Abstract 16335: Increased Oxidative Stress in Heart Failure With Normal Left Ventricular Ejection Fraction
Backgrounds: Effective treatments have not been established for patients with heart failure with normal left ventricular ejection fraction (HFNEF) because precise pathophysiological mechanisms underlying HFNEF remain unclear. Oxidative stress has been shown to be associated with heart failure (HF) with reduced left ventricular (LV) ejection fraction (EF), however relationship between oxidative stress and HFNEF remains unknown. We investigated impact of oxidative stress on HFNEF.
Methods and Results: We assessed oxidative stress by measuring urine 8-hydroxy-2’-deoxyguanosine (u8-OHdG) (ng/mg•Cr) and evaluated cardiac functions by echocardiography to measure the ratio of early transmitral flow velocity to tissue Doppler early diastolic mitral annular velocity (E/e’) in HFNEF patients without coronary artery disease (n=79, New York Heart Association class II: n=54, class III or IV; n=25) (age 69±12, E/e’ 16.0 [13.4-18.7], B-type natriuretic peptide (BNP) 244 [53-406] pg/ml) and non-HF patients (n=47) (age 62±12, E/e’ 9.0 [8.1-11.0], BNP 21 [9-30] pg/ml). For the diagnosis of HFNEF, we applied the diagnostic criteria of the European Working Group to HFNEF published in 2007. u8-OHdG levels were significantly higher in HFNEF patients than non-HF patients (14.2 [12.3-19.9] versus 12.2 [10.2-19.2] ng/mg•Cr, P<0.05). Stepwise backward multivariate linear regression analysis showed that u8-OHdG levels independently correlated with LV mass indexes (LVMI) (beta=0.37, P<0.001) (model R2=0.154). HFNEF patients with history of decompensated congestive HF (n=32) had significantly higher u8-OHdG levels than those without the events (n=47) (17.4 [13.3-23.4] versus 13.4 [11.7-16.4] ng/mg•Cr, P=0.01). Stepwise upward multiple logistic regression analysis identified that BNP (odds ratio (OR) 2.5 [95% confidence interval (CI) 1.3-4.6], P=0.004), LVEF (OR 0.87 [95% CI 0.78-0.98], P=0.02), and u8-OHdG (OR 8.1 [95% CI 1.6-42.1], P=0.01) were independently associated with the history of hospitalized HF events.
Conclusions: Oxidative stress assessed by u8-OHdG levels was significantly elevated in patients with HFNEF, which independently correlated with LVMI. Oxidative stress could be a key component in the pathogenesis of HFNEF.
- © 2011 by American Heart Association, Inc.