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Δ∂ÀÃ√™ 20 ñ ¢EKEMBƒIO™ 2008
2 12 19
¶·Ú¿ÁÔÓÙ˜ ∫ÈÓ‰‡ÓÔ˘
∫ÏÈÓÈΤ˜ ªÂϤÙ˜
£Âڷ›· - º¿Ú̷η
¶ÚÔÙÂÈÓfiÌÂÓË μÈ‚ÏÈÔÁÚ·Ê›·
32
À‡ı˘ÓÔ˜ ™‡ÓÙ·Í˘ HÏ›·˜ XÂÈÌÒÓ·˜ K·Ú‰ÈÔÏfiÁÔ˜ YÔÙ¤Ú·Ú¯Ô˜ Â.·.
¶∞ƒ∞°√¡Δ∂™ ∫π¡¢À¡√À ∏ ¢È·¯Â›ÚÈÛË Ù˘ ¢˘ÛÏÈȉ·ÈÌ›·˜ ÛÙË ÃÚfiÓÈ· ¡ÂÊÚÈ΋ ¡fiÛÔ
2
Managing Dyslipidemia in Chronic Kidney Disease ( C.K.D) Charles R. Harper, Terry A. Jacobson Journal of the American College of Cardiology 2008(June 24);51:2375-84 ∂È̤ÏÂÈ·: ª·Ú›· ¶·ÓÙÂÚ‹, ∂ÌÌ·ÓÔ˘‹Ï °·ÓˆÙ¿Î˘
∫§π¡π∫∂™ ª∂§∂Δ∂™ ¢ÈÔÈÎËÙÈÎfi ™˘Ì‚Ô‡ÏÈÔ ∂ÏÏËÓÈ΋˜ ∂Ù·ÈÚ›·˜ ∞ıËÚÔÛÎÏ‹ÚˆÛ˘ °ÂÓÔ‚¤Ê· KÔÏÔ‚Ô‡ ¶Úfi‰ÚÔ˜ ªˆ˘Û‹˜ ∂ÏÈÛ¿Ê ∞ÓÙÈÚfi‰ÚÔ˜ HÏ›·˜ XÂÈÌÒÓ·˜ °ÂÓÈÎfi˜ °Ú·ÌÌ·Ù¤·˜ ¢ËÌÔÛı¤Ó˘ ¶·Ó·ÁȈٿÎÔ˜ ∂ȉÈÎfi˜ °Ú·ÌÌ·Ù¤·˜ ∂ϤÓË ªÈÏÈ·ÓÔ‡ Δ·Ì›·˜ μ·Û›Ï˘ Õı˘ÚÔ˜ ª¤ÏÔ˜ ª·ÓÒÏ˘ °·ÓˆÙ¿Î˘ ª¤ÏÔ˜ ∞ÛÙ¤ÚÈÔ˜ ∫·Ú·ÁÈ¿ÓÓ˘ ª¤ÏÔ˜ μ·Û›Ï˘ ¡ÈÎÔÏ¿Ô˘ ª¤ÏÔ˜ ÃÚ‹ÛÙÔ˜ ¶›ÙÛ·‚Ô˜ ª¤ÏÔ˜ ∞ϤͷӉÚÔ˜ ΔÛÂϤ˘ ª¤ÏÔ˜
°Ï˘Î·ÈÌÈÎfi˜ ŒÏÂÁ¯Ô˜ Î·È ∫·Ú‰È·ÁÁÂȷ΋ ¡fiÛÔ˜: ∞ÔÙÂϤÛÌ·Ù· ªÂÏÂÙÒÓ ACCORD Î·È ADVANCE
12
ÕÚ˘-¢ËÌ‹ÙÚÈÔ˜ ∞ÁÁÔ˘Ú›‰Ë˜, ∂ÈÛÙËÌÔÓÈÎfi˜ ™˘ÓÂÚÁ¿Ù˘ ÙÔ˘ ∂Í. π·ÙÚ›Ԣ ÙˆÓ ¢È·Ù·Ú·¯ÒÓ ÙÔ˘ ªÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ §Èȉ›ˆÓ ÙÔ˘ ¶·ÓÂÈÛÙËÌÈ·ÎÔ‡ °ÂÓÈÎÔ‡ ¡ÔÛÔÎÔÌ›Ԣ πˆ·ÓÓ›ÓˆÓ ªˆ˘Û‹˜ ∂ÏÈÛ¿Ê, ∫·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ ΔÔ̤·˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ
ªÂϤÙË GISSI-HF
15
(Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza cardiaca) GISSI-HF Investigators Lancet 2008;372:1223-1239 ∂È̤ÏÂÈ·: ∏Ï›·˜ ÃÂÈÌÒÓ·˜
ªÂϤÙË BEAUTIFUL
17
(morBidity-mortality EvAlUaTion of the If inhibitor ivabradine in patients with coronary disease and left-ventricULar dysfunction) Fox K, Ford I, Steg PG, Tendera M, Ferrari R, on behalf of the BEAUTIFUL investigators. Lancet 2008;372:807-821. ∂È̤ÏÂÈ·: ∏Ï›·˜ ÃÂÈÌÒÓ·˜
ªÂϤÙË SEAS
18
(Simvastatin and Ezetimibe in Aortic Stenosis) Rossebo AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, Gerdts E, Gohlke-Borwolf C, Holme I, Kesaniemi YA, Malbecq K, Nienaber CA, Ray S, Skjaerpe T, Wachtell K, Willenheimer R, for the SEAS Investigators N Engl J Med 2008;359:1-14 ∂È̤ÏÂÈ·: ∏Ï›·˜ ÃÂÈÌÒÓ·˜
£∂ƒ∞¶∂π∞ - º∞ƒª∞∫∞ ∂›‰Ú·ÛË ÙˆÓ ∞ÓÙÈ˘ÂÚÙ·ÛÈÎÒÓ º·ÚÌ¿ÎˆÓ ÛÙÔ ªÂÙ·‚ÔÏÈÛÌfi Ù˘ °Ï˘Îfi˙˘
19
ÕÚ˘-¢ËÌ‹ÙÚÈÔ˜ ∞ÁÁÔ˘Ú›‰Ë˜, ∂ÈÛÙËÌÔÓÈÎfi˜ ™˘ÓÂÚÁ¿Ù˘ ÙÔ˘ ∂Í. π·ÙÚ›Ԣ ÙˆÓ ¢È·Ù·Ú·¯ÒÓ ÙÔ˘ ªÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ §Èȉ›ˆÓ ÙÔ˘ ¶·ÓÂÈÛÙËÌÈ·ÎÔ‡ °ÂÓÈÎÔ‡ ¡ÔÛÔÎÔÌ›Ԣ πˆ·ÓÓ›ÓˆÓ ªˆ˘Û‹˜ ∂ÏÈÛ¿Ê, ∫·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ ΔÔ̤·˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ ∂›Ó·È ∂ÊÈÎÙ‹ Ë Δ·˘Ùfi¯ÚÔÓË ∞ÓÙÈÌÂÙÒÈÛË Ù˘ ∞ıËÚÔÛÎÏ‹ÚˆÛ˘ Î·È Ù˘ √ÛÙÂÔfiÚˆÛ˘;
26
¶·Ó·ÁÈÒÙ˘ ∞Ó·ÁÓˆÛÙ‹˜, ∂˘ÛÙ¿ıÈÔ˜ ¶·ÁÎÔ˘Ú¤ÏÈ·˜, ÷ڿϷÌÔ˜ ∫Ô˘Ì·Ú¿˜, £ˆÌ¿˜ °ÎfiÛÈÔ˜, μ·Û›ÏÂÈÔ˜ Õı˘ÚÔ˜, ∞ÛÙ¤ÚÈÔ˜ ∫·Ú·ÁÈ¿ÓÓ˘ μ’ ¶ÚÔ·È‰Â˘ÙÈ΋ ¶·ıÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ∞¶£, πÔÎÚ¿ÙÂÈÔ ¡ÔÛÔÎÔÌ›Ô, £ÂÛÛ·ÏÔÓ›ÎË.
O ƒfiÏÔ˜ Ù˘ ™ÂÈÚÔÓÔÏ·ÎÙfiÓ˘ ÛÙËÓ ∞ÓıÂÎÙÈ΋ ∞ÚÙËÚȷ΋ À¤ÚÙ·ÛË
29
ª·Ú›· Δ˙‹ÌÔ˘, ÷ڿϷÌÔ˜ ∫Ô˘Ì·Ú¿˜, £ÂÔ‰ÒÚ· °Ú›‚·, ∫ˆÓÛÙ·ÓÙ›ÓÔ˜ ∫·ÚÁÈÒÙ˘, μ·Û›ÏÂÈÔ˜ Õı˘ÚÔ˜, ∞ÛÙ¤ÚÈÔ˜ ∫·Ú·ÁÈ¿ÓÓ˘ μ’ ¶ÚÔ·È‰Â˘ÙÈ΋ ¶·ıÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ∞¶£, πÔÎÚ¿ÙÂÈÔ ¡ÔÛÔÎÔÌ›Ô, £ÂÛÛ·ÏÔÓ›ÎË.
¶POTEINOMENH BIB§IO°PAºIA
32
Ó Û˘Ì‚¿·Ú‰È·ÁÁÂÈ·ÎÒ Î Ô ˘Ó ‰ ›Ó Î ˘„ËÏfi Ô ·˘ÛÙÔÓ ·˘ÍËÌ¤Ó ÛÔ ¤¯Ô˘Ó Ôχ ÏÔ fi fi ¡ Ú ‹ · ÈÎ Ú ÓÙ Ô ÂÊ ¡ ‡ ÒÓ ·˘Ô˘Ó ÚˆÙ Â ÃÚÔÓ›· ›· ÙˆÓ ·ÛıÂÓ ÂÙ·È fiÙÈ ·›˙ √È ·ÛıÂÓ›˜ Ì ›Ó · · Ê ÂÚ ı È· Ë Ù ›‰ Û ÏÈ Ô ·Â›· ·›Ô Ï›ı ÙÔ˘. Δ· ÙÔÓ ·ÎÚÔÁˆÓÈ l) fiÔ˘ Ë ıÂÚ Ó ÓÙˆÓ Î·È ı·Ó¿ /d ‡ g Ô m ÂÏ Ù 0 Ô 0 (5 · È· Ï˘ÎÂÚ›‰ ·Ó ·Ó Ë È ÛÙ·Ù›Ó˜ VANCE ÂÍ¤Ù·Û Ì ˘„ËÏ¿ ÙÚÈÁ Ùfi ΛӉ˘ÓÔ. √ D ˜ A ÂÈ È Û · Ò Î Ù D È R O ÂÚ ¤Ù˜ ACC fi ÙȘ ™¢2 ÚÔ√ͤ·. √È ÌÂÏ ÙÒÓ, ÂÎÙfi˜ · ·ÛıÂÓ›˜ Ì ¿ Â Ú Û · Ó È § ˆ ¯ 3 fi Ù ˆ Û fiÙÈ Ë ÈÌÈÎÒÓ rozil ‹ ÍË ÙˆÓ ÁÏ˘Î· Ó· ·Ô‰Â›ÍÔ˘Ó Â›Ó·È gemfib ¢ ˜ ›Ù ˆ Ì Â fi Ó Ó Ë · Ù ˘¯ È· ·Â›· Á ÚÔÛʤ‰È·, ·¤Ù Ù·Ù›Ó˜ ‰ÂÓ ÂÈıÂÙÈ΋ ıÂÚ Âȷο ÂÂÈÛfi Û Á È Á √ È· . ‰ Ú ˘˜ · Ô Î ı ‹ · ÙÂÚ· Ù ˆ-3 ÏÈË Ù˘ Û˘Ó Ï·Ì‚¿ÓÂÈ Î·Ï‡ , ·ÓÙ›ıÂÙ· Ù· Â›Ó·È Î·Ï‡ÙÂÚ · ‹ ÂÈ Á Î ˆ Ú Á ¿ · Ó ‹ · ÈΠډȷ΋ ˜ ·Ú¿ÁÏ˘Î·ÈÌ ÙÂÛÙË̤ÓË Î· È ·ÓÂÍ¿ÚÙËÙÔ ÂÓÙ·ÙÈ΋ ˘Ô · Î Ó· › ÂÁ · Â Ù Ì Ë ˜ ٠› Ófi Û ·ÛıÂÓ ‰È·Î‹ Û˘¯ ˘ ·ÚÈÛÙÂÚÔ˘Ó fiÊÂÏÔ˜ fiÙËÙ·. ∏ Î·Ú ÏÂÈÙÔ˘ÚÁ›· Ù ÈÌ Ë Û ¤Ó ÓË Ì ı Û Ó Â· Ë Ú Ù Ë ÂÈÒÓÔ˘Ó ÓfiÛÔ Î·È Â ÙËÓ ÂΉ‹ÏˆÛË ˜ ›· ˆ · Ì ÓÈ fi · È ·Ú¿ Ôͤ· Ì ¯ ÂÊ fi Ù Û ,  ÂÈÛfi‰È· Û ·ÛıÂÓ›˜ Ì ÛË ÛÈÌ‚·ÛÙ·ÛÙÂÊ·ÓÈ·›· Â Ë Á · ‹ Ù Ú È Ô ¯ Ó ÁˆÓ ÎÈÓ‰‡ÓÔ˘ Ò Ë ÂÈ S Ì A Ë ÌÂϤÙË SE ∏ È‚·ÌÚ·‰›Ó ›‰·˜ ‰ÂÓ ÂË ·˘ÙÔ‡˜. ™ÙË Ï‚ ˜ · ‚ › ˜ ÂÓ Ú¿˜ ÎÔÈÏ›·˜. ı ‹ Û ÈÎ · Ù Ú ˘˜ Ô ¤ÓˆÛË · ¿ÚÎÂÈ·˜ ÛÙÔ fi‰È·. ¢˘ÏËÚ˘ÓÙÈ΋ ÛÙ Î Û Â Ì Î·Ú‰È·Î‹˜ ·Ó ˜ ÚˆÙÈο ÂÂÈÛ Â› ÏË ÂÓ Î ı Û Û Ô · Ú Ë Â ı Û · ˜ · ˜. Ë Ù ÈÌ›Ì ¿‰· ıÂڷ›· Ì›ˆÛ fï˜ Ì Ô ˜ · Ó ÂÈ Ë Ù›Ó˘ Î·È Â˙ÂÙ ı Ù Û ¿ ˘ Ô Ô È‰ ηÚÎ›Ó ¤ÏÈÍË Ù˘ ‚·Ï‚ ÁÈ· ÙËÓ ·ÓÙÈÂÚÈÛÙ·ÙÈÎÒÓ · Ó Î ˆ · Ù Ì Ú Ë Ú¤·Û ÙËÓ ÂÍ ¿ Û Ê ÍË ‡ ¿ · ÈÎ Ë Ô˘ ÙÂÏÂÛÌ·Ù · ·ÔÙ¤ÏÂÛ ˘ÚËÙÈο, ·Ô ‰È·Ù·Ú·¯‹˜ Ù ÈÔ · ‰ Ù Ë ¿ ÛÌÂÓ¤˜ ‡ÚËÌ Ù ÈÎ ‰ Ófi · ˙È · Èı ˘Ó ÙËÓ Ù¤˜ Î·È Ù· ıÂÈ È·ÛÙ·ÏÙÈÎÔ› ‚ ÛÙÔ˜, ·˘Í¿ÓÔ ‰ fi Ô Î ÂÈ Á Ïfi Á √È ‚-·ÔÎÏÂÈÛ Ë · Ì È · √ ¯ .  ‰È·‚‹ÙË ˘¤ÚÙ·Û˘ Ì È Û·Î¯·ÚÒ‰Ë ÂÓÛ›Ó˘ ‚ÂÏÙÈÒ · Ù Î Ô · ÂÈ Ì Á ÌÂÙÒÈÛË Ù˘ Á fi Î · · ˜ Ë ‹ Ù Ô‰Ô¯¤ˆÓ Ù˘ ÁÏ˘Îfi˙˘ ÎÔÈÓÒÓ ·ıÔÍË ÓÈÛÙ¤˜ ÙˆÓ ˘ Ú ˆ · Á · ‡ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÓÙ ∏ · ˜ È Ô ˙Ë È ÙËÓ Ù˘ ÁÏ˘Îfi ÔÈ ·-ª∂∞ η , ‰ËÌÈÔ˘ÚÁ› ÌÂÙ·‚ÔÏÈÛÌfi Ë Û Ô Ù ˆ ·ÔÎÏÂÈÛÙ¤˜, Ú È fi · Î ÂÔ ›· Ù Û Û ÈÁ·È ÛÙË Ô ˘ÏÈÓÔ¢·ÈÛıË . Δ· ̤¯ÚÈ ÛÙ ÔÛÎÏ‹ÚˆÛË Î ˘˜ Ú Ô Ë Ù ı ÓÔ˘Ó ÙËÓ ÈÓÛÔ · ‹ Ó ÈÛ Ë Ù Ò Û ÂÙ ·ÓÙÈÌ Ì¤Ì˯·ÓÈÛÌÒÓ ËÓ Ù·˘Ùfi¯ÚÔÓË ÎÒÓ Î·È ÔÚÈÛ Ù ÓÈ Û Ô Ê Ê˘ÛÈÔÏÔÁÈÎÒÓ ˘Ó Û Ô ˆ ‡ ÈÊ ¯ ‰ Ô Ù Ó Ë ÈÓÒÓ, Ùˆ ÂÈÒÓ Ô˘ ı· Û ÛËÌ·ÓÙÈ΋ ı¤Û ËÛË ÙˆÓ ÛÙ·Ù Á ÂÈ ‹ Ú ¤¯ Ô ÂÏ›‰· ıÂÚ· Ù ¯ · Î Ë Ù Û ÓË Ó fi ÚÔÓÔÏ·ÎÙ ÓÈÛÙ‹ Ô˘ ·ÊÔÚÔ‡ ÙÈο. ∏ ÛÂÈ ÙÂÚÔ ·ÓÙ·Áˆ fi ˘Ó Ú Ó ̋˜ ‰Â‰Ô̤ӷ Ú · Ô ı Ù ÂÓ Â Ì È ÌÂϤÙ˜ Ù·ÛÈÎÒÓ Â›Ó· ̤ÓÔÓÙ·È Î·È Ó· ∞ ÓˆÓ ·ÓÙÈ˘ÂÚ . À ∞ ˜ ‹ . Ù˘ ·ÓıÂÎÙÈÎ Ó ÂÏÂÚÂÓfiÓË Ë ÃÂÈÌÒÓ·˜ Ù ÛÙË Ú‡ıÌÈÛË , ˜ ˜ · ÓË › fi Ï ÂÚ ∏ Ù Û Ô Ï‰ · ˜ Ë ÓÙ ÙˆÓ ˘Ô‰Ô¯¤ˆ ÓÙ·Í˘
˘ T˘ ™‡ÓÙ·Í
Y‡ı˘ÓÔ˜ ™‡
¢∂∫∂ªμƒπ√™ 2008
∏ ¢È·¯Â›ÚÈÛË Ù˘ ¢˘ÛÏÈȉ·ÈÌ›·˜ ÛÙË ÃÚfiÓÈ· ¡ÂÊÚÈ΋ ¡fiÛÔ Managing Dyslipidemia in Chronic Kidney Disease ( C.K.D)
Charles R. Harper, Terry A. Jacobson Journal of the American College of Cardiology 2008(June 24);51:2375-84 ∏ ›وÛË Ù˘ ¯ÚfiÓÈ·˜ ÓÂÊÚÈ΋˜ ÓfiÛÔ˘ (á¡) ·˘Í¿ÓÂÈ ‰È·ÚÎÒ˜ (>10% ÙÔ˘ ÁÂÓÈÎÔ‡ ÏËı˘ÛÌÔ‡ ÛÙȘ ∏¶∞ ¤¯ÂÈ Î¿ÔÈÔ˘ ÛÙ·‰›Ô˘ á¡) (1,2). ∞Ó Î·È ÌÂÚÈÎÔ› ·ÛıÂÓ›˜ Ì á¡ ı· ·Ó·Ù‡ÍÔ˘Ó ÙÂÏÈο ÓfiÛÔ ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘, ÔÈ ÂÚÈÛÛfiÙÂÚÔÈ ı· Âı¿ÓÔ˘Ó ·fi ηډȷÁÁÂȷ΋ ÓfiÛÔ Ôχ ÚÈÓ Êı¿ÛÔ˘Ó Û ·ÈÌԉȇÏÈÛË (3). √È ·ÛıÂÓ›˜ Ì á¡ ¤¯Ô˘Ó Ì›˙ÔÓ˜ ÚÔ·ıËÚÔÁfiÓ˜ ‰È·Ù·Ú·¯¤˜ ÙˆÓ ÏÈȉ›ˆÓ Ô˘ Â›Ó·È ‰˘Ó·ÙfiÓ Ó· ·ÓÙÈÌÂÙˆÈÛıÔ‡Ó Ì ηٿÏÏËÏË ·ÁˆÁ‹, ˆÛÙfiÛÔ ÔÏÏÔ› ÎÏÈÓÈÎÔ› Â›Ó·È ·ÓÙ›ıÂÙÔÈ ÛÙËÓ ÂÈıÂÙÈ΋ ˘ÔÏÈȉ·ÈÌÈ΋ ıÂڷ›·, ÚÔ‚¿ÏÏÔÓÙ·˜ ı¤Ì·Ù· Ô˘ ·ÊÔÚÔ‡Ó ÙËÓ ·ÛÊ¿ÏÂÈ· ‹ ÙËÓ ¤ÏÏÂÈ„Ë ‰Â‰ÔÌ¤ÓˆÓ ÁÈ· ÙÔ Â·ÎfiÏÔ˘ıÔ ÎÏÈÓÈÎfi fiÊÂÏÔ˜ ÙˆÓ ˘ÔÏÈȉ·ÈÌÈÎÒÓ Ê·ÚÌ¿ÎˆÓ Û ·ÛıÂÓ›˜ Ì á¡ (4). ™ÙËÓ ·Ó·ÛÎfiËÛË ·˘Ù‹ ı· Á›ÓÂÈ ·Ó·ÊÔÚ¿ ÛÙË ÛÙ·‰ÈÔÔ›ËÛË Ù˘ á¡, ÛÙËÓ Â›ÙˆÛË Ù˘ ηډȷÁÁÂȷ΋˜ ÓfiÛÔ˘ Î·È ÛÙ· ¯·Ú·ÎÙËÚÈÛÙÈο Ù˘ ‰˘ÛÏÈȉ·ÈÌ›·˜ Û ·˘Ù‹ ÙËÓ ÔÌ¿‰· ·ÛıÂÓÒÓ. ∞ÎfiÌË ı· Á›ÓÂÈ ·Ó·ÊÔÚ¿ ÛÙ· ‰Â‰Ô̤ӷ ·Ó·ÊÔÚÈο Ì ÙËÓ ˘ÔÏÈȉ·ÈÌÈ΋ ıÂڷ›·, Î·È Û˘˙‹ÙËÛË ÁÈ· ÙËÓ ·ÛÊ¿ÏÂÈ· Î·È ÙȘ ıÂڷ¢ÙÈΤ˜ ÛÙÚ·ÙËÁÈΤ˜.
Δ·ÍÈÓfiÌËÛË Ù˘ ÛÔ‚·ÚfiÙËÙ·˜ Ù˘ á¡ ™‡Ìʈӷ Ì ÙÔ National Kidney Foundation (NKF), ÁÈ· ÙË ‰È¿ÁÓˆÛË Ù˘ á¡ ··ÈÙÔ‡ÓÙ·È ¤Ó· ·fi Ù· ·Ú·Î¿Ùˆ 2 ¯·Ú·ÎÙËÚÈÛÙÈο: 1) ¡ÂÊÚÈ΋ ‚Ï¿‚Ë ÁÈ· >3 Ì‹Ó˜ Ô˘ ÂȂ‚·ÈÒÓÂÙ·È Ì ‚ÈÔ„›· ‹ ‰Â›ÎÙ˜ ηٷÛÙÚÔÊ‹˜ fiˆ˜ ÌÈÎÚÔ·Ï‚Ô˘ÌÈÓÔ˘Ú›· Ì ‹ ¯ˆÚ›˜ Ì›ˆÛË ÙÔ˘ Ú˘ıÌÔ‡ Ù˘ ÛÂÈÚ·Ì·ÙÈ΋˜ ‰È‹ıËÛ˘ (glomerular filtration rate [GFR]) ‹ 2) GFR <60ml/min/1.73 m2 ÁÈ· >3 Ì‹Ó˜ (¶›Ó·Î·˜ 1). ∞ÛıÂÓ›˜ Ì ÛÙ¿‰ÈÔ 1 á¡ ¤¯Ô˘Ó Ê˘ÛÈÔÏÔÁÈ΋ GFR, Û˘Óԉ¢fiÌÂÓË ·fi ÚˆÙÂ˚ÓÔ˘Ú›· ‹
2
¶›Ó·Î·˜ 1: ™Ù¿‰È· ÃÚfiÓÈ·˜ ¡ÂÊÚÈ΋˜ ¡fiÛÔ˘. (5) ™Ù¿‰ÈÔ
¶ÂÚÈÁÚ·Ê‹
GFR ml/min/1.73 m2
∂ÈÔÏ·ÛÌfi˜ (∏¶∞) ÃÈÏÈ¿‰Â˜ %
1
¡ÂÊÚÈ΋ ‚Ï¿‚Ë ÌÂ Ê˘ÛÈÔÏÔÁÈ΋ ‹ ·˘ÍË̤ÓË GFR
≥90
5.900
3.3
2
¡ÂÊÚÈ΋ ‚Ï¿‚Ë Ì ‹È· Ì›ˆÛË GFR
60-89
5.300
3.0
3
ª¤ÙÚÈ· Ì›ˆÛË GFR ™Ô‚·Ú‹ Ì›ˆÛË GFR
30-59
7.600
4.3
15-29
400
0.2
¡ÂÊÚÈ΋ ·Ó¿ÚÎÂÈ·
<15 ‹ ·ÈÌÔοı·ÚÛË
300
0.1
4 5
GFR: Ú˘ıÌfi˜ ÛÂÈÚ·Ì·ÙÈ΋˜ ‰È‹ıËÛ˘
·fi ¿ÏÏÔ˘˜ ‰Â›ÎÙ˜ ÓÂÊÚÈ΋˜ ‚Ï¿‚˘. ™Ù¿‰ÈÔ 2 á¡ (‹È·) ‰È·ÁÈÁÓÒÛÙÂÙ·È fiÙ·Ó Ë GFR Â›Ó·È 6089 ml/min/1.73 m2. ∞ÛıÂÓ›˜ Ì ÛÙ¿‰ÈÔ 3 á¡ (̤ÙÚÈ·), ¤¯Ô˘Ó GFR 30 - 59 ml/min/1.73 m2. ∏ ‰È¿ÁÓˆÛË ÛÔ‚·Ú‹˜ ÓfiÛÔ˘ (ÛÙ¿‰ÈÔ 4) Ù›ıÂÙ·È Ì GFR 15 - 29 ml/min/1.73 m2. ÃÚfiÓÈ· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· ‹ ÛÙ·‰›Ô˘ 5 á¡, ÔÚ›˙ÂÙ·È Û·Ó GFR <15 ml/min/1.73 m2. ∏ ›وÛË ÙÔ˘ ÛÙ·‰›Ô˘ 5 á¡ (ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· ‹ ·ÈÌÔοı·ÚÛË) Â›Ó·È 0.1% Î·È ÙˆÓ ÛÙ·‰›ˆÓ 1 - 4 Â›Ó·È 11% ÛÙÔ ÏËı˘ÛÌfi ÙˆÓ ∏¶∞ (5).
∂ȉËÌÈÔÏÔÁ›· Ù˘ ηډȷÁÁÂȷ΋˜ ÓfiÛÔ˘ Û ·ÛıÂÓ›˜ Ì á¡ ∞ÈÌÔηı·ÚfiÌÂÓÔÈ ·ÛıÂÓ›˜ (ÛÙ·‰›Ô˘ 5 á¡) ¤¯Ô˘Ó ȉȷÈÙ¤Úˆ˜ ˘„ËÏ‹ ÓÔÛËÚfiÙËÙ· Î·È ıÓËÙfiÙËÙ· ÏfiÁˆ ηډȷÁÁÂÈ·ÎÒÓ Û˘Ì‚¿ÓÙˆÓ. μ·ÛÈ˙fiÌÂÓÔÈ Û ÛÙÔȯ›· ·fi ÙËÓ U.S. Renal Data System Coordinating Center Case-Mix Adequacy Study, Ë Â›ÙˆÛË Ù˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘ (™¡) Â›Ó·È 40% Î·È Ë Î·Ú‰È·ÁÁÂȷ΋ ıÓËÙfiÙËÙ· Â›Ó·È Î·Ù¿ 10 - 30 ÊÔÚ¤˜ ˘„ËÏfiÙÂÚË ·' fiÙÈ ÛÙÔ ÁÂÓÈÎfi ÏËı˘ÛÌfi ·ÓÂÍ¿ÚÙËÙ· ʇÏÔ˘, ËÏÈΛ·˜, ÂıÓÈÎfiÙË-
Ù·˜ Î·È ·ÚÔ˘Û›·˜ ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË (™¢) (6). ∏ ·‡ÍËÛË ÙÔ˘ ̤ÛÔ˘ fiÚÔ˘ ËÏÈΛ·˜ ÛÙÔÓ ÏËı˘ÛÌfi Î·È Ë ÂȉËÌ›· ÙÔ˘ ™¢ ¤¯Ô˘Ó ·˘Í‹ÛÂÈ ÛËÌ·ÓÙÈο ÙËÓ Â›ÙˆÛË Ù˘ ‹È·˜ Î·È Ì¤ÙÚÈ·˜ á¡ ÛÙȘ ∏¶∞. ™Â ÚÔÔÙÈ΋ ÏËı˘ÛÌȷ΋ ÌÂϤÙË ·ÙfiÌˆÓ ËÏÈΛ·˜ > 65 ÂÙÒÓ Ô˘ ·Ú·ÎÔÏÔ˘ı‹ıËÎ·Ó ÁÈ· 7 ¯ÚfiÓÈ·, á¡ Ô˘ ÔÚ›ÛÙËÎÂ Û·Ó ÎÚ·ÙÈÓ›ÓË >1,5 mg/dl ÛÙÔ˘˜ ¿Ó‰Ú˜ Î·È >1,3 mg/dl ÛÙȘ Á˘Ó·›Î˜, ‚Ú¤ıËΠ۠ÔÛÔÛÙfi 11% (7). √È ·ÛıÂÓ›˜ Ì á¡ Â›Ó·È ÂÚÈÛÛfiÙÂÚÔ ÂÈÚÚ›˜ ÛÙËÓ ·Ó¿Ù˘ÍË Û˘ÌÊÔÚËÙÈ΋˜ ηډȷ΋˜ ·Ó¿ÚÎÂÈ·˜, ηډȷÁÁÂȷ΋˜ ÓfiÛÔ˘, ÂÚÈÊÂÚÈ΋˜ ·ÁÁÂȷ΋˜ ÓfiÛÔ˘ (¶›Ó·Î·˜ 2) (8). ∏ Û˘Û¯¤ÙÈÛË ·˘Ù‹ ·Ú·Ì¤ÓÂÈ Î·È ÌÂÙ¿ ·fi ‰ÈfiÚıˆÛË ÁÈ· ÙÔ˘˜ ÎÏ·ÛÛÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘, Û˘ÌÂÚÈÏ·Ì‚·ÓÔ̤Ó˘ Ù˘ ËÏÈΛ·˜. ¶·ÚfiÌÔÈ· Â˘Ú‹Ì·Ù· ·Ó·Ê¤ÚıËÎ·Ó Î·È ÛÙËÓ ÌÂϤÙË ARIC (Atherosclerosis Risk in Communities Study), Ë ÔÔ›· ¤‰ÂÈÍ fiÙÈ Ë ÌÂȈ̤ÓË GFR Û¯ÂÙÈ˙fiÙ·Ó ·ÓÂÍ¿ÚÙËÙ· Ì ÙËÓ ·Ó¿Ù˘ÍË ·ıËÚÔÛÎÏËÚˆÙÈ΋˜ ηډȷÁÁÂȷ΋˜ ÓfiÛÔ˘ (9). √ Û‡Ó‰ÂÛÌÔ˜ ÌÂٷ͇ ‰˘ÛÏÈȉ·ÈÌ›·˜ Î·È ·‡ÍËÛ˘ ÙÔ˘ ηډȷÁÁÂÈ·ÎÔ‡ ÎÈÓ‰‡ÓÔ˘ Û ·ÛıÂÓ›˜ Ì á¡ Â›Ó·È ‰‡ÛÎÔÏÔ Ó· ÂÎÙÈÌËı›
¶∞ƒ∞°√¡Δ∂™ ∫π¡¢À¡√À ¶›Ó·Î·˜ 2: ƒ˘ıÌfi˜ ∫·Ú‰È·ÁÁÂÈ·ÎÒÓ ™˘Ì‚¿ÓÙˆÓ* ÙÔ 2000 Î·È 2001. (8) √Ì¿‰·
√∂ª
∞∂∂/Δπ∞
¶∞¡ ∞ıËÚ/ο ∞™ £¿Ó·ÙÔÈ
ªË ‰È·‚‹Ù˘/ÌË Ã¡¡
1.6
7.6
6.9
14.1
5.5
¢È·‚‹Ù˘/ÌË Ã¡¡
3.2
13.1
12.8
25.3
8.1
ªË-‰È·‚‹Ù˘/á¡
3.9
16.6
19.9
35.7
17.7
¢È·‚‹Ù˘/á¡
6.9
22.0
26.6
49.1
19.9
*ƒ˘ıÌfi˜ ·Ó·Ê¤ÚÂÙ·È ·Ó¿ 100 ·ÓıÚˆÔ¤ÙË √∂ª: Ô͇ ¤ÌÊÚ·ÁÌ· Ì˘Ôηډ›Ô˘, ∞∂∂/Δπ∞: ·ÁÁÂÈ·Îfi ÂÁÎÂÊ·ÏÈÎfi ÂÂÈÛfi‰ÈÔ/·ÚÔ‰ÈÎfi ÈÛ¯·ÈÌÈÎfi ÂÂÈÛfi‰ÈÔ, ¶∞¡: ÂÚÈÊÂÚÈ΋ ·ÁÁÂȷ΋ ÓfiÛÔ˜, ∞ıËÚ/η ∞™: ·ıËÚˆÛÎÏËÚˆÙÈο ·ÁÁÂȷο Û˘Ì‚¿ÓÙ· á¡: ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ÓfiÛÔ˜.
Û ÌÂÁ¿ÏÔ ‚·ıÌfi, ÂÍ ·ÈÙ›·˜ ÙˆÓ ÔÏÏ·ÏÒÓ ¿ÏÏˆÓ ·Ú·ÁfiÓÙˆÓ ÎÈÓ‰‡ÓÔ˘, Û˘ÌÂÚÈÏ·Ì‚·ÓÔÌ¤ÓˆÓ ÙÔ˘ ·˘ÍË̤ÓÔ˘ ÔÍÂȉˆÙÈÎÔ‡ stress, Ù˘ ÊÏÂÁÌÔÓ‹˜, Ù˘ Ê˘ÛÈ΋˜ ·‰Ú¿ÓÂÈ·˜, Ù˘ ·Ó·ÈÌ›·˜, Ù˘ ·Û‚¤ÛÙˆÛ˘ ÙˆÓ ·ÁÁ›ˆÓ, Ù˘ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘ ÂÓ‰ÔıËÏ›Ô˘ Î·È Ù˘ Ì›ˆÛ˘ Ù˘ ‰È·ıÂÛÈÌfiÙËÙ·˜ ÙÔ˘ ¡√. ∂ȉËÌÈÔÏÔÁÈΤ˜ ÌÂϤÙ˜ ¤¯Ô˘Ó ‰Â›ÍÂÈ fiÙÈ ·ÛıÂÓ›˜ Û ·ÈÌԉȇÏÈÛË ¤¯Ô˘Ó ηχÙÂÚË ÂÈ‚›ˆÛË ·Ó Ù· ›‰· ÔÏÈ΋˜ ¯ÔÏËÛÙÂÚfiÏ˘ Â›Ó·È ˘„ËÏ¿. øÛÙfiÛÔ Ù· Â˘Ú‹Ì·Ù· ·˘Ù¿ ‰ÂÓ Â›Ó·È ÛËÌ·ÓÙÈο ÌÂÙ¿ ÙË ‰ÈfiÚıˆÛË ÁÈ· ÙË ÊÏÂÁÌÔÓ‹ Î·È ÙË ‰È·ÙÚÔÊ‹ (10,11).
Δ· ¯·Ú·ÎÙËÚÈÛÙÈο Ù˘ ‰˘ÛÏÈȉ·ÈÌ›·˜ ÛÙË Ã¡¡
·ÔÏÈÔÚˆÙÂ˚ÓÒÓ ·˘ÙÒÓ ÛÙȘ ı¤ÛÂȘ ·Ú·ÁˆÁ‹˜ Ù˘ HDL-¯ÔÏËÛÙÂÚfiÏ˘ ÛÙÔ ‹·Ú (15). ŒÓ·˜ ¿ÏÏÔ˜ ·Ú¿ÁˆÓ Ô˘ Û˘ÓÂÈÛʤÚÂÈ ÛÙ· ¯·ÌËÏ¿ ›‰· HDL-¯ÔÏËÛÙÂÚfiÏ˘ ÛÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜ Â›Ó·È Ë ·ÚÔ˘Û›· ÊÏÂÁÌÔÓ‹˜. ∏ ¯ÚfiÓÈ· ÊÏÂÁÌÔÓ‹ ¤¯ÂÈ Û·Ó ·ÔÙ¤ÏÂÛÌ· ÙË Ì›ˆÛË Ù˘ ÏÂ˘ÎˆÌ·Ù›Ó˘, ÊÔÚ¤· ÂχıÂÚ˘ ¯ÔÏËÛÙÂÚfiÏ˘ ·fi ÙÔ˘˜ ÈÛÙÔ‡˜ ÛÙËÓ HDL-¯ÔÏËÛÙÂÚfiÏË, Ì ·ÔÙ¤ÏÂÛÌ· ¯·ÌËÏ‹ HDL-¯ÔÏËÛÙÂÚfiÏË ÛÙÔ Ï¿ÛÌ· (12). Δ· ·˘ÍË̤ӷ ›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÛÙÔ Ï¿ÛÌ· ÂÍËÁÔ‡ÓÙ·È ·fi ÙË ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË Ù˘ apoC-III. ∏ apoC-III Â›Ó·È ¤Ó·˜ ·ÔÙÂÏÂÛÌ·ÙÈÎfi˜ ·Ó·ÛÙÔϤ·˜ Ù˘ ÏÈÔÚˆÙÂ˚ÓÈ΋˜ ÏÈ¿Û˘, ÂÓ˙‡ÌÔ˘ Ô˘ Â›Ó·È ˘Â‡ı˘ÓÔ ÁÈ· ÙÔÓ Î·Ù·‚ÔÏÈÛÌfi ÙˆÓ ÏÔ‡ÛÈˆÓ ÛÂ
ÙÚÈÁÏ˘ÎÂÚ›‰È· ÌÔÚ›ˆÓ (16). À¿Ú¯ÂÈ ·ÚÈıÌfi˜ Î·È ¿ÏÏˆÓ ·Ú·ÁfiÓÙˆÓ Ô˘ Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙËÓ ·‡ÍËÛË ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Û ·ÛıÂÓ›˜ Ì á¡, Ë ÂÚÈÁÚ·Ê‹ ÙˆÓ ÔÔ›ˆÓ ÍÂʇÁÂÈ ·fi ÙÔ ÛÎÔfi ·˘Ù‹˜ Ù˘ ·Ó·ÛÎfiËÛ˘.
∞ԉ›ÍÂȘ Ù˘ ıÂڷ›·˜ ·ÈÌÔηı·ÚfiÌÂÓˆÓ ·ÛıÂÓÒÓ (á¡ ÛÙ·‰›Ô˘ 5) ∞Ó Î·È ÔÈ ·ÈÌÔηı·ÚfiÌÂÓÔÈ ·ÛıÂÓ›˜ ¤¯Ô˘Ó ˘„ËÏ‹ ÓÔÛËÚfiÙËÙ· Î·È ıÓËÙfiÙËÙ· ·fi ηډȷÁÁÂȷο Û˘Ì‚¿ÓÙ·, ÔÈ ·fi„ÂȘ ÁÈ· ÙËÓ ˘ÔÏÈȉ·ÈÌÈ΋ ıÂڷ›· ‰È›ÛÙ·ÓÙ·È. À¿Ú¯Ô˘Ó ‰Â‰Ô̤ӷ Ô˘ ˘ÔÛÙËÚ›˙Ô˘Ó ÔʤÏË ·fi ÙË ıÂڷ›· Ù˘ ‰˘ÛÏÈȉ·ÈÌ›·˜ Û ·ÛıÂÓ›˜ Ì á¡ ÛÙ·‰›Ô˘ 5. ™ÙËÓ U.S Renal Data System Dialysis Morbidity and Mortality Study, 3700 ·ÛıÂÓ›˜ Û ·ÈÌԉȇÏÈÛË ·Ú·ÎÔÏÔ˘ı‹ıËÎ·Ó ÁÈ· 2 ¯ÚfiÓÈ·. ∏ ÔÌ¿‰· ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ¤Ï·‚ ÛÙ·Ù›ÓË, ›¯Â ÂÏ¿ÙÙˆÛË ÙÔ˘ Û¯ÂÙÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘ ÛÙË Û˘ÓÔÏÈ΋ ıÓËÙfiÙËÙ· ηٿ 32%, ÂÓÒ Ë ÔÌ¿‰· Ô˘ ¤Ï·‚ ÊÈÌÚ¿ÙË ‰ÂÓ ·ÚÔ˘Û›·Û Ì›ˆÛË ÛÙËÓ Î·Ú‰È·ÁÁÂȷ΋ ‹ ÛÙË Û˘ÓÔÏÈ΋ ıÓËÛÈÌfiÙËÙ· (17). ™ÙË Dialysis Outcomes Practice Patterns Study, 9.800 ·ÛıÂÓ›˜ Û ·ÈÌԉȇÏÈÛË ·Ú·ÎÔÏÔ˘ı‹ıËηÓ
¶›Ó·Î·˜ 3: ªË¯·ÓÈÛÌÔ› ‰˘ÛÏÈȉ·ÈÌ›·˜ ÛÙËÓ ÃÚfiÓÈ· ¡ÂÊÚÈ΋ ¡fiÛÔ ∏ á¡ ÚÔηÏ› Ï‹ÚË ·ÔÚÚ‡ıÌÈÛË ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ ÏÈÔÚˆÙÂ˚ÓÒÓ Ì ·ÔÙ¤ÏÂÛÌ· ÙȘ ÔÏϷϤ˜ ·ÓˆÌ·Ï›Â˜ ·˘ÙÒÓ ÙˆÓ ÌÔÚ›ˆÓ (¶›Ó·Î·˜ 3) (12). ∏ ‰˘ÛÏÈȉ·ÈÌ›· ·Ó·Ù‡ÛÛÂÙ·È Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙˆÓ ÚÒÈÌˆÓ ÛÙ·‰›ˆÓ á¡ Î·È ÔÈ ÛËÌ·ÓÙÈΤ˜ ·ÏÏ·Á¤˜ ÛÙ· ÌfiÚÈ· ÙˆÓ ·ÔÏÈÔÚˆÙÂ˚ÓÒÓ ÚÔËÁÔ‡ÓÙ·È Û˘Ó‹ıˆ˜ ÙˆÓ ·ÏÏ·ÁÒÓ ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ ÏÈȉ›ˆÓ ÛÙÔ ·›Ì· (13,14). ∏ ÂÏ¿ÙÙˆÛË Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ ÙˆÓ ˘„ËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙÂ˚ÓÒÓ (HDL) Î·È Ë ·‡ÍËÛË ÙˆÓ ÏÔ‡ÛÈˆÓ Û ÙÚÈÁÏ˘ÎÂÚ›‰È· ÏÈÔÚˆÙÂ˚ÓÒÓ ·ÔÙÂÏÔ‡Ó Ì›˙ÔÓ˜ ‰È·Ù·Ú·¯¤˜ ÙˆÓ ÏÈȉ›ˆÓ ÛÙË Ã¡¡. ™ËÌ·ÓÙÈÎfi ÚfiÏÔ ÁÈ· Ù· ¯·ÌËÏ¿ ›‰· HDL-¯ÔÏËÛÙÂÚfiÏ˘ Ê·›ÓÂÙ·È Ó· ·›˙ÂÈ Ë ÂÏ¿ÙÙˆÛË Ù˘ Û˘ÁΤÓÙÚˆÛ˘ ÙˆÓ ·ÔÏÈÔÚˆÙÂ˚ÓÒÓ (apo) A-I Î·È apoA-II, ÔÈ Ôԛ˜ ·ÔÙÂÏÔ‡Ó Î‡ÚÈ· Û˘ÛÙ·ÙÈο ÙˆÓ HDL ۈ̷Ùȉ›ˆÓ. Œ¯ÂÈ ‰Âȯı› fiÙÈ ·ÛıÂÓ›˜ Ì á¡, ¤¯Ô˘Ó ÌÂȈ̤ÓË ÁÔÓȉȷ΋ ¤ÎÊÚ·ÛË ÙˆÓ
¶ÚˆÙ½ÓË
∞ÏÏ·Á‹
¢Ú¿ÛË ÛÙ· ÏÈ›‰È· ‹ ÏÈÔÚˆÙ½Ó˜ Ï¿ÛÌ·ÙÔ˜
ApoA-1 LCAT CETP ACAT LPL
↓ ↓ ↑ ↑ ↓
VLDL receptor Hepatic lipase
↓ ↓
LRP ApoCII/CIII ratio Pre-‚ HDL
↓ ↓ ↑
↓ HDL ↓ HDL-C, HDL-2/HDL-3 ↓ HDL-C ↑ VLDL-C, HDL-C Trig (↑ ·fiÛ·Û˘ TG ·fi VLDL Î·È CM) 1VLDL, Trig ↑ IDL, CM ˘ÔÏ›ÌÌ·Ù·, HDL-TG, Trig, LDL-TG ↑ IDL, CM ˘ÔÏ›ÌÌ·Ù· ↑ Trig (↑ LPL ‰Ú·ÛÙÈÎfiÙËÙ·) ↑ Trig (↑ LPL ‰Ú·ÛÙÈÎfiÙËÙ·)
↓ = Ì›ˆÛË, ↑ = ·‡ÍËÛË, ACAT = acyl-CoA (cholesterol acyl) transferase; Apo = apoprotein, CETP = cholesterol ester transferase protein, CM = ¯˘ÏÔÌÈÎÚ¿, DGAT = acyl-CoA diglycerol acyl transferase; HDL = ˘„ËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙ½ÓË, HDL-C = ˘„ËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙ½ÓË ¯ÔÏËÛÙÂÚfiÏË, HDL-TG = ˘„ËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙ½ÓË ÙÚÈÁÏ˘ÎÂÚ›‰È·, IDL = ÂӉȿÌÂÛ˘ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙ½ÓË, LCAT = lecithin cholesterol acyl transferase, LDL-TG = ¯·ÌËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙ½ÓË ÙÚÈÁÏ˘ÎÂÚ›‰È·; LP = ÏÈÔÚˆÙ½Ó˜ LPL = lipoprotein lipase; LRP = ÚˆÙ½ÓË Û¯ÂÙÈ˙fiÌÂÓË Ì ÙÔÓ ˘Ô‰Ô¯¤· ¯·ÌËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙ½Ó˘, Trig = ÙÚÈÁÏ˘ÎÂÚ›‰È·, VLDL = Ôχ ¯·ÌËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙ½ÓË, VLDL-C = Ôχ ¯·ÌËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙ½ÓË ¯ÔÏËÛÙÂÚfiÏË, VLDLTG = Ôχ ¯·ÌËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙ½ÓË ÙÚÈÁÏ˘ÎÂÚ›‰È·.
