бювивй, бдв бдбд fi бд йебдappleбд
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- Ethan O’Brien’
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1 б воб втбєбюв в втв бювивй, бдв бдбд fi бд йебдappleбд виappleбдвпбд appleбдвибд- в вибд б вийев ви, в бд бд, б бд ви бп игбдви бд б вибд бє б бдви в бдappleбдв вови, б йебд б бдбд: б вийев ви, бп игбдви бд б вибд бє, б бд в бдappleбдfi во, игбдбдйе 48, бд, б.: , , Fax: , , б -mail: в в бювивй (Hcy) бд в бд йев бдв appleви в apple appleв ви игйе. H apple appleв ви игйе, бдfi бювивй бд бдбд вибдбд бдв бдбд fi бдбдappleв бд appleбдв бд бдбдfiapple. бю бд бдfi в ви appleви Hcy вив бдв бдбд fi в в бдappleв в вийе, бд в - бд fi бдв бдбд fi бдapple бдfi бдбд fiбд бд йеfiбд appleбдвибдв вибд. б бдappleйебд в вп в бдfi вп йебд- appleбд бд вив бд appleappleв бд Hcy бд в бдappleйе fi бд applefiбд в ви. б виfi fi в в бд впви бдвпви appleв в бдв бдбд fiви (CVD), fiapple бд CRP (C-бдв бд appleвй), IL-6 (ви-6) бд Lp(a) (appleappleвй-бд). б вп бд в впбд в йебдappleбд бд fi йе appleв бд fiви ви бдвпви apple- в в CVD, fi йебдappleбд бд applefi йебд в applefiбд бдв бдбд fiви appleбдвибдв вибд. в бдв в вибд apple- бд бд бдйе бдбд ви впйе бдвпви appleв в бдйе бд appleв бд йебдappleбд бдв бдбдfi в бд appleбдвибд вибд. б в в вп: вивй, бдв бдбд fi, йебдappleбд виappleбдвпбд, fiappleбдви в в ви - игбдfi вивй в бювивй (Hcy) бд в бд йев бдв appleви в apple appleв ви йе. в йе- вп бд fi в fi в в бдв бдбд. б, 100. в бд бдв appleв ви 2.7. йе, бд бдвивп 3.2., бдбдв fi впбд 3.6., бд в бд бд бд бдбдвп (бд 100.) appleв ви йе. в бд в fi appleви в в йе Hcy бдapplefi йе бд вл- бдбд бд вибд appleбдapple 181
2 бювивй, бдв бдбд fi бд йебдappleбд виappleбдвпбд ви бд ви., fiapple ви DNA, appleвк, apple- в бд вив бдбд (Hankey and Eikelboom, 1999). бю в бдв Hcy бд в в, в бдвив бд appleбдбдйеви- (Hankey et al., 2004), fiapple бдбд б fi- бд 1. в вив Hcy appleвпбд appleбдви- впвл вп в бдвивп, в вивпбд вив appleбдбдв fi (Moat et al., 2004). в вивй ви appleвпбд (thcy) бдбдв бд в в йе, ви- в в в, бдбдйебд бд в в вивй бдбд (Hankey and Eikelboom, 1999). вт б fiбд 2 appleбдвивпвлбд в вп в Hcy appleви вив appleвпбд ви бдбд. б, 98-99% Hcy ви в в (в вив = ви-, вп в вив бд = Hcy вивлвив appleвй вивй) бд виapplefiapple бдбд- йебд (вив = вивй). в в appleв apple бд бд appleвп вп бдapplefi бд. имвив йев бд в Hcy - бдв 5 бд 15 mol/l, appleйевив в бд < 10 mol/l. б fi в Hcy бд mol/l вп бд appleбд вивкбдбд, mol/l бд в вп вивкбдбд, mol/l бд бд вивкбдбд. бд бдбд вивкбдбд appleбдвивпвлбд в бдбд 1. в вивй (thcy) ви бд- бд бдвивп бд. бд appleappleв бд thcy ви впв бд 10% вив бд бдapplefi вибд- в бд бд. вт fiappleбдви appleбдбд- бд бдв thcy бдвп в впбд appleбдвибд applefiв ви. б appleбдвп-, в бд, appleвп впбдбд, бдвп бд в вп fi fiapple бдappleвпбд, бдбдв в бд бд виappleйевив fi