÔÌ›· (¶›Ó·Î·˜ 1) √È ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ, Û˘ÌÂÚÈÏ·Ì‚·ÓÔÌ¤ÓˆÓ ÙˆÓ ÚÔ‚ÏËÌ¿ÙˆÓ ·fi ÙÔ˘˜ ̇˜, ·Ú·ÙËÚ‹ıËÎ·Ó Û ›ÛÔ ÔÛÔÛÙfi Î·È ÛÙȘ ‰‡Ô ÔÌ¿‰Â˜. ∂› ÙÔ˘ ÈÂÛÙËÚ›Ô˘: ∂ÓÒ Â›¯Â ‰Ôı› Ë ‡ÏË ÙÔ˘ ÂÚÈÔ‰ÈÎÔ‡ ÛÙÔ Ù˘ÔÁÚ·ÊÂ›Ô Î·È Ï›ÁÔ ÚÈÓ ÙËÓ ÂÎÙ‡ˆÛË, ÛÙȘ 30 ∞˘ÁÔ‡ÛÙÔ˘ 2008, ·Ó·ÎÔÈÓÒıËÎ·Ó ÛÙÔ ∂˘Úˆ·˚Îfi ∫·Ú‰ÈÔÏÔÁÈÎfi ™˘Ó¤‰ÚÈÔ, ÛÙÔ ªfiÓ·¯Ô, Ù· ·ÔÙÂϤÛÌ·Ù· Ù˘ ÌÂϤÙ˘ GISSI-HF, Ù· ÔÔ›· ÂȂ‚·ÈÒÓÔ˘Ó Ù· Â˘Ú‹Ì·Ù· Ù˘ CORONA. ∏ GISSI-HF ‰ÈÂÍ‹¯ıË ÛÙËÓ πÙ·Ï›·, Â›Ó·È ÔÏ˘ÎÂÓÙÚÈ΋ ÌÂϤÙË, Ù˘¯·ÈÔÔÈË̤ÓË Î·È ÂÚȤϷ‚ 4.574 ·ÛıÂÓ›˜ ¿Óˆ ÙˆÓ 18 ÂÙÒÓ, Ì ¯ÚfiÓÈ· ηډȷ΋ ·ÓÂ¿ÚÎÂÈ· ÏÂÈÙÔ˘ÚÁÈÎÔ‡ ÛÙ·‰›Ô˘ ππ ¤ˆ˜ IV ηٿ NYHA, ·ÓÂÍ¿ÚÙËÙ· ·ÈÙÈÔÏÔÁ›·˜ Î·È ÎÏ¿-

p

ÛÌ·ÙÔ˜ Â͈ı‹Ûˆ˜. √È ÌÈÛÔ› ·ÛıÂÓ›˜ ¤Ï·‚·Ó 10 mg ÚÔÛÔ˘‚·ÛÙ·Ù›Ó˘ ËÌÂÚËÛ›ˆ˜ Î·È ÔÈ ¿ÏÏÔÈ ÌÈÛÔ› ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ. ∏ ̤ÛË ‰È¿ÚÎÂÈ· ·Ú·ÎÔÏÔ‡ıËÛ˘ ‹Ù·Ó 3,9 ¤ÙË Î·È ˆ˜ ÚˆÙ‡ÔÓÙ· ηٷÏËÎÙÈο ÛËÌ›· ›¯·Ó ÔÚÈÛı› Ô ·ÚÈıÌfi˜ ÙˆÓ ı·Ó¿ÙˆÓ Î·È ÙÔ ¿ıÚÔÈÛÌ· ÙˆÓ ı·Ó¿ÙˆÓ Î·È ÙˆÓ ÂÈÛ·ÁˆÁÒÓ Û ÓÔÛÔÎÔÌ›· ÁÈ· ηډȷÁÁÂȷο ·›ÙÈ·. ¢ÂÓ ·Ú·ÙËÚ‹ıËΠη̛· ‰È·ÊÔÚ¿ ÌÂٷ͇ ÙˆÓ ‰‡Ô ÔÌ¿‰ˆÓ ÛÙ· ÚˆÙ‡ÔÓÙ· ηٷÏËÎÙÈο ÛËÌ›·. √ ·ÚÔ˘ÛÈ·ÛÙ‹˜ ηıËÁËÙ‹˜ Gianni Tognoni ¯·Ú·ÎÙ‹ÚÈÛ ٷ Â˘Ú‹Ì·Ù· Ù˘ ÌÂϤÙ˘ Ô˘‰¤ÙÂÚ· Î·È fi¯È ·ÚÓËÙÈο, ‰Â‰Ô̤ÓÔ˘ fiÙÈ ÔÈ ·ÛıÂÓ›˜ Ô˘ ‹Ú·Ó ÚÔÛÔ˘‚·ÛÙ·Ù›ÓË ‰ÂÓ ˘¤ÛÙËÛ·Ó Î·ÌÈ¿ ‚Ï¿‚Ë, Ô Û¯ÔÏÈ·ÛÙ‹˜ fï˜ ηıËÁËÙ‹˜ Phillip PoolWilson › fiÙÈ ÔÈ ·ÛıÂÓ›˜ Ô˘ ‚Ú›ÛÎÔÓÙ·È ‹‰Ë ˘fi ·˘Ù‹ ÙËÓ ·ÁˆÁ‹ ı· Ú¤ÂÈ «Èı·Ófiٷٷ» Ó· ÙËÓ ‰È·Îfi„Ô˘Ó. ™Â ¤Ó· ¿ÏÏÔ ÛΤÏÔ˜ Ù˘ ›‰È·˜ ÌÂϤÙ˘ ‰È·ÈÛÙÒıËΠfiÙÈ 1 ÁÚ·ÌÌ¿ÚÈÔ ˆ-3 ÏÈ·ÚÒÓ ÔͤˆÓ ÙËÓ Ë̤ڷ ÛÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜ Ì›ˆÛ ÙÔ˘˜ ı·Ó¿ÙÔ˘˜ ηٿ 9% (p=0.041) Î·È ÙÔ ¿ıÚÔÈÛÌ· ı·Ó¿ÙˆÓ Î·È ÂÈÛ·ÁˆÁÒÓ Û ÓÔÛÔÎÔÌ›· ηٿ 8% (p=0.009). ¶ÂÚÈÛÛfiÙÂÚ· ÁÈ· ÙË ÛËÌ·ÓÙÈ΋ ·˘Ù‹ ÌÂϤÙË ı· ·Ó·Ê¤ÚÔ˘Ì ÛÙÔ ÂfiÌÂÓÔ Ù‡¯Ô˜. ™˘ÌÂÚ·ÛÌ·ÙÈο, Ë ÚÔÛÔ˘‚·ÛÙ·Ù›ÓË ‰ÂÓ ÚÔÛʤÚÂÈ Î·Ó¤Ó· fiÊÂÏÔ˜ Û ·ÛıÂÓ›˜ Ì ηډȷ΋ ·ÓÂ¿ÚÎÂÈ· ÔÔÈ·Û‰‹ÔÙ ·ÈÙÈÔÏÔÁ›·˜ ‹ ‚·Ú‡ÙËÙ·˜. ∂È̤ÏÂÈ·: ∏Ï›·˜ ÃÂÈÌÒÓ·˜

17

™∂¶Δ∂ªμƒπ√™ 2008

¢ÔÌ‹ Î·È §ÂÈÙÔ˘ÚÁ›· ÙˆÓ À„ËÏ‹˜ ¶˘ÎÓfiÙËÙ·˜ §ÈÔÚˆÙÂ˚ÓÒÓ ÛÙÔ ªÂÙ·‚ÔÏÈÎfi ™‡Ó‰ÚÔÌÔ ∫ˆÓÛÙ·ÓÙ›ÓÔ˜ §·Áfi˜, ∂ÈÛÙËÌÔÓÈÎfi˜ ™˘ÓÂÚÁ¿Ù˘ ÙÔ˘ π·ÙÚ›Ԣ ¢È·Ù·Ú·¯ÒÓ ÙÔ˘ ªÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ §Èȉ›ˆÓ, ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô πˆ·ÓÓ›ÓˆÓ ªˆ˘Û‹˜ ∂ÏÈÛ¿Ê, ∫·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜, ΔÔ̤·˜ ¶·ıÔÏÔÁ›·˜, π·ÙÚÈ΋ ™¯ÔÏ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ

∂ÈÛ·ÁˆÁ‹ ¶ÚfiÛÊ·Ù˜, ÌÂÁ¿Ï˜, ÚÔÔÙÈΤ˜, ÂȉËÌÈÔÏÔÁÈΤ˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ Ë Ì›ˆÛË Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ ÙˆÓ ˘„ËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙÂ˚ÓÒÓ (high dencity lipoproteins, HDL) ηٿ 1 mg/dl ·˘Í¿ÓÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ηډȷÁÁÂȷ΋˜ ÓfiÛÔ˘ ηٿ 3% ÛÙȘ Á˘Ó·›Î˜ Î·È 2% ÛÙÔ˘˜ ¿ÓÙÚ˜ (1). ªÂ›ˆÛË Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ ÙˆÓ HDL (HDL ¯ÔÏËÛÙÂÚfiÏ˘) Î·È ·‡ÍËÛË ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ·Ú·ÙËÚÂ›Ù·È Û˘¯Ó¿ ÛÙ· Ï·›ÛÈ· Ù˘ ·ıËÚˆÁfiÓÔ˘ ‰˘ÛÏÈȉ·ÈÌ›·˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘ (ªÂÙ™) (2). ¡ÂfiÙÂÚ· ‰Â‰Ô̤ӷ ¤‰ÂÈÍ·Ó fiÙÈ Ô ÚfiÏÔ˜ ÙˆÓ HDL Â›Ó·È ÔχÏÔÎÔ˜, ·ÊÔ‡ ·˘Ù¿ Ù· ۈ̷ٛ‰È· ÂÌÊ·Ó›˙Ô˘Ó ‰Ú¿ÛÂȘ ¤Ú· ·fi ÙËÓ ·Ó¿ÛÙÚÔÊË ÌÂÙ·ÊÔÚ¿ Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ Î·È Û˘ÁÎÂÎÚÈ̤ӷ ·ÓÙÈÔÍÂȉˆÙÈΤ˜ Î·È ·ÓÙÈÊÏÂÁÌÔÓÒ‰ÂȘ ‰Ú¿ÛÂȘ (3). ™‡Ìʈӷ Ì ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ Û ·ÛıÂÓ›˜ Ì ªÂÙ™ ·Ú·ÙËÚÂ›Ù·È Ì›ˆÛË Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘ Î·È ÂÍ·Ûı¤ÓËÛË ÙˆÓ ·ÓÙÈÔÍÂȉˆÙÈÎÒÓ Î·È ·ÓÙÈÊÏÂÁÌÔÓˆ‰ÒÓ È‰ÈÔÙ‹ÙˆÓ ÙˆÓ HDL ۈ̷Ùȉ›ˆÓ (4,5). ™ÙË Û˘Ó¤¯ÂÈ· ı· Û˘˙ËÙËıÔ‡Ó Ù· ÓÂfiÙÂÚ· ‰Â‰Ô̤ӷ fiÛÔÓ ·ÊÔÚ¿ ÙË ‰ÔÌ‹ Î·È ÏÂÈÙÔ˘ÚÁ›· ÙˆÓ HDL ˘fi Ê˘ÛÈÔÏÔÁÈΤ˜ Û˘Óı‹Î˜ Î·È Î˘Ú›ˆ˜ Û ·ÛıÂÓ›˜ Ì ªÂÙ™.

ªÂÙ·‚ÔÏÈÛÌfi˜ HDL √ Û¯ËÌ·ÙÈÛÌfi˜ ÙˆÓ HDL ۈ̷Ùȉ›ˆÓ ÍÂÎÈÓ¿ Ì ÙË Û‡ÓıÂÛË Ù˘ ·ÔÏÈÔÚˆÙ½Ó˘ ∞1 (apoA1) Î·È ÙËÓ ·ÂÏ¢ı¤ÚˆÛ‹ Ù˘ ÛÙÔ Ï¿ÛÌ·. ∏ apoA1 Â›Ó·È ÌÈ· ÚˆÙ½ÓË Ì 243 ·ÌÈÓÔͤ· Ô˘ Û˘ÓÙ›ıÂÙ·È Î‡ÚÈ· ÛÙÔ ‹·Ú, ·ÏÏ¿ Î·È ÛÙ· ·ÙÙ·Ú· ÙÔ˘ ÂÓÙ¤ÚÔ˘. ∂›Û˘ Ë apoA1 ·ÂÏ¢ıÂÚÒÓÂÙ·È

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ÛÙÔ ·›Ì· ηٿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ηٷ‚ÔÏÈÛÌÔ‡ ÙˆÓ ¯˘ÏÔÌÈÎÚÒÓ (6). ∏ apoA1 Û˘Ó‰¤ÂÙ·È Ì ʈÛÊÔÏÈ›‰È· Î·È ¯ÔÏËÛÙÂÚfiÏË Ì ·ÔÙ¤ÏÂÛÌ· ÙÔ Û¯ËÌ·ÙÈÛÌfi ÙˆÓ ·Ú¯¤ÁÔÓˆÓ, ‰ÈÛÎÔÂȉÒÓ ÌÔÚÊÒÓ ÙˆÓ HDL (pre-‚ HDL). √È ·Ú¯¤ÁÔÓ˜ ÌÔÚʤ˜ ÙˆÓ HDL ·ÔÙÂÏÔ‡ÓÙ·È ·fi apoA1, ʈÛÊÔÏÈ›‰È· Î·È ÌÈÎÚ¤˜ ÔÛfiÙËÙ˜ ÂχıÂÚ˘ ¯ÔÏËÛÙÂÚfiÏ˘ (7). Δ· ۈ̷ٛ‰È· ·˘Ù¿ ÚÔÛÏ·Ì‚¿ÓÔ˘Ó ÂÈÚfiÛıÂÙË ¯ÔÏËÛÙÂÚfiÏË Î·È ÊˆÛÊÔÏÈ›‰È· ·fi ÙȘ ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜, ‰È·Ì¤ÛÔ˘ ÙˆÓ ÌÂÙ·ÊÔÚ¤ˆÓ ABCA1 (ATP-binding cassette A1) Ô˘ Û˘Ó‰¤ÔÓÙ·È Ì ÙËÓ apoA1 Î·È ·˘Í¿ÓÔ˘Ó Û ̤ÁÂıÔ˜ (8). ™ÙË Û˘Ó¤¯ÂÈ· Ì ÙË ‰Ú¿ÛË ÙÔ˘ ¤Ó˙˘ÌÔ˘ ÏÂΛıÈÓÔ-¯ÔÏÂÛÙ¤Ú˘Ï-·Î˘ÏÔÙÚ·ÓÛÊÂÚ¿ÛË (lecithin:cholesterol acyltransferase, LCAT) Ë ¯ÔÏËÛÙÂÚfiÏË ÙˆÓ HDL ۈ̷Ùȉ›ˆÓ ÂÛÙÂÚÔÔÈÂ›Ù·È Î·È ÔÈ ÂÛÙ¤Ú˜ ¯ÔÏËÛÙÂÚfiÏ˘ Ô˘ Û¯ËÌ·Ù›˙ÔÓÙ·È ÌÂÙ·ÎÈÓÔ‡ÓÙ·È ÛÙÔ ÂÛˆÙÂÚÈÎfi ÙˆÓ ÛˆÌ·Ùȉ›ˆÓ. ∏ ÌÂٷΛÓËÛË ·˘Ù‹ ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙÔ Û¯ËÌ·ÙÈÛÌfi ÙˆÓ ÒÚÈ̈Ó, ÌÈÎÚÒÓ, ÛÊ·ÈÚÈÎÒÓ HDL ۈ̷Ùȉ›ˆÓ, Ù· ÔÔ›· ·ÓÙÈÛÙÔÈ¯Ô‡Ó ÛÙÔ ˘ÔÎÏ¿ÛÌ· HDL3 Ô˘ Ï·Ì‚¿ÓÂÙ·È Î·Ù¿ ÙËÓ ÈÛÔ˘ÎÓÈ΋ ˘ÂÚÊ˘ÁÔΤÓÙÚËÛË ‚·ıÌ›‰ˆÛ˘ ˘ÎÓÔÙ‹ÙˆÓ (isopycnic dencity gradient ultracentrifugation) ÙˆÓ ÏÈÔÚˆÙÂ˚ÓÒÓ (8). Δ· HDL3 ۈ̷ٛ‰È· Û˘Ó¯›˙Ô˘Ó Ó· ÚÔÛÏ·Ì‚¿ÓÔ˘Ó ¯ÔÏËÛÙÂÚfiÏË ‰È·Ì¤ÛÔ˘ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ABCG1/G4 (ATP-binding cassette G1/G4), Ì ·ÔÙ¤ÏÂÛÌ· ÙË ‰ËÌÈÔ˘ÚÁ›· ÙˆÓ ÒÚÈ̈Ó, ÌÂÁ¿ÏˆÓ, ÛÊ·ÈÚÈÎÒÓ HDL ۈ̷Ùȉ›ˆÓ, Ô˘ ·ÓÙÈÛÙÔÈ¯Ô‡Ó ÛÙÔ ˘ÔÎÏ¿ÛÌ· HDL2 Ù˘ ˘ÂÚÊ˘ÁÔΤÓÙÚËÛ˘ (9). Δ· ÌÂÁ¿Ï·, ÛÊ·ÈÚÈο HDL2 ۈ̷ٛ‰È· ·ÏÏËÏÂȉÚÔ‡Ó Ì ÙȘ

ÏÔ‡ÛȘ Û ÙÚÈÁÏ˘ÎÂÚ›‰È· ÏÈÔÚˆÙ½Ó˜ (low density lipoproteins, LDL Î·È very low density lipoproteins, VLDL) ·ÓÙ·ÏÏ¿˙ÔÓÙ·˜ ÂÛÙ¤Ú˜ ¯ÔÏËÛÙÂÚfiÏ˘ Ì ÙÚÈÁÏ˘ÎÂÚ›‰È·, ‰È·Ì¤ÛÔ˘ ÙÔ˘ ¤Ó˙˘ÌÔ˘ ÌÂÙ·ÊÔÚ¿˜ ÂÛÙ¤ÚˆÓ ¯ÔÏËÛÙÂÚfiÏ˘ (cholesteryl ester transfer protein, CETP) (10). ΔÂÏÈο Ù· HDL2 ۈ̷ٛ‰È· ·ÏÏËÏÂȉÚÔ‡Ó Ì ٷ Ë·ÙÈο ·ÙÙ·Ú· Ì ÂȉÈÎÔ‡˜ ˘ԉԯ›˜ (scavenger receptors type B1, SRB1), ‰È·Ì¤ÛÔ˘ ÙˆÓ ÔÔ›ˆÓ ·Ô‰›‰Ô˘Ó ÂÛÙ¤Ú˜ ¯ÔÏËÛÙÂÚfiÏ˘ ÛÙ· Ë·ÙÔ·ÙÙ·Ú· Î·È ÌÂÙ·ÙÚ¤ÔÓÙ·È ¿ÏÈ ÛÙ· HDL3 ۈ̷ٛ‰È· (11). Δ· ʈÛÊÔÏÈ›‰È· Î·È Ù· ÙÚÈÁÏ˘ÎÂÚ›‰È· Ô˘ ·Ô̤ÓÔ˘Ó ÛÙ· HDL3 ۈ̷ٛ‰È· ˘‰ÚÔχÔÓÙ·È Ì ÙË ‰Ú¿ÛË Ù˘ Ë·ÙÈ΋˜ ÏÈ¿Û˘ (hepatic lipase, HL) Î·È Ù˘ ÚˆÙ½Ó˘ ÌÂÙ·ÊÔÚ¿˜ ʈÛÊÔÏÈȉ›ˆÓ (phospholipid transfer protein, PLTP) Î·È ÙÂÏÈο ·Ô‰ÂÛ̇ÂÙ·È Ë apoA1 (8), ÁÈ· Ó· ÍÂÎÈÓ‹ÛÂÈ Ë ·Ú·ÁˆÁ‹ ·Ú¯¤ÁÔÓˆÓ HDL, ÂÓÒ ¤Ó· ÔÛÔÛÙfi ·˘Ù‹˜ Ù˘ ·ÔÏÈÔÚˆÙ½Ó˘ ·Ô‚¿ÏÏÂÙ·È ·fi ÙÔ˘˜ ÓÂÊÚÔ‡˜ Ì ۈÏËÓ·Úȷ΋ ·¤ÎÎÚÈÛË ‹ ÛÂÈÚ·Ì·ÙÈ΋ ‰È‹ıËÛË (3).

∞ÓÙÈ·ıËÚÔÁfiÓ˜ ‰Ú¿ÛÂȘ ÙˆÓ HDL Δ· HDL ۈ̷ٛ‰È· ÂÈÙÂÏÔ‡Ó ÙÔÓ Ì˯·ÓÈÛÌfi Ù˘ ·Ó¿ÛÙÚÔÊ˘ ÌÂÙ·ÊÔÚ¿˜ Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ ·fi ÙÔ˘˜ ÂÚÈÊÂÚÈÎÔ‡˜ ÈÛÙÔ‡˜ ÚÔ˜ Ù· Ë·ÙÔ·ÙÙ·Ú·. √È Úfi‰ÚÔ̘ ÌÔÚʤ˜ ÙˆÓ HDL ۈ̷Ùȉ›ˆÓ ÚÔÛÏ·Ì‚¿ÓÔ˘Ó ¯ÔÏËÛÙÂÚfiÏË Î·È ÊˆÛÊÔÏÈ›‰È· ·fi Ù· ·ÙÙ·Ú· ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ÈÛÙÒÓ ‰È·Ì¤ÛÔ˘ ÙˆÓ ABCA1 ÌÂÙ·ÊÔÚ¤ˆÓ (8), ÂÓÒ ÔÈ ÈÔ ÒÚÈ̘ ÌÔÚʤ˜ ÚÔÛÏ·Ì‚¿ÓÔ˘Ó Ù· ÂÓ‰Ô΢ÙÙ¿ÚÈ· ÏÈ›‰È· ‰È·Ì¤ÛÔ˘ ÙˆÓ ˘Ô-

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∂ÈÎfiÓ· 1. ™¯ËÌ·ÙÈ΋ ·ÂÈÎfiÓÈÛË Ù˘ ÂÙÂÚÔÁ¤ÓÂÈ·˜, ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ Î·È ÙˆÓ ‚ÈÔÏÔÁÈÎÒÓ ‰Ú¿ÛÂˆÓ ÙˆÓ ˘ÔÎÏ·ÛÌ¿ÙˆÓ ÙˆÓ ˘„ËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙ½ÓÒÓ (HDL). √È ·ÏÏËÏÔÌÂÙ·ÙÚÔ¤˜ ÌÂٷ͇ Ù˘ ÂχıÂÚ˘ ·ÔÏÈÔÚˆÙ›Ó˘ ∞1, ÙˆÓ ·Ú¯¤ÁÔÓˆÓ, ‰ÈÛÎÔÂȉÒÓ, Ùˆ¯ÒÓ Û ÏÈ›‰È· pre-‚ HDL, ÙˆÓ ÌÈÎÚÒÓ, ˘ÎÓÒÓ HDL3 Î·È ÙˆÓ ÌÂÁ¿ÏˆÓ HDL2 Á›ÓÔÓÙ·È ‰È·Ì¤ÛÔ˘ ÙˆÓ ÂÓ˙‡ÌˆÓ ÏÂΛıÈÓÔ-¯ÔÏÂÛÙ¤Ú˘Ï-·Î˘ÏÔÙÚ·ÓÛÊÂÚ¿ÛË (LCAT), ÙÔ˘ ÂÓ˙‡ÌÔ˘ ÌÂÙ·ÊÔÚ¿˜ ÂÛÙ¤ÚˆÓ ¯ÔÏËÛÙÂÚfiÏ˘ (CETP), Ù˘ ÚˆÙ›Ó˘ ÌÂÙ·ÊÔÚ¿˜ ʈÛÊÔÏÈȉ›ˆÓ (PLTP), Ù˘ Ë·ÙÈ΋˜ Î·È Ù˘ ÂÓ‰ÔıËÏȷ΋˜ ÏÈ¿Û˘ (HL Î·È EL ·ÓÙ›ÛÙÔȯ·), ÙˆÓ ÌÂÙ·ÊÔÚ¤ˆÓ ABCA1 Î·È ÙˆÓ ˘Ô‰Ô¯¤ˆÓ SRB1 Î·È Ê·›ÓÔÓÙ·È ÛÙÔ Û¯‹Ì· ÌÂ Û˘Ó¯›˜ ÁÚ·Ì̤˜. ™ÙÔ Û¯‹Ì· ·ÂÈÎÔÓ›˙ÔÓÙ·È ÔÈ ‚ÈÔÏÔÁÈΤ˜ ‰Ú¿ÛÂȘ ÙˆÓ HDL ۈ̷Ùȉ›ˆÓ.

