Why are South Asians more susceptible to heart attacks? A study by researchers from University of Toronto, published on February 12, 2023 in the American Journal of Cardiology, throws up yet another interesting observation on this question. Comparing 60 South Asian and 60 white European-origin adults, they observed differences in blood cells of the two groups. South Asians had less progenitor stem cells and monocytes than the white patients.
Further, the monocytes were of a kind which caused inflammation rather than the kind which helped to heal injured blood vessel walls. The authors suggest that greater propensity for blood vessel injury, with diminished ability to heal lesions, may be responsible for South Asians exhibiting a higher risk of heart attacks.
Reports of persons with South Asian ethnicity manifesting early onset and extensive coronary artery disease first emerged in migrant Indians. In the 1950s, reports came from Uganda and Malaya of higher levels of coronary artery pathology in autopsied persons of Indian origin compared to other ethnic groups.
Over the next 20 years, reports of higher and earlier heart attack rates among South Asians came from the UK, Singapore, Mauritius, US, Canada, Fiji and other countries with large numbers of migrants. This was in comparison with white Caucasians, Chinese, Malays, Africans and Hispanics.
Explanations emerged through studies which observed that South Asian migrants had higher rates of diabetes and pre-diabetes, insulin resistance in skeletal muscle and liver, higher levels of body fat, less lean muscle mass and more belly fat around the abdominal organs (visceral adiposity).
Blood chemistry typically showed low levels of HDL cholesterol, high levels of triglycerides and elevated lipoprotein ‘a’ (Lp ‘a’). Within the LDL fraction of blood cholesterol, the highly atherogenic ‘small dense LDL’ sub-fraction was more prominent than the less damaging ‘big buoyant LDL’ sub-fraction.
Are all of these high-risk indices genetically determined? The coupling of excess coronary risk and high prevalence of diabetes and pre-diabetes raised genetic predisposition as a popular hypothesis. The fact that these features were seen across different climes and times of migration, from first generation to third generation migrants, reinforced this hypothesis. However, strongly predictive genetic markers could not be identified. Even a cluster of candidate genes could not account for more than 10 percent of variance.
Higher risk of visceral adiposity, insulin resistance and diabetes is also associated with poor intra-uterine and early childhood undernutrition of a child. This is known to have an epigenetic imprint on gene expression that predisposes to diabetes and coronary heart disease in adult life. While enabling an undernourished baby to conserve limited nutrients available for glucose-dependant brain growth, lean muscle mass is reduced (as muscles burn up glucose).
This is essential for initial survival but can pre-dispose to a metabolic mismatch when the child later accesses more food. While this is a demonstrated risk pathway, it is not clear how much this has contributed to higher coronary risk in different Indian population sub-groups.
The migrant experience stoked interest in within-India studies. Population surveys conducted in early 1990s showed higher prevalence of coronary heart disease and risk factors in urban Delhi and urban Vellore, compared to rural Haryana and rural Vellore. Visceral adiposity, low HDL and high triglyceride levels were noted as risk markers in both urban and rural populations, but were more marked in the urban samples.
Later, studies comparing Indians residing in India with similar Indian migrants in other countries—especially Punjabis and Gujaratis in the UK—revealed a rising rural-urban migrant gradient of coronary risk factors. This suggested that urban acculturation and altered living habits, driven by rising incomes, were propellants of coronary risk.
This was reinforced by rural-urban migrant studies in India. Factory workers in three Indian cities were compared to their rural siblings, who stayed on in the villages. Within five years of migration to cities for employment, the urban workers had higher levels of many coronary risk factors compared to their non-migrant rural siblings. This suggested that changing diet, physical activity and stress patterns associated with urban migration had a marked influence on coronary risk, even when the genetic background was similar.
Interestingly, recent studies in the US suggest that the nature of migrants also influences the acculturation pattern and behavioural risks. While the migrants from India to other countries in the last century comprised a varying mix of semiskilled workers and professionals, recent Indian migrants to the US have mostly been highly qualified professionals.
Migration to the US in the 20th century occurred in a social milieu when most Americans were consuming unhealthy diets and had coronary-prone lifestyles. However, recent migrants are adopting healthier living habits which are now more popular with richer and more educated Americans: better diets, more physical activity, less smoking and stress-coping practices of yoga and meditation. The interplay of any genetic influence with a healthy lifestyle will manifest in this group.
In India, too, we see different types of gene-environment interactions based on disparities in income and education, varied patterns of diet, physical activity and exposure to air pollution.
However, efforts to reduce coronary risk must proceed on the understanding that a predisposition (whether polygenic or epigenetic) does seem to provide the background against which modifiable factors (diet, physical activity, smoking, stress, sleep, air pollution) operate to manifest amplified or attenuated risk. Physical activity, for example, significantly reduces insulin resistance in the skeletal muscle and a healthy diet modifies most of the biochemical risk factors.
The recent Canadian study suggests that South Asians not only have higher incidence of diabetes but also have a lower ability to heal blood vessel injury, whether caused by diabetes or other risk factors. Since 90 percent of South Asians and 60 percent of Caucasians in the study had diabetes, it is not clear how much the blood cell abnormalities are related to diabetes or to an earlier predisposition that leads to coronary artery disease irrespective of diabetes.
A comparative study of South Asians and Caucasians without diabetes will help to reveal to what extent the progenitor and monocyte cell abnormalities are genetically pre-determined or are modifiable through healthy living habits. Till then, we may recall Mark Twain’s comment: “There is something fascinating about science. A trifling investment of fact can generate vast returns of conjecture.”
Prof K Srinath Reddy
(Author of Pulse to Planet, Honorary Distinguished Professor at the Public Health Foundation of India)