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Frailty for cardiovascular risk stratification in CKM syndrome stages 0-3: a UK Biobank prospective cohort study

Junhong Wang1, Ying Zhao2, Zongzong Ma3

  • 1Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.

Frontiers in Cardiovascular Medicine
|August 20, 2026
PubMed

Insights

Frailty, a condition sharing mechanisms with cardiovascular-kidney-metabolic (CKM) syndrome, significantly increases cardiovascular disease risk. Both physical frailty and frailty index predict higher risks in individuals with CKM stages 0-3.

Area of Science:

  • Gerontology
  • Cardiology
  • Metabolic Health

Background:

  • Frailty shares pathophysiological mechanisms with cardiovascular-kidney-metabolic (CKM) syndrome.
  • Frailty may contribute to cardiovascular risk, but evidence in early CKM stages is limited.

Purpose of the Study:

  • To investigate the association of physical frailty and frailty index with cardiovascular outcomes in individuals with CKM stages 0-3.
  • To determine if frailty assessment aids cardiovascular risk stratification in the CKM continuum.

Main Methods:

  • Prospective cohort study of 330,197 participants with CKM stages 0-3 from UK Biobank.
  • Physical frailty assessed via modified Fried phenotype; frailty index via 49-item deficit model.
  • Incident cardiovascular disease (CVD) identified via ICD-10 codes; associations analyzed using Cox models.

Main Results:

  • Both physical frailty and frailty index significantly increased risks of CVD and its subtypes (all p < 0.001).
  • Each one-score increase in physical frailty associated with 21% higher CVD risk (HR 1.21); each 0.1-unit frailty index increase with 40% higher risk (HR 1.40).
  • Significant dose-response relationships observed; frailty index showed greater incremental predictive value.

Conclusions:

  • Physical frailty and frailty index are independently associated with increased CVD risks in individuals with CKM stages 0-3.
  • Frailty assessment offers complementary information for cardiovascular risk stratification within the CKM continuum.
Abstract

Keywords:
CKM syndromeUK Biobankcardiovascular diseasefrailty indexphysical frailty

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