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Winter 2025
Winter 2025 Issue Not Just a Skin Condition Untangling the Connection Between Psoriasis and Heart Disease Psoriasis is often thought of as a skin disease; however, the disease is a chronic proinflammatory autoimmune disease with wide-ranging effects, including on the cardiovascular system.1 Research shows that patients with psoriasis experience myocardial infarction five years earlier, on average, than patients without psoriasis.2 Furthermore, those with severe psoriasis have an additional 6.2% absolute risk of a major cardiac event over 10 years compared with people in the general population.3 Standard risk calculators give a cardiovascular disease (CVD) risk score based on traditional heart disease risk factors such as obesity, lipid levels, and hypertension. However, updated guidelines now recognize that certain conditions are risk enhancers that increase the likelihood of cardiovascular events—and psoriasis is one of these risk-enhancing conditions.4,5 “We have now recognized that psoriasis … is more than skin deep,” says Brittany Weber, MD, PhD, an assistant professor of medicine at Harvard Medical School. Psoriasis Basics The mechanisms behind the development of the disease aren’t fully understood, but it appears to stem from an interaction between genes and environmental factors. These factors cause the dysregulation of dendritic cells, which triggers an inflammatory cascade and the expression of cytokines such as interleukin (IL)-12 and IL-23.8 These cytokines induce T cell activation and the proliferation of T helper (Th) cells, which in turn prompt the proliferation of keratinocytes and cause the progression of psoriasis.8 Psoriasis and Heart Disease Risk “We know that patients with psoriasis also have increased prevalence of traditional cardiovascular risk factors,” Weber says. “Obesity, diabetes, hypertension, hyperlipidemia—all of these factors that would promote cardiovascular disease in the general population are common in patients with psoriasis.”9 A 2012 study of nearly 3,000 patients with moderate to severe psoriasis found that 59% had at least two typical cardiovascular risk factors and 29% had at least three.10 The same study found that a significant number of people in the study population didn’t know they had heart disease risk factors, and an even larger number (ranging from 19% of those with diabetes to 39% of those with hyperlipidemia) weren’t being treated pharmacologically for these risk factors.10 While the prevalence of traditional risk factors is high in psoriasis, it’s still higher in PsA. Hypertension, dyslipidemia, diabetes, and obesity are all significantly more common in patients with PsA than in those with psoriasis but without PsA.11 In one study that compared patients with PsA to those with psoriasis but without PsA, participants with PsA had double the levels of C-reactive protein and 30% higher carotid plaque than those who had psoriasis but not PsA.12 This could imply that the link between psoriasis and heart disease is indirect and that patients with psoriasis and PsA have elevated cardiovascular risk solely because they have a high burden of traditional risk factors. But the real story is more complicated. “Even after you adjust for all those [traditional risk] factors, having psoriasis puts you at excess risk,” Weber says. The first evidence of an independent effect of psoriasis on heart disease came in a landmark 2006 study that demonstrated that individuals with psoriasis have a 50% higher risk of myocardial infarction compared with those without, even after controlling for factors such as hypertension, diabetes, hyperlipidemia, smoking, and body mass index.13 The study found a dose effect, where the risk of myocardial infarction was higher for those with more severe psoriasis compared with those with mild disease. Not all research in the intervening years has found an independent link between psoriasis and CVD.14,15 However, a meta-analysis of 75 studies encompassing approximately 500,000 psoriasis patients supports the link, finding that patients with psoriasis are at approximately 50% higher risk of CVD compared with those without.16 A separate meta-analysis confirmed that those with severe psoriasis are at the highest risk and face a threefold higher risk of myocardial infarction, a 60% higher risk of stroke, and a 40% increased risk of cardiovascular mortality compared with those without psoriasis.17 In sum, the link between psoriasis and heart disease is two-fold: psoriasis is associated with a higher burden of traditional heart disease risk factors, but psoriasis is also an independent risk enhancer for heart disease. Mechanisms: How Psoriasis Affects Cardiovascular Function Of particular note is the impact psoriatic inflammation has on the endothelium, the thin layer of cells that line the inside of blood vessels. The endothelium is responsible for regulating blood flow, vascular permeability, and immune cell activation, 18 and its