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Semin Vasc Med 2004; 4(2): 135-144
DOI: 10.1055/s-2004-835371
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001 USA.

The Lost Promise of Hormone Replacement Therapy and Heart Disease

Angela H.E.M Maas1
  • 1Department of Cardiology, Isala Klinieken, Zwolle, The Netherlands
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Publication History

Publication Date:
11 October 2004 (online)

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Since the first secondary prevention trials were published in 1998, the prospect of hormone replacement therapy to prevent atherosclerotic heart disease in postmenopausal women has changed dramatically. Early harmful effects of hormone replacement therapy and lack of beneficial effects on coronary heart disease event rates in high-risk women have challenged the beneficial results gleaned from observational studies in the past. In this article, the effects of estrogens on lipids, hemostatic parameters, inflammation, and the vascular wall are described. The discrepancies that have arisen between the previous observational studies and recent randomized clinical trials are discussed: The current available data indicate that estrogens are beneficial to healthy endothelium but are harmful once atherosclerotic disease has developed.

KEYWORDS

Estrogen - atherosclerosis - hormone replacement therapy - coronary heart disease

REFERENCES

  • 1 The North American Menopause Society (NAMS) . Report from the NAMS advisory panel on postmenopausal hormone therapy.  Menopause. 2003;  10 6-12
    CrossrefPubMedGoogle Scholar
  • 2 Michels K B, Manson J E. Postmenopausal hormone therapy. A reversal of fortune.  Circulation. 2003;  107 1830-1833
    CrossrefPubMedGoogle Scholar
  • 3 Grodstein F, Clarkson T B, Manson J E. Understanding the divergent data on postmenopausal hormone therapy.  N Engl J Med. 2003;  348 645-650
    CrossrefPubMedGoogle Scholar
  • 4 Shearman A M, Cupples L A, Demissie S et al.. Association between estrogen receptor α variation and cardiovascular disease.  JAMA. 2003;  290 2263-2270
    CrossrefPubMedGoogle Scholar
  • 5 Herrington D M. Role of estrogen receptor-α in pharmacogenetics of estrogen action.  Curr Opin Lipidol. 2003;  14 145-150
    CrossrefPubMedGoogle Scholar
  • 6 Wenger N K. Coronary heart disease: an older women's major health risk.  BMJ. 1997;  315 1085-1090
    PubMedGoogle Scholar
  • 7 Schouw van der Y T, Graaf van der Y, Steyerberg E W, Eijkemans M J, Banga J D. Age at menopause as a risk factor for cardiovascular mortality.  Lancet. 1996;  347 714-718
    CrossrefPubMedGoogle Scholar
  • 8 Hu F B, Grodstein F, Hennekens C H et al.. Age at menopause and risk of cardiovascular disease.  Arch Intern Med. 1999;  159 1061-1066
    CrossrefPubMedGoogle Scholar
  • 9 Hanke H, Hanke S, Ickrath O et al.. Estradiol concentrations in premenopausal women with coronary heart disease.  Coron Artery Dis. 1997;  8 511-515
    PubMedGoogle Scholar
  • 10 Bairey Merz C N, Johnson B D, Sharaf B L et al.. Hypoestrogenemia of hypothalamic origin and coronary artery disease in premenopausal women: a report from the NHLBI-sponsored WISE study.  J Am Coll Cardiol. 2003;  41 413-419
    PubMedGoogle Scholar
  • 11 Barrett-Connor E, Goodman-Gruen D. Prospective study of endogenous sex hormones and fatal cardiovascular disease in postmenopausal women.  BMJ. 1995;  311 1193-1196
    PubMedGoogle Scholar
  • 12 Rexrode K M, Manson J E, Lee I M et al.. Sex hormone levels and cardiovascular events in postmenopausal women.  Circulation. 2003;  108 1688-1693
    CrossrefPubMedGoogle Scholar
  • 13 Willerson J T, Kereiakes D J. Endothelial dysfunction.  Circulation. 2003;  108 2060-2061
