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Reduction in arterial stiffness and vascular age by naltrexone-induced interruption of opiate agonism: a cohort study.

ABSTRACT: To prospectively assess if opiate antagonist treatment or the opiate-free status could reverse opiate-related vasculopathy.Longitudinal Open Observational, Serial 'N of One', over 6.5 years under various treatment conditions: opiate dependence, naltrexone and opiate-free.Primary care, Australia.20 opiate-dependent patients (16 males: 16 cases of buprenorphine 4.11±1.17 mg, two of methadone 57.5±12.5 mg and two of heroin 0.75±0.25 g).Studies of central arterial stiffness and vascular reference age (RA) were performed longitudinally by SphygmoCor Pulse Wave Analysis (AtCor, Sydney).Primary outcome was vascular age and arterial stiffness accrual under different treatment conditions.The mean chronological age (CA) was 33.62±2.03 years. The opiate-free condition was associated with a lower apparent vascular age both in itself (males: p=0.0402 and females: p=0.0360) and in interaction with time (males: p=0.0001 and females: p=0.0004), and confirmed with other measures of arterial stiffness. The mean modelled RA was 38.82, 37.73 and 35.05 years in the opiate, naltrexone and opiate-free conditions, respectively. The opiate-free condition was superior to opiate agonism after full multivariate adjustment (p=0.0131), with modelled RA/CA of 1.0173, 0.9563 and 0.8985 (reductions of 6.1% and 11.9%, respectively).Data demonstrate that opiate-free status improves vascular age and arterial stiffness in previous chronic opiate users. The role of opiate antagonist treatment in achieving these outcomes requires future clarification and offers hope of novel therapeutic remediation.

SUBMITTER: Reece AS

PROVIDER: S-EPMC3612814 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Reduction in arterial stiffness and vascular age by naltrexone-induced interruption of opiate agonism: a cohort study.

Reece Albert Stuart AS Hulse Gary Kenneth GK

BMJ open 20130321 3

<h4>Objective</h4>To prospectively assess if opiate antagonist treatment or the opiate-free status could reverse opiate-related vasculopathy.<h4>Design</h4>Longitudinal Open Observational, Serial 'N of One', over 6.5 years under various treatment conditions: opiate dependence, naltrexone and opiate-free.<h4>Setting</h4>Primary care, Australia.<h4>Participants</h4>20 opiate-dependent patients (16 males: 16 cases of buprenorphine 4.11±1.17 mg, two of methadone 57.5±12.5 mg and two of heroin 0.75±0 ...[more]

PMID: 23524044

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Project description: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.ParticipantsControlsGeneral 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.

Dataset Information

Reduction in arterial stiffness and vascular age by naltrexone-induced interruption of opiate agonism: a cohort study.

Publications

Reduction in arterial stiffness and vascular age by naltrexone-induced interruption of opiate agonism: a cohort study.

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