title: Low paraoxonase activity predicts coronary events in the Caerphilly Prospective Study.
abstract: BACKGROUND
  The hypothesis that paraoxonase (PON1) has a role in preventing atherosclerosis is based on experimental, transgenic, and case-control studies but has not previously been tested prospectively.
  
  
  RESULTS
  The Caerphilly Prospective Study is a cohort study of men aged 49 to 65 years observed for coronary heart disease (CHD) events (fatal and nonfatal myocardial infarction) over a mean period of 15 years. Serum PON1 activity toward paraoxon was measured in 1353 participants. PON1 activity was 20% lower in the 163 men who had a coronary event (P=0.039). Men in the highest quintile of PON1 activity had a decreased risk compared with those in the lowest quintile (OR 0.57 [95% CI, 0.33 to 0.96]). The inverse relationship between quintiles of serum PON1 activity and CHD risk was graded, the median change in OR across each quintile being 0.87 (0.77 to 0.98). After adjustment for all other CHD risk factors, including HDL cholesterol, this median value became 0.90 (0.78 to 1.02). PON1 was most predictive of a new CHD event in patients at highest risk by virtue of preexisting CHD (adjusted median OR for each quintile, 0.74 [0.59 to 0.93]; n=313) or the presence of other risk factors. For the highest tertile of CHD risk (n=390) calculated by the Framingham equation, adjusted median OR for each quintile was 0.84 (0.66 to 1.05); n=390.
  
  
  CONCLUSIONS
  Low serum PON1 activity toward paraoxon is an independent risk factor for coronary events in men at high risk because of preexisting disease or other CHD risk factors.
authors.affiliation: University Department of Medicine, Manchester Royal Infirmary, University of Manchester, Oxford Rd, Manchester M13 9WL, UK.
authors.forename: Bharti
authors.initials: B
authors.lastname: Mackness
authors.forename: Paul
authors.initials: P
authors.lastname: Durrington
authors.forename: Patrick
authors.initials: P
authors.lastname: McElduff
authors.forename: John
authors.initials: J
authors.lastname: Yarnell
authors.forename: Naheed
authors.initials: N
authors.lastname: Azam
authors.forename: Michael
authors.initials: M
authors.lastname: Watt
authors.forename: Michael
authors.initials: M
authors.lastname: Mackness
mesh_terms: D000368:Aged; D043303:Aryldialkylphosphatase; D051152:Clusterin; D015331:Cohort Studies; D003327:Coronary Disease / Q000175:diagnosis* / Q000201:enzymology*; D004950:Esterases / Q000097:blood*; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000097:blood; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones; D014280:Triglycerides; D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human