Associations Between the Cyclic Guanosine Monophosphate Pathway and Cardiovascular Risk Factors: MESA

• Type of Material: Article
• Authors: Wendy Ying, Johns Hopkins School of Medicine; Di Zhao, Johns Hopkins Bloomberg School of Public Health; Pamela Ouyang, Johns Hopkins School of Medicine; Vinita Subramanya, Emory University; Dhananjay Vaidya, Johns Hopkins School of Medicine; Chiadi E Ndumele, Johns Hopkins School of Medicine; Eliseo Guallar, Johns Hopkins Bloomberg School of Public Health; Kavita Sharma, Johns Hopkins School of Medicine; Sanjiv J Shah, Northwestern University Feinberg School of Medicine; David A Kass, Johns Hopkins School of Medicine; Ron C Hoogeveen, Baylor College of Medicine; Joao A Lima, Johns Hopkins School of Medicine; Susan R Heckbert, University of Washington School of Medicine; Christopher R Defilippi, Inova Heart and Vascular Institute; Wendy S Post, Johns Hopkins School of Medicine; Erin D Michos, Johns Hopkins School of Medicine
• Language: English
• Date: 2019-12-17
• Publisher: American Heart Association, Inc
• Publication Version: Final Published Version
• Copyright Statement: © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1161/JAHA.119.013149
• Title of Journal or Parent Work: Journal of the American Heart Association
• Volume: 8
• Issue: 24
• Start Page: e013149
• End Page: e013149
• Grant/Funding Information: This work was funded by the American Heart Association Go Red for Women Strategically Focused Research Network grant 16SFRN27870000. The MESA study was supported by contracts HHSN268201500003I, N01‐HC‐95159, N01‐HC‐95160, N01‐HC‐95161, N01‐HC‐95162, N01‐HC‐95163, N01‐HC‐95164, N01‐HC‐95165, N01‐HC‐95166, N01‐HC‐95167, N01‐HC‐95168, and N01‐HC‐95169 from the National Heart, Lung, and Blood Institute; and by grants UL1‐TR‐000040, UL1‐TR‐001079, and UL1‐TR‐001420 from the National Center for Advancing Translational Sciences. Drs Michos and Zhao are additionally funded by the Blumenthal Scholars Award in Preventive Cardiology at Johns Hopkins University.
• Keywords: sex hormones; cGMP; N‐terminal pro‐B type NP; cardiovascular disease risk factors; Middle Aged; Risk Factors; Prospective Studies; Signal Transduction; Cardiovascular Diseases; Aged; Female; Male; epidemiology; Humans; Cyclic GMP
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Medicine and Surgery

Abstract

Background-—cGMP mediates numerous cardioprotective functions and is a potential therapeutic target for cardiovascular disease. Preclinical studies suggest that plasma cGMP is reflective of natriuretic peptide stimulation. Epidemiologic associations between cGMP and natriuretic peptide, as well as cardiovascular disease risk factors, are unknown. Methods and Results-—We measured plasma cGMP in 542 men and 496 women free of cardiovascular disease and heart failure in MESA (Multi-Ethnic Study of Atherosclerosis). Cross-sectional associations of N-terminal pro-B type natriuretic peptide, sex hormones, and cardiovascular disease/heart failure risk factors with log(cGMP) were analyzed using multivariable linear regression models. Mean (SD) cGMP was 4.7 (2.6) pmol/mL, with no difference between the sexes. After adjusting for cardiovascular risk factors, N-terminal pro-B type natriuretic peptide was significantly positively associated with cGMP (P<0.05). Higher blood pressure and lower estimated glomerular filtration rate were associated with higher cGMP (P<0.05). Triglyceride levels, total/high-density lipoprotein cholesterol ratio, presence of diabetes mellitus, and the homeostatic model assessment of insulin resistance were inversely associated with cGMP (P<0.05). Among women, free testosterone and dehydroepiandrosterone were inversely associated with cGMP, while sex hormone binding globulin was positively associated (P<0.05). Conclusions-—In a community-cohort, plasma cGMP was associated with natriuretic peptide signaling. Higher blood pressure and greater renal dysfunction were positively associated with cGMP, while adverse metabolic risk factors were inversely associated. Increased androgenicity in postmenopausal women was inversely associated with cGMP. These novel associations further our understanding of the role of cGMP in a general population.