Evaluation of Lpa and other independent risk factors for CHD in Asian Indians and their USA counterparts

Conventional risk factors for coronary heart disease (CHD) do not completely account for the observed increase in premature CHD in people from the Indian subcontinent or for Asian Indians who have immigrated to the USA. The objective of this study was to determine the effect of immigration to the USA on plasma levels of lipoprotein a (Lpa) and other independent risk factors for CHD in Asian Indians. Three subject groups were studied: group 1, 57 subjects living in India and diagnosed with CHD (CHD patients); group 2, 46 subjects living in India and showing no symptoms of CHD (control subjects); group 3, 206 Asian Indians living in the USA. Fasting blood samples were drawn to determine plasma levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein LDL cholesterol (LDL-Chol), high density lipoprotein HDL cholesterol (HDL-Chol), apolipoprotein B-100 (apoB-100), and Lpa. Apolipoprotein a (apoa) size polymorphism was determined by immunoblotting. Plasma TG, apoB-100, and Lpa concentrations were higher in CHD patients than in control and USA groups. CHD patients had higher levels of TC and LDL-Chol and lower HDL-Chol than control subjects. However, the USA population had higher levels of TC, LDL-Chol, and apoB-100 and lower HDL-Chol than control subjects. Plasma Lpa levels were inversely correlated with the relative molecular weight of the more abundant of each subject's two apoa isoforms (MAI), and CHD patients showed higher frequencies of lower relative molecular weights among MAI. Our observed changes in lipid profiles suggest that immigrating to the USA may place Asian Indians at increased risk for CHD. This study suggests that elevated plasma Lpa confers genetic predisposition to CHD in Asian Indians, and nutritional and environmental factors further increase the risk of CHD. This is the first report implicating MAI size as a predictor for development of premature CHD in Asian Indians. Including plasma Lpa concentration and apoa phenotype in screening procedures may permit early detection and preventive treatment of CHD in this population. —Hoogeveen, R. C., J. K. Gambhir, D. S. Gambhir, K. T. Kimball, K. Ghazzaly, J. W. Gaubatz, M. Vaduganathan, R. S. Rao, M. Koschinsky, and J. D. Morrisett. Evaluation of Lpa and other independent risk factors for CHD in Asian Indians and their USA counterparts. J. Lipid Res. 2001. 42: 631–638. Conventional risk factors for coronary heart disease (CHD) do not completely account for the observed increase in premature CHD in people from the Indian subcontinent or for Asian Indians who have immigrated to the USA. The objective of this study was to determine the effect of immigration to the USA on plasma levels of lipoprotein a (Lpa) and other independent risk factors for CHD in Asian Indians. Three subject groups were studied: group 1, 57 subjects living in India and diagnosed with CHD (CHD patients); group 2, 46 subjects living in India and showing no symptoms of CHD (control subjects); group 3, 206 Asian Indians living in the USA. Fasting blood samples were drawn to determine plasma levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein LDL cholesterol (LDL-Chol), high density lipoprotein HDL cholesterol (HDL-Chol), apolipoprotein B-100 (apoB-100), and Lpa. Apolipoprotein a (apoa) size polymorphism was determined by immunoblotting. Plasma TG, apoB-100, and Lpa concentrations were higher in CHD patients than in control and USA groups. CHD patients had higher levels of TC and LDL-Chol and lower HDL-Chol than control subjects. However, the USA population had higher levels of TC, LDL-Chol, and apoB-100 and lower HDL-Chol than control subjects. Plasma Lpa levels were inversely correlated with the relative molecular weight of the more abundant of each subject's two apoa isoforms (MAI), and CHD patients showed higher frequencies of lower relative molecular weights among MAI. Our observed changes in lipid profiles suggest that immigrating to the USA may place Asian Indians at increased risk for CHD. This study suggests that elevated plasma Lpa confers genetic predisposition to CHD in Asian Indians, and nutritional and environmental factors further increase the risk of CHD. This is the first report implicating MAI size as a predictor for development of premature CHD in Asian Indians. Including plasma Lpa concentration and apoa phenotype in screening procedures may permit early detection and preventive treatment of CHD in this population. —Hoogeveen, R. C., J. K. Gambhir, D. S. Gambhir, K. T. Kimball, K. Ghazzaly, J. W. Gaubatz, M. Vaduganathan, R. S. Rao, M. Koschinsky, and J. D. Morrisett. Evaluation of Lpa and other independent risk factors for CHD in Asian Indians and their USA counterparts. J. Lipid Res. 2001. 