AI: ·ÔÏÈÔÚˆÙ›ÓË AI, CE: ÂÛÙ¤Ú˜ ¯ÔÏËÛÙÂÚfiÏ˘, FC: ÂχıÂÚË ¯ÔÏËÛÙÂÚfiÏË, PL: ʈÛÊÔÏÈ›‰È·, PON1: ·Ú·ÔÍÔÓ¿ÛË 1. (¶ÚÔÛ·ÚÌÔÁ‹ ·fi Kontush et al, 2005, Nat Clin Pract Cardiovasc Med 2006; 3: 144-153)

‰Ô¯¤ˆÓ ABCG1/G4 (9). Δ· ÒÚÈÌ· HDL ۈ̷ٛ‰È· ¤¯Ô˘Ó ÙËÓ ÈηÓfiÙËÙ· Ó· ·Ô‰›‰Ô˘Ó Ù· ÏÈ›‰È· Ô˘ ÌÂٷʤÚÔ˘Ó ÛÙ· Ë·ÙÔ·ÙÙ·Ú· ‰È·Ì¤ÛÔ˘ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ SRB1. ∏ ÈηÓfiÙËÙ· ÙˆÓ HDL ۈ̷Ùȉ›ˆÓ Ó· ÚÔÛÏ·Ì‚¿ÓÔ˘Ó ‹ Ó· ·Ô‰›‰Ô˘Ó ÏÈ›‰È· Â›Ó·È ·ÓÙÈÛÙÚfiʈ˜ ·Ó¿ÏÔÁË Ì ÙËÓ ÔÛfiÙËÙ· ÏÈȉ›ˆÓ Ô˘ ÂÚȤ¯Ô˘Ó (12). Δ· ÌÈÎÚ¿-˘ÎÓ¿ Î·È Ùˆ¯¿ Û ÏÈ›‰È· HDL3 ۈ̷ٛ‰È· ÚÔÛÏ·Ì‚¿ÓÔ˘Ó ¯ÔÏËÛÙÂÚfiÏË Î·È ÊˆÛÊÔÏÈ›‰È· ·fi Ù· ·ÙÙ·Ú· ÙˆÓ ÈÛÙÒÓ Î·È ÌÂÙ·ÙÚ¤ÔÓÙ·È ÛÙ· ÌÂÁ¿Ï·, ÏÔ‡ÛÈ· Û ÏÈ›‰È· HDL2 ۈ̷ٛ‰È·, Ù· ÔÔ›· ÛÙÔ ‹·Ú ·Ô‰›‰Ô˘Ó Ù· ÏÈ›‰È· ÛÙ· Ë·ÙÔ·ÙÙ·Ú· (11). ∂ÈϤÔÓ Ù· HDL ۈ̷ٛ‰È· ÂÌÊ·Ó›˙Ô˘Ó ·ÓÙÈÔÍÂȉˆÙÈ΋ ‰Ú¿ÛË, ·ÊÔ‡ ·Ó·ÛÙ¤ÏÏÔ˘Ó ÙËÓ ÔÍ›‰ˆÛË ÙˆÓ LDL (13). Δ· Û˘ÛÙ·ÙÈο ÙˆÓ HDL Ô˘ ¤¯Ô˘Ó ·ÓÙÈÔÍÂȉˆÙÈΤ˜ ȉÈfiÙËÙ˜ Â›Ó·È Ë apoA1 ηıÒ˜ Î·È ÔÚÈṲ̂ӷ ¤Ó˙˘Ì· Ô˘ ‚Ú›ÛÎÔÓÙ·È ÛÙ· HDL ۈ̷ٛ‰È·. ™˘ÁÎÂÎÚÈ̤ӷ Ë apoA1 ‰Ú· ÚÔÛÏ·Ì‚¿ÓÔÓÙ·˜ Ù· ÔÍÂȉˆÌ¤Ó· ʈÛÊÔÏÈ›‰È· ·fi ÙȘ LDL ‹ Ù· ·ÙÙ·Ú· ÙÔ˘ ·ÚÙËÚÈ·ÎÔ‡ ÙÔȯÒ-

Ì·ÙÔ˜ Î·È Ù· ÌÂٷʤÚÂÈ ÛÙÔ ‹·Ú (13). Δ· ¤Ó˙˘Ì· ÙˆÓ HDL Ô˘ ÂÌÊ·Ó›˙Ô˘Ó ·ÓÙÈÔÍÂȉˆÙÈΤ˜ ȉÈfiÙËÙ˜ Â›Ó·È Ë ·Î¤Ù˘ÏÔ-˘‰ÚÔÏ¿ÛË ÙÔ˘ ·Ú¿ÁÔÓÙ· ÂÓÂÚÁÔÔ›ËÛ˘ ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ ( platelet -activating factor acetyl-hydrolase, PAF-AH), Ë ·Ú·ÔÍÔÓ¿ÛË-1 (paraoxonase-1, PON1) Î·È Ë LCAT. ∏ ·ÓÙÈÔÍÂȉˆÙÈ΋ ÙÔ˘˜ ‰Ú¿ÛË ·ÊÔÚ¿ ΢ڛˆ˜ ÙËÓ ˘‰ÚfiÏ˘ÛË ÙˆÓ ÔÍÂȉˆÌ¤ÓˆÓ ʈÛÊÔÏÈȉ›ˆÓ (13). Δ· ¤Ó˙˘Ì· ·˘Ù¿ ‰ÂÓ ÂÌÊ·Ó›˙Ô˘Ó ÔÌÔÈfiÌÔÚÊË Î·Ù·ÓÔÌ‹ ÛÙȘ HDL, ·ÊÔ‡ Û ÌÂÁ·Ï‡ÙÂÚË ·Ó·ÏÔÁ›· ‚Ú›ÛÎÔÓÙ·È ÛÙ· ÌÈÎÚ¿ HDL3 ۈ̷ٛ‰È·. ΔÔ Â‡ÚËÌ· ·˘Ùfi ˘Ô‰ËÏÒÓÂÈ fiÙÈ Ë ·ÓÙÈÔÍÂȉˆÙÈ΋ ÈηÓfiÙËÙ· ÙˆÓ HDL ÔÊ›ÏÂÙ·È Î˘Ú›ˆ˜ ÛÙ· HDL3 ۈ̷ٛ‰È· (14). ΔÔ Û˘Ì¤Ú·ÛÌ· ·˘Ùfi ÂÓÈÛ¯‡ÂÙ·È ·Ó Ï¿‚Ô˘Ì ˘fi„Ë fiÙÈ Ù· ۈ̷ٛ‰È· ·˘Ù¿, Ô˘ Â›Ó·È Ùˆ¯¿ Û ÏÈ›‰È·, ·ÚÔ˘ÛÈ¿˙Ô˘Ó ·˘ÍË̤ÓË ÈηÓfiÙËÙ· ÚfiÛÏ˄˘ ÙˆÓ ÔÍÂȉˆÌ¤ÓˆÓ ʈÛÊÔÏÈȉ›ˆÓ ·fi Ù· ·ÙÙ·Ú· ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ÈÛÙÒÓ (12). Δ· HDL ۈ̷ٛ‰È· ÂÌÊ·Ó›˙Ô˘Ó, Â›Û˘, ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë ‰Ú¿ÛË. ∏ ·ÓÙÈÊÏÂÁÌÔÓ҉˘ ‰Ú¿-

ÛË ÙÔ˘˜ Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ÈηÓfiÙËÙ· ÙÔ˘˜ Ó· ·Ó·ÛÙ¤ÏÏÔ˘Ó ÙËÓ ¤ÎÊÚ·ÛË ÙˆÓ ÌÔÚ›ˆÓ ÚÔÛÎfiÏÏËÛ˘, Ì ·ÔÙ¤ÏÂÛÌ· Ó· ÌÂÈÒÓÂÙ·È Ë ‰È›ۉ˘ÛË ÙˆÓ Ì·ÎÚÔÊ¿ÁˆÓ ÛÙÔ ÙÔ›¯ˆÌ· ÙˆÓ ·ÁÁ›ˆÓ Î·È Ë ·Ú·ÁˆÁ‹ ÂχıÂÚˆÓ ÚÈ˙ÒÓ Ô͢ÁfiÓÔ˘ (15). ∏ Ì›ˆÛË Ù˘ ¤ÎÊÚ·Û˘ ÙˆÓ ÌÔÚ›ˆÓ ÚÔÛÎfiÏÏËÛ˘ ÔÊ›ÏÂÙ·È ÛÙËÓ ·ÚÔ˘Û›· Ù˘ apoA1, ·ÏÏ¿ Î·È ÊˆÛÊÔÏÈȉ›ˆÓ, fiˆ˜ Ë 1-ʈÛÊÔÚÈ΋ ÛÊÈÁÁÔÛ›ÓË (sphingosine-1-phosphate) Î·È Ë ÛÊÈÁÁfiÛ˘ÏÔ-ʈÛÊfiÚ˘ÏÔ¯ÔÏ›ÓË (sphingosyl-phosphorylcholine) (16). ∂ÈÚfiÛıÂÙ· Ë ·ÓÙÈÊÏÂÁÌÔÓ҉˘ ‰Ú¿ÛË Ê·›ÓÂÙ·È fiÙÈ ÂÓÈÛ¯‡ÂÙ·È Î·È ·fi ¿ÏÏÔ˘˜ Ì˯·ÓÈÛÌÔ‡˜ (˘‰ÚfiÏ˘ÛË ÙˆÓ ÔÍÂȉˆÌ¤ÓˆÓ ʈÛÊÔÏÈȉ›ˆÓ ·fi Ù· ¤Ó˙˘Ì· PAF-AH, PON1 Î·È LCAT, Ì›ˆÛË Ù˘ ¤ÎÎÚÈÛ˘ ÙˆÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ Ì Â·ÁˆÁ‹ ÙÔ˘ ·Ú¿ÁÔÓÙ·-‚ ·Ó¿Ù˘Í˘ ÙˆÓ fiÁÎˆÓ (tumor growth factor-‚, TGF-‚), Ì›ˆÛË Ù˘ ÈÓÙÂÚÏ¢ΛÓ˘-6, ·Ó·ÛÙÔÏ‹ Ù˘ Û‡ÓıÂÛ˘ ÙÔ˘ ·Ú¿ÁÔÓÙ· ÂÓÂÚÁÔÔ›ËÛ˘ ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ Î·È Ì›ˆÛË Ù˘ ¤ÎÎÚÈÛ˘ Ù˘ ÚˆÙ½Ó˘ MCP-1) (12). Δ· ‰Â‰Ô̤ӷ Ô˘ ˘¿Ú¯Ô˘Ó

19

™∂¶Δ∂ªμƒπ√™ 2008

∂ÈÎfiÓ· 2. ™¯ËÌ·ÙÈ΋ ·ÂÈÎfiÓÈÛË ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ ˘„ËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙÂÈÓÒÓ (HDL) ÛÙÔ ÌÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ (ªÂÙ™).™ÙÔ Û¯‹Ì· ·ÂÈÎÔÓ›˙ÂÙ·È Ì ÛÙÈÎÙ¤˜ ÁÚ·Ì̤˜ Ô Ê˘ÛÈÔÏÔÁÈÎfi˜ ·ÎÏÔ˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ HDL ۈ̷Ùȉ›ˆÓ. ªÂ Û˘Ó¯›˜ ÁÚ·Ì̤˜ ·ÂÈÎÔÓ›˙ÂÙ·È Ë Â›‰Ú·ÛË Ù˘ ÊÏÂÁÌÔÓ‹˜, ÙÔ˘ ·Ì˘ÏÔÂȉԇ˜ ∞, ÙÔ˘ ÔÍÂȉˆÙÈÎÔ‡ stress, Ù˘ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜ Î·È Ù˘ ˘ÂÚÁÏ˘Î·ÈÌ›·˜ Ì ÙÂÏÈÎfi ·ÔÙ¤ÏÂÛÌ· ÙÔ Û¯ËÌ·ÙÈÛÌfi ÙˆÓ ‰˘ÛÏÂÈÙÔ˘ÚÁÈÎÒÓ HDL3.

ABCA1: ˘Ô‰Ô¯¤·˜ ATP-binding cassette transporter A1, AI: ·ÔÏÈÔÚˆÙ›ÓË AI, CE: ÂÛÙ¤Ú˜ ¯ÔÏËÛÙÂÚfiÏ˘, CETP: ¤Ó˙˘ÌÔ ÌÂÙ·ÊÔÚ¿˜ ÂÛÙ¤ÚˆÓ ¯ÔÏËÛÙÂÚfiÏ˘, EL: ÂÓ‰ÔıËÏȷ΋ ÏÈ¿ÛË, FC: ÂχıÂÚË ¯ÔÏËÛÙÂÚfiÏË, HL: Ë·ÙÈ΋ ÏÈ¿ÛË, LCAT: ÏÂΛıÈÓ-¯ÔÏÂÛÙ¤Ú˘Ï-·Î˘ÏÔÙÚ·ÓÛÊÂÚ¿ÛË, PL: ʈÛÊÔÏÈ›‰È·, PLTP: ¶ÚˆÙ›ÓË ÌÂÙ·ÊÔÚ¿˜ ʈÛÊÔÏÈȉ›ˆÓ, PON1: ·Ú·ÔÍÔÓ¿ÛË 1, SAA: ·Ì˘ÏÔÂȉ¤˜ ∞, SR-BI: ˘Ô‰Ô¯¤·˜ scavenger receptor type BI. (¶ÚÔÛ·ÚÌÔÁ‹ ·fi Kontush et al, 2005, Nat Clin Pract Cardiovasc Med 2006; 3: 144-153)

˘ÔÛËÌ·›ÓÔ˘Ó fiÙÈ Ë ·ÓÙÈÊÏÂÁÌÔÓ҉˘ ‰Ú¿ÛË ¯·Ú·ÎÙËÚ›˙ÂÈ Î˘Ú›ˆ˜ Ù· HDL3 ۈ̷ٛ‰È· (12).

¢˘ÛÏÂÈÙÔ˘ÚÁÈΤ˜ HDL ™ÙÔ ÌÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ (ªÂÙ™) Ù· ۈ̷ٛ‰È· ÙˆÓ HDL ÂÌÊ·Ó›˙Ô˘Ó ‰ÔÌÈΤ˜ Î·È ÏÂÈÙÔ˘ÚÁÈΤ˜ ÌÂÙ·‚ÔϤ˜ ·fi ÙË ÊÏÂÁÌÔÓ‹ Î·È ÙËÓ ·ÓÙ›‰Ú·ÛË ÔÍ›·˜ Ê¿Û˘, ÔÈ Ôԛ˜ ·ÊÔÚÔ‡Ó fiÏ· Ù· Û˘ÛÙ·ÙÈο ÙÔ˘˜ (17,18). ¶Ú¿ÁÌ·ÙÈ, Ù· HDL ۈ̷ٛ‰È· ÂÌÏÔ˘Ù›˙ÔÓÙ·È Ì ÙÚÈÁÏ˘ÎÂÚ›‰È·. ∞˘Ùfi˜ Ô ÂÌÏÔ˘ÙÈÛÌfi˜ ÔÊ›ÏÂÙ·È ÛÙ· ·˘ÍË̤ӷ Â›‰· ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÛÙÔ ·›Ì·, ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙË ÌÂÙ·‚ÔÏ‹ Ù˘ ÏÂÈÙÔ˘ÚÁ›·˜ ÙˆÓ ÂÓ˙‡ÌˆÓ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙÔ ÌÂÙ·‚ÔÏÈÛÌfi ÙˆÓ ÏÈÔÚˆÙÂ˚ÓÒÓ. ªÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ Û ¿ÙÔÌ· Ì ªÂÙ™ ·ÏÏ¿ Î·È Û ÂÚÈÙÒÛÂȘ ÔͤԘ stress ÛÙ· Ï·›ÛÈ· Ù˘ ·ÓÙ›‰Ú·Û˘ ÔÍ›·˜ Ê¿Û˘ ·˘Í¿ÓÂÙ·È Ë ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ CETP. ∫·Ù¿ Û˘Ó¤ÂÈ· ·˘Í¿ÓÂÙ·È Ë ÂÚÈÂÎÙÈÎfiÙËÙ· ÙˆÓ HDL Û ÙÚÈÁÏ˘ÎÂÚ›‰È·, ÂÓÒ ÌÂÈÒÓÂÙ·È Ë ÂÚÈÂÎÙÈÎfiÙËÙ· ÙÔ˘˜ Û ÂÛÙ¤Ú˜ ¯ÔÏËÛÙÂÚfiÏ˘ (19). ™ÙËÓ ·‡ÍËÛË Ù˘

20

ÂÚÈÂÎÙÈÎfiÙËÙ·˜ ÙˆÓ HDL Û ÙÚÈÁÏ˘ÎÂÚ›‰È· Û˘Ì‚¿ÏÏÂÈ Â›Û˘ Î·È Ë ÂÏ·Ùو̤ÓË ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ÏÈÔÚˆÙÂ˚ÓÈ΋˜ Î·È Ù˘ Ë·ÙÈ΋˜ ÏÈ¿Û˘, ηıÒ˜ Î·È Ù˘ LCAT Ô˘ ·Ú·ÙËÚÔ‡ÓÙ·È Û ÂÚÈÙÒÛÂȘ ÊÏÂÁÌÔÓ‹˜ (17,18). ∂ÈÚfiÛıÂÙ· ÛÙÔ ªÂÙ™ ·Ú·ÙËÚÂ›Ù·È Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ Ù˘ apoA1 ÙˆÓ HDL ۈ̷Ùȉ›ˆÓ (4,5). ∏ Ì›ˆÛË ·˘Ù‹ ÔÊ›ÏÂÙ·È Û ÂÏ·Ùو̤ÓË Û‡ÓıÂÛË Î·È Û ·˘ÍË̤ÓÔ Î·Ù·‚ÔÏÈÛÌfi Ù˘ apoA1, ÛÙ· Ï·›ÛÈ· Ù˘ ‰È·Ù·Ú·¯‹˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ HDL (12), ·ÏÏ¿ Î·È ÛÙËÓ ·ÓÙÈηٿÛÙ·ÛË Ù˘ ·fi ÙÔ ·Ì˘ÏÔÂȉ¤˜-· (17,18). ΔÔ ·Ì˘ÏÔÂȉ¤˜-· Â›Ó·È ÌÈ· ÚˆÙ½ÓË ÔÍ›·˜ Ê¿Û˘ Ô˘ ·Ú¿ÁÂÙ·È ÛÙÔ ‹·Ú Î·È ÛÂ Û˘Óı‹Î˜ ÊÏÂÁÌÔÓ‹˜ Ù· Â›‰· Ù˘ ÛÙÔÓ ÔÚfi ÙÔ˘ ·›Ì·ÙÔ˜ ·˘Í¿ÓÔÓÙ·È ¤ˆ˜ 1000 ÊÔÚ¤˜. ΔÔ ·Ì˘ÏÔÂȉ¤˜-· ÌÔÚ› Ó· ·ÓÙÈηٷÛÙ‹ÛÂÈ ÙËÓ apoA1 Î·È ¿ÏϘ ÏÈÔÚˆÙ½Ó˜ ÛÙËÓ ÂÈÊ¿ÓÂÈ· ÙˆÓ HDL ۈ̷Ùȉ›ˆÓ (20). ŒÙÛÈ ÚÔηÏÂ›Ù·È ÌÈ· ÛÂÈÚ¿ ·ÏÏ·ÁÒÓ ÛÙË ÏÂÈÙÔ˘ÚÁ›· ÙˆÓ HDL Ô˘ ı· Û˘˙ËÙËıÔ‡Ó ÛÙË Û˘Ó¤¯ÂÈ· Î·È ÔÈ Ôԛ˜ ÌÂÈÒÓÔ˘Ó ÙËÓ ÚÔÛٷ٢-

