Disclosures: Mehta is a full-time U.S. government employee and has served as a consultant for Amgen, Eli Lilly, and Leo Pharma receiving grants/other payments; as a principal investigator and/or investigator for AbbVie, Celgene, Janssen Pharmaceuticals Inc., and Novartis receiving grants and/or research funding; and as a principal investigator for the National Institute of Health receiving grants and/or research funding. Gelfand reports he served as a consultant for BMS, Boehringer Ingelheim, GSK, Janssen Biologics, Novartis, UCB (DSMB) and Pfizer; receives research grants (to the trustees of the University of Pennsylvania) from AbbVie, Janssen, Novartis, Celgene, Ortho Dermatologics and Pfizer; and received payment for continuing medical education work related to psoriasis that was supported indirectly by Lilly and Ortho Dermatologics.
September 22, 2020
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Treating psoriasis inflammation can reduce cardiovascular risks

Disclosures: Mehta is a full-time U.S. government employee and has served as a consultant for Amgen, Eli Lilly, and Leo Pharma receiving grants/other payments; as a principal investigator and/or investigator for AbbVie, Celgene, Janssen Pharmaceuticals Inc., and Novartis receiving grants and/or research funding; and as a principal investigator for the National Institute of Health receiving grants and/or research funding. Gelfand reports he served as a consultant for BMS, Boehringer Ingelheim, GSK, Janssen Biologics, Novartis, UCB (DSMB) and Pfizer; receives research grants (to the trustees of the University of Pennsylvania) from AbbVie, Janssen, Novartis, Celgene, Ortho Dermatologics and Pfizer; and received payment for continuing medical education work related to psoriasis that was supported indirectly by Lilly and Ortho Dermatologics.
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The association between psoriatic disease and cardiovascular disease has been known for the past decade, but new research aims to determine if long-term psoriasis treatment affects heart health.

“Inflammation has long been associated with the development of atherosclerosis ... and psoriasis itself is a chronic inflammatory disease,” said Nehal N. Mehta, MD, MSCE, FAHA, of the NIH. “What we have found over 10 years of work is that when one has psoriasis in the severe form, which means more than 10% of their body is covered, there is approximately a 50% to 60% increased risk of first heart attack and stroke and that which occurs between 40 and 50 years of age.”

Nehal N. Mehta, MD, MSCE, FAHA, of the National Institutes of Health, says treating psoriasis and inflammation can reduce increased cardiovascular disease risks.
Nehal N. Mehta, MD, MSCE, FAHA, of the National Institutes of Health, says treating psoriasis and inflammation can reduce increased cardiovascular disease risks.
Source: Storytellez Production.

Patients with mild-to-moderate psoriasis have also shown related complications due to inflammation such as joint disease, diabetes, heart disease and depression.

While originally believed to be solely a skin issue, psoriatic disease is now known to affect multiple systems in the body including the joints, the brain and the heart.

“We first coined the phrase ‘psoriasis is more than skin deep’ 12 years ago because there is a lot more going on beyond what you are seeing on the skin,” Mehta said.

Studies have shown more cardiovascular risk factors in psoriasis patients, as well as an association between psoriasis and obesity and diabetes. In addition, those with psoriasis were having heart attacks about a decade sooner than those without psoriasis.

Joel M. Gelfand, MD, MSCE, FAAD
Joel M. Gelfand

“When you study thousands of patients over time, you can show that they have higher rates of major cardiovascular events and mortality that seems to be independent of the individual risk factors that drive cardiovascular disease like blood pressure or smoking, and the risk is higher the more severe your skin disease is,” Joel M. Gelfand, MD, MSCE, FAAD, of Penn Medicine, said.

Treating psoriasis to prevent cardiovascular disease

Mehta and Gelfand are working on studying how different treatments for psoriasis can affect cardiovascular disease risk. They hypothesize that controlling inflammation would reduce cardiovascular disease.

“Ideally, we would do large-scale, randomized, placebo-controlled trials to prove those taking these treatments have a lower rate of vascular events over time compared to placebo,” Gelfand sad. “But that is very hard to do in psoriasis because you can’t give them placebo for their psoriasis for years.”

Studies outside of psoriasis, however, have shown that controlling inflammation can lower cardiovascular risk.

The CANTOS trial compared canakinumab, which targets interleukin-1, to placebo in patients who had previously had myocardial infarction and found the treatment group had a significantly lower rate of new cardiovascular events than the placebo group.

The COLCOT trial assigned patients with a recent myocardial infarction to receive low-dose colchicine or placebo. It also found a lower rate of recurrence in those on the inflammatory reducing medication.

“That is two proof-of-principle studies that show just treating inflammation can lower the risk of cardiovascular events in people at high risk of cardiovascular disease. We know from this emerging data that if you lower inflammation in those patients with say, canakinumab, you can lower the risk of heart attacks and strokes,” Gelfand said. “If they studied a TNF inhibitor or an IL-17 inhibitor, maybe they would have found similar findings, but we just don’t know the answer to that yet.”

Mehta and Gelfand are using surrogate marker studies to determine if different psoriasis treatments affect cardiovascular disease pathways such as glucose, cholesterol and inflammatory pathways.

Thus far their research has found that adalimumab, a tumor necrosis factor (TNF) inhibitor, and ultraviolet light photo therapy both have the potential to reduce inflammatory makers related to cardiovascular disease, according to Gelfand. Photo therapy also showed signs of improving high density lipoproteins (HDL), the ‘good’ cholesterol, and lower aortic vascular inflammation by FDG PET CT. The IL-12 and IL-23 inhibitor ustekinumab showed transient benefit for aortic vascular inflammation at 12 weeks, but this was not sustained at 1-year follow up. And secukinumab, an IL-17 inhibitor showed neutral effects on cardiovascular risk factors and vascular inflammation following 1-year of treatment.

