Low paraoxonase activity predicts coronary events in the Caerphilly Prospective Study.
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.
Mackness
Bharti
B
University Department of Medicine, Manchester Royal Infirmary, University of Manchester, Oxford Rd, Manchester M13 9WL, UK.
Durrington
Paul
P
McElduff
Patrick
P
Yarnell
John
J
Azam
Naheed
N
Watt
Michael
M
Mackness
Michael
M
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
C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones; D014280:Triglycerides; D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human