Coronary endothelial dysfunction appears to be a manifestation of a systemic process: A report from the Women's Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction (WISE-CVD) study

• Type of Material: Article
• Authors: Sawan Jalnapurkar, Cedars-Sinai Medical Center; Sofy Landes, Cedars-Sinai Medical Center; Janet Wei, Cedars-Sinai Medical Center; Puja Mehta, Emory University; Chrisandra Shufelt, Cedars-Sinai Medical Center; Margo Minissian, Cedars-Sinai Medical Center; Carl J. Pepine, University of Florida; Eileen Handberg, University of Florida; Galen Cook-Wiens, Cedars-Sinai Medical Center; George Sopko, National Heart, Lung, and Blood Institute; C. Noel Bairey Merz, Cedars-Sinai Medical Center
• Language: English
• Date: 2021-09-27
• Publisher: Public Library of Science (PLoS)
• Publication Version: Final Published Version
• Copyright Statement: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
• License: Creative Commons Universal : Public Domain Dedication
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0257184
• Title of Journal or Parent Work: PLoS One
• Volume: 16
• Issue: 9
• Grant/Funding Information: This work was supported by contracts from the National Heart, Lung and Blood Institutes nos. N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164, grants U0164829, U01 HL649141, U01 HL649241, K23 HL105787, K23 HL125941, K23 HL127262, K23HL151867 T32 HL69751, R01 HL090957, 1R03 AG032631, R01 HL146158, R01HL124649, PR150224P1 (CDMRP-DoD), U54 AG065141, GCRC grant MO1-RR00425 from the National Center for Research Resources, the National Center for Advancing Translational Sciences Grant UL1TR000124, and grants from the Gustavus and Louis Pfeiffer Research Foundation, Danville, NJ, The Women’s Guild of Cedars-Sinai Medical Center, Los Angeles, CA, The Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, PA, and QMED, Inc., Laurence Harbor, 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 Society for Women’s Health Research (SWHR), Washington, D.C., the Linda Joy Pollin Women’s Heart Health Program, the Erika Glazer Women’s Heart Health Project, and the Adelson Family Foundation, Cedars-Sinai Medical Center, Los Angeles, California. 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, the National Institutes of Health, or the U.S. Department of Health and Human Services. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Background Coronary microvascular dysfunction (CMD) is prevalent in symptomatic women with ischemia but no obstructive coronary artery disease (INOCA). Urine albumin-creatinine ratio (UACR) is a measure of renal microvascular endothelial dysfunction. Both are predictors of adverse cardiovascular events. It is unknown if CMD could be a manifestation of a systemic process. We evaluated the relationship between renal microvascular dysfunction and CMD as measured by invasive coronary function testing (CFT). Methods and results We measured urine albumin and creatinine to provide UACR in 152 women enrolled in the Women’s Ischemia Syndrome Evaluation–Coronary Vascular Dysfunction (WISE-CVD) study (2008–2015) with suspected INOCA who underwent CFT. Invasive CFT measures of endothelial and non-endothelial dependent coronary microvascular function were obtained. Subjects were divided into those with detectable (≥20 mg/g) and undetectable urine albumin (<20 mg/g). The group mean age was 54 ± 11 years, with a moderate cardiac risk factor burden including low diabetes prevalence, and a mean UACR of 12 ± 55 mg/g (range 9.5–322.7 mg/g). Overall, coronary endothelial-dependent variables (change in coronary blood flow and coronary diameter in response to cold pressor testing) had significant inverse correlations with log UACR (r = -0.17, p = 0.05; r = -0.18, p = 0.03, respectively). Conclusions Among women with INOCA and relatively low risk factor including diabetes burden, renal microvascular dysfunction, measured by UACR, is related to coronary endothelial-dependent CMD. These results suggest that coronary endothelial-dependent function may be a manifestation of a systemic process. Enhancing efferent arteriolar vasodilatation in both coronary endothelial-dependent function and renal microvascular dysfunction pose potential targets for investigation and treatment.