Lipoprotein(a) and Women
- Elevated lipoprotein(a) (Lp(a)) is one of the foremost risk factors for premature CAD (coronary artery disease) in women as well as peripheral, and cerebrovascular disease.1-7
- High levels of Lp(a) is a strong risk factor for the occurrence and recurrence of coronary events and the need for coronary procedures (such as angioplasty, stent, or bypass surgery) in postmenopausal women.8 High Lp(a) level confer a 3-fold risk of CAD in diabetic women as measured by coronary artery calcium score (heart scan).9
- Heart attack in premenopausal women is 10 times less common than men of comparable age except among Asian Indian women.10 The risk from elevated Lp(a) appears to be double in premenopausal women than in postmenopausal women.11-13
- The risk of CAD is markedly increased as high as 100-fold among women who have very high levels of Lp(a) (>55mg/dl) and very high TC/HDL ratio (>5.8).2, 3 High prevalence of this combination accounts for their very high risk of severe CAD in Asian Indian women, young and old alike.10, 14-16
- Elevated Lp(a) level is also a major determinant of thromboembolic complications during pregnancy, including heart attack.4, 17, 18 There is a 2-fold increase in Lp(a) during normal pregnancy, which may influence fibrinolysis.
- Other conditions in women associated with elevated Lp(a) include endometriosis, antiphospholipid antibody syndrome, severe preeclampsia, eclampsia, HELLP Syndrome, and recurrent miscarriages.19-25
- The increased risk of CAD in postmenopausalwomen appears to be mediated in part by a 25% increase in theLp(a) levels that occurs after menopause.26
- In subjects with high Lp(a) levels, estrogen replacement therapy resultsin a 50% reduction in Lp(a) levels as well a 50% reduction in coronary events and need for coronary interventions such as angioplasty and bypass surgery.27 However, estrogen therapy is currently not recommended as a treatment for elevated Lp(a).15
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2. Wang XL, Cranney G, Wilcken DE. Lp(a) and conventional risk profiles predict the severity of coronary stenosis in high-risk hospital-based patients. Aust N Z J Med. 2000;30(3):333-338.
3. Solymoss BC, Marcil M, Wesolowska E, Gilfix BM, Lesperance J, Campeau L. Relation of coronary artery disease in women 60 years of age to the combined elevation of serum lipoprotein (a) and total cholesterol to high-density cholesterol ratio. Am J Cardiol. 1993;72(17):1215-1219.
4. Sakai Y, Tomobuchi Y, Toyoda Y, Shinozaki M, Hano T, Nishio I. A premenopausal woman presenting with acute myocardial infarction of three different coronary vessels within 1 year: role of lipoprotein(a). Jpn Circ J. Nov 1998;62(11):849-853.
5. Labeur C, De Bacquer D, De Backer G, et al. Plasma lipoprotein(a) values and severity of coronary artery disease in a large population of patients undergoing coronary angiography. Clin Chem. 1992;38(11):2261-2266.
6. Sunayama S, Daida H, Mokuno H, et al. Lack of increased coronary atherosclerotic risk due to elevated lipoprotein(a) in women > or = 55 years of age. Circulation. 1996;94(6):1263-1268.
7. Bostom AG, Gagnon DR, Cupples LA, et al. A prospective investigation of elevated lipoprotein (a) detected by electrophoresis and cardiovascular disease in women:The Framingham Heart Study. Circulation. 1994;90(4):1688-1695.
8. 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(14):1845-1852.
9. Qasim AN, Martin SS, Mehta NN, et al. Lipoprotein(a) is strongly associated with coronary artery calcification in type-2 diabetic women. Int J Cardiol. Mar 18 2010.
10. Enas EA, Senthilkumar A, Juturu V, Gupta R. Coronary artery disease in women. Indian Heart J. May-Jun 2001;53(3):282-292.
11. Orth-Gomer K, Mittleman MA, Schenck-Gustafsson K, et al. Lipoprotein(a) as a determinant of coronary heart disease in young women. Circulation. 1997;95(2):329-334.
12. Salobir B, Sabovic M, Peternel P, Stegnar M. Fibrinolytic parameters and lipoprotein(a) in young women with myocardial infarction. Angiology. Mar-Apr 2002;53(2):157-163.
13. Hahmann HW, Schatzer-Klotz D, Bunte T, Becker D, Schieffer HJ. The significance of high levels of lipoprotein (a) compared with established risk factors in premature coronary artery disease: differences between men and women. Atherosclerosis. May 1999;144(1):221-228.
14. Palaniappan L, Anthony MN, Mahesh C, et al. Cardiovascular risk factors in ethnic minority women aged less-than-or- equal30 years. Am J Cardiol. 2002;89(5):524-529.
15. Enas EA. Lipoprotein(a) as a determinant of coronary heart disease in young women: a stronger risk factor than diabetes? Circulation. Jan 27 1998;97(3):293-295.
16. Pinto RJ, Bhagwat AR, Loya YS, Sharma S. Coronary artery disease in premenopausal Indian women: risk factors and angiographic profile. Indian Heart J. 1992;44(2):99-101.
17. Ogunyemi D, Cuellar F, Ku W, Arkel Y. Association between inherited thrombophilias, antiphospholipid antibodies, and lipoprotein A levels and venous thromboembolism in pregnancy. Am J Perinatol. Jan 2003;20(1):17-24.
18. Berg K, Roald B, Sande H. High Lp(a) lipoprotein level in maternal serum may interfere with placental circulation and cause fetal growth retardation. Clin Genet. 1994;46(1 Spec No):52-56.
19. van Pampus MG, Koopman MM, Wolf H, Buller HR, Prins MH, van den Ende A. Lipoprotein(a) concentrations in women with a history of severe preeclampsia–a case control study. Thromb Haemost. 1999;82(1):10-13.
20. Crook D, Howell R, Sidhu M, Edmonds DK, Stevenson JC. Elevated serum lipoprotein(a) levels in young women with endometriosis. Metabolism. 1997;46(7):735-739.
21. Atsumi T, Khamashta MA, Andujar C, et al. Elevated plasma lipoprotein(a) level and its association with impaired fibrinolysis in patients with antiphospholipid syndrome. J Rheumatol. 1998;25(1):69-73.
22. Yamazaki M, Asakura H, Jokaji H, et al. Plasma levels of lipoprotein(a) are elevated in patients with the antiphospholipid antibody syndrome. Thromb Haemost. Apr 1994;71(4):424-427.
23. Szczepanski M, Bauer A, Gardas A, Duchinski T. Antiphospholipid antibodies and lipoprotein (a) in women with recurrent fetal loss. Int J Gynaecol Obstet. Apr 1998;61(1):39-44.
24. Husby H, Roald B, Schjetlein R, Nesheim BI, Berg K. High levels of Lp(a) lipoprotein in a family with cases of severe pre- eclampsia. Clin Genet. 1996;50(1):47-49.
25. Kaminski K, Czuba B, Fiegler P. Predictive usefulness of lipoproteins a -Lp (a) in cases of preeclampsia. Ginekol Pol. 2000;71(8):777-782.
26. Kim CJ, Ryu WS, Kwak JW, Park CT, Ryoo UH. Changes in Lp(a) lipoprotein and lipid levels after cessation of female sex hormone production and estrogen replacement therapy. Arch Intern Med. 1996;156(5):500-504.
27. Taskinen MR, Puolakka J, Pyorala T, et al. Hormone replacement therapy lowers plasma Lp(a) concentrations. Comparison of cyclic transdermal and continuous estrogen-progestin regimens. Arterioscler Thromb Vasc Biol. 1996;16(10):1215-1221.