Combined effect of posttraumatic stress disorder and prescription opioid use on risk of cardiovascular disease.

Aim Prescription opioid analgesic use (OAU) is associated with increased risk of cardiovascular disease (CVD). OAU is more common in patients with than without posttraumatic stress disorder (PTSD), and PTSD is associated with higher CVD risk. We determined whether PTSD and OAU have an additive or multiplicative association with incident CVD. Methods and results Veterans Health Affairs patient medical record data from 2008 to 2015 was used to identify 2861 patients 30-70 years of age, free of cancer, CVD and OAU for 12 months before index date. We defined a four-level exposure variable: 1) no PTSD/no OAU, 2) OAU alone, 3) PTSD alone and 4) PTSD+OAU. Cox proportional hazard models estimated the association between the exposure variable and incident CVD. The mean age was 49.0 (+/- 11.0), 85.7% were male and 58.3% were White, 34.4% had no PTSD/no OAU, 32.9% had PTSD alone, 10.6% had OAU alone, and 22.1% had PTSD+OAU. Compared with patients with no PTSD/no OAU, those with PTSD alone were not at increased risk of incident CVD (hazard ratio = 0.82; 95% confidence interval (CI): 0.63-1.17); however, OAU alone and PTSD+OAU were both significantly associated with incident CVD (hazard ratio = 1.99; 95% CI:1.36-2.92 and hazard ratio = 2.20; 95% CI: 1.61-3.02). There was no significant additive or multiplicative PTSD and OAU association with incident CVD. Conclusion OAU is associated with nearly a two-fold increased risk of CVD in patients with and without PTSD. Despite no additive or multiplicative interaction effects, the high prevalence of OAU in PTSD may represent a novel contributor to the elevated CVD burden among patients with PTSD.