Oxidative Stress Is Associated With Diastolic Dysfunction in Women With Ischemia With No Obstructive Coronary Artery Disease

• Type of Material: Article
• Authors: Mohamad Raad, Emory University; Ahmed AlBadri, Emory University; Janet Wei, Cedars Sinai Smidt Heart Institute; Puja Mehta, Emory University; Jenna Maughan, Cedars Sinai Smidt Heart Institute; Adit Gadh, Cedars Sinai Smidt Heart Institute; Louise Thomson, Cedars Sinai Smidt Heart Institute; Dean Jones, Emory University; Arshed Quyyumi, Emory University; Carl J. Pepine, University of Florida; C. Noel Bairey Merz, Cedars Sinai Smidt Heart Institute
• Language: English
• Date: 2020-05-18
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1161/JAHA.119.015602
• Title of Journal or Parent Work: JOURNAL OF THE AMERICAN HEART ASSOCIATION
• Volume: 9
• Issue: 10
• Start Page: e015602
• End Page: e015602
• Grant/Funding Information: AlBadri is supported by American Heart Association Postdoctoral Fellowship Award Grant (18POST34080330). This work was also supported by contracts from the National Heart, Lung, and Blood Institute nos. N01‐HV‐68161, N01‐HV‐68162, N01‐HV‐68163, N01‐HV‐68164, grants U0164829, U01 HL649141, U01 HL649241, K23HL105787, T32HL69751, R01 HL090957, 1R03AG032631 from the National Institute on Aging, GCRC grant M01‐RR00425 from the National Center for Research Resources, the National Center for Advancing Translational Sciences Grant UL1TR000124 and UL1TR001427, and grants from the Gustavus and Louis Pfeiffer Research Foundation, Danville, NJ, the Edythe L. Broad and the Constance Austin Women's Heart Research Fellowships, Cedars‐Sinai Medical Center, Los Angeles, California, the Barbra Streisand Women's Cardiovascular Research and Education Program, Cedars‐Sinai Medical Center, Los Angeles, The Linda Joy Pollin Women's Heart Health Program, and the Erika Glazer Women's Heart Health Project, Cedars‐Sinai Medical Center, Los Angeles, California. Dr Pepine is supported by the Gatorade Trust and the PCORnet‐One Florida Clinical Research Consortium CDRN‐1501‐26692, University of Florida, Gainesville, FL. Quyyumi is supported by National Institutes of Health (NIH) grants 5P01HL101398‐02, 1P20HL113451‐01, 1R56HL126558‐01, 1RF1AG051633‐01, R01 NS064162‐01, R01 HL89650‐01, HL095479‐01, 1U10HL110302‐01, 1DP3DK094346‐01, and 2P01HL086773‐06A1. This work is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or National Institutes of Health.
• Keywords: INOCA; MORTALITY; HEART-FAILURE; oxidative stress; Cardiovascular System & Cardiology; REACTIVITY; PLASMA; Life Sciences & Biomedicine; ATHEROSCLEROSIS; METHODOLOGY; Science & Technology; RISK; GLUTATHIONE; Cardiac & Cardiovascular Systems; cardiac MRI; diastolic dysfunction; MICROVASCULAR DYSFUNCTION; WISE
• Research Categories: Gender Studies; Health Sciences, Medicine and Surgery

Abstract

BACKGROUND: Women with signs and symptoms of ischemia and no obstructive coronary artery disease often have evidence of diastolic dysfunction. Oxidative stress (OS) is associated with cardiovascular risk factors and adverse outcomes. The relationship between systemic OS and diastolic dysfunction is unknown. METHODS AND RESULTS: A subgroup of women (n=75) with suspected ischemia and no obstructive coronary artery disease who had both cardiac magnetic resonance imaging and OS measurements were enrolled in the WISE-CVD (Women Ischemia Syndrome Evaluation—Coronary Vascular Dysfunction) study. Left ventricular end-diastolic pressure was measured invasively. Left ventricular end-diastolic volume and peak filling rate were assessed using cardiac magnetic resonance imaging. Aminothiol levels of plasma cystine and glutathione were measured as markers of OS. Spearman correlation and linear regression analyses were conducted. The group mean age was 54±11 years, and 61% had a resting left ventricular end-diastolic pressure >12 mm Hg. Cystine levels correlated negatively with the peak filling rate (r=−0.31, P=0.007) and positively with left ventricular end-diastolic pressure (r=0.25; P=0.038), indicating that increased OS was associated with diastolic dysfunction. After multivariate adjustment including multiple known risk factors for diastolic dysfunction and cardiovascular medications, cystine levels continued to be associated with peak filling rate (β=−0.27, P=0.049) and left ventricular end-diastolic pressure (β=0.25; P=0.035). Glutathione levels were not associated with indices of diastolic function. CONCLUSIONS: OS, measured by elevated levels of cystine, is associated with diastolic dysfunction in women with evidence of ischemia and no obstructive coronary artery disease, indicating the role of OS in patients with ischemia and no obstructive coronary artery disease. Its role in the progression of heart failure with preserved ejection fraction should be explored further.