Psoriasis and cardiovascular disease: an association or a reason to treat?

Worldwide psoriasis is a common systemic inflammatory illness. The majority of recent studies have shown an association between psoriasis and coronary artery disease (CAD). It has been hypothesized that the association between psoriasis and CAD is due to chronic systemic inflammation. As a risk factor for CAD, psoriasis represents a disease that could potentially be modified, thereby decreasing the risk of morbidity and mortality due to CAD, a very important public health concern. In fact, this should be a directly testable hypothesis, which as a question is ‘Does the aggressive treatment of psoriasis prevent CAD? ’. The study by Abuabara et al. attempted to answer this question. This well-conducted study published in this issue of the BJD evaluated more than 25 000 individuals with psoriasis who are at highest risk for CAD – those with severe to moderate disease. They conducted this study using administrative claims data from a very large healthcare insurance programme. They basically compared two broad classes of therapy: those receiving light therapy and those receiving systemic agents such as ‘biologics’, methotrexate and ciclosporin. They assumed that the systemic therapies would have a greater effect on the systemic inflammatory components of psoriasis. While it is up to the reader to review this study comprehensively, overall they did not find a decreased risk of myocardial infarction in those treated with systemic agents compared with those who received light therapy. A more nuanced view might be that there was a trend toward an overall 30% increase among systemic therapy users and about a 30% decrease in a subset of those at highest risk of CAD, those aged < 50 years. Interestingly, a very recent meta-analysis of randomized clinical trials (RCT) appeared in JAMA on this same topic. This meta-analysis of available RCTs evaluated a newer class of biologic, antagonistic monoclonal antibodies to interleukin (IL)-12 and IL-23. The results were somewhat similar. No significant difference in the rate of a composite cardiovascular disease endpoint was noted in those treated with these newer biologics compared with those treated with standard care or placebo therapies. The authors of this study noted that they did not have access to all studies that have been conducted and opined in their comment section that studies for one of these agents (briakinumab) had been discontinued due to concerns about a potential association with cardiovascular disease. So what should a careful clinician conclude from these studies? First and foremost, at this time, the majority of evidence suggests that an association exists between having moderate to severe psoriasis and an increased risk of CAD. Unfortunately, neither of these new studies help us understand if psoriasis is a modifiable risk factor for CAD. Both of these studies fail to demonstrate that successful treatment of psoriasis (i.e. a risk factor for CAD) diminishes the risk of developing CAD. The studies might even raise a concern about an increased risk of CAD after treatment with some of the systemic agents. There are, however, many reasons why CAD risk reduction has not been noted. It is possible that some treatments for psoriasis increase the risk of CAD. It is possible that both psoriasis and CAD are physiologically unrelated outcomes of another process. For example, obesity, which has been associated with both disease processes, may cause both diseases but treating one does not affect the prognosis of the other. Attempts to control statistically for obesity have not shown this to be true but these attempts may have been insufficient. It could also be possible that the genetic tendency to develop psoriasis and CAD are linked (found close together on a common chromosome), such that one is not really on the causal pathway for the other but that they occur in genetically similar people. There could be many other explanations including the most common concern of nearly every study that the study was not designed well enough to test the study question properly. We really will not know the answer to this fascinating and important question until more investigations are complete.