42: 631–638. A high incidence of coronary heart disease (CHD) has been observed among Asian Indians immigrating to the USA (1Enas E.A. Garg A. Davidson M.A. Nair V.M. Huet B.A. Ysuf S. Coronary heart disease and its risk factors in first-generation immigrant Asian Indians to the United States of America.Indian Heart J. 1996; 48: 343-353Google Scholar, 2McKeigue P.M. Miller G.J. Marmot M.G. Coronary artery disease in south Asians overseas: a review.J. Clin. Epidemiol. 1989; 41: 597-598Google Scholar, 3Balarajan R. Ethnic difference in mortality from ischaemic heart disease in England and Wales.Br. Med. J. 1991; 302: 560-564Google Scholar) and among native people remaining within the Indian subcontinent (4Chadha S. Radhakrishnan S. Ramachandran K. Kaul U. Gopinath N. Epidemiological study of coronary heart disease in urban population of Delhi.Indian J. Med. Res. 1990; 92: 424-430Google Scholar, 5Gupta R. Prakash H. Majumdar S. Sharma S. Gupta V.P. Prevalence of coronary heart disease and coronary risk factors in an urban population of Rajasthan.Indian Heart J. 1995; 47: 331-338Google Scholar, 6Bhatia M.L. Prevalence of coronary heart disease in India: a contemporary view.Indian Heart J. 1995; 47: 339-342Google Scholar). The mortality rate for CHD in Asian Indians from Singapore is 4 times higher than in Chinese residents from Singapore, and 20 times higher than in blacks from South Africa (7Enas E.A. Dhawan J. Petkar S. Coronary artery disease in Asian Indians: lessons learnt and the role of lipoprotein a.Indian Heart J. 1997; 49: 25-34Google Scholar). Moreover, CHD in Asian Indians occurs prematurely and is often more severe than in Europeans (8Hughes L.O. Raval U. Raftery E.B. First myocardial infarction in Asian and white men.Br. Med. J. 1989; 298: 1345-1350Google Scholar, 9Lawrence R.E. Littler W.A. Acute myocardial infarction in Asians and whites in Birmingham.Br. Med. J. 1985; 290: 1472Google Scholar). The prevalence of CHD within India is significantly higher in southern compared with northern areas (10Begom R. Singh R.B. Prevalence of coronary artery disease and risk factors in urban population of south and north India.Acta Cardiol. 1995; 3: 227-240Google Scholar), and studies have shown that the incidence of CHD in India is higher in urban regions than in rural parts (6Bhatia M.L. Prevalence of coronary heart disease in India: a contemporary view.Indian Heart J. 1995; 47: 339-342Google Scholar, 11Reddy K.S. Cardiovascular disease in India.World Health Stat. Q. 1993; 46: 101-107Google Scholar). Prevalence of CHD in urban regions of Kerala is as high as 14%, whereas rural Kerala has a prevalence of 7% (10Begom R. Singh R.B. Prevalence of coronary artery disease and risk factors in urban population of south and north India.Acta Cardiol. 1995; 3: 227-240Google Scholar, 12Raman Kutty V. Balakrishnan K.G. Jayashree A.K. Thomas J. Prevalence of coronary heart disease in the rural population of Trivandrum, Kerala, India.Int. J. Cardiol. 1993; 39: 59-70Google Scholar). Traditional risk factors for CHD such as obesity, insulin-dependent diabetes mellitus, smoking, hypertension, and elevated plasma Chol or low density lipoprotein cholesterol (LDL-Chol) levels do not explain the observed increase in CHD incidence among Asian Indians. Earlier reports have shown that serum levels of total Chol (TC) and other blood lipids are normal to low in Asian Indians, and that the incidence of diabetes does not explain the excess cardiac mortality observed in this population compared with subjects of European origin (2McKeigue P.M. Miller G.J. Marmot M.G. Coronary artery disease in south Asians overseas: a review.J. Clin. Epidemiol. 