Exploring Psoriasis and Cardiovascular Comorbidity

Patients with psoriatic disease are at increased risk for a number of other serious, chronic health conditions, as well as overall mortality.¹ One of those comorbidities, research shows, is cardiovascular disease, the leading cause of death in the United States. 

In 2006, Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania Perelman School of Medicine in Philadelphia, conducted one of the first major large-scale epidemiological studies examining this association.¹ “We demonstrated that having psoriasis is associated with an overall higher risk of cardiovascular events, and that risk is higher in people with more severe disease, independent of other risk factors, such as smoking, obesity, and hypertension,” Dr Gelfand said. These results have been confirmed multiple times since then,² yet despite this evidence, screening and management of cardiac risk factors for patients with psoriasis is still lacking. 

Exploring the Link

As with many health problems, the relationship between psoriasis and cardiac disease is multifactorial, said Dr Gelfand. He identified several likely components:

• Chronic inflammation. “Psoriasis affects several immune pathways and the T_H1 inflammatory pathways are well-established to drive cardiac risk,” said Dr Gelfand. “IL-6 and IL-1 in blood are causally related to heart disease and people with psoriasis have higher amounts of those inflammatory markers in their blood.”
• Oxidative stress. The epidermal hyperproliferation or scaling that is a hallmark of psoriasis has been shown to cause oxidative stress, as well as an increase in uric acid, which is thought to be toxic to epithelium and cardiac cells.
• Angiogenesis. There is a theory that this process, which is key to the pathogenesis of psoriasis, promotes vascular disease in a broader sense,³ Dr Gelfand said.
• Genetics. Certain genetic components of psoriasis overlap with those of cardiovascular disease and other disease that are independent risk factors, such as diabtes.⁴
• The stress associated with living with psoriatic disease. While causation has not been proven, there is an association between psoriasis and higher rates of other independent risk factors for CVD, including smoking, alcohol use, and a higher body mass index. Psoriatic arthritis, a comorbidity of psoriasis, is also associated with these risk factors. It has also been suggested that the stress of living with psoriatic disease may partially explain the risk of CVD.

Emerging Therapies

It is not yet known whether managing psoriatic disease will lead to a corresponding reduction in cardiovascular risk, but research is underway to help identify the key pathways involved. “This will hopefully help us identify which therapies are most likely to lower cardiovascular risk,” said Dr Gelfand. “So far, the best data come from TNF [tumor necrosis factor] inhibitors. Patients who go on TNF inhibitors are less likely to have cardiac events than patients on other therapies.” Although the data are encouraging, Dr Gelfand said, ultimately, they are only observational, and a causal relationship cannot be guaranteed. “We want the best data possible to make a recommendation,” he said. But that could take time. Unlike psoriasis trials, those related to cardiovascular disease must be longer in duration (a minimum of 5 years) and involve many more patients.

In the meantime, Dr Gelfand and colleagues are conducting a series of randomized placebo-controlled trials of psoriasis treatments to dissect their impact on key pathways of cardiovascular disease. For example, in a randomized, double-blind, placebo-controlled study, Dr Gelfand and his colleagues found that patients who took ustekinumab (Stelera) had a 19% improvement in aortic inflammation, a key marker for future cardiovascular events, compared with a placebo control group.⁵ Dr Gelfand said the effect was similar to what you would see when putting a patient on a statin. Dr Gelfand cautions, however, that these are only surrogate markers of cardiovascular risk, which sometimes fail to accurately predict what really matters, which are cardiovascular events and mortality. Until further research results are in and conclusive, proper screening and management of psoriasis with regard to cardiovascular risk are vital. 

Figure. Psoriasis coverage and severity for mild, moderate, and severe psoriasis by body surface area.

