Impact of Opioid Pharmacotherapy on Arterial Stiffness and Vascular Ageing: Cross-Sectional and Longitudinal Studies

Whilst there is a small literature on the cardiovascular toxicity of opiates, there is no detailed antemortem data on non-cardiovascular patient populations. A cross-sectional and longitudinal naturalistic observational study was performed comparing methadone (N = 71)-, buprenorphine (N = 593)-, naltrexone (N = 23)-treated patients with controls (N = 576) on indices of arterial stiffness and vascular age by Pulse Wave Analysis in primary care, 2006-2011. Controls were younger 29.96 +/- A 0.45 (mean +/- A SEM) vs. 34.00 +/- A 0.34-39.22 +/- A 1.11 years (all P < 0.005) and had fewer smokers (15.9 % vs. 86.9 %-92.96 %, all P < 0.0001). The sex ratio was similar (69.6 vs. 67.7 % male, P = 0.46). These baseline differences were controlled for by multiple regression. Linear regression of vascular age, central augmentation pressure, central augmentation index and other measures against chronologic age showed significant protective effects by treatment group against the treatment standard of methadone, in both sexes in additive and interactive models (all P < 0.02). Interactive terms in treatment type remained significant including all conventional risk factors accounting for differing opiate exposures. The principal findings from multiple regression were confirmed in the time series analysis up to 5 years by repeated measures nonlinear regression. These studies show that the deleterious impact of chronic opiate pharmacotherapy on vascular age and arterial stiffness varies significantly by treatment type.