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DOI: 10.1055/s-0037-1614426
Lipoprotein(a) Levels and Isoforms and Fibrinolytic Activity in Postmenopause – Influence of Hormone Replacement Therapy
Summary
Epidemiological studies suggest that hormone replacement therapy (HRT) decreases the risk of cardiovascular disease in postmenopausal women via several mechanisms, including modifications in the fibrinolytic system and lipoprotein(a) [Lp(a)] levels. The aim of this study was to examine the influence of the levels and isoforms of Lp(a) on fibrinolytic activity in 91 postmenopausal women in comparison with premenopause and analyze the effect of HRT on those parameters. In postmenopause, an increase in plasma Lp(a) and plasminogen activator inhibitor-1 (PAI-1) levels was found. A significant inverse correlation was observed between Lp(a) or PAI-1 levels and plasmin generation. Plasma samples with low molecular weight (MW) apo(a) isoforms showed higher plasmin inhibition than plasmas with high MW apo(a) isoforms and similar levels of total Lp(a) and PAI-1. HRT induced a significant decrease in Lp(a) and PAI-1 levels and an increase in estradiol levels, as well as an increase in fibrinolytic activity. A significant correlation was found between the percentages of variation in Lp(a) levels and in plasmin generation and between the percentages of variation in PAI-1 levels and in the euglobulin lysis time under HRT. In conclusion, the increase in fibrinolytic activity observed in women under HRT could be explained by two independent mechanisms: (a) the decrease in PAI-1 and (b) the decrease in the inhibition of plasmin generation due to the decrease in Lp(a) levels.
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References
- 1 Winkler UH. Menopause, hormone replacement therapy and cardiovascular disease: a review of haemostaseological findings. Fibrinolysis 1992; 6 (Suppl. 03) Sup 5-10.
- 2 Nabulsi AA, Folsom AR, White A, Patsch W, Heiss G, Wu KK, Szklo M. Association of hormone-replacement therapy with various cardiovascular risk factors in postmenopausal women. N Engl J Med 1993; 328: 1069-75.
- 3 Psaty BM, Heckbert SR, Atkins D, Siscovick DS, Koepsell TD, Wahl PW, Longstreth WF, Weiss NS, Wagner EH, Prentice R, Furberg CD. A review of the association of estrogens and progestins with cardiovascular disease in postmenopausal women. Arch Intern Med 1993; 153: 1421-7.
- 4 Gensini GF, Micheli S, Prisco D, Abbate R. Menopause and risk of cardiovascular disease. Thromb Res 1996; 84: 1-19.
- 5 Wenger NK, Speroff L, Packard B. Cardiovascular health and disease in women. N Engl J Med 1993; 329: 247-56.
- 6 The postmenopausal estrogen/progestin interventions. Trial writing group. Effects of estrogen or estrogen/progestin regimens on hearth disease risk factors in postmenopausal women. JAMA 1995; 273: 199-208.
- 7 Grodstein F, Stampfer MJ, Manson JE, Colditz GA, Willett WC, Rosner B, Speizer FE, Hennekens CH. Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. N Engl J Med 1996; 335: 453-61.
- 8 Grodstein F, Stampfer MJ, Colditz GA, Willett WC, Manson JE, Joffe M, Rosner B, Fuchs C, Hankinson SE, Huinter DJ, Hennekens CH, Speizer FE. Postmenopausal hormone therapy and mortality. N Engl J Med 1997; 336: 1769-75.
- 9 Heckbert SR, Weiss NS, Koepsell TD, Lemaitre RN, Smith NL, Siscovick DS, Lin D, Psaty BM. Duration of estrogen replacement therapy in relation to the risk of incident myocardial infarction in postmenopausal women. Arch Intern Med 1997; 157: 1330-6.
- 10 Chae CV, Ridker PM, Manson JE. Postmenopausal hormone replacement therapy and cardiovascular disease. Thromb Haemost 1997; 78: 770-80.
