Reece A S, Hulse G K
School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, WA, Australia.
J Clin Pharm Ther. 2014 Apr;39(2):158-67. doi: 10.1111/jcpt.12121. Epub 2013 Dec 16.
Despite intriguing initial and associational studies, there remains little research on opiate-related arterial dysfunction and no longitudinal studies. As opiates act potently via P16INK4A/CDKN2A identified on GWAS screens, and as arterial ageing is a surrogate for organismal ageing, this area is of general concern.
Thirty-eight male controls compared with 198 opiate-dependent male patients were studied longitudinally using SphygmoCor pulse wave analysis.
Healthy male controls and opiate-dependent male patients were studied on 125 and 625 occasions, respectively. The mean (±SEM) chronological age (CA) was 42·32 ± 2·22 for controls and 35·04 ± 0·61 for opiate dependent (P = 0·0029). 94·4% and 13·2% smoked tobacco (P < 0·0001). Controlling for BMI and CA, there was a significant time: addictive status interaction for vascular age (P = 0·0127) and central augmentation pressure and index (both P < 0·02). Central systolic and diastolic pressures were also worse over time by addictive status (P < 0·005). At repeated measures multiple regression adjusted for classical risk factors, opiate dose and duration of opiate use remained significant. The dose-duration effect was significant in 8 terms and by time. A similar model quadratic in opiate duration was more powerfully predictive, suggesting the salience of the duration of opiate treatment (AIC 191·6898 and 191·5966, P = 0·0116).
Data suggest that increased length of opiate dependence is associated with advanced vascular stiffness and ageing and are therefore consistent with accelerated ageing organismally. The superiority of power functions of the opiate duration of exposure underscores the significance of the duration of treatment and of putative senescence induction.
尽管最初有一些引人关注的研究及相关性研究，但关于阿片类药物相关的动脉功能障碍的研究仍然很少，且尚无纵向研究。由于阿片类药物通过全基因组关联研究（GWAS）筛选出的P16INK4A/CDKN2A发挥强大作用，且动脉老化是机体老化的一个替代指标，因此该领域受到广泛关注。
采用SphygmoCor脉搏波分析对38名男性对照者和198名阿片类药物依赖男性患者进行纵向研究。
分别对健康男性对照者和阿片类药物依赖男性患者进行了125次和625次研究。对照组的平均（±标准误）实际年龄（CA）为42.32±2.22岁，阿片类药物依赖组为35.04±0.61岁（P = 0.0029）。94.4%的对照组和13.2%的阿片类药物依赖组吸烟（P < 0.0001）。在控制体重指数（BMI）和实际年龄后，血管年龄存在显著的时间：成瘾状态交互作用（P = 0.0127），中心增强压及指数也存在显著交互作用（P均< 0.02）。随着时间推移，成瘾状态导致中心收缩压和舒张压也变差（P < 0.005）。在对经典危险因素进行调整的重复测量多元回归分析中，阿片类药物剂量和使用时间仍然具有显著性。剂量 - 时间效应在8个指标及按时间分析时均具有显著性。一个以阿片类药物使用时间为二次项的类似模型预测能力更强，表明阿片类药物治疗时间的重要性（赤池信息准则分别为191.6898和191.5966，P = 0.0116）。
数据表明，阿片类药物依赖时间延长与血管僵硬度增加和老化相关，因此与机体加速老化一致。阿片类药物暴露时间的幂函数的优越性强调了治疗时间和假定的衰老诱导的重要性。