ÙÈ΋ ÙÔ˘˜ ‰Ú¿ÛË ÛÙ· ·ÁÁ›·. √È ‰ÔÌÈΤ˜ ÌÂÙ·‚ÔϤ˜ ·ÊÔÚÔ‡Ó Â›Û˘ Î·È Ù· ¤Ó˙˘Ì· ÙˆÓ HDL. ∏ PAF-AH, Ë PON-1, Ë LCAT ÂÌÊ·Ó›˙Ô˘Ó ‰ÔÌÈΤ˜ ÌÂÙ·‚ÔϤ˜ Î·È Û˘ÁÎÂÎÚÈ̤ӷ ÔÍ›‰ˆÛË ·fi Ù· ·ÙÙ·Ú· ÙÔ˘ ·ÁÁÂÈ·ÎÔ‡ ÙÔȯÒÌ·ÙÔ˜ ‹ ÁÏ˘ÎÔ˙˘Ï›ˆÛË, ÂÍ·ÈÙ›·˜ Ù˘ ˘ÂÚÁÏ˘Î·ÈÌ›·˜ Ô˘ Û˘¯Ó¿ Û˘Óԉ‡ÂÈ ÙÔ ªÂÙ™ (12). ∞ÎfiÌË, Ù· Â›‰· ÙˆÓ ÂÓ˙‡ÌˆÓ Ô˘ ‚Ú›ÛÎÔÓÙ·È ÛÙ· HDL ۈ̷ٛ‰È· ÌÂÈÒÓÔÓÙ·È ÛÂ Û˘Óı‹Î˜ ÊÏÂÁÌÔÓ‹˜ ‹ ÌÂÙ·‚ÔÏÈ΋˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ (17,18). ΔÔ Û‡ÓÔÏÔ ÙˆÓ ‰ÔÌÈÎÒÓ ·ÏÏÔÈÒÛÂˆÓ ÙˆÓ HDL ۈ̷Ùȉ›ˆÓ Ô‰ËÁ› Û ÌÈ· ÛÂÈÚ¿ ·ÏÏ·ÁÒÓ ÛÙÔ ÌÂÙ·‚ÔÏÈÛÌfi ÙÔ˘˜, ÛÙȘ ÏÂÈÙÔ˘ÚÁ›Â˜ ÙÔ˘˜ Î·È ÛÙËÓ ÔÛfiÙËÙ· Î·È Î·Ù·ÓÔÌ‹ Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘. ∏ ·‡ÍËÛË ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÙˆÓ HDL ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙË Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ HDL ÛÙÔ ·›Ì·, ηıÒ˜ ÌÂÈÒÓÂÙ·È Ë ‰ÔÌÈ΋ ÛÙ·ıÂÚfiÙËÙ· ÙˆÓ ÛˆÌ·Ùȉ›ˆÓ Î·È Ô ¯ÚfiÓÔ˜ ·Ú·ÌÔÓ‹˜ ÙÔ˘˜ ÛÙËÓ Î˘ÎÏÔÊÔÚ›· (21). ∏ Ì›ˆÛË Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘ Û˘Óԉ‡ÂÙ·È ·fi ·Ó¿ÏÔÁË Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ HDL2

¶∞£√ºÀ™π√§√°π∞ ۈ̷Ùȉ›ˆÓ, ÂÓÒ Ù· Â›‰· ÙˆÓ HDL3 ۈ̷Ùȉ›ˆÓ ÌÂÈÒÓÔÓÙ·È Û ÌÈÎÚfiÙÂÚÔ ‚·ıÌfi. ΔÔ Â‡ÚËÌ· ·˘Ùfi ÔÊ›ÏÂÙ·È Û ·˘ÍË̤ÓË ÏÈfiÏ˘ÛË ÙˆÓ ÏÔ‡ÛÈˆÓ Û ÙÚÈÁÏ˘ÎÂÚ›‰È· HDL2 ۈ̷Ùȉ›ˆÓ, Ô˘ Ô‰ËÁ› ÛÙÔ ·˘ÍË̤ÓÔ Û¯ËÌ·ÙÈÛÌfi ÌÈÎÚÒÓ HDL3 ۈ̷Ùȉ›ˆÓ. √È HDL, ·ÎfiÌË, ÂÌÊ·Ó›˙Ô˘Ó ·˘ÍË̤ÓÔ Ú˘ıÌfi ·Ô‚ÔÏ‹˜ ·fi ÙËÓ Î˘ÎÏÔÊÔÚ›·, ·ÊÔ‡ Ë ‰ÔÌÈ΋ ·ÛÙ¿ıÂÈ· ÙˆÓ ÏÔ‡ÛÈˆÓ Û ÙÚÈÁÏ˘ÎÂÚ›‰È· HDL ‰È¢ÎÔχÓÂÈ ÙËÓ ·Ô‰¤ÛÌ¢ÛË Ù˘ apoA1 ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÏÈfiÏ˘Û˘ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÛÙ· Ë·ÙÈο ÙÚȯÔÂȉ‹ (4,5,21). À¿Ú¯Ô˘Ó Â›Û˘ ÂӉ›ÍÂȘ fiÙÈ Ù· ÏÔ‡ÛÈ· Û ÙÚÈÁÏ˘ÎÂÚ›‰È· HDL ۈ̷ٛ‰È· ¤¯Ô˘Ó ÌÂȈ̤ÓË ÈηÓfiÙËÙ· Ó· ·Ô‰›‰Ô˘Ó ÂÛÙ¤Ú˜ ¯ÔÏËÛÙÂÚfiÏ˘ ÛÙ· ·ÙÙ·Ú· ‰È·Ì¤ÛÔ˘ ÙˆÓ SRB1 ˘Ô‰Ô¯¤ˆÓ (22). ªÂ ÙÔÓ ›‰ÈÔ ÙÚfiÔ Ê·›ÓÂÙ·È fiÙÈ Âȉڿ Î·È Ë ·ÓÙÈηٿÛÙ·ÛË Ù˘ apoA1 ·fi ÙÔ ·Ì˘ÏÔÂȉ¤˜-· (23), ÂÓÒ ·Ú¿ÏÏËÏ· ·˘Í¿ÓÂÙ·È Ë ÈηÓfiÙËÙ· ÙˆÓ HDL ۈ̷Ùȉ›ˆÓ Ó· ·ÏÏËÏÂȉÚÔ‡Ó Ì ٷ Ì·ÎÚÔÊ¿Á· ·Ô‰›‰ÔÓÙ·˜ Û ·˘Ù¿ ÂÛÙ¤Ú˜ ¯ÔÏËÛÙÂÚfiÏ˘ (24). ∞˘Ù¤˜ ÔÈ ‰‡Ô ·Ú·ÙËÚ‹ÛÂȘ Â›Ó·È Èı·Ófi Ó· ·ÓÙÈηÙÔÙÚ›˙Ô˘Ó ÌÈ· ıÂÌÂÏÈÒ‰Ë ·ÏÏ·Á‹ ÛÙÔ ÌÂÙ·‚ÔÏÈÛÌfi Î·È ÙË ‰Ú¿ÛË ÙˆÓ HDL ۈ̷Ùȉ›ˆÓ. º·›ÓÂÙ·È ‰ËÏ·‰‹ fiÙÈ ÛÂ Û˘Óı‹Î˜ ÊÏÂÁÌÔÓ‹˜ ¤ˆ˜ ¤Ó· ‚·ıÌfi ·Ó·ÛÙ¤ÏÏÂÙ·È Ë ·Ó¿ÛÙÚÔÊË ÌÂÙ·ÊÔÚ¿ ¯ÔÏËÛÙÂÚfiÏ˘ Î·È Ù· HDL ۈ̷ٛ‰È· ·ÓÙ› Ó· ÌÂٷʤÚÔ˘Ó ÙË ¯ÔÏËÛÙÂÚfiÏË ÛÙ· Ë·ÙÔ·ÙÙ·Ú· ÙËÓ Î·Ù¢ı‡ÓÔ˘Ó ÛÙ· ·ÙÙ·Ú· ÙÔ˘ ·ÓÔÛÔÔÈËÙÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ (13,24). ∏ ·ÏÏ·Á‹ ·˘Ù‹ ·Ó·ÛÙ¤ÏÏÂÈ ÙËÓ ·ÓÙÈ·ıËÚˆÁfiÓÔ ‰Ú¿ÛË ÙˆÓ HDL ۈ̷Ùȉ›ˆÓ Î·È Ô‰‹ÁËÛ ÛÙË ‰È·Ù‡ˆÛË ÙÔ˘ fiÚÔ˘ «‰˘ÛÏÂÈÙÔ˘ÚÁÈΤ˜» (dysfunctional) HDL (13). Δ· HDL ۈ̷ٛ‰È· Ô˘ ‰˘ÛÏÂÈÙÔ˘ÚÁÔ‡Ó ÂÌÊ·Ó›˙Ô˘Ó Â›Û˘ ÌÂȈ̤ÓË ·ÓÙÈÔÍÂȉˆÙÈ΋ Î·È ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë ‰Ú¿ÛË ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙˆÓ ÌÂÙ·‚ÔÏÒÓ ÛÙËÓ ÔÛfiÙËÙ·, ‰ÔÌ‹ Î·È ÏÂÈÙÔ˘ÚÁ›· Ù˘ apoA1 Î·È ÙˆÓ ÂÓ˙‡ÌˆÓ ÙÔ˘˜ (12). √È Èı·ÓÔ› Ì˯·ÓÈÛÌÔ› Ô˘ ÂÍËÁÔ‡Ó ÙË Ì›ˆÛË Ù˘ ·ÓÙÈÔÍÂȉˆÙÈ΋˜ ÈηÓfiÙËÙ·˜ ÙˆÓ HDL ۈ̷Ùȉ›ˆÓ Â›Ó·È Ë ÂÏ·Ùو̤ÓË ‰ÔÌÈ΋ ÛÙ·ıÂÚfiÙËÙ· Ù˘ apoA1 Î·È Ë ÌÂÙ·‚ÔÏ‹ Ù˘ ÛÙÂÚÂÔ‰ÔÌ‹˜ Ù˘, Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ·ÏÏ·Á‹ Ù˘ ÏÈȉȷ΋˜ Û‡ÛÙ·Û˘ ÙˆÓ HDL, Ë

·ÓÙÈηٿÛÙ·Û‹ Ù˘ ·fi ÙÔ ·Ì˘ÏÔÂȉ¤˜-·, ÔÈ ‰ÔÌÈΤ˜ ÌÂÙ·‚ÔϤ˜ ÙˆÓ ÂÓ˙‡ÌˆÓ ÙˆÓ HDL Î·È Ë Â·ÎfiÏÔ˘ıË Ì›ˆÛË Ù˘ ˘‰ÚÔÏ˘ÙÈ΋˜-·ÓÙÈÔÍÂȉˆÙÈ΋˜ ÙÔ˘˜ ÈηÓfiÙËÙ·˜ (12). ªÂ ·Ó¿ÏÔÁÔ ÙÚfiÔ Ê·›ÓÂÙ·È fiÙÈ ÌÂÈÒÓÂÙ·È Î·È Ë ·ÓÙÈÊÏÂÁÌÔÓ҉˘ ‰Ú¿ÛË ÙˆÓ HDL (12). ∏ Ì›ˆÛË ·˘Ù‹ ‰ÂÓ Ê·›ÓÂÙ·È Ó· Û¯ÂÙ›˙ÂÙ·È Ì ÙË ‰Ú¿ÛË Ù˘ PON-1. ΔÔ Â‡ÚËÌ· ·˘Ùfi ·ÔÙÂÏ› ¤Ó‰ÂÈÍË fiÙÈ Ë ‰Ú¿ÛË Ù˘ PON-1 ‰ÂÓ Â›Ó·È Î·ıÔÚÈÛÙÈ΋ ÁÈ· ÙËÓ ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë ÈηÓfiÙËÙ· ÙˆÓ HDL ۈ̷Ùȉ›ˆÓ (25).

™˘ÌÂÚ¿ÛÌ·Ù· √È ‰È¿ÊÔÚ˜ ÌÔÚʤ˜ ÙˆÓ HDL Ô˘ ΢ÎÏÔÊÔÚÔ‡Ó Î·ıÒ˜ ˆÚÈÌ¿˙Ô˘Ó Î·È Î·ıÒ˜ ÌÂÙ·‚¿ÏÏÂÙ·È ÙÔ ÂÚȯfiÌÂÓÔ ÙÔ˘˜ Û ¯ÔÏËÛÙÂÚfiÏË, ¿Ú· Î·È ÙÔ Ì¤ÁÂıfi˜ ÙÔ˘˜, Û˘ÌÌÂÙ¤¯Ô˘Ó Û ‰È·ÊÔÚÂÙÈÎfi ‚·ıÌfi ÛÙÔÓ ÚÔÛٷ٢ÙÈÎfi ÚfiÏÔ ÙˆÓ HDL (12). Δ· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ˘¿Ú¯Ô˘Ó Ó¤· ‰Â‰Ô̤ӷ Ô˘ ˘Ô‰ÂÈÎÓ‡Ô˘Ó fiÙÈ Ù· ÌÈÎÚ¿ HDL3 ۈ̷ٛ‰È· Â›Ó·È ÙÔ ÎÏ¿ÛÌ· Ô˘ Â›Ó·È ˘‡ı˘ÓÔ ÁÈ· ÙËÓ ·ÓÙÈÔÍÂȉˆÙÈ΋ Î·È ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë ‰Ú¿ÛË ÙˆÓ HDL (4,5,12). øÛÙfiÛÔ ·˘Ù¿ Ù· ۈ̷ٛ‰È· ÂËÚ¿˙ÔÓÙ·È ·fi ÙÔ ÔÍÂȉˆÙÈÎfi stress Î·È ÙË ÊÏÂÁÌÔÓ‹, Ì ·ÔÙ¤ÏÂÛÌ· ÙË Ì›ˆÛË ÙÔ˘ ÚÔÛٷ٢ÙÈÎÔ‡ ÚfiÏÔ˘ ÙˆÓ HDL Û ·˘Ù¤˜ ÙȘ Û˘Óı‹Î˜ (4,5,12). Àfi Ê˘ÛÈÔÏÔÁÈΤ˜ Û˘Óı‹Î˜ Ù· ÌÈÎÚ¿ HDL ۈ̷ٛ‰È· ¤¯Ô˘Ó ÙËÓ Ù¿ÛË Ó· ÚÔÛÏ·Ì‚¿ÓÔ˘Ó ¯ÔÏËÛÙÂÚfiÏË ·fi Ù· ÂÚÈÊÂÚÈο ·ÙÙ·Ú· Î·È Ó· ·˘Í¿ÓÔ˘Ó Û ̤ÁÂıÔ˜. ∏ ‰ËÌÈÔ˘ÚÁ›· ÙˆÓ ÌÂÁ¿ÏˆÓ HDL ۈ̷Ùȉ›ˆÓ ÛËÌ·ÙÔ‰ÔÙ› Î·È ÙË ÌÂÙ·ÙÚÔ‹ ÙÔ˘˜ ·fi ·ÓÙÈÔÍÂȉˆÙÈÎÔ‡˜-·ÓÙÈÊÏÂÁÌÔÓÒ‰ÂȘ ·Ú¿ÁÔÓÙ˜ Û ÌÂÙ·ÊÔÚ›˜ ÙˆÓ ÂÛÙ¤ÚˆÓ Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ ÚÔ˜ ÙÔ ‹·Ú Î·È ¤ÙÛÈ ÔÏÔÎÏËÚÒÓÂÙ·È Ë ·Ó¿ÛÙÚÔÊË ÌÂÙ·ÊÔÚ¿ Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ (12). ™ÙÔ ªÂÙ™ Ô Ê˘ÛÈÔÏÔÁÈÎfi˜ ·ıËÚÔÚÔÛٷ٢ÙÈÎfi˜ ÚfiÏÔ˜ ÙˆÓ HDL ‰È·Ù·Ú¿ÛÛÂÙ·È Î·È ÛÙË ı¤ÛË ÙÔ˘ ÂÌÊ·Ó›˙ÔÓÙ·È Ó¤Â˜ ȉÈfiÙËÙ˜ Ô˘ Â¿ÁÔ˘Ó ÙËÓ ·ıËڈ̿وÛË (12). Œ¯ÂÈ ‰È·Ù˘ˆı› ÌÈ· ˘fiıÂÛË Ô˘ ÂȯÂÈÚ› Ó· ÂÍËÁ‹ÛÂÈ ·˘Ù¿ Ù· Â˘Ú‹Ì·Ù·. ™‡Ìʈӷ Ì ·˘Ù‹Ó ÙËÓ ˘fiıÂÛË, Ë ·ÏÏ·Á‹ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ ÏÈÔÚˆÙÂ˚ÓÒÓ ·Ú·ÙËÚÂ›Ù·È ÛÙ· Ï·›ÛÈ· ÂÓfi˜ ÂÍÂÏÈÎÙÈÎÔ‡ Ì˯·ÓÈÛÌÔ‡ ÙÔ˘ ·ÓÔÛÔÔÈËÙÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜

Ì ÛÎÔfi ÙËÓ ÚÔÛÙ·Û›· ÂÓ¿ÓÙÈ· ÛÙÔ ‚Ï·ÙÈÎfi ·Ú¿ÁÔÓÙ· Î·È ÙËÓ ÂȉÈfiÚıˆÛË ÙˆÓ ÈÛÙÈÎÒÓ ‚Ï·‚ÒÓ Ô˘ ÚÔηÏ›. ∏ ·Ó¿ÛÙÚÔÊË ÌÂÙ·ÊÔÚ¿ ¯ÔÏËÛÙÂÚfiÏ˘ ·Ó·ÚÔÛ·ÚÌfi˙ÂÙ·È ÚÔ˜ Ù· Ì·ÎÚÔÊ¿Á·, ·ÓÙ› ÁÈ· Ù· Ë·ÙÈο ·ÙÙ·Ú·, ‰È·Ì¤ÛÔ˘ Ù˘ Ì›ˆÛ˘ ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ HDL2 ۈ̷Ùȉ›ˆÓ Î·È ÁÂÓÈÎfiÙÂÚ· Ù˘ Ì›ˆÛ˘ Ù˘ ÈηÓfiÙËÙ·˜ ÙˆÓ HDL ÁÈ· ·fi‰ÔÛË ÂÛÙ¤ÚˆÓ ¯ÔÏËÛÙÂÚfiÏ˘ ÛÙ· Ë·ÙÈο ·ÙÙ·Ú·. ∞˘Ùfi˜ Ô Ì˯·ÓÈÛÌfi˜ Û˘Ì‚¿ÏÏÂÈ ÛÙË ‰È·Ù‹ÚËÛË Ù˘ ÔÌÔÈÔÛÙ·Û›·˜ ÙˆÓ ÈÛÙÒÓ Î·Ù¿ ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÔͤˆÓ ‚Ï·ÙÈÎÒÓ Î·Ù·ÛÙ¿ÛˆÓ. ŸÌˆ˜ Û ̷ÎÚÔ¯ÚfiÓȘ ηٷÛÙ¿ÛÂȘ (fiˆ˜ Ë ÂÍÂÏÈÛÛfiÌÂÓË ·ıËڈ̷ÙÈ΋ Ͽη) Ë ·Ó·ÚÔÛ·ÚÌÔÁ‹ Ù˘ ·Ó¿ÛÙÚÔÊ˘ ÌÂÙ·ÊÔÚ¿˜ Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ ÚÔ˜ Ù· Ì·ÎÚÔÊ¿Á· ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û ¯ÚfiÓȘ ÌÂÙ·‚ÔϤ˜ ÙˆÓ ÏÈÔÚˆÙÂ˚ÓÈÎÒÓ ÛˆÌ·Ùȉ›ˆÓ Î·È ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ ÏÈȉ›ˆÓ ÛÙÔ Ï¿ÛÌ·, fiˆ˜ ·Ú·ÙËÚÂ›Ù·È ÛÙÔ ªÂÙ™. ¢ËÏ·‰‹ Ë ¯ÚfiÓÈ· ·ÓÙ›‰Ú·ÛË Á›ÓÂÙ·È ‚Ï·ÙÈ΋ Î·È ÂÈÙ·¯‡ÓÂÈ ÙËÓ ·ıËڈ̷ÙÈ΋ ÓfiÛÔ (17,18). ™ÙË ‰˘ÛÏÈȉ·ÈÌ›· Ì ¯·ÌËÏ‹ HDL, Ë ÔÛÔÙÈ΋ Ì›ˆÛË Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘ ·ÓÙÈηÙÔÙÚ›˙ÂÈ ÙË Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ ÌÂÁ¿ÏˆÓ, ÏÔ‡ÛÈˆÓ Û ¯ÔÏËÛÙÂÚfiÏË ÛˆÌ·Ùȉ›ˆÓ(4,5). Δ·˘Ùfi¯ÚÔÓ·, Ê·›ÓÂÙ·È fiÙÈ ˘Ô‰ËÏÒÓÂÈ Î·È ÙËÓ ÔÈÔÙÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ÌÈÎÚÒÓ ÛˆÌ·Ùȉ›ˆÓ Î·È ÙË Ì›ˆÛË Ù˘ ·ÓÙÈ-·ıËÚˆÁfiÓÔ˘ ÈηÓfiÙËÙ·˜ ÙÔ˘˜ (4,12). ŒÙÛÈ, ·Ó Î·È ÔÈ ÌÂÙÚ‹ÛÂȘ Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘ Ô˘ Ú·ÁÌ·ÙÔÔÈÔ‡ÓÙ·È Û ηıËÌÂÚÈÓ‹ ‚¿ÛË ÛÙ· È·ÙÚÈο ÂÚÁ·ÛÙ‹ÚÈ· ÌÂÙÚÔ‡Ó ÌfiÓÔ ÙËÓ ÔÛfiÙËÙ¿ Ù˘, ›Ûˆ˜ ÌÔÚԇ̠ӷ ıˆڋÛÔ˘Ì fiÙÈ Ù· ¯·ÌËÏ¿ Â›‰· Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘ ÛÙÔ ªÂÙ™ ÂÎÊÚ¿˙Ô˘Ó Î·È ÙËÓ ÔÈÔÙÈ΋ ‰È·Ù·Ú·¯‹ ÙˆÓ HDL, ‰È·Ì¤ÛÔ˘ ÙÔ˘ ÎÔÈÓÔ‡ ·ıÔÊ˘ÛÈÔÏÔÁÈÎÔ‡ Ì˯·ÓÈÛÌÔ‡ Ô˘ ÂËÚ¿˙ÂÈ ÙËÓ ÔÛfiÙËÙ· Î·È ÙË ÏÂÈÙÔ˘ÚÁ›· ÙˆÓ HDL ۈ̷Ùȉ›ˆÓ.

