Panic disorder and incident coronary heart disease: a systematic review and meta-regression in 1 131 612 persons and 58 111 cardiac events

Background: Substantial healthcare resources are devoted to panic disorder (PD) and coronary heart disease (CHD); however, the association between these conditions remains controversial. Our objective was to conduct a systematic review of studies assessing the association between PD, related syndromes, and incident CHD. Method: Relevant studies were retrieved from Medline, EMBASE, SCOPUS and PsycINFO without restrictions from inception to January 2015 supplemented with hand-searching. We included studies that reported hazard ratios (HR) or sufficient data to calculate the risk ratio and 95% confidence interval (CI) which were pooled using a random-effects model. Studies utilizing self-reported CHD were ineligible. Twelve studies were included comprising 1 131 612 persons and 58 111 incident CHD cases. Results: PD was associated with the primary incident CHD endpoint [adjusted HR (aHR) 1.47, 95% CI 1.24-1.74, p < 0.00001] even after excluding angina (aHR 1.49, 95% CI 1.22-1.81, p < 0.00001). High to moderate quality evidence suggested an association with incident major adverse cardiac events (MACE; aHR 1.40, 95% CI 1.16-1.69, p = 0.0004) and myocardial infarction (aHR 1.36, 95% CI 1.12-1.66, p = 0.002). The risk for CHD was significant after excluding depression (aHR 1.64, 95% CI 1.45-1.85) and after depression adjustment (aHR 1.38, 95% CI 1.03-1.87). Age, sex, length of follow-up, socioeconomic status and diabetes were sources of heterogeneity in the primary endpoint. Conclusions: Meta-analysis showed that PD was independently associated with incident CHD, myocardial infarction and MACE; however, reverse causality cannot be ruled out and there was evidence of heterogeneity.