    CrossrefPubMedGoogle Scholar
  • 14 Burke A P, Farb A, Malcom G, Virmani R. Effect of menopause on plaque morphologic characteristics in coronary atherosclerosis.  Am Heart J. 2001;  141 S58-S62
    CrossrefPubMedGoogle Scholar
  • 15 Matthews K A, Meilahn E N, Kuller L H, Kelsey S F, Caggiula A W, Wing R R. Menopause and risk factors for coronary heart disease.  N Engl J Med. 1989;  321 641-646
    CrossrefPubMedGoogle Scholar
  • 16 Meilahn E N, Kuller L H, Matthews K A, Kiss J E. Hemostatic factors according to menopausal status and use of hormone replacement therapy.  Ann Epidemiol. 1992;  2 445-455
    PubMedGoogle Scholar
  • 17 Hak A E, Polderman K H, Westendorp I C et al.. Increased plasma homocysteine after menopause.  Atherosclerosis. 2000;  149 163-168
    CrossrefPubMedGoogle Scholar
  • 18 Mendelsohn M E, Karas R H. The protective effects of estrogen on the cardiovascular system.  N Engl J Med. 1999;  340 1801-1811
    CrossrefPubMedGoogle Scholar
  • 19 Williams J K, Adams M R, Herrington D M, Clarkson T B. Short-term administration of estrogen and vascular responses of atherosclerotic coronary arteries.  J Am Coll Cardiol. 1992;  20 452-457
    PubMedGoogle Scholar
  • 20 Collins P, Rosano G M, Sarrel P M et al.. 17 beta-Estradiol attenuates acetylcholine-induced coronary arterial constriction in women but not in men with coronary heart disease.  Circulation. 1995;  1 24-30
    PubMedGoogle Scholar
  • 21 Herrington D M, Espeland M A, Crouse III J R et al.. Estrogen replacement and brachial artery flow-mediated vasodilatation in older women.  Arterioscler Thromb Vasc Biol. 2001;  21 1955-1961
    PubMedGoogle Scholar
  • 22 Koh K K. Can a healthy endothelium influence the cardiovascular effects of hormone replacement therapy?.  Int J Cardiol. 2003;  87 1-8
    CrossrefPubMedGoogle Scholar
  • 23 Koh K K, Kang M H, Jin K D et al.. Vascular effects of estrogen in type II diabetic postmenopausal women.  J Am Coll Cardiol. 2001;  38 1409-1415
    CrossrefPubMedGoogle Scholar
  • 24 Koh K K. Effects of estrogen on the vascular wall: vasomotor function and inflammation.  Cardiovasc Res. 2002;  55 714-726
    CrossrefPubMedGoogle Scholar
  • 25 Mikkola T S, Clarkson T B. Estrogen replacement therapy, atherosclerosis and vascular function.  Cardiovasc Res. 2002;  53 605-619
    CrossrefPubMedGoogle Scholar
  • 26 Mori T, Durand J, Chen Y F, Thompson J A, Bakir S, Oparil S. Effects of short-term estrogen treatment on the neointimal response to balloon injury of the rat carotid artery.  Am J Cardiol. 2000;  85 1276-1279
    CrossrefPubMedGoogle Scholar
  • 27 Chandrasekar B, Nattel S, Tanguay J F. Coronary artery endothelial protection after local delivery of 17 beta-estradiol during balloon angioplasty in a porcine model: a potential new pharmacologic approach to improve endothelial function.  J Am Coll Cardiol. 2001;  38(5) 1570-1576
    CrossrefPubMedGoogle Scholar
  • 28 Losordo D W, Kearny M, Kim E A, Jekanowski J, Isner J M. Variable expression of the estrogen receptor in normal and atherosclerotic coronary arteries of premenopausal women.  Circulation. 1994;  89 1501-1510
    CrossrefPubMedGoogle Scholar
  • 29 The Writing Group for the PEPI-trial . Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women.  JAMA. 1995;  273 199-208
    CrossrefPubMedGoogle Scholar
  • 30 Shlipak M G, Chaput L A, Vittinghof E et al.. Lipid changes on hormone therapy and coronary heart disease events in the Heart and Estrogen/Progestin Replacement Study (HERS).  Am Heart J. 2003;  146 870-875
    CrossrefPubMedGoogle Scholar
  • 31 Bittner V. Estrogens, lipids and cardiovascular disease: no easy answers.  J Am Coll Cardiol. 2001;  37 431-433