3
¢∂∫∂ªμƒπ√™ 2008
ÁÈ· 5 ¯ÚfiÓÈ·. √ Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜ Ù˘ Û˘ÓÔÏÈ΋˜ ıÓËÙfiÙËÙ·˜ ÌÂÈÒıËΠηٿ 31% (p = 0.0001) ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ¤Ï·‚·Ó ÛÙ·Ù›ÓË Û ۯ¤ÛË Ì ÂΛÓÔ˘˜ Ô˘ ‰ÂÓ ¤Ï·‚·Ó (18). ∏ ÌÂϤÙË 4D (Die Deutsche Diabetes Dialyse Study) Â›Ó·È Ë ÌfiÓË ÚÔÔÙÈ΋ Ù˘¯·ÈÔÔÈË̤ÓË ÂÏÂÁ¯fiÌÂÓË ÎÏÈÓÈ΋ ÌÂϤÙË Ì ÛÙ·Ù›ÓË Û ·ÈÌÔηı·ÚfiÌÂÓÔ ÏËı˘ÛÌfi (¶›Ó·Î·˜ 4) (19). ™ÙË ÌÂϤÙË Û˘ÌÌÂÙ›¯·Ó Û˘ÓÔÏÈο 1.200 ·ÛıÂÓ›˜ ÌÂ Ù‡Ô 2 ™¢ Û ·ÈÌԉȇÏÈÛË. Δ˘¯·ÈÔÔÈ‹ıËÎ·Ó Û ·˘ÙÔ‡˜ Ô˘ ¤Ï·‚·Ó atorvastatin 20 mg/ËÌÂÚËÛ›ˆ˜ ‹ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ ÁÈ· 4 ¯ÚfiÓÈ·. ™Â ·ÓÙ›ıÂÛË Ì ÙȘ ÌÂϤÙ˜ ·Ú·Ù‹ÚËÛ˘, Ë atorvastatin Ì›ˆÛ ÌË ÛËÌ·ÓÙÈο ÙÔ Û¯ÂÙÈÎfi ΛӉ˘ÓÔ Î·Ù¿ 8% (95% CI 0.77 - 1.10; p = 0.37) ÙÔ˘ Û˘Ó‰˘·Ṳ̂ÓÔ˘ ÚˆÙ·Ú¯ÈÎÔ‡ ηٷÏËÎÙÈÎÔ‡ ÛËÌ›Ԣ (ηډȷÎfi˜ ı¿Ó·ÙÔ˜, ÌË ı·Ó·ÙËÊfiÚÔ ¤ÌÊÚ·ÁÌ· Ì˘Ôηډ›Ô˘ [∂ª], ·ÁÁÂÈ·Îfi ÂÁÎÂÊ·ÏÈÎfi ÂÂÈÛfi‰ÈÔ [∞∂∂]). ∂ÈϤÔÓ, Ë atorvastatin ·‡ÍËÛ ÙÔÓ Û¯ÂÙÈÎfi ΛӉ˘ÓÔ ı·Ó·ÙËÊfiÚˆÓ ∞∂∂ (RR 2.03; 95% CI 1.05 - 3.93; p = 0.04). ∫·È ÛÙȘ ‰‡Ô ÔÌ¿‰Â˜ ÙÔ 21% ÙˆÓ ı·Ó¿ÙˆÓ ‹Ù·Ó ÂÍ·ÈÙ›·˜ ∂ª, ·Ó Î·È ÙÔ 60% ·Ô‰fiıËΠ۠·ÈÊÓ›‰ÈÔ Î·Ú‰È·Îfi ı¿Ó·ÙÔ (19). ∞˘Ùfi ˘Ô‰ËÏÒÓÂÈ fiÙÈ Î‡ÚÈ· ·ÈÙ›· ηډȷÁÁÂÈ·ÎÔ‡ ı·Ó¿ÙÔ˘ ÛÙÔ˘˜ ·ÈÌÔηı·ÚfiÌÂÓÔ˘˜ ·ÛıÂÓ›˜ ›Ûˆ˜ Â›Ó·È Ë ·ÚÚ˘ıÌ›· Î·È fiÙÈ ·˘Ù‹ Ë ·ÈÙ›· ı·Ó¿ÙÔ˘ ‰ÂÓ Â›Ó·È ·Ó·ÛÙÚ¤„ÈÌË Ì ÛÙ·Ù›Ó˜. ªÈ· ¿ÏÏË ÂÍ‹ÁËÛË ÙˆÓ ·ÚÓËÙÈÎÒÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ Â›Ó·È fiÙÈ Ô ÏËı˘ÛÌfi˜ Ù˘ ÌÂϤÙ˘ 4D ›¯Â Ôχ ÚÔ¯ˆÚË̤ÓË ·ıËÚÔÛÎÏËÚˆÙÈ΋ ÓfiÛÔ ÁÈ· Ó· ˆÊÂÏËı› ·fi ÙËÓ ıÂڷ›·. √È ·ÛıÂÓ›˜ ¢ڛÛÎÔÓÙÔ Û ÚfiÁÚ·ÌÌ· ·ÈÌÔοı·ÚÛ˘ ÙÔ˘Ï¿¯ÈÛÙÔÓ ÁÈ· 2 ¯ÚfiÓÈ·, 50% ‹Ù·Ó ηÓÈÛÙ¤˜ Î·È 50% ›¯·Ó ÈÛÙÔÚÈÎfi ∂ª. ∏ OPACH (Omega-3 Fatty Acids as Secondary Prevention Against Cardiovascular Events in Patients Who Undergo Chronic Hemodialysis) ‹Ù·Ó ÌÈ· ÚfiÛÊ·ÙË Ù˘¯·ÈÔÔÈË̤ÓË, ‰ÈÏ¿ Ù˘ÊÏ‹, ÂÏÂÁ¯fiÌÂÓË Ì ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ ÌÂϤÙË, Û 206 ¯ÚÔÓ›ˆ˜ ·ÈÌÔηı·ÚfiÌÂÓÔ˘˜ ·ÛıÂÓ›˜ (20). √È Û˘ÌÌÂÙ¤¯ÔÓÙ˜ ¤Ï·‚·Ó ˆÌ¤Á·-3 ÏÈ·Ú¿ Ôͤ· (ˆ-3 §√) Û ‰fiÛË 1.7g/ËÌÂÚËÛ›ˆ˜ ‹ ÂÏ·ÈfiÏ·‰Ô ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ. ∞Ó Î·È ‰ÂÓ ˘‹Ú¯Â ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÛÙÔ Û˘Ó‰˘·Ṳ̂ÓÔ ÚˆÙ·Ú¯ÈÎfi ÙÂÏÈÎfi ÛËÌÂ›Ô ÙÔ˘ ηډȷÁÁÂÈ·ÎÔ‡ Û˘Ì‚¿ÓÙÔ˜ ‹
4
ı·Ó¿ÙÔ˘ (62 Û˘Ì‚¿ÓÙ· ÛÙËÓ ÔÌ¿‰· ÙˆÓ ˆ-3 §√ Î·È 59 ÛÙËÓ ÔÌ¿‰· ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘), ·Ú·ÙËÚ‹ıËΠ̛ˆÛË Î·Ù¿ 70% (95% CI 0.10 - 0.92; p = 0.036) ÙÔ˘ Û¯ÂÙÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ∂ª. ∂ÈϤÔÓ Ë Û˘¯ÓfiÙËÙ· ·ÓÂÈı‡ÌËÙˆÓ ÂÓÂÚÁÂÈÒÓ ‰ÂÓ ‹Ù·Ó ÛËÌ·ÓÙÈο ˘„ËÏfiÙÂÚË Ù˘ ÔÌ¿‰·˜ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘. √ ÌÈÎÚfi˜ ·ÚÈıÌfi˜ Û˘ÌÌÂÙ¯fiÓÙˆÓ Î·È ÔÈ ÌÈÎÚ¤˜ ·ÏÏ·Á¤˜ ÙˆÓ ÏÈÔÚˆÙÂ˚ÓÒÓ Ô˘ ·Ú·ÙËÚ‹ıËÎ·Ó Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÌÂϤÙ˘, ·ÔÙÂÏÔ‡Ó ·ÛıÂÓ‹ ÛËÌ›· Ù˘ ÌÂϤÙ˘. ¢‡Ô ÌÂÁ¿Ï˜ ÌÂϤÙ˜ Û¯ÂÙÈο Ì ÙË ¯Ú‹ÛË ÛÙ·ÙÈÓÒÓ Û ·ÈÌÔηı·ÚfiÌÂÓÔ˘˜ ·ÛıÂÓ›˜ ‚Ú›ÛÎÔÓÙ·È Û ÂͤÏÈÍË. ∏ ÚÒÙË, AURORA (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: an Assessment of Survival and Cardiovascular Events), fiÔ˘ Ï·Ì‚¿ÓÔ˘Ó Ì¤ÚÔ˜ 2.700 ·ÈÌÔηı·ÚfiÌÂÓÔÈ Ì ÙË Ï‹„Ë ‹ fi¯È rosuvastatin 10 mg/ ËÌÂÚËÛ›ˆ˜ (21) Î·È Ë ‰Â‡ÙÂÚË, SHARP (Study of Heart and Renal Protection), ÛÙËÓ ÔÔ›· ı· ˘¿Ú¯ÂÈ ÌÈ· ÔÌ¿‰· Ì 3.000 ·ÛıÂÓ›˜ Û ·ÈÌÔοı·ÚÛË Ô˘ Ù˘¯·ÈÔÔÈ‹ıËÎ·Ó Ó· Ï¿‚Ô˘Ó simvastatin 20 mg/ ËÌÂÚËÛ›ˆ˜ ‹ simvastatin 20 mg/ ËÌÂÚËÛ›ˆ˜ Î·È ezetimibe (22).
∞ԉ›ÍÂȘ Ù˘ ıÂڷ›·˜ ·ÛıÂÓÒÓ Ì ‹È· ¤ˆ˜ Î·È Ì¤ÙÚÈ· á¡ (ÛÙ·‰›Ô˘ 1-4) ™Â ·ÛıÂÓ›˜ ÚÒÈÌÔ˘ ÛÙ·‰›Ô˘ á¡ ˘¿Ú¯Ô˘Ó ÛÙÔȯ›· Ô˘ ·ÓÙÏÔ‡ÓÙ·È ·fi ˘ÔÔÌ¿‰Â˜ ·Ó·Ï‡ÛÂˆÓ ÌÂÏÂÙÒÓ ‰Â˘ÙÂÚÔÁÂÓÔ‡˜ ÚfiÏ˄˘ (¶›Ó·Î·˜ 4). ∏ Heart Protection Study Û˘ÌÂÚȤϷ‚ 20.000 μÚÂÙ·ÓÔ‡˜ ¿Ó‰Ú˜ Î·È Á˘Ó·›Î˜ 40-80 ÂÙÒÓ Ô˘ ‹Ù·Ó Û ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ı·Ó¿ÙÔ˘ ·fi ηډȷÁÁÂȷ΋ ÓfiÛÔ, Û˘Ó›· ™¢, ™¡, ‹ ¿ÏÏ˘ ·ıËÚÔÛÎÏËÚˆÙÈ΋˜ ÓfiÛÔ˘ (23). ∏ 5ÂÙ‹˜ ·˘Ù‹ ÌÂϤÙË, ÂÎÙ›ÌËÛ ÙÔ fiÊÂÏÔ˜ Ù˘ Ì›ˆÛ˘ Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ Ì simvastatin 40 mg/ËÌÂÚËÛ›ˆ˜. ΔÔ ÚˆÙ‡ÔÓ Î·Ù·ÏËÎÙÈÎfi ÛËÌÂ›Ô ‹Ù·Ó Ë Û˘ÓÔÏÈ΋ ıÓËÙfiÙËÙ·, Ù· ı·Ó·ÙËÊfiÚ· Î·È ÌË ·ÁÁÂȷο Û˘Ì‚¿ÓÙ·. ∞˘Ù‹ Ë ÌÂÁ¿ÏË ÏËı˘ÛÌȷ΋ ÌÂϤÙË ÂÚÈ›¯Â ˘ÔÔÌ¿‰· 1.329 ·ÛıÂÓÒÓ Ì á¡ Ì ÎÚ·ÙÈÓ›ÓË 1,3 - 2,3 mg/dl. ¶·Ú·ÙËÚ‹ıËΠ̛ˆÛË ÙÔ˘ Û¯ÂÙÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘ ηٿ 28% (95% CI 0.72 - 0.85;
p = 0.05). ∏ Û˘¯ÓfiÙËÙ· ÙˆÓ Û˘Ì‚¿ÓÙˆÓ ‹Ù·Ó 39,2% ÛÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘ Î·È 28% ÛÙËÓ ÔÌ¿‰· Ì simvastatin, Ì Ì›ˆÛË ÙÔ˘ ·fiÏ˘ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ (∞∫) Ô˘ ¤Êı·Û ÙÔ 11% Î·È ÙÔÓ ·ÚÈıÌfi ÙˆÓ ·ÛıÂÓÒÓ Ô˘ Ú¤ÂÈ Ó· ıÂڷ¢ıÔ‡Ó ÛÙÔ 9. ∏ Ì›ˆÛË ÙÔ˘ ∞∫ ·˘Ù‹, Â›Ó·È ·ÍÈÔÛËÌ›ˆÙË Û˘ÁÎÚÈÙÈο Ì ÙËÓ Ì›ˆÛË ÙÔ˘ ∞∫ (5.4%) Ù˘ Û˘ÓÔÏÈ΋˜ ÌÂϤÙ˘. ™ÙË ÌÂϤÙË CARE (Cholesterol and Recurrent Events), ¿Óˆ ·fi 4.000 ·ÛıÂÓ›˜ Ì ÚÔËÁËı¤Ó ∂ª Î·È ÔÏÈ΋ ¯ÔÏËÛÙÂÚfiÏË <240 mg/dl Ù˘¯·ÈÔÔÈ‹ıËÎ·Ó Û pravastatin 40 mg/ËÌÂÚËÛ›ˆ˜ ‹ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ Î·È ·Ú·ÎÔÏÔ˘ı‹ıËÎ·Ó ÁÈ· 5 ¯ÚfiÓÈ· (¶›Ó·Î·˜ 4). ªÈ· ˘ÔÔÌ¿‰· 1.700 ·ÛıÂÓÒÓ Ì οı·ÚÛË ÎÚ·ÙÈÓ›Ó˘ <75 ml/min ÂÎÙÈÌ‹ıËÎÂ. ™ÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜ Ì ‹È· á¡, Ë ıÂڷ›· Ì pravastatin 40 mg/ËÌÂÚËÛ›ˆ˜ Ì›ˆÛ ÙÔ Û¯ÂÙÈÎfi ΛӉ˘ÓÔ Î·Ù¿ 28% (95% CI 0.55 - 0.95; p = 0.02) Î·È ÙÔÓ ∞∫ ηٿ 4%, ÛÙÔ ÚˆÙ‡ÔÓ ÙÂÏÈÎfi ÛËÌÂ›Ô (ı¿Ó·ÙÔ˜ ·fi ™¡ ‹ Û˘Ìو̷ÙÈÎfi ÌË ı·Ó·ÙËÊfiÚÔ ∂ª) (24). H ÌfiÓË ‰ËÌÔÛÈÂ˘Ì¤ÓË ÚÔÔÙÈ΋ Ù˘¯·ÈÔÔÈË̤ÓË ÎÏÈÓÈ΋ ÌÂϤÙË Ô˘ ÂÎÙ›ÌËÛ ÙË ıÂڷ›· Ì ÛÙ·Ù›Ó˜ Û ·ÛıÂÓ›˜ Ì ‹È· á¡ Â›Ó·È Ë PREVEND IT (Prevention of Renal and Vascular End Stage Disease Intervention Trial) (¶›Ó·Î·˜ 4) (25). ™ÙË ÌÂϤÙË ·˘Ù‹ ÚˆÙÔÁÂÓÔ‡˜ ÚfiÏ˄˘, 2Ã2 ·Ú·ÁÔÓÙÈ΋, 864 ·ÛıÂÓ›˜ Ì ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›· Ù˘¯·ÈÔÔÈ‹ıËÎ·Ó Û fosinopril 20 mg/d ‹ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ Î·È Û pravastatin 40 mg/ËÌÂÚËÛ›ˆ˜ ‹ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ. √È ·ÛıÂÓ›˜ ·Ú·ÎÔÏÔ˘ı‹ıËÎ·Ó ÁÈ· 4 ¯ÚfiÓÈ·. ∏ ¯ÔÚ‹ÁËÛË pravastatin 40 mg/ËÌÂÚËÛ›ˆ˜ ›¯Â Û·Ó ·ÔÙ¤ÏÂÛÌ· ÌË ÛËÌ·ÓÙÈ΋ Ì›ˆÛË Î·Ù¿ 13% (0.87 [95% CI 0.49 to 1.57]; p = 0.649) ÙÔ˘ ÚˆÙ‡ÔÓÙÔ˜ ÙÂÏÈÎÔ‡ ÛËÌ›Ԣ Ù˘ ηډȷÁÁÂȷ΋˜ ıÓËÙfiÙËÙ·˜ Î·È ÓÔÛËÏ›·˜ ηډȷÁÁÂȷ΋˜ ÓÔÛËÚfiÙËÙ·˜. ΔÔ ÌË ÛËÌ·ÓÙÈÎfi ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ, ÏfiÁˆ ÙÔ˘ ÌÈÎÚÔ‡ ·ÚÈıÌÔ‡ ÙˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ Û˘Ì‚¿ÓÙˆÓ, ÂÚÈÔÚ›˙ÂÈ ÙËÓ ÌÂϤÙË. ∏ ÌÂϤÙË ALERT (Assessment of Lescol in Renal Transplant Trial) ‹Ù·Ó ÌÈ· Ù˘¯·ÈÔÔÈË̤ÓË ‰ÈÏ¿ Ù˘ÊÏ‹ ÌÂϤÙË, Ì 2.102 ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓÔ˘˜ ·ÛıÂÓ›˜. √È Û˘ÌÌÂÙ¤¯ÔÓÙ˜, ›¯·Ó ̤ÛË ÙÈÌ‹ ¯·ÌËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙ½ÓË
¶∞ƒ∞°√¡Δ∂™ ∫π¡¢À¡√À (LDL) ¯ÔÏËÛÙÂÚfiÏË 160 mg/dl Î·È Ì¤ÛË ÎÚ·ÙÈÓ›ÓË 1,6 mg/dl (26). ™ÙË 5-ÂÙ‹ ·˘Ù‹ ÌÂϤÙË, Ë Ù˘¯·ÈÔÔ›ËÛË Û fluvastatin 40 Î·È 80 mg/ËÌÂÚËÛ›ˆ˜ ›¯Â Û·Ó ·ÔÙ¤ÏÂÛÌ· ÙË ÌË ÛËÌ·ÓÙÈ΋ Ì›ˆÛË Î·Ù¿ 17% (p = 0.139) ÙÔ˘ Û˘Ó‰˘·Ṳ̂ÓÔ˘ ÚˆÙ·Ú¯ÈÎÔ‡ ÙÂÏÈÎÔ‡ ÛËÌ›Ԣ (ηډȷÎfi˜ ı¿Ó·ÙÔ˜, ÌË ı·Ó·ÙËÊfiÚÔ ∂ª ‹ ÂÂÌ‚¿ÛÂȘ ÛÙ· ÛÙÂÊ·ÓÈ·›·). ªÈ· ˘Ô·Ó¿Ï˘ÛË Ù˘ ALERT Ô˘ ¯ÚËÛÈÌÔÔ›ËÛÂ Û·Ó ÚˆÙ‡ÔÓ ÙÂÏÈÎfi ÛËÌÂ›Ô ÙÔÓ Î·Ú‰È·Îfi ı¿Ó·ÙÔ Î·È ÙÔ ÌË ı·Ó·ÙËÊfiÚÔ ∂ª, ¤‰ÂÈÍ ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ηٿ 35% (p = 0.005) (27). ™ÙË ÌÂϤÙË VA-HIT (Veterans' Affairs High-Density Lipoprotein Intervention Trial) ¿Óˆ ·fi 2.500 ¿Ó‰Ú˜ Ù˘¯·ÈÔÔÈ‹ıËÎ·Ó Û gemfimbrozil 1200 mg/ËÌÂÚËÛ›ˆ˜ ‹ ÂÈ-
ÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ. ∏ post hoc ·Ó¿Ï˘ÛË Û ÌÈ· ˘ÔÔÌ¿‰· 1.000 ·Ó‰ÚÒÓ Ì οı·ÚÛË ÎÚ·ÙÈÓ›Ó˘ <75 ml/min ¤‰ÂÈÍÂ, fiÙÈ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ‹È· ¤ˆ˜ ̤ÙÚÈ· á¡, ÌÂÈÒıËÎÂ Ô Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜ ηٿ 27% (0.73 [95% CI 0.56 to 0.96]; p = 0.02) Î·È Ô ∞∫ ı·Ó·ÙËÊfiÚÔ˘ Î·È ÌË ∂ª ηٿ 6.3% (¶›Ó·Î·˜ 4) (28). ∏ SHARP Â›Ó·È ÎÏÈÓÈ΋ ÌÂϤÙË Û ÂͤÏÈÍË, ÛÙËÓ ÔÔ›· ÌÈ· ˘ÔÔÌ¿‰· Ì ‹È· ‹ ̤ÙÚÈ· á¡ (ÎÚ·ÙÈÓ›ÓË >1,5 mg/dl) ¤¯ÂÈ Ù˘¯·ÈÔÔÈËı› Û simvastatin 20 mg/ËÌÂÚËÛ›ˆ˜ ‹ simvastatin 20 mg/ËÌÂÚËÛ›ˆ˜ Î·È ezetimibe 10 mg/ËÌÂÚËÛ›ˆ˜. ™ÙËÓ ›‰È· ÌÂϤÙË ı· ˘¿ÚÍÂÈ ÌÈ· ÂÈÚfiÛıÂÙË ÔÌ¿‰· Ì 3.000 ·ÛıÂÓ›˜ Û ·ÈÌÔοı·ÚÛË (22).
¢Â‰Ô̤ӷ ·ÛÊ¿ÏÂÈ·˜ Û ·ÛıÂÓ›˜ Ì á¡ ∞ÛÊ¿ÏÂÈ· ÛÙË ıÂڷ›· Ì ÛÙ·Ù›ÓË. ŸÏ˜ ÔÈ ÛÙ·Ù›Ó˜ ¤¯Ô˘Ó ¯ÚËÛÈÌÔÔÈËı› Ì ·ÛÊ¿ÏÂÈ· Û ·ÛıÂÓ›˜ Ì ÛÙ·‰›Ô˘ 1 Î·È 2. ¶ÚÔÎÂÈ̤ÓÔ˘ ÁÈ· ·ÛıÂÓ›˜ ÛÙ·‰›Ô˘ 3 - 5, ÏfiÁˆ ÙˆÓ ‰È·ÊÔÚÒÓ ÛÙȘ Ê·ÚÌ·ÎÔÎÈÓËÙÈΤ˜ ÙÔ˘˜ ȉÈfiÙËÙ˜, ›Ûˆ˜ ··ÈÙÂ›Ù·È ÚÔÛ·ÚÌÔÁ‹ ÛÙȘ ‰fiÛÂȘ ÙÔ˘˜. √È ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ ÙˆÓ ÛÙ·ÙÈÓÒÓ Â›Ó·È ‰ÔÛÔÂÍ·ÚÙÒÌÂÓ˜ Î·È Û¯ÂÙ›˙ÔÓÙ·È Ì ٷ ·˘ÍË̤ӷ ›‰· ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ ÛÙÔ Ï¿ÛÌ·. √È ÛÙ·Ù›Ó˜ Ô˘ ¤¯Ô˘Ó ΢ڛˆ˜ ÓÂÊÚÈ΋ ·¤ÎÎÚÈÛË Â›Ó·È ÏÔÁÈÎfi Ó· ¯ÚÂÈ¿˙ÔÓÙ·È Ú‡ıÌÈÛË (¶›Ó·Î·˜ 5). ∏ atorvastatin ¤¯ÂÈ <2% ÓÂÊÚÈ΋ ·¤ÎÎÚÈÛË Î·È ‰ÂÓ
¶›Ó·Î·˜ 4: ∫ÏÈÓÈΤ˜ ÌÂϤÙ˜ ÌÂÙ·‚ÔÏ‹˜ ÙˆÓ ÏÈȉ›ˆÓ Û ·ÛıÂÓ›˜ Ì ÃÚfiÓÈ· ¡ÂÊÚÈ΋ ¡fiÛÔ ªÂϤÙË
¶ÏËı˘ÛÌfi˜
™¯Â‰È·ÛÌfi˜
¶ÚˆÙ·Ú¯ÈÎfi ηٷÏËÎÙÈÎfi ÛËÌ›Ô
¢È¿ÚÎÂÈ· (Ì‹Ó˜)
£Âڷ›·
RRR 95% CI
ARR
n = 1.255 ‰È·‚ËÙÈÎÔ› Û ·ÈÌÔοı·ÚÛË
Δ∂ª
∫·Ú‰È·ÎÔ› ı¿Ó·ÙÔÈ, ı·Ó·ÙËÊfiÚÔ ∞∂∂, ª£∂ª ‹ ∞∂∂
48
Atorvastatin 20 mg/d
8% 0.77-1.10 (p = 0.37)
NA
PREVEND IT (25)
n = 1.439, ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›·, GFR ≥60
Δ∂ª, 2 x 2 ·Ú·ÁÔÓÙÈ΋
∫·Ú‰È·ÁÁÂȷ΋ ıÓËÙfiÙËÙ· Î·È ÓÔÛËÏ›·
46
Pravastatin 40 mg/d
13% 0.49-1.57 (p = 0.649)
NA
HPS (23)
n= 1.329, Cr 1.3-2.3, ™¡, ‰È·‚‹Ù˘, ‹ ¿ÏÏË ·ÔÊÚ·ÎÙÈ΋ ·ÁÁÂȷ΋ ÓfiÛÔ˜
Δ∂ª ˘ÔÔÌ¿‰·, 2x2 ·Ú·ÁÔÓÙÈ΋
√ÏÈ΋ ıÓËÛÈÌfiÙËÙ·, Ì›˙ÔÓ· ·ÁÁÂȷο Û˘Ì‚¿ÓÙ·
60
Simvastatin 40 mg/d
28% (p = 0.05)
11%
CARE (24)
n = 1.711, ™¡, GFR ≤75 ml/min
Post-hoc ·Ó¿Ï˘ÛË ˘ÔÔÌ¿‰·˜ Δ∂ª
™ÙÂÊ·ÓÈ·›ÔÈ ı¿Ó·ÙÔÈ ‹ Û˘Ìو̷ÙÈÎfi ª£∂ª
58.9
Pravastatin 40 mg/d
28% 0.55-0.95 (p = 0.02)
4%
ALERT (26)
n = 2.102, ·ÛıÂÓ›˜ Ì ÓÂÊÚÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË
Δ∂ª
∫·Ú‰È·Îfi˜ ı¿Ó·ÙÔ˜, ª£∂ª, ηډȷΤ˜ ÂÂÌ‚¿ÛÂȘ
60
Fluvastatin 40-80 mg/d
17% 0.64-1.06 (p = 0.139)
NA
Post-hoc ·Ó¿Ï˘ÛË ˘ÔÔÌ¿‰·˜ Δ∂ª
™ÙÂÊ·ÓÈ·›ÔÈ ı¿Ó·ÙÔÈ, ª£∂ª
60
Gemfibrozil 1,200 mg/d
27% 0.56-0.96 (p = 0.02)
6.3%
Δ∂ª
√ÏÈο ηډȷÁÁÂȷο Û˘Ì‚¿ÓÙ· Î·È ı¿Ó·ÙÔ˜
24
n-3 PUFA 1.7 g/d
-3% 0.72-1.48 (p = 0.85)
NA
ªÂϤÙ˜ ÛÙ·ÙÈÓÒÓ 4D (19)
ÕÏϘ ÌÂϤÙ˜ VA-HIT (28)
OPACH (20)
n = 1.046, ¿Ó‰Ú˜ Ì ™¡, CrCl <75 ml/min n = 206, ÛÙÂÊ·ÓÈ·›ÔÈ ·ÛıÂÓ›˜ Û ·ÈÌÔοı·ÚÛË
Δ∂ª = Ù˘¯·ÈÔÔÈË̤ÓË ÂÏÂÁ¯fiÌÂÓË ÌÂϤÙË, RRR = Ì›ˆÛË Û¯ÂÙÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘, ARR = Ì›ˆÛË ·fiÏ˘ÙÔ˘ ÎÈÓ‰‡ÓÔ˘, ™¡ = ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ˜, Cr = ÎÚ·ÙÈÓ›ÓË ÔÚÔ‡, CrCl = οı·ÚÛË ÎÚ·ÙÈÓ›Ó˘, GFR = Ú˘ıÌfi˜ ÛÂÈÚ·Ì·ÙÈ΋˜ ‰È‹ıËÛ˘, n-3 PUFA = ˆÌ¤Á·-3 ÔÏ˘·ÎfiÚÂÛÙ· ÏÈ·Ú¿ Ôͤ·, NA = ÌË ‰È·ı¤ÛÈÌ·; ª£∂ª = ÌË ı·Ó·ÙËÊfiÚÔ ¤ÌÊÚ·ÁÌ· Ì˘Ôηډ›Ô˘.
5
¢∂∫∂ªμƒπ√™ 2008
··ÈÙÂ›Ù·È Ú‡ıÌÈÛË Û GFR <30 ml/min/1,73m2 (29). ∂›Û˘ ÔÈ ÛÙ·Ù›Ó˜ Ô˘ ÌÂÙ·‚ÔÏ›˙ÔÓÙ·È ·fi ÙÔ Î˘Ùfi¯ÚˆÌ· P450-3A4 (cytochrome p450-3A4 [CYP-3A4]) ÌÔÚ› ÈÔ Û˘¯Ó¿ Ó· ·ÚÔ˘ÛÈ¿ÛÔ˘Ó ·ÚÂÓ¤ÚÁÂȘ ÂÍ·ÈÙ›·˜ Ù˘ ·ÏÏËÏ›‰Ú·Û˘ ÙÔ˘˜ Ì ʿÚ̷η Ô˘ ÌÂÙ·‚ÔÏ›˙ÔÓÙ·È ÛÙËÓ ›‰È· Ô‰fi. ∏ fluvastatin, fiˆ˜ Î·È Ë atorvastatin, ¤¯ÂÈ ÂÏ¿¯ÈÛÙË ·¤ÎÎÚÈÛË ·fi ÙÔ˘˜ ÓÂÊÚÔ‡˜, ›Û˘ ‰ÂÓ ¯ÚËÛÈÌÔÔÈ› ÙÔ CYP-3A4 ÁÈ· Ó· ÌÂÙ·‚ÔÏÈÛı› (¶›Ó·Î·˜ 5) Î·È ‰ÂÓ ¤¯ÂÈ ÂÓÂÚÁÔ‡˜ ÌÂÙ·‚Ôϛ٘ ÛÙËÓ Î˘ÎÏÔÊÔÚ›· (30,31). ∂ÈϤÔÓ Ë ‰fiÛË Ù˘ ‰ÂÓ ·ÏÏ¿˙ÂÈ Û ·ÈÌÔηı·ÚfiÌÂÓÔ˘˜ ·ÛıÂÓ›˜ ‹ Û ·ÛıÂÓ›˜ Ì ÂÚÈÙÔÓ·˚΋ οı·ÚÛË (30,31). ∂ÚˆÙ‹Ì·Ù· Û¯ÂÙÈο Ì ÙË ‰Ú¿ÛË ÙˆÓ ÛÙ·ÙÈÓÒÓ ÛÙË Ê˘ÛÈ΋ ÈÛÙÔÚ›· Ù˘ á¡ ÚÔοÏÂÛÂ Ë ‰È·›ÛÙˆÛË fiÙÈ ÚÔηÏÔ‡Ó ‹È· ·ÚÔ‰È΋ ÛˆÏËÓ·Úȷ΋ ÚˆÙÂ˚ÓÔ˘Ú›· Û ÌÂÚÈÎÔ‡˜ ·ÛıÂÓ›˜ (32). Δ· ÂÚˆÙ‹Ì·Ù· ·˘Ù¿ ÈÛÙ‡ÂÙ·È fiÙÈ ı· ··ÓÙËıÔ‡Ó Ì ÙË Û˘ÌÏ‹ÚˆÛË ÔÚÈÛÌ¤ÓˆÓ ÌÂÁ¿ÏˆÓ ÎÏÈÓÈÎÒÓ ÌÂÏÂÙÒÓ (.¯. Ë ÌÂϤÙË SHARP). ¢Â‰Ô̤ӷ fï˜ ·fi ÙȘ post hoc ·Ó·Ï‡ÛÂȘ ÌÂÁ¿ÏˆÓ ÎÏÈÓÈÎÒÓ ÌÂÏÂÙÒÓ Ì ηډȷÁÁÂȷο ÙÂÏÈο ÛËÌ›·, ÚÔÙ›ÓÔ˘Ó fiÙÈ ÔÈ ÛÙ·Ù›Ó˜ ÚÔÊ˘Ï¿ÛÛÔ˘Ó ÙË ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›· Î·È ÌÂÈÒÓÔ˘Ó ÙËÓ ÚˆÙÂ˚ÓÔ˘Ú›· Ì ÙËÓ ¿ÚÔ‰Ô ÙÔ˘ ¯ÚfiÓÔ˘. ∏ Pravastatin Pooling Project ‹Ù·Ó post hoc ·Ó¿Ï˘ÛË ‰Â‰ÔÌ¤ÓˆÓ ·fi 3 Ù˘¯·ÈÔÔÈË̤Ó˜ ÂÏÂÁ¯fiÌÂÓ˜ ÌÂϤÙ˜ Û‡ÁÎÚÈÛ˘ pravastatin 40 mg/ËÌÂÚËÛ›ˆ˜ Ì ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ, Û 18.000 ·ÛıÂÓ›˜ Ì ÚÔËÁËı¤Ó ∂ª (33). H pravastatin Ì›ˆÛ ÙÔ Ú˘ıÌfi Ù˘ ·ÒÏÂÈ·˜ Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ ηٿ 8% (0.08 ml/min/1.73 m2/¤ÙÔ˜, 95% CI 0.01 - 0.15) Î·È ÙÔ Û¯ÂÙÈÎfi ΛӉ˘ÓÔ
ÁÈ· ÔÍ›· ÓÂÊÚÈ΋ ‚Ï¿‚Ë Î·Ù¿ 60% (95% CI 0.41 - 0.86; p = 0.005). ™Â ÚfiÛÊ·ÙË ÌÂÙ·-·Ó¿Ï˘ÛË, ·Ó·ÁÓˆÚ›ÛÙËÎ·Ó 22 ÌÂϤÙ˜ ÂÏÂÁ¯fiÌÂÓ˜ Ì ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ Ô˘ ÌÂϤÙËÛ·Ó ÙÔ ÓÂÊÚÈÎfi fiÊÂÏÔ˜ ÙˆÓ ÛÙ·ÙÈÓÒÓ. √È ÛÙ·Ù›Ó˜ ÂÏ¿ÙÙˆÛ·Ó ÙÔ Ú˘ıÌfi Ì›ˆÛ˘ Ù˘ GRF ηٿ 1.23 ml/min/1.73 m2/ÂÙËÛ›ˆ˜ Û˘ÁÎÚÈÙÈο Ì ÙÔ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ. ∏ ÛËÌ·ÓÙÈ΋ fï˜ ÂÙÂÚÔÁ¤ÓÂÈ· ÌÂٷ͇ ÙˆÓ ÌÂÏÂÙÒÓ ÂÚÈÔÚ›˙Ô˘Ó ÙËÓ ÈÛ¯‡ ·˘Ù‹˜ Ù˘ ·Ó·ÛÎfiËÛ˘ (34). √È ÚÔÙÂÈÓfiÌÂÓÔÈ ÓÂÊÚÈÎÔ› ÚÔÛٷ٢ÙÈÎÔ› Ì˯·ÓÈÛÌÔ› ‚·Û›ÛÙËÎ·Ó Û in vitro ·Ú·ÙËÚ‹ÛÂȘ fiÙÈ ÔÈ ÛÙ·Ù›Ó˜ ÂÌÔ‰›˙Ô˘Ó ÙË Ê˘ÛÈÔÏÔÁÈ΋ ·ӷÚÚfiÊËÛË Ù˘ ÏÂ˘ÎˆÌ·Ù›Ó˘ ÛÙÔ ÂÁÁ‡˜ ÛˆÏËÓ¿ÚÈÔ. ΔÔ Ì‚·ÏÔÓÈÎfi, ÂӉȿÌÂÛÔ˜ ÌÂÙ·‚ÔÏ›Ù˘ ÛÙË ‚ÈÔÛ‡ÓıÂÛË Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘, Â›Ó·È ··Ú·›ÙËÙÔ ÛÙË Ê˘ÛÈÔÏÔÁÈ΋ ·ӷÚÚfiÊËÛË Ù˘ ÏÂ˘ÎˆÌ·Ù›Ó˘ ÛÙÔ ÂÁÁ‡˜ ÛˆÏËÓ¿ÚÈÔ Î·È Â›Ó·È ÌÂȈ̤ÓÔ Û ·ÛıÂÓ›˜ Ô˘ Ï·Ì‚¿ÓÔ˘Ó ÛÙ·Ù›ÓË (35). ™Â in vitro ÌÂϤÙ˜ Ê¿ÓËΠfiÙÈ Ë Â·Ó·ÚÚfiÊËÛ˘ ÙˆÓ ÚˆÙÂ˚ÓÒÓ ÛÙ· ÂÁÁ‡˜ ÛˆÏËÓ¿ÚÈ· Â›Ó·È ÚÔÊÏÂÁÌÔÓ҉˘ ηٿÛÙ·ÛË, ÂÔ̤ӈ˜ Ë ·Ó·ÛÙÔÏ‹ Ù˘ ·ӷÚÚfiÊËÛ˘ Ù˘ ÚˆÙ½Ó˘ ÛÙ· ÛˆÏËÓ¿ÚÈ· ›Ûˆ˜ ‰Ú· ÓÂÊÚÔÚÔÛٷ٢ÙÈο Ì·ÎÚÔ¯ÚfiÓÈ·. ™˘ÌÂÚ·ÛÌ·ÙÈο, ·Ó Î·È ÔÈ ÛÙ·Ù›Ó˜ ·Ú¯Èο ·˘Í¿ÓÔ˘Ó ÙË ÛˆÏËÓ·Úȷ΋ ÚˆÙÂ˚ÓÔ˘Ú›·, Û ‚¿ıÔ˜ ¯ÚfiÓÔ˘ ÌÔÚ› Ó· ÌÂÈÒÓÔ˘Ó ÙË ÊÏÂÁÌÔÓ‹, ÙËÓ ÂÚ·ÈÙ¤Úˆ ›ÓˆÛË Î·È Ó· ¤¯Ô˘Ó Û·Ó Â·ÎfiÏÔ˘ıÔ ÙË Ì›ˆÛË Ù˘ ÚˆÙÂ˚ÓÔ˘Ú›·˜ (36).
∏ ·ÛÊ¿ÏÂÈ· ÙˆÓ ·Ú·ÁÒÁˆÓ ÙÔ˘ ÊÈÌÚÈÎÔ‡ ÔͤԘ. Δ· ·Ú¿ÁˆÁ· ÙÔ˘ ÊÈÌÚÈÎÔ‡ ÔͤԘ, ÁÓˆÛÙ¿ Û·Ó ÊÈÌÚ¿Ù˜, ÂÓÂÚ-
¶›Ó·Î·˜ 5: º·ÚÌ·ÎÔÎÈÓËÙÈ΋ ÛÙ·ÙÈÓÒÓ. (31) Rosuva Atorva Simva T 1/2, h
Lova
Prava
Fluva
20.8
15-30
2-3
2.9
1.3-2.8
0.5-2.3
¡ÂÊÚÈ΋ ·Ô‚ÔÏ‹, %
10
<2
13
10
20
6
CYP-3A4 ÌÂÙ·‚ÔÏÈÛÌfi˜
Ÿ¯È
¡·È
¡·È
¡·È
Ÿ¯È
Ÿ¯È
CYP ÌÂÙ·‚ÔÏÈÛÌfi˜
2CY9
3A4
3A4
3A4
ı›ˆÛË
2CY9
Atorva = atorvastatin, CYP = ΢Ùfi¯ÚˆÌ· P450; CYP-3A4 = ΢Ùfi¯ÚˆÌ· p4503A4; Fluva = Fluvastatin, Lova = lovastatin, Prava = pravastatin, Rosuva = rosuvastatin, Simva = simvastatin, T 1/2 = ¯ÚfiÓÔ˜ ËÌ›ÛÂÈ·˜ ˙ˆ‹˜.
6
ÁÔÔÈÔ‡Ó ÂȉÈÎÔ‡˜ ÌÂÙ·ÁÚ·ÊÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ Ô˘ ·Ó‹ÎÔ˘Ó ÛÙËÓ ÔÌ¿‰· ÙˆÓ ˘ÚËÓÈÎÒÓ ˘Ô‰Ô¯¤ˆÓ, ÙÔ˘˜ peroxisome proliferators activated receptor-· (PPAR·), ÌÂÙ·‚ÔÏ›˙ÔÓÙ·È Î·È ·Ô‚¿ÏÏÔÓÙ·È ·fi ÙÔ˘˜ ÓÂÊÚÔ‡˜ (37,38). ÷ڷÎÙËÚÈÛÙÈÎfi Ù˘ ηÙËÁÔÚ›·˜ ·˘Ù‹˜ Â›Ó·È Ë Ù¿ÛË Ó· ÚÔηÏÔ‡Ó ÌÈ· ÌÈÎÚ‹, ·ÓÙÈÛÙÚÂÙ‹ ·‡ÍËÛË Ù˘ ÎÚ·ÙÈÓ›Ó˘ ÙÔ˘ ÔÚÔ‡. ™ÙȘ ∏¶∞, Â›Ó·È ‰È·ı¤ÛÈ̘ Ë fenofibrate Î·È Ë gemfibrozil. H gemfibrozil Û ۯ¤ÛË Ì ÙËÓ fenofibrate ‰ÂÓ ÚÔηÏ› ·‡ÍËÛË Ù˘ ÎÚ·ÙÈÓ›Ó˘, fï˜ ÚÔηÏ› Ú·‚‰ÔÌ˘fiÏ˘ÛË fiÙ·Ó Û˘Ó‰˘·ÛÙ› Ì ÛÙ·Ù›ÓË, ÂÍ·ÈÙ›·˜ Ù˘ Ê·ÚÌ·ÎÔÎÈÓËÙÈ΋˜ ·ÏÏËÏ›‰Ú·Û˘ (¶›Ó·Î·˜ 6) (39). ∂ȉÈÎfiÙÂÚ·, Ë gemfibrozil ·˘Í¿ÓÂÈ ÙË Û˘ÁΤÓÙÚˆÛË Ù˘ ÛÙ·Ù›Ó˘ ÛÙÔ Ï¿ÛÌ·, ÂÓÒ Ë ‰Ú¿ÛË Ù˘ fenofibrate ÛÙË Û‡˙¢ÍË Ì ÁÏ˘ÎÔ˘ÚÔÓÈÎfi Ô͇ ÙˆÓ ÛÙ·ÙÈÓÒÓ Â›Ó·È ÂÏ¿¯ÈÛÙË (¶›Ó·Î·˜ 6) (40). ™ÙË ÌÂϤÙË FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) Ô˘ ÔÏÔÎÏËÚÒıËΠ۠5 ¯ÚfiÓÈ·, 9.700 ·ÛıÂÓ›˜ ÌÂ Ù‡Ô˘ 2 ™¢ Ô˘ ‰ÂÓ ÂÏ¿Ì‚·Ó·Ó ÛÙ·Ù›ÓË Î·Ù¿ ÙËÓ ¤Ó·ÚÍË, Ù˘¯·ÈÔÔÈ‹ıËÎ·Ó Ó· Ï¿‚Ô˘Ó micronized fenofibrate 200 mg/ËÌÂÚËÛ›ˆ˜ ‹ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ (41). Δ· ›‰· ÎÚ·ÙÈÓ›Ó˘ Ï¿ÛÌ·ÙÔ˜ ·Ú·ÎÔÏÔ˘ıÔ‡ÓÙ·Ó ÛÙÂÓ¿ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÌÂϤÙ˘. ΔÂÏÈο Ë ÎÚ·ÙÈÓ›ÓË ·Ú¤ÌÂÈÓ ηٿ ̤ÛÔ fiÚÔ 0,11- 0,14 mg/dl ˘„ËÏfiÙÂÚË ÛÙËÓ ÔÌ¿‰· Ù˘ fenofibrate (1,03 vs 0,90 mg/dl, p <0.001) ·fi ÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘. Δ¤ÏÔ˜, Û ˘ÔÔÌ¿‰· 661 ·ÛıÂÓÒÓ Ô˘ ÌÂÏÂÙ‹ıËÎ·Ó ÁÈ· 8 ‚‰ÔÌ¿‰Â˜ ÌÂÙ¿ ·fi ÙË ‰È·ÎÔ‹ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ Ù˘ ÌÂϤÙ˘, Ë ÎÚ·ÙÈÓ›ÓË Ï¿ÛÌ·ÙÔ˜ ·ӋÏı ·fi ÙÔ 1,03 ÛÙÔ 0,89 mg/dl, ÁÂÁÔÓfi˜ Ô˘ ˘Ô‰ËÏÒÓÂÈ fiÙÈ ÙÔ Ê¿ÚÌ·ÎÔ ‰ÂÓ ÚÔηÏ› Ì·ÎÚÔ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ‚Ï¿‚Ë. ªÂÚÈÎÔ› ÂÚ¢ÓËÙ¤˜ ˘ÔÛÙËÚ›˙Ô˘Ó fiÙÈ Ë ·‡ÍËÛË Ù˘ ÎÚ·ÙÈÓ›Ó˘ Ô˘ ÚÔηÏÂ›Ù·È ·fi ÙȘ ÊÈÌÚ¿Ù˜, ÔÊ›ÏÂÙ·È ÛÙË ÌÂȈ̤ÓË ·Ú·ÁˆÁ‹ ·ÁÁÂÈԉȷÛÙ·ÏÙÈÎÒÓ ÚÔÛÙ·ÁÏ·Ó‰ÈÓÒÓ. ∂ÓÒ ¿ÏÏÔÈ, fiÙÈ ÔÈ ·ÁˆÓÈÛÙ¤˜ ÙˆÓ PPAR-· ˘Ô‰Ô¯¤ˆÓ ·˘Í¿ÓÔ˘Ó ÙËÓ ·Ú·ÁˆÁ‹ Ù˘ ÎÚ·ÙÈÓ›Ó˘ ¯ˆÚ›˜ Ó· ÌÂÈÒÓÔ˘Ó ÙËÓ GFR (42). ªÈÎÚ‹ ·Ó·‰ÚÔÌÈ΋ ÌÂϤÙË ¤‰ÂÈÍ fiÙÈ Ë gemfibrozil ÏÈÁfiÙÂÚÔ Èı·Ó¿ ·˘Í¿ÓÂÈ ÙËÓ ÎÚ·ÙÈÓ›ÓË Û˘ÁÎÚÈÙÈο Ì ÙËÓ fenofibrate, ÂÓ ÙÔ‡ÙÔȘ ÓÂfiÙÂÚ˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ ÙËÓ ·˘Í¿ÓÂÈ ·ÏÏ¿ Û ÌÈÎÚfiÙÂ-
¶∞ƒ∞°√¡Δ∂™ ∫π¡¢À¡√À ÚÔ ‚·ıÌfi (43). ™ËÌ·ÓÙÈÎfiÙÂÚ· Â›Ó·È Ù· ·ÔÙÂϤÛÌ·Ù· Ê·ÚÌ·ÎÔÎÈÓËÙÈÎÒÓ ÌÂÏÂÙÒÓ Ì gemfibrozil Û ·ÛıÂÓ›˜ Ì á¡, Ô˘ ¤‰ÂÈÍ·Ó fiÙÈ Ë ·¤ÎÎÚÈÛË Ù˘ gemfibrozil Â›Ó·È ÌÂȈ̤ÓË Û ÌÈÎÚfiÙÂÚÔ ‚·ıÌfi ·fi ÙËÓ ·¤ÎÎÚÈÛË Ù˘ fenofibrate (43). ªÂϤÙ˜ Û ·ÛıÂÓ›˜ Ì GFR <50 ml/min/1.73 m2 (̤ÙÚÈ· á¡) ¤‰ÂÈÍ·Ó ÌÂȈ̤ÓÔ ‚·ıÌfi ·¤ÎÎÚÈÛ˘ Ù˘ fenofibrate Î·È Û˘ÛÛÒÚÂ˘Û‹ Ù˘ ÛÂ Û˘Ó¯‹ ¯Ú‹ÛË (38). §fiÁˆ ÙˆÓ Ê·ÚÌ·ÎÔÎÈÓËÙÈÎÒÓ ·˘ÙÒÓ ¯·Ú·ÎÙËÚÈÛÙÈÎÒÓ, ÙÔ NKF Î·È Ë ¡LA (National Lipid Association) Âͤ‰ˆÛ·Ó Ô‰ËÁ›Â˜ ÁÈ· ÙËÓ ÚÔÛÂÎÙÈ΋ ¯Ú‹ÛË ÊÈÌÚ·ÙÒÓ Û ·ÛıÂÓ›˜ Ì á¡ (29) Î·È ¤¯Ô˘Ó ˆ˜ ÂÍ‹˜: Û ·ÛıÂÓ›˜ Ì GFR 60 90 ml/min/1.73 m2, Ì›ˆÛË Ù˘ ‰fiÛ˘ Ù˘ fenofibrate ηٿ 50%, ÁÈ· GFR 15 - 59 ml/min/1.73 m2, Ì›ˆÛË Ù˘ ‰fiÛ˘ ηٿ 75% Î·È ÁÈ· GFR <15 ml/min/1.73 m2, Ó· ·ÔʇÁÂÙ·È. ™‡Ìʈӷ Ì ÙȘ Û˘ÛÙ¿ÛÂȘ ÙÔ˘ NKF, Ë ÊÈÌÚ¿ÙË ÂÎÏÔÁ‹˜ Û ·ÛıÂÓ›˜ Ì á¡ Â›Ó·È Ë gemfibrozil, ¯ˆÚ›˜ Ó· ··ÈÙÂ›Ù·È ÚÔÛ·ÚÌÔÁ‹ Ù˘ ‰fiÛ˘ ·Ó¿ÏÔÁ· Ì ÙËÓ GFR (29). √È ÚfiÛÊ·Ù˜ Û˘ÛÙ¿ÛÂȘ Ù˘ NLA Ô˘ ·ÊÔÚÔ‡Ó ÙËÓ fenÔfibrate Â›Ó·È ·ÚfiÌÔȘ Ì ÙȘ Ô‰ËÁ›Â˜ ÙÔ˘ NKF, ‰È·Ê¤ÚÔ˘Ó ›Ûˆ˜ Û fiÙÈ ·ÊÔÚ¿ ÙË ¯Ú‹ÛË Ù˘ gemfibrozil. ™˘ÓÈÛÙÒÌÂÓË ‰fiÛË Ù˘ gemfibrozile Û ·ÛıÂÓ›˜ Ì GFR <60 ml/min/1.73 m2 Â›Ó·È 600 mg/ËÌÂÚËÛ›ˆ˜ (50% Ì›ˆÛË) Î·È ·ÔÊ˘Á‹ fiÏˆÓ ÙˆÓ ÊÈÌÚ·ÙÒÓ Û GFR <15 ml/min/1.73 m2. ∂ÈϤÔÓ ı· Ú¤ÂÈ Ó· ˘ÔÏÔÁ›˙ÂÙ·È Ë ÎÚ·ÙÈÓ›ÓË ÚÈÓ ÙËÓ ¤Ó·ÚÍË Ù˘ ÊÈÌÚ¿Ù˘ (39). Δ¤ÏÔ˜, ˘¿Ú¯ÂÈ ÂӉȷʤÚÔÓ ÁÈ· ÙËÓ Ù¿ÛË Ô˘ ¤¯ÂÈ Ë fenofibrate Ó· ·˘Í¿ÓÂÈ ÂÚ·ÈÙ¤Úˆ Ù· ‹‰Ë ·˘ÍË̤ӷ ›‰· Ù˘ ÔÌÔ΢ÛÙ½Ó˘ (44). Δ· ·˘ÍË̤ӷ ›‰· ÔÌÔ΢ÛÙ½Ó˘ ıˆÚÔ‡ÓÙ·È ·Ú¿ÁÔÓÙ·˜ ÎÈÓ‰‡ÓÔ˘ ηډȷÁ-
ÁÂȷ΋˜ ÓfiÛÔ˘ Î·È ˘ÂÚËÎÙÈÎfiÙËÙ·˜. ™ÙË ÌÂϤÙË FIELD, Ë ÔÌÔ΢ÛÙ½ÓË Ï¿ÛÌ·ÙÔ˜ ÛÙËÓ ÔÌ¿‰· Ù˘ fenofibrate, ‹Ù·Ó ηٿ ̤ÛÔ fiÚÔ 3.7 Ìmol ˘„ËÏfiÙÂÚË, ˆÛÙfiÛÔ 8 ‚‰ÔÌ¿‰Â˜ ÌÂÙ¿ ÙËÓ ‰È·ÎÔ‹ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘, Ù· ›‰¿ Ù˘ ¤ÂÛ·Ó ÛÙ· ÚÈÓ ·fi ÙËÓ ¤Ó·ÚÍË Â›Â‰· (41). ΔÔ ›‰ÈÔ ¤‰ÂÈÍ·Ó Î·È ¿ÏϘ ÌÂϤÙ˜ Ì fenofibrate, ÂÓÒ ÌÂϤÙ˜ Ì ¿ÏϘ ÊÈÌÚ¿Ù˜ ‰ÂÓ ¤‰ÂÈÍ·Ó ÛÙ·ıÂÚ‹ ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ Ù˘ ÔÌÔ΢ÛÙ½Ó˘ (45). ∏ ÎÏÈÓÈ΋ ÛËÌ·Û›· ·˘Ù‹˜ Ù˘ ·‡ÍËÛ˘ Ù˘ ÔÌÔ΢ÛÙ½Ó˘ Ì fenofÈbrate Â›Ó·È ·Û·Ê‹˜, ·ÏÏ¿ ÙfiÛÔ ÛÙËÓ FIELD fiÛÔ Î·È ÛÙËÓ Coronary Drug Project (46) Ì clofibrate, ·Ú·ÙËÚ‹ıËΠÌÈÎÚ‹ ·ÏÏ¿ ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË Ù˘ ıÚÔÌ‚ÔÂÌ‚ÔÏÈ΋˜ ÓfiÛÔ˘ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ Ï¿Ì‚·Ó·Ó ÊÈÌÚ¿ÙË.
