Broader Understanding of Heart Disease Risk
Framingham Heart Study provides many insights, but doesn’t explain ethnic minorities’ high disease rates
Jan. 25, 2016
By Sumathi Reddy

When R. Shankar Nair was diagnosed with a partially blocked artery in June, his doctor knew what the main contributing factor was. “Being South Asian was the big risk factor,” says the 71-year-old patient, who is slim and active and has never had a cardiac problem before. “There’s really nothing else.” Dr. Nair, who has a Ph.D. in civil engineering, is one of about 900 South Asians participating in a long-term, federally funded study trying to explain why South Asians have such high rates of cardiovascular disease that can’t be explained by traditional risk factors such as smoking, high blood pressure or obesity.

The study began in 2010 with the recruitment of South Asian men and women around Chicago and San Francisco with no previous cardiac problems. It is called Mediators of Atherosclerosis in South Asians Living in America (aptly shortened to the acronym, Masala, which is also the name of an Indian spice mix).

Dr. Alka Kanaya is principal investigator for the Masala study, which is looking at why South Asians have relatively high rates of heart disease. ‘If we can figure out what these factors are that really impact heart disease [in South Asians] then we can start targeting interventions specific to lowering those risk factors,’ she says. South Asians represent about 60% of the world’s heartdisease patients, according to World Health Organization statistics. In the U.S., South Asian men and women have the highest mortality rates from coronary heart disease compared with whites and other ethnic groups, studies have found.

“South Asians have higher rates of cardiovascular disease but no one knows why,” says Alka Kanaya, principal investigator for the Masala study and a professor of medicine, epidemiology and biostatistics at University of California, San Francisco. Researchers at Northwestern University in Chicago also are participating in the study. More than 70 years after the seminal Framingham Heart Study, whose participants were largely white, researchers are trying to shed light on cardiovascular risk factors for other ethnic groups. The Framingham study began in 1948 with about 5,200 men and women from the town of Framingham, Mass., and led to the identification of many of the now established risk factors for coronary heart disease, including high blood pressure and cholesterol levels and smoking.

“We have good data on Caucasians but relatively less information on other ethnic groups,” says David Herrington, a cardiovascular medicine professor at Wake Forest School of Medicine, in Winston-Salem, N.C. Dr. Herrington is one of about 300 researchers working on another federally funded study following four separate groups: Caucasians, African-Americans, Hispanics and ChineseAmericans. The study, called the Multi-Ethnic Study of Atherosclerosis, or Mesa, began following 6,814 people without coronary disease more than 15 years ago, Dr. Herrington says. Its main focus is tracking measures of vascular disease through imaging, including CT-scans looking for calcium in coronary arteries and ultrasounds looking for thickening in arteries to the brain.

The Masala and Mesa researchers are collaborating, including using the same protocols and research methods to enable them to compare data among the various ethnic groups, Dr. Kanaya says. R. Shankar Nair had no warning when he was diagnosed with a partially blocked artery in June. He is participating in a study to learn why South Asians have such high rates of heart disease that can’t be explained by traditional risk factors such as obesity.

Masala was born out of a 2006 pilot study that followed for 2½ years 150 South Asians in the San Francisco area who didn’t have documented heart disease. The study found that despite having on average a relatively low body weight and high socioeconomic status, South Asians had more risk factors for cardiovascular disease, including Type 2 diabetes and high blood pressure, than other ethnic groups. However, these traditional risk factors haven’t been able to explain the high rates of cardiovascular disease in South Asians, so there was a need to do a more in depth search for other explanations.

The Masala researchers completed their first round of data collection on the study’s participants in 2013 and are currently in the second round, which includes collecting genetic samples, doing CT-scans of the heart and conducting glucose-tolerance tests. The researchers have published 14 papers so far. Among the participants, there have been 35 recorded cardiovascular events, including heart attacks. Among the findings so far: Prevalence of diabetes among South Asians is much higher than in ethnic groups in the Mesa study; blood pressure in South Asians is similar to the AfricanAmerican group but higher than in the other groups; and coronary artery calcium scores are comparable to the Caucasian group and higher than the other Mesa groups.

When Heart Disease Doesn’t Follow the Rules Traditional risk factors for heart disease, such as high blood pressure and obesity, don’t explain very high rates of the disease in South Asians.  South Asian men and women represent about 60% of the world’s heart-disease patients. In the U.S., they have higher mortality rates from heart disease than whites and other ethnic groups.  Caucasians in the U.S. have a 6% prevalence of diabetes and African-Americans have 18%. For South Asians, it is 23%, between the ages of 45 and 84.  Early findings of an ongoing study show that South Asians in the U.S. have a lower BMI than most other ethnic groups but have more visceral fat around the abdominal organs, more fat in the liver and less lean-muscle mass.

South Asians in the U.S. with very traditional cultural beliefs, or those who are the least traditional, have thicker walls of their carotid arteries, which is a risk factor for stroke. Those who hold moderate cultural views have thinner walls. A 2014 study in the journal Diabetes Care found that South Asians had a much higher prevalence of diabetes than whites and higher than African-Americans. That can’t be explained by traditional risk factors, the Masala researchers concluded. Instead, it may be caused by lower beta-cell function in the pancreas and “an inability to compensate adequately for higher glucose levels from insulin resistance,” the study said.

Another study, published in the International Journal of Obesity in December, found that South Asians’ body composition is very different from that of other ethnic groups, Dr. Kanaya says. Even though South Asians have a relatively low body-mass index, they have more visceral fat around the abdominal organs and fat in the liver, and less lean-muscle mass, she says. Researchers want to know if that type of fat leads to more inflammation and insulin resistance, which could be causing cardiovascular disease, says Namratha Kandula, the principal investigator at the Northwestern University Masala site and an associate professor of medicine at Feinberg School of Medicine. “The assumption has always been that the reason South Asians have more heart disease is because they have more diabetes and insulin resistance,” Dr. Kandula says.

The Masala researchers also are looking at behavioral and sociocultural factors, including diet, cultural beliefs, religion and spirituality. A paper published in the Journal of Clinical and Experimental Research in Cardiology in 2014 found that South Asians who were very traditional in their cultural beliefs, as well as those who were the least traditional culturally, had relatively thick carotid artery walls, which is a risk factor for stroke. People who held moderately traditional beliefs had the thinnest carotid artery walls.

“If we can figure out what these factors are that really impact heart disease then we can start targeting interventions specific to lowering those risk factors,” Dr. Kanaya says. Studies of South Asians in other countries, including the United Kingdom, have similarly found higher rates of heart disease, Dr. Kandula says. Quality studies in South Asian countries such as India and Pakistan are now emerging and may provide important comparisons to South Asians living abroad.

“There’s probably a strong genetic component to the increased heart disease risk in South Asians that’s exacerbated by the environment and the Western lifestyle,” Dr. Kandula says. Studies of heart disease risk in various ethnic groups can also benefit people outside those groups, researchers say. “Differences across ethnicities tell us something important about biology that could be exploited in different ways,” says Dr. Herrington, of the Mesa study. “The subtleties and the differences between ethnicities can be very informative and can help us in ways that studying one ethnicity cannot.” Write to Sumathi Reddy at sumathi.reddy@wsj.com