- 11 Vaziri SM, Evans JC, Larson MG, Wilson PWF. The impact of female hormone usage on the lipid profile: the Framingham Offspring Study. Arch Intern Med 1993; 153: 2200-6.
- 12 Meade TW. Hormone replacement therapy and haemostatic function. Thromb Haemost 1997; 78: 765-9.
- 13 Hamsten A. The hemostatic system and coronary heart disease. Thromb Res 1993; 70: 1-38.
- 14 Meade TW, Ruddock V, Stirling Y, Chakrabani R, Miller GJ. Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. Lancet 1993; 342: 1076-9.
- 15 Hamsten A, Walldius G, Szamosi A, Blombäck M, De Faire U, Dahlen G, Landou Ch, Wiman B. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 1987; 2: 3-9.
- 16 Aznar J, Estellés A, Tormo G, Sapena P, Tormo V, Blanch S, España F. Plasminogen activator inhibitor activity and other fibrinolytic variables in patients with coronary artery disease. Brit Heart J 1988; 59: 535-41.
- 17 Aznar J, Estellés A. Role of plasminogen activator inhibitor type 1 in the pathogenesis of coronary artery disease. Haemostasis 1994; 24: 243-51.
- 18 Lee AJ, Lowe GOD, Smith WCS, Tunstall-Pedoe H. Plasma fibrinogen in women: relationship with oral contraception, the menopause and hormone replacement therapy. Br J Haematol 1993; 83: 616-21.
- 19 Scarabin PY, Plu-Bureau G, Bara L, Bonithon-Kopp C, Guize L, Samama MM. Haemostatic variables and menopausal status: influence of hormone replacement therapy. Thromb Haemost 1993; 70: 584-7.
- 20 Gilabert J, Estellés A, Cano A, España F, Barrachina R, Grancha S, Aznar J, Tortajada M. The effect of estrogen replacement therapy with or without progestogen on the fibrinolytic system and coagulation inhibitors in postmenopausal status. Am J Obstet Gynecol 1995; 173: 1849-54.
- 21 Kim CJ, Jang HC, Cho DH, Min YK. Effects of hormone replacement therapy on lipoprotein(a) and lipids in postmenopausal women. Arterioscler Thromb 1994; 14: 275-81.
- 22 Berg K. A new serum system in man: the Lp system. Acta Pathol Microbiol Scand 1963; 59: 369-82.
- 23 Utermann G, Weber W. Protein composition of Lp(a) lipoprotein from human plasma. FEBS Lett 1983; 154: 357-61.
- 24 Dahlen GH, Guyton JR, Attar M, Farmer JA, Kautz JA, Gotto AM. Association of levels of lipoprotein Lp(a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiography. Circulation 1986; 74: 758-65.
- 25 Rosengren A, Wilhelmsen L, Eriksson E, Risberg B, Wedel H. Lipoprotein(a) and coronary heart disease: a prospective case control study in a general population sample of middle aged men. Br Med J 1990; 301: 1248-51.
- 26 McLean JW, Tomlinson JE, Kuang W, Eaton DL, Chen EY, Fless GM, Scanu AM, Lawn RM. cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature 1987; 330: 132-7.
- 27 Miles LA, Fless GM, Levin EG, Scanu AM, Plow EF. A potential basis for the thrombotic risks associated with lipoprotein(a). Nature 1989; 339: 301-3.
- 28 Hajjar KA, Gavish D, Breslow JL, Nachman RL. Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis. Nature 1989; 339: 303-5.
- 29 Harpel PC, Gordon BR, Parker TS. Plasmin catalyzes binding of lipoprotein(a) to immobilized fibrinogen an fibrin. Proc Natl Acad Sci USA 1989; 86: 3847-51.
- 30 Loscalzo J, Weinfeld M, Fless GM, Scanu AM. Lipoprotein(a) fibrin binding, and plasminogen activation. Arteriosclerosis 1990; 10: 240-5.
