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™YNTAKTIKH E¶ITPO¶H ¢È¢ı˘ÓÙ‹˜ ™‡ÓÙ·Í˘ XÂÈÌÒÓ·˜ HÏ›·˜ K·Ú‰ÈÔÏfiÁÔ˜ YÔÙ¤Ú·Ú¯Ô˜ Â.·.
M¤ÏË Õı˘ÚÔ˜ B·Û›ÏÂÈÔ˜ AÓ·ÏËÚˆÙ‹˜ ¢È¢ı˘ÓÙ‹˜ E™Y K·Ú‰ÈÔÏÔÁÈÎfi TÌ‹Ì· B’ ¶ÚÔ·È‰Â˘ÙÈ΋˜ KÏÈÓÈ΋˜ A¶£ IÔÎÚ¿ÙÂÈÔ NÔÛÔÎÔÌÂ›Ô £ÂÛÛ·ÏÔӛ΢
E¶I¢HMIO§O°IA – ¶APA°ONTE™ KIN¢YNOY TÚfiÔ˜ ˙ˆ‹˜ ÙˆÓ ÁËÚ·ÈfiÙÂÚˆÓ ÂÓËϛΈÓ: MÔÚԇ̠ӷ ÂËÚ¿ÛÔ˘Ì ÙÔÓ Î·Ú‰È·ÁÁÂÈ·Îfi ΛӉ˘ÓÔ ÛÙÔ˘˜ ÁËÚ·ÈfiÙÂÚÔ˘˜ ÂÓ‹ÏÈΘ; – Mzaffarian D, Fried LP, Burke GL, Fitzpatrick A, Siscovick DS Am J Geriatr Cardiol 2004;13:153-60 – EÈ̤ÏÂÈ· HÏ›·˜ XÂÈÌÒÓ·˜
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¶·¯˘Û·ÚΛ· Î·È MÂÙ·‚ÔÏÈÎfi ™‡Ó‰ÚÔÌÔ Û ·È‰È¿ Î·È ÂÊ‹‚Ô˘˜ – Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, Yeckel CW, Allen K, Lopes M, Savoye M, Morrison J, Sherwin RS, Caprio S N Engl J Med 2004;350:2362-74 – EÈ̤ÏÂÈ· HÏ›·˜ XÂÈÌÒÓ·˜
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EÈÔÏ·ÛÌfi˜ ÙÔ˘ MÂÙ·‚ÔÏÈÎÔ‡ ™˘Ó‰ÚfiÌÔ˘ Û ·ÛıÂÓ›˜ Ì ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ, ·ÁÁÂȷΤ˜ ÂÁÎÂÊ·ÏÈΤ˜ ·ı‹ÛÂȘ, ÂÚÈÊÂÚÈ΋ ·ÚÙËÚÈÔ¿ıÂÈ· ‹ ·Ó‡ڢÛÌ· Ù˘ ÎÔÈÏȷ΋˜ ·ÔÚÙ‹˜ Gorter PM, Olijhoek JK, van der Graaf Y, Algra A, Rabelink TJ, Visseren FLJ. Atherosclerosis 2004;173:363-369 – EÈ̤ÏÂÈ· HÏ›·˜ XÂÈÌÒÓ·˜
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™˘Û¯¤ÙÈÛË ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÓËÛÙ›·˜ Î·È ¯ˆÚ›˜ ÓËÛÙ›· Ì ٷ ı·Ó·ÙËÊfiÚ· Î·È ÌË ı·Ó·ÙËÊfiÚ· ÛÙÂÊ·ÓÈ·›· ÂÂÈÛfi‰È· – Eberly LE, Stamler J, Neaton JD Arch Intern Med 2003;163:1077-83 – EÈ̤ÏÂÈ· HÏ›·˜ XÂÈÌÒÓ·˜
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¶A£OºY™IO§O°IA ¶ÔÛÔÙÈΤ˜ Î·È ÔÈÔÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙˆÓ ÏÈȉ›ˆÓ Û ·ÛıÂÓ›˜ Ì ÔÍ›˜ ÏÔÈÌÒÍÂȘ º. AÔÛÙfiÏÔ˘, E. §˘ÌÂÚfiÔ˘ÏÔ˜, M. EÏÈÛ¿Ê ¢˘ÛÏÈȉ·ÈÌ›· Î·È Î·Ú‰È·Î‹ ·Ó¿ÚÎÂÈ·: Y¿Ú¯ÂÈ Û˘Û¯¤ÙÈÛË; – I. ™Îԇ̷˜, X. ¶›ÙÛ·‚Ô˜, X. ™ÙÂÊ·Ó¿‰Ë˜ A‰ÈÔÓÂÎÙ›ÓË: ÕÏÏË Ì›· ÔÚÌfiÓË ÙÔ˘ ÏÈÒ‰Ô˘˜ ÈÛÙÔ‡; – EÈÚ. °·˙‹, M. EÏÈÛ¿Ê
°·ÓˆÙ¿Î˘ EÌÌ·ÓÔ˘‹Ï E›ÎÔ˘ÚÔ˜ K·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜ I·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ HÚ·ÎÏ›Ԣ ¶ÂÚÈÊÂÚÂÈ·Îfi ¶·ÓÂÈÛÙËÌÈ·Îfi NÔÛÔÎÔÌÂ›Ô HÚ·ÎÏ›Ԣ KÚ‹Ù˘
EÏÈÛ¿Ê Mˆ˘Û‹˜ K·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜ I·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ Iˆ·ÓÓ›ÓˆÓ ¶ÂÚÈÊÂÚÂÈ·Îfi ¶·ÓÂÈÛÙËÌÈ·Îfi NÔÛÔÎÔÌÂ›Ô Iˆ·ÓÓ›ÓˆÓ
KÔÏÔ‚Ô‡ °ÂÓÔ‚¤Ê· K·Ú‰ÈÔÏfiÁÔ˜ YԉȢı‡ÓÙÚÈ· A’ K·Ú‰ÈÔÏÔÁÈ΋˜ KÏÈÓÈ΋˜ Î·È ˘Â‡ı˘ÓÔ˜ §Èȉ·ÈÌÈÎÔ‡ I·ÙÚ›Ԣ øÓ·Û›Ԣ K·Ú‰ÈÔ¯ÂÈÚÔ˘ÚÁÈÎÔ‡ K¤ÓÙÚÔ˘
MÈÏÈ·ÓÔ‡ EϤÓË K·Ú‰ÈÔÏfiÁÔ˜ EÈÌÂÏËÙ‹˜ A’ Ù˘ K·Ú‰ÈÔÏÔÁÈ΋˜ KÏÈÓÈ΋˜ Î·È ˘Â‡ı˘ÓÔ˜ §Èȉ·ÈÌÈÎÔ‡ I·ÙÚ›Ԣ T˙·Ó›Ԣ NÔÛÔÎÔÌ›Ԣ ¶ÂÈÚ·ÈÒ˜
¶›ÙÛ·‚Ô˜ XÚ‹ÛÙÔ˜ AÓ·ÏËÚˆÙ‹˜ K·ıËÁËÙ‹˜ K·Ú‰ÈÔÏÔÁ›·˜, I·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ AıËÓÒÓ IÔÎÚ¿ÙÂÈÔ NÔÛÔÎÔÌÂ›Ô AıËÓÒÓ
°ÔÓ›‰È· Î·È ™ÙÂÊ·ÓÈ·›· NfiÛÔ˜ – °. KÔÏÔ‚Ô‡, K. AÓ·ÁÓˆÛÙÔÔ‡ÏÔ˘ E›‰Ú·ÛË ÙÔ˘ ·Ó·ÛÙÔϤ· Ù˘ ÚˆÙ½Ó˘ ÌÂÙ·ÊÔÚ¿˜ ÙˆÓ ÂÛÙ¤ÚˆÓ ¯ÔÏËÛÙÂÚfiÏ˘ ÛÙËÓ ˘„ËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙ½ÓË Brousseau ME, Schaefer EJ, Wolfe ML, Bloedon LT, Digenio AG, Clark RW, Mancuso JP, Rader DJ N Engl J Med 2004;350:1505-1515 – EÈ̤ÏÂÈ· K·ÙÂÚ›Ó· AÓ·ÁÓˆÛÙÔÔ‡ÏÔ˘
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BA™IKH EPEYNA H ›‰Ú·ÛË Ù˘ Û˘Á¯ÔÚ‹ÁËÛ˘ ·ÏÎÔfiÏ Î·È ÁÂÌÊÈÌÚÔ˙›Ï˘ Û ·ÚÔ˘Ú·›Ô˘˜ (Wistar rats) °. KÔÏÔ‚Ô‡, ¢. Mȯ·ËÏ›‰Ë˜, N. K·Ê·ÏÙ‹˜, E. A‰·ÌÔÔ‡ÏÔ˘, E. °È·˙ÈÙ˙fiÁÏÔ˘, A. X·Ù˙¿ÎË, N. ¶ÈÏ¿Ù˘, A. M·ÚÁ¤ÏË, K. ™·Ï¤·, M. M˘ÎÔÓÈ¿Ù˘, ¢. KfiÎÎÈÓÔ˜ In vivo, 2004;18:49-54 – EÈ̤ÏÂÈ· KϤÏÈ· ¢. ™·Ï¤·
¢IAITA K·Ê½ÓË, OÈÓfiÓÂ˘Ì· Î·È ™·Î¯·Ú҉˘ ¢È·‚‹Ù˘ Ù‡Ô˘ 2 – EÈÚ. °·˙‹, M. EÏÈÛ¿Ê AÔÙÂϤÛÌ·Ù· Ù˘ ·Ú·ÙÂٷ̤Ó˘ ÚfiÛÏ˄˘ ˘ÂÚ‚¿ÏÏÔ˘Û·˜ ÔÛfiÙËÙ·˜ ÙÚÔÊ‹˜ ÛÙ· ›‰· ÙˆÓ ÏÈÔÚˆÙÂ˚ÓÒÓ ÙÔ˘ Ï¿ÛÌ·ÙÔ˜ Û ÌÔÓÔ˙˘ÁˆÙÈÎÔ‡˜ ‰È‰‡ÌÔ˘˜ Teràn-Garcia M, Després J-P, Coullard C, Tremblay A, Bouchard C Atherosklerosis 2004;173:277-283 – EÈ̤ÏÂÈ· HÏ›·˜ XÂÈÌÒÓ·˜
£EPA¶EIA — ºAPMAKA
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™˘Û¯¤ÙÈÛË ÌÂٷ͇ Ù˘ ıÂڷ›·˜ Ì ÛÙ·Ù›Ó˜ Î·È Ù˘ ¤Î‚·Û˘ ÙˆÓ ÔͤˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ Û˘Ó‰ÚfïÓ: The GRACE Study – Spencer FA, Jeanna Allegrone J, Goldberg RJ, et al Ann Intern Med 2004;140:857-866 – EÈ̤ÏÂÈ· B·Û›ÏÂÈÔ˜ Õı˘ÚÔ˜
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MÔÓÙ¤ÏÔ Úfi‚Ï„˘ ÔÏÈ΋˜ ıÓËÙfiÙËÙ·˜ Û ·ÛıÂÓ›˜ Ì Ôͤ· ÛÙÂÊ·ÓÈ·›· Û‡Ó‰ÚÔÌ·: The GRACE Study Kim A. Eagle KA, Lim MJ, et al JAMA 2004;291:2727-2733 – EÈ̤ÏÂÈ· B·Û›ÏÂÈÔ˜ Õı˘ÚÔ˜
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¢È·ÊÔÚÂÙÈ΋ ıÂڷ›· Î·È ¤Î‚·ÛË ·ÛıÂÓÒÓ Ì ¤ÌÊÚ·ÁÌ· Ì˘Ôηډ›Ô˘ ¯ˆÚ›˜ ·Ó¿Û·ÛË ÙÔ˘ ST ‰È·ÛÙ‹Ì·ÙÔ˜, ·Ó¿ÏÔÁ· Ì ÙȘ ·ÏÏ·Á¤˜ ÛÙÔ HK° Acute Coronary Syndromes [ACOS] Registry Wienbergen H, Gitt AK, Schiele R, et al Am J Cardiol 2004;93:1543-1546 – EÈ̤ÏÂÈ· B·Û›ÏÂÈÔ˜ Õı˘ÚÔ˜
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OÈ ÛÙ·Ù›Ó˜ ¤¯Ô˘Ó ÌÈ· ÚfiÛıÂÙË ˘ÔÙ·ÛÈ΋ ‰Ú¿ÛË Û ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ̷ÎÚÔ¯ÚfiÓÈ· ıÂڷ›· Ì ·ÓÙÈ˘ÂÚÙ·ÛÈο Ê¿Ú̷η Ikeda T, Sakurai J, Nakayama D, Takahashi Y, Matsuo K, Shibuya Y, Gomi T, Moriya H and Kobayashi S Am Heart J 2004;17:502-6 – EÈ̤ÏÂÈ· HÏ›·˜ XÂÈÌÒÓ·˜
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E›‰Ú·ÛË Ù˘ ·ÛÈÚ›Ó˘ ÛÙËÓ ÂÌÊ¿ÓÈÛË Î·È ¤Î‚·ÛË ÙˆÓ ÔͤˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ Û˘Ó‰ÚfïÓ: The Global Registry of Acute Coronary Events [GRACE] Spencer FA, Santopinto JJ, Gore JM, et al for the GRACE Investigators Am J Cardiol 2000;90:1056-1061 – EÈ̤ÏÂÈ· B·Û›ÏÂÈÔ˜ Õı˘ÚÔ˜
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E›‰Ú·ÛË Ù˘ ‰fiÛ˘ Ù˘ ·ÛÈÚ›Ó˘ Û ÌÔÓÔıÂڷ›· ‹ ÛÂ Û˘Á¯ÔÚ‹ÁËÛË Ì ÎÏÔȉÔÁÚ¤ÏË Û ·ÛıÂÓ›˜ Ì Ôͤ· ÛÙÂÊ·ÓÈ·›· Û‡Ó‰ÚÔÌ·: the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study – Peters RJ, Mehta SR, Fox KA, et al; Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) Trial Investigators Circulation 2003;108:1682-1687 – EÈ̤ÏÂÈ· B·Û›ÏÂÈÔ˜ Õı˘ÚÔ˜
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H ›‰Ú·ÛË Ù˘ ÌÔÓÔıÂڷ›·˜ Ì ÎÏÔȉÈÁÚ¤ÏË ‹ ·ÛÈÚ›ÓË Î·È ÙÔ˘ Û˘Ó‰˘·ÛÌÔ‡ ÙÔ˘˜ ÛÙË ÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ Û ·ÛıÂÓ›˜ Ì ÂÚÈÊÂÚÈ΋ ·ÁÁÂÈÔ¿ıÂÈ· Jagroop IA, Matsagas MI, Geroulakos G, Mikhailidis DP Platelets 2004;15:117-125 – EÈ̤ÏÂÈ· B·Û›ÏÂÈÔ˜ Õı˘ÚÔ˜
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·fi ÛÈÌfiÙËÙ· Ë Ó ı È · Î fiÙËÙ· ÏÈÎfi Ô ÌÂÙ·‚Ô ÛÙË ÓÔÛËÚ T Ô . Ï ˜ fi Â Ú ÈÎ Ï fi Î·È ·ÓÙÈÎ ˜ ÂÓ‹ χ Û˘¯Ófi Ú·ÈfiÙÂÚÔ˘ ·Ù›˙ÂÈ ÛËÌ Ô Ë Ì Á · È Ú ˜ ‰ · ˘ ›Ó È· Ô Â Ù ‰ Û ˙ˆ‹˜ E›Û˘ Ú›Ô˘ Ë Î·È O ÙÚfiÔ˜ ÂÊ‹‚Ô˘˜. È ÌÈÛÔ›  ·Ù· ·ÎfiÌ O Ì È ‹ . · Û Ô Î Ô Û Ó fi È¿ Ó ¿ ȉ È·Î ·ÙÈ΋ Û · Ϥ˜ ÙÈηډȷÁÁ ÏË ·ıËÚˆÌ Ô. OÈ ˘„Ë Ù¿ Û˘¯Ófi Ë Â Ì ‰ Î Ô Î Ú ¤ Ú ‰ · ¿ Ó È ‡ ÈÎ · Û , Â›Ó Ó ·fi ÎÏÈÓ ›˜ ÓËÛÙ›· ÂÙ·‚ÔÏÈÎfi ˘ Ú Ì Ô Û‡Ó‰ÚÔÌÔ ˆ ¯ fi ¯ Û ¿  · ›Ù Ó ˘  ˘ ¿Û¯Ô Ș ÛÙ›· ÏÈΘ Ô ËÏÈΛ·˜, ˜ ÏÔÈÌÒÍÂ Ô‡Ó Û ÓË ˜ ı ›Â ÛÙÔ˘˜ ÂÓ‹ ˆ Â Ë Ù Í Ú ‹ Ô Ù Ù Â È Ú Ì O · ˜ Í ·˘Ù¤ ÙˆÓ ÈÛfi‰È·. ‡˜, ·Ó ·›Ì·, ›ÙÂ Ë ÌÂϤÙË ÓÈ·›·  ·fi ·˘ÙÔ · È Ô Ê Ù · Â Û Î Ù Û Ó ˜  ›ˆ ¿ ˝Ó ÌÔ‡ ˘ÎÂÚȉ ÏÏÔÓÙÈÎ ÔÚˆÙ ÌÂÙ·‚ÔÏÈÛ Ì¤˜ ÙÚÈÁÏ ¿ ÙȘ ÏÈ ›· ÁÈ· Ì ˘ Í Ô ÈÎ · Ù Ù Ô È ‹ Û · ÈÎ Ô Î Ù Û ÁÓˆ ÚfiÏÔÁ›·˜ Ô Î·È ¤¯Ô˘Ó ÚÔ ÂÈ· ̤ۈ ÈÔÙÈο fiÛ Î ·ıÔÊ˘ÛÈÔ Ô Ú ˜ ¿ Ë Ù Ô Â Û Ó Ë fi · Û Ù Ë ‡Ó Ù·Ófi Ó ÛÙËÓ Ú‰È·Î‹ ÙÚÔÔÔÈÔ ÂÈ ÛÙËÓ Î· ˜ ‚ÔËıÔ‡ ¯ÚfiÓÈ· η ¿ ı ›Ó Â Ë Ù Û Ô · Ù ‚ Ó Û ‡ ˜ Ô È ¿ Á O Ë Ó Ì ıËڈ̿و ¿ıÂÈ·˜. ·È̛˜ Ô‰ · ÈÔ ÌÂÙ·‚ÔÏÒ È‰ ˜ ‰ Ë Ú È Ù Ï · Û Î Ë ˘ „ ‰ ˜ ÚfiÏË È· ¯·ÈÌÈ΋ ›ˆÓ. OÈ ˜ Ì ÙËÓ Ë) Â›Ó·È Ì Ô˘ Î·È ÈÛ È· ÙˆÓ ÏÈȉ ›Ó Â Û Ù Î fi Î Ó Ú Â ¿ Ó ˜ Ô Â ›· Ó È Ìfi ΋˜ · ›ÓË (Ï ÂÊ·ÓÈ· ÌÂÙ·‚ÔÏÈÛ ·‰ÈÔÓÂÎÙ ÎÏËÛ˘ ÛÙ Ù˘ ηډȷ Ô Ù H Û ›· .  ˜ Ș ‹  · Ù Û Ú ˘ ¿  ·È ı ÙˆÓ ¤˜ ‰Ú ¤Ú·Ó · ›وÛË ÚfiÏË„Ë Î È ÛËÌ·ÓÙÈÎ ÓÈÛÌÔ‡˜ Ó Â Ë · ¯ Ù ¯ ¤ Û Ë , Ì Ô · Ï Â Ú fi Ì · Ú Î·È Ô·ÙÙ ÓÙÈÎfi Ô˜ ›Û˘ ·ÏÏ¿ ·fi Ù· ÏÈ ·ÚfiÓ Ù‡¯ Ù›˙ÂÈ ÛËÌ· È · · Ì Ù Ô · Â Ù Ú Û ›Ó ‰ È Ú È· Î · ÂÎ ›ˆÓ Î·È ‰ Ë Ù˘ η·Ì‚¿ÓÔÓÙ Û È‰ ÈÏ ¤ Ú ¯ È Ô˘Û›· Ô˘ Â Û Ï Ó Ë ˘ ˆ , Ô Ù Ô ÓfiÛ · ÚÔ˘ Î·È ı¤Ì·Ù· ÛÙÂÊ·ÓÈ·›· ÔÙÂϤÛÌ·Ù ˆÓ. ÕÏÏ· Ë ÙÔ˘ ۷ί¿ Ù · Ù ¿  · Ì Ù Ì Ë Û , Ó Ô 2 Ó Â˜ ÁÔÓȉ›ˆ Ù‡Ô˘ È·ÎÒÓ ÔÈ ÓÂfiÙÂÚ Ë ‰È·‚‹ÙË ¯¤Û˘ ÙˆÓ Î·Ú‰È·ÁÁÂ È ‰ Û · Ò Î ˜ Ú Ë Ó · Ù ¯ ˆ Î Ë ›‰ · Û ÙÔÓ Û ÛÎfiË ˜ ıÂÚÌ Ó‰ÔÓ·È Ë ·Ó· ÔÛfiÙËÙ· ‡Ì·ÙÔ˜ Ì ÒÓ ÛÙËÓ Â Â ˜ ÈÓ Ó · Ù Û · Ô ˘ Ù ÈÓ Ô Û Ï Ô Ï Ó ¿ÚÈ ÙÔ˘ ÂÚ‚¿ ÛË Ùˆ Ê½Ó˘ η ÂÙÈ΋ ‰Ú¿ fiÛÏ˄˘ ˘ ÚÔÛÙ¤ıËΠÁ Ú Ú Â ˜ ˘ Ô ˜ Â Ï Ë ¤ Ó Â Ù ¤ ÈÍ Ì ÙÂÙ· Ó. ™ÙÔ Ô˙›Ï˘ CE ¤‰Â Ù˘ ·Ú· Û˘Ó‰Úfï È ÁÂÌÊÈÚ ÂϤÙË GRA Ó · Ì Î ›ˆ H ˜ È· . Ô Ó ˜ Ù Â · · Ù Ê Ì ¤ ÂÏ ÔÓ‡ ¤ˆÓ ÛÙ ÎÏÈÓÈΤ˜ Ì ‹ÁËÛË ÔÈÓ Ú ÛË ÙˆÓ ÔÍ Ô · ¯ ‚ Á Î ˘ ¤ Û ‹ Ë Î Ó·˜ È· ·ÊÔÚ¿ Ù ›·˜ XÂÈÌÒ ˘ Ï ÓÔÛÔÎÔÌÂ Ô H ˜ · Ó ˘ ͢ ‹˜ ¤Ú ً˜ ™‡ÓÙ· ıÚÔ ‚·ÛÈÎ Ó ˘ ı ˘ È ¢ ›Ô˘˜. Û ·ÚÔ˘Ú·
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·ıËÚÔÛÎÏ‹ÚˆÛË ™E¶TEMBPπ√™ 2004
™˘Û¯¤ÙÈÛË ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÓËÛÙ›·˜ Î·È ¯ˆÚ›˜ ÓËÛÙ›· Ì ٷ ı·Ó·ÙËÊfiÚ· Î·È ÌË ı·Ó·ÙËÊfiÚ· ÛÙÂÊ·ÓÈ·›· ÂÂÈÛfi‰È· Eberly LE, Stamler J, Neaton JD, for the Multiple Risk Factor Intervention Trial Research Group Arch Intern Med 2003;163:1077-83
√ ÚfiÏÔ˜ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÛÙËÓ Úfi‚ÏÂ„Ë ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘ ·ÓÂÍ¿ÚÙËÙ· ·fi ÙÔ˘˜ ηıÈÂڈ̤ÓÔ˘˜ Ì›˙ÔÓ˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ (ÔÏÈ΋ ¯ÔÏËÛÙÂÚfiÏË, LDL - ¯ÔÏËÛÙÂÚfiÏË, ·ÚÙËÚȷ΋ ›ÂÛË Î·È Î¿ÓÈÛÌ·) ‰ÂÓ Â›Ó·È ·fiÏ˘Ù· ÍÂηı·ÚÈṲ̂ÓÔ˜. ªÔÏÔÓfiÙÈ Û¯Â‰fiÓ fiϘ ÔÈ ÌÂϤÙ˜ ¤¯Ô˘Ó ‰Â›ÍÂÈ fiÙÈ Û ÌÔÓÔ·Ú·ÁÔÓÙÈ΋ ·Ó¿Ï˘ÛË Ù· ·˘ÍË̤ӷ ÙÚÈÁÏ˘ÎÂÚ›‰È· Â›Ó·È ·Ú¿ÁÔÓÙ·˜ ÎÈÓ‰‡ÓÔ˘, Ï›Á˜ ÌfiÓÔ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ ÂÍ·ÎÔÏÔ˘ıÔ‡Ó Ó· ÚÔ‚Ï¤Ô˘Ó ÙÔÓ Î›Ó‰˘ÓÔ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘ fiÙ·Ó Ï·Ì‚¿ÓÔÓÙ·È ˘fi„Ë Ë LDL-¯ÔÏËÛÙÂÚfiÏË, Ë HDL-¯ÔÏËÛÙÂÚfiÏË Î·È ¿ÏÏÔÈ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘. ¶Ï¤ÔÓ ·˘ÙÔ‡ ‰ÂÓ ¤¯ÂÈ ·ÎfiÌË ÚÔÛ‰ÈÔÚÈÛı› ·Ó Ù· ›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÓËÛÙ›·˜ ‹ Ù· ›‰· ¯ˆÚ›˜ ÓËÛÙ›· ‰›ÓÔ˘Ó ÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÏËÚÔÊÔڛ˜ ÁÈ· ÙÔÓ Î›Ó‰˘ÓÔ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘. °È· ‰ÈÂÚ‡ÓËÛË ÙÔ˘ ÂÚˆÙ‹Ì·ÙÔ˜ ·˘ÙÔ‡ ¤ÁÈÓ ·Ó¿Ï˘ÛË ‰Â‰ÔÌ¤ÓˆÓ Ù˘ ÌÂϤÙ˘ Multiple Risk Factor Intervention Trial (MRFIT). ∞fi ÙÔ 1973 ̤¯ÚÈ ÙÔ 1975 ¤ÁÈÓ ÚÔηٷÚÎÙÈ΋ ÂͤٷÛË 361.662 ·ÛıÂÓÒÓ Û 22 ΤÓÙÚ·, Û 18 fiÏÂȘ ÙˆÓ ∏¶∞. ªÂÙ¿ ·fi 3 ÂÈÛΤ„ÂȘ-ÂÍÂÙ¿ÛÂȘ Ù˘¯·ÈÔÔÈ‹ıËÎ·Ó ÛÙË ÌÂϤÙË 12.866 ·ÛıÂÓ›˜. ∞fi ·˘ÙÔ‡˜ Û 2863 ¿ÙÔÌ· ›¯Â Á›ÓÂÈ Ì¤ÙÚËÛË ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ‰‡Ô ÊÔÚ¤˜: ÛÙËÓ ÚÒÙË ÚÔηٷÚÎÙÈ΋ ÂͤٷÛË Ï‹ÊıËΠ·›Ì· ¯ˆÚ›˜ Ó· ¤¯ÂÈ ˙ËÙËı› ·fi ÙÔ˘˜ ·ÛıÂÓ›˜ Ó· Â›Ó·È ÓËÛÙÈÎÔ› Î·È ·˘Ù‹ Ë ÙÈÌ‹ ıˆڋıËΠ4
ˆ˜ «¯ˆÚ›˜ ÓËÛÙ›·», ·Ó Î·È ‰ÂÓ Î·Ù·ÁÚ¿ÊËÎÂ Ë ÒÚ· ÙÔ˘ ÙÂÏÂ˘Ù·›Ô˘ Á‡̷ÙÔ˜ Î·È ÛÙË ‰Â‡ÙÂÚË Â›Û΄Ë, ÛÙËÓ ÔÔ›· ›¯Â ˙ËÙËı› ·fi ÙÔ˘˜ ·ÛıÂÓ›˜ Ó· Â›Ó·È ÓËÛÙÈÎÔ› 12 ‹ ÂÚÈÛÛfiÙÂÚ˜ ÒÚ˜. ™Â 54 ·fi ·˘ÙÔ‡˜ Ù· ÛÙÔȯ›· ‹Ù·Ó ÂÏÏÈ‹ Î·È Ë ·Ó¿Ï˘ÛË ¤ÁÈÓ ÛÙ· ˘fiÏÔÈ· 2.809 ¿ÙÔÌ·. ∏ ̤ÛË ÙÈÌ‹ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÓËÛÙ›·˜ ‹Ù·Ó 187 mg/dL Î·È ÙˆÓ ¯ˆÚ›˜ ÓËÛÙ›· 284 mg/dL. ªÂ fiÚÈÔ Ù· 200 mg/dL Ô ÂÈÔÏ·ÛÌfi˜ Ù˘ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜ ‹Ù·Ó 31% ÁÈ· ÙËÓ Ì¤ÙÚËÛË ÓËÛÙ›·˜ Î·È 61% ÁÈ· ÙËÓ Ì¤ÙÚËÛË ¯ˆÚ›˜ ÓËÛÙ›·. ¶·Ú·ÙËÚ‹ıËÎ·Ó 175 ÛÙÂÊ·ÓÈ·›· Û˘Ì‚¿Ì·Ù· (ı·Ó·ÙËÊfiÚ· Î·È ÌË) ÛÙ· 8 ¯ÚfiÓÈ· Î·È 328 ı¿Ó·ÙÔÈ ÛÙ· 25 ¯ÚfiÓÈ·. ™Â Û‡ÁÎÚÈÛË Ì ÙÈ̤˜ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ < 200 mg/dL ÔÈ ˘„ËÏfiÙÂÚ˜ ÙÈ̤˜ ÂÌÊ¿ÓÈÛ·Ó ‰ÈÔÚıˆÌ¤ÓÔ Ì ÙÔ˘˜ ¿ÏÏÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÏfiÁÔ ÎÈÓ‰‡-
