Data from: Reduction in arterial stiffness and vascular age by naltrexone-induced interruption of opiate agonism

Objective: To prospectively assess if opiate antagonist treatment or the opiate-free status could reverse opiate-related vasculopathy. Design: Longitudinal Open Observational, Serial “N of One”, over 6.5 years under various treatment conditions: opiate dependence, naltrexone and opiate-free. Setting: Primary care, Australia. Participants: 20 opiate dependent patients (16 males: 16 cases of buprenorphine 4.11+1.17mg, two of methadone 57.5+12.5mg and two of heroin 0.75+0.25g). Intervention: Studies of Central Arterial Stiffness and vascular reference age (RA) were performed longitudinally by SphygmoCor Pulse Wave Analysis (AtCor, Sydney). Primary Outcomes: Primary outcome was vascular age and arterial stiffness accrual under different treatment conditions. Results: 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, females: P=0.0360) and in interaction with time (males: P=0.0001; 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). Conclusions: 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.研究目的：前瞻性评估阿片类拮抗剂（opiate antagonist）治疗或无阿片状态能否逆转阿片相关血管病变（vasculopathy）。 研究设计：纵向开放观察性、系列单病例（N of 1）研究，历时6.5年，涵盖三种不同治疗状态：阿片依赖、纳曲酮（naltrexone）治疗及无阿片状态。 研究地点：澳大利亚基层医疗场所。 研究对象：20例阿片依赖患者（其中男性16例，均接受丁丙诺啡（buprenorphine）治疗，剂量为4.11±1.17mg；女性4例，其中2例接受美沙酮（methadone）治疗，剂量为57.5±12.5mg，2例使用海洛因（heroin），剂量为0.75±0.25g）。 干预措施：采用澳大利亚悉尼AtCor公司生产的SphygmoCor脉搏波分析系统，纵向检测中心动脉僵硬度（central arterial stiffness）及血管参考年龄（vascular reference age, RA）。 主要结局指标：主要结局为不同治疗状态下的血管年龄及动脉僵硬度累积进展情况。 研究结果：研究对象的平均实际年龄（chronological age, CA）为33.62±2.03岁。无阿片状态下的表观血管年龄更低：单独分析时（男性：P=0.0402，女性：P=0.0360），且与时间存在交互作用（男性：P=0.0001；女性：P=0.0004），该结果经其他动脉僵硬度检测指标验证。三种治疗状态下的平均模拟血管参考年龄分别为：阿片依赖组38.82岁、纳曲酮组37.73岁、无阿片组35.05岁。经完全多变量校正后，无阿片状态的效果优于阿片激动剂治疗（P=0.0131），其模拟血管参考年龄/实际年龄比值分别为1.0173（阿片依赖组）、0.9563（纳曲酮组）及0.8985（无阿片组），较阿片依赖组分别降低6.1%及11.9%。 结论：本研究数据表明，无阿片状态可改善既往慢性阿片使用者的血管年龄及动脉僵硬度。阿片类拮抗剂治疗在实现上述结局中的作用有待未来研究阐明，但其为新型治疗干预策略提供了潜在希望。