- 31 Rouy D, Grailhe P, Nigon F, Chapman J, AngleS-Cano E. Lipoprotein (a) impairs the generation of plasmin by fibrin-bound t-PA: In vitro studies in a plasma milieu. Arterioscler Thromb 1991; 11: 629-38.
- 32 Edelberg JM, Pizzo SV. Lipoprotein(a): the link between impaired fibrinolysis and atherosclerosis. Fibrinolysis 1991; 5: 135-43.
- 33 Hervio LH, Durlach V, Girard-Globa A, AngléS-Cano E. Multiple binding with identical linkage: A mechanism that explains the effect of lipoprotein(a) on fibrinolysis. Biochemistry 1995; 34: 13353-8.
- 34 Utermann G, Kraft HG, Menzel HJ, Hopferwieser T, Seitz C. Genetics of the quantitative Lp(a) lipoprotein trait. I. Relation of Lp(a) glycoprotein phenotypes to Lp(a) lipoprotein concentrations in plasma. Hum Genet 1988; 78: 41-6.
- 35 Kamboh I M, Ferrel RE, Kottke BA. Expressed hypervariable polymorphism of apolipoprotein(a). Am J Hum Genet 1991; 49: 1063-74.
- 36 Marcovina SM, Zhang ZH, Gaur VP, Albers JJ. Identification of 34 apolipoprotein(a) isoforms: differential expression of apolipoprotein(a) alleles between american blancks and whites. Biochem Biophys Res Comm 1993; 191: 1192-6.
- 37 Koschinsky ML, Beisiegel V, Henne-Bruns D, Eaton DL, Lawn M. Apolipoprotein(a) size heterogeneity is related to variable number of repeat sequences in its mRNA. Biochemistry 1990; 29: 640-4.
- 38 Mooser V, Mancini FP, Bopp S, Pethö-Schramm A, Guerra R, Boerwinkle E, Müller H, Hobbs H. Sequence polymorphisms in the apo(a) gene associated with specific levels of Lp(a) in plasma. Hum Mol Genet 1995; 4: 173-81.
- 39 Aznar J, Estellés A, Bretó M, España F, Alós T. Euglobulin clot lysis induced by tissue-type plasminogen activator is reduced in subjects with increased levels of lipoprotein(a). Thromb Res 1992; 66: 569-82.
- 40 Aznar J, Estellés A, Bretó M, España F. Euglobulin clot lysis induced by tissue-type plasminogen activator in subjects with increased levels and different isoforms of lipoprotein(a). Thromb Res 1993; 72: 459-65.
- 41 Szczeklik A, Radwan J, Kubicka A, Libura M, Sacha T, Swadzba J, Undas A, Szczeklik J, Jodlowski J. Plasma fibrinolytic activity in healthy subjects with high and low lipoprotein(a) concentrations. Thromb Res 1992; 66: 391-5.
- 42 Terres W, Krewitt M, Hamm CW. Effects of lipoprotein(a) on in vitro lysis of whole blood thrombi from healthy volunteers. Thromb Res 1993; 69: 479-87.
- 43 Stegnar M, Ambrozic J, Berger B, Keber I. In vitro plasma and euglobulin clot lysis in subjects with elevated lipoprotein(a). Fibrinolysis 1995; 9: 304-8.
- 44 Hervio L, Chapman M, Thillet J, Loyau S, AngléS-Cano E. Does apolipo-protein(a) heterogeneity influence lipoprotein(a) effects on fibrinolysis?. Blood 1993; 82: 392-7.
- 45 Hervio L, Girard-Globa A, Durlach V, AngléS-Cano E. The antifibrinolytic effect of lipoprotein(a) in heterozygous subjects is modulated by the relative concentration of each of the apolipoprotein(a) isoforms and their affinity for fibrin. Eur J Clin Invest 1996; 26: 411-7.
- 46 Palabrica TM, Liu AC, Aronovitz MJ, Furie B, Lawn RM, Furie BC. Antifibrinolytic activity of apolipoprotein(a) in vivo: Human apolipoprotein(a) transgenic mice are resistant to tissue plasminogen activator-mediated thrombolysis. Nature Med 1995; 1: 256-9.