ÓÔ˘ (hazard ratio) ÛÙÂÊ·ÓÈ·›·˜ ıÓËÛÈÌfiÙËÙ·˜ 1,24 (P=0,09) ÔÈ ÙÈ̤˜ ÓËÛÙ›·˜ Î·È 1,26 (ƒ= 0,07) ÔÈ ÙÈ̤˜ ¯ˆÚ›˜ ÓËÛÙ›·. °È· Ù· ı·Ó·ÙËÊfiÚ· Î·È ÌË ı·Ó·ÙËÊfiÚÈ· ÂÂÈÛfi‰È· Ì·˙› Ô ÏfiÁÔ˜ ÎÈÓ‰‡ÓÔ˘ ‹Ù·Ó ÌÂÁ·Ï‡ÙÂÚÔ˜ Î·È ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈÎfi˜: 1,64 (ƒ=0,004) ÁÈ· ÙÈ̤˜ ÓËÛÙ›·˜ Î·È 1,46 (ƒ=0,03) ÁÈ· ÙȘ ÙÈ̤˜ ¯ˆÚ›˜ ÓËÛÙ›·. ™˘ÌÂÚ·›ÓÂÙ·È fiÙÈ ÙfiÛÔ ÔÈ ÙÈ̤˜ ÓËÛÙ›·˜ fiÛÔ Î·È ÔÈ ¯ˆÚ›˜ ÓËÛÙ›· ¤¯Ô˘Ó ÙËÓ ›‰È· ÚÔÁÓˆÛÙÈ΋ ·Í›· Î·È ·˘Ùfi ÌÔÚ› Ó· ‰È¢ÎÔχÓÂÈ ÙȘ ÂȉËÌÈÔÏÔÁÈΤ˜ ÌÂϤÙ˜, ÛÙȘ Ôԛ˜ Ë ·ÈÌÔÏË„›· Û ʿÛË ÓËÛÙ›·˜ ÌÔÚ› Ó· Â›Ó·È ‰‡ÛÎÔÏË Û ÌÂÁ¿ÏÔ ·ÚÈıÌfi ·ÙfïÓ. ¶¤Ú·Ó ·˘ÙÔ‡, ÌÂÚÈο ¿ÙÔÌ· ÌÔÚ› Ó· ¤¯Ô˘Ó ˘„ËÏfi ΛӉ˘ÓÔ Î·È Ó· ÌË ÂÓÙÔÈÛıÔ‡Ó ÂÂȉ‹ ÔÈ ÙÈ̤˜ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÓËÛÙ›·˜ Â›Ó·È <200 mg/dL ·ÏÏ¿ ÌÂÙ·ÁÂ˘Ì·ÙÈο Â›Ó·È ˘„ËϤ˜. ∂È̤ÏÂÈ·: ∏Ï›·˜ ÃÂÈÌÒÓ·˜
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¶ÔÛÔÙÈΤ˜ Î·È ÔÈÔÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙˆÓ ÏÈȉ›ˆÓ Û ·ÛıÂÓ›˜ Ì ÔÍ›˜ ÏÔÈÌÒÍÂȘ º. ∞ÔÛÙfiÏÔ˘, ∂ȉÈ΢fiÌÂÓË ÛÙËÓ ¶·ıÔÏÔÁ›· ∂. §˘ÌÂÚfiÔ˘ÏÔ˜, ∂ȉÈ΢fiÌÂÓÔ˜ ÛÙËÓ ¶·ıÔÏÔÁ›· ª. ∂ÏÈÛ¿Ê, ∫·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ ¶ÔÏϤ˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ ·ÛıÂÓ›˜ Ì ÏÔÈÌÒÍÂȘ Û˘¯Ó¿ ÂÌÊ·Ó›˙Ô˘Ó ÔÛÔÙÈΤ˜ Î·È ÔÈÔÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙˆÓ ÏÈȉ›ˆÓ. ¶Ú¿ÁÌ·ÙÈ, ‹‰Ë ·fi ÙÔ 1920 ·Ó·Ê¤ÚıËÎ·Ó ÌÂÙ·‚ÔϤ˜ ÙˆÓ ÂȤ‰ˆÓ Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ Û ·ÛıÂÓ‹ Ì ÌÈÎÚԂȷ΋ Ó¢ÌÔÓ›·.1 ∆· ‚È‚ÏÈÔÁÚ·ÊÈο ‰Â‰Ô̤ӷ ‰Â›¯ÓÔ˘Ó Ì ۷ʋÓÂÈ· fiÙÈ ÔÈ ÔÌÔÈÔÛÙ·ÙÈΤ˜ ÌÂÙ·‚ÔϤ˜ Ô˘ ·Ú·ÙËÚÔ‡ÓÙ·È Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ì›·˜ ÔÍ›·˜ Ïԛ̈͢ ÂËÚ¿˙Ô˘Ó ÛËÌ·ÓÙÈο ÙÔ ÌÂÙ·‚ÔÏÈÛÌfi ÙˆÓ ÏÈȉ›ˆÓ Î·È ·ÓÙ›ÛÙÚÔÊ· fiÙÈ ÔÈ ÌÂÙ·‚ÔϤ˜ ÙˆÓ ÏÈȉ›ˆÓ Ô˘ ·Ú·ÙËÚÔ‡ÓÙ·È Û ·ÛıÂÓ›˜ Ì ÏÔÈÌÒÍÂȘ ÂÌϤÎÔÓÙ·È ÛÙË ‰È·‰Èηۛ· Ù˘ ÊÏÂÁÌÔÓ‹˜. ŒÙÛÈ, Èı·Ó¿ ÛÙÔ Ì¤ÏÏÔÓ ÔÈ ÔÛÔÙÈΤ˜ Î·È ÔÈÔÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙˆÓ ÏÈȉ›ˆÓ ı· ·ÔÙÂϤÛÔ˘Ó ‰Â›ÎÙ˜ Ù˘ ÂÎÙ›ÌËÛ˘ Ù˘ ÛÔ‚·ÚfiÙËÙ·˜ Ì›·˜ ÔÍ›·˜ Ïԛ̈͢. À¿Ú¯Ô˘Ó ÔÏÏÔ› Ì˯·ÓÈÛÌÔ› ‰È·Ì¤ÛÔ˘ ÙˆÓ ÔÔ›ˆÓ Ë Ïԛ̈ÍË ÌÔÚ› Ó· ÂËÚ¿ÛÂÈ ÙÔ ÌÂÙ·‚ÔÏÈÛÌfi ÙˆÓ ÏÈȉ›ˆÓ Î·È ÏÈÔÚˆÙÂ˚ÓÒÓ. ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÔÍ›·˜ Ê¿Û˘ Ì›·˜ ÊÏÂÁÌÔÓ‹˜ ·Ú·ÙËÚÔ‡ÓÙ·È ÛËÌ·ÓÙÈΤ˜ ÌÂÙ·‚ÔϤ˜ Ù˘ Û˘ÁΤÓÙÚˆÛ˘ ÔÏÏÒÓ ÚˆÙÂ˚ÓÒÓ ÛÙÔ Ï¿ÛÌ·, ÔÈ Ôԛ˜ Â›Ó·È ÁÓˆÛÙ¤˜ ˆ˜ ÚˆÙ½Ó˜ ÔÍ›·˜ Ê¿Û˘. √È ÚˆÙ½Ó˜ ÔÍ›·˜ Ê¿Û˘ ‰È·ÎÚ›ÓÔÓÙ·È Û ıÂÙÈΤ˜ (·˘Í¿ÓÔÓÙ·È) Î·È ·ÚÓËÙÈΤ˜ (ÂÏ·ÙÙÒÓÔÓÙ·È). √È ÌÂÙ·‚ÔϤ˜ ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ ÚˆÙÂ˚ÓÒÓ ÔÍ›·˜ Ê¿Û˘ ÔÊ›ÏÔÓÙ·È Î˘Ú›ˆ˜ Û ‰È·Ù·Ú·¯¤˜ Ù˘ ·Ú·ÁˆÁ‹˜ ÙÔ˘˜ ·fi Ù· Ë·ÙÔ·ÙÙ·Ú·. ŒÙÛÈ, ÔÈ ÔÍ›˜ ÌÂÙ·‚ÔϤ˜ ·˘ÙÒÓ ÙˆÓ ·Ú·Ì¤ÙÚˆÓ ·ÓÙ·Ó·ÎÏÔ‡Ó ÙËÓ ·ÚÔ˘Û›· Î·È ÙË ‚·Ú‡ÙËÙ· Ù˘ ÊÏÂÁÌÔÓ‹˜ Î·È ÌÔÚ› Ó· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó ˆ˜ ‰Â›ÎÙ˜ ÁÈ· ÙË ‰È¿ÁÓˆÛË Î·È ·ÓÙÈÌÂÙÒÈÛË ·ÛıÂÓÒÓ Ì ÔÍ›· Ïԛ̈ÍË. √È Î˘ÙÙ·ÚÔΛÓ˜ ·ÔÙÂÏÔ‡Ó ‰È·Î˘ÙÙ·ÚÈο ·ÁÁÂÏÈÔÊfiÚ· ÔÏ˘ÂÙ›‰È· Ô˘ ·Ú¿ÁÔÓÙ·È ·fi ÂÓÂÚÁÔÔÈË̤ӷ ·ÙÙ·Ú·, ΢ڛˆ˜ ·fi
Ù· Ì·ÎÚÔÊ¿Á· Î·È Ù· ÌÔÓÔ·ÙÙ·Ú· ÙˆÓ ÂÚÈÔ¯ÒÓ Ù˘ ÊÏÂÁÌÔÓ‹˜ Î·È ¤¯Ô˘Ó ÔÏÏ·ÏÔ‡˜ ÛÙfi¯Ô˘˜ Î·È ÏÂÈÙÔ˘ÚÁ›Â˜. √È Î˘ÙÙ·ÚÔΛÓ˜ ·ÔÙÂÏÔ‡Ó ÙÔ˘˜ ·ÚÈÔ˘˜ ·Ú¿ÁÔÓÙ˜ Ô˘ ÚÔ¿ÁÔ˘Ó ÙËÓ ·Ú·ÁˆÁ‹ ÙˆÓ ÚˆÙÂ˚ÓÒÓ ÔÍ›·˜ Ê¿Û˘. ™ÙȘ ÏÔÈÌÒÍÂȘ ·Ú¿ÁÂÙ·È Î˘Ú›ˆ˜ Ë Interleukin-6 (IL-6), Ë Interleukin1b (IL-1b), Ô Tumor Necrosis Factor-· (TNF-a), Ë Interferon-Á (INFÁ), Ô Transforming Growth Factor‚ (TGF-‚) Î·È Èı·Ó¿ Ë Interleukin8 (IL-8).2 ∏ πL-6 Â›Ó·È Ì›· ·fi ÙȘ ÈÔ ÛËÌ·ÓÙÈΤ˜ ΢ÙÙ·ÚÔΛÓ˜ Ô˘ ÂÌϤÎÔÓÙ·È ÛÙË ‰È·‰Èηۛ· Ù˘ ÊÏÂÁÌÔÓ‹˜. ∂ÈϤÔÓ, Ë IL-6 ¿ÁÂÈ ÙË ‰Ú·ÛÙËÚÈfiÙËÙ· ÙˆÓ LDL (low density lipoproteins) ˘Ô‰Ô¯¤ˆÓ Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·˘ÍË̤ÓË ÚfiÛÏË„Ë ÙˆÓ LDL ·fi Ù· Ë·ÙÔ·ÙÙ·Ú· Î·È ÙËÓ ·ÔÌ¿ÎÚ˘ÓÛ‹ ÙÔ˘˜ ·fi ÙÔ Ï¿ÛÌ·.3 ∏ ·‡ÍËÛË Ù˘ ¤ÎÎÚÈÛ˘ Ù˘ IL-6 ÌÔÚ› Ó· ÂÍËÁ‹ÛÂÈ ÙË ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙˆÓ ÂȤ‰ˆÓ Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ Û ·ÛıÂÓ›˜ Ì Ôͤ· ÊÏÂÁÌÔÓÒ‰Ë ÓÔÛ‹Ì·Ù·. ¶Ú¤ÂÈ Ó· ÂÈÛËÌ·Óı› fiÙÈ ·˘Ù‹ Ë Ì›ˆÛË ÙˆÓ ÂȤ‰ˆÓ Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ ·ÔÙÂÏ› ¤Ó· ηÎfi ÚÔÁÓˆÛÙÈÎfi ‰Â›ÎÙË Û Â̇ÚÂÙÔ˘˜ Ï¢ÎÔÂÓÈÎÔ‡˜ ·ÛıÂÓ›˜.4 ∞ÍÈÔÛËÌ›ˆÙ˜ Â›Ó·È Â›Û˘ ÔÈ ÔÛÔÙÈΤ˜ Î·È ÔÈÔÙÈΤ˜ ÌÂÙ·‚ÔϤ˜ ÙˆÓ ∏DL (high density lipoproteins). √È ·Ú¯¤ÁÔÓ˜ HDL ÂÚȤ¯Ô˘Ó ·ÔÏÈÔÚˆÙ½Ó˜ Î·È ÊˆÛÊÔÏÈ›‰È· Î·È ÂÎÙfi˜ ·fi ÙË ÌÂÙ·ÊÔÚ¿ Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ ·fi ÙÔ˘˜ ÂÚÈÊÂÚÈÎÔ‡˜ ÈÛÙÔ‡˜ ÛÙÔ ‹·Ú, ‰È·‰Ú·Ì·Ù›˙Ô˘Ó ÛËÌ·ÓÙÈÎfi ÚfiÏÔ, ÛÙÔÓ ÂÚÈÔÚÈÛÌfi ÙˆÓ ‚Ï·ÙÈÎÒÓ ÂȉڿÛÂˆÓ Ì›·˜ ÔÍ›·˜ Ïԛ̈͢. ¶Ú¿ÁÌ·ÙÈ, ÔÈ HDL ÂÍÔ˘‰ÂÙÂÚÒÓo˘Ó ÔÚÈṲ̂ÓÔ˘˜ ·Ú¿ÁÔÓÙ˜ Ô˘ ¢ԉÒÓÔ˘Ó ÙË ÊÏÂÁÌÔÓ‹, ηıÒ˜ Î·È ÚÔ˚fiÓÙ· ÔÍ›‰ˆÛ˘.5 Ÿˆ˜ Â›Ó·È ÁÓˆÛÙfi, ÛÙȘ ∏DL ˘¿Ú¯Ô˘Ó ·ÚÎÂÙ¤˜ ÚˆÙ½Ó˜, fiˆ˜ Ë ƒ√¡ (paraoxo-
nase), Ë PAF-AH (platelet-activating-factor acetylhydrolase), Ë protectin (CD59), Ë ÛÂÚÔ˘ÏÔÏ·ÛÌ›ÓË, Ë ÙÚ·ÓÛÊÂÚ›ÓË, ηıÒ˜ Î·È Ë ·ÔÏÈÔÚˆÙ½ÓË j.5 √È ·Ú¿ÁÔÓÙ˜ ·˘ÙÔ› ·ÛÎÔ‡Ó ÚÔÛٷ٢ÙÈ΋ ‰Ú¿ÛË ÛÙȘ ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜, ·ÊÔ‡ ·ÔÌ·ÎÚ‡ÓÔ˘Ó ÙȘ ÂχıÂÚ˜ Ú›˙˜ Ô͢ÁfiÓÔ˘ Î·È ¤ÙÛÈ ‰ÚÔ˘Ó ˆ˜ ·ÓÙÈÔÍÂȉˆÙÈΤ˜ Ô˘Û›Â˜. øÛÙfiÛÔ, Û ÔÍ›˜ ÏÔÈÌÒÍÂȘ ÔÈ ∏DL ˘Ê›ÛÙ·ÓÙ·È ÔÈÔÙÈΤ˜ ÌÂÙ·‚ÔϤ˜ Ì ·ÔÙ¤ÏÂÛÌ· Ó· ÌÂÈÒÓÂÙ·È Ë ·ÓÙÈÔÍÂȉˆÙÈ΋ ‰Ú¿ÛË ÙÔ˘˜, ‰ËÏ·‰‹ Ó· ÂÚÈÔÚ›˙ÂÙ·È Ë ÈηÓfiÙËÙ¿ ÙÔ˘˜ Ó· ·Ó·ÛÙ¤ÏÏÔ˘Ó ÙËÓ ÔÍ›‰ˆÛË ÙˆÓ LDL. ¶Ú¿ÁÌ·ÙÈ ÌÂϤÙË Û ÂÈÚ·Ì·Ùfi˙ˆ· Ô˘ ÌÔχÓıËÎ·Ó Ì Influenza A ¤‰ÂÈÍ fiÙÈ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÔÍ›·˜ Ïԛ̈͢ ·Ú·ÙËÚÂ›Ù·È Ì›ˆÛË Ù˘ ‰Ú·ÛÙËÚÈfiÙËÙ·˜ Ù˘ PON, Ù˘ PAF-AH, Ù˘ ÛÂÚÔ˘ÏÔÏ·ÛÌ›Ó˘ Î·È Ù˘ Apo j ÙˆÓ HDL.6 ∂ÈÚfiÛıÂÙ·, ÚfiÛÊ·ÙË ÌÂϤÙË ¤‰ÂÈÍ fiÙÈ Ë Ì›ˆÛË Ù˘ PON Ô˘ ·Ú·ÙËÚÂ›Ù·È Û ÊÏÂÁÌÔÓÒ‰ÂȘ ηٷÛÙ¿ÛÂȘ ÔÊ›ÏÂÙ·È Û ̛· ‰È·Ì¤ÛÔ˘ ÙˆÓ ÊÏÂÁÌÔÓˆ‰ÒÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ Ì›ˆÛË Ù˘ ·Ú·ÁˆÁ‹˜ Ù˘ ·fi Ù· Ë·ÙÔ·ÙÙ·Ú·.7 √È ∏DL ÌÔÚ› ›Û˘ Ó· ‰ÂÛÌÂ‡Ô˘Ó ·Ú¿ÁÔÓÙ˜ Ô˘ ÂÓÂÚÁÔÔÈÔ‡Ó ÙË ÊÏÂÁÌÔÓ‹, fiˆ˜ ÙȘ ÏÈÔÔÏ˘Û·Î¯·Ú›‰Â˜ ÙˆÓ ÌÂÌ‚Ú·ÓÒÓ ÙˆÓ Gram (-) ‚·ÎÙËÚȉ›ˆÓ. ¶ÂÈÚ·Ì·ÙÈΤ˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ Ù· ·˘ÍË̤ӷ ›‰· ÙˆÓ ∏DL ÚÔÛÙ·ÙÂ‡Ô˘Ó ·fi Ù· ı·Ó·ÙËÊfiÚ· ·ÔÙÂϤÛÌ·Ù· ÙˆÓ ÂÓ‰ÔÙÔÍÈÓÒÓ Û ÂÚÈÙÒÛÂȘ ÛËÙÈÎÔ‡ shock.8 ∂ÈÚfiÛıÂÙ· Ë ¯ÔÚ‹ÁËÛË ·Ó·Û˘Ó‰˘·Ṳ̂Ó˘ HDL Û ÛËÙÈÎÔ‡˜ ·ÛıÂÓ›˜ ›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙË Ì›ˆÛË Ù˘ ÊÏÂÁÌÔÓÒ‰Ô˘˜ ·¿ÓÙËÛ˘ Û ÏÈÔÔÏ˘Û·Î¯·Ú›‰Â˜.9 ™Â ·ÛıÂÓ›˜ Ì ÔÍ›˜ ÏÔÈÌÒÍÂȘ ›Û˘ ·Ú·ÙËÚÂ›Ù·È Ì›ˆÛË ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ HDL Î·È Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘. ∏ ÂÏ¿ÙÙˆÛË ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ HDL Èı·Ó¿ ÔÊ›ÏÂÙ·È Û Ì›ˆÛË Ù˘ ÂÓÂÚÁfiÙËÙ·˜
5
·ıËÚÔÛÎÏ‹ÚˆÛË ™E¶TEMBPπ√™ 2004
Ù˘ LCAT (lecithin cholesterol acyltransferase), Ë ÔÔ›· ¯·Ú·ÎÙËÚ›˙ÂÙ·È ˆ˜ Ì›· ·ÚÓËÙÈ΋ ÚˆÙ½ÓË ÔÍ›·˜ Ê¿Û˘. ∏ Apolipoprotein (∞po) Aπ ·ÔÙÂÏ› ÙÔ Î‡ÚÈÔ Û˘ÛÙ·ÙÈÎfi ÙˆÓ HDL Î·È ÂÓÂÚÁÔÔÈ› ÙËÓ LCAT. ™Â ÔÍ›· Ïԛ̈ÍË Ë ÌÂȈ̤ÓË ÂÓÂÚÁfiÙËÙ· Ù˘ LCAT ÚÔηÏ› Ì›ˆÛË Ù˘ ÂÛÙÂÚÔÔÈË̤Ó˘ ¯ÔÏËÛÙÂÚfiÏ˘ ÙˆÓ HDL. ∏ Ì›ˆÛË Ù˘ ÂÓÂÚÁfiÙËÙ·˜ Ù˘ LCAT Û ·ÛıÂÓ›˜ Ì ÔÍ›˜ ÏÔÈÌÒÍÂȘ Èı·Ó¿ ÔÊ›ÏÂÙ·È: ·) ÛÙȘ ΢ÙÙ·ÚÔΛÓ˜ (΢ڛˆ˜ ÛÙËÓ IL-2), ÌÂÙ·‚ÔÏ‹ Ù˘ Û‡ÛÙ·Û˘ ÙˆÓ HDL Î·È Á) Ù¤ÏÔ˜ ÛÙËÓ ·ÓÙÈηٿÛÙ·ÛË Ù˘ Apo A-I (Ô˘ ÂÓÂÚÁÔÔÈ› ÙËÓ LCAT) ·fi ·Ì˘ÏÔÂȉ¤˜ A(SAA).5 ™Â ÂÈÚ·Ì·Ùfi˙ˆ· ÛÙ· ÔÔ›· ¯ÔÚËÁ‹ıËΠÂÓ‰ÔÙÔÍ›ÓË Î·È ∆¡F ÒÛÙ ӷ ‰ËÌÈÔ˘ÚÁËıÔ‡Ó Û˘Óı‹Î˜ ÔÍ›·˜ Ïԛ̈͢ ·Ú·ÙËÚ‹ıËΠ̛ˆÛË Ù˘ ‰Ú·ÛÙËÚÈfiÙËÙ·˜ Ù˘ LCAT Î·È Ì›ˆÛË ÙˆÓ HDL. ∆· ÂÏ·Ùو̤ӷ ›‰· ÙˆÓ HDL Û ¿ÙÔÌ· Ì ÔÈÎÔÁÂÓ‹ ¤Ó‰ÂÈ· Ù˘ LCAT ÂÓÈÛ¯‡Ô˘Ó ÙËÓ ¿Ô„Ë fiÙÈ Ë LCAT ÂÌϤÎÂÙ·È ÛÙËÓ ÂÏ¿ÙÙˆÛË ÙˆÓ HDL (5). ∆¤ÏÔ˜ ÔÈ HDL ÌÔÚ› Ó· ‰ÂÛ̇ÔÓÙ·È ·fi ÙÔ˘˜ ÌÈÎÚÔÔÚÁ·ÓÈÛÌÔ‡˜ Î·È Ó· Û˘ÛÛˆÚ‡ÔÓÙ·È ÛÙÔ˘˜ ÚÔۂ‚ÏË̤ÓÔ˘˜ ÈÛÙÔ‡˜ Ì ·ÔÙ¤ÏÂÛÌ· Ó· ÂÏ·ÙÙÒÓÔÓÙ·È Ù· ›‰¿ ÙÔ˘˜ ÛÙÔ Ï¿ÛÌ·.10 ∂ÈÚfiÛıÂÙ· Û ·ÛıÂÓ›˜ Ì ÏÔÈÌÒÍÂȘ ·Ú·ÙËÚÂ›Ù·È ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ.11 ∏ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·, Ë ÔÔ›· Û˘¯Ó¿ Û˘Óԉ‡ÂÈ ÙȘ ÛËÙÈΤ˜ ηٷÛÙ¿ÛÂȘ, ÔÊ›ÏÂÙ·È Â›Ù Û ·‡ÍËÛË Ù˘ Ë·ÙÈ΋˜ ·Ú·ÁˆÁ‹˜ ÙˆÓ ÏÔ‡ÛÈˆÓ Û ÙÚÈÁÏ˘ÎÂÚ›‰È· ÏÈÔÚˆÙÂ˚ÓÒÓ, ›ÙÂ Û˘¯ÓfiÙÂÚ· Û ÂÈ‚Ú¿‰˘ÓÛË Ù˘ ·ÔÌ¿ÎÚ˘ÓÛ‹˜ ÙÔ˘˜ ·fi ÙÔ Ï¿ÛÌ·. ¶Ú¿ÁÌ·ÙÈ, Ë Ì›ˆÛË Ù˘ ‰Ú·ÛÙËÚÈfiÙËÙ·˜ Ù˘ ÏÈÔÚˆÙÂ˚ÓÈ΋˜ ÏÈ¿Û˘ ·ÔÙÂÏ› ÙÔÓ ÈÔ ÛËÌ·ÓÙÈÎfi Ì˯·ÓÈÛÌfi ·‡ÍËÛ˘ ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Û ÛËÙÈÎÔ‡˜ ·ÛıÂÓ›˜.12 ŒÙÛÈ, ¤¯ÂÈ ·Ó·ÊÂÚı› Ì›ˆÛË Ù˘ ‰Ú·ÛÙËÚÈfiÙËÙ·˜ Ù˘ ÏÈÔÚˆÙÂ˚ÓÈ΋˜ ÏÈ¿Û˘ Û ÂÈÚ·Ì·Ùfi˙ˆ· Ô˘ ÌÔχÓıËÎ·Ó ·fi Trypanosoma brucei. H Ì›ˆÛË ·˘Ù‹ ›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙË Ì›ˆÛË Ù˘ ÏÈfiÏ˘Û˘, ÙËÓ ÂÈ‚Ú¿‰˘ÓÛË Ù˘ ÌÂÙ·ÙÚÔ‹˜ ÙˆÓ Ôχ ¯·ÌËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙÂ˚ÓÒÓ [very low-density lipoprotein cholesterol (VLDL)] Û LDL Î·È ÙËÓ ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÛÙÔ Ï¿ÛÌ·.13 ™Â ·ÛıÂÓ›˜ Ì ÙÔ Û‡Ó‰ÚÔÌÔ Ù˘
6
›ÎÙËÙ˘ ·ÓÔÛÔ·Ó¿ÚÎÂÈ·˜ Ë ·‡ÍËÛË ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Ô˘ ·Ú·ÙËÚ‹ıËΠÔÊ›ÏÔÓÙ·Ó Û ·‡ÍËÛË Ù˘ ·Ú·ÁˆÁ‹˜ Î·È Ì›ˆÛË ÙÔ˘ ηٷ‚ÔÏÈÛÌÔ‡ ÙˆÓ ÏÔ‡ÛÈˆÓ Û ÙÚÈÁÏ˘ÎÂÚ›‰È· ÏÈÔÚˆÙÂ˚ÓÒÓ, ÌÂÙ·‚ÔϤ˜ Ô˘ Û˘Û¯ÂÙ›˙ÔÓÙ·Ó Ì ٷ ›‰· Ù˘ INF-a.14,15 √È ÌÂÙ·‚ÔϤ˜ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Û ·ÛıÂÓ›˜ Ì ÔÍ›˜ ÏÔÈÌÒÍÂȘ ·Ô‰›‰ÔÓÙ·È ÛÙËÓ ·‡ÍËÛË ÙˆÓ ÊÏÂÁÌÔÓˆ‰ÒÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ Ô˘ ÚÔ¿ÁÔ˘Ó ÙËÓ ·‡ÍËÛË Ù˘ Ë·ÙÈ΋˜ ·Ú·ÁˆÁ‹˜ ÙˆÓ ÏÔ‡ÛÈˆÓ Û ÙÚÈÁÏ˘ÎÂÚ›‰È· ÏÈÔÚˆÙÂ˚ÓÒÓ Î·È ÌÂÈÒÓÔ˘Ó ÙÔÓ Î·Ù·‚ÔÏÈÛÌfi ÙÔ˘˜.11 ∏ ·‡ÍËÛË Ù˘ Û˘ÁΤÓÙÚˆÛ˘ ÙˆÓ ÏÔ‡ÛÈˆÓ Û ÙÚÈÁÏ˘ÎÂÚ›‰È· ÏÈÔÚˆÙÂ˚ÓÒÓ ÌÔÚ› Ó· ÂÍËÁ‹ÛÂÈ Î·È ÙËÓ ·‡ÍËÛË Ù˘ Û˘ÁΤÓÙÚˆÛ˘ ÙˆÓ ÌÈÎÚÒÓ ˘ÎÓÒÓ ·ıËÚÔÁfiÓˆÓ LDL Ô˘ ¤¯ÂÈ ·Ú·ÙËÚËı› Û ·ÛıÂÓ›˜ Ì ÙÔ Û‡Ó‰ÚÔÌÔ Ù˘ ›ÎÙËÙ˘ ·ÓÔÛÔ·Ó¿ÚÎÂÈ·˜.14,16 ∏ ·‡ÍËÛË Ù˘ ∞po E Û ·ÛıÂÓ›˜ Ì ÔÍ›· Ïԛ̈ÍË ÌÔÚ› Ó· ÔÊ›ÏÂÙ·È Û ·‡ÍËÛË Ù˘ Û‡ÓıÂÛ‹˜ Ù˘ ÂÍ·ÈÙ›·˜ ÂÓÂÚÁÔÔ›ËÛ˘ ÙˆÓ Ì·ÎÚÔÊ¿ÁˆÓ.17 Ÿˆ˜ ·Ó·Ê¤ÚıËÎÂ, ÔÈ ÏÈÔÔÏ˘Û·Î¯·Ú›‰Â˜ (LPS) Â›Ó·È ÔÈ Î‡ÚÈÔÈ ·Ú¿ÁÔÓÙ˜ Ô˘ ÚÔ¿ÁÔ˘Ó ÙËÓ ·Ú·ÁˆÁ‹ ÙˆÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ ·fi Ù· Ì·ÎÚÔÊ¿Á· Û ÂÚÈÙÒÛÂȘ Gram (-) ÛË„·ÈÌ›·˜. ∏ ∞po E ‰ÂÓ ÂËÚ¿˙ÂÈ ÌfiÓÔ ÙÔ ÌÂÙ·‚ÔÏÈÛÌfi ÙˆÓ ÏÈȉ›ˆÓ, ·ÏÏ¿ ÂËÚ¿˙ÂÈ Î·È ÙËÓ ÂͤÏÈÍË ÙˆÓ ÏÔÈÌÒ͈Ó, ·ÊÔ‡ ‰ÂÛ̇ÂÈ ÙȘ LPS Î·È ÙȘ ηÙ¢ı‡ÓÂÈ ·fi Ù· Ì·ÎÚÔÊ¿Á· ÛÙ· Ë·ÙÔ·ÙÙ·Ú·.18 ∂ÈÚfiÛıÂÙ·, Û ÂÈÚ·Ì·Ùfi˙ˆ· Ë Apo E ·Ó·ÛÙ¤ÏÏÂÈ ÙËÓ ·Ú·ÁˆÁ‹ ÙˆÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ. ∆· Â˘Ú‹Ì·Ù· ·˘Ù¿ ÂÓÈÛ¯‡Ô˘Ó ÙËÓ ¿Ô„Ë fiÙÈ Ë ∞po E ‰È·‰Ú·Ì·Ù›˙ÂÈ ÛËÌ·ÓÙÈÎfi
ÚfiÏÔ ÛÙËÓ ¿Ì˘Ó· ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ Û ÛËÙÈΤ˜ ηٷÛÙ¿ÛÂȘ. ¶Ú¿ÁÌ·ÙÈ, Ë ¯ÔÚ‹ÁËÛË ·Ó·Û˘Ó‰˘·Ṳ̂Ó˘ ∞po E Ê·›ÓÂÙ·È fiÙÈ Â›Ó·È ¯Ú‹ÛÈÌË ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÂÓ‰ÔÙÔÍÈÓ·ÈÌ›·˜.18 ∂ÈϤÔÓ, ·˘ÙÔ¿ÓÔÛÔÈ Ì˯·ÓÈÛÌÔ› Â›Ó·È ‰˘Ó·Ùfi Ó· ÂËÚ¿ÛÔ˘Ó ÙÔ ÌÂÙ·‚ÔÏÈÛÌfi ÙˆÓ ÏÈȉ›ˆÓ Û ·ÛıÂÓ›˜ Ì ÏÔÈÌÒÍÂȘ. ¶Ú¿ÁÌ·ÙÈ, Û ·ÛıÂÓ›˜ Ì ÔÍ›· Ïԛ̈ÍË Â›Ó·È ‰˘Ó·ÙfiÓ Ó· ·Ú·ÙËÚËıÔ‡Ó ·˘ÙÔ¿ÓÔÛ˜ ‰È·Ù·Ú·¯¤˜, fiˆ˜ ıÂÙÈ΋ ¿ÌÂÛË ·ÓÙ›‰Ú·ÛË Coombs, ‰È·Ù·Ú·¯¤˜ ÛÙËÓ ËÏÂÎÙÚÔÊfiÚËÛË ÙˆÓ ÚˆÙÂ˚ÓÒÓ Î·È ıÂÙÈÎÔÔ›ËÛË ÙÔ˘ ÚÂ˘Ì·ÙÔÂȉ‹ ·Ú¿ÁÔÓÙ·. ∞˘Ù¤˜ ÔÈ ·ÓÔÛÔÏÔÁÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÂËÚ¿˙Ô˘Ó ÙÔ ÌÂÙ·‚ÔÏÈÛÌfi ÙˆÓ ÏÈÔÚˆÙÂ˚ÓÒÓ Ì ‰È¿ÊÔÚÔ˘˜ Ì˯·ÓÈÛÌÔ‡˜: ‰ËÌÈÔ˘ÚÁ›· ·ÓÔÛÔÛ˘ÌÏÂÁÌ¿ÙˆÓ ÙˆÓ HDL Ì ·ÓÔÛÔÛÊ·ÈÚ›Ó˜ Î·È ÂÈÙ¿¯˘ÓÛË ÙÔ˘ ηٷ‚ÔÏÈÛÌÔ‡ ÙˆÓ HDL,10,19 ›‰Ú·ÛË ÛÙÔ˘˜ ˘Ô‰Ô¯Â›˜ Ô˘ ÂËÚ¿˙Ô˘Ó ÙËÓ ·ÔÌ¿ÎÚ˘ÓÛË ÙˆÓ ÂӉȿÌÂÛ˘ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙÂ˚ÓÒÓ [intermediate- density lipoprotein (IDL)], ÙˆÓ LDL Î·È ÙˆÓ ˘ÔÏÂÈÌÌ¿ÙˆÓ (remnants) ÙˆÓ ¯˘ÏÔÌÈÎÚÒÓ, ηıÒ˜ Î·È Ì›ˆÛË Ù˘ ÂÓÂÚÁfiÙËÙ·˜ Ù˘ ÏÈÔÚˆÙÂ˚ÓÈ΋˜ ÏÈ¿Û˘.20,21 √È Î˘ÙÙ·ÚÔΛÓ˜ Ê·›ÓÂÙ·È fiÙÈ ÂËÚ¿˙Ô˘Ó Â›Û˘ Î·È Ù· ›‰· Ù˘ ÏÈÔÚˆÙ½Ó˘ (a) [Lp (a)]. ¶Ú¿ÁÌ·ÙÈ, ÂÈÚ·Ì·ÙÈΤ˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ Ô ∆NF Î·È Ô TGF-‚1 ·˘Í¿ÓÔ˘Ó, ÂÓÒ Ë πL-6 ÂÏ·ÙÙÒÓÂÈ Ù· ›‰· Ù˘ Lp(a).22 ∂ÈÚfiÛıÂÙ· Û ÛËÙÈÎÔ‡˜ ·ÛıÂÓ›˜ Î·È Û ·ÛıÂÓ›˜ Ì ÂÁη‡Ì·Ù· ‰È·ÈÛÙÒıËΠfiÙÈ ÔÈ ÌÂÙ·‚ÔϤ˜ Ù˘ Lp(a) Â›Ó·È Ù˘ÈΤ˜ ÙˆÓ ·ÚÓËÙÈÎÒÓ ÚˆÙÂ˚ÓÒÓ ÔÍ›·˜ Ê¿Û˘.23 ¶Ú¤ÂÈ Ó· ÙÔÓÈÛı› fiÙÈ ÂÍ·ÎÔÏÔ˘ıÔ‡Ó Ó· ˘¿Ú¯Ô˘Ó ÔÏÏ¿ ÂÚˆÙËÌ·ÙÈο fiÛÔÓ ·ÊÔÚ¿ ÙÔ˘˜ ˘ÔΛÌÂÓÔ˘˜ Ì˯·ÓÈÛÌÔ‡˜ Ô˘ ÂÌϤÎÔÓÙ·È ÛÙȘ ÔÈÔÙÈΤ˜ Î·È ÔÛÔÙÈΤ˜ ÌÂÙ·‚ÔϤ˜ ÙˆÓ ÏÈȉ›ˆÓ Û ·ÛıÂÓ›˜ Ì ÔÍ›˜ ÏÔÈÌÒÍÂȘ. °È· ·Ú¿‰ÂÈÁÌ· ÛÙË ‰ÈÂıÓ‹ ‚È‚ÏÈÔÁÚ·Ê›· ‰ÂÓ ˘¿Ú¯Ô˘Ó ‰Â‰Ô̤ӷ ÁÈ· ÙȘ ÂӉ¯fiÌÂÓ˜ ÌÂÙ·‚ÔϤ˜ ÙˆÓ ÏÈȉ›ˆÓ Û ·ÛıÂÓ›˜ Ì ÂȉÈΤ˜ ÏÔÈÌÒÍÂȘ .¯. Û ·ÛıÂÓ›˜ Ì ‚ÚԢΤÏψÛË Î·È ÏÔÈÌÒ‰Ë ÌÔÓÔ˘Ú‹ÓˆÛË. À¿Ú¯Ô˘Ó ˆÛÙfiÛÔ ÔÚÈṲ̂ӷ ‰Â‰Ô̤ӷ Ô˘ ¤¯Ô˘Ó Û¯¤ÛË Ì ÙË ÛÏ·¯ÓÈ΋ ÏÂ˚ÛÌ·Ó›·ÛË: ™˘ÁÎÂÎÚÈ̤ӷ Û ÂÈÚ·Ì·Ùfi˙ˆ· (Û·ÏÔ˘˜) Ô˘ ÌÔχÓıËÎ·Ó ·fi Leishmania infantum ·Ú·ÙË-