dysfunction is involved in the pathology of multiple immune-mediated CVDs.19 In psoriasis, high levels of circulating cytokines activate endothelial cells, which in turn begin secreting adhesion molecules (such as ICAM-1 VCAM-1) that attract immune cells, contributing to further inflammation and causing plaque formation in the blood vessel wall.18,19 Many of the mechanisms involved still aren’t well understood, but current research suggests that endothelial dysfunction is exacerbated by the activation of platelets.20 “Platelets are involved in blood clotting. … But platelets are also involved in the development of atherosclerosis,” explains Michael Garshick, MD, a cardiologist and assistant professor at NYU Langone Health, whose lab is currently investigating the role of platelets in psoriasis. Platelets become hyperactive—“extra jumpy,” he says—in the presence of proinflammatory circulating molecules. Once activated, they express adhesion molecules that enable them to stick to the endothelium,20 which promotes the buildup of atherosclerotic plaques in artery walls. Meanwhile, these hyperactive platelets also secrete proinflammatory molecules, creating a feedback loop that perpetuates inflammatory processes.21 Inflammation stemming from psoriasis also damages blood vessels in another way, namely, by causing oxidative stress. Oxidative stress reduces the bioavailability of nitric oxide, a critical molecule for vasodilation. This reduction in nitric oxide leads to stiffening and constriction of blood vessels, adding yet another factor that paves the way for atherosclerosis.19 Managing Cardiovascular Risk in Psoriasis To date, there is very little clinical or observational data about how treatment of modifiable risk factors impacts CVD outcomes in psoriasis22; however, given the safety profile of statins, diabetes medications, and blood pressure medications, there’s every reason to prescribe them for high-risk patients with psoriasis, Garshick explains. In particular, since psoriasis is linked to dyslipidemia and high coronary plaque, clinicians should evaluate psoriasis patients for potential statin therapy. The available evidence indicates that statins are equally effective at lowering lipids in psoriasis patients as in nonpsoriasis patients,23 and some evidence suggests they reduce the risk of myocardial infarction.24 To determine which psoriasis patients should be prescribed a statin, some guidelines (namely, from the European Society of Cardiology, the European Society of Atherosclerosis, and the European League Against Rheumatism) recommend using a standard cardiovascular risk calculator and then multiplying the calculated risk by 1.5 to account for the increased risk conferred by psoriasis. Other guidelines don’t give a specific adjustment factor but do recognize that psoriasis confers added risk; these guidelines suggest that if a patient scores at intermediate risk on a standard CVD risk calculator but also has psoriasis, the psoriasis diagnosis favors starting a statin.25 Anti-Inflammatory Treatments Classical antirheumatic drugs used to treat psoriasis include methotrexate, cyclosporine, and acitretin. The latter two are considered controversial and can negatively impact CVD risk. However, limited evidence suggests that methotrexate may protect against vascular disease in psoriasis.26 A systematic review and meta-analysis found that patients with psoriasis, rheumatoid arthritis, or polyarthritis had a 21% lower risk of CVD and an 18% lower risk of myocardial infarction when treated with methotrexate.27 Of note, however, is that all of the studies included in the meta-analysis were observational. Several biologics—namely, those targeting TNF, IL-17, and IL-23—also have potential to reduce cardiovascular risk. In one observational study of 9,000 patients with psoriasis, myocardial infarction was reduced by 50% in those on a TNF inhibitor compared with those receiving a topical therapy.24 Similarly, a meta-analysis encompassing about 50,000 patients with psoriasis found that TNF inhibitors were linked to a significantly lower risk of cardiovascular events as well as a lower risk of mortality.28 On the other hand, one of the few placebo-controlled trials available found that three months of TNF inhibitors resulted in skin improvement and reduction in circulating inflammatory molecules in patients with psoriasis, but it didn’t bring any improvement in vascular arterial inflammation.29 Thus, the results are mixed, and it’s still not clear whether TNF inhibitors ultimately reduce cardiovascular risk. The story is similar with IL-17 inhibitors. A prospective, observational study of 215 patients found that patients treated with biologics showed a greater reduction in coronary plaque indices than those treated with nonbiologic treatments. It also showed that IL-17 inhibitors were more effective than TNF inhibitors.30 Similarly, the CARIMA study found that treatment with secukinumab, an IL-17 inhibitor, improved endothelial function in patients with psoriasis