- 47 Soma MR, Osnago-Gadda I, Paoletti R, Fumagalli R, Morriset J, Meschia M. The lowering of lipoprotein(a) induced by estrogen plus progesterone replacement therapy in postmenopausal women. Arch Intern Med 1993; 153: 1462-8.
- 48 Taskinen MR, Puolakka J, Pyörälä T, Luototla H, Björn M, Kääriäinen J, Lahdenperä J, Ehnholm C. Hormone replacement therapy lowers plasma Lp(a) concentrations. Comparison of cyclic transdermal and continous estrogen-progestin regimens. Arterioscler Thromb Vasc Biol 1996; 16: 1215-21.
- 49 Sacks FM, McPherson R, Walsh BW. Effects of postmenopausal estrogen replacement on plasma Lp(a) lipoprotein concentrations. Arch Intern Med 1994; 154: 1106-10.
- 50 Kim CJ, Min YK, Ryu WS, Kwak JW, Ryoo UH. Effect of hormone replacement therapy on lipoprotein(a) and lipid levels in postmenopausal women. Influence of various progestogen and duration of therapy. Arch Intern Med 1996; 156: 1693-700.
- 51 Haines CJ, Chung TK, Masarei JR, Tomlinson B, Lau JT. An examination of the effect of combined cyclical hormone replacement therapy on lipo-protein(a) and other lipoproteins. Atherosclerosis 1996; 119: 215-22.
- 52 Honggi W, Lippuner K, Riesen W, Jaeger P, Birkhouser MH. Long-term influence of the different postmenopausal hormone replacement regimens on serum lipids and lipoprotein(a): a randomised study. Br J Obstet Gynaecol 1997; 104: 708-17.
- 53 Gebara OCE, Mittleman MA, Sutherland P, Lipinska I, Matheney T, Xu P, Welty FK, Wilson PWF, Levy D, Muller JE, Tofler GH. Association between increased estrogen status and increased fibrinolytic potential in the Framingham offsprimg study. Circulation 1995; 91: 1952-8.
- 54 Shahar E, Folsom AR, Salomaa VV, Stinson VL, McGovern PG, Shimakawa T, Chambless LE, Wu KK. Relation of hormone-replacement therapy to measures of plasma fibrinolytic activity. Circulation 1996; 93: 1970-5.
- 55 Kon Koh K, Mincemoyer R, Bui MN, Csako G, Pucino F, Guetta V, Waclawiv M, Cannon III RO. Effects of hormone-replacement therapy on fibrinolysis in postmenopausal women. N Engl J Med 1997; 336: 690-3.
- 56 Scarabin PY, Alhencgelas M, Plubureau G, Taisne P, Agher R, Aiach M. Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial. Arterioscler Thromb Vasc Biol 1997; 17: 3071-8.
- 57 Stroop DM, Glueck CJ, MsCray C, Speirs J, Schumacher HR. Measurement of lipoprotein (a): comparison of MacraTM and Imubind® methods. Ann Clin Lab Sci 1996; 26: 329-39.
- 58 Falcó C, Estellés A, Dalmau J, España F, Aznar J. Influence of lipoprotein (a) levels and isoforms on fibrinolytic activity. Study in families with high lipoprotein (a) levels. Thromb Haemost 1998; 79: 818-23.
- 59 Estellés A, Gilabert J, Aznar J, Loskutoff DJ, Schleef R. Changes in the plasma levels of type 1 and type 2 plasminogen activator inhibitors in normal pregnancy and in patients with severe preeclampsia. Blood 1989; 74: 1332-8.
- 60 Friberger P, Knoss M, Gustavsson S, Aurell L, Claeson G. Methods for determination of plasmin, antiplasmin and plasminogen by means of substrate S-2251. Haemostasis 1978; 7: 138-45.