The Importance of Screening

Preventing cardiovascular disease is a major public health goal, and now dermatologists have a role to play in achieving that goal. Both the American Heart Association and the American College of Cardiology define psoriasis as a risk enhancer for atherosclerotic cardiovascular disease. “The cardiology community is recognizing that psoriasis patients need more aggressive efforts to prevent cardiovascular disease, and that is really powerful, and good news for our patients,” said Dr Gelfand. 

As such, it is vital to make sure that in patients with psoriasis, traditional risk factors for cardiovascular disease are all identified and managed appropriately. The worse a patient’s psoriasis is (Figure), the more likely it is that they are experiencing other risk factors that are not being controlled. “We need to alert patients that having this disease means they have a higher risk of several comorbidities, two of the most significant and preventable being diabetes and cardiac events,” said Dr Gelfand. “Patients should be screened on age-appropriate recommendations. Those with more severe disease, such as psoriasis affecting more than 10% of the body surface area or who may be candidates for systemic therapy or phototherapy, should have earlier and more frequent screening.”

The new guidelines released by the American Academy of Dermatology and National Psoriasis Foundation earlier this year address these concerns. Cardiovascular risk assessment is now advised for all patients with psoriasis, and includes screening for hypertension, diabetes, and hyperlipidemia. Clinicians are also recommended to introduce a 1.5 multiplication factor into risk models when assessing patients with moderate to severe psoriasis (defined as having 10% or more affected body surface area or requiring systemic or phototherapy), and to refer them to their primary doctor or cardiologist when warranted.⁶ 

Because absolute risk of cardiovascular events attributable to psoriasis increases with age, and thus becomes more clinically important for patients in their 50s, 60s, and 70s, most patients aged 40 or older are recommended to the cardiovascular prevention clinic in his practice, said Dr Gelfand. While more research needs to be done to see if improving psoriasis alone impacts cardiovascular risk, addressing independent risk factors such as cholesterol, body weight, diabetes, and smoking, can definitely help, he said. 

“It’s a holistic approach, and a key part is therapeutic lifestyle changes,” said Dr Gelfand. “Dermatologists are often the only doctors seeing these patients in their 20s and 30s, and we have an opportunity to help them make changes that can have a huge impact on living a healthier, longer life,” he said. “My patients really appreciate this information. We’re viewing them as more than just skin, and many will take this advice to heart and make major changes. They’re very grateful to me and my team for putting them on that path. A lot of patients credit us with having saved their lives. It’s a very gratifying way to help patients.” 

References

1. Noe MH, Shin DB, Wan MT, Gelfand JM. Objective measures of psoriasis severity predict mortality: a prospective population-based cohort study. J Investig Dermatol. 2018;138(1):228-230. doi:10.1016/j.jid.2017.07.841

2. Miller IM, Ellervik C, Yazdanyar S, Jemec GB. Meta-analysis of psoriasis, cardiovascular disease, and associated risk factors. J Am Acad Dermatol. 2013;69(6):1014-1024. doi:10.1016/j.jaad.2013.06.053

3. Malecic N, Young HS. Excessive angiogenesis associated with psoriasis as a cause for cardiovascular ischaemia. Exp Dermatol. 2017;26(4):299-304. doi:10.1111/exd.13310

4. Eirís N, González-Lara L, Santos-Juanes J, Queiro R, Coto E, Coto-Segura P. Genetic variation at IL12B, IL23R and IL23A is associated with psoriasis severity, psoriatic arthritis and type 2 diabetes mellitus. J Dermatol Sci. 2014;75(3):167-172. doi:10.1016/j.jdermsci.2014.05.010

5. University of Pennsylvania School of Medicine. Drug that treats psoriasis also reduces aortic vascular inflammation. https://www.pennmedicine.org/news/news-releases/2018/february/drug-that-treats-psoriasis-also-reduces-aortic-vascular-inflammation. Published February 16, 2018. Accessed June 24, 2019.

6. Elmets CA, Leonardi CL, Davis DMR, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. J Am Acad Dermatol. 2019;80(4):1073-1113. doi:10.1016/j.jaad.2018.11.058