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Management of Hypercholesterolaemia in Postmenopausal Women

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Abstract

Increased rates of coronary heart disease (CHD) occur with advancing age in both sexes, although CHD rates in women lag behind those of men by about 10 years. There is a sharp increase in CHD rate among women after approximately 50 years of age. The reasons for this are not completely understood and are undoubtedly multifactorial.

Cross-sectional data from large-scale population studies suggest that around the time of the menopause, low-density lipoprotein (LDL)-cholesterol levels increase by approximately 15 to 25%. Because this increase is larger than that observed in men over the same age span and closely approximates that observed in women after oophorectomy, it is likely that reduced circulating estrogen levels associated with menopause play a role in the adverse changes in both blood lipid levels and CHD incidence.

There is clear evidence that treating hypercholesterolemia reduces cardiovascular risk in women, as well as in men. In the US National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines, diet and other lifestyle changes are recommended as first-line therapy. If the treatment goals cannot be achieved through non-pharmacological measures, drug therapy should be added.

Of the available lipid-lowering agents, HMG CoA reductase inhibitors (statins) are the clear choice to decrease LDL-cholesterol levels. However the favourable effects of statins on high-density lipoprotein (HDL)-cholesterol and triglyceride levels are more modest, and statins are not known to decrease lipoprotein (a) [Lp(a)] levels. Estrogen or hormone replacement therapy (ERT/HRT) and nicotinic acid improve LDL- and HDL-cholesterol levels and also decrease Lp(a) levels. However, ERT/HRT is no longer recommended as first-line therapy for decreasing CHD risk. Nicotinic acid is particularly useful for decreasing triglyceride levels (as are fibrates) and raising HDL-cholesterol levels. Bile-acid sequestrants reduce LDL-cholesterol and slightly increase HDL-cholesterol levels. Both bile acid sequestrants and ERT/HRT tend to raise triglyceride levels, therefore they should be used cautiously in women with hypertriglyceridaemia.

Treatment should be individualised for each patient. It is important to evaluate the primary form of dyslipidaemia, other CHD risk factors, comorbidities, and the extent of lipid improvement needed in order to reach treatment goals. The effects of each type of therapy and potential adverse effects should also be considered.

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References

  1. Heart and stroke statistical update. Dallas (TX): American Heart Association, 2001: 1–38

  2. Khaw KT, Barrett-Connor E. Sex differences, hormones, and heart disease. In: Marmot M, Elliott P, editors. Coronary heart disease epidemiology: from aetiology to public health. New York (NY): Oxford University Press, 1992: 274–286

    Google Scholar 

  3. Seed M. Postmenopausal hormone replacement therapy, coronary heart disease and plasma lipoproteins. Drugs 1994; 47Suppl. 2: 25–34

    Article  PubMed  Google Scholar 

  4. Stampfer MJ, Colditz GA, Willett WC. Menopause and heart disease. A review. Ann N Y Acad Sci 1990; 592: 193–203

    Article  PubMed  CAS  Google Scholar 

  5. Barrett-Connor E. Sex differences in coronary heart disease: why are women so superior?. The 1995 Ancel Keys Lecture. Circulation 1997; 95: 252–64

    Article  PubMed  CAS  Google Scholar 

  6. Carr MC, Kim KH, Zambon A, et al. Changes in LDL density across the menopausal transition. J Investig Med 2000; 48: 245–50

    PubMed  CAS  Google Scholar 

  7. Gerhard M, Ganz P. How do we explain the clinical benefits of estrogen? From bedside to bench. Circulation 1995; 92: 5–8

    Article  PubMed  CAS  Google Scholar 

  8. Stevenson JC, Crook D, Godsland IF. Influence of age and menopause on serum lipids and lipoproteins in healthy women. Atherosclerosis 1993; 98: 83–90

    Article  PubMed  CAS  Google Scholar 

  9. Krauss RM. Dense low density lipoproteins and coronary artery disease. Am J Cardiol 1995; 75: B53–7

    Article  Google Scholar 

  10. National Cholesterol Education Program. Summary of the Second Report of the National Cholesterol Panel (NCEP) on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA 1993; 269: 3015–23

    Article  Google Scholar 

  11. Hoerger TJ, Bala MV, Bray JW, et al. Treatment patterns and distribution of low-density lipoprotein cholesterol levels in treatment-eligible United States adults. Am J Cardiol 1998; 82: 61–5