- 61 Dahlen G, Guyton JR, Attar M, Farmer JA, Kautz JA, Gotto AM. Association of levels of lipoprotein Lp(a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiography. Circulation 1986; 74: 758-65.
- 62 Harpel PC, Hermann A, Zhang X, Ostfeld I, Borth W. Lipoprotein(a), plasmin modulation and atherogenesis. Thrombos Haemost 1995; 74: 382-6.
- 63 Hajjar KA, Nachman RL. The role of lipoprotein(a) in atherogenesis and thrombosis. Ann Rev Med 1996; 47: 423-42.
- 64 Speroff L. Quality of life issues in the management of the menopause. In: Women’s health today (Proc XIV World Congress of Gynecology & Obstetrics). Popkin D, Peddle L. eds Parthenon Pubs group; New York: 1994: pp 271-90.
Correspondence to:
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References
- 1 Winkler UH. Menopause, hormone replacement therapy and cardiovascular disease: a review of haemostaseological findings. Fibrinolysis 1992; 6 (Suppl. 03) Sup 5-10.
- 2 Nabulsi AA, Folsom AR, White A, Patsch W, Heiss G, Wu KK, Szklo M. Association of hormone-replacement therapy with various cardiovascular risk factors in postmenopausal women. N Engl J Med 1993; 328: 1069-75.
- 3 Psaty BM, Heckbert SR, Atkins D, Siscovick DS, Koepsell TD, Wahl PW, Longstreth WF, Weiss NS, Wagner EH, Prentice R, Furberg CD. A review of the association of estrogens and progestins with cardiovascular disease in postmenopausal women. Arch Intern Med 1993; 153: 1421-7.
- 4 Gensini GF, Micheli S, Prisco D, Abbate R. Menopause and risk of cardiovascular disease. Thromb Res 1996; 84: 1-19.
- 5 Wenger NK, Speroff L, Packard B. Cardiovascular health and disease in women. N Engl J Med 1993; 329: 247-56.
- 6 The postmenopausal estrogen/progestin interventions. Trial writing group. Effects of estrogen or estrogen/progestin regimens on hearth disease risk factors in postmenopausal women. JAMA 1995; 273: 199-208.
- 7 Grodstein F, Stampfer MJ, Manson JE, Colditz GA, Willett WC, Rosner B, Speizer FE, Hennekens CH. Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. N Engl J Med 1996; 335: 453-61.
- 8 Grodstein F, Stampfer MJ, Colditz GA, Willett WC, Manson JE, Joffe M, Rosner B, Fuchs C, Hankinson SE, Huinter DJ, Hennekens CH, Speizer FE. Postmenopausal hormone therapy and mortality. N Engl J Med 1997; 336: 1769-75.
- 9 Heckbert SR, Weiss NS, Koepsell TD, Lemaitre RN, Smith NL, Siscovick DS, Lin D, Psaty BM. Duration of estrogen replacement therapy in relation to the risk of incident myocardial infarction in postmenopausal women. Arch Intern Med 1997; 157: 1330-6.
- 10 Chae CV, Ridker PM, Manson JE. Postmenopausal hormone replacement therapy and cardiovascular disease. Thromb Haemost 1997; 78: 770-80.
- 11 Vaziri SM, Evans JC, Larson MG, Wilson PWF. The impact of female hormone usage on the lipid profile: the Framingham Offspring Study. Arch Intern Med 1993; 153: 2200-6.
- 12 Meade TW. Hormone replacement therapy and haemostatic function. Thromb Haemost 1997; 78: 765-9.
- 13 Hamsten A. The hemostatic system and coronary heart disease. Thromb Res 1993; 70: 1-38.
- 14 Meade TW, Ruddock V, Stirling Y, Chakrabani R, Miller GJ. Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. Lancet 1993; 342: 1076-9.
- 15 Hamsten A, Walldius G, Szamosi A, Blombäck M, De Faire U, Dahlen G, Landou Ch, Wiman B. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 1987; 2: 3-9.