    CrossrefPubMedGoogle Scholar
  • 32 Shlipak M G, Simon J A, Vittinghof E et al.. Estrogen and progestin, lipoprotein (a) and the risk of recurrent coronary heart disease events after menopause.  JAMA. 2000;  283 1845-1852
    CrossrefPubMedGoogle Scholar
  • 33 Rosano G M, Fini M, Onorati D, Mercuro G. Hormone replacement therapy and/or lipid-lowering drugs for menopausal women with hypercholesterolaemia.  Eur Heart J. 2000;  2 (Suppl G) G17-G22
    PubMedGoogle Scholar
  • 34 Herrington D M, Howard T D, Hawkins G A et al.. Estrogen-receptor polymorphisms and effects of estrogen replacement on high-density lipoprotein cholesterol in women with coronary disease.  N Engl J Med. 2002;  346 967-974
    CrossrefPubMedGoogle Scholar
  • 35 Rosendaal F R, Helmerhorst F M, Vandenbroucke J P. Female hormones and thrombosis.  Arterioscler Thromb Vasc Biol. 2002;  22 201-210
    CrossrefPubMedGoogle Scholar
  • 36 Scarabin P Y, Oger E, Plu-Bureau G. Differential association of oral and transdermal oestrogen replacement therapy with venous thromboembolism risk.  Lancet. 2003;  362 428-432
    CrossrefPubMedGoogle Scholar
  • 37 Psaty B M, Smith N L, Lemaitre R N et al.. Hormone replacement therapy, prothrombotic mutations, and the risk of incident nonfatal myocardial infarction in postmenopausal women.  JAMA. 2001;  285 906-913
    CrossrefPubMedGoogle Scholar
  • 38 Ridker P M, Hennekens C H, Rifai N, Buring J E, Manson J E. Hormone replacement therapy and increased plasma concentration of C-reactive protein.  Circulation. 1999;  100 713-716
    PubMedGoogle Scholar
  • 39 Cushman M, Legault C, Barrett-Connor E et al.. Effect of postmenopausal hormones on inflammation-sensitive proteins. The postmenopausal estrogen/progestin interventions (PEPI) study.  Circulation. 1999;  100 717-722
    CrossrefPubMedGoogle Scholar
  • 40 Vongpatanasin W, Tuncel M, Wang Z, Arbique D, Mehrad B, Jialal I. Differential effects of oral versus transdermal estrogen replacement therapy on C-reactive protein in postmenopausal women.  J Am Coll Cardiol. 2003;  41 1358-1363
    CrossrefPubMedGoogle Scholar
  • 41 Caulin-Glaser T, Farrell W J, Pfau S E et al.. Modulation of circulating cellular adhesion molecules in postmenopausal women with coronary artery disease.  J Am Coll Cardiol. 1998;  31 1555-1560
    CrossrefPubMedGoogle Scholar
  • 42 Pradhan A D, Manson J E, Rossouw J E et al.. Inflammatory biomarkers, hormone replacement therapy and incident coronary heart disease. Prospective analysis from the Women's Health Initiative observational study.  JAMA. 2002;  288 980-987
    CrossrefPubMedGoogle Scholar
  • 43 Zanger D, Yang B K, Ardans J et al.. Divergent effects of hormone therapy on serum markers of inflammation in postmenopausal women with coronary artery disease on appropriate medical management.  J Am Coll Cardiol. 2000;  36 1797-1802
    CrossrefPubMedGoogle Scholar
  • 44 Stampfer M J, Colditz G A. Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence.  Prev Med. 1991;  20 47-63
    CrossrefPubMedGoogle Scholar
  • 45 Langer R D. Hormone replacement and the prevention of cardiovascular disease.  Am J Cardiol. 2002;  89(suppl) 36E-46E
    CrossrefPubMedGoogle Scholar
  • 46 Grodstein F, Stampfer M J, Manson J E et al.. Postmenopausal estrogen and progestin use and the risk of cardiovascular disease.  N Engl J Med. 1996;  335 453-461
    CrossrefPubMedGoogle Scholar
  • 47 Heckbert S R, Weiss N S, Koepsell T D et al.. Duration of estrogen replacement therapy in relation to the risk of incident myocardial infarction in postmenopausal women.  Arch Intern Med. 1997;  157 1330-1336
    CrossrefPubMedGoogle Scholar