appleбдв вив бдв thcy. бювивй бд б appleвпйебд б в бд 35 appleappleви fiбд в бдвиappleйе впapple fi вивкбдбд appleвмappleвп бдappleвп- йебд, бдйе appleбдбдйе fi: бдйе вивибд бд appleв вивп appleappleв бд thcy appleвп- бд в ви бдвив appleapple бдappleвпйебд бд applefiви йебдвпви бдapplefi в бдбд ви вибд- в ви (McCully, 1969; McCully and Wilson, 1975). Tбд бдвив бд appleappleв бд вивй бдбд в ви вийе бдйев бд йев -, бдйе apple бдбдfi бдfi apple- fiв бд в бдбд ви вибдв ви - appleбдвибдв вибд (Ridker et al., 1999; Cattaneo, 2001). б appleв в в в ви в fi fi fi бд вивкбдбд, бд- вп бд appleбд бдв thcy влбд бд- в бдбд fi (Boushey, 1995). бю Ridker бд вивп ви (1998) бд appleapple в в впбд 3, в бд бд appleappleв бд ви- вй 122 appleбдвибдв вибд appleви виappleв бд бдбдfi бдfi applefiв в бдбд ви вибдв ви бд 244 appleбдвибдв вибд в бд бд бд в applefi бдappleбд appleви appleбдв бд ви. бд- appleбд fi вибд appleви бд thcy >20.7 б fiбд 1. бєбдвп в fi appleбдбдйеви вивй бдappleвп бд йевивпв бд бдapplefi бдвй (бдв бд appleви appleви- бд ви appleбд) бдapplefi 5-йеви-бдвмв виfi ( бдв бд бдви appleбдбдappleбд fiви ви в бд бд- впбд бдapplefi бд 12 ). вт бд в fi в бдвив вивй бдвлбд вибдйе в вп- -вийевп вибдйе бд бдappleбд ви бд
3 б fiбд 2. бю в бдв в apple ви Hcy appleвпбд ви бдбд. mol/l (95 бдбдбд йев ) бд fi - в ви 2.6 бд бдбдfi бдfi applefiв / в - бдбд ви вибдв ви в вибд appleви бд вив в Hcy. бю apple- в apple в ви бдapplefi бдвив Hcy бд бд- вп бдapplefi впви в appleв в appleбдвп в в ви бд бдв бдбд fi (вп- appleбд, виappleбдбд, бдбдв в бд-, бдбд виappleв бд). игв бд вп в ви бдappleв fi бдв thcy appleбд fi бдйевп- бд, fi бд appleв впйе бд йеfi (Symons, 2002). бю Faraci бдбдв fi виappleвивкбдбд appleбд appleбдбд вобю (в в ви б влви) бдapplefi в йе бд бд в бдви ( в appleбдбд- вобю) appleвпбд в fi stress (Faraci, 2003). бю в вибдв бд бдбдв fi бдвив - вив бд Hcy appleбд бд apple бд в бдв appleбд- бд вибд (ви ви TNF-бд) бд appleвк appleви appleвпви бдбд - вивп. вт бд вп в Faraci appleвп- виappleбд вивк вивп ви бд- бдв бд appleви appleвпбд бдapplefi виapple- вивкбдбд appleбдбдfiвлбд, в бд виappleбд ви бдбдв бд бд впбд в бдfiбд бдв бд ви- в бд (Faraci, 2004). вт в бдбд 2 бдбдв бд appleбдбдвп appleйебд бд в apple Hcy appleвп бдйев бд йев. в вив Hcy appleвпбд бд бдfi- вибд бдбдappleбдбд бд в ви впв в бд бд, бд apple бдfi бдapplefi бдви appleбдви- бд вибд. б applefi бдвивп в бдбдбд fi виappleвп- бд в бдв Hcy бд вибд ви в ви (Andersson et al., 1992; Hak et al., 2001). бєбдв бдбд fi бд вибд в бд applefi appleви appleв apple бд, appleбд - бд appleapple бдв бдбд fiви (CVD) вибд в. втв бд бд бдбд- вп ви в ви 2003 б бд бєбдв - б бдбд (American Heart Association) бдв бдбд fi бд 1 бдбд йебдвпви вибд бд бд бдapplefi бдfi бд - fiбд (Heart Disease and Stroke Statistics, 2003 Update). в бдfi applefi йебдвп бдapplefi бдв бдбд fi в йе, виfi бдйеfi вибд appleви appleйебдви бдapplefi бдви ви- бдвивпбд, fi бд ви appleйевив (Heart Disease and Stroke Statistics, 2003 Update). игбд appleв б бдв в впapple в apple бдв бдбд fiви. бю applefi appleapple- 183
