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Cyclic Guanosine Monophosphate and Risk of Incident Heart Failure and Other Cardiovascular Events: the ARIC Study

BACKGROUND: Cyclic guanosine monophosphate (cGMP) is a second messenger regulated through natriuretic peptide and nitric oxide pathways. Stimulation of cGMP signaling is a potential therapeutic strategy for heart failure with preserved ejection fraction (HFpEF) and atherosclerotic cardiovascular dis...

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Autores principales: Zhao, Di, Guallar, Eliseo, Vaidya, Dhananjay, Ndumele, Chiadi E., Ouyang, Pamela, Post, Wendy S., Lima, Joao A., Ying, Wendy, Kass, David A., Hoogeveen, Ron C., Shah, Sanjiv J., Subramanya, Vinita, Michos, Erin D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033823/
https://www.ncbi.nlm.nih.gov/pubmed/31928156
http://dx.doi.org/10.1161/JAHA.119.013966
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author Zhao, Di
Guallar, Eliseo
Vaidya, Dhananjay
Ndumele, Chiadi E.
Ouyang, Pamela
Post, Wendy S.
Lima, Joao A.
Ying, Wendy
Kass, David A.
Hoogeveen, Ron C.
Shah, Sanjiv J.
Subramanya, Vinita
Michos, Erin D.
author_facet Zhao, Di
Guallar, Eliseo
Vaidya, Dhananjay
Ndumele, Chiadi E.
Ouyang, Pamela
Post, Wendy S.
Lima, Joao A.
Ying, Wendy
Kass, David A.
Hoogeveen, Ron C.
Shah, Sanjiv J.
Subramanya, Vinita
Michos, Erin D.
author_sort Zhao, Di
collection PubMed
description BACKGROUND: Cyclic guanosine monophosphate (cGMP) is a second messenger regulated through natriuretic peptide and nitric oxide pathways. Stimulation of cGMP signaling is a potential therapeutic strategy for heart failure with preserved ejection fraction (HFpEF) and atherosclerotic cardiovascular disease (ASCVD). We hypothesized that plasma cGMP levels would be associated with lower risk for incident HFpEF, any HF, ASCVD, and coronary heart disease (CHD). METHODS AND RESULTS: We conducted a case–cohort analysis nested in the ARIC (Atherosclerosis Risk in Communities) study. Plasma cGMP was measured in 875 participants at visit 4 (1996–1998), with oversampling of incident HFpEF cases. We used Cox proportional hazard models to assess associations of cGMP with incident HFpEF, HF, ASCVD (CHD+stroke), and CHD. The mean (SD) age was 62.4 (5.6) years and median (interquartile interval) cGMP was 3.4 pmol/mL (2.4–4.6). During a median follow‐up of 9.9 years, there were 283 incident cases of HFpEF, 329 any HF, 151 ASCVD, and 125 CHD. In models adjusted for CVD risk factors, the hazard ratios (95% CI) associated with the highest cGMP tertile compared with lowest for HFpEF, HF, ASCVD, and CHD were 1.88 (1.17–3.02), 2.18 (1.18–4.06), 2.84 (1.44–5.60), and 2.43 (1.19–5.00), respectively. In models further adjusted for N‐terminal‐proB‐type natriuretic peptide, associations were attenuated for HFpEF and HF but remained statistically significant for ASCVD (2.56 [1.26–5.20]) and CHD (2.25 [1.07–4.71]). CONCLUSIONS: Contrary to our hypothesis, higher cGMP levels were associated with incident CVD in a community‐based cohort. The associations of cGMP with HF or HFpEF may be explained by N‐terminal‐proB‐type natriuretic peptide, but not for ASCVD and CHD.
