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Getting at the Heart of Psoriasis

A look at cardiovascular health and psoriatic disease.

Psoriasis is more than skin deep. Its complete toll is experienced by individuals living with psoriasis and their loved ones.

A growing body of research suggests the chronic inflammation occurring in patients with psoriasis involves not only skin manifestation but the rest of the body as well. [1] For example, psoriasis is considered an independent risk enhancer for individuals with an intermediate 10-year risk of cardiovascular (CV) disease, according to the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. [2] Likewise, cardiovascular disease is not just heart disease. It refers to a spectrum of conditions including heart disease and heart attack, stroke, heart failure, arrhythmia and heart valve problems. [3] In 1961, the first connection among psoriasis, psoriatic arthritis (PsA) and cardiovascular disease was found. [4] Since then, this connection has been the focus of much research and recent advances.

The CV and Psoriasis Link

The link to CV disease in patients who are living with psoriasis and PsA continues to be elucidated. [5] “Psoriasis clearly increases the risk of cardiovascular disease between 1.5 and twofold. This risk is highest in patients with severe psoriasis and in patients with psoriatic arthritis,” says Daniella Schwartz, M.D., assistant clinical investigator for the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (NIH).

“In recent years, the role of low-grade inflammation in the development of atherosclerosis and cardiovascular disease has become very clear,” she continues. “About 20 to 30 percent of the risk of a heart attack, or myocardial infarction (generally, not just in psoriasis), is due to residual inflammation.” A recent study of 260 patients with psoriasis (Teklu et al., 2020) found elevated biomarkers of systemic inflammation, C-reactive protein (CRP) and GlycA in the subset of patients with psoriasis and cardiometabolic syndrome (defined as a combination of diabetes, obesity and elevated cholesterol and blood pressure). [8]

These types of studies contribute to the idea that systemic inflammation has a larger role in psoriasis-associated CV risk. “Inflammatory disease severity and extracutaneous inflammation (outside the skin) are associated with a higher risk of CV disease,” Dr. Schwartz says. “Moreover, multiple advanced imaging studies, including PET-CT studies at the NIH and elsewhere, reveal subclinical vascular inflammation in patients with psoriasis that is an important biomarker of CV disease risk.”

Screening for Cardiovascular Disease

Nearly three-fourths of patients with severe psoriasis (defined as greater than 10 percent body surface area involvement) are undertreated or not receiving any treatment for their psoriasis, putting them at increased risk for CV disease risk. [6] [7] “Underdiagnosis can lead to undertreatment and increased morbidity in patients with psoriasis,” says Dr. Schwartz.

People with PsA may be at an even greater risk. Yet the majority of patients living with psoriasis are not routinely screened for CV disease risk factors, even when studies have shown these individuals are more likely to have cardiometabolic syndrome. In fact, 2019 Guidelines from the American College of Cardiology (ACC) and the American Heart Association (AHA) recommend that patients be routinely assessed for cardiovascular risk factors as well as the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) starting at age 40. For patients between the ages of 20 and 39, ACC/AHA recommends assessing traditional ASCVD risk factors every four to six years. [9]

Some in the world of psoriasis research have argued for more frequent screening in psoriasis patients because the risk of CV disease is often underestimated. [3] [10] [11] Dr. Schwartz agrees. “This is important because patients with psoriasis are at a higher cardiovascular risk than would be apparent from clinical risk scores, which do not incorporate disease severity or otherwise account for the effect of systemic inflammation,” she says. Recommendations for psoriasis-specific screening guidelines include screening frequency that is dependent on psoriasis severity, corrections to existing risk scores with a 1.5x multiplier, and other factors.

CV disease risk factors such as high cholesterol can be treated with traditional cholesterol-lowering agents like statins. Moreover, a meta-analysis showed statins may have added benefits and improve severe psoriasis. [12] Further studies on statins and psoriasis are underway.

As for what patients can do to address their risk factors for CV disease, Dr. Schwartz says that “traditional cardiovascular risk reduction is definitely helpful. This includes diet and exercise. It’s also important for psoriasis patients to advocate for themselves when being screened for CV disease.”

Does Treatment Affect Risk?

Often, psoriasis treatments are relegated to being elective or cosmetic, but another important consideration is whether psoriasis treatments decrease CV disease risk. So far, studies have shown mixed results. Some preliminary data found that treatments like methotrexate (MTX) and etanercept, a biologic tumor necrosis factor (TNF)-alpha inhibitor, protected the heart, but other treatments may increase the burden of CV disease.

“This is an emerging area with incomplete data, and many studies assess surrogate measures of CV events (i.e., advanced imaging) rather than actual events,” Dr. Schwartz notes. “This is because many biological therapies for psoriasis are relatively new, with the exception of disease-modifying anti-rheumatic drugs (DMARDs) and TNF inhibitors, and extremely long-term follow-up of 10 to 20 years is often required for assessment of CV events. With these caveats, treatment with anti-inflammatory therapies does appear to reduce the risk of vascular inflammation and major CV events in patients with psoriasis. However, the type of therapy matters. For example, biological therapies and DMARDs appear to improve outcomes, whereas corticosteroids and nonsteroidal anti-inflammatory drugs worsen outcomes.” 

