Association of distinct biomarker profiles with all-cause and cause-specific mortality in older adults: Prospective cohort study across 12 countries.

Abstract

Background and aim: Biomarkers may help predict mortality risk in older adults, yet their combined effects remain unclear. This study aims to identify distinct biomarker profiles in older adults and assess their association with all-cause and cause-specific mortality risk.

Methods and results: We analyzed data from 12,960 older adults (67.8 ± 9.4 years, 58 % women) from 11 European countries and Israel participating in Survey of Health, Ageing and Retirement in Europe. Seven biomarkers were assessed from dried blood spot samples. K-means cluster analysis identified nine distinct biomarker profiles. Cox regression and Fine and Gray subdistribution hazard models assessed the association between biomarker profiles and all-cause and cause-specific mortality, respectively, adjusting for relevant covariates. During a median follow-up of 6.3 years, 1270 (9.8 %) died. Compared to the largest cluster (n = 7005) with generally normal biomarker levels, clusters characterized by elevated C-reactive protein (CRP) and cystatin C showed increased risk of all-cause mortality, cardiovascular disease mortality and to some extent cancer mortality. A cluster with elevated glycated hemoglobin (HbA1c) (n = 1959) showed slightly increased mortality risk (HR 1.29, 95%CI 1.08-1.54). A cluster with high triglyceride and total cholesterol (n = 1622) showed decreased cancer mortality risk (SHR 0.60, 95 % CI: 0.38-0.96).

Conclusions: Biomarker profiles characterized by elevated inflammatory and renal function markers were strongly associated with increased mortality risk, even when other biomarkers were within normal ranges. Surprisingly, high levels of triglyceride and total cholesterol may be protective against cancer mortality. These findings highlight the importance of considering multiple biomarkers simultaneously in mortality risk stratification for older adults.