Abstract 17217: Serum Paraoxonase 1 (PON1) Activity is Associated With Indices of Hypertensive Heart Disease and Cardiac Remodeling in the Dallas Heart Study Population
Introduction: A recent study in clinic patients found serum activity of the anti-oxidative, anti-inflammatory HDL-associated enzyme paraoxonase 1 (PON1) inversely associated with plasma brain natriuretic peptide (BNP), a marker of heart failure, and predictive of cardiovascular events. We tested whether PON1 protects from hypertensive heart disease in a population sample.
Methods: The Dallas Heart Study measured blood biomarkers at baseline in a population sample of 3480 subjects. Left ventricular mass and ejection fraction were measured by cardiac MRI. Serum PON1 activity was measured by the standard arylesterase enzymatic assay. Incident deaths and causes of death were ascertained for 9 years from baseline through the National Death Index where ICD-9 codes I10 –I13.1 indicated hypertensive heart disease. Multivariable models controlled for age, sex, race, cystatin-C, LDL, HDL, high sensitivity C-reactive protein and uncontrolled hypertension. Preliminary mechanistic studies explored effect modification of 34 biomarkers by PON1.
Results: In a general linear model PON1 activity was independently associated inversely with log Pro-BNP (standardized r = -0.11, s.e. 0.015, P<0.001) and log BNP (std r = -0.07, s.e. 0.017, P<0.001). It was also inversely associated with left ventricular mass (std r = -0.05, s.e. 0.012, P<0.001) but not with ejection fraction (std r = -0.02, s.e. 0.018, P=0.19). In multivariable logistic regression low PON1 activity predicted the 28 incident deaths from hypertensive heart disease (odds ratio for PON1 activity below the median = 3.58, 95% CI 1.42 – 9.05, P=0.007). Significant interactions indicated that high PON1 activity mitigates the strong association of log Pro-BNP with periostin, a matricellular protein associated with cardiac fibrotic remodeling (Pinteraction < 0.001, Fig.).
Conclusions: The findings suggest that PON1, a component of HDL, may protect from hypertensive heart disease by mitigating cardiac remodeling.
Author Disclosures: J.F. Teiber: None. G.L. Kramer: None. J.A. de Lemos: Consultant/Advisory Board; Modest; Novo Nordisc, St. Jude Medical. Research Grant; Significant; Roche Diagnostics, Abbott Diagnostics. M.H. Drazner: None. R.W. Haley: None.
- © 2015 by American Heart Association, Inc.