  • 48 Humphrey L L, Chan B K, Sox H C. Postmenopausal hormone replacement therapy and the primary prevention of cardiovascular disease.  Ann Intern Med. 2002;  137 273-284
    PubMedGoogle Scholar
  • 49 Løkkegaard E, Pedersen A T, Heitmann B L et al.. Relation between hormone replacement therapy and ischemic heart disease in women: prospective observational study.  BMJ. 2003;  326 426
    CrossrefPubMedGoogle Scholar
  • 50 Hodis H N, Mack W J, Lobo R A et al.. Estrogen in the prevention of atherosclerosis. A randomized, double-blind, placebo-controlled trial.  Ann Intern Med. 2001;  135 939-953
    CrossrefPubMedGoogle Scholar
  • 51 Mack W J, Hameed A B, Xiang M et al.. Does elevated body mass modify the influence of postmenopausal estrogen replacement on atheroaclerosis progression: results from the estrogen in the prevention of atherosclerosis trial.  Atherosclerosis. 2003;  168(1) 91-98
    CrossrefPubMedGoogle Scholar
  • 52 Writing Group for the Women's Health Initiative Investigators . Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial.  JAMA. 2002;  288 321-333
    CrossrefPubMedGoogle Scholar
  • 53 Manson J E, Hsia J, Johnson K C et al.. Estrogen plus progestin and the risk of coronary heart disease.  N Engl J Med. 2003;  349 523-534
    CrossrefPubMedGoogle Scholar
  • 54 Kleerekoper M. Lessons from the skeleton: was the Women's Health Initiative (WHI) a primary prevention trial?.  Osteoporos Int. 2002;  13 685-687
    CrossrefPubMedGoogle Scholar
  • 55 Grodstein F, Manson J E, Stampfer M J. Postmenopausal hormone use and secondary prevention of coronary events in the Nurses' Health study.  Ann Intern Med. 2001;  135 1-8
    PubMedGoogle Scholar
  • 56 Shlipak M G, Angeja B G, Go A S, Frederick P D, Canto J G, Grady D. Hormone therapy and in-hospital survival after myocardial infarction in postmenopausal women.  Circulation. 2001;  104 2300-2304
    CrossrefPubMedGoogle Scholar
  • 57 Chilvers C E, Knibb R C, Armstrong S J, Woods K L, Ligan R F. Postmenopausal hormone replacement therapy and risk of acute myocardial infaction-a case control study of women in the East Midlands, UK.  Eur Heart J. 2003;  24 2197-2205
    CrossrefPubMedGoogle Scholar
  • 58 O'Keefe J H, Kim S C, Hall R R, Cochran V C, Lawhorn S L, McCallister B D. Estrogen replacement therapy after coronary angioplasty in women.  J Am Coll Cardiol. 1997;  29 1-5
    CrossrefPubMedGoogle Scholar
  • 59 Abu-Halawa S A, Thompson K, Kirkeeide R L et al.. Estrogen replacement therapy and outcome of coronary balloon angioplasty in postmenopausal women.  Am J Cardiol. 1998;  82 409-413
    CrossrefPubMedGoogle Scholar
  • 60 Khan M A, Liu M W, Singh D et al.. Long-term (three years) effect of estrogen replacement therapy on major adverse cardiac events in postmenopausal women after intracoronary stenting.  Am J Cardiol. 2000;  86 330-333
    CrossrefPubMedGoogle Scholar
  • 61 Sullivan J M, El-Zeky F, van der Zwaag R, Ramanathan K B. Effect on survival of estrogen replacement therapy after coronary artery bypass grafting.  Am J Cardiol. 1997;  79 847-850
    CrossrefPubMedGoogle Scholar
  • 62 Ferrara A, Quesenberry C P, Karter A J, Njoroge C W, Jacobson A S, Selby J V. Current use of unopposed estrogen and estrogen plus progestin and the risk of acute myocardial infarction among women with diabetes. The Northern California Kaiserpermanente Diabetes Registry, 1995-1998.  Circulation. 2003;  107 43-48
    CrossrefPubMedGoogle Scholar
  • 63 Alexander K P, Newby L K, Hellkamp A S et al.. Initiation of hormone replacement therapy after acute myocardial infarction is associated with more cardiac events during follow-up.  J Am Coll Cardiol. 2001;  38 1-7
    CrossrefPubMedGoogle Scholar
