PracticeUpdate.com

Peter Libby MD

In a recent article published in the European Journal of Heart Failure, Dr. Usman Khalid and colleagues interrogated the national database of Denmark to probe the link between psoriasis and the risk for heart failure.¹ They followed a cohort for 14 years and identified psoriasis diagnoses by identifying individuals who received prescriptions for topical vitamin D preparations, a first-line therapy for psoriasis in Denmark. They defined severe psoriasis as those who had hospitalization coded for psoriasis or psoriatic arthritis. They studied only incident psoriasis or heart failure by excluding those with either diagnosis at baseline. Heart failure was ascertained by admissions to hospital coded as heart failure. The study had considerable power; almost 5.5 million individuals were analyzed and over 65,000 patients were categorized as having new-onset psoriasis. Of some 180,000 admissions for new-onset heart failure, 13,075 occurred in individuals with psoriasis, and 236 were in patients categorized as having severe psoriasis. The crude hazard ratio (HR) in the reference population was 2.82, in those with mild psoriasis, 4.22, and in those with severe psoriasis, 4.7. After adjustment for a variety of potential confounders, the HR of developing incident heart failure with those identified as having psoriasis was 1.22, and 1.55 for those defined as having severe psoriasis. A variety of sensitivity analyses affirmed the major conclusions of the study.

The association between rheumatic diseases including psoriasis and cardiovascular disease has received increasing attention, as complications of cardiovascular disease account for much morbidity and mortality in this population.² In the specific case of psoriasis, as in other rheumatologic diseases, previous work has documented an association with atherothrombotic events. This large national cohort study supports a relationship between psoriasis and heart failure.

This investigation demonstrates the advantages of having a coordinated national healthcare system that permits querying an unbiased sample of an entire national population. Certain limitations of this study are evident to all cardiologist readers. The case detection for psoriasis depends on an indirect criterion, prescriptions for a particular medication, rather than a formal rheumatologic diagnosis. Likewise, the identification of heart failure in all population studies presents challenges. Hospital coding has obvious limitations in this regard. The Framingham study has promulgated one set of formal definitions for heart failure in observational cohort investigations. Such instruments were not applied in this large national study.

It would be interesting to attempt to analyze echocardiograms, which should be available for the patients admitted for heart failure, to define the proportion of cases that present with findings of heart failure with preserved systolic function vs those with reduced systolic function. Moreover, such a retrospective analysis could disclose whether patients with psoriasis who present with heart failure have regional wall motion abnormalities consistent with ischemic damage, or have electrocardiographic evidence of prior myocardial infarction. Such information would provide some mechanistic insight into the pathogenesis of the heart failure in patients with psoriasis.

From a mechanistic perspective, contemporary understanding of inflammation in cardiovascular disease provides a framework for understanding links between rheumatologic disorders such as psoriasis and heightened risk for atherosclerosis and other cardiovascular diseases. Systemic or remote inflammation can have “echoes” at the level of atherosclerotic lesions, boosting local inflammation in ways that may render plaques more likely to rupture and cause thrombotic complications.^3,4 Systemic inflammatory conditions also stimulate the acute phase response in the liver. The hepatocytes under these conditions produce heightened levels of fibrinogen, the precursor of clots, and of the major endogenous inhibitor of fibrinolysis, plasminogen activator inhibitor-1. The authors invoke T-cell mediated adaptive immunity in the pathogenesis of psoriasis. They mention in particular T-helper 1 (T_H1) cells and T_H17 lymphocytes. The key cytokines elaborated by these cellular players implicated in psoriasis, including interferon gamma and tumor necrosis factor (TNF), drive aspects of atherogenesis (IL-17 is more controversial as a promoter of this process). Pro-inflammatory cytokines such as TNF are associated with heart failure. Whether they represent a consequence rather than cause of incident heart failure remains debatable. Yet, once unleashed, inflammatory mediators may aggravate aspects of remodeling of the myocardium involved in heart failure pathogenesis and its progression.

As all good studies, this one raises new questions, in particular regarding the etiology of the heart failure associated with psoriasis and the mechanisms that link these disorders. Heightened awareness of the cardiovascular risk of patients with rheumatologic diseases offers the possibility of early intervention with evidence-based therapies to improve outcomes in these patients. We also need studies in patients with rheumatologic diseases to evaluate the efficacy of such therapies in this particular patient population.

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