“These trials are important because it shows some evidence we might find beneficial. In general, what we found was very reassuring,” Gelfand said. “It has given us hope about certain mechanisms potentially being useful in cardiovascular risk protection in psoriasis.”

A net benefit

Some biologic psoriasis treatments carry additional risks; however, the overall benefits usually outweigh those risks.

TNF inhibitors can lead to a slight increase in LDL cholesterol and weight gain, especially in those overweight or with diabetes. All biologics have a small risk of infection and cancer, according to Mehta.

“Overall, these are safe medicines,” he said. “There are not many negatives associated with them. All of the countries around the world have started to approve biologics as first-line therapy for severe psoriasis, so we know other countries are understanding this importance.”

Treating psoriasis and the inflammation associated with it also has secondary heart health benefits, according to Mehta.

Coronary and metabolic health benefits come from a healthier lifestyle, which tends to come with the clearing of psoriasis symptoms.

“The minute the skin starts clearing we start seeing people exercise more. We start seeing people’s moods get better. We start seeing people actually feel a little bit more agile – they feel like they want to do more,” Mehta said. “The patient side gets better, and you are withdrawing a tremendous amount of systemic inflammation, you are deriving a benefit over time on coronary health and metabolic health. I think it’s a net benefit if the patient is willing to take injectable medications.”

For those who prefer not to treat severe psoriasis with biologic therapy, treatment of the disease should still be sought.

“In that case, I just say to make sure you treat with photo therapy or topicals. Just make sure you treat your psoriasis, period,” Mehta said. “Untreated plaques increase systemic inflammation.”

Heart health screening

Cardiovascular risk factors are easily identified with basic health screenings; however, many are underdiagnosed. Screening for diabetes, high cholesterol and high blood pressure in psoriasis patients, and treating those risk factors accordingly, is paramount to the overall health of a patient.

“We know with psoriasis these risk factors tend to be underdiagnosed and that the worse your skin disease is, the higher risk is of not having these risk factors detected,” Gelfand said. “Then, if you do have these risk factors detected, the likelihood of having them adequately treated goes down as your skin disease gets worse. This is the exact opposite of the phenomena we want to have happen.”

Screenings for cholesterol, blood pressure and hemoglobin A1C, or another diabetes test, should be completed for all psoriasis patients, and these tests should be completed as often as recommended by the American Heart Association based on age and relative health of the patient.

“After the age of 40, the key thing is estimating someone’s risk of having a cardiovascular event and deciding if they need to go on a lipid-lowering medication like a statin,” Gelfand said.

In the general population, only about 30% of individuals who should be on statins are, and in the psoriasis population, that number is only 25%, he added.

“That’s a huge practice gap. We could extend life expectancy and lower cardiovascular events and strokes in people with psoriasis if we could get 75% of them who should be on statins to be on them,” Gelfand said.

These screenings can be completed by any specialist or primary care physician, but psoriatic disease specialists should be aware of this increased cardiovascular risk, educate patients and take them into consideration when treating the disease.

Living a heart-healthy lifestyle

Patients should also be made aware that these risk factors are common with their psoriasis diagnosis and be encouraged to mitigate these factors with a healthy lifestyle as outlined by the American Heart Association.

“Patients should be aware this exists and should talk to their doctor about what they are willing to do for their health,” Mehta said. “Follow a heart-healthy diet, exercise regularly, stop smoking, treat inflammatory disease and get your routine, preventative health maintenance done.”

Nehal N. Mehta, MD, MSCE, FAHA
Nehal N. Mehta

It is also important to see a primary care physician regularly and to keep on top of one’s personal health metrics.

“Everyone should know what their blood pressure is, what their cholesterol is, and if they have signs of diabetes,” Gelfand said. “Once you have that baseline you can determine how often to get these things checked.”

One plaque is too much

The National Psoriasis Foundation recently granted funding for interview studies and surveys to better understand how to optimize cardiovascular disease prevention in psoriasis and psoriatic arthritis patients, Gelfand said.

Researchers will evaluate how to approach lowering cardiovascular risk.

“The ultimate goal will be a clinical trial that would test a new strategy of how to lower cardiovascular risk in our patients,” he said.

As these studies continue, Mehta maintains that treating inflammation will continue to benefit heart health in the long run.

“Patients should be empowered to know we are pretty certain we can say untreated psoriasis is dangerous,” he said. “We used to say ‘psoriasis is more than skin deep,’ we now are starting to learn that ‘even one plaque is too much.’ The most important message is ‘don’t let your psoriasis go untreated.’”

References:

Ridker, P, et al. N Engl J Med. 2017; doi: 10.1056/NEJMoa1707914.

Tardif J, et al. N. Engl J Med. 2019; doi: 10.1056/NEJMoa1912388.

For more information:

Nehal N. Mehta, MD, MSCE, FAHA, can be reached at the National Institutes of Health, building 10, room 5-5140, 10 Center Drive, Bethesda, MD, 20914; email: Nehal.mehta@nih.gov.

Joel M. Gelfand, MD, MSCE, FAAD, can be reached at Penn Dermatology Perelman, South Pavilion, 1st floor, 3400 Civic Center Blvd., Philadelphia, PA 19104; email: joel.gelfand@pennmedicine.upenn.edu; twitter: @DrJoelGelfand.