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spelling pubmed-70338232020-02-27 Cyclic Guanosine Monophosphate and Risk of Incident Heart Failure and Other Cardiovascular Events: the ARIC Study Zhao, Di Guallar, Eliseo Vaidya, Dhananjay Ndumele, Chiadi E. Ouyang, Pamela Post, Wendy S. Lima, Joao A. Ying, Wendy Kass, David A. Hoogeveen, Ron C. Shah, Sanjiv J. Subramanya, Vinita Michos, Erin D. J Am Heart Assoc Original Research BACKGROUND: Cyclic guanosine monophosphate (cGMP) is a second messenger regulated through natriuretic peptide and nitric oxide pathways. Stimulation of cGMP signaling is a potential therapeutic strategy for heart failure with preserved ejection fraction (HFpEF) and atherosclerotic cardiovascular disease (ASCVD). We hypothesized that plasma cGMP levels would be associated with lower risk for incident HFpEF, any HF, ASCVD, and coronary heart disease (CHD). METHODS AND RESULTS: We conducted a case–cohort analysis nested in the ARIC (Atherosclerosis Risk in Communities) study. Plasma cGMP was measured in 875 participants at visit 4 (1996–1998), with oversampling of incident HFpEF cases. We used Cox proportional hazard models to assess associations of cGMP with incident HFpEF, HF, ASCVD (CHD+stroke), and CHD. The mean (SD) age was 62.4 (5.6) years and median (interquartile interval) cGMP was 3.4 pmol/mL (2.4–4.6). During a median follow‐up of 9.9 years, there were 283 incident cases of HFpEF, 329 any HF, 151 ASCVD, and 125 CHD. In models adjusted for CVD risk factors, the hazard ratios (95% CI) associated with the highest cGMP tertile compared with lowest for HFpEF, HF, ASCVD, and CHD were 1.88 (1.17–3.02), 2.18 (1.18–4.06), 2.84 (1.44–5.60), and 2.43 (1.19–5.00), respectively. In models further adjusted for N‐terminal‐proB‐type natriuretic peptide, associations were attenuated for HFpEF and HF but remained statistically significant for ASCVD (2.56 [1.26–5.20]) and CHD (2.25 [1.07–4.71]). CONCLUSIONS: Contrary to our hypothesis, higher cGMP levels were associated with incident CVD in a community‐based cohort. The associations of cGMP with HF or HFpEF may be explained by N‐terminal‐proB‐type natriuretic peptide, but not for ASCVD and CHD. John Wiley and Sons Inc. 2020-01-13 /pmc/articles/PMC7033823/ /pubmed/31928156 http://dx.doi.org/10.1161/JAHA.119.013966 Text en © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Research
Zhao, Di
Guallar, Eliseo
Vaidya, Dhananjay
Ndumele, Chiadi E.
Ouyang, Pamela
Post, Wendy S.
Lima, Joao A.
Ying, Wendy
Kass, David A.
Hoogeveen, Ron C.
Shah, Sanjiv J.
Subramanya, Vinita
Michos, Erin D.
Cyclic Guanosine Monophosphate and Risk of Incident Heart Failure and Other Cardiovascular Events: the ARIC Study
title Cyclic Guanosine Monophosphate and Risk of Incident Heart Failure and Other Cardiovascular Events: the ARIC Study
title_full Cyclic Guanosine Monophosphate and Risk of Incident Heart Failure and Other Cardiovascular Events: the ARIC Study
title_fullStr Cyclic Guanosine Monophosphate and Risk of Incident Heart Failure and Other Cardiovascular Events: the ARIC Study
title_full_unstemmed Cyclic Guanosine Monophosphate and Risk of Incident Heart Failure and Other Cardiovascular Events: the ARIC Study
title_short Cyclic Guanosine Monophosphate and Risk of Incident Heart Failure and Other Cardiovascular Events: the ARIC Study
title_sort cyclic guanosine monophosphate and risk of incident heart failure and other cardiovascular events: the aric study
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033823/
https://www.ncbi.nlm.nih.gov/pubmed/31928156
http://dx.doi.org/10.1161/JAHA.119.013966
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