¶A£OºY™IO§O°IA Ú‹ıËÎ·Ó ·˘ÍË̤ӷ ›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÛÙÔ Ï¿ÛÌ·.24 ∆Ô ›‰ÈÔ ·ÔÙ¤ÏÂÛÌ· ·Ú·ÙËÚ‹ıËΠ۠ÔÓÙÈÎÔ‡˜ Ô˘ ÌÔχÓıËÎ·Ó Î·È ÓfiÛËÛ·Ó ·fi ÏÂ˚ÛÌ·Ó›·ÛË.25 √È Bekaert Î·È Û˘ÓÂÚÁ¿Ù˜ ÌÂϤÙËÛ·Ó ÙÔ ÏÈȉ·ÈÌÈÎfi ÚÔÊ›Ï Û ·È‰È¿ Ì ÛÏ·¯ÓÈ΋ ÏÂ˚ÛÌ·Ó›·ÛË. ¢È·ÈÛÙÒıËΠ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ, ÂÏ¿ÙÙˆÛË Ù˘ ∏DL ¯ÔÏËÛÙÂÚfiÏ˘, Ù˘
ÔÏÈ΋˜ ¯ÔÏËÛÙÂÚfiÏ˘, ηıÒ˜ Î·È ÙˆÓ ∞po Aπ Î·È ∞po AII, ÂÓÒ Ù· ›‰· Ù˘ Apo B ·Ú¤ÌÂÈÓ·Ó ·ÌÂÙ¿‚ÏËÙ·.26 ∂ÈÚfiÛıÂÙ· ¤¯ÂÈ ·Ú·ÙËÚËı› ·‡ÍËÛË Ù˘ ∞po E ÙÔ˘ ÔÚÔ‡ Û ·È‰È¿ Ì ÛÏ·¯ÓÈ΋ ÏÂ˚ÛÌ·Ó›·ÛË.27 ¶Ú¤ÂÈ Â›Û˘ Ó· ·Ó·ÊÂÚı› fiÙÈ Û ·ÛıÂÓ›˜ Ô˘ ¤·Û¯·Ó ·fi ÛÏ·¯ÓÈ΋ ÏÂ˚ÛÌ·Ó›·ÛË ·Ú·ÙËÚ‹ıËÎ·Ó È‰È·›ÙÂÚ· ·˘ÍË̤ӷ ›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ
ÛÙËÓ ÔÍ›· Ê¿ÛË Ù˘ ÓfiÛÔ˘.28,29 ¶ÚfiÛÊ·ÙË ÌÂϤÙË Ì·˜ Û ¤Ó· ·ÛıÂÓ‹ Ì ηϷ-·˙¿Ú ÂȂ‚·›ˆÛ ٷ ·ÔÙÂϤÛÌ·Ù· ÙˆÓ ÚÔËÁÔ‡ÌÂÓˆÓ ÌÂÏÂÙÒÓ. ∂ÈϤÔÓ ‰È·ÈÛÙÒıËΠ̛ˆÛË ÙˆÓ ÂȤ‰ˆÓ Ù˘ Lp(a). ŒÙÛÈ ‰È·Ù˘ÒıËÎÂ Ë ¿Ô„Ë fiÙÈ Ë Lp(a) ÌÔÚ› Ó· ·ÔÙÂÏ› Ì›· ·ÚÓËÙÈ΋ ÚˆÙ½ÓË ÔÍ›·˜ Ê¿Û˘ Û ·ÛıÂÓ›˜ Ì ÛÏ·¯ÓÈ΋ ÏÂ˚ÛÌ·Ó›·ÛË.21
Inflammation–induced proatherogenic changes of lipoproteins. JID 2000;181: 462-72. Robin AP, Askanazi J, Greenwood MR, Carpentier YA, Gump FE, Kinney JM. Lipoprotein lipase activity in surgical patients: influence of trauma and infection. Surgery. 1981; 90(2): 401-8. Rouzer CA, Cerami A. Hypertriglyceridemia associated with Trypanosoma brucei infection in rabbits: role of detective triglyceride removal. Mol Biochem Parasitol 1980;2:31-8. Grunfeld C, Pang M, Doerrler W, Shigenaga JK, Jensen P, Feingold KR. Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. J Clin Endocrinol Metab 1992;74: 1045-52. Hellerstein MK, Grunfeld C, Wu K, et al. Increased de novo hepatic lipogenesis in human immunodeficiency virus infection. J Clin Endocrinol Metab 1993;76: 55965. Feingold KR, Krauss RM, Pang M, Doerrler W, Jensen P, Grunfeld C. The hypertriglyceridemia of acquired immunodeficiency syndrome is associated with an increased prevalence of low density lipoprotein subclass pattern B. J Clin Endocrinol Metab 1993;76: 1423-7. van Dijk KW, Hofker MH, Havekes LM. Dissection of the complex role of apoliprotein E in lipoprotein metabolism and atherosclerosis using mouse models. Curr Atheroscler Rep 1999:1(2):101-7. Van Oosten M, Rensen PC, Van Amersfoort ES, Van Eck M, Van Dam AM, Breve JJ, Vogel T, Panet A, Van Berkel TJ. Apolipoprotein E protects against bacterial lipopolysaccharide-indused lethality. A new therapeutic approach to treat gram-negative sepsis. J Biol Chem 2001; 276(12): 8820-4. Noseda G. Anti-lipoprotein autoantibodies with hypolipidemia in infectious rheumatism. Schweiz Med Wochenshr. 1975;105(31Suppl):1-58. Okamoto Y, Tominaga K, Uemura S, Metsuoka H, Tsujii T, Nakano H. Hypertriglyceridemia caused by the autoantibody to lipases for plasma lipo-
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°ÂÓÓËı›˜ ÛÙË °ÂÚÌ·Ó›· Ô ·ÌÂÚÈηÓfi˜ ‚ÈÔ¯ËÌÈÎfi˜ KONRAD EMIL BLOCH Î·È Ô ÁÂÚÌ·Ófi˜ ‚ÈÔ¯ËÌÈÎfi˜ FEODOR FELIX KONRAD LYNEN ÙÈÌ‹ıËÎ·Ó Ì ÙÔ ‚Ú·‚Â›Ô NfiÌÂÏ º˘ÛÈ΋˜ ‹ I·ÙÚÈ΋˜ ÙÔ 1964, ÁÈ· ÙËÓ ÂÚÁ·Û›· ÙÔ˘˜ ¿Óˆ ÛÙË ¯ÔÏËÛÙÂÚfiÏË. 7
·ıËÚÔÛÎÏ‹ÚˆÛË ™E¶TEMBPπ√™ 2004
¢˘ÛÏÈȉ·ÈÌ›· Î·È Î·Ú‰È·Î‹ ·Ó¿ÚÎÂÈ·: Y¿Ú¯ÂÈ Û˘Û¯¤ÙÈÛË; πˆ¿ÓÓ˘ ™Îԇ̷˜, Y‡ı˘ÓÔ˜ §Èȉ·ÈÌÈÎÔ‡ I·ÙÚ›Ԣ πÔÎÚ·Ù›Ԣ ¡ÔÛÔÎÔÌ›Ԣ ∞ıËÓÒÓ ÃÚ‹ÛÙÔ˜ ¶›ÙÛ·‚Ô˜, ∞Ó·ÏËÚˆÙ‹˜ K·ıËÁËÙ‹˜ K·Ú‰ÈÔÏÔÁ›·˜ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ XÚÈÛÙfi‰Ô˘ÏÔ˜ ™ÙÂÊ·Ó¿‰Ë˜, K·ıËÁËÙ‹˜ K·Ú‰ÈÔÏÔÁ›·˜ ¶·ÓÂÈÛÙËÌ›Ô˘ AıËÓÒÓ, ¢È¢ı˘ÓÙ‹˜ A K·Ú‰ÈÔÏÔÁÈ΋˜ KÏÈÓÈ΋˜ ¶·ÓÂÈÛÙËÌ›Ô˘ AıËÓÒÓ ∏ ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌ›· ·ÔÙÂÏ› ¤Ó·Ó ·fi ÙÔ˘˜ ·ÚÈÔ˘˜ Î·È ·ÓÂÍ¿ÚÙËÙÔ˘˜ ·Ú¿ÁÔÓÙ˜ Ô˘ Úԉȷı¤ÙÔ˘Ó ÛÙËÓ ÂÌÊ¿ÓÈÛË Ù˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘ (™¡) Î·È ÛÙÔÓ ı¿Ó·ÙÔ ·fi ·˘Ù‹ 1. ∏ Û¯¤ÛË fï˜ ÌÂٷ͇ ¯ÔÏËÛÙÂÚfiÏ˘ Î·È Î·Ú‰È·Î‹˜ ·Ó¿ÚÎÂÈ·˜ (∫∞) ‰ÂÓ Â›Ó·È ÙfiÛÔ ÍÂοı·ÚË. ∂ÓÒ Ë Framingham study 2 ¤‰ÂÈÍ fiÙÈ Ë ‰˘ÛÏÈȉ·ÈÌ›· ·ÔÙÂÏ› ·Ú¿ÁÔÓÙ· Ô˘ Úԉȷı¤ÙÂÈ ÛÙËÓ ·Ó¿Ù˘ÍË ∫∞, ¿ÏϘ ÌÂϤÙ˜ ·¤Ù˘¯·Ó Ó· ‰Â›ÍÔ˘Ó ·˘Ù‹ ÙËÓ Û¯¤ÛË 3-5. ÕÏψÛÙ ‰ÂÓ ¤¯ÂÈ ‰ÈÂÚ¢ÓËı› Û˘ÛÙËÌ·ÙÈο Ë ÛËÌ·Û›· ÙˆÓ ÏÈȉ›ˆÓ Î·È ÙˆÓ ÏÈÔÚˆÙÂ˚ÓÒÓ ÁÈ· ÙÔ˘˜ ·ÛıÂÓ›˜ Ì ¯ÚfiÓÈ· ∫∞. ™ÙȘ ‰˘ÙÈΤ˜ ÎÔÈӈӛ˜, Ì›· ·fi ÙȘ ·ÚȘ ·Èٛ˜ ¯ÚfiÓÈ·˜ ηډȷ΋˜ ·Ó¿ÚÎÂÈ·˜ (Ã∫∞) ·ÔÙÂÏ› Ë ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ˜, Ë ÔÔ›· Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ÂÌÊ¿ÓÈÛË ·˘Ù‹˜ ̤ۈ ÙˆÓ ÔͤˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ Û˘Ó‰ÚfiÌˆÓ ¶Ú¿ÁÌ·ÙÈ ÛÙË ÌÂϤÙË SOLVD6 ¤‰Â›¯ıË fiÙÈ ÙÔ Ô͇ ¤ÌÊÚ·Á· (√∂ª) Î·È Ë ·ÛÙ·ı‹˜ ÛÙËı¿Á¯Ë ·˘Í¿ÓÔ˘Ó ÙÔÓ Î›Ó‰˘ÓÔ ı·Ó¿ÙÔ˘ Î·È Ù˘ ÂÈÛ·ÁˆÁ‹˜ Û ÓÔÛÔÎÔÌÂ›Ô ÁÈ· Ã∫∞. ª¿ÏÈÛÙ· ÙÔ √∂ª ˘ÂÚ‰ÈÏ·ÛÈ¿˙ÂÈ ÙÔÓ ÂÙ‹ÛÈÔ Î›Ó‰˘ÓÔ ÂÈÛ·ÁˆÁ‹˜ Û ÓÔÛÔÎÔÌÂ›Ô ÁÈ· Ã∫∞ (·fi 8,6% Û 20,5%, RR 2,1). ¶·ÚfiÌÔÈ· Â˘Ú‹Ì·Ù· ¤‰ÂÈÍÂ Î·È Ë ÌÂϤÙË 4S7. ™ÙËÓ ÔÌ¿‰· ÙÔ˘ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘, 52% ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ·Ó¤Ù˘Í·Ó ∫∞ ·ÚÔ˘Û›·Û·Ó √∂ª ÌÂÙ¿ ÙËÓ Ù˘¯·ÈÔÔ›ËÛ‹ ÙÔ˘˜8. ∞ÓÙ›ıÂÙ· ÛÙËÓ ÔÌ¿‰· ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ‰ÂÓ ·Ó¤Ù˘Í·Ó Ã∫∞, ÙÔ ÔÛÔÛÙfi ÙÔ˘ ∂ª ‹Ù·Ó ÌfiÓÔ 16%. ∆¤ÏÔ˜ Ë ™¡ Â›Ó·È Î‡ÚÈÔ˜ Î·È ·ÓÂÍ¿ÚÙËÙÔ˜ ·Ú¿ÁˆÓ ÁÈ· ·Ó¿Ù˘ÍË Ã∫∞ Û ˘ÂÚ‹ÏÈΘ. ª¿ÏÈÛÙ· Ô Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜ (RR) ·Ó¿Ù˘Í˘ Ã∫∞, Û 2902 ¿ÙÔÌ· 81 ÂÙÒÓ ‹Ù·Ó 4,0 9. √È ÛÙ·Ù›Ó˜ ̤ۈ Ù˘ Ì›ˆÛ˘ ÙˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ Û˘Ó‰ÚfïÓ, Ê·›ÓÂÙ·È fiÙÈ Û˘ÓÂÈÛʤÚÔ˘Ó ÛÙËÓ Ì›ˆÛË Ù˘ ›وÛ˘ Ù˘ Ã∫∞. ∞˘Ùfi ·ÎÚÈ‚Ò˜ ‰›¯ıË ÛÙËÓ 4S, ÛÙËÓ ÔÔ›· Ë Â›ÙˆÛË Ù˘ Ã∫∞ ηٿ ÙËÓ ‰È¿ÚÎÂÈ· Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ ‹Ù·Ó 10,3% ÁÈ· Ù· ¿ÙÔÌ· Ô˘ ¤Ï·‚·Ó ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ Î·È 8,3% ÁÈ· ÙËÓ ÔÌ¿‰· Ù˘ ÛÈÌ‚·ÛÙ·Ù›Ó˘, Ú¿ÁÌ· Ô˘ ÌÂÙ·ÊÚ¿˙ÂÙ·È Û 19% Ì›ˆÛË Ù˘ Ã∫∞
8
(P<0,015)8. ∆Ô ›‰ÈÔ Â‰Â›¯ıË Î·È ÛÙËÓ ÌÂϤÙË CARE, ÛÙËÓ ÔÔ›· Ë Â›ÙˆÛË Ã∫∞ Û ¿ÙÔÌ· 65-75 ÂÙÒÓ (1283 ·ÛıÂÓ›˜) ‹Ù·Ó 13,8% Î·È 10,9% ÁÈ· ÙÔ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ Î·È ÙËÓ Ú·‚·ÛÙ·Ù›ÓË ·ÓÙ›ÛÙÔȯ·, Ú¿ÁÌ· Ô˘ ÌÂÙ·ÊÚ¿˙ÂÙ·È Û ̛· Ì›ˆÛË 21% Ù˘ ›وÛ˘ Ã∫∞ (P=0,10)10. ¶ÚfiÛÊ·Ù· Ô Aronow Î·È Û˘ÓÂÚÁ¿Ù˜ ÌÂϤÙËÛ·Ó ÙËÓ Â›ÙˆÛË Ã∫∞, 11 Û 448 ¿Ó‰Ú˜ Î·È 922 Á˘Ó·›Î˜ ̤Û˘ ËÏÈΛ·˜ 81±9 ÂÙÒÓ Ì LDL > 125 mg/dl, ÔÈ ÔÔ›ÔÈ ·Ú·ÎÔÏÔ˘ı‹ıËÎ·Ó ÚÔÔÙÈο ÁÈ· 36±21 Ì‹Ó˜ Î·È ÂÎ ÙˆÓ ÔÔ›ˆÓ ÂÚ›Ô˘ ÔÈ ÌÈÛÔ› ¤Ï·‚·Ó ÛÙ·Ù›ÓË. TÔ ÎÏ¿ÛÌ· Â͈ı‹Ûˆ˜ ÙˆÓ ıÂڷ¢ÔÌ¤ÓˆÓ Ì ÛÙ·Ù›ÓË ‹Ù·Ó 48±14% ÂÓÒ ·˘ÙÒÓ Ô˘ ‰ÂÓ ¤Ï·‚·Ó ÛÙ·Ù›ÓË 48±13% (P= NS). √È ·Ú¯ÈΤ˜ Î·È ÙÂÏÈΤ˜ ÙÈ̤˜ LDL, HDL Î·È TGL ÙˆÓ ·ÙfiÌˆÓ ˘fi ÛÙ·Ù›ÓË ‹Ù·Ó ·ÓÙ›ÛÙÔȯ· 152±26 Î·È 98±17 mg/dl (P< 0,0001), 40±9 Î·È 44±10 mg/dl Î·È 123±51 ¤Ó·ÓÙÈ 108±45 mg/dl. ∞ÓÙ›ıÂÙ· ÛÙËÓ ÔÌ¿‰· ¯ˆÚ›˜ ÛÙ·Ù›ÓË ‰ÂÓ ˘‹Ú¯·Ó ‰È·ÊÔÚ¤˜ ÛÙȘ ÚÔ·Ó·ÊÂÚı›Û˜ ÙÈ̤˜. ∏ Û˘¯ÓfiÙËÙ· Ù˘ Ã∫∞ Û 36 Ì‹Ó˜ ·Ú·ÎÔÏÔ‡ıËÛ˘ ‹Ù·Ó 42% ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ ¤Ï·‚·Ó ÛÙ·Ù›ÓË Î·È 31% Û ·˘ÙÔ‡˜ Ô˘ ¤Ï·‚·Ó, ‰ËÏ·‰‹ Ì›· Ì›ˆÛË 26% ÛÙËÓ Â›ÙˆÛË Ã∫∞ (P< 0,0001). ª¿ÏÈÛÙ· ‰›¯ıË fiÙÈ ·ÓÂÍ¿ÚÙËÙÔÈ ÚÔ‚ÏÂÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ ÁÈ· Ã∫∞ ‹Ù·Ó Ë ËÏÈΛ·, ÙÔ Î¿ÓÈÛÌ·, Ë ·ÚÙËÚȷ΋ ˘¤ÚÙ·ÛË, Ô Û·Î¯·Ú҉˘ ‰È·‚‹Ù˘, Ë ·Ú¯È΋ ÙÈÌ‹ LDL (Risk ratio: 1,01 ÁÈ· οı 1 mg/dl ·‡ÍËÛË) Ë ·Ú¯È΋ ÙÈÌ‹ HDL (Risk ratio: 0,96 ÁÈ· οı 1 mg/dl ·‡ÍËÛË) Î·È Ë ¯Ú‹ÛË ÛÙ·ÙÈÓÒÓ (risk ratio: 0,52). ∏ ¢ÓÔ˚΋ ‰Ú¿ÛË ÙˆÓ ÛÙ·ÙÈÓÒÓ ÙfiÛÔ ÛÙËÓ ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ ¯ˆÚ›˜ ÂÌÊ·Ó‹ Ã∫∞, ·ÎfiÌË Î·È Û ¿ÙÔÌ· Ì «Ê˘ÛÈÔÏÔÁÈ΋» LDL ¯ÔÏËÛÙÂÚfiÏË, fiÛÔ Î·È ÛÙËÓ ÚfiÏË„Ë Ù˘ Ã∫∞ ÛÙ· ¿ÙÔÌ· ·˘Ù¿, Û‹ÌÂÚ· ¤¯ÂÈ ÙÂÎÌËÚȈı›. ∂ÚˆÙËÌ·ÙÈÎfi ·Ú·Ì¤ÓÂÈ Â¿Ó Ù· ÔʤÏË ·fi ÙȘ ÛÙ·Ù›Ó˜ ÂÍ·ÎÔÏÔ˘ıÔ‡Ó Ó· ˘Ê›ÛÙ·ÓÙ·È fiÙ·Ó ·Ó·Ù˘¯ı› Ã∫∞. µ¤‚·È· Ô Horwich Î·È Û˘ÓÂÚÁ¿Ù˜12 Û 5 ¤ÙË ·Ú·ÎÔÏÔ‡ıËÛ˘ 1,134 ·ÛıÂÓÒÓ Ì ÚÔ¯ˆÚË̤ÓË Ã∫∞ ÙÔ˘˜ ÔÔ›Ô˘˜ ¯ÒÚÈÛ·Ó ÛÂ
¤ÓÙ ÔÌ¿‰Â˜, ·Ó¿ÏÔÁ· Ì ÙȘ ÙÈ̤˜ Ù˘ ÔÏÈ΋˜ ¯ÔÏËÛÙÂÚfiÏ˘, η٤ÏËÍ·Ó ÛÙÔ Û˘Ì¤Ú·ÛÌ· fiÙÈ ·ÛıÂÓ›˜ Ì ÚÔ¯ˆÚË̤ÓË Ã∫∞ Î·È TC >190 mg/dl ›¯·Ó ηχÙÂÚË ÂÈ‚›ˆÛË ·fi ·˘ÙÔ‡˜ Ì ¯·ÌËÏfiÙÂÚË TC. ª¿ÏÈÛÙ· Ë TC ·ÔÙÂÏÔ‡Û ¤Ó·Ó ·ÓÂÍ¿ÚÙËÙÔ ÚÔÁÓˆÛÙÈÎfi ·Ú¿ÁÔÓÙ· ıÓËÙfiÙËÙ·˜ ÁÈ· ·˘ÙÔ‡˜ ÙÔ˘˜ ·ÛıÂÓ›˜. √È Û˘ÁÁÚ·Ê›˜ ˘ÔÛÙ‹ÚÈÍ·Ó Ù· ·ÔÙÂϤÛÌ·Ù· Ù˘ ÌÂϤÙ˘ ÙÔ˘˜, ÂÛÙÈ¿˙ÔÓÙ·˜ ÛÙÔÓ ÚfiÏÔ Ô˘ ·›˙Ô˘Ó ÔÈ ÏÈÔÚˆÙ½Ó˜ ÛÙËÓ ˘Ô‚¿ıÌÈÛË Ù˘ ·ÓÔÛÔÏÔÁÈ΋˜ ÊÏÂÁÌÔÓÒ‰Ô˘˜ ·¿ÓÙËÛ˘. ∏ ‰Ú¿ÛË ·˘Ù‹ Ê·›ÓÂÙ·È fiÙÈ ‰ÈÂÎÂÚ·ÈÒÓÂÙ·È Ì¤Ûˆ Ù˘ ·ÏÏËÏ›‰Ú·Û˘ ÙˆÓ ÏÈÔÚˆÙÂÈÓÒÓ Î·È ÙˆÓ ‚·ÎÙËÚȉȷÎÒÓ ÏÈÔÔÏ˘Û·Î¯·Ú›‰ˆÓ. Œ¯ÂÈ ‰Âȯı› fiÙÈ Ë LDL Î·È Ë HDL Û˘Ó‰ÂfiÌÂÓ˜ Ì ÙȘ ÏÈÔÔÏ˘Û·Î¯·Ú›‰Â˜, ÚÔÊ˘Ï¿ÛÛÔ˘Ó ¤Ó·ÓÙÈ ÙˆÓ ¿ÌÂÛˆÓ ÙÔÍÈÎÒÓ ‰Ú¿ÛÂˆÓ ·˘ÙÒÓ ÛÙ· ÂÓ‰ÔıËÏȷο ·ÙÙ·Ú·13,14. ∂›Ó·È ÛËÌ·ÓÙÈÎfi Ó· ÙÔÓÈÛı› fiÙÈ ÔÈ Û˘ÁÁÚ·Ê›˜ ÂÈÛËÌ·›ÓÔ˘Ó fiÙÈ Ù· ·ÔÙÂϤÛÌ·Ù· Ù˘ ÌÂϤÙ˘ ‰ÂÓ Ú¤ÂÈ Ó· ÂÚÌËÓ¢ıÔ‡Ó Û·Ó ÚÔÙÚÔ‹ ·ÔÊ˘Á‹˜ ÙˆÓ ˘ÔÏÈȉ·ÈÌÈÎÒÓ Î·È Î˘Ú›ˆ˜ ÙˆÓ ÛÙ·ÙÈÓÒÓ Û ·ÛıÂÓ›˜ Ì Ã∫∞. ™Â ÚfiÛÊ·ÙË ÌÂϤÙË ÛÂ Â›Ì˘Â˜ Ì ∫∞ ÔÈ ÛÙ·Ù›Ó˜ ‚ÂÏÙ›ˆÛ·Ó ÙËÓ Û˘ÛÙÔÏÈ΋ Î·È ‰È·ÛÙÔÏÈ΋ ÏÂÈÙÔ˘ÚÁ›· Ù˘ ·ÚÙËÚȷ΋˜ ÎÔÈÏ›·˜. 16 ™‹ÌÂÚ· Ù›ıÂÙ·È ÙÔ ÂÚÒÙËÌ·: ¤¯Ô˘Ó ı¤ÛË ÔÈ ÛÙ·Ù›Ó˜ ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ Ã∫∞; ∞˘Ùfi Á›ÓÂÙ·È ÂÓÙÔÓfiÙÂÚÔ ÁÓˆÚ›˙ÔÓÙ·˜, fiˆ˜ ÚԷӷʤÚıËÎÂ, fiÙÈ ÔÈ ÛÙ·Ù›Ó˜ ‚ÔËıÔ‡Ó, ̤ۈ Ù˘ Ì›ˆÛ˘ ÙˆÓ ÔͤˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ ÂÂÈÛÔ‰›ˆÓ, ÛÙËÓ Ì›ˆÛË Ù˘ ›وÛ˘ Ù˘ Ã∫∞. µ¤‚·È· ‰ÂÓ ˘¿Ú¯Ô˘Ó ÌÂÁ¿Ï˜ ÌÂϤÙ˜ Ô˘ Ó· ¤¯Ô˘Ó Û·Ó ·ÓÙÈΛÌÂÓÔ ÙÔÓ ÚfiÏÔ ÙˆÓ ÛÙ·ÙÈÓÒÓ ÛÙËÓ Ã∫∞. ¶·Ú fiÏ· ·˘Ù¿ ˘¿Ú¯Ô˘Ó ÂӉ›ÍÂȘ Ô˘ Û˘ÓËÁÔÚÔ‡Ó ÚÔ˜ ·˘Ù‹Ó ÙËÓ Î·Ù‡ı˘ÓÛË. ∞. ™‹ÌÂÚ· ÈÛÙ‡ÂÙ·È, fiÙÈ Ù· Ôͤ· ÛÙÂÊ·ÓÈ·›· ÂÂÈÛfi‰È· ·ÔÙÂÏÔ‡Ó ÛËÌ·ÓÙÈÎfi Ì˯·ÓÈÛÌfi Âȉ›ӈÛ˘ Û ·ÛıÂÓ›˜ Ì ‹È· Ã∫∞ Î·È ‰˘ÛÏÂÈÙÔ˘ÚÁ›· Ù˘ ·ÚÈÛÙÂÚ‹˜ ÎÔÈÏÈ¿˜. ™’ ·˘ÙÔ‡˜ ÙÔ˘˜ ·ÛıÂÓ›˜ ˘¿Ú¯Ô˘Ó ·Ô‰Â›ÍÂȘ fiÙÈ ÔÈ ÛÙ·Ù›Ó˜ ‰È·ÙËÚÔ‡Ó ÙËÓ ÈηÓfiÙËÙ· ÙÔ˘˜ Ó· ÚÔ-
¶A£OºY™IO§O°IA Ï·Ì‚¿ÓÔ˘Ó Ù· Ôͤ· ÈÛ¯·ÈÌÈο ÂÂÈÛfi‰È· Î·È ¤ÙÛÈ Ó· ÚÔÊ˘Ï¿ÛÛÔ˘Ó ÙËÓ ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ· Ù˘ ·ÚÈÛÙÂÚ‹˜ ÎÔÈÏ›·˜. ∞˘Ùfi ¤‰ÂÈÍÂ Ë ÌÂϤÙË CARE17 Ô˘ ÂÚȤϷ‚Â Î·È 706 ·ÛıÂÓ›˜ Ì ∫∂ (ÎÏ¿ÛÌ· Â͈ı‹Ûˆ˜ ·ÚÈÛÙÂÚ¿˜ ÎÔÈÏ›·˜) <40% Î·È >25%. ∏ Ú·‚·ÛÙ·Ù›ÓË Ì›ˆÛ ٷ ÛÙÂÊ·ÓÈ·›· Û˘Ì‚¿Ì·Ù· ÂÍ›ÛÔ˘, ÙfiÛÔ Û ·˘ÙÔ‡˜ Ì ∫∂>40 fiÛÔ Î·È ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ∫∂<40. µ¤‚·È· Û‹ÌÂÚ· ‰ÂÓ ˘¿Ú¯Ô˘Ó ÌÂϤÙ˜ ÛÙ·ÙÈÓÒÓ, Ô˘ Ó· ÂÛÙÈ¿˙Ô˘Ó ÛÙËÓ ‰Ú¿ÛË ÙÔ˘˜ Û ·ÛıÂÓ›˜ Ì Ôχ ¯·ÌËÏfi ∫∂, οو ÙˆÓ 25%. ™Ù· ¿ÙÔÌ· ·˘Ù¿ Ì Ôχ ¯·ÌËÏfi ∫∂ Ù· Ó¤· ÛÙÂÊ·ÓÈ·›· ÂÂÈÛfi‰È· Ê·›ÓÂÙ·È fiÙÈ Â›Ó·È ·Û˘Ó‹ıË Î·È Ë ÚfiÔ‰Ô˜ Ù˘ ÓfiÛÔ˘ Á›ÓÂÙ·È Ì¤Ûˆ ¿ÏÏˆÓ Ì˯·ÓÈÛÌÒÓ 18. µ. ∏ ·Ó·ÛÙÚ¤„ÈÌË ÈÛ¯·ÈÌ›· Î·È ÙÔ Ì˘ÔοډÈÔ Û ¯ÂÈÌÂÚ›· Ó¿ÚÎË Ê·›ÓÂÙ·È fiÙÈ ·ÔÙÂÏÔ‡Ó ÂÈϤÔÓ Ì˯·ÓÈÛÌÔ‡˜ ÛÙÔ˘˜ ÔÔ›Ô˘˜ ÌÔÚ› Ó· ‰Ú¿ÛÔ˘Ó ÔÈ ÛÙ·Ù›Ó˜ Î·È Ó· ‚ÂÏÙÈÒÛÔ˘Ó ÙËÓ ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ· Ù˘ ·ÚÈÛÙÂÚ‹˜ ÎÔÈÏ›·˜. ¶Ú¿ÁÌ·ÙÈ ÔÈ ÛÙ·Ù›Ó˜ ÌÂÈÒÓÔ˘Ó ÙËÓ ÛȈËÚ¿ ·Ó·ÛÙÚ¤„ÈÌÔ ÈÛ¯·ÈÌ›·. ¶Ú¤ÂÈ Ó· ÙÔÓÈÛı› fï˜ fiÙÈ Ë Û˘¯ÓfiÙËÙ· Î·È Ë Èı·Ó‹ ·ıÔÊ˘ÛÈÔÏÔÁÈ΋ ÛÔ˘‰·ÈfiÙËÙ· Ù˘ Â›Ó·È ˘fi ‰ÈÂÚ‡ÓËÛË ÛÙËÓ Ã∫∞.19 ∞ÓÙ›ıÂÙ· ÙÔ Ì˘ÔοډÈÔ Û ¯ÂÈÌÂÚ›· Ó¿ÚÎË Â›Ó·È Û˘¯Ófi ÛÙËÓ Ã∫∞, Ë ‰Â ·Ó·ÛÙÚÔÊ‹ ÙÔ˘ ‚ÂÏÙÈÒÓÂÈ ÙËÓ ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ· Ù˘ ·ÚÈÛÙÂÚ‹˜ ÎÔÈÏ›·˜.20 ∞Ô̤ÓÂÈ fï˜ Ó· ·Ô‰Âȯı› ÙÔ Â·Ó ÔÈ ÛÙ·Ù›Ó˜, ̤ۈ Ù˘ ‚ÂÏÙ›ˆÛ˘ ÙˆÓ ·ÓˆÙ¤Úˆ, ‚ÂÏÙÈÒÓÔ˘Ó ÙËÓ ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ· Ù˘ ·ÚÈÛÙÂÚ‹˜ ÎÔÈÏ›·˜. °. √È ÛÙ·Ù›Ó˜ ÂÓ¤¯ÔÓÙ·È Û ‰ÈÂÚÁ·Û›Â˜, ¿Û¯ÂÙ˜ ·fi ÙËÓ ·ÓÙÈÈÛ¯·ÈÌÈ΋ ÙÔ˘˜ ‰Ú¿ÛË, ÔÈ Ôԛ˜ Ê·›ÓÂÙ·È fiÙÈ ÂËÚ¿˙Ô˘Ó Â˘ÓÔ˚ο ÙËÓ ·ıÔÊ˘ÛÈÔÏÔÁ›· Ù˘ Ã∫∞. ŒÙÛÈ ¤Ú· ·fi ÙË ‚ÂÏÙ›ˆÛË Ù˘ ÂÓ‰ÔıËÏȷ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ Î·È ÙËÓ ÛÙ·ıÂÚÔÔ›ËÛË Ù˘ ·ıËڈ̷ÙÈ΋˜ Ͽη˜, ÂÓ¤ÚÁÂȘ Ô˘ ¤¯Ô˘Ó Û·Ó Î‡ÚÈÔ ÛÙfi¯Ô ÙËÓ ‚ÂÏÙ›ˆÛË Ù˘ ÈÛ¯·ÈÌ›·˜, ÔÈ ÛÙ·Ù›Ó˜ Ê·›ÓÂÙ·È fiÙÈ Ì ¤Ó· ·ÚÈıÌfi ÂÈÚfiÛıÂÙˆÓ ‰Ú¿ÛÂˆÓ ÂÈ‚Ú·‰‡ÓÔ˘Ó ÙËÓ ÂͤÏÈÍË Ù˘ Ã∫∞. 1. ¢Ú¿ÛÂȘ ÛÙËÓ ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ· ÙÔ˘ Ì˘ÔηډȷÎÔ‡ ΢ÙÙ¿ÚÔ˘: ∂›Ó·È ÁÓˆÛÙfi fiÙÈ ÔÈ ÏÈÔÚˆÙ½Ó˜ ·ÔÙÂÏÔ‡Ó ÚÔÂÍ¿Ú¯ÔÓ Û˘ÛÙ·ÙÈÎfi ÙˆÓ Î˘ÙÙ·ÚÈÎÒÓ ÌÂÌ‚Ú·ÓÒÓ Î·È Û˘ÓÂÒ˜ ·›˙Ô˘Ó ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ· ÙÔ˘ ΢ÙÙ¿ÚÔ˘. ªÂÁ¿ÏË ÔÛfiÙËÙ· ¯ÔÏËÛÙÂÚfiÏ˘ ÛÙȘ ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ ÂËÚ¿˙ÂÈ Ù· ¤Ó˙˘Ì· Ô˘ ··ÈÙÔ‡ÓÙ·È ÁÈ· ÙËÓ ·Ú·ÁˆÁ‹ ÂÓ¤ÚÁÂÈ·˜ Î·È ÙËÓ ÌÂٷΛÓËÛË ÙÔ˘ Ca++ ‰È· ̤ÛÔ˘ ÂȉÈÎÒÓ Î·Ó·ÏÈÒÓ, Ì ‰˘ÓËÙÈÎfi ·ÔÙ¤ÏÂ-
