Cardiovascular Risk and Psoriasis

Abstract

Psoriasis is a chronic inflammatory disease. Classic manifestations are erythematous patches of skin with periods of exacerbation and remission. The inflammatory process is evidenced by the increase in several markers such as cell adhesion molecules, cytokines, chemokines, and other molecules of the acute phase such as fibrinogen, C-reactive protein (CRP), and serum amyloid A protein. C-reactive protein levels correlate with an increase in potential cardiovascular (CV) risk predictors based on evidence obtained in experimental animals, which have demonstrated a role of toll-like receptor (TLR) type 2 and 4 in the development and progression of atherosclerosis. C-reactive protein promotes endothelial dysfunction by reducing endothelial nitric oxide synthetase expression and activity, reducing prostacyclin release from endothelial cells, increasing plasminogen activator inhibitor 1 expression and activity, endothelin 1 and interleukin 1 release, and by promoting cellular adhesion between endothelial cells and monocytes with increase in the size of atherosclerotic plaques; moreover a novel marker of endothelial dysfunction, endocan, was recently proposed to stratify CV risk in patients with psoriasis, since serum endocan levels correlated with the Psoriasis Area and Severity Index (PASI), CRP, and carotid intima–media thickness. It follows that psoriasis alone, or in combination with other risk factors, may play a role in the development and progression of CV disease but its exact contribution is not clear. Therefore, we performed a search of the literature, selecting the publications that we thought to be of interest. We carried out a systematic search in PubMed and Embase using the keywords ‘‘psoriasis,’’ ‘‘autoimmune disease,’’ ‘‘cardiovascular disease,’’ ‘‘diabetes,’’ ‘‘hypertension,’’ ‘‘high blood pressure,’’ ‘‘dyslipidaemia,’’ ‘‘metabolic syndrome,’’ and ‘‘obesity.’’ We found 231 articles of interest but we selected only 19 as the most representative. Several authors have highlighted the association between coronary heart disease (CHD) and psoriasis. However, there is no single definition of the parameters of severity of the psoriasis or a homogeneity of patient selection in different studies. In 1978, McDonald and Calabresi studied 323 hospitalized patients with psoriasis and showed an association with arterial and venous vascular diseases. Further studies have revealed a correlation between this disease and atherosclerosis, focusing on CHD. The main limitation of these studies was that they could not conclusively define a significant correlation between the 2 conditions mainly because they did not sufficiently take into account the presence of confounding factors, such as the presence of CV risk factors. This correlation, however, was established by Gelfand et al in 2006. Their objective was to ‘‘determine within a population-based cohort if psoriasis is an independent risk factor for acute myocardial infarction (AMI).’’ They studied 130 976 patients with psoriasis of whom 3827 had a severe form (ie, on systemic therapy). Patients were matched with 556 995 controls and followed for a mean of 5.4 years. There was an increased risk of AMI in patients with moderate and severe psoriasis. The authors concluded that psoriasis may be considered as an independent risk factor for AMI. A subsequent study in 2008 examined 2 large US databases and showed an increase in CV risk in patients with mild psoriasis. In 2009, Prodanovich et al in an observational study of 3236 patients with psoriasis reported a higher prevalence of traditional CV risk factors (diabetes mellitus, hypertension, dyslipidemia, and smoking) compared with controls. This association was known from previous studies but the new element was the association of psoriasis with an increased prevalence not only of myocardial ischemia but also of cerebrovascular and peripheral arterial disease. The conclusion was that psoriasis is associated with atherosclerosis. A study published in 2012 compared the severity of psoriasis (PASI score) with coronary flow reserve (CFR). In patients with reduced CFR (<2.5) psoriasis was more severe (higher PASI score). According to the authors in young