  • 64 Heckbert S R, Kaplan R C, Weiss N S et al.. Risk of recurrent coronary events in relation to use and recent initiation of postmenopausal hormone therapy.  Arch Intern Med. 2001;  161 1709-1713
    CrossrefPubMedGoogle Scholar
  • 65 Hulley S, Grady D, Bush T et al.. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/Progestin Replacement Study (HERS) Research Group.  JAMA. 1998;  280 605-613
    CrossrefPubMedGoogle Scholar
  • 66 Herrington D M, Vittinghoff E, Lin F et al.. Statin therapy, cardiovascular events and total mortality in the Heart and Estrogen/Progestin Replacement Study (HERS).  Circulation. 2002;  105 2962-2967
    CrossrefPubMedGoogle Scholar
  • 67 Libby P, Aikawa M. Mechanisms of plaque stabilization with statins.  Am J Cardiol. 2003;  91(suppl) 4B-8B
    PubMedGoogle Scholar
  • 68 Koh K K, Schenke W H, Waclawiw M A, Csako G, Cannon III R O. Statin attenuates increase in C-reactive protein during estrogen replacement therapy in postmenopausal women.  Circulation. 2002;  105 1531-1533
    CrossrefPubMedGoogle Scholar
  • 69 Grady D, Herrington D, Bittner V et al.. Cardiovascular disease outcomes during 6.8 years of hormone therapy. Heart and Estrogen/progestin Replacement Study follow-up (HERS II).  JAMA. 2002;  288 49-57
    CrossrefPubMedGoogle Scholar
  • 70 Furberg C D, Vittinghoff E, Davidson M et al.. Subgroup interactions in the Heart and Estrogen/progestin replacement study.  Circulation. 2002;  105 917-922
    CrossrefPubMedGoogle Scholar
  • 71 Herrington D M, Reboussin D M, Brosnihan K B et al.. Effects of estrogen replacement on the progression of coronary-artery atherosclerosis.  N Engl J Med. 2000;  343 522-529
    CrossrefPubMedGoogle Scholar
  • 72 Hodis H N, Mack W J, Azen S P et al.. Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women.  N Engl J Med. 2003;  349 535-545
    CrossrefPubMedGoogle Scholar
  • 73 Waters D D, Alderman E L, Hsia J et al.. Effects of hormone replacement therapy and antioxidant supplements on coronary atherosclerosis in postmenopausal women.  JAMA. 2002;  288 2432-2440
    CrossrefPubMedGoogle Scholar
  • 74 Angerer P, Stork S, Kothny W, Schmitt P, von Schacky C. Effect of oral postmenopausal hormone replacement on progression of atherosclerosis: a randomized, controlled trial.  Arterioscler Thromb Vasc Biol. 2001;  21 262-268
    PubMedGoogle Scholar
  • 75 Cherry N, Gilmour K, Hannaford P et al.. Oestrogen therapy for prevention of reinfarction in postmenopausal women: a randomized placebo controlled trial.  Lancet. 2002;  360 2001-2008
    CrossrefPubMedGoogle Scholar
  • 76 Viscoli C M, Brass L M, Kernan W N, Sarrel P M, Suissa S, Horwitz R I. A clinical trial of estrogen-replacement therapy after ischemic stroke.  N Engl J Med. 2001;  345 1243-1249
    CrossrefPubMedGoogle Scholar
  • 77 Hodis H N, Mack W J, Lobo R. What is the cardioprotective role of hormone replacement therapy?.  Curr Atheroscler Rep. 2003;  5 56-66
    PubMedGoogle Scholar
  • 78 Lindenfeld J A, Ghali J K, Krause-Steinrauf H J et al.. Hormone replacement therapy is associated with improved survival in women with advanced heart failure.  J Am Coll Cardiol. 2003;  42 1238-1245
    CrossrefPubMedGoogle Scholar
  • 79 Petitti D B. New hope for hormone replacement and the heart? Editorial.  J Am Coll Cardiol. 2003;  42 1246-1248
    CrossrefPubMedGoogle Scholar
  • 80 Miettinen T A, Pyorala K, Olsson A G et al.. Cholesterol-lowering therapy in women and elderly patients with myocardial infarction or angina pectoris.  Circulation. 1997;  96 4211-4218
    PubMedGoogle Scholar
  • 81 Lewis S J, Sacks F M, Mitchell J S et al.. Effect of pravastatin on cardiovascular events in women after myocardial infarction: the Cholesterol and Recurrent Events (CARE) trial.  J Am Coll Cardiol. 1998;  32 140-146