∏ ·ÛÊ¿ÏÂÈ· ÙÔ˘ Û˘Ó‰˘·ÛÌÔ‡ ÛÙ·Ù›Ó˘ Ì ÊÈÌÚ¿ÙË ∞ÛıÂÓ›˜ Ì á¡ ¤¯Ô˘Ó Û˘¯Ó¿ ÌÈÎÙ‹ ‰˘ÛÏÈȉ·ÈÌ›· Î·È Û ·ÛıÂÓ›˜ ˘„ËÏÔ‡ ηډȷÁÁÂÈ·ÎÔ‡ ÎÈÓ‰‡ÓÔ˘ ›Ûˆ˜ ··ÈÙÂ›Ù·È Û˘Á¯ÔÚ‹ÁËÛË ÛÙ·Ù›Ó˘ Ì ÊÈÌÚ¿ÙË, Ì ·ÔÙ¤ÏÂÛÌ· Ó· Â›Ó·È ÛËÌ·ÓÙÈÎfi Ó· ÁÓˆÚ›˙Ô˘Ì ÙËÓ ·ÛÊ¿ÏÂÈ· Ù˘ Û˘Á¯ÔÚ‹ÁËÛ˘ ·˘Ù‹˜. Ÿˆ˜ ·Ó·Ê¤ÚıËΠÈÔ ¿Óˆ, ˘¿Ú¯Ô˘Ó ¢‰È¿ÎÚÈÙ˜ Ê·ÚÌ·ÎÔÎÈÓËÙÈΤ˜ ‰È·ÊÔÚ¤˜ ÌÂٷ͇ ÙˆÓ ÊÈÌÚ·ÙÒÓ fiÙ·Ó Û˘Ó‰˘¿˙ÔÓÙ·È Ì ÛÙ·Ù›Ó˜ (¶›Ó·Î·˜ 6). ∏ gemfibrozil ·˘Í¿ÓÂÈ Ù· ›‰· fiÏˆÓ ÙˆÓ ÛÙ·ÙÈÓÒÓ ÛÙÔ Ï¿ÛÌ·, Ì ÂÍ·›ÚÂÛË Ù˘ fluvastatin Ì ·ÔÙ¤ÏÂÛÌ· Ó· ·˘Í¿ÓÂÈ ÙÔÓ Î›Ó‰˘ÓÔ Ú·‚‰ÔÌ˘fiÏ˘Û˘ (47). ΔÔ ·ÔÙ¤ÏÂÛÌ· ·˘Ùfi ‰ÂÓ ·Ú·ÙËÚÂ›Ù·È Ì ÙË fenofibrate Î·È ‰Â Û¯ÂÙ›˙ÂÙ·È Ì ÙÔ CYP-3A4, ·ÏÏ¿ ÔÊ›ÏÂÙ·È ÛÙËÓ ·Ó·ÛÙÔÏ‹ Ù˘ Ô‰Ô‡ Û‡˙¢Í˘ Ì ÙÔ ÁÏ˘ÎÔ˘ÚÔÓÈÎfi Ô͇ Ô˘ ÂÌϤÎÂÙ·È ÛÙÔ ÌÂÙ·‚ÔÏÈÛÌfi ÙˆÓ ÛÙ·ÙÈÓÒÓ (47). ™‡Ìʈӷ Ì ÙÔ NKF, ÊÈÌÚ¿ÙË ÂÎÏÔÁ‹˜ Â›Ó·È Ë gemfibrozil, fiÙ·Ó fï˜
¶›Ó·Î·˜ 6: º·ÚÌ·ÎÔÎÈÓËÙÈ΋ ·ÏÏËÏ›‰Ú·ÛË ÛÙ·ÙÈÓÒÓ/ÊÈÌÚ·ÙÒÓ. (47) Atorvastatin Simvastatin Pravastatin Rosuvastatin Fluvastatin Lovastatin Cerivastatin
Gemfibrozil ↑ Cmax ηٿ 1.8 ↑ Cmax ηٿ 2 ↑ Cmax ηٿ 2 ↑ Cmax ηٿ 2 ∫·Ì›· ‰Ú¿ÛË ↑ Cmax ηٿ 2.8 ↑ Cmax ηٿ 2-3
Fenofibrate ∫·Ì›· ‰Ú¿ÛË ∫·Ì›· ‰Ú¿ÛË ∫·Ì›· ‰Ú¿ÛË ∫·Ì›· ‰Ú¿ÛË ∫·Ì›· ‰Ú¿ÛË ªË ‰È·ı¤ÛÈÌË ∫·Ì›· ‰Ú¿ÛË
↓ = Ì›ˆÛË, ↑ = ·‡ÍËÛË, Cmax = ̤ÁÈÛÙË Û˘ÁΤÓÙÚˆÛË.
ı· Ú¤ÂÈ Ó· Á›ÓÂÈ Û˘Ó‰˘·ÛÌfi˜ Ì ÛÙ·Ù›ÓË, ÚÔÙÈÌ¿Ù·È Ë fenofibrate. ∂Ó ÙÔ‡ÙÔȘ ·ÌÊfiÙÂÚ˜ (ÛÙ·Ù›Ó˜ Î·È ÊÈÌÚ¿Ù˜) Û¯ÂÙ›˙ÔÓÙ·È ·ÓÂÍ¿ÚÙËÙ· Ì ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ Ì˘Ô¿ıÂÈ·˜ Î·È Ú·‚‰ÔÌ˘fiÏ˘Û˘ fiÙ·Ó Û˘Ó‰˘¿˙ÔÓÙ·È. °È· ÙÔ Ì¤ÁÈÛÙÔ Ù˘ ·ÛÊ¿ÏÂÈ·˜ ÛÙË Û˘Ó‰˘·Ṳ̂ÓË ıÂڷ›·, Ë NLA Û˘ÛÙ‹ÓÂÈ Ó· ÌË ¯ÔÚËÁÂ›Ù·È Ë Ì¤ÁÈÛÙË ‰fiÛË Ù˘ ÛÙ·Ù›Ó˘ ÛÙÔ Û˘Ó‰˘·ÛÌfi Ì ÊÈÌÚ¿ÙË (39).
∏ ·ÛÊ¿ÏÂÈ· ÙˆÓ ¿ÏÏˆÓ ˘ÔÏÈȉ·ÈÌÈÎÒÓ Ê·ÚÌ¿ÎˆÓ √È ÈÔÓÙÔ·ÓÙ·ÏÏ·ÎÙÈΤ˜ ÚËÙ›Ó˜ (colesevelam Î·È cholestyramine) Â›Ó·È ÁÂÓÈο ·ÛÊ·Ï›˜ Û ·ÛıÂÓ›˜ Ì á¡, ÂÂȉ‹ ‰ÂÓ ·ÔÚÚÔÊÔ‡ÓÙ·È Û˘ÛÙËÌ·ÙÈο. ∂ÓÙÔ‡ÙÔȘ, ÌÔÚ› Ó· ·˘Í‹ÛÔ˘Ó Ù· ›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Î·È ·ÓÙ‰›ÎÓ˘ÓÙ·È Û ·ÛıÂÓ›˜ Ì ˘„ËÏ¿ ›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ (48). ™Â ÚfiÛÊ·ÙË ÌÂϤÙË, 36 ·ÈÌÔηı·ÚfiÌÂÓÔÈ ·ÛıÂÓ›˜ ÂÏ¿Ì‚·Ó·Ó 1.5 g colesevelam ËÌÂÚËÛ›ˆ˜ ÚÔÁÂ˘Ì·ÙÈο ÁÈ· 6 Ì‹Ó˜. √È ÂÚ¢ÓËÙ¤˜ ‰È·›ÛÙˆÛ·Ó Ì›ˆÛË Ù˘ non-HDL ηٿ 20% (p <0.0001) Î·È Ù˘ ‰È¿ÌÂÛ˘ ÙÈÌ‹˜ Ù˘ CRP ηٿ 63% (p = 0.0259) (49). À¿Ú¯Ô˘Ó ÂÚÈÔÚÈṲ̂ӷ ‰Â‰Ô̤ӷ fiÛÔÓ ·ÊÔÚ¿ ÙË ‰Ú¿ÛË Î·È ÙËÓ ·ÛÊ¿ÏÂÈ· ÙÔ˘ ÓÈÎÔÙÈÓÈÎÔ‡ ÔͤԘ ÛÙË Ã¡¡. º·ÚÌ·ÎÔÎÈÓËÙÈΤ˜ ÌÂϤÙ˜ ‰ÂÈÎÓ‡Ô˘Ó fiÙÈ 34% ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ ÂÎÎÚ›ÓÂÙ·È ·fi ÙÔ˘˜ ÓÂÊÚÔ‡˜. ™‡Ìʈӷ Ì ÙȘ Ô‰ËÁ›Â˜ ÙÔ˘ NKF, ÁÈ· ÙÔ˘˜ ·ÛıÂÓ›˜ Ì GFR <15 ml/min/1.73 m2, Ë ‰fiÛË ı· Ú¤ÂÈ Ó· ÌÂÈÒÓÂÙ·È Î·Ù¿ 50%, ¿Ïψ˜ ‰ÂÓ ··ÈÙÂ›Ù·È ·ÏÏ·Á‹ Ù˘ ‰fiÛ˘ (29). À¿Ú¯Ô˘Ó ÌÈÎÚ¤˜ ÌÂϤÙ˜ Ì ezetimibe Ô˘ ‰Â›¯ÓÔ˘Ó fiÙÈ Â›Ó·È ·ÛÊ·Ï‹˜ Î·È Î·Ï¿ ·ÓÂÎÙ‹ ÛÙË Ì¤ÙÚÈ· ¤ˆ˜ Î·È ÛÔ‚·Ú‹ á¡ Î·È fiÙÈ ‰ÂÓ ··ÈÙÂ›Ù·È ÚÔÛ·ÚÌÔÁ‹ Ù˘ ‰fiÛ˘ Û ÌÂȈ̤ÓË GFR. ™ÙË ÌÂϤÙË UKHARP II (United Kingdom Heart and Renal Protection II), ÌÂÏÂÙ‹ıËÎ·Ó ÁÈ· 6 Ì‹Ó˜ 203 ·ÛıÂÓ›˜ Ì ‰È·ÊfiÚÔ˘ ‚·ıÌÔ‡ ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· (50). ™ÙË ÌÂϤÙË Û˘ÌÂÚÈÏ‹ÊıËÎ·Ó 152 ·ÛıÂÓ›˜ Ì ›‰· ÎÚ·ÙÈÓ›Ó˘ >1,7 mg/dl, 18 Û ÂÚÈÙÔÓ·˚΋ οı·ÚÛË Î·È 33 Û ·ÈÌԉȇÏÈÛË. ∏ ÔÌ¿‰· ÂϤÁ¯Ô˘ Ù¤ıËΠ۠simvastatin 20 mg/ ËÌÂÚËÛ›ˆ˜ Î·È Ë ˘fi ÌÂϤÙË ÔÌ¿‰· ÛÂ Û˘Ó‰˘·ÛÌfi simvastatin 20 mg Î·È ezetimibe 10 mg/ËÌÂÚËÛ›ˆ˜.
7
¢∂∫∂ªμƒπ√™ 2008
™ÙËÓ ÔÌ¿‰· Ô˘ ‹Ú ÙÔ Û˘Ó‰˘·ÛÌfi, Ë LDL-¯ÔÏËÛÙÂÚfiÏË ÌÂÈÒıËΠηٿ 21% ÂÚÈÛÛfiÙÂÚÔ (p = 0.0001) ·fi ÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘ ¯ˆÚ›˜ Ó· ·Ú·ÙËÚËıÔ‡Ó ÂÈϤÔÓ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ.
¢È·¯Â›ÚÈÛË ÙˆÓ ÏÈȉ›ˆÓ Û ·ÛıÂÓ›˜ Ì á¡ ÛÙ·‰›Ô˘ 3 - 4 (GFR:15-50 ml/min/1,73m2) Δ· NKF Î·È National Cholesterol Education Program Adult Treatment Panel (ATP) III, ¤¯Ô˘Ó ÂΉÒÛÂÈ ·ÚfiÌÔȘ Ô‰ËÁ›Â˜ ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ‰˘ÛÏÈȉ·ÈÌ›·˜ ÛÙË Ì¤ÙÚÈ· á¡, ˆÛÙfiÛÔ (ÔÈ Ô‰ËÁ›Â˜) ÂÌÊ·Ó›˙Ô˘Ó ÛËÌ·ÓÙÈΤ˜ ‰È·ÊÔÚ¤˜. (29,51). ™‡Ìʈӷ Ì ÙȘ Û˘ÛÙ¿ÛÂȘ ÙÔ˘ NKF, Ë Ã¡¡ ıˆÚÂ›Ù·È ÈÛÔ‰‡Ó·ÌÔ ™¡ Î·È ··ÈÙÂ›Ù·È ÂÙ‹ÛÈÔ˜ ÏÈȉ·ÈÌÈÎfi˜ ¤ÏÂÁ¯Ô˜. Ÿˆ˜ Â›Ó·È ÁÓˆÛÙfi, Û οı ·ÛıÂÓ‹ Ì ‰˘ÛÏÈȉ·ÈÌ›· ··ÈÙÂ›Ù·È ¤ÏÂÁ¯Ô˜ ÁÈ· ‰Â˘ÙÂÚÔ·ı›˜ ·Èٛ˜ ‰˘ÛÏÈȉ·ÈÌ›·˜ (˘Ôı˘ÚÂÔÂȉÈÛÌfi˜, ‰È·‚‹Ù˘, ıÂڷ›· Ì ÎÔÚÙÈÎÔÛÙÂÚÔÂȉ‹, protease inhibitors, beta-blockers, ‰ÈÔ˘ÚËÙÈο, ÔÈÛÙÚÔÁfiÓ· ). À„ËÏ‹ LDL-C. ∞Ó Î·È ÔÈ ·ÛıÂÓ›˜ Ì á¡ ¤¯Ô˘Ó Û˘¯Ó¿ ÔÏϷϤ˜ ‰È·Ù·Ú·¯¤˜ ÙˆÓ ÏÈȉ›ˆÓ, ÚˆÙ·Ú¯ÈÎfi˜ ÛÙfi¯Ô˜ Â›Ó·È Ë Ì›ˆÛË Ù˘ LDL-¯ÔÏËÛÙÂÚfiÏ˘. ™‡Ìʈӷ Ì ÙÔ NKF Ë LDL-¯ÔÏËÛÙÂÚfiÏË ı· Ú¤ÂÈ Ó· ÌÂÈÒÓÂÙ·È Û ›‰· <100 mg/dl Î·È Â› ÙÔ˘ ·ÚfiÓÙÔ˜, ‰ÂÓ Û˘ÛÙ‹ÓÂÙ·È ÂÈıÂÙÈÎfiÙÂÚÔ˜ ÛÙfi¯Ô˜ Û ·ÛıÂÓ›˜ Ì á¡ Î·È Û˘Ìو̷ÙÈ΋ ·ıËÚÔÛÎÏËÚˆÙÈ΋ ÓfiÛÔ (30). μ¿ÛÂÈ ÙˆÓ ÙÚÔÔÔÈËÌ¤ÓˆÓ Ô‰ËÁÈÒÓ ATP III, ›Ûˆ˜ Â›Ó·È Û˘ÓÂÙfi, ÔÈ ·ÛıÂÓ›˜ Ì á¡ Î·È ·ıËÚÔÛÎÏËÚˆÙÈ΋ ÓfiÛÔ Ó· ıÂڷ‡ÔÓÙ·È Ì ÛÙfi¯Ô LDL-¯ÔÏËÛÙÂÚfiÏ˘ <70 mg/dl. √È ÛÙ·Ù›Ó˜, fiˆ˜ Î·È ÛÙÔ ÁÂÓÈÎfi ÏËı˘ÛÌfi, Â›Ó·È Ô ·ÎÚÔÁˆÓÈ·›Ô˜ Ï›ıÔ˜ ÛÙË ıÂڷ›· Ù˘ ‰˘ÛÏÈȉ·ÈÌ›·˜. ™˘Ó‹ıˆ˜ ÁÈ· Ó· ÂÈÙ¢¯ı› Ô ÛÙfi¯Ô˜ ··ÈÙÂ›Ù·È Ô Û˘Ó‰˘·ÛÌfi˜ Ì ÙËÓ ·ÏÏ·Á‹ ÙÔ˘ ÙÚfiÔ˘ ˙ˆ‹˜. ™Â ·ÛıÂÓ›˜ Ì á¡ ÌÔÚÔ‡Ó Ó· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó Ì ·ÛÊ¿ÏÂÈ· fiϘ ÔÈ ÛÙ·Ù›Ó˜. ∂Ó ÙÔ‡ÙÔȘ Û ÚÔ¯ˆÚË̤ÓË Ã¡¡ (GFR <30 ml/min/1,73m2) ÏÂÔÓÂÎÙÔ‡Ó ÔÚÈṲ̂Ó˜ ÛÙ·Ù›Ó˜, ÏfiÁˆ ‰È·ÊÔÚÒÓ ÛÙȘ Ê·ÚÌ·ÎÔÎÈÓËÙÈΤ˜ ÙÔ˘˜ ȉÈfiÙËÙ˜. ¶ÚÔÎÂÈ̤ÓÔ˘ ÁÈ· ÙËÓ atorvastatin, ÂÂȉ‹ Ë ·¤ÎÎÚÈÛ‹ Ù˘ ·fi ÙÔ˘˜ ÓÂÊÚÔ‡˜
8
Â›Ó·È Ìˉ·ÌÈÓ‹, ‰ÂÓ ··ÈÙÂ›Ù·È ÚÔÛ·ÚÌÔÁ‹ Ù˘ ‰fiÛ˘ Û ·ÛıÂÓ›˜ Ì ÌÂȈ̤ÓË GFR ‹ ·ÈÌԉȇÏÈÛË (¶›Ó·Î·˜ 7). ∞Ó ··ÈÙÂ›Ù·È Û˘Ó‰˘·ÛÌfi˜ Ì gemfibrozil, Ë fluvastatin ·ÔÙÂÏ› ÙËÓ Ï¤ÔÓ ·ÛÊ·Ï‹ ÂÈÏÔÁ‹. ÕÏϘ ÛÙ·Ù›Ó˜ ··ÈÙÔ‡Ó ÚÔÛ·ÚÌÔÁ‹ Ù˘ ‰fiÛ˘ Ì ÙËÓ ÂͤÏÈÍË Ù˘ á¡ (30) (¶›Ó·Î·˜ 7). ™Â ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ ¤¯ÂÈ ÂÈÙ¢¯ı› Ô ÛÙfi¯Ô˜ Ì atorvastatin ‹ fluvastatin, ÌÔÚ› Ó· ÚÔÛÙÂı› Ì ·ÛÊ¿ÏÂÈ· ezetimibe ‹ ÚËÙ›ÓË (¶›Ó·Î·˜ 8). ∏ ¯Ú‹ÛË ÙˆÓ ÚËÙÈÓÒÓ ÌÔÚ› Ó· Â›Ó·È ÂÚÈÔÚÈṲ̂ÓË ÏfiÁˆ ÙÔ˘ fiÙÈ ÌÔÚ› Ó· ·˘Í‹ÛÔ˘Ó Ù· ÙÚÈÁÏ˘ÎÂÚ›‰È· ‹ Ó· ÌÂÈÒÛÔ˘Ó ÙËÓ ·ÔÚÚfiÊËÛË ¿ÏÏˆÓ Ê·ÚÌ¿ÎˆÓ (48). ªÈÎÙ‹ ‰˘ÛÏÈȉ·ÈÌ›·. √È ÂÚÈÛÛfiÙÂÚÔÈ ·ÛıÂÓ›˜ Ì á¡ ¤¯Ô˘Ó ‰È·Ù·Ú·¯¤˜ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ, Ù˘ HDL-¯ÔÏËÛÙÂÚfiÏ˘ ηıÒ˜ Î·È ˘„ËÏ¿ ›‰· LDL-¯ÔÏËÛÙÂÚfiÏ˘ (ÌÈÎÙ‹ ‰˘ÛÏÈȉ·ÈÌ›·). ªÂÙ¿ ÙËÓ Â›Ù¢ÍË ÙÔ˘ ÛÙfi¯Ô˘ ÁÈ· ÙËÓ LDL-¯ÔÏËÛÙÂÚfiÏË, Ô ÂfiÌÂÓÔ˜ ÛÙfi¯Ô˜ Â›Ó·È Ë non-HDL, Ë ÔÔ›· Â›Ó·È Ë ÌfiÓË ÏÈȉ·ÈÌÈ΋ ·Ú¿ÌÂÙÚÔ˜ Ô˘ Û˘Û¯ÂÙ›˙ÂÙ·È ıÂÙÈο Ì ÙËÓ Î·Ú‰È·ÁÁÂȷ΋ ıÓËÙfiÙËÙ· Û ·ÈÌÔηı·ÚfiÌÂÓÔ˘˜ ·ÛıÂÓ›˜ (52). ∂›Ó·È ÁÓˆÛÙfi fiÙÈ ÔÈ Ôχ ¯·ÌËÏ‹˜ (VLDL) Î·È ÂӉȿÌÂÛ˘ (IDL) ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙ½Ó˜, Â›Ó·È ·˘ÍË̤Ó˜ Û ·ÛıÂÓ›˜ Ì á¡ Ì ÌÈÎÙ‹ ‰˘ÛÏÈȉ·ÈÌ›· Î·È ÂÔ̤ӈ˜ Ë non-HDL ›Ûˆ˜ Â›Ó·È Î·Ï‡ÙÂÚÔ˜ ‰Â›ÎÙ˘ ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ ·ıËÚÔÁÒÓˆÓ ÏÈÔÚˆÙÂ˚ÓÒÓ. μ¿ÛÂÈ ÙˆÓ Û˘ÛÙ¿ÛÂˆÓ ÙÔ˘ NKF, ıÂڷ¢ÙÈÎfi˜ ÛÙfi¯Ô˜ ÁÈ· ÙËÓ LDL-¯ÔÏËÛÙÂÚfiÏË Î·È ÙËÓ nonHDL Û ·ÛıÂÓ›˜ Ì á¡ Â›Ó·È <100 mg/dl Î·È <130 mg/dl ·ÓÙ›ÛÙÔȯ· (30). ∞ÛıÂÓ›˜ Ì ÌÈÎÙ‹ ‰˘ÛÏÈȉ·ÈÌ›· Û˘¯Ó¿ ¯ÚÂÈ¿˙ÔÓÙ·È Û˘Ó‰˘·Ṳ̂ÓË ıÂڷ›· Ì ÛÙ·Ù›ÓË Î·È Î¿ÔÈÔ ¿ÏÏÔ ˘ÔÏÈȉ·ÈÌÈÎfi Ê¿ÚÌ·ÎÔ Ô˘ ı· ÌÔÚÔ‡Û ӷ Â›Ó·È ezetimibe, ÊÈÌÚ¿ÙË, ÓÈÎÔÙÈÓÈÎfi Ô͇, ‹ ˆ-3 §√. ∞Ó Î·È Ë ezetimibe ¤¯ÂÈ Ìˉ·ÌÈÓ‹ ›‰Ú·ÛË ÛÙËÓ HDL-¯ÔÏËÛÙÂÚfiÏË Î·È Ù· ÙÚÈÁÏ˘ÎÂÚ›‰È·, Ë ÚÔÛı‹ÎË Ù˘ Û ÛÙ·Ù›ÓË ¤¯ÂÈ Û·Ó ·ÔÙ¤ÏÂÛÌ· ÛËÌ·ÓÙÈ΋ Ì›ˆÛË Ù˘ non-HDL, ‰Â˘ÙÂÚ‡ÔÓÙ· ÛÙfi¯Ô ÛÙË ÌÈÎÙ‹ ‰˘ÛÏÈȉ·ÈÌ›· (¶›Ó·Î·˜ 8). √ Û˘Ó‰˘·ÛÌfi˜ ÛÙ·Ù›Ó˘ Î·È ezetimibe Â›Ó·È Û¯ÂÙÈο ·ÛÊ·Ï‹˜ Î·È Î·Ï¿ ·ÓÂÎÙfi˜ Û á¡ (50). Δ· ˆ-3 §√ ›Û˘ ÌÔÚÔ‡Ó Ó· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó
ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÛÙ·Ù›ÓË. ∞Ó Î·È Ù· ‰ËÌÔÛÈÂ˘Ì¤Ó· ÛÙÔȯ›· Â›Ó·È Ï›Á·, ‰ÂÓ ˘¿Ú¯ÂÈ ÂÚÈÔÚÈÛÌfi˜ ÁÈ·Ù› ‰ÂÓ ÂÌÊ·Ó›˙Ô˘Ó ÛËÌ·ÓÙÈΤ˜ ·ÏÏËÏÂȉڿÛÂȘ Ì ÙȘ ÛÙ·Ù›Ó˜ Î·È ‰ÂÓ ··ÈÙÂ›Ù·È ÚÔÛ·ÚÌÔÁ‹ Ù˘ ‰fiÛ˘ ÙÔ˘˜ Û ¤ÎÙˆÛË Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ (53). √È ÊÈÌÚ¿Ù˜ ÌÔÚÔ‡Ó Ó· ‰ÔıÔ‡Ó ÛÙË ÌÈÎÙ‹ ‰˘ÛÏÈȉ·ÈÌ›· Ì ÚÔÛÔ¯‹ ÂÂȉ‹ ÌÂÙ·‚ÔÏ›˙ÔÓÙ·È Î˘Ú›ˆ˜ ÛÙÔ˘˜ ÓÂÊÚÔ‡˜. ™‡Ìʈӷ Ì ÙȘ Ô‰ËÁ›Â˜ ÙÔ˘ NKF, ÊÈÌÚ¿ÙË ÂÎÏÔÁ‹˜ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì á¡ Â›Ó·È Ë gemfibrozil (29). À¿Ú¯Ô˘Ó ·ÌÊÈÛ‚ËÙ‹ÛÂȘ Û¯ÂÙÈο Ì ÙËÓ ·ÛÊ¿ÏÂÈ· Ù˘ fenofibrate, ÏfiÁˆ Ù˘ Ù¿Û˘ Ù˘ Ó· ·˘Í¿ÓÂÈ ÙËÓ ÎÚ·ÙÈÓ›ÓË Î·È ÙËÓ ÔÌÔ΢ÛÙ½ÓË Û ÌÂÁ·Ï‡ÙÂÚÔ ‚·ıÌfi ·fi fiÙÈ Ë gemfibrozil. √ ·˘ÍË̤ÓÔ˜ ΛӉ˘ÓÔ˜ Ú·‚‰ÔÌ˘fiÏ˘Û˘ ÛÙË Û˘Ó‰˘·Ṳ̂ÓË ıÂڷ›· (ÛÙ·Ù›ÓË Ì ÊÈÌÚ¿ÙË) ··ÈÙ› ÛÙÂÓ‹ ·Ú·ÎÔÏÔ‡ıËÛË ÙˆÓ ·ÛıÂÓÒÓ Î·È ¿ÌÂÛË ·Ó·ÊÔÚ¿ ÙˆÓ Ì˘˚ÎÒÓ Û˘Ìو̿وÓ. ¶ÏÂÔÓ¤ÎÙËÌ· Ê·›ÓÂÙ·È Ó· ¤¯ÂÈ Ë fenofibrate ÛÙÔ Û˘Ó‰˘·ÛÌfi, ÏfiÁˆ ÌË ·ÏÏËÏ›‰Ú·Û‹˜ Ù˘ Ì ÙȘ ÛÙ·Ù›Ó˜ (47). ŸÙ·Ó ¯ÔÚËÁÂ›Ù·È Ë gemfibrozil, ÚÔÙÈÌ¿Ù·È Ë fluvastatin Û·Ó ÛÙ·Ù›ÓË Û˘Á¯ÔÚ‹ÁËÛ˘, ÂÂȉ‹ ‰ÂÓ ˘¿Ú¯ÂÈ ·ÏÏËÏ›‰Ú·ÛË Î·È ¤¯Ô˘Ó ·Ó·ÊÂÚı› ÏÈÁfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ Ú·‚‰ÔÌ˘fiÏ˘Û˘ Û˘ÁÎÚÈÙÈο Ì ¿ÏϘ ÛÙ·Ù›Ó˜. ∂Í·ÈÙ›·˜ Ù˘ ¯·ÌËÏ‹˜ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜ Ù˘ fluvastatin ÛÙË Ì›ˆÛË Ù˘ LDL-¯ÔÏËÛÙÂÚfiÏ˘, Û˘¯Ó¿ ··ÈÙÂ›Ù·È ÙÚ›ÙÔ Ê¿ÚÌ·ÎÔ Ô˘ ÌÔÚ› Ó· Â›Ó·È Ë ezetimibe (¶›Ó·Î·˜ 8). ∂Âȉ‹ Ë Ã¡¡ ·ÔÙÂÏ› ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ ÁÈ· Ú·‚‰ÔÌ˘fiÏ˘ÛË, Ô Û˘Ó‰˘·ÛÌfi˜ ÌÈ·˜ ÛÙ·Ù›Ó˘ Ì ÊÈÌÚ¿ÙË ··ÈÙ› ȉȷ›ÙÂÚË ÚÔÛÔ¯‹. ∏ ÓÈ·Û›ÓË ıˆÚÂ›Ù·È ÌÈ· ÂÈÏÔÁ‹ ÛÙË ıÂڷ›· Ù˘ ÌÈÎÙ‹˜ ‰˘ÛÏÈȉ·ÈÌ›·˜. Œ¯ÂÈ Ê·Ó› fiÙÈ ·˘Í¿ÓÂÈ ÙËÓ HDL-¯ÔÏËÛÙÂÚfiÏË Î·È ÌÂÈÒÓÂÈ Î·È ÙË lipoprotein(a) Î·È Ù· ÙÚÈÁÏ˘ÎÂÚ›‰È·, Ô˘ Â›Ó·È ·˘ÍË̤ӷ ÛÙË Ã¡¡, ·ÏÏ¿ Ë ¯Ú‹ÛË Ù˘ Â›Ó·È ÂÚÈÔÚÈṲ̂ÓË ÏfiÁˆ Ù˘ η΋˜ ·ÓÔ¯‹˜. √‰ËÁ›Â˜ ÙÔ˘ NKF ˘ÔÛÙËÚ›˙Ô˘Ó Ì›ˆÛË Ù˘ ‰fiÛ˘ ηٿ 50% ÁÈ· GFR <15 mg/ml/1.73 m2. √È ÚËÙ›Ó˜ ‰ÂÓ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È Û˘Ó‹ıˆ˜ ÛÙË ÌÈÎÙ‹ ‰˘ÛÏÈȉ·ÈÌ›· ÂÍ·ÈÙ›·˜ Ù˘ Ù¿Û˘ Ó· ·˘Í¿ÓÔ˘Ó Ù· ÙÚÈÁÏ˘ÎÂÚ›‰È· (29). ¶Ôχ ˘„ËÏ¿ ÙÚÈÁÏ˘ÎÂÚ›‰È·. √ ÚˆÙ·Ú¯ÈÎfi˜ ÛÙfi¯Ô˜ Û ·ÛıÂÓ›˜ Ì ΔG >500 mg/dl Â›Ó·È Ë ÚfiÏË„Ë
¶∞ƒ∞°√¡Δ∂™ ∫π¡¢À¡√À Ù˘ ·ÁÎÚ·ٛÙȉ·˜ (51). £Âڷ›· ÂÎÏÔÁ‹˜ Â›Ó·È ÔÈ ÊÈÌÚ¿Ù˜ ÂÂȉ‹ Â›Ó·È Î·ÏÏ›ÙÂÚ· ·ÓÂÎÙ¤˜ ·fi ÙË ÓÈ·Û›ÓË Î·È ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙÂÚ˜ ·fi ÙȘ ÛÙ·Ù›Ó˜. ™˘Á¯ÚfiÓˆ˜ ÏfiÁˆ ·ÛÊ¿ÏÂÈ·˜ ÚÔÙ›ÓÂÙ·È Ë gemfibrozil ·ÓÙ› Ù˘ fenofibrate (¶›Ó·Î·˜ 8). ∞Ó Î·È ÌÂÚÈΤ˜ ÌÂϤÙ˜ ˘ÔÛÙËÚ›˙Ô˘Ó fiÙÈ Ë ‰fiÛË Ù˘ gemfibrozil ‰Â ¯ÚÂÈ¿˙ÂÙ·È Ó· ÌÂȈı› Û ÛÔ‚·Ú‹ á¡, Ë NLA Safety Task Force on LipidLowering Drugs, ˘ÔÛÙËÚ›˙ÂÈ fiÙÈ Ë gemfibrozil Ú¤ÂÈ Ó· ÌÂÈÒÓÂÙ·È Û 600 mg/ËÌÂÚËÛ›ˆ˜ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì GFR <60 ml/min/1.73 m2 Î·È Ó· ·ÔʇÁÂÙ·È fiÙ·Ó Ë GFR Â›Ó·È <15 ml/min/1.73 m2 (30). Δ¤ÏÔ˜, ·Ó Ú¤ÂÈ Ó· ‰Ôı› Ë fenofibrate, Ë ‰fiÛË ‰ÂÓ ı· Ú¤ÂÈ Ó· ÍÂÂÚÓ¿ÂÈ Ù· 48 mg/ËÌÂÚËÛ›ˆ˜ Ì ÚÔÛÂÎÙÈ΋ ·Ú·ÎÔÏÔ‡ıËÛË Ù˘ ÎÚ·ÙÈÓ›Ó˘ (39). ªÈ· ¿ÏÏË ÂÈÏÔÁ‹ Û Ôχ ˘„ËÏ¿ ›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Â›Ó·È Ë ıÂڷ›· Ì ˆ-3 §√. Δ· ·ÚÈ· Û˘ÛÙ·ÙÈο ÙˆÓ È¯ı˘¤Ï·ÈˆÓ Â›Ó·È ÙÔ ÂÈÎÔ-
Û·-ÂÓÙ·-ÂÓ-Ô˚Îfi Ô͇ (EPA) Î·È ÙÔ ÂÈÎÔÛȉ˘·-ÂÍ·-ÂÓ-Ô˚Îfi Ô͇ (DHA). ø-3 §√ Û ‰fiÛË 4 g ËÌÂÚËÛ›ˆ˜, Ì ÙË ÌÔÚÊ‹ η„Ô˘ÏÒÓ È¯ı˘ÂÏ·›ˆÓ ÌÂÈÒÓÔ˘Ó Ù· ÙÚÈÁÏ˘ÎÂÚ›‰È· ηٿ 35 - 45% (54), Â›Ó·È ·ÛÊ·Ï‹ Û ·ÛıÂÓ›˜ Ì á¡ Î·È ¤¯Ô˘Ó ÂÏ¿¯ÈÛÙË ·ÏÏËÏ›‰Ú·ÛË Ì ¿ÏÏ· Ê¿Ú̷η. ª¤¯ÚÈ ÚfiÛÊ·Ù·, Ì›˙ˆÓ ÂÚÈÔÚÈÛÌfi˜ ·ÔÙÂÏÔ‡ÛÂ Ë ÌÔÚÊ‹ ÙÔ˘˜, ÂÚÈ›¯·Ó ÌfiÓÔ 200 - 300 mg ˆ-3 §√ ·Ó¿ ο„Ô˘Ï· Ì ·ÔÙ¤ÏÂÛÌ· Ó· ··ÈÙÔ‡ÓÙ·È 12 - 16 ο„Ô˘Ï˜ ËÌÂÚËÛ›ˆ˜. ™‹ÌÂÚ· ˘¿Ú¯ÂÈ ‰È·ı¤ÛÈÌË ÌÔÚÊ‹ Ô˘ ÂÚȤ¯ÂÈ 900 mg, Î·È ··ÈÙÔ‡ÓÙ·È ÌfiÓÔ 4 ο„Ô˘Ï˜ ËÌÂÚËÛ›ˆ˜ (54). ¢È·¯Â›ÚËÛË ÙˆÓ ÏÈȉ›ˆÓ Û ·ÛıÂÓ›˜ Ì ·ÈÌÔ‰È¿Ï˘ÛË (™Ù·‰›Ô 5, GFR <15 ml/min/1.73 m2) ™Â ·ÛıÂÓ›˜ ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘ á¡ ˘¿Ú¯Ô˘Ó ÂÚÈÛÛfiÙÂÚÔÈ ÂÚÈÔÚÈÛÌÔ›. ™Â ·ÛıÂÓ›˜ Ì ˘„ËÏ‹ LDL¯ÔÏËÛÙÂÚfiÏË, ÂÈϤÁÂÙ·È ÛÙ·Ù›ÓË Ì ÂÚÈÔÚÈṲ̂ÓË ÓÂÊÚÈ΋ ·¤Î-
ÎÚÈÛË, fiˆ˜ Ë atorvastatin ‹ Ë fluvastatin (¶›Ó·Î·˜ 8). μ·ÛÈÎfi ÚfiÏÔ ÛÙË ÌÈÎÙ‹ ‰˘ÛÏÈȉ·ÈÌ›· ¤¯Ô˘Ó Ù· ˆ-3 §√, ÁÈ·Ù› Û‡Ìʈӷ Ì ÙȘ Ô‰ËÁ›Â˜ Ù˘ NLA, ÔÈ ÊÈÌÚ¿Ù˜ Ú¤ÂÈ Ó· ·ÔʇÁÔÓÙ·È Û GFR <15 ml/min/1.73 m2 (39). ™Â ·ÛıÂÓ›˜ Ì Ôχ ˘„ËÏ¿ ›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ, ¯ÔÚËÁÔ‡ÓÙ·È 3-4 g ˆ-3 §√ ËÌÂÚËÛ›ˆ˜ Î·È ÂÊfiÛÔÓ Ú¤ÂÈ Ó· ‰Ôı› ÌÈ· ÊÈÌÚ¿ÙË, ÚÔÙÈÌ¿Ù·È Ë gemfimprozil Û ÌÂȈ̤ÓË ‰fiÛË 600 mg ËÌÂÚËÛ›ˆ˜. ™˘ÌÂÚ¿ÛÌ·Ù· ∏ Û˘¯ÓfiÙËÙ· Ù˘ á¡ ‰È·ÚÎÒ˜ ·˘Í¿ÓÂÈ ÛÙȘ ∏¶∞, Ì ÔÛÔÛÙfi ÏËı˘ÛÌÔ‡ ¿Óˆ ÙÔ˘ 10% Ó· ¿Û¯ÂÈ ·fi οÔÈÔ ÛÙ¿‰ÈÔ ÓÂÊÚÈ΋˜ ÓfiÛÔ˘. √È ·ÛıÂÓ›˜ Ì á¡ ¤¯Ô˘Ó Ôχ ˘„ËÏfi ΛӉ˘ÓÔ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ Û˘Ì‚¿ÓÙˆÓ Î·È ı·Ó¿ÙÔ˘. ∂Í·ÈÙ›·˜ ÙÔ˘ ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ Ô˘ ‰È·ÙÚ¤¯Ô˘Ó, ÙÔ NKF ¤¯ÂÈ Î·ıÔÚ›ÛÂÈ ÙËÓ Ã¡¡ Û·Ó ÈÛÔ‰‡Ó·ÌÔ Î·Ú‰È·ÁÁÂȷ΋˜ ÓfiÛÔ˘ Î·È ÌÂϤ-
¶›Ó·Î·˜ 7: ΔÚÔÔÔ›ËÛË ‰fiÛ˘ ˘ÔÏÈȉ·ÈÌÈÎÒÓ Ê·ÚÌ¿ÎˆÓ ÛÙËÓ Ã¡¡. (29) º¿ÚÌ·ÎÔ
GFR 60-90 ml/min/1.73 m2
GFR 15-59 ml/min/1.73 m2
GFR <15 ml/min/1.73 m2
Atorvastatin
Ÿ¯È
Ÿ¯È
Ÿ¯È
Fluvastatin
Ÿ¯È
¢ÂÓ Î·ıÔÚ›˙ÂÙ·È
¢ÂÓ Î·ıÔÚ›˙ÂÙ·È
↓ ‰fiÛ˘ ÛÙÔ ó Û GFR <30 ml/min/1.73 m2
Lovastatin
Ÿ¯È
↓ ¤ˆ˜ 50%
↓ ¤ˆ˜ 50%
↓ ‰fiÛ˘ ÛÙÔ ó Û GFR <30 ml/min/1.73 m2
Pravastatin
Ÿ¯È
Ÿ¯È
Ÿ¯È
Rosuvastatin
Ÿ¯È
5-10 mg
5-10 mg
Simvastatin
Ÿ¯È
Ÿ¯È
5 mg
™Ù·Ù›Ó˜
ŒÓ·ÚÍË Ì 10 mg/ËÌ. Û GFR <60 ml/min/1.73 m2 ŒÓ·ÚÍË Ì 5 mg/ËÌ. Û GFR <30 ml/min/1.73 m2, ̤ÁÈÛÙË ‰fiÛË 10 mg/ËÌ. ŒÓ·ÚÍË Ì 5 mg ·Ó Ë GFR <10 ml/min/1.73 m2
ÕÏÏ· Nicotinic acid
Ÿ¯È
Ÿ¯È
↓ ¤ˆ˜ 50%
Cholestyramine
Ÿ¯È
Ÿ¯È
Ÿ¯È
¢ÂÓ ·ÔÚÚÔÊ¿Ù·È ¢ÂÓ ·ÔÚÚÔÊ¿Ù·È
34% ÓÂÊÚÈ΋ ·¤ÎÎÚÈÛË
Colesevelam
Ÿ¯È
Ÿ¯È
Ÿ¯È
Ezetimibe
Ÿ¯È
Ÿ¯È
Ÿ¯È
Fenofibrate
↓ ¤ˆ˜ 50%
↓ ¤ˆ˜ 25%
∞ÔÊ˘Á‹
ªÔÚ› Ó· ↑ ÙËÓ ÎÚ·ÙÈÓ›ÓË
Gemfibrozil
Ÿ¯È
Ÿ¯È
Ÿ¯È
NLA Û˘ÛÙ‹ÓÂÈ ‰fiÛË 600 mg/ËÌ Û GFR 15-59 ml/min/1.73 m2 Î·È Ó· ·ÔʇÁÂÙ·È Û GFR <15 ml/min/1.73 m2
ø̤Á·-3 §√
Ÿ¯È
Ÿ¯È
Ÿ¯È
↓ = Ì›ˆÛË, ↑ = ·‡ÍËÛË, á¡ = ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ÓfiÛÔ˜, §√ = ÏÈ·Ú¿ Ôͤ·, GFR = Ú˘ıÌfi˜ ÛÂÈÚ·Ì·ÙÈ΋˜ ‰È‹ıËÛ˘, NLA = National Lipid Association.
9
¢∂∫∂ªμƒπ√™ 2008
¶›Ó·Î·˜ 8: ¶ÚÔÙÂÈÓfiÌÂÓÔ˜ ıÂڷ¢ÙÈÎfi˜ ·ÏÁfiÚÈıÌÔ˜ ‰È·¯Â›ÚÈÛ˘ ÙˆÓ ÏÈȉ›ˆÓ Û ·ÛıÂÓ›˜ Ì á¡ (ÛÙ¿‰ÈÔ 3-5) ¢È·Ù·Ú·¯‹ ÏÈȉ›ˆÓ
£Âڷ¢ÙÈ΋ ÂÈÏÔÁ‹ (ÛÙÔ ¶›Ó·Î· 7 Ë ÚÔÛ·ÚÌÔÁ‹ ÙˆÓ ‰fiÛˆÓ)
ª¤ÙÚÈ· ¤ˆ˜ ™Ô‚·Ú‹ á¡, ÛÙ¿‰ÈÔ 3-4 (GFR 15-59 ml/min/1.73 m2) ∞˘ÍË̤ÓË LDL-C
1) Atorvastatin, ÚÔÛı‹ÎË ezetimibe ·Ó ‰ÂÓ ÂÈÙ¢¯ı› Ô ÛÙfi¯Ô˜ Ù˘ LDL-C 2) Fluvastatin, ÚÔÛı‹ÎË ezetimibe ·Ó ‰ÂÓ ÂÈÙ¢¯ı› Ô ÛÙfi¯Ô˜ Ù˘ LDL-C
ªÈÎÙ‹ ‰˘ÛÏÈȉ·ÈÌ›·* (·Ó ‰ÂÓ ÂÈÙ¢¯ı› Ô ÛÙfi¯Ô˜ Ù˘ non-HDL†)
1) Atorvastatin ‹ fluvastatin + ezetimibe 2) Fluvastatin + gemfibrozil 600 mg/day + ezetimibe ·Ó ‰ÂÓ ÂÈÙ¢¯ı› Ô ÛÙfi¯Ô˜ Ù˘ non-HDL 3) Statin + ˆÌ¤Á·-3 ÏÈ·Ú¿ Ôͤ·, ÚÔÛı‹ÎË ezetimibe ·Ó ‰ÂÓ ÂÈÙ¢¯ı› Ô ÛÙfi¯Ô˜ Ù˘ non-HDL 4) Statin + fenofibrate 48 mg/day, ÚÔÛı‹ÎË ezetimibe ·Ó ‰ÂÓ ÂÈÙ¢¯ı› Ô ÛÙfi¯Ô˜ Ù˘ non-HDL
¶Ôχ ˘„ËÏ¿ ÙÚÈÁÏ˘ÎÂÚ›‰È· (>500 mg/dl)
1) Gemfibrozil 600 mg/ËÌ 2) ø̤Á·-3 ÏÈ·Ú¿ Ôͤ· 3-4 g/ËÌ 3) Fenofibrate 48 mg/ËÌ
á¡ ÛÙ·‰›Ô˘ 5 (·ÈÌÔοı·ÚÛË ‹ GFR <15 ml/min/1.73 m2) ∞˘ÍË̤ÓË LDL-C
Atorvastatin (10-80 mg/day) ‹ fluvastatin 40 mg/day, ÚÔÛı‹ÎË ezetimibe ·Ó ‰ÂÓ ÂÈÙ¢¯ı› Ô ÛÙfi¯Ô˜ Ù˘ LDL-C
ªÈÎÙ‹ ‰˘ÛÏÈȉ·ÈÌ›·
Atorvastatin ‹ fluvastatin 40 mg/ËÌ, ÚÔÛı‹ÎË ezetimibe 10 mg/ËÌ. ‹ ˆÌ¤Á·-3 ÏÈ·Ú¿ Ôͤ· 3-4 g/ËÌ. ·Ó ‰ÂÓ ¤¯ÂÈ ÂÈÙ¢¯ı› Ô ÛÙfi¯Ô˜ Ù˘ non-HDL
¶Ôχ ˘„ËÏ¿ ÙÚÈÁÏ˘ÎÂÚ›‰È·
ø̤Á·-3 ÏÈ·Ú¿ Ôͤ· 3-4 g/ËÌÂÚËÛ›ˆ˜ ‹ gemfibrozil 600 mg/ËÌÂÚËÛ›ˆ˜
*ªÈÎÙ‹ ‰˘ÛÏÈȉ·ÈÌ›· = elevated triglycerides and low HDL with or without elevated LDL. †Non-HDL = ÔÏÈ΋ ¯ÔÏËÛÙÂÚfiÏË - HDL-¯ÔÏËÛÙÂÚfiÏË, á¡ = ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ÓfiÛÔ˜, GFR = Ú˘ıÌfi˜ ÛÂÈÚ·Ì·ÙÈ΋˜ ‰È‹ıËÛ˘; HDL = ˘„ËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙ½ÓË, LDL-C = ¯·ÌËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙ½ÓË ¯ÔÏËÛÙÂÚfiÏË. Ù˜ ˘ÔÛÙËÚ›˙Ô˘Ó fiÙÈ Ë Ã¡¡ Û˘ÁηٷϤÁÂÙ·È ÛÙȘ ÓfiÛÔ˘˜ ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ fiˆ˜ Ô Û·Î¯·Ú҉˘ ‰È·‚‹Ù˘ (8). ∞Ó Î·È ÔÏÏÔ› ¿ÏÏÔÈ ·Ú¿ÁÔÓÙ˜ ÂÎÙfi˜ ÙˆÓ ÏÈȉ›ˆÓ Û˘Ì‚¿ÏÏÔ˘Ó ÛÙÔÓ ·˘ÍË̤ÓÔ Î·Ú‰È·ÁÁÂÈ·Îfi ΛӉ˘ÓÔ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì á¡, Ù· ÏÈ›‰È· Ê·›ÓÂÙ·È fiÙÈ ·›˙Ô˘Ó ÚˆÙ‡ÔÓÙ· ÚfiÏÔ. Δ· ·ÔÙÂϤÛÌ·Ù· ÚÒÈÌˆÓ ÂȉËÌÈÔÏÔÁÈÎÒÓ ÌÂÏÂÙÒÓ Ô˘ ¤‰ÂÈÍ·Ó fiÙÈ Ù· ˘„ËÏ¿ ›‰· ¯ÔÏËÛÙÂÚfiÏ˘ ·ÔÙÂÏ› ÏÂÔÓ¤ÎÙËÌ· Û ·ÛıÂÓ›˜ Û ·ÈÌÔοı·ÚÛË, Ì¿ÏÏÔÓ Û‡Á¯˘ÛË ÚÔοÏÂÛ·Ó. √È ÛÔ‚·Ú¤˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ ÏÈÔÚˆÙÂ˚ÓÒÓ Ô˘ ·Ú·ÙËÚÔ‡ÓÙ·È Û ·ÛıÂÓ›˜ Ì á¡, ¤¯Ô˘Ó Û·Ó ·ÔÙ¤ÏÂÛÌ· Ù·
˘„ËÏ¿ ÙÚÈÁÏ˘ÎÂÚ›‰È· Î·È ¯·ÌËÏ‹ HDL-¯ÔÏËÛÙÂÚfiÏË. √È ÛÙ·Ù›Ó˜ ·ÔÙÂÏÔ‡Ó ÙÔÓ ·ÎÚÔÁˆÓÈ·›Ô Ï›ıÔ ÛÙË ıÂڷ›· ÙˆÓ ·ÛıÂÓÒÓ Ì á¡ , ÂÎÙfi˜ ·fi ÙȘ ÂÚÈÙÒÛÂȘ ·ÛıÂÓÒÓ Ì ˘„ËÏ¿ ÙÚÈÁÏ˘ÎÂÚ›‰È· (>500 mg/dl) fiÔ˘ Ë ıÂڷ›· Â›Ó·È gemfibrozil ‹ ˆ-3 §√. §fiÁˆ Ù˘ ·˘ÍË̤Ó˘ ›وÛ˘ ÙˆÓ ˘„ËÏÒÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÛÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜, Â›Ó·È ÛËÌ·ÓÙÈÎfi Ó· ˘ÔÏÔÁ›˙ÂÙ·È Ë nonHDL Î·È Ó· ·ÔÙÂÏ› ‰Â˘ÙÂÚ‡ÔÓÙ· ÛÙfi¯Ô ıÂڷ›·˜. ∂Ӊ›ÍÂȘ ·fi ·Ó·Ï‡ÛÂȘ ˘ÔÔÌ¿‰ˆÓ ·ÚÎÂÙÒÓ ÛËÌ·ÓÙÈÎÒÓ ÌÂÏÂÙÒÓ ˘ÔÛÙËÚ›˙Ô˘Ó ÙË ıÂڷ›· Ù˘ ‰˘ÛÏÈȉ·ÈÌ›·˜ Û ‹È· Î·È Û ̤ÙÚÈ· á¡. ∏ ÔÌ¿‰· ·˘Ù‹ ·ÓÙÈ-
ÚÔۈ‡ÂÈ ¿ÏψÛÙ ÙËÓ ÏÂÈÔÓfiÙËÙ· ÙˆÓ ·ÛıÂÓÒÓ Ì á¡. ŸÛÔÓ ·ÊÔÚ¿ ÙÔ˘˜ ·ÛıÂÓ›˜ Û ·ÈÌÔοı·ÚÛË, › ÙÔ˘ ·ÚfiÓÙÔ˜, ‰ÂÓ ˘¿Ú¯Ô˘Ó ·Ô‰Â›ÍÂȘ ÁÈ· ÙÔ fiÊÂÏÔ˜ Ù˘ ıÂڷ›·˜, ‰‡Ô fï˜ ÌÂÁ¿Ï˜ ÌÂϤÙ˜ Ì ·ÛıÂÓ›˜ Û ·ÈÌԉȇÏÈÛË Â›Ó·È Û ÂͤÏÈÍË. ª¤¯ÚȘ fiÙÔ˘ ÔÏÔÎÏËÚˆıÔ‡Ó Î·È ÏfiÁˆ ÙÔ˘ fiÙÈ ÔÈ ÛÙ·Ù›Ó˜ Â›Ó·È ÁÂÓÈο ·ÛÊ·Ï›˜ Î·È ÌÂÈÒÓÔ˘Ó ÙÔÓ Î·Ú‰È·ÁÁÂÈ·Îfi ΛӉ˘ÓÔ Û ÌË ·ÈÌÔηı·ÚfiÌÂÓÔ˘˜ ·ÛıÂÓ›˜, Â›Ó·È ÏÔÁÈÎfi Ó· ÂÍ·ÎÔÏÔ˘ı‹ÛÔ˘Ó Ó· ¯ÔÚËÁÔ‡ÓÙ·È ÛÙÔ˘˜ ·ÈÌÔηı·ÚfiÌÂÓÔ˘˜. ∂È̤ÏÂÈ·: ª·Ú›· ¶·ÓÙÂÚ‹, ∂ÌÌ·ÓÔ˘‹Ï °·ÓˆÙ¿Î˘
μÈ‚ÏÈÔÁÚ·Ê›· 1.
