Nehal N. Mehta, MD, MSCE, attended an accelerated seven-year biomedical program where he received his Bachelor of Arts in 1997 with honors and Doctor in Medicine in 2001 with Distinction from The George Washington University, and a Master of Science in Clinical Epidemiology in genetic epidemiology from the University of Pennsylvania in 2009. Following medical school, Mehta did his internship, residency and chief medical residency in internal medicine at the University of Pennsylvania Hospital, followed by a fellowship in cardiovascular diseases, nuclear cardiology and preventive cardiology. Following this, he did a post-doctoral fellowship in genetic epidemiology with a focus on inflammation and lipoproteins at the University of Pennsylvania's Center for Clinical Epidemiology and Biostatistics (CCEB) and Institute of Translational Medicine and Therapeutics.

In 2006, as a cardiology fellow, Mehta received the ACC's Merck Award for metabolic syndrome research. In 2009, Mehta joined the faculty in cardiovascular medicine at the University of Pennsylvania School of Medicine and at the CCEB as an associate scholar. That same year, he received his K23 career development award from the National Institutes of Health (NIH). In 2012, Mehta received the inaugural Lasker Clinical Research Scholar award, a 12-year, $24 million grant, joining the NIH Bethesda Labs Intramural Research Program in the National Heart, Lung, and Blood Institute's (NHLBI) Cardiovascular Branch. In 2018, he earned the NHLBI Orloff Science Award, and later that year the NIH Director's Awards for providing the first-in-human evidence that treatment of skin inflammation improved coronary vascular health. That same year, Mehta became a member of the American Society of Clinical Investigation. In 2019, Mehta became the first Lasker Senior Investigator after receiving tenure from the NIH. The long-term goals of Mehta's clinical translational imaging program are to improve risk stratification and risk prediction for cardiovascular disease in young people with inflammatory diseases.

In the following interview, Mehta discusses his training, his clinical and research focus in cardio-inflammation, and his career as a physician-scientist in cardiology.

How did you start considering cardiology as a potential specialty?
During my second year of medical school, I was randomly assigned to take notes for an EKG lecture. The normal physiology of the heart, in particular electro-mechanical coupling, was very interesting to me and showed a 1:1 effect between conduction and myocardium. After completing my core clerkships, I noted that practicing cardiology involved both acute and chronic care. Additionally, best yet, at the end of my third year, I found a great mentor named Alan Wasserman, MD, FACC, who was a cardiologist. He guided me through a W.T. Gill Research Fellowship and he opened my eyes to how a cardiologist who cares for patients can also perform meaningful research. In this case of my first mentor, he showed me that reperfusion of an occluded artery impacted multiple areas of the heart, each of which had a clinical corollary, again noting a 1:1 relationship.

How did you develop your research and clinical focus in cardiology and inflammation?
Early in my fellowship, I became very interested in obesity-related heart disease as a fellow at the University of Pennsylvania, and it was here that I found my second mentor, Muredach Reilly, MBBCh. In cardiology clinic, I cared for many patients who had suffered a heart attack and who were obese with a paucity of cardiovascular risk factors. I suspected inflammation as a key driver but was not sure of the source. When examining this adipose tissue directly by biopsy, there was evidence of many types of inflammatory cells. This led to a 2009 publication where we reported the presence of adipose tissue inflammation in humans following an acute inflammation challenge with lipopolysaccharide that drove cardiometabolic diseases. However, the human model we were using was challenging since it used an acute inflammatory stimulus to mimic chronic inflammation. Because of this, I turned to psoriasis, a highly underrecognized and undertreated common inflammatory skin disease. In 2009, we reported that a patient with severe psoriasis has about a two-fold increase of dying from a heart attack between 40 and 50.

What is the current state of affairs of cardio-inflammatory diseases like psoriasis?
Ten years ago, our growing field had coined the phrase "more than skin-deep" meaning inflammation in the skin equated to inflammation in the blood. A few years later, we noted that even one skin plaque might be too many meaning that even small plaque can drive inflammation and secrete pro-inflammatory cytokines. We discovered that a particular type of neutrophil, a low-density granulocyte, was driving development of early, high-risk coronary plaque called the lipid-rich necrotic core. Later, we found that these high-risk, non-calcified plaques were more prevalent in young patients, and development about a decade sooner in those with psoriasis. Most recently, we demonstrated that treatment of the skin disease modulated these high-risk coronary plaques.

The recent ACC/American Heart Association (AHA) guidelines recognized psoriasis as a disease that warrants early initiation of a statin. This guideline recognizes the importance of inflammation as a driver and over a decade of work by our team and others. In planned and ongoing clinical trials, we are testing the effects of statins and anti-inflammatory therapies to reduce cardiovascular risk on in vivo atherosclerosis progression. Currently, we are utilizing artificial intelligence algorithms to provide more personalized care to recognize who will benefit from earlier intervention to reduce high-risk plaque development in these at-risk patients.

How do you balance your roles as a clinician and scientist?
I think that this is the most difficult part of translational research since one is juggling jobs as both a physician and a scientist. Clinically, I am the Director of the NHLBI Cardiovascular Image Quantification Program situated within the NIH Clinical Center, as well as see patients enrolled on our many protocols at the NIH studying atherosclerosis progression using CCTA. I also attend on the coronary care unit at the George Washington University Hospital quarterly. From a research standpoint, I direct two labs, one imaging lab to quantify PET, CT, MRI, and CCTA and the other a basic laboratory which studies lipoprotein function and cellular immunology to understand the early effects of lipid-inflammation on vascular disease progression. Being at the NIH permits me to have funding for my scientific research as well as see patients which facilitates the clinical research program itself. Another key element for balance is saying no. When you are a junior physician, it is hard to say no since you are in a building phase and need exposure as well as opportunities for academic promotion. But it is important to find time to focus on writing grants and papers rather than delivering talks so that you develop your expertise.

Do you have any parting thoughts for medical students and trainees?
My advice is to find the place you love to be the most (hospital, office, reading room, laboratory, etc.) and build around that center. I loved my outpatient practice, so my first steps were to build a strong relationship with my patients as their clinician. Over time, I was able to take blood samples and vascular images to better answer my questions. Before realizing it, I combined my clinical practice with my translational research, and I had preliminary data to write my first grant. I continue that model to this day and have now incorporated inpatient clinical practice into our research program. Finally, our research has influenced guidelines from the ACC, AHA, American College of Radiology and American Academy of Dermatology. As you train, you will get more exposure to different centers and environments. It is important to try to find a home that keeps you happy and productive throughout your career. And lastly, be aware of burnout, know how to reduce the impact of it, so as your career grows, health and wellness stay as important as academic career growth!

This article was authored by Samip Sheth, medical student at Georgetown University in Washington, DC, and chair of ACC's Medical Student Leadership Group.

"It was a great honor to speak with Dr. Mehta who has established, led, and grown the field of cardio-inflammation. His work in psoriasis demonstrates to trainees how to craft an untold story in medicine through scientific discovery and advancement." – Samip Sheth