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

Abstract

ObjectiveTo characterise and compare the potentiation of arterial stiffness and vascular ageing by opioids in men and women.DesignCross-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).SettingPrimary care.ParticipantsControls: 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.InterventionsNil.Primary outcome measuresVascular Reference Age (RA) and the ratio of vascular age to chronological age (RA/CA).Secondary outcome measuresArterial stiffness including Augmentation Index.ResultsAfter 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.ConclusionsData 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.

Commentary on Baghaieet al. (2017): Out of the shadows, into the limelight—sobering salience of meta‐analysis of chronic periodontitis in drug addiction

“…Indeed, principal component analysis of combined indices of dental, mental and hair ageing show significant differences from controls (22% older, P < 0.0005) [7]. This association of addiction with accelerated ageing has been demonstrated elsewhere [7,9].The authors were able to warn that advanced dental decay beyond what might be expected for patient age should indicate to dental clinicians that patients may be involved in substance use. This directly implicates the clinical utility of the association of clinical dental biomarkers with accelerated ageing in addiction [1].…”

“…Indeed, principal component analysis of combined indices of dental, mental and hair ageing show significant differences from controls (22% older, P < 0.0005) [7]. This association of addiction with accelerated ageing has been demonstrated elsewhere [7,9].…”

Cardiovascular disease among people with drug use disorders

“…Their odds of having CVD in the youngest age bracket were also significantly higher than that of the men. This is an issue that requires further study, since there is evidence that the long-term effects of opioids on the cardiovascular system are more serious in women than in men (Khademi et al 2012;Reece and Hulse 2014).…”

“…Injection use may lead to venous disease (Pieper et al 2007), and thrombosis, septicaemia or endocarditis (Salmon et al 2009), involving both infectious and inflammatory mechanisms. Additionally, lifetime opioid exposure is associated with increased arterial stiffness and vascular age (Reece and Hulse 2014) in a dose-dependent fashion (Reece and Hulse 2013). High doses of methadone may cause QT interval prolongation (Kao et al 2013;Roy et al 2012).…”

Therapies in early development for the treatment of opiate addiction

“…This increased consumption has led to a rise in the number of heroin users seeking rehabilitation to 87% [1]. Accordingly, opioid dependence is a condition of increasing public health importance, as opiate users are at an increased risk of death from multiple causes compared with nonusers [2]. The role of pharmacological interventions to treat addictive disorders has become more important over the last decade, with a growing number of pharmacological agents becoming available.…”