    Article  PubMed  CAS  Google Scholar 

  12. Sempos CT, Cleeman JI, Carroll MD, et al. Prevalence of high blood cholesterol among US adults: an update based on guidelines from the second report of the National Cholesterol Education Program Adult Treatment Panel. JAMA 1993; 269: 3009–14

    Article  PubMed  CAS  Google Scholar 

  13. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001; 285: 2486–97

    Google Scholar 

  14. Pearson T, Laurora IM, Chu H, et al. The lipid treatment assessment project (L-TAP): a multi-center survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals. Arch Intern Med 2000; 160: 459–67

    Article  PubMed  CAS  Google Scholar 

  15. Marcelino JJ, Feingold KR. Inadequate treatment with 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors by health care providers. Am J Med 1996; 100: 605–10

    Article  PubMed  CAS  Google Scholar 

  16. Schectman G, Hiatt J. Drug therapy for hypercholesterolemia in patients with cardiovascular disease: factors limiting achievement of lipid goals. Am J Med 1996; 100: 197–204

    Article  PubMed  CAS  Google Scholar 

  17. Pasternak RC, Brown LE, Stone PH, et al. Effect of combination therapy with lipid-reducing drugs in patients with coronary heart disease and ‘normal’ cholesterol levels. Ann Intern Med 1996; 125: 529–40

    PubMed  CAS  Google Scholar 

  18. Hulley S. Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998; 280: 605–13

    Article  PubMed  CAS  Google Scholar 

  19. The Expert Panel. Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Arch Intern Med 1988; 148: 36–69

    Article  Google Scholar 

  20. Schrott HG, Bittner V, Vittinghoff E, et al. Adherence to National Cholesterol Education Program treatment goals in postmenopausal women with heart disease. JAMA 1997; 277: 1281–6

    Article  PubMed  CAS  Google Scholar 

  21. Miller M, Byington R, Hunninghake D, et al. Sex bias and underutilization of lipid-lowering therapy in patients with coronary artery disease at academic medical centers in the United States and Canada. Arch Intern Med 2000; 160: 343–7

    Article  PubMed  CAS  Google Scholar 

  22. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383–9

    Google Scholar 

  23. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland coronary prevention study group. N Engl J Med 1995; 333: 1301–7

    Article  PubMed  CAS  Google Scholar 

  24. Lewis SJ, Sacks FM, Mitchell JS, 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: 140–6

    Article  PubMed  CAS  Google Scholar 

  25. Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels. JAMA 1998; 279: 1615–22

    Article  PubMed  CAS  Google Scholar 

  26. Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998; 339: 1349–57

    Article  Google Scholar 

  27. Guyton JR. Effect of niacin on atherosclerotic cardiovascular disease. Am J Cardiol 1998; 82(12A): U18–23

    Article  Google Scholar 

  28. Rackley CE. Monotherapy with HMG-CoA reductase inhibitors and secondary prevention in coronary artery disease. Clin Cardiol 1996; 19: 683–9

    Article  PubMed  CAS  Google Scholar 

  29. Manninen V, Elo MO, Frick MH, et al. Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study. JAMA 1988; 260: 641–51

    Article  PubMed  CAS  Google Scholar 

  30. Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia. N Engl J Med 1987; 317: 1237–45

    Article  PubMed  CAS  Google Scholar 

  31. Mosca L, Grundy SM, Judelson D, et al. Guide to preventive cardiology for women. J Am Coll Cardiol 1999; 33: 1751–5

    Article  PubMed  CAS  Google Scholar 

  32. Bucher HC, Griffith LE, Guyatt GH. Systematic review on the risk and benefit of different cholesterol-lowering interventions. Arterioscler Thromb Vasc Biol 1999; 19: 187–95

    Article  PubMed  CAS  Google Scholar 

  33. Kristal AR, White E, Shattuck AL, et al. Long term maintenance of a low-fat diet: durability of fat-related maintenance habits in the Women’s Health Trial. J Am Diet Assoc 1992; 92: 553–9

    PubMed  CAS  Google Scholar 

  34. Allison TG, Squires RW, Johnson BD, et al. Achieving National Cholesterol Education Program goals for low-density lipoprotein cholesterol in cardiac patients: importance of diet, exercise, weight control, and drug therapy. Mayo Clin Proc 1999; 74: 466–73

