title: Impact of lifetime opioid exposure on arterial stiffness and vascular age: cross-sectional and longitudinal studies in men and women.
abstract: OBJECTIVE
  To characterise and compare the potentiation of arterial stiffness and vascular ageing by opioids in men and women.
  
  
  METHODS
  Cross-sectional and longitudinal studies of 576 clinical controls and 687 opioid-dependent patients (ODP) on 710 and 1305 occasions, respectively, over a total of 2382 days (6.52 years), 2006-2011. Methodology Radial pulse wave analysis with Atcor SphygmoCor system (Sydney).
  
  
  METHODS
  Primary care.
  
  
  METHODS
  
  
  
  METHODS
  General practice patients with non-cardiovascular disorders, and university student controls. ODP: Patients undergoing clinical management of their opioid dependence. CONTROLS had lower chronological ages (CAs) than ODP (30.0±0.5 vs 34.5±0.3, mean±SEM, p<0.0001). 69.6% and 67.7% participants were men, and 16% and 92.3% were smokers (p<0.0001) for controls and ODP, respectively. 86.3%, 10.3% and 3.4% of ODP were treated with buprenorphine (6.98±0.21 mg), methadone (63.04±4.01 mg) or implant naltrexone, respectively. Body mass index (BMI) was depressed in ODP.
  
  
  METHODS
  Nil.
  
  
  METHODS
  Vascular Reference Age (RA) and the ratio of vascular age to chronological age (RA/CA).
  
  
  METHODS
  Arterial stiffness including Augmentation Index.
  
  
  RESULTS
  After BMI adjustment, RA in ODP was higher as a function of CA and of time (both p<0.05). Modelled mean RA in control and ODP was 35.6 and 36.3 years (+1.97%) in men, and 34.5 and 39.2 years (+13.43%) in women, respectively. Changes in RA and major arterial stiffness indices were worse in women both as a factor (p = 0.0036) and in interaction with CA (p = 0.0040). Quadratic, cubic and quartic functions of opioid exposure duration outperformed linear models with RA/CA over CA and over time. The opioid dose-response relationship persisted longitudinally after multiple adjustments from p=0.0013 in men and p=0.0073 in women.
  
  
  CONCLUSIONS
  Data show that lifetime opioid exposure, an interactive cardiovascular risk factor, particularly in women, is related to linear, quadratic, cubic and quartic functions of treatment duration and is consistent with other literature of accelerated ageing in patients with OD.
authors.affiliation: School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Albert Stuart
authors.initials: AS
authors.lastname: Reece
authors.affiliation: School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Gary Kenneth
authors.initials: GK
authors.lastname: Hulse
mesh_terms: D000328:Adult; D000367:Age Factors; D000701:Analgesics, Opioid / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects*; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D013997:Time Factors; D059289:Vascular Stiffness / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid
keywords: acceleration of ageing; arterial stiffness; biological age; heroin; opiate dependence; vascular ageing