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Lp (a) in Indians

Heart Disease Among Asian Indians 

  •  Asian Indians develop premature CAD (coronary artery disease) at a very young age, lower body mass index (BMI), and lower waist circumference. Traditional risk factors for CAD have consistently failed to completely explain this Asian Indian paradox. (Figure 003)
  • Numerous studies in the past decade indicate that elevated blood level lipoprotein(a) (Lp(a)) confers genetic predisposition to CAD in Asian Indians, and nutritional and environmental factors further increase the risk of CAD.1-3
  • Enas et al4 were the first to report high levels of Lp(a) in Asian Indians in the CADI Study.4 Asian Indians have Lp(a) levels intermediate between whites and blacks. However, blacks have a lower rate of CAD despite having the highest levels of Lp(a), which appears to be due to the presence of less dangerous large isoforms and high HDL levels.1, 5, 6
  • Numerous studies since then have consistently reported elevated Lp(a) levels in Asian Indians in  the US,7 Canada,8 Singapore,9 UK,10 Australia, and India, regardless of their migration status.1, 2, 9, 11-19  A genetic determination of Lp(a) levels in Asian Indians is strongly supported by identical Lp(a) levels in several countries, with an approximate median level of 20 mg/dL.
  • In the U.K, Lp(a) levels in Asian Indians are significantly higher than whites but identical to their siblings living in India.13Also, Asian Indians with CAD and their offspring in the U.K. had higher Lp(a) levels than white CAD patients and their offspring.20
  • Numerous case control and angiographic studies have shown Lp(a) to be a powerful risk factor for premature CAD and stroke among Asian Indians.2, 11, 12, 21-25
  • Lipoprotein(a) level is one of the few risk factors that is highly correlated with angiographic severity of CAD in Indians.26, 27
  • More than 10 angiographic and case-control studies in India have shown elevated Lp(a) levels to be the most powerful risk factor for premature CAD, especially in those younger than 40 years of age.3, 12
  • Blood level of Lp(a) is an independent risk factor for clinical and subclinical heart disease in diabetic patients in India.14, 28
  • Small Lp(a) isoforms are more common and strongly correlated with CAD and the risk is further increased with low HDL. Low HDL is found in 92% of Indians and the combination of high Lp(a) and low HDL2b is found in 42% of Indians.2, 29, 30
  • The combination of high levels of Lp(a) and  homocysteine,  and high prevalence of diabetes, metabolic syndrome, and Asian Indian dyslipidemia— and the synergistic interaction among these risk factors—best explains the high prevalence of premature, severe, diffuse, multi-vessel malignant CAD among Indians globally.3, 31, 32

Sources 

1. Enas EA, Chacko V, Senthilkumar A, Puthumana N, Mohan V. Elevated lipoprotein(a)–a genetic risk factor for premature vascular disease in people with and without standard risk factors: a review. Dis Mon. Jan 2006;52(1):5-50.

2. Hoogeveen RC, Gambhir JK, Gambhir DS, et al. Evaluation of Lp[a] and other independent risk factors for CHD in Asian Indians and their USA counterparts. J Lipid Res. 2001;42(4):631-638.

3. Enas EA. Lipoprotein(a) is an important genetic risk factor for coronary artery disease in Asian Indians. Am  J  Cardiol. 2001;88:201-202.

4. Enas EA, Yusuf S, Garg A, Davidson L, Thomas J, Pearson T. Lipoprotein (a) levels in Indian physicians: Comparison with Black and White physicians in the U.S.A. Indian Heart J. 1994;46 suppl:185(abstract).

5. Enas EA, Mehta J. Malignant coronary artery disease in young Asian Indians: Thoughts on pathogenesis, prevention,  and treatment. Clin Cardiol. 1995;18:131-135.

6. Jha P, Enas E, Yusuf S. Coronary Artery Disease in Asian Indians: Prevalence and Risk Factors. Asian Am Pac Isl J Health. Autumn 1993;1(2):163-175.

7. Chuang CZ, Subramaniam PN, LeGardeur BY, Lopez A. Risk factors for coronary artery disease and levels of lipoprotein(a) and fat-soluble antioxidant vitamins in Asian Indians of USA. Indian Heart J. 1998;50(3):285-291.

8. Anand S, Enas EA, Pogue J, Haffner S, Pearson T, Yusuf S. Elevated lipoprotein(a) levels in South Asians in North America. Metabolism. 1998;47(2):182-184.

9.  Hughes K, Aw TC, Kuperan P, Choo M. Central obesity, insulin resistance, syndrome X, lipoprotein(a), and cardiovascular risk in Indians, Malays, and Chinese in Singapore. J Epidemiol Community Health. 1997;51(4):394-399.