1989; 41: 597-598Google Scholar, 13Forouchi N. McKeigue P.M. How far can risk factors account for excess coronary mortality in south Asians?.Can. J. Cardiol. 1997; 13: 47BGoogle Scholar). Several studies have identified additional CHD risk factors in Asian Indians, including high prevalence of upper body obesity with an increase in waist-to-hip ratio, low levels of high density lipoprotein cholesterol (HDL-Chol), hyperinsulinemia, increased insulin resistance, and non-insulin-dependent diabetes mellitus (NIDDM), especially when subjects are exposed to urban life styles (14Laws A. Jeppesen J.L. Maheux P.C. Schaaf P. Chen Y.D. Reaven G.M. Resistance to insulin stimulated glucose uptake and dyslipidemia in Asian Indians.Arterioscler. Thromb. 1994; 14: 917-922Google Scholar, 15McKeigue P.M. Shah B. Marmot M.G. Relation of central obesity insulin resistance with high diabetes prevalence and cardiovascular risk in south Asia.Lancet. 1991; 336: 383-386Google Scholar, 16Mohan V. Sharp P.S. Cloke H.R. Burrin J.M. Schemer B. Kohner E.M. Serum immunoreactive insulin responses to a glucose load in Asian Indian and European type 2 (non insulin dependent) diabetic patients and control subjects.Diabetologia. 1987; 29: 235-237Google Scholar). Immigration has been selective for urban professionals: 2.5% of Asian Indians in the USA are physicians, and most of the other immigrants are engineers, computer specialists, and businessmen before arrival. Other ethnic groups also tend to develop metabolic abnormalities after migrating to urban environments, but they do not appear to develop premature CHD at rates as high as those of Asian Indians (1Enas E.A. Garg A. Davidson M.A. Nair V.M. Huet B.A. Ysuf S. Coronary heart disease and its risk factors in first-generation immigrant Asian Indians to the United States of America.Indian Heart J. 1996; 48: 343-353Google Scholar). Lipoprotein a (Lpa) is a cholesterol ester-rich lipoprotein composed of an LDL particle and a large hydrophilic glycoprotein, apolipoprotein a (apoa) (17Utermann G. Lipoproteina.in: Scriver C.R. Beaudet A. Sly W.S. Valle D. The Metabolic Basis of Inherited Disease. McGraw-Hill, Scholar, K. Lpa an Lipoprotein Scholar). plasma levels of Lpa an increased risk of CHD and studies that Lpa is an independent risk for this disease J.L. J.M. plasma lipoprotein a and coronary heart disease in and a Med. 1996; Scholar, N. G. Lpa concentration and plasma lipid levels in to coronary heart disease in a Chinese for the role of the apoa in coronary heart Clin. Scholar). of the high plasma Lpa concentrations and the factors plasma Lpa levels have been the subject of is in size of polymorphism in the T. of size as by Clin. 1991; Scholar, K. S. the in Scholar). in the of their each of a of The of apoa to and to is a of the apoa and D. J.L. of and its role in 1989; Scholar, J.M. M. of 1989; Scholar). has been observed that the size of an apoa is inversely to the plasma concentration of Lpa G. Lpa in to concentrations in Clin. 1987; Scholar). has been that of the in plasma Lpa levels can to or the J. G. for than of in plasma Clin. Scholar). of the in plasma Lpa levels has been to the size polymorphism in the apoa G. of the Lpa lipoprotein of Lpa to normal lipid 1989; Scholar). of plasma Lpa levels is to by ethnic origin and studies that south Asians living in have elevated plasma levels of Lpa compared with whites E.A. J. S. T. S. levels in south Asians in 47: Scholar). Moreover, a study has that the serum Lpa is an independent risk for CHD in Asian Indians diagnosed with V. R. G. M. E.A. is an independent risk for coronary artery disease in patients in south Scholar). This study showed that Lpa levels were significantly higher in patients with CHD compared with patients CHD and control subjects. plasma Lpa levels are correlated with apoa size is that this may in for the of Asian Indians to develop premature CHD. are studies on plasma Lpa levels in Asian Indians and have been no reports on apoa size in Asian Indian CHD The study was to the role of risk factors for especially plasma Lpa levels and apoa size in Asian Indian CHD patients control as as in Asian Indians immigrating to the USA. This is the first report on the of apoa polymorphism to the in plasma Lpa levels in Asian Indian CHD patients and control as as first-generation Asian Indian immigrants to the USA. A total