ÛÌ· ÙËÓ ·ÚÓËÙÈ΋ ‰Ú¿ÛË ÛÙËÓ Î·Ú‰È·Î‹ ÏÂÈÙÔ˘ÚÁ›·.21 2. ¡ÂÔ·ÁÁÂÈÔÁ¤ÓÓÂÛË: Œ¯ÂÈ ‰Âȯı› fiÙÈ ÔÈ ÛÙ·Ù›Ó˜ ÚÔηÏÔ‡Ó ‰ËÌÈÔ˘ÚÁ›· Ó¤ˆÓ ·ÁÁ›ˆÓ ÛÙ· ÈÛ¯·ÈÌÈο ¿ÎÚ·, ̤ۈ, ÙÔ˘Ï¿¯ÈÛÙÔÓ Î·Ù¿ ¤Ó· ÌÂÁ¿ÏÔ Ì¤ÚÔ˜, Ù˘ ÈηÓfiÙËÙ¿˜ ÙÔ˘˜ Ó· ÎÈÓËÙÔÔÈÔ‡Ó ·ÁÁÂÈÔ‚Ï·ÛÙÈο ΢ÙÙ·ÚÈο ÛÙÂϤ¯ÔÈ ·fi ÙÔ Ì˘ÂÏfi ÙˆÓ ÔÛÙÒÓ. 22 3. ÀÔ‚¿ıÌÈÛË ÙˆÓ ∞∆1 ˘Ô‰Ô¯¤ˆÓ. ∂‰Â›¯ıË fiÙÈ Ë ·ÙÔÚ‚·ÛÙ·Ù›ÓË ˘Ô‚·ıÌ›˙ÂÈ ÙÔ˘˜ ∞∆1 ˘Ô‰Ô¯Â›˜ ÛÙ· ·ÁÁÂȷο Ï›· Ì˘˚ο ·ÙÙ·Ú·. ∂¿Ó ÏËÊı› ˘ fi„ÈÓ ÙÔ ıÂڷ¢ÙÈÎfi ·ÔÙ¤ÏÂÛÌ· ÛÙËÓ Ã∫∞ ·fi ÙËÓ ·Ó·ÛÙÔÏ‹ ÙÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜ ÚÂÓ›Ó˘-·ÁÁÂÈÔÙ·Û›Ó˘-·Ï‰ÔÛÙÂÚfiÓ˘, Ê·›ÓÂÙ·È fiÙÈ ÔÈ ÂÓ ÏfiÁˆ ˘Ô‰Ô¯Â›˜ ·›˙Ô˘Ó ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ Â› Ù· ¯Â›Úˆ ÂͤÏÈÍË Ù˘ Ã∫∞. 23 4. ∞ÔηٿÛÙ·ÛË Ù˘ ·˘ÙÔÓfiÌÔ˘ Ó¢ÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜. ∏ Ã∫∞ Û˘Óԉ‡ÂÙ·È ·fi ˘ÂÚÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ·˘ÙÔÓfiÌÔ˘ Û˘Ì·ıËÙÈÎÔ‡ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ Î·È Ì›ˆÛË ·ÓÙ›ÛÙÔȯ· ÙÔ˘ ·Ú·Û˘Ì·ıËÙÈÎÔ‡.24 ∂›Ó·È ÁÓˆÛÙfi fiÙÈ Ë ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ·˘ÙÔÓfiÌÔ˘ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ Û˘Óԉ‡ÂÙ·È ·fi ·‡ÍËÛË ÙˆÓ ·ÈÊÓȉ›ˆÓ ı·Ó¿ÙˆÓ. ∏ ‚ÂÏÙ›ˆÛË ÏÔÈfiÓ Ù˘ ·˘ÙÔÓfiÌÔ˘ Ó¢ÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ ‰˘ÓËÙÈο ı· ‰Ú¿ÛÂÈ Â˘ÓÔ˚ο Î·È Èı·ÓÒ˜ ı· ÂÚÈÔÚ›ÛÂÈ ÙÔ˘˜ ·ÈÊÓȉ›Ô˘˜ ı·Ó¿ÙÔ˘˜. √È ÛÙ·Ù›Ó˜ ¤¯Ô˘Ó ‰Â›ÍÂÈ, Û ÌÈÎÚ¤˜ ‚¤‚·È· ÌÂϤÙ˜, fiÙÈ ‚ÂÏÙÈÒÓÔ˘Ó ÙËÓ ·˘ÙfiÓÔÌË Ó¢ÚÈ΋ ÏÂÈÙÔ˘ÚÁ›· Û ¿ÙÔÌ· Ì ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ.25 ª¿ÏÈÛÙ· Ë ÛÈÌ‚·ÛÙ·Ù›ÓË Ì›ˆÛ ÙËÓ ·˘ÙfiÓÔÌË Û˘Ì·ıËÙÈ΋ ‰Ú·ÛÙËÚÈfiÙËÙ· Û ÎÔÓ›ÎÏÔ˘˜, ÛÙÔ˘˜ ÔÔ›Ô˘˜ ÚÔÎÏ‹ıËΠ∫∞ Ì ‚ËÌ·ÙÔ‰fiÙËÛË.26 5. ∞Ó·ÛÙÔÏ‹ ÙˆÓ ÚÔÊÏÂÁÌÔÓˆ‰ÒÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ. ∏ ÊÏÂÁÌÔÓ‹ Ê·›ÓÂÙ·È fiÙÈ ·›˙ÂÈ ¤Ó· ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ÚfiÔ‰Ô Ù˘ Ã∫∞. ª¿ÏÈÛÙ· ˘¿Ú¯Ô˘Ó ÔÚÈṲ̂Ó˜ ÂӉ›ÍÂȘ fiÙÈ ÔÈ ÚÔÊÏÂÁÌÔÓÒ‰ÂȘ ΢ÙÙ·ÚÔΛÓ˜ ÂÓÂÚÁÔÔÈÔ‡ÓÙ·È ·fi ÏÈÔÔÏ˘Û·Î¯·Ú›‰Â˜,27 Ô˘ ÂÈÛ¤Ú¯ÔÓÙ·È ÛÙËÓ Î˘ÎÏÔÊÔÚ›· ÙˆÓ ·ÛıÂÓÒÓ Ì Ã∫∞, ̤ۈ ÙÔ˘ ÔȉËÌ·ÙÒ‰Ô˘˜ ÂÓÙÂÚÈÎÔ‡ ÙÔȯÒÌ·ÙÔ˜. ŸÙ·Ó Ë ÊÏÂÁÌÔÓ҉˘ ·¿ÓÙËÛË Á›ÓÂÈ ˘ÂÚÂÓÂÚÁ‹˜ ·Ú¯›˙ÂÈ Ó· ¤¯ÂÈ Î·Ù·ÛÙÚÔÊÈο ·ÔÙÂϤÛÌ·Ù·. ∏ ‰Ú·ÛÙÈÎfiÙËÙ· ÙÔ˘ TNF· Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ‚·Ú‡ÙËÙ· Ù˘ Ã∫∞ Î·È Ê·›ÓÂÙ·È fiÙÈ Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ Âȉ›ӈÛË Ù˘ Ã∫∞ ̤ۈ Ù˘ ÚÔ·ÔÙˆÙÈ΋˜ Î·È Ù˘ ·ÚÓËÙÈ΋˜ ÈÓÔÙÚfiÔ˘ ‰Ú¿Û˘ ÙÔ˘. 15 ŒÙÛÈ Ô ∆¡F·, ÙÔ˘ ÔÔ›Ô˘, fiˆ˜ ÚԷӷʤÚıËÎÂ, Ë ¤ÎÊÚ·ÛË ÙÔ˘ ÁÔÓȉ›Ô˘ ·˘Í¿ÓÂÙ·È ÛÙÔ Ì˘ÔοډÈÔ
Ù˘ ·Ó·ÚÎÔ‡Û˘ ηډȿ˜, ÂËÚ¿˙ÂÈ ÙËÓ ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ· Ù˘ ·ÚÈÛÙÂÚ‹˜ ÎÔÈÏ›·˜ Î·È ÚÔηÏ› ÛËÙÈ΋ Ì˘ÔηډÈÔ¿ıÂÈ·, ̤ۈ Ó¤ÎÚˆÛ˘, ·fiÙˆÛ˘ Î·È ·ıÔÏÔÁÈ΋˜ ›ÓˆÛ˘.28 µÚ¤ıËΠfiÙÈ ÔÈ ÛÙ·Ù›Ó˜ ¤¯Ô˘Ó ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë ‰Ú¿ÛË Î·È ÌÂÈÒÓÔ˘Ó Ù· ›‰· ÙÔ˘ ∆¡F· Î·È ¿ÏÏˆÓ ÚÔÊÏÂÁÌÔÓˆ‰ÒÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ fiˆ˜ Ë πL6 (ÈÓÙÂÚÏ¢ΛÓË 6).29 ¢. ™‹ÌÂÚ· ˘¿Ú¯Ô˘Ó ÚÔÎÏÈÓÈο ‰Â‰Ô̤ӷ fiÙÈ ÔÈ ÛÙ·Ù›Ó˜ ˆÊÂÏÔ‡Ó Û Ã∫∞. √È ÛÙ·Ù›Ó˜ ‚ÂÏÙÈÒÓÔ˘Ó ÙËÓ ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ· Ù˘ ·ÚÈÛÙÂÚ‹˜ ÎÔÈÏ›·˜ Û ÂÈÚ·Ì·ÙÈο ÌÔÓ٤Ϸ Ã∫∞ Û ˙Ò· Ô˘ Ë Ã∫∞ Â›Ó·È ·ÔÙ¤ÏÂÛÌ· ÂÌÊÚ¿ÁÌ·ÙÔ˜ Ô˘ ÚÔÎÏ‹ıËΠ·fi ÛÙÚ·ÁÁ·ÏÈÛÌfi ÛÙÂÊ·ÓÈ·›·˜ ·ÚÙËÚ›·˜. Î·È ·ıÔÏÔÁÈ΋˜ ÎÔÈÏȷ΋˜ ·Ó·‰È·ÌfiÚʈÛ˘. ∏ ÊÏÔ˘‚·ÛÙ·Ù›ÓË30 Ì›ˆÛ ÙËÓ ıÓËÙfiÙËÙ· Û ÔÓÙÈÎÔ‡˜, ÂÈÙ˘Á¯¿ÓÔÓÙ·˜ Ì›ˆÛË ·. Ù˘ ‰È¿Ù·Û˘ Ù˘ ·ÚÈÛÙÂÚ¿˜ ÎÔÈÏ›·˜, ‚. Ù˘ ˘ÂÚÙÚÔÊ›·˜ ÙˆÓ Ì˘Ô΢ÙÙ¿ÚˆÓ Î·È Á. Ù˘ ‰È·Ì¤ÛÔ˘ ÈÓÒÛˆ˜. ¶·ÚfiÌÔÈ· ·ÔÙÂϤÛÌ·Ù· ·Ú·ÙËÚ‹ıËηÓ, Ì ÙËÓ ÛÂÚÈ‚·ÛÙ·Ù›ÓË, Û ·ÚÔ˘Ú·›Ô˘˜ Ì Ã∫∞ ÌÂÙ¿ ∂ª. ª¿ÏÈÛÙ· Û˘Óԉ‡ÙËÎ·Ó ·fi Ì›ˆÛË Ù˘ ÂÓ·fiıÂÛ˘ ·ıÔÏÔÁÈÎÔ‡ ÎÔÏÏ·ÁfiÓÔ˘ Û ۯ¤ÛË Ì ÙËÓ ÔÌ¿‰· Ì·ÚÙ‡ÚˆÓ. ¶Ú¤ÂÈ Ó· ÙÔÓÈÛı›, fiÙÈ ·Ú fiÏÔ Ô˘ Ë Ã∫∞ ÚÔÎÏ‹ıËΠ·fi ¤Ó· ·Ú¯ÈÎfi ÂÂÈÛfi‰ÈÔ ÈÛ¯·ÈÌ›·˜ Ë ÂÌÊÚ¿ÁÌ·ÙÔ˜, Ë Û˘Ó¯È˙fiÌÂÓË ·ıÔÏÔÁÈ΋ ÎÔÈÏȷ΋ ·Ó·‰È·ÌfiÚʈÛË ‰ÂÓ ÔÊÂÈÏfiÙ·Ó ÛÂ Û˘Ó¯È˙fiÌÂÓË ÈÛ¯·ÈÌ›·. ŒÙÛÈ Ë Â˘ÂÚÁÂÙÈ΋ ‰Ú¿ÛË ÙˆÓ ÛÙ·ÙÈÓÒÓ Ê·›ÓÂÙ·È fiÙÈ Â›Ó·È ·ÓÂÍ¿ÚÙËÙÔ˜ ·fi ÙËÓ ‰Ú¿ÛË ÙˆÓ ÛÙËÓ ÈÛ¯·ÈÌ›·. ∞˘Ùfi ˘ÔÛÙËÚ›˙ÂÈ Ì›· ‰Ú¿ÛË ÙˆÓ ÛÙ·ÙÈÓÒÓ ÛÙÔ Ì˘ÔοډÈÔ, ¿Û¯ÂÙË ·fi ·˘Ù‹ ÛÙ· ÛÙÂÊ·ÓÈ·›· ·ÁÁ›·. ∂. À¿Ú¯Ô˘Ó ÎÏÈÓÈο ÛÙÔȯ›· fiÙÈ ÔÈ ÛÙ·Ù›Ó˜ ÔÊÂÏÔ‡Ó ÛÙË Ã∫∞ ·Ú fiÙÈ ‰ÂÓ ˘¿Ú¯Ô˘Ó ÌÂÁ¿Ï˜ ÌÂϤÙ˜. 1. ¶ÚfiÏË„Ë Ó¤·˜ ηډȷ΋˜ ·Ó¿ÚÎÂÈ·˜. ∏ Ì›ˆÛË Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ Ì ÛÙ·Ù›Ó˜ ¤¯ÂÈ Û·Ó ·ÔÙ¤ÏÂÛÌ· Ì›· ÛËÌ·ÓÙÈ΋ Ì›ˆÛË Ù˘ ıÓËÙfiÙËÙ·˜ Î·È ÙˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ ÙÂÏÈÎÒÓ ÛËÌ›ˆÓ, Û ۯ¤ÛË Ì ÙÔ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ, Û ·ÛıÂÓ›˜ Ì ۯÂÙÈο ηÏfi ∫∂ Î·È Ê˘ÛÈÔÏÔÁÈ΋ Ë ˘„ËÏ‹ ¯ÔÏËÛÙÂÚfiÏË. ∏ ÌÂϤÙË 4S Ì ÙËÓ ÛÈÌ‚·ÛÙ·Ù›ÓË, ·Ó Î·È Û ÌÂÙ·Ó¿Ï˘ÛË, ¤‰ÂÈÍ ̛· ÛËÌ·ÓÙÈ΋ Ì›ˆÛË Ù˘ ·Ó¿Ù˘Í˘ ∫∞ Û ¿ÙÔÌ· Ì ۯÂÙÈο ηÏfi ∫∂ ηٿ ÙËÓ Â›ÛÔ‰Ô ÛÙË ÌÂϤÙË, Û ۯ¤ÛË Ì ÙÔ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ. 8
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·ıËÚÔÛÎÏ‹ÚˆÛË ™E¶TEMBPπ√™ 2004
2. ∫·ı˘ÛÙ¤ÚËÛË Ù˘ ÂͤÏÈ͢ Ù˘ Ã∫∞. ™ÙËÓ ÌÂϤÙË 4S 8 Ô Î›Ó‰˘ÓÔ˜ ı·Ó¿ÙÔ˘ ·ÛıÂÓÒÓ ÔÈ ÔÔ›ÔÈ ·Ó¤Ù˘Í·Ó Ã∫∞ ‹Ù·Ó 25,5% ÛÙËÓ ÔÌ¿‰· Ù˘ ÛÈÌ‚·ÛÙ·Ù›Ó˘ Î·È 31,9% ÛÙËÓ ÙÔ˘ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘. ∂ÈϤÔÓ Û ̛· ÌÈÎÚ‹ ÌÂϤÙË ·ÛıÂÓÒÓ ÌÂÙ¿ ∂ª 31 ÔÈ ·ÛıÂÓ›˜ Ì ∫∂ < 40% ·ÚÔ˘Û›·Û·Ó ‚ÂÏÙ›ˆÛË ÌÂÙ¿ 12 ‚‰ÔÌ¿‰Â˜ ıÂڷ›·˜ Ì ÛÈÌ‚·ÛÙ·Ù›ÓË. µ¤‚·È· ÙÔ ÌÂÁ¿ÏÔ ÂÚÒÙËÌ· Ô˘ ·Ó·Î‡ÙÂÈ Â›Ó·È, Â¿Ó ÔÈ ·ÛıÂÓ›˜ Ì Ã∫∞ ¤¯Ô˘Ó ÙÈ̤˜ ¯ÔÏËÛÙÂÚfiÏ˘ Ï¿ÛÌ·ÙÔ˜, Ô˘ Ó· ‰ÈηÈÔÏÔÁÂ›Ù·È Ë ıÂڷ›· Ì ÛÙ·Ù›Ó˜, ‰ÈfiÙÈ ˘¿Ú¯ÂÈ
¤ÓÙÔÓË ·ÌÊÈÛ‚‹ÙËÛË ÁÈ· ÙËÓ ‰Ú¿ÛË ÙˆÓ ÛÙ·ÙÈÓÒÓ Û Ôχ ¯·ÌËϤ˜ ÙÈ̤˜ ¯ÔÏËÛÙÂÚfiÏ˘. ™‹ÌÂÚ· Â›Ó·È ÁÓˆÛÙfi fiÙÈ ·ÛıÂÓ›˜ Ì Ã∫∞ ¤¯Ô˘Ó ¯·ÌËÏfiÙÂÚË ÔÏÈ΋ ¯ÔÏËÛÙÂÚfiÏË ·fi ÙÔ˘ ÛÙÂÊ·ÓÈ·›Ô˘˜ ¯ˆÚ›˜ Ã∫∞. Œ¯ÂÈ ‰Âȯı› Ì›· ¿ÌÂÛË Û¯¤ÛË ÌÂٷ͇ ¯ÔÏËÛÙÂÚfiÏ˘ Ï¿ÛÌ·ÙÔ˜ Î·È ÚÔÁÓÒÛˆ˜.32 ŒÙÛÈ Â¿Ó Î¿ÔÈÔ˜ ‰Â¯ı› fiÙÈ ÙÔ ÌÂÁ·Ï‡ÙÂÚÔ fiÊÂÏÔ˜ ·fi ÙȘ ÛÙ·Ù›Ó˜ ·ÚÔ˘ÛÈ¿˙ÂÙ·È Û ·ÛıÂÓ›˜ Ì ÙȘ ˘„ËÏfiÙÂÚ˜ ·Ú¯ÈΤ˜ ÙÈ̤˜ LDL Ë Ì ÙËÓ ÌÂÁ·Ï‡ÙÂÚË ÙÒÛË, ÙfiÙ ‰ÂÓ ¤¯Ô˘Ó Ó· ÎÂÚ‰›ÛÔ˘Ó ÔÏÏ¿ ·fi ÙȘ ÛÙ·Ù›Ó˜ ¿ÙÔÌ· Ì Ã∫∞ Î·È Ì¿ÏÈÛÙ· ȉȷ›ÙÂÚ· ÚÔ¯ˆÚË̤ÓË. ∞ÓÙ›ıÂÙ·
Â¿Ó ÙÔ fiÊÂÏÔ˜ Â›Ó·È ·ÔÙ¤ÏÂÛÌ· ÙˆÓ ÏÂÈÔÙÚÔÈÎÒÓ ‰Ú¿ÛÂˆÓ ·˘ÙÒÓ Î·È fi¯È Ù˘ ‰Ú¿Û˘ ÛÙ· ÏÈ›‰È·, ÙfiÙÂ Ë ÙÈÌ‹ Ù˘ ·Ú¯È΋˜ ¯ÔÏËÛÙÂÚfiÏ˘ ‰ÂÓ Â›Ó·È ÙfiÛÔ ÎÚÈÙÈ΋ ÁÈ· ÙËÓ ‰Ú¿ÛË ÙˆÓ ÛÙËÓ ÂͤÏÈÍË Ù˘ Ã∫∞.
low-density lipoprotein cholesterol ≥ 125 mg/dl treated with statins versus no lipidlowering drug. Am J Cardiol 2002;90: 147-149. Horwich TB, Hamilton MA, Maclellan WR, Fonarow GC. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure. J Card Fail 2002;8(4):216-224. Van Lenten BJ, Fogelman AM, Haberland ME Edwards PA: The role of lipoproteins and receptor-mediated endocytosis in the transport of bacterial lipopolysaccharide. Proc Natl Acad Sci U S A 1986; 83:2704-2708. Netea MG, Demacker PNM, Kullberg BJ, Boerman OC, Verschueren I, Stalenhoef AFH, van der Meer JWM: Low density lipoprotein receptor-deficient mice are protected against lethal endotoxemia and severe gram-negative infections. J Clin Invest 1996;97:1366-1372. Feldman AM, Combes A, Wagner D, Kadakomi T, Kubota T, Li YY, McTiernan C: The role of tumor necrosis factor in the pathophysiology of heart failure. J Am Coll Cardiol 2000;35:537-544. Bauersachs J, Gallupo P, Fraccarollo D, Christ M, Ertl G: Improvement of left ventricular remodeling and function by hydroxymethosglutaryl coenzyme A reductase inhibition with cerivastatin in rats with heart failure after myocardial infraction. Circulation 2001:104:982-985. Sachs FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infraction in patients with average cholesterol levels: Cholesterol and recurrent events trial investigators. N Engl J Med 1996;335: 1001-9. Krum H, McMurray JJ. Statins and chronic heart failure: Do we need a large-scale outcome trial? J Am Coll Cardiol 2002; 39(10):1567-1573. Van Boven AJ, Jukema JW, Zwinderman AH, Crijns HJ, Lie KI, Bruschke AV. Reduction of transient myocardial ischemia with pravastatin in addition to the conventional treatment in patients with angina pectoris. Circulation 1996;94:1503-5. Rahimtoola SH. From coronary artery disease to heart failure: role of the hibernating myocardium. Am J Cardiol 1995;75: 16E-22E. Lars Bastiaanse EM, Atsma DE, Kuijpers MMC, et al. The effect of sarcolemmal cholesterol content on intracellular cal-
cium ion concentration in cultured cardiomyocytes. Arch Biochem Biophys 1994;313:58-63. Kureishi Y, Luo Z, Shoijima I, et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med 2000;6; 1004-10. Strehlow K, Wassmann S, Bohm M, Nickenig G. Angiotensin AT1 receptor overexpression in hypercholesterolaemia. Ann Med 2000;32:386-9. Floras JS. Clinical aspects of sympathetic activation and parasympathetic withdrawal in heart failure. J Am Coll Cardiol 1993;4 Suppl A:72A-84A. Pehlivanidis AN, Athyros VG, Demitriadis DS, Papageorgiou AA, Bouloukos VJ, Kontopoulos AG. Heart rate variability after long-term treatment with atorvastatin in hypercholesterolemic patients with or without coronary artery disease. Atherosclerosis 2001;157:463-9. Pliquet RU, Cornish KG, Peuler JD, Zucker IH. Simvastatin normalizes autonomic control in experimental heart failure. Circulation 2003;107:2493-2498. Von Haeling S, Anker SD, Bassenge E. Statins and the role of nitric oxide in chronic heart failure. Heart Failure Reviews 2003;8:99-106. Torre-Armione G, Bozkurt B, Deswal A, Mann DL. An overview of tumor necrosis factor alpha and the failing human heart. Curr Opin Cardiol 1999;14:206-10. Rosnenson RS, Tangney CC, Casey LC. Inhibition of proinflammatory cytocine production by pravastatin. Lancet 1999; 353:983-4. Hayashidani S, Tsutsui H, Shiomi T, et al. Fluvastatin a 3-hydroxy-3methylglutaryl coenzyme a reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infraction. Circulation 2002;105:868-73. De Lorgeril M, Salen P, Bontemps L, Belichard P, Geyssant A, Itti R. Effects of lipid-lowering drugs on left ventricular function and exercise tolerance in dyslipidemic coronary patients. J Cardiovasc Pharmacol 1999;33:473-8. Vredevoe DL, Woo MA, Doering LV, Brecht ML, Hamilton MA, Fonarow GC. Skin test anergy in advanced heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 1998;82:323-8.
∆ÂÏÂÈÒÓÔÓÙ·˜ Ú¤ÂÈ Ó· ÙÔÓÈÛı› fiÙÈ ·Ú fiÏÔ Ô˘ ÂÏÏÂ›Ô˘Ó ÌÂÁ¿Ï˜ ÌÂϤÙ˜ Ô˘ ı· ··ÓÙÔ‡Û·Ó ¤Ú·Ó οı ·ÌÊÈ‚ÔÏ›·˜ ÛÙÔ Â¿Ó ÔÈ ÛÙ·Ù›Ó˜ ¤¯Ô˘Ó ı¤ÛË ÛÙËÓ ıÂڷ›· Ù˘ Ã∫∞, Û‹ÌÂÚ· ¤¯Ô˘Ì ϛÁ· ‚¤‚·È· ÛÙÔȯ›·, Ù· ÔÔ›· fï˜ ˘·ÈÓ›ÛÛÔÓÙ·È ÙËÓ Â˘ÂÚÁÂÙÈ΋ ‰Ú¿ÛË ÙˆÓ ÛÙ·ÙÈÓÒÓ ÛÙËÓ ·ıÔÏÔÁÈ΋ ·˘Ù‹ ηٿÛÙ·ÛË.