10. Shaukat M, de Bono D. Are Indo-origin especially susceptible to coronary artery disease? Postgrad Med. 1994;70:315 – 318.

11. Gupta R. Coronary heart disease epidemiology in India: Lessons learnt and future directions. In: A K, ed. Current Perspectives in Cardiology. Chennai: Cardiological Society of India; 2000:97-108.

12. Gambhir JK, Kaur H, Gambhir DS, Prabhu KM. Lipoprotein(a) as an independent risk factor for coronary artery disease in patients below 40 years of age. Indian Heart J. 2000;52(4):411-415.

13. Bhatnagar D, Anand IS, Durrington PN, et al. Coronary risk factors in people from the Indian subcontinent living in west London and their siblings in India. Lancet. 1995;345(8947):405-409.

14. Mohan V, Deepa R, Haranath SP, et al. Lipoprotein(a) is an independent risk factor for coronary artery disease in NIDDM patients in South India. Diabetes Care. Nov 1998;21(11):1819-1823.

15. Anand SS, Enas EA, Pogue J, Haffner S, Pearson T, Yusuf S. Elevated lipoprotein(a) levels in South Asians in North America. Metabolism. Feb 1998;47(2):182-184.

16. Anand SS, Yusuf S, Vuksan V, et al. Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic groups in Canada: the Study of Health Assessment and Risk in Ethnic groups (SHARE). Lancet. 2000;356(9226):279-284.

17. Sandholzer C, Hallman DM, Saha N, et al. Effects of the apolipoprotein(a) size polymorphism on the lipoprotein(a) concentration in 7 ethnic groups. Hum Genet. 1991;86(6):607-614.

18. 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.

19. Chambers J. C., Kooner JS. Diabetes, insulin resistance and vascular disease among Indian Asians and Europeans. Semin Vasc Med. May 2002;2(2):199-214.

20.Shaukat  N, de Bono DP, Jones DR. Like father like son? Sons of patients of European or Indian origin with coronary artery disease reflect their parents’ risk factor patterns. Br Heart J. 1995;74(3):318-323.

21. Gupta R, Gupta VP. Meta-analysis of coronary heart disease prevalence in India. Indian Heart J. 1996;48(3):241-245.

22. Gambhir JK, Kaur H, Prabhu KM, Morrisett JD, Gambhir DS. Association between lipoprotein(a) levels, apo(a) isoforms and family history of premature CAD in young Asian Indians. Clin Biochem. Feb 5 2008.

23. Gambhir JK, Gambhir D, Morreset J. Lipoprotein(a) in normal indian subjects and and patints with coronary artery disease. Indian Heart  J. 1998;50:563.

24. Gambhir JK, Kaur H, Prabhu K. Lipoprotein(a) levels and Apo-A isoform size as risk factors for premature coronary artery disease in native Indians and immigrants in U.S.A. Indian H  J. 2001;53:573.

25. Christopher R, Kailasanatha KM, Nagaraja D, Tripathi M. Case-control study of serum lipoprotein(a) and apolipoproteins A-I and B in stroke in the young. Acta Neurol Scand. Aug 1996;94(2):127-130.

26. Gupta R, Vasisht S, Bahl VK, Wasir HS. Correlation of lipoprotein(a) to angiographically defined coronary artery disease in Indians. Int J Cardiol. 1996;57(3):265-270.

27. Geethanjali FS, Luthra K, Lingenhel A, et al. Analysis of the apo(a) size polymorphism in Asian Indian populations: association with Lp(a) concentration and coronary heart disease. Atherosclerosis. Jul 2003;169(1):121-130.

28. Velmurugan K, Deepa R, Ravikumar R, et al. Relationship of lipoprotein(a) with intimal medial thickness of the carotid artery in Type 2 diabetic patients in south India. Diabet Med. Jun 2003;20(6):455-461.

29. Superko HR, Enas EA, Kotha P, Bhat NK, Garrett B. High-density lipoprotein subclass distribution in individuals of asian Indian descent: the National Asian Indian Heart Disease Project. Prev Cardiol. Spring 2005;8(2):81-86.

30. Enas EA, Chacko V, Pazhoor SG, Chennikkara H, Devarapalli HP. Dyslipidemia in South Asian patients. Curr Atheroscler Rep. Nov 2007;9(5):367-374.

31.  Enas EA. How to Beat the Heart Disease Epidemic among South Asians: A Prevention and Management Guide for Asian Indians and their Doctors. Downers Grove: Advanced Heart Lipid Clinic  USA; 2010.

32. Bhalodkar NC, EA E. Malignant Coronary Artery Disease and the Asian Indian Paradox  Proceedings of the 13th International Congress on Heart Disease Conference, New Trends in Research, Diagnosis, and Treatment 2007:157-164.

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