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Sex differences in associations between creatinine and cystatin C-based kidney function measures with stroke and
Jennifer Susan Lees1, Nicole L De La Mata2, Michael K Sullivan1
1School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
Insights
Cystatin C-based kidney function estimates (eGFRCys) better predict stroke and bleeding risk than creatinine-based estimates (eGFRCr), especially in women. This can improve clinical decisions and risk stratification.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Epidemiology
Background:
- Kidney function estimation is crucial for cardiovascular risk stratification.
- Creatinine-based estimated glomerular filtration rate (eGFRCr) is widely used but may have limitations.
- Cystatin C-based (eGFRCys) and combined (eGFRCr-Cys) measures offer alternative assessments of kidney function.
Purpose of the Study:
- To evaluate if eGFRCr, eGFRCys, or eGFRCr-Cys improve risk stratification for stroke and major bleeding.
- To investigate potential sex differences in the additive value of these kidney function biomarkers.
Main Methods:
- Utilized UK Biobank participants with baseline kidney function measures and no prior stroke or major bleeding.
- Employed cause-specific Cox proportional hazards models to assess associations with ischemic stroke, hemorrhagic stroke, major bleeding, and all-cause mortality.
- Compared risk associations across eGFRCr, eGFRCys, and eGFRCr-Cys.
Main Results:
- eGFRCys showed a stronger association with ischemic stroke risk than eGFRCr, particularly in women.
- eGFRCys and eGFRCr-Cys demonstrated stronger associations with major bleeding and all-cause mortality than eGFRCr in both sexes.
- Sex-specific interaction effects were observed for eGFRCys and eGFRCr-Cys, but not eGFRCr, regarding ischemic stroke risk.
Conclusions:
- eGFRCys and eGFRCr-Cys provide superior risk stratification for ischemic stroke and major bleeding compared to eGFRCr.
- The underestimation of risk by eGFRCr in women highlights the importance of cystatin C measurement.
- Incorporating cystatin C measurements may enhance clinical decision-making for cardiovascular risk assessment, especially in women.
Purpose:
We sought to explore whether adding kidney function biomarkers based on creatinine (eGFRCr), cystatin C (eGFRCys) or a combination of the two (eGFRCr-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 eGFRCr, eGFRCys and eGFRCr-Cys (mL/min/1.73 m2) 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. eGFRCys was more strongly associated with ischaemic stroke than eGFRCr: 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 m2 decline in eGFRCys). This interaction effect was also demonstrated for eGFRCr-Cys, but not eGFRCr. eGFRCys and eGFRCr-Cys were more strongly associated with major bleeding and all-cause mortality than eGFRCr in both men and women. Event numbers were small for haemorrhagic stroke.
Discussion:
To a greater degree than is seen in men, eGFRCr underestimates risk of ischaemic stroke and major bleeding in women compared to eGFRCys. 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.
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