4 бювивй, бдв бдбд fi бд йебдappleбд виappleбдвпбд ви бд ви. в бдбд 1. б бд бювивкбдбд. бдв бдбд fiви вибд бдв бдбдбд fi йевп, ви впв виfi вп бд в бдбд ви вибдв ви. б appleapplefiйебд, ви- бд бд appleвп йеfiбд бд бдвп виfiбд в бдвивп бдв. б, 38% вибд йебд appleйевпви fi fi в ви вп бдapplefi в бд бдfi бдв вп в бдбд, в йебд ви fi 25% бдв (Bello and Mosca, 2004). в appleapple бдв бдбд fiви бдвивп бдвпбд бд fiappleбдви- вибдбд. б, fi fi бд - бд fiappleбдви, fi applefi бдвив - бд appleйебдfiбд бд бдв бдбдвп вибд- бдбд (Kannel et al., 1976). в в бдapplefi 1993 Wenger бд вивп ви (Wenger et al., 1993) бдв бд fi бдв бдбд fi бд 1 бдбд йебдвпви бд вибд appleви бд бд- в 60. бдappleбд виappleбдвпбд (бю) бд бдв бдбд fi в йебдappleбд виappleбдвпбд (бю) в в appleв бд applefi бдв бдбд- fiви appleбдвибд вибд в - ви в вп fi. appleбдбдappleвп appleбдйе бд вп в в - apple вивлбд в в бд (Stampfer et al., 1991; Van Baal et al., 2000). вт вп- apple appleв в в бдбдв бд бд - бдвп 50% appleйебдfiбд бд бдв бдбд fi appleбдвибдв вибд appleви вп- бдбд йебдappleбд fiбд в бдвив appleви в впбдбд (Grodstein et al., 1997; Genazzani et al., 2000). б йебд fi бдappleв - бдбд appleв вибд бдapplefi 2 вп вибдappleв в : HERS (Heart and Estrogen/Progestin Replacement Study) (Hulley et al., 1998) бд WHI (Women Health Initiative) Study (Writing Group for Womenбпs Health Initiative Investigators, 2002). в HERS впбд бд бдв вибдappleв в бю бд в виappleбдйе applefi бдв бдбд fiви. б fi fi йев appleвп бд бдви appleви в в йебд в в ви- бд в (HERS бд WHI), в вибд бд бдбд fi в бд бдвпв б бд- в бдбдfi бєв в ви бд бдв бдбд fi, бдйе бд в бдви бю. - вив бдвп appleбдвп в в ви бд бдвпappleви бдв бдбд fiви бд: - вивй (Hcy), C-бдв бд appleвй (CRP), appleappleвй (бд) (Lp-a) бд ви 6 (IL- 6) (Davison and Davis, 2003). вибд fi бю бд бд appleappleв бд Hcy бдбд; бю Davison бд Davis, в бд впйе бдбдfiapple, бдбд fi бд в бдв в бд - fiбд в ви вп в бдвп appleв бд thcy (Davison and Davis, 2003). вт в виappleв бд- бд бдв бд Evio бд вивп (2000) - бд appleв бд йебдappleбд 184
5 в бдбд 2. в йебд бд в apple Hcy appleвп бдappleвпйебд. вив бд Hcy. бд бдв fi бд йеfi 42 appleбдвибд- в вибд, apple вибдappleбд apple в fi (бдapplefi fiбд бдapplefi в в бд). втвиappleв бдбд fi бд бдapplefi ви в в бд (бдвп бд бд бдapplefi fiбд) вп вивпбдбд в appleвп- бд Hcy (Evio et al., 2000). б йебд бд appleбдбдappleвп, бдapplefi fi- бд fi ( йебдappleбд - вивлвив fi бдбд - бдв fi) йебдappleбд бдвл appleбд- fi (в виapplefi йеfi) в йе fi appleбдв Hcy - appleбдвибдв вибд бд вп вп -. бю Yildirir бд вивп (2002) в - бд бд appleappleв бд Hcy 