    PubMed  CAS  Google Scholar 

  35. Ripsin CM, Keenan JM, Jacobs DR, et al. Oat products and lipid lowering: a meta-analysis. JAMA 1992; 267: 3317–25

    Article  PubMed  CAS  Google Scholar 

  36. Anderson JW, Allgood LD, Lawrence A, et al. Cholesterol-lowering effects of psyllium intake adjunctive to diet therapy in men and women with hypercholesterolemia: meta-analysis of 8 controlled trials. Am J Clin Nutr 2000; 71: 472–9

    PubMed  CAS  Google Scholar 

  37. Davidson MH, Dugan LD, Burns JH, et al. The hypercholesterolemic effects of β-glucan in oatmeal and oat bran. JAMA 1991, 265(14): 1833–9

    Article  PubMed  CAS  Google Scholar 

  38. Davidson MH, Dugan LD, Burns JH, et al. Apsyllium-enriched cereal for the treatment of hypercholesterolemia in children: a controlled, double-blind, crossover study. Am J Clin Nutr 1996; 63: 96–102

    PubMed  CAS  Google Scholar 

  39. Davidson MH, Maki KC, Kong JC, et al. Long-term effects of consuming foods containing psyllium seed husk on serum lipids in subjects with hypercholesterolemia. Am J Clin Nutr 1998; 67: 367–76

    PubMed  CAS  Google Scholar 

  40. Davidson MH, McDonald A. Fiber: forms and functions. Nutr Res 1998; 18: 617–24

    Article  CAS  Google Scholar 

  41. Maki KC, Davidson MH, Malik KC, et al. Cholesterol lowering with high-viscosity hydroxypropylmethylcellulose. Am J Cardiol 1999; 84: 1198–203

    Article  PubMed  CAS  Google Scholar 

  42. Maki KC, Davidson MH, Torri S, et al. High-molecular weight hydroxypropylmethylcellulose taken with or between meals is hypocholesterolemic in adult men. J Nutr 2000; 130: 1705–10

    PubMed  CAS  Google Scholar 

  43. Maki KC, Davidson MH, Umporowicz DM, et al. Lipid responses to plant sterol-enriched reduced-fat spreads incorporated into a NCEP Step 1 diet. Am J Clin Nutr 2001; 74: 33–43

    PubMed  CAS  Google Scholar 

  44. Blair SN, Capuzzi DM, Gottlieb SO. Incremental reduction of serum total cholesterol and low-density lipoprotein cholesterol with the addition of plant stanol ester-containing spread to statin therapy. Am J Cardiol 2000; 86: 46–52

    Article  PubMed  CAS  Google Scholar 

  45. Miettinen TA, Puska P, Gylling H, et al. Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population. N Engl J Med 1995; 333: 1308–12

    Article  PubMed  CAS  Google Scholar 

  46. Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. JAMA 1995; 273: 199–208

    Article  Google Scholar 

  47. Herrington DM, Reboussin DM, Brosnihan B, et al. Effects of estrogen replacement on the progression of coronary-artery atherosclerosis. N Engl J Med 2000; 343: 522–9

    Article  PubMed  CAS  Google Scholar 

  48. Shlipak MG, Simon JA, Vittinghoff E, et al. Estrogen and progestin, lipoprotein(a), and the risk of recurrent coronary heart disease events after menopause. JAMA 2000; 283: 1845–52

    Article  PubMed  CAS  Google Scholar 

  49. Mijatovic V, van der Mooren MJ, Kenemans P, et al. Raloxifene lowers serum lipoprotein(a) in healthy postmenopausal women: a randomized, double-blind, placebo-controlled comparison with conjugated equine estrogens. Menopause 1999; 6: 134–7

    Article  PubMed  CAS  Google Scholar 

  50. Davidson MH, Maki KC, Marx P, et al. Effects of continuous estrogen and estrogen-progestin replacement regimens on cardiovascular risk markers in postmenopausal women. Arch Intern Med 2000; 160: 3315–25

    Article  PubMed  CAS  Google Scholar 

  51. Stevenson JC, Crook D, Godsland IF, et al. Oral versus transdermal hormone replacement therapy. Int J Fertil Menopausal Stud 1993; 38Suppl. 1: 30–5

