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.Objective: 本研究旨在前瞻性评估阿片类拮抗剂治疗或无阿片状态能否逆转阿片相关血管病变。Design: 本研究为纵向开放观察性、系列单病例（N of 1）研究，历时6.5年以上，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。Setting: 研究地点为澳大利亚基层医疗环境。Participants: 共纳入20名阿片依赖患者（16名男性：其中16例接受丁丙诺啡（buprenorphine）治疗，给药剂量为4.11±1.17mg；2例接受美沙酮（methadone）治疗，剂量为57.5±12.5mg；2例吸食海洛因，日均用量0.75±0.25g）。Intervention: 采用澳大利亚悉尼AtCor公司的SphygmoCor脉搏波分析（Pulse Wave Analysis）技术，纵向检测中心动脉僵硬度及血管参考年龄（reference age, RA）。Primary Outcomes: 主要结局指标为不同治疗状态下的血管年龄及动脉僵硬度累积情况。Results: 受试者的平均实际年龄（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），且与随访时间存在交互效应（男性：P=0.0001；女性：P=0.0004），该结果经其他动脉僵硬度指标验证。阿片依赖、纳曲酮治疗、无阿片状态下的平均模拟血管参考年龄分别为38.82岁、37.73岁及35.05岁。经完全多变量校正后，无阿片状态的疗效优于阿片类激动剂治疗（P=0.0131），对应的模拟血管参考年龄/实际年龄比值分别为1.0173、0.9563及0.8985（较阿片依赖组分别降低6.1%及11.9%）。Conclusions: 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具体作用有待未来进一步阐明，但其为新型治疗干预手段带来了潜在希望。