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What We Are Learning About Psoriasis and Heart Disease

Part 2: A deep dive into the largest single grant investment in the history of NPF – the Psoriasis Prevention Initiative.

“Nearly two decades,” says Joel Gelfand, M.D., FAAD, professor of dermatology and epidemiology at the Perelman School of Medicine at the University of Pennsylvania, when asked how long he and his team have been involved in research related to cardiovascular mortality and psoriatic disease.

Based on evolving science in the late 1990s and early 2000s, Dr. Gelfand and his research team developed the hypothesis a little less than 20 years ago that psoriasis could potentially promote cardiovascular disease. The science linked chronic inflammation to atherosclerosis (buildup of fat and cholesterol in artery walls) and cardiovascular events. At the same time, a researcher by the name of Goran Hansson, M.D., Ph.D., had published a journal article explaining the immune pathophysiology (physical processes) of atherosclerosis. “And it was just like a diagram of psoriasis. That laid an impression in my head,” says Dr. Gelfand.

Dr. Gelfand’s interest in cardiovascular inflammation and psoriatic disease really started back when he was a medical student in the 1990s. That was when he realized there was a potential connection, and he began working with other senior dermatologists to research it. Using data in United Kingdom medical records and leveraging other work, Dr. Gelfand found that people with psoriasis have a higher risk of heart attack, stroke, and cardiovascular mortality.

“These risk factors appear to be independent of traditional risk factors we can identify in medical practice and seem to be more significant in people with more severe diseases based on treatment patterns,” Dr. Gelfand says.

Over time, his research began to show how body surface area (BSA) measurements had important implications for cardiovascular health going forward. Findings from a prospective cohort study involving 9,000 patients and their general practitioners showed that “for every 10% increase you have in BSA, you have a 20% risk of developing diabetes over time, and it is independent of your body mass index,” Dr. Gelfand says. This risk is distinct from that of other inflammatory diseases: “People with psoriasis have a high risk of diabetes. People with rheumatoid arthritis do not,” he says.

Dr. Gelfand suspects there may be something specific about psoriatic inflammation that seems to promote diabetes. Furthermore, data have shown that patients with a BSA of more than 10% are associated with a higher risk of mortality during four or five years of follow-up, independent of all other mortality risk factors.

“It’s pretty striking that a simple estimate by a [general practitioner] can have such important prognostic implications for a person’s health over time,” Dr. Gelfand says.

Almost in parallel, one of the next steps in psoriatic disease research was happening: trying to get a better understanding of how biologic treatment correlated with psoriasis from a cardiovascular perspective and working to understand what the treatments do to cardiovascular risk in patients with psoriasis. It was at this time – 2008 – that Dr. Gelfand connected with Nehal Mehta, M.D., MSCE, FAHA, a senior investigator for the Section of Inflammation and Cardiometabolic Diseases with the National Institutes of Health (NIH) Heart, Lung, and Blood Institute (NHLBI). Dr. Mehta was studying models of provoked inflammation and did an independent study with Dr. Gelfand.

“The paradigm we tried to build was the idea that with psoriasis disease we could take inflammation away in very specific ways,” says Dr. Gelfand. “We can remove it through blocking TNF [tumor necrosis factor]. We can remove it by blocking IL-17 or IL-23 [interleukins] or something like that and see what it does to the cardiovascular system, and we do it in a placebo control trial.”

This served as a good model for understanding how inflammation impacts cardiovascular disease, and as a result, a series of randomized placebo-controlled trials have been conducted. “We call them vascular inflammation in psoriasis, or VIP trials,” Dr. Gelfand says.

Data from these trials have shown that TNF inhibitors and phototherapy have pretty profound impacts on inflammation in the blood in a way that should improve cardiovascular risk over time.

“Interestingly, phototherapy was the only one to improve lipid metabolism and actually improve good cholesterol, which is a really fascinating finding,” Dr. Gelfand says. “It also improved key inflammatory markers of cardiovascular risk, like c-reactive protein in IL-6. Then we showed some inflammatory pathway benefits for ustekinumab, a therapy that blocks IL-12 and IL-23.”

Interestingly, data showed a neutral signal for IL-17 inhibitors, “so even though they are incredibly effective at skin disease, they don’t seem to move the needle on any of the key pathways of vascular disease risk that we measure in psoriasis,” he says.

But what about traditional cardiovascular risk factors? “One of the things we’ve shown is that BSA plays a role in the likelihood of having metabolic syndrome and having components of metabolic syndrome like insulin resistance, being overweight, or having dyslipidemia,” Dr. Gelfand says. However, despite having higher risks of cardiovascular diseases and higher rates of cardiovascular risk factors, psoriasis patients with high blood pressure are less likely to have their blood pressure adequately controlled.

“The patients are doing worse as their skin condition severity gets worse. So one of the things we’ve recognized for patients with psoriasis is that this is really a systemic disease. It’s not just their skin that is affected; they have a variety of metabolic issues that go on, somehow related to psoriasis and its severity,” Dr. Gelfand says. “There is evidence that shows that the best way of lowering cardiovascular risk like [elevated] blood pressure and elevated cholesterol is with a statin, and we do this really poorly in psoriasis. And we do it even worse when disease gets worse and people are at the worsened risk.”

