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European Heart Journal 2000 21(12):975-980; doi:10.1053/euhj.1999.1988
Copyright © 2000 by the European Society of Cardiology.
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Cell adhesion molecules in relation to simvastatin and hormone replacement therapy in coronary artery disease

E Sbarounia,f1, C Kroupisb, Z.S Kyriakidesa, K Koniavitoub and D.T Kremastinosa

a 2nd Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece
b Department of Immunology, Onassis Cardiac Surgery Center, Athens, Greece

revised August 12, 1999; accepted August 13, 1999

Abstract

Aims To assess the effect of simvastatin, hormone replacement therapy and their combination on soluble cell adhesion molecules and plasma lipids, in hypercholesterolaemic post-menopausal women with coronary artery disease.

Methods We studied 16 post-menopausal women with coronary artery disease and hypercholesterolaemia (total cholesterol >200mg.dl–1and LDL cholesterol >130mg.dl–1). We compared simvastatin (20mg daily) with hormone replacement therapy (0·625mg conjugated oestrogen and 2·5mg medroxyprogesterone acetate daily) and their combination, in a randomized, crossover, placebo controlled study. Each treatment period was 8 weeks long with a 4 week washout interval between treatments. Circulating cell adhesion molecules and plasma lipids were evaluated at the end of each treatment period.

Results All three active treatments—simvastatin, hormone replacement therapy and the combination therapy—significantly reduced total and LDL cholesterol, compared to placebo (P<0·001). Only hormone replacement therapy, alone and in combination with simvastatin, significantly decreased lipoprotein(a) when compared to placebo (P<0·05), whereas simvastatin had no significant effect. Likewise, hormone replacement therapy and the combination therapy significantly reduced the intercellular adhesion molecule (ICAM-1) plasma levels (P=0·03 and P=0·02, respectively), while simvastatin, which was superior to hormone replacement therapy in lowering total and LDL cholesterol, did not modify ICAM-1 levels; the combination therapy was not more effective than hormone replacement therapy alone in ICAM-1 reduction. Neither the effect, on any treatment when compared to placebo, of VCAM-1 nor E-selectin levels differed significantly.

Conclusions Hormone replacement therapy may limit the inflammatory response to injury by modulating the expression of cell adhesion molecules from the endothelial cells, possibly in association with lipoprotein (a) reduction.

Key Words: Statins, hormone replacement therapy, cell adhesion molecules, coronary artery disease, lipids

f1 Correspondence: E. Sbarouni, Onassis Cardiac Surgery Center, 2nd Department of Cardiology, 356 Sygrou Ave, 17674 Athens, Greece.

