Psoriasis and Cardiovascular Disease: epidemiological studies.

Atherosclerosis and PS are prevalent chronic immunoinflammatory diseases with pathophysiological, clinical and epidemiological similarities. Results suggest that PS may be an independent risk factor for cardiovascular disease. Participation of similar immunoinflammatory and prothrombotic mechanisms in PS and cardiovascular disease is supported by evidence that treatment with methotrexate in patients with PS is associated with reduced cardiovascular risk. Furthermore, PS is associated with surrogate markers of cardiovascular disease, e.g. endothelial dysfunction and coronary calcification, and with markers of increased platelet activity. However, results of epidemiological studies of the risk of cardiovascular disease in PS have been conflicting, and surveillance bias has been proposed to contribute to the observed association. Although similar considerations of shared immunoinflammatory pathways with PS can be applied to AF and VTE very little is known about the interaction between PS and these common diseases. With the underlying hypothesis that PS had detrimental effects on all prespecified adverse cardiovascular endpoints the objective of the current thesis was to examine in these patients: 1) the risk of atherothrombotic events and compare it with the risk in patients with DM; 2) the risk of AF and ischaemic stroke; 3) the risk of VTE; and 4) the prognosis after first-time MI. By use of the unique Danish nationwide registries approximately 40,000 patients with PS, including approximately 3000 patients with severe PS were identified in the study period 1997-2006. Paper I provided a comparison of cardiovascular risk between patients with PS, approximately 127,000 patients with DM, and the general population, respectively. Patients with PS were at increased risk of all endpoints including, MI, stroke, invasive coronary revascularization, cardiovascular death, and a composite cardiovascular endpoint (MI, stroke, and cardiovascular death). For the composite endpoint the rate ratios (RRs) were 1.20 (95% confidence interval [CI] 1.14-1.25), 1.58 (CI 1.36-1.85), and 1.59 (CI1.56-1.63) for mild PS, severe PS, and DM, respectively. Paper II documented an up to 2.5 fold increase in risk of AF and ischaemic stroke in patients with PS, with the highest risk estimates for young patients with severe disease. The main results of paper III were that patients with PS had an increased risk of VTE with RR 1.35 (CI 1.21-1.49) and RR 2.06 (CI 1.63-2.61) for mild and severe PS, respectively. Paper IV on post-MI prognosis included 615 patients with PS and a recent MI. The results documented that after first-time MI, these patients had an increased risk of a composite of recurrent MI, stroke, and cardiovascular death with hazard ratio 1.26 (CI 1.12-1.41) as compared to patients without PS. In conclusion, this thesis demonstrated that all patients with PS were at increased risk of atherothrombotic events and that the risk with severe PS was comparable to that of patients with DM. Furthermore, the thesis provided novel evidence of PS as a possible risk factor for AF and VTE. Finally, we demonstrated an association between PS and adverse prognosis following first-time MI. The results add importantly to evidence indicating that PS is an independent cardiovascular risk factor and should form the background for studies of interventions aimed at improved primary and secondary prevention of cardiovascular disease in patients with PS.