2.
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11
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12
∫§π¡π∫∂™ ª∂§∂Δ∂™ Û˘ÁÎÂÎÚÈ̤ÓÔ˘ Ê·ÚÌ¿ÎÔ˘ ÁÈ· ÙËÓ Â›Ù¢ÍË ÙˆÓ ÛÙfi¯ˆÓ, ÛÙË ÌÂϤÙË ADVANCE fiÏÔÈ ÔÈ ·ÛıÂÓ›˜ Ô˘ ·Ó‹Î·Ó ÛÙËÓ ÔÌ¿‰· ÂÓÙ·ÙÈ΋˜ ıÂڷ›·˜ ¤Ú ӷ ¿ÚÔ˘Ó ÛÔ˘ÏÊÔÓ˘ÏÔ˘Ú›· (ÁÏÈÎÏ·˙›‰Ë) ηٿ ÙËÓ ¤ÓÙ·ÍË ÙÔ˘˜ ÛÙË ÌÂϤÙË. ™ÙË ÌÂϤÙË ADVANCE Ë ıÂڷ›· Ì ıÂÈ·˙ÔÏȉÈÓ‰ÈfiÓË ‹Ù·Ó ÂÚÈÔÚÈṲ̂ÓË (<20% ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ¤Ï·‚·Ó ̤ÚÔ˜ ÛÙË ÌÂϤÙË), ÂÓÒ ÛÙË ÌÂϤÙË ACCORD ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ Ë ÚÔÛÈÁÏÈÙ·˙fiÓË ÛÙÔ 92% ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ·Ó‹Î·Ó ÛÙËÓ ÔÌ¿‰· ÂÈıÂÙÈ΋˜ ıÂڷ›·˜ Î·È ÛÙÔ 58% ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ·Ó‹Î·Ó ÛÙËÓ ÔÌ¿‰· Ù˘ Û˘Ó‹ıÔ˘˜ ·ÁˆÁ‹˜. ™ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ Û˘ÌÌÂÙ›¯·Ó ÛÙË ÌÂϤÙË ACCORD ¤ÁÈÓ ›Û˘ Ù˘¯·ÈÔÔ›ËÛË fiÛÔÓ ·ÊÔÚ¿ ÙË ¯ÔÚ‹ÁËÛË ÂÈıÂÙÈ΋˜ ‹ Û˘Ó‹ıÔ˘˜ ıÂڷ›·˜ ÁÈ· ÙË Ì›ˆÛË Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘, ηıÒ˜ Î·È fiÛÔÓ ·ÊÔÚ¿ ÙË ¯ÔÚ‹ÁËÛË Ê·ÈÓÔÊÈÌÚ¿Ù˘ ‹ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘. ∞ÓÙ›ÛÙÔȯ·, ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ Û˘ÌÌÂÙ›¯·Ó ÛÙË ÌÂϤÙË ADVANCE ¤ÁÈÓÂ Ù˘¯·ÈÔÔ›ËÛË fiÛÔÓ ·ÊÔÚ¿ ÙË ¯ÔÚ‹ÁËÛË Û˘Ó‰˘·ÛÌÔ‡ ÂÚÈÓÙÔÚ›Ï˘ Î·È ÈÓ‰··Ì›‰Ë˜ ‹ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘.9 ΔÔ Î‡ÚÈÔ Î·Ù·ÏËÎÙÈÎfi ÛËÌÂ›Ô ÛÙË ÌÂϤÙË ADVANCE ‹Ù·Ó Ô Û˘Ó‰˘·ÛÌfi˜ Ì·ÎÚÔ·ÁÁÂÈ·ÎÒÓ Î·È ÌÈÎÚÔ·ÁÁÂÈ·ÎÒÓ Û˘Ì‚·Ì¿ÙˆÓ. ™ÙËÓ ÔÌ¿‰· Ù˘ ÂÈıÂÙÈ΋˜ ıÂڷ›·˜ ·Ú·ÙËÚ‹ıËΠ̛· ηٿ 10% Ì›ˆÛË ÙÔ˘ ·ÚÈÔ˘ ηٷÏËÎÙÈÎÔ‡ ÛËÌ›Ԣ (Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜: 0.90, 95% ‰È¿ÛÙËÌ· ÂÌÈÛÙÔÛ‡Ó˘: 0.82-0.98, p=0.01) Û ۇÁÎÚÈÛË Ì ÙËÓ ÔÌ¿‰· Ù˘ Û˘Ó‹ıÔ˘˜ ·ÁˆÁ‹˜. øÛÙfiÛÔ, ·˘Ùfi ÙÔ ·ÔÙ¤ÏÂÛÌ· ÔÊ›ÏÂÙ·È ÛÙË ÌÂÁ¿ÏË Ì›ˆÛË ÌÈ·˜ ÌÈÎÚÔ·ÁÁÂȷ΋˜ ÂÈÏÔ΋˜, Ù˘ ÓÂÊÚÔ¿ıÂÈ·˜ (Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜: 0.86, 95% ‰È¿ÛÙËÌ· ÂÌÈÛÙÔÛ‡Ó˘: 0.77-0.97, p=0.01). ŸÛÔÓ ·ÊÔÚ¿, ‰ËÏ·‰‹, Ù· ηډȷÁÁÂȷο Û˘Ì‚¿Ì·Ù· ÛÙË ÌÂϤÙË ADVANCE ‰ÂÓ ·Ú·ÙËÚ‹ıËΠÛËÌ·ÓÙÈ΋ Ì›ˆÛË (Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜: 0.94, 95% ‰È¿ÛÙËÌ· ÂÌÈÛÙÔÛ‡Ó˘: 0.841.06, p=0.32). øÛÙfiÛÔ, Ë ÌÂϤÙË ADVANCE ¤‰ÂÈÍ ÙÔÓ È‰È·›ÙÂÚÔ ÚfiÏÔ Ô˘ ‰È·‰Ú·Ì·Ù›˙ÂÈ Ô Î·Ïfi˜ ÁÏ˘Î·ÈÌÈÎfi˜ ¤ÏÂÁ¯Ô˜ fiÛÔÓ ·ÊÔÚ¿ ÙË Ì›ˆÛË ÙˆÓ ÌÈÎÚÔ·ÁÁÂÈ·ÎÒÓ ÂÈÏÔÎÒÓ Û ·ÛıÂÓ›˜ Ì ™¢2. ∞ÓÙ›ıÂÙ·, ÛÙË ÌÂϤÙË ACCORD,
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£¿Ó·ÙÔÈ Î·Ú‰È·ÁÁÂȷ΋˜ ·ÈÙÈÔÏÔÁ›·˜
135 (2.6)
94 (1.8)
1.35 (1.04-1.76)
0.02
ªË ı·Ó·ÙËÊfiÚ· ÂÌÊÚ¿ÁÌ·Ù· ÙÔ˘ Ì˘Ôηډ›Ô˘
186 (3.6)
235 (4.6)
0.76 (0.62-0.92)
0.004
67 (1.3)
61 (1.2)
1.06 (0.75-1.50)
0.74
152 (3.0)
124 (2.4)
1.18 (0.93-1.49)
0.17
ªË ı·Ó·ÙËÊfiÚ· ·ÁÁÂȷο ÂÁÎÂÊ·ÏÈο ÂÂÈÛfi‰È· £·Ó·ÙËÊfiÚ· ‹ ÌË ı·Ó·ÙËÊfiÚ· ÂÂÈÛfi‰È· Û˘ÌÊÔÚËÙÈ΋˜ ηډȷ΋˜ ·Ó¿ÚÎÂÈ·˜
ΔÚÔÔÔ›ËÛË ·fi N ∂ngl J Med 2008;358:2545-59
·Ú·ÙËÚ‹ıËΠ·‡ÍËÛË Ù˘ ÔÏÈ΋˜ ıÓËÙfiÙËÙ·˜ ÛÙËÓ ÔÌ¿‰· Ù˘ ÂÈıÂÙÈ΋˜ ıÂڷ›·˜. §fiÁˆ Ù˘ ·˘ÍË̤Ó˘ ıÓËÙfiÙËÙ·˜ Ë ÌÂϤÙË ‰È·ÎfiËΠ17 Ì‹Ó˜ ÚÈÓ ÙËÓ ÔÏÔÎÏ‹ÚˆÛ‹ Ù˘ Î·È ÔÈ ·ÛıÂÓ›˜ Û˘Ó¤¯ÈÛ·Ó Ì ÙË Û˘Ó‹ıË ·ÁˆÁ‹. À¿Ú¯ÂÈ fï˜ Ì›· ·ÓٛʷÛË fiÛÔÓ ·ÊÔÚ¿ Ù· ‰Â˘ÙÂÚ‡ÔÓÙ· ηٷÏËÎÙÈο ÛËÌ›·. °È· ·Ú¿‰ÂÈÁÌ·, Ë Â›ÙˆÛË ı·Ó¿ÙˆÓ ·fi ÔÔÈÔ‰‹ÔÙ ·›ÙÈÔ, ηıÒ˜ Î·È ÙˆÓ ı·Ó¿ÙˆÓ ηډȷÁÁÂȷ΋˜ ·ÈÙÈÔÏÔÁ›·˜ ‹Ù·Ó ÛËÌ·ÓÙÈο ˘„ËÏfiÙÂÚË ÛÙËÓ ÔÌ¿‰· Ù˘ ÂÈıÂÙÈ΋˜ ıÂڷ›·˜ Û ۇÁÎÚÈÛË Ì ÙËÓ ·ÓÙ›ÛÙÔÈ¯Ë Ù˘ ÔÌ¿‰·˜ Û˘Ó‹ıÔ˘˜ ·ÁˆÁ‹˜ (p=0.04 Î·È p=0.02 ·ÓÙ›ÛÙÔȯ·), ÂÓÒ Ë Â›ÙˆÛË ÙˆÓ ÌË ı·Ó·ÙËÊfiÚˆÓ ÂÌÊÚ·ÁÌ¿ÙˆÓ ÙÔ˘ Ì˘Ôηډ›Ô˘ ‹Ù·Ó ÛËÌ·ÓÙÈο ÌÈÎÚfiÙÂÚË (p=0.004) ÛÙËÓ ÔÌ¿‰· ÂÈıÂÙÈ΋˜ ıÂڷ›·˜ Û ۇÁÎÚÈÛË Ì ÙËÓ ·ÓÙ›ÛÙÔÈ¯Ë Ù˘ ÔÌ¿‰·˜ Û˘Ó‹ıÔ˘˜ ·ÁˆÁ‹˜ (¶›Ó·Î·˜ 2). ¢È·Ù˘ÒıËÎÂ Ë ¿Ô„Ë fiÙÈ Ë ˘ÔÁÏ˘Î·ÈÌ›· Â›Ó·È Èı·Ó¿ Ë Î‡ÚÈ· ·ÈÙ›· Ù˘ ·˘ÍË̤Ó˘ ıÓËÙfiÙËÙ·˜ Ô˘ ·Ú·ÙËÚ‹ıËΠÛÙË ÌÂϤÙË ACCORD, ηıÒ˜ Ô Û˘Ó‰˘·ÛÌfi˜ ÛÔ˘ÏÊÔÓ˘ÏÔ˘Ú›·˜ Ì ÈÓÛÔ˘Ï›ÓË, Ô ÔÔ›Ô˜ ·ÔÙÂÏÔ‡-
Û ÙÔ ‚·ÛÈÎfi ıÂڷ¢ÙÈÎfi Û¯‹Ì· Ù˘ ÂÈıÂÙÈ΋˜ ıÂڷ›·˜, Û˘Û¯ÂÙ›˙ÂÙ·È Ì ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ˘ÔÁÏ˘Î·ÈÌ›·˜. ÕÏϘ ÌÂϤÙ˜ ÛÙÔ Ì¤ÏÏÔÓ ı· ‰Â›ÍÔ˘Ó Â¿Ó Ú¿ÁÌ·ÙÈ Ë ˘ÔÁÏ˘Î·ÈÌ›· ·ÔÙÂÏ› ¤Ó· ·fi ÙÔ˘˜ ·ÚÈÔ˘˜ ·Ú¿ÁÔÓÙ˜ ·˘ÍË̤Ó˘ ıÓËÙfiÙËÙ·˜ Û ÂÚÈÙÒÛÂȘ ÂÈıÂÙÈ΋˜ ÁÏ˘Î·ÈÌÈ΋˜ ·ÁˆÁ‹˜ . ™ÙË ÌÂϤÙË ADVANCE Ô ÛÙfi¯Ô˜ fiÛÔÓ ·ÊÔÚ¿ ÙË ÁÏ˘ÎÔ˙˘ÏȈ̤ÓË ·ÈÌÔÛÊ·ÈÚ›ÓË ÛÙËÓ ÔÌ¿‰· Ù˘ ÂÈıÂÙÈ΋˜ ıÂڷ›·˜ ‹Ù·Ó <6.5%, ÂÓÒ ÛÙË ÌÂϤÙË ACCORD Ô ›‰ÈÔ˜ ÛÙfi¯Ô˜ ‹Ù·Ó <6.0%. ΔÔ ÔÛÔÛÙfi Ì›ˆÛ˘ Ù˘ ÁÏ˘ÎÔ˙˘ÏȈ̤Ó˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ ›Û˘ ‰È¤ÊÂÚ ÛËÌ·ÓÙÈο ÛÙȘ ‰‡Ô ÌÂϤÙ˜. ™ÙË ÌÂϤÙË ACCORD ÔÈ ·ÛıÂÓ›˜ Ô˘ ·Ó‹Î·Ó ÛÙËÓ ÔÌ¿‰· Ù˘ ÂÈıÂÙÈ΋˜ ıÂڷ›·˜ ÂÌÊ¿ÓÈÛ·Ó Ì›ˆÛË Ù˘ ÁÏ˘ÎÔ˙˘ÏȈ̤Ó˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ ηٿ 1.4 % Û 4 Ì‹Ó˜, ÂÓÒ ÛÙË ÌÂϤÙË ADVANCE Ë ·ÓÙ›ÛÙÔÈ¯Ë Ì›ˆÛË ‹Ù·Ó ÌfiÏȘ 0.5 % ÙÔ˘˜ ÚÒÙÔ˘˜ 6 Ì‹Ó˜ Î·È 0.6% ÛÙÔ˘˜ 12 Ì‹Ó˜ ·ÁˆÁ‹˜. ∞Í›˙ÂÈ Ó· ÛËÌÂȈı› fiÙÈ ÔÈ ·ÛıÂÓ›˜ Ù˘ ÔÌ¿‰·˜ Ù˘ ÂÈıÂÙÈ΋˜ ıÂڷ›·˜ ÛÙË ÌÂϤÙË ADVANCE ¤Ù˘¯·Ó ÙÔ˘˜ ıÂÚ·-
13
¢∂∫∂ªμƒπ√™ 2008
¢ÙÈÎÔ‡˜ ÛÙfi¯Ô˘˜ fiÛÔÓ ·ÊÔÚ¿ ÙË Ì›ˆÛË Ù˘ ÁÏ˘ÎÔ˙˘ÏȈ̤Ó˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ Û ۇÁÎÚÈÛË Ì ÙÔ˘˜ ·ÛıÂÓ›˜ Ù˘ ÔÌ¿‰·˜ Û˘Ó‹ıÔ˘˜ ·ÁˆÁ‹˜, ÂÓÒ ÛÙË ÌÂϤÙË ACCORD ÌfiÓÔ ¤Ó·˜ ÌÈÎÚfi˜ ·ÚÈıÌfi˜ ·ÛıÂÓÒÓ Ù˘ ÔÌ¿‰·˜ Ù˘ ÂÈıÂÙÈ΋˜ ıÂڷ›·˜ ¤Ù˘¯Â ÙÔ˘˜ ›‰ÈÔ˘˜ ÛÙfi¯Ô˘˜. ŒÓ· ÂÚÒÙËÌ· Ô˘ ÚÔ·ÙÂÈ ·fi ÙËÓ ·Ó¿Ï˘ÛË ·˘ÙÒÓ ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ Â›Ó·È Â¿Ó Ô ‚·ıÌfi˜ Ì›ˆÛ˘ Ù˘ ÁÏ˘ÎÔ˙˘ÏȈ̤Ó˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ ÌÔÚ› Ó· ÂÍËÁ‹ÛÂÈ ÙȘ ‰È·ÊÔÚ¤˜ ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ ÛÙȘ ‰‡Ô ÌÂϤÙ˜ fiÛÔÓ ·ÊÔÚ¿ Ù· ηډȷÁÁÂȷο ηٷÏËÎÙÈο ÛËÌ›·. Δ¤ÏÔ˜, ·Í›˙ÂÈ Ó· ·Ó·ÊÂÚıÔ‡Ó ÔÈ ÌÂÙ·‚ÔϤ˜ ÙÔ˘ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜ ÛÙȘ ‰‡Ô ÌÂϤÙ˜. ™ÙË ÌÂϤÙË ACCORD, Ë Ì¤ÛË ·‡ÍËÛË ÙÔ˘ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜ (kg) ÛÙËÓ ÔÌ¿‰· Ù˘ ÂÈıÂÙÈ΋˜ ıÂڷ›·˜ Î·È ÛÙËÓ ÔÌ¿‰· Û˘Ó‹ıÔ˘˜ ·ÁˆÁ‹˜ ‹Ù·Ó 3.5 kg Î·È 0.4 kg ·ÓÙ›-
ÛÙÔȯ·. ∞Í›˙ÂÈ Ó· ÛËÌÂȈı› fiÙÈ ÙÔ 27.8% ÙˆÓ ·ÛıÂÓÒÓ Ù˘ ÔÌ¿‰·˜ Ù˘ ÂÈıÂÙÈ΋˜ ıÂڷ›·˜ ÂÌÊ¿ÓÈÛ ·‡ÍËÛË ‚¿ÚÔ˘˜ ¿Óˆ ·fi 10 kg, ÂÓÒ ÙËÓ ›‰È· ·‡ÍËÛË ÛˆÌ·ÙÈÎÔ‡ ‚¿ÚÔ˘˜ ÂÌÊ¿ÓÈÛ ÌfiÓÔ ÙÔ 14.1 % ÙˆÓ ·ÛıÂÓÒÓ Ù˘ ÔÌ¿‰·˜ Û˘Ó‹ıÔ˘˜ ·ÁˆÁ‹˜ (p<0.001). ¶Èı·Ó¿, Ë Ì¤ÛË ·‡ÍËÛË ÙÔ˘ ‚¿ÚÔ˘˜ ηٿ 3.5 kg ÛÙËÓ ÔÌ¿‰· Ù˘ ÂÈıÂÙÈ΋˜ ıÂڷ›·˜ ÔÊ›ÏÂÙ·È ÛÙË ¯ÔÚ‹ÁËÛË ÁÏÈÙ·˙fiÓ˘ Î·È ÈÓÛÔ˘Ï›Ó˘. ™ÙË ÌÂϤÙË ADVANCE, ·Ú·ÙËÚ‹ıËΠ̛· ‰È·ÊÔÚ¿ ÌfiÓÔ Î·Ù¿ 0.7 kg ÛÙÔ ÛˆÌ·ÙÈÎfi ‚¿ÚÔ˜ ÛÙËÓ ÔÌ¿‰· Ù˘ ÂÈıÂÙÈ΋˜ ıÂڷ›·˜ Û ۇÁÎÚÈÛË Ì ÙËÓ ÔÌ¿‰· Û˘Ó‹ıÔ˘˜ ·ÁˆÁ‹˜ (p<0.001). ŸÌˆ˜ Ë ÌÂÙ·‚ÔÏ‹ ÙÔ˘ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜ ‹Ù·Ó ·ÌÂÏËÙ¤· Î·È ÛÙȘ ‰‡Ô ÔÌ¿‰Â˜. ∫·È ÔÈ ‰‡Ô ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ Ë Ì›ˆÛË Ù˘ ÁÏ˘ÎÔ˙˘ÏȈ̤Ó˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ οو ·fi 7% Û ·ÛıÂÓ›˜ ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ ÌÂ
™¢2 ‰ÂÓ ÌÂÈÒÓÂÈ Ù· ηډȷÁÁÂȷο Û˘Ì‚¿Ì·Ù·. ∂›Û˘, ·˘Ù¤˜ ÔÈ ‰‡Ô ÌÂϤÙ˜ ‰ÂÓ Î·Ù¤ÏËÍ·Ó Û ıÂڷ¢ÙÈÎÔ‡˜ ÛÙfi¯Ô˘˜ fiÛÔÓ ·ÊÔÚ¿ ÙÔ ÁÏ˘Î·ÈÌÈÎfi ¤ÏÂÁ¯Ô Û ·ÛıÂÓ›˜ ¯·ÌËÏÔ‡ ÎÈÓ‰‡ÓÔ˘. Δ¤ÏÔ˜, Ô ÎÏÈÓÈÎfi˜ ÁÈ·ÙÚfi˜ Ô˘ ·ÓÙÈÌÂÙˆ›˙ÂÈ ·ÛıÂÓ›˜ Ì ™¢2 Ú¤ÂÈ Ó· ÂÈÎÂÓÙÚÒÓÂÙ·È ÛÙË ‰È·ÎÔ‹ ÙÔ˘ ηӛÛÌ·ÙÔ˜, ÛÙȘ ‰È·ÈÙËÙÈΤ˜ Ô‰ËÁ›Â˜, ÛÙÔÓ ¤ÏÂÁ¯Ô Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘ Î·È ÛÙË ¯ÔÚ‹ÁËÛË ·ÛÈÚ›Ó˘ Î·È ÛÙ·Ù›Ó˘. Δ· ÔʤÏË Û ¤Ó· ·ÛıÂÓ‹ Ì ™¢2 Ô ÔÔ›Ô˜ ·›ÚÓÂÈ ·ÛÈÚ›ÓË, Ì›· ÛÙ·Ù›ÓË Î·È ¤¯ÂÈ Î·Ï¿ Ú˘ıÌÈṲ̂ÓË ·ÚÙËÚȷ΋ ˘¤ÚÙ·ÛË Â›Ó·È Ôχ ÌÂÁ·Ï‡ÙÂÚ· fiÛÔÓ ·ÊÔÚ¿ ÙË Ì›ˆÛË ÙˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ Û˘Ì‚·Ì¿ÙˆÓ, ·ÊÔ‡ fiϘ ·˘Ù¤˜ ÔÈ ıÂڷ¢ÙÈΤ˜ ÚÔÛÂÁÁ›ÛÂȘ ͯˆÚÈÛÙ¿ ÌÂÈÒÓÔ˘Ó ÙÔÓ Î·Ú‰È·ÁÁÂÈ·Îfi ΛӉ˘ÓÔ.10 11
in type 2 diabetes. N Engl J Med 2008;358:2545-59. 5. Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008;358:2560-72. 6. Standards of medical care in diabetes-2008. Diabetes Care 2008;31 Suppl 1:S12-54. 7. Ryden L, Standl E, Bartnik M, Van den Berghe G, Betteridge J, de Boer MJ, et al. Guidelines on diabetes, prediabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J 2007;28:88-136.
8. Dluhy RG, McMahon GT. Intensive glycemic control in the ACCORD and ADVANCE trials. N Engl J Med 2008;358:2630-3. 9. Patel A, MacMahon S, Chalmers J, Neal B, Woodward M, Billot L, et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet 2007;370:82940. 10. Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med 2008;358:580-91. 11. Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003;348:383-93.
μÈ‚ÏÈÔÁÚ·Ê›· 1. Selvin E, Marinopoulos S, Berkenblit G, Rami T, Brancati FL, Powe NR, et al. Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med 2004;141:421-31. 2. Gerstein HC, Pogue J, Mann JF, Lonn E, Dagenais GR, McQueen M, et al. The relationship between dysglycaemia and cardiovascular and renal risk in diabetic and non-diabetic participants in the HOPE study: a prospective epidemiological analysis. Diabetologia 2005;48:1749-55. 3. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. Bmj 2000;321:405-12. 4. Gerstein HC, Miller ME, Byington RP, Goff DC, Jr., Bigger JT, Buse JB, et al. Effects of intensive glucose lowering
35Ô ¶·ÓÂÏÏ‹ÓÈÔ π·ÙÚÈÎfi ™˘Ó¤‰ÚÈÔ ∏ π·ÙÚÈ΋ ∂Ù·ÈÚ›· ∞ıËÓÒÓ ÔÚÁ·ÓÒÓÂÈ ÙÔ 35Ô ∂Ù‹ÛÈÔ ¶·ÓÂÏÏ‹ÓÈÔ π·ÙÚÈÎfi ™˘Ó¤‰ÚÈÔ ÛÙÔ •ÂÓÔ‰Ô¯Â›Ô Hilton, 5-9 ª·˝Ô˘ 2009. ΔÔ ™˘Ó¤‰ÚÈÔ ÂÚÈÏ·Ì‚¿ÓÂÈ ¢È·Ï¤ÍÂȘ, ¢ÈÂÙ·ÈÚÈΤ˜ ™˘˙ËÙ‹ÛÂȘ, ™ÙÚÔÁÁ˘Ï¿ ΔÚ·¤˙È·, ™˘ÌfiÛÈ·, ∫ÏÈÓÈο ºÚÔÓÙÈÛÙ‹ÚÈ·, ™ÂÌÈÓ¿ÚÈ· Î·È ∂χıÂÚ˜ ∞Ó·ÎÔÈÓÒÛÂȘ. ∏ÌÂÚÔÌËÓ›· ÀÔ‚ÔÏ‹˜ ¶ÂÚÈÏ‹„ˆÓ: 16 π·ÓÔ˘·Ú›Ô˘ 2009.
14
∫§π¡π∫∂™ ª∂§∂Δ∂™
ªÂϤÙË GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza ¡ell'Insufficienza Cardiaca) GISSI-HF Investigators Lancet 2008;372:1223-1239 ¶ÚfiÎÂÈÙ·È ÁÈ· ÌÈ· ÔÏ˘ÎÂÓÙÚÈ΋, Ù˘¯·ÈÔÔÈË̤ÓË, ‰ÈÏ¿ Ù˘ÊÏ‹, ÂÏÂÁ¯fiÌÂÓË Ì ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ ÎÏÈÓÈ΋ ÌÂϤÙË Ô˘ ‰ÈÂÍ‹¯ıË ÛÙËÓ πÙ·Ï›· Î·È ÂÚȤϷ‚ ·ÛıÂÓ›˜ Ì ηډȷ΋ ·Ó¿ÚÎÂÈ· ÏÂÈÙÔ˘ÚÁÈÎÔ‡ ÛÙ·‰›Ô˘ ηٿ ¡À∏∞ II ¤ˆ˜ IV. ™ÎÔfi˜ Ù˘ ÌÂϤÙ˘ ‹Ù·Ó Ó· ÂÚ¢ӋÛÂÈ Â¿Ó Ë ÚÔÛı‹ÎË ÛÙ·Ù›Ó˘ ‹ ˆ-3 ÏÈ·ÚÒÓ ÔͤˆÓ ÛÙËÓ Î·ıÈÂڈ̤ÓË Ê·Ú̷΢ÙÈ΋ ·ÁˆÁ‹ Ù˘ ηډȷ΋˜ ·Ó¿ÚÎÂÈ·˜ ÌÔÚ› Ó· ‚ÂÏÙÈÒÛÂÈ ·ÎfiÌË ÂÚÈÛÛfiÙÂÚÔ ÙËÓ ÚfiÁÓˆÛË ÙˆÓ ·ÛıÂÓÒÓ Î·È Ó· ÌÂÈÒÛÂÈ ÙË ıÓËÛÈÌfiÙËÙ· ‹/Î·È ÙË ÓÔÛËÚfiÙËÙ·. ™ÙË ÌÂϤÙË ÂÓÙ¿¯ıËÎ·Ó 7.046 ·ÛıÂÓ›˜ Î·È ÙˆÓ ‰‡Ô ʇψÓ, ËÏÈΛ·˜ 18 ÂÙÒÓ Î·È ¿Óˆ Ì ÎÏÈÓÈΤ˜ ÂӉ›ÍÂȘ ‹ ÈÛÙÔÚÈÎfi ηډȷ΋˜ ·Ó¿ÚÎÂÈ·˜ ÔÈ·Û‰‹ÔÙ ·ÈÙÈÔÏÔÁ›·˜ Î·È Â˘Ú›ÛÎÔÓÙ·Ó ˘fi Ï‹ÚË Ê·Ú̷΢ÙÈ΋ ·ÁˆÁ‹, Û‡Ìʈӷ Ì Ù˘ Ô‰ËÁ›Â˜ Ù˘ ESC. ªÂÙ¿ ÙÔÓ ·ÔÎÏÂÈÛÌfi ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ‹Ù·Ó ‹‰Ë ˘fi ıÂڷ›· Ì ÛÙ·Ù›ÓË, fiÛˆÓ Â›¯·Ó ·ÓÙ¤Ó‰ÂÈÍË Ó· Ï¿‚Ô˘Ó ÛÙ·Ù›ÓË Î·È fiÛˆÓ ‰ÂÓ ˘¤ÁÚ·„·Ó ÙËÓ ÂÓËÌÂڈ̤ÓË Û˘ÁηٿıÂÛË, ÔÈ ˘fiÏÔÈÔÈ Î·Ù·ÓÂÌ‹ıËÎ·Ó Ù˘¯·›· Û ‰‡Ô ÔÌ¿‰Â˜ Î·È ÔÈ ÌÈÛÔ› (n=2.285) ¤Ï·‚·Ó ÚÔÛÔ˘‚·ÛÙ·Ù›ÓË 10 mg ÙËÓ Ë̤ڷ Î·È ÔÈ ¿ÏÏÔÈ (n=2.289) ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ. ªÂ ‰Â‡ÙÂÚË Ù˘¯·›· ηٷÓÔÌ‹ ÙÔ˘ Û˘ÓfiÏÔ˘ ÙˆÓ ·ÛıÂÓÒÓ, ·ÊÔ‡ ·ÔÎÏ›ÛıËÎ·Ó fiÛÔÈ ·ÚÓ‹ıËÎ·Ó Ó· Û˘ÌÌÂÙ¿Û¯Ô˘Ó, ÔÈ ÌÈÛÔ› (n=3.494) ¤Ï·‚·Ó 1 g ˆ-3 ÔÏ˘·ÎfiÚÂÛÙ· ÏÈ·Ú¿ Ôͤ· Ì·ÎÚ¿˜ ·Ï‡ÛÔ˘ (ÂÈÎÔÛÈÂÓÙ·ÓÔ˚Îfi Î·È ÂÈÎÔÛȉ˘ÔÂÍ·ÓÔ˚Îfi Û ·Ó·ÏÔÁ›· 1:1,2) Î·È ÔÈ ¿ÏÏÔ ÌÈÛÔ› (n=3.481) fiÌÔÈ·˜ ÂÌÊ¿ÓÈÛ˘ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ. ¶ÚˆÙ‡ÔÓÙ· ηٷÏËÎÙÈο ÛËÌ›· ÔÚ›ÛıËÎ·Ó ‰‡Ô: Ô ·ÚÈıÌfi˜ ÙˆÓ ı·Ó¿ÙˆÓ ÔÔÈ·Û‰‹ÔÙ ·ÈÙÈÔÏÔÁ›·˜ Î·È ÙÔ ¿ıÚÔÈÛÌ· ÙˆÓ ı·Ó¿ÙˆÓ ÔÔÈ·Û‰‹ÔÙ ·ÈÙÈÔÏÔÁ›·˜ Î·È ÙˆÓ ÂÈÛ·ÁˆÁÒÓ Û ÓÔÛÔÎÔÌ›· ÏfiÁˆ ηډȷÁÁÂȷ΋˜ ¿ıËÛ˘. ¢Â˘ÙÂÚ‡ÔÓÙ· ηٷÏËÎÙÈο ÛËÌ›· ηıÔÚ›ÛıËÎ·Ó ÔÏÏ¿ Î·È ÂÚÈÏ¿Ì‚·Ó·Ó ÙËÓ Î·Ú‰È·ÁÁÂȷ΋ ıÓËÛÈÌfiÙËÙ·, ÙÔ ¿ıÚÔÈÛÌ· ηډȷÁÁÂÈ·ÎÒÓ ı·Ó¿ÙˆÓ Î·È ÂÈÛ·Áˆ-
ÁÒÓ ÛÙÔ ÓÔÛÔÎÔÌÂ›Ô ÁÈ· ÔÔÈ·‰‹ÔÙ ·ÈÙ›·, ÙÔÓ ·ÈÊÓ›‰ÈÔ Î·Ú‰È·Îfi ı¿Ó·ÙÔ, ÙÔ Ô͇ ¤ÌÊÚ·ÁÌ· ÙÔ˘ Ì˘Ôηډ›Ô˘, ÙÔ ·ÁÁÂÈ·Îfi ÂÁÎÂÊ·ÏÈÎfi, ÙË ÓÔÛËÏ›· ÁÈ· ηډȷ΋ ·Ó¿ÚÎÂÈ·, ÙË ÓÔÛËÏ›· ÁÈ· ηډȷÁÁÂÈ·Îfi ÓfiÛËÌ· Î·È ÙË ÓÔÛËÏ›· ÁÈ· ÔÔÈ·‰‹ÔÙ ·ÈÙ›·. ∏ ·Ú·ÎÔÏÔ‡ıËÛË ‹Ù·Ó ·fi 3 ̤¯ÚÈ 4,5 ¤ÙË (‰È¿ÌÂÛË ÙÈÌ‹ 3,9 ¤ÙË). ™ÙËÓ ÔÌ¿‰· Ù˘ ÚÔÛÔ˘‚·ÛÙ·Ù›Ó˘ Ë LDL-¯ÔÏËÛÙÂÚfiÏË ‹Ù·Ó ηٿ 32% ¯·ÌËÏfiÙÂÚË ÙÔÓ ÚÒÙÔ
¯ÚfiÓÔ Î·È Î·Ù¿ 27% ÙÔÓ ÙÚ›ÙÔ ¯ÚfiÓÔ. ™Â ÌÈ· ÔÌ¿‰· 626 ·ÛıÂÓÒÓ ÛÙÔ˘˜ ÔÔ›Ô˘˜ ÌÂÙÚ‹ıËÎÂ Ë hsCRP ‚Ú¤ıËΠηٿ 0,45 mg/L ¯·ÌËÏfiÙÂÚË ÛÙËÓ ÔÌ¿‰· Ù˘ ÚÔÛÔ˘‚·ÛÙ·Ù›ÓË Û˘ÁÎÚÈÙÈο Ì ·˘ÙÔ‡˜ Ô˘ ‹Ú·Ó ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ. ™ÙËÓ ¤Î‚·ÛË ÙˆÓ ·ÛıÂÓÒÓ fï˜ Ë ÚÔÛÔ˘‚·ÛÙ·Ù›ÓË ‰ÂÓ Â›¯Â η̛· ›‰Ú·ÛË. ¢Â ‰È·ÈÛÙÒıËΠ‰È·ÊÔÚ¿ ÌÂٷ͇ ÙˆÓ ‰‡Ô ÔÌ¿‰ˆÓ Û ηӤӷ ·fi Ù· ÚˆÙ‡ÔÓÙ· ‹ ‰Â˘ÙÂÚ‡ÔÓÙ· ηٷÏËÎÙÈο ÛËÌ›·
∂ÈÎfiÓ· 1. ∫·Ì‡Ï˜ Kaplan-Meier ÁÈ· ÙÔÓ ¯ÚfiÓÔ Ì¤¯ÚÈ ÙÔÓ ı¿Ó·ÙÔ ·fi ÔÔÈ·‰‹ÔÙ ·ÈÙ›· (∞) Î·È ÁÈ· ÙÔÓ ¯ÚfiÓÔ Ì¤¯ÚÈ ÙÔÓ ı¿Ó·ÙÔ ·fi ÔÔÈ·‰‹ÔÙ ·ÈÙ›· Û˘Ó ÂÈÛ·ÁˆÁ¤˜ ÛÙÔ ÓÔÛÔÎÔÌÂ›Ô ÁÈ· ηډȷÁÁÂȷο ÓÔÛ‹Ì·Ù· (μ) Û ·ÛıÂÓ›˜ Ô˘ ¤Ï·‚·Ó ÚÔÛÔ˘‚·ÛÙ·Ù›ÓË ‹ placebo.
15
¢∂∫∂ªμƒπ√™ 2008
(∂ÈÎfiÓ· 1). ∏ ÌÂϤÙË CORONA, Ë ÔÔ›· ›¯Â ·ÚfiÌÔÈÔ Û¯Â‰È·ÛÌfi Î·È ‰ËÌÔÛȇıËΠÌÂÚÈÎÔ‡˜ Ì‹Ó˜ ÚÈÓ, ‰ÂÓ ¤‰ÂÈÍ ›Û˘ ηӤӷ fiÊÂÏÔ˜ ·fi ÙËÓ ÚÔÛÔ˘‚·ÛÙ·Ù›ÓË ÛÙÔ˘˜ ηډȷÁÁÂÈ·ÎÔ‡˜ ı·Ó¿ÙÔ˘˜, ›¯Â fï˜ ‰Â›ÍÂÈ Î¿ÔÈ· Ì›ˆÛË ÛÙȘ ÂÈÛ·ÁˆÁ¤˜ ÛÙÔ ÓÔÛÔÛÎÔÌ›Ô. ¶ÚÈÓ ÙËÓ ‰ËÌÔÛ›Â˘ÛË ÙˆÓ ÌÂÏÂÙÒÓ ·˘ÙÒÓ ˘‹Ú¯·Ó ·ÚÎÂÙ¤˜ ÂӉ›ÍÂȘ ·fi ÂÈÚ·Ì·ÙÈΤ˜ ÌÂϤÙ˜, ÌÂϤÙ˜ ·Ú·Ù‹ÚËÛ˘, ‰Â˘ÙÂÚ‡ԢÛ˜ (post hoc) ·Ó·Ï‡ÛÂȘ ÎÏÈÓÈÎÒÓ ÌÂÏÂÙÒÓ Î·Ú‰È·Î‹˜ ·Ó¿ÚÎÂÈ·˜ Î·È ÌÈÎÚ¤˜ ÚÔÔÙÈΤ˜ Ù˘¯·ÈÔÔÈË̤Ó˜ ÌÂϤÙ˜ fiÙÈ ÔÈ ÛÙ·Ù›Ó˜ Â›Ó·È ‰˘Ó·ÙfiÓ Ó· ˆÊÂÏÔ‡Ó ÛÙËÓ Î·Ú‰È·Î‹ ·Ó¿ÚÎÂÈ·. √È ÂӉ›ÍÂȘ ·˘Ù¤˜ ÂÓÈÛ¯‡ÔÓÙ·Ó ·fi ÙËÓ ıˆÚËÙÈ΋ ¿Ô„Ë Ô˘ ˘ÔÛÙ‹ÚÈ˙ fiÙÈ ÔÈ ÏÂÈÔÙÚÔÈΤ˜ ‰Ú¿ÛÂȘ ÙˆÓ ÛÙ·ÙÈÓÒÓ (·ÓÙÈÊÏÂÁÌÔÓ҉˘ ‰Ú¿ÛË, ‚ÂÏÙ›ˆÛË Ù˘ ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ·˜ ÙÔ˘ ÂÓ‰ÔıËÏ›Ô˘, ·Ó·ÛÙÔÏ‹ Ù˘ Ó¢ÚÔÔÚÌÔÓÈ΋˜ ‰Ú·ÛÙËÚÈÔÔ›ËÛ˘, ·ÓÙÈÔÍÂȉˆÙÈ΋ Î·È ·ÓÙÈ·ıËÚÔÛÎÏËÚˆÙÈ΋ ‰Ú¿ÛË), ÂÓ‰¤¯ÂÙ·È Ó· ‚ÂÏÙÈÒÓÔ˘Ó ÙËÓ ¤Î‚·ÛË ·ÛıÂÓÒÓ Ì ηډȷ΋ ·Ó¿ÚÎÂÈ·. Δ· Â˘Ú‹Ì·Ù· Û˘ÓÂÒ˜ ‰ÂÓ Â›Ó·È Ù· ·Ó·ÌÂÓfiÌÂÓ· Î·È ‰ÂÓ ÌÔÚÔ‡Ó Â‡ÎÔÏ· Ó· ÂÍËÁËıÔ‡Ó. √È ÛÙ·Ù›Ó˜ Û·ÊÒ˜ ˆÊÂÏÔ‡Ó ÛÙËÓ ÚfiÏË„Ë Ù˘ ηډȷÁÁÂȷ΋˜ ·Ó¿ÚÎÂÈ·˜, ÌÂÈÒÓÔÓÙ·˜ Ù· ÂÌÊÚ¿ÁÌ·Ù·, Ê·›ÓÂÙ·È fï˜ fiÙÈ fiÙ·Ó Ë Î·Ú‰È·Î‹ ·Ó¿ÚÎÂÈ· ÂÁηٷÛÙ·ı› ‰ÂÓ Â›Ó·È ÈηӤ˜ Ó· ·Ó·Îfi„Ô˘Ó ÙËÓ ÔÚ›· Ù˘ ÓfiÛÔ˘. √È ÏÂÁfiÌÂÓ˜ ÏÂÈÔÙÚÔÈΤ˜ ‰Ú¿ÛÂȘ ¤¯Ô˘Ó ·Ô‰Âȯı› Û ˘ÔηٿÛٷٷ (surrogate) ÙÂÏÈο ÛËÌ›·, fi¯È fï˜ Û ÎÏÈÓÈο Û˘Ì‚¿Ì·Ù·. ∞fi ÙËÓ ¿ÏÏË ÏÂ˘Ú¿ ÛÙȘ ÂȉËÌÈÔÏÔÁÈΤ˜ ÌÂϤÙ˜ ¤¯ÂÈ Ê·Ó› fiÙÈ ÔÈ ·ÛıÂÓ›˜ Ì ٷ ¯·ÌËÏfiÙÂÚ· ›‰· ¯ÔÏËÛÙÂÚfiÏ˘ ¤¯Ô˘Ó ÙË ¯ÂÈÚfiÙÂÚË ÚfiÁÓˆÛË. ÿÛˆ˜ ÔÈ ÏÈÔÚˆÙ½Ó˜ ÂÍÔ˘‰ÂÙÂÚÒÓÔ˘Ó ÂÓ‰ÔÙÔ͛Ә Ô˘ ÂÈÛ¤Ú¯ÔÓÙ·È ÛÙËÓ Î˘ÎÏÔÊÔÚ›· ·fi ÙÔ ÔȉËÌ·Ù҉˜ ¤ÓÙÂÚÔ ÛÙËÓ Î·Ú‰È·Î‹ ·Ó¿ÚÎÂÈ·. ¶¿ÓÙˆ˜ Î·È ÛÙȘ ‰‡Ô ÌÂϤÙ˜ ‰ÂÓ ·Ú·ÙËÚ‹ıËÎ·Ó ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ ·fi ÙË ÚÔÛÔ˘‚·ÛÙ·Ù›ÓË ÂÚÈÛÛfiÙÂÚ˜ ·fi ÙÔ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ, Ú¿ÁÌ· Ô˘ ·Ô‰ÂÈÎÓ‡ÂÈ fiÙÈ ÔÈ ÛÙ·Ù›Ó˜ Â›Ó·È ÙÔ˘Ï¿¯ÈÛÙÔÓ ·ÛÊ·Ï›˜ ÛÙËÓ Î·Ú‰È·Î‹ ·Ó¿ÚÎÂÈ·. Δ· ˆ-3 ÏÈ·Ú¿ Ôͤ·, Û ·ÓÙ›ıÂÛË Ì ÙËÓ ÚÔÛÔ˘‚·ÛÙ·Ù›ÓË, ‰ÂÓ Ì›ˆÛ·Ó ÙËÓ LDL-¯ÔÏËÛÙÂÚfiÏË, ·Ô‰Â›¯ıËÎ·Ó fï˜ ·ÔÙÂÏÂÛÌ·-
16
∂ÈÎfiÓ· 2. ∫·Ì‡Ï˜ Kaplan-Meier ÁÈ· ÙÔÓ ¯ÚfiÓÔ Ì¤¯ÚÈ ÙÔÓ ı¿Ó·ÙÔ ·fi ÔÔÈ·‰‹ÔÙ ·ÈÙ›· (∞) Î·È ÁÈ· ÙÔÓ ¯ÚfiÓÔ Ì¤¯ÚÈ ÙÔÓ ı¿Ó·ÙÔ ·fi ÔÔÈ·‰‹ÔÙ ·ÈÙ›· Û˘Ó ÂÈÛ·ÁˆÁ¤˜ ÛÙÔ ÓÔÛÔÎÔÌÂ›Ô ÁÈ· ηډȷÁÁÂȷο ÓÔÛ‹Ì·Ù· (μ) Û ·ÛıÂÓ›˜ Ô˘ ¤Ï·‚·Ó ˆ-3 ÏÈ·Ú¿ Ôͤ· ‹ placebo.
