Diminished Antioxidant Activity of High-Density Lipoprotein–Associated Proteins in Systolic Heart Failure
Circulation: 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. Methods and 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.
Tang, W.H. Wilson; Wu, Yuping; Mann, Shirley; Pepoy, Michael; Shrestha, Kevin; Borowski, Allen G.; and Hazen, Stanley L., "Diminished Antioxidant Activity of High-Density Lipoprotein–Associated Proteins in Systolic Heart Failure" (2011). Mathematics Faculty Publications. 184.
This research was supported by National Institutes of Health grants 1P01 HL098055-01, P01 HL076491-055328, P01 HL087018-020001, 1R01 DK080732-01A1, P50 HL077107-050004, and 1RO1 HL103931-01 and the Cleveland Clinic Clinical Research Unit of the Cleveland Clinic/Case Western Reserve University CTSA 1UL1RR024989.