46 appleбдвибдв ви- бд вп бдapplefi бдapplefi ви fiбд ви- влвив fi appleйе - в виapplefi бд в бдappleбд Hcy (бд в ви впв ) вп бдapplefi 6 (Yildirir et al., 2002). бю Madsen бд вивп (2002) бд вибдappleв в 209 вибд- в бд бд appleappleв бд вивй вп бдapplefi 5 в 7 fiбд per os йебдappleбд. бдapple- бд fi 103 (бдapplefi 209) вибд appleви в бд- бд бю бд fi в вив thcy в 106 вибд appleви в в бдбд бдбд йебдappleбд (Madsen et al., 2002). в fi apple в бдвп Hcy. б виfi appleв ви бдapplefi бд вибдappleв в Celik бд вибд (2002) apple вив бд бд бдappleв бдбд appleви fi-, Ca +2 вивлвив fi бд appleappleв бд Hcy appleвибд вибд. в йе fi fi бд вивлвив бд fiбд бд Hcy бдвп 29%, fi бд Ca +2 бд appleбдв бд вп ви 4% (Celik et al.,2002). в бдбд бд бдбд (SERMs: Selective Estrogen Receptor Modulators) appleбд- в Hcy ви appleвпбд (Albert, 2000; Walsh et al., 2000). бю De Leo бд вивп (2001) вибдappleбд 45 appleбдвибдв ви- бд 60-70, бд ви бд- бд 60 mg/day ( 26 бдapplefi 45) placebo ( виapplefiapple 19) бд в бд fi. игв бд - вивй бд appleв бдfi apple ви бдвп 3 бд бд fi бдвив appleви впбдбд бдбд appleбдвибдбд бдвп 20% thcy (De Leo et al., 2001). бю в вивп бд вивп (2003) бд appleapple в бдв бд ви- appleв бдбд fi вибд appleви бд бдви- в thcy бд в бдбд 18 йебдappleбд бд- бд впбд вп ви 28% ( thcy) (Christodoulakos et al., 2003). втви- вп (бд fi вибд в appleви в бдбд бдбд) appleбдбдбд бд вп ви 14.5% thcy вп бдapplefi йебдappleбд 18. иг вп бд appleв бд вибдбд, fi Hcy бд бдв fi бдвп applefi в - бдв бдбд fiви бд бю -, fi йебд appleв бд fi йевп бдappleв бд- 185
6 бювивй, бдв бдбд fi бд йебдappleбд виappleбдвпбд ви бд ви. в бдбд 3. б appleв бд в бд в йебдappleбд ви в. [ бдв, бдвп-,, + appleбдfi: бд appleйе appleбдfiви йебдappleбд fiбд, CRP: C бдв бд apple- вй, thcy: вивй бдбд, IL-6: ви 6, Lp(a): appleappleвй (бд)]. бд бдapplefi бю applefi бдв бдбд- fiви appleбдвибдв вибд. б ви- fi fi в в бд appleви в вп - fi, fi бд SERMs ви виapplefi- appleви бдвпви appleбдвп в в ви бд бдв бдбд fi бд в бдв. б в в applefi вибд ви виapplefiappleви бдвпви appleв в [CRP, IL-6, Lp(a)] fiбд в йебдappleбд ( fiбд, fi, SERMs). б applefi ви в в CRP apple бд бдappleв - йе виfi applefi в (Albert, 2000). игбд бдбдв CRP apple бд бд бдбдв вибд appleви в ви в ви в впappleбд бдйебд appleвпбд, fi вл- fi бд бдбд бдapplefiбд-йеfi (Ridker, 2001). в CRP в вийе бд- в бд бдйеви (Van der Meer et al., 2002; Sitzer et al., 2002; Rerkasem et al., 2002). б бдappleбд бдбд appleбдбдв fi йебдappleбд бдapplefi fiбд appleбд appleбдвибдв вибд бд бдв CRP (Vehkavaara et al., 2001; Herrington et al., 2001; Skouby et al., 2002). бд в бдв вп fiбд в appleвпвлви CRP (Vehkavaara et al., 2001; Decensi et al., 2002), fi бдвивп (Prelevic et al., 2002), бдбд в appleвпвл (Walsh et al., 2000). в вибд ви 6 (IL-6) бд в бд виfi appleбдв бд appleбд бдв бд - бд вп бд в бд в бд