ÙÈο Î·È Ì›ˆÛ·Ó ηٿ 9% ÙÔ˘˜ ı·Ó¿ÙÔ˘˜ (p=0,04) Î·È Î·Ù¿ 8% ÙÔ ¿ıÚÔÈÛÌ· ı·Ó¿ÙˆÓ Î·È ÓÔÛËÏÂÈÒÓ (p=0,009) (∂ÈÎfiÓ· 2). ™Â ·fiÏ˘ÙÔ˘˜ ·ÚÈıÌÔ‡˜, ÁÈ· Ó· ·ÔÊ¢¯ı› ¤Ó·˜ ı¿Ó·ÙÔ˜ ¯ÚÂÈ¿˙ÂÙ·È Ó· Ï·Ì‚¿ÓÔ˘Ó ˆ-3 ÏÈ·Ú¿ Ôͤ· 56 ¿ÙÔÌ· (¡¡Δ) › 3,9 ¯ÚfiÓÈ· Î·È ÁÈ· Ó· ·ÔÊ¢¯ı› ¤Ó·˜ ı¿Ó·ÙÔ˜ ‹ ÌÈ· ÂÈÛ·ÁˆÁ‹ Û ÓÔÛÔÎÔÌÂ›Ô ¯ÚÂÈ¿˙ÂÙ·È Ó· ıÂڷ‡ÔÓÙ·È 44 ¿ÙÔÌ·. ∂˘ÓÔ˚ο ·ÔÙÂϤÛÌ·Ù· ÙˆÓ ˆ-3 ÏÈ·ÚÒÓ ÔͤˆÓ ¤¯Ô˘Ó ‰È·ÈÛÙˆı› Î·È ÛÙȘ ÌÂϤÙ˜ GISSI-P Î·È DART Û ·ÛıÂÓ›˜ ÌÂÙ¿ ¤ÌÊÚ·ÁÌ· ÙÔ˘ Ì˘Ôηډ›Ô˘ Î·È ÛÙË ÌÂϤÙË JELIS Û ·ÛıÂÓ›˜ Ì ˘ÂÚÏÈȉ·ÈÌ›· Î·È Ì ‹ ¯ˆÚ›˜ ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ (ÚˆÙÔÁÂÓ‹˜ Î·È ‰Â˘ÙÂÚÔÁÂÓ‹˜ ÚfiÏË„Ë). ™˘ÌÂÚ·ÛÌ·ÙÈο, ÛÙËÓ Î·Ú‰È·Î‹
·Ó¿ÚÎÂÈ· Â›Ó·È ˆÊ¤ÏÈÌ· Ù· ˆ-3 ÔÏ˘·ÎfiÚÂÛÙ· ÏÈ·Ú¿ Ôͤ· Û ‰fiÛË 1 g ÙËÓ Ë̤ڷ, ·ÏÏ¿ ÔÈ ÛÙ·Ù›Ó˜ ‰ÂÓ ÚÔÛʤÚÔ˘Ó fiÊÂÏÔ˜. √È ıÂÚ¿ÔÓÙ˜ È·ÙÚÔ› ‰ÂÓ ‰ÈηÈÔÏÔÁÔ‡ÓÙ·È Ó· ·Ú¯›ÛÔ˘Ó ÛÙ·Ù›ÓË Û ¤Ó·Ó ·ÛıÂÓ‹ Ì ÂÁηÙÂÛÙË̤ÓË Î·Ú‰È·Î‹ ·Ó¿ÚÎÂÈ· ÔÔÈ·Û‰‹ÔÙ ·ÈÙÈÔÏÔÁ›·˜ ‹ ÏÂÈÙÔ˘ÚÁÈÎÔ‡ ÛÙ·‰›Ô˘, ‰ÂÓ Â›Ó·È fï˜ ۷ʤ˜ ·Ó Ú¤ÂÈ Ó· ‰È·ÎfiÙÔ˘Ó ÙȘ ÛÙ·Ù›Ó˜ Û ·ÛıÂÓ›˜ Ô˘ ‹‰Ë ‚Ú›ÛÎÔÓÙ·È Û ıÂڷ›· Ì ٷ Ê¿Ú̷η ·˘Ù¿ Î·È ÂΉËÏÒÓÔ˘Ó Î·Ú‰È·Î‹ ·Ó¿ÚÎÂÈ·. ™ÙȘ ÂÚÈÙÒÛÂȘ ·˘Ù¤˜ ·ʛÂÙ·È ÛÙËÓ ÎÏÈÓÈ΋ ÎÚ›ÛË ÙÔ˘˜ Ó· ÂÎÙÈÌ‹ÛÔ˘Ó ÙÔÓ Î›Ó‰˘ÓÔ ·ıËÚÔıÚÔÌ‚ˆÙÈÎÔ‡ ÂÂÈÛÔ‰›Ô˘ Û οıÂ Û˘ÁÎÂÎÚÈ̤ÓÔ ·ÛıÂÓ‹. ∂È̤ÏÂÈ·: ∏Ï›·˜ ÃÂÈÌÒÓ·˜
∫§π¡π∫∂™ ª∂§∂Δ∂™
ªÂϤÙË BEAUTIFUL (morBidity-mortality EvAlUaTion of the If inhibitor ivabradine in patients with coronary disease and left-ventricULar dysfunction) Fox K, Ford I, Steg PG, Tendera M, Ferrari R, on behalf of the BEAUTIFUL investigators. Lancet 2008;372:807-821. ™ÎÔfi˜ ·˘Ù‹˜ Ù˘ ÔÏ˘ÎÂÓÙÚÈ΋˜ Ù˘¯·ÈÔÔÈË̤Ó˘, ‰ÈÏ¿ Ù˘ÊÏ‹˜, ÂÏÂÁ¯fiÌÂÓ˘ Ì placebo ÎÏÈÓÈ΋˜ ÌÂϤÙ˘ ‹Ù·Ó Ó· ÂÚ¢ӋÛÂÈ Â¿Ó Ë È‚·ÌÚ·‰›ÓË ÌÔÚ› Ó· ÌÂÈÒÛÂÈ ÙËÓ Î·Ú‰È·ÁÁÂȷ΋ ÓÔÛËÚfiÙËÙ· Î·È ıÓËÛÈÌfiÙËÙ· Û ·ÛıÂÓ›˜ Ì ÛÙ·ıÂÚ‹ ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ Î·È Û˘ÛÙÔÏÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· Ù˘ ·ÚÈÛÙÂÚ¿˜ ÎÔÈÏ›·˜. ∏ È‚·ÌÚ·‰›ÓË (ivabradine) Â›Ó·È ¤Ó· Ê¿ÚÌ·ÎÔ Ô˘ ·Ó·ÛÙ¤ÏÏÂÈ ÙÔ Ú‡̷ If ÛÙÔÓ ÊÏ‚fiÎÔÌ‚Ô Î·È Ì ÙÔÓ Ì˯·ÓÈÛÌfi ·˘Ùfi ÌÂÈÒÓÂÈ ÙËÓ Î·Ú‰È·Î‹ Û˘¯ÓfiÙËÙ· (∫™), ¯ˆÚ›˜ Ó· ÂËÚ¿˙ÂÈ ÙË Û˘ÛÙ·ÏÙÈÎfiÙËÙ· ÙÔ˘ Ì˘Ôηډ›Ô˘ ‹ ÙȘ ÂÚÈÊÂÚÈΤ˜ ·ÁÁÂȷΤ˜ ·ÓÙÈÛÙ¿ÛÂȘ. ∏ ÌÂϤÙË ÂÚȤϷ‚ 10.917 ·ÛıÂÓ›˜ Î·È ÙˆÓ ‰‡Ô ʇψÓ, ¿Óˆ ÙˆÓ 55 ÂÙÒÓ (‹ ¿Óˆ ÙˆÓ 18 ÂÙÒÓ ·Ó ›¯·Ó ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË) Ì ÛÙ·ıÂÚ‹ ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ (ÛÙ·ıÂÚ‹ ÎÏÈÓÈ΋ ÂÈÎfiÓ· ÙÔ˘˜ ÙÂÏÂ˘Ù·›Ô˘˜ ÙÔ˘Ï¿¯ÈÛÙÔÓ 3 Ì‹Ó˜ Î·È ˘fi ÛÙ·ıÂÚ‹ ·ÁˆÁ‹ › ¤Ó· Ì‹Ó·), Ô˘ ÂÌÊ¿ÓÈ˙·Ó ÎÏ¿ÛÌ· ÂÍÒıËÛ˘ <40% Î·È ÙÂÏԉȷÛÙÔÏÈ΋ ‰È¿ÌÂÙÚÔ ·ÚÈÛÙÂÚ¿˜ >56 mm. √È ·ÛıÂÓ›˜ ¤Ú ӷ Â›Ó·È Û ÊÏ‚ÔÎÔÌ‚ÈÎfi Ú˘ıÌfi Î·È Ó· ¤¯Ô˘Ó ηډȷ΋ Û˘¯ÓfiÙËÙ· > 60/1’. √È 5.479 ·ÛıÂÓ›˜ ¤Ï·‚·Ó 5 mg È‚·ÌÚ·‰›Ó˘ ‰‡Ô ÊÔÚ¤˜ ÙËÓ Ë̤ڷ Ì ÚÔÔÙÈ΋ Ó· ·˘ÍËı› Ë ‰fiÛË Û 7,5 mg fiÔ˘ ‹Ù·Ó ·ÓÂÎÙ‹ ‹ fiÌÔÈ·˜ ÌÔÚÊ‹˜ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ. ŸÏÔÈ ÔÈ ·ÛıÂÓ›˜ ¤Ï·‚·Ó ÙËÓ
ηıÈÂڈ̤ÓË Ê·Ú̷΢ÙÈ΋ ·ÁˆÁ‹. ΔÔ 87% ÙˆÓ ·ÛıÂÓÒÓ Ï¿Ì‚·Ó ‚-·Ó·ÛÙÔÏ›˜. ¶ÚˆÙ‡ÔÓ Î·Ù·ÏËÎÙÈÎfi ÛËÌÂ›Ô ÔÚ›ÛıËΠÙÔ ¿ıÚÔÈÛÌ· ÙˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ ı·Ó¿ÙˆÓ Î·È ÙˆÓ ÂÈÛ·ÁˆÁÒÓ Û ÓÔÛÔÎÔÌÂ›Ô ÁÈ· Ô͇ ¤ÌÊÚ·ÁÌ· ÙÔ˘ Ì˘Ôηډ›Ô˘ ‹ ηډȷ΋ ·Ó¿ÚÎÂÈ· (ÓÂÔÂÌÊ·ÓÈ˙fiÌÂÓË ‹ ÂȉÂÈÓˆı›۷). ¢Â˘ÙÂÚ‡ÔÓÙ· ηٷÏËÎÙÈο ÛËÌ›· ÔÚ›ÛıËÎ·Ó ÔÏÏ¿, fiˆ˜ ı¿Ó·ÙÔÈ ·fi fiÏ· Ù· ·›ÙÈ·, ηډȷÁÁÂÈ·ÎÔ› ı¿Ó·ÙÔÈ, ηډȷÎÔ› ı¿Ó·ÙÔÈ, ÛÙÂÊ·ÓÈ·›· ·ӷÁÁ›ˆÛË Î·È ‰È¿ÊÔÚ· Û‡ÓıÂÙ· ÙÂÏÈο ÛËÌ›·. ∏ ̤ÛË ·Ú·ÎÔÏÔ‡ıËÛË ‹Ù·Ó 19 Ì‹Ó˜. ∏ È‚·ÌÚ·‰›ÓË Ì›ˆÛ ÙËÓ Î·Ú‰È·Î‹ Û˘¯ÓfiÙËÙ· ηٿ 6 ÛÊ/1’ ÛÙÔ˘˜ 12 Ì‹Ó˜, ‰ÂÓ ÂËÚ¤·Û fï˜ ÙÔ ÚˆÙ‡ÔÓ Î·Ù·ÏËÎÙÈÎfi ÛËÌÂ›Ô (ÏfiÁÔ˜ ÎÈÓ‰‡ÓÔ˘ 1,00). ™˘Ì‚¿Ì·Ù· ÂÌÊ¿ÓÈÛ·Ó 1233 ·ÛıÂÓ›˜ ÛÙËÓ ÔÌ¿‰· Ù˘ È‚·ÌÚ·‰›Ó˘ (22,5%) Î·È 1239 ·ÛıÂÓ›˜ ÛÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘ (22,8%), p=0,70. ¢ÂÓ ÂËÚ¤·Û ›Û˘ Ë È‚·ÌÚ·‰›ÓË Î·Ó¤Ó· ‰Â˘ÙÂÚ‡ÔÓ Î·Ù·ÏËÎÙÈÎfi Û˘Ì‚¿Ó ÛÙÔ Û‡ÓÔÏÔ ÙˆÓ ·ÛıÂÓÒÓ ˆ˜ ÔÌ¿‰·, ›¯Â fï˜ οÔÈ· ¢ÓÔ˚΋ ‰Ú¿ÛË ÛÙËÓ ÔÌ¿‰· ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ›¯Â ∫™ ÌÂÁ·Ï‡ÙÂÚË ÙˆÓ 70 ÛÊ/1’. ™ÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜ ·Ú·ÙËÚ‹ıËΠ̛ˆÛË ÙˆÓ ÂÈÛ·ÁˆÁÒÓ Û ÓÔÛÔÎÔÌÂ›Ô ÁÈ· ı·Ó·ÙËÊfiÚÔ ‹ ÌË ı·Ó·ÙËÊfiÚÔ ¤ÌÊÚ·ÁÌ· ÙÔ˘ Ì˘ÔηÚ-
‰›Ô˘ ηٿ 36% (p=0,001) Î·È ÙˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ ·ӷÁÁÂÈÒÛÂˆÓ 30% (p=0,016), ‰ÂÓ ·Ú·ÙËÚ‹ıËΠfï˜ fiÊÂÏÔ˜ Ô‡ÙÂ Î·È Û ·˘ÙÔ‡˜ ÙÔ˘˜ ·ÛıÂÓ›˜ ÛÙË ÓÔÛËÚfiÙËÙ· Î·È ıÓËÛÈÌfiÙËÙ· ·fi ηډȷ΋ ·Ó¿ÚÎÂÈ·. ™ÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘ (5.438 ¿ÙÔÌ·) ¤ÁÈÓ ·Ó¿Ï˘ÛË Ù˘ ¤Î‚·Û˘ ·Ó¿ÏÔÁ· Ì ÙËÓ Î·Ú‰È·Î‹ Û˘¯ÓfiÙËÙ·. ¢È·ÈÛÙÒıËΠfiÙÈ ÔÈ ·ÛıÂÓ›˜ Ì 70 ÛʇÍÂȘ ·Ó¿ ÏÂÙfi Î·È ¿Óˆ ›¯·Ó ·˘ÍË̤ÓÔ Î·Ù¿ 34% ΛӉ˘ÓÔ Î·Ú‰È·ÁÁÂÈ·ÎÔ‡ ı·Ó¿ÙÔ˘, ηٿ 53% Èı·ÓfiÙËÙ· ÂÈÛ·ÁˆÁ‹˜ Û ÓÔÛÔÎÔÌÂ›Ô ÁÈ· ηډȷ΋ ·Ó¿ÚÎÂÈ·, ηٿ 46% ΛӉ˘ÓÔ ÂÌÊÚ¿ÁÌ·ÙÔ˜ ÙÔ˘ Ì˘Ôηډ›Ô˘ Î·È Î·Ù¿ 38% Èı·ÓfiÙËÙ· Ó· ˘Ô‚ÏËıÔ‡Ó Û ÛÙÂÊ·ÓÈ·›· ·ӷÁÁ›ˆÛË, fiÏ· ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο. °È· οı 5 ÛÊ/1’ ·‡ÍËÛË Ù˘ ∫™ ·Ú·ÙËÚ‹ıËΠ·‡ÍËÛË ÙÔ˘ ηډȷÁÁÂÈ·ÎÔ‡ ı·Ó¿ÙÔ˘ ηٿ 8% (p=0,0005), ÙˆÓ ÓÔÛËÏÂÈÒÓ ÁÈ· ηډȷ΋ ·Ó¿ÚÎÂÈ· ηٿ 16%, ÙˆÓ ÂÌÊÚ·ÁÌ¿ÙˆÓ Î·Ù¿ 7% Î·È ÙˆÓ Â·Ó·ÁÁÂÈÒÛÂˆÓ Î·Ù¿ 8%. ™˘ÌÂÚ·›ÓÂÙ·È fiÙÈ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ Î·È Û˘ÛÙÔÏÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· Ù˘ ·ÚÈÛÙÂÚ¿˜ ÎÔÈÏ›·˜, Ë ·˘ÍË̤ÓË ∫™ Â›Ó·È ·ÓÂÍ¿ÚÙËÙÔ˜ ·Ú¿ÁÔÓÙ·˜ ÎÈÓ‰‡ÓÔ˘ ‰˘ÛÌÂÓÔ‡˜ ¤Î‚·Û˘. ∂È̤ÏÂÈ·: ∏Ï›·˜ ÃÂÈÌÒÓ·˜
17
¢∂∫∂ªμƒπ√™ 2008
ªÂϤÙË SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) Rossebo AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, Gerdts E, Gohlke-Borwolf C, Holme I, Kesaniemi YA, Malbecq K, Nienaber CA, Ray S, Skjaerpe T, Wachtell K, Willenheimer R, for the SEAS Investigators N Engl J Med 2008;359:1-14
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¶ÔÛÔÛÙfi ·ÛıÂÓÒÓ ∞ÚÈıÌfi˜ ·ÙfïÓ
ŒÙË ÛÙË ÌÂϤÙË
∞ÚÈıÌfi˜ ·ÙfïÓ
ŒÙË ÛÙË ÌÂϤÙË
D. £¿Ó·ÙÔ˜ ·fi fiÏ· Ù· ·›ÙÈ· ¶ÔÛÔÛÙfi ·ÛıÂÓÒÓ
C. ÈÛ¯·ÈÌÈο ηډȷÁÁÂȷο Û˘Ì‚¿Ì·Ù·
∞ÚÈıÌfi˜ ·ÙfïÓ
B. ™¯ÂÙÈ˙fiÌÂÓ· Ì ÙËÓ ·ÔÚÙÈ΋ ‚·Ï‚›‰· Û˘Ì‚¿Ì·Ù·
¶ÔÛÔÛÙfi ·ÛıÂÓÒÓ
A. ªÂ›˙ÔÓ· ηډȷÁÁÂȷο Û˘Ì‚¿Ì·Ù·
¶ÔÛÔÛÙfi ·ÛıÂÓÒÓ
∏ ÌÂϤÙË SEAS ۯ‰ȿÛÙËΠÁÈ· Ó· ÌÂÏÂÙ‹ÛÂÈ ÙÔ ·ÔÙ¤ÏÂÛÌ· Ù˘ Ì·ÎÚÔ¯ÚfiÓÈ·˜ ÂÓÙ·ÙÈ΋˜ ˘ÔÏÈȉ·ÈÌÈ΋˜ ·ÁˆÁ‹˜ Ì ÛÈÌ‚·ÛÙ·Ù›ÓË Î·È Â˙ÂÙÈÌ›ÌË ÛÙËÓ ¤Î‚·ÛË ·ÛıÂÓÒÓ Ì ·Û˘Ìو̷ÙÈ΋ ‹È· ÚÔ˜ ̤ÙÚÈ· ÛÙ¤ÓˆÛË Ù˘ ·ÔÚÙÈ΋˜ ‚·Ï‚›‰·˜. ∂›Ó·È ÌÈ· ÔÏ˘ÎÂÓÙÚÈ΋, ‰ÈÏ¿ Ù˘ÊÏ‹, Ù˘¯·ÈÔÔÈË̤ÓË ÌÂϤÙË, ÛÙËÓ ÔÔ›· ÂÓÙ¿¯ıËÎ·Ó 1873 ·ÛıÂÓ›˜, ¿Ó‰Ú˜ Î·È Á˘Ó·›Î˜ ËÏÈΛ·˜ 45-85 ÂÙÒÓ. ∞ÔÎÏ›ÛıËÎ·Ó ·ÛıÂÓ›˜ Ì ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ, ÂÚÈÊÂÚÈ΋ ·ÚÙËÚÈÔ¿ıÂÈ·, ·ÁÁÂÈ·Îfi ÂÁÎÂÊ·ÏÈÎfi ÂÂÈÛfi‰ÈÔ ‹ ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË Î·È (ÁÈ· ËıÈÎÔ‡˜ ÏfiÁÔ˘˜) fiÛÔÈ Â›¯·Ó Û·Ê‹ ¤Ó‰ÂÈÍË ˘ÔÏÈȉ·ÈÌÈ΋˜ ·ÁˆÁ‹˜. √È ·ÛıÂÓ›˜ ηٷÓÂÌ‹ıËÎ·Ó Ù˘¯·›· Û ·Ó·ÏÔÁ›· 1:1 Ó· Ï¿‚Ô˘Ó 40 mg ÛÈÌ‚·ÛÙ·Ù›Ó˘ Î·È 10 mg Â˙ÂÙÈÌ›Ì˘ ËÌÂÚËÛ›ˆ˜ ›Ù ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ. ∏ ̤ÛË ‰È¿ÚÎÂÈ· ·Ú·ÎÔÏÔ‡ıËÛ˘ ‹Ù·Ó 52,2 Ì‹Ó˜ Î·È Ë ÂÏ¿¯ÈÛÙË 4 ¯ÚfiÓÈ·. ΔÔ ÚˆÙ‡ÔÓ Î·Ù·ÏËÎÙÈÎfi ÛËÌÂ›Ô ‹Ù·Ó ÙÔ ¿ıÚÔÈÛÌ· ÙˆÓ «ÌÂÈ˙fiÓˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ Û˘Ì‚¿ÓÙˆÓ», Ù· ÔÔ›· ÌÔÚÔ‡Ó Ó· ‰È·ÎÚÈıÔ‡Ó Û ·˘Ù¿ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙËÓ ÛÙ¤ÓˆÛË Ù˘ ·ÔÚÙÈ΋˜ ‚·Ï‚›‰·˜ (¯ÂÈÚÔ˘ÚÁÈ΋ ·ÓÙÈηٿÛÙ·ÛË Ù˘ ‚·Ï‚›‰·˜, ÓÔÛËÏ›· ÁÈ· ηډȷ΋ ·Ó¿ÚÎÂÈ· Î·È Î·Ú‰È·ÁÁÂÈ·ÎÔ› ı¿Ó·ÙÔÈ) Î·È Û ·ıËÚÔÛÎÏËÚˆÙÈο Û˘Ì‚¿Ì·Ù· (·ÔÚÙÔÛÙÂÊ·ÓÈ·›· ·Ú¿Î·Ì„Ë, ‰È·‰ÂÚÌÈ΋ ÛÙÂÊ·ÓÈ·›· ·ÁÁÂÈÔÏ·ÛÙÈ΋ Î·È ÌË ·ÈÌÔÚÚ·ÁÈÎfi ·ÁÁÂÈ·Îfi ÂÁÎÂÊ·ÏÈÎfi). ¢Â˘ÙÂÚ‡ÔÓÙ· ηٷÏËÎÙÈο ÛËÌ›· ÔÚ›ÛıËÎ·Ó ÙÔ ¿ıÚÔÈÛÌ· ÙˆÓ Û¯ÂÙÈ˙fiÌÂÓˆÓ Ì ÙË ÛÙ¤ÓˆÛË Ù˘ ‚·Ï‚›‰·˜ Û˘Ì‚·Ì¿ÙˆÓ Î·È ¯ˆÚÈÛÙ¿ Ù· ·ıËÚÔÛÎÏËÚˆÙÈο Û˘Ì‚¿Ì·Ù·. ™ÙËÓ ÔÌ¿‰· Ô˘ ¤Ï·‚ ÙË ÛÈÌ‚·ÛÙ·Ù›ÓË Î·È Â˙ÂÙÈÌ›ÌË ÌÂÈÒıËÎÂ Ë LDL-¯ÔÏËÛÙÂÚfiÏË Î·Ù¿ 61%. ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÌÂϤÙ˘ ÙÔ ÚˆÙ‡ÔÓ Î·Ù·ÏËÎÙÈÎfi ÛËÌÂ›Ô ·Ú·ÙËÚ‹ıËΠ۠333 ·ÛıÂÓ›˜ Ù˘ ÔÌ¿‰·˜ ÂÓÂÚÁÔ‡ ıÂڷ›·˜ (35,3%) Î·È Û 355 ÛÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘ (38,2%, p=0,59). ¢ÂÓ ·Ú·ÙËÚ‹ıËΠ‰È·ÊÔÚ¿ Ô‡Ù ÛÙ· ÂÂÈÛfi‰È· Ù· Û¯ÂÙÈ˙fiÌÂÓ· Ì ÙË ‚·Ï‚ȉԿıÂÈ· Ù˘ ·ÔÚÙ‹˜, ·-
ŒÙË ÛÙË ÌÂϤÙË
∞ÚÈıÌfi˜ ·ÙfïÓ
ŒÙË ÛÙË ÌÂϤÙË
∂ÈÎfiÓ· 1. ∫·Ì‡Ï˜ Kaplan-Meier ÁÈ· ÙÔ ÚˆÙ‡ÔÓ (∞) Î·È Ù· ‰Â˘ÙÂÚ‡ÔÓÙ· (μ Î·È C) ηٷÏËÎÙÈο ÛËÌ›· Î·È ÙÔ ¯ÚfiÓÔ Ì¤¯ÚÈ ÙÔÓ ı¿Ó·ÙÔ ·fi ÔÔÈ·‰‹ÔÙ ·ÈÙ›· (D) Û ·ÛıÂÓ›˜ Ô˘ ¤Ï·‚·Ó ÛÈÌ‚·ÛÙ·Ù›ÓË Î·È Â˙ÂÙÈÌ›ÌË ‹ placebo.
Ú·ÙËÚ‹ıËΠfï˜ ÛÙ·ÙÈÛÙÈÎÒ˜ ÛËÌ·ÓÙÈ΋ ‰È·ÊÔÚ¿ ÛÙ· ·ıËÚÔÛÎÏËÚˆÙÈο ÂÂÈÛfi‰È· (148 ÛÙËÓ ÔÌ¿‰· Ù˘ ÂÓÂÚÁÔ‡ ıÂڷ›·˜ Î·È 187 ÛÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘, p=0,02) (EÈÎfiÓ· 1). ŒÓ· ÌË ·Ó·ÌÂÓfiÌÂÓÔ Î·È ·ÓËÛ˘¯ËÙÈÎfi ‡ÚËÌ· ‹Ù·Ó Ë ÂÌÊ¿ÓÈÛË ÂÚÈÛÛfiÙÂÚˆÓ ÂÚÈÛÙ·ÙÈÎÒÓ Î·ÚΛÓÔ˘ ÛÙËÓ ÔÌ¿‰· Ù˘ ˘ÔÏÈȉ·ÈÌÈ΋˜ ıÂڷ›·˜ Û˘ÁÎÚÈÙÈο Ì ÙËÓ ÔÌ¿‰· ÙÔ˘ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ (105 ¤Ó·ÓÙÈ 70, p=0,01). ∏ ‰È·ÊÔÚ¿ ÌÂٷ͇ ÙˆÓ ‰‡Ô ÔÌ¿‰ˆÓ ‰ÂÓ ÔÊ›ÏÂÙ·È Û οÔÈÔÓ È‰È·›ÙÂÚÔ Ù‡Ô Î·ÚΛÓÔ˘ Î·È ‰ÂÓ ‰È¢ڇÓıËΠ̠ÙËÓ ¿ÚÔ‰Ô ÙÔ˘ ¯ÚfiÓÔ˘. √È ·Ú·ÙËÚ‹ÛÂȘ ·˘Ù¤˜ Î·È Ô ÌÈÎÚfi˜ Û˘ÓÔÏÈÎfi˜ ·ÚÈıÌfi˜ ÙˆÓ Î·ÚÎ›ÓˆÓ Î¿ÓÔ˘Ó ·ÚÎÂÙ¿ ÌÂÁ¿ÏË ÙËÓ Èı·ÓfiÙËÙ· Ó· Â›Ó·È ÙÔ Â‡ÚËÌ· Ù˘¯·›Ô. ¶·Ú' fiÏ· ·˘Ù¿, ÙÔ Â‡ÚËÌ· ·ÓËÛ‡¯ËÛ ÙËÓ ÂÈÛÙËÌÔÓÈ΋ ÎÔÈÓfiÙËÙ· Î·È ÙȘ ÂÔÙ‡ԢÛ˜ ·Ú¯¤˜ Î·È ÁÈ' ·˘Ùfi ¤ÁÈÓ ·ÔÙ‡ÊψÛË ÙˆÓ ÂÚÈÛÙ·ÙÈÎÒÓ Î·ÚΛ-
ÓÔ˘ Ô˘ ¤¯Ô˘Ó ηٷÁÚ·Ê› ̤¯ÚÈ ÙÒÚ· Û ‰‡Ô ÌÂÁ¿Ï˜ ÎÏÈÓÈΤ˜ ÌÂϤÙ˜, Ù˘ SHARP (Study of Heart And Renal Protection) Î·È Ù˘ IMPROVE-IT (IMProved Reduction of Outcomes: Vitorin Efficacy International Trial) Ô˘ ‚Ú›ÛÎÔÓÙ·È Û ÂͤÏÈÍË Î·È ÛÙȘ Ôԛ˜ ‰ÔÎÈÌ¿˙ÂÙ·È Ô Û˘Ó‰˘·ÛÌfi˜ ÛÈÌ‚·ÛÙ·Ù›Ó˘ Î·È Â˙ÂÙÈÌ›Ì˘. Δ· ÂÚÈÛÙ·ÙÈο ·fi ÙȘ ÌÂϤÙ˜ ·˘Ù¤˜, ÏfiÁˆ ÙÔ˘ ÌÂÁ¤ıÔ˘˜ ÙˆÓ ÌÂÏÂÙÒÓ, Â›Ó·È ÙÂÙÚ·Ï¿ÛÈ· Û ·ÚÈıÌfi ·fi ·˘Ù¿ Ù˘ SEAS Î·È ·Ó·Ï‡ıËÎ·Ó ·fi ÌÈ· ·ÓÂÍ¿ÚÙËÙË ·Î·‰ËÌ·˚΋ ÂÈÛÙËÌÔÓÈ΋ ÔÌ¿‰· (ÙËÓ Clinical Trial Service Unit ÙÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ Ù˘ √ÍÊfiډ˘) fiÏ· Ì·˙›. ∞fi ÙËÓ ·Ó¿Ï˘ÛË ·˘Ù‹ ‰ÂÓ ÚԤ΢„ ηÌÈ¿ ¤Ó‰ÂÈÍË fiÙÈ Ë ıÂڷ›· ÌÂ Û˘Ó‰˘·ÛÌfi ÛÈÌ‚·ÛÙ·Ù›Ó˘ Î·È Â˙ÂÙÈÌ›Ì˘ ·˘Í¿ÓÂÈ ÙÔ˘˜ ηÚΛÓÔ˘˜, Ú¿ÁÌ· Ô˘ ÂȂ‚·ÈÒÓÂÈ fiÙÈ ÙÔ Â‡ÚËÌ· Ù˘ SEAS ‹Ù·Ó Ù˘¯·›Ô. ∂È̤ÏÂÈ·: ∏Ï›·˜ ÃÂÈÌÒÓ·˜
£∂ƒ∞¶∂π∞ - º∞ƒª∞∫∞
∂›‰Ú·ÛË ÙˆÓ ∞ÓÙÈ˘ÂÚÙ·ÛÈÎÒÓ º·ÚÌ¿ÎˆÓ ÛÙÔ ªÂÙ·‚ÔÏÈÛÌfi Ù˘ °Ï˘Îfi˙˘ ÕÚ˘-¢ËÌ‹ÙÚÈÔ˜ ∞ÁÁÔ˘Ú›‰Ë˜, ∂ÈÛÙËÌÔÓÈÎfi˜ ™˘ÓÂÚÁ¿Ù˘ ÙÔ˘ ∂Í. π·ÙÚ›Ԣ ÙˆÓ ¢È·Ù·Ú·¯ÒÓ ÙÔ˘ ªÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ §Èȉ›ˆÓ ÙÔ˘ ¶·ÓÂÈÛÙËÌÈ·ÎÔ‡ °ÂÓÈÎÔ‡ ¡ÔÛÔÎÔÌ›Ԣ πˆ·ÓÓ›ÓˆÓ
ªˆ˘Û‹˜ ∂ÏÈÛ¿Ê, ∫·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ ΔÔ̤·˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ
∂ÈÛ·ÁˆÁ‹ ∏ ›وÛË Ù˘ ·¯˘Û·ÚΛ·˜ ¤¯ÂÈ ‰ÈÏ·ÛÈ·Ûı› Ù· ÙÂÏÂ˘Ù·›· 20 ¯ÚfiÓÈ·. √È ·¯‡Û·ÚÎÔÈ Û ۇÁÎÚÈÛË Ì ٷ Ê˘ÛÈÔÏÔÁÈÎÔ‡ ‚¿ÚÔ˘˜ ¿ÙÔÌ· ¤¯Ô˘Ó 3.5 ÊÔÚ¤˜ ÌÂÁ·Ï‡ÙÂÚË Èı·ÓfiÙËÙ· Ó· ÂÌÊ·Ó›ÛÔ˘Ó ˘¤ÚÙ·ÛË , ÂÓÒ Ù·˘Ùfi¯ÚÔÓ· ¿Óˆ ·fi ÙÔ 60% ÙˆÓ ·¯‡Û·ÚÎˆÓ ·ÙfiÌˆÓ ¤¯ÂÈ ·˘ÍË̤ӷ ›‰· ·ÚÙËÚȷ΋˜ ›ÂÛ˘.1 2 ∂ÈÚfiÛıÂÙ· ÔÈ ·ÛıÂÓ›˜ Ì ˘¤ÚÙ·ÛË ¤¯Ô˘Ó ·˘ÍË̤ÓË Â›ÙˆÛË ‰È·Ù·Ú·¯‹˜ ·ÓÔ¯‹˜ ÛÙË ÁÏ˘Îfi˙Ë Î·È Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË Ù‡Ô˘ 2 (™¢2).3 4 ∏ ˘¤ÚÙ·ÛË, Ë ÎÔÈÏȷ΋ ·¯˘Û·ÚΛ· Î·È Ë ‰È·Ù·Ú·¯‹ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ ˘‰·Ù·ÓıÚ¿ÎˆÓ Â›Ó·È ¯·Ú·ÎÙËÚÈÛÙÈο ÙÔ˘ ÌÂÙ·‚ÔÏÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘. ¶·Ï·ÈfiÙÂÚ˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ Ë ıÂڷ›· Ì ‰È·ÊÔÚÂÙÈΤ˜ ηÙËÁÔڛ˜ ·ÓÙÈ˘ÂÚÙ·ÛÈÎÒÓ Ê·ÚÌ¿ÎˆÓ ¤¯ÂÈ ·ÔÙ¤ÏÂÛÌ· ÔÈΛϘ ÂȉڿÛÂȘ ÛÙÔ ÌÂÙ·‚ÔÏÈÛÌfi Ù˘ ÁÏ˘Îfi˙˘.5 ∞˘Ù¤˜ ÔÈ ÂȉڿÛÂȘ Û˘Û¯ÂÙ›˙ÔÓÙ·È Ì ÌÂÙ·‚ÔϤ˜ Ù˘ ÈÓÛÔ˘ÏÈÓÔ¢·ÈÛıËÛ›·˜. ∏ ·‡ÍËÛË Ù˘ ÁÏ˘Îfi˙˘ ÙÔ˘ ÔÚÔ‡ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ·ÓÙÈ˘ÂÚÙ·ÛÈ΋˜ ıÂڷ›·˜ Èı·Ó¿ ·ÔÙÂÏ› ÚÔÁÓˆÛÙÈÎfi ‰Â›ÎÙË ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ÂÌÊÚ¿ÁÌ·ÙÔ˜ ÙÔ˘ Ì˘Ôηډ›Ô˘.6 ∏ ·ÓÙ›ÛÙ·ÛË ÛÙËÓ ÈÓÛÔ˘Ï›ÓË ¤¯ÂÈ Â›Û˘ Û˘Û¯ÂÙÈÛı› Ì ÂÓ‰ÔıËÏȷ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·, Ë ÔÔ›· ıˆÚÂ›Ù·È ÚÔÁÓˆÛÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÌÂÏÏÔÓÙÈο ηډȷÁÁÂȷο Û˘Ì‚¿Ì·Ù·.7 ªÂ ‚¿ÛË Ù· ·Ú·¿Óˆ ‰Â‰Ô̤ӷ Â›Ó·È ÛËÌ·ÓÙÈÎfi Ó· ·Ó·ÁÓˆÚ›˙ÂÈ Ô ÎÏÈÓÈÎfi˜ ÁÈ·ÙÚfi˜ ÙȘ ÂӉ¯fiÌÂÓ˜ ‰˘ÛÌÂÓ›˜ ÌÂÙ·‚ÔÏÈΤ˜ ÂȉڿÛÂȘ ·˘ÙÒÓ ÙˆÓ Ê·Ú̿ΈÓ. ™ÙÔ ¿ÚıÚÔ ·˘Ùfi ı· ·ÚÔ˘ÛÈ·ÛıÔ‡Ó Í¯ˆÚÈÛÙ¿ ÔÈ ÂȉڿÛÂȘ Ô˘ ¤¯Ô˘Ó ÔÈ Î·ÙËÁÔڛ˜ ÙˆÓ ·ÓÙÈ˘ÂÚÙ·ÛÈÎÒÓ Ê·ÚÌ¿ÎˆÓ ÛÙÔ ÌÂÙ·‚ÔÏÈÛÌfi Ù˘ ÁÏ˘Îfi˙˘.