∂›ÏÔÁÔ˜ ΔÔ ªÂÙ™ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÙËÓ ·ıËÚÔÁfiÓÔ ‰˘ÛÏÈȉ·ÈÌ›·, Ì ÙËÓ ·‡ÍËÛË ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Î·È ÙË Ì›ˆÛË Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘, Ë ÔÔ›· Â¿ÁÂÈ ÙËÓ ÊÏÂÁÌÔÓ‹ Î·È ÙËÓ ÂΉ‹ÏˆÛË ÙÔ˘ ÔÍÂȉˆÙÈÎÔ‡ ÛÙÚ˜. ™ÙȘ Û˘Óı‹Î˜ ·˘Ù¤˜ ·Ú·ÙËÚÂ›Ù·È ÔÛÔÙÈ΋

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™∂¶Δ∂ªμƒπ√™ 2008

Ì›ˆÛË Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘, Ì ·Ó¿ÏÔÁË Ì›ˆÛË ÙˆÓ HDL2 ۈ̷Ùȉ›ˆÓ. Δ· Â›‰· ÙˆÓ HDL3 ÂËÚ¿˙ÔÓÙ·È Û ÌÈÎÚfiÙÂÚÔ ‚·ıÌfi, ·ÏÏ¿ Ë ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘˜ ‰È·Ù·Ú¿ÛÛÂÙ·È Ì ·ÔÙ¤ÏÂÛÌ· ·˘Ù¿ Ù· ۈ̷ٛ‰È· Ó· ¯¿ÓÔ˘Ó ÙȘ ·ÓÙÈÔÍÂȉˆÙÈΤ˜ Î·È ·ÓÙÈÊÏÂÁÌÔÓÒ‰ÂȘ ȉÈfiÙËÙ˜. ∂›Û˘ Ë ·Ó¿ÛÙÚÔÊË ÌÂÙ·ÊÔÚ¿ Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ ÚÔ˜ ÙÔ ‹·Ú ÌÂÈÒÓÂÙ·È Î·È Ë ¯ÔÏËÛÙÂÚfiÏË Î·Ù¢ı‡ÓÂÙ·È ÚÔ˜ Ù· ·ÙÙ·Ú· ÙÔ˘ ·ÓÔÛÔÔÈËÙÈÎÔ‡ Û˘-

ÛÙ‹Ì·ÙÔ˜. √È Ì˯·ÓÈÛÌÔ› Ì ÙÔ˘˜ ÔÔ›Ô˘˜ ÂÍËÁÔ‡ÓÙ·È ÔÈ ·Ú·¿Óˆ ·ÏÏ·Á¤˜ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÙËÓ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· ÙÔ˘ ªÂÙ™ Î·È ÙËÓ ·ÓÙ›‰Ú·ÛË Ù˘ ÔÍ›·˜ Ê¿Û˘ Î·È Ù˘ ÊÏÂÁÌÔÓ‹˜, Ô˘ ÚÔηÏÔ‡Ó ‰ÔÌÈΤ˜ Î·È ÏÂÈÙÔ˘ÚÁÈΤ˜ ÌÂÙ·‚ÔϤ˜ ÛÙ· HDL ۈ̷ٛ‰È·. º·›ÓÂÙ·È fiÙÈ ÚfiÎÂÈÙ·È ÁÈ· Ì˯·ÓÈÛÌÔ‡˜ Ô˘ ·ÔÛÎÔÔ‡Ó ÛÙË ‰È·Ù‹ÚËÛË Ù˘ ÔÌÔÈÔÛÙ·Û›·˜ ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡, ·ÏÏ¿ Ë ¯ÚfiÓÈ· Â›‰Ú·ÛË ÙÔ˘˜ ÛÙÔ ÌÂÙ·‚ÔÏÈÛÌfi ÙˆÓ ÏÈÔÚˆ-

μÈ‚ÏÈÔÁÚ·Ê›· 1. Chapman MJ et al. Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid--a position paper developed by the European Consensus Panel on HDL-C. Curr Med Res Opin 2004; 20: 1253-1268.

2. Gazi I et al. Concentration and relative distribution of low-density lipoprotein subfractions in patients with metabolic syndrome defined according to the National Cholesterol Education Program criteria. Metabolism 2006; 55: 885-891.

3. Link JJ et al. HDL cholesterol: physiology, pathophysiology, and management. Curr Probl Cardiol 2007; 32: 268-314.

4. Hansel B et al. Metabolic syndrome is associated with elevated oxidative stress and dysfunctional dense highdensity lipoprotein particles displaying impaired antioxidative activity. J Clin Endocrinol Metab 2004; 89: 4963-4971.

5. de Souza JA et al. Metabolic syndrome features small, apolipoprotein A-Ipoor, triglyceride-rich HDL3 particles with defective anti-apoptotic activity.

Atherosclerosis 2007; (article in press).

6. Segrest JP et al. The amphipathic helix in the exchangeable apolipoproteins: a review of secondary structure and function. J Lipid Res 1992; 33: 141-166.

7. Segrest JP et al. Structure and function of apolipoprotein A-I and high-density lipoprotein. Curr Opin Lipidol 2000; 11: 105-115.

8. von Eckardstein A et al. High density lipoproteins and arteriosclerosis. Role of cholesterol efflux and reverse cholesterol transport. Arterioscler Thromb Vasc Biol 2001; 21: 13-27.

9. Wang N et al. ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to highdensity lipoproteins. Proc Natl Acad Sci U S A 2004; 101: 9774-9779.

10. Barter PJ et al. Targeting cholesteryl ester transfer protein for the prevention and management of cardiovascular disease. J Am Coll Cardiol 2006; 47: 492-499.

11. Williams DL et al. Scavenger receptor BI and cholesterol trafficking. Curr Opin Lipidol 1999; 10: 329-339.

12. Kontush A et al. Antiatherogenic small, dense HDL--guardian angel of the arterial wall? Nat Clin Pract Cardiovasc Med 2006; 3: 144-153.

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13. Navab M et al. The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL. J Lipid Res 2004; 45: 993-1007.

14. Kontush A et al. Small, dense HDL particles exert potent protection of atherogenic LDL against oxidative stress.

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15. Barter PJ et al. Antiinflammatory properties of HDL. Circ Res 2004; 95: 764772.

16. Nofer JR et al. Atheroprotective effects of high-density lipoprotein-associated lysosphingolipids. Trends Cardiovasc Med 2005; 15: 265-271.

17. Khovidhunkit W et al. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. J Lipid Res 2004; 45: 1169-1196.

18. Esteve E et al. Dyslipidemia and inflammation: an evolutionary conserved mechanism. Clin Nutr 2005; 24: 16-31.

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20. Malle E et al. Serum amyloid A (SAA): an acute phase protein and apolipoprotein. Atherosclerosis 1993; 102: 131146.

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22. Greene DJ et al. Elevated triglyceride content diminishes the capacity of high density lipoprotein to deliver cholesteryl esters via the scavenger receptor class B type I (SR-BI). J Biol Chem 2001; 276: 4804-4811.

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25. Ansell BJ et al. Inflammatory/ antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than highdensity lipoprotein cholesterol levels and are favorably affected by simvastatin treatment. Circulation 2003; 108: 2751-2756.

ÙÂ˚ÓÒÓ Ô‰ËÁ› ÛÙËÓ ÌÂÙ¿ÙˆÛ‹ ÙÔ˘˜ Û Ì˯·ÓÈÛÌÔ‡˜ Ô˘ ¢ԉÒÓÔ˘Ó ÙËÓ ÂͤÏÈÍË Ù˘ ·ıËڈ̷ÙÈ΋˜ Ͽη˜. ∏ ηٷÓfiËÛË ÙˆÓ ·Ú·¿Óˆ Ì˯·ÓÈÛÌÒÓ Û ‚¿ıÔ˜ ı· ‰ËÌÈÔ˘ÚÁ‹ÛÂÈ Î·Ï‡ÙÂÚ˜ ÚÔ¸Ôı¤ÛÂȘ ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ·ıËÚˆÁfiÓÔ˘ ‰˘ÛÏÈȉ·ÈÌ›·˜ Î·È ÙËÓ ÂÚ·ÈÙ¤Úˆ Ì›ˆÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË Ù˘ ηډȷÁÁÂȷ΋˜ ÓfiÛÔ˘.

¶ƒ√∫§π¡π∫∏ ∂ƒ∂À¡∞

Δ›ÙÏÔÈ ∞˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ŒÓ·ÓÙÈ ¢È·ÊfiÚˆÓ ªÔÚÊÒÓ √ÍÂȉˆÌ¤Ó˘ LDL Û ∞ÛıÂÓ›˜ Ì √͇ ™ÙÂÊ·ÓÈ·›Ô ™‡Ó‰ÚÔÌÔ. ∏ ∂›‰Ú·ÛË Ù˘ ∞ÙÔÚ‚·ÛÙ·Ù›Ó˘ ∞. ¶··ı·Ó·Û›Ô˘, π. °Ô˘‰¤‚ÂÓÔ˜, ∞. ΔÛÂϤ˘1 ∫·Ú‰ÈÔÏÔÁÈ΋ ∫ÏÈÓÈ΋, π·ÙÚÈ΋ ™¯ÔÏ‹, ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô πˆ·ÓÓ›ÓˆÓ 1

∂ÚÁ·ÛÙ‹ÚÈÔ μÈÔ¯ËÌ›·˜, ΔÌ‹Ì· ÃËÌ›·˜, ¶·ÓÂÈÛÙ‹ÌÈÔ πˆ·ÓÓ›ÓˆÓ

∂ÈÛ·ÁˆÁ‹ ∏ ÔÍÂȉˆÌ¤ÓË ÌÔÚÊ‹ Ù˘ ¯·ÌËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙ½Ó˘ (oxLDL) ‰È·‰Ú·Ì·Ù›˙ÂÈ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ·ıÔÁ¤ÓÂÈ· Ù˘ ·ıËÚÔÛÎÏ‹ÚˆÛ˘ (1,2). ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÔÍ›‰ˆÛ˘ ÙfiÛÔ ÙÔ ÏÈȉȷÎfi ÂÚȯfiÌÂÓÔ, fiÛÔ Î·È Ë ·ÔÏÈÔÚˆÙ½ÓË B-100 (∞poB100) Ù˘ LDL ˘Ê›ÛÙ·ÓÙ·È ¯ËÌÈΤ˜ ÙÚÔÔÔÈ‹ÛÂȘ ‰È·Ì¤ÛÔ˘ ·ÓÙȉڿÛÂˆÓ ÛÙȘ Ôԛ˜ Û˘ÌÌÂÙ¤¯Ô˘Ó ÔÈ ÂχıÂÚ˜ Ú›˙˜. ªÈ· ·fi ·˘Ù¤˜ ÙȘ ÙÚÔÔÔÈ‹ÛÂȘ Â›Ó·È Ë ˘ÂÚÔÍ›‰ˆÛË ÙˆÓ ÔÏ˘·ÎfiÚÂÛÙˆÓ ÏÈ·ÚÒÓ ÔͤˆÓ Ù· ÔÔ›· Â›Ó·È ÂÛÙÂÚÔÔÈË̤ӷ ÛÙËÓ sn-2 ı¤ÛË ÌÔÚ›ˆÓ ʈÛÊ·Ùȉ˘ÏÔ¯ÔÏ›Ó˘ (PC) ÚÔ˜ Ù· ·ÓÙ›ÛÙÔȯ· ˘‰ÚÔ¸ÂÚÔÍ›‰È·. Δ· ˘‰ÚÔ¸ÂÚÔÍ›‰È· ÛÙË Û˘Ó¤¯ÂÈ· ‰È·ÛÒÓÙ·È, Ì ·ÔÙ¤ÏÂÛÌ· ÙÔÓ Û¯ËÌ·ÙÈÛÌfi ‚ÈÔÏÔÁÈο ÂÓÂÚÁÒÓ ÔÍÂȉˆÌ¤ÓˆÓ ʈÛÊÔÏÈȉ›ˆÓ (oxPL) Î·È ·Ï‰Â¸‰ÒÓ, fiˆ˜ Ë ÌËÏÔÓÈ΋ ‰È·Ï‰Â˛‰Ë (MDA) Î·È Ë 4-˘‰ÚÔ͢ÓÔÓÂÓ¿ÏË (4-∏¡∂) (2). ªÈ· ·fi ÙȘ ÛËÌ·ÓÙÈÎfiÙÂÚ˜ ‰ÈÂÚÁ·Û›Â˜ Ô˘ Ï·Ì‚¿ÓÂÈ ¯ÒÚ· ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÔÍ›‰ˆÛ˘ Ù˘ LDL, Â›Ó·È Ë ˘‰ÚfiÏ˘ÛË ÙˆÓ Û¯ËÌ·ÙÈ˙fiÌÂÓˆÓ oxPL Î·È Ë ·Ú·ÁˆÁ‹ Ï˘ÛÔʈÛÊ·Ùȉ˘ÏÔ¯ÔÏ›Ó˘ (lyso-PC), ÌÈ· ·ÓÙ›‰Ú·ÛË Ô˘ ηٷχÂÙ·È ·fi ÙË ÊˆÛÊÔÏÈ¿ÛË ∞2 Ô˘ Â›Ó·È Û˘Ó‰Â‰Â̤ÓË ÛÙËÓ LDL (ÏÈÔÚˆÙÂ˚ÓÈ΋ ʈÛÊÔÏÈ¿ÛË ∞2, Lp-PLA2) (3). ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÔÍ›‰ˆÛ˘ Ù˘ LDL, Ë ÂÓÂÚÁfiÙËÙ· ÙÔ˘ ÂÓ˙‡ÌÔ˘ ÌÂÈÒÓÂÙ·È, Û˘ÓÂÒ˜ Ô ‚·ıÌfi˜ Ù˘ ÔÍ›‰ˆÛ˘ Ù˘ LDL ÂËÚ¿˙ÂÈ ÛËÌ·ÓÙÈο ÙËÓ ÂÓÂÚÁfiÙËÙ· ÙÔ˘ ÂÓ˙‡ÌÔ˘ Î·È ÂÔ̤ӈ˜ Ù· Â›‰· ÙˆÓ Û¯ËÌ·ÙÈ˙fiÌÂÓˆÓ oxPL Î·È lyso-PC ÛÙËÓ oxLDL (4). ªÈ· ÛËÌ·ÓÙÈ΋ ȉÈfiÙËÙ· Ù˘ oxLDL Â›Ó·È Ë ÂÌÊ¿ÓÈÛË ·ÓÙÈÁÔÓÈ-

ÎfiÙËÙ·˜ Ë ÔÔ›· ¤¯ÂÈ ˆ˜ Û˘Ó¤ÂÈ· ÙÔ Û¯ËÌ·ÙÈÛÌfi ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ Ù˘ oxLDL (5) ™ËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ·ÓÙÈÁÔÓÈÎfiÙËÙ· Ù˘ oxLDL ‰È·‰Ú·Ì·Ù›˙Ô˘Ó ÙfiÛÔ Ù· oxPL fiÛÔ Î·È Ë lyso-PC Û˘ÌÌÂÙ¤¯ÔÓÙ·˜ ÛÙÔ Û¯ËÌ·ÙÈÛÌfi ‰È·ÊfiÚˆÓ ·ÓÙÈÁÔÓÈÎÒÓ ÂÈÙfiˆÓ ÛÙ· ۈ̷ٛ‰È· Ù˘ oxLDL (6, 7). ªÂ ‰Â‰Ô̤ÓÔ fiÙÈ Ë Lp-PLA2 Ô˘ Û˘Ó‰¤ÂÙ·È ÛÙËÓ LDL Â›Ó·È Ô Î‡ÚÈÔ˜ ·Ú¿ÁÔÓÙ·˜ Ô˘ ηıÔÚ›˙ÂÈ Ù· Â›‰· ÙˆÓ oxPL Î·È lyso-PC ÛÙËÓ oxLDL, ÙÔ ¤Ó˙˘ÌÔ ·˘Ùfi ÌÔÚ› Ó· ÂËÚ¿˙ÂÈ ÙÔ Â›‰Ô˜ ÙˆÓ ·ÓÙÈÁÔÓÈÎÒÓ ÂÈÙfiˆÓ, ηıÒ˜ Î·È ÙÔ˘˜ Ù›ÙÏÔ˘˜ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ Ù˘ oxLDL (8). ¶ÔÏϤ˜ ÌÂϤÙ˜ ¤¯Ô˘Ó ·Ó·ÊÂÚı› ÛÙËÓ ·ÚÔ˘Û›· ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ Ù˘ ¤ÓÙÔÓ· ÔÍÂȉˆÌ¤Ó˘ LDL ÛÙÔÓ ÔÚfi ·ÛıÂÓÒÓ Ì ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ ·ÏÏ¿ Î·È ÛÙÔÓ ÔÚfi ˘ÁÈÒÓ ÂıÂÏÔÓÙÒÓ (1, 2, 9, 10). π‰È·›ÙÂÚ· Û ·ÛıÂÓ›˜ ÌÂÙ¿ ·fi Ô͇ ÛÙÂÊ·ÓÈ·›Ô Û‡Ó‰ÚÔÌÔ (√™™) ·Ú·ÙËÚÂ›Ù·È ‚Ú·¯˘ÚfiıÂÛÌË ·‡ÍËÛË ÙÔ˘ Ù›ÙÏÔ˘ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ Ï‹Úˆ˜ oxLDL ηıÒ˜ Î·È ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ oxPL ÛÙÔ Ï¿ÛÌ· (5). ∂›Ó·È ÁÓˆÛÙfi fiÙÈ Ë ¿ÌÂÛË ¯ÔÚ‹ÁËÛË ÛÙ·ÙÈÓÒÓ ‚ÂÏÙÈÒÓÂÈ ÙËÓ ÚfiÁÓˆÛË ·ÛıÂÓÒÓ ÌÂÙ¿ ·fi √™™. √È ˘ÔΛÌÂÓÔÈ Ì˯·ÓÈÛÌÔ› ‰ÂÓ Â›Ó·È ·fiÏ˘Ù· ÁÓˆÛÙÔ› ·ÏÏ¿ Ê·›ÓÂÙ·È fiÙÈ ‰ÂÓ Û¯ÂÙ›˙ÔÓÙ·È ÌfiÓÔ Ì ÙËÓ ˘ÔÏÈȉ·ÈÌÈ΋ ‰Ú¿ÛË ÙˆÓ ÛÙ·ÙÈÓÒÓ ·ÏÏ¿ Î·È Ì ‰È¿ÊÔÚ˜ ·ÓÙÈÊÏÂÁÌÔÓÒ‰ÂȘ (11), ·ÓÔÛÔÙÚÔÔÔÈËÙÈΤ˜ Î·È ·ÓÙÈÔÍÂȉˆÙÈΤ˜ ‰Ú¿ÛÂȘ Ô˘ Ù· Ê¿Ú̷η ·˘Ù¿ ÂÌÊ·Ó›˙Ô˘Ó (12, 13). ™Â ˘ÔÔÌ¿‰· ·ÛıÂÓÒÓ Ù˘ ÌÂϤÙ˘ MIRACL, Ë ¯ÔÚ‹ÁËÛË ·ÙÔÚ‚·ÛÙ·Ù›Ó˘ Û ·ÛıÂÓ›˜ ÌÂÙ¿ ·fi √™™, ¤¯ÂÈ Û˘Ó‰˘·ÛÙ› Ì Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ oxPL ÙÔ˘ ÔÚÔ‡ (14). ™ÙȘ ÌÂϤÙ˜ ·˘Ù¤˜ ÁÈ· ÙÔÓ

ÚÔÛ‰ÈÔÚÈÛÌfi ÙˆÓ Ù›ÙÏˆÓ ÙˆÓ ·˘ÙÔÓ·ÓÙÈÛˆÌ¿ÙˆÓ ¯ÚËÛÈÌÔÔÈ‹ıËΠÏ‹Úˆ˜ ÔÍÂȉˆÌ¤ÓË LDL, ‰ËÏ·‰‹ oxLDL ÏÔ‡ÛÈ· Û ·Ï‰Â˛‰Â˜. ¢ÂÓ Â›Ó·È fï˜ ̤¯ÚÈ Û‹ÌÂÚ· ÁÓˆÛÙ‹ Ë Â›‰Ú·ÛË Ù˘ ¯ÔÚ‹ÁËÛ˘ ÛÙ·ÙÈÓÒÓ ÛÙÔ˘˜ Ù›ÙÏÔ˘˜ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ‹È· ÔÍÂȉˆÌ¤ÓˆÓ ÌÔÚÊÒÓ LDL Û ·ÛıÂÓ›˜ ÌÂÙ¿ ·fi Ô͇ ÛÙÂÊ·ÓÈ·›Ô ÂÂÈÛfi‰ÈÔ. ™ÎÔfi˜ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘ ‹Ù·Ó Ó· ÌÂÏÂÙËıÔ‡Ó ÔÈ Ù›ÙÏÔÈ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ‹È· ÔÍÂȉˆÌ¤ÓˆÓ ÌÔÚÊÒÓ LDL, ‰ËÏ·‰‹ ÌÔÚÊÒÓ Ù˘ oxLDL ÏÔ‡ÛÈˆÓ Û ÔxPL ‹/Î·È lyso-PC Û ·ÛıÂÓ›˜ Ì Ô͇ ÛÙÂÊ·ÓÈ·›Ô ÂÂÈÛfi‰ÈÔ. ∂›Û˘ ÌÂÏÂÙ‹ıËÎÂ Ë Û˘ÌÂÚÈÊÔÚ¿ ÙÔ˘ Ù›ÙÏÔ˘ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ·˘ÙÒÓ ÛÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ¯ÚfiÓÔ˘ ÌÂÙ¿ ·fi ÙÔ ÛÙÂÊ·ÓÈ·›Ô ÂÂÈÛfi‰ÈÔ Î·ıÒ˜ Î·È Ë Â›‰Ú·ÛË Ù˘ ¯ÔÚ‹ÁËÛ˘ ·ÙÔÚ‚·ÛÙ·Ù›Ó˘ ÛÙȘ ·Ú·¿Óˆ Èı·Ó¤˜ ÌÂÙ·‚ÔϤ˜.

