Tracing the Path From Inflamed Skin to Heart Disease

Five Questions with Dr. Nehal Mehta

By Brooke Worthing

Thursday, August 29, 2019

Most Americans know someone who has been affected by heart disease. Despite its status as the leading cause of death in the U.S. today, rates of heart disease have actually been steadily falling since they hit their peak in 1968. In fact, between 1970 and 2005, the life expectancy of the average American increased over 70 percent due in part to reductions in heart disease-related deaths.

Research conducted by IRP scientists has played a key role in curbing the heart disease epidemic by helping identify now well-known risk factors for heart disease, such as high blood pressure, obesity, and physical inactivity. However, not all risk factors are so commonly known. A 2017 study by IRP Lasker Clinical Research Scholar Nehal Mehta, M.D., M.S.C.E., revealed that untreated psoriasis — a chronic, relapsing, inflammatory skin disease — is linked to an elevated risk for premature coronary artery disease. Dr. Mehta’s research demonstrated a strong link between psoriasis-induced skin inflammation and and inflammation of the blood vessels, a precursor to heart disease. Through this study, the largest ongoing study of individuals with psoriasis to-date, Dr. Mehta’s team has concluded that controlling psoriasis-associated skin disease could be an important means of reducing cardiac risk in this population.

In recognition of August as National Psoriasis Awareness Month, I spoke with Dr. Mehta to discuss how he discovered the link between psoriasis and cardiac risk, his continued investigation of that relationship, and his motivation to study the cardiovascular system in the first place.

Did something personal or societal prompt you to start performing cardiology research?

“It was a societal issue that prompted me to study this topic. Before coming to the NIH, I worked in Philadelphia as a cardiologist at the University of Pennsylvania. During that time, I noticed that around 75 percent of my patients who were having heart attacks were obese, so I became interested in understanding how fat itself drives heart attacks. We found that the connection may be in part through elevated inflammation driven by the fat itself.

“The second piece of why I became interested in this topic is that society is getting older and more obese, and as a result there is more inflammation within the body as it ages, leading to an increased risk for heart disease.” 

How has your work linking psoriasis and heart disease affected advancements in heart healthcare?

“In 2015, our whole-body scans showed that the effects of psoriasis reach far beyond the skin. The data from our first positron emission tomography (PET) study showed that individuals with psoriasis also have inflammation scattered throughout the body. These data in part led the Word Health Organization to redefine psoriasis as a serious autoimmune disease.

“The next major impact occurred in 2018 when the 2018 American College of Cardiology/American Heart Association (ACC/AHA) Multisociety Guideline on the Management of Blood Cholesterol identified psoriasis as a high-risk condition for developing heart disease, thereby qualifying this population for early initiation of statin therapy. That was an exciting development because it prompted cardiologists to begin identifying psoriasis as a high-risk condition and educating those with psoriasis about their future risks of heart disease.”

What was the most challenging aspect of this study?

“The challenge of starting any large cohort study is getting the ‘set-up’ correct. In each patient, we examine blood for advanced cholesterol testing, degree of inflammation, diabetes risk, and then get images of the body with computed tomography (CT), magnetic resonance imaging (MRI), and PET scans. These tests have advanced our understanding of heart disease progression in states of chronic inflammation. Therefore, we spend considerable time on our infrastructure and workflow, since managing follow up for hundreds of patients at exact time intervals over multiple years requires organization.

“Second, our colleagues in dermatology and rheumatology refer many patients to our study, and despite the time investment required from patients (a two-day initial visit), the unique results available to both patients and providers balance out this time investment. Patients themselves enjoy contributing knowledge to our scientific understanding.

“I would also say that keeping up with modern science has been a challenge. We wrote the protocol for this study in 2012, and recently I’ve spent most of my time making sure that our study remains a contemporary cardiovascular study. This is a tough thing to do because one can get very complacent and simply stop progressing forward, and we don’t want that. Rather, staying contemporary is a challenge we spend an immense amount of time on as I visit programs domestically and internationally to extend our observations. For example, recently we realized that we needed to modify some of the blood tubes we use for our study because newer blood tubes facilitate the cutting-edge research we are able to do in 2019.

“It is important to stay contemporary, but also to stay true to the original research question. It’s definitely a fine balance.”

What particular tools or collaborations were important in conducting this research?

“Our research has been sped up by the fact that we’re at this amazing place, the NIH, which has allowed me to conduct advanced cardiac imaging and characterization of blood vessels before clinical disease to help predict a person’s risk for cardiovascular disease. When I moved my program to the NIH, I was able to have one of few combined PET-MRI scanners in the world, as well as advanced coronary computed tomography angiogram (CTA) scanner platforms not available outside of research. I believe that having access to these tools accelerated my discoveries. The availability of high-grade imaging at the NIH Clinical Center and the NIH’s commitment to me have been extremely helpful.

“I now have a flow cytometry lab where I’m conducting advanced immune phenotyping and vascular imaging, through which we have been able to view arterial plaque and the immune cells that influence it, which is pretty powerful.

“I think that being at the NIH, and the opportunities that it’s given me, have been the best things that could’ve happened to me in my career. Being here allows me to have awesome collaborations with people who otherwise wouldn’t be so quick to share their expertise, knowledge, and intellectual property. The spirit of the Intramural Research Program, along with people trusting the NIH, has been truly incredible.”

How have you continued to study this topic, and what are your plans to study it in the future?

“In 2019, we published a paper that showed treating skin disease in psoriasis reduces heart disease. Our next steps are to understand other factors that might mitigate coronary risk. The idea that one has the ability to mitigate heart disease by treating an inflammatory condition affecting a distant part of the body is really cool to me.

“Right now, the billion-dollar question in cardiology is, ‘Why are people still having heart attacks without having classic risk factors for heart attack?’ In fact, we currently only understand factors that explain roughly 64 percent of heart attacks, so there is still about a 36 percent risk for heart attack that we don’t understand. We’re looking to understand how to define and address risk due to inflammation that we could treat. Through this research, I’m hoping to inform the field about discovering novel pathways so that those in drug development can start targeting them.

“Overall, we need to reduce the risk of heart attacks. I recently read that the highest rates of acute heart attack are happening in younger, obese people between the ages of 35 and 45. We clearly have an inflammatory epidemic driving vascular risk, and we need to understand it. It’s for that reason that my next steps are to dig deep during my tenure at the NIH and finish what I started. I wanted to start my research with a clinical program that defined the link between heart disease and inflammation. Now I have to figure out why that link exists.”

Head over to our Accomplishments page for more information on Dr. Mehta’s research, or listen to his interview on our Speaking of Science podcast. You can also subscribe to our weekly newsletter to stay up-to-date on the latest breakthroughs in the NIH Intramural Research Program.

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