Association of proBNPage with all-cause and cardiovascular mortality among US adults: an analysis of data from the National Health and Nutrition Examination Survey.

OBJECTIVE

Biological age assessed by the Klemera and Doubal method (KDM) and phenotypic age (PhenoAge) was considered as a marker for ageing-related outcomes because it reflects different aspects of biological ageing and health, which are associated with increased risk of death. proBNPage based on N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a novel index for biological age estimation. However, the independence of its relationship with clinical outcomes from established risk factors, KDM or PhenoAge remains uncertain. Their identification could provide valuable information to prognosis.

DESIGN, SETTING AND PARTICIPANTS: This study analysed data from the general population included in the National Health and Nutrition Examination Survey (NHANES). Participants who took part in the cross-sectional survey from 1999 to 2004 were included, and all-cause as well as cardiovascular mortality was recorded (up to 31 December 2019).

OUTCOME MEASURES

All-cause and cardiovascular mortality were considered as outcomes. Clinical risk factors were collected, and biological age was estimated by proBNPage, KDM and PhenoAge. Cox proportional hazards models were used to determine the relationship between proBNPage and outcomes with adjustment for risk factors or other biological age indexes. Restricted cubic spline (RCS) analysis based on multivariate Cox regressions was performed to examine whether there was a non-linear relationship between proBNPage and outcomes.

RESULTS

A total of 9 925 participants were included in this study. The association between proBNPage and outcomes remained significant after adjusting for risk factors, including NT-proBNP (for all-cause mortality, HR 1.14; 95% CI 1.10 to 1.17; for cardiovascular mortality, HR 1.20; 95% CI 1.14 to 1.27). Similar results were obtained after adjusting for KDM plus NT-proBNP (for all-cause mortality, HR 1.31; 95% CI 1.22 to 1.41; for cardiovascular mortality, HR 1.21; 95% CI 1.11 to 1.28) or PhenoAge plus NT-proBNP (for all-cause mortality, HR 1.21; 95% CI 1.16 to 1.28; for cardiovascular mortality, HR 1.35; 95% CI 1.24 to 1.47). These findings were confirmed in most subgroups. A non-linear relationship was observed between proBNPage and all-cause and cardiovascular mortality with an inflection point.

CONCLUSIONS

A non-linear positive relationship was observed between proBNPage and clinical outcomes. After adjusting for established risk factors and other biological age estimation indices (KDM or PhenoAge), proBNPage was significantly associated with mortality. The results remain similar after further adjustment for NT-proBNP. These results suggest that proBNPage is a useful surrogate for biological age estimation.