ÀÏÈÎfi Î·È Ì¤ıÔ‰Ô˜ ¶ÏËı˘ÛÌfi˜ Ù˘ ÌÂϤÙ˘ ÀÏÈÎfi Ù˘ ÌÂϤÙ˘ ·ÔÙ¤ÏÂÛ·Ó ÂÓ‹ÓÙ·-¤ÓÙ (55) ·ÛıÂÓ›˜ (̤ÛË ËÏÈΛ· 58,9±9 ¤ÙË, 42-78 ÂÙÒÓ, 49 ¿Ó‰Ú˜, 6 Á˘Ó·›Î˜) Ì √™™. √È ·ÛıÂÓ›˜ ·˘ÙÔ› ›¯·Ó ÂχıÂÚÔ ·ÙÔÌÈÎfi ·Ó·ÌÓËÛÙÈÎfi ηډȷÁÁÂȷ΋˜ ‹ ¿ÏÏ˘ ÓfiÛÔ˘ ‹ ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË, ‰ÂÓ ‹Ù·Ó Û ÔÔÈ·‰‹ÔÙ ·ÁˆÁ‹ ÚÈÓ ÙÔ ÂÂÈÛfi‰ÈÔ Î·È ÂÈÛ‹¯ıËÛ·Ó ÛÙËÓ ÌÔÓ¿‰· ·Ú·ÎÔÏÔ‡ıËÛ˘ ηډÈÔ·ıÒÓ ÙÔ˘ ¶·ÓÂÈÛÙËÌÈ·ÎÔ‡ ¡ÔÛÔÎÔÌ›Ԣ πˆ·ÓÓ›ÓˆÓ Ì ÙÂÎÌËÚȈ̤ÓË ‰È¿ÁÓˆÛË ÔͤԘ ÛÙÂÊ·ÓÈ·›Ô˘ Û˘Ó‰ÚfiÌÔ˘ ¯ˆÚ›˜ ÂÌ̤ÓÔ˘Û· ·Ó¿Û·ÛË ÙÔ˘ ‰È·ÛÙ‹Ì·ÙÔ˜ ST ÛÙÔ ËÏÂÎÙÚÔηډÈÔÁÚ¿ÊËÌ· (NSTEMI) Û ‰È¿ÛÙËÌ· ÏÈÁfiÙÂÚÔ ÙˆÓ 2

23

∞ÔÚÚfiÊËÛË, 234 nm

™∂¶Δ∂ªμƒπ√™ 2008

XÚfiÓÔ˜ (ÏÂÙ¿) ∂ÈÎfiÓ· 1. ™ÈÁÌÔÂȉ›˜ ηÌ‡Ï˜ ÔÍ›‰ˆÛ˘ Ù˘ LDL Ì ‹ ¯ˆÚ›˜ ·ÂÓÂÚÁÔÔÈË̤ÓË ÙËÓ PAF-AH Î·È ÛËÌ›· ·ÔÌfiÓˆÛ˘ ÙˆÓ ·ÓÙÈÁfiÓˆÓ oxLDL Î·È oxLDL(-) (‰Â˜ ΛÌÂÓÔ) ˆÚÒÓ ·fi ÙËÓ ¤Ó·ÚÍË ÙˆÓ Û˘Ìو̿وÓ. ∞ÛıÂÓ›˜, ÔÈ ÔÔ›ÔÈ ÌÂÙ¿ ÙËÓ ·Ú¯È΋ ÂÎÙ›ÌËÛË ‰ÂÓ Û˘ÌÏ‹ÚˆÓ·Ó Ù· ÎÚÈÙ‹ÚÈ· ‰È¿ÁÓˆÛ˘ NSTEMI, ·ÔÎÏ›ÛÙËÎ·Ó ·fi ÙËÓ ÌÂϤÙË. ŸÏÔÈ ÔÈ ·ÛıÂÓ›˜ ˘Ô‚Ï‹ıËÎ·Ó Û ‰È·ÁÓˆÛÙÈ΋ ·ÁÁÂÈÔÁÚ·Ê›· ÙˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ ·ÁÁ›ˆÓ Î·È ‰È·‰ÂÚÌÈ΋ ·ÁÁÂÈÔÏ·ÛÙÈ΋ Ì ¯Ú‹ÛË ÂÓ‰ÔÚfiÛıÂÛ˘ (stent) ÂÓÙfi˜ 24 ˆÚÒÓ ·fi ÙËÓ ÂÈÛ·ÁˆÁ‹ ÙÔ˘˜ ÛÙË ÌÔÓ¿‰·. ∞ÛıÂÓ›˜ Ô˘ ˘Ô‚Ï‹ıËÎ·Ó Û ·ÔÚÙÔÛÙÂÊ·ÓÈ·›· ·Ú¿Î·Ì„Ë Â›Ù ÛÙË ‰È¿ÚÎÂÈ· Ù˘ ÓÔÛËÏ›·˜ ÙÔ˘˜, ›Ù ÛÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘, ηıÒ˜ Î·È ·ÛıÂÓ›˜ Ì «Ê˘ÛÈÔÏÔÁÈο» ÛÙÂÊ·ÓÈ·›· ·ÁÁ›· (Ï›· ÛÙÂÊ·ÓÈ·›· ·ÁÁ›· ÌÂ Ê˘ÛÈÔÏÔÁÈ΋ ‰È¿ÌÂÙÚÔ ·˘ÏÔ‡ ÛÙË ÛÙÂÊ·ÓÈÔÁÚ·Ê›·) ·ÔÎÏ›ÛÙËÎ·Ó Â›Û˘ ·fi ÙË ÌÂϤÙË. √È ·ÛıÂÓ›˜ ηٿ ÙËÓ ÂÚ›Ô‰Ô ·Ú·ÎÔÏÔ‡ıËÛ˘ ‹Ù·Ó Û ·ÁˆÁ‹ Ì ·ÛÈÚ›ÓË (100 mg/̤ڷ), ÎÏÔȉÔÁÚ¤ÏË (75 mg/̤ڷ), Î·È ‚-·ÔÎÏÂÈÛÙ‹. ∞ÙÔÚ‚·ÛÙ·Ù›ÓË ¯ÔÚËÁ‹ıËΠ۠fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓ›˜ ÛÙË ‰È¿ÚÎÂÈ· Ù˘ ÓÔÛËÏ›·˜ ÙÔ˘˜ (3-5 ̤Ú˜). ªÂÙ¿ ÙËÓ ¤ÍÔ‰Ô ·fi ÙÔ ÓÔÛÔÎÔÌ›Ô

24

Ë Û˘Ó¤¯ÈÛË Ù˘ ˘ÔÏÈȉ·ÈÌÈ΋˜ ·ÁˆÁ‹˜ ‹Ù·Ó ÛÙËÓ Â˘ı‡ÓË ÙˆÓ ıÂÚ·fiÓÙˆÓ È·ÙÚÒÓ ÙÔ˘˜. √È ·ÛıÂÓ›˜ Ù¤ıËÎ·Ó Û ·Ú·ÎÔÏÔ‡ıËÛË ÁÈ· ‰È¿ÛÙËÌ· 6 ÌËÓÒÓ. ¢Â›ÁÌ·Ù· ÔÚÔ‡ Û˘ÏϤ¯ıËÎ·Ó Î·Ù¿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ (ÂÓÙfi˜ 30 ÏÂÙÒÓ ·fi ÙËÓ ÂÌÊ¿ÓÈÛ‹ ÙÔ˘˜ ÛÙ· Â›ÁÔÓÙ· È·ÙÚ›· ÙÔ˘ ÓÔÛÔÎÔÌ›Ԣ) Î·È ÛÙÔÓ 1Ô , 3Ô Î·È 6Ô Ì‹Ó· ÌÂÙ¿. ™ÙÔ˘˜ ·ÛıÂÓ›˜ ¤ÁÈÓ ηٷÁÚ·Ê‹ fiÏˆÓ ÙˆÓ ÎÏ·ÛÈÎÒÓ ·Ú·ÁfiÓÙˆÓ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ (·ÚÙËÚȷ΋ ˘¤ÚÙ·ÛË, οÓÈÛÌ·, ÎÏËÚÔÓÔÌÈÎfi ÈÛÙÔÚÈÎfi ÚÒÈÌ˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘ Î·È Ô ‰Â›ÎÙ˘ Ì¿˙·˜ ÛÒÌ·ÙÔ˜), ÂÓÒ ÚÔÛ‰ÈÔÚ›ÛÙËΠÙÔ ÏÈȉ·ÈÌÈÎfi ÚÔÊ›Ï ÙÔ˘˜, Û οı ¯ÚÔÓÈ΋ ÛÙÈÁÌ‹. √È ·ÛıÂÓ›˜ ¯ˆÚ›ÛÙËÎ·Ó Û ‰‡Ô ÔÌ¿‰Â˜ Ì ‚¿ÛË ÙË ˘ÔÏÈȉ·ÈÌÈ΋ ·ÁˆÁ‹ ÛÙËÓ ÔÔ›· ›¯·Ó ˘Ô‚ÏËı› ηٿ ÙËÓ ÂÚ›Ô‰Ô ·Ú·ÎÔÏÔ‡ıËÛ˘. ™ÙËÓ ÚÒÙË ÔÌ¿‰· ÂÓÙ¿¯ıËÎ·Ó 34 ·ÛıÂÓ›˜, ÔÈ ÔÔ›ÔÈ ‹Ù·Ó Û ·ÁˆÁ‹ Ì ·ÙÔÚ‚·ÛÙ·Ù›ÓË Î·ı' fiÏË ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ ¯ˆÚ›˜ ‰È·ÎÔ¤˜ (fiÏÔÈ ÔÈ ·ÛıÂÓ›˜ ¤Ï·‚·Ó 20-40 mg/̤ڷ). ™ÙË ‰Â‡ÙÂÚË ÔÌ¿‰· Û˘ÌÂ-

ÚÈÂÏ‹ÊıËÎ·Ó ÔÈ 21 ·ÛıÂÓ›˜, ÔÈ ÔÔ›ÔÈ Â›¯·Ó ‰È·Îfi„ÂÈ ÙËÓ ·ÁˆÁ‹ Ì ·ÙÔÚ‚·ÛÙ·Ù›ÓË ÂÓÙfi˜ ‰‡Ô ¤ˆ˜ ÙÂÛÛ¿ÚˆÓ ËÌÂÚÒÓ ÌÂÙ¿ ÙËÓ ¤ÍÔ‰fi ÙÔ˘˜ ·fi ÙÔ ÓÔÛÔÎÔÌÂ›Ô Î·È ‰ÂÓ ¤Ï·‚·Ó ηıfiÏÔ˘ ˘ÔÏÈȉ·ÈÌÈ΋ ·ÁˆÁ‹ ηı' fiÏË ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÍ¿ÌËÓ˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘. ∞ÛıÂÓ›˜ ÔÈ ÔÔ›ÔÈ Ï¿Ì‚·Ó·Ó ÛÙ·Ù›Ó˜ ÂÚÈÛÙ·Ûȷο, ‹ ˘Ô‚Ï‹ıËÎ·Ó Û ¿ÏÏË ˘ÔÏÈȉ·ÈÌÈ΋ ·ÁˆÁ‹ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ ·ÔÎÏ›ÛÙËÎ·Ó ·fi ÙË ÌÂϤÙË.

¶ÂÈÚ·Ì·ÙÈ΋ ‰È·‰Èηۛ· ∏ ÂÈÚ·Ì·ÙÈ΋ ‰È·‰Èηۛ· Ô˘ ·ÎÔÏÔ˘ı‹ıËΠ¤¯ÂÈ ·Ó·Ï˘ÙÈο ÂÚÈÁÚ·Ê› Û ÚÔËÁÔ‡ÌÂÓ˜ ÌÂϤÙ˜ Ì·˜ (8, 15, 16). ™˘ÓÔÙÈο Ë ÔÍ›‰ˆÛË Ù˘ LDL Ú·ÁÌ·ÙÔÔÈ‹ıËΠ̠‹ ¯ˆÚ›˜ ·ÂÓÂÚÁÔÔÈË̤ÓË ÙËÓ ÂÓ‰ÔÁÂÓ‹ LpPLA2 (4). ¶·Ú·Û΢¿ÛıËÎ·Ó ÙÚÂȘ ÌÔÚʤ˜ oxLDL Ì ÂÓÂÚÁfi ÙËÓ ÂÓ‰ÔÁÂÓ‹ Lp-PLA2, Ë oxLDLL (ÛÙÔ Ù¤ÏÔ˜ Ù˘ Ï·Óı¿ÓÔ˘Û·˜ Ê¿Û˘), Ë oxLDLP (ÛÙÔ Ù¤ÏÔ˜ Ù˘ ÂÎıÂÙÈ΋˜ Ê¿Û˘) Î·È Ë oxLDLD (ÛÙÔ Ù¤ÏÔ˜ Ù˘ Ê¿Û˘ ·ÔÈÎÔ‰fiÌËÛ˘). √È ›‰È˜ ÌÔÚʤ˜ ·Ú·-

¶ƒ√∫§π¡π∫∏ ∂ƒ∂À¡∞ ¶›Ó·Î·˜ 1 ÷ڷÎÙËÚÈÛÙÈο ÙÔ˘ ÏËı˘ÛÌÔ‡ Ù˘ ÌÂϤÙ˘ √Ì¿‰· ·ÛıÂÓÒÓ Ô˘ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË (n=34)

√Ì¿‰· ·ÛıÂÓÒÓ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË (n=21)

p-value

∏ÏÈΛ· (¤ÙË) ÕÓ‰Ú˜/°˘Ó·›Î˜

58,2±8,97 30/4

60,1±9,22 19/2

0,453 0,285

¶·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ À¤ÚÙ·ÛË (n,%) ∂ÓÂÚÁÔ› ηÓÈÛÙ¤˜ (n,%) ∫ÏËÚÔÓÔÌÈÎfi ÈÛÙÔÚÈÎfi (n,%) BMI (kg/m2)

11 (32,3%) 26 (76,4%) 6 (17,6%) 26,9±2,37

7 (33,3%) 14 (66,7%) 6 (28,5%) 27,8±2,24

0,584 0,252 0,266 0,218

248,5±52,7 165,5±49,4 49,2±8,7 193,1±122,9 133,6±23,7 119,5±28,1 44,3±21,9 1,36±0,27 9,9±8,5

212,2±42,2 134,9±28,8 45,8±11,0 158,8±97,9 128,6±22,7 101,4±31,2 37,4±28,6 1,4±0,37 8,6±4,5

0,007 0,013 0,240 0,259 0,474 0,005 0,387 0,534 0,462

2,11±1,48

2,73±1,18

0,274

§Èȉ·ÈÌÈÎfi ÚÔÊ›Ï √ÏÈ΋ ¯ÔÏËÛÙÂÚfiÏË(mg/dl) LDL ¯ÔÏËÛÙÂÚfiÏË (mg/dl) HDL ¯ÔÏËÛÙÂÚfiÏË (mg/dl) ΔÚÈÁÏ˘ÎÂÚ›‰È·(mg/dl) ∞po A-I (mg/dl) ∞po B (mg/dl) ∞ÔÏÈÔÚˆÙ½ÓË E (mg/dl) LDL / ApoB Lp(a) (mg/dl) CRP (mg/l)

Û΢¿ÛıËÎ·Ó ÌÂÙ¿ ·fi ÚÔËÁÔ‡ÌÂÓË ·ÂÓÂÚÁÔÔ›ËÛË Ù˘ Lp-PLA2 [oxLDL(-)], Ë oxLDL(-)L (ÛÙÔ Ù¤ÏÔ˜ Ù˘ Ï·Óı¿ÓÔ˘Û·˜ Ê¿Û˘), Ë oxLDL(-)P (ÛÙÔ Ù¤ÏÔ˜ Ù˘ ÂÎıÂÙÈ΋˜ Ê¿Û˘) Î·È Ë oxLDL(-)D (ÛÙÔ Ù¤ÏÔ˜ Ù˘ Ê¿Û˘ ·ÔÈÎÔ‰fiÌËÛ˘), (∂ÈÎfiÓ· 1). ∂›Û˘ ·Ú·Û΢¿ÛÙËÎÂ Ë LDL ÙÚÔÔÔÈË̤ÓË Ì MDA (MDA-LDL). Δ· ·˘ÙÔ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ Ê˘ÛÈ΋˜ LDL (natLDL), fiÏˆÓ ÙˆÓ ÌÔÚÊÒÓ oxLDL Î·È MDA-LDL ÚÔÛ‰ÈÔÚ›ÛÙËÎ·Ó Ì ̤ıÔ‰Ô ELISA. Δ· ·ÔÙÂϤÛÌ·Ù· ÂÎÊÚ¿ÛÙËÎ·Ó ˆ˜ Ô ÏfiÁÔ˜ ÙˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ oxLDL/ natLDL (17-19). Δ· Â›‰· ÔxLDL ÛÙÔÓ ÔÚfi ÚÔÛ‰ÈÔÚ›ÛÙËÎ·Ó Ì ELISA Ì ÙË ¯Ú‹ÛË ÂÌÔÚÈÎÔ‡ kit (Mercodia® Oxidized LDL ELISA, Mercodia AB). Δ· ·ÔÙÂϤÛÌ·Ù· ÂÎÊÚ¿ÛÙËÎ·Ó Û U/l. ∏ ÂÓÂÚÁfiÙËÙ· Ù˘ Lp-PLA2 ÙÔ˘ ÔÚÔ‡ ÚÔÛ‰ÈÔÚ›ÛÙËΠ̠ÙË Ì¤ıÔ‰Ô È˙ËÌ·ÙÔÔ›ËÛ˘ Ì ÙÚȯψÚÔÍÂÈÎfi Ô͇ (TCA), fiˆ˜ ¤¯ÂÈ ÚÔËÁÔ‡ÌÂÓ· ÂÚÈÁÚ·Ê› (4). √È ÏÈȉ·ÈÌÈΤ˜ ·Ú¿ÌÂÙÚÔÈ, Ù· Â›‰· ÙˆÓ ·ÔÏÈÔÚˆÙÂ˚ÓˆÓ Î·È Ù· Â›‰· Ù˘ ˘„ËÏ‹˜ ¢·ÈÛıËÛ›·˜ CRP ÚÔÛ‰ÈÔÚ›ÛÙË-

Î·Ó fiˆ˜ ¤¯Ô˘Ì ÂÚÈÁÚ¿„ÂÈ Û ÚÔËÁÔ‡ÌÂÓË ÌÂϤÙË (16).

™Ù·ÙÈÛÙÈ΋ ·Ó¿Ï˘ÛË √È Û˘Ó¯›˜ ÌÂÙ·‚ÏËÙ¤˜ ÂÎÊÚ¿ÛÙËÎ·Ó ˆ˜ ̤ÛÔÈ fiÚÔÈ ± Ù˘È΋ ·fiÎÏÈÛË (mean ± standard deviation), ÂÓÒ ÔÈ ‰È·ÎÚÈÙ¤˜ ÌÂÙ·‚ÏËÙ¤˜ ÂÎÊÚ¿ÛÙËÎ·Ó ˆ˜ ·fiÏ˘ÙÔÈ ·ÚÈıÌÔ›. √È Ù›ÙÏÔÈ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ÂÎÊÚ¿ÛÙËÎ·Ó ˆ˜ ̤ÛÔÈ fiÚÔÈ ± Ù˘È΋ ·fiÎÏÈÛË. °È· ÙË Û‡ÁÎÚÈÛË ÙˆÓ ‰È·ÊfiÚˆÓ ÌÂÙ·‚ÏËÙÒÓ ÌÂٷ͇ ÙˆÓ ‰‡Ô ÔÌ¿‰ˆÓ ηٿ ÙË ÛÙÈÁÌ‹ ÚÈÓ ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂÚ·›·˜ Ú·ÁÌ·ÙÔÔÈ‹ıËΠStudent's t-test (ÁÈ· ÙȘ Û˘Ó¯›˜ ÌÂÙ·‚ÏËÙ¤˜) Î·È x2-test (ÁÈ· ÙȘ ‰È·ÎÚÈÙ¤˜ ÌÂÙ·‚ÏËÙ¤˜). ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ ÁÈ· οı ÔÌ¿‰· ·ÛıÂÓÒÓ ¯ˆÚÈÛÙ¿, ‰È·ÊÔÚ¤˜ ÛÙȘ ÙÈ̤˜ ÙˆÓ ÌÂÙ·‚ÏËÙÒÓ Û οı ¯ÚÔÓÈ΋ ÛÙÈÁÌ‹ ÂÎÙÈÌ‹ıËÎ·Ó Ì ÙË ‚Ô‹ıÂÈ· Ù˘ ·Ó¿Ï˘Û˘ Ù˘ ‰È·Î‡Ì·ÓÛ˘ ÁÈ· Â·Ó·Ï·Ì‚·ÓfiÌÂÓ˜ ÌÂÙÚ‹ÛÂȘ (repeated measures analysis of variances - ANOVA). °È· ÙËÓ ÂÎÙ›ÌËÛË Ù˘¯fiÓ ‰È·ÊÔÚÒÓ ÛÙȘ ÌÂÙ·‚ÔϤ˜ ÙˆÓ ‰È·ÊfiÚˆÓ ·Ú·Ì¤ÙÚˆÓ Û οı ¯ÚÔÓÈ΋ ÛÙÈÁÌ‹ ÌÂٷ͇ ÙˆÓ

‰‡Ô ÔÌ¿‰ˆÓ ·ÛıÂÓÒÓ Ù˘ ÌÂϤÙ˘ Ú·ÁÌ·ÙÔÔÈ‹ıËΠ·Ó¿Ï˘ÛË Û˘ÌÌÂÙ·‚ÏËÙ‹˜ (analysis of covariance, ANCOVA), Ï·Ì‚¿ÓÔÓÙ·˜ ˆ˜ Û˘ÌÌÂÙ·‚ÏËÙ‹ ÙȘ ÙÈ̤˜ οı ÌÂÙ·‚ÏËÙ‹˜ ÚÈÓ ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂÚ·›·˜, ÒÛÙ ӷ Á›ÓÂÈ ‰ÈfiÚıˆÛË ˆ˜ ÚÔ˜ ·˘Ù¤˜. ∏ ÛÙ·ÙÈÛÙÈ΋ ÂÂÍÂÚÁ·Û›· ¤ÁÈÓ Ì ÙËÓ ‚Ô‹ıÂÈ· ÙÔ˘ ÛÙ·ÙÈÛÙÈÎÔ‡ ÏÔÁÈÛÌÈÎÔ‡ ®SPSS 11.0 software (SPSS INC., Chicago, III). ™Â οı ÂÚ›ÙˆÛË p-value <0,05 ıˆڋıËΠÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈÎfi.

