ObjectiveThe aim of this study was to study the prospective association between N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and changes in weight and obesity risk in a community‐based population.MethodsData from 9,681 participants from the Atherosclerosis Risk in Communities Study were analyzed at two time points 6 years apart. Among people without obesity at baseline, multivariable logistic regression models were used to examine the association between baseline levels of NT‐proBNP and incident obesity. A multivariable linear regression model was used to examine the association between changes in NT‐proBNP (visit 2 serum and visit 4 plasma samples) and changes in weight.ResultsThe prevalence of obesity increased from 28% to 35% in the 6‐year follow‐up period. Compared with individuals in the highest NT‐proBNP quartile, those in the lowest were more likely to have obesity at baseline (odds ratio 1.25; 95% CI: 1.08‐1.45) and, among people who did not have obesity at baseline, were more likely to develop obesity at follow‐up (odds ratio 1.35; 95% CI: 1.07‐1.69). Changes in NT‐proBNP were inversely associated with weight change.ConclusionsIn this prospective study, lower levels of NT‐proBNP were associated with higher risk of obesity, and changes in NT‐proBNP were inversely associated with changes in weight. This suggests that natriuretic peptides or their pathways may be potential targets in the treatment of obesity.

Introduction: Natriuretic peptides are regulators of the cardiovascular system that are also related to adiposity and insulin resistance. NT-proBNP levels are inversely associated with adiposity and increase with weight loss, which may have hemodynamic implications in obesity. However, it is unclear if the changes in NT-proBNP with weight loss are independent of changes in insulin resistance and related metabolic risk factors. Hypothesis: NT-proBNP increases with surgical weight loss are partially independent of changes in other metabolic risk factors. Methods: We investigated 71 patients from the BARI-Heart Study, a prospective cohort with anthropometrics, metabolic risk factors and biomarkers before and after bariatric surgery. We compared data between pre- and post-surgical visits (1-2 weeks and 6 months, respectively) using t-tests, and performed regression analysis examining the association of changes adiposity measures with NT-proBNP before and after adjusting for metabolic risk factors. Results: After bariatric surgery, major reductions in weight, body-mass index (BMI) and body fat percentage (BFP) (mean change) were observed (Table 1), whereas NT-proBNP levels increased (mean change +61 pg/mL, SD 104). There were significant reductions post-surgery in HOMA-IR (from 9.9 to 2.6; p <0.0001), as well as in triglycerides, total cholesterol, glucose, and blood pressure (all p<0.05). A negative correlation between changes in ln-NT-proBNP and BFP was found ( r -0.27; p=0.03). In regression analysis, the inverse association remained statistically significant after adjustment for changes in the other metabolic risk factors (Table 2). Conclusions: Reductions in adiposity are linked to increases in NT-proBNP independent of changes in metabolic risk factors. The mechanisms and cardiovascular implications of this direct link between weight loss and NT-proBNP deserve further investigation.

Introduction: Natriuretic peptides (NPs) are biochemical markers of cardiac function and NTproBNP strongly predicts heart failure. NPs also have a role in the adipose tissue, stimulating lipolysis, mitochondrial biogenesis and browning of adipocytes. Cross-sectional studies have demonstrated that diabetes and higher levels of adiposity are paradoxically associated with lower levels of BNP and NT-proBNP, suggesting that NPs may protect against metabolic dysregulation. Methods: We hypothesized that increases in NT-proBNP over time would be associated with decreases in weight and a lower risk of obesity in a community-based population. We analyzed data from 10,093 participants from the Atherosclerosis Risk in Communities (ARIC) Study with measurements of NT-proBNP at two time points 6-years apart (visit 2, 1990-92 and visit 4, 1996-98). Multivariable regression models were used, and sensitivity analysis excluding patients with heart failure was performed. Results: Mean age at baseline (1990-1992) was 57 years (SD 6), 57% were women and 78% were white. The prevalence of obesity increased from 28% to 35% in the 6-year follow up period. Higher baseline levels of NT-proBNP were associated with reduced risk of obesity after adjustment for other risk factors ( Table ). There was an inverse association between change in NT-proBNP levels between the visits and weight change ( Figure ). Results were similar after excluding cases of heart failure. Conclusions: We found inverse associations of NT-proBNP levels with weight change and incidence of obesity. Our results suggest that NPs or their pathways may be potential targets in the treatment of obesity. Nonetheless, the molecular networks involving the natriuretic system are complex and additional work, especially intervention studies, are needed to address the clinical relevance of this finding.