Study By Shweta Bansal, MD interviewed by Rajam Ramamurthy, MD

People of South Asian Decent at High Risk for Cardiovascular Disease Shining light on the “Masala” Study

Shweta Bansal, MD is interviewed by Rajam Ramamurthy, MD

Cardiovascular disease (CVD) is the number one killer in the general population. People of South Asian ancestry (India, Bangladesh, Bhutan, the Maldives, Nepal, Pakistan and Sri Lanka), are one of the fastest growing populations in the U.S. They are at an even higher risk of CVD compared to other racial and ethnic groups. To probe into this, in 2010, Alka Kanaya, MD, Professor of Medicine, Epidemiology and Biostatistics at the University of California, San Francisco, in collaboration with Namratha Kandula, MD, MPH, a Professor of Medicine and Preventive Medicine at Northwestern University, launched a prospective cohort study titled the “MASALA” (Mediators of Atherosclerosis in South Asians Living in America). The word masala roughly translates to “a mixture of spices” identified with south Asian cuisine.

Shweta Bansal, MD, Professor of Medicine at the University of Texas Health, chaired the CME program committee for the 40th annual AAPI convention held in San Antonio, Texas in June 2022 and invited Dr. Kanaya to address the MASALA study. Rajam Ramamurthy, MD interviewed Dr. Bansal, MD to shed some light on the burning issue (No pun intended) of high CVD risk in South Asians, exclusively for this issue of San Antonio Medicine magazine.

Dr. Ramamurthy: Based on your recent conversations with Dr. Kanaya and your extensive work with Cardiometabolic disorders, what is the status of CVD in South Asians?

Dr. Bansal: South Asians represent approximately 25% of the world's population – yet they account for 60% of the world's heart disease patients. In a large UK Biobank prospective cohort study, approximately 8,000 middle-aged South Asian participants free of atherosclerotic cardiovascular disease at the time of enrollment, while receiving contemporary medical care experienced a CVD event at over a twofold higher rate compared to participants with European ancestry over a follow-up of 11 years.1

Dr. Ramamurthy: Indeed, a very high rate. What has been identified in the MASALA study or UK Biobank cohort as risk factors that South Asian groups have for CVD?

Dr. Bansal: We have learned that South Asians have excess metabolic perturbations and cardiovascular risk factors at a lower value of body mass index (BMI) as compared to white populations. The prevalence of type 2 diabetes (T2DM) was 27% in South Asians compared with 8.0% in non-Hispanic white individuals after adjustment for age, sex and BMI in a recent US study.2 This prevalence was similar in South Asians residing in Ontario, Canada.3 The MASALA study found that South Asians developed T2DM at an average of nine years earlier than white participants, and at an average BMI of 24 kg/m2 compared with a BMI of 30 kg/m2 for an equivalent incidence rate in white people.4 In the UK Biobank study, hypertension, diabetes and central adiposity accounted for most of the CVD risks in South Asians compared to Europeans.1

Dr. Ramamurthy: Does the MASALA study shed any light on the reasoning behind this disproportionately higher rate of T2DM and other risk factors?

Dr. Bansal: In the MASALA study, investigators found that South Asian people seem to have more fat deposited in organs like the liver, heart, muscle tissue and around the abdominal visceral organs, as compared to people from US racial and ethnic groups in the MESA (Multiethnic Study of Atherosclerosis) study who deposit fat under their skin.5 Ectopic and visceral fat has long been linked with an exaggerated inflammatory state and insulin resistance that leads to increased metabolic risks and overall mortality.6,7 In the MASALA study, hepatic and visceral fat were independently associated with both incidental and progressive diabetes.

MASALA investigators discuss diet as an important risk factor. They found three major types of dietary patterns that MASALA participants are consuming. One is a Western diet with more animal fats, proteins, meat and alcohol. A second dietary pattern is vegetarian, but too many high-fat dairy types of dishes, sugar and refined carbohydrates, a traditional South Asian diet. And the third pattern, is a more prudent diet with whole grains, nuts, fruits and vegetables. Of these three dietary patterns, the first two patterns are associated with a higher risk of visceral fat and diabetes.8 An additional factor is physical activity, participants in MASALA study had significantly lower metabolic equivalent tasks as compared to MESA study participants of other US races and ethnicity.

Dr. Ramamurthy: BMI is a measure to identify folks with higher fat mass, and you said that T2DM and CVD occur at a lower BMI in South Asians. How well does the BMI capture excess ectopic and visceral fat in South Asians?

Dr. Bansal: Very good question. Ectopic and visceral fat does not contribute as much to the total weight as does the subcutaneous fat but exerts a much higher risk of CVD. In 2000, the World Health Organization (WHO) Consultative Committee opined a BMI value of ≥23 kg/m2 and ≥25 kg/m2 to denote overweight and obese, respectively in Asians.9 Subsequently, the WHO proposed that each country decide to define obesity for its population along the BMI continuum ranging from 23.0 to 27.5 kg/m2. A BMI of over 27 per meter square body surface denotes obesity in South Asians.

Dr. Ramamurthy: What about the role of genetics and a widespread belief of small coronary arteries in South Asians?

