Abstract
Lipoprotein Lp(a) excess has been identified as a powerful predictor of premature atherosclerotic vascular diseases. To evaluate this in a North-Indian population, 130 CAD patients and 130 controls were analyzed. The size of the apo(a) phenotypic isoforms was inversely proportional to Lp(a) concentrations. The mean concentration of Lp(a) in the CAD patients was 42±34 mg/dl whereas in the normal subjects it was much lower, 27±27 mg/dl. 157 subjects out of the total 260 subjects showed plasma levels of >20mg/dl. The frequency of high Lp(a) levels was much higher in patients(73%) than controls (43%). These data suggest (1) that there is heterogeneity of the Lp(a) polymorphism, (2) Higher Lp(a) levels were found in patients than in the controls, (3) Patients showed 1.5 fold increase in Lp(a) levels as compared to the controls. We conclude that low molecular weight apo(a) isoforms are significantly associated with increased risk of CAD in the North-Indian population.
Keywords: Lipoprotein(a), Apolipoprotein(a), Cholesterol, Coronary artery disease
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References
- 1.Utermann G. In: Lipoprotein (a). The metabolic and molecular basis of inherited disease. Scriver C.R., Beaudet A.L., Sly W.S., Stanbury J.B., Wyngarden J.B., Fredrickson D.S., editors. New Delhi: McGrawHill Inc; 1994. pp. 1887–1912. [Google Scholar]
- 2.Boerwinkle E., Leffert C.C., Lin J., Lackner C., Chiesa G., Hobbs H.H. Apolipoprotein(a) gene accounts for greater than 90% of the variation in plasma lipoprotein(a) concentrations. J. Clin. Invest. 1992;90:52–60. doi: 10.1172/JCI115855. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Brewer, H.B.Jr (1992) Effectiveness of diets and drugs in the treatment of patient with elevated Lp(a) levels. In: Lipoprotein(a), Ed. A.M.Scanu, Academic Press Inc, P.211–220.
- 4.Kemmler H.G., Seitz C. Lp(a) glycoprotein phenotypes: inheritance and relation to LP(a)-lipoprotein. J. Clin. Invest. 1987;80:458–465. doi: 10.1172/JCI113093. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Lackner C., Boerwinkle E., Leffert C.C., Rahjnig T., Hobbs H.H. Molecular basis of apoliproprotein (a) isoform heterogeneity as resolved by pulsed-field gel electrophoresis. J.Clin. Invest. 1991;87:2153–2161. doi: 10.1172/JCI115248. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Smith E.B., Cochran S. Factors influencing the accumulation in fibrous plaques of lipid, derived from low-density lipoproteins: preferential immobilization of Lp(a) Atherosclerosis. 1990;84:173–181. doi: 10.1016/0021-9150(90)90088-Z. [DOI] [PubMed] [Google Scholar]
- 7.Graininger D.J., Kirchenloke H.L., Metcalfe J.C., Weissberg P.L., Wade D.P., Lawn R.M. Proliferation of human smooth muscle cells promoted by LP(a) Science. 1993;260:1655–1658. doi: 10.1126/science.8503012. [DOI] [PubMed] [Google Scholar]
- 8.Kostner G.M. Interaction of LP(a) and LDL with glycosaminoglycans and proteoglycans from human aorta. Arteriorscelerosis. 1988;8:851–857. doi: 10.1161/01.atv.8.6.851. [DOI] [PubMed] [Google Scholar]
- 9.Salonen E.M., Jauhianen M., Zardil F., Vohevi A., Ehnholm C. LP(a) binds to fibronectin and has serine protease activity, capable of cleaving it. EMBO J. 1984;8:4035–4040. doi: 10.1002/j.1460-2075.1989.tb08586.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Miles L.A., Plow E.F. LP(a):an interloper into the fibrinolytic system? Thromb. and Haemostatasis. 1990;63(3):331–335. [PubMed] [Google Scholar]
