As a preventive cardiologist focused on lifestyle changes to improve cardiac health, Romit Bhattacharya, MD, tries to practice what he preaches. When he’s not at the lab or clinic, he might be found conducting business from his treadmill desk at home in Cambridge, using every opportunity he can to “reduce my sedentary time,” as he puts it.

That’s where he is when he arrives to our video interview in full stride, as if it’s the most natural thing in the world — and it turns out it is. Over the next 30 minutes of nearly nonstop talking, his pace doesn’t falter in steps, voice, or breath. (Go ahead, try doing that.)

It’s a fitting backdrop to a discussion of his work as a clinician-scientist at Mass General Brigham (MGB), where he investigates how lifestyle interventions can prevent cardiac disease. He’s particularly interested in the mechanisms underlying how dietary patterns influence cardiovascular health.

Bhattacharya, an instructor in medicine, is using a 2023 Harvard Catalyst K12/CMeRIT award to study whether diet plays a causal role in developing a specific type of precancerous acquired mutations that are increasingly seen as important contributors to cardiovascular disease.

You’re taking aim at one of the most complex questions in cardiovascular medicine: How dietary factors influence cardiac risk. What drives you to tackle that topic?

Every day we make tens of thousands of decisions about our health. Most of those decisions are about our lifestyle. Analyses from the American Heart Association and others suggest that the majority of cardiovascular disease risk may be related to our lifestyle and habits.

“Analyses from the American Heart Association and others suggest that the majority of cardiovascular disease risk may be related to our lifestyle and habits.”

And yet, we haven’t made as much progress in characterizing these lifestyle determinants as we have in other areas such as genetics, where we have quantifiable data. It’s very difficult for a doctor to advise you to eat exactly this food or avoid exactly that food.

I’m aiming to characterize the complexity of the effects of diet on heart disease risk and improve how actionable our advice to patients can be. We know that one’s whole dietary pattern is more important than any one food – so I would love for the research to be able to better grasp the complexity of our diets and the combinations and quantities of foods that are most health-promoting.

How does your K12 award advance the long-term goals of this research?

We’re really diving into the unknown. All of us have genetic risks that we inherit from our parents. But we also acquire genetic variants during our lifetime. These somatic variants seem to make a big contribution to our risk for cancers across all tissue types.

Somatic variants occur throughout the body, in the gut, in our skin, and in our immune cells, where they can lead to a condition called clonal hematopoiesis, which is a known precursor to cancer. We’re trying to understand how these variants develop and how they also relate to cardiovascular disease risk.

The K12 project looks specifically at the relationship between dietary risk factors and the presence of these acquired mutations in our immune cells. We have published preliminary data, suggesting that people who eat a healthier diet, that is a diet rich in fruits and vegetables with less red meat, processed and high-salt foods, were less likely to have mutations.

Of course, that’s just an association. We’re now trying to use causal inference methods and human genetics, specifically a method called Mendelian Randomization, to investigate whether a dietary pattern is truly causal in the development of clonal hematopoiesis or is simply an associated factor.

What for you has been the biggest value of the K12 training award?

I’ve only been on the K12 for a short time, and I have to say it has been really exciting. I’ve had other grants in the past, and having the money and protected time to be able to perform this work is a privilege in an of itself.

The K12 takes that a step further. With its partnership with the GRASP grant writing program, as well as the K12 lab meetings, I feel like I’m gaining a really strong understanding of what it takes to build a career in this field and what the logistics of that are. How do you write grants? Who reads those grants and how can you address their questions? What types of other funding mechanisms might best align with your work?

I’m learning to think about grants as not just something you have to get to do your work, but as mechanisms that have been designed by generations of researchers before you to help you achieve your goals in a stepwise fashion, to think about what training and what resources you’re going to need along the way.

“I feel like I’m gaining a really strong understanding of what it takes to build a career in this field and what the logistics of that are.”

The course uses role-playing scenarios where you are in the seat of the NIH and foundation reviewers who are going to be judging your grants. It teaches you how to review a grant. Once you start reviewing other people’s grants, even fictional ones, you start gaining an in-depth understanding of what makes a grant not just good, but an elegant and accurate reflection of the thought process and scientific approach behind it. How truly does it state your intentions and what you plan to do?

That process of learning and being coached through how to build a career, how to review grants, and how to write them yourself is incredibly powerful. I didn’t learn that in medical school. I didn’t learn it in residency or fellowship.

What made you want to get into translational research?

I came to Massachusetts General Hospital as a clinician. I really wanted to work toward caring for patients and making their lives better. Patients would often come to me with very fundamental questions about how to take care of their health and I realized I just wasn’t satisfied with the answers.

So I think my interest in translational research was generated in part from just wanting to be able to more confidently answer the questions that my patients were asking me.

We have made a lot of progress in specific disease processes, but in the most common decisions that we have to make about our health, around diet, exercise, sleep, stress, we have we rely on colloquial or passed-down wisdom and much less upon scientific data.

A lot of work has been at the epidemiologic level. But now with the advent of large databases, high-throughput data science, and even wearable and passive data-collection technologies, we’re able to better spend time with our patients, so to speak, in their home environments. The goal is to understand how they are behaving at home and how that is associated with disease risk.

I’m really excited to be taking on a new clinical leadership role as associate director of the Cardiac Lifestyle Program at Mass General Brigham (MGB), which develops behavioral intervention programs for individuals at a high risk for cardiovascular disease. It helps me liaise my clinical and research work.

We’ve also partnered with an oncology group at MGB that focuses on people who have the types of mutations seen in clonal hematopoiesis and go on to develop precancerous diseases called myeloproliferative neoplasms. We’re running a clinical intervention for some of these individuals to see if a comprehensive 12-week program which  encompasses diet, exercise, sleep, and stress-reduction interventions helps them in the long term.

How might this work change clinical practice for heart disease prevention?

If we discover, for instance, that vitamin C and D12 can be helpful in reducing the risk of these acquired mutations–and maybe that’s even the mechanism through which a healthy diet reduces cardiovascular risk–then there may be simple dietary instructions we can provide to people.

This has been the Holy Grail, right? To be able to tell someone: “Based on your personalized risk factors, engaging in these specific preventive behaviors may reduce your risk long-term.”

And wouldn’t it be great if the treatment we’re prescribing is truly in line with what Hippocrates purportedly said: “Let food be thy medicine”? Wouldn’t it be great if the therapy was something with a low risk of side effects, like eating more oranges?