For now, Dr. Schwartz says, “I would encourage all patients and physicians to aggressively pursue a treat-to-target approach for psoriasis and PsA. Remember that it is not ‘just’ a rash, and that poorly controlled skin disease probably translates to poorly controlled systemic inflammation and increased CV risk. These recommendations are strongly based on the most recent American Academy of Dermatology and National Psoriasis Foundation (NPF), NPF/American College of Rheumatology and European League Against Rheumatism guidelines.”

Further inquiry is warranted into psoriasis treatments and heart health because if there are benefits, it would reinforce that psoriasis treatment – like psoriasis – is more than skin deep. This would also likely contribute to a greater prevalence of individuals getting treatment. [13]

There is a growing understanding of the link among psoriasis, PsA and heart disease. We are learning that not only is it important to treat psoriatic disease, but also to treat the patient as a whole. This includes evaluating for major comorbidities, such as CV disease.

“Remember that traditional risk factors tend to underestimate CV disease risk and that many patients are underdiagnosed and undertreated,” says Dr. Schwartz. “Patients should encourage their health care provider to consider psoriasis as a diabetes equivalent when calculating individual risk of CV disease. This means that goals for blood pressure, blood sugar and cholesterol treatments will be different from those of a patient without psoriasis – and that their [health care provider] may have a lower threshold to refer a patient for stress testing or imaging of coronary arteries.”

Dr. Schwartz’s parting words for patients and their loved ones are: “Don’t be afraid to advocate for yourself when it comes to CV risk screening and reduction. The evaluation and treatment of psoriasis and PsA is a rapidly evolving clinical field with new diagnostic studies and treatments emerging every year. Use patient education and advocacy resources, such as NPF, NIH and the American College of Rheumatology, to inform yourself about these developments, and talk to your physician(s) if you have any questions or concerns.”

References:

1.            Takeshita J, Grewal S, Langan SM, et al. Psoriasis and comorbid diseases: Epidemiology. J Am Acad Dermatol. 2017;76(3):377-390. doi:10.1016/j.jaad.2016.07.064.

2.            Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in J Am Coll Cardiol. 2019 Jun 25;73(24):3234-3237]. J Am Coll Cardiol. 2019;73(24):3168-3209. doi:10.1016/j.jacc.2018.11.002.

3.            What is Cardiovascular Disease? www.heart.org. https://www.heart.org/en/health–topics/consumer–healthcare/what–is–cardiovascular–disease. Accessed January 14, 2021.

4.            Reed WB, Becker SW, Rohde R, Heiskell CL. Psoriasis and arthritis. Clinicopathologic study. Arch Dermatol. 1961;83:541-548. doi:10.1001/archderm.1961.01580100005001.

5.            Teklu M, Zhou W, Kapoor P, et al. Metabolic Syndrome and its Factors are Associated with Non-Calcified Coronary Plaque Burden in Psoriasis: An Observational Cohort Study [published online ahead of print, 2020 Dec 21]. J Am Acad Dermatol. 2020;S0190-9622(20)33238-2. doi:10.1016/j.jaad.2020.12.044.

6. Horn EJ, Fox KM, Patel V, Chiou CF, Dann F, Lebwohl M. Are patients with psoriasis undertreated? Results of National Psoriasis Foundation survey. J Am Acad Dermatol. 2007;57(6):957-962. doi:10.1016/j.jaad.2007.06.042.

7. Takeshita J, Wang S, Shin DB, et al. Effect of psoriasis severity on hypertension control: a population-based study in the United Kingdom. JAMA Dermatol. 2015;151(2):161-169. doi:10.1001/jamadermatol.2014.2094.

8.            Langan SM, Seminara NM, Shin DB, et al. Prevalence of metabolic syndrome in patients with psoriasis: a population-based study in the United Kingdom. J Invest Dermatol. 2012;132(3 Pt 1):556-562. doi:10.1038/jid.2011.365.

9.            Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in Circulation. 2019 Sep 10;140(11):e649-e650] [published correction appears in Circulation. 2020 Jan 28;141(4):e60] [published correction appears in Circulation. 2020 Apr 21;141(16):e774]. Circulation. 2019;140(11):e596-e646. doi:10.1161/CIR.0000000000000678.

10.         Mehta NN, Krishnamoorthy P, Yu Y, et al. The impact of psoriasis on 10-year Framingham risk. J Am Acad Dermatol. 2012;67(4):796-798. doi:10.1016/j. jaad.2012.05.016.

11.         Takeshita J, Grewal S, Langan SM, et al. Psoriasis and comorbid diseases: Implications for management. J Am Acad Dermatol. 2017;76(3):393-403. doi:10.1016/j. jaad.2016.07.065.

12.         Ports WC, Fayyad R, DeMicco DA, Laskey R, Wolk R. Effectiveness of Lipid-Lowering Statin Therapy in Patients With and Without Psoriasis. Clin Drug Investig. 2017;37(8):775-785. doi:10.1007/s40261-017-0533-0.

13. Margolis D, Bilker W, Hennessy S, Vittorio C, Santanna J, Strom BL. The risk of malignancy associated with psoriasis. Arch Dermatol. 20

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