NEW YORK – A collaboration between cardiologists and genetic researchers across the US is collecting biological samples and other data from South Asian patients in the hopes of uncovering genetic factors associated with the high risk of cardiovascular disease in this population.
The biobank and data repository project, involving the Broad Institute, Massachusetts General Hospital (MGH), Harvard Medical School, Stanford Medicine, Cedars-Sinai's Smidt Heart Institute, and Yale School of Medicine, will fuel research into the genetic and lifestyle factors underpinning cardiovascular disease risk in South Asians.
As part of the OurHealth study, investigators are gathering genetic, medical history, and lifestyle data, specifically on adults living in the US with South Asian ancestry. Armed with this information, investigators hope they'll eventually be able to develop new strategies for preventing and managing cardiovascular disease risk.
It's unclear why patients of South Asian ancestry are disproportionately affected by cardiovascular disease, said Romit Bhattacharya, medical director of the OurHealth study and associate director of the cardiac lifestyle program at MGH, which is leading the project with the Broad Institute. That's in part because they've been underrepresented in genetic studies.
"Quite frankly, it just hasn't really been examined very closely," Bhattacharya said.
The OurHealth study launched about a year ago to answer that question. Since the study began in late 2023, investigators have recruited more than 1,500 participants. Ultimately, the aim within OurHealth is to gather data on tens of thousands of patients from across the US with ancestry from Bangladesh, Bhutan, India, the Maldives, Nepal, Pakistan, and Sri Lanka. Patients sign up online and fill out questionnaires about their lifestyle and health remotely. For the genetics component, investigators mail at-home test kits that participants use to collect saliva samples for genetic sequencing.
Already, the first 664 participants who completed the baseline survey represent 362 unique South Asian region-language-religion groups, according to an abstract that researchers presented on enrollment so far at an American Heart Association conference in November.
Investigators are getting the word out to South Asians in the US by partnering with community-based organizations, academic medical centers, and promoting the project online, Bhattacharya said.
One community partner, the South Asian Heart Center at El Camino Health in Mountain View, California, is raising awareness about the OurHealth study among its patient population by promoting the project at community events and on social media. Sometimes, physicians from the heart center will invite OurHealth researchers to its events to recruit participants.
The South Asian Heart Center, which was founded in 2006, aims to research and prevent heart disease and diabetes in the South Asian community through lifestyle and education programs. Ashish Mathur, cofounder and executive director of the South Asian Heart Center, said he's hopeful the OurHealth study will uncover genetic traits that predispose patients to cardiovascular disease. If so, the center may incorporate those findings into risk screenings designed for South Asian patients. "Our hope is that, once [the researchers] get a significant enough genetic sample size, we'll finally be able to get to the answer that we've all been looking for," he said.
Historically, high rates of cardiovascular disease among South Asians largely have been "chalked up" to diets rich in carbohydrates and saturated fat, Bhattacharya said. However, in recent years, research has demonstrated that even when people with South Asian ancestry have few other known risk factors, the disparity remains.
That awareness has become more pronounced as people with South Asian ancestry live in various other regions of the world and embrace local diets and other lifestyle changes, yet "there still seems to be a very high rate of cardiovascular disease in this population," Bhattacharya said.
The American College of Cardiology and the American Heart Association in their 2019 guidelines on preventing cardiovascular disease categorized South Asian ancestry as a "risk-enhancing factor," alongside chronic kidney disease, a family history of premature cardiovascular disease, and other factors, which can inform decision-making for patients who are otherwise borderline or at intermediate risk.
Meanwhile, South Asians have been underrepresented in genetic research and in clinical trials, making it difficult to parse what is contributing to the high risk of cardiovascular disease. The disparity can be obscured in some cases, since data on South Asians are often grouped under a broader Asian category, and people of Asian ancestry, in aggregate, tend to have lower risk on account of low cardiovascular disease rates among East Asians.
There have been some successful studies that sought to illuminate the scope of this problem. The longitudinal Mediators of Atherosclerosis in South Asians Living in America, or MASALA, Study launched in 2010 to investigate behavioral, social, cultural, and clinical risk factors that could explain high rates of heart disease in South Asians in the US. In the UK, investigators from the Genes & Health study, which launched in 2015, are analyzing the genetics of 100,000 people of Bangladeshi and Pakistani ancestry. Data from this study have shown that, compared to patients of European ancestry, patients in the cohort were more likely to have variants in the CYP2C19 gene that make them unlikely to respond well to Bristol Myers Squibb/Sanofi-Aventis' Plavix (clopidogrel), a widely prescribed anti-platelet drug used to treat heart problems.
For OurHealth, Bhattacharya said investigators will create an anonymized genomic dataset from the large South Asian study cohort recruited in the US and compare the data to information on other populations to try to pinpoint the genetic basis and hereditary risk factors for cardiovascular disease in this population. The researchers are hoping this analysis will uncover novel genetic variants and pathways involved in the pathophysiology of cardiovascular disease, which then could be used to guide care decisions, whether through lifestyle management or development of new targeted therapeutics, Bhattacharya said. Investigators are also hunting for genetic markers that could be used to create ancestry-specific polygenic risk scores to be used alongside other risk factors to identify patients likely to develop heart disease.
As investigators undertake these activities, they plan to update participants about their research and discoveries within the OurHealth study.
Bhattacharya noted that pathogenic or protective variants identified in OurHealth could also inform prevention and treatment strategies for heart disease, diabetes, and other cardiometabolic diseases broadly, even for those without South Asian ancestry. These conditions are a problem for patients across racial and ethnic groups. In fact, heart disease is the leading cause of death in the US, according to the US Centers for Disease Control and Prevention.
Insights from OurHealth could drive the discovery of new targets for drug development or information to guide lifestyle management activities. For example, Bhattacharya cited previous research unrelated to OurHealth, in which a research team studying adults of Pakistani ancestry discovered the protective effect of certain APOC3 mutations against coronary heart disease, which has contributed to the development of drugs that aim to address elevated triglyceride levels by targeting APOC3.
"By studying the groups of people who have [cardiovascular diseases] at the highest rates, we may discover novel pathways," Bhattacharya said. "It's important on a global scale."