Cemal Ozemek1, Kerry L Hildreth1, Daniel W Groves2, Kerrie L Moreau3. 1. University of Colorado School of Medicine at the Anschutz Medical Campus, Division of Geriatric Medicine, 12631 East 17th Ave., Aurora, CO, 80045, United States. 2. University of Colorado, Anschutz Medical Campus, Division of Cardiology, 12631 East 17th Ave. B130, Aurora, CO, 80045, United States. 3. University of Colorado School of Medicine at the Anschutz Medical Campus, Division of Geriatric Medicine, 12631 East 17th Ave., Aurora, CO, 80045, United States; Denver Veterans Administration Medical Center, Geriatric Research Education Clinical Center (GRECC), 1055 Clermont St, Denver, CO, 80220, United States. Electronic address: Kerrie.Moreau@ucdenver.edu.
Abstract
OBJECTIVES: We tested the hypothesis that oxidative stress contributes to reductions in left ventricular diastolic (LV) function in estrogen-deficient postmenopausal women, related in part to reduced nitric oxide (NO) bioavailability. STUDY DESIGN: LV diastolic function - recorded using transthoracic echocardiography and determined as the peak early (E) to late (A) mitral inflow velocity ratio and the E to peak early (e') mitral annular velocity ratio - and brachial artery flow mediated dilation (FMD), a biomarker of NO bioavailability, were measured during acute systemic infusions of saline (control) and ascorbic acid (experimental model to decrease oxidative stress) in healthy premenopausal women (N=14, 18-40 years) and postmenopausal women (N=23, 45-75 years). RESULTS: The E/A ratio was lower (1.16[1.06-1.33] vs 1.65[1.5-2.3]; median[interquartile range]) and the E/e' ratio was elevated (8.8[7.6-9.9] vs. 6.6[5.5-7.3]) in postmenopausal compared with premenopausal women, indicating reduced LV diastolic function. E/A and E/e' were correlated with FMD (r=0.54 and r=-0.59, respectively, both P<0.01). Ascorbic acid infusion improved both FMD (5.4±2.0% to 7.8±2.6%) and E/e' (to 8.1[7.2-9.7], P=0.01) in postmenopausal women but not in premenopausal women. Ascorbic acid did not change E/A in either group. CONCLUSION: The current study provides evidence that oxidative stress contributes to reduced LV diastolic function in estrogen-deficient postmenopausal women, possibly by reducing the availability of NO.
OBJECTIVES: We tested the hypothesis that oxidative stress contributes to reductions in left ventricular diastolic (LV) function in estrogen-deficient postmenopausal women, related in part to reduced nitric oxide (NO) bioavailability. STUDY DESIGN: LV diastolic function - recorded using transthoracic echocardiography and determined as the peak early (E) to late (A) mitral inflow velocity ratio and the E to peak early (e') mitral annular velocity ratio - and brachial artery flow mediated dilation (FMD), a biomarker of NO bioavailability, were measured during acute systemic infusions of saline (control) and ascorbic acid (experimental model to decrease oxidative stress) in healthy premenopausal women (N=14, 18-40 years) and postmenopausal women (N=23, 45-75 years). RESULTS: The E/A ratio was lower (1.16[1.06-1.33] vs 1.65[1.5-2.3]; median[interquartile range]) and the E/e' ratio was elevated (8.8[7.6-9.9] vs. 6.6[5.5-7.3]) in postmenopausal compared with premenopausal women, indicating reduced LV diastolic function. E/A and E/e' were correlated with FMD (r=0.54 and r=-0.59, respectively, both P<0.01). Ascorbic acid infusion improved both FMD (5.4±2.0% to 7.8±2.6%) and E/e' (to 8.1[7.2-9.7], P=0.01) in postmenopausal women but not in premenopausal women. Ascorbic acid did not change E/A in either group. CONCLUSION: The current study provides evidence that oxidative stress contributes to reduced LV diastolic function in estrogen-deficient postmenopausal women, possibly by reducing the availability of NO.
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