Coronary Artery Disease in South Asians

Commentary by Muhammad Ghumman MD, PGY-3

Faculty Peer Reviewed

South Asia (India, Pakistan, Bangladesh, Sri Lanka, and Nepal) comprises 25% of the global population yet contributes nearly 60% of the global cardiovascular disease burden. There are over 3 million South Asians living in North America (2 million in United States and nearly a quarter million in New York City alone). It is important to recognize that South Asians develop coronary artery disease (CAD) at a younger age, die from CAD at younger ages, and have higher overall CAD-associated mortality.(1-6)

Numerous studies have demonstrated higher CAD rates amongst South Asians at all ages. Prevalence of CAD in rural South Asia is 3-4%, while the CAD prevalence amongst urban South Asians and South Asian immigrants to the western world approaches 10%. (2,7,8) The Coronary Artery Disease in Indians (CADI) study demonstrated a CAD prevalence of 10% amongst first generation South Asian immigrants to the United States, compared to a 2.5% CAD prevalence among the general population in the Framingham study.(2) The higher prevalence is further magnified in younger South Asians. United Kingdom mortality data demonstrates 3 times higher CAD prevalence for South Asians younger than 40 years and 1.5 times higher CAD prevalence for South Asians older than 60 years. Contribution of the younger age group to overall CAD-associated mortality is significantly higher in South Asians. A 1990 World Health Organization showed that the proportion of cardiovascular deaths occurring before 70 years of age was 26% in developing countries but 52% in India.

Despite the increased prevalence of CAD, rates of many traditional CAD risk factors such as smoking, hypertension, and obesity are not higher among South Asians. Smoking is actually lower amongst South Asians and virtually nonexistent among South Asian females.(7,12,17) Diabetes Mellitus (DM) however is significantly more common among South Asians, having a 2% prevalence in rural South Asia but approaching a 20% prevalence in urban South Asia and amongst immigrant South Asians.(7,11,12,13) While total cholesterol and LDL levels may be similar to other ethnic groups, South Asians have characteristic lipid profiles increasing their risk for CAD: higher triglyceride levels, higher lipoprotein(a) levels, increased ratio of apolipoprotein B to apolipoprotein A-1 (apoB/apoA-1), smaller HDL and LDL particle size, and lower levels of HDL.(14,15,16,25) These factors are rarely screened for or targeted by most physicians. Lipoprotein(a) is an emerging independent and compounding risk factor for the development of CAD and, unlike other lipids, its levels are almost entirely determined by genetics. South Asians have the second highest levels of lipoprotein(a) after African Americans and this may explain some of the increased CAD risk in these ethnic groups. Lipoprotein(a) is proposed to be an independent CAD risk factor and also thought to multiply the effect of traditional CAD risk factors (low HDL, high LDL, DM). Screening for lipoprotein(a) is most important in younger South Asians since the lipoprotein(a)-associated CAD risk is highest between 45-55 years of age and declines in old age. (24,25) Because of the multiplicative effect of lipoprotein(a) on other CAD risk factors, South Asians have a higher CAD risk at any given level of LDL and total cholesterol. Physicians should be aware that this leads to a significant underestimation of CAD risk in South Asians by the Framingham risk score.

Most of the increased CAD risk in South Asians can be explained by a higher prevalence of traditional risk factors, especially at a younger age. INTERHEART study (9) (an international case-control study examining risk factors for initial MI in 52 countries, including 12,000 cases of initial MI and 14,000 controls) demonstrated that over 90% of global MI risk can be attributed to 9 modifiable risk factors (smoking, DM, lipids, central obesity, hypertension, diet, physical activity, alcohol consumption, and psychosocial factors). This was true for all populations including South Asians. However, South Asians presented with initial MI at earlier ages (53 yrs vs. 58 yrs) and this can be explained by the presence of more risk factors at an earlier age. Protective factors (moderate daily alcohol consumption, regular physical activity, daily intake of fruits and vegetables) were significantly lower among South Asians. Harmful factors were significantly higher in South Asians (DM and elevated apoB/apoA-1 ratio). When compared to other risk factors, elevated apoB/apoA-1 ratio had the single highest attributable risk in South Asians. When compared to other ethnic groups, certain risk factors had higher attributable risk in South Asians: apoB/apoA-1 ratio, low daily consumption of fruits and vegetables, lack of regular exercise, and high waist hip ratios (marker of central obesity which predisposes to insulin resistance).