as measured by flow-mediated dilation.31 But again, the research is not uniform. One placebo-controlled trial found that psoriasis patients treated with secukinumab showed no improvement in aortic vascular inflammation or biomarkers of cardiovascular biomarkers compared with those on placebo.32 Therefore, the jury is still out on whether treating inflammation in psoriasis is a reliable way to reduce CVD risk. The Problem of Underscreening It’s not clear exactly why underscreening is so prevalent, Gelfand says, who is also the medical director of the Psoriasis and Phototherapy Treatment Center, Department of Dermatology, University of Pennsylvania. One possibility is that clinicians aren’t fully aware of the heightened cardiovascular risk linked to psoriasis. “This data [on the connection between heart disease and psoriasis] does go back about two decades now, and guidelines have been out for seven years at this point,” Gelfand says. Still, “not enough clinicians know.” Some evidence also suggests that clinicians may be hesitant to pursue screening because of concerns that they will not have the time or expertise to act on the results.35 Patients overwhelmed with their skin disease may play a role as well. “A patient with psoriatic disease can be very used to going to their rheumatologist and dermatologist, and they have all these appointments, and it doesn’t really give them time to talk about the other stuff that is going on, specifically high blood pressure, high cholesterol, diabetic risk, etc,” Garshick says. “These patients think they are okay just going to the dermatologist and the rheumatologist” and don’t realize they still need to see a primary care provider for cardiac screenings. Gelfand’s research suggests that a care coordination model can be very helpful in addressing these factors. “Care coordination models are accepted as being extremely valuable for patients with comorbidities,” Gelfand says. “In psoriasis, [cardiovascular risk factors] are basically comorbidities.” Patients with psoriasis often spend most of their time in specialty care settings with dermatologists, who, according to Gelfand, “may not be comfortable interpreting these screening tests and certainly do not want to manage hypertension and hyperlipidemia. So, the idea in the study is to have the dermatologist be the one who initiates screening. But then, if things are abnormal, the care coordinator works with the patient to educate them on what the results mean, what is recommended in terms of lifestyle changes and medications, and then connect them back to a primary care doctor or a preventive cardiologist or some other clinician who can then put that guideline-based plan in action.” Takeaways for Physicians • Educate psoriasis patients about their increased cardiovascular risks. “Patient awareness is key,” Weber says. “Spend the extra few minutes in the office to discuss it with the patient. Make sure the patient is aware that there is a link between psoriasis and cardiovascular disease” and what they can do to reduce their risk. • Treat traditional risk factors diligently, both through lifestyle modification and medication. “Start with a healthful diet, exercise, and weight management because many people with psoriasis are obese,” Gelfand says. For diet, a Mediterranean diet is a good recommendation. Exercise can be a challenge with psoriasis because of skin and joint inflammation, Gelfand explains, so anti-inflammatory treatments that help clear the disease are critical. For managing weight, medication may be necessary. “There is a genetic relationship between psoriasis and obesity, so it’s likely that our patients may have a harder time losing weight for that reason.” In patients who struggle to lose weight through lifestyle modification alone, GLP1 agonists are often important, he suggests. The good news, according to Garshick, is that a range of new treatments for treating the cardiometabolic complications of psoriasis are now available—GLP-1 agonists like Ozempic, for example—that are improving the lives of psoriasis patients and alleviating the burden of the disease. — Jamie Santa Cruz is a freelance writer based in Parker, Colorado.
References 2. Karbach S, Hobohm L, Wild J, et al. Impact of psoriasis on mortality rate and outcome in myocardial infarction. J Am Heart Assoc. 2020;9(18):e016956. 3. Mehta NN, Yu Y, Pinnelas R, et al. Attributable risk estimate of severe psoriasis on major cardiovascular events. Am J Med. 2011;124(8):775.e1-775.e6. 4. 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. 5. Piepoli MF, Hoes AW, Agewall S, et al. European guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2016;37(29):2315-2381. 6. Greb JE, Goldminz AM, Elder JT, et al. Psoriasis. Nat Rev Dis Primers. 2016;2:16082. 7. Karmacharya P, Chakradhar R, Ogdie A. The epidemiology of psoriatic arthritis: a literature review. Best Pract Res Clin Rheumatol. 2021;35(2):101692. 8. Weber B, Merola JF, Husni ME, Di Carli M, Berger JS, Garshick MS. Psoriasis and cardiovascular disease: novel mechanisms and evolving therapeutics. Curr Atheroscler Rep. 2021;23(11):67. 