Reece Albert Stuart, Hulse Gary Kenneth
School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley WA 6009, Australia.
J Clin Med Res. 2013 Oct;5(5):356-67. doi: 10.4021/jocmr1496w. Epub 2013 Aug 5.
Despite intriguing observational cross-sectional data there are no longitudinal studies of opiate related arterial disease. As opiates act via P16INK4A/CDKN2A, and vascular ageing has been thought to be a surrogate for organismal ageing, the subject has far-reaching implications.
Pulse Wave Analysis (PWA) by radial arterial tonometry (SphygmoCor) was performed on control and opiate dependent patients.
A total of 37 controls were compared with 93 opiate dependents. They were studied on 117 and 275 occasions respectively up to 1,797 days. The mean (± S.E.M.) ages were 38.72 ± 2.64 and 33.78 ± 0.90 years (P = 0.0260), 91.4% and 10.8% smoked (P < 0.0001). Body mass index rose more in controls (P = 0.0185) and in interaction with time (P = 0.0025). When controlled for time and BMI, opiate dependency status was shown to be associated with vascular age and central arterial stiffness and pressure indices (all P < 0.05). When repeated measures multiple regression was performed on all traditional cardiovascular risk factors, the opiate dose-duration interaction was significant and appeared in 12 terms in the final model. It was also independently significant (P = 0.0153). Opiate dose or duration appeared in a further 15 terms. The model was shown to be significantly improved by the inclusion of terms for opiate dependency (A.I.C. 71.10 v 54.31, P < 0.0001).
These data confirm increased vascular stiffness and ageing in a longitudinal study, and thereby imply advanced organismal ageing. These multivariate studies are consistent with opiate dependency as an interactive and multivariate cardiovascular risk factor and emphasize the role of treatment duration.
尽管有有趣的观察性横断面数据，但尚无关于阿片类药物相关动脉疾病的纵向研究。由于阿片类药物通过P16INK4A/CDKN2A起作用，且血管老化一直被认为是机体老化的替代指标，因此该主题具有深远意义。
对对照组和阿片类药物依赖患者进行经桡动脉压测定（SphygmoCor）的脉搏波分析（PWA）。
共将37名对照组患者与93名阿片类药物依赖者进行了比较。分别在长达1797天的时间里对他们进行了117次和275次研究。平均（±标准误）年龄分别为38.72±2.64岁和33.78±0.90岁（P = 0.0260），吸烟者比例分别为91.4%和10.8%（P < 0.0001）。对照组的体重指数上升幅度更大（P = 0.0185），且与时间存在交互作用（P = 0.0025）。在对时间和体重指数进行控制后，阿片类药物依赖状态被证明与血管年龄、中心动脉僵硬度和压力指数相关（所有P < 0.05）。当对所有传统心血管危险因素进行重复测量多元回归分析时，阿片类药物剂量-持续时间交互作用显著，且在最终模型的12个项中出现。其也具有独立显著性（P = 0.0153）。阿片类药物剂量或持续时间在另外15个项中出现。通过纳入阿片类药物依赖项，模型得到显著改善（A.I.C. 71.10对54.31，P < 0.0001）。
这些数据在纵向研究中证实了血管僵硬度增加和老化，从而意味着机体老化进程加快。这些多变量研究表明阿片类药物依赖是一种交互性和多变量的心血管危险因素，并强调了治疗持续时间的作用。