    PubMed  Google Scholar 

  52. Ridker PM, Hennekens CH, Rifai N, et al. Hormone replacement therapy and increased plasma concentration of C-reactive protein. Circulation 1999; 100: 713–6

    Article  PubMed  CAS  Google Scholar 

  53. Baycol® [prescribing information]. West Haven (CT): Bayer Corporation, 2000

  54. Lescol® [prescribing information]. East Hanover (NJ): Novartis, 2000

  55. Lipitor® [prescribing information]. Morris Plains (NJ): ParkeDavis, 1999

  56. Mevacor® [prescribing information]. Whitehouse Station (NJ): Merck & Co., Inc., 1999

  57. Pravacho® [prescribing information]. Princeton (NJ): Bristol-Myers Squibb Company, 1999

  58. Zocor® [prescribing information]. Whitehouse Station (NJ): Merck & Co, Inc, 1999

  59. Davidson MH, Nawrocki JW, Weiss SR, et al. Effectiveness of atorvastatin for decreasing low density lipoprotein cholesterol to NCEP treatment goals. Am J Cardiol 1997; 80: 347–8

    Article  PubMed  CAS  Google Scholar 

  60. Collins R, Peto R, Armitage J. The MRC/BHF Heart Protection Study: preliminary results. Int J Clin Pract 2002; 56: 53–6

    PubMed  Google Scholar 

  61. Clearfield M, Downs JR, Weis S, et al. Air Force/Texas Coronary Atherosclerosis Prevention Study(AFCAPS/TEXCAPS): efficacy and tolerability of long-term treatment with lovastatin in women. J Womens Health Gend Based Med 2001; 10: 971–81

    Article  PubMed  CAS  Google Scholar 

  62. Davidson MH, Maki KC. Cardiovascular risk factors: evaluation and treatment goals. In: Kris-Etherton PM, Burns J, editors. Cardiovascular nutrition: strategies and tools for disease management and prevention. Chicago (IL): American Dietetic Association, 1998: 3–16

    Google Scholar 

  63. Roberts WC. The rule of 5 and the rule of 7 in lipid-lowering by statin drugs. Am J Cardiol 1997; 80: 106–7

    Article  PubMed  CAS  Google Scholar 

  64. Davidson M, Ma P, Stein EA, et al. Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with Rosuvastatin versus Atorvastatin in patients with type IIa or IIb hypercholesterolemia. Am J Cardiol 2002; 89: 268–75

    Article  PubMed  CAS  Google Scholar 

  65. Segrest JP. Use of nicotinic acid, bile acid-binding resins, and fibrates. Clin Rev 2000 Spring: 52–57

    Google Scholar 

  66. Niaspan® [prescribing information]. Miami (FL): Kos Pharmaceuticals, Inc, 1999

  67. Guyton JR, Blazing MA, Hagar J, et al. Extended-release niacin vs gemfibrozil for the treatment of low levels of high-density lipoprotein cholesterol. Niaspan-Gemfibrozil Study Group. Arch Intern Med 2000; 160(8): 1177–84

    Article  PubMed  CAS  Google Scholar 

  68. Coronary Drug Project Research Group. Clofibrate and niacin in coronary heart disease. JAMA 1975; 231: 360–6

    Article  Google Scholar 

  69. Knopp RH. Clinical profiles of plain versus sustained-release niacin (Niaspan) and the physiologic rationale for nighttime dosing. Am J Cardiol 1998; 82(12A): U24–8

    Article  Google Scholar 

  70. Fruchart JC, Brewer Jr HB, Leitersdorf E. Consensus for the use of fibrates in the treatment of dyslipoproteinemia and coronary heart disease. Fibrate Consensus Group. Am J Cardiol 1998; 81: 912–7

    Article  PubMed  CAS  Google Scholar 

  71. Lopid® [prescribing information]. Morris Plains (NJ): ParkeDavis, 1999

  72. Tricor® [prescribing information]. North Chicago (IL): Abbott Laboratories, 1998

  73. Elisaf M, Tsimichodimos V, Bairaktari E, et al. Effect of micronized fenofibrate and losartan combination on uric acid metabolism in hypertensive patients with hyperuricemia. J Cardiovasc Pharmacol 1999; 34: 60–3

