The Psoriatic March: How a Skin Disease Reaches the Heart

Key Takeaways:

• The psoriatic march is a model proposed in 2011 in which systemic inflammation from severe psoriasis causes insulin resistance, which triggers endothelial dysfunction, atherosclerosis, and finally heart attack or stroke; its authors stress that the chain is not yet formally proven.
• In a United Kingdom population cohort of more than 130,000 people with psoriasis, a 30-year-old with severe psoriasis had about three times the risk of a heart attack of a peer without it (adjusted relative risk 3.10), even after accounting for blood pressure, diabetes, cholesterol, smoking, and body mass index.
• A 2013 meta-analysis of nine studies found that severe psoriasis was associated with a 70 percent higher risk of myocardial infarction, a 56 percent higher risk of stroke, and a 39 percent higher risk of cardiovascular death.

World Psoriasis Day falls on October 29, and the week leading up to it is a good time to look past the skin. Psoriasis is usually filed under dermatology, yet the red, scaling plaques are only the visible edge of an immune process that runs through the entire body. In 2011, Boehncke and colleagues gave that idea a name, the psoriatic march, and laid it out as a sequence. Inflammatory signals produced in abundance in active psoriatic skin, TNF-alpha, IL-6, and IL-17 chief among them, do not stay in the skin. They spill into the circulation, where they interfere with insulin signaling in muscle, liver, and fat and produce insulin resistance. Insulin resistance in turn damages the endothelium, the single layer of cells lining every artery, which loses some of its ability to relax, to make nitric oxide, and to repel the inflammatory cells and cholesterol particles that seed plaque. Over years, a dysfunctional endothelium becomes atherosclerosis, and atherosclerosis becomes heart attack and stroke. On this view, the plaque on the elbow and the plaque in the coronary artery are two readouts of the same underlying fire. The authors were careful to call it a concept rather than a proven pathway, but it gave a set of puzzling epidemiological findings a biological spine.

Those findings are substantial. The pivotal study came from a British general-practice database that followed nearly 557,000 people without psoriasis alongside about 127,000 with mild disease and roughly 3,800 with severe disease, defined as ever needing systemic therapy. After adjusting for hypertension, diabetes, prior heart attack, high cholesterol, age, sex, smoking, and body mass index, psoriasis remained an independent predictor of myocardial infarction, and the excess risk was sharpest in the young. A 30-year-old with severe psoriasis carried an adjusted relative risk of 3.10, about triple that of a peer without it; by age 60 the figure had fallen to 1.36, because heart attacks from ordinary causes have become common by then. A later meta-analysis pooling nine observational studies, more than 200,000 patients with mild psoriasis and more than 17,000 with severe psoriasis, found that severe disease was associated with a 70 percent higher risk of heart attack, a 56 percent higher risk of stroke, and a 39 percent higher risk of dying from cardiovascular causes. Even mild psoriasis carried a smaller but measurable increase. These are relative risks layered on top of the usual risk factors, which is exactly why they matter most for younger adults whose standard risk calculators read reassuringly low.

Can treating psoriasis slow the psoriatic march?

That is the question everyone wants answered, and the honest reply is that the evidence is promising but not yet definitive. The data above are observational, and the meta-analysis authors themselves flagged uneven adjustment for confounders across studies; people with severe psoriasis often carry more of the traditional risk factors as well, and no statistical model removes all of that. What has been measured is suggestive. In a prospective cohort of 134 adults with moderate to severe psoriasis, most of whom looked low-risk by conventional scoring, one year of biologic therapy was associated with a significant reduction in coronary artery inflammation measured by a CT-based marker of the fat surrounding the vessels, and the effect held across the different biologic classes. That is an imaging signal, not a reduction in heart attacks, and the study was not randomized. The practical conclusion does not have to wait for a definitive trial, however. Joint dermatology and psoriasis-foundation guidelines already direct clinicians to screen people with psoriasis for cardiovascular and metabolic risk factors, including blood pressure, lipids, blood sugar, and weight, with counseling that includes quitting smoking, and they suggest multiplying a standard ten-year heart-risk estimate by 1.5 for people with more extensive disease, rather than treating the skin in isolation. If you live with moderate or severe psoriasis, it is reasonable to know your numbers earlier than a peer would, to treat each one deliberately, and to regard good control of the skin as part of a cardiovascular plan, not merely a cosmetic one.

References:

1. Boehncke, W. H., Boehncke, S., Tobin, A. M., & Kirby, B. (2011). The ‘psoriatic march’: A concept of how severe psoriasis may drive cardiovascular comorbidity. Experimental Dermatology, 20(4), 303-307.
2. Gelfand, J. M., Neimann, A. L., Shin, D. B., Wang, X., Margolis, D. J., & Troxel, A. B. (2006). Risk of myocardial infarction in patients with psoriasis. JAMA, 296(14), 1735-1741.
3. Armstrong, E. J., Harskamp, C. T., & Armstrong, A. W. (2013). Psoriasis and major adverse cardiovascular events: A systematic review and meta-analysis of observational studies. Journal of the American Heart Association, 2(2), e000062.
4. Elnabawi, Y. A., Oikonomou, E. K., Dey, A. K., Mancio, J., Rodante, J. A., Aksentijevich, M., et al. (2019). Association of biologic therapy with coronary inflammation in patients with psoriasis as assessed by perivascular fat attenuation index. JAMA Cardiology, 4(9), 885-891.
5. Elmets, C. A., Leonardi, C. L., Davis, D. M. R., Gelfand, J. M., Lichten, J., Mehta, N. N., et al. (2019). Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. Journal of the American Academy of Dermatology, 80(4), 1073-1113.