of Asian Indians in this of 57 subjects living in the northern regions of India and who were diagnosed with CHD on the of a coronary 2 was composed of 46 control subjects who showed no symptoms of cardiovascular disease and were residents of north was composed of 206 Asian Indians living in the USA and who were at in the of the of their place of within the Indian subcontinent and for of the USA Asian Indian subjects of group were north or south Kerala, or or or or The procedures were in with the of the on and with the of as in in the USA group an before a cardiovascular of a and of a blood not blood lipid were in each the of samples from were blood samples were in Plasma was by low at for at and at Plasma were for TC J. J. for the of serum total cholesterol with 29: Scholar), HDL-Chol J. for of lipoprotein Scholar), and U. G. P. W. for the of serum total triglyceride with Clin. Clin. Scholar) by the LDL-Chol was by the and D. of the concentration of lipoprotein in the of the Scholar) and for the of Lpa cholesterol of serum on of lipoprotein cholesterol by the 1994; Scholar), is Lpa Plasma Lpa levels were by and of Scholar), and to total Lpa by a of Plasma apoB-100 levels were determined by a from The relative molecular weights of apoa isoforms were determined by a of an V.P. of of blacks and Res. 1993; Scholar, J. M.L. W. of and of their molecular weights to plasma levels of Lipid Res. 1990; Scholar). This high are of apoa isoforms that by in isoforms were to the total of in their as determined by with apoa molecular weight and from The two isoforms of each subject were as or the was times more abundant than the as by Plasma Lpa and apoa isoforms Lpa were to and apoa were by and were with The of risk factors on the prevalence of within each were by of were by were with and the The of the study are in The Asian Indian subjects in the CHD group were who were and had higher of diabetes and compared with the Asian Indian control group and USA The USA group had significantly but a higher incidence of of cardiovascular disease than the Asian Indian CHD group and control of Asian Indian study glucose than body of a group of 57 patients with coronary heart disease (CHD) living in northern a group of 46 subjects CHD living in northern a group of 206 Asian Indian subjects living in the not blood glucose than body in a a group of 57 patients with coronary heart disease (CHD) living in northern a group of 46 subjects CHD living in northern a group of 206 Asian Indian subjects living in the not blood The plasma lipid profiles of the study are shown in CHD patients had significantly higher plasma levels compared with subjects of the control and USA Asian Indian groups. for plasma levels in study were TC and LDL-Chol levels were significantly higher for the CHD and USA groups the control subjects had higher plasma levels of HDL-Chol compared with CHD patients and USA Asian Indians of and Plasma apoB-100 levels were significantly higher for CHD patients USA Asian Indian and control groups of and Plasma levels of Lpa were the lower concentrations in study groups and from to from to and from to in the and USA The CHD patients had higher plasma levels of compared with the USA and control study in Lpa and levels CHD patients and control subjects not at the The of subjects with plasma Lpa levels was in the CHD group control and USA Asian Indian groups and plasma lipid from the USA study population were on the of place of no were in plasma levels of TG, TC, or However, plasma levels of apoB-100, and were significantly lower in USA Asian Indian subjects in the regions of the Indian lipid of Asian Indian study Asian from control group higher than total USA Asian Indian group from control group from control group from control group higher than total USA Asian Indian group from control group from control group from control group was not but was from the total Lpa is to the but can to the total plasma Chol higher than total USA Asian Indian group from and India within the USA Asian Indian group from control group higher than total USA Asian Indian group from and India within the USA Asian Indian group higher than total USA Asian Indian group from and India within the USA Asian Indian group a group of 57 patients with coronary heart disease (CHD) living