Diminished antioxidant activity of high-density lipoprotein-associated proteins in systolic heart failure.
BACKGROUND
Diminished serum arylesterase activity, catalyzed by the high-density lipoprotein-associated paraoxonase-1, is associated with heightened systemic oxidative stress and atherosclerosis risk. In the present study, we sought to determine the prognostic role of serum arylesterase activity in subjects with systolic heart failure, particularly in relation to established cardiac biomarkers.


RESULTS
We measured serum arylesterase activity in 760 subjects with impaired left ventricular systolic function (left ventricular ejection fraction <50%), and prospectively followed major adverse cardiac events (including death, nonfatal myocardial infarction, and stroke) for 3 years. In our study cohort (mean age, 64±11 years; 74% men; median left ventricular ejection fraction, 35%; median creatinine clearance, 96 mg/dL), mean serum arylesterase activity (98±25 μmol/L/min/mL) was lower compared with that in healthy control subjects (mean, 115±26 μmol/L/min/mL, P<0.01) but higher compared with advanced decompensated heart failure subjects (mean, 69±22 μmol/L/min/mL, P<0.01). Within our cohort, there was modest correlation between serum arylesterase activity and high-density lipoprotein cholesterol (r=0.33, P<0.01) as well as B-type natriuretic peptide (r=-0.23, P<0.01). Lower serum arylesterase activity was a strong predictor of poorer outcomes (hazard ratio, 2.94; 95% confidence interval, 1.54, 5.62; P<0.001). After adjusting for traditional risk factors, medication use, B-type natriuretic peptide, and creatinine clearance, lower serum arylesterase still conferred an increased risk of major adverse cardiac events at 3 years (hazard ratio, 2.69; 95% confidence interval, 1.37 to 5.28; P=0.004).


CONCLUSIONS
In patients with systolic heart failure, decreased serum arylesterase activity, a measure of diminished antioxidant properties of high-density lipoprotein, predicts higher risk of incident long-term adverse cardiac event independent of established clinical and biochemical risk factors.
Center for Cardiovascular Diagnostics and Prevention, Department of Cell Biology, Lerner Research Institute, the Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. tangw@ccf.org
W H Wilson
WH
Tang
Yuping
Y
Wu
Shirley
S
Mann
Michael
M
Pepoy
Kevin
K
Shrestha
Allen G
AG
Borowski
Stanley L
SL
Hazen
D000368:Aged; D000975:Antioxidants / Q000378:metabolism*; D043303:Aryldialkylphosphatase / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D002265:Carboxylic Ester Hydrolases / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D054143:Heart Failure, Systolic / Q000150:complications / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology; D013318:Stroke Volume / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000378:metabolism*
D000975:Antioxidants; D015415:Biomarkers; D008075:Lipoproteins, HDL; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase; D043303:Aryldialkylphosphatase