∞ÔÙÂϤÛÌ·Ù· ∫ÏÈÓÈο Î·È ‚ÈÔ¯ËÌÈο ¯·Ú·ÎÙËÚÈÛÙÈο ÙÔ˘ ÏËı˘ÛÌÔ‡ Ù˘ ÌÂϤÙ˘ Δ· ¯·Ú·ÎÙËÚÈÛÙÈο ÙÔ˘ ÏËı˘ÛÌÔ‡ Ù˘ ÌÂϤÙ˘ Ê·›ÓÔÓÙ·È ÛÙÔÓ ¶›Ó·Î· 1. ¢ÂÓ ·Ú·ÙËÚ‹ıËÎ·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜ ‰È·ÊÔÚ¤˜ ÌÂٷ͇ ÙˆÓ ‰‡Ô ÔÌ¿‰ˆÓ ·ÛıÂÓÒÓ Ù˘ ÌÂϤÙ˘, fiÛÔÓ ·ÊÔÚ¿ ÙËÓ ËÏÈΛ·, ÙÔ Ê‡ÏÔ, ÙÔÓ ‰Â›ÎÙË Ì¿˙·˜ ÛÒÌ·ÙÔ˜ Î·È ÙËÓ Â›ÙˆÛË Ù˘ ·ÚÙËÚȷ΋˜ ˘¤ÚÙ·Û˘, ÙÔ˘ ηÓ›ÛÌ·ÙÔ˜ Î·È ÙÔ˘ ÎÏËÚÔÓÔÌÈÎÔ‡ ÈÛÙÔÚÈÎÔ‡ ÚÒÈ-

25

™∂¶Δ∂ªμƒπ√™ 2008

¶›Ó·Î·˜ 2 ªÂÙ·‚ÔϤ˜ ÙˆÓ ÏÈȉ·ÈÌÈÎÒÓ ·Ú·Ì¤ÙÚˆÓ Î·È Ù˘ CRP ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘. √Ì¿‰· ·ÛıÂÓÒÓ Ô˘ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË ∫·Ù¿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ 1 Ì‹Ó·˜ TCHL (mg/dl)

√Ì¿‰· ·ÛıÂÓÒÓ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË

∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ 3 Ì‹Ó˜

∫·Ù¿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ 6 Ì‹Ó˜

∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ 1 Ì‹Ó·˜

3 Ì‹Ó˜

6 Ì‹Ó˜

248,5±52,7

169,5±55 *

158,4±32,4 *

188,5±42,3 *

212,2±42,2

201,3±29,3 227,0±31,1

220,9±52,3

LDL-C (mg/dl) 165,5±49,4

100,0±40 *

90,4±27,4 *

110,1±30,9 *

134,9±28,8

121,6±32,7 138,7±22,5

134,6±43,3

HDL-C (mg/dl)

38,6±8,6 *

39,8±7,6 *

42,3±7,7 *

45,8±11,0

193,1±122,9 154,8±73,8

129,0±39,3

130,4±49

158,8±97,9

185,2±90,4 221,1±131

162,5±106,9

Apo A (mg/dl) 133,6±23,7 127,5±21,1 ^ 128,9±21,7 ^ 130,1±23,7 ^ Apo B (mg/dl) 119,5±28,1 90,4±43,2 *

TRG (mg/dl)

49,2±8,7

42,6±7,8

38,7±8,7

53,7±16,5

128,6±22,7

135,5±18,3 140,1±23,1

141,2±23,2

76,48±24,15 *

92,5±28,3 *

101,4±31,2

93,6±24,7

97,9±35,2

98,4±33,2

Apo E (mg/dl)

44,3±21,9

29,8±13 *

26,6±10,6 *

32,7±14,1 *

37,4±28,6

33,4±12,2

46,0±39,0

44,1±38,4

LDL / ∞poB

1,36±0,27

1,14±0,29

1,25±0,27

1,19±0,29

1,40±0,37

1,39±0,82

1,75±1,58

1,36±1,2

Lp(a) (mg/dl)

9,9±8,5

9,4±9,1

9,5±8,7

9,5±9,2

8,6±4,5

8,5±4,8

8,1±4,4

8,4±4,3

CRP (mg/L)

2,11±1,48

0,90±0,58 $

0,91±0,60 $

0,93±0,64 $

2,73±1,18

1,49±0,79

∧

1,62±0,77

∧

1,64±0,85 ∧

TCHL: ÔÏÈ΋ ¯ÔÏËÛÙÂÚfiÏË, LDL-C: LDL ¯ÔÏËÛÙÂÚfiÏË, HDL-C: HDL ¯ÔÏËÛÙÂÚfiÏË Î·È TRG: ÙÚÈÁÏ˘ÎÂÚ›‰È·. *p=0,0001, #p=0,01,$p=0,02, ∧p=0,04, Û ۇÁÎÚÈÛË Ì ÙËÓ ·ÓÙ›ÛÙÔÈ¯Ë ÙÈÌ‹ ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘

Ì˘ ηډȷÁÁÂȷ΋˜ ÓfiÛÔ˘. ŸÏÔÈ ÔÈ ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘ ‹Ù·Ó ÂχıÂÚÔÈ ÌÂÈ˙fiÓˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ ÂÂÈÛÔ‰›ˆÓ ηı' fiÏË ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÍ¿ÌËÓ˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘. √È ·ÛıÂÓ›˜ Ô˘ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË Û ۇÁÎÚÈÛË Ì ·˘ÙÔ‡˜ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó, ÂÌÊ¿ÓÈ˙·Ó ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘, ˘„ËÏfiÙÂÚ· Â›‰· ÔÏÈ΋˜ ¯ÔÏËÛÙÂÚfiÏ˘, LDL ¯ÔÏËÛÙÂÚfiÏ˘ Î·È apo μ (¶›Ó·Î·˜ 1). ∞ÓÙ›ıÂÙ·, ‰ÂÓ ·Ú·ÙËÚ‹ıËÎ·Ó ÛËÌ·ÓÙÈΤ˜ ‰È·ÊÔÚ¤˜ ÌÂٷ͇ ÙˆÓ ‰‡Ô ÔÌ¿‰ˆÓ ·ÛıÂÓÒÓ Ù˘ ÌÂϤÙ˘ fiÛÔÓ ·ÊÔÚ¿ ÙȘ ˘fiÏÔÈ˜ ÏÈȉ·ÈÌÈΤ˜ ·Ú·Ì¤ÙÚÔ˘˜ Î·È Ù· Â›‰· CRP ÔÚÔ‡ (¶›Ó·Î·˜ 1). ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ ·Ú·ÙËÚ‹ıËÎÂ, fiˆ˜ ·Ó·ÌÂÓfiÙ·Ó, ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙˆÓ ÏÈȉ·ÈÌÈÎÒÓ ·Ú·Ì¤ÙÚˆÓ ÛÙËÓ ÔÌ¿‰· ÙˆÓ ·ÛıÂÓÒÓ Ô˘ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË (¶›Ó·Î·˜ 2). ∏ ÛËÌ·ÓÙÈ΋ ·˘Ù‹ Ì›ˆÛË ·ÊÔÚÔ‡Û ٷ Â›‰· ÔÚÔ‡ Ù˘ ÔÏÈ΋˜, LDL Î·È HDL ¯ÔÏËÛÙÂÚfiÏ˘, ηıÒ˜ Â›Û˘ Î·È ·˘Ù¿ ÙˆÓ ∞po A-I, ∞po B Î·È ∞po E. √È ‰È·ÊÔÚ¤˜ ·˘Ù¤˜ ·Ú·ÙËÚ‹ıËÎ·Ó ·fi ÙÔÓ ÚÒÙÔ Ì‹Ó· Î·È ‰È·ÙËÚ‹ıËÎ·Ó Î·ı' fiÏË ÙË ‰È¿ÚÎÂÈ· Ù˘ Â-

26

ÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ ¶›Ó·Î·˜ 2). ∞ÓÙ›ıÂÙ· ‰ÂÓ ·Ú·ÙËÚ‹ıËÎ·Ó ÛËÌ·ÓÙÈΤ˜ ÌÂÙ·‚ÔϤ˜ ÛÙ· Â›‰· ÙˆÓ ÏÈȉ·ÈÌÈÎÒÓ ·Ú·Ì¤ÙÚˆÓ ÛÙËÓ ÔÌ¿‰· ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË. (¶›Ó·Î·˜ 2).

∂›‰· ÔÍÂȉˆÌ¤Ó˘ LDL ÔÚÔ‡ ™ÙË Ì¤ÙÚËÛË Î·Ù¿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘, ÔÈ ·ÛıÂÓ›˜ Ô˘ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË Û ۇÁÎÚÈÛË Ì ·˘ÙÔ‡˜ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó, ÂÌÊ¿ÓÈ˙·Ó ˘„ËÏfiÙÂÚ· Â›‰· oxLDL ÔÚÔ‡ (41,7±10,1 U/l ¤Ó·ÓÙÈ 32,8±7,3 U/l ·ÓÙ›ÛÙÔȯ·, p=0,02), ÁÂÁÔÓfi˜ Ô˘ Ê·›ÓÂÙ·È Ó· ÔÊ›ÏÂÙ·È ÛÙ· ˘„ËÏfiÙÂÚ· Â›‰· ÔÏÈ΋˜ ¯ÔÏËÛÙÂÚfiÏ˘ Ô˘ ÔÈ ·ÛıÂÓ›˜ ·˘ÙÔ› ·ÚÔ˘Û›·˙·Ó, ηıÒ˜ ‚Ú¤ıËΠÈÛ¯˘Ú‹ Û˘Û¯¤ÙÈÛË ÙˆÓ ÂÈ¤‰ˆÓ Ù˘ oxLDL ÌfiÓÔ Ì ٷ Â›‰· Ù˘ ÔÏÈ΋˜ ¯ÔÏËÛÙÂÚfiÏ˘ ÔÚÔ‡ ÙfiÛÔ Î·Ù¿ ÙË ¯ÚÔÓÈ΋ ÛÙÈÁÌ‹ Ù˘ ¤Ó·Ú͢ (r=0,584, p=0,002) fiÛÔ Î·È ÛÙÔÓ ÚÒÙÔ, ÙÚ›ÙÔ Î·È ¤ÎÙÔ Ì‹Ó· ·Ú·ÎÔÏÔ‡ıËÛ˘ (r=0,430, p=0,036 r=0,505, p=0,012 Î·È r=0,512, p=0,021 ·ÓÙ›ÛÙÔȯ·). ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ ÛÙÔ˘˜

·ÛıÂÓ›˜ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË, ·Ú·ÙËÚ‹ıËΠÛÙ·‰È·Î‹ ·‡ÍËÛË ÙˆÓ ÂÈ¤‰ˆÓ Ù˘ oxLDL ÔÚÔ‡ Û ۇÁÎÚÈÛË Ì ÙËÓ ÙÈÌ‹ ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘, ÙfiÛÔ ÛÙÔÓ 1Ô Ì‹Ó· (35,4±12 U/l ·‡ÍËÛË +8,2%±4,1%, p=0,03), fiÛÔ Î·È ÛÙÔÓ 3Ô Ì‹Ó· (41,4±16,8 U/l, ·‡ÍËÛË +27,4%±6,8%, p=0,01) ‹ ÙÔÓ 6Ô Ì‹Ó· ·Ú·ÎÔÏÔ‡ıËÛ˘ (44,2±17,2 U/l, ·‡ÍËÛË +34,7% ±8,3% p=0,01) (∂ÈÎfiÓ· 2). ∞ÓÙ›ıÂÙ·, ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË ·Ú·ÙËÚ‹ıËΠÚÔԉ¢ÙÈ΋ Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ ·˘ÙÒÓ, ·fi ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘, ÛÙÔÓ 1Ô Ì‹Ó· (35,2±12,7 U/l, Ì›ˆÛË 15,3%±7,2%, p=0,04), ÛÙÔÓ 3Ô Ì‹Ó· (31±12 U/l, Ì›ˆÛË 25,6%±8,7%, p=0,04) ¤ˆ˜ Î·È ÛÙÔÓ 6Ô Ì‹Ó· ·Ú·ÎÔÏÔ‡ıËÛ˘ (29,2±11,7 U/l, Ì›ˆÛË -30%± 6,7%, p=0,03) (∂ÈÎfiÓ· 2). Ÿˆ˜ ÚԤ΢„ ·fi ÙËÓ ·Ó¿Ï˘ÛË ANCOVA, ÌÂٷ͇ ÙˆÓ ‰‡Ô ÔÌ¿‰ˆÓ Ù˘ ÌÂϤÙ˘, ÔÈ ÌÂÙ·‚ÔϤ˜ ÛÙ· Â›‰· Ù˘ oxLDL ÙÔ˘ ÔÚÔ‡ ‰È¤ÊÂÚ·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο Û οı ¯ÚÔÓÈ΋ ÛÙÈÁÌ‹, ‹ÙÔÈ ÛÙÔÓ 1Ô Ì‹Ó· (-15,3% ±7,2%, ¤Ó·ÓÙÈ +8,2%±4,1%, ÁÈ· ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ Ï¿Ì‚·Ó·Ó Î·È ·˘ÙÔ‡˜ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó ·ÙÔÚ-

¶ƒ√∫§π¡π∫∏ ∂ƒ∂À¡∞ ¶›Ó·Î·˜ 3 Δ›ÙÏÔÈ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ‰È·ÊfiÚˆÓ ÌÔÚÊÒÓ LDL ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘ √Ì¿‰· ·ÛıÂÓÒÓ Ô˘ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË ∫·Ù¿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘

√Ì¿‰· ·ÛıÂÓÒÓ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË

∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ 1 Ì‹Ó·˜

∫·Ù¿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘

3 Ì‹Ó˜

6 Ì‹Ó˜

∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘

1 Ì‹Ó·˜

3 Ì‹Ó˜

6 Ì‹Ó˜

Anti- oxLDLL

0,986±0,179 0,982±0,194

1,041±0,216

1,019±0,110

0,893±0,163

1,066±0,276*

0,968±0,223

0,925±0,278

Anti- oxLDLP

1,089±0,226 1,137±0,247

1,073±0,181

1,110±0,158

0,962±0,186

1,127±0,274*

1,032±0,218

1,001±0,316

Anti- oxLDLD

1,222±0,380 1,232±0,351

1,187±0,261

1,169±0,298

0,994±0,284 1,224±0,481** 1,103±0,293

1,068±0,455

Anti- oxLDL(-)L 1,047±0,154 1,023±0,179

1,066±0,185

1,026±0,168

0,953±0,208

Anti- oxLDL(-)P 1,205±0,278 1,213±0,289

1,210±0,276

1,202±0,287

1,033±0,250

1,246±0,440* 1,236±0,268*

Anti- oxLDL(-)D 1,307±0,319 1,376±0,372

1,243±0,309

1,312±0,398

1,220±0,382

1,434±0,431# 1,452±0,309# 1,379±0,244$

Anti-MDA-LDL 1,274±0,211 1,214±0,189

1,292±0,206

1,299±0,201

1,208±0,155

1,055±0,213

1,197±0,158

1,122±0,210# 1,178±0,175*

1,197±0,139

1,158±0,413$

1,182±0,121

*p=0,01, #p=0,02, **p=0,03, $p=0,04 Û ۇÁÎÚÈÛË Ì ÙËÓ ·ÓÙ›ÛÙÔÈ¯Ë ÙÈÌ‹ ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘

‚·ÛÙ·Ù›ÓË ·ÓÙ›ÛÙÔȯ·, p=0,01), ÛÙÔÓ 3Ô Ì‹Ó· (-25,6±8,7% ¤Ó·ÓÙÈ +27,4±6,8%, ÁÈ· ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ Ï¿Ì‚·Ó·Ó Î·È ·˘ÙÔ‡˜ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË ·ÓÙ›ÛÙÔȯ· p=0,003) Î·È ÛÙÔÓ 6Ô Ì‹Ó· ·Ú·ÎÔÏÔ‡ıËÛ˘ (-30%±6,7% ¤Ó·ÓÙÈ +34,7%±8,3%, ÁÈ· ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ Ï¿Ì‚·Ó·Ó Î·È ·˘ÙÔ‡˜ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË ·ÓÙ›ÛÙÔȯ·, p=0,003 ∂ÈÎfiÓ· 2),

Δ›ÙÏÔÈ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ‰È·ÊfiÚˆÓ ÌÔÚÊÒÓ oxLDL ™ÙËÓ ÔÌ¿‰· ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË, ·Ú·ÙËÚ‹ıËÎ·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜ ·˘Í‹ÛÂȘ ÙÔÓ 1Ô Ì‹Ó· ·Ú·ÎÔÏÔ‡ıËÛ˘ Û ۇÁÎÚÈÛË Ì ÙȘ ·ÓÙ›ÛÙÔȯ˜ ÙÈ̤˜ ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘, ÛÙ· Â›‰· anti-oxLDLL, antioxLDLP, anti-oxLDLD, antioxLDL(-)P Î·È anti-oxLDL(-)D (¶›Ó·Î·˜ 3). ™ÙËÓ ›‰È· ÔÌ¿‰· ·ÛıÂÓÒÓ, ÔÈ Ù›ÙÏÔÈ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÙˆÓ oxLDLL, oxLDLP Î·È oxLDLD, ÂÌÊ¿ÓÈÛ·Ó Êı›ÓÔ˘Û· ÔÚ›· ÙfiÛÔ ÛÙÔ˘˜ 3 fiÛÔ Î·È ÛÙÔ˘˜ 6 Ì‹Ó˜ ·Ú·ÎÔÏÔ‡ıËÛ˘, Ì ·ÔÙ¤ÏÂÛÌ· Ó· ÌËÓ ·Ú·ÙËÚÔ‡ÓÙ·È ÛÙÔ˘˜ Û˘ÁÎÂÎÚÈ̤ÓÔ˘˜ Ì‹Ó˜ ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜ ‰È·ÊÔÚ¤˜ Û ۇÁÎÚÈÛË Ì ÙȘ ·ÓÙ›ÛÙÔȯ˜ ÙÈ̤˜ ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ (¶›Ó·-

η˜ 3, ∂ÈÎfiÓ· 3) ∞ÓÙ›ıÂÙ·, ÔÈ Ù›ÙÏÔÈ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÙˆÓ oxLDL(-)P Î·È oxLDL(-)D ‰Â ÌÂÈÒıËÎ·Ó ÌÂÙ¿ ÙÔÓ ÚÒÙÔ Ì‹Ó· ·Ú·ÎÔÏÔ‡ıËÛ˘, ·ÏÏ¿ ·Ú¤ÌÂÈÓ·Ó ÛÙ·ÙÈÛÙÈο ˘„ËÏfiÙÂÚÔÈ Û ۇÁÎÚÈÛË Ì ÙȘ ·Ú¯ÈΤ˜ ÙÔ˘˜ ÙÈ̤˜ ÙfiÛÔ ÛÙÔ˘˜ 3 Ì‹Ó˜ fiÛÔ Î·È ÛÙÔ˘˜ 6 Ì‹Ó˜ ·Ú·ÎÔÏÔ‡ıËÛ˘ (¶›Ó·Î·˜ 3). ™Â ·ÓÙ›ıÂÛË Ì ٷ ·Ú·¿Óˆ, ÔÈ Ù›ÙÏÔÈ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ oxLDL(-)L ‹Ù·Ó Û˘Ó¯Ҙ ·˘Í·ÓfiÌÂÓÔÈ Î·ı' fiÏË ÙË ‰È¿ÚÎÂÈ· Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ (¶›Ó·Î·˜ 3). ∏ Û˘Ó¯‹˜ ·˘Ù‹ ·‡ÍËÛË ‹Ù·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ ÛÙÔ˘˜ 3 Î·È ÙÔ˘˜ 6 Ì‹Ó˜, ·ÏÏ¿ fi¯È ÛÙÔÓ ÚÒÙÔ Ì‹Ó· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ (¶›Ó·Î·˜ 3). ¶Ú¤ÂÈ Ó· ÛËÌÂȈı› fiÙÈ ÛÙÔ˘˜ ·ÛıÂÓ›˜ ÔÈ ÔÔ›ÔÈ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË, ÔÈ Ù›ÙÏÔÈ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ fiÏˆÓ ÙˆÓ ÌÔÚÊÒÓ ÔÍÂȉˆÌ¤Ó˘ LDL ·Ú¤ÌÂÈÓ·Ó Û Â›‰· ·ÚfiÌÔÈ· Ì ٷ ·Ú¯Èο, ηı' fiÏË ÙË ‰È¿ÚÎÂÈ· Ù˘ ÌÂϤÙ˘ (¶›Ó·Î·˜ 3). ¢ÂÓ ·Ú·ÙËÚ‹ıËÎ·Ó ‰È·ÊÔÚ¤˜ ÛÙÔ˘˜ Ù›ÙÏÔ˘˜ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ Ù˘ MDA-LDL ÛÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ Û ηÌÈ¿ ·fi ÙȘ ÔÌ¿‰Â˜ Ù˘ ÌÂϤÙ˘ (¶›Ó·Î·˜ 3). √È ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË, Û˘ÁÎÚÈÓfiÌÂÓÔÈ Ì ·˘ÙÔ‡˜ Ô˘ Ï¿Ì‚·Ó·Ó, ÂÌÊ¿ÓÈÛ·Ó ÛÙÔÓ 1Ô Ì‹Ó· ·Ú·ÎÔÏÔ‡ıËÛ˘ ÛÙ·ÙÈÛÙÈο ÌÂÁ·Ï‡ÙÂÚ˜ % ÌÂÙ·‚ÔϤ˜ ÙˆÓ Ù›ÙÏˆÓ ÙˆÓ

·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ oxLDLL (24,8±30,6% ¤Ó·ÓÙÈ 3±25% ·ÓÙ›ÛÙÔȯ·, p=0,012), oxLDLP (21,2 ±17% ¤Ó·ÓÙÈ 8,8±30% ·ÓÙ›ÛÙÔȯ·, p=0,012), Î·È oxLDLD (34,9 ±47,5% ¤Ó·ÓÙÈ 4,5±28,2% ·ÓÙ›ÛÙÔȯ·, p=0,035). √È ·Ú·¿Óˆ ÌÂÙ·‚ÔϤ˜ ‰ÂÓ ‹Ù·Ó ϤÔÓ ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜ ÛÙÔÓ 3Ô Î·È 6Ô Ì‹Ó· ·Ú·ÎÔÏÔ‡ıËÛ˘ fiˆ˜ ÚԤ΢„ ·fi ÙËÓ ·Ó¿Ï˘ÛË ANCOVA Î·È ÌÂÙ¿ ÙË Î·Ù¿ÏÏËÏË ‰ÈfiÚıˆÛË ˆ˜ ÚÔ˜ ÙȘ ÙÈ̤˜ ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ (∂ÈÎfiÓ· 3). ŸÛÔÓ ·ÊÔÚ¿ ÙÔ˘˜ Ù›ÙÏÔ˘˜ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÙˆÓ ‰È·ÊfiÚˆÓ ÌÔÚÊÒÓ oxLDL(-), ÔÈ ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË, Û˘ÁÎÚÈÓfiÌÂÓÔÈ, Ì ·˘ÙÔ‡˜ Ô˘ Ï¿Ì‚·Ó·Ó, ÂÌÊ¿ÓÈÛ·Ó ÛÙ·ÙÈÛÙÈο ÌÂÁ·Ï‡ÙÂÚ˜ % ÌÂÙ·‚ÔϤ˜ ÙˆÓ Ù›ÙÏˆÓ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ Ù˘ oxLDL(-) P (26,8±55.2% ¤Ó·ÓÙÈ 2±28,6% ·ÓÙ›ÛÙÔȯ·, p=0,012) Î·È oxLDL(-)D (31,1±41,5% ¤Ó·ÓÙÈ 2,72± 23,4% ·ÓÙ›ÛÙÔȯ·, p=0,022) ÛÙÔÓ 1Ô Ì‹Ó· ·Ú·ÎÔÏÔ‡ıËÛ˘. √È ‰È·ÊÔÚ¤˜ ·˘Ù¤˜ ·Ú¤ÌÂÈÓ·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜ ÁÈ· ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË ÙfiÛÔ ÛÙÔÓ 3Ô Ì‹Ó· (oxLDL(-)P: 21,8 ±26,9% ¤Ó·ÓÙÈ 0,9± 25,4% ·ÓÙ›ÛÙÔȯ·, p=0,031, oxLDL(-)D: 24,5±34,1% ¤Ó·ÓÙÈ 7,8±27,4% ·ÓÙ›ÛÙÔȯ·, p=0,02) fiÛÔ Î·È ÛÙÔÓ 6Ô Ì‹Ó· ·Ú·ÎÔÏÔ‡ıËÛ˘ (oxLDL(-)P: 24,6±27,9% ¤Ó·ÓÙÈ 8,1±32,1% ·ÓÙ›ÛÙÔȯ·,

27

% ÌÂÙ·‚ÔÏ‹ ·fi Ù· Â›‰· ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ÌÂϤÙ˘

™∂¶Δ∂ªμƒπ√™ 2008

∞ÛıÂÓ›˜ Ô˘ ¤·ÈÚÓ·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË ∞ÛıÂÓ›˜ ¯ˆÚ›˜ ˘ÔÏÈȉ·ÈÌÈ΋ ·ÁˆÁ‹

$

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3 Ì‹Ó˜

6 Ì‹Ó˜

¶ÂÚ›Ô‰Ô˜ ·Ú·ÎÔÏÔ‡ıËÛ˘ ∂ÈÎfiÓ· 2. ªÂÙ·‚ÔϤ˜ (%) ÙˆÓ ÂÈ¤‰ˆÓ Ù˘ oxLDL ÔÚÔ‡ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ Û ۇÁÎÚÈÛË Ì ÙȘ ·ÓÙ›ÛÙÔȯ˜ ÙÈ̤˜ ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ (*p=0,01, **p=0,03, #p=0,04 Û ۇÁÎÚÈÛË Ì ÙËÓ ·ÓÙ›ÛÙÔÈ¯Ë ÙÈÌ‹ ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘, _p=0,003, $p=0,01 Û ۇÁÎÚÈÛË Ì ÙËÓ ·ÓÙ›ÛÙÔÈ¯Ë ÙÈÌ‹ ÙˆÓ ·ÛıÂÓÒÓ Ô˘ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË). p=0,04, oxLDL(-)D: 25,7± 40,3% ¤Ó·ÓÙÈ 8,5± 27,3% ·ÓÙ›ÛÙÔȯ·, p=0,04 - ∂ÈÎfiÓ· 3). ∂ÈÚfiÛıÂÙ·, ÔÈ ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË, Û ۇÁÎÚÈÛË Ì ·˘ÙÔ‡˜ Ô˘ Ï¿Ì‚·Ó·Ó, ÂÌÊ¿ÓÈÛ·Ó ÛÙ·ÙÈÛÙÈο ˘„ËÏfiÙÂÚ˜ % ÌÂÙ·‚ÔϤ˜ ÙÔ˘ Ù›ÙÏÔ˘ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ Ù˘ oxLDL(-)L, ÛÙÔÓ 3Ô Ì‹Ó· (15,5±21,4% ¤Ó·ÓÙÈ 1,65±18% ·ÓÙ›ÛÙÔȯ·, p=0,05) Î·È ÛÙÔÓ 6Ô Ì‹Ó· (28±43,2% ¤Ó·ÓÙÈ 1,7±23,9% ·ÓÙ›ÛÙÔȯ·, p=0,01), ·ÏÏ¿ fi¯È ÛÙÔÓ 1Ô Ì‹Ó· ·Ú·ÎÔÏÔ‡ıËÛ˘ (8±45,6% ¤Ó·ÓÙÈ 0,13±23,7% ·ÓÙ›ÛÙÔȯ·, p=0,152 - ∂ÈÎfiÓ· 3).