ÛÙË Û˘Û¯¤ÙÈÛË ÌÂٷ͇ Ù˘ ¯ÔÚ‹ÁËÛ˘ ıÂÈ·˙ȉÈÎÒÓ ‰ÈÔ˘ÚËÙÈÎÒÓ Î·È ÛÙËÓ ÂÌÊ¿ÓÈÛË ‰È·Ù·Ú·¯‹˜ ·ÓÔ¯‹˜ ÛÙË ÁÏ˘Îfi˙Ë ‹ ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË. ¶Ú¿ÁÌ·ÙÈ, ÛÙË ÌÂϤÙË ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) Ë Â›ÙˆÛË ÙÔ˘ ™¢2 ‹Ù·Ó ÌÂÁ·Ï‡ÙÂÚË ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ‹Ú·Ó ¯ÏˆÚÔı·ÏȉfiÓË Û ۇÁÎÚÈÛË Ì ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ¤Ï·‚·Ó ›Ù ·ÌÏԉțÓË Â›Ù ÏÈÛÈÓÔÚ›ÏË (¶›Ó·Î·˜ 1).8 ™ÙË ÌÂϤÙË SHEP (Systolic Hypertension in the Elderly Program), ÌÂÙ¿ ·fi Ì·ÎÚÔ¯ÚfiÓÈ· ıÂڷ›· (14 ¯ÚfiÓÈ·), ÙÔ 13% ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ‹Ú ¯ÏˆÚÔı·ÏȉfiÓË ÂÌÊ¿ÓÈÛ ‰È·‚‹ÙË Û ۇÁÎÚÈÛË Ì ÙÔ 8.7% ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ‹Ú ıÂڷ›· Ì ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ (p<0.0001).9 10 ™Â ÌÈ· ÌÂÁ¿ÏË ¤Ú¢ӷ (NHS I: Á˘Ó·›Î˜ ËÏÈΛ·˜ 30-55 ÂÙÒÓ, NHS II: Á˘Ó·›Î˜ ËÏÈΛ·˜ 25-42 ÂÙÒÓ, HPFS: ¿ÓÙÚ˜ ËÏÈΛ·˜ 40-75 ÂÙÒÓ) ÛÙËÓ ÔÔ›· Û˘ÌÌÂÙ›¯·Ó 19.472 ¿Ó‰Ú˜ Î·È 55.344 Á˘Ó·›Î˜ Î·È ÛÙËÓ ÔÔ›· ¤ÁÈÓ ‰ÈfiÚıˆÛË ÁÈ· ÙÔ ‰Â›ÎÙË Ì¿˙·˜ ÛÒÌ·ÙÔ˜, ÔÈ ·ÛıÂÓ›˜ Ô˘ ¤·ÈÚÓ·Ó ıÂÈ·˙ȉÈο ‰ÈÔ˘ÚËÙÈο ›¯·Ó ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÁÈ· ÙËÓ ÂÌ-
Ê¿ÓÈÛË Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË Û ۇÁÎÚÈÛË Ì ٷ ¿ÙÔÌ· Ô˘ ‰ÂÓ ¤·ÈÚÓ·Ó ·˘Ù¿ Ù· Ê¿Ú̷η [NHS I: Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜: 1.20 (95% ‰È¿ÛÙËÌ· ÂÌÈÛÙÔÛ‡Ó˘ 1.081.33), NHS II: Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜: 1.45 (95% ‰È¿ÛÙËÌ· ÂÌÈÛÙÔÛ‡Ó˘ 1.17-1.79), HPFS: Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜: 1.36 (95% ‰È¿ÛÙËÌ· ÂÌÈÛÙÔÛ‡Ó˘ 1.17-1.58)].11 ∂ÈϤÔÓ, Û ̛· ÚfiÛÊ·ÙË ¤Ú¢ӷ 2.624 ·ÛıÂÓÒÓ Ô˘ ‹Ú·Ó ıÂÈ·˙ȉÈο ‰ÈÔ˘ÚËÙÈο, Ô ÏËı˘ÛÌfi˜ Ù˘ ÌÂϤÙ˘ ¯ˆÚ›ÛıËΠ۠ÙÂÙ·ÚÙËÌfiÚÈ· Ì ‚¿ÛË ÙÔ ‰Â›ÎÙË Ì¿˙·˜ ÛÒÌ·ÙÔ˜ (·fi 25.9kg/m2 ÛÙÔ ÚÒÙÔ ÙÂÙ·ÚÙËÌfiÚÈÔ ¤ˆ˜ Î·È ¿Óˆ ·fi 32.3kg/m2 ÛÙÔ ÙÂÏÂ˘Ù·›Ô ÙÂÙ·ÚÙËÌfiÚÈÔ). √È ÙÈ̤˜ ÁÏ˘Îfi˙˘ ÓËÛÙ›·˜ ·˘Í¿ÓÔÓÙ·Ó Ì ÙËÓ ·‡ÍËÛË ÙÔ˘ ‰Â›ÎÙË Ì¿˙·˜ ÛÒÌ·ÙÔ˜, ÂÓÒ Ù·˘Ùfi¯ÚÔÓ· ˘‹Ú¯Â ÛÙ·‰È·Î‹ ·‡ÍËÛË ÛÙÔ Ì¤ÁÂıÔ˜ Ù˘ ÌÂÙ·‚ÔÏ‹˜ Ù˘ ÁÏ˘Îfi˙˘ ÓËÛÙ›·˜ ÌÂÙ¿ ÙË ¯ÔÚ‹ÁËÛË ıÂÈ·˙ȉÈÎÒÓ ‰ÈÔ˘ÚËÙÈÎÒÓ ·Ú¿ÏÏËÏ· Ì ÙËÓ ·‡ÍËÛË ÙÔ˘ ‰Â›ÎÙË Ì¿˙·˜ ÛÒÌ·ÙÔ˜.12 ™ÙËÓ ·Ú·¿Óˆ ÌÂϤÙË ‰ÂÓ ·Ú·ÙËÚ‹ıËÎÂ Û˘Û¯¤ÙÈÛË ÌÂٷ͇ Ù˘ ·‡ÍËÛ˘ Ù˘ ÁÏ˘Îfi˙˘ ÓËÛÙ›·˜ ÌÂÙ¿ ·fi ÙË ¯ÔÚ‹ÁËÛË ıÂÈ·˙È-
¶›Ó·Î·˜ 1: °Ï˘Îfi˙Ë ÓËÛÙ›·˜ Û ÌË ‰È·‚ËÙÈÎÔ‡˜ ·ÛıÂÓ›˜ Ì ·Ú¯Èο ›‰· ÁÏ˘Îfi˙˘ ÓËÛÙ›·˜ <126 mg/dl (ÌÂϤÙË ALLHAT) ÃψÚÔı·ÏȉfiÓË ∞ÌÏԉțÓË
§ÈÛÈÓÔÚ›ÏË
∞ÚÈıÌfi˜ ·ÛıÂÓÒÓ(%) ™ÙËÓ ¤Ó·ÚÍË Ù˘ ÌÂϤÙ˘
6766 (100)
3954 (100)
4096 (100)
ªÂÙ¿ 2 ¤ÙË
3074 (45.4)
1787 (45.2)
1737 (42.4)
ªÂÙ¿ 4 ¤ÙË
2606 (40.3)
1567 (39.6)
1464 (35.7)
ª¤ÛË ÙÈÌ‹ mg/dl (±ÛÙ·ıÂÚ‹ ·fiÎÏÈÛË) ∞Ú¯Èο ›‰·
93.1 (11.7)
93.0 (11.4)
93.3 (11.8)
2 ¤ÙË
102.2 (27.1)
99.0 (22.5)
97.4 (20.0)
4 ¤ÙË
104.4 (28.5)
103.1 (27.7)
100.5 (19.5)
∞ÚÈıÌfi˜ ·ÛıÂÓÒÓ (%) Ì ÁÏ˘Îfi˙Ë ÓËÛÙ›·˜ ≥126 mg/dl
£ÂÈ·˙ȉÈο ‰ÈÔ˘ÚËÙÈο ¶ÔÏϤ˜ ÌÂϤÙ˜ ¤¯Ô˘Ó ·Ó·ÊÂÚı›
2 ¤ÙË
295 (9.6)
132 (7.4)
101 (5.8)
4 ¤ÙË
302 (11.6)
154 (9.8)
119 (8.1)
19
¢∂∫∂ªμƒπ√™ 2008
¶›Ó·Î·˜ 2: ∫¿ÏÈÔ, mEq/L (ÌÂϤÙË ALLHAT) ÃψÚÔı·ÏȉfiÓË ∞ÌÏԉțÓË
§ÈÛÈÓÔÚ›ÏË
∞ÚÈıÌfi˜ ·ÛıÂÓÒÓ(%) ™ÙËÓ ¤Ó·ÚÍË Ù˘ ÌÂϤÙ˘
14487 (95.0)
8586 (94.9)
8573 (94.7)
ªÂÙ¿ 2 ¤ÙË
9877 (64.7)
5794 (64.0)
5516 (60.9)
ªÂÙ¿ 4 ¤ÙË
8315 (54.5)
4919 (54.4)
4616 (51.0)
ª¤ÛË ÙÈÌ‹ (±ÛÙ·ıÂÚ‹ ·fiÎÏÈÛË) ∞Ú¯Èο ›‰·
4.3 (0.7)
4.3 (0.7)
4.4 (0.7)
2 ¤ÙË
4 (0.7)
4.3 (0.7)
4.5 (0.7)
4 ¤ÙË
4.1 (0,7)
4.4 (0.7)
4.5 (0.7)
∞ÚÈıÌfi˜ ·ÛıÂÓÒÓ (%) Ì οÏÈÔ<3.5mEq/L ™ÙËÓ ¤Ó·ÚÍË Ù˘ ÌÂϤÙ˘
493 (3.4)
292 (3.4)
223 (2.6)
2 ¤ÙË
1254 (12.7)
151 (2.6)
83 (1.5)
4 ¤ÙË
707 (8.5)
93 (1.9)
37 (0.8)
‰ÈÎÒÓ ‰ÈÔ˘ÚËÙÈÎÒÓ Ì ÙË ‰ÔÛÔÏÔÁ›· ÙˆÓ Û˘ÁÎÂÎÚÈÌ¤ÓˆÓ Ê·Ú̿ΈÓ. øÛÙfiÛÔ ¿ÏÏÔÈ ÂÚ¢ÓËÙ¤˜ ·Ó¤ÊÂÚ·Ó Ì›· ‰ÔÛÔÂÍ·ÚÙÒÌÂÓË ·‡ÍËÛË Ù˘ ÁÏ˘Îfi˙˘ ÙÔ˘ ÔÚÔ‡ Û ·ÛıÂÓ›˜ Ô˘ ‹Ú·Ó ¯ÏˆÚÔı·ÏȉfiÓË.13 ™Â Ì›· ¿ÏÏË ÌÂϤÙË, Ë ¯ÔÚ‹ÁËÛË ‚ÂÓ‰ÚÔÊıÔÚÈÔÌÂıÂÈ·˙›‰Ë˜ (10 mg/Ë̤ڷ) ÁÈ· 10 ‚‰ÔÌ¿‰Â˜ ›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ·‡ÍËÛË Ù˘ ÁÏ˘Îfi˙˘ ÙÔ˘ ÔÚÔ‡ ηٿ 7%, ÂÓÒ Ë ¯ÔÚ‹ÁËÛË 1.25 mg/Ë̤ڷ ‰ÂÓ Â›¯Â η̛· ›‰Ú·ÛË ÛÙ· ›‰· Ù˘ ÁÏ˘Îfi˙˘ ÙÔ˘ ÔÚÔ‡.14 ¶Ú¤ÂÈ Ó· ÂÈÛËÌ·Óı› fiÙÈ Ô Neutel Û ̛· ÌÂÙ·-·Ó¿Ï˘ÛË 9 Ù˘¯·ÈÔÔÈËÌ¤ÓˆÓ ÎÏÈÓÈÎÒÓ ÌÂÏÂÙÒÓ
‰È·›ÛÙˆÛ fiÙÈ ÌÂÙ¿ ÙË ¯ÔÚ‹ÁËÛË ˘‰ÚԯψÚÔıÂÈ·˙›‰Ë˜ (12.5 mg/Ë̤ڷ) ˆ˜ ÌÔÓÔıÂڷ›·, ÔÈ ÌÂÙ·‚ÔϤ˜ Ù˘ ÁÏ˘Îfi˙˘ Û ۇÁÎÚÈÛË Ì ٷ ·Ú¯Èο ›‰· ‰ÂÓ ‹Ù·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜.15 ™Â Ì›· ÔÏ˘·Ú·ÁÔÓÙÈ΋ ·Ó¿Ï˘ÛË ‚Ú¤ıËΠfiÙÈ Ù· ¯·ÌËÏ¿ ›‰· ÙÔ˘ Î·Ï›Ô˘ ·ÔÙÂÏÔ‡Ó ÛËÌ·ÓÙÈÎfi ÚÔÁÓˆÛÙÈÎfi ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ™¢2 ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ·›ÚÓÔ˘Ó ıÂÈ·˙ȉÈο ‰ÈÔ˘ÚËÙÈο.12 ™ÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜ Ë ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ Ù˘ ÁÏ˘Îfi˙˘ ÓËÛÙ›·˜ Û˘Û¯ÂÙ›ÛıËΠ̠ÙËÓ ÂÌÊ¿ÓÈÛË ˘ÔηÏÈ·ÈÌ›·˜, ÂÓÒ ·ÔηٷÛÙ¿ıËÎÂ
¶›Ó·Î·˜ 3: ∫›Ó‰˘ÓÔ˜ ÂÌÊ¿ÓÈÛ˘ ™¢2 Û 3804 ˘ÂÚÙ·ÛÈÎÔ‡˜ ·ÛıÂÓ›˜ ·Ó¿ÏÔÁ· Ì ÙË Ê·Ú̷΢ÙÈ΋ ·ÓÙÈ˘ÂÚÙ·ÛÈ΋ ıÂڷ›· (ÌÂϤÙË ARIC) ∞ÓÙÈ˘ÂÚÙ·ÛÈ΋
™¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜ (95% ‰È¿ÛÙËÌ· ÂÌÈÛÙÔÛ‡Ó˘)
ıÂڷ›·
ªÔÓÙ¤ÏÔ 1
∫·Ì›·
1.0
·-ª∂∞
0.99 (0.73-1.35)
‚-·ÔÎÏÂÈÛÙ¤˜ 1.26 (1.03-1.52) ∞ÓÙ·ÁˆÓÈÛÙ¤˜ 1.17 (0.85-1.62) ‰È·‡ÏˆÓ Ca++ £ÂÈ·˙ȉÈο ‰ÈÔ˘ÚËÙÈο
0.95 (0.77-1.17)
ªÔÓÙ¤ÏÔ 2 1.0
ªÔÓÙ¤ÏÔ 3 1.0
0.96 (0.71-1.31) 0.98 (0.72-1.34) †
1.25 (1.03-1.52) † 1.28 (1.04-1.57) † 1.16 (0.84-1.60) 1.17 (0.83-1.66) 0.93 (0.76-1.15) 0.91 (0.73-1.13)
*ªÔÓÙ¤ÏÔ1: ‰ÈÔÚıˆÌ¤ÓÔ ˆ˜ ÚÔ˜ ÙËÓ ËÏÈΛ·, ÙÔ Ê‡ÏÔ, ÙË Ê˘Ï‹ Î·È ÙË ¯Ú‹ÛË ¿ÏÏˆÓ ·ÓÙÈ˘ÂÚÙ·ÛÈÎÒÓ Ê·Ú̿ΈÓ. ªÔÓÙ¤ÏÔ 2: ‰ÈÔÚıˆÌ¤ÓÔ ˆ˜ ÚÔ˜ ÙȘ ·Ú·Ì¤ÙÚÔ˘˜ ÙÔ˘ ÌÔÓÙ¤ÏÔ˘ 1, ÙÔ ‰Â›ÎÙË Ì¿˙·˜ ÛÒÌ·ÙÔ˜, ÙÔ ÏfiÁÔ ÂÚÈ̤ÙÚÔ˘ ̤Û˘ ÚÔ˜ ÂÚ›ÌÂÙÚÔ ÈÛ¯›Ô˘, ÙÔ ÌÔÚʈÙÈÎfi ›‰Ô, ÙÔ Î¿ÓÈÛÌ·, ÙË ¯Ú‹ÛË ·ÏÎÔfiÏ Î·È ÙË Ê˘ÛÈ΋ ηٿÛÙ·ÛË. ªÔÓÙ¤ÏÔ 3: ‰ÈÔÚıˆÌ¤ÓÔ ˆ˜ ÚÔ˜ ÙÔ ÌÔÓÙ¤ÏÔ 2, ÙË Û˘ÛÙÔÏÈ΋ ·ÚÙËÚȷ΋ ›ÂÛË, ÙË ‰È·ÛÙÔÏÈ΋ ·ÚÙËÚȷ΋ ›ÂÛË, ÙË Û˘ÁΤÓÙÚˆÛË ÈÓÛÔ˘Ï›Ó˘ ÓËÛÙ›·˜ ÛÙÔÓ ÔÚfi Î·È ÛÙËÓ ·ÚÔ˘Û›· ‹ ·Ô˘Û›· ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌ›·˜, ηډȷÁÁÂȷ΋˜ ÓfiÛÔ˘, Ó¢ÌÔÓÈ΋˜ ÓfiÛÔ˘, ÓÂÊÚÈ΋˜ ·Ó¿ÚÎÂÈ·˜ Î·È ÔÈÎÔÁÂÓÂÈ·ÎÔ‡ ÈÛÙÔÚÈÎÔ‡ ‰È·‚‹ÙË. **·-ª∂∞: ·Ó·ÛÙÔÏ›˜ ÌÂÙ·ÙÚÂÙÈÎÔ‡ ÂÓ˙‡ÌÔ˘ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘. †P<0.05 Û ۇÁÎÚÈÛË Ì ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ Ï¿Ì‚·Ó·Ó η̛· ·ÓÙÈ˘ÂÚÙ·ÛÈ΋ ·ÁˆÁ‹
20
ÓÔÚÌÔÁÏ˘Î·ÈÌ›· ÌÂÙ¿ ÙË ¯ÔÚ‹ÁËÛË Î·Ï›Ô˘.3 16 ∏ Ì›ˆÛË ÙˆÓ ÂȤ‰ˆÓ ÙÔ˘ Î·Ï›Ô˘ Â›Ó·È Û˘¯Ó‹ ·ÚÂÓ¤ÚÁÂÈ· ÙˆÓ ıÂÈ·˙ȉÈÎÒÓ ‰ÈÔ˘ÚËÙÈÎÒÓ. ÀÔÏÔÁ›˙ÂÙ·È fiÙÈ ÛËÌ·ÓÙÈÎfi ÔÛÔÛÙfi ·ÛıÂÓÒÓ Ô˘ ·›ÚÓÂÈ ıÂÈ·˙ȉÈο ‰ÈÔ˘ÚËÙÈο ·Ó·Ù‡ÛÛÂÈ ˘ÔηÏÈ·ÈÌ›· (∫+ <3.5mmol/L).17 √ ˘ÔΛÌÂÓÔ˜ Ì˯·ÓÈÛÌfi˜ Ù˘ ˘ÔηÏÈ·ÈÌ›·˜ Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ·˘ÍË̤ÓË ÓÂÊÚÈ΋ ·¤ÎÎÚÈÛË ÙÔ˘ Î·Ï›Ô˘. ∏ ‰Ú¿ÛË ÙˆÓ ıÂÈ·˙ȉÈÎÒÓ ‰ÈÔ˘ÚËÙÈÎÒÓ ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·‡ÍËÛË Ù˘ Û˘ÁΤÓÙÚˆÛ˘ ÙÔ˘ Ó·ÙÚ›Ô˘ ÛÙ· ¿ˆ ÂÛÂÈڷ̤ӷ ÛˆÏËÓ¿ÚÈ·, Ë ÔÔ›· Ô‰ËÁ› Û ·‡ÍËÛË Ù˘ ÓÂÊÚÈ΋˜ ·¤ÎÎÚÈÛ˘ ÙÔ˘ Î·Ï›Ô˘. ∂ÈÚfiÛıÂÙ·, Û ·¿ÓÙËÛË ÛÙË Û˘ÛÙÔÏ‹ ÙÔ˘ fiÁÎÔ˘ ÙÔ˘ ·›Ì·ÙÔ˜, ·˘Í¿ÓÂÙ·È Ë ¤ÎÎÚÈÛË Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘, Ë ÔÔ›· Ì ÙË ÛÂÈÚ¿ Ù˘ ÚÔηÏ› ÂÚ·ÈÙ¤Úˆ ·‡ÍËÛË Ù˘ ·¤ÎÎÚÈÛ˘ ÙÔ˘ Î·Ï›Ô˘. ∏ ·‡ÍËÛË Ù˘ ÓÂÊÚÈ΋˜ ·¤ÎÎÚÈÛ˘ ÙÔ˘ Î·Ï›Ô˘ Ô˘ ÔÊ›ÏÂÙ·È ÛÙ· ıÂÈ·˙ȉÈο ‰ÈÔ˘ÚËÙÈο Èı·Ó¿ Âȉڿ ‰˘ÛÌÂÓÒ˜ ÛÙÔ ÌÂÙ·‚ÔÏÈÛÌfi Ù˘ ÁÏ˘Îfi˙˘, ηıÒ˜ ÂÏ·ÙÙÒÓÂÙ·È ÙfiÛÔ Ë ¤ÎÎÚÈÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘ ÂÍ·ÈÙ›·˜ Ù˘ Ì›ˆÛ˘ ÙÔ˘ Î·Ï›Ô˘ fiÛÔ Î·È Ë ÈÓÛÔ˘ÏÈÓÔ¢·ÈÛıËÛ›· ÛÙÔ˘˜ ÂÚÈÊÂÚÈÎÔ‡˜ ÈÛÙÔ‡˜. ™ÙË ÌÂϤÙË ALLHAT Û˘ÁÎÚ›ıËÎ·Ó Ù· ›‰· ÙÔ˘ Î·Ï›Ô˘ Û ·ÛıÂÓ›˜ Ô˘ ¤·ÈÚÓ·Ó Â›Ù ¯ÏˆÚÔı·ÏȉfiÓË Â›Ù ·ÌÏԉțÓË Â›Ù ÏÈÛÈÓÔÚ›ÏË (¶›Ó·Î·˜ 2).8 ∞Ó·ÛÙÔÏ›˜ ÙˆÓ ‚-·‰ÚÂÓÂÚÁÈÎÒÓ ˘Ô‰Ô¯¤ˆÓ (‚-·ÔÎÏÂÈÛÙ¤˜) ™Â ·ÚÎÂÙ¤˜ ÌÂϤÙ˜ Û ˘ÂÚÙ·ÛÈÎÔ‡˜ ·ÛıÂÓ›˜ ·Ú·ÙËÚ‹ıËΠ̛ˆÛË ÛÙËÓ ÈÓÛÔ˘ÏÈÓÔ¢·ÈÛıËÛ›· ÌÂÙ¿ ÙË ¯ÔÚ‹ÁËÛË ÙfiÛÔ ÙˆÓ ÌË ÂÎÏÂÎÙÈÎÒÓ ‚-·ÔÎÏÂÈÛÙÒÓ18 fiÛÔ Î·È ÙˆÓ ‚1 ÂÎÏÂÎÙÈÎÒÓ ·ÔÎÏÂÈÛÙÒÓ.19-21 Δ· ‰Â‰Ô̤ӷ ·˘Ù¿ ‰Â›¯ÓÔ˘Ó fiÙÈ ÔÈ ‚-·ÔÎÏÂÈÛÙ¤˜ ¤¯Ô˘Ó ‰˘ÛÌÂÓ›˜ ÂȉڿÛÂȘ ÛÙÔ ÌÂÙ·‚ÔÏÈÛÌfi Ù˘ ÁÏ˘Îfi˙˘ ˘ÂÚÙ·ÛÈÎÒÓ ·ÛıÂÓÒÓ, ·ÏÏ¿ Î·È ·ÛıÂÓÒÓ Ì ™¢2. ™Â Ì›· ÌÂÁ¿ÏË ÌÂϤÙË (NHS I, NHS II, HPFS), ÛÙËÓ ÔÔ›· Û˘ÌÌÂÙ›¯·Ó 19.472 ¿Ó‰Ú˜ Î·È 55.344 Á˘Ó·›Î˜, ÔÈ ˘ÂÚÙ·ÛÈÎÔ› ·ÛıÂÓ›˜ Ô˘ ¤·ÈÚÓ·Ó ‚-·ÔÎÏÂÈÛÙ¤˜ ›¯·Ó ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ™¢2 Û ۇÁÎÚÈÛË Ì ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ ¤·ÈÚÓ·Ó ·˘Ù¿ Ù· Ê¿Ú̷η.11 ¶·ÚfiÌÔÈ·, ÛÙË ÌÂϤÙË ARIC (Atherosclerosis Risk in Communities study) Ë ¯ÔÚ‹ÁËÛË
£∂ƒ∞¶∂π∞ - º∞ƒª∞∫∞ ‚-·ÔÎÏÂÈÛÙÒÓ Û˘Óԉ‡ÔÓÙ·Ó ·fi ¶›Ó·Î·˜ 4: ™¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ‰È·‚‹ÙË, ÁÈ· ı¿Ó·ÙÔ Ì›· ηٿ 28% ·‡ÍËÛË ÙÔ˘ ÎÈÓ‰‡- Î·È ÁÈ· ÙËÓ Â›Ù¢ÍË ÓÔÚÌÔÁÏ˘Î·ÈÌ›·˜ (ÌÂϤÙË DREAM) ÓÔ˘ ÂÌÊ¿ÓÈÛ˘ ™¢2 Û ۇÁÎÚÈÛË ŒÎ‚·ÛË ƒ·ÌÈÚ›ÏË ∂ÈÎÔÓÈÎfi ™¯ÂÙÈÎfi˜ P Ì ٷ ¿ÙÔÌ· Ô˘ ‰ÂÓ ¤·ÈÚÓ·Ó ·˘Ê¿ÚÌ·ÎÔ Î›‰˘ÓÔ˜ Ù‹ ÙË ıÂڷ›· (¶›Ó·Î·˜ 3).22 ™ÙË ÌÂϤÙË INVEST (Inter¡=2623 ¡=2646 (95% ‰È¿ÛÙËÌ· national VErapamil SR-TrandonaÂÌÈÛÙÔÛ‡Ó˘) pril Study) Ë ¯ÔÚ‹ÁËÛË ‚ÂÚ··Ì›¢È·‚‹Ù˘, 449 (17.1) 489 (18.5) 0.91 (0.80-1.03) NS Ï˘ ›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· Ì›· ηٿ n(%) 15% Ì›ˆÛË Ù˘ ›وÛ˘ ÓÂÔÂÌÊ·ÓÈ˙fiÌÂÓÔ˘ ‰È·‚‹ÙË Û ۇ£¿Ó·ÙÔ˜, 31 (1.2) 32 (1.2) 0.98 (0.60-1.60) NS ÁÎÚÈÛË Ì ÙËÓ ÔÌ¿‰· Ô˘ ‹Ú n(%) 23 ·ÁˆÁ‹ Ì ·ÙÂÓÔÏfiÏË. ∂›Ù¢ÍË 1116 (42.5) 1012 (38.2) 1.16 (1.07-1.27) 0.001 ¶Ú¤ÂÈ Ó· ·Ó·ÊÂÚı›, fiÙÈ ÔÈ ÓÂfiÙÂÚÔÈ ‚-·ÔÎÏÂÈÛÙ¤˜, fiˆ˜ Ë Î·Ú- ÓÔÚÌÔÁÏ˘Î·ÈÌ›·˜, n(%) ‚ÂÓÙÈÏfiÏË, Ê·›ÓÂÙ·È Ó· ‚ÂÏÙÈÒÓÔ˘Ó ÙËÓ ÈÓÛÔ˘ÏÈÓÔ¢·ÈÛıËÛ›·. ¶Ú¿ÁÌ·ÙÈ, Û 72 ˘ÂÚÙ·ÛÈÎÔ‡˜ ·ÛıÂÓ›˜ †¶ÚÈÓ ÙË ‰È¿ÁÓˆÛË ÙÔ˘ ™¢2, 26 ı¿Ó·ÙÔÈ ·Ú·ÙËÚ‹ıËÎ·Ó ÛÙËÓ ÔÌ¿‰· Ù˘ Ú·ÌÈÚ›Ï˘ Î·È 28 ı¿Ó·ÙÔÈ ·Ú·ÙËÚ‹ıËÎ·Ó ÛÙËÓ ÔÌ¿‰· ÙÔ˘ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ ¯ˆÚ›˜ ‰È·‚‹ÙË, Ë ¯ÔÚ‹ÁËÛË Î·Ú‚ÂÓÙÈÏfiÏ˘ ·‡ÍËÛ ηٿ 14% ÙËÓ Â˘- Ù˘ ÁÏ˘Îfi˙˘ ̤۷ ·fi ÌÈ· ÔÈÎÈ- Kurtz Î·È Pravenec, ÁÈ· ·Ú¿‰ÂÈÁ·ÈÛıËÛ›· ÛÙËÓ ÈÓÛÔ˘Ï›ÓË, ÂÓÒ Ë ¯Ô- Ï›· Ì˯·ÓÈÛÌÒÓ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì·, ·Ú·Ù‹ÚËÛ·Ó fiÙÈ ÔÈ ·-ª∂∞ Ú‹ÁËÛË ÌÂÙÔÚÔÏfiÏ˘ Ô‰‹ÁËÛ Ì ÙËÓ ·Ó·ÛÙÔÏ‹ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›- ÌÔÚÔ‡Ó Ó· ÂËÚ¿ÛÔ˘Ó ıÂÙÈο Û Ì›ˆÛ‹ Ù˘.24 ¶·ÚfiÌÔÈ· ·ÔÙÂ- Ó˘ ππ.27 √È ·-ª∂∞ ‚ÂÏÙÈÒÓÔ˘Ó ÙËÓ ÙÔ ÌÂÙ·‚ÔÏÈÛÌfi Ù˘ ÁÏ˘Îfi˙˘ ‰È·Ï¤ÛÌ·Ù· ·Ú·ÙËÚ‹ıËÎ·Ó fiÙ·Ó Û˘- ÈÓÛÔ˘ÏÈÓÔ¢·ÈÛıËÛ›· ΢ڛˆ˜ ÛÙÔ˘˜ ̤ÛÔ˘ Ù˘ Ô‰Ô‡ Ù˘ ‚Ú·‰˘ÎÈÓ›Ó˘ ÁÎÚ›ıËÎÂ Ë Î·Ú‚ÂÓÙÈÏfiÏË Ì ÙËÓ ÛÎÂÏÂÙÈÎÔ‡˜ Ì˘˜. ∞˘Ù‹ Ë ‰Ú¿ÛË ‚ÂÏÙÈÒÓÔÓÙ·˜ ÙËÓ ·ÈÌ·ÙÈ΋ ÚÔ‹ ·ÙÂÓÔÏfiÏË.25 ™ÙË ÌÂϤÙË GEMINI ÙˆÓ ·-ª∂∞ ‰È·ÈÛÙÒıËΠÛÙË ÌÂ- ÛÙÔ˘˜ ÛÎÂÏÂÙÈÎÔ‡˜ Ì˘˜.30 ∞ÓÙ›ıÂ(Glycemic Effects in Diabetes Me- ϤÙË HOPE (Heart Outcomes Pre- Ù·, Ë ÙÂÏÌÈÛ·ÚÙ¿ÓË Ê·›ÓÂÙ·È Ó· litus: Carvedilol-metoprolol Compa- vention Evaluation), ÛÙËÓ ÔÔ›· ‰Ú· ‰È·Ì¤ÛÔ˘ Ù˘ ÂÓÂÚÁÔÔ›ËÛ˘ rison in Hypertensives) 1235 ˘ÂÚ- ·Ú·ÙËÚ‹ıËΠ̛· Ì›ˆÛË Ù˘ ÂÌ- ÙˆÓ PPAR-Á ˘Ô‰Ô¯¤ˆÓ30 Ì ¢ÂÚÙ·ÛÈÎÔ› ·ÛıÂÓ›˜ Ì ™¢2, Ô˘ ‹‰Ë Ê¿ÓÈÛ˘ ™¢2 Û ·ÛıÂÓ›˜ Ô˘ ‹- ÁÂÙÈο ·ÔÙÂϤÛÌ·Ù· Û ÔÚÈṲ̂¤·ÈÚÓ·Ó ·-ª∂∞ ‹ ·ÓÙ·ÁˆÓÈÛÙ¤˜ Ú·Ó Ú·ÌÈÚ›ÏË Û ۇÁÎÚÈÛË Ì Ó˜ ÎÏÈÓÈΤ˜ Î·È ÚÔÎÏÈÓÈΤ˜ ÌÂÏ¤ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›- ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ‹Ú·Ó ÂÈÎÔÓÈÎfi Ù˜.31 ¶Ú¿ÁÌ·ÙÈ, Û ÔÚÈṲ̂Ó˜ ÌÂÓ˘ Ù˘¯·ÈÔÔÈ‹ıËÎ·Ó Û ηڂÂÓÙÈ- Ê¿ÚÌ·ÎÔ [102 ·ÛıÂÓ›˜ (3.6%) ϤÙ˜ ÛÙȘ Ôԛ˜ ¯ÔÚËÁ‹ıËΠÏfiÏË (‰fiÛË ÙÈÙÏÔÔ›ËÛ˘ 6.25 mg ÛÙËÓ ÔÌ¿‰· Ù˘ Ú·ÌÈÚ›Ï˘ ¤Ó·ÓÙÈ ÙÂÏÌÈÛ·ÚÙ¿ÓË ˆ˜ ÌÔÓÔıÂڷ›· ¤ˆ˜ 25 mg) ‹ ÌÂÙÔÚÔÏfiÏË (‰fiÛË 155 ·ÛıÂÓÒÓ (5,4%) ÛÙËÓ ÔÌ¿‰· Û ÌË ‰È·‚ËÙÈÎÔ‡˜ ˘ÂÚÙ·ÛÈÎÔ‡˜ ÙÈÙÏÔÔ›ËÛ˘ 50 mg ¤ˆ˜ 200 mg) 2 ÙÔ˘ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘, Û¯ÂÙÈ- ·ÛıÂÓ›˜ ·Ú·ÙËÚ‹ıËΠ‚ÂÏÙ›ˆÛË ÊÔÚ¤˜ ÙË Ì¤Ú·. ªÂÙ¿ ·fi 5 Ì‹Ó˜ Îfi˜ ΛӉ˘ÓÔ˜: 0.66, p<0.001].28 Ù˘ ÈÓÛÔ˘ÏÈÓÔ¢·ÈÛıËÛ›·˜.32 ıÂڷ›· ÔÈ ·ÛıÂÓ›˜ Ô˘ ¤·ÈÚ™ÙË ÌÂϤÙË DREAM (Diabetes Ó·Ó Î·Ú‚ÂÓÙÈÏfiÏË ·ÚÔ˘Û›·Û·Ó Reduction Assessment with Rami∞Ó·ÛÙÔÏ›˜ ÙˆÓ ‰È·‡ÏˆÓ Ì›ˆÛË Ù˘ ·ÓÙ›ÛÙ·Û˘ ÛÙËÓ ÈÓ- pril and Rosiglitazone Medication), ·Û‚ÂÛÙ›Ô˘ ÛÔ˘Ï›ÓË, ·ÏÏ¿ Î·È ÂÏ¿ÙÙˆÛË ÙˆÓ ˆÛÙfiÛÔ, ‰È·ÈÛÙÒıËΠfiÙÈ Ë ¯ÔÂȤ‰ˆÓ Ù˘ ÁÏ˘ÎÔ˙˘ÏȈ̤Ó˘ ·È- Ú‹ÁËÛË 15 mg Ú·ÌÈÚ›Ï˘ ÙËÓ √È ·Ó·ÛÙÔÏ›˜ ÙˆÓ ‰È·‡ÏˆÓ ·Û‚ÂÌÔÛÊ·ÈÚ›Ó˘ (HbA1c), ÂÓÒ ÔÈ Ë̤ڷ ÁÈ· 3 ¯ÚfiÓÈ· ‰ÂÓ Ì›ˆÛ ÛÙ›Ô˘ Ê·›ÓÂÙ·È fiÙÈ ÌÂÈÒÓÔ˘Ó ÙËÓ ·ÛıÂÓ›˜ Ô˘ ‹Ú·Ó ÌÂÙÔÚÔÏfiÏË ÙËÓ Èı·ÓfiÙËÙ· ÂÌÊ¿ÓÈÛ˘ ™¢2 ·ÂÏ¢ı¤ÚˆÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘, ‰ÂÓ ÂÌÊ¿ÓÈÛ·Ó ÌÂÙ·‚ÔÏ‹ Ù˘ ÈÓ- ÛÙÔ˘˜ ·ÛıÂÓ›˜ ¯ˆÚ›˜ ηډȷÁÁÂÈ- ÁÂÁÔÓfi˜ ÙÔ ÔÔ›Ô ÂÍÈÛÔÚÚÔÂ›Ù·È ÛÔ˘ÏÈÓÔ·ÓÙ›ÛÙ·Û˘ Ì ·Ú¿ÏÏËÏË ·Î‹ ÓfiÛÔ. ∞Í›˙ÂÈ Ó· ÛËÌÂȈı›, ·fi ÙËÓ ÈηÓfiÙËÙ· ÙÔ˘˜ Ó· ·˘Í¿·‡ÍËÛË Ù˘ ÁÏ˘ÎÔ˙˘ÏȈ̤Ó˘ ·È- fï˜, fiÙÈ Ë Â›Ù¢ÍË ÓÔÚÌÔÁÏ˘- ÓÔ˘Ó ÙËÓ ÚfiÛÏË„Ë Ù˘ ÁÏ˘Îfi˙˘ 33 34 ÌÔÛÊ·ÈÚ›Ó˘ (HbA1c).26 ηÈÌ›·˜ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ‹- ÛÙÔ˘˜ ÂÚÈÊÂÚÈÎÔ‡˜ ÈÛÙÔ‡˜. ∂ÈÚfiÛıÂÙ·, ·Ó·Ê¤ÚÂÙ·È fiÙÈ Ú·Ó Ú·ÌÈÚ›ÏË Î·È Â›¯·Ó Ê˘ÛÈÔÏÔ- ŒÙÛÈ ÔÈ ·Ó·ÛÙÔÏ›˜ ÙˆÓ ‰È·‡ÏˆÓ ÔÚÈṲ̂ÓÔÈ ‚-·ÔÎÏÂÈÛÙ¤˜, fiˆ˜ Ë ÁÈο ›‰· ÁÏ˘Îfi˙˘ ÓËÛÙ›·˜ ·Û‚ÂÛÙ›Ô˘ ‰ÂÓ ÂËÚ¿˙Ô˘Ó ‰˘ÈÓ‰ÔÏfiÏË, Ô˘ ¤¯Ô˘Ó ÂÓ‰ÔÁÂÓ‹ ‹Ù·Ó ÌÂÁ·Ï‡ÙÂÚË Û ۇÁÎÚÈÛË Ì ÛÌÂÓÒ˜ ÙÔ ÌÂÙ·‚ÔÏÈÛÌfi Ù˘ ÁÏ˘Û˘Ì·ıËÙÈÎÔÌÈÌËÙÈ΋ ‰Ú¿ÛË, ÂÌ- ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ‹Ú·Ó ÂÈÎÔÓÈÎfi Îfi˙˘.35-37 Ê·Ó›˙Ô˘Ó ÏÈÁfiÙÂÚ˜ ‰˘ÛÌÂÓ›˜ Ê¿ÚÌ·ÎÔ (¶›Ó·Î·˜ 4).29 ™Â Ì›· ÌÂϤÙË 16.176 ÛÙÂÊ·ÓÈÂȉڿÛÂȘ ÛÙËÓ ÈÓÛÔ˘ÏÈÓÔ¢·È∂ӉȷʤÚÔÓ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÔÚÈ- ·›ˆÓ ·ÛıÂÓÒÓ Ì ˘¤ÚÙ·ÛË Ë ¯ÔÛıËÛ›· Î·È Û ¿ÏϘ ÌÂÙ·‚ÔÏÈΤ˜ Ṳ̂Ó˜ ÌÂϤÙ˜, ÛÙȘ Ôԛ˜ ·Ó·- Ú‹ÁËÛË ‚ÂÚ··Ì›Ï˘ ›¯Â ÌÈÎÚfi·Ú·Ì¤ÙÚÔ˘˜ Û ۇÁÎÚÈÛË Ì ¿Ï- ʤÚÔÓÙ·È ‰È·ÊÔÚÂÙÈÎÔ› Ì˯·ÓÈÛÌÔ› ÙÂÚË Èı·ÓfiÙËÙ· Ó· Ô‰ËÁ‹ÛÂÈ ÏÔ˘˜ ‚-·ÔÎÏÂÈÛÙ¤˜.18 ‰Ú¿Û˘ ·˘ÙÒÓ ÙˆÓ Î·ÙËÁÔÚÈÒÓ ÛÙËÓ ÂÌÊ¿ÓÈÛË ™¢2 ·fi ÙË ıÂÚ·23 ·ÓÙÈ˘ÂÚÙ·ÛÈÎÒÓ Ê·ÚÌ¿ÎˆÓ ÛÙÔ Â›· Ì ·ÙÂÓÔÏfiÏË (¶›Ó·Î·˜ 5). ∞Ó·ÛÙÔÏ›˜ ÙÔ˘ ÌÂÙ·ÙÚÂÙÈÎÔ‡ ÂÓ- ÌÂÙ·‚ÔÏÈÛÌfi Ù˘ ÁÏ˘Îfi˙˘. √È ™ÙËÓ ›‰È· ÌÂϤÙË Ë ÚÔÛı‹ÎË ˙‡ÌÔ˘ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘ (·-ª∂∞) Î·È ·ÓÙ·ÁˆÓÈÛÙ¤˜ ÙˆÓ ˘Ô‰Ô¯¤¶›Ó·Î·˜ 5: μÂÚ··Ì›ÏË ¤Ó·ÓÙÈ ·ÙÂÓÔÏfiÏ˘ (ÌÂϤÙË INVEST) ˆÓ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘ ππ μÂÚ··Ì›ÏË ∞ÙÂÓÔÏfiÏË √È ·-ª∂∞ Î·È ÔÈ ·ÓÙ·ÁˆÓÈÛÙ¤˜ ÙˆÓ ∞ÚÈıÌfi˜ ·ÛıÂÓÒÓ 8098 8078 ˘Ô‰Ô¯¤ˆÓ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘ ππ ∂ÌÊ¿ÓÈÛË ™¢2 569 (7%) 665(8.2%) ‰ÚÔ˘Ó Â˘ÓÔ˚ο ÛÙÔ ÌÂÙ·‚ÔÏÈÛÌfi
21
¢∂∫∂ªμƒπ√™ 2008
¶›Ó·Î·˜ 6: μ·ÏÛ·ÚÙ¿ÓË ¤Ó·ÓÙÈ ·ÌÏԉțÓ˘ (ÌÂϤÙË VALUE) μ·ÏÛ·ÚÙ¿ÓË (n=7622)
∞ÌÏԉțÓË (n=7576)
∞Ú¯È΋ ÙÈÌ‹ Δ¤ÏÔ˜ ÌÂϤÙ˘ ∞Ú¯È΋ ÙÈÌ‹ Δ¤ÏÔ˜ ÌÂϤÙ˘ °Ï˘Îfi˙Ë (mg/dl) 124,2 (±52.2) 120.6 (±46.8) 124.2 (±50.4) 124,2 (±48.6) ·-ª∂∞ (ÙÚ·ÓÙÔÏ·Ú›ÏË) ÛÙË ıÂڷ›· Ì ‚ÂÚ··Ì›ÏË Ì›ˆÛ ÙÔÓ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ™¢2 (ηٿ 44% Ì ÚÔÛı‹ÎË 2 mg ÙÚ·ÓÙÔÏ·Ú›Ï˘ Û 180 mg ‚ÂÚ··Ì›Ï˘ ÙËÓ Ë̤ڷ Î·È Î·Ù¿ 42% Ì ÚÔÛı‹ÎË 4 mg ÙÚ·ÓÙÔÏ·Ú›Ï˘ Û 240 mg ‚ÂÚ··Ì›Ï˘ ÙËÓ Ë̤ڷ), ÂÓÒ Ë ÚÔÛı‹ÎË ˘‰ÚԯψÚÔıÂÈ·˙›‰Ë˜ ÛÙËÓ ·ÙÂÓÔÏfiÏË ·‡ÍËÛ ÙÔÓ Î›Ó‰˘ÓÔ (ηٿ 7% Ì ÚÔÛı‹ÎË 12.5 mg ˘‰ÚԯψÚÔıÂÈ·˙›‰Ë˜ Û 50mg ·ÙÂÓÔÏfiÏ˘ ÙËÓ Ë̤ڷ Î·È Î·Ù¿ 38% Ì ÚÔÛı‹ÎË 25 mg ˘‰ÚԯψÚÔıÂÈ·˙›‰Ë˜ Û 100 mg ·ÙÂÓÔÏfiÏ˘ ÙËÓ Ë̤ڷ).23 ™Â Ì›· ¿ÏÏË ÌÂϤÙË (VALUE), Ë ıÂڷ›· Ì ·ÓÙ·ÁˆÓÈÛÙ‹ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘ (‚·ÏÛ·ÚÙ¿ÓË) Û˘Û¯ÂÙ›ÛıËΠ̛̠ˆÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÂÌÊ¿ÓÈÛ˘ ™¢2 Û ۇÁÎÚÈÛË Ì ÙË ıÂڷ›· Ì ·ÌÏԉțÓË (¶›Ó·Î·˜ 6).38 ∞ÓÙ·ÁˆÓÈÛÙ¤˜ ÙˆÓ ·-·‰ÚÂÓÂÚÁÈÎÒÓ ˘Ô‰Ô¯¤ˆÓ ∏ ÌÂϤÙË ALS ¤‰ÂÈÍ fiÙÈ Ë Ú·˙ÔÛ›ÓË ‚ÂÏÙÈÒÓÂÈ ÙËÓ Â˘·ÈÛıËÛ›· ÛÙËÓ ÈÓÛÔ˘Ï›ÓË Û ·ÛıÂÓ›˜ Ì ȉÈÔ·ı‹ ˘¤ÚÙ·ÛË.39 ∏ ÙÂÚ·˙ÔÛ›ÓË Ê·›ÓÂÙ·È Ó· ÌËÓ ¤¯ÂÈ Î¿ÔÈ· ›‰Ú·ÛË ÛÙËÓ ÈÓÛÔ˘ÏÈÓÔ¢·ÈÛıËÛ›·,40 ÂÓÒ ‰ÂÓ ˘¿Ú¯Ô˘Ó ‰Â‰Ô̤ӷ fiÛÔÓ ·ÊÔÚ¿ ÙËÓ Ù·ÌÛÔ˘ÏÔÛ›ÓË. Δ¤ÏÔ˜ Ë Ô˘Ú·È‰›ÏË ·ÚfiÙÈ ‰ÂÓ ¤¯ÂÈ ÂȉڿÛÂȘ ÛÙÔ ÌÂÙ·‚ÔÏÈÛÌfi Ù˘ ÁÏ˘Îfi˙˘, ÂËÚ¿˙ÂÈ ¤Ó· ¿ÏÏÔ Î·Ú‰È·ÁÁÂÈÎfi ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘, ÙÔ ÈÓˆ‰ÔÁfiÓÔ.41
¢ÈÂÁ¤ÚÙ˜ ÙˆÓ ÎÂÓÙÚÈÎÒÓ ·-·‰ÚÂÓÂÚÁÈÎÒÓ ˘Ô‰Ô¯¤ˆÓ ∏ ÎÏÔÓȉ›ÓË Ê·›ÓÂÙ·È Ó· ¤¯ÂÈ Ô˘‰¤ÙÂÚ˜ ÂȉڿÛÂȘ ÛÙÔ ÌÂÙ·‚ÔÏÈÛÌfi Ù˘ ÁÏ˘Îfi˙˘.42 ™Â Ì›· ÚfiÛÊ·ÙË ÌÂϤÙË, ÛÙËÓ ÔÔ›· Û˘ÌÌÂÙ›¯·Ó 108 Á˘Ó·›Î˜ (55 ÌË ‰È·‚ËÙÈΤ˜ ˘ÂÚÙ·ÛÈΤ˜ Á˘Ó·›Î˜ Î·È 53 ÓÔÚÌÔÙ·ÛÈΤ˜ Á˘Ó·›Î˜), ‰ÈÂÚ¢ӋıËÎÂ Ë ‰Ú¿ÛË Ù˘ ÌÔÍÔÓȉ›Ó˘ ÛÙ· ›‰· Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ ÙÔ˘ ÔÚÔ‡. ∏ ¯ÔÚ‹ÁËÛË 0.4 mg ÙËÓ Ë̤ڷ ÌÔÍÔÓȉ›Ó˘ ÁÈ· 12 ‚‰ÔÌ¿‰Â˜ ÛÙȘ ˘ÂÚÙ·ÛÈΤ˜ Á˘Ó·›Î˜ ›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· Ì›· Ì›ˆÛË Ù˘ ÁÏ˘Îfi˙˘ ÓËÛÙ›·˜ ηٿ 2.1% (±16.7%, p<0.05),( ¶›Ó·Î·˜ 7).43 ¡ÂÔÂÌÊ·ÓÈ˙fiÌÂÓÔ˜ ۷ί·Ú҉˘ ‰È·‚‹Ù˘ Î·È Î·Ú‰È·ÁÁÂȷο Û˘Ì‚¿Ì·Ù· ∂›Ó·È ÛËÌ·ÓÙÈÎfi Ó· ·Ó·Ï˘ı› Ë Â›‰Ú·ÛË ÙÔ˘ ÓÂÔÂÌÊ·ÓÈ˙fiÌÂÓÔ˘ ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË Û ˘fi ıÂڷ›· ˘ÂÚÙ·ÛÈÎÔ‡˜ ·ÛıÂÓ›˜ fiÛÔÓ ·ÊÔÚ¿ ÙËÓ ÂÌÊ¿ÓÈÛË Î·Ú‰È·ÁÁÂÈ·ÎÒÓ Û˘Ì‚·Ì¿ÙˆÓ. ¢È¿ÊÔÚ˜ ÌÂϤÙ˜ ·Ó·Ê¤ÚÔ˘Ó ·‡ÍËÛË ÙÔ˘ ηډȷÁÁÂÈ·ÎÔ‡ ÎÈÓ‰‡ÓÔ˘ ÛÙÔ˘˜ ·Ú·¿Óˆ ·ÛıÂÓ›˜. ¶ÚfiÛÊ·Ù·, Û ̛· ÌÂϤÙË ‰È¿ÚÎÂÈ·˜ 28 ÂÙÒÓ ‰ÈÂÚ¢ӋıËÎÂ Ë Â›‰Ú·ÛË ÙÔ˘ ÓÂÔÂÌÊ·ÓÈ˙fiÌÂÓÔ˘ ™¢2 ÛÙ· ηډȷÁÁÂȷο Û˘Ì‚¿Ì·Ù·. ™ÙË ÌÂϤÙË ·˘Ù‹ Û˘ÌÌÂÙ›¯·Ó 754 ·ÛıÂÓ›˜ Ô˘ ¤·ÈÚÓ·Ó ·ÓÙÈ˘ÂÚÙ·ÛÈ΋ ·ÁˆÁ‹. Δ· ·ÓÙÈ˘ÂÚÙ·ÛÈο Ê¿Ú̷η Ô˘ ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó ‹Ù·Ó Ù· ıÂÈ·˙ȉÈο ‰ÈÔ˘ÚËÙÈο, ÔÈ ‚-·ÔÎÏÂÈÛÙ¤˜,
¶›Ó·Î·˜ 7: ∂›Â‰· ÁÏ˘Îfi˙˘ ÚÈÓ Î·È ÌÂÙ¿ ÙË ¯ÔÚ‹ÁËÛË 0.4 mg ÌÔÍÔÓȉ›Ó˘ n= 51
°Ï˘Îfi˙Ë ÓËÛÙ›·˜ (mg/dl) ∞‰ÈÔÓÂÎÙ›ÓË (Ìg/dl)
22
¶ÚÈÓ ÙË ¯ÔÚ‹ÁËÛË ÌÔÍÔÓȉ›Ó˘
ªÂÙ¿ ÙË ¯ÔÚ‹ÁËÛË ÌÔÍÔÓȉ›Ó˘
ªÂÙ·‚ÔÏ‹ (%)
P
98.5±12.6
95.2±12.6
2.1±16.7
<0.05
6.21±0.85
6.63±0.60
8.5±16.3
0.01
ÔÈ ·Ó·ÛÙÔÏ›˜ ÙˆÓ ‰È·‡ÏˆÓ ·Û‚ÂÛÙ›Ô˘ Î·È ÔÈ ·Ó·ÛÙÔÏ›˜ ÙÔ˘ ÌÂÙ·ÙÚÂÙÈÎÔ‡ ÂÓ˙‡ÌÔ˘ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘. ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÌÂϤÙ˘ 148 ·ÛıÂÓ›˜ (20.4%) ÂÌÊ¿ÓÈÛ·Ó ™¢2, Ô ÔÔ›Ô˜ Û˘Û¯ÂÙ›ÛıËΠıÂÙÈο Ì ÙÔ ‰Â›ÎÙË Ì¿˙·˜ ÛÒÌ·ÙÔ˜, Ù· ›‰· ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Î·È ÙË ¯ÔÚ‹ÁËÛË ‚-·Ó·ÛÙÔϤˆÓ. √ ÓÂÔÂÌÊ·ÓÈ˙fiÌÂÓÔ˜ ™¢2 ÛÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜ Û˘Û¯ÂÙ›ÛıËΠıÂÙÈο Ì ÙËÓ ÂÌÊ¿ÓÈÛË ·ÁÁÂÈ·ÎÔ‡ ÂÁÎÂÊ·ÏÈÎÔ‡ ÂÂÈÛÔ‰›Ô˘ (Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜: 1.67, 95% ‰È¿ÛÙËÌ· ÂÌÈÛÙÔÛ‡Ó˘: 1.1-2.6, p<0.05), ÂÌÊÚ¿ÁÌ·ÙÔ˜ ÙÔ˘ Ì˘Ôηډ›Ô˘ (Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜: 1.66, 95% ‰È¿ÛÙËÌ· ÂÌÈÛÙÔÛ‡Ó˘: 1.1-2.5, p<0.05) Î·È ÙËÓ ÔÏÈ΋ ıÓËÙfiÙËÙ· (Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜: 1.42, 95% ‰È¿ÛÙËÌ· ÂÌÈÛÙÔÛ‡Ó˘: 1.1-1.9, p<0.05).44 ∂ÈÚfiÛıÂÙ· ÌÈ· ¿ÏÏË ÌÂϤÙË, ÛÙËÓ ÔÔ›· Û˘ÌÌÂÙ›¯·Ó 795 ·ÛıÂÓ›˜ Ì ˘¤ÚÙ·ÛË ¤‰ÂÈÍ fiÙÈ Ë ÂÌÊ¿ÓÈÛË ™¢2 ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ıÂڷ›·˜ ·ÔÙÂÏ› ÛËÌ·ÓÙÈÎfi ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË Î·Ú‰È·ÁÁÂȷ΋˜ ÓfiÛÔ˘. ™˘ÁÎÂÎÚÈ̤ӷ, Ô Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜ ÁÈ· ηډȷÁÁÂȷο Û˘Ì‚¿Ì·Ù· ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ÂÌÊ¿ÓÈÛ·Ó ‰È·‚‹ÙË Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ıÂڷ›·˜ ‹Ù·Ó 2.92 (95% ‰È¿ÛÙËÌ· ÂÌÈÛÙÔÛ‡Ó˘: 1.33-6.41, p=0.007) Û ۇÁÎÚÈÛË Ì ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ ÂÌÊ¿ÓÈÛ·Ó ‰È·‚‹ÙË. Δ·˘Ùfi¯ÚÔÓ·, ·ÚfiÌÔÈÔ˜ ‹Ù·Ó Î·È Ô Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜ ÁÈ· ηډȷÁÁÂȷο Û˘Ì‚¿Ì·Ù· ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ›¯·Ó ‰È·‚‹ÙË Î·Ù¿ ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂڷ›·˜: 3.57 (95% ‰È¿ÛÙËÌ· ÂÌÈÛÙÔÛ‡Ó˘: 1.65-7.73, p=0.001) Û ۇÁÎÚÈÛË Ì ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ ÂÌÊ¿ÓÈÛ·Ó ‰È·‚‹ÙË.45 ™˘ÁÎÂÓÙÚˆÙÈο ‰Â‰Ô̤ӷ ÁÈ· ÙËÓ Â›‰Ú·ÛË ÙˆÓ ·ÓÙÈ˘ÂÚÙ·ÛÈÎÒÓ Ê·ÚÌ¿ÎˆÓ ÛÙËÓ ÂÌÊ¿ÓÈÛË Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË ™Â Ì›· ÚfiÛÊ·ÙË ÌÂÙ·-·Ó¿Ï˘ÛË, 22 ÎÏÈÓÈÎÒÓ ÌÂÏÂÙÒÓ, ‰ÈÂÚ¢ӋıËÎÂ Ë ÂÌÊ¿ÓÈÛË ™¢2 Û 143.153 ÌË ‰È·‚ËÙÈÎÔ‡˜ ˘ÂÚÙ·ÛÈÎÔ‡˜ ·ÛıÂÓ›˜ (¶›Ó·Î·˜ 8).46 ∏ ÌÂÙ·-·Ó¿Ï˘ÛË ¤‰ÂÈÍ fiÙÈ ÔÈ ·ÓÙ·ÁˆÓÈÛÙ¤˜ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘ Î·È ÔÈ ·Ó·ÛÙÔÏ›˜ ÙÔ˘ ÌÂÙ·ÙÚÂÙÈÎÔ‡ ÂÓ˙‡ÌÔ˘ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘ Â›Ó·È Ù· ·ÓÙÈ˘ÂÚÙ·ÛÈο Ê¿Ú̷η Ô˘ Û¯ÂÙ›˙ÔÓÙ·È ÏÈÁfiÙÂÚÔ Ì ÙËÓ ÂÌÊ¿ÓÈÛË ™¢2 ÛÙÔ˘˜ ˘ÂÚÙ·ÛÈÎÔ‡˜ ·ÛıÂÓ›˜ (Î·È Ì¿ÏÈÛÙ· Ê·›ÓÂÙ·È fiÙÈ ·ÛÎÔ‡Ó ÚÔ-
£∂ƒ∞¶∂π∞ - º∞ƒª∞∫∞ ¶›Ó·Î·˜ 8: ªÂϤÙ˜
ŒÙÔ˜ ‰ËÌÔÛ›Â˘Û˘
¢È¿ÚÎÂÈ· º¿ÚÌ·ÎÔ 1 (¤ÙË)
∂ÌÊ¿ÓÈÛË ™¢2, Ó (%)
º¿ÚÌ·ÎÔ 2
∂ÌÊ¿ÓÈÛË º¿ÚÌ·ÎÔ 3 ∂ÌÊ¿ÓÈÛË ™¢2,Ó (%) ™¢2, Ó (%)
AASK
2006
3.8
ACE in h.
45 (11)
‚-blocker
70 (7.2)
CCB
32 (15.8)
ALLHAT
2002
4.0
ACE inh.
119 (3)
CCB
154 (3.8)
diuretic
302 (4.4)
ALPINE
2003
1.0
ARB
1 (0.5)
Diuretic
8 (4)
ANBP-2
2005
4.1
ACE inh.
138 (4.9)
Diuretic
200 (7.1)
ASCOT
2005
5.5
‚-blocker
799(11.3)
CCB
567 (8)
CAPPP
1999
6.1
ACE inh.
337 (6.5)
‚-blocker
380 (7.2)
CHARM
2003
3.1
ARB
163(6)
Placebo
202 (7.4)
DREAM
2006
3.0
ACE inh.
449 (17.1)
Placebo
489 (18.4)
EWPHE
1991
4.7
Diuretic
29 (6.9)
Placebo
20 (4.8)
FEVER
2005
3.3
CCB
177 (3.6)
Placebo
154 (3.1)
HAPPHY
1987
3.8
‚-blocker
86 (2.6)
Diuretic
75 (2.3)
HOPE
2001
4.5
ACE inh.
102 (3.6)
Placebo
155 (5.3)
INSIGHT
2000
3.0
CCB
136 (5.4)
Diuretic
176 (7)
INVEST
2003
4.0
‚-blocker
665 (8.2)
CCB
569 (7)
LIFE
2002
4.8
ARB
242 (6)
‚-blocker
320 (8)
MRC-E
1992
5.8
‚-blocker
37 (3)
Diuretic
43 (4)
placebo
34 (1.5)
NORDIL
2000
4.5
‚-blocker
251 (5)
CCB
216 (4.2)
CCB
95 (4.8)
or diuretic PEACE
2004
4.8
ACE inh.
335 (9.7)
Placebo
399 (11.5)
SCOPE
2003
3.7
ARB
93 (4.3)
Placebo
115 (5.3)
SHEP
1998
3.0
Diuretic
140 (8.6)
Placebo
118 (7.4)
STOP-2
1999
4.0
ACE inh.
93 (4.7)
‚-blocker
97 (4.9)
or diuretic VALUE
2004
4.2
ARB
690 (13.6)
CCB
845 (16.7)
ARB: ·ÓÙ·ÁˆÓÈÛÙ¤˜ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘ ππ, CCB: ·ÓÙ·ÁˆÓÈÛÙ¤˜ ÙˆÓ ‰È·‡ÏˆÓ ·Û‚ÂÛÙ›Ô˘, ACE inhibitor: ·Ó·ÛÙÔÏ›˜ ÙÔ˘ ÌÂÙ·ÙÚÂÙÈÎÔ‡ ÂÓ˙‡ÌÔ˘ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘, diuretic: ‰ÈÔ˘ÚËÙÈο, placebo: ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ, ‚-blocker: ‚-·ÔÎÏÂÈÛÙ¤˜ Lancet 2007;369:201-7
Ûٷ٢ÙÈ΋ ‰Ú¿ÛË). ∞ÎÔÏÔ˘ıÔ‡Ó ÔÈ ·Ó·ÛÙÔÏ›˜ ÙˆÓ ‰È·‡ÏˆÓ ·Û‚ÂÛÙ›Ô˘ Î·È Ë ıÂڷ›· Ì ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ (Ô˘‰¤ÙÂÚË Â›‰Ú·ÛË). Δ¤ÏÔ˜ Ù· ·ÓÙÈ˘ÂÚÙ·ÛÈο Ê¿Ú̷η Ô˘ ¤¯Ô˘Ó ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·‡ÍËÛË Ù˘ ›وÛ˘ ÓÂÔÂÌÊ·ÓÈ˙fiÌÂÓÔ˘ ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË Â›Ó·È ÔÈ ‚-·ÔÎÏÂÈÛÙ¤˜ Î·È Ù· ıÂÈ·˙ȉÈο ‰ÈÔ˘ÚËÙÈο (¶›Ó·Î·˜ 9).