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Pekkanen J, Linn S, Heiss G, Suchindram CM, Leon A, Rifkind BM, Tyroler HA: Ten-year mortality from cardiovas cular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease. N Eng J Med 1990;322: 1700-1707 Kannel WB, Belanger AJ.Epidemiology of heart failure. Am Heart J 1991;121: 951-7 Hoffman RM, Psaty BM, Kronmal RA: Modifiable risk factors for incident heart failure in the coronary artery surgery study. Arch Intern Med 1994; 154:417-423 Wilhelmsen L, Rosengren A, Eriksson H, Lappas G: Heart failure in the general population of men-morbidity ,risk factors and prognosis. J Inter Mad 2001;249: 253-61 Couglin SS, Neaton JD, Sengupta A, Kuller LH: Predictors of mortality from idiopathic dilated cardiomyopathy in 356222 men screened for the multiple risk factor intervention trial. Am J Epidemiol 1994;139:166-172 Yusuf S, Pepine CJ, Garces C, et al. Effect of enalapril on myocardial infarction and unstable angina in patients with low ejection fractions. Lancet 1992; 340:1173-8 Scandinavian Simvastatin Survival Study Investigators. Randomized trial of cholesterol in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344:1383-9 Kjekshus J, Pedersen TR, Olsson AG, Faergeman O, Pyorala K. The effects of simvastatin on the incidence of heart failty in patients with conarary heart disease. J Card Fail 1997;3:249-54 Aronow WS, Ahn C, Kronzon I. Comparison of incidences of congestive heart failure in older African-Americans, Hispanics, and whites. Am J Cardiol 1999;84: 611-612. Lewis SJ, Moye LA, Sacks FM, Johnstone DE, Timmis G, Mitchell J, Limacher M, Kell S, Glasser SP, Grant J, et al, for the CARE Investigators. Effect of pravastatin on cardiovascular events in older patients with myocardial infraction and cholesterol levels in the average range. Results of the Cholesterol and Recurrent Events (CARE) trial. Ann Intern Med 1998;129:681-689. Aronow WS, Ahn C. Frequency of congestive heart failure in older persons with prior myocardial infraction and serum
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∞‰ÈÔÓÂÎÙ›ÓË: ÕÏÏË Ì›· ÔÚÌfiÓË ÙÔ˘ ÏÈÒ‰Ô˘˜ ÈÛÙÔ‡; ∂ÈÚ‹ÓË °·˙‹: ∂ÈÛÙËÌÔÓÈÎfi˜ ™˘ÓÂÚÁ¿Ù˘ ÙÔ˘ π·ÙÚ›Ԣ §Èȉ›ˆÓ ªˆ˘Û‹˜ ∂ÏÈÛ¿Ê: ∫·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜
∏ ·ıËڈ̷ÙÈ΋ ÓfiÛÔ˜ ·ÔÙÂÏ› ÙËÓ Î‡ÚÈ· ·ÈÙ›· ıÓËÛÈÌfiÙËÙ·˜ ÛÙȘ ·Ó·Ù˘Á̤Ó˜ ¯ÒÚ˜ [1]. ¶ÔÏϤ˜ ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ Ú·ÁÌ·ÙÔÔÈ‹ıËÎ·Ó Ù· ÙÂÏÂ˘Ù·›· ¤ÙË Ì ÛÎÔfi ÙË ‰ÈÂÚ‡ÓËÛË ÙˆÓ Èı·ÓÒÓ ·Ú·ÁfiÓÙˆÓ ÎÈÓ‰‡ÓÔ˘ Ô˘ ÂÌϤÎÔÓÙ·È ÛÙËÓ ·ıÔÁ¤ÓÂÈ· Ù˘ ηډȷÁÁÂȷ΋˜ ÓfiÛÔ˘. ¶ÚfiÛÊ·Ù· ‰È·ÈÛÙÒıËΠfiÙÈ Ô ÏÈ҉˘ ÈÛÙfi˜ ‰ÂÓ ·ÔÙÂÏ› ·Ï¿ Ì›· ·Ôı‹ÎË Ï›Ô˘˜, ·ÏÏ¿ fiÙÈ Â›Ó·È ¤Ó· ÂÓ‰ÔÎÚÈÓ¤˜ fiÚÁ·ÓÔ Ô˘ ·Ú¿ÁÂÈ Ì›· ÛÂÈÚ¿ ·fi ‚ÈÔÏÔÁÈο ‰Ú·ÛÙÈΤ˜ ÚˆÙ½Ó˜, ÔÈ Ôԛ˜ Û˘ÓÔÏÈο ÔÓÔÌ¿˙ÔÓÙ·È ·‰ÈÔ΢ÙÔΛÓ˜ [2]. ™ÙȘ ·‰ÈÔ΢ÙÔΛÓ˜ Û˘ÌÂÚÈÏ·Ì‚¿ÓÔÓÙ·È Ë ÏÂÙ›ÓË, Ô ·Ú¿ÁÔÓÙ·˜ Ó¤ÎÚˆÛ˘ fiÁΈÓ-· (tumor necrosis factor-·, TNF-·), Ô ·Ó·ÛÙÔϤ·˜ ÂÓÂÚÁÔÔ›ËÛ˘ ÙÔ˘ Ï·ÛÌÈÓÔÁfiÓÔ˘ Ù‡Ô˘ 1 (plasminogen-activator inhibitor type 1, PAI-1), Ë ÈÓÙÂÚÏ¢ΛÓË 6 (interleukin 6, IL-6), Ë ·‰È„›ÓË, Ë ÚÂ˙ÈÛÙ›ÓË Î·È Ë ·‰ÈÔÓÂÎÙ›ÓË [2, 3]. ∏ ·‰ÈÔÓÂÎÙ›ÓË ·Ú¿ÁÂÙ·È ·ÔÎÏÂÈÛÙÈο ·fi ÙÔ ÏÈÒ‰Ë ÈÛÙfi Î·È ·ÂÏ¢ıÂÚÒÓÂÙ·È ÛÙË Û˘ÛÙËÌ·ÙÈ΋ ΢ÎÏÔÊÔÚ›·, fiÔ˘ ·Ó¢ڛÛÎÂÙ·È Û ˘„ËÏ¿ ›‰· (5-10 Ìg/ ml) Î·È ·ÔÙÂÏ› ÙÔ 0.01% fiÏˆÓ ÙˆÓ ÚˆÙÂ˚ÓÒÓ ÙÔ˘ Ï¿ÛÌ·ÙÔ˜ [3, 4]. TÔ ÁÔÓ›‰ÈÔ Ô˘ Έ‰ÈÎÔÔÈ› ÙËÓ ¤ÎÊÚ·ÛË Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ ‚Ú›ÛÎÂÙ·È ÛÙÔ ¯ÚˆÌfiۈ̷ 3q27, ÛÙÔ ÔÔ›Ô ÂÓÙÔ›˙ÂÙ·È Â›Û˘ Î·È ÙÔ ÁÔÓ›‰ÈÔ Ô˘ Û˘Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ÂÌÊ¿ÓÈÛË ÙÔ˘ ÌÂÙ·‚ÔÏÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘ Î·È ÙÔ˘ ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË Ù‡Ô˘ 2 [6, 7]. ∏ Û‡ÓıÂÛË Î·È Ë ¤ÎÎÚÈÛË Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ ·fi Ù· ÏÈÔ·ÙÙ·Ú· Ú˘ıÌ›˙ÂÙ·È
Ì ‰È¿ÊÔÚÔ˘˜ ÙÚfiÔ˘˜. °È· ·Ú¿‰ÂÈÁÌ·, Ô ·Ú¿ÁÔÓÙ·˜ ·‡ÍËÛ˘ Ô˘ ÌÔÈ¿˙ÂÈ Ì ÙËÓ ÈÓÛÔ˘Ï›ÓË (insulin-like growth factor-1, IGF-1) ·˘Í¿ÓÂÈ ÙË Û‡ÓıÂÛË Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘, Û ·ÓÙ›ıÂÛË Ì ÙÔÓ TNF-·, Ù· ÁÏ˘ÎÔÎÔÚÙÈÎÔÂȉ‹ Î·È ÙÔ˘˜ ‚-·‰ÚÂÓÂÚÁÈÎÔ‡˜ ·ÁˆÓÈÛÙ¤˜ Ô˘ ·Ó·ÛÙ¤ÏÏÔ˘Ó ÙË Û‡ÓıÂÛ‹ Ù˘ [3, 8]. ∆¤ÏÔ˜ Ë ÈÓÛÔ˘Ï›ÓË ÂËÚ¿˙ÂÈ ÙË Û‡ÓıÂÛË Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘. øÛÙfiÛÔ, ÔÚÈṲ̂Ó˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ Ë ÈÓÛÔ˘Ï›ÓË ÚÔ¿ÁÂÈ ÙË Û‡ÓıÂÛË Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘, ÂÓÒ ¿ÏϘ ÌÂϤÙ˜ ‰È·Ù‡ˆÛ·Ó ÙËÓ ¿Ô„Ë fiÙÈ Ë ÈÓÛÔ˘Ï›ÓË ·Ó·ÛÙ¤ÏÏÂÈ ÙË Û‡ÓıÂÛ‹ Ù˘ [9, 10].
ªÂÙ·‚ÔÏÈΤ˜ ‰Ú¿ÛÂȘ Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ Ÿˆ˜ Â›Ó·È ÁÓˆÛÙfi, Ë ‰È·‰Èηۛ· Ù˘ ·ıËÚÔÛÎÏ‹ÚˆÛ˘ ÂÚÈÏ·Ì‚¿ÓÂÈ 3 ÛÙ¿‰È·: ÚÔÛÎfiÏÏËÛË ÙˆÓ ÌÔÓÔ΢ÙÙ¿ÚˆÓ ÛÙ· ÂÓ‰ÔıËÏȷο ·ÙÙ·Ú·, Ê·ÁÔ·ÙÙˆÛË Ù˘ ÔÍÂȉˆÌ¤Ó˘ LDL ·fi Ù· Ì·ÎÚÔÊ¿Á· Î·È ÔÏÏ·Ï·ÛÈ·ÛÌfi˜ ÙˆÓ Ï›ˆÓ Ì˘ÈÎÒÓ Î˘ÙÙ¿ÚˆÓ ÙÔ˘ ·ÁÁÂÈ·ÎÔ‡ ÙÔȯÒÌ·ÙÔ˜ [4]. ∏ ·‰ÈÔÓÂÎÙ›ÓË Ê·›ÓÂÙ·È fiÙÈ ‰È·‰Ú·Ì·Ù›˙ÂÈ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ·Ó·ÛÙÔÏ‹ ÙˆÓ ·Ú·¿Óˆ Ê·ÈÓÔ̤ӈÓ. ∏ ·‰ÈÔÓÂÎÙ›ÓË ÛÂ Ê˘ÛÈÔÏÔÁÈο ›‰· ÛÙÔ Ï¿ÛÌ· ·Ó·ÛÙ¤ÏÏÂÈ ÙËÓ ¤ÎÊÚ·ÛË ÙˆÓ ÌÔÚ›ˆÓ ÚÔÛÎfiÏÏËÛ˘ (intracellular adhesion molecule-1, ICAM-1; vascular cellular adhesion molecule-1, VCAM-1; E-selectin), ηıÒ˜ Î·È ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ ˘ÚËÓÈÎÔ‡ ·Ú¿ÁÔÓÙ· ε (nuclear factor ε, NFε)
Î·È ¤ÙÛÈ ÂÌÔ‰›˙ÂÈ ÙËÓ ÚÔÛÎfiÏÏËÛË ÙˆÓ ÌÔÓÔ΢ÙÙ¿ÚˆÓ ÛÙ· ÂÓ‰ÔıËÏȷο ·ÙÙ·Ú· ÙÔ˘ ·ÁÁÂÈ·ÎÔ‡ ÙÔȯÒÌ·ÙÔ˜ [4]. ∏ ‰Ú¿ÛË Ù˘ ·˘Ù‹ Èı·Ó¿ ÔÊ›ÏÂÙ·È ÛÙËÓ ÈηÓfiÙËÙ¿ Ù˘ Ó· ·Ó·ÛÙ¤ÏÏÂÈ ÙËÓ ·Ú·ÁˆÁ‹ Î·È ÙË ‰Ú·ÛÙÈÎfiÙËÙ· ÙÔ˘ TNF-·. ∂ÈϤÔÓ, Ë ·‰ÈÔÓÂÎÙ›ÓË ·Ó·ÛÙ¤ÏÏÂÈ ÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ scavenger receptor class A-1 (SR-A1) ÙˆÓ Ì·ÎÚÔÊ¿ÁˆÓ Ì ·ÔÙ¤ÏÂÛÌ· ÙË ÌÂȈ̤ÓË ÚfiÛÏË„Ë Ù˘ ÔÍÂȉˆÌ¤Ó˘ LDL ·fi Ù· Ì·ÎÚÔÊ¿Á· Î·È ÙËÓ ·Ó·ÛÙÔÏ‹ Ù˘ ‰ËÌÈÔ˘ÚÁ›·˜ ÙˆÓ ·ÊÚˆ‰ÒÓ Î˘ÙÙ¿ÚˆÓ, ÂÓÒ Â›Û˘ Ë ·‰ÈÔÓÂÎÙ›ÓË ·Ó·ÛÙ¤ÏÏÂÈ ÙÔÓ ÔÏÏ·Ï·ÛÈ·ÛÌfi ÙˆÓ Ï›ˆÓ Ì˘ÈÎÒÓ Î˘ÙÙ¿ÚˆÓ ÙÔ˘ ÙÔȯÒÌ·ÙÔ˜ ÙˆÓ ·ÁÁ›ˆÓ [4, 5] (¶›Ó·Î·˜). H ·‰ÈÔÓÂÎÙ›ÓË ÚÔηÏ› Ì›ˆÛË ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ ÏÈ·ÚÒÓ ÔͤˆÓ ÛÙÔ Ï¿ÛÌ·, ηıÒ˜ Î·È Ì›ˆÛË ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÛÙÔ ‹·Ú Î·È ÛÙÔ˘˜ ÛÎÂÏÂÙÈÎÔ‡˜ ̇˜, Ì ·ÔÙ¤ÏÂÛÌ· ÙË ‚ÂÏÙ›ˆÛË Ù˘ ¢·ÈÛıËÛ›·˜ ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ÈÛÙÒÓ ÛÙË ‰Ú¿ÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘ [11, 12]. ∏ ·‡ÍËÛË Ù˘ ¢·ÈÛıËÛ›·˜ ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ÈÛÙÒÓ ÛÙË ‰Ú¿ÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘ ¢ԉÒÓÂÙ·È Â›Û˘ ·fi ÙËÓ ÈηÓfiÙËÙ· Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ Ó· ·Ó·ÛÙ¤ÏÏÂÈ ÙË ÁÏ˘ÎÔÓÂÔÁ¤ÓÂÛË ÛÙÔ ‹·Ú Î·È ÙË ‰Ú¿ÛË ÙÔ˘ TNF-· ÛÙÔ ÏÈÒ‰Ë ÈÛÙfi [3].
∫ÏÈÓÈ΋ ÛËÌ·Û›· Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ ¶·ıÔÏÔÁÈΤ˜ ηٷÛÙ¿ÛÂȘ Ô˘ Û˘Óԉ‡ÔÓÙ·È ·fi ˘„ËÏ¿ ›‰· ·‰ÈÔÓÂÎÙ›Ó˘ ÛÙÔ Ï¿ÛÌ· Â›Ó·È Ë
¶π¡∞∫∞™ ª∂∆∞µ√§π∫∂™ ¢ƒ∞™∂π™ ∆H™ ∞¢π¶√¡∂∫∆π¡∏™ ñ ∞Ó·ÛÙÔÏ‹ Ù˘ ¤ÎÊÚ·Û˘ ÙˆÓ ÌÔÚ›ˆÓ ÚÔÛÎfiÏÏËÛ˘ (ICAM-1*, VCAM-1, E-selectin) ñ AÓ·ÛÙÔÏ‹ Ù˘ ÂÓÂÚÁÔÔ›ËÛ˘ ÙÔ˘ ¡FÎB ñ ∞Ó·ÛÙÔÏ‹ Ù˘ ¤ÎÊÚ·Û˘ ÙÔ˘ SR-A1 ÙˆÓ Ì·ÎÚÔÊ¿ÁˆÓ ñ ∞Ó·ÛÙÔÏ‹ ÙÔ˘ ÔÏÏ·Ï·ÛÈ·ÛÌÔ‡ ÙˆÓ Ï›ˆÓ Ì˘ÈÎÒÓ Î˘ÙÙ¿ÚˆÓ ÙÔ˘ ÙÔȯÒÌ·ÙÔ˜ ÙˆÓ ·ÁÁ›ˆÓ * ICAM-1: Intracellular adhesion molecule-1, VCAM-1: Vascular cellular adhesion molecule-1, NFÎB: Nuclear factor ε, SR-A1: Scavenger receptor class A-1
11
·ıËÚÔÛÎÏ‹ÚˆÛË ™E¶TEMBPπ√™ 2004
¯ÚfiÓÈ· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ·, Ô Û·Î¯·Ú҉˘ ‰È·‚‹Ù˘ Ù‡Ô˘ 1, ηıÒ˜ Î·È Ë Ó¢ÚÔÁÂÓ‹˜ ·ÓÔÚÂÍ›· [11]. ∞ÓÙ›ıÂÙ· ¯·ÌËÏ¿ ›‰· ·‰ÈÔÓÂÎÙ›Ó˘ ÛÙÔ Ï¿ÛÌ· ·Ú·ÙËÚÔ‡ÓÙ·È Û ·ıÔÏÔÁÈΤ˜ ηٷÛÙ¿ÛÂȘ Ô˘ Û˘Óԉ‡ÔÓÙ·È ·fi ·ÓÙ›ÛÙ·ÛË ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ÈÛÙÒÓ ÛÙË ‰Ú¿ÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘, fiˆ˜ Ë ·¯˘Û·ÚΛ·, ÙÔ ÌÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ Î·È Ô Û·Î¯·Ú҉˘ ‰È·‚‹Ù˘ Ù‡Ô˘ 2 [4, 11, 12, 13, 14]. ∂ÈÚfiÛıÂÙ·, Ë Û˘ÁΤÓÙÚˆÛË Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ Â›Ó·È È‰È·›ÙÂÚ· ¯·ÌËÏ‹ Û ·ÛıÂÓ›˜ Ì ÁÓˆÛÙ‹ ηډȷÁÁÂȷ΋ ÓfiÛÔ, ÂÓÒ ¿ÙÔÌ· Ì ˘Ô·‰ÈÔÓÂÎÙÈÓ·ÈÌ›· (< 4 Ìg/ml) ÂÌÊ·Ó›˙Ô˘Ó ‰ÈÏ¿ÛÈ· ›وÛË ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘, ·ÓÂÍ¿ÚÙËÙ· ·fi ÙËÓ ·ÚÔ˘Û›· ¿ÏÏˆÓ ÁÓˆÛÙÒÓ ·Ú·ÁfiÓÙˆÓ ÎÈÓ‰‡ÓÔ˘ [15, 16]. ¶ÔÏϤ˜ ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó ÙËÓ ‡·ÚÍË ·ÚÓËÙÈ΋˜ Û˘Û¯¤ÙÈÛ˘ ÌÂٷ͇ ÙˆÓ ÂȤ‰ˆÓ Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ Î·È Ù˘ Û˘ÁΤÓÙÚˆÛ˘ Ù˘ ÁÏ˘Îfi˙˘, Ù˘ ÈÓÛÔ˘Ï›Ó˘ Î·È ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÛÙÔ Ï¿ÛÌ·, ÂÓÒ ˘¿Ú¯ÂÈ ıÂÙÈ΋ Û˘Û¯¤ÙÈÛË ÙˆÓ ÂȤ‰ˆÓ Ù˘ Ì ÙË Û˘ÁΤÓÙÚˆÛË Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘ [6, 11, 15, 17]. ∂ÈϤÔÓ, Ë Û˘ÁΤÓÙÚˆÛË Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ ÛÙÔ Ï¿ÛÌ· ÂÌÊ·Ó›˙ÂÈ ·ÚÓËÙÈ΋ Û˘Û¯¤ÙÈÛË Ì ÙÔÓ ·ıËڈ̷ÙÈÎfi ‰Â›ÎÙË (ÔÏÈ΋ ¯ÔÏËÛÙÂÚfiÏË/ HDL ¯ÔÏËÛÙÂÚfiÏË) Î·È Ì ٷ ›‰· ÙˆÓ ·ÔÏÈÔÚˆÙÂ˚ÓÒÓ (apo) µ Î·È ∂ Î·È ıÂÙÈ΋ Û˘Û¯¤ÙÈÛË Ì ٷ ›‰· Ù˘ ·ÔÏÈÔÚˆÙ½Ó˘ ∞-1 Û ÌË ‰È·‚ËÙÈΤ˜ Á˘Ó·›Î˜ [17].
ÎÒÓ ÈÛÙÒÓ ÛÙË ‰Ú¿ÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘, ·ÓÂÍ¿ÚÙËÙ· ·fi ÙËÓ ËÏÈΛ·, ÙÔ Ê‡ÏÔ Î·È ÙÔ ‰Â›ÎÙË Ì¿˙·˜ ÛÒÌ·ÙÔ˜ (Body Mass Index, BMI) [14, 19, 20]. ¡ÂfiÙÂÚ· ‰Â‰Ô̤ӷ ˘ÔÛÙËÚ›˙Ô˘Ó ÙËÓ ¿Ô„Ë fiÙÈ Ë Û˘ÁΤÓÙÚˆÛË Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ ÛÙÔ Ï¿ÛÌ· ÚԉȷÁÚ¿ÊÂÈ Èı·Ó¤˜ ÌÂÏÏÔÓÙÈΤ˜ ÌÂÙ·‚ÔϤ˜ ÛÙÔ ‚·ıÌfi Ù˘ ¢·ÈÛıËÛ›·˜ ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ÈÛÙÒÓ ÛÙË ‰Ú¿ÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘, ÂÓÒ ˘„ËÏ¿ ›‰· Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ ÛÙÔ Ï¿ÛÌ· Û˘Û¯ÂÙ›˙ÔÓÙ·È Ì ÌÂȈ̤ÓÔ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË Ù‡Ô˘ 2 [21, 22] . ∂ÈϤÔÓ, Ë Û˘ÁΤÓÙÚˆÛË Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ Èı·Ó¿ ·ÔÙÂÏ› ¤Ó· ¯Ú‹ÛÈÌÔ ‰Â›ÎÙË Ô˘ ÌÔÚ› Ó· ÚԂϤ„ÂÈ Ì›· ˘ÔΛÌÂÓË ‰È·Ù·Ú·¯‹ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ ˘‰·Ù·ÓıÚ¿ÎˆÓ Û ¿ÙÔÌ· ÌÂ Ê˘ÛÈÔÏÔÁÈ΋ ‰ÔÎÈÌ·Û›· ·ÓÔ¯‹˜ ÁÏ˘Îfi˙˘, ÂÓÒ ·Ú·ÏÏ·Á¤˜ Ù˘ ¤ÎÊÚ·Û˘ ÙÔ˘ ˘Â‡ı˘ÓÔ˘ ÁÔÓȉ›Ô˘ Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ ÂËÚ¿˙Ô˘Ó ÙËÓ ÂÌÊ¿ÓÈÛË ˘ÂÚÁÏ˘Î·ÈÌ›·˜ ÛÙÔ Ì¤ÏÏÔÓ [7, 23]. ∏ Û˘Û¯¤ÙÈÛË ÌÂٷ͇ Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ Î·È Ù˘ ·ÓÙ›ÛÙ·Û˘ ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ÈÛÙÒÓ ÛÙË ‰Ú¿ÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘ ÂȂ‚·ÈÒÓÂÙ·È ·fi ÌÂϤÙ˜ Ô˘ ¤‰ÂÈÍ·Ó ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ ÛÙÔ Ï¿ÛÌ· ÌÂÙ¿ ÙË ¯ÔÚ‹ÁËÛË ÁÏÈÙ·˙ÔÓÒÓ, Ê·ÚÌ¿ÎˆÓ Ô˘ ¤¯Ô˘Ó ÙËÓ ÈηÓfiÙËÙ· Ó· ·˘Í¿ÓÔ˘Ó ÙËÓ Â˘·ÈÛıËÛ›· ÛÙËÓ ÈÓÛÔ˘Ï›ÓË ÙfiÛÔ Û ‰È·‚ËÙÈÎÔ‡˜ ·ÛıÂÓ›˜ fiÛÔ Î·È Û ˘ÁÈ›˜ Ì¿ÚÙ˘Ú˜ [2, 24, 25, 26, 27].
¶Ú¤ÂÈ Ó· ÛËÌÂȈı› fiÙÈ Ù· ›‰· Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ Â›Ó·È ¯·ÌËÏfiÙÂÚ· ÛÙÔ˘˜ ¿Ó‰Ú˜ Û ۇÁÎÚÈÛË Ì ÙȘ Á˘Ó·›Î˜ Î·È ·˘Ù‹ Ë ‰È·ÊÔÚ¿ Èı·Ó¿ ÔÊ›ÏÂÙ·È ÛÙËÓ Â›‰Ú·ÛË ÙˆÓ ·Ó‰ÚÔÁfiÓˆÓ [18].
∞‰ÈÔÓÂÎÙ›ÓË Î·È ·ÓÙ›ÛÙ·ÛË ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ÈÛÙÒÓ ÛÙË ‰Ú¿ÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘ Ÿˆ˜ ¤¯ÂÈ ‹‰Ë ·Ó·ÊÂÚı›, Ë Û˘ÁΤÓÙÚˆÛË Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ ÛÙÔ Ï¿ÛÌ· ÂÌÊ·Ó›˙ÂÈ ·ÚÓËÙÈ΋ Û˘Û¯¤ÙÈÛË Ì ٷ ›‰· Ù˘ ÈÓÛÔ˘Ï›Ó˘. ∂ÈϤÔÓ ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ Ù· ›‰· Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ Û˘Û¯ÂÙ›˙ÔÓÙ·È ·ÚÓËÙÈο Ì ÙÔ ‰Â›ÎÙË HOMA (Homeostasis Model Assessment), Ô˘ ·ÔÙÂÏ› ÙÔÓ ÈÔ ÚÔÛÈÙfi ÛÙËÓ ÎÏÈÓÈ΋ Ú¿ÍË ‰Â›ÎÙË Ù˘ ·ÓÙ›ÛÙ·Û˘ ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ÛÙË ‰Ú¿ÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘ Û ÌË ‰È·‚ËÙÈÎÔ‡˜ ·ÛıÂÓ›˜. ∆· ‰Â‰Ô̤ӷ ·˘Ù¿ ÂȂ‚·ÈÒÓÔ˘Ó Ù· ·ÔÙÂϤÛÌ·Ù· ·Ï·ÈÔÙ¤ÚˆÓ ÌÂÏÂÙÒÓ Ô˘ ¤‰ÂÈÍ·Ó ıÂÙÈ΋ Û˘Û¯¤ÙÈÛË ÌÂٷ͇ ÙˆÓ ÂȤ‰ˆÓ Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ ÛÙÔ Ï¿ÛÌ· Î·È Ù˘ ¢·ÈÛıËÛ›·˜ ÙˆÓ ÂÚÈÊÂÚÈ-
12
∞‰ÈÔÓÂÎÙ›ÓË Î·È ·¯˘Û·ÚΛ· Œ¯ÂÈ ‹‰Ë ·Ó·ÊÂÚı› fiÙÈ Ë ·¯˘Û·ÚΛ· Û˘Óԉ‡ÂÙ·È ·fi ¯·ÌËÏ¿ ›‰· ·‰ÈÔÓÂÎÙ›Ó˘ Ï¿ÛÌ·ÙÔ˜, ·Ó Î·È Ë ·‰ÈÔÓÂÎÙ›ÓË ·Ú¿ÁÂÙ·È ·ÔÎÏÂÈÛÙÈο ·fi ÙÔ ÏÈÒ‰Ë ÈÛÙfi [4, 28]. ™˘ÁÎÂÎÚÈ̤ӷ, Ù· ›‰· Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ Û˘Û¯ÂÙ›˙ÔÓÙ·È ·ÚÓËÙÈο Ì ÙËÓ ÎÂÓÙÚÈÎÔ‡ Ù‡Ô˘ ·¯˘Û·ÚΛ· Î·È Î˘Ú›ˆ˜ Ì ÙËÓ ÂÚÈ·ÁÁÂȷ΋ ·Ú¿ Ì ÙËÓ ˘Ô‰fiÚÈ· ÂÓ·fiıÂÛË Ï›Ô˘˜ [12, 29]. À¿Ú¯Ô˘Ó ·ÓÙÈÎÚÔ˘fiÌÂÓ· ‰Â‰Ô̤ӷ Û¯ÂÙÈο Ì ÙËÓ Â›‰Ú·ÛË Ù˘ ·ÒÏÂÈ·˜ ‚¿ÚÔ˘˜ ÛÙ· ›‰· Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ ÛÙÔ Ï¿ÛÌ·. √È ÂÚÈÛÛfiÙÂÚ˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘
·ÎfiÌË Î·È ÌÂÙ¿ ·fi ‹È· Ì›ˆÛË ÙÔ˘ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜ [30, 31, 32]. À¿Ú¯Ô˘Ó fï˜ ÌÂϤÙ˜ Ô˘ ‰ÂÓ ¤‰ÂÈÍ·Ó Î·Ì›· ÌÂÙ·‚ÔÏ‹ ÙˆÓ ÂȤ‰ˆÓ Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘, ÂÓÒ Ì›· ÌÂϤÙË ¤‰ÂÈÍ ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ Ù˘ ÌÂÙ¿ ·fi ·ÒÏÂÈ· ‚¿ÚÔ˘˜ ÌfiÓÔ Û ‰È·‚ËÙÈÎÔ‡˜ ·ÛıÂÓ›˜ [33, 34].
∞‰ÈÔÓÂÎÙ›ÓË Î·È ¿ÏÏÔÈ ÁÓˆÛÙÔ› ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË Î·Ú‰È·ÁÁÂȷ΋˜ ÓfiÛÔ˘ ÷ÌËÏ¿ ›‰· ·‰ÈÔÓÂÎÙ›Ó˘ ÛÙÔ Ï¿ÛÌ· Û˘Û¯ÂÙ›˙ÔÓÙ·È Ì ¯·ÌËÏ¿ ›‰· HDL ¯ÔÏËÛÙÂÚfiÏ˘ Î·È ˘„ËÏ¿ ›‰· ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ, ‰È·Ù·Ú·¯¤˜ Ô˘ Û˘¯Ó¿ ·Ú·ÙËÚÔ‡ÓÙ·È Û ·ÛıÂÓ›˜ Ì ÌÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ [2, 23, 35]. Œ¯ÂÈ ‰È·Ù˘ˆı› Ë ˘fiıÂÛË fiÙÈ Ë ˘Ô·‰ÈÔÓÂÎÙÈÓ·ÈÌ›· ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙË ‰˘ÛÏÈȉ·ÈÌ›· Èı·Ó¿ ÂÈÙ·¯‡ÓÂÈ ÙËÓ ÂͤÏÈÍË Ù˘ ·ıËڈ̷ÙÈ΋˜ ÓfiÛÔ˘ Û ·ÛıÂÓ›˜ Ì ÌÂÙ·‚ÔÏÈÎfi Û‡Ó‰ÚÔÌÔ [2, 35]. ∂ÈϤÔÓ, ¯·ÌËÏ¿ ›‰· ·‰ÈÔÓÂÎÙ›Ó˘ ·Ú·ÙËÚÔ‡ÓÙ·È Û ·ÛıÂÓ›˜ Ì ÔÚȷ΋ ·ÚÙËÚȷ΋ ˘¤ÚÙ·ÛË, ÙfiÛÔ Û˘ÛÙÔÏÈ΋ fiÛÔ Î·È ‰È·ÛÙÔÏÈ΋, ¤Ó· ÁÂÁÔÓfi˜ Ô˘ ÂÈÛËÌ·›ÓÂÈ fiÙÈ Ë ·‰ÈÔÓÂÎÙ›ÓË ÌÔÚ› Ó· ‰È·‰Ú·Ì·Ù›˙ÂÈ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ÂͤÏÈÍË Ù˘ ˘¤ÚÙ·Û˘ [36, 37]. Ÿˆ˜ Â›Ó·È ÁÓˆÛÙfi, Ë C ·ÓÙȉÚÒÛ· ÚˆÙ½ÓË (CRP) ·ÔÙÂÏ› ·ÍÈfiÈÛÙÔ ‰Â›ÎÙË ÊÏÂÁÌÔÓ‹˜ Î·È ·ÓÂÍ¿ÚÙËÙÔ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË Î·Ú‰È·ÁÁÂȷ΋˜ ÓfiÛÔ˘. ¶ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ ˘¿Ú¯ÂÈ ·ÓÙ›ÛÙÚÔÊË Û˘Û¯¤ÙÈÛË ÌÂٷ͇ ÙˆÓ ÂȤ‰ˆÓ Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ ÛÙÔ Ï¿ÛÌ· Î·È ÙˆÓ ÂȤ‰ˆÓ Ù˘ CRP, ηıÒ˜ Î·È ÌÂٷ͇ Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ Î·È Ù˘ ÈÓÙÂÚÏ¢ΛÓ˘ 6, ÂÓfi˜ ¿ÏÏÔ˘ ‰Â›ÎÙË ÊÏÂÁÌÔÓ‹˜ [38, 39]. ∆· ·Ú·¿Óˆ ‰Â‰Ô̤ӷ ÂÓÈÛ¯‡Ô˘Ó ÙËÓ ¿Ô„Ë fiÙÈ Ë ·‰ÈÔÓÂÎÙ›ÓË ‰È·ı¤ÙÂÈ ·ÓÙÈÊÏÂÁÌÔÓÒ‰ÂȘ ȉÈfiÙËÙ˜. ∏ ˘Ô·‰ÈÔÓÂÎÙÈÓ·ÈÌ›· Û˘Û¯ÂÙ›˙ÂÙ·È Â›Û˘ Ì ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÂÓ‰ÔıËÏ›Ô˘. ™˘ÁÎÂÎÚÈ̤ӷ ¤¯ÂÈ ‰È·ÈÛÙˆı› ‰È·Ù·Ú·¯‹ Ù˘ ÂÍ·ÚÙÒÌÂÓ˘ ·fi ÙÔ ÂÓ‰Ôı‹ÏÈÔ ·ÁÁÂÈԉȷÛÙÔÏ‹˜ Û ¿ÙÔÌ· Ì ¯·ÌËϤ˜ Û˘ÁÎÂÓÙÚÒÛÂȘ ·‰ÈÔÓÂÎÙ›Ó˘ ÛÙÔ Ï¿ÛÌ·, ·ÓÂÍ¿ÚÙËÙ· ·fi ÙËÓ ‡·ÚÍË ‹ fi¯È ·ÓÙ›ÛÙ·Û˘ ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ÈÛÙÒÓ ÛÙË ‰Ú¿ÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘ [40, 41, 42]. ¶Èı·Ó¿ ÛÙÔ Ì¤ÏÏÔÓ Ë Ì¤ÙÚËÛË ÙˆÓ ÂȤ‰ˆÓ Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ Ó· ·ÔÙÂÏ› ¤Ó· ¯Ú‹ÛÈÌÔ ‰Â›ÎÙË ÂÎÙ›ÌËÛ˘ Ù˘ ÂÓ‰ÔıËÏȷ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ [41]. ™˘ÌÂÚ¿ÛÌ·Ù· ∏ ·‰ÈÔÓÂÎÙ›ÓË Â›Ó·È Ì›· ‚·ÛÈ΋ ·‰ÈÔ΢ÙÔΛÓË Ô˘ ·Ú¿ÁÂÙ·È ·ÔÎÏÂÈ-
¶A£OºY™IO§O°IA ÛÙÈο ·fi ÙÔ ÏÈÒ‰Ë ÈÛÙfi Î·È ·ÓȯÓ‡ÂÙ·È ÛÙÔ Ï¿ÛÌ· Û ˘„ËÏ¿ ›‰·. ∏ ·‰ÈÔÓÂÎÙ›ÓË ÛÂ Ê˘ÛÈÔÏÔÁÈΤ˜ Û˘ÁÎÂÓÙÚÒÛÂȘ ÛÙÔ Ï¿ÛÌ· ¤¯ÂÈ ·ÓÙÈ·ıËڈ̷ÙÈΤ˜ Î·È ·ÓÙÈÊÏÂÁÌÔÓÒ‰ÂȘ ‰Ú¿ÛÂȘ. ∞ÛıÂÓ›˜ Ì ·ı‹-
ÛÂȘ Ô˘ Û˘Óԉ‡ÔÓÙ·È ·fi ˘Ô·‰ÈÔÓÂÎÙÈÓ·ÈÌ›· ÂÌÊ·Ó›˙Ô˘Ó ·˘ÍË̤ÓË Â›ÙˆÛË Î·Ú‰È·ÁÁÂȷ΋˜ ÓfiÛÔ˘. ªÂÏÏÔÓÙÈο Ë ·‰ÈÔÓÂÎÙ›ÓË ÌÔÚ› Ó· ·ÔÙÂϤÛÂÈ ¤Ó· ¯Ú‹ÛÈÌÔ Î·È Â˘·›ÛıËÙÔ ‰Â›ÎÙË ÚÒÈÌ˘ ·ıËڈ̷ÙÈ-
΋˜ ÓfiÛÔ˘. ∞·ÈÙÔ‡ÓÙ·È ÂÚÈÛÛfiÙÂÚ˜ ÌÂϤÙ˜ ÁÈ· Ó· ‰È·ÈÛÙˆı› Ë ÂӉ¯fiÌÂÓË ıÂڷ¢ÙÈ΋ ¯Ú‹ÛË Ù˘ ·‰ÈÔÓÂÎÙ›Ó˘ Û ·ÛıÂÓ›˜ Ì ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË Î·Ú‰È·ÁÁÂȷ΋˜ ÓfiÛÔ˘.