- 16 Aznar J, Estellés A, Tormo G, Sapena P, Tormo V, Blanch S, España F. Plasminogen activator inhibitor activity and other fibrinolytic variables in patients with coronary artery disease. Brit Heart J 1988; 59: 535-41.
- 17 Aznar J, Estellés A. Role of plasminogen activator inhibitor type 1 in the pathogenesis of coronary artery disease. Haemostasis 1994; 24: 243-51.
- 18 Lee AJ, Lowe GOD, Smith WCS, Tunstall-Pedoe H. Plasma fibrinogen in women: relationship with oral contraception, the menopause and hormone replacement therapy. Br J Haematol 1993; 83: 616-21.
- 19 Scarabin PY, Plu-Bureau G, Bara L, Bonithon-Kopp C, Guize L, Samama MM. Haemostatic variables and menopausal status: influence of hormone replacement therapy. Thromb Haemost 1993; 70: 584-7.
- 20 Gilabert J, Estellés A, Cano A, España F, Barrachina R, Grancha S, Aznar J, Tortajada M. The effect of estrogen replacement therapy with or without progestogen on the fibrinolytic system and coagulation inhibitors in postmenopausal status. Am J Obstet Gynecol 1995; 173: 1849-54.
- 21 Kim CJ, Jang HC, Cho DH, Min YK. Effects of hormone replacement therapy on lipoprotein(a) and lipids in postmenopausal women. Arterioscler Thromb 1994; 14: 275-81.
- 22 Berg K. A new serum system in man: the Lp system. Acta Pathol Microbiol Scand 1963; 59: 369-82.
- 23 Utermann G, Weber W. Protein composition of Lp(a) lipoprotein from human plasma. FEBS Lett 1983; 154: 357-61.
- 24 Dahlen GH, Guyton JR, Attar M, Farmer JA, Kautz JA, Gotto AM. Association of levels of lipoprotein Lp(a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiography. Circulation 1986; 74: 758-65.
- 25 Rosengren A, Wilhelmsen L, Eriksson E, Risberg B, Wedel H. Lipoprotein(a) and coronary heart disease: a prospective case control study in a general population sample of middle aged men. Br Med J 1990; 301: 1248-51.
- 26 McLean JW, Tomlinson JE, Kuang W, Eaton DL, Chen EY, Fless GM, Scanu AM, Lawn RM. cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature 1987; 330: 132-7.
- 27 Miles LA, Fless GM, Levin EG, Scanu AM, Plow EF. A potential basis for the thrombotic risks associated with lipoprotein(a). Nature 1989; 339: 301-3.
- 28 Hajjar KA, Gavish D, Breslow JL, Nachman RL. Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis. Nature 1989; 339: 303-5.
- 29 Harpel PC, Gordon BR, Parker TS. Plasmin catalyzes binding of lipoprotein(a) to immobilized fibrinogen an fibrin. Proc Natl Acad Sci USA 1989; 86: 3847-51.
- 30 Loscalzo J, Weinfeld M, Fless GM, Scanu AM. Lipoprotein(a) fibrin binding, and plasminogen activation. Arteriosclerosis 1990; 10: 240-5.
- 31 Rouy D, Grailhe P, Nigon F, Chapman J, AngleS-Cano E. Lipoprotein (a) impairs the generation of plasmin by fibrin-bound t-PA: In vitro studies in a plasma milieu. Arterioscler Thromb 1991; 11: 629-38.
- 32 Edelberg JM, Pizzo SV. Lipoprotein(a): the link between impaired fibrinolysis and atherosclerosis. Fibrinolysis 1991; 5: 135-43.
- 33 Hervio LH, Durlach V, Girard-Globa A, AngléS-Cano E. Multiple binding with identical linkage: A mechanism that explains the effect of lipoprotein(a) on fibrinolysis. Biochemistry 1995; 34: 13353-8.
