Abstract 16186: Dyslipidemia May Represent a Cyclic GMP Deficiency State: Insights From a General Community
Introduction: The second messenger 3’,5’ cyclic guanosine monophosphate (cGMP) is the effector molecule for several pathways including the cardiac hormones atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP). Once released by the heart, ANP and BNP induce vasodilation and natriuresis. Importantly, they also possess metabolic properties enhancing lipolysis and insulin sensitivity. Moreover, the carriers of the ANP genetic variant rs5068, which is associated with increased plasma levels of natriuretic peptides (NPs), have higher HDL-cholesterol levels and decreased risk for obesity and metabolic syndrome (MS). Conversely, epidemiologic studies have shown that NPs plasma levels are decreased in MS, diabetes and obesity describing these diseases as “NPs deficiency states”. To date, the relationship between circulating cGMP levels and the metabolic phenotype is unknown.
Hypothesis: Circulating cGMP levels are decreased in metabolic diseases consistent with a cGMP deficiency.
Methods: We assessed plasma cGMP values in a community-based cohort from Olmsted County, MN (n= 1910) and analyzed the relationship with metabolic parameters and diseases.
Results: Values of cGMP positively correlated with ANP (beta estimate (BE): 0.15; 95% CI, 0.12-0.18; p< 0.0001) and BNP (BE: 0.18; 95% CI, 0.13-0.22; p< 0.0001) circulating levels. In the age-and-sex-adjusted analysis, cGMP levels were inversely related with total cholesterol (BE: -5.4; 95% LCL -7.1, 95% UCL -3.8; p< 0.0001), LDL cholesterol (BE: -3.9; 95% LCL -5.4, 95% UCL -2.4 ; p< 0.0001) and triglycerides (BE: -8.8; 95% LCL -12.7, 95% UCL -4.9 ; p< 0.0001). Further adjustment for NPs levels confirmed the association between cGMP and lipid values. Plasma cGMP levels did not correlate with body mass index, diabetes, obesity, glucose and insulin levels.
Conclusion: The second messenger cGMP is inversely related to total cholesterol, LDL cholesterol and triglycerides. Our findings suggest that the cGMP system may play a key role in metabolic homeostasis involving the NPs as well as other pathways. Lack of appropriate activation of cGMP may be a causative or facilitating factor of metabolic disease. Potentiating the activity of the cGMP pathway might lead to an improved metabolic risk profile.
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.