in northern a group of 46 subjects CHD living in northern a group of 206 Asian Indian subjects living in the from control group higher than total USA Asian Indian group was not but was from the total Lpa is to the but can to the total plasma Chol from and India within the USA Asian Indian group in a a group of 57 patients with coronary heart disease (CHD) living in northern a group of 46 subjects CHD living in northern a group of 206 Asian Indian subjects living in the of to the of risk factors on the prevalence of CHD among Asian Indians living in India their USA the India the of CHD increased an of times for of and were times in than increase in TC and LDL-Chol the risk for CHD increased by and in this study population. the risk for CHD increased by for increase in the of the plasma Lpa and subjects in the India group had for risk factors not and diabetes and were from the the USA diabetes was to a predictor of CHD at the and the risk for CHD was times in than in of the subjects in this study population had CHD a not for this risk of risk factors on the prevalence of CHD in Asian and changes in of of in of Asian Indian subjects living in northern USA Asian Indian subjects living in the not blood and changes in of in of Lpa. in a India Asian Indian subjects living in northern USA Asian Indian subjects living in the not blood The molecular weights of apoa isoforms were determined in and the of subjects or two isoforms were and of CHD and of control and and of the USA Asian Indian study apoa in and of the subjects in the and USA Asian Indian The detection of a apoa was and the was to apoa isoforms in from to The apoa size of the study are shown in of each subject's two the more abundant and abundant are shown in and the of MAI are shown in were compared in of the of MAI was in the CHD group compared with in the control group and the and for the CHD group were and compared with and for the control suggest that CHD patients had a higher of apoa isoforms with compared with the control This was further by MAI among the CHD and control groups and the CHD the of MAI was lower than the in the control an of for of of this not were observed for the and The USA group had MAI and MAI that more those of the control subjects than the CHD subjects of the USA Asian Indian study population were to place of from the regions of India had the apoa compared with subjects in or India and This higher prevalence of high molecular weight apoa isoforms in the subjects in India the plasma Lpa concentrations in this also the relative of apoa isoforms to the control of plasma Lpa 4 the apoa size and plasma Lpa A was the more abundant apoa size and plasma Lpa concentration the of the of MAI size polymorphism to the in plasma Lpa concentration was to an of abundant apoa with plasma levels of this was and of the Lpa levels by in size polymorphism The incidence of premature CHD in Asian Indians is among the for ethnic group E.A. Ysuf S. J. of the group on coronary artery disease in south Heart J. 1996; 48: Scholar). to other ethnic higher in immigrant Asian Indians compared with the native people of the of immigration (1Enas E.A. Garg A. Davidson M.A. Nair V.M. Huet B.A. Ysuf S. Coronary heart disease and its risk factors in first-generation immigrant Asian Indians to the United States of America.Indian Heart J. 1996; 48: 343-353Google Scholar, 2McKeigue P.M. Miller G.J. Marmot M.G. Coronary artery disease in south Asians overseas: a review.J. Clin. Epidemiol. 1989; 41: 597-598Google Scholar, 3Balarajan R. Ethnic difference in mortality from ischaemic heart disease in England and Wales.Br. Med. J. 1991; 302: 560-564Google Scholar). to that in to nutritional and environmental factors increased of and higher life genetic factors may also to the increased prevalence of CHD in the Asian Indian population. The plasma lipid of the CHD population showed significantly higher levels of TG, TC, LDL-Chol, and apoB-100, as as a lower plasma HDL-Chol than the control are not elevated plasma levels of TC and LDL-Chol and low HDL-Chol levels are to correlated with an increased risk for CHD. is that the plasma lipid of the USA Asian Indian study group showed a to that of the CHD group in with that of the Asian Indian control subjects. Asian Indians living in the USA had higher plasma levels of TG, TC, and LDL-Chol, as as lower HDL-Chol levels than the subjects in the control for plasma TG, TC, and LDL-Chol were within the normal in study groups. This is in with studies that have plasma levels of Chol and other blood lipids to in the low to normal in immigrant Asian Indians (2McKeigue P.M. Miller G.J. Marmot M.G. Coronary artery disease in south Asians overseas: a review.J. Clin. Epidemiol. 