Dr. Bansal: While cardiovascular disease can be passed down in families, researchers have yet to find a specific genetic cause that would make South Asians more at risk than other groups. In small angiogram studies, Indo-Asian patients were found to have generally smaller coronary arteries; however, after correction for body surface area, none of these differences in size were statistically significant. Thus, the smaller coronary arteries in Indo-Asian patients were explained by body size alone and were not due to ethnic origin per se.10

Dr. Ramamurthy: If it is not clearly genetics, are there any additional risk factors other than diet and low exercise contributing to high ectopic and/or visceral fat, T2DM, hypertension and CVD in South Asians?

Dr. Bansal: Sure, although the genetics are not yet clear, there are few conditions that might have some genetic predisposition and disproportionately increase the risk of CVD among South Asians. T2DM comes in different subtypes based on the clinical characteristics. The most common subtypes that South Asians have, at least from the data in MASALA, is the insulin-deficient subtype with the lowest beta cell function. This observation suggests that there are unidentified factors causing diabetes other than visceral fat because visceral fat usually associates with insulin resistant T2DM. Another condition with potential genetic predisposition is the pattern of dyslipidemia in South Asians, which is characterized by elevated levels of triglycerides and lipoprotein little ‘a’ [L p(a)], and low levels of high-density lipoprotein (HDL) cholesterol, a higher atherogenic particle burden despite comparable low-density lipoprotein cholesterol levels compared with other ethnic subgroups. HDL particles also appear to be smaller, dysfunctional and proatherogenic in South Asians. Lp(a) is highly atherogenic and its levels are primarily genetically determined. South Asian immigrants have Lp(a) levels that are similar to those in their counterparts in their home country and higher than those in Caucasians.11 Other potential contributing factors could be related to those stress factors typically associated with immigrant populations of systemic discrimination, perception of biomedicine and cultural factors in South Asians.

Dr. Ramamurthy: Thank you very much for sharing these important findings. Do you have some last words for our readers of the San Antonio Medicine magazine?

Dr. Bansal: Given that genetic factors can’t be changed, it is important to change this risk profile which leads to excess ectopic fat deposit, one of the important links and mediators of high CVD. To identify this risk profile, awareness and early screening are the key factors. Culturally appropriate interventions to alter deleterious dietary patterns and increased physical activity can be cornerstones to improving metabolic risk factors in the rapidly growing and high-risk US South Asian population.

References: 1. Patel, A.P., et al., Quantifying and Understanding the Higher Risk of Atherosclerotic Cardiovascular Disease Among South Asian Individuals: Results From the UK Biobank Prospective Cohort

Study. Circulation, 2021. 144(6): p. 410-422. 2. Cheng, Y.J., et al., Prevalence of Diabetes by Race and Ethnicity in the United States, 2011-2016. JAMA, 2019. 322(24): p. 23892398. 3. Oza-Frank, R. and K.M. Narayan, Overweight and diabetes prevalence among US immigrants. Am J Public Health, 2010. 100(4): p. 661-8. 4. Chiu, M., et al., Deriving ethnic-specific BMI cutoff points for as-

sessing diabetes risk. Diabetes Care, 2011. 34(8): p. 1741-8. 5. Mongraw-Chaffin, M., et al., Relation of Ectopic Fat with Atherosclerotic Cardiovascular Disease Risk Score in South Asians Living in the United States (from the Mediators of Atherosclerosis in

South Asians Living in America [MASALA] Study). Am J Cardiol, 2018. 121(3): p. 315-321. 6. Frayn, K.N., Visceral fat and insulin resistance--causative or correlative? Br J Nutr, 2000. 83 Suppl 1: p. S71-7. 7. Liu, J., et al., Impact of abdominal visceral and subcutaneous adipose tissue on cardiometabolic risk factors: the Jackson Heart

Study. J Clin Endocrinol Metab, 2010. 95(12): p. 5419-26. 8. Gadgil, M.D., et al., Dietary patterns are associated with metabolic risk factors in South Asians living in the United States. J Nutr, 2015. 145(6): p. 1211-7. 9. The Asia-Pacific perspective : redefining obesity and its treatment. , in World Health Organization. Regional Office for the Western

Pacific. 2000. 10.Lip, G.Y., et al., Do Indo-Asians have smaller coronary arteries?

Postgrad Med J, 1999. 75(886): p. 463-6. 11.Bilen, O., A. Kamal, and S.S. Virani, Lipoprotein abnormalities in

South Asians and its association with cardiovascular disease: Current state and future directions. World J Cardiol, 2016. 8(3): p. 247-57.

Shweta Bansal, MD completed Internal Medicine Residency and Nephrology Fellowship from the University of Colorado, Denver. Currently, she is a clinical Professor of Medicine, Director of the Home Dialysis Program at UT Health San Antonio, the co-director of the Annual Cardiorenal Connections (CRC) meeting that aims to bridge heart, kidney and metabolic disorders and a member of BCMS.

Rajam Ramamurthy, MD is Professor Emeritus of Pediatrics and Neonatology at UT Health San Antonio. She is an active member of the BCMS Publications Committee.