title: Duration of opiate exposure as a determinant of arterial stiffness and vascular age in male opiate dependence: a longitudinal study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Thirty-eight male controls compared with 198 opiate-dependent male patients were studied longitudinally using SphygmoCor pulse wave analysis.
  
  
  CONCLUSIONS
  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).
  
  
  CONCLUSIONS
  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.
authors: School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, WA, Australia.
authors: A S
authors: AS
authors: Reece
authors: G K
authors: GK
authors: Hulse
mesh_terms: D000328:Adult; D000375:Aging / Q000187:drug effects*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects; D016022:Case-Control Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D015999:Multivariate Analysis; D009293:Opioid-Related Disorders / Q000150:complications*; D012307:Risk Factors; D013997:Time Factors; D059289:Vascular Stiffness / Q000187:drug effects*
chemical_list: D000701:Analgesics, Opioid
keywords: arterial stiffness; dependence; heroin; human ageing; opiates; vascular ageing