Sex-specific associations of obesity and N-terminal pro-B-type natriuretic peptide levels in the general population

Background: Obese subjects have lower natriuretic peptide levels, but males and females have different anthropometric characteristics and fat distribution. Whether obesity-associated lowering of natriuretic peptides differs among males and females is unknown. Therefore, we investigated sex-specific associations of obesity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels among adults in the general population. Methods and results: Using 8260 participants (50.1% females) from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort, we evaluated the relationship of NT-proBNP levels with obesity-associated parameters, i.e. waist circumference (WC), body mass index (BMI) and body weight in the overall population, and in males and females separately. NT-proBNP levels were higher in females (median, interquartile range: 50.5, 28.2–87.0 ng/L) than in males (24.3, 10.1–54.6 ng/L; P < 0.001). In the overall population, NT-proBNP levels were significantly lower in heavier individuals and displayed a ‘U-shaped’ relationship with increasing WC, but were not associated with BMI. After sex stratification, there was no significant association between NT-proBNP concentrations and anthropometric measures in females. However, in males increasing WC and BMI were associated with higher NT-proBNP levels (P < 0.05) while increasing body weight was associated with slightly lower NT-proBNP levels (P < 0.05). Age strongly confounded the association of NT-proBNP levels with obesity, and age-associated increases in NT-proBNP were significantly higher in males than in females (P < 0.001). In multivariable adjusted analyses, the inverse association of obesity and NT-proBNP levels was also significantly modified by sex: NT-proBNP levels were lower with increasing WC, BMI and body weight among females compared with males (P _interaction < 0.05). After also accounting for BMI, abdominal obesity was associated with lower NT-proBNP levels in females, but not in males (P _interaction < 0.001). Conclusions: Natriuretic peptide deficiency in obesity mostly pertains to females with abdominal obesity, whereas the relationship between obesity and natriuretic peptides appears to be more complex in males.