˙ȉÈο ‰ÈÔ˘ÚËÙÈο, Ù· ÔÔ›· Â›Ó·È ·ÔÙÂÏÂÛÌ·ÙÈο Ê¿Ú̷η ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ˘¤ÚÙ·Û˘, ¤¯Ô˘Ó ¯·ÌËÏfi ÎfiÛÙÔ˜, Ë ·‡ÍËÛË Ù˘ Èı·ÓfiÙËÙ·˜ ÚfiÎÏËÛ˘ ‰È·Ù·Ú·¯‹˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ Ù˘
¶›Ó·Î·˜ 9: ™¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ™¢2 Ì ‚¿ÛË ÙËÓ Â›‰Ú·ÛË ÙˆÓ ‰ÈÔ˘ÚËÙÈÎÒÓ (ÚÔÛ·ÚÌÔṲ̂ÓÔ ·fi Elliott et all, Lancet 2007;369:201-7) ™¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜
™˘ÌÂÚ¿ÛÌ·Ù· ∏ ÂÈÏÔÁ‹ Ù˘ ·ÓÙÈ˘ÂÚÙ·ÛÈ΋˜ ıÂڷ›·˜ ¤¯ÂÈ ÌÂÁ¿ÏË ÛËÌ·Û›· ÂÂȉ‹ ÂËÚ¿˙ÂÈ ÙË ÓÔÛËÚfiÙËÙ·, ÙË ıÓËÛÈÌfiÙËÙ·, ·ÏÏ¿ Î·È ÙÔ ÎfiÛÙÔ˜ Ù˘ È·ÙÚÈ΋˜ ÊÚÔÓÙ›‰·˜. ¶·ÚfiÙÈ ÔÈ ‚-·ÔÎÏÂÈÛÙ¤˜ Î·È Ù· ıÂÈ·-
ÁÏ˘Îfi˙˘ ‹ ·ÎfiÌ· Î·È Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË, Ì ÙË ¯ÔÚ‹ÁËÛË ÙÔ˘˜ ÛÙËÓ Ô˘Û›· ·˘Í¿ÓÂÈ ÙÔ ÎfiÛÙÔ˜ Ù˘ È·ÙÚÈ΋˜ ÊÚÔÓÙ›‰·˜. ∏ Û˘Ó‡·ÚÍË ˘¤ÚÙ·Û˘ Î·È ™¢2 ·˘Í¿ÓÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈ-
Diuretic μ-blocker Placebo CCB ACE inhibitor ARB
1 0.90 0.77 0.75 0.67 0.57
95% ‰È¿ÛÙËÌ· ÂÌÈÛÙÔÛ‡Ó˘
P
(0.75-1.09) (0.63-0.94) (0.62-0.90) (0.56-0.80) (0.46-0.72)
0.30 0.009 0.002 <0.0001 <0.0001
23
¢∂∫∂ªμƒπ√™ 2008
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∞¡∞∫§∏™∏ ∫À∫§√º√ƒπ∞™ Δ√À RIMONABANT √ ∂˘Úˆ·˚Îfi˜ √ÚÁ·ÓÈÛÌfi˜ º·ÚÌ¿ÎˆÓ (EMEA) ·Ó·Î¿ÏÂÛ ÛÙȘ 23 √ÎÙˆ‚Ú›Ô˘ 2008 ÙËÓ ¿‰ÂÈ· ΢ÎÏÔÊÔÚ›·˜ ÙÔ˘ Rimonabant, ÙÔ ÔÔ›Ô Î˘ÎÏÔÊÔÚÔ‡Û ·fi ÙÔÓ πÔ‡ÓÈÔ ÙÔ˘ 2006 Û 18 ¯ÒÚ˜-̤ÏË Ù˘ ∂˘Úˆ·˚΋˜ ŒÓˆÛ˘ Ì ÙÔ fiÓÔÌ· Acomplia ·fi ÙË Ê·Ú̷΢ÙÈ΋ ÂÙ·ÈÚ›· Sanofi-Aventis. ™‡Ìʈӷ Ì ÙËÓ ·fiÊ·ÛË ÙÔ˘ ∂ª∂∞, Ù· ÛÙÔȯ›· Ô˘ Û˘ÁÎÂÓÙÚÒıËÎ·Ó ·fi ÙȘ ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ Ô˘ ÚfiÛÊ·Ù· ÔÏÔÎÏËÚÒıËÎ·Ó Î·È ÔÈ ·Ó·ÊÔÚ¤˜ ·ÓÂÈı˘Ì‹ÙˆÓ ÂÓÂÚÁÂÈÒÓ ÌÂÙ¿ ÙËÓ Î˘ÎÏÔÊÔÚ›· ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ ¤‰ÂÈÍ·Ó fiÙÈ ÙÔ fiÊÂÏÔ˜ ‰ÂÓ Â›Ó·È ÌÂÁ·Ï‡ÙÂÚÔ ·fi ÙÔÓ Î›Ó‰˘ÓÔ Ô˘ Û˘Ó¿ÁÂÙ·È Ë Ï‹„Ë ÙÔ˘. √È ÂÚÈÙÒÛÂȘ „˘¯È·ÙÚÈÎÒÓ ‰È·Ù·Ú·¯ÒÓ ÛÙÔ˘˜ ·¯˘Û¿ÚÎÔ˘˜ Î·È ˘¤Ú‚·ÚÔ˘˜ Ô˘ ¤Ï·‚·Ó Acomplia ÛÙȘ ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ ‹Ù·Ó ‰ÈÏ¿ÛÈÔ˜ ·˘ÙÒÓ Ô˘ ·Ú·ÙËÚ‹ıËÎ·Ó Û fiÛÔ˘˜ ¤Ï·‚·Ó placebo. ∞fi ÙȘ ·Ó·ÊÔÚ¤˜ Ù˘ Ê·ÚÌ·ÎÔ·ÁÚ‡ÓËÛ˘ Ê¿ÓËΠfiÙÈ Ë Î·Ù¿ıÏÈ„Ë Û fiÛÔ˘˜ Ï¿Ì‚·Ó·Ó ÙÔ Ê¿ÚÌ·ÎÔ Â›Ó·È ÈÔ Û˘¯Ó‹ ·fi fiÙÈ ¤‰ÂÈÍ·Ó ÔÈ ·Ú¯ÈΤ˜ ÎÏÈÓÈΤ˜ ÌÂϤÙ˜, ‚¿ÛÂÈ ÙˆÓ ÔÔ›ˆÓ ‰fiıËÎÂ Ë ¤ÁÎÚÈÛË Ù˘ ΢ÎÏÔÊÔÚ›·˜. ∞fi ÙËÓ ¿ÏÏË ÏÂ˘Ú¿, ÙÔ fiÊÂÏÔ˜ ·Â‰Â›¯ıË ÌÈÎÚfiÙÂÚÔ ÙÔ˘ ·Ó·ÌÂÓÔ̤ÓÔ˘, ÂÂȉ‹ Ë ÎÏÈÓÈ΋ ÂÌÂÈÚ›· ¤‰ÂÈÍ fiÙÈ ÔÈ ·ÛıÂÓ›˜ Ï·Ì‚¿ÓÔ˘Ó ÙÔ Ê¿ÚÌ·ÎÔ ÁÈ· ‚Ú·¯‡ ÌfiÓÔ ‰È¿ÛÙËÌ·. ∏ ÙÂÏÈ΋ Û‡ÛÙ·ÛË ÙÔ˘ ∂ª∂∞ ÚÔ˜ ÙÔ˘˜ ıÂÚ·Â˘Ù¤˜ ÁÈ·ÙÚÔ‡˜ Â›Ó·È Ó· ÌË Û˘ÓÙ·ÁÔÁÚ·ÊÔ‡Ó ÙÔ Ê¿ÚÌ·ÎÔ Û Ӥ· ÂÚÈÛÙ·ÙÈο Î·È Ó· ·ÍÈÔÏÔÁ‹ÛÔ˘Ó Î·Ù¿ ÂÚ›ÙˆÛË fiÛÔ˘˜ ·ÛıÂÓ›˜ Â›Ó·È ‹‰Ë ˘fi ·ÁˆÁ‹. ™ÙÔ˘˜ ·ÛıÂÓ›˜ Û˘ÛÙ‹ÓÂÙ·È Ó· ÌË ‰È·Îfi„Ô˘Ó ·fi ÌfiÓÔÈ ÙÔ˘˜ ÙÔ Ê¿ÚÌ·ÎÔ ·ÏÏ¿ Ó· Û˘Ì‚Ô˘Ï¢ıÔ‡Ó ÙÔÓ ıÂÚ¿ÔÓÙ· È·ÙÚfi ÙÔ˘˜. ∏ Sanofi-Aventis, Û ‰ÂÏÙ›Ô Ù‡Ô˘ Ô˘ Âͤ‰ˆÛ ÙËÓ ›‰È· Ë̤ڷ, ·Ó·ÎÔ›ÓˆÛ fiÙÈ Û˘ÌÌÔÚÊÒÓÂÙ·È Ì ÙËÓ ·fiÊ·ÛË ÙÔ˘ ∂ª∂∞, ¯·Ú·ÎÙËÚ›˙ÂÈ fï˜ ÙËÓ ¿ÚÛË Ù˘ ¿‰ÂÈ·˜ ΢ÎÏÔÊÔÚ›·˜ ÙÔ˘ Acomplia ÚÔÛˆÚÈÓ‹ Î·È ‰ÂÛ̇ÂÙ·È fiÙÈ ı· Û˘ÁÎÂÓÙÚÒÛÂÈ ÂÚÈÛÛfiÙÂÚ· ÛÙÔȯ›·, ÒÛÙ ӷ ·Ô‰Â›ÍÂÈ ÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· Î·È ·ÛÊ¿ÏÂÈ· ÙÔ˘ Û΢¿ÛÌ·ÙÔ˜ Î·È Ó· ÂÙ‡¯ÂÈ ·Ó·ıÂÒÚËÛË Ù˘ ·fiÊ·Û˘. £· Û˘Ó¯›ÛÂÈ ÙȘ ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ Ô˘ ‰ÈÂÍ¿ÁÔÓÙ·È ÂÎÙfi˜ ·fi ·˘Ù¤˜ Ù˘ Ê¿Û˘ IV Î·È ‰ËÏÒÓÂÈ fiÙÈ Â›Ó·È ÂÂÈṲ̂ÓË ˆ˜ ÙÔ Acomplia ı· ·Ô‰Âȯı› ÙÂÏÈο ¯Ú‹ÛÈÌÔ Ê¿ÚÌ·ÎÔ ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ·¯˘Û·ÚΛ·˜ ÛÙ· ¿ÙÔÌ· ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘. ∏ ·Ï‹ıÂÈ· Â›Ó·È fiÙÈ Ù· ·ÔÙÂϤÛÌ·Ù· ÙˆÓ ÙÂÏÂ˘Ù·›ˆÓ ÎÏÈÓÈÎÒÓ ÌÂÏÂÙÒÓ Â›Ó·È ·ÓÙÈÊ·ÙÈο. ∏ ÌÂϤÙË ADAGIO-LIPIDS, Ô˘ ·Ó·ÎÔÈÓÒıËΠÂÓˆÚ›ÙÂÚ· ʤÙÔ˜ ÛÙÔ 77th European Atherosclerosis Society Congress, ¤‰ÂÈÍ ‚ÂÏÙ›ˆÛË ÙˆÓ ÏÈȉ·ÈÌÈÎÒÓ ·Ú·Ì¤ÙÚˆÓ Î·È ÂÏ¿ÙÙˆÛË ÙÔ˘ ÎÔÈÏÈ·ÎÔ‡ Ï›Ô˘˜ ·ÏÏ¿ Ë ÌÂϤÙË STRADIVARIUS, Ë ÔÔ›· ¤ÁÈÓ Ì ÂÓ‰·ÁÁÂÈ·Îfi ˘ÂÚ˯ÔÁÚ¿ÊËÌ· Î·È ·ÚÔ˘ÛÈ¿ÛıËΠÛÙÔ Û˘Ó¤‰ÚÈÔ ÙÔ˘ ACC 2008, ‰ÂÓ ¤‰ÂÈÍ fiÊÂÏÔ˜ fiÛÔÓ ·ÊÔÚ¿ ÛÙËÓ ÂͤÏÈÍË Ù˘ ·ıËÚÔÛÎÏ‹ÚˆÛ˘.
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¢∂∫∂ªμƒπ√™ 2008
∂›Ó·È ∂ÊÈÎÙ‹ Ë Δ·˘Ùfi¯ÚÔÓË ∞ÓÙÈÌÂÙÒÈÛË Ù˘ ∞ıËÚÔÛÎÏ‹ÚˆÛ˘ Î·È Ù˘ √ÛÙÂÔfiÚˆÛ˘; ¶·Ó·ÁÈÒÙ˘ ∞Ó·ÁÓˆÛÙ‹˜, ∂˘ÛÙ¿ıÈÔ˜ ¶·ÁÎÔ˘Ú¤ÏÈ·˜, ÷ڿϷÌÔ˜ ∫Ô˘Ì·Ú¿˜, £ˆÌ¿˜ °ÎfiÛÈÔ˜, μ·Û›ÏÂÈÔ˜ Õı˘ÚÔ˜, ∞ÛÙ¤ÚÈÔ˜ ∫·Ú·ÁÈ¿ÓÓ˘ μ’ ¶ÚÔ·È‰Â˘ÙÈ΋ ¶·ıÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ∞¶£, πÔÎÚ¿ÙÂÈÔ ¡ÔÛÔÎÔÌ›Ô, £ÂÛÛ·ÏÔÓ›ÎË. ∏ ·ıËÚÔÛÎÏ‹ÚˆÛË Î·È Ë ÔÛÙÂÔfiÚˆÛË, ‰‡Ô ÔÏ˘·Ú·ÁÔÓÙÈΤ˜ Î·È ÂÎÊ˘ÏÈÛÙÈΤ˜ ηٷÛÙ¿ÛÂȘ, ·ÔÙÂÏÔ‡Ó Ì›˙ÔÓ· ÚÔ‚Ï‹Ì·Ù· ˘Á›·˜ ÛÙÔ Û‡Á¯ÚÔÓÔ ÎfiÛÌÔ. ∏ Ù·˘Ùfi¯ÚÔÓË ·ÚÔ˘Û›· ÙÔ˘˜ ÛÙÔ ›‰ÈÔ ¿ÙÔÌÔ ‰ÂÓ ÂÍËÁÂ›Ù·È ÌfiÓÔ ˆ˜ ·ÔÙ¤ÏÂÛÌ· Ù˘ ‰È·‰Èηۛ·˜ Ù˘ Á‹Ú·ÓÛ˘ ‹ Ù˘ ‰Ú¿Û˘ ÎÔÈÓÒÓ ·Ú·ÁfiÓÙˆÓ ÎÈÓ‰‡ÓÔ˘. √È ÔÓÙfiÙËÙ˜ ·˘Ù¤˜ ‰È¤ÔÓÙ·È ·fi ÎÔÈÓÔ‡˜ ·ıÔÁÂÓÂÙÈÎÔ‡˜ Ì˯·ÓÈÛÌÔ‡˜, fiˆ˜ Ë ·Ú¿ÏÏËÏË ‰È·‰Èηۛ· Ù˘ ·ۂ¤ÛÙˆÛ˘ ÙˆÓ ÔÛÙÒÓ Î·È ÙˆÓ ·ÁÁ›ˆÓ (‰Ú¿ÛË Ô˘ÛÈÒÓ, fiˆ˜ Gla ÚˆÙ½Ó˜, ÔÛÙÂÔÔÓÙ›ÓË, ÔÛÙÂÔÚÔÙÂÁÂÚ›ÓË), Ë ÂÏ¿ÙÙˆÛË ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ ÔÈÛÙÚÔÁfiÓˆÓ, Ë Â›‰Ú·ÛË ÙˆÓ ÚÔ˚fiÓÙˆÓ ÔÍ›‰ˆÛ˘ ÙˆÓ ÏÈȉ›ˆÓ (ÌÂÚÈÎÒ˜ ÔÍÂȉˆÌ¤ÓË LDL, ÈÛÔÚÔÛÙ¿Ó˜), Ë ÊÏÂÁÌÔÓ‹, Ë ·‡ÍËÛË Ù˘ ÔÌÔ΢ÛÙ½Ó˘, ÔÈ ÔÏ˘ÌÔÚÊÈÛÌÔ› Ù˘ ‚ÈÙ·Ì›Ó˘ D Î·È Ë ÂÏ¿ÙÙˆÛË Ù˘ ‚ÈÙ·Ì›Ó˘ ∫1. ∂ÈϤÔÓ ¤¯ÂÈ Û˘˙ËÙËı› Ë Â˘ÂÚÁÂÙÈ΋ ›‰Ú·ÛË ÔÚÈÛÌ¤ÓˆÓ Î·ÙËÁÔÚÈÒÓ Ê·ÚÌ¿ÎˆÓ ÛÙË Ì›ˆÛË Ù˘ ÔÛÙÈ΋˜ Ì¿˙·˜ (√ª) Î·È ÛÙËÓ ·ÁÁÂȷ΋ ÓfiÛÔ. ™ÙËÓ ·ÚÔ‡Û· ·Ó·ÛÎfiËÛË ·Ó·Ï‡ÔÓÙ·È ÔÈ Èı·Ó¤˜ ÎÔÈÓ¤˜ ıÂڷ¢ÙÈΤ˜ ÚÔÛÂÁÁ›ÛÂȘ ÙˆÓ ‰‡Ô ·˘ÙÒÓ ·ıÔÏÔÁÈÎÒÓ Î·Ù·ÛÙ¿ÛˆÓ. √ ÚfiÏÔ˜ ÙˆÓ ÛÙ·ÙÈÓÒÓ ÛÙËÓ ÂÏ¿ÙÙˆÛË Ù˘ ηډȷÁÁÂȷ΋˜ ıÓËÛÈÌfiÙËÙ·˜ Â›Ó·È ÁÓˆÛÙfi˜2. Δ· Ê¿Ú̷η ·˘Ù¿ fï˜ ÂÌÊ·Ó›˙Ô˘Ó ÛËÌ·ÓÙÈ΋ ¢ÂÚÁÂÙÈ΋ ‰Ú¿ÛË Î·È ÛÙÔÓ ÔÛÙÈÎfi ÌÂÙ·‚ÔÏÈÛÌfi3,4. §·Ì‚¿ÓÔÓÙ·˜ ˘fi„Ë ÙÔÓ ·ıÔÁÂÓÂÙÈÎfi ÚfiÏÔ Ù˘ ˘ÂÚÏÈȉ·ÈÌ›·˜ ÛÙË Ì›ˆÛË Ù˘ √ª1, Ë È‰ÈfiÙËÙ· ÙˆÓ Ê·ÚÌ¿ÎˆÓ ·˘ÙÒÓ ı· ÌÔÚÔ‡Û ӷ ·Ô‰Ôı› ÛÙËÓ ˘ÔÏÈȉ·ÈÌÈ΋ ÙÔ˘˜ ‰Ú¿ÛË. º·›ÓÂÙ·È fï˜ fiÙÈ Â›Ó·È ·ÓÂÍ¿ÚÙËÙË. ™˘ÁÎÂÎÚÈ̤ӷ, fiˆ˜ Â›Ó·È ÁÓˆÛÙfi, Ô Ì˯·ÓÈÛÌfi˜ ‰Ú¿Û˘ ÙˆÓ ÛÙ·ÙÈÓÒÓ ¤ÁÎÂÈÙ·È ÛÙË ·Ó·ÛÙÔÏ‹ Ù˘ ·Ó·ÁˆÁ¿Û˘ ÙÔ˘ 3-hydroxy-3-methylglutaryl coenzyme A (HMGCÔ∞), ÙÔ˘ ÂÓ˙‡ÌÔ˘ Ô˘ ÂÌϤÎÂÙ·È ÛÙË ‚ÈÔÛ‡ÓıÂÛË Ù˘ ¯ÔÏË-
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ÛÙÂÚfiÏ˘ Î·È Î·Ù·Ï‡ÂÈ ÙË ÌÂÙ·ÙÚÔ‹ ÙÔ˘ HMG-CÔ∞ Û Ì‚·ÏÔÓÈÎfi Ô͇. ∂ÎÙfi˜ ·fi ÙËÓ ÂÏ¿ÙÙˆÛË Ù˘ ·Ú·ÁˆÁ‹˜ ¯ÔÏËÛÙÂÚfiÏ˘, Ë ·Ó·ÛÙÔÏ‹ ÙÔ˘ Ì‚·ÏÔÓÈÎÔ‡ Ô‰ËÁ› ÛÙË Ì›ˆÛË Ù˘ Û‡ÓıÂÛ˘ ÛËÌ·ÓÙÈÎÒÓ ‰È¿ÌÂÛˆÓ ÚÔ˚fiÓÙˆÓ, fiˆ˜ ÙˆÓ ÈÛÔÚÂÓÔ˚‰ÒÓ farnesyl pyrophosphate Î·È geranylgeranyl pyrophosphate.5 ∞˘Ù¿ Ì ÙË ÛÂÈÚ¿ ÙÔ˘˜ ÂÌϤÎÔÓÙ·È ÛÙË ‰È·ÌfiÚʈÛË (prenylation) ·ÚÎÂÙÒÓ ÚˆÙÂ˚ÓÒÓ, fiˆ˜ ÔÈ Ras, Rho Î·È Rac, ÔÈ Ôԛ˜ Ú˘ıÌ›˙Ô˘Ó Ì›· ÔÈÎÈÏ›· ΢ÙÙ·ÚÈÎÒÓ ÏÂÈÙÔ˘ÚÁÈÒÓ, fiˆ˜ ÙËÓ Î˘ÙÙ·ÚÈ΋ ÛËÌ·ÙÔ‰fiÙËÛË, ÙË ‰È·ÊÔÚÔÔ›ËÛË Î·È ÙÔÓ ÔÏÏ·Ï·ÛÈ·ÛÌfi6. √È ÚˆÙ½Ó˜ ·˘Ù¤˜ Â›Ó·È ··Ú·›ÙËÙ˜ Î·È ÁÈ· ÙË ÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ÔÛÙÂÔÎÏ·ÛÙÒÓ. ΔÔ ÁÂÁÔÓfi˜ ·˘Ùfi Â›Ó·È ÛÂ Û˘Ìʈӛ· Ì οÔȘ ·Ú·ÙËÚ‹ÛÂȘ fiÙÈ ÔÈ ÛÙ·Ù›Ó˜ ·Ó·ÛÙ¤ÏÏÔ˘Ó ÙËÓ ÔÛÙÂÔÎÏ·ÛÙÈ΋ ‰Ú·ÛÙËÚÈfiÙËÙ· in vitro7. ∂›Û˘, ÔÈ ÛÙ·Ù›Ó˜ ÚÔ¿ÁÔ˘Ó Î·È ÙÔÓ ÔÛÙÈÎfi ·Ó·‚ÔÏÈÛÌfi, Èı·ÓÒ˜ ̤ۈ Ù˘ ·‡ÍËÛ˘ Ù˘ BMP-2, ÌÈ·˜ ÚˆÙ½Ó˘ Ô˘ ÂÌϤÎÂÙ·È ÛÙÔ Û¯ËÌ·ÙÈÛÌfi ÙÔ˘ ÔÛÙÔ‡ Î·È ÙÔ˘ ¯fiÓ‰ÚÔ˘8. ™Â Ì›· ÚÔÔÙÈ΋ ÌÂϤÙË, Ë ¯ÔÚ‹ÁËÛË ÛÈÌ‚·ÛÙ·Ù›Ó˘ Û˘Û¯ÂÙ›ÛÙËΠ̠ÙËÓ ·‡ÍËÛË Ù˘ ÔÛÙÂÔηÏÛ›Ó˘ (ÂÓfi˜ ‰Â›ÎÙË ÙÔ˘ ÔÛÙÈÎÔ‡ ·Ó·‚ÔÏÈÛÌÔ‡ Î·È Ù˘ ÔÛÙÂÔ‚Ï·ÛÙÈ΋˜ ‰Ú·ÛÙËÚÈfiÙËÙ·˜) 9, ÁÂÁÔÓfi˜ ÙÔ ÔÔ›Ô ¤Ú¯ÂÙ·È ÛÂ Û˘Ìʈӛ· Ì ̛· ¿ÏÏË ÌÂϤÙË Û ıËÏ˘ÎÔ‡˜ Â›Ì˘Â˜ ÛÙÔ˘˜ ÔÔ›Ô˘˜ ·Ú·ÙËÚ‹ıËΠ·‡ÍËÛË Ù˘ Ì¿˙·˜ ÛÙ· ÛÔÁÁÒ‰Ë ÔÛÙ¿10. ∂ÈϤÔÓ, Ë ¯ÔÚ‹ÁËÛË ·ÙÔÚ‚·ÛÙ·Ù›Ó˘ ·fi ¿ÏÏÔ˘˜ ÂÚ¢ÓËÙ¤˜ Û˘Óԉ‡ÙËΠ·fi ·‡ÍËÛË Ù˘ Û˘ÁΤÓÙÚˆÛ˘ Ù˘ ‚ÈÙ·Ì›Ó˘ D11. ª›· ·Ó¿Ï˘ÛË 4 ÌÂÁ¿ÏˆÓ ÚÔÔÙÈÎÒÓ ÌÂÏÂÙÒÓ, ÂÍ¿ÏÏÔ˘, ηٷ‰ÂÈÎÓ‡ÂÈ fiÙÈ ÔÈ ÛÙ·Ù›Ó˜ Èı·ÓfiÓ Ó· ÚÔÏ·Ì‚¿ÓÔ˘Ó ÙËÓ ÂÌÊ¿ÓÈÛË ÔÛÙÂÔÔÚˆÙÈÎÒÓ Î·Ù·ÁÌ¿ÙˆÓ. ™Â ηıÂÌÈ¿ ÌÂϤÙË Í¯ˆÚÈÛÙ¿ ˘‹ÚÍ ̛· ‰˘Ó·ÌÈ΋ Ù¿ÛË ÚÔ˜ ÙËÓ Î·Ù‡ı˘ÓÛË Ù˘ ÂÏ¿ÙÙˆÛ˘
ÙˆÓ Î·Ù·ÁÌ¿ÙˆÓ ÈÛ¯›Ô˘ ÛÙȘ Á˘Ó·›Î˜ Ô˘ ·Ó¤ÊÂÚ·Ó ¯Ú‹ÛË ÛÙ·Ù›Ó˘, ·ÎfiÌ· Î·È ÌÂÙ¿ ·fi ÚÔÛ·ÚÌÔÁ‹ ÁÈ· ÁÓˆÛÙÔ‡˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘12. ∂ÈÚfiÛıÂÙ·, Û ̛· ÌÂÁ¿ÏË ·Ó·‰ÚÔÌÈ΋ ·Ó¿Ï˘ÛË Ê¿ÓËΠfiÙÈ Ë ¤ÎıÂÛË ÛÙË ‰Ú¿ÛË ÙˆÓ ÛÙ·ÙÈÓÒÓ ·ÎfiÌ· Î·È ÁÈ· ÌÈÎÚfi ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· (·fi Ï›Á˜ ‚‰ÔÌ¿‰Â˜ ¤ˆ˜ Ï›ÁÔ˘˜ Ì‹Ó˜) Û˘Û¯ÂÙ›ÛÙËΠ̛̠ˆÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÁÈ· οٷÁÌ·, ÁÂÁÔÓfi˜ ÙÔ ÔÔ›Ô ‰Â ‰È·ÈÛÙÒıËΠÌÂÙ¿ ·fi Ï‹„Ë ÊÈÌÚ·ÙÒÓ ‹ ¿ÏÏˆÓ ˘ÔÏÈȉ·ÈÌÈÎÒÓ Ê·Ú̿ΈÓ3. ∞Í›˙ÂÈ Ó· ÛËÌÂȈı› ¿ÓÙˆ˜ fiÙÈ Ù· ‰Â‰Ô̤ӷ ·˘Ù¿ ‰ÂÓ ÂȂ‚·ÈÒıËÎ·Ó ·fi Ì›· ÌÂÁ¿ÏË Ù˘¯·ÈÔÔË̤ÓË ÌÂϤÙË Ô˘ ·ÊÔÚÔ‡Û ÛÙË ¯Ú‹ÛË Ú·‚·ÛÙ·Ù›Ó˘, ·Ó Î·È ÂÚÈÏ¿Ì‚·Ó ÌË ÔÛÙÂÔÔÚˆÙÈÎÔ‡˜ ·ÛıÂÓ›˜13. ∏ Û˘ÁÎÂÎÚÈ̤ÓË ÛÙ·Ù›ÓË Ê·›ÓÂÙ·È fiÙÈ ‰ÂÓ Â›Ó·È ·ÔÙÂÏÂÛÌ·ÙÈ΋ ÛÙËÓ ·‡ÍËÛË Ù˘ BMP2, ‰ÈfiÙÈ Û˘Ó‰¤ÂÙ·È ÏÈÁfiÙÂÚÔ Ì ÙȘ ÚˆÙ½Ó˜ ÙÔ˘ Ï¿ÛÌ·ÙÔ˜ Û˘ÁÎÚÈÙÈο Ì ¿ÏϘ ÛÙ·Ù›Ó˜, fiˆ˜ ÏÔ‚·ÛÙ·Ù›ÓË, ÛÈÌ‚·ÛÙ·Ù›ÓË Î·È ÊÏÔ˘‚·ÛÙ·Ù›ÓË14. ª›· ÌÂÙ·Ó¿Ï˘ÛË 19 ÌÂÏÂÙÒÓ ÂͤٷÛ ÙËÓ Â›‰Ú·ÛË ÙˆÓ ÛÙ·ÙÈÓÒÓ ÛÙËÓ √ª Î·È ÛÙÔÓ Î›Ó‰˘ÓÔ Î·Ù¿ÁÌ·ÙÔ˜, ·fi ÙȘ Ôԛ˜ ÔÈ 12 η٤‰ÂÈÍ·Ó ÙËÓ Â˘ÂÚÁÂÙÈ΋ ÙÔ˘˜ ‰Ú¿ÛË Û ·ÓÙ›ıÂÛË Ì 1 Ô˘ ¤‰ÂÈÍ ÂÈΛӉ˘ÓË ‰Ú¿ÛË, ÂÓÒ Û 6 ÌÂϤÙ˜ ÔÈ ÛÙ·Ù›Ó˜ ‰ÂÓ Â›¯·Ó η̛· ›‰Ú·ÛË ÛÙËÓ √ª. ∂ÈϤÔÓ, ‰È·ÈÛÙÒıËÎ·Ó ‰È·ÊÔÚ¤˜ ÛÙË ‰Ú¿ÛË ÙÔ˘˜ ·Ó¿ÏÔÁ· Ì ÙȘ ÏÈÔÊÈÏÈΤ˜ ‹ ˘‰ÚÔÊÈÏÈΤ˜ ÙÔ˘˜ ȉÈfiÙËÙ˜. ™˘ÁÎÂÎÚÈ̤ӷ, ÔÈ ÏÈfiÊÈϘ ÛÙ·Ù›Ó˜ (ÛÈÌ‚·ÛÙ·Ù›ÓË, ÏÔ‚·ÛÙ·Ù›ÓË) Û˘Û¯ÂÙ›ÛÙËÎ·Ó Ì ·‡ÍËÛË Ù˘ √ª ÛÙÔÓ ·˘¯¤Ó· ÙÔ˘ ÌËÚÈ·›Ô˘ (ÂÚ›Ô˘ 0,2 SD Û ۯ¤ÛË Ì ÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘), Û ·ÓÙ›ıÂÛË Ì ÙȘ ˘‰ÚfiÊÈϘ (·ÙÔÚ‚·ÛÙ·Ù›ÓË, ÊÏÔ˘‚·ÛÙ·Ù›ÓË, Ú·‚·ÛÙ·Ù›ÓË). ∏ √ª, fï˜, ÛÙËÓ ÔÛÊ˘˚΋ ÌÔ›Ú· ·˘Í‹ıËΠÔÚȷο, ÁÂÁÔÓfi˜ Ô˘ ‰Â›¯ÓÂÈ fiÙÈ Èı·ÓfiÓ ÔÈ ÛÙ·Ù›Ó˜ ‰ÚÔ˘Ó Î˘-
£∂ƒ∞¶∂π∞ - º∞ƒª∞∫∞ Ú›ˆ˜ ÛÙ· ÊÏÔÈÒ‰Ë ÔÛÙ¿. ¶¿ÓÙˆ˜, Ë ·Û˘Ìʈӛ· Ô˘ ·Ú·ÙËÚ‹ıËΠÛÙȘ ÌÂϤÙ˜ ·˘Ù¤˜ ·Ô‰›‰ÂÙ·È Û ·ÚÎÂÙÔ‡˜ ¿ÏÏÔ˘˜ ·Ú¿ÁÔÓÙ˜, fiˆ˜ Â›Ó·È Ë ‰È·ÊÔÚÂÙÈ΋ ÚfiÛÏË„Ë ÙˆÓ ÛÙ·ÙÈÓÒÓ ·fi Ù· ÔÛÙ¿, Ë ‰È·ÊÔÚÂÙÈ΋ ‚ÈԉȷıÂÛÈÌfiÙËÙ¿ ÙÔ˘˜ Î·È ‰Ú¿ÛË ÛÙÔ˘˜ ÔÛÙÂÔ‚Ï¿ÛÙ˜ Î·È ÔÛÙÂÔÎÏ¿ÛÙ˜, ηıÒ˜ ›Û˘ Î·È Û ÔÈΛÏÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘, ‰ÔÛÔÏÔÁ›· Î·È ‰È¿ÚÎÂÈ· ¯ÔÚ‹ÁËÛ˘ Û οı ¿ÙÔÌÔ15. ∏ ÂÏ¿ÙÙˆÛË ÙÔ˘ Ì‚·ÏÔÓÈÎÔ‡ ÔͤԘ, Ô˘ Ô‰ËÁ› ÛÙËÓ ·Ó·ÛÙÔÏ‹ Ù˘ ÔÛÙÂÔÎÏ·ÛÙÈ΋˜ ‰Ú·ÛÙËÚÈfiÙËÙ·˜, ·ÔÙÂÏ› ›Û˘ ¤Ó· ÛËÌ·ÓÙÈÎfi ‚ÈÔÏÔÁÈÎfi «ÌÔÓÔ¿ÙÈ» Î·È ÁÈ· ÙË ‰Ú¿ÛË ÙˆÓ ‰ÈʈÛÊÔÓÈÎÒÓ, Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È Â˘Ú¤ˆ˜ ÁÈ· ÙË ıÂڷ›· Ù˘ ÔÛÙÂÔfiÚˆÛ˘. Δ· ‰ÈʈÛÊÔÓÈο Ê·›ÓÂÙ·È fiÙÈ ·Ó·ÛÙ¤ÏÏÔ˘Ó ÙËÓ ÚfiÔ‰Ô Ù˘ ·ıËÚÔÛÎÏ‹ÚˆÛ˘ ÛÙ· ÂÈÚ·Ì·Ùfi˙ˆ· Î·È Ë Â›‰Ú·ÛË ·˘Ù‹ ÛÙÔ ·ÚÙËÚÈ·Îfi ÙÔ›¯ˆÌ· Â›Ó·È ·ÓÂÍ¿ÚÙËÙË Ù˘ ˘·Û‚ÂÛÙÈ·ÈÌÈ΋˜ ÙÔ˘˜ ‰Ú¿Û˘16. √ ÚÔÛٷ٢ÙÈÎfi˜ ÙÔ˘˜ ÚfiÏÔ˜ ÛÙ· ·ÁÁ›· Û˘Ó›ÛÙ·Ù·È ÛÙËÓ Â›Ù·ÛË Ù˘ ·fiÙˆÛ˘ ÙˆÓ Ì·ÎÚÔÊ¿ÁˆÓ ΢ÙÙ¿ÚˆÓ Î·È Ù˘ ÚfiÏ˄˘ Û¯ËÌ·ÙÈÛÌÔ‡ ÙˆÓ ·ÊÚˆ‰ÒÓ Î˘ÙÙ¿ÚˆÓ, ̤ۈ ·Ó·ÛÙÔÏ‹˜ Ù˘ ÚfiÛÏ˄˘ Ù˘ LDL17. ™Â Ì›· ÌÂϤÙË, Ë ÂÙÈÓ‰ÚÔÓ¿ÙË, ¤Ó· ·fi Ù· Ê¿Ú̷η Ù˘ ηÙËÁÔÚ›·˜ ·˘Ù‹˜, Û˘Û¯ÂÙ›ÛÙËΠ̠ÙËÓ ·Ó·ÛÙÔÏ‹ Ù˘ ·ıËÚÔÛÎÏ‹ÚˆÛ˘ fiÙ·Ó ¯ÔÚËÁ‹ıËΠ۠·ÛıÂÓ›˜ Ì ¯·ÌËÏ‹ √ª18. ¢ÂÓ Â›Ó·È ·ÎÚÈ‚Ò˜ ÁÓˆÛÙfi ÁÈ·Ù› Ù· ‰ÈʈÛÊÔÓÈο ¤¯Ô˘Ó ÌfiÓÔ ·ÓÙÈÔÛÙÂÔÎÏ·ÛÙÈ΋ ‰Ú¿ÛË, Û ۇÁÎÚÈÛË Ì ÙȘ ÛÙ·Ù›Ó˜ Ô˘ ¤¯Ô˘Ó Î·È ·Ó·‚ÔÏÈ΋, ·Ú¿ ÙÔÓ ÎÔÈÓfi ÌÔÚÈ·Îfi Ì˯·ÓÈÛÌfi ‰Ú¿Û˘. ¶Èı·ÓÔÏÔÁÂ›Ù·È fiÙÈ ˘¿Ú¯ÂÈ ‰È·ÊÔÚÂÙÈ΋ ¢·ÈÛıËÛ›· ÙˆÓ
ÔÛÙÂÔÎÏ·ÛÙÒÓ Î·È ÙˆÓ ÔÛÙÂÔ‚Ï·ÛÙÒÓ ÛÙË ‰Ú¿ÛË ÙˆÓ ÛÙ·ÙÈÓÒÓ Î·È ÙˆÓ ‰ÈʈÛÊÔÓÈÎÒÓ15. Δ· ·ÈÛÈfi‰ÔÍ· ·˘Ù¿ ÌËӇ̷ٷ ̤ÓÂÈ Ó· ÂȂ‚·ÈˆıÔ‡Ó ·fi ÌÂÁ¿Ï˜ Ù˘¯·ÈÔÔÈË̤Ó˜ ÚÔÔÙÈΤ˜ ÌÂϤÙ˜. ™ËÌ·ÓÙÈο ÛÙÔȯ›· ¤¯Ô˘Ó ÚÔ·„ÂÈ Û¯ÂÙÈο Ì ÙÔ ÚfiÏÔ ÔÚÈÛÌ¤ÓˆÓ Î·ÙËÁÔÚÈÒÓ ·ÓÙÈ˘ÂÚÙ·ÛÈÎÒÓ Ê·ÚÌ¿ÎˆÓ ÛÙËÓ ·‡ÍËÛË Ù˘ √ª, ·Ó Î·È ‰ÂÓ ¤¯ÂÈ ·Ô‰Âȯı› fiÙÈ Ë ˘¤ÚÙ·ÛË ·ÔÙÂÏ› ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ·Ó¿Ù˘ÍË Ù˘ ÔÛÙÂÔfiÚˆÛ˘. ™˘ÁÎÂÎÚÈ̤ӷ, ÔÈ ‚-·ÔÎÏÂÈÛÙ¤˜ ¤¯ÂÈ ‚ÚÂı› fiÙÈ ÚÔ¿ÁÔ˘Ó ÙÔÓ ÔÛÙÈÎfi ·Ó·‚ÔÏÈÛÌfi Î·È ÂÈ‚Ú·‰‡ÓÔ˘Ó ÙÔÓ ÔÛÙÈÎfi ηٷ‚ÔÏÈÛÌfi ÛÙ· ÂÈÚ·Ì·Ùfi˙ˆ·, ηıÒ˜ ›Û˘ Û˘Ó‰¤ÔÓÙ·È Ì ÙË Ì›ˆÛË Î·Ù·ÁÌ¿ÙˆÓ ÛÙÔ˘˜ ·ÓıÚÒÔ˘˜19. ∏ ‰Ú¿ÛË ÙÔ˘˜ ·˘Ù‹ ·Ô‰›‰ÂÙ·È Èı·ÓfiÓ ÛÙË Ú‡ıÌÈÛË Ù˘ ÔÛÙÈ΋˜ ·Ó·Î·Ù·Û΢‹˜ ̤ۈ ÙÔ˘ Û˘Ì·ıËÙÈÎÔ‡ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜, ÂÊfiÛÔÓ Û˘Ì·ıËÙÈΤ˜ Ó¢ÚÈΤ˜ ›Ó˜ ˘¿Ú¯Ô˘Ó ÛÙ· ÔÛÙ¿ Î·È Ë ‚-·‰ÚÂÓÂÚÁÈ΋ ‰È¤ÁÂÚÛË Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ ÔÛÙÂÔÎÏ·ÛÙÒÓ20. ™ËÌ·ÓÙÈο ‰Â‰Ô̤ӷ ÚÔ·ÙÔ˘Ó Â›Û˘ ·fi ÙË Â›‰Ú·ÛË ÙˆÓ ıÂÈ·˙ȉÈÎÒÓ ‰ÈÔ˘ÚËÙÈÎÒÓ ÛÙËÓ ÚfiÏË„Ë Ù˘ ÔÛÙÂÔfiÚˆÛ˘ ÛÙȘ ÌÂÙÂÌÌËÓÔ·˘ÛȷΤ˜ Á˘Ó·›Î˜21, ȉÈfiÙËÙ· Ô˘ ‰ÂÓ ·Ô‰›‰ÂÙ·È ÌfiÓÔ ÛÙËÓ ·‡ÍËÛË Ù˘ ·ӷÚÚfiÊËÛ˘ ÙÔ˘ ·Û‚ÂÛÙ›Ô˘ ÛÙÔ ¿ˆ ÂÛÂÈڷ̤ÓÔ ÛˆÏËÓ¿ÚÈÔ, ̤ۈ Ù˘ ·Ó·ÛÙÔÏ‹˜ Ù˘ ·ÓÙÏ›·˜ Û˘ÓÌÂÙ·ÊÔÚ¿˜ Na+-Cl- (Na+-Cl- cotransporter, NCC), ·ÏÏ¿ Î·È ÛÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ ÔÛÙÂÔ‚Ï·ÛÙÒÓ (ÔÈ ÔÔ›ÔÈ Â›Û˘ Ê·›ÓÂÙ·È fiÙÈ ÂÎÊÚ¿˙Ô˘Ó ÙËÓ NCC)22. √ÛÔÓ ·ÊÔÚ¿ ÛÙÔ˘˜ ·ÓÙ·ÁˆÓÈÛÙ¤˜ ÙˆÓ ˘Ô‰Ô-
¯¤ˆÓ Ù‡Ô˘ ∞Δ1 Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘ ππ (∞ππ), Ê·›ÓÂÙ·È fiÙÈ ÂÏ·ÙÙÒÓÔ˘Ó ÙËÓ ÔÛÙÈ΋ ·ÒÏÂÈ·, ·ÊÔ‡ Î·È Ë ∞ππ ÂÈÙ›ÓÂÈ ÙËÓ ÔÛÙÂÔÎÏ·ÛÙÈ΋ ‰Ú·ÛÙËÚÈfiÙËÙ·23. °È· ÙÔ˘˜ ·Ó·ÛÙÔÏ›˜ ÙÔ˘ ÌÂÙ·ÙÚÂÙÈÎÔ‡ ÂÓ˙‡ÌÔ˘ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘ π (∞-ª∂∞) ˘¿Ú¯Ô˘Ó ·ÌÊÈÏÂÁfiÌÂÓ· ÛÙÔȯ›·24. Δ¤ÏÔ˜, Ó¤ÔÈ ıÂڷ¢ÙÈÎÔ› ÔÚ›˙ÔÓÙ˜ ·ÓÔ›ÁÔÓÙ·È Ì ÙËÓ ·Ó·Î¿Ï˘„Ë Ê·ÚÌ¿ÎˆÓ Ô˘ ı· ·Ó·ÛÙ¤ÏÏÔ˘Ó ÙËÓ ÂͤÏÈÍË ÙˆÓ ·ıËڈ̷ÙÈÎÒÓ Ï·ÎÒÓ Î·È Ù·˘Ùfi¯ÚÔÓ· ı· ÂÓÈÛ¯‡Ô˘Ó ÙËÓ √ª. ™˘ÓÔÙÈο ·Ó·Ê¤ÚÔÓÙ·È Ë ÙÂÚÈ·Ú·Ù›‰Ë (Û˘ÓıÂÙÈÎfi ·Ó¿ÏÔÁÔ Ù˘ ·Ú·ıÔÚÌfiÓ˘), Ë ·Ó·Û˘Ó‰˘·Ṳ̂ÓË ÔÛÙÂÔÚÔÙÂÁÂÚ›ÓË Î·È ÔÈ ·Ó·ÛÙÔÏ›˜ Ù˘ 12/15 ÏÈÔ͢ÁÂÓ¿Û˘ Î·È ÙˆÓ ·ÓÙ·ÁˆÓÈÛÙÒÓ Ù˘ ÔÌ¿‰·˜ ÙˆÓ Wnt ÌÔÚ›ˆÓ, Ô˘ ÂÌϤÎÔÓÙ·È ÛÙË ‰È·‰Èηۛ· Ù˘ ÔÛÙÈ΋˜ ·Ó·Î·Ù·Û΢‹˜8. ™˘ÌÂÚ·ÛÌ·ÙÈο, Ë ·Ú·‰Ô¯‹ Ù˘ ‡·Ú͢ ÎÔÈÓÒÓ ·ıÔÊ˘ÛÈÔÏÔÁÈÎÒÓ Ì˯·ÓÈÛÌÒÓ Ô˘ ‰È¤Ô˘Ó ÙËÓ ·ıËÚÔÛÎÏ‹ÚˆÛË Î·È ÙËÓ ÔÛÙÂÔfiÚˆÛË, ¤Ú·Ó ÙÔ˘ ¯·Ú·ÎÙËÚÈÛÌÔ‡ ÙÔ˘˜ ˆ˜ «ÓÔÛËÌ¿ÙˆÓ ÊıÔÚ¿˜», ‰ËÌÈÔ˘ÚÁ› ÊÈÏfi‰ÔÍÔ˘˜ ۯ‰ȷÛÌÔ‡˜ ÁÈ· ˘ÈÔı¤ÙËÛË ıÂÚ·ÂÈÒÓ Ô˘ ı· ÛÙÔ¯Â‡Ô˘Ó ÛÙËÓ Ù·˘Ùfi¯ÚÔÓË ·ÓÙÈÌÂÙÒÈÛ‹ ÙÔ˘˜. Δ· ̤¯ÚÈ ÛÙÈÁÌ‹˜ ‰Â‰Ô̤ӷ Ô˘ ·ÊÔÚÔ‡Ó ÛÙË ¯ÔÚ‹ÁËÛË ÙˆÓ ÛÙ·ÙÈÓÒÓ, ÙˆÓ ‰ÈʈÛÊÔÓÈÎÒÓ Î·È ÔÚÈÛÌ¤ÓˆÓ ·ÓÙÈ˘ÂÚÙ·ÛÈÎÒÓ Â›Ó·È ÂÓı·ÚÚ˘ÓÙÈο. ∞·ÈÙÔ‡ÓÙ·È fï˜ ÌÂÁ¿Ï˜ Ù˘¯·ÈÔÔÈË̤Ó˜ ÚÔÔÙÈΤ˜ ÌÂϤÙ˜ ÁÈ· ÙËÓ ÙÂÏÈ΋ ÂÊ·ÚÌÔÁ‹ ÙÔ˘˜ ÛÙËÓ ·Ú¿ÏÏËÏË ÚfiÏË„Ë ÙˆÓ ÂÈÏÔÎÒÓ Ô˘ Û˘ÓÔ‰Â‡Ô˘Ó ÙȘ ‰‡Ô ·˘Ù¤˜ ·ıÔÏÔÁÈΤ˜ ÔÓÙfiÙËÙ˜.
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14. Pedersen TR. Statin drugs and the risk of fracture. 4S Study Group. JAMA 2000;284:1921-1922. 15. Uzzan B, Cohen R, Nicolas P, Cucherat M, Perret GY. Effects of statins on bone mineral density: a meta-analysis of clinical studies. Bone 2007;40:1581-1587. 16. Ylitalo R. Bisphosphonates and atherosclerosis. Gen Pharmacol 2002;35:287-296. 17. Luckman SP, Hughes DE, Coxon FP Graham R, Russell G, Rogers MJ. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res 1998;13: 581-589. 18. Koshiyama H, Nakamura Y, Tanaka S. Decrease in carotid intima-media thickness after 1-year therapy with etidronate for osteopenia associated with type 2 diabetes. J Clin Endocrinol Metab 2000;85:2793-2796. 19. Bonnet N, Gadois C, McCloskey E, Lemineur G, Lespessailles E, Courteix D, Benhamou CL. Protective effect of beta blockers in postmenopausal women: influence on fractures, bone density, micro and macroarchitecture. Bone 2007;40:1209-1216. 20. Togari A. Adrenergic regulation of bone metabolism: possible involvement of sympathetic innervation of osteoblastic and osteoclastic cells. Microsc Res Tech 2002;58:77-84.
21. Bolland MJ, Ames RW, Horne AM, OrrWalker BJ, Gamble GD, Reid IR. The effect of treatment with a thiazide diuretic for 4 years on bone density in normal postmenopausal women. Osteoporos Int 2007;18:479-486. 22. Dvorak MM, De Joussineau C, Carter DH, Pisitkun T, Knepper MA, Gamba G, Kemp PJ, Riccardi D. Thiazide diuretics directly induce osteoblast differentiation and mineralized nodule formation by targeting a NaCl cotransporter in bone. J Am Soc Nephrol 2007;18:2509-2516. 23. Shimizu H, Nakagami H, Osako MK, Hanayama R, Kunugiza Y, Kizawa T, Tomita T, Yoshikawa H, Ogihara T, Morishita R. Angiotensin II accelerates osteoporosis by activating osteoclasts. FASEB J 2008;6:2465-2475. 24. Pérez-Castrill_n JL, Silva J, Justo I, Sanz A, Mart_n-Luquero M, Igea R, Escudero P, Pueyo C, D_az C, Hern_ndez G, Due_as A. Effect of quinapril, quinapril-hydrochlorothiazide, and enalapril on bone mass of hypertensive subjects: relationship with angiotensin converting enzyme polymorphisms. Am J Hypertens 2003;16: 453-459.
