Abstract 10036: Olmesartan Improves Not Only Vascular Endothelial Dysfunction but Cardiac Diastolic Dysfunction in Hypertensive Heart Failure With Preserved Ejection Fraction - ORION Study

Abstract

Introduction: The optimal treatment for heart failure (HF) with preserved left ventricular (LV) ejection fraction (EF) (HFpEF) has not been established. Using an experimental model of HFpEF, we previously reported a novel mechanism underlying reversal of endothelial dysfunction and HFpEF by AT1 receptor blocker (ARB). By performing this study (ORION: OlmesaRtan Improvement endothelial functiON with hypertension study), we examined the effects of ARB on hypertensive HFpEF patients, focusing on reactive oxygen species (ROS). Methods and Results: We examined prospectively 20 hypertensive HFpEF patients, taking any renin-angiotensin system inhibitors, switched to appreciable amounts of highly-selective ARB; olmesartan (average dosage amounts: 22.9 mg/day) for 3 months. Despite no additive hypotensive effects of olmesartan, endothelial dysfunction assessed by fingertrip digital reactive hyperemia (RH) peripheral arterial tonometry using Endo-PAT2000 was significantly reversed (RH-index; 1.57±0.34 to 1.87±0.50, P=0.034), accompanied by significant reduction of serum derivatives of reactive oxidative metabolites levels, novel biomarker of ROS (362.8±13.7 to 302.1±9.4 unit called the Carratelli unit [U.CARR], P=0.001). Olmesartan treatments significantly improved cardiac diastolic function evaluated by the ratio of early transmitral flow velocity to tissue doppler early diastolic mitral annular velocity (15.4 to 11.0, P<0.001) but not LVEF and LV anterior wall thickness in echocardiography, and decreased plasma B-type natriuretic peptide levels (214.9 to 191.4, P<0.05) in HFpEF patients. Additionaly, olmesartan significantly increased plasma superoxide dismutase activity (2.39±0.73 to 3.06±0.78 U/mL, P=0.02) and adiponectin levels (2.66±1.55 to 4.12±1.99 μg/mL, P<0.05), but not affect plasma nitrates and nitrites (NO3-/NO2-) levels (53.2±28.1 to 62.9±28.4 μmol/L). Conclusions: These data suggested that strong AT1 receptor blockade by olmesartan restored not only endothelial dysfunction but cardiac diastolic dysfunction in HFpEF beyond hypotensive effects. Increased in SOD activities and adiponectin levels, but not nitric oxide levels, might contribute to these beneficial effects of olmesartan.