Tackling the Problem

Dr. Gelfand explains that he “had no plans to try and tackle this problem. It’s a really hard problem, which is taking a population of people at risk for an outcome who were not getting properly treated, and then narrowing that evidence-to-practice gap.”

But when NPF announced the PPI grant, Dr. Gelfand realized it was an incredible opportunity. “If we could improve blood pressure management and cholesterol management, diet, and exercise in people living with psoriasis, we could substantially improve their well-being, health, and longevity, potentially,” he says.

The initial idea was to have dermatologists screen people for cholesterol levels and prescribe a statin when needed. Previous research by Alexa Kimball, M.D., president and CEO of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, using a clinical trial population had shown that a small percentage of people with psoriasis who should be on a statin were not actually taking one. With the help of Rinad Beidas, Ph.D., who is founder and director of the Penn Implementation Science Center at the Leonard Davis Institute and associate director at the Center for Health Incentives and Behavioral Economics, Dr. Gelfand and his team did a series of engagement work.

The findings from their quantitative interviews with patients, dermatologists, and rheumatologists were that these issues matter a lot. “Stakeholders, clinicians, and patients would all like better education and screening for cardiovascular risk factors in the context of receiving care for psoriatic disease,” Dr. Gelfand says. “But it would be difficult for rheumatologists or dermatologists to really meaningfully engage in the treatment of cardiovascular risk factors.”

A good point was brought up during these interviews: If dermatologists and rheumatologists are treating lipids of patients, but not blood pressure, then maybe they aren’t really doing the patient a favor by solving only part of the problem. This led to a crucial next step for the research team – a stakeholder meeting at the NHLBI. Here different experts came together, all trying to tackle a similar problem, and the concept of a care coordinator was introduced in this context as a potential solution.

What Is a Care Coordinator?

A care coordinator is a person who helps patients navigate the complex needs of their health care management. “In the field of general medicine, this model has been shown repeatedly to be very effective,” Dr. Gelfand says.

For example, a care coordinator could help a patient with diabetes and depression navigate among behavioral health, endocrinology (the study of the system that controls hormones in the body), and internal medicine. “They get better outcomes not only on their depression but also their diabetes. Their A1Cs get better, and their mood gets better – really powerful findings,” he says.

In the U.S. health care system, patients with psoriasis are in a unique situation. “They are sort of stuck in a specialty care system, which is not really well-geared to manage prevention of heart disease at all and not well-connected to their primary care doctors,” says Dr. Gelfand. “They are getting a lot of their focused care in psoriatic disease.”

One innovation Dr. Gelfand and the team proposed to NPF was that a centralized care coordinator could be embedded in the Patient Navigator Center at NPF. “The idea here is that the dermatologist or rheumatologist would do what we encourage them to do, which is the standard of care in the guidelines: Educate the patient about the fact that psoriatic disease puts him at higher risk for cardiovascular risk factors and cardiovascular events, and order simple screenings checking for diabetes, cholesterol levels, and blood pressure. If any of those things are abnormal, refer them to the care coordinator,” Dr. Gelfand explains.

If this part of the project were to come to fruition, the role of the care coordinator could be to speak with patients, review their risk factors, calculate their risk of having cardiovascular disease during the next 10 years as well as during their lifetime, and compare that with what the risk optimally should be. The care coordinator could also provide a series of recommendations and connect the individual back with the relevant provider.

“I think leveraging what we learned during the pandemic about virtual care, telemedicine, video consultations, etc., is a real opportunity for us as researchers and clinicians and the NPF as advocates to really advance the well-being of patients more holistically,” Dr. Gelfand says.

His ultimate vision for this type of care is to see it generalized to other aspects of health care for patients with psoriasis, such as behavioral health or rheumatology. Going beyond that, this care could help patients with other medical conditions and considerations.

PPI Team Science

Collaboration is a key part of PPI and the foundation of this research work. “I think a lot of the discovery in medicine is often at the edges of different disciplines that haven’t been connected to each other,” Dr. Gelfand says.

The PPI team working beside Dr. Gelfand includes:

Alexis Ogdie-Beatty, M.D., MSCE, is a rheumatologist who will be using her expertise to help lead considerations for patients with PsA.

Dr. Beidas, Ph.D., is a clinical psychologist and implementation scientist and has done this work in other fields before.

Dr. Mehta, M.D., MSCE, FAHA, is a prevention cardiologist who speaks to patients daily about diet, exercise, medical therapy, and more. His insights and others will be used to build the scripts for the care coordinator.

Dr. April Armstrong, M.D., MPH, is a dermatologist who has been very engaged in studies using telemedicine. She will be helping to determine how best to use simple approaches to bring care to patients, such as a collaboration with Lemonaid Health, a telehealth medicine service.

Dr. John Barbieri, M.D., MBA, is a dermatologist and epidemiologist who will be helping to strategize how complex care is delivered in the U.S. health care system.

2021 Research Symposium Recap

The NPF Research Symposium included sections related to clinical, translational, and basic research, as well as guest speakers.

Read more

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