- 11.Gotoh T., Kuroda T., Yamasawa M., Nishinaga M., Yamada S., Matsuo H., Hosoe M., Itoh Y., Kawai T., Igarashi M., Shimada K. Correlation between lipoprotein (a) and aortic valve sclerosis assessed by echocardiography (the JMS cardiac echo and whort study) Amer. J. Cardiology. 1995;76:928–932. doi: 10.1016/S0002-9149(99)80263-X. [DOI] [PubMed] [Google Scholar]
- 12.Schaefer E.J., Lamon-Fava S., Jenner J.L., McNamara J.R., Ordovas J.M., Lippel K., Levy R.I. Lipoprotein (a) levels and risk of coronary heart disease in men. J. Amer. Med. Assoc. 1994;271:999–1003. doi: 10.1001/jama.271.13.999. [DOI] [PubMed] [Google Scholar]
- 13.Utermann G. The mysteries of lipoprotein (a) Science. 1989;246:904–910. doi: 10.1126/science.2530631. [DOI] [PubMed] [Google Scholar]
- 14.Moliterno D.J., Jokinen E.V., Miserez A.Z., Lange R.A., Willard J.E., Boerwinkle E., Hillis D., Hobbs H.H. No association between plasma lipoprotein(a) concentrations and the presence or absence of coronary atherosclerosis in African-Americans. Arterioscler. Thromb. Vasc. Biol. 1995;15:850–855. doi: 10.1161/01.atv.15.7.850. [DOI] [PubMed] [Google Scholar]
- 15.Kronenberg F., Lobentanz E.M., Konig P., Utermann G., Dieplinger H. Effect of sample storage on the measurement of lipoprotein (a), apolipoprotein B and A-IV, total and high density lipoprotein cholesterol and triglycerides. J. Lipid Res. 1994;35:1318–1328. [PubMed] [Google Scholar]
- 16.Kamboh M.I., Ferrell R.E., Kottke B.A. Expressed hypervariable polymorphism of apolipoprotein(a) Amer.J.Hum. Genet. 1991;49:1063–1074. [PMC free article] [PubMed] [Google Scholar]
- 17.Amemiya H., Arinami T., Kikuchi S., Yamakawa-Kobayashi K., Li L., Fujiwara H., Hiroe M., Marumo F., Hamaguchi H. Apolipoprotein(a) size and pentanucleotide repeat polymorphisms are associated with the degree of atherosclerosis in coronary heart disease. Arteriorscelrosis. 1996;123:181–191. doi: 10.1016/0021-9150(96)05806-6. [DOI] [PubMed] [Google Scholar]
- 18.Ridker P.M., Hennekens C.H., Stampfer M.J. A prospective study of lipoprotein(a) and the risk of myocardial infarction. J. Amer. Med. Assoc. 1993;270:2195–2199. doi: 10.1001/jama.270.18.2195. [DOI] [PubMed] [Google Scholar]
- 19.Alfthan G., Pekkanen J., Jauhianen M., Pitkaniemi K.M., Toumiletho J., Salonen J.T., Ehnholm C. Relation of serum homocysteine and lipoprotein(a) concentrations to atherosclerotic disease in a prospective Finnish population based study. Atherosclerosis. 1994;106:9–19. doi: 10.1016/0021-9150(94)90078-7. [DOI] [PubMed] [Google Scholar]
- 20.Klausen I.C., Beisiegel U., Menzel M.J., Rosseneu M., Nicaud V., Faergeman O. Apo(a) phenotypes and LP(a) concentrations in offspring of men with and without myocardial infarction. The EARS study. Arterioscler. Thromb. Vasc. Biol. 1995;15:1001–1008. doi: 10.1161/01.atv.15.8.1001. [DOI] [PubMed] [Google Scholar]
- 21.Kraft H.G., Lingenhel A., Pang R.W.C., Delport R., Trommsdorff M., Vermaak H., Janus E.D., Utermann G. Frequency distributions of apolipoprotein(a) kringle IV repeat alleles and their effects on Lipoprotein(a) levels in Caucasian, Asian and African populations: The distribution of Null alleles is non-random. Eur.J.Hum.Genet. 1996;4:74–87. doi: 10.1159/000472175. [DOI] [PubMed] [Google Scholar]