¶ƒ√∂π¢√¶√π∏™∏ (FDA ALERT [08/08/2008]) √ ∞ÌÂÚÈηÓÈÎfi˜ √ÚÁ·ÓÈÛÌfi˜ º·ÚÌ¿ÎˆÓ Î·È ΔÚÔÊ›ÌˆÓ (FDA) Âͤ‰ˆÛ ÙËÓ 08/08/2008 ·Ó·ÎÔ›ÓˆÛË-ÚÔÂȉÔÔ›ËÛË ÚÔ˜ ÙÔ˘˜ ·ÁÁÂÏ̷ٛ˜ ˘Á›·˜ Î·È ÚÔ˜ ÙÔ ÎÔÈÓfi ÁÈ· ÙÔÓ Î›Ó‰˘ÓÔ Ú·‚‰ÔÌ˘fiÏ˘Û˘ ·fi ÙËÓ Û˘Á¯ÔÚ‹ÁËÛË ·ÌȈ‰·ÚfiÓ˘ Î·È ÛÈÌ‚·ÛÙ·Ù›Ó˘, ȉ›ˆ˜ fiÙ·Ó Ë ‰fiÛË Ù˘ ÛÈÌ‚·ÛÙ·Ù›Ó˘ Â›Ó·È > 20 mg ËÌÂÚËÛ›ˆ˜. ¢ÂÓ Â›Ó·È ÁÓˆÛÙfi ·Ó ÔÈ ‰È¿ÊÔÚ˜ ‰fiÛÂȘ Ù˘ ·ÌȈ‰·ÚfiÓ˘ ÙÚÔÔÔÈÔ‡Ó ÙÔÓ Î›Ó‰˘ÓÔ. ∏ Ú·‚‰ÔÌ˘fiÏ˘ÛË ÌÔÚ› Ó· ÚÔηϤÛÂÈ ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· Î·È Ó· Ô‰ËÁ‹ÛÂÈ Û ı¿Ó·ÙÔ. ∏ ·ÓÂÈı‡ÌËÙË ÂÓ¤ÚÁÂÈ· ÔÊ›ÏÂÙ·È ÛÙËÓ ·Ó·ÛÙÔÏ‹ ÙÔ˘ ΢ÙÙÔ¯ÚÒÌ·ÙÔ˜ P450 3A4 (CYP3A4) Ô˘ ÚÔηÏ› Ë ·ÌȈ‰·ÚfiÓË. √È È·ÙÚÔ› Ô˘ Û˘ÓÙ·ÁÔÁÚ·ÊÔ‡Ó ÛÈÌ‚·ÛÙ·Ù›ÓË Ú¤ÂÈ Ó· ÚˆÙÔ‡Ó ·Ó Ô ·ÛıÂÓ‹˜ ¢ڛÛÎÂÙ·È Û ·ÁˆÁ‹ Ì ·ÌȈ‰·ÚfiÓË Î·È ÛÙȘ ÂÚÈÙÒÛÂȘ ·˘Ù¤˜ Ó· ÌË ¯ÔÚËÁÔ‡Ó ‰fiÛË ÛÈÌ‚·ÛÙ·Ù›Ó˘ ÌÂÁ·Ï‡ÙÂÚË ·fi 20 mg ËÌÂÚËÛ›ˆ˜, Ó· ÂÓËÌÂÚÒÓÔ˘Ó ÙÔÓ ·ÛıÂÓ‹ fiÙÈ Ú¤ÂÈ Ó· ·Ó·Ê¤ÚÂÈ ·Ì¤Ûˆ˜ ·Ó ÂÌÊ·Ó›ÛÂÈ ·ÓÂÍ‹ÁËÙË Ì˘·ÏÁ›·, Ì˘˚΋ ¢·ÈÛıËÛ›· ‹ Ì˘˚΋ ÎfiˆÛË Î·È Ó· ÙÔÓ ¤¯Ô˘Ó ˘fi Ù·ÎÙÈ΋ ·Ú·ÎÔÏÔ‡ıËÛË.
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£∂ƒ∞¶∂π∞ - º∞ƒª∞∫∞
O ƒfiÏÔ˜ Ù˘ ™ÂÈÚÔÓÔÏ·ÎÙfiÓ˘ ÛÙËÓ ∞ÓıÂÎÙÈ΋ ∞ÚÙËÚȷ΋ À¤ÚÙ·ÛË ª·Ú›· Δ˙‹ÌÔ˘, ÷ڿϷÌÔ˜ ∫Ô˘Ì·Ú¿˜, £ÂÔ‰ÒÚ· °Ú›‚·, ∫ˆÓÛÙ·ÓÙ›ÓÔ˜ ∫·ÚÁÈÒÙ˘, μ·Û›ÏÂÈÔ˜ Õı˘ÚÔ˜, ∞ÛÙ¤ÚÈÔ˜ ∫·Ú·ÁÈ¿ÓÓ˘ μ’ ¶ÚÔ·È‰Â˘ÙÈ΋ ¶·ıÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ∞¶£, πÔÎÚ¿ÙÂÈÔ ¡ÔÛÔÎÔÌ›Ô, £ÂÛÛ·ÏÔÓ›ÎË. ø˜ ·ÓıÂÎÙÈ΋ ·ÚÙËÚȷ΋ ˘¤ÚÙ·ÛË (∞À) ÔÚ›˙ÂÙ·È Ë ‡·ÚÍË ·ÚÙËÚȷ΋˜ ›ÂÛ˘ (∞¶) ≥ 140/90 mmHg ‹ ∞¶ ≥ 130/80 mmHg Û ·ÛıÂÓ›˜ Ì ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË (™¢) ‹ ÓÂÊÚÈ΋ ÓfiÛÔ, ·Ú¿ ÙË ıÂڷ›· Ì ÙÚ›· ÙÔ˘Ï¿¯ÈÛÙÔÓ ·ÓÙÈ˘ÂÚÙ·ÛÈο Ê¿Ú̷η, ÛÙȘ ̤ÁÈÛÙ˜ ‰fiÛÂȘ, ·fi Ù· ÔÔ›· ÙÔ ¤Ó· Ú¤ÂÈ Ó· Â›Ó·È ÔˆÛ‰‹ÔÙ ‰ÈÔ˘ÚËÙÈÎfi1. √ ·ÎÚÈ‚‹˜ ÂÈÔÏ·ÛÌfi˜ Ù˘ ·ÓıÂÎÙÈ΋˜ ∞À ÛÙÔ ÁÂÓÈÎfi ˘ÂÚÙ·ÛÈÎfi ÏËı˘ÛÌfi ‰ÂÓ Â›Ó·È ÙÂÎÌËÚȈ̤ÓÔ˜, ˆÛÙfiÛÔ Î·Ù·ÁÚ¿ÊÂÙ·È Û ÔÛÔÛÙfi 15% ÙˆÓ ˘ÂÚÙ·ÛÈÎÒÓ ·ÛıÂÓÒÓ Ô˘ Û˘ÌÌÂÙ¤¯Ô˘Ó Û ÌÂϤÙ˜ ·Ú·Ù‹ÚËÛ˘2. ™Â ÌÂÁ¿Ï˜ ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ Ô˘ ·ÊÔÚÔ‡Ó ·ÛıÂÓ›˜ ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘, ‰È·ÈÛÙÒÓÂÙ·È ·ÔÙ˘¯›· ›Ù¢Í˘ ÙˆÓ ıÂڷ¢ÙÈÎÒÓ ÛÙfi¯ˆÓ Ù˘ ∞¶ Û ÔÛÔÛÙfi 40%3,4 Î·È ¤ˆ˜ 60% Û ·ÛıÂÓ›˜ ¿Óˆ ÙˆÓ 60 ÂÙÒÓ5. Δ· ÛÙÔȯ›· ·˘Ù¿ ‰Â›¯ÓÔ˘Ó fiÙÈ Ë ·ÓıÂÎÙÈ΋ ∞À ·ÔÙÂÏ› Û˘¯Ófi ÎÏÈÓÈÎfi Úfi‚ÏËÌ·, ÂÓÒ ·Ó·Ì¤ÓÂÙ·È ¿ÓÔ‰Ô˜ ÛÙÔÓ ÂÈÔÏ·ÛÌfi ·Ú¿ÏÏËÏ· Ì ÙË Á‹Ú·ÓÛË ÙÔ˘ ÏËı˘ÛÌÔ‡ Î·È ÙËÓ ·‡ÍËÛË ÙÔ˘ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜ (™μ), ‰Â‰Ô̤ÓÔ˘ fiÙÈ Ë ÌÂÁ¿ÏË ËÏÈΛ· Î·È Ë ·¯˘Û·ÚΛ· Â›Ó·È ÔÈ Î˘ÚÈfiÙÂÚÔÈ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ Ô˘ Û˘Ì‚¿ÏÏÔ˘Ó ÛÙËÓ ÂÌÊ¿ÓÈÛË Î·È ÂÁηٿÛÙ·Û‹ Ù˘5. ∏ ‡·ÚÍË ÁÚ·ÌÌÈ΋˜ Û˘Û¯¤ÙÈÛ˘ ÌÂٷ͇ ÙÔ˘ ‡„Ô˘˜ Ù˘ ∞¶ Î·È ÙÔ˘ ηډȷÁÁÂÈ·ÎÔ‡ ÎÈÓ‰‡ÓÔ˘ Â›Ó·È Ï¤ÔÓ ÙÂÎÌËÚȈ̤ÓË1, ÁÂÁÔÓfi˜ Ô˘ ÂÍËÁ› ÙËÓ ·Ó·ÁηÈfiÙËÙ· ¯ÔÚ‹ÁËÛ˘ Û˘Ó‰˘·ÛÌÔ‡ ÙÚÈÒÓ ‹ ÂÚÈÛÛÔÙ¤ÚˆÓ ·ÓÙÈ˘ÂÚÙ·ÛÈÎÒÓ Ê·ÚÌ¿ÎˆÓ ÁÈ· ÙËÓ Â›Ù¢ÍË ÙˆÓ ÚÔÙÂÈÓfiÌÂÓˆÓ ÛÙfi¯ˆÓ Û ·ÛıÂÓ›˜ Ì ·ÓıÂÎÙÈ΋ ∞À6. ¶ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ Ë ÛÂÈÚÔÓÔÏ·ÎÙfiÓË, Ô ÚÒÙÔ˜ ·ÓÙ·ÁˆÓÈÛÙ‹˜ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘, Û ËÌÂÚ‹ÛÈ· ‰fiÛË 25-50 mg, Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ÂÈÚfiÛıÂÙË ÂÏ¿ÙÙˆÛË Ù˘ ∞¶ Û ·ÛıÂÓ›˜ Ô˘ Ï·Ì‚¿ÓÔ˘Ó Î·Ù¿ ̤ÛÔ fiÚÔ ÙÚ›· ·ÓÙÈ˘ÂÚÙ·-
ÛÈο Ê¿Ú̷η6-9. ™Ù· ·Ú·¿Óˆ ‰Â‰Ô̤ӷ ‚·Û›˙ÔÓÙ·È ÔÈ ÙÂÏÂ˘Ù·›Â˜ ηÙ¢ı˘ÓÙ‹ÚȘ ÁÚ·Ì̤˜ Ù˘ ∂˘Úˆ·˚΋˜ ∞ÓÙÈ˘ÂÚÙ·ÛÈ΋˜ ∂Ù·ÈÚ›·˜ Î·È Ù˘ ∂˘Úˆ·˚΋˜ ∫·Ú‰ÈÔÏÔÁÈ΋˜ ∂Ù·ÈÚ›·˜, Ô˘ Û˘ÛÙ‹ÓÔ˘Ó ÙË ÛÂÈÚÔÓÔÏ·ÎÙfiÓË ˆ˜ ·ÓÙÈ˘ÂÚÙ·ÛÈÎfi Ê¿ÚÌ·ÎÔ Ù¤Ù·ÚÙ˘ ÁÚ·ÌÌ‹˜10. ∏ ÌÂÁ·Ï‡ÙÂÚË Î·È ÈÔ ÚfiÛÊ·ÙË ·Ó¿Ï˘ÛË11 fiÏˆÓ ÙˆÓ ‰ËÌÔÛÈ¢ı¤ÓÙˆÓ Ì¤¯ÚÈ ÙÒÚ· ÁÈ· ÙË ¯Ú‹ÛË Ù˘ ÛÂÈÚÔÓÔÏ·ÎÙfiÓ˘ ÛÙËÓ ·ÓıÂÎÙÈ΋ ∞À ÚÔ¤Ú¯ÂÙ·È ·fi ˘ÔÔÌ¿‰· ·ÛıÂÓÒÓ Ù˘ ÌÂϤÙ˘ ASCOT-BPLA (Anglo-Scandinavian Cardiac Outcomes TrialBlood Pressure Lowering Arm)12. ™ÙË ÌÂϤÙË ·˘Ù‹ Û˘ÁÎÚ›ıËÎÂ Ë ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· Ù˘ ·ÙÂÓÔÏfiÏ˘ Ì ‹ ¯ˆÚ›˜ ıÂÈ·˙ȉÈÎfi ‰ÈÔ˘ÚËÙÈÎfi ¤Ó·ÓÙÈ Ù˘ ·ÌÏԉțÓ˘ Ì ‹ ¯ˆÚ›˜ ÂÚÈÓ‰ÔÚ›ÏË ÛÙËÓ ÚfiÏË„Ë ÙˆÓ ÌÂÈ˙fiÓˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ Û˘Ì‚·Ì¿ÙˆÓ Û 19.257 ˘ÂÚÙ·ÛÈÎÔ‡˜ ·ÛıÂÓ›˜, Ì ÙÚÂȘ ‹ ÂÚÈÛÛfiÙÂÚÔ˘˜ ·Ú¿ÁÔÓÙ˜ ηډȷÁÁÂÈ·ÎÔ‡ ÎÈÓ‰‡ÓÔ˘ Î·È ¯ˆÚ›˜ ÈÛÙÔÚÈÎfi ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘. ø˜ ·ÓÙÈ˘ÂÚÙ·ÛÈÎfi Ê¿ÚÌ·ÎÔ ÙÚ›Ù˘ ÁÚ·ÌÌ‹˜ ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ Ë ‰ÔÍ·˙ÔÛ›ÓË ÁÈ· Ó· ÂÈÙ¢¯ıÔ‡Ó Ù· ÂÈı˘ÌËÙ¿ ›‰· Ù˘ ∞¶ Û ÂÚ›ÙˆÛË ·ÔÙ˘¯›·˜ Ì ÙÔ˘˜ ·Ú¯ÈÎÔ‡˜ Ê·Ú̷΢ÙÈÎÔ‡˜ Û˘Ó‰˘·ÛÌÔ‡˜. ™Â 1.141 ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘ ASCOT-BPLA (̤ÛË ËÏÈΛ· 63 ¤ÙË, 77% ¿Ó‰Ú˜, 40% Ì ™¢), Ô˘ ‰ÂÓ ÂÈÙ‡¯ıËÎ·Ó ÔÈ ÛÙfi¯ÔÈ Ù˘ ·ÓÙÈ˘ÂÚÙ·ÛÈ΋˜ ·ÁˆÁ‹˜ Ì ÙÔ Û˘Ó‰˘·ÛÌfi ÙˆÓ ·Ú·¿Óˆ ·ÓÙÈ˘ÂÚÙ·ÛÈÎÒÓ Ê·ÚÌ¿ÎˆÓ ÛÙȘ ̤ÁÈÛÙ˜ ‰fiÛÂȘ, ¯ÔÚËÁ‹ıËΠÛÂÈÚÔÓÔÏ·ÎÙfiÓË (25 mg/ËÌ.), Ì ̤ÛË ‰È¿ÚÎÂÈ· ıÂڷ›·˜ Ù· 1,3 ¤ÙË11. ¢È·ÈÛÙÒıËΠÂÏ¿ÙÙˆÛË Ù˘ Û˘ÛÙÔÏÈ΋˜ ·ÚÙËÚȷ΋˜ ›ÂÛ˘ (™∞¶) ηٿ 21,9 mmHg Î·È Ù˘ ‰È·ÛÙÔÏÈ΋˜ ·ÚÙËÚȷ΋˜ ›ÂÛ˘ (¢∞¶) ηٿ 9,5 mmHg. ∞Ó¿ÏÔÁË ÂÏ¿ÙÙˆÛË Ù˘ ∞¶ ηٷÁÚ¿ÊËÎÂ Î·È Û ˘ÔÔÌ¿‰Â˜ ·ÛıÂÓÒÓ Ô˘ ÂÈϤ¯ıËÎ·Ó Ì ‚¿ÛË ÙËÓ ËÏÈΛ·, ÙÔ Ê‡ÏÔ, ÙÔ Î¿-
ÓÈÛÌ·, ÙËÓ ·ÚÔ˘Û›· ‹ ·Ô˘Û›· ™¢ Î·È ÛÂ Ù˘¯·ÈÔÔÈË̤Ó˜ ÔÌ¿‰Â˜ ·ÛıÂÓÒÓ ·Ó¿ÏÔÁ· Ì ÙË ¯ÔÚ‹ÁËÛË ·ÙÂÓÔÏfiÏ˘ ‹ ·ÌÏԉțÓ˘. Δ· ·ÔÙÂϤÛÌ·Ù· ·˘Ù¿ Ù˘ ÌÂϤÙ˘ ASCOT-BPLA Û˘ÌʈÓÔ‡Ó Ì ·Ú·ÙËÚ‹ÛÂȘ ÌÈÎÚfiÙÂÚˆÓ ÌÂÏÂÙÒÓ ÁÈ· ÙÔ ÚfiÏÔ Ù˘ ÛÂÈÚÔÓÔÏ·ÎÙfiÓ˘ ÛÙËÓ ·ÓıÂÎÙÈ΋ ∞À6-9. ™Â Ì›· Ù¤ÙÔÈ· ÌÂϤÙË6, Ë ËÌÂÚ‹ÛÈ· ¯ÔÚ‹ÁËÛË ÛÂÈÚÔÓÔÏ·ÎÙfiÓ˘ Û ‰fiÛË 25 mg/ËÌ. ¤ÊÂÚ Ì›ˆÛË Ù˘ ™∞¶ Î·È Ù˘ ¢∞¶ ηٿ 21,7 mmHg Î·È 8,5 mmHg, ·ÓÙ›ÛÙÔȯ·, Û ÔÌ¿‰· 114 ˘ÂÚÙ·ÛÈÎÒÓ ·ÛıÂÓÒÓ Ô˘ ‹Ù·Ó ‹‰Ë Û ·ÁˆÁ‹ Ì ·Ó·ÛÙÔÏ›˜ ÙÔ˘ ÌÂÙ·ÙÚÂÙÈÎÔ‡ ÂÓ˙‡ÌÔ˘ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘ I (·-ª∂∞) ÛÂ Û˘Ó‰˘·ÛÌfi Ì ¿ÏÏ· ·ÓÙÈ˘ÂÚÙ·ÛÈο Ê¿Ú̷η. øÛÙfiÛÔ, Ë ·ÍÈÔÏfiÁËÛË ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ ÙˆÓ ·Ú·¿Óˆ ÌÂÏÂÙÒÓ ı· Ú¤ÂÈ Ó· Á›ÓÂÈ Ì ȉȷ›ÙÂÚË ÚÔÛÔ¯‹2. ∂Í·ÈÙ›·˜ Ù˘ ·Ô˘Û›·˜ ÔÌ¿‰·˜ ÂϤÁ¯Ô˘ Ì ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ, Ë ÂÏ¿ÙÙˆÛË Ù˘ ∞¶ ı· ÌÔÚÔ‡Û ıˆÚËÙÈο Ó· ÔÊ›ÏÂÙ·È Û ¿ÏÏÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÂÎÙfi˜ Ù˘ ıÂڷ›·˜ Ì ÛÂÈÚÔÓÔÏ·ÎÙfiÓË, fiˆ˜ ÛÙËÓ Èı·ÓfiÙËÙ· ‡·Ú͢ ÌÂıÔ‰ÔÏÔÁÈÎÒÓ ·ÙÂÏÂÈÒÓ (bias). ∂›Û˘, ÛÙȘ ÌÂϤÙ˜ ·˘Ù¤˜ ‰ÂÓ ‰È¢ÎÚÈÓ›˙ÂÙ·È ·Ó ›¯·Ó ·ÔÎÏÂÈÛı› Ï‹Úˆ˜ Ù· ‰Â˘ÙÂÚÔ·ı‹ ·›ÙÈ· Ù˘ ∞À, ÂÓÒ Û ÔÚÈṲ̂Ó˜ ‰ÂÓ ˘¿Ú¯Ô˘Ó ÛÙÔȯ›· ÁÈ· ÙËÓ ‹‰Ë ˘¿Ú¯Ô˘Û· ·ÓÙÈ˘ÂÚÙ·ÛÈ΋ ·ÁˆÁ‹ ÙˆÓ ·ÛıÂÓÒÓ ÚÈÓ ·fi ÙËÓ ÚÔÛı‹ÎË Ù˘ ÛÂÈÚÔÓÔÏ·ÎÙfiÓ˘6,11. ™Â Ì›· Ù˘¯·ÈÔÔÈË̤ÓË Î·È ÂÏÂÁ¯fiÌÂÓË Ì ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ ÌÂϤÙË13 ÂÍÂÙ¿ÛÙËÎ·Ó ÔÈ ÂȉڿÛÂȘ Ù˘ ÛÂÈÚÔÓÔÏ·ÎÙfiÓ˘ Î·È Ù˘ ·ÌÈÏÔÚ›‰Ë˜ ͯˆÚÈÛÙ¿ Î·È ÙÔ˘ Û˘Ó‰˘·ÛÌÔ‡ ÙÔ˘˜ ÛÙËÓ ÂÏ¿ÙÙˆÛË Ù˘ ∞¶. ¢È·ÈÛÙÒıËΠÂÏ¿ÙÙˆÛË Ù˘ ™∞¶ Î·È Ù˘ ¢∞¶ ηٿ 9,8 mmHg Î·È 3,4 mmHg ÁÈ· ÙËÓ ·ÌÈÏÔÚ›‰Ë, ·ÓÙ›ÛÙÔȯ·, Î·È Î·Ù¿ 4,6 mmHg Î·È 1,8 mmHg ÁÈ· ÙË ÛÂÈÚÔÓÔÏ·ÎÙfiÓË,
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¢∂∫∂ªμƒπ√™ 2008
·ÓÙ›ÛÙÔȯ·. ∏ ÂÏ¿ÙÙˆÛË Ù˘ ∞¶ Ì ÙË ÛÂÈÚÔÓÔÏ·ÎÙfiÓË ‹Ù·Ó ÏÈÁfiÙÂÚÔ ÂÓÙ˘ˆÛȷ΋ Û ۇÁÎÚÈÛË Ì ÂΛӘ Ô˘ ηٷÁÚ¿ÊËÎ·Ó ÛÙȘ ·ÓÔȯ٤˜, ÌË ÂÏÂÁ¯fiÌÂÓ˜ ÌÂϤÙ˜. Δ· ¢ÓÔ˚ÎfiÙÂÚ· ·ÔÙÂϤÛÌ·Ù· Ù˘ ‰Ú¿Û˘ Ù˘ ÛÂÈÚÔÓÔÏ·ÎÙfiÓ˘ ÛÙËÓ ÂÏ¿ÙÙˆÛË Ù˘ ∞¶ Ô˘ ·Ú·ÙËÚ‹ıËΠÛÙȘ ÌË ÂÏÂÁ¯fiÌÂÓ˜ ÌÂϤÙ˜ Ê·›ÓÂÙ·È Ó· ÂËÚ¿˙ÔÓÙ·È ·fi: ·) ÙËÓ Èı·Ó‹ ‡·ÚÍË ‰Â˘ÙÂÚÔ·ıÒÓ ÌÔÚÊÒÓ ∞À, ‚) ÙËÓ ˘¿Ú¯Ô˘Û· ·ÓÙÈ˘ÂÚÙ·ÛÈ΋ ·ÁˆÁ‹, Á) ÙËÓ ÂÈÏÔÁ‹ ÙÔ˘ ÏËı˘ÛÌÔ‡ ÌÂϤÙ˘ Î·È ‰) ÙË Û˘Ó‡·ÚÍË ÌÂÙ·‚ÔÏÈÎÒÓ ‰È·Ù·Ú·¯ÒÓ fiˆ˜ ·¯˘Û·ÚΛ·, ™¢ Ù‡Ô˘ 2 ‹ ¿ÏÏˆÓ ·ıÔÏÔÁÈÎÒÓ Î·Ù·ÛÙ¿ÛÂˆÓ fiˆ˜ ÙÔ Û‡Ó‰ÚÔÌÔ ¿ÓÔÈ·˜ ηٿ ÙÔÓ ‡ÓÔ (™∞À) Î.¿2. ∂ÎÙÈÌ¿Ù·È fiÙÈ ÙÔ 5-10% ÙˆÓ ÂÚÈÙÒÛÂˆÓ Ù˘ ·ÓıÂÎÙÈ΋˜ ∞À ÔÊ›ÏÂÙ·È Û ‰Â˘ÙÂÚÔ·ı‹ ·›ÙÈ·1. ªÂٷ͇ ·˘ÙÒÓ Ô ÚˆÙÔ·ı‹˜ ˘ÂڷωÔÛÙÂÚÔÓÈÛÌfi˜ Ê·›ÓÂÙ·È Ó· Â›Ó·È Û˘¯ÓfiÙÂÚÔ˜ ·fi fi,ÙÈ ·Ú¯Èο ıˆڋıËÎÂ14-15. ™‡Ìʈӷ Ì ÚfiÛÊ·Ù˜ ¤Ú¢Ó˜, Ô ÂÈÔÏ·ÛÌfi˜ ÙÔ˘ ·ÁÁ›˙ÂÈ ÙÔ 10-15% ÙˆÓ ÂÓÒ ˘ÂÚÙ·ÛÈÎÒÓ ·ÛıÂÓÒÓ5, ·Ó¤Ú¯ÂÙ·È ÛÙÔ 40% ÙˆÓ ·ÛıÂÓÒÓ Ì ·ÓıÂÎÙÈ΋ ∞À16. ™˘ÓÂÒ˜ ‰ÂÓ ·ÔÎÏ›ÂÙ·È Ë Èı·Ó‹ Û˘ÌÌÂÙÔ¯‹ ·ÛıÂÓÒÓ Ì ·‰È¿ÁÓˆÛÙÔ ˘ÂڷωÔÛÙÂÚÔÓÈÛÌfi Ó· Ô‰‹ÁËÛ Û ÌÂÁ·Ï‡ÙÂÚË ·ÓÙ·fiÎÚÈÛË ÛÙË ‰Ú¿ÛË Ù˘ ÛÂÈÚÔÓÔÏ·ÎÙfiÓ˘. ™Â ÚfiÛÊ·ÙË ÌÂϤÙË ‚Ú¤ıËΠfiÙÈ Ë ¯ÔÚ‹ÁËÛË Ù˘ ÛÂÈÚÔÓÔÏ·ÎÙfiÓ˘ Û ‰fiÛË 25-50 mg/ËÌ., › 6 Ì‹Ó˜, ÚÔοÏÂÛ ÂÏ¿ÙÙˆÛË Ù˘ ™∞¶ Î·È Ù˘ ¢∞¶ ηٿ 25±20 mmHg Î·È 12±12 mmHg, ·ÓÙ›ÛÙÔȯ·, Û ¿ÙÔÌ· Ì ·ÓıÂÎÙÈ΋ ∞À Ì ‹ ¯ˆÚ›˜ ÚˆÙÔ·ı‹ ˘ÂڷωÔÛÙÂÚÔÓÈÛÌfi, Ô˘ ‹Ù·Ó ‹‰Ë Û ·ÁˆÁ‹ Ì ‰ÈÔ˘ÚËÙÈο ÛÂ Û˘Ó‰˘·ÛÌfi Ì ·-ª∂∞ ‹ Ì ·ÓÙ·ÁˆÓÈÛÙ¤˜ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ∞Δ1 Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘ ππ17 . ŸÛÔÓ ·ÊÔÚ¿ ÛÙËÓ ÂÈÏÔÁ‹ ÙÔ˘ ÏËı˘ÛÌÔ‡ ÌÂϤÙ˘ ÁÈ· ÙË ‰È·ÌfiÚʈÛË ÙˆÓ ·Ú·¿Óˆ ·ÔÙÂÏÂÛÌ¿ÙˆÓ, ·Í›˙ÂÈ Ó· ÛËÌÂȈı› fiÙÈ Û ̛· ·fi ÙȘ ÚÔ·Ó·ÊÂÚfiÌÂÓ˜ ÌÂϤÙ˜, Ë ·fiÊ·ÛË Ó· ¯ÔÚËÁËı› ÛÂÈÚÔÓÔÏ·ÎÙfiÓË ‚·Û›ÛÙËΠÛÙËÓ ËÏÈΛ· ÙˆÓ ·ÛıÂÓÒÓ, ÂÍ·ÈÙ›·˜ ÙÔ˘ ‰ÈÛÙ·ÁÌÔ‡ Ó· ¯ÔÚËÁËı› Û ӤԢ˜ ¿Ó‰Ú˜ ·ÛıÂÓ›˜, ÏfiÁˆ ÙˆÓ ·ÓÂÈı‡ÌËÙˆÓ ÂÓÂÚÁÂÈÒÓ ÛÙË ÛÂÍÔ˘·ÏÈ΋ ÏÂÈÙÔ˘ÚÁ›·6. °È· ÙÔ ÏfiÁÔ ·˘Ùfi, Ë Ì¤ÛË ËÏÈΛ· ÙˆÓ Û˘ÌÌÂÙ¯fiÓÙˆÓ
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‹Ù·Ó 62,5 ¤ÙË. ¶·ÚfiÌÔÈ·, ÛÙÔÓ ˘ÔÏËı˘ÛÌfi Ù˘ ÌÂϤÙ˘ ASCOT-BPLA, Ë Ì¤ÛË ËÏÈΛ· ÙˆÓ ·ÛıÂÓÒÓ ‹Ù·Ó Ù· 63 ¤ÙË11. Δ· ÛÙÔȯ›· ·˘Ù¿, ÂӉ¯Ô̤ӈ˜, Ô‰‹ÁËÛ·Ó Û ˘ÂÚÂÎÙ›ÌËÛË ÙˆÓ ÏÂÔÓÂÎÙËÌ¿ÙˆÓ Ù˘ ÛÂÈÚÔÓÔÏ·ÎÙfiÓ˘, ÂÂȉ‹ Ë ÌÂÁ¿ÏË ËÏÈΛ· (> 60 ÂÙÒÓ) Â›Ó·È ÈÛ¯˘Úfi˜ ÚÔÁÓˆÛÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ Ù˘ ·ÓıÂÎÙÈ΋˜ ∞À2. ™‡Ìʈӷ Ì ÂȉËÌÈÔÏÔÁÈο ‰Â‰Ô̤ӷ, Ë Â›ÙˆÛË Ù˘ ·ÓıÂÎÙÈ΋˜ ∞À Â›Ó·È È‰È·›ÙÂÚ· ˘„ËÏ‹ Û 2 ‚·ÛÈΤ˜ ÏËı˘ÛÌȷΤ˜ ÔÌ¿‰Â˜: ·) Û ¿ÙÔÌ· > 60 ÂÙÒÓ Î·È Û ¿ÙÔÌ· Ì ™¢ Ù‡Ô˘ 2. ™˘¯Ó‹ ÌÂÙ·‚ÔÏÈ΋ ‰È·Ù·Ú·¯‹ ÌÂٷ͇ ÙˆÓ 2 ÔÌ¿‰ˆÓ Â›Ó·È Ë ·¯˘Û·ÚΛ·, ΢ڛˆ˜ Ë ÎÂÓÙÚÈÎÔ‡ Ù‡Ô˘18. ™ÙÔÓ ˘ÔÏËı˘ÛÌfi Ù˘ ÌÂϤÙ˘ ASCOT-BPLA, ÙÔ 40% ÙˆÓ ·ÛıÂÓÒÓ ¤·Û¯Â ·fi ™¢ Ù‡Ô˘ 211. ∞Ó¿ÏÔÁ· ‹Ù·Ó Ù· ÔÛÔÛÙ¿ ÙˆÓ ·ÛıÂÓÒÓ Ì ™¢ Ù‡Ô˘ 2 ÛÙȘ ÌÈÎÚfiÙÂÚ˜ ÌÂϤÙ˜6-9, ÂÓÒ ÂÚÈÛÛfiÙÂÚÔÈ ·fi ÙÔ 50% ‹Ù·Ó ·¯‡Û·ÚÎÔÈ. Δ· ¯·Ú·ÎÙËÚÈÛÙÈο ·˘Ù¿, ÂÍ·ÈÙ›·˜ Ù˘ Èı·Ó‹˜ Û˘Û¯¤ÙÈÛ˘ Ì ·˘ÍË̤Ó˜ Û˘ÁÎÂÓÙÚÒÛÂȘ ·Ï‰ÔÛÙÂÚfiÓ˘ Ï¿ÛÌ·ÙÔ˜, ÂӉ¯Ô̤ӈ˜ Ô‰‹ÁËÛ·Ó Û ÌÂÁ·Ï‡ÙÂÚË ·ÓÙ·fiÎÚÈÛË ÛÙË ‰Ú¿ÛË Ù˘ ÛÂÈÚÔÓÔÏ·ÎÙfiÓ˘2. ¶Ú¿ÁÌ·ÙÈ, ÔÏϤ˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó Û·Ê‹ Û˘Û¯¤ÙÈÛË ÌÂٷ͇ ÙˆÓ ·ÓıÚˆÔÌÂÙÚÈÎÒÓ ·Ú·Ì¤ÙÚˆÓ Ù˘ ÎÂÓÙÚÈ΋˜ ·¯˘Û·ÚΛ·˜ Î·È ÙˆÓ ·˘ÍËÌ¤ÓˆÓ Û˘ÁÎÂÓÙÚÒÛÂˆÓ Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘ Ï¿ÛÌ·ÙÔ˜ Û ¿ÙÔÌ· Ì ∞À, Ô˘ ‰ÂÓ ÂÚÈÔÚ›˙ÂÙ·È ÛÙȘ Ù˘ÈΤ˜ ÂÚÈÙÒÛÂȘ ÙÔ˘ ÚˆÙÔ·ıÔ‡˜ ˘ÂڷωÔÛÙÂÚÔÓÈÛÌÔ‡. ™Â ÚfiÛÊ·ÙË ÌÂϤÙË Ô˘ ·ÊÔÚÔ‡Û 397 ·ÊÚÈηÓÈ΋˜ ηٷÁˆÁ‹˜ ∞ÌÂÚÈηÓÔ‡˜ (47% Ì ∞À, 50% Á˘Ó·›Î˜ Î·È 17% Ì ÌÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ) ‰È·ÈÛÙÒıËΠfiÙÈ ÔÈ ·ÛıÂÓ›˜ Ì ∞À ÂÌÊ¿ÓÈÛ·Ó ÌÂÁ·Ï‡ÙÂÚË ÂÚ›ÌÂÙÚÔ Ì¤Û˘ Î·È ‰Â›ÎÙË Ì¿˙·˜ ÛÒÌ·ÙÔ˜ (body mass index, μªπ), ‰˘ÛÏÈȉ·ÈÌ›· Î·È ·ÓÙ›ÛÙ·ÛË ÛÙËÓ ÈÓÛÔ˘Ï›ÓË ÛÂ Û˘Ó‰˘·ÛÌfi Ì ˘„ËÏfiÙÂÚ· ›‰· ·Ï‰ÔÛÙÂÚfiÓ˘ Ï¿ÛÌ·ÙÔ˜ Û ۇÁÎÚÈÛË Ì ٷ ÓÔÚÌÔÙ·ÛÈο ¿ÙÔÌ·19. ∞ÓÙÈÊ·ÙÈο ‰Â‰Ô̤ӷ ÚԤ΢„·Ó ÁÈ· ÙȘ ÙÈ̤˜ Ù˘ ‰Ú·ÛÙÈÎfiÙËÙ·˜ ÚÂÓ›Ó˘ Ï¿ÛÌ·ÙÔ˜ (plasma renin activity, PRA). Δ¤ÏÔ˜, Ù· ¿ÙÔÌ· Ì ÌÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ ÂÌÊ¿ÓÈÛ·Ó ˘„ËÏfiÙÂÚË ·Ï‰ÔÛÙÂÚfiÓË Ï¿ÛÌ·ÙÔ˜ Î·È ˘„ËÏfiÙÂÚÔ ÏfiÁÔ ·Ï‰ÔÛÙÂÚfiÓ˘/PRA Û ۇÁÎÚÈÛË ÌÂ
Ù· ¿ÙÔÌ· ¯ˆÚ›˜ ÙÔ Û‡Ó‰ÚÔÌÔ. ∏ ıÂÙÈ΋ Û˘Û¯¤ÙÈÛË Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘ Ï¿ÛÌ·ÙÔ˜ Ì ÙȘ ·Ú·¿Óˆ ·ÓıÚˆÔÌÂÙÚÈΤ˜ ·Ú·Ì¤ÙÚÔ˘˜ Î·È ÌÂÙ·‚ÔÏÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÛÙÔ˘˜ ˘ÂÚÙ·ÛÈÎÔ‡˜ ·ÛıÂÓ›˜, ˘Ô‰ËÏÒÓÂÈ fiÙÈ Ë ·Ï‰ÔÛÙÂÚfiÓË Èı·ÓfiÓ Ó· ÂÌϤÎÂÙ·È ÛÙÔ˘˜ Ì˯·ÓÈÛÌÔ‡˜ Ì ÙÔ˘˜ ÔÔ›Ô˘˜ Ë ·¯˘Û·ÚΛ· ÚÔηÏ› ∞À2. ¶ÚÔ·ÙÂÈ Â›Û˘ ÙÔ ÂÚÒÙËÌ· ÁÈ· ÙÔ ÂÚ¤ıÈÛÌ· Ô˘ ÚÔηÏ› ·‡ÍËÛË Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘ Ï¿ÛÌ·ÙÔ˜ ÛÙÔ˘˜ ˘ÂÚÙ·ÛÈÎÔ‡˜ ·ÛıÂÓ›˜ ¯ˆÚ›˜ ÙËÓ ·Ú¿ÏÏËÏË ·‡ÍËÛË Ù˘ PRA, ‰ËÏ·‰‹ ¯ˆÚ›˜ ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜ ÚÂÓ›Ó˘-·ÁÁÂÈÔÙÂÓÛ›Ó˘-·Ï‰ÔÛÙÂÚfiÓ˘ (™ƒ∞∞). √ÚÈṲ̂ÓÔÈ ÂÚ¢ÓËÙ¤˜ ıˆÚÔ‡Ó fiÙÈ Ë ˘„ËÏ‹ ·Ï‰ÔÛÙÂÚfiÓË Î·È Ë Û¯ÂÙÈο ¯·ÌËÏ‹ PRA ·ÓÙ·Ó·ÎÏÔ‡Ó ÌÈ· ‹È· ·Ú·ÏÏ·Á‹ ÙÔ˘ ÚˆÙÔ·ıÔ‡˜ ˘ÂڷωÔÛÙÂÚÔÓÈÛÌÔ‡, Ô˘ ÂӉ¯Ô̤ӈ˜ Û˘Ó‰¤ÂÙ·È Â›Ù Ì ÙË ÌÔÚȷ΋ ÔÈÎÈÏfiÙËÙ· Ù˘ ÊÏÔÈÔÙÚfiÔ˘ ÔÚÌfiÓ˘ (ACTH) ›Ù Ì ÙË ÁÂÓÂÙÈ΋ ÔÈÎÈÏÔÌÔÚÊ›· ÙˆÓ ÁÔÓȉ›ˆÓ Ô˘ Έ‰ÈÎÔÔÈÔ‡Ó ÙË Û˘ÓıÂÙ¿ÛË Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘. ∞˘Ù¤˜ ÔÈ ‰‡Ô ÌÔÚ› Ó· ÂÈʤÚÔ˘Ó ·‡ÍËÛË Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘, ¯ˆÚ›˜ ÙË ÌÂÛÔÏ¿‚ËÛË Â͈ÁÂÓÒÓ Ú˘ıÌÈÛÙÒÓ, fiˆ˜ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘ ππ (∞ππ), ÙÔ˘ Î·Ï›Ô˘ Î·È Ù˘ ACTH20. ∂Ӊ›ÍÂȘ ÁÈ· ÙËÓ Èı·Ó‹ ‡·ÚÍË Ì˯·ÓÈÛÌÒÓ ·ÓÂÍ¿ÚÙËÙˆÓ ÙÔ˘ ™ƒ∞∞ Ô˘ ÚÔηÏÔ‡Ó ·‡ÍËÛË Ù˘ ¤ÎÎÚÈÛ˘ Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘ Û ·¯‡Û·Úη ¿ÙÔÌ· ÚԤ΢„·Ó ·fi ÚfiÛÊ·ÙË ÌÂϤÙË ÛÙËÓ ÔÔ›· Û˘ÁÎÚ›ıËÎ·Ó Ù· ›‰· Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘ Ï¿ÛÌ·ÙÔ˜, Ù˘ PRA, Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘, ÙˆÓ ÏÈÔÚˆÙÂ˚ÓÒÓ ¯·ÌËÏ‹˜ ˘ÎÓfiÙËÙ·˜ (LDL) Û ·¯‡Û·ÚΘ ˘ÂÚÙ·ÛÈΤ˜ Î·È ·¯‡Û·ÚΘ ÓÔÚÌÔÙ·ÛÈΤ˜ Á˘Ó·›Î˜21. ™ÙȘ ·¯‡Û·ÚΘ ˘ÂÚÙ·ÛÈΤ˜ Á˘Ó·›Î˜ ‰È·ÈÛÙÒıËÎ·Ó ¯·ÌËÏ‹ PRA, ·˘ÍË̤ÓÔ˜ ÏfiÁÔ˜ ·ÏÔ‰ÔÛÙÂÚfiÓ˘/PRA Î·È ˘„ËϤ˜ ÙÈ̤˜ LDL Û ۯ¤ÛË Ì ÙȘ ·¯‡Û·ÚΘ ÓÔÚÌÔÙ·ÛÈΤ˜ Á˘Ó·›Î˜. ™ÙËÓ ›‰È· ÌÂϤÙË, ·Ó·Ê¤ÚÂÙ·È Û ÂÈÚ·Ì·ÙÈÎfi Â›Â‰Ô fiÙÈ ÔÈ LDL ÏÈÔÚˆÙ½Ó˜ ·˘Í¿ÓÔ˘Ó ÙËÓ Â˘·ÈÛıËÛ›· ÙˆÓ ÊÏÔÈÔÂÈÓÂÊÚȉȷÎÒÓ Î‡ÙÙ·ÚˆÓ ÛÙË ‰Ú¿ÛË Ù˘ ∞ππ Î·È ÙËÓ ÂÍ·ÚÙÒÌÂÓË ·fi ÙËÓ ∞ππ ¤ÎÎÚÈÛË Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘. Δ· ÛÙÔȯ›· ·˘Ù¿ Ô‰‹ÁËÛ·Ó ÛÙËÓ ˘fiıÂÛË fiÙÈ Ë ·‡ÍËÛË ÙÔ˘ ÏfiÁÔ˘ ·Ï‰ÔÛÙÂÚfiÓ˘/PRA ÔÊ›ÏÂÙ·È Â›Ù ÛÙȘ ˘„Ë-
∫§π¡π∫∂™ ª∂§∂Δ∂™ Ϥ˜ ÙÈ̤˜ ÙˆÓ LDL ›Ù ÛÙËÓ ·ÚÔ˘Û›· ¿ÏÏˆÓ ‰Ú·ÛÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ Ô˘ ÚÔ¤Ú¯ÔÓÙ·È ·fi ÙÔ ÛÏ·¯ÓÈÎfi ÏÈÒ‰Ë ÈÛÙfi. ∞Ó·ÊÔÚÈο Ì ÙÔ ÙÂÏÂ˘Ù·›Ô, ¤¯ÂÈ ·Ô‰ÂȯÙ› in vitro fiÙÈ Ë ÔÍ›‰ˆÛË ÙˆÓ ÂχıÂÚˆÓ ÏÈ·ÚÒÓ ÔͤˆÓ ÙÔ˘ ÛÏ·¯ÓÈÎÔ‡ Ï›Ô˘˜ ·fi Ù· Ë·ÙÔ·ÙÙ·Ú· Ô‰ËÁ› ÛÙËÓ ·Ú·ÁˆÁ‹ ÂÓÂÚÁÒÓ Ú˘ıÌÈÛÙÒÓ ÁÈ· ÙËÓ ¤ÎÎÚÈÛË Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘ ¯ˆÚ›˜ ÙË ÌÂÛÔÏ¿‚ËÛË ÙÔ˘ ™ƒ∞∞22. ∏ ÂÓ‰ÔÎÚÈÓÈ΋ ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÛÏ·¯ÓÈÎÔ‡ ÏÈÒ‰Ô˘˜ ÈÛÙÔ‡ Â›Ó·È ·Ô‰Â‰ÂÈÁ̤ÓË ‹‰Ë ·fi ÙËÓ ÚÔËÁÔ‡ÌÂÓË ‰ÂηÂÙ›·23. ªÂϤÙ˜ Û ÂÈÚ·Ì·Ùfi˙ˆ·24 Î·È Û ·ÓıÚÒÔ˘˜23 ¤‰ÂÈÍ·Ó fiÙÈ Ô ÛÏ·¯ÓÈÎfi˜ ÏÈ҉˘ ÈÛÙfi˜ ·ÔÙÂÏ› ÛËÌ·ÓÙÈ΋ Â͈˷ÙÈ΋ ËÁ‹ ·Ú·ÁˆÁ‹˜ ·ÁÁÂÈÔÙÂÓÛÈÓÔÁfiÓÔ˘ (AGT), Ë ·Ú·ÁˆÁ‹ ÙÔ˘ ÔÔ›Ô˘ ·˘Í¿ÓÂÈ ÛËÌ·ÓÙÈο ÛÙËÓ ·¯˘Û·ÚΛ·. ∂Ӊ¯Ô̤ӈ˜ Ó· ¢ı‡ÓÂÙ·È ÁÈ· Ù· ·˘ÍË̤ӷ ΢ÎÏÔÊÔÚÔ‡ÓÙ· ›‰· ÙÔ˘ AGT Î·È Î·Ù' ¤ÎÙ·ÛË Ù˘ ∞ππ Î·È Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘ Ï¿ÛÌ·ÙÔ˜ ÛÙ· ·¯‡Û·Úη Û ۇÁÎÚÈÛË Ì ٷ ÏÂÙfiۈ̷
¿ÙÔÌ· Î·È ÛÙËÓ ¿ÓÔ‰Ô Ù˘ ∞¶ ̤ۈ Ù˘ ÂÓÂÚÁÔÔ›ËÛ˘ ÙÔ˘ ™ƒ∞∞24. ™‡Ìʈӷ Ì ÚfiÛÊ·Ù· ÛÙÔȯ›·, Ô ÛÏ·¯ÓÈÎfi˜ ÏÈ҉˘ ÈÛÙfi˜ Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ∞À ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi: 1) ‰È·Ù·Ú·¯‹ Ù˘ ·Ú·ÁˆÁ‹˜ ‚ÈÔ‰Ú·ÛÙÈÎÒÓ ÌÔÚ›ˆÓ ÁÈ· ·Ú¿‰ÂÈÁÌ· ÙÔ˘ AGT Ô˘ fiˆ˜ ·Ó·Ê¤ÚıËΠÂÌϤÎÂÙ·È ÛÙÔ Ì˯·ÓÈÛÌfi ·‡ÍËÛ˘ Ù˘ ∞¶ Ì ÙË ÌÂÛÔÏ¿‚ËÛË ÙÔ˘ ™ƒ∞∞ Î·È ÙËÓ ÂÌÊ¿ÓÈÛË ÙÔ˘ ˘ÂڷωÔÛÙÂÚÔÓÈÛÌÔ‡, 2) ¤ÎÙÔË ÂÓ·fiıÂÛË Ï›Ô˘˜ ÛÙÔ˘˜ ÛÎÂÏÂÙÈÎÔ‡˜ ̇˜ Î·È ÙÔ ‹·Ú Ô˘ Ô‰ËÁ› Û ˘ÂÚÈÓÛÔ˘ÏÈÓ·ÈÌ›· Î·È ·‡ÍËÛË Ù˘ ∞¶ Ì ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ Û˘Ì·ıËÙÈÎÔ‡ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ Î·È 3) ‰È‹ıËÛË ·fi Ì·ÎÚÔÊ¿Á· ·ÙÙ·Ú·, Ë ÔÔ›· ÚÔηÏ› ·ÓÙ›ÛÙ·ÛË ÛÙËÓ ÈÓÛÔ˘Ï›ÓË, ˘ÂÚÈÓÛÔ˘ÏÈÓ·ÈÌ›· Î·È ·‡ÍËÛË ÙÔ˘ ÔÍÂȉˆÙÈÎÔ‡ stress Ô˘ Ô‰ËÁÔ‡Ó Û ·‡ÍËÛË Ù˘ ∞¶24. ΔÔÓ›˙ÂÙ·È fiÙÈ Ù· ·Ú·¿Óˆ ¯·Ú·ÎÙËÚÈÛÙÈο Û¯ÂÙ›˙ÔÓÙ·È ÌÂ Û˘ÁÎÂÎÚÈ̤ÓË ÌÔÚÊÔÏÔÁ›· ÙÔ˘ ÏÈÒ‰Ô˘˜ ÈÛÙÔ‡, Ô˘ ·ÔÙÂÏ›ٷÈ
·fi ¢ÌÂÁ¤ıË ÏÈÔ·ÙÙ·Ú·. μÚ¤ıËΠfiÙÈ ÙÔ Ì¤ÁÂıÔ˜ ÙˆÓ ÏÈÔ΢ÙÙ¿ÚˆÓ Û¯ÂÙ›˙ÂÙ·È ÁÚ·ÌÌÈο Ì ÙËÓ ·Ú·ÁˆÁ‹ ÙÔ˘ AGT, ÙËÓ ¤ÎÙÔË ÂÓ·fiıÂÛË Ï›Ô˘˜ Î·È ÙÔ ‚·ıÌfi Ù˘ ÏÈȉÈ΋˜ ‰È‹ıËÛ˘, ÂÓÒ Ë Î·Ù·ÛÙÔÏ‹ ÙÔ˘ ™ƒ∞∞ Ì ·ª∂∞ ‹ Ô ·ÔÎÏÂÈÛÌfi˜ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ∞Δ1 Ù˘ ∞ππ Ô‰ËÁÔ‡Ó Û ÂÏ¿ÙÙˆÛË ÙÔ˘ ÌÂÁ¤ıÔ˘˜ ÙˆÓ Î˘ÙÙ¿ÚˆÓ, ÔÌ·ÏÔÔ›ËÛË Ù˘ ∞¶ Î·È ·‡ÍËÛË Ù˘ ¢·ÈÛıËÛ›·˜ ÛÙËÓ ÈÓÛÔ˘Ï›ÓË23. ™˘ÌÂÚ·ÛÌ·ÙÈο, Ê·›ÓÂÙ·È fiÙÈ Ë ÛÂÈÚÔÓÔÏ·ÎÙfiÓË Î·Ù¤¯ÂÈ ÛËÌ·ÓÙÈ΋ ı¤ÛË ÛÙË Ú‡ıÌÈÛË Ù˘ ·ÓıÂÎÙÈ΋˜ ∞À Î·È ÂȉÈο Û ÂÚÈÙÒÛÂȘ Ì ¯·Ú·ÎÙËÚÈÛÙÈο ·˘ÍË̤Ó˘ ¤ÎÎÚÈÛ˘ ·Ï‰ÔÛÙÂÚfiÓ˘, fiˆ˜ Û ·ÛıÂÓ›˜ Ì ڈÙÔ·ı‹ ˘ÂڷωÔÛÙÂÚÔÓÈÛÌfi, ·¯˘Û·ÚΛ·, ™¢ Ù‡Ô˘ 2, Î.¿. ∞ӷ̤ÓÔÓÙ·È Î·È ÓÂfiÙÂÚ˜ ÌÂϤÙ˜ Ì ÙÔ ÓÂfiÙÂÚÔ ·ÓÙ·ÁˆÓÈÛÙ‹ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘, ÙËÓ ÂÏÂÚÂÓfiÓË, Û ·ÛıÂÓ›˜ Ì ·ÓıÂÎÙÈ΋ ∞À.
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