References

  1. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362:801–809[CrossRef][Medline]
  2. Albelda SM, Smith CW, Ward PA. Adhesion molecules and inflammatory injury. FASEB J. 1994;8:504–512[Abstract]
  3. Blann AD, McCollum CN. Circulating endothelial cell/leukocyte adhesion molecules in atherosclerosis. Thromb Haemost. 1994;72:151–154[Web of Science][Medline]
  4. Hackman A, Abe Y, Insull W. Levels of soluble cell adhesion molecules in patients with dyslipidemia. Circulation. 1996;93:1334–1338[Abstract/Free Full Text]
  5. Hwang SJ, Ballantyne CM, Sharrett R. Circulating adhesion molecules VCAM-1, ICAM-1, and E-Selectin in carotid atherosclerosis and incident coronary heart disease cases. Circulation. 1997;96:4219–4225[Abstract/Free Full Text]
  6. Morisaki N, Saito I, Tamura K. New indices of ischemic heart disease and aging; studies on the serum levels of soluble intercellular adhesion molecule 1 (ICAM-1) and soluble vascular adhesion molecule-1 (VCAM-1) in patients with hypercholesterolemia and ischemic heart disease. Atherosclerosis. 1997;131:43–48[CrossRef][Web of Science][Medline]
  7. Lancet. 1994;344:1383–1389[CrossRef][Web of Science][Medline]
  8. Sacks MF, Pfeffer MA, Moye LA. for the Cholesterol and Recurrent Events Trial Investigators. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996;335:1001–1009[Abstract/Free Full Text]
  9. Downs JR, Clearfield M, Weis S. Primary prevention of acute coronary events with lovostatin in men and women with average cholesterol levels. JAMA. 1998;279:1615–1622[Abstract/Free Full Text]
  10. Rosensen RS, Tagney CC. Antithrombotic properties of statins. JAMA. 1998;279:1643–1650[Abstract/Free Full Text]
  11. Grodstein F, Stampfer MJ. The epidemiology of coronary artery disease and estrogen replacement therapy in postmenopausal women. Prog Cardiovasc Dis. 1995;38:199–210[CrossRef][Web of Science][Medline]
  12. Sullivan J, Vander Zwaag R, Hughes JP. Estrogen replacement and coronary artery disease: effect on survival in postmenopausal women. Arch Intern Med. 1990;150:2257–2262
  13. Hulley S, Grady D, Bush T. Randomized trial of estrogen plus progestin for the secondary prevention of the coronary heart disease in postmenopausal women. JAMA. 1998;280:605–613[Abstract/Free Full Text]
  14. Barrett-Connor E, Bush TL. Estrogen and coronary artery disease. JAMA. 1991;265:1861–1867[Abstract/Free Full Text]
  15. Samaan SA, Crawford MH. Estrogen and cardiovascular function in menopause. J Am Coll Cardiol. 1995;26:1403–1410[Abstract]
  16. Guetta V, Cannon RO. Cardiovascular effects of estrogen and lipid-lowering therapies in postmenopausal women. Circulation. 1996;93:1928–1937[Free Full Text]
  17. Koh KK, Cardillo C, Bui MN. Vascular effects of estrogen and cholesterol-lowering therapies in hypercholesterolemic postmenopausal women. Circulation. 1999;99:354–360[Abstract/Free Full Text]
  18. Kwang KK, Bui MN, Mincemoyer R, Cannon RO. Effects of hormone therapy on inflammatory cell adhesion molecules in postmenopausal healthy women. Am J Cardiol. 1997;80:1505–1507[CrossRef][Web of Science][Medline]
  19. Shwaery GT, Vita JA, Keaney JF. Antioxidant protection of LDL by physiological concentrations of 17b-estradiol. Circulation. 1997;95:1378–1385[Abstract/Free Full Text]
  20. Keaney JF, Shwaery GT, Xu A. 17B-estradiol preserves endothelial vasodilator function and limits low-density lipoprotein oxidation in hypercholesterolemic swine. Circulation. 1994;89:2251–2259[Abstract/Free Full Text]
  21. Sack MN, Rader DJ, Cannon RO. Oestrogen and inhibition of oxidation of low-density lipoproteins in postmenopausal women. Lancet. 1994;343:269–270[CrossRef][Web of Science][Medline]
  22. Guetta V, Panza JA, Waclawiw MA, Cannon RO. Effect of combined 17B-estradiol and vitamin E on low-density lipoprotein oxidation in postmenopausal women. Am J Cardiol. 1995;75:1274–1276[CrossRef][Web of Science][Medline]
  23. Jang Y, Lincoff M, Plow E, Topol E. Cell adhesion molecules in coronary artery disease. J Am Coll Cardiol. 1994;24:1591–1601[Abstract]
  24. Caulin-Glaser T, Farrell WJ, Pfau SE. Modulation of circulating cellular adhesion molecules in postmenopausal women with coronary artery disease. J Am Coll Cardiol. 1998;31:1555–1560[Abstract/Free Full Text]
  25. Sampietro T, Tyoni M, Ferdeghini M. Plasma cholesterol regulates soluble cell adhesion molecule expression in familial hypercholesterolemia. Circulation. 1997;96:1381–1385[Abstract/Free Full Text]
  26. Takami S, Yamashita S, Kihara S. Lipoprotein(a) enhances the expression of intercellular adhesion molecule-1 in cultured human umbilical vein endothelial cells. Circulation. 1998;97:721–728[Abstract/Free Full Text]
  27. Caulin-Glaser T, Watson CA, Pardi R, Bender JR. Effects of 17B-estradiol on cytokine-induced endothelial cell adhesion molecule expression. J Clin Invest. 1996;98:36–42[Web of Science][Medline]
  28. Cid MC, Kleinman HK, Grant DS, Schopner HW, Fauci AS, Hoffman GS. Estradiol enhances leukocyte binding to tumor necrosis factor (TNF)-stimulated endothelial cells via an increase in TNF-induced adhesion molecules E-selectin, intercellular adhesion molecule type 1 and soluble vascular adhesion molecule type 1. J Clin Invest. 1994;93:17–25[Web of Science][Medline]
  29. Simoncini T, Maffei S, Basta G. Effects of sex steroid hormones on vascular cell adhesion molecule-1 gene expression in activated endothelial cells (Abstr). Eur Heart J. 1998;19:488
  30. Ridker PM, Hennekens CH, Roitman-Jonshon B, Stampfer MJ, Allen J. Plasma concentration of soluble intercellular adhesion molecule 1 and the risks of future myocardial infarction in apparently healthy men. Lancet. 1998;351:88–92[CrossRef][Web of Science][Medline]
  31. Ridker PM. Intercellular adhesion molecule (ICAM-1) and the risks of developing atherosclerotic disease. Eur Heart J. 1998;19:1119–1121[Free Full Text]
  32. Circulation. 1994;2:1333–1445
  33. Mosca L, Grundy S, Judelshon D. Guide to preventive cardiology for women. Circulation. 1999;99:2480–2484[Free Full Text]

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