Overall obesity rates (by BMI standards) are actually lower in South Asians however central obesity rates are significantly higher in South Asians and are associated with development of insulin resistance, metabolic syndrome, and a 2-3 fold increased CAD risk. (18) This population has a “thin-fat phenotype (low in muscle, high in fat even if BMI<25), thus BMI should be replaced by waist circumference or waist-hip ratios as a screening tool for obesity. The South Asian diet also predisposes towards developing dyslipidemia and thus increases CAD risk. Use of saturated and trans fats is very common, whole milk and clarified butter (ghee) are commonly used, and deep frying is utilized for many South Asian dishes. Even vegetables are prepared with liberal amounts of saturated and trans fats, explaining similar rates of dyslipidemia and CAD among South Asian vegetarians and non-vegetarians. Furthermore, protective effects of fruits and vegetables may be negated by long cooking times which denature protective nutrients. Regular physical exercise is rare in this population and almost nonexistent in women due to cultural limitations.

South Asian migration to more affluent areas (from rural South Asia to urban South Asia and from South Asia to the western world) leads to significantly higher rates of CAD pointing towards genetic and environmental interplay. This genetically susceptible population develops CAD risk factors at higher rates under certain urban environmental factors (reduced energy requirements due to lack of physical activity coupled with a higher caloric intake > central obesity > insulin resistance > DM > higher rates of CAD). The propensity towards developing insulin resistance may be partially explained by the “fetal origins hypothesis” which postulates that malnourished fetuses in developing countries adapt to impaired nutrition by becoming relatively insulin resistant. However, this adaptation may persist into adult life even when calories are abundant thus leading to insulin resistance and adult onset DM. Interestingly, CAD associated mortality in adult life decreases as birth weights increase.

While traditional risk factors account for the majority of CAD in South Asians, some novel risk factors are also under study: smaller coronary artery diameter,(21-23) higher homocysteine levels, and higher CRP levels. CAD risk in South Asians may be increased by a prothrombotic milieu (7,19) (higher levels of homocysteine, lipoprotein(a), plasminogen activator inhibitor-1, and smaller HDL and LDL particles) along with a proinflammatory state (20) (higher levels of adipose tissue-produced adipokines such as CRP, leptin, interleukin-6, tumor necrosis factor-alpha). Smaller mean coronary artery diameter has also been proposed as a risk factor for CAD in South Asians. A 2005 study done at Long Island Jewish Medical Center compared coronary artery diameters of 274 Whites to 149 South Asians referred for chest pain, cardiomyopathy, or valvular heart disease.(21) Only normal coronary angiograms were included in the study. South Asians had significantly smaller coronary artery diameters, even when corrected for body surface area. Two previous studies had shown smaller coronary artery diameters in South Asians, but the trend was not significant when corrected for body surface area.(22, 23) Smaller coronary arteries would theoretically require a lower atheroma burden to develop critical stenosis, possibly leading to premature CAD.

Conclusions
South Asians have higher rates, higher associated mortality, and earlier onset of CAD due to genetic predisposition and lifestyle factors. Nine modifiable risk factors (Smoking, DM, lipids, central obesity, hypertension, diet, physical activity, alcohol consumption, psychosocial factors) account for over 90% of CAD in all populations. South Asians have more traditional risk factors at an earlier age, explaining premature CAD in this group. Dyslipidemia, particularly high lipoprotein(a) levels and elevated apoB/apoA-1 ratio, has higher attributable CAD risk in South Asians as compared to other ethnic groups.

-The traditional risk factors should be screened for and modified in all populations, but especially so in South Asians who have higher prevalence of these risk factors at younger ages.

-Targeting only LDL and HDL values is not adequate. A detailed lipid profile should be obtained and modified accordingly [lipoprotein(a) levels, HDL and LDL particle size, apoB/apoA-1 ratio]

-In addition to LDL goals, non-LDL cholesterol elevation should be followed and modified. This can be achieved by measuring either non-HDL cholesterol levels or Apo-B levels, both of which are markers of non-LDL cholesterol.

-Non-HDL cholestrol goal is 30 higher than LDL goal for that patient.

-Apo-B goal levels are as follows
<80 for high risk (CAD or DM)
<90 for moderate risk (>2 CAD risk factors)
<105 for low moderate risk (1-2 CAD risk factors)
<120 for low risk (0-1 CAD risk factors)

-Lipoprotein levels should be assessed in any patient with personal or family history of CAD but no evidence of dyslipidemia, in patients with premature end-organ damage due to hypertension, and in patients with dyslipidemia resistant to traditional lipid lowering agents. Lipoprotein(a) is not lowered by statins or bile acid sequestrants, nicotinic acid must be used.

-Waist-hip ratio or waist circumference rather than BMI should be used to screen for central obesity.

-Metabolic syndrome is very prevalent in South Asians and should be screened for accordingly.

-South Asians would benefit greatly from weight loss and regular physical activity (decreased central obesity and its associated atherosclerosis risk) as well as dietary modifications (decreased intake of saturated and trans fats, shorter vegetable cooking times, increased intake of raw vegetables) .

-Framingham risk score significantly underestimates CAD risk in South Asians.

-More stringent cardiovascular risk assessment and modification, especially at younger ages should be considered in all South Asians.

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Reviewed by William Slater MD, Associate Professor of Medicine, Division of Cardiology

 

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