Background— Experimental studies suggest that the natriuretic peptides influence lipid and fatty acid metabolism. Although it has been shown that obese individuals have reduced natriuretic peptide levels, conflicting data exist on the relation of natriuretic peptide levels to other metabolic risk factors.

Methods and Results— We examined the association of plasma levels of B-type natriuretic peptide and N-terminal pro-atrial natriuretic peptide with metabolic risk factors, the metabolic syndrome, and insulin resistance in 3333 Framingham study participants free of heart failure (mean age, 58 years; 54% women). Regression analyses were performed, with adjustment for clinical and echocardiographic variables. Plasma natriuretic peptide levels were inversely associated with all components of the metabolic syndrome except for elevated blood pressure. Adjusted natriuretic peptide levels were lower in persons with the metabolic syndrome compared with those without the metabolic syndrome: In men, B-type natriuretic peptide was 24% lower (P<0.001) and N-terminal pro-atrial natriuretic peptide was 16% lower (P<0.001); in women, B-type natriuretic peptide was 29% lower (P<0.001) and N-terminal pro-atrial natriuretic peptide was 18% lower (P<0.001). Individuals with insulin resistance, as indicated by an elevated homeostasis model assessment (HOMA-IR) index, had lower levels of B-type natriuretic peptide (P=0.009 in men, P<0.001 in women) and N-terminal pro-atrial natriuretic peptide (P<0.001 in men, P=0.001 in women).

Conclusions— Having several metabolic risk factors is associated with low circulating natriuretic peptide levels, even after adjustment for body mass index. These findings raise the possibility that reduced natriuretic peptide activity is a manifestation of the metabolic syndrome, which may have important clinical and pathophysiological implications.