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·ıËÚÔÛÎÏ‹ÚˆÛË ™E¶TEMBPπ√™ 2004
°ÔÓ›‰È· Î·È ™ÙÂÊ·ÓÈ·›· ¡fiÛÔ˜ °ÂÓÔ‚¤Ê· ∫ÔÏÔ‚Ô‡, ∫·Ú‰ÈÔÏfiÁÔ˜ ÀԉȢı‡ÓÙÚÈ·, À‡ı˘ÓË §Èȉ·ÈÌÈÎÔ‡ π·ÙÚ›Ԣ ∫·ÙÂÚ›Ó· ∞Ó·ÁÓˆÛÙÔÔ‡ÏÔ˘, MSc, ªÔÚÈ·Îfi˜ µÈÔÏfiÁÔ˜ - °ÂÓÂÙÈÛÙ‹˜ øÓ¿ÛÂÈÔ ∫·Ú‰ÈÔ¯ÂÈÚÔ˘ÚÁÈÎfi ∫¤ÓÙÚÔ
∏ ·ıËڈ̿وÛË ÙˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ ·ÁÁ›ˆÓ Â›Ó·È Ë Û˘¯ÓfiÙÂÚË ·ÈÙ›· Ù˘ ÈÛ¯·ÈÌÈ΋˜ ηډÈÔ¿ıÂÈ·˜. √È ÛËÌÂÚÈÓ¤˜ ÌÂϤÙ˜ ÂÈÎÂÓÙÚÒÓÔÓÙ·È ÛÙËÓ ·ıËڈ̷ÙÈ΋ Ͽη Î·È ÙËÓ Î·Ù·ÔϤÌËÛ‹ Ù˘. ¶¿Óˆ ·fi 200 ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ¤¯Ô˘Ó ÂÚÈÁÚ·Ê›, Ô˘ Ô‰ËÁÔ‡Ó ÛÙÔÓ ÚfiˆÚÔ Û¯ËÌ·ÙÈÛÌfi Ù˘ ·ıËڈ̷ÙÈ΋˜ Ͽη˜. √È ÈÔ Î·Ï¿ ÌÂÏÂÙË̤ÓÔÈ ·Ú¿ÁÔÓÙ˜ ›ӷÈ: Ë ·˘ÍË̤ÓË Û˘ÁΤÓÙÚˆÛË ÛÙÔ Ï¿ÛÌ· Ù˘ ÔÏÈ΋˜ ¯ÔÏËÛÙÂÚfiÏ˘ Î·È Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ ¯·ÌËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙ½Ó˘, ÙÔ Î¿ÓÈÛÌ·, Ô Û·Î¯·Ú҉˘ ‰È·‚‹Ù˘, Ë ·ÚÙËÚȷ΋ ˘¤ÚÙ·ÛË, Ë ˘ÂÚÔÌÔ΢ÛÙÂ˚Ó·ÈÌ›· Î·È ¿ÏÏ·. √ ÚfiÏÔ˜ ÙˆÓ ÁÔÓȉ›ˆÓ ÛÙËÓ ÂÌÊ¿ÓÈÛË ÙˆÓ Î·Ú‰ÈÔ·ıÂÈÒÓ ‰ÂÓ ÌÔÚ› ϤÔÓ Ó· ·ÌÊÈÛ‚ËÙËı›. Œ¯Ô˘Ó ·Ó·ÁÓˆÚÈÛı› ·ÚÎÂÙ¤˜ ÁÔÓȉȷΤ˜ ÌÂÙ·ÏÏ¿ÍÂȘ Ô˘ Â›Ó·È ˘Â‡ı˘Ó˜ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ÚÒÈÌ˘ ·ıËڈ̿وÛ˘. √È ÈÔ ÁÓˆÛÙ¤˜ Â›Ó·È ÔÈ ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ ÁÔÓ›‰ÈÔ ÙÔ˘ LDL ˘Ô‰Ô¯¤·, Ô˘ ÚÔηÏÔ‡Ó ÙËÓ ÔÈÎÔÁÂÓ‹ ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌ›·. ∏ ·ÔÏÈÔÚˆÙ½ÓË µ (apoB) Â›Ó·È Ì›· ·fi ÙȘ ·ÔÏÈÔÚˆÙ½Ó˜ Ô˘ ·›˙Ô˘Ó ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙÔ ÌÂÙ·‚ÔÏÈÛÌfi ÙˆÓ ÏÈÔÚˆÙÂ˚ÓÒÓ. ∏ ÔÈÎÔÁÂÓ‹˜ ¤ÏÏÂÈ„Ë Ù˘ apoB–100 Â›Ó·È Ì›· ·˘ÙÔÛˆÌÈ΋ ÂÈÎÚ·ÙÔ‡ÌÂÓË ÎÏËÚÔÓÔÌÈ΋ ÓfiÛÔ˜. ∏ ÌÂÙ¿ÏÏ·ÍË ·˘Ù‹ ÚÔηÏ› ÌÂȈ̤ÓË ÚfiÛ‰ÂÛË Ù˘ LDL Ì ÙÔÓ LDL-˘Ô‰Ô¯¤· Î·È ÁÈ’·˘Ùfi ¤¯ÂÈ Û˘Û¯ÂÙÈÛÙ› Ì ˘ÂÚÏÈȉ·ÈÌ›· Î·È ÚÒÈÌË ·ÚÙËÚÈÔÛÎÏ‹ÚˆÛË. ∆· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ¤ÁÈÓ ÌÂÁ¿ÏË ÚfiÔ‰Ô˜ ÛÙËÓ ·Ó‡ÚÂÛË Ó¤ˆÓ ·Ú·ÁfiÓÙˆÓ ÎÈÓ‰‡ÓÔ˘ Ù˘ ·ıËÚÔÛÎÏ‹ÚˆÛ˘ Î·È ÛÙÔÓ ÔÚÈÛÌfi ÙÔ˘ ÚfiÏÔ˘ ÙˆÓ ·Ú·‰ÔÛÈ·ÎÒÓ ·Ú·ÁfiÓÙˆÓ ÎÈÓ‰‡ÓÔ˘. π‰È·ÈÙ¤Úˆ˜, ·˘ÙÒÓ Ô˘ Â›Ó·È Â˘¿ÏˆÙÔÈ ÛÙË ÁÔÓȉȷ΋ ›‰Ú·ÛË, fiˆ˜ Ë
›‰Ú·ÛË ÙÔ˘ ÔÏ˘ÌÔÚÊÈÛÌÔ‡ Ù˘ ·ÔÏÈÔÚˆÙ½Ó˘ ∂ (apo∂) ÛÙ· ηډȷÁÁÂȷο ÓÔÛ‹Ì·Ù·, ¤Ú· ·fi ÂΛӢ ÛÙ· ÏÈ›‰È·. ∏ apoE ÂÌÊ·Ó›˙ÂÙ·È ÛÙo Ï¿ÛÌ· Û ¤ÍÈ Î‡ÚȘ ÈÛoÌÔÚʤ˜, ÔÈ Ôԛ˜ Έ‰ÈÎÔÔÈÔ‡ÓÙ·È ·fi ÙÚ›· ·ÏÏËÏfiÌÔÚÊ· ÁÔÓ›‰È·: Â2, Â3 Î·È Â4 (Â2/2; Â3/3; Â4/4; Â2/3; Â3/4; Â2/4). √ ÔÏ˘ÌÔÚÊÈÛÌfi˜ ÙÔ˘ ÁÔÓȉ›Ô˘ Ù˘ apoE ÂÍËÁ› ·fi 4% ¤ˆ˜ 15% Ù˘ ·fiÎÏÈÛ˘ ÙˆÓ ÂȤ‰ˆÓ Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘ ¯·ÌËÏ‹˜ ˘ÎÓfiÙËÙ·˜ ÏÈÔÚˆÙ½Ó˘. √ Utermann Î·È Û˘ÓÂÚÁ¿Ù˜ ‹Ù·Ó ÔÈ ÚÒÙÔÈ Ô˘ ¤‰ÂÈÍ·Ó fiÙÈ ÔÈ ÈÛÔÌÔÚʤ˜ Ù˘ apoE ÂϤÁ¯ÔÓÙ·È ÁÔÓȉȷο Î·È ÂËÚ¿˙Ô˘Ó ÙÔÓ Î›Ó‰˘ÓÔ ÁÈ· ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ. ¶ÔÏϤ˜ ÌÂϤÙ˜ ¤¯Ô˘Ó Û˘Û¯ÂÙ›ÛÂÈ ÙËÓ ·ÚÔ˘Û›· ÙÔ˘ Â4 ·ÏÏËÏfiÌÔÚÊÔ˘ Ì ÌÂÁ·Ï‡ÙÂÚÔ Î›Ó‰˘ÓÔ ÁÈ· ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ. ÕÏϘ ¤Ú¢Ó˜, Û˘ÌÂÚÈÏ·Ì‚·ÓÔÌ¤ÓˆÓ Î·È ÙˆÓ ‰ÈÎÒÓ Ì·˜ ÌÂÏÂÙÒÓ, ‰ÂÓ ‚Ú‹Î·Ó Î·Ì›· Û˘Û¯¤ÙÈÛË. ª›· Ó¤· ÂÔ¯‹ ÛÙËÓ ¤Ú¢ӷ Ù˘ HDL (·Ú·‰ÔÛÈ·Îfi˜ ·Ú¿ÁÔÓÙ·˜ ÎÈÓ‰‡ÓÔ˘) ÍÂΛÓËÛ ·‰È·ÌÊÈÛ‚‹ÙËÙ· ÙÔ 1994 Ì ÙË ÎψÓÔÔ›ËÛË, ·fi ÙÔ˘˜ Luciani MF Î·È Û˘ÓÂÚÁ¿Ù˜, ÙÔ˘ ÁÔÓȉ›Ô˘ Ô˘ Έ‰ÈÎÔÔÈ› ÙËÓ ÚˆÙ½ÓË Ú‡ıÌÈÛ˘ Ù˘ ÂÎÚÔ‹˜ Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘. ∆Ô ÁÔÓ›‰ÈÔ ÔÓÔÌ¿˙ÂÙ·È Ô ATP-Û˘Ó‰ÂfiÌÂÓÔ˜ ÌÂÙ·ÊÔÚ¤·˜ ∞1 (ATP-binding cassette transporter A1 ‹ ABCA1). ªÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ ÁÔÓ›‰ÈÔ ABCA1 ·ÔÙÂÏÔ‡Ó ÙË ÁÂÓÂÙÈ΋ ‚¿ÛË Ù˘ ÓfiÛÔ˘ Ù˘ ∆·ÁÁ¤Ú˘. √È ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ ÁÔÓ›‰ÈÔ ÙÔ˘ ABCA1 Úԉȷı¤ÙÔ˘Ó Î·È Û¯ÂÙ›˙ÔÓÙ·È Ì ÙËÓ ÚÒÈÌË ·ıËÚÔÛÎÏ‹ÚˆÛË. ∆Ô ÁÔÓ›‰ÈÔ ÙÔ˘ ·ÁÁÂÈÔÙ·ÛÈÓÔÁfiÓÔ˘, (angiotensinogen, AGT), ·Ó‹ÎÂÈ ÛÙÔ Û‡ÛÙËÌ· ÚÂÓ›Ó˘-·ÁÁÂÈÔÙ·Û›Ó˘ ÙÔ ÔÔ›Ô Û˘Û¯ÂÙ›˙Â-
Ù·È Ì ÙË ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ Î·È ÙËÓ ˘¤ÚÙ·ÛË. ∆Ô ·ÁÁÂÈÔÙ·ÛÈÓÔÁfiÓÔ ·ÚÔ˘ÛÈ¿˙ÂÈ ‰‡Ô ‚·ÛÈÎÔ‡˜ ÔÏ˘ÌÔÚÊÈÛÌÔ‡˜, ª235∆ Î·È ∆174ª. √È Èı·ÓÔ› ÁÔÓfiÙ˘ÔÈ ÙÔ˘ ÔÏ˘ÌÔÚÊÈÛÌÔ‡ ›ӷÈ: ª/ª, ª/∆ ‹ ∆/∆. ™Â ¿ÙÔÌ· Ì ÁÔÓfiÙ˘Ô ∆/∆, ¤¯ÂÈ ‚ÚÂı› fiÙÈ Ô Î›Ó‰˘ÓÔ˜ ÁÈ· ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ Â›Ó·È 2.6 ÊÔÚ¤˜ ÌÂÁ·Ï‡ÙÂÚÔ˜ Û˘ÁÎÚÈÙÈο Ì ¿ÙÔÌ· ª/∆ ‹ ª/ª, ÂÓÒ, Ô Î›Ó‰˘ÓÔ˜ ÁÈ· ¤ÌÊÚ·ÁÌ· ÙÔ˘ Ì˘Ôηډ›Ô˘ ·˘Í¿ÓÂÙ·È Î·Ù¿ 3.4 ÊÔÚ¤˜. ∂›Û˘, Ô ÁÔÓfiÙ˘Ô˜ ∆/∆ ¤¯ÂÈ Û˘Û¯ÂÙÈÛÙ› Ì ·˘ÍË̤ӷ ›‰· ·ÁÁÂÈÔÙ·ÛÈÓÔÁfiÓÔ˘ ÛÙÔ Ï¿ÛÌ·, ÁÂÁÔÓfi˜ Ô˘ Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ˘ÂÚ‰Ú·ÛÙËÚÈÔÔ›ËÛË fiÏÔ˘ ÙÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜. √È ‰È·Ù·Ú·¯¤˜ ÛÙË Ê˘ÛÈÔÏÔÁÈ΋ ÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ Î·È ÙˆÓ ÂÓ‰ÔıËÏÈ·ÎÒÓ Î˘ÙÙ¿ÚˆÓ Û˘Ì‚¿ÏÏÔ˘Ó ÛÙËÓ ·Ó¿Ù˘ÍË Î·Ú‰È·ÁÁÂÈ·ÎÒÓ ÂÂÈÛÔ‰›ˆÓ. ∂ÓÂÚÁÔÔÈË̤ӷ ·ÈÌÔÂÙ¿ÏÈ· Î·È ÂÓ‰ÔıËÏȷο ·ÙÙ·Ú· ÂÎÊÚ¿˙Ô˘Ó ÛÙËÓ ÂÈÊ¿ÓÂÈ¿ ÙÔ˘˜ ÙȘ ƒ Î·È ∂-ÛÂÏÂÎÙ›Ó˜. ™˘ÁÎÂÎÚÈ̤ӷ, Ë ƒ-ÛÂÏÂÎÙ›ÓË ·Ú¿ÁÂÙ·È Î·È ÛÙ· ‰‡Ô ·Ú·¿Óˆ, ÂÓÒ Ë ∂-ÛÂÏÂÎÙ›ÓË ÌfiÓÔ ÛÙ· ÂÓ‰ÔıËÏȷο ·ÙÙ·Ú·. Œ¯ÂÈ ·Ú·ÙËÚËı› fiÙÈ Ë ¤ÎÊÚ·ÛË ÙˆÓ ƒ Î·È ∂-ÛÂÏÂÎÙÈÓÒÓ ·˘Í¿ÓÂÙ·È ÛÙËÓ ‡·ÚÍË ·ıËڈ̷ÙÈ΋˜ Ͽη˜ Î·È ·˘ÍË̤ӷ ›‰· ÙˆÓ ÌÔÚ›ˆÓ ÛÙÔ Ï¿ÛÌ· ¤¯Ô˘Ó ‚ÚÂı› Û ·ÛıÂÓ›˜ Ì ¤ÌÊÚ·ÁÌ· ÙÔ˘ Ì˘Ôηډ›Ô˘ Î·È ·ÛÙ·ı‹ ÛÙËı¿Á¯Ë. ∞ÚÎÂÙÔ› ÔÏ˘ÌÔÚÊÈÛÌÔ› ¤¯Ô˘Ó ·ÓȯÓ¢Ù› ÛÙ· ÁÔÓ›‰È· ÙˆÓ ƒ Î·È ∂-ÛÂÏÂÎÙÈÓÒÓ, ·ÏÏ¿ ·ÎfiÌ· Ô ·ÎÚÈ‚‹˜ ÙÔ˘˜ ÚfiÏÔ˜ ‰ÂÓ ¤¯ÂÈ ÚÔÛ‰ÈÔÚÈÛÙ›. ÃÚÂÈ¿˙ÔÓÙ·È Î·È ¿ÏϘ ÌÂϤÙ˜ Ô˘ ı· ÂÚÈÏ·Ì‚¿ÓÔ˘Ó fiÏ· fiÛ· ¤¯Ô˘Ó ·Ó·ÊÂÚı›, fiˆ˜ ›Û˘ Î·È ÙËÓ ·ÏÏËÏ›‰Ú·ÛË Î·È Ì ¿ÏÏ· ÁÔÓ›‰È·.
µÈ‚ÏÈÔÁÚ·Ê›· 1.
2.
14
Wilson PW. Established risk factors and coronary artery disease: the Framingham Study. Am J Hypertens 1994;7:7S-12S. Navab M, Berliner JA, Watson AD, Hama
SY, Territo MC, Lusis AJ, Shih DM, Van Lenten BJ, Frank JS, Demer LL, Edwards PA, Fogelman AM. The Yin and Yang of oxidation in the development of the fatty
streak. A review based on the 1994 George Lyman Duff Memorial Lecture. Arterioscler Thromb Vasc Biol. 1996; 16:831-842.
·ıËÚÔÛÎÏ‹ÚˆÛË
BA™IKH EPEYNA
™E¶TEMBPπ√™ 2004
∏ ›‰Ú·ÛË Ù˘ Û˘Á¯ÔÚ‹ÁËÛ˘ ·ÏÎÔfiÏ Î·È ÁÂÌÊÈÌÚÔ˙›Ï˘ Û ·ÚÔ˘Ú·›Ô˘˜ (wistar rats) °. KoÏÔ‚Ô‡, ¢. Mȯ·ËÏ›‰Ë˜, N. K·Ê·ÏÙ‹˜, E. A‰·ÌÔÔ‡ÏÔ˘, E. °È·˙ÈÙ˙fiÁÏÔ˘, A. ÷Ù˙¿ÎË, N. ¶ÈÏ¿Ù˘, A. M·ÚÁ¤ÏË, K. ™·Ï¤·, M. M˘ÎÔÓÈ¿Ù˘, ¢. ∫fiÎÎÈÓÔ˜ In vivo, 2004;18:49-54. ∏ ηٷӿψÛË ·ÏÎÔfiÏ (Alc) ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙË ¯ÔÚ‹ÁËÛË ÙÔ˘ ˘ÔÏÈȉ·ÈÌÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ ÁÂÌÊÈÌÚÔ˙›ÏË (Gem) ·Ú·ÙËÚÂ›Ù·È Ôχ Û˘¯Ó¿ Û ‰˘ÛÏÈȉ·ÈÌÈÎÔ‡˜ ·ÛıÂÓ›˜. ™ÎÔfi˜ Ù˘ ÂÚÁ·Û›·˜ ‹Ù·Ó Ë ÌÂϤÙË ÙˆÓ ÂÈÙÒÛÂˆÓ ÙÔ˘ Û˘Ó‰˘·ÛÌÔ‡ ·˘ÙÔ‡ Û ·ÚÔ˘Ú·›Ô˘˜, ‰Â‰Ô̤ÓÔ˘ fiÙÈ ÙÔ ·ÏÎÔfiÏ Î·È Ë ÁÂÌÊÈÌÚÔ˙›ÏË Â›Ó·È Ô˘Û›Â˜ Ô˘ ÌÔÚÔ‡Ó Ó· ‰È·Ù·Ú¿ÍÔ˘Ó ÙËÓ Ë·ÙÈ΋ ÏÂÈÙÔ˘ÚÁ›·.
‰· ÂϤÁ¯Ô˘ ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó 13 ·ÎfiÌ· ·ÚÛÂÓÈÎÔ› ·ÚÔ˘Ú·›ÔÈ. ªÂÙ¿ ·fi 8 ‚‰ÔÌ¿‰Â˜, ÌÂÙÚ‹ıËÎ·Ó Ù· ›‰· Ù˘ ·ÌÈÓÔÙÚ·ÓÛÊÂÚ¿Û˘ Ù˘ ·Ï·Ó›Ó˘ (ALT), Ù˘ ·ÌÈÓÔÙÚ·ÓÛÊÂÚ¿Û˘ ÙÔ˘ ·Û·ÚÙÈÎÔ‡ ÔͤԘ (AST), Ù˘ ·ÏηÏÈ΋˜ ʈÛÊ·Ù¿Û˘ (AP), Ù˘ ÔÏÈ΋˜ ¯ÔÏËÛÙÂÚfiÏ˘ (TC) Î·È ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ (TG) ÛÙÔ ·›Ì· Î·È ·ÍÈÔÏÔÁ‹ıËηÓ, ÈÛÙÔÏÔÁÈο, ‰Â›ÁÌ·Ù· ‹·ÙÔ˜ fiÏˆÓ ÙˆÓ ÂÈÚ·Ì·Ùfi˙ˆˆÓ.
°È· ÙÔ ÛÎÔfi ·˘Ùfi ·ÚÛÂÓÈÎÔ› ·ÚÔ˘Ú·›ÔÈ (n=40) ¯ˆÚ›ÛÙËÎ·Ó ÌÂ Ù˘¯·›Ô ÙÚfiÔ Û 4 ›Û˜ ÔÌ¿‰Â˜. ª¤Ûˆ ÂÓfi˜ ÛÙÔÌ·¯ÈÎÔ‡ ۈϋӷ, Ù· ÂÈÚ·Ì·Ùfi˙ˆ· ÂÏ¿Ì‚·Ó·Ó ηıËÌÂÚÈÓ¿: 1) 2 ml ÔÏ˘·Èı˘ÏÂÓÔÁÏ˘ÎfiÏ˘ (Peg), ÔÌ¿‰· Peg, 2) 2 ml Peg + 2 ml ‰È·Ï‡ÌÌ·ÙÔ˜ 25% v/v ηı·Ú‹˜ ·ÏÎÔfiÏ˘ Û ÓÂÚfi, ÔÌ¿‰· Alc+Peg, 3) 2 ml ‰È·Ï‡Ì·ÙÔ˜ Gem Û Peg (3.4 mg/100g ‚¿ÚÔ˘˜ ÛÒÌ·ÙÔ˜), ÔÌ¿‰· Gem+Peg, 4) 2 ml ‰È·Ï‡Ì·ÙÔ˜ Gem Û Peg + 2 ml Alc, ÔÌ¿‰· Gem+Alc+Peg. ø˜ ÔÌ¿-
∆· ·ÔÙÂϤÛÌ·Ù· ¤‰ÂÈÍ·Ó fiÙÈ Ë ÔÌ¿‰· ÂϤÁ¯Ô˘ ›¯Â ÙÔ ÌÈÎÚfiÙÂÚÔ ‰Â›ÎÙË Ì¿˙·˜ ÛÒÌ·ÙÔ˜ ·fi fiϘ ÙȘ ÔÌ¿‰Â˜ (P<0.001). √È ÔÌ¿‰Â˜ Gem+Peg Î·È Gem +Alc+Peg ›¯·Ó ˘„ËÏfiÙÂÚ· ›‰· AP Û ۇÁÎÚÈÛË Ì ÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘ (P=0.005, Î·È p=0.018, ·ÓÙ›ÛÙÔȯ·) Î·È Ë ÔÌ¿‰· Peg ¯·ÌËÏfiÙÂÚ· ›‰· AP Û˘ÁÎÚÈÙÈο Ì ÙËÓ ÔÌ¿‰· Gem+ Peg (P=0.041) (EÈÎfiÓ· 1). ŸÏ˜ ÔÈ ÔÌ¿‰Â˜ ÂÌÊ¿ÓÈÛ·Ó ¯·ÌËÏfiÙÂÚË Û˘ÁΤÓÙÚˆÛË ALT Û ۇÁÎÚÈÛË Ì ÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘
(P<0.001). ∆· ›‰· TC ‹Ù·Ó ¯·ÌËÏfiÙÂÚ· ÛÙȘ ÔÌ¿‰Â˜ Ô˘ ¯ÔÚËÁ‹ıËΠGem (Gem+Peg Î·È Gem+Alc+Peg), Û˘ÁÎÚÈÓfiÌÂÓ· Ì ÂΛӷ Ù˘ ÔÌ¿‰·˜ ÂϤÁ¯Ô˘ (P=0.002 Î·È P=0.039, ·ÓÙ›ÛÙÔȯ·), fiˆ˜ ›Û˘ ¯·ÌËÏfiÙÂÚ· ·ÚÔ˘ÛÈ¿ÛÙËÎ·Ó Î·È ÛÙËÓ ÔÌ¿‰· Gem+Peg Û˘ÁÎÚÈÙÈο Ì ÙȘ ÔÌ¿‰Â˜ Peg Î·È Alc+Peg (P=0.047 Î·È P=0.01, ·ÓÙ›ÛÙÔȯ·) (EÈÎfiÓ· 2). ∆· ›‰· AST Î·È TG ‹Ù·Ó ·ÚfiÌÔÈ· Û fiϘ ÙȘ ÔÌ¿‰Â˜. ∫·Ù¿ ÙËÓ ÈÛÙÔÏÔÁÈ΋ ÂͤٷÛË ÙˆÓ ‰ÂÈÁÌ¿ÙˆÓ ‹·ÙÔ˜ ‰ÂÓ ÚԤ΢„·Ó ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. ™˘ÌÂÚ·ÛÌ·ÙÈο, Ë Ì¤ÙÚÈ· ηٷӿψÛË Alc ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙË ¯ÔÚ‹ÁËÛË Gem Û ηıËÌÂÚÈÓ‹ ‚¿ÛË, ·Â‰Â›¯ıÂÈ ·ÛÊ·Ï‹˜ ÛÙÔ˘˜ ·ÚÔ˘Ú·›Ô˘˜. ∂ÈϤÔÓ, Ë ¯ÔÚ‹ÁËÛË Peg Ê·›ÓÂÙ·È Ó· ÂÌÔ‰›˙ÂÈ ÙËÓ ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ TG Î·È AST ÛÙÔ Ï¿ÛÌ·, Ô˘ ÚÔηÏÂ›Ù·È ·fi ÙÔ ·ÏÎÔfiÏ. ∂È̤ÏÂÈ·: ∫ϤÏÈ· ¢. ™·Ï¤·
P = 0.018
P = 0.018
100 90
P = 0.041
70
P = 0.005
80 70
50
60
TC (mg/dl)
AP [mlU/ml]
P = 0.041 P = 0.041
60
50 40 30 20
40 30 20 10
10 0 0
ol ntr Co
g Pe
eg +P c l A
Groups
g g Pe Pe lc+ m+ A e G m+ Ge
∂ÈÎfiÓ· 1: ∂›Â‰· ·ÏηÏÈ΋˜ (AP) Û fiϘ ÙȘ ÔÌ¿‰Â˜.
16
ol ntr Co
g Pe
eg eg eg +P +P +P c l c m l A A Ge m+ Ge Groups
∂ÈÎfiÓ· 2. ∂›Â‰· ÔÏÈ΋˜ ¯ÔÏËÛÙÂÚfiÏ˘ (TC) Û fiϘ ÙȘ ÔÌ¿‰Â˜.
¢IAITA
∞ÔÙÂϤÛÌ·Ù· Ù˘ ·Ú·ÙÂٷ̤Ó˘ ÚfiÛÏ˄˘ ˘ÂÚ‚¿ÏÏÔ˘Û·˜ ÔÛfiÙËÙ·˜ ÙÚÔÊ‹˜ ÛÙ· ›‰· ÙˆÓ ÏÈÔÚˆÙÂ˚ÓÒÓ ÙÔ˘ Ï¿ÛÌ·ÙÔ˜ Û ÌÔÓÔ˙˘ÁˆÙÈÎÔ‡˜ ‰È‰‡ÌÔ˘˜ Teràn-Garcia M, Després J-P, Couillard C, Tremblay A, Bouchard C. Atherosclerosis 2004;173:277-283
∆Ô ÛˆÌ·ÙÈÎfi ‚¿ÚÔ˜ ÙÔ˘˜ ·˘Í‹ıËΠηٿ 8,1 kg (P<0,001), ·fi Ù· ÔÔ›· Ù· 5,4 kg (P<0,001) ‹Ù·Ó ϛԘ Î·È Ù· 2,7 kg ÌË ÏÈ҉˘ ÈÛÙfi˜. ∏ ÂÚ›ÌÂÙÚÔ˜ ̤Û˘ ·˘Í‹ıËΠηٿ 8,2 cm Î·È ÙÔ ˘Ô‰fiÚÈÔ Î·È ÙÔ ÛÏ·¯ÓÈÎfi ϛԘ ÂÚ›Ô˘ ‰ÈÏ·ÛÈ¿ÛıËÎ·Ó (̤ÙÚËÛË Ì ·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›· ÎÔÈÏ›·˜). ∆· ÏÈ›‰È· Î·È ÔÈ ÏÈÔÚˆÙ½Ó˜ ÌÂÙ·‚Ï‹ıËÎ·Ó ÚÔ˜ ÙË ‰˘ÛÌÂÓ‹ ηÙ‡ı˘ÓÛË. ∆· ÙÚÈÁÏ˘ÎÂÚ›‰È· ·˘Í‹ıËÎ·Ó Î·Ù¿ 50 mg% ÂÚ›Ô˘ (P<0,05). ∂›Û˘ ·˘Í‹ıËÎ·Ó Ë ÔÏÈ΋ ¯ÔÏËÛÙÂÚfiÏË, Ë VLDL¯ÔÏËÛÙÂÚfiÏË, Ë LDL-¯ÔÏËÛÙÂÚfiÏË Î·È Ë Apo B ÂÓÒ ÌÂÈÒıËÎÂ Ë HDL¯ÔÏËÛÙÂÚfiÏË Î·È Ë ∏DL-Apo-AI (P<0,05). √ ÏfiÁÔ˜ ÔÏÈ΋ ¯ÔÏËÛÙÂ-
¢›‰˘ÌÔÈ A MÂÙ·‚ÔÏ‹ ÙÔ˘ OÏ.XÔÏ/HDL-XÔÏ
12 ˙¢Á¿ÚÈ· Ó·ÚÒÓ ·ÚÚ¤ÓˆÓ ÌÔÓÔ˙˘ÁˆÙÈÎÒÓ ‰È‰‡ÌˆÓ ËÏÈΛ·˜ 21±2 ÂÙÒÓ ˘Ô‚Ï‹ıËÎ·Ó Â› 100 Ë̤Ú˜ Û ˘ÂډȷÙÚÔÊ‹ (1000 ıÂÚÌ›‰Â˜ ÙËÓ Ë̤ڷ ÂÚÈÛÛfiÙÂÚ˜ ·fi ÙȘ ÂÓÂÚÁÂȷΤ˜ ÙÔ˘˜ ·Ó¿ÁΘ, ÔÈ Ôԛ˜ ›¯·Ó ÌÂÙÚËı› ÂÓˆÚ›ÙÂÚ·) Î·È ÂÚÈÔÚÈÛÌfi Ù˘ ۈ̷ÙÈ΋˜ ‰Ú·ÛÙËÚÈfiÙËÙ·˜. ∏ Û‡ÛÙ·ÛË Ù˘ ‰È·ÙÚÔÊ‹˜ ÙÔ˘˜ ηٿ ̤ÛÔ fiÚÔ ‹Ù·Ó (50±3% ˘‰·Ù¿ÓıڷΘ, 15±3% Ï¢ÎÒÌ·Ù· 35±3% Ï›Ë.)
