Impact of lifetime opioid exposure on arterial stiffness and vascular age: cross-sectional and longitudinal studies in men and women

Objective: To characterise and compare the potentiation of arterial stiffness and vascular ageing by opioids in men and women. Design: Cross-sectional and longitudinal studies of 576 clinical controls and 687 opioid-dependent patients (ODP) on 710 and 1305 occasions, respectively, over a total of 2382 days (6.52 years), 2006-2011. Methodology Radial pulse wave analysis with Atcor SphygmoCor system (Sydney). Setting: Primary care. Participants: Controls: General practice patients with non-cardiovascular disorders, and university student controls. ODP: Patients undergoing clinical management of their opioid dependence. Controls had lower chronological ages (CAs) than ODP (30.0 +/- 0.5 vs 34.5 +/- 0.3, mean +/- SEM, p<0.0001). 69.6% and 67.7% participants were men, and 16% and 92.3% were smokers (p<0.0001) for controls and ODP, respectively. 86.3%, 10.3% and 3.4% of ODP were treated with buprenorphine (6.98 +/- 0.21 mg), methadone (63.04 +/- 4.01 mg) or implant naltrexone, respectively. Body mass index (BMI) was depressed in ODP. Interventions: Nil. Primary outcome measures: Vascular Reference Age (RA) and the ratio of vascular age to chronological age (RA/CA). Secondary outcome measures: Arterial stiffness including Augmentation Index. Results: After BMI adjustment, RA in ODP was higher as a function of CA and of time (both p<0.05). Modelled mean RA in control and ODP was 35.6 and 36.3 years (+1.97%) in men, and 34.5 and 39.2 years (+13.43%) in women, respectively. Changes in RA and major arterial stiffness indices were worse in women both as a factor (p = 0.0036) and in interaction with CA (p = 0.0040). Quadratic, cubic and quartic functions of opioid exposure duration outperformed linear models with RA/CA over CA and over time. The opioid dose-response relationship persisted longitudinally after multiple adjustments from p=0.0013 in men and p=0.0073 in women. Conclusions: Data show that lifetime opioid exposure, an interactive cardiovascular risk factor, particularly in women, is related to linear, quadratic, cubic and quartic functions of treatment duration and is consistent with other literature of accelerated ageing in patients with OD.