Abstract 11957: Oxidative Stress Independently Predicts Diastolic Dysfunction in Women With Signs and Symptoms of Ischemia Without Obstructive Coronary Artery Disease: Results From the NHLBI-Sponsored Women Ischemia Syndrome Evaluation (WISE) Study
Background: The pathophysiology of diastolic dysfunction is incompletely understood and therapeutic strategies are limited. Recent evidence suggests that endothelial, as well as cardiomyocyte dysfunction plays a role in the development of diastolic dysfunction. Oxidative stress has been linked to endothelial dysfunction, cardiomyocyte dysfunction, and atherosclerosis. We evaluated the association between oxidative stress and diastolic function in women with signs and symptoms of myocardial ischemia and no obstructive CAD.
Methods: Seventy-three women with signs and symptoms of myocardial ischemia and no obstructive CAD (stenosis ≤50%) by angiography, with normal systolic function, enrolled in the NHLBI-sponsored WISE from 2009-2012 were studied. Left ventricular end diastolic pressure (LVEDP) was measured, and blood was collected for cystine and glutathione levels as markers of oxidative stress. All underwent rest cine cardiac MRI (1.5 T) via a standardized protocol and diastolic filling parameters (peak filling rate [PFR] and time to peak filing rate [tPFR]) were obtained.
Results: Mean age was 54±10 years, BMI was 30±8; 32% had hypertension, 11% diabetes, 41% hyperlipidemia, and 3% were smokers. The mean PFR, tPFR and LVEDP were 3.1±0.6 EDV/sec, 197±26 sec and 16±5 mmHg, respectively. Cardiac MRI evidence of diastolic dysfunction (PFR≤3.3 EDV/sec or tPFR>229 sec) was present in 64% patients. Cystine levels correlated negatively with PFR (r= -0.32, p=0.006) and positively with LVEDP (r=0.27, p=0.02). In multivariate regression analyses, after adjusting for age, race, smoking, hypertension, diabetes and hyperlipidemia, cystine was an independent predictor of PFR (β=-0.28, p=0.024) and LVEDP (β=0.33, p=0.014). A 10%-increase in cystine level was associated with a 3.5% decrease in PFR or 3.9% increase in LVEDP. Glutathione did not correlate with PFR, tPFR, or LVEDP.
Conclusion: In women with signs and symptoms of ischemia without obstructive CAD, elevated cystine, a marker of oxidative stress, independently predicts diastolic dysfunction. Further prospective studies are warranted to investigate the role of oxidative stress in the pathophysiology of diastolic dysfunction and related adverse outcomes.
- © 2013 by American Heart Association, Inc.