    Article  PubMed  CAS  Google Scholar 

  74. Genest J Jr, Nguyen NH, Theroux P, et al. Effect of micronized fenofibrate on plasma lipoprotein levels and hemostatic parameters in patients with low levels of high-density lipoprotein cholesterol in the fed and fasted state. J Cardiovasc Pharmacol 2000; 35: 164–72

    Article  PubMed  CAS  Google Scholar 

  75. Farnier M, Bonnefous F, Debbas N, et al. Comparative efficacy and safety of micronized fenofibrate and simvastatin in patients with primary type IIa or Iib hyperlipidemia. Arch Intern Med 1994; 154: 441–9

    Article  PubMed  CAS  Google Scholar 

  76. Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N Engl J Med 341: 410–8

  77. National Institutes of Health. Third report of the Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). Bethesda (MD): National Cholesterol Education Program, National Heart Lung, and Blood Institute; 2001 May. NIH Publication No.: 01–3670

    Google Scholar 

  78. Aldridge MA, Ito MK. Colesevelam hydrochloride: a novel bile acid-binding resin. Ann Pharmacother 2001; 35: 898–907

    Article  PubMed  CAS  Google Scholar 

  79. The Lipid Research Clinics coronary primary prevention trial results I. Reduction in incidence of coronary heart disease. JAMA 1984; 251: 351–64

    Google Scholar 

  80. Davidson MH, Dillon MA, Gordon B, et al. Colesevelam hydrochloride (Cholestagel): a new, potent bile acid sequestrant associated with a low incidence of gastrointestinal side effects. Arch Intern Med 1999; 159: 1893–900

    Article  PubMed  CAS  Google Scholar 

  81. Davidson MH, Testolin LM, Maki KC, et al. A comparison of estrogen replacement, pravastatin, or combined therapy for the management of hypercholesterolemia in postmenopausal women. Arch Intern Med 1997; 157: 1186–92

    Article  PubMed  CAS  Google Scholar 

  82. Davidson MH, Maki KC, Hunninghake DB, et al. Effects of low dose simvastatin and hormone replacement therapy on serum lipids in postmenopausal women with hypercholesterolemia. J Am Coll Cardiol 2000; 35Suppl. A: A330

    Google Scholar 

  83. Darling GM, Johns JA, McCloud PI, et al. Estrogen and progestin compared with simvastatin for hypercholesterolemia in postmenopausal women. N Engl J Med 1997; 337: 595–601

    Article  PubMed  CAS  Google Scholar 

  84. Sbarouni E, Kyriakides ZS, Kremastinos DT. The effect of hormone replacement therapy alone and in combination with simvastatin on plasma lipids of hypercholesterolemic post-menopausal women with coronary artery disease. J Am Coll Cardiol 1998; 32: 1244–50

    Article  PubMed  CAS  Google Scholar 

  85. Guyton JR, Capuzzi DM. Treatment of hyperlipidemia with combined niacin-statin regimens. Am J Cardiol 1998; 82(12A): U82–4

    Article  Google Scholar 

  86. McKenney JM. Lipid management: tools for getting to the goal. Am J Manag Care 2001; 7: S299–306

    PubMed  CAS  Google Scholar 

  87. Blum CB. Comparison of properties of four inhibitors of 3-hydroxy-3-methylglutarul-coenzyme A reductase. Am J Cardiol 1994; 73: D3–11

    Article  Google Scholar 

  88. Davidson MH. Does differing metabolism by cytochrome P450 have clinical importance? Curr Atheroscler Rep 2000; 1: 14–9

    Article  Google Scholar 

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Acknowledgements

The authors have received research grants and speaking and/or consulting honoraria from manufacturers of statins, fibrates, bile-acid sequestrants, nicotinic acid and hormone replacement therapies, as well as manufacturers of adjunctive therapies such as soluble fibers and sterol/stanol products.

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  1. Chicago Center for Clinical Research, 515 N. State Street, Suite 2700, Chicago, Illinois, 60610, USA

    Michael H. Davidson, Kevin C. Maki, Sherry Katz Karp & Kate A. Ingram

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Davidson, M.H., Maki, K.C., Karp, S.K. et al. Management of Hypercholesterolaemia in Postmenopausal Women. Drugs Aging 19, 169–178 (2002). https://doi.org/10.2165/00002512-200219030-00002

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