ÚfiÏË/HDL ¯ÔÏËÛÙÂÚfiÏË ·˘Í‹ıËΠηٿ 20% (P<0,001). ∞fi Ù· ˘ÔÎÏ¿ÛÌ·Ù· Ù˘ HDL, ÌÂÈÒıËΠÛËÌ·ÓÙÈο Ë HDL3, ÂÓÒ Ë HDL2 Î·È Ô ÏfiÁÔ˜ HDL2/HDL3 ‰ÂÓ ÌÂÙ·‚Ï‹ıËÎ·Ó ÛËÌ·ÓÙÈο. ∏ ÌË ÌÂÙ·‚ÔÏ‹ ÙÔ˘ ÏfiÁÔ˘ HDL2-¯ÔÏËÛÙÂÚfiÏË/ HDL3¯ÔÏËÛÙÂÚfiÏË Â›Ó·È ‰ËψÙÈ΋ ÌË ÌÂÙ·‚ÔÏ‹˜ ÙÔ˘ ηٷ‚ÔÏÈÛÌÔ‡ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Î·È Ë ·‡ÍËÛË ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ Ï¿ÛÌ·Ù· ÔÊ›ÏÂÙ·È Û ˘ÂÚ·Ú·ÁˆÁ‹ Ù˘ VLDL ÏfiÁˆ ÙÔ˘ ¯ÚÔÓ›Ô˘ ÂÓÂÚÁÂÈ·ÎÔ‡ ÏÂÔÓ¿ÛÌ·ÙÔ˜ Î·È Ù˘ ·˘ÍË̤Ó˘ ÚÔÛÊÔÚ¿˜ ˘ÔÛÙÚÒÌ·ÙÔ˜. ∏ ·˘-
¢›‰˘ÌÔÈ B
MÂÙ·‚ÔÏ‹ ÙÔ˘ OÏ.XÔÏ/HDL-XÔÏ MÂÙ·‚ÔÏ‹ ÙÔ˘ HDL-XÔÏ2/HDL-XÔÏ3
∂›Ó·È ÁÓˆÛÙfi fiÙÈ Ë ·˘ÍË̤ÓË ÚfiÛÏË„Ë ıÂÚÌ›‰ˆÓ Î·È ÎÔÚÂÛÌ¤ÓˆÓ ÏÈ·ÚÒÓ ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÌÂȈ̤ÓË ÛˆÌ·ÙÈ΋ ‰Ú·ÛÙËÚÈfiÙËÙ· Ô‰ËÁ› ÛÙËÓ ·‡ÍËÛË Ù˘ ıÓËÛÈÌfiÙËÙ·˜ ·fi ηډȷÁÁÂȷο ÓÔÛ‹Ì·Ù·. ¶·Ú¿ÏÏËÏ· Â›Ó·È ÁÓˆÛÙfi fiÙÈ ˘¿Ú¯ÂÈ ÛËÌ·ÓÙÈ΋ ‰È·ÊÔÚ¿ ÛÙËÓ ·ÓÙ·fiÎÚÈÛË ÙˆÓ ‰È·ÊfiÚˆÓ ·ÙfiÌˆÓ ÛÙÔ˘˜ ÂÚÈ‚·ÏÏÔÓÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜: › ·Ú·‰Â›ÁÌ·ÙÈ, ¿ÏÏÔÈ Â›Ó·È Â˘·›ÛıËÙÔÈ Î·È ¿ÏÏÔÈ ·ÓıÈÛÙ¿ÌÂÓÔÈ ÛÙË ‰È·ÈÙËÙÈ΋ ¯ÔÏËÛÙÂÚfiÏË. ∏ ÌÂϤÙË ÙˆÓ ÌÔÓÔ˙˘ÁˆÙÈÎÒÓ ‰È‰‡ÌˆÓ ÚÔÛʤÚÂÈ ÙËÓ ‰˘Ó·ÙfiÙËÙ· ‰ÈÂÚ‡ÓËÛ˘ ÙÔ˘ ÚfiÏÔ˘ ÙˆÓ ÁÂÓÂÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ ÛÙË ‰ÂÎÙÈÎfiÙËÙ· ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ ÛÙÔ˘˜ ÂÚÈ‚·ÏÏÔÓÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜.
¢›‰˘ÌÔÈ A
¢›‰˘ÌÔÈ B MÂÙ·‚ÔÏ‹ ÙÔ˘ HDL-XÔÏ2/HDL-XÔÏ3
EÈÎfiÓ· 1. OÌÔÈfiÙËÙ· Ù˘ ·ÓÙ·fiÎÚÈÛ˘ ÙÔ˘ ÏfiÁÔ˘ OÏ.XÔÏ/HDL-XÔÏ Î·È HDL-XÔÏ2/HDL-XÔÏ3 ÛÙÔÓ ˘ÂÚÛÈÙÈÛÌfi 24 Ó·ÚÒÓ ÂÓËÏ›ÎˆÓ ·Ó‰ÚÒÓ (12 ˙‡ÁË ÌÔÓÔ-ˆÔÁÂÓÒÓ ‰È‰‡ÌˆÓ).
ÍË̤ÓË Î˘ÎÏÔÊÔÚ›· ÙˆÓ ˘ÔÏÂÈÌÌ¿ÙˆÓ VLDL Èı·ÓÒ˜ ÚÔηÏ› ηٷ‚ÔÏ‹ ÙˆÓ Ë·ÙÈÎÒÓ ApoB/E ˘Ô‰Ô¯¤ˆÓ Î·È Ì ÙÔÓ ÙÚfiÔ ·˘Ùfi ·‡ÍËÛË Ù˘ LDL-¯ÔÏËÛÙÂÚfiÏ˘ Î·È Ù˘ LDL-Apo-B ¶·Ú·ÙËÚ‹ıËÎ·Ó ÛËÌ·ÓÙÈΤ˜ ‰È·ÊÔÚ¤˜ ÌÂٷ͇ ÙˆÓ ·ÙfïÓ: ÌÂÚÈο ¿ÙÔÌ· ÂÌÊ¿ÓÈÛ·Ó ÛËÌ·ÓÙÈ΋ Âȉ›ӈÛË ÙˆÓ ÙÈÌÒÓ ÙˆÓ ÏÈȉ›ˆÓ ÂÓÒ ¿ÏÏ· ›¯·Ó ÌÈÎÚ¤˜ ÌfiÓÔ ÌÂÙ·‚ÔϤ˜. ∂› ·Ú·‰Â›ÁÌ·ÙÈ Ù· fiÚÈ· ·ÍÈÔÈÛÙ›·˜ Ù˘ Ì›·˜ ÛÙ·ıÂÚ¿˜ ·fiÎÏÈÛ˘ ÛÙË ÌÂÙ·‚ÔÏ‹ ÙˆÓ ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ ÂÎÙ›ÓÔÓÙ·È ·fi ÙË Ì›ˆÛË Î·Ù¿ 24mg% ̤¯ÚÈ ·‡ÍËÛË Î·Ù¿ 125 mg%. ∆Ô ›‰ÈÔ Â˘Ú¤· fiÚÈ· ·ÍÈÔÈÛÙ›·˜ ·Ú·ÙËÚ‹ıËÎ·Ó ÛÙȘ ÌÂÙ·‚ÔϤ˜ ÙÔ˘ ÏfiÁÔ˘ ÔÏÈ΋ ¯ÔÏËÛÙÂÚfiÏË/ HDL-¯ÔÏËÛÙÂÚfiÏË: ÌÂÚÈο ¿ÙÔÌ· ›¯·Ó Ì›ˆÛË 0,20 ÂÓÒ ¿ÏÏ· ·‡ÍËÛË 1,74. ªÂ ¿ÏÏ· ÏfiÁÈ· Ë ·Ú·ÙÂٷ̤ÓË ˘ÂÚ‚¿ÏÏÔ˘Û· Ï‹„Ë ÙÚÔÊÒÓ Û ÌÂÚÈο ¿ÙÔÌ· ‰ÂÓ ÌÂÙ¤‚·Ï ٷ ÏÈ›‰È· ÂÓÒ ÛÙ· ÂÚÈÛÛfiÙÂÚ· ¤ÊÂÚ ÛÔ‚·Ú¤˜ ÌÂÙ·‚ÔϤ˜. ∏ ÌÂÙ·‚ÏËÙfiÙËÙ· ÛÙËÓ ·ÓÙ·fiÎÚÈÛË ‰ÂÓ ‹Ù·Ó Ù˘¯·›·. √È ÌÔÓÔ˙˘ÁˆÙÈÎÔ› ‰›‰˘ÌÔÈ Â›¯·Ó ·ÚfiÌÔȘ ·Ú¯ÈΤ˜ ÙÈ̤˜ ÏÈȉ›ˆÓ Î·È ·ÚÔ˘Û›·Û·Ó ÛËÌ·ÓÙÈο ·ÚfiÌÔȘ ÌÂÙ·‚ÔϤ˜ ÌÂÙ¿ ÙËÓ ·Ú¤Ì‚·ÛË. ™ÙËÓ EÈÎfiÓ· 1 Ê·›ÓÂÙ·È Ë ÔÌÔÈfiÙËÙ· Ù˘ ·ÓÙ·fiÎÚÈÛ˘ ÙˆÓ ‰È‰‡ÌˆÓ ÛÙËÓ ˘ÂډȷÙÚÔÊ‹. √È ‰È·ÊÔÚ¤˜ ÌÂٷ͇ ÙˆÓ ˙¢Á·ÚÈÒÓ ‹Ù·Ó 12 ÊÔÚ¤˜ ÌÂÁ·Ï‡ÙÂÚ˜ ·fi ÙȘ ‰È·ÊÔÚ¤˜ ÂÓÙfi˜ ÙˆÓ ˙¢Á·ÚÈÒÓ. ∞˘Ùfi ‰Â›¯ÓÂÈ fiÙÈ Ù· ÁÔÓ›‰È·, Ù· ÔÔ›· ̤ÓÂÈ Ó· ÂÓÙÔÈÛıÔ‡Ó ÔÈ· ›ӷÈ, ηıÔÚ›˙Ô˘Ó fiÛÔ ‰ÂÎÙÈÎfi Â›Ó·È Î¿ı ¿ÙÔÌÔ ÛÙËÓ Â›‰Ú·ÛË ÙˆÓ ÂÚÈ‚·ÏÏÔÓÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ. £· ‹Ù·Ó ÛËÌ·ÓÙÈÎfi Î·È ı· ›¯Â ÎÏÈÓÈÎfi ÂӉȷʤÚÔÓ ·Ó ÌÔÚÔ‡Û ·fi ÚÈÓ Ó· ‰È·ÁÓˆÛı› ÔÈ· ¿ÙÔÌ· Â›Ó·È Â˘¿ÏˆÙ· ÛÙËÓ Î·Î‹ ‰È·ÙÚÔÊ‹ Î·È ÔÈ· ·ÓıÂÎÙÈο. ∂È̤ÏÂÈ·: ∏Ï›·˜ ÃÂÈÌÒÓ·˜
19
¢IAITA
∫·Ê½ÓË, √ÈÓfiÓÂ˘Ì· Î·È ™·Î¯·Ú҉˘ ¢È·‚‹Ù˘ Ù‡Ô˘ 2 ∂ÈÚ‹ÓË °·˙‹, ∂ÈÛÙËÌÔÓÈÎfi˜ ™˘ÓÂÚÁ¿Ù˘ ÙÔ˘ π·ÙÚ›Ԣ §Èȉ›ˆÓ ªˆ˘Û‹˜ ∂ÏÈÛ¿Ê, ∫·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜
∏ ›وÛË ÙÔ˘ ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË Ù‡Ô˘ 2 (™¢) ¤¯ÂÈ ·˘ÍËı› ÛËÌ·ÓÙÈο ÙȘ ÙÂÏÂ˘Ù·›Â˜ ‰ÂηÂٛ˜ Ì ·ÔÙ¤ÏÂÛÌ· Ô ™¢ Ó· ·ÔÙÂÏ› ¤Ó· ·fi Ù· Û˘¯ÓfiÙÂÚ· ¯ÚfiÓÈ· ÓÔÛ‹Ì·Ù· ÛÙȘ ·Ó·Ù˘Á̤Ó˜ ÎÔÈӈӛ˜ [1]. ¶·Ú¿ ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÙÔ ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi ™¢ Ù‡Ô˘ 2 ‰È·‰Ú·Ì·Ù›˙ÂÈ Î·ıÔÚÈÛÙÈÎfi ÚfiÏÔ ÛÙÔÓ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ™¢, ÔÈ ‰È·ÙÚÔÊÈΤ˜ Û˘Ó‹ıÂȘ Î·È Ô ÙÚfiÔ˜ ˙ˆ‹˜ ·ÔÙÂÏÔ‡Ó Â›Û˘ ȉȷ›ÙÂÚ· ÛËÌ·ÓÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ [2, 3]. ∂ÎÙfi˜ ·fi ÙËÓ ·¯˘Û·ÚΛ·, Ë Î·ıÈÛÙÈ΋ ˙ˆ‹, ÙÔ Î¿ÓÈÛÌ· Î·È Ë ÏÔ‡ÛÈ· Û ˘‰·Ù¿ÓıڷΘ Î·È ÎÔÚÂṲ̂ӷ ÏÈ·Ú¿ Ôͤ· Î·È Ùˆ¯‹ ÛÂ Ê˘ÙÈΤ˜ ›Ó˜ Î·È ÔÏ˘·ÎfiÚÂÛÙ· ÏÈ·Ú¿ Ôͤ· ‰›·ÈÙ· ·ÔÙÂÏÔ‡Ó Â›Û˘ ·ÓÂÍ¿ÚÙËÙÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ™¢ Ù‡Ô˘ 2 [2]. OÈ ÌÈÎÚÔ- Î·È Ì·ÎÚÔ·ÁÁÂȷΤ˜ ÂÈÏÔΤ˜ ÙÔ˘ ™¢ ·ÔÙÂÏÔ‡Ó ÙȘ ·ÚȘ ·Èٛ˜ ÓÔÛËÚfiÙËÙ·˜ Î·È ıÓËÙfiÙËÙ·˜ Û ·˘ÙÔ‡˜ ÙÔ˘˜ ·ÛıÂÓ›˜, ÂÓÒ Ë Û˘¯ÓfiÙÂÚË ·ÈÙ›· Ù‡ÊψÛ˘ ÛÙȘ ·Ó·Ù˘Á̤Ó˜ ¯ÒÚ˜ Â›Ó·È Ë ‰È·‚ËÙÈ΋ ·ÌÊÈ‚ÏËÛÙÚÔÂȉԿıÂÈ· [4]. ∆· ·ÔÙÂϤÛÌ·Ù· Ù˘ ÌÂϤÙ˘ UKPDS ¤‰ÂÈÍ·Ó fiÙÈ Ë Â›ÙˆÛË ·˘ÙÒÓ ÙˆÓ ÂÈÏÔÎÒÓ ÌÂÈÒÓÂÙ·È ÛËÌ·ÓÙÈο Ì ÙÔÓ Â·Ú΋ ÁÏ˘Î·ÈÌÈÎfi ¤ÏÂÁ¯Ô [5].
∫·ÊÂ˚ÓË Î·È ™¢ H ηٷӿψÛË Î·Ê¤ ¤¯ÂÈ Û˘Û¯ÂÙÈÛı› Ì ÙÔÓ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ™¢, ·ÊÔ‡ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ Ë Î·Ê½ÓË ÚÔηÏ› Ì›ˆÛË Ù˘ ¢·ÈÛıËÛ›·˜ ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ÈÛÙÒÓ ÛÙË ‰Ú¿ÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘ [6]. ™˘ÁÎÂÎÚÈ̤ӷ, Ë ÔÍ›· ¯ÔÚ‹ÁËÛË Î·Ê½Ó˘ ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û Ì›ˆÛË Ù˘ ¢·ÈÛıËÛ›·˜ ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ÈÛÙÒÓ ÛÙË ‰Ú¿ÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘ Î·È Û ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ ˘‰·Ù·ÓıڿΈÓ, Èı·Ó¿ ÂÍ·ÈÙ›·˜ Ù˘ ȉÈfiÙËÙ·˜ Ù˘ ηÊÂ˚Ó˘ Ó· ·Ó·ÛÙ¤ÏÏÂÈ ÙË ‰Ú¿ÛË ÙÔ˘ ˘Ô‰Ô¯¤· Ù˘ ·‰ÂÓÔÛ›Ó˘ ∞1 Ì ·ÔÙ¤ÏÂÛÌ· Ó· ·ÚÂÌÔ‰›˙ÂÙ·È Ë ÚfiÛÏË„Ë Ù˘
ÁÏ˘Îfi˙˘ ·fi ÙÔ˘˜ ÛÎÂÏÂÙÈÎÔ‡˜ ̇˜ [6, 7, 8]. øÛÙfiÛÔ, ÈÔ ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ Ë Â›‰Ú·ÛË Ù˘ ηÊÂ˚Ó˘ ÛÙËÓ Â˘·ÈÛıËÛ›· ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ÈÛÙÒÓ ÛÙË ‰Ú¿ÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘ in vivo ÂÍ·ÚÙ¿Ù·È Î˘Ú›ˆ˜ ·fi Ù· ˘„ËÏ¿ ›‰· Ù˘ ÂÈÓÂÊÚ›Ó˘ ÛÙÔ Ï¿ÛÌ· ·Ú¿ ·fi ÙËÓ ·Ó·ÛÙÔÏ‹ ÙÔ˘ ˘Ô‰Ô¯¤· Ù˘ ·‰ÂÓÔÛ›Ó˘ ∞1, ·ÊÔ‡ Ë ‰È·Ù·Ú·¯‹ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ ˘‰·Ù·ÓıÚ¿ÎˆÓ ‚ÂÏÙÈÒÓÂÙ·È Ì ÙË ¯ÔÚ‹ÁËÛË ÙÔ˘ ‚-·‰ÚÂÓÂÚÁÈÎÔ‡ ·Ó·ÛÙÔϤ· ÚÔÚ·ÓÔÏfiÏË [9]. ¶Ú¤ÂÈ Â›Û˘ Ó· ÂÈÛËÌ·Óı› fiÙÈ Ë Î·Ê½ÓË ·˘Í¿ÓÂÈ ÙË ıÂÚÌÔÁ¤ÓÂÛË Î·È ÙËÓ Î·Ù·Ó¿ÏˆÛË ÂÓ¤ÚÁÂÈ·˜ Ì ·ÔÙ¤ÏÂÛÌ· ÙË ‰È·Ù‹ÚËÛË ‹ Î·È ÙË Ì›ˆÛË ÙÔ˘ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜ [10, 11]. EÈϤÔÓ Ë Î·ÊÂ˚ÓË ÚÔηÏ› ÔÍ›‰ˆÛË ÙˆÓ ÏÈ·ÚÒÓ ÔͤˆÓ Î·È ÎÈÓËÙÔÔ›ËÛË ÙÔ˘ ÁÏ˘ÎÔÁfiÓÔ˘ ÛÙÔ˘˜ ̇˜, ÂÓÒ ·˘Í¿ÓÂÈ ÙËÓ ·ÂÏ¢ı¤ÚˆÛË ÙˆÓ ÏÈ·ÚÒÓ ÔͤˆÓ ·fi ÙÔ˘˜ ÂÚÈÊÂÚÈÎÔ‡˜ ÈÛÙÔ‡˜ [10, 11, 12]. ª›· ÚfiÛÊ·ÙË ÂȉËÌÈÔÏÔÁÈ΋ ÌÂϤÙË ¤‰ÂÈÍ ̛· ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ ·ÓÙ›ÛÙÚÔÊË Û˘Û¯¤ÙÈÛË ÌÂٷ͇ Ù˘ ηٷӿψÛ˘ ηʤ Î·È ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÂÌÊ¿ÓÈÛ˘ ™¢ Ù‡Ô˘ 2 [14]. ™˘ÁÎÂÎÚÈ̤ӷ, Ù· ·ÔÙÂϤÛÌ·Ù· ·˘Ù‹˜ Ù˘ ÌÂϤÙ˘ ¤‰ÂÈÍ·Ó Ì›· Ì›ˆÛË Î·Ù¿ 50% ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÂÌÊ¿ÓÈÛ˘ ™¢ Ù‡Ô˘ 2 Û ¿ÙÔÌ· Ô˘ Î·Ù·Ó¿ÏˆÓ·Ó ÂÚÈÛÛfiÙÂÚ˜ ·fi 7 Îԇ˜ ηʤ ËÌÂÚËÛ›ˆ˜ Û ۇÁÎÚÈÛË Ì ٷ ¿ÙÔÌ· Ô˘ Î·Ù·Ó¿ÏˆÓ·Ó 2 ‹ ÏÈÁfiÙÂÚ˜ Îԇ˜ ηʤ [14]. ∆Ô ÌÂÈÔÓ¤ÎÙËÌ· ·˘Ù‹˜ Ù˘ ÌÂϤÙ˘ ‹Ù·Ó fiÙÈ ‰ÂÓ ÂÎÙÈÌ‹ıËÎÂ Ë ÔÛfiÙËÙ· Ù˘ ηÊ½Ó˘ Ô˘ ÚÔ¤Ú¯ÂÙ·È ·fi ¿ÏϘ ËÁ¤˜ (ÙÛ¿È, ·Ó·„˘ÎÙÈο). ∂ÈϤÔÓ, Ì›· ÚfiÛÊ·ÙË ÌÂÙ··Ó¿Ï˘ÛË ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ Ù˘ ηٷÁÚ·Ê‹˜ ÙˆÓ Ó¤ˆÓ ÂÚÈÛÙ·ÙÈÎÒÓ ™¢ Ù‡Ô˘ 2 Û ·ÁÁÂÏ̷ٛ˜ ˘Á›·˜ (Health Professionals Follow-up Study, HPFS, Nurses’ Health Study, NHS) ¤‰ÂÈÍ ̛· ·ÚÓËÙÈ΋ Û˘Û¯¤ÙÈÛË ÌÂٷ͇ Ù˘ ›وÛ˘ ÙÔ˘ ™¢ Ù‡Ô˘ 2 Î·È Ù˘
ηٷӿψÛ˘ ηÊÂ˚Ó˘ [15]. ™˘ÁÎÂÎÚÈ̤ӷ, Ô ÌÈÎÚfiÙÂÚÔ˜ Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜ ÂÌÊ¿ÓÈÛ˘ ™¢ Ù‡Ô˘ 2 ·Ú·ÙËÚ‹ıËΠ۠¿Ó‰Ú˜ Ô˘ Î·Ù·Ó¿ÏˆÓ·Ó ÂÚÈÛÛfiÙÂÚ˜ ·fi 6 Îԇ˜ ηʤ ÙËÓ Ë̤ڷ (0,46 Û ۇÁÎÚÈÛË Ì 1 Ô˘ ‹Ù·Ó Ô Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜ Û fiÛÔ˘˜ ‰ÂÓ ¤ÈÓ·Ó Î·Ì›· ÎÔ‡· ηʤ ÙËÓ Ë̤ڷ), ÂÓÒ ÛÙȘ Á˘Ó·›Î˜ Ô ÌÈÎÚfiÙÂÚÔ˜ Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜ ·Ú·ÙËÚ‹ıËΠÛÙËÓ ÔÌ¿‰· Ô˘ ηٷӿψÓ 4-5 Îԇ˜ ηʤ ËÌÂÚËÛ›ˆ˜ (0,70 Û ۇÁÎÚÈÛË Ì 1 ÛÙËÓ ÔÌ¿‰· Ô˘ ‰ÂÓ ¤ÈÓ η̛· ÎÔ‡· ηʤ) [15]. ∞˘Ù‹ Ë ·ÚÓËÙÈ΋ Û˘Û¯¤ÙÈÛË ‹Ù·Ó ·ÓÂÍ¿ÚÙËÙË ·fi ¿ÏÏÔ˘˜ ·Ú¿ÁÔÓÙ˜, fiˆ˜ Ô ‰Â›ÎÙ˘ Ì¿˙·˜ ÛÒÌ·ÙÔ˜, ÙÔ Î¿ÓÈÛÌ· Î·È ¿ÏÏÔÈ ‰È·ÙÚÔÊÈÎÔ› ·Ú¿ÁÔÓÙ˜. ¶Ú¤ÂÈ Ó· ÂÈÛËÌ·Óı› fiÙÈ Ô Î·Ê¤˜ ÂÚȤ¯ÂÈ ÔÚÈṲ̂ӷ Û˘ÛÙ·ÙÈο Ô˘ ÌÔÚÔ‡Ó Ó· ÂÍËÁ‹ÛÔ˘Ó ÌÂÚÈΤ˜ ·fi ÙȘ ¢ÂÚÁÂÙÈΤ˜ ÙÔ˘ ȉÈfiÙËÙ˜. °È· ·Ú¿‰ÂÈÁÌ·, Ô Î·Ê¤˜ ÂÚȤ¯ÂÈ ÛËÌ·ÓÙÈΤ˜ ÔÛfiÙËÙ˜ Î·Ï›Ô˘, ÓÈ·Û›Ó˘, Ì·ÁÓËÛ›Ô˘ Î·È ·ÓÙÈÔÍÂȉˆÙÈÎÒÓ Ô˘ÛÈÒÓ fiˆ˜ ÙÔÎÔÊÂÚfiϘ. √È Ô˘Û›Â˜ ·˘Ù¤˜ Ê·›ÓÂÙ·È fiÙÈ Û˘ÓÙÂÏÔ‡Ó ÛÙË ‚ÂÏÙ›ˆÛË Ù˘ ¢·ÈÛıËÛ›·˜ ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ÈÛÙÒÓ ÛÙË ‰Ú¿ÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘ [16].
∞ÏÎÔfiÏ Î·È ™¢ ŒÓ·˜ ¿ÏÏÔ˜ ·Ú¿ÁÔÓÙ·˜ Ô˘ Ê·›ÓÂÙ·È Ó· ÂËÚ¿˙ÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ™¢ Ù‡Ô˘ 2 Â›Ó·È ÙÔ ÔÈÓfiÓÂ˘Ì·. ∆· ̤¯ÚÈ ÙÒÚ· ‰Â‰Ô̤ӷ ‰Â›¯ÓÔ˘Ó fiÙÈ Ë Ì¤ÙÚÈ· ηٷӿψÛË ÔÈÓÔÓ‡̷ÙÔ˜ Û˘Û¯ÂÙ›˙ÂÙ·È Ì ÌÂȈ̤ÓÔ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ™¢, ÂÓÒ Ë ˘ÂÚ‚ÔÏÈ΋ ηٷӿψÛË ÔÈÓÔÓ‡̷ÙÔ˜ ·˘Í¿ÓÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ™¢ [17]. ∂ÈϤÔÓ, Ë ÚfiÛÏË„Ë ÌÈÎÚ‹˜ ÔÛfiÙËÙ·˜ ÔÈÓÔÓ‡̷ÙÔ˜ ‰ÂÓ Ê·›ÓÂÙ·È Ó· ÂËÚ¿˙ÂÈ ÙÔ ÁÏ˘Î·ÈÌÈÎfi ¤ÏÂÁ¯Ô Û ·ÛıÂÓ›˜ Ì ™¢ Ù‡Ô˘ 2 [17]. M›· ÚfiÛÊ·ÙË ·Ó·ÛÎfiËÛË Ù˘ ‚È‚ÏÈÔÁÚ·Ê›·˜ ¤‰ÂÈÍ fiÙÈ Ë Ì¤ÙÚÈ·
17
·ıËÚÔÛÎÏ‹ÚˆÛË ™E¶TEMBPπ√™ 2004
ηٷӿψÛË ÔÈÓÔÓ‡̷ÙÔ˜ (1-3 ·ÏÎÔÔÏÔ‡¯· ÔÙ¿ ÙËÓ Ë̤ڷ) Û˘Û¯ÂÙ›˙ÂÙ·È Ì ¤Ó· ηٿ 33%-56% ÌÈÎÚfiÙÂÚÔ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ™¢ Ù‡Ô˘ 2 Û ۇÁÎÚÈÛË Ì ÙËÓ Ï‹ÚË ·Ô¯‹ ·fi ÙÔ ÔÈÓfiÓÂ˘Ì· [17]. ∂ÈÚfiÛıÂÙ·, Ë Î·Ù·Ó¿ÏˆÛË ÂÚÈÛÛfiÙÂÚˆÓ ·fi 3 ·ÏÎÔÔÏÔ‡¯ˆÓ ÔÙÒÓ ÙËÓ Ë̤ڷ ·˘Í¿ÓÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ™¢ ηٿ 43% Û ۇÁÎÚÈÛË Ì ÙË Ì¤ÙÚÈ· ηٷӿψÛË ÔÈÓÔÓ‡̷ÙÔ˜ [17]. ∆Ô ÁÂÁÔÓfi˜ fiÙÈ Ë Ì¤ÙÚÈ· ηٷӿψÛË ·ÏÎÔfiÏ Û˘Û¯ÂÙ›˙ÂÙ·È Ì ¯·ÌËÏfiÙÂÚÔ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ™¢ Ù‡Ô˘ 2 ¤¯ÂÈ Û·Ê‹ ‚ÈÔÏÔÁÈ΋ ÂÍ‹ÁËÛË. ∏ ·ÓÙ›ÛÙ·ÛË ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ÈÛÙÒÓ ÛÙË ‰Ú¿ÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘ ·ÔÙÂÏ› ÛËÌ·ÓÙÈÎfi ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ™¢ [18]. ™Â ÔÏϤ˜ ÌÂϤÙ˜ Ë Ì¤ÙÚÈ· ηٷӿψÛË ÔÈÓÔÓ‡̷ÙÔ˜ ¤¯ÂÈ Û˘Û¯ÂÙÈÛı› Ì ·‡ÍËÛË Ù˘ ¢·ÈÛıËÛ›·˜ ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ÈÛÙÒÓ ÛÙË ‰Ú¿ÛË Ù˘ ÈÓÛÔ˘Ï›Ó˘ [19, 20, 21]. ∂ÈϤÔÓ, Ú¤ÂÈ Ó· ÂÈÛËÌ·Óı› fiÙÈ Ë ˘ÂÚ‚Ô-
ÏÈ΋ ηٷӿψÛË ÔÈÓÔÓ‡̷ÙÔ˜ Û˘Óԉ‡ÂÙ·È Û˘¯Ó¿ ·fi ·¯˘Û·ÚΛ·, ΢ڛˆ˜ ÎÂÓÙÚÈÎÔ‡ Ù‡Ô˘, Ô˘ ·ÔÙÂÏ› ÈÛ¯˘Úfi ÚԉȷıÂÛÈÎfi ·Ú¿ÁÔÓÙ· ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ™¢ Ù‡Ô˘ 2 [22].
·ÎfiÌË Ë Â›‰Ú·ÛË ÙÔ˘ ÔÈÓÔÓ‡̷ÙÔ˜ Û ¿ÏϘ ÂÈÏÔΤ˜ ÙÔ˘ ™¢, fiˆ˜ Ë ‰È·‚ËÙÈ΋ ·ÌÊÈ‚ÏËÛÙÚÔÂȉԿıÂÈ· Î·È Ë ‰È·‚ËÙÈ΋ Ó¢ÚÔ¿ıÂÈ·.