вийе CRP, в appleбдfi fi бд бдбдбд fi (Yudkin, 2000), бдйе appleбд бдв ви в fiви бд бдвивп fiбд ви бдбд, бдйеfi бд виfiбд бдappleбд-. впбд виappleйебдвпви виapplefiви - appleв, бд бдвив бд appleappleв бд IL-6 влбд бд ви, виappleв бд бд в в appleви appleбдвибдбд, бдбдвп appleви бдappleв appleбдвп в в ви бд бдв бд- бд fi (Yudkin et al., 2000). в - йебдappleбд в бдв в в бд- IL-6 бдвп (Zanger et al., 2000; Walsh et al., 2001) бдвивп (Pradham et al., 2001), бд (Straub et al., 2000; Scheidt-Nave et al., 2001). вибд appleбдвпбд в в ви, бд apple бдбдappleйе бдбд бд Lp(a), appleви в fiapple бд вивй бдвиfiбд бдйе- в бд appleйев в fi. в бдappleappleappleвй (бд) appleви бд бд appleappleвй (бд) в бд fiбд appleбдfi бд бдбдвлбд in vitro в. ви- бд в бд бдappleв бд бдбд в fi- ви, бдв бдappleappleappleвй (бд) в appleбд бдapplefi fi apple ви appleбд- fiви (Sangrar et al., 1995). бю Shlipak бд ви- вп 2000 JAMA бдв бд fi бд бдви- в бд appleappleв бд appleappleвй (бд) влбд бдвив бдв бд бдбдбд fi вибд-. вт fi в appleви бдбдappleйебд в бдapple- йе бд бд ви appleви бдв - бд виappleв бдбд fi appleбдв apple йебдappleбд бдapplefi fiбд - в бдв вп в appleбд бдв Lp(a). 186
7 б appleвп вп бд бдвп Lp(a) (Perrone et al.,1996; Hanggi et al., 1997; Llyod et al., 2000), вп appleбдбдйе (Walsh et al., 1998; Prelevic et al., 2002; Vigna et al., 2002; Smolders et al., 2002). вт appleбдбд 3 бдбд виappleвп бд бдappleв - бдбд в бд в йебд- appleбд ви appleбдбдappleвп appleбдв в appleви впвлбд бд вибдбд fiбд бдвп apple appleбдвп бд бд- в бдбд fi. б applefi бдвив appleвив бдfi бд- бд бд бд CRP(high sensitivity) (Willerson and Ridker, 2004). втвиappleвпбдбд втвивлбд йебд в бд fi в бд бд applefi- бд вивп бдappleв бдбд бдбдв в ви в бдв бд бд бдв бдбд fiви (Taubes, 2002). в apple- бдбдfi бдви apple бд бд в applefi бд applefi в appleбд- бдв бдбд fiви. б appleви в - бд бдfiбд fi бд вп в - [thcy,crp, IL-6, Lp(a)] бд бдвп apple в бдв appleбдбдв - бд apple в бдв бдбд fiви. б бд бдappleбдбд apple бд бдбдйев бд бд бдйев вив в бдвивп в fi appleйевиfi, бдвпбд бд бд в. игв бдвив йебд бдбд fi бд бд appleбд в в бд вп бд бд в бд- йебдappleбд (бю). б йебд виappleвп- бдв в appleapple бю ви в. б appleв apple бд бдappleв йе fi в йе вив в йебд ви appleapple бдв бдбд fiви - appleбдвибдв вибд. б appleбп fiбд бд appleбдбдappleвп виappleбдбд fi в - впвлбд в вибд thcy apple в бд appleбдв apple йебдappleбд, бд appleви в в в бдapple apple- fi в бд бдв бдбд fi. в - йебдappleбд appleбд вивй, бдвп бдвиfi в бд бдfi fi бдвп applefi- бдв бдбд fiви. имбдбд, apple appleбдfi, fi йебдappleбд appleв apple бд - бд appleбдвибдв вибд fi бд applefi бдв бдбд вибдвп, бдвп fi бд ви appleбдбдвп fiви: (бд) бд бдбд бд виappleвп, fiapple вп, вив в, бдйебд appleбд, () бд applefi applefi бд () бд applefi бдбд ви ви- в вибд (apple бд). Homocysteine, cardiovascular