- 34 Utermann G, Kraft HG, Menzel HJ, Hopferwieser T, Seitz C. Genetics of the quantitative Lp(a) lipoprotein trait. I. Relation of Lp(a) glycoprotein phenotypes to Lp(a) lipoprotein concentrations in plasma. Hum Genet 1988; 78: 41-6.
- 35 Kamboh I M, Ferrel RE, Kottke BA. Expressed hypervariable polymorphism of apolipoprotein(a). Am J Hum Genet 1991; 49: 1063-74.
- 36 Marcovina SM, Zhang ZH, Gaur VP, Albers JJ. Identification of 34 apolipoprotein(a) isoforms: differential expression of apolipoprotein(a) alleles between american blancks and whites. Biochem Biophys Res Comm 1993; 191: 1192-6.
- 37 Koschinsky ML, Beisiegel V, Henne-Bruns D, Eaton DL, Lawn M. Apolipoprotein(a) size heterogeneity is related to variable number of repeat sequences in its mRNA. Biochemistry 1990; 29: 640-4.
- 38 Mooser V, Mancini FP, Bopp S, Pethö-Schramm A, Guerra R, Boerwinkle E, Müller H, Hobbs H. Sequence polymorphisms in the apo(a) gene associated with specific levels of Lp(a) in plasma. Hum Mol Genet 1995; 4: 173-81.
- 39 Aznar J, Estellés A, Bretó M, España F, Alós T. Euglobulin clot lysis induced by tissue-type plasminogen activator is reduced in subjects with increased levels of lipoprotein(a). Thromb Res 1992; 66: 569-82.
- 40 Aznar J, Estellés A, Bretó M, España F. Euglobulin clot lysis induced by tissue-type plasminogen activator in subjects with increased levels and different isoforms of lipoprotein(a). Thromb Res 1993; 72: 459-65.
- 41 Szczeklik A, Radwan J, Kubicka A, Libura M, Sacha T, Swadzba J, Undas A, Szczeklik J, Jodlowski J. Plasma fibrinolytic activity in healthy subjects with high and low lipoprotein(a) concentrations. Thromb Res 1992; 66: 391-5.
- 42 Terres W, Krewitt M, Hamm CW. Effects of lipoprotein(a) on in vitro lysis of whole blood thrombi from healthy volunteers. Thromb Res 1993; 69: 479-87.
- 43 Stegnar M, Ambrozic J, Berger B, Keber I. In vitro plasma and euglobulin clot lysis in subjects with elevated lipoprotein(a). Fibrinolysis 1995; 9: 304-8.
- 44 Hervio L, Chapman M, Thillet J, Loyau S, AngléS-Cano E. Does apolipo-protein(a) heterogeneity influence lipoprotein(a) effects on fibrinolysis?. Blood 1993; 82: 392-7.
- 45 Hervio L, Girard-Globa A, Durlach V, AngléS-Cano E. The antifibrinolytic effect of lipoprotein(a) in heterozygous subjects is modulated by the relative concentration of each of the apolipoprotein(a) isoforms and their affinity for fibrin. Eur J Clin Invest 1996; 26: 411-7.
- 46 Palabrica TM, Liu AC, Aronovitz MJ, Furie B, Lawn RM, Furie BC. Antifibrinolytic activity of apolipoprotein(a) in vivo: Human apolipoprotein(a) transgenic mice are resistant to tissue plasminogen activator-mediated thrombolysis. Nature Med 1995; 1: 256-9.
- 47 Soma MR, Osnago-Gadda I, Paoletti R, Fumagalli R, Morriset J, Meschia M. The lowering of lipoprotein(a) induced by estrogen plus progesterone replacement therapy in postmenopausal women. Arch Intern Med 1993; 153: 1462-8.
- 48 Taskinen MR, Puolakka J, Pyörälä T, Luototla H, Björn M, Kääriäinen J, Lahdenperä J, Ehnholm C. Hormone replacement therapy lowers plasma Lp(a) concentrations. Comparison of cyclic transdermal and continous estrogen-progestin regimens. Arterioscler Thromb Vasc Biol 1996; 16: 1215-21.
