This nationwide study of the impact of psoriasis on prognosis following PCI demonstrated an increased risk of all-cause mortality and of a composite of death, myocardial infarction, and stroke, respectively, in patients with severe disease compared to subjects without psoriasis. The post-PCI prognosis in patients with mild psoriasis was comparable to that of patients without psoriasis. Furthermore, patients with severe psoriasis were less likely to receive beta-blockers, statins and platelet inhibitors after PCI.
Psoriasis and atherosclerosis are chronic inflammatory diseases characterized by T-helper (Th) 1-/Th17-driven inflammation and there is an apparent overlap of inflammatory mechanisms in these diseases [1, 2]. Psoriasis has previously been associated with increased prevalence of conventional cardiovascular risk factors as well as cardiovascular morbidity and mortality [4–9, 13–16]. Inflammation has also been suggested to contribute to post-PCI complications including restenosis, in-stent thrombosis and mortality . Very limited data are available, however, on the impact of inflammatory diseases on the prognosis after PCI. A small study of patients with systemic lupus erythematosus demonstrated a worse 1-year outcome compared to controls while a very small study of patients with rheumatoid arthritis found no differences between groups [18, 19]. On the other hand, the current demonstration of impaired prognosis after PCI in patients with severe psoriasis is likely to contribute to the adverse contemporary post-myocardial infarction prognosis found in patients with this disease, as well as in post-myocardial infarction subjects with systemic lupus erythematosus and rheumatoid arthritis [12, 20–22].
In the present study, patients with psoriasis were more likely to receive statins, angiotensin converting enzyme (ACE) inhibitors/angiotensin 2 receptor antagonists, glucose-lowering drugs, and platelet inhibitors at baseline before index PCI than patients without psoriasis, supportive of previous reports of an increased prevalence of hypertension, hypercholesterolemia and diabetes mellitus in patients with psoriasis [7, 23–29]. Also, in patients with psoriasis there was a higher proportion of NSAID users and medically managed depression compared to patients without psoriasis, both of which have been associated with impaired prognosis in patients with coronary artery disease [30–32]. After adjustments for these and other measured confounders, however, we found that severe psoriasis was a risk factor for adverse prognosis following first-time PCI, this suggests that the poor prognosis observed was not mainly driven by these differences in comorbidity. It is noteworthy that the proportion of high risk patients, i.e., where the index PCI was performed in the setting of MI, and that the rates of (index) primary PCI procedures (indicative of ST elevation myocardial infarction) were similar between patients with severe psoriasis and patients without psoriasis. Also, the proportion of patients treated with loop diuretics was similar irrespective of psoriasis status. This indicates a comparable distribution of severe congestive heart failure and is an important observation since we were unable to control for baseline and post-PCI left ventricular ejection fraction. Repeat revascularization rates after index PCI were also not statistically different between patients with and without psoriasis, but our study suggested differences in post-PCI pharmacological treatment, with patients with severe psoriasis receiving less beta-blockers, statins, and platelet inhibitors (Table 2). Although the reasons underlying the latter observation were not examined, significant chronic comorbidity has been associated with suboptimal post-myocardial infarction care and this particular finding may be an example of the treatment-risk paradox in coronary artery disease, i.e., that patients at increased risk receive relatively less evidence-based treatment . In contrast, our previous report on prognosis after myocardial infarction in patients with psoriasis in the time period 2002–06 demonstrated no significant differences in post-myocardial infarction medical treatment, but that study included fewer patients and did not specifically evaluate the impact of psoriasis severity. Importantly, the analyses that controlled for these differences in post-PCI treatment gave results comparable to the primary analysis indicating that the impaired post-PCI prognosis in patients with severe psoriasis was not mainly driven by these differences. Taken together, the current finding of impaired post-PCI prognosis in patients with severe psoriasis therefore supports the notion that psoriasis-driven chronic inflammation per se may be an important determinant of the observed differences in post-PCI prognosis. This interpretation of the data reflects the sum of other current evidence on mechanisms underlying increased risk of cardiovascular disease in patients with chronic inflammatory diseases [3, 6–11, 14, 15]. Accepted risk scores for prognosis after myocardial infarction may therefore underestimate the risk in these patients, as is the case for primary prevention, where traditional risk factor algorithms for coronary artery disease, e.g., the Framingham risk score, are unlikely to capture the full extent of increased risk [13, 34–36].
Important strengths of the present study included the large number of participants, the ability to evaluate a psoriasis activity dose–response effect, the nationwide coverage in prospectively recorded registries, the contemporary clinical setting, and the completeness of follow-up. Furthermore, the use of nationwide registries of hospitalization data and dispensed prescriptions from all pharmacies in Denmark where healthcare is readily accessible and essentially free of charge minimized selection bias related to factors such as gender, age, socioeconomic status, healthcare insurance provision and job situation. Some limitations of our study should also be acknowledged. The results relied on the accuracy of the underlying registration in the registers, e.g., in terms of the study population and outcome measures. The register coding of revascularization procedures has not been validated but it is highly unlikely that the coding of these expensive and very specific treatments are erroneous. Also, misclassification in relation to psoriasis status is likely to be non-differential. The examined psoriasis cohort was based on prescriptions filled for topical vitamin D derivatives and our results may not apply to patients treated with other first-line antipsoriatic drugs, e.g., topical corticosteroids. However, there is no obvious reason to suspect important differences in baseline characteristics between patients treated with topical vitamin D or other first-line antipsoriatic drugs. Importantly, we have previously demonstrated that the criteria for the psoriasis diagnosis and severity classification in our registries were valid . Because the Danish population is predominantly of Caucasian descent, the results should only be extrapolated to other ethnicities with caution. Finally, we were unable to account for some important cardiovascular risk factors, e.g., family history, obesity, and smoking, and other prognostic variables including coronary pathologic findings, PCI procedural variables, and left ventricular ejection fraction, and we cannot exclude the possibility unmeasured and/or residual confounding contributed to our findings. However, information on strong predictors of post-PCI adverse events, i.e., hypertension, diabetes mellitus, renal failure, and adherence to dual anti-platelet therapy were included .