disease and hormone replacement therapy in postmenoposal women E. Deligeoroglou, P. Tsimaris, A. Deliveliotou 2nd Department Obstetrics and Gynaecology, Areteio Hospital, Athens, Greece Correspondence: E. Deligeoroglou, б reteio Hospital, 48 игarathonos str., Brilissia, Athens, Greece el.: , , Fax: , , edeligeo@aretaieio.uoa.gr Summary Homocysteine (Hcy) is a sulfated amino acid and is deriving from methionine. The production pathway of Hcy from methionine, the Hcyбпs metabolism, as well as the association of Hcy with cardiovascular disease (CVD) are extensively illustrated in this review article. The precise mechanism by which Hcy is involved in the pathogenesis and establishment of CVD, which is the leading cause of morbidity and mortality in postmenopausal women, is not yet completely understood. We reviewed the effect of all different kind of hormone replacement therapy on homocysteine blood levels and we concluded that the majority of them lead to a remarkable reduction. This does not apply to the HRT effect on other independent predictive factors of cardiovascular disease, such as CRP, IL-6 and Lp (a). Hormone replacement therapy should only be recommended safely for CVD prevention in postmenopausal women, if a positive correlation of HRT with all predictive factors of CVD is established. More research is needed in order to clarify the exact role of each independent predictive factor, as well as the hormone replacement therapy effect on cardiovascular system of postmenopausal women. 187
8 бювивй, бдв бдбд fi бд йебдappleбд виappleбдвпбд ви бд ви. Key words: homocysteine, cardiovascular disease, hormone replacement therapy, menopause. бдбд Albert, M.A. (2000) The role of C-reactive protein in cardiovascular risk. Curr. Cardiol. Rep. 2, Andersson, A., Brattstrom, L., Israelsson, B. et al (1992) Plasma homocysteine before and after methionine loading with regard to age, gender, and menopausal status. Eur. J. Clin. Invest. 22, Bello, N. and Mosca, L.(2004) Epidemiology of coronary heart disease in women. Progr. Cardiovasc. Dis. 46, Boushey, C.J., Beresford, S.A., Omenn, G.S. et al. (1995) A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA, 274, Cattaneo, M. (2001) Hyperhomocysteinemia and thrombosis. Lipid, 36(Suppl 1), Celik, H., Ayar, A., Tug, N. et al. (2002) Effects of tibolone on plasma homocysteine levels in postmenopausal women. Fertil. Steril. 78, Christodoulakos, G., Lambrinoudaki, I., Panoulis, C., et al. (2003) Effect of raloxifene, estrogen, and hormone replacement therapy on serum homocysteine levels in postmenopausal women. Fertil. Steril. 79, Davison, S. and Davis, S.R. (2003) New markers for cardiovascular disease risk in women: impact of endogenous estrogen status and exogenous postmenopausal hormone therapy. J. Clin. Endocrinol. Metab. 