Sulzberger lecturer links psoriasis, CV disease

Joel M. Gelfand, MD, MSCE

Like the start of a snowstorm, evidence is accumulating that psoriasis is linked to cardiovascular and cardiometabolic disease, and the severity of psoriasis increases the risk of heart disease.

Now, a blizzard of data from a new trial is making it clear that severe skin inflammation is subtracting years from the lives of patients with psoriasis. Joel M. Gelfand, MD, MSCE, traced the growth of evidence Sunday during his Marion B. Sulzberger, MD, Memorial Award and Lectureship, “Getting to the Heart (and Other Comorbidities) of Psoriasis.”

“Patients with more severe psoriasis die about five years younger than they should based on their risk factors for mortality. The risk is similar to the risk conferred by diabetes, which everyone knows is a major risk factor for heart disease,” Dr. Gelfand said in an interview before his lecture. He is a professor of dermatology and epidemiology and vice chair for clinical research at the University of Pennsylvania Perelman School of Medicine.

Dr. Gelfand tapped data collected since the 1980s in the electronic medical records of general practitioners in the United Kingdom. He published a 2006 article in the Journal of the American Medical Association demonstrating that as psoriasis severity increases so does the risk of heart attack, independent of traditional cardiovascular risk factors. This paradigm-shifting research has since been confirmed by dozens of studies conducted around the world, including multiple meta-analyses.

In a Late-breaking Research symposium on Saturday, Dr. Gelfand and post-doctoral researcher Megan Noe, MD, presented their most recent data. They have been following 9,000 patients with psoriasis prospectively since 2009 to determine how simple measures of psoriasis severity predict future morbidity.

“Strikingly, if you have more than 10 percent of your body surface area (BSA) involved with psoriasis, you have a 90 percent higher risk of dying in the next three to four years, independent of concurrent health conditions, smoking, or obesity. That is pretty powerful,” Dr. Gelfand said.

When more than 10 percent of the BSA is affected by psoriasis, the risk of mortality exceeds recent estimates of the risk of mortality conferred by poorly controlled hypertension, he noted. No excess mortality was seen in patients with moderate (3-10 percent BSA) or mild (less than 3 percent BSA) psoriasis, which emphasizes the importance of targeting patients with more severe psoriasis for preventive health efforts.

“How could you have a major organ malfunction for decades with no consequence?” Dr. Gelfand asked.

Research also shows that three key aspects of psoriasis pathophysiology — inflammation, epidermal proliferation, and angiogenesis — involve pathways that are also known to increase the risk of cardiovascular disease, he said.

“The thinking is that it is a systemic disease that is not only in the skin but is a marker for risk of other problems over time, based on the epidemiological data, the genetic data, and the pathophysiological data,” Dr. Gelfand said.

This means that patients need to be educated about the risks of future comorbidity in psoriasis, and dermatologists need to become more involved in screening patients for cardiovascular risk factors, he said.

“That does not mean dermatologists must do the screening, but it does mean you need to educate patients to go see a general practitioner and have this done,” Dr. Gelfand said. “We know many psoriasis patients have not had their cholesterol or blood pressure checked, and you may be their only doctor.

“We also need to stay tuned to the literature to see where things go with our treatment algorithms. Ultimately, what we need to understand is which strategies will not just improve your skin but will lower your risk of morbidity and mortality, and other major health problems over time.”

To further understand how psoriasis treatment impacts CV risk, Dr. Gelfand established a long-standing collaboration with his former student, Nehal N. Mehta, MD, MSCE, cardiologist and chief of the Section of Inflammation and Cardiometabolic Disease at the National Institutes of Health.

“Work that Nehal and I have done has shown that if you have psoriasis, you are more likely to have increases in aortic inflammation as measured by FDG PET/CT that is equivalent to approximately a decade of aging. More recently, his group showed that this correlates with your disease severity. The higher your PASI is, the higher your aortic inflammation is, independent of your traditional cardiovascular risk factors,” Dr. Gelfand said.

This finding is important because aortic inflammation is predictive of future major cardiovascular events and is known to improve when patients use treatments known to lower cardiovascular risk, such as statins.

“Other research teams have confirmed what we have done with PET scans,” Dr. Gelfand said. “They also added to our work by showing there is increased subcutaneous fat inflammation underneath the plaque of psoriasis. Again, this makes a connection between the skin and adipose.”

Dr. Gelfand also discussed research from the Vascular Inflammation in Psoriasis (VIP) trial that was first released during the Annual Meeting. VIP is a randomized, controlled trial with three arms that used FDG PET/CT to study the effects of adalimumab versus phototherapy versus placebo on the primary outcome of aortic inflammation at 12 weeks. A related, extended trial, VIP-E, examined the results in the same patients after 52 weeks of adalimumab treatment.

At the end of the study, the patients in the adalimumab arm had no significant change in aortic inflammation based on a comparison of their baseline scans at the start of the trial and at its conclusion. That showed that adalimumab did not have a statin-like effect, he said.

Other studies are looking at the effects of phototherapy, apremilast, ustekinumab, and new IL-17 inhibitors on cardiovascular events. In addition, observational data shows that TNF inhibitors seems to be associated with a reduction in risk of cardiovascular disease and that methotrexate may be cardio-protective as well, he said.

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