Profiles in research: Anand Rohatgi, M.D., M.S.C.S.

Researchers have established low-density lipoprotein cholesterol’s (LDL-C) important role in heart disease. By lowering the so-called bad cholesterol with lifestyle modifications and cholesterol-lowering drugs, people can reduce their cardiovascular disease risk.

That’s vital information in the fight against cardiovascular disease, but it’s only one piece of the puzzle.

The problem is cardiovascular disease remains the leading cause of death among men and women, according to Anand Rohatgi, M.D., M.S.C.S., associate professor of cardiology, UT Southwest Medical Center, Dallas, Texas.

What scientists haven’t yet figured out is high-density lipoprotein cholesterol’s (HDL-C) role in heart health. Studies suggest the “good” cholesterol might have the power to remove cholesterol from arteries and plaques, which is called reverse cholesterol transport, according to Dr. Rohatgi.

“But we don’t really have any therapies that target that and work that way. HDL hasn’t gotten a lot of attention because it has been unclear how to measure it and how to define what it does,” Dr. Rohatgi said.

The AHA Institute for Precision Cardiovascular Medicine has provided Dr. Rohatgi and colleagues with not only the financial resources to do his work, but also large frameworks of patient data and sophisticated research tools needed to find out what HDL-C can do and, eventually, how to harness it to remove bad cholesterol. That wasn’t possible with research methods of the past, he said.

“HDL is complex. It’s not just a carrier of cholesterol. It has proteins on it and a lot of other particles that allow it to do what it does,” Dr. Rohatgi said. “With today’s advanced research tools, we can use a person’s genetics to figure out if they have mutations that make their HDL better or worse in terms of moving cholesterol. We can use a technique called deep phenotyping to measure specific cholesterol entities that are on the HDL particles or work with the HDL particles.”

Through the Institute, Dr. Rohatgi has access to important health information from more than 15,000 adults.

“Using these large cohorts of people with available specimens and the deep phenotyping approach, we’ll better understand HDL’s precise function not just for the population as a whole but for specific individuals,” he said. “Our goals are use genetics, lipid metabolites, specific proteins and to combine them to get a very precise, unique signature for each person in terms of that person’s ability to remove cholesterol from plaques.”

The researchers will look at how the HDL-C signature might be different among people according to gender or ethnicity. Among the next steps in the research will be to figure out whether a person’s HDL-C profile better predicts an individual’s heart disease and stroke risk than what’s available today.

“Hopefully, we’ll be able to use this knowledge to promote development of new therapies that can target removing cholesterol effectively and decrease heart disease,” Dr. Rohatgi said.

"Once we identify one of these mutations, we can look at a combination of [them] and try to gauge a person's risk even before [they] have the disease. That’s the world of precision medicine."

"I've been fortunate to obtain funding for a project focusing specifically on using imaging to identify new patterns of cardiotoxicity in breast cancer patients."

“Part of precision medicine is not only looking at genetic variants, but also taken into account the gene and environment interactions that may also contribute to the risk for this disease.”