√ ÚfiÏÔ˜ Ù˘ Lp-PLA2 √È ÌÔÚʤ˜ oxLDL(-) ÔÈ Ôԛ˜ ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó ˆ˜ ·ÓÙÈÁfiÓ·, ·Ú·Û΢¿ÛÙËÎ·Ó ·ÊÔ‡ ÚÒÙ· ›¯Â ·ÂÓÂÚÁÔÔÈËı› Ë ÂÓ‰ÔÁÂÓ‹˜ Lp-PLA2. √È ÌÔÚʤ˜ ·˘Ù¤˜ Â›Ó·È ÏÔ‡ÛȘ Û oxPL ·ÏÏ¿ fi¯È Û lyso-PC (8). ∞ÓÙ›ıÂÙ· ÔÈ ÌÔÚʤ˜ Ù˘ oxLDL Ì ÂÓÂÚÁfi ÙËÓ Lp-PLA2 Â›Ó·È ÏÔ‡ÛȘ Û lysoPC, Ë ÔÔ›· ·ÔÙÂÏ› Î·È ÙÔ ÚÔ˚fiÓ Ù˘ Â›‰Ú·Û˘ Ù˘ LpPLA2 ÛÙ· oxPL. Δ· Â›‰· Ù˘ ÂÓÂÚÁfiÙËÙ·˜ Ù˘ Lp-PLA2 ÙÔ˘ ÔÚÔ‡, ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘,

28

‰Â ‰È¤ÊÂÚ·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂٷ͇ ÙˆÓ ‰‡Ô ÔÌ¿‰ˆÓ Ù˘ ÌÂϤÙ˘. ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘, Ë ÂÓÂÚÁfiÙËÙ· ÙÔ˘ ÂÓ˙‡ÌÔ˘ ‰Â ÌÂÙ·‚Ï‹ıËΠÛËÌ·ÓÙÈο ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË, (∂ÈÎfiÓ· 4). ∞ÓÙ›ıÂÙ·, ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË, ·Ú·ÙËÚ‹ıËΠÛËÌ·ÓÙÈ΋ Ì›ˆÛË Ù˘ ÂÓÂÚÁfiÙËÙ·˜ ÙÔ˘ ÂÓ˙‡ÌÔ˘ ÙÔÓ ÚÒÙÔ Ì‹Ó· Û ۇÁÎÚÈÛË Ì ÙËÓ ÙÈÌ‹ ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘, (Ì›ˆÛË Î·Ù¿ 23±11,1%, p=0,004). ∏ Ì›ˆÛË ·˘Ù‹ ‰È·ÙËÚ‹ıËΠÙÔÓ 3Ô Ì‹Ó· (Ì›ˆÛË Î·Ù¿ 16±7,4%, p=0,02) Î·È ÙÔÓ 6Ô Ì‹Ó· ·Ú·ÎÔÏÔ‡ıËÛ˘ (Ì›ˆÛË Î·Ù¿ 18±6,2%, p=0,005), Ì ·ÔÙ¤ÏÂÛÌ· ÔÈ % ÌÂÙ·‚ÔϤ˜ Ù˘ ÂÓÂÚÁfiÙËÙ·˜ ÙÔ˘ ÂÓ˙‡ÌÔ˘ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË, Û ۇÁÎÚÈÛË Ì ·˘ÙÔ‡˜ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó, ‰È¤ÊÂÚ·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο Û οı ¯ÚÔÓÈ΋ ÛÙÈÁÌ‹ Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ (∂ÈÎfiÓ· 4).

™˘˙‹ÙËÛË ™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË ‰ÈÂÚ¢ӋıËÎ·Ó ÁÈ· ÚÒÙË ÊÔÚ¿ ÔÈ Ù›ÙÏÔÈ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ‹È· ÔÍÂȉˆÌ¤ÓˆÓ ÌÔÚÊÒÓ LDL, ÛÂ

·ÛıÂÓ›˜ Ì √™™. Δ· ·ÔÙÂϤÛÌ·Ù· ‰Â›¯ÓÔ˘Ó fiÙÈ ÔÈ Ù›ÙÏÔÈ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ fiÏˆÓ ÙˆÓ ÌÔÚÊÒÓ oxLDL ·˘Í¿ÓÔÓÙ·È ÙÔÓ ÚÒÙÔ Ì‹Ó· ÌÂÙ¿ ·fi √™™. ∞ÍÈÔÛËÌ›ˆÙÔ Â›Ó·È fiÙÈ ÔÈ Ù›ÙÏÔÈ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÙˆÓ ÌÔÚÊÒÓ oxLDL ÏÔ‡ÛÈˆÓ Û lyso-PC Ê·›ÓÂÙ·È fiÙÈ ÌÂÈÒÓÔÓÙ·È ÛÙË Û˘Ó¤¯ÂÈ·, ÂÓÒ ÔÈ ·ÓÙ›ÛÙÔȯÔÈ Ù›ÙÏÔÈ ¤Ó·ÓÙÈ ÙˆÓ ÌÔÚÊÒÓ oxLDL ÏÔ‡ÛÈˆÓ Û oxPL [oxLDL(-)] ‰È·ÙËÚÔ‡ÓÙ·È Û ˘„ËÏ¿ Â›‰· ÁÈ· ÙÔ˘Ï¿¯ÈÛÙÔÓ 6 Ì‹Ó˜ ÌÂÙ¿ ÙÔ √™™. ∂ÈÚfiÛıÂÙ·, Ë Û˘ÁÎÂÎÚÈ̤ÓË ÌÂϤÙË ˘Ô‰ÂÈÎÓ‡ÂÈ ÁÈ· ÚÒÙË ÊÔÚ¿ fiÙÈ Ë ¯ÔÚ‹ÁËÛË ·ÙÔÚ‚·ÛÙ·Ù›Ó˘ ÙÚÔÔÔÈ› ÙË Û˘ÁÎÂÎÚÈ̤ÓË ·ÓÔÛÔÏÔÁÈ΋ ·fiÎÚÈÛË ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡, ·ÊÔ‡ ·Ó·ÛÙ¤ÏÏÂÈ Î¿ı ·‡ÍËÛË ÙÔ˘ Ù›ÙÏÔ˘ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ fiÏˆÓ ÙˆÓ ÌÔÚÊÒÓ oxLDL Û ·ÛıÂÓ›˜ ÌÂÙ¿ ·fi √™™. √È ΔÛÈ̛η˜ Î·È Û˘Ó. (5) ¤¯Ô˘Ó ‰Â›ÍÂÈ fiÙÈ Û ·ÛıÂÓ›˜ ÌÂÙ¿ ·fi √™™ ·Ú·ÙËÚÂ›Ù·È ‚Ú·¯˘ÚfiıÂÛÌË ·‡ÍËÛË ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ Ï‹Úˆ˜ ÔÍÂȉˆÌ¤Ó˘ LDL (ÔÍ›‰ˆÛË ÙÔ˘Ï¿¯ÈÛÙÔÓ ÁÈ· 12 ÒÚ˜). ™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË ÔÈ ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË ÂÌÊ¿ÓÈÛ·Ó ÌÈ· ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË ÙˆÓ Ù›ÙψÓ

% ÌÂÙ·‚ÔÏ‹ ·fi ÙȘ ÙÈ̤˜ ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘

¶ƒ√∫§π¡π∫∏ ∂ƒ∂À¡∞

¤Ó·ÓÙÈ LDLL

¤Ó·ÓÙÈ LDLD

∞ÛıÂÓ›˜ Ô˘ ÂÏ¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË

ŒÓ·ÚÍË

·Ú·ÎÔÏÔ‡ıËÛ˘ % ÌÂÙ·‚ÔÏ‹ ·fi ÙȘ ÙÈ̤˜ ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘

¤Ó·ÓÙÈ LDLP ∞ÛıÂÓ›˜ Ô˘ ‰ÂÓ ÂÏ¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË

1 Ì‹Ó·˜

3 Ì‹Ó˜

6 Ì‹Ó˜

ŒÓ·ÚÍË ·Ú·ÎÔÏÔ‡ıËÛ˘

ÂÚ›Ô‰Ô˜ ·Ú·ÎÔÏÔ‡ıËÛ˘

¤Ó·ÓÙÈ LDL(-)L

ŒÓ·ÚÍË

1 Ì‹Ó·˜

3 Ì‹Ó˜

1 Ì‹Ó·˜

3 Ì‹Ó˜

6 Ì‹Ó˜

ÂÚ›Ô‰Ô˜ ·Ú·ÎÔÏÔ‡ıËÛ˘

ŒÓ·ÚÍË ·Ú·ÎÔÏÔ‡ıËÛ˘

¤Ó·ÓÙÈ LDL(-)P

6 Ì‹Ó˜

·Ú·ÎÔÏÔ‡ıËÛ˘

ŒÓ·ÚÍË

1 Ì‹Ó·˜

3 Ì‹Ó˜

3 Ì‹Ó˜

6 Ì‹Ó˜

ÂÚ›Ô‰Ô˜ ·Ú·ÎÔÏÔ‡ıËÛ˘

¤Ó·ÓÙÈ LDL(-)D

6 Ì‹Ó˜

·Ú·ÎÔÏÔ‡ıËÛ˘ ÂÚ›Ô‰Ô˜ ·Ú·ÎÔÏÔ‡ıËÛ˘

1 Ì‹Ó·˜

ŒÓ·ÚÍË

1 Ì‹Ó·˜

3 Ì‹Ó˜

6 Ì‹Ó˜

·Ú·ÎÔÏÔ‡ıËÛ˘ ÂÚ›Ô‰Ô˜ ·Ú·ÎÔÏÔ‡ıËÛ˘

ÂÚ›Ô‰Ô˜ ·Ú·ÎÔÏÔ‡ıËÛ˘

∂ÈÎfiÓ· 3 ªÂÙ·‚ÔϤ˜ (%), ÙˆÓ Ù›ÙÏˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ‰È·ÊfiÚˆÓ ÌÔÚÊÒÓ oxLDL ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ Û ۇÁÎÚÈÛË Ì ·˘Ù¤˜ ÙˆÓ Ù›ÙÏˆÓ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ Î·Ù¿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ ÛÙȘ ‰‡Ô ÔÌ¿‰Â˜ Ù˘ ÌÂϤÙ˘ (*p=0,01, **p=0,02, #p=0,03 $p=0,04 &p=0,05 Û ۇÁÎÚÈÛË Ì ÙËÓ ·ÓÙ›ÛÙÔÈ¯Ë ÙÈÌ‹ ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ÂÏ¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË ÁÈ· ÙË ‰Â‰Ô̤ÓË ¯ÚÔÓÈ΋ ÛÙÈÁÌ‹ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ fiÏˆÓ ÙˆÓ ÌÔÚÊÒÓ ÙfiÛÔ Ù˘ oxLDL fiÛÔ Î·È Ù˘ oxLDL(-), ÛÙÔÓ ÚÒÙÔ Ì‹Ó· ·Ú·ÎÔÏÔ‡ıËÛ˘. ∂›Ó·È ÁÓˆÛÙfi fiÙÈ Ù· Ôͤ· ÛÙÂÊ·ÓÈ·›· ÂÂÈÛfi‰È· ÔÊ›ÏÔÓÙ·È Û ڋÍË ÌÈ·˜ ·ıËڈ̷ÙÈ΋˜ Ͽη˜, Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·ÂÏ¢ı¤ÚˆÛË ÛÙËÓ Î˘ÎÏÔÊÔÚ›· ‰È·ÊfiÚˆÓ ÛÙÔȯ›ˆÓ Ù˘, fiˆ˜ ۈ̷Ùȉ›ˆÓ oxLDL Ì ¤ÓÙÔÓË ·ÓÙÈÁÔÓÈÎfiÙËÙ· (5, 20, 21), Ù· ÔÔ›· Ê˘ÛÈÔÏÔÁÈο ˘¿Ú¯Ô˘Ó ÛÙÔ Ï¿ÛÌ· Û Ôχ ÌÈÎÚ¤˜ ÔÛfiÙËÙ˜ (14). ¶·ÚfiÌÔÈ· ·‡ÍËÛË ·Ú·ÙËÚ‹ıËΠÂ›Û˘ Î·È Û ·ÛıÂÓ›˜ ÌÂÙ¿ ·fi ‰È·‰ÂÚÌÈ΋ ·ÁÁÂÈÔÏ·ÛÙÈ΋ ÙˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ ·ÁÁ›ˆÓ, ÌÈ· ‰È·‰Èηۛ· Ô˘ Â›Ó·È ÁÓˆÛÙfi fiÙÈ Û¯ÂÙ›˙ÂÙ·È Ì ۇÓıÏÈ„Ë Ù˘ ·ıËڈ̷ÙÈ΋˜ Ͽη˜ (22). ∏ ¤ÓÙÔÓË ·ÓÙÈÁÔÓÈÎfiÙËÙ· Ù˘ ÔxLDL, fiˆ˜ ‹‰Ë ¤¯ÂÈ ·Ó·ÊÂÚı›, ÔÊ›ÏÂÙ·È ÛÙ· oxPL, ÛÙË lyso-PC Î·È ÛÙȘ ‰Ú·ÛÙÈΤ˜ ·Ï‰Â˛‰Â˜ Ô˘ ·˘Ù¿ Ù· ۈ̷ٛ‰È· ÂÚȤ¯Ô˘Ó (23). ∏ ·Ú¯È΋ ·˘Ù‹ ·‡ÍËÛË ÏÔÈfiÓ ÛÙÔ˘˜ Ù›ÙÏÔ˘˜ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÙˆÓ ·Ú·¿Óˆ ·ÓÙÈÁfiÓˆÓ, Ô˘ ·Ú·ÙËÚÂ›Ù·È ÙfiÛÔ ÛÙËÓ ‰È΋ Ì·˜ ÌÂϤÙË fiÛÔ Î·È Û ¿ÏϘ (5, 7, 22), Ê·›ÓÂÙ·È fiÙÈ Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ·ÓÔÛÔÏÔÁÈ΋ ·ÓÙ›‰Ú·ÛË ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ ¤Ó·ÓÙÈ ¤ÓÙÔÓ· ‚ÈÔ‰Ú·ÛÙÈÎÒÓ Û˘ÛÙ·-

ÙÈÎÒÓ Ù˘ oxLDL Ù· ÔÔ›· ÂÈÛ¤Ú¯ÔÓÙ·È ÛÙËÓ Î˘ÎÏÔÊÔÚ›· ·fi ÙÔ ·ÚÙËÚÈ·Îfi ÙÔ›¯ˆÌ·. ¢ÂÓ Â›Ó·È ÁÓˆÛÙfi fï˜ ̤¯ÚÈ ÛÙÈÁÌ‹˜ ·Ó ·˘Ù‹ Ë ·ÓÔÛÔÏÔÁÈ΋ ·ÓÙ›‰Ú·ÛË ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡, ‰Ú· ¢ÓÔ˚ο ·ÔÌ·ÎÚ‡ÓÔÓÙ·˜ ·fi ÙËÓ Î˘ÎÏÔÊÔÚ›· ÙËÓ oxLDL ‹ ·Ï¿ ·ÔÙÂÏ› ¤Ó· ÂÈϤÔÓ ¯·Ú·ÎÙËÚÈÛÙÈÎfi Ù˘ ÊÏÂÁÌÔÓÒ‰Ô˘˜ ‰ÈÂÚÁ·Û›·˜ Î·È ÙÔ˘ ¤ÓÙÔÓÔ˘ ÔÍÂȉˆÙÈÎÔ‡ ÛÙÚ˜ Ô˘ ·Ú·ÙËÚÂ›Ù·È ÌÂÙ¿ ·fi √™™. ™ÙË ÌÂϤÙË Ì·˜ ‰Â›ÎÙË ·˘ÍË̤Ó˘ ÊÏÂÁÌÔÓÒ‰Ô˘˜ ‰ÈÂÚÁ·Û›·˜ ÌÂÙ¿ ÙÔ ÂÂÈÛfi‰ÈÔ ·ÔÙÂÏÔ‡Ó Ù· ·˘ÍË̤ӷ Â›‰· CRP Ô˘ ÂÌÊ·Ó›˙Ô˘Ó fiÏÔÈ ÔÈ ·ÛıÂÓ›˜ Î·È Ù· ÔÔ›· ÌÂÈÒÓÔÓÙ·È ÛÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ Î·È ÛÙȘ ‰‡Ô ÔÌ¿‰Â˜ Ù˘ ÌÂϤÙ˘. ¶Ú¤ÂÈ Ó· ÛËÌÂȈı› fï˜ fiÙÈ Ù· ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙˆÓ ‰È·ÊfiÚˆÓ ÌÔÚÊÒÓ oxLDL Û˘ÌÂÚÈʤÚÔÓÙ·È ‰È·ÊÔÚÂÙÈο Û ۯ¤ÛË Ì ·˘Ù¿ ¤Ó·ÓÙÈ ÙˆÓ ‰È·ÊfiÚˆÓ ÌÔÚÊÒÓ oxLDL(-) ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË. ¶Ú¿ÁÌ·ÙÈ Ù· Â›‰· ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÙˆÓ ÌÔÚÊÒÓ oxLDL ÂÌÊ·Ó›˙Ô˘Ó ÌÂÙ¿ ÙËÓ ·Ú¯È΋ (ÛÙÔÓ 1Ô Ì‹Ó·) ·‡ÍËÛË, ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÛÙÔ˘˜ 3 Î·È 6 Ì‹Ó˜, ÂÈÛÙÚ¤ÊÔÓÙ·˜ ÛÙȘ ·Ú¯È-

Τ˜ ÙÔ˘ ÙÈ̤˜. ∞ÓÙ›ıÂÙ·, ÔÈ Ù›ÙÏÔÈ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÙˆÓ ‰È·ÊfiÚˆÓ ÌÔÚÊÒÓ oxLDL(-) ·Ú·Ì¤ÓÔ˘Ó Û ·˘ÍË̤ӷ Â›‰· ηı' fiÏË ÙË ‰È¿ÚÎÂÈ· Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘,. ∫·ıÒ˜ ÔÈ ÌÔÚʤ˜ Ù˘ oxLDL Â›Ó·È ÏÔ‡ÛȘ Û lyso-PC (·ÊÔ‡ Ë Lp-PLA2 ‰ÂÓ ¤¯ÂÈ ·ÂÓÂÚÁÔÔÈËı›), ÂÓÒ ÔÈ ÌÔÚʤ˜ Ù˘ oxLDL(-) Â›Ó·È ÏÔ‡ÛȘ Û ÔxPL, Ê·›ÓÂÙ·È fiÙÈ ˘¿Ú¯ÂÈ ‰È·ÊÔÚÂÙÈ΋ ·ÓÔÛÔÏÔÁÈ΋ ·¿ÓÙËÛË ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ ÛÙ· ‰È·ÊÔÚÂÙÈο ·˘Ù¿ ·ÓÙÈÁfiÓ· ÛÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ¯ÚfiÓÔ˘ ÌÂÙ¿ ·fi √™™. ŒÙÛÈ, Ë ·ÓÙ›‰Ú·ÛË ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ ÛÙËÓ lyso-PC Ê·›ÓÂÙ·È Ó· Â›Ó·È ÔÍ›· Î·È Ó· ÂÍ·Ï›ÊÂÙ·È Ì ÙÔÓ ¯ÚfiÓÔ, ÂÓÒ Ë ‰È·Ù‹ÚËÛË ·˘ÍËÌ¤ÓˆÓ ÂÈ¤‰ˆÓ ¤Ó·ÓÙÈ ÙˆÓ oxPL ηı' fiÏË ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘, ˘Ô‰ËÏÒÓÂÈ ÌÈ· ¯ÚfiÓÈ· ·ÓÔÛÔÏÔÁÈ΋ ·fiÎÚÈÛË ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ ÛÙÔ Ô͇ ÛÙÂÊ·ÓÈ·›Ô ÂÂÈÛfi‰ÈÔ. ∏ ¯ÔÚ‹ÁËÛË ·ÙÔÚ‚·ÛÙ·Ù›Ó˘ Ê·›ÓÂÙ·È fiÙÈ ÙÚÔÔÔÈ› ÛËÌ·ÓÙÈο ÙËÓ ·Ú·¿Óˆ ·ÓÔÛÔÏÔÁÈ΋ ·¿ÓÙËÛË ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ ÌÂÙ¿ ·fi √™™. ¶Ú¿ÁÌ·ÙÈ, ÛÙÔ˘˜ ·ÛıÂÓ›˜ ÔÈ ÔÔ›ÔÈ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË ‰ÂÓ ·Ú·ÙËÚ‹ıËΠηÌÈ¿ ÌÂÙ·‚ÔÏ‹ ÙˆÓ Ù›ÙÏˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ fiÏˆÓ ÙˆÓ ÌÔÚÊÒÓ ÙfiÛÔ Ù˘ oxLDL, fiÛÔ Î·È Ù˘ oxLDL(-) ηı' fiÏË ÙË

