Frailty as a Risk-Enhancing Factor Across the Cardiovascular-Kidney-Metabolic Framework: Findings from the UK Biobank

Area of Science:

• Gerontology
• Cardiology
• Metabolic Health

Background:

• Frailty is linked to increased cardiovascular disease (CVD) risk.
• The role of frailty within the cardiovascular-kidney-metabolic (CKM) framework is not well understood.
• Understanding frailty's impact across CKM stages is crucial for comprehensive risk assessment.

Purpose of the Study:

• To investigate the association between frailty and incident CVD.
• To examine this association across different stages of the CKM framework.
• To determine if frailty is an independent risk factor for CVD within the CKM context.

Main Methods:

• Prospective cohort study of 408,163 UK Biobank participants without baseline CVD.
• Frailty assessed using Fried frailty phenotype (robust, pre-frail, frail).
• CKM stages (0-3) defined by AHA criteria; incident CVD ascertained via hospital and mortality records; Cox models used for analysis.

Main Results:

• Over 15.1 years, 61,766 participants developed CVD.
• 15-year CVD incidence: 13.1% (robust), 17.7% (pre-frail), 30.5% (frail).
• Pre-frailty and frailty significantly associated with higher CVD risk (HR 1.24, 1.85 respectively) across all CKM stages.

Conclusions:

• Frailty is consistently associated with incident CVD across the entire CKM spectrum.
• Frailty identifies additional cardiovascular vulnerability beyond traditional CKM variables.
• Frailty serves as a complementary, risk-enhancing factor within the CKM framework.