88, De Leo, V., Morgante, G., Lanzetta, D. et al. (2001) Randomized control study of the effects of Raloxifene on serum lipids and homocysteine in older women. Am. J. Obstet. Gynecol. 184, Decensi, A., Omodei, U., Robertson, C. et al. (2002). Effect of transdermal estradiol and oral conjugated estrogen on C-reactive protein in retinoid-placebo trial in healthy women. Circulation, 106, Evio, S., Tiitinen, A., Turpeinen, U. et al. (2000). Failure of the combination of sequential oral and transdermal estradiol plus norethisterone acetate to affect plasma homocysteine levels. 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9 Ridker, P., Manson, J.E., Buring, J.E. et al.(1999) Homocysteine and risk of cardiovascular disease among postmenopausal women. JAMA, 281, Ridker, P.M., Glynn, R.J. and Hennekens, C.H. (1998) C- reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation, 97, Ridker, P.M. (2001) High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation, 103, Sangrar, W., Bajzar, L., Nesheim, M. et al. (1995) Antifibrinolytic effect of recombinant lipoprotein (a) in vitro is primarily due to attenuation of t-pa-mediated Glu-plasminogen activation. Biochemistry, 94, Scheidt-Nave, C., Bismar, H., Leidig-Bruckner, G. et al. (2001) Serum interleukin-6 is a major predictor of bone loss in women specific to the first decade past menopause. J. Clin. Endocrinol. Metab. 86, Shlipak, M., Simon, J., Vittinghoff, E. et al. 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(2000) The effects of hormone replacement therapy and raloxifene on C-reactive protein and homocysteine in healthy postmenopausal women: a randomized, controlled study. J. Clin. Endocrinol. Metab. 85, Wenger, N.K., Speroff, L. and Packard, B. (1993) Cardiovascular health and disease in women. N. Engl. J. Med. 329, Willerson, J.T. and Ridker, P.M. (2004) Inflammation as a cardiovascular risk factor. Circulation, 109(21Suppl. 1):,II2-10. Writing Group for Womenбпs Health Initiative Investigators: Rossouw, J.E., Anderson, G.L., Prentice, R.L. et al. (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA, 288, Yildirir, A., Aybar, F., Tokgozoglu, L. et al. (2002) Effects of hormone replacement therapy on plasma homocysteine and C-reactive protein levels. Gynecol. Obstet. Invest. 53, Yudkin, J.S., Kumari, M., Humphries, S.E. et al. (2000) Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis, 148, Zanger D., Yang B.K., Ardans J. et al. (2000) Divergent effects of hormone replacement therapy on serum markers of inflammation in postmenopausal women with coronary artery disease on appropriate medical management. J. Am. Coll. Cardiol. 36, бєб б б в бєб 13/6/2005 б б еёвоб б в бюб бєв 7/7/
The WHI 12 Years Later: What Have We Learned about Postmenopausal HRT?
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