Scientific Rationale
Cardiometabolic health represents a central physiological system underlying aging-related morbidity and mortality. Cardiometabolic burden-including adiposity, dysregulated glucose, blood pressure, lipid metabolism, and kidney dysfunctions-accumulates dynamically across adulthood. While recent studies increasingly consider multiple factors, they often aggregate exposures at isolated time points or summarize them using static indices. Such approaches may inadequately capture long-term exposure patterns, timing, and inter-person heterogeneity that are critical for understanding aging processes, highlighting the need for a life-course trajectory-based approach.
Age-related outcomes encompass not only clinically defined diseases (e.g. ASCVD and stroke) but also cognitive and functional changes that collectively shape quality of life (e.g. dementia and frailty). Focusing exclusively on disease endpoints may underestimate the broader impact of long-term cardiometabolic exposure on aging. Evaluating a spectrum of age-related outcomes enables a more comprehensive assessment on how cardiometabolic health trajectories influence both pathological and healthy aging.
UK Biobank offers a unique platform to address these questions through repeated cardiometabolic measurements, comprehensive outcome ascertainment, and the capacity for refined phenotyping within a clinical epidemiology framework.
Research Objectives
1.To characterize life-course cardiometabolic health trajectories across adulthood using repeated clinical and biomarker data.
2.To examine the association between cardiometabolic health trajectories and a range of age-related outcomes.
3.To assess heterogeneity in aging-related outcomes according to timing and progression of cardiometabolic burden, including potential modification by social and lifestyle risk factors.
4.To explore whether refined phenotyping approaches may enhance risk stratification for age-related outcomes.