Abstract 16098: Circulating Cyclic GMP: Relationship With Cardiovascular and Renal Disease in the General Community
Introduction: The 3’,5’ cyclic guanosine monophosphate (cGMP) is a second messenger for several physiological pathways, among which the atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) predominate. These two peptides are released by the heart as a compensatory response to volume overload and they induce vasodilation and natriuresis. In the PARADIGM trial, the angiotensin-neprilysin inhibitor LCZ696, which mediated an increase in BNP and cGMP levels, was associated with reduced mortality and hospitalization in heart failure (HF) underscoring cGMP as a therapeutic target in cardiovascular (CV) disease. To date, the relationship between circulating cGMP levels and the CV and renal phenotype is unknown.
Hypothesis: In CV and renal diseases, circulating cGMP is elevated as a compensatory response.
Methods: We evaluated cGMP levels in a community cohort (n=1910) from Olmsted County, MN and assessed relationships with cardiorenal parameters and diseases.
Results: In the age-and-sex-adjusted analysis, plasma cGMP was associated with HF (OR: 1.5; 95% CI, 1.1-2; p=0.01), myocardial infarction (MI) (OR: 1.4; 95% CI, 1.1-1.7; p=0.004), hypertension (HTN) (OR: 1.2; 95% CI, 1.1-1.3; p=0.0008), impaired glomerular filtration rate (GFR) (OR: 1.2; 95% CI, 1-1.4; p=0.008) and ejection fraction < 40% (OR: 2.2; 95% CI, 1.5-3.2; p< 0.0001). Importantly, cGMP values positively correlated with ANP (beta estimate: 0.1; 95% CI, 0.1-0.2; p< 0.0001) and BNP (beta estimate: 0.2; 95% CI, 0.1-0.2; p< 0.0001) circulating levels. After adjusting for ANP and BNP, cGMP levels remained associated with HTN (OR: 1.2; 95% CI, 1-1.3; p=0.006) and impaired GFR (OR: 1.2; 95% CI, 1-1.4; p=0.009).
Conclusions: In a community cohort from Olmsted County, MN, circulating levels of cGMP are associated with HF, MI and impaired ventricular function. Independent of ANP and BNP plasma values, cGMP levels are positively associated with HTN and impaired GFR. Through the ANP and BNP pathway as well as other pathways cGMP may be a mediator of the compensatory and protective response to compromised CV and renal homeostasis. Augmenting this cGMP compensatory response may be a relevant therapeutic target. Further, cGMP may also serve as a novel biomarker for cardiorenal diseases.
Author Disclosures: V. Cannone: None. C.G. Scott: None. K.R. Bailey: None. D.M. Heublein: None. M.M. Redfield: None. R.J. Rodeheffer: None. J. Stasch: None. J.C. Burnett Jr.: None.
- © 2016 by American Heart Association, Inc.