Idea Transcript
Clin. C'ardiol. 18, 131-135 (1995)
Malignant Coronary Artery Disease in Young Asian Indians: Thoughts on Pathogenesis, Prevention, and Therapy ENASA.ENAS,M.D.,F.A.C.C.,ANDJAW~AKMEHTA,M.D.,PH.D.:~
Coronaiy Artery Disease in Asian Indians (CADI)Study, Woodridge, Illinois, and *Division of Cardiology, University of Florida College of Medicine, Gainesville, Florida, USA
Summary: Asian Indians have the highest rates of coronary artery disease (CAD) of any ethnic group studied, despite the fact that nearly half ofthis group are life-long vegetarians. CAD occurs early in age and generally follows a malignant course. Altho~ighthe incidence of classic risk factors is low, high triglyceride and low high-density lipoprotein cholesterol levels, high lipoprotein(a) levels, hyperinsulinemia, and apple-type obesity all show a substantial prevalence in this population. Aggressive mtdification of life style beginning before adolescence seemsjustified in view ofthe malignant nature of CAD in this population. Pharmacologic intervention similar to that of secondary prevention of CAD seems justified as primary prevention i n high-risk Asian Indians. Key words: coronary artery disease, Asian Indians, lipoptotein(a1
Introduction One-fifth of the world's population lives in India and a population equal to that of Australia is added to this every year. About 15 million Asian Indians live outside India, including one million in the USA. Of these, 27,000 are physicians and constitute 5% of the physician population of the USA. Asian Indians (people lkom the subcontinent of India, Pakistan, and Bangladesh) have one of the highest rates of coronary artery disease (CAI)) of any ethnic group studied, despite the fact that nearly half are life-long vegetarians. In this article we review the incidence. prevalence, hospitalization, and mortality from CAD among A\ian Indians and present some thoughts on prevention of and therapy for malignant premature CAD in this population.
Addre\\ for reprints:
Enas A. Inas, M.D., EA.C.C 3.510 I i o h n Rd, Suite 301 Woodridge, IL 60.517, USA Received: June 10, 1YY4 Accepted: June 13, 1994
High Incidence of CAD in Asian Indian Men and Women Several studies have reported high rates of CAD in this population. For example, men in New Delhi, North India were found to have four times higher (2.5 vs. 9.7%) prevalence of CAD than in Framingham, Mass.'s2 The hospitalizationrate for CAD at Christian Medical College Vellore, South India, has increased from 4% of all cardiac admissions in 1960 to 33% in 1 989.3 The prevalence of CAD among male physicians who were born in India and migrated to the United States is three to four times higher than that of the general physician population of the United The hospitalization rate for CAD in the United States among Asian Indians who are not physicians is four times higher than that of Caucasians, Japanese, and Filipinos, and five times higher than that of Chinese and other Asians6 In a prospective study of men in Trinidad, the incidence of CAD per 1 ,OOO person years was found to be 16.4 in men of Indian descent, 6.8 in men of African descent, 6.2 in those of European descent, and 2.4 in men of mixed d e ~ c e n t . ~ The high rates of CAD mortality in the U.K., four to five times greater than in France, may be partly due to very high CAD mortality rates in Asian Indians. Indeed, the standardized mortality ratio (SMR) for CAD among Asian Indian males in the U.K. is twice the national average between the ages of 30 and 39 and more than three times the national average between the ages of 20 and 29, despite universal access to similar advanced health care under the National Health Service.* The CAD rates are high in Asian Indian women a well. For example, the prevalence of CAD in women in New Delhi is about lo%.' The S M R for CAD among Asian Indian immigrant women in the U.K. is 1.5 times higher than of native British women and 2.6 times higher than of the immigrant American women.* Asian Indian women in South Africa also have the highest SMR for CAD of all ethnic groups: 4 times higher than that of U.S. women, 14 times higher than that of French wonien, and 2 1 times higher than that of Japanese women.9 The most striking feature of CAD in Asian Indians is its predilection for accelerated atherosclerosis resulting in an unusually high rate of premature morbidity and mortality.8-'3Atherosclerosis in young Asian Indians is very severe, extensive, virulent, and rapidly progressive as illustrated by the following case.
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Clin. Cardiol. Vol. 18, March 1995
Case Report A 39-year-old Asian Indian psychiatrist, a life-time nonsmoker, with a family history of premature CAD was hospitalized with an acute inferior myocardial infarction (MI). He was 5' 7" tall and weighed 180 pounds. He had no hypertension or diabetes. His total cholesterolwas 208 mg/dl, high-density lipoprotein (HDL) 28 mg/dl, and triglyceride 152 mg/dl. His coronary angiogram showed total occlusion of the right coronary artery with no significant disease in other vessels. Four weeks after the uncomplicated MI, he was able to exercise I2 min on treadmill (Bruce protocol) without ischemic changes on the electrocardiogram.His advised medical management consisted of a low-fat diet, exercise, weight reduction, and cholesterollowering medication. Nine years later the patient developed severe exertional dyspnea and fatigue. A thallium perfusion scan showed extensive defects in the anterior inferior, posterior, and lateral walls, and in the septum with minimal change between rest and exercise. A two-dimensional echocardiogram confinned extensive wall motion abnormalities with an ejection fraction of25%. Left ventricular angiogram showed a mildly dilated cavity with posterior, badar, anterolateral akinesia, and apical dyskinesia.The estimated ejection kaction was 2530%. Leti ventricular end-diaqtolic pressure was 36 mmHg. Coronary angiogram showed severe diffuse disease with total occlusion of all three major coronary arteries. The patient underwent quadruple aortocoronary bypass suQery, but sought permanent disability due to persistent symptoms. Lipoprotein (a) [Lp(a)] level was found to be I02 mg/dl in the patient and 90 mg/dl in his 18-year-old son.