¶Ú¤ÂÈ Ó· ÂÈÛËÌ·Óı› fiÙÈ ¤Ú·Ó Ù˘ ¢ÓÔ˚΋˜ ›‰Ú·Û˘ Ù˘ ̤ÙÚÈ·˜ ηٷӿψÛ˘ ÔÈÓÔÓ‡̷ÙÔ˜ ÛÙÔÓ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ™¢, Ë Ì¤ÙÚÈ· ηٷӿψÛË ·ÏÎÔÔÏÔ‡¯ˆÓ ÔÙÒÓ Û˘Û¯ÂÙ›˙ÂÙ·È Ì ̛· ·ÍÈÔÛËÌ›ˆÙË Ì›ˆÛË Ù˘ ›وÛ˘ Ù˘ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘ Î·È Ì›· ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ ı·Ó¿ÙˆÓ Û ‰È·‚ËÙÈÎÔ‡˜ ·ÛıÂÓ›˜ [17]. ∏ ÚÔÛٷ٢ÙÈ΋ ·˘Ù‹ ‰Ú¿ÛË ÙÔ˘ ÔÈÓÔÓ‡̷ÙÔ˜ ÚÔ·ÙÂÈ Èı·Ó¿ ·fi ÙËÓ ·‡ÍËÛË Ù˘ HDL ¯ÔÏËÛÙÂÚfiÏ˘, ÙË ÌÂȈ̤ÓË Û˘ÛÛÒÚ¢ÛË ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ Î·È ÙËÓ ·˘ÍË̤ÓË ÈÓˆ‰fiÏ˘ÛË, ÌÂÙ·‚ÔϤ˜ Ô˘ ·Ú·ÙËÚÔ‡ÓÙ·È Û ¿ÙÔÌ· Ô˘ ηٷӷÏÒÓÔ˘Ó Ì¤ÙÚȘ ÔÛfiÙËÙ˜ ÔÈÓÔÓ‡̷ÙÔ˜ [23, 24, 25]. øÛÙfiÛÔ, ‰ÂÓ ¤¯ÂÈ ÂÍ·ÎÚÈ‚ˆı›
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™˘Û¯¤ÙÈÛË ÌÂٷ͇ Ù˘ ıÂڷ›·˜ Ì ÛÙ·Ù›Ó˜ Î·È Ù˘ ¤Î‚·Û˘ ÙˆÓ ÔͤˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ Û˘Ó‰ÚfïÓ: The GRACE Study Spencer FA, Jeanna Allegrone J, Goldberg RJ, et al; the GRACE Investigators Ann Intern Med 2004;140:857-866 √È ÛÙ·Ù›Ó˜, fiÙ·Ó ¯ÔÚËÁËıÔ‡Ó ÚÒÈÌ· Û ·ÛıÂÓ›˜ Ì Ôͤ· ÛÙÂÊ·ÓÈ·›· Û‡Ó‰ÚÔÌ· (√™™) Û˘Ì‚¿ÏÏÔ˘Ó ÛÙËÓ ÂÏ¿ÙÙˆÛË Ù˘ Û˘¯ÓfiÙËÙ·˜ ÂÌÊ¿ÓÈÛ˘ Ó¤ˆÓ ÈÛ¯·ÈÌÈÎÒÓ ÂÂÈÛÔ‰›ˆÓ.
™˘ÌÌÂÙ›¯·Ó 94 ¡ÔÛÔÎÔÌ›· ·fi 14 ÃÒÚ˜ Ô˘ Â›Ó·È ÂÓÙ·Á̤ӷ ÛÙÔ Global Registry of Acute Coronary Events (GRACE) Î·È ÌÂÏÂÙ‹ıËÎ·Ó 19.537 ·ÛıÂÓ›˜ Ì √™™ ·fi ÙÔ 1999 ¤ˆ˜ ÙÔ 2002. ∆Ô Û‡ÓıÂÙÔ ÚˆÙÔÁÂÓ¤˜ ÙÂÏÈÎfi ÛËÌÂ›Ô ‹Ù·Ó (Ó¤Ô) ¤ÌÊÚ·ÁÌ· Ì˘Ôηډ›Ô˘ (∂ª) + ÂÓ‰ÔÓÔÛÔÎÔÌÂȷ΋ ıÓËÙfiÙËÙ· + ·ÁÁÂÈ·Îfi ÂÁÎÂÊ·ÏÈÎfi ÂÂÈÛfi‰ÈÔ. ∫·Ù·ÁÚ¿ÊËÎ·Ó Â›Û˘ Ù· Û˘ÛÙ·ÙÈο ÙÔ˘ ÚˆÙÔÁÂÓÔ‡˜ ÙÂÏÈÎÔ‡ ÛËÌ›Ԣ Î·È ÔÈ ÂÈÏÔΤ˜ ÙˆÓ √™™. √È ·ÛıÂÓ›˜ Ô˘ ¤·ÈÚÓ·Ó ÛÙ·Ù›Ó˜ ÚÈÓ ÂΉËψı› ÙÔ √™™ Î·È Û˘Ó¤¯ÈÛ·Ó Ó· ÙȘ ·›ÚÓÔ˘Ó ÌÂÙ¿ ·fi ·˘Ùfi, ›¯·Ó ÂÏ¿ÙÙˆÛË Ù˘ ıÓËÙfiÙËÙ·˜ > 50% Î·È ÙÔ˘ Ó¤Ô˘ ∂ª ηٿ 34% ÛÙË ‰È¿ÚÎÂÈ· Ù˘
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∂ÍÂÙ¿ÛÙËÎÂ Ë Û˘Û¯¤ÙÈÛË ÌÂٷ͇ Ù˘ ÚÔËÁÔ‡ÌÂÓ˘ Ï‹„˘ ÛÙ·ÙÈÓÒÓ, Ù˘ ÚÒÈÌ˘ ÂÓ‰ÔÓÔÛÔÎÔÌÂȷ΋˜ ¯ÔÚ‹ÁËÛ‹˜ ÙÔ˘˜ Î·È Ù˘ ÌË Ï‹„˘ ÛÙ·ÙÈÓÒÓ Ì Ӥ· ÈÛ¯·ÈÌÈο Û˘Ì‚¿Ì·Ù· Û ·ÛıÂÓ›˜ Ì √™™.
GRACE Study: EÓ‰ÔÓÔÛÔÎÔÌÂȷ΋ NÔÛËÚfiÙËÙ· & £ÓËÙfiÙËÙ· ÌÂÙ¿ ·fi O™™: EÏ¿ÙÙˆÛË Û¯ÂÙÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘ Û ·ÛıÂÓ‹˜ ÛÙ·Ù›Ó˜ (n=4.056) ¤Ó·ÓÙÈ ÌË Ï‹„˘ ÛÙ·ÙÈÓÒÓ (n=15.481)
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Spencer FA, et al: Annals of Internal Medicine 2004;140:857-866
∂ÈÎfiÓ· 1 ÓÔÛËÏ›·˜ ÙÔ˘˜, Û ۇÁÎÚÈÛË Ì ÂΛÓÔ˘˜ Ô˘ ‰ÂÓ ¤·ÈÚÓ·Ó ÚÈÓ Ô‡Ù ‹Ú·Ó ÛÙ·Ù›Ó˜ ÂÓ‰ÔÓÔÛÔÎÔÌÂȷο (∂ÈÎfiÓ· 1).
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√È ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ ¤·ÈÚÓ·Ó ÛÙ·Ù›Ó˜ ÚÈÓ ·ÏÏ¿ ¿Ú¯ÈÛ·Ó ÂÓ‰ÔÓÔÛÔÎÔÌÂȷο ›¯·Ó ηχÙÂÚË ¤Î‚·ÛË ·fi ÂΛÓÔ˘˜ Ô˘ ‰ÂÓ ¤·ÈÚÓ·Ó Î·È ‰ÂÓ ‹Ú·Ó ηıfiÏÔ˘ ÛÙ·Ù›Ó˜. ∆¤ÏÔ˜ ÔÈ ·ÛıÂÓ›˜ Ô˘ ¤·ÈÚÓ·Ó ÛÙ·Ù›Ó˜ ÚÈÓ Î·È ‰ÂÓ
∆· ÛÙÔȯ›· ·˘Ù¿ ˘ÔÛÙËÚ›˙Ô˘Ó ÙËÓ ˘fiıÂÛË fiÙÈ ÔÈ ÛÙ·Ù›Ó˜ ÂËÚ¿˙Ô˘Ó Â˘ÓÔ˚ο ÙÔ˘˜ ·ıÔÊ˘ÛÈÔÏÔÁÈÎÔ‡˜ Ì˯·ÓÈÛÌÔ‡˜ Ô˘ ÚÔηÏÔ‡Ó Ù· √™™ Î·È ÙȘ ÂÈÏÔΤ˜ ÙÔ˘˜. EÈ̤ÏÂÈ·: B·Û›ÏÂÈÔ˜ Õı˘ÚÔ˜
TÔ ‚Ú·‚Â›Ô NfiÌÂÏ º˘ÛÈ΋˜ ‹ I·ÙÚÈ΋˜ ‰fiıËΠÙÔ 1998 ·fi ÎÔÈÓÔ‡ ÛÙÔ˘˜ AÌÂÚÈηÓÔ‡˜ ÂÈÛÙ‹ÌÔÓ˜ ROBERT F FURCHGOTT ·fi ÙË N¤· YfiÚÎË, LUIS J IGNARRO Î·È FERID MURAD ·fi ÙÔ §Ô˜ ÕÓÙ˙ÂϘ ÁÈ· ÙȘ ·Ó·Î·Ï‡„ÂȘ ÙÔ˘˜ Ô˘ ·ÊÔÚÔ‡Ó ÛÙÔ ÌÔÓÔÍ›‰ÈÔ ÙÔ˘ ·˙ÒÙÔ˘ (NO) Û·Ó signaling ÌfiÚÈÔ ÛÙÔ Î·Ú‰È·ÁÁÂÈ·Îfi Û‡ÛÙËÌ·.
20
·ıËÚÔÛÎÏ‹ÚˆÛË ™E¶TEMBPπ√™ 2004
¶ƒ√∆∂π¡√ª∂¡∏ µπµ§π√°ƒ∞ºπ∞ 1: Kinlay S, Schwartz GG, Olsson AG, Rifai N, Sasiela WJ, Szarek M, Ganz P, Libby P. Effect of Atorvastatin on Risk of Recurrent Cardiovascular Events After an Acute Coronary Syndrome Associated With High Soluble CD40 Ligand in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study. Circulation. 2004 Jul 19 [Epub ahead of print] 2: Manuel-Y-Keenoy B, Vinckx M, Vertommen J, Van Gaal L, De Leeuw I. Impact of Vitamin E supplementation on lipoprotein peroxidation and composition in Type 1 diabetic patients treated with Atorvastatin. Atherosclerosis. 2004 Aug; 175(2):369-76. 3: Schneider JG, Von Eynatten M, Parhofer KG, Volkmer JE, Schiekofer S, Hamann A, Nawroth PP, Dugi KA. Atorvastatin improves diabetic dyslipidemia and increases lipoprotein lipase activity in vivo. Atherosclerosis. 2004 Aug;175(2):325-31. 4: Kajinami K, Brousseau ME, Ordovas JM, Schaefer EJ. Interactions between common genetic polymorphisms in ABCG5/ G8 and CYP7A1 on LDL cholesterol-lowering response to atorvastatin. Atherosclerosis. 2004 Aug; 175(2):287-93. 5: Raal FJ. A single-centre retrospective observational study to evaluate the change in total cholesterol and LDL cholesterol in hyperlipidaemic patients switched from atorvastatin to simvastatin. Cardiovasc J S Afr. 2004 MayJun;15(3):118-23. 6: Tekten T, Ceyhan C, Ercan E, Onbasili AO, Turkoglu C. The effect of atorvastatin on platelet function in patients with coronary artery disease. Acta Cardiol. 2004 Jun;59(3):311-5. 7: Claeys MJ, Cosyns B, Hoffer E, Carlier M, Missault L, Cools F, De Meester A, Vermeersch P, Gobin E, Dewit B; Belgian Young Cardiologists' Club. Short-term effect of atorvastatin on ischaemic threshold in hypercholesterolaemic patients with stable ischaemic heart disease. Acta Cardiol. 2004 Jun;59(3):269-74. 8: Seyfried D, Han Y, Lu D, Chen J, Bydon A, Chopp M. Improvement in neurological outcome after administration of atorvastatin following experimental intracerebral hemorrhage in rats. J Neurosurg. 2004 Jul;101(1): 104-7. 9: Nitta K, Akiba T, Nihei H. Colestimide co-administered with atorvastatin attenuates the progression of vascular calcification in haemodialysis patients. Nephrol Dial Transplant. 2004 Aug;19(8):2156. 10: Mehra MR, Raval NY. Metaanalysis of statins and survival in de novo cardiac transplantation. Transplant Proc. 2004 Jun; 36(5):153941. 11: Ercan E, Tengiz I, Altuglu I, Sekuri C, Aliyev E, Ercan HE, Akin M. Atorvastatin treatment decreases inflammatory and proteolytic activity in patients with hypercholesterolemia. Kardiol Pol. 2004 May;60(5):454-8. 12: Tekin A, Tekin G, Guzelsoy D, Kaya A, Gurel CV, Yigit Z, Ulutin T. Effects of atorvastatin (10 mg) on hemostatic and inflammatory parameters in hyperlipidemic patients with angiographically proven coronary artery disease. Am J Cardiol. 2004 Jul 15;94(2):206-9. 13: Wong WM, Wai-Hung Shek T, Chan KH, Chau E, Lai KC. Rhabdomyolysis triggered by cytomegalovirus infection in a heart transplant patient on concomitant cyclosporine and atorvastatin therapy. J Gastroenterol Hepatol. 2004 Aug;19(8): 952-3. 14: Ferdinand KC. The importance of aggressive lipid management in patients at risk: evidence from recent clinical trials. Clin Cardiol. 2004 Jun;27(6 Suppl 3):III12-5. 15: Kural BV, ORem C, Uydu HA, Alver A, ORem A. The effects of lipid-lowering therapy on
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paraoxonase activities and their relationships with the oxidant-antioxidant system in patients with dyslipidemia. Coron Artery Dis. 2004 Aug;15(5):277-283. 16: Zhou MS, Jaimes EA, Raij L. Atorvastatin Prevents End-Organ Injury in Salt-Sensitive Hypertension. Role of eNOS and Oxidant Stress. Hypertension. 2004 Jul 6 [Epub ahead of print] 17: Jacobs MB. Atorvastatin-induced polyneuropathy. Ann Intern Med. 2004 Jul 6;141(1):77. 18: Lappegard KT, Hvassing T, Mollnes TE. Statin drugs do not affect serum complement activation in vitro. Scand J Immunol. 2004 JulAug;60(1-2):178-83. 19: [No authors listed] Amlodipine/atorvastatin (Caduet). Med Lett Drugs Ther. 2004 Jul 5;46(1186):56. 20: Imanishi T, Hano T, Sawamura T, Nishio I. Oxidized low-density lipoprotein induces endothelial progenitor cell senescence, leading to cellular dysfunction. Clin Exp Pharmacol Physiol. 2004 Jul;31(7):407-13. 21: Hayashi A, Suzuki M, Ogawa Y, Sonoda R, Sasamata M. Post-stroke atorvastatin treatment reduces neurological deficits and mortality rate in the stroke-prone spontaneously hypertensive rat. J Pharm Pharmacol. 2004 Jul;56(7):893-8. 22: Athyros VG, Mikhailidis DP, Papageorgiou AA, Bouloukos VI, Pehlivanidis AN, Symeonidis AN, Elisaf M. Effect of statins and ACE inhibitors alone and in combination on clinical outcome in patients with coronary heart disease. J Hum Hypertens. 2004 Jul 1 [Epub ahead of print] 23: van Tits LJ, Smilde TJ, van Wissen S, de Graaf J, Kastelein JJ, Stalenhoef AF. Effects of atorvastatin and simvastatin on low-density lipoprotein subfraction profile, low-density lipoprotein oxidizability, and antibodies to oxidized low-density lipoprotein in relation to carotid intima media thickness in familial hypercholesterolemia. J Investig Med. 2004 Apr;52(3):177-84. 24: Athyros VG, Mikhailidis DP, Papageorgiou AA, Symeonidis AN, Pehlivanidis AN, Bouloukos VI, Elisaf M. The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease. A subgroup analysis of the Greek atorvastatin and coronary heart disease evaluation (GREACE) study. J Clin Pathol. 2004 Jul;57(7):728-34. 25: Molloy KJ, Thompson MM, Schwalbe EC, Bell PR, Naylor AR, Loftus IM. Comparison of levels of matrix metalloproteinases, tissue inhibitor of metalloproteinases, interleukins, and tissue necrosis factor in carotid endarterectomy specimens from patients on versus not on statins preoperatively. Am J Cardiol. 2004 Jul 1;94(1): 144-6. 26: Schwartz GG, Bolognese MA, Tremblay BP, Caplan R, Hutchinson H, Raza A, Cressman M. Efficacy and safety of rosuvastatin and atorvastatin in patients with hypercholesterolemia and a high risk of coronary heart disease: a randomized, controlled trial. Am Heart J. 2004 Jul; 148(1):e4. 27: Dujovne CA. Treatment of Familial Hypercholesterolemia and Other Genetic Dyslipidemias. Curr Treat Options Cardiovasc Med. 2004 Aug;6(4):269-278. 28: Rundek T, Naini A, Sacco R, Coates K, DiMauro S. Atorvastatin decreases the coenzyme Q10 level in the blood of patients at risk for cardiovascular disease and stroke. Arch Neurol. 2004 Jun;61(6):889-92. 29: Rodenburg J, Wiegman A, Vissers MN, Kastelein JJ, Stalenhoef AF. A boy with autosomal recessive hypercholesterolaemia. Neth J Med. 2004 Mar;62(3):89-93.
30: McCarey DW, McInnes IB, Madhok R, Hampson R, Scherbakov O, Ford I, Capell HA, Sattar N. Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial. Lancet. 2004 Jun 19;363(9426):2015-21. 31: Klareskog L, Hamsten A. Statins in rheumatoid arthritis--two birds with one stone? Lancet. 2004 Jun 19;363(9426):2011-2. 32: Berthold HK, Unverdorben S, Zittermann A, Degenhardt R, Baumeister B, Unverdorben M, Krone W, Vetter H, Gouni-Berthold I. Agedependent effects of atorvastatin on biochemical bone turnover markers: a randomized controlled trial in postmenopausal women. Osteoporos Int. 2004 Jun;15(6):45967. 33: Piperi C, Kalofoutis C, Skenderi K, Economidou O, Kalofoutis A. Beneficial effects of raloxifene and atorvastatin on serum lipids and HDL phospholipids levels of postmenopausal women. J Obstet Gynaecol. 2004 Jun;24(4):414-9. 34: Olsson A, Casciano R, Stern L, Svangren P. A pharmacoeconomic evaluation of aggressive cholesterol lowering in Sweden. Int J Cardiol. 2004 Jul;96(1):51-7. 35: Saltzman EA, Guay AT, Jacobson J. Improvement in erectile function in men with organic erectile dysfunction by correction of elevated cholesterol levels: a clinical observation. J Urol. 2004 Jul;172(1):255-8. 36: Daskalopoulou SS, Athyros VG, Elisaf M, Mikhailidis DP. Uric acid levels and vascular disease. Curr Med Res Opin. 2004 Jun;20(6):951-4. 37: Ose L. Diagnostic, clinical, and therapeutic aspects of familial hypercholesterolemia in children. Semin Vasc Med. 2004 Feb;4(1):517. 38: For the Pravastatin or Atorvastatin Evaluation Infection Therapy-Thrombolysis in Myocardial Infarction. 22 Investigators. Comparison of Intensive and Moderate Lipid Lowering With Statins After Acute Coronary Symptoms. Obstet Gynecol Surv. 2004 Jul;59(7):522-524. 39: Jayaram S, Jain MM, Naikawadi AA, Gawde A, Desai A. Comparative evaluation of the efficacy, safety, and tolerability of rosuvastatin 10 mg with atorvastatin 10 mg in adult patients with hypercholesterolaemia: the first Indian study. J Indian Med Assoc. 2004 Jan;102(1):48-50, 52. 40: Ballantyne CM, Blazing MA, King TR, Brady WE, Palmisano J. Efficacy and safety of ezetimibe co-administered with simvastatin compared with atorvastatin in adults with hypercholesterolemia. Am J Cardiol. 2004 Jun 15;93(12):1487-94. 41: Bruni F, Pasqui AL, Pastorelli M, Bova G, Di Renzo M, Cercigani M, Leo A, Auteri A, Puccetti L. Effect of atorvastatin on different fibrinolyis mechanisms in hypercholesterolemic subjects. Int J Cardiol. 2004 Jun 3;95(2):269-74. 42: Tanaka K, Honda M, Takabatake T. Anti-apoptotic effect of atorvastatin, a 3-hydroxy-3methylglutaryl coenzyme a reductase inhibitor, on cardiac myocytes through protein kinase C activation. Clin Exp Pharmacol Physiol. 2004 May-Jun;31(5-6): 360-4. 43: Kendrach MG, Kelly-Freeman M. Approximate equivalent rosuvastatin doses for temporary statin interchange programs. Ann Pharmacother. 2004 Jul;38(7):1286-92. 44: Fehr T, Kahlert C, Fierz W, Joller-Jemelka HI, Riesen WF, Rickli H, Wuthrich RP, Ammann P. Statin-induced immunomodulatory effects on human T cells in vivo. Atherosclerosis. 2004 Jul;175(1):83-90.
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IATPOI KA§§ITEXNE™
IATPOI KA§§ITEXNE™
°ÈÒÚÁÔ˜ K. X·Ù˙¿Î˘ °ÂÓÓ‹ıËΠÛÙËÓ ∫Ú‹ÙË. ∞fi Ù· ·È‰Èο ÙÔ˘ ¯ÚfiÓÈ· ›¯Â ÌÂÁ¿ÏË Ù¿ÛË ÛÙË ˙ˆÁÚ·ÊÈ΋ Î·È ‰¤¯ıËΠٷ ÚÒÙ· Ì·ı‹Ì·Ù· Û ËÏÈΛ· 12 ÂÙÒÓ ÛÙÔ ƒ¤ı˘ÌÓÔ. ∞ÚÁfiÙÂÚ·, ÌÂÙ¿ ÙËÓ ∫·ÙÔ¯‹, ‚Ú¤ıËΠÛÙËÓ ∞ı‹Ó· Ó· ÛÔ˘‰¿˙ÂÈ ÁÈ·ÙÚfi˜, Î·È Û˘Á¯ÚfiÓˆ˜ Ó· ·Û¯ÔÏÂ›Ù·È Ì ÙËÓ ˙ˆÁÚ·ÊÈ΋, ·Ó·˙ËÙÒÓÙ·˜ ÌfiÓÔ˜ ÙÔ˘, ÙÔ ‰ÈÎfi ÙÔ˘ ‰ÚfiÌÔ. ∆ÂÏ›ˆÛ ÁÈ·ÙÚfi˜ ÙÔ 1954, ÁÓˆÚ›ÛÙËΠ̠ÙÔÓ ∆¿ÛÔ §Ô˘Î›‰Ë Ô˘ ÙÔÓ ‰›‰·ÍÂ Î·È ÙÔ˘ ¤‰ˆÛ ÙÔ ¯¿ÚÈÛÌ· Ù˘ ¯ÚˆÌ·ÙÈ΋˜ ·ÚÌÔÓ›·˜ Î·È ÎÏÈ̿ΈÛ˘. ªÂÙ¿ ÙË ÁÓˆÚÈÌ›· ÙÔ˘ Ì ÙÔ ÌÂÁ¿ÏÔ £¿ÓÔ ∆Û›ÁÁÔ, ÂËÚ¿ÛÙËΠ·fi ÙË ˙ˆÁÚ·ÊÈ΋ ÙÔ˘ ηÈ, ·ÊÔ‡ ¤ÁÈÓÂ Ô ÌÔÓ·‰ÈÎfi˜ Ì·ıËÙ‹˜ ÙÔ˘, ·ÎÔÏÔ‡ıËÛÂ, ‚Ú›ÛÎÔÓÙ·˜ ÙÔ ‰ÈÎfi ÙÔ˘ ‰ÚfiÌÔ, Ì›· Ù¯ÓÔÙÚÔ›· ·Ú¿ÏÏËÏ· ÚˆÙÔÔÚȷ΋, Ì ÙÔ˘ ‰·ÛοÏÔ˘ ÙÔ˘. ∞ÚÁfiÙÂÚ· ¿Ú¯ÈÛ ӷ ˙ˆÁÚ·Ê›˙ÂÈ Ì ٷ ‰¿ÎÙ˘Ï· Î·È ÙË Û¿ÙÔ˘Ï·, ÂÙÒÓÙ·˜ ¿Óˆ ÛÙÔ ÌÔ˘Û·Ì¿ Ù· ¯ÚÒÌ·Ù·, Û ·¯‡ ÛÙÚÒÌ·, Î·È ·ÎÔÏÔ˘ıÒÓÙ·˜ Ì›· ·ÔÎÏÂÈÛÙÈο ÂÍÚÂÛÈÔÓÈÛÙÈ΋ ¤ÎÊÚ·ÛË, ‰È΋ ÙÔ˘, Ì ÔÏÏ¿ ÛÙÔȯ›· ÈÌÚÂÛÈÔÓÈÛÌÔ‡, ·ÔÛÒÓÙ·˜ ·ÓÙÔ‡ ÙȘ ÈÔ ÎÔϷ΢ÙÈΤ˜ Î·È ‰Èı˘Ú·Ì‚ÈΤ˜ ÎÚÈÙÈΤ˜. √ ÕÁÁÂÏÔ˜ ¢fiÍ·˜, ›¯Â ÁÚ¿„ÂÈ ÙÔÓ πÔ‡ÏÈÔ ÙÔ˘ 1965 ÛÙËÓ "∞ıËÓ·˚΋": «∏ ˙ˆÁÚ·ÊÈ΋ ÙÔ˘ °ÈÒÚÁÔ˘ ÷Ù˙¿ÎË ·ÚÔ˘ÛÈ¿˙ÂÈ ¤Ó· ·Ïfi Î·È ¤ÓÙÔÓ· ¯ÚˆÌ·ÙÈÎfi Û‡ÓÔÏÔ Ô˘ ˘Ô‚¿ÏÏÂÈ ÙËÓ ·ÙÌfiÛÊ·ÈÚ· Î·È Ô‰ËÁ› ÙËÓ ·›ÛıËÛË Î·È ÙË ÛΤ„Ë Û ÚÔÂÎÙ¿ÛÂȘ Ô˘ ıÂÚÌ·›ÓÔ˘Ó ÙËÓ ·ÓıÚÒÈÓË ·Ó¿Û·…». √ ™Ù¤ÏÈÔ˜ §˘‰¿Î˘, ∫·ıËÁËÙ‹˜ Ù˘ πÛÙÔÚ›·˜ Ù˘ ∆¤¯Ó˘ ÛÙÔ ¶·ÓÂÈÛÙ‹ÌÈÔ ∞ıËÓÒÓ: «TÔ ·ÛÙfi˙Ô ¯ÚÒÌ· Ï¿ıÂÈ ÙÔ ÌÔÙ›‚Ô ÙÔ˘, ÚÔÛ‰›‰ÔÓÙ¿˜ ÙÔ˘ ·Ó·ÁÏ˘ÊÈÎfiÙËÙ· Î·È Ì›· ȉÈfiÙ˘Ë Ï·ÛÙÈÎfiÙËÙ·. ªÚÔÛÙ¿ Û ¤Ó· ÊfiÓÙÔ, ηٿÏÏËÏÔ Ó· ÚÔ‚¿ÏÏÂÈ Î·È Ó· ·Ó·‰Â›ÍÂÈ ÙÔ ı¤Ì·, ·ÔÌÔÓÒÓÔÓÙ·È ÔÈ ÊÔÚ›˜ ÙˆÓ ¯ÚˆÌ·ÙÈÎÒÓ ·ÏÌÒÓ, Ô˘ ˙ˆÓÙ·ÓÂ‡Ô˘Ó Î·È ÂÌ„˘¯ÒÓÔ˘Ó ÙËÓ ÂÈÎfiÓ·. ∏ ‰È›ۉ˘ÛË ÛÙËÓ ÙÚ›ÙË ‰È¿ÛÙ·ÛË ‰ËÌÈÔ˘ÚÁ› ÙËÓ ·›ÛıËÛË ÙÔ˘ ‚¿ıÔ˘˜ ·Ú¿ ÙËÓ ÚÔ‚ÔÏ‹ ÙÔ˘ ÚÒÙÔ˘ ΢ڛˆ˜ ÂÈÎÔÓÈÛÙÈÎÔ‡ ÂȤ‰Ô˘». ∏ ∫·Ú·‚È¿ ÛÙÔÓ ∆‹ÏÂÊÔ ÛÙËÓ "∫·ıËÌÂÚÈÓ‹" Ù˘ 2·˜ πÔ˘Ó›Ô˘ 1987: «√ °ÈÒÚÁÔ˜ ÷Ù˙¿Î˘ Ì¿Á„ Ì ٷ ÏÔ˘ÏÔ‡‰È· ÙÔ˘, ÛÙȘ ·›ıÔ˘Û˜ Ù¤¯Ó˘ "∂ȉ·". §Ô˘ÏÔ‡‰È· ·Ó¿ÁÏ˘Ê· Ì ÙÔ ¿ıÔ˜ Ù˘ ¿ÓÔÈ͢, Úfi‚·ÏÏ·Ó ˙ˆÁÚ·ÊÈṲ̂ӷ fi¯È Ì ٷ ·Ú·‰ÔÛȷο ÈӤϷ, ·ÏÏ¿ Ì ÙËÓ Û¿ÙÔ˘Ï· Î·È Ù· ‰¿ÎÙ˘Ï¿ ÙÔ˘. √È ÙÚÂȘ ·›ıÔ˘Û˜ Ù˘ "ÁηÏÂÚ›" ÛÙÔ ∫ÔψӿÎÈ ÊˆÙÈṲ̂Ó˜ ÁÈ· ÙËÓ ÂÚ›ÛÙ·ÛË Ì ÚÔ‚ÔÏ›˜ ·ÚÔ˘Û›·˙·Ó, ı¤·Ì· Ê·ÓÙ·ÛÌ·ÁÔÚÈÎfi Î·È Ì ٷ ÏÔ˘ÏÔ‡‰È· Ù˘, Ó· ·ÔÛÔ‡Ó ÙÔÓ ı·˘Ì·ÛÌfi fiÏˆÓ ÙˆÓ ÂˆÓ‡ÌˆÓ ÊÈÏfiÙ¯ӈӻ. ∆Ô 1992 Û˘ÌÌÂÙ›¯Â ÛÙËÓ Ù¤Ù·ÚÙË ªÂÛÔÁÂȷ΋ ªÈÂÓ¿Ï ÁÈ· Ù· 500 ¯ÚfiÓÈ· ·fi ÙÔÓ ∫ÔÏfiÌ‚Ô fiÔ˘ Î·È ‰È·ÎÚ›ıËΠ̠ÙÔ ¤ÚÁÔ ÙÔ˘ "∆ÚÂȘ ∫·Ú·‚¤Ï˜". ∆Ô 1993 ÚÔÛÎÏ‹ıËΠ·fi ÙÔ˘˜ Lions £ÂÛÛ·ÏÔӛ΢ Î·È ÙÔ ›‰Ú˘Ì· Ford Î·È ·ÚÔ˘Û›·Û ÙË ‰Ô˘ÏÂÈ¿ ÙÔ˘ ÛÙË Û˘ÌÚˆÙÂ‡Ô˘Û· Ì ÌÂÁ¿ÏË ÂÈÙ˘¯›·. ∆Ô 1998 ¤ÎıÂÛ ٷ ¤ÚÁ· ÙÔ˘ ÛÙËÓ ·›ıÔ˘Û· "Grekiska Kulturhuset St Johannes Theologen" ÛÙËÓ ™ÙÔίfiÏÌË ÚÔÛÎÂÎÏË̤ÓÔ˜ ·fi ÙÔ ÔÏÈÙÈÛÙÈÎfi ΤÓÙÚÔ Ù˘ ∂ÏÏËÓÈ΋˜ ÚÂۂ›·˜ Ù˘ ™Ô˘Ë‰›·˜. ∞ÎÔÏÔ‡ıËÛ·Ó ·ÙÔÌÈΤ˜ Î·È ÔÌ·‰ÈΤ˜ ÂÎı¤ÛÂȘ Û ∞ı‹Ó· Î·È ¿ÏϘ fiÏÂȘ. Œ¯ÂÈ ÛÙÔ ÂÓÂÚÁËÙÈÎfi ÙÔ˘ 55 ÂÎı¤ÛÂȘ ·ÙÔÌÈΤ˜ Î·È ÔÌ·‰ÈΤ˜, ÛÙÔ ÂÛˆÙÂÚÈÎfi Î·È Â͈ÙÂÚÈÎfi (°·ÏÏ›·, πÙ·Ï›·, πÛ·Ó›·, ∫·Ó·‰¿, ™Ô˘Ë‰›· Î·È ·ÏÏÔ‡) Î·È ÔÏÏ¿ ¤ÚÁ· ÙÔ˘ ÎÔÛÌÔ‡Ó ÌÂÁ¿Ï˜ ȉȈÙÈΤ˜ Û˘ÏÏÔÁ¤˜ Î·È ÈÓ·ÎÔı‹Î˜ Û ÔÏfiÎÏËÚÔ ÙÔÓ ÎfiÛÌÔ.
EΉ›‰ÂÙ·È ·fi ÙȘ È·ÙÚÈΤ˜ ÂΉfiÛÂȘ “B·ÁÈÔÓ¿ÎË” Ì ¯ÔÚËÁ›· Ù˘ PFIZER HELLAS. OÈ ·fi„ÂȘ ÛÙÔ Î›ÌÂÓÔ ÂÎÊÚ¿˙Ô˘Ó ÌfiÓÔ ÙÔ˘˜ Û˘ÁÁÚ·Ê›˜ Î·È ‰ÂÓ ·ÓÙÈÚÔÛˆÂ‡Ô˘Ó ÙË ¯ÔÚËÁfi ÂÙ·ÈÚ›·.