- 49 Sacks FM, McPherson R, Walsh BW. Effects of postmenopausal estrogen replacement on plasma Lp(a) lipoprotein concentrations. Arch Intern Med 1994; 154: 1106-10.
- 50 Kim CJ, Min YK, Ryu WS, Kwak JW, Ryoo UH. Effect of hormone replacement therapy on lipoprotein(a) and lipid levels in postmenopausal women. Influence of various progestogen and duration of therapy. Arch Intern Med 1996; 156: 1693-700.
- 51 Haines CJ, Chung TK, Masarei JR, Tomlinson B, Lau JT. An examination of the effect of combined cyclical hormone replacement therapy on lipo-protein(a) and other lipoproteins. Atherosclerosis 1996; 119: 215-22.
- 52 Honggi W, Lippuner K, Riesen W, Jaeger P, Birkhouser MH. Long-term influence of the different postmenopausal hormone replacement regimens on serum lipids and lipoprotein(a): a randomised study. Br J Obstet Gynaecol 1997; 104: 708-17.
- 53 Gebara OCE, Mittleman MA, Sutherland P, Lipinska I, Matheney T, Xu P, Welty FK, Wilson PWF, Levy D, Muller JE, Tofler GH. Association between increased estrogen status and increased fibrinolytic potential in the Framingham offsprimg study. Circulation 1995; 91: 1952-8.
- 54 Shahar E, Folsom AR, Salomaa VV, Stinson VL, McGovern PG, Shimakawa T, Chambless LE, Wu KK. Relation of hormone-replacement therapy to measures of plasma fibrinolytic activity. Circulation 1996; 93: 1970-5.
- 55 Kon Koh K, Mincemoyer R, Bui MN, Csako G, Pucino F, Guetta V, Waclawiv M, Cannon III RO. Effects of hormone-replacement therapy on fibrinolysis in postmenopausal women. N Engl J Med 1997; 336: 690-3.
- 56 Scarabin PY, Alhencgelas M, Plubureau G, Taisne P, Agher R, Aiach M. Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial. Arterioscler Thromb Vasc Biol 1997; 17: 3071-8.
- 57 Stroop DM, Glueck CJ, MsCray C, Speirs J, Schumacher HR. Measurement of lipoprotein (a): comparison of MacraTM and Imubind® methods. Ann Clin Lab Sci 1996; 26: 329-39.
- 58 Falcó C, Estellés A, Dalmau J, España F, Aznar J. Influence of lipoprotein (a) levels and isoforms on fibrinolytic activity. Study in families with high lipoprotein (a) levels. Thromb Haemost 1998; 79: 818-23.
- 59 Estellés A, Gilabert J, Aznar J, Loskutoff DJ, Schleef R. Changes in the plasma levels of type 1 and type 2 plasminogen activator inhibitors in normal pregnancy and in patients with severe preeclampsia. Blood 1989; 74: 1332-8.
- 60 Friberger P, Knoss M, Gustavsson S, Aurell L, Claeson G. Methods for determination of plasmin, antiplasmin and plasminogen by means of substrate S-2251. Haemostasis 1978; 7: 138-45.
- 61 Dahlen G, Guyton JR, Attar M, Farmer JA, Kautz JA, Gotto AM. Association of levels of lipoprotein Lp(a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiography. Circulation 1986; 74: 758-65.
- 62 Harpel PC, Hermann A, Zhang X, Ostfeld I, Borth W. Lipoprotein(a), plasmin modulation and atherogenesis. Thrombos Haemost 1995; 74: 382-6.
- 63 Hajjar KA, Nachman RL. The role of lipoprotein(a) in atherogenesis and thrombosis. Ann Rev Med 1996; 47: 423-42.
- 64 Speroff L. Quality of life issues in the management of the menopause. In: Women’s health today (Proc XIV World Congress of Gynecology & Obstetrics). Popkin D, Peddle L. eds Parthenon Pubs group; New York: 1994: pp 271-90.