1989; 41: 597-598Google Scholar, E.A. J. S. T. S. levels in south Asians in 47: Scholar) as as residents of India K. P. M. obesity, insulin resistance, and cardiovascular risk in Indians, and Chinese in Epidemiol. 1997; Scholar). However, of the subjects in the USA Asian Indian study population had high plasma levels of TC and had plasma LDL-Chol levels The prevalence of high plasma levels of TC and LDL-Chol in Asian Indian group was to that of the CHD group and but was higher than that of the control group and that Asian Indians living in the USA may at increased risk for CHD. Plasma Lpa levels were the lower concentrations in study and the was higher in the CHD population the USA Asian Indian and control groups. are in with for plasma Lpa levels in Asian Indians E.A. J. S. T. S. levels in south Asians in 47: Scholar, V. R. G. M. E.A. is an independent risk for coronary artery disease in patients in south Scholar), but are lower than by this and for W. of plasma lipoprotein levels to and to apolipoprotein 1985; Scholar, N. A. W. H. G. isoforms risk for coronary heart a study in Thromb. Scholar). were to of CHD among Asian Indians living in India their USA counterparts. TC, LDL-Chol, and plasma Lpa were risk factors for CHD among Asian Indians living in India and subjects in this study population had for risk factors not and diabetes and had to from the the USA diabetes was to a predictor of CHD with a for incidence of CHD in than in However, that or 7% of the USA study had CHD. is that to of CHD of the low incidence of CHD in the USA of the subjects in this study population had CHD and a not for this risk size were in study groups of apoa isoforms have been in from the USA and T. of size as by Clin. 1991; Scholar, A. E.A. of apoa polymorphism and the control of plasma Lpa for a Thromb. Scholar). A significantly higher of the CHD patients lower molecular weight apoa isoforms compared with the USA Asian Indian and control groups. USA Asian Indians who were in India the of high molecular weight apoa isoforms compared with those in south or The high plasma Lpa levels in the CHD patients and the low plasma Lpa levels in USA Asian Indians in India are of an apoa size and plasma Lpa concentration in Asian Indian is that apoa size is inversely correlated with plasma Lpa and has been that of the in plasma Lpa levels can to apoa size polymorphism G. of the Lpa lipoprotein of Lpa to normal lipid 1989; Scholar). However, a study has shown that the of apoa size to the control of plasma Lpa concentration was lower than the in plasma Lpa concentration was not the apoa size A. E.A. of apoa polymorphism and the control of plasma Lpa for a Thromb. Scholar). to a more of the of apoa size with plasma Lpa concentration in study each subject's two apoa isoforms as more or abundant apoa isoforms or and the relative of apoa isoforms to the control of plasma Lpa levels in study groups. A was MAI and plasma Lpa levels the and plasma Lpa was of MAI and size polymorphism were and are significantly lower than those by and G. of the Lpa lipoprotein of Lpa to normal lipid 1989; Scholar). Our were from 2 whereas and of the of to the of a J. 39: Scholar) their by a Our that MAI size polymorphism is a predictor of plasma Lpa levels in Asian Indians. the from study suggest that elevated plasma levels of Lpa a genetic predisposition to CHD in Asian Indians. The for CHD risk of Lpa may that risk among Asian Indians. A more for this population may Lpa. The effect of nutritional and environmental with a genetic may Asian Indians living in the USA at increased risk for premature CHD. and of plasma Lpa as of a screening of independent risk factors for may in the of who are to CHD. Asian Indians appear to a population for the of Lpa and premature CHD. This study was in by to from the and from the The the of A. R. and in study subjects.