Sex differences in associations between creatinine and cystatin C-based kidney function measures with stroke and...

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.