Malignant Atherosclerosisin Young Asian Indians Premature CAD is defined as CAD occurring below the age of65 in women and 55 in men. CAD in the young is defined as CAD occurring in patients < 40 years of age14 and may represent the most severe form of premature CAD. Of all cases of CAD in the West, less than 5% occur in the young.14The largest and most recent data from Texas involving 5,316 patients showed a prevalence of CAD in the young of only 2%.Is However, CAD in the young is being recognized with increa$ingfrequency and is as high as 12% in India.I6 In an angiographic study of patients with CAD under 40 ycars of age in Malaysia, 56% were Asian Indians, although Asian Indians comprise only 10% of the population. After taking into account the distribution of population of Malaysia, young Asian Indians had a 15-foldhigher rate of CAD compared with Chinese and a l0-fold higherrate compared with Malays.l' Similarly, a review of patients hospitalized with a diagnosis of MI in Quatar showed that 23% were under40 years of age, and 7 1 % of these were Asian Indians, although these immigrants fonn only a very small minority ofthe population." In studies in the U.K., first MI was noted to occur on an average of5 years earlier, and its occurrence before age 40 was 10-fold higher in Indians than in Caucasians.17 Asian Indians had a substantially higher frequency oftriple-vessel CAD (54 vs. 2 1%) and athero-
ma scores in coronary arteries (3.66 vs. 1.97). Infarct size assessed by peak creatine kinase or degree of ventricular dysfunction was also significantlygreater in Asian Indians. The first MI in this population was usually massive, resulting in a high rate of death or disability. Many Asian Indians were found to be unsuitablefor coronary artery bypass surgery because of the severity of CAD, and 25% of these patients died soon afterward (vs. 6% of Caucasians),indicating the severe nature of the disease. I
Angiographic Data from India Data from India seem to confirm the extensive and severe CAD among young I n d i a n ~ ~which ~ - * ~seems to occur early in life. In an angiographic study of 1,066consecutive male patients at Christian Medical College, Vellore, significant CAD was noted in 877 subjects.Ofthese, 55% were < SO y e a of age, 34% were < 45 years of age, and I2 % were 60 mg/dl). It is important to note that the Indian vegetarians are no exception as they have the same high rate of CAD as nonvegetarians." Since HDL cholesterol and Lp(a) are not amenable to dietary modification,increased physical activity may be more important in this population. This will also help raise the HDL cholesterol, lower triglyceride levels, and mod@ insulin resistance. However, diet does influence the serum levels of LDL and triglyceride. If one Fails to achieve the optimum lipid protile with life-style modification,then aggressivephmacologic treatment, often with multiple medications, may be necessary. This is particularly true in patients with premature CAD and others undergoing coronluy angioplasty,coronary bypass surgery, or other revascularization procedures. The adverse effects of Lp(a) can be reduced by lowering LDL cholesterol substantially."3 Safe and effective medications to lower LDL, such as cholestyramine and hydroxymethyl glutaryl (HMG) coenzyme A reductase inhibitors are now available."" Though more difficult to take in large doses, moderate doses of niacin can lower the levels ofLp(a) and triglycerideand raise HDL cholesterol. Together with an HMG coenzyme A
reductase inhibitor, niacin can help optimize the lipid profile in most individuals.
Conclusions Asian Indians have the highest rate of CAD of any ethnic groups studied thus far. Coronary atherosclerosis in this population occurs early and is very severe, extensive, and follows a malignant course with high mortality. Though conventional risk factors, such as high cholesterol, hypertension, and cigarette smoking, have failed to explain the excess risk of CAD fully, the importance of these risk factors cannot be ignored. Diabetes, insulin resistance, high triglyceride, low HDL cholesterol, and abdominal obesity are also important risk factors in the genesis of CAD in Asian Indians, but cannot account for the 5-1 0-fold higher rate of CAD in individuals under 40 years of age. A genetic predisposition to CAD is suggested by the high levels of Lp(a). Measurements of Lp(a) may offer a unique opportunity to implement early high-risk prevention strategies in Asian Indians3' and should be included in all future studies in assessing the lipid-related risk of CAD in Asian Indians. Since Lp(a) levels are not influenced by diet and environmental factors, pharmacologic means may have to be instituted in high-risk individuals earlier than in other populations. Guidelines developed for pharmacologic treatment of dyslipidemias in Caucasians may be too generous for this population. Aggressive modification of life style and careful evaluation of all lipoproteins, including Lp(a), beginning before adolescence, seem justified in view of the malignant nature of atherosclerosis in this population. Pharmacologic intervention similarto that of secondary prevention of CAD, such as an LDL goal of 100 mg/dl, seems justified as primary prevention in high-risk individuals.
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