29

™∂¶Δ∂ªμƒπ√™ 2008

% ÌÂÙ·‚ÔÏ‹ ·fi ÙȘ ÙÈ̤˜ ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ÌÂϤÙ˘

∞ÛıÂÓ›˜ Ô˘ ¤·ÈÚÓ·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË ∞ÛıÂÓ›˜ ¯ˆÚ›˜ ˘ÔÏÈȉ·ÈÌÈ΋ ·ÁˆÁ‹

1 Ì‹Ó·˜

3 Ì‹Ó˜

6 Ì‹Ó˜

¶ÂÚ›Ô‰Ô˜ ·Ú·ÎÔÏÔ‡ıËÛ˘ ∂ÈÎfiÓ· 4. ªÂÙ·‚ÔϤ˜ (%) Ù˘ ÂÓÂÚÁfiÙËÙ·˜ Ù˘ Lp-PLA2 ÛÙȘ ‰‡Ô ÔÌ¿‰Â˜ Ù˘ ÌÂϤÙ˘ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ (*p=0,002, **p=0,03, #p=0,04 Û ۇÁÎÚÈÛË Ì ÙËÓ ·ÓÙ›ÛÙÔÈ¯Ë ÙÈÌ‹ ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó ÛÙ·Ù›Ó˜ ÛÙËÓ Î¿ı ‰Â‰Ô̤ÓË ÛÙÈÁÌ‹) ‰È¿ÚÎÂÈ· Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘. √È Ì˯·ÓÈÛÌÔ› Ì ÙÔ˘˜ ÔÔ›Ô˘˜ ÌÔÚ› Ë ·ÙÔÚ‚·ÛÙ·Ù›ÓË Î·È ÁÂÓÈÎfiÙÂÚ· ÔÈ ÛÙ·Ù›Ó˜ Ó· ÂÌÔ‰›ÛÔ˘Ó ÌÈ· Ù¤ÙÔÈ· ·‡ÍËÛË Â›Ó·È ÔÈΛÏÔÈ (13). ¶Ú¿ÁÌ·ÙÈ, Ë Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ LDL ¯ÔÏËÛÙÂÚfiÏ˘ ÔÚÔ‡ Ô˘ Ù· Ê¿Ú̷η ·˘Ù¿ ÂÈÙ˘Á¯¿ÓÔ˘Ó, Ô‰ËÁ› Û Ì›ˆÛË Ù˘ ‰È·ı¤ÛÈÌ˘ ÔÛfiÙËÙ·˜ LDL ÁÈ· ÔÍ›‰ˆÛË Î·È Î·Ù¿ Û˘Ó¤ÂÈ· Û Ì›ˆÛË Ù˘ oxLDL. ™Â ˘ÔÔÌ¿‰· ·ÛıÂÓÒÓ Ù˘ ÌÂϤÙ˘ MIRACL, Ë ¯ÔÚ‹ÁËÛË ·ÙÔÚ‚·ÛÙ·Ù›Ó˘ ÌÂÙ¿ ·fi Ô͇ ÛÙÂÊ·ÓÈ·›Ô ÂÂÈÛfi‰ÈÔ, ¤¯ÂÈ Û˘Ó‰˘·ÛÙ› Ì Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ oxPL ÙÔ˘ ÔÚÔ‡ (14). ∂ÈÚfiÛıÂÙ· Â›Ó·È ÁÓˆÛÙfi fiÙÈ ÔÈ ÛÙ·Ù›Ó˜ ÂÌÊ·Ó›˙Ô˘Ó ·ÓÙÈÊÏÂÁÌÔÓÒ‰ÂȘ Î·È ·ÓÔÛÔÙÚÔÔÔÈËÙÈΤ˜ ‰Ú¿ÛÂȘ (12, 24, 25). ∏ ¯ÔÚ‹ÁËÛË ÙÔ˘˜ Ô‰ËÁ› Û ÙÚÔÔÔ›ËÛË Ù˘ ÂÓÂÚÁÔÔ›ËÛ˘ ÙˆÓ Î˘ÙÙ¿ÚˆÓ ÙÔ˘ ·ÓÔÛÔÔÈËÙÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜, ‰Ú¿ÛË Ô˘ ·ÊÔÚ¿ ÙfiÛÔ Ù· B fiÛÔ Î·È T ÏÂÌÊÔ·ÙÙ·Ú· (13). ∏ ¯ÔÚ‹ÁËÛË ·ÙÔÚ‚·ÛÙ·Ù›Ó˘ ÛÙËÓ ·ÚÔ‡Û· ÌÂϤÙË Û˘Ó‰˘¿ÛÙËΠ̠ÌÈ· ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ Ù˘ ÔxLDL ÔÚÔ‡ Î·È Ù˘ CRP, Ê·ÈÓfiÌÂÓÔ ÙÔ ÔÔ›Ô ¤¯ÂÈ ·Ú·ÙËÚËı› Î·È Û ¿ÏϘ

30

ÌÂϤÙ˜ (12), Î·È Û¯ÂÙ›˙ÂÙ·È Ì ÙË Ì›ˆÛË Ô˘ ÚÔηÏÔ‡Ó ÔÈ ÛÙ·Ù›Ó˜ ÙfiÛÔ ÙÔ˘ ÔÍÂȉˆÙÈÎÔ‡ ÛÙÚ˜ fiÛÔ Î·È Ù˘ ÊÏÂÁÌÔÓ‹˜ ÌÂÙ¿ ·fi √™™ (26). ∂ÈÚfiÛıÂÙ· Ë ÌË ·‡ÍËÛË ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÙˆÓ ‰È·ÊfiÚˆÓ ÌÔÚÊÒÓ oxLDL, ‰ËÏ·‰‹ ÌÔÚÊÒÓ ÏÔ‡ÛÈˆÓ Û lysoPC, ÌÔÚ› Ó· ÔÊ›ÏÂÙ·È Î·È ÛÙË Ì›ˆÛË Ù˘ ÂÓÂÚÁfiÙËÙ·˜ Ù˘ LpPLA2, Ë ÔÔ›· ·Ú·ÙËÚ‹ıËΠÌfiÓÔ ÛÙËÓ ÔÌ¿‰· ·ÛıÂÓÒÓ Ô˘ Ï¿Ì‚·Ó·Ó ·ÙÔÚ‚·ÛÙ·Ù›ÓË Î·È Ë ÔÔ›· Â›Ó·È ÁÓˆÛÙfi fiÙÈ ÚÔηÏÂ›Ù·È ·fi ÙȘ ÛÙ·Ù›Ó˜ (27-29). Δ· Â›‰· Ù˘ Lp-PLA2 ·ÔÙÂÏÔ‡Ó ·ÓÂÍ¿ÚÙËÙÔ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙË ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ (30), ·ÏÏ¿ Ë Ì›ˆÛË ÙÔ˘˜ Ì ÙË ¯ÔÚ‹ÁËÛË ÛÙ·ÙÈÓÒÓ ‰ÂÓ ¤¯ÂÈ ·ÎfiÌË Û˘Ó‰Âı› Ì ¢ÓÔ˚ο ÎÏÈÓÈο ‹ ·ıÔÊ˘ÛÈÔÏÔÁÈο ·ÔÙÂϤÛÌ·Ù· (27). ∏ ·ÚÔ‡Û· ÌÂϤÙË ˘Ô‰ÂÈÎÓ‡ÂÈ ÁÈ· ÚÒÙË ÊÔÚ¿ fiÙÈ Ë Ì›ˆÛË Ù˘ ÂÓÂÚÁfiÙËÙ·˜ Ù˘ Lp-PLA2 ·fi ÙȘ ÛÙ·Ù›Ó˜ ÌÔÚ› Ó· Û˘Ó‰¤ÂÙ·È Ì ÙËÓ Ì›ˆÛË Ù˘ ·ÓÙÈÁÔÓÈÎfiÙËÙ·˜ Ù˘ oxLDL Ë ÔÔ›· ÔÊ›ÏÂÙ·È ÛÙËÓ lyso-PC. ™˘ÌÂÚ·ÛÌ·ÙÈο, ÛÙÔ˘˜ ·ÛıÂÓ›˜ ÌÂÙ¿ ·fi Ô͇ ÛÙÂÊ·ÓÈ·›Ô Û‡Ó‰ÚÔÌÔ, ·Ú·ÙËÚÂ›Ù·È ·‡ÍËÛË

ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ fiÏˆÓ ÙˆÓ ÌÔÚÊÒÓ ÔÍÂȉˆÌ¤Ó˘ LDL, Èı·ÓÒ˜ ˆ˜ ·¿ÓÙËÛË ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ ÛÙË Ú‹ÍË Ù˘ ·ıËڈ̷ÙÈ΋˜ Ͽη˜ Î·È Ù˘ ·ÂÏ¢ı¤ÚˆÛ˘ ÛÙËÓ Î˘ÎÏÔÊÔÚ›· ‚ÈÔ‰Ú·ÛÙÈÎÒÓ Û˘ÛÙ·ÙÈÎÒÓ Ù˘, fiˆ˜ Ù· oxPL Î·È Ë lyso-PC. °È· Ù· ·˘ÙÔ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙˆÓ oxPL, Ë ·‡ÍËÛË ·˘Ù‹ ‰È·ÙËÚÂ›Ù·È ¤ˆ˜ Î·È 6 Ì‹Ó˜ ÌÂÙ¿ ·fi ÙÔ Ô͇ ÛÙÂÊ·ÓÈ·›Ô Û‡Ó‰ÚÔÌÔ, ÂÓÒ Â›Ó·È ·ÚÔ‰È΋ ÁÈ· Ù· ·˘ÙÔ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ Ù˘ lysoPC, ÁÂÁÔÓfi˜ Ô˘ ˘Ô‰ËÏÒÓÂÈ fiÙÈ Ë Lp-PLA2 Ô˘ Û˘Ó‰¤ÂÙ·È ÛÙËÓ LDL ‰È·‰Ú·Ì·Ù›˙ÂÈ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ·ÓÔÛÔÏÔÁÈ΋ ·¿ÓÙËÛË ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ ¤Ó·ÓÙÈ Ù˘ oxLDL, ÌÂÙ¿ ·fi Ô͇ ÛÙÂÊ·ÓÈ·›Ô ÂÂÈÛfi‰ÈÔ. ∏ ¿ÌÂÛË ¯ÔÚ‹ÁËÛË ·ÙÔÚ‚·ÛÙ·Ù›Ó˘ ÛÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜ ·Ó·ÛÙ¤ÏÏÂÈ ÙËÓ ·Ú·¿Óˆ ·ÓÔÛÔÏÔÁÈ΋ ·fiÎÚÈÛË, ÌÈ· ‰Ú¿ÛË Ù˘ ÔÔ›·˜ Ë ÎÏÈÓÈ΋ ÛËÌ·Û›· ı· Ú¤ÂÈ Ó· ·Ô‰Âȯı› Û ÌÂÁ¿Ï˘ ¤ÎÙ·Û˘ ÎÏÈÓÈΤ˜ ÌÂϤÙ˜.

¶ƒ√∫§π¡π∫∏ ∂ƒ∂À¡∞ μÈ‚ÏÈÔÁÚ·Ê›· 1. Choy P, Siow Y, Mymin D, Karmin O. Lipids and atherosclerosis. Biochem Cell Biol 2004; 82: 212-24.

2. Navab M, Ananthramaiah GM, Reddy ST, Van Lenten BJ, Ansell BJ, Fonarow GC, Vahabzadeh K, Hama S, Hough G, Kamranpour N, Berliner JA, Lusis AJ, Fogelman AM. The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL. J Lipid Res 2004; 45: 993-1007.

3. Tselepis AD, John Chapman M. Inflammation, bioactive lipids and atherosclerosis: potential roles of a lipoprotein-associated phospholipase A2, platelet activating factor-acetylhydrolase. Atheroscler Suppl 2002; 3: 57-68.

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6. Itabe H, Takano T. Oxidized low density lipoprotein: the occurrence and metabolism in circulation and in foam cells.

J Atheroscler Thromb 2000; 7: 12331.

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8. Lourida ES, Papathanasiou AI, Goudevenos JA, Tselepis AD. The low-density lipoprotein (LDL)-associated PAF-acetylhydrolase activity and the extent of LDL oxidation are important determinants of the autoantibody titers against oxidized LDL in patients with coronary artery disease.

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10. Itabe H. Oxidized low-dnsity lipoproteins: what is understood and what remains to be clarified. Biol Pharm Bull 2003; 26: 1-9.

11. Riesen W, Engler H, Risch M, Korte W, Noseda G. Short-term effects of atorvastatin on C-reactive protein. Eur Heart J 2002; 23: 794-9.

12. Ndrepepa G, Braun S, vonBeckerath N, Mehilli J, Gorchakova O, Vogt W, Schomig A, Kastrati A. Oxidized low density lipoproteins, statin therapy and severity of coronary artery disease.

Clinica Chimica Acta 2005; in press.

13. Palinski W, Tsimikas S. Immunomodulatory effects of statins: Mechanisms and potential impact on arteriosclerosis. J Am Soc Nephrol 2002; 13: 1673-81.

14. Tsimikas S, Witztum JL, Miller ER, Sasiela WJ, Szarek M, Olsson AG, Schwartz GG. High-dose atorvastatin reduces total plasma levels of oxidized phospholipids and immune complexes present on apolipoprotein B-100 in patients with acute coronary syndromes in the MIRACL trial.

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™∂¶Δ∂ªμƒπ√™ 2008

¶ƒ√Δ∂π¡√ª∂¡∏ μπμ§π√°ƒ∞ºπ∞ 1: Goldstein LB, Amarenco P, Szarek M, Callahan A 3rd, Hennerici M, Sillesen H, Zivin JA, Welch KM; SPARCL Investigators. Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study. Neurology.

2008 Jun 10;70(24 Pt 2):2364-70.

2: Song YB, On YK, Kim JH, Shin DH, Kim JS, Sung J, Lee SH, Kim WS, Lee YT. The effects of atorvastatin on the occurrence of postoperative atrial fibrillation after off-pump coronary artery bypass grafting surgery. Am Heart J. 2008 Aug;156(2):373.e9-16.

3: Athyros VG, Kakafika AI, Karagiannis A, Mikhailidis DP. Do we need to consider inflammatory markers when we treat atherosclerotic disease? Atherosclerosis. 2008 Sep 10;200 (1):1-12.

4: Targher G, Arcaro G. Non-alcoholic fatty liver disease and increased risk of cardiovascular disease. Atherosclerosis 2007 Apr;191(2):235-40.

5: Targher G. Non-alcoholic fatty liver disease, the metabolic syndrome and the risk of cardiovascular disease: the plot thickens. Diabet Med. 2007 Jan; 24(1):1-6.

6: Zebrack JS, Anderson JL. Role of inflammation in cardiovascular disease: how to use C-reactive protein in clinical practice. Prog Cardiovasc Nurs. 2002 Fall;17(4):174-85.

7: Choi SH, Chae A, Miller E, Messig M, Ntanios F, DeMaria AN, Nissen SE, Witztum JL, Tsimikas S. Relationship between biomarkers of oxidized lowdensity lipoprotein, statin therapy, quantitative coronary angiography, and atheroma: volume observations from the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) study. J Am Coll Cardiol. 2008 Jul 1;52(1):24-32.

8:

Graham KL, Lee LY, Higgins JP, Steinman L, Utz PJ, Ho PP. Failure of oral atorvastatin to modulate a murine model of systemic lupus erythematosus. Arthritis Rheum. 2008 Jul;58(7): 2098-104.

9: Molokhia M, McKeigue P, Curcin V, Majeed A. Statin induced myopathy and myalgia: time trend analysis and comparison of risk associated with statin class from 1991-2006. PLoS ONE. 2008 Jun 25;3(6):e2522.

10: Gfimez-Hernàndez A, Sànchez-Galàn E, Ortego M, Martin-Ventura JL, BlancoColio LM, Tarin-Vicente N, JiménezNacher JJ, Lfipez-Bescos L, Egido J, ~fin J. Effect of intensive atorvastatin Tun therapy on prostaglandin E2 levels and metalloproteinase-9 activity in the plasma of patients with non-ST-elevation acute coronary syndrome. Am J Cardiol. 2008 Jul 1;102(1):12-8.

11: Bachmann JM, Majmudar M, Tompkins C, Blumenthal RS, Marine JE. Lipid-altering therapy and atrial fibrillation. Cardiol Rev. 2008 Jul-Aug;16(4):197-204.

12: Read WL, Baggstrom MQ, Fracasso PM, Govindan R. A phase I study of bexarotene and rosiglitazone in patients with refractory cancers. Chemotherapy.

2008;54(3):236-41.

13: Foody JM, Joyce AT, Rudolph AE, Liu LZ, Benner JS. Persistence of atorvastatin and simvastatin among patients with and without prior cardiovascular diseases: a US managed care study.

Curr Med Res Opin. 2008 Jul;24(7): 1987-2000.

14: Mayne J, Dewpura T, Raymond A, Cousins M, Chaplin A, Lahey KA, Lahaye SA, Mbikay M, Ooi TC, Chrétien M. Plasma PCSK9 levels are significantly modified by statins and fibrates in humans.

Lipids Health Dis. 2008 Jun 11;7:22.

15: Kapoor S. Atorvastatin and celecoxib: a future role in cancer chemoprevention.

Int J Cancer. 2008 Aug 1;123(3):737.

16: Peura P, Martikainen J, Soini E, Hallinen T, Niskanen L. Cost-effectiveness of statins in the prevention of coronary heart disease events in middle-aged Finnish men. Curr Med Res Opin. 2008 Jun; 24(6):1823-32.

17: Kruger PS; STATInS Investigators. Re: Statins and sepsis. Br J Anaesth. 2008 Jun;100(6):862.

18: Athyros VG, Kakafika AI, Papageorgiou AA, Paraskevas KI, Tziomalos K, Anagnostis P, Pagourelias E, Koumaras C, Karagiannis A, Mikhailidis DP. Effects of statin treatment in men and women with stable coronary heart disease: a subgroup analysis of the GREACE Study. Curr Med Res Opin. 2008 Jun;24(6):1593-9.

19: Qunibi W, Moustafa M, Muenz LR, He DY, Kessler PD, Diaz-Buxo JA, Budoff M; CARE-2 Investigators.

A 1-year randomized trial of calcium acetate versus sevelamer on progression of coronary artery calcification in hemodialysis patients with comparable lipid control: the Calcium Acetate Renagel Evaluation-2 (CARE-2) study. Am J Kidney Dis. 2008 Jun;51(6):952-65.

20: Kadoglou NP, Gerasimidis T, Moumtzouoglou A, Kapelouzou A, Sailer N, Fotiadis G, Vitta I, Katinios A, Kougias P, Bandios S, Voliotis K, Karayannacos PE, Liapis CD. Intensive lipid-lowering therapy ameliorates novel calcification markers and GSM score in patients with carotid stenosis. Eur J Vasc Endovasc Surg. 2008 Jun;35(6):661-8.

21: Stanca CM, Bach N, Allina J, Bodian C, Bodenheimer H Jr, Odin JA. Atorvastatin does not improve liver biochemistries or Mayo Risk Score in primary biliary cirrhosis. Dig Dis Sci. 2008 Jul;53(7):1988-93.

22: Müller K, Skepper JN, Tang TY, Graves MJ, Patterson AJ, Corot C, Lancelot E, Thompson PW, Brown AP, Gillard JH. Atorvastatin and uptake of ultrasmall superparamagnetic iron oxide nanoparticles (Ferumoxtran-10) in human monocyte-macrophages: implications for magnetic resonance imaging. Biomaterials. 2008 Jun;29(17):2656-62.

23: Parini P, Gustafsson U, Davis MA, Larsson L, Einarsson C, Wilson M, Rudling M, Tomoda H, Omura S, Sahlin S, Angelin B, Rudel LL, Eriksson M. Cholesterol synthesis inhibition elicits an integrated molecular response in human livers including decreased ACAT2.

Arterioscler Thromb Vasc Biol. 2008 Jun;28(6):1200-6.

24: Goulas A, Kosmidou M, Hatzitolios AI, Molyva D, Fidani L, Giannopoulos S, Mirtsou V. Glutathione S-transferase null and cholesteryl ester transfer protein TaqI B polymorphisms and lipid response to atorvastatin in Greek dyslipidaemic patients. Basic Clin Pharmacol Toxicol. 2008 Jun;102(6):559-62.

25: Hashimoto T, Toya Y, Kihara M, Yabana M, Inayama Y, Tanaka K, Iwatsubo K, Yanagi M, Oshikawa J, Kokuho T, Kuji T, Yoshida S, Tamura K, Umemura S. Behçet's disease complicated by IgA nephropathy with nephrotic syndrome.

Clin Exp Nephrol. 2008 Jun;12(3):224-7.

26: Ford JS, Tayek JA. Lipophilicity and cardiovascular outcome in patients with CHF. Am Heart J. 2008 Aug;156(2):e7; author reply e9.

27: Sànchez CA, Rodriguez E, Varela E, ~o Zapata E, Pàez A, Massfi FA, Montan LF, Lfiopez-Marure R. Statin-induced inhibition of MCF-7 breast cancer cell proliferation is related to cell cycle arrest and apoptotic and necrotic cell death mediated by an enhanced oxidative stress. Cancer Invest. 2008 Aug; 26(7): 698-707.

28: Nozue T, Michishita I, Ito Y, Hirano T. Effects of statin on small dense lowdensity lipoprotein cholesterol and remnant-like particle cholesterol in heterozygous familial hypercholesterolemia. J Atheroscler Thromb. 2008 Jun;15(3): 146-53.

29: Montero J, Morales A, Llacuna L, Lluis ~ez G, Antonsson JM, Terrones O, Basan B, Prieto J, Garcia-Ruiz C, Colell A, Fernàndez-Checa JC. Mitochondrial cholesterol contributes to chemotherapy resistance in hepatocellular carcinoma. Cancer Res. 2008 Jul 1;68(13): 5246-56.

30: Tsai CT, Lai LP, Hwang JJ, Wang YC, Chiang FT, Lin JL. Atorvastatin prevents atrial fibrillation in patients with bradyarrhythmias and implantation of an atrialbased or dual-chamber pacemaker: a prospective randomized trial. Am Heart J. 2008 Jul;156(1):65-70.

∂È̤ÏÂÈ·: μ·Û›ÏÂÈÔ˜ Õı˘ÚÔ˜

32

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