9. Masson W, Lobo M, Molinero G. Psoriasis and cardiovascular risk: a comprehensive review. Adv Ther. 2020;37(5):2017-2033. 10. Kimball AB, Szapary P, Mrowietz U, et al. Underdiagnosis and undertreatment of cardiovascular risk factors in patients with moderate to severe psoriasis. J Am Acad Dermatol. 2012;67(1):76-85. 11. Husted JA, Thavaneswaran A, Chandran V, et al. Cardiovascular and other comorbidities in patients with psoriatic arthritis: a comparison with patients with psoriasis. Arthritis Care Res (Hoboken). 2011;63(12):1729-1735. 12. Eder L, Jayakar J, Shanmugarajah S, et al. The burden of carotid artery plaques is higher in patients with psoriatic arthritis compared with those with psoriasis alone. Ann Rheum Dis. 2013;72(5):715-720. 13. Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296(14):1735-1741. 14. Stern RS. Psoriasis is not a useful independent risk factor for cardiovascular disease. J Invest Dermatol. 2010;130:917-919. 15. Wakkee M, Herings RMC, Nijsten T. Psoriasis may not be an independent risk factor for acute ischemic heart disease hospitalizations: results of a large population-based Dutch cohort. J Invest Dermatol. 2010;130:962-967. 16. 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. 17. Samarasekera EJ, Neilson JM, Warren RB, Parnham J, Smith CH. Incidence of cardiovascular disease in individuals with psoriasis: a systematic review and meta-analysis. J Invest Dermatol. 2013;133(10):2340-2346. 18. Long SY, Shang L, Shi H, Zhao S, Cao J, He Y. The future landscape of endothelial cells research in psoriasis: bibliometric analysis and literature review. Clin Cosmet Investig Dermatol. 2023;16:3107-3120. 19. Orlando G, Molon B, Viola A, Alaibac M, Angioni R, Piaserico S. Psoriasis and cardiovascular diseases: an immune-mediated cross talk? Front Immunol. 2022;13:868277. 20. Garshick MS, Tawil M, Barrett TJ, et al. Activated platelets induce endothelial cell inflammatory response in psoriasis via COX-1. Arterioscler Thromb Vasc Biol. 2020;40(5):1340-1351. 21. Jiang Z, Jiang X, Chen A, He W. Platelet activation: a promoter for psoriasis and its comorbidity, cardiovascular disease. Front Immunol. 2023;14:1238647. 22. Garshick MS, Ward NL, Krueger JG, Berger JS. Cardiovascular risk in patients with psoriasis: JACC review topic of the week. J Am Coll Cardiol. 2021;77(13):1670-1680. 23. 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. 24. Wu JJ, Poon KY, Channual JC, Shen AY. Association between tumor necrosis factor inhibitor therapy and myocardial infarction risk in patients with psoriasis. Arch Dermatol. 2012;148(11):1244-1250. 25. 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;73(24):3234-3237]. J Am Coll Cardiol. 2019;73(24):3168-3209. 26. Prodanovich S, Ma F, Taylor JR, Pezon C, Fasihi T, Kirsner RS. Methotrexate reduces incidence of vascular diseases in veterans with psoriasis or rheumatoid arthritis [published correction appears in J Am Acad Dermatol. 2005;52(4):670]. J Am Acad Dermatol. 2005;52(2):262-267. 27. Micha R, Imamura F, Wyler von Ballmoos M, et al. Systematic review and meta-analysis of methotrexate use and risk of cardiovascular disease. Am J Cardiol. 2011;108(9):1362-1370. 28. Yang ZS, Lin NN, Li L, Li Y. The effect of TNF inhibitors on cardiovascular events in psoriasis and psoriatic arthritis: an updated meta-analysis. Clin Rev Allergy Immunol. 2016;51(2):240-247. 29. Mehta NN, Shin DB, Joshi AA, et al. Effect of 2 psoriasis treatments on vascular inflammation and novel inflammatory cardiovascular biomarkers: a randomized placebo-controlled trial. Circ Cardiovasc Imaging. 2018;11(6):e007394. 30. Elnabawi YA, Dey AK, Goyal A, et al. Coronary artery plaque characteristics and treatment with biologic therapy in severe psoriasis: results from a prospective observational study. Cardiovasc Res. 2019;115(4):721-728. 31. von Stebut E, Reich K, Thaçi D, et al. Impact of secukinumab on endothelial dysfunction and other cardiovascular disease parameters in psoriasis patients over 52 weeks. J Invest Dermatol. 2019;139(5):1054-1062. 32. Gelfand JM, Shin DB, Duffin KC, et al. A randomized placebo-controlled trial of secukinumab on aortic vascular inflammation in moderate-to-severe plaque psoriasis (VIP-S). J Invest Dermatol. 2020;140(9):1784-1793.e2. doi:10.1016/j.jid.2020.01.025 33. Eder L, Harvey P, Chandran V, et al. Gaps in diagnosis and treatment of cardiovascular risk factors in patients with psoriatic disease: an international multicenter study. J Rheumatol. 2018;45(3):378-384. 34. Song WB, Peck GM, Neopaney A, et al. Regional variation in cardiovascular risk factor screening by dermatologists for psoriasis patients in the United States. J Invest Dermatol. 2023;143(9):1816-1819. 35. Gustafson AC, Gelfand JM, Davies J, et al. Specialist and patient perspectives on strategies to improve cardiovascular disease prevention among persons living with psoriatic disease. J Psoriasis Psoriatic Arthritis. 2022;7(4):174-186. |
