Anthropometric adiposity measures and natriuretic peptides in heart failure screening: population-based evidence from the PORTHOS study

BACKGROUND: Obesity is linked to heart failure, particularly with preserved ejection fraction, but is associated with lower natriuretic peptide levels, potentially leading to underdiagnosis. AIMS: To examine the association between adiposity measures-body mass index, waist circumference, and waist-to-height ratio-and N-terminal pro-B-type natriuretic peptide levels, and to determine if lower cut-offs should be used to rule out heart failure in individuals with obesity. METHODS: PORTHOS is a 2023 population-based study in Portugal including adults aged 50 years or older. Participants underwent N-terminal pro-B-type natriuretic peptide screening, followed by clinical and echocardiographic assessment in those with levels >= 125 pg/mL, self-reported heart failure, or a 5% random sample with levels <125 pg/mL. RESULTS: Among 2498 participants, obesity prevalence range from 25% using body mass index ≥30 kg/m² to >70% using waist-to-height ratio ≥0.6. Body mass index showed a strong inverse association with N-terminal pro-B-type natriuretic peptide, with approximately 50 pg/mL lower levels per 5 kg/m² increase. Individuals with obesity and peptide levels < 125 pg/mL had higher odds of heart failure symptoms (odds ratio 1.97, 95% confidence interval 1.15-3.38) and echocardiographic abnormalities (odds ratio 3.63, 95% confidence interval 1.27-10.4) than lean participants with levels >= 125 pg/mL, despite being 9 years younger and having fourfold lower median peptide levels (59 vs 235 pg/mL). CONCLUSIONS: Obesity is associated with lower N-terminal pro-B-type natriuretic peptide levels despite a higher burden of symptoms and structural abnormalities. Fixed cut-offs do not reliably exclude heart failure in individuals with obesity.