Abstract
Purpose: We sought to explore whether adding kidney function biomarkers based on creatinine (eGFR Cr ), cystatin C (eGFR Cys ) or a combination of the two (eGFR Cr-Cys ) could improve risk stratification for stroke and major bleeding, and whether there were sex differences in any additive value of kidney function biomarkers. Method: We included participants from the UK Biobank who had not had a previous ischaemic or haemorrhagic stroke or major bleeding episode, and who had kidney function measures available at baseline. Cause-specific Cox proportional hazards models tested associations between eGFR Cr , eGFR Cys and eGFR Cr-Cys (mL/min/1.73 m 2 ) with ischaemic and haemorrhagic stroke, major bleeding (gastrointestinal or intracranial, including haemorrhagic stroke) and all-cause mortality. Findings: Among 452,879 eligible participants, 246,244 (54.4%) were women. Over 11.5 (IQR 10.8-12.2) years, there were 3706 ischaemic strokes, 795 haemorrhagic strokes, 26,025 major bleeding events and 28,851 deaths. eGFR Cys was more strongly associated with ischaemic stroke than eGFR Cr : an effect that was more pronounced in women (men - HR: 1.16, 95% CI: 1.12-1.19; female to male comparison - HR: 1.11, 95% CI: 1.05-1.16, per 10 mL/min/1.73 m 2 decline in eGFR Cys ). This interaction effect was also demonstrated for eGFR Cr-Cys , but not eGFR Cr . eGFR Cys and eGFR Cr-Cys were more strongly associated with major bleeding and all-cause mortality than eGFR Cr in both men and women. Event numbers were small for haemorrhagic stroke. Discussion: To a greater degree than is seen in men, eGFR Cr underestimates risk of ischaemic stroke and major bleeding in women compared to eGFR Cys . The difference between measures is likely explained by non-GFR biology of creatinine and cystatin C. Conclusion: Enhanced measurement of cystatin C may improve risk stratification for ischaemic stroke and major bleeding and clinical treatment decisions in a general population setting, particularly for women.
10 Authors
- Jennifer Susan Lees
- Nicole L De La Mata
- Michael K Sullivan
- Melanie L Wyld
- Brenda M Rosales
- Rachel Cutting
- James Alan Hedley
- Elaine Rutherford
- Patrick Barry Mark
- Angela C Webster
1 Application
Application ID | Title |
69891 | LEAP-CKD: Lifestyle, Environment And Physiology: an exploration of the association with future chronic kidney disease |