    CrossrefPubMedGoogle Scholar
  • 82 Million Women Study Collaborators . Breast cancer and hormone-replacement therapy in the Million Women Study.  Lancet. 2003;  362 419-427
    CrossrefPubMedGoogle Scholar
  • 83 Chlebowski R T, Hendrix S L, Langer R D et al.. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women. The Women's Health Initiative Randomized trial.  JAMA. 2003;  289 3243-3253
    CrossrefPubMedGoogle Scholar
  • 84 Grady D. Postmenopausal hormones-therapy for symptoms only.  N Engl J Med. 2003;  348 1835-1837
    CrossrefPubMedGoogle Scholar
  • 85 Kronenberg F, Fugh-Berman A. Complementary and alternative medicine for menopausal symptoms: a review of randomized, controlled trials.  Ann Intern Med. 2002;  137 805-813
    PubMedGoogle Scholar
  • 86 Cummings S R, Eckert S, Krueger K A et al.. The effect of raloxifene on risk of breast cancer in postmenopausal women. Results from the MORE randomized trial.  JAMA. 1999;  281 2189-2197
    CrossrefPubMedGoogle Scholar
  • 87 Walsh B W, Kuller L H, Wild R A et al.. Effects of raloxifene on serum lipids and coagulation factors in healthy postmenopausal women.  JAMA. 1998;  279 1445-1451
    CrossrefPubMedGoogle Scholar
  • 88 Walsh B W, Paul S, Wild R A et al.. The effects of hormone replacement therapy and raloxifene on C-reactive protein and homocysteine in healthy postmenopausal women: a randomized, controlled trial.  J Clin Endocrinol Metab. 2000;  85 214-218
    CrossrefPubMedGoogle Scholar
  • 89 De Valk-de Roo G W, Stehouwer C D, Meijer P et al.. Both Raloxifene and Estrogen reduce major cardiovascular risk factors in healthy postmenopausal women.  Arterioscler Thromb Vasc Biol. 1999;  19 2993-3000
    PubMedGoogle Scholar
  • 90 Sarrel P M, Nawaz H, Chan W, Fuchs M, Katz D L. Raloxifene and endothelial function in healthy postmenopausal women.  Am J Obstet Gynecol. 2003;  188 304-309
    CrossrefPubMedGoogle Scholar
  • 91 Griffiths K A, Sader M A, Skilton M R, Harmer J A, Celermajer D S. Effects of Raloxifene on endothelium-dependent dilatation, lipoproteins, and markers of vascular function in postmenopausal women with coronary artery disease.  J Am Coll Cardiol. 2003;  42 698-704
    CrossrefPubMedGoogle Scholar
  • 92 Barrett-Connor E, Grady D, Sashegyi A et al.. Raloxifene and cardiovascular events in osteoporotic postmenopausal women. Four years results from the MORE randomized trial.  JAMA. 2002;  287 847-857
    CrossrefPubMedGoogle Scholar
  • 93 Mosca L, Barrett-Connor E, Wenger N K et al.. Design and methods of the Raloxifene Use for the Heart (RUTH) study.  Am J Cardiol. 2001;  88 392-395
    CrossrefPubMedGoogle Scholar
  • 94 Wenger N K, Barrett-Connor E, Collins P et al.. Baseline characteristics of participants in the Raloxifene Use for The the Heart (RUTH) Trial.  Am J Cardiol. 2002;  90 1204-1210
    CrossrefPubMedGoogle Scholar
  • 95 Stampfer M J, Hu F B, Manson J E, Rimm E B, Willett W C. Primary prevention of coronary heart disease in women through diet and lifestyle.  N Engl J Med. 2000;  343 16-22
    CrossrefPubMedGoogle Scholar
  • 96 Hu F B, Manson J E, Stampfer M J et al.. Diet, lifestyle, and the risk of type 2 diabetes mellitus in women.  N Engl J Med. 2001;  345 790-797
    CrossrefPubMedGoogle Scholar
  • 97 Bittner V. Women and coronary heart disease risk factors.  J Cardiovasc Risk. 2002;  9 315-322
    CrossrefPubMedGoogle Scholar
  • 98 Mosca L, Appel L J, Benjamin E J et al.. Evidence-based guidelines for cardiovascular disease prevention in women.  Circulation. 2004;  109 672-693
    CrossrefPubMedGoogle Scholar

Angela H.E.M MaasM.D. 

Dr. van Heesweg 2, 8025 AB Zwolle, The Netherlands

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