@article{Lees2023,

title = {Sex differences in associations between creatinine and cystatin C-based kidney function measures with stroke and major bleeding},

author = {Jennifer Susan Lees and Nicole L De La Mata and Michael K Sullivan and Melanie L Wyld and Brenda M Rosales and Rachel Cutting and James Alan Hedley and Elaine Rutherford and Patrick Barry Mark and Angela C Webster},

doi = {10.1177/23969873231173282},

issn = {2396-9881},

year  = {2023},

date = {2023-09-00},

urldate = {2023-09-00},

journal = {European Stroke Journal},

volume = {8},

number = {3},

pages = {756--768},

publisher = {SAGE Publications},

abstract = {<jats:sec><jats:title>Purpose:</jats:title><jats:p> We sought to explore whether adding kidney function biomarkers based on creatinine (eGFR<jats:sub>Cr</jats:sub>), cystatin C (eGFR<jats:sub>Cys</jats:sub>) or a combination of the two (eGFR<jats:sub>Cr-Cys</jats:sub>) could improve risk stratification for stroke and major bleeding, and whether there were sex differences in any additive value of kidney function biomarkers. </jats:p></jats:sec><jats:sec><jats:title>Method:</jats:title><jats:p> 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<jats:sub>Cr</jats:sub>, eGFR<jats:sub>Cys</jats:sub> and eGFR<jats:sub>Cr-Cys</jats:sub> (mL/min/1.73 m<jats:sup>2</jats:sup>) with ischaemic and haemorrhagic stroke, major bleeding (gastrointestinal or intracranial, including haemorrhagic stroke) and all-cause mortality. </jats:p></jats:sec><jats:sec><jats:title>Findings:</jats:title><jats:p> 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<jats:sub>Cys</jats:sub> was more strongly associated with ischaemic stroke than eGFR<jats:sub>Cr</jats:sub>: 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<jats:sup>2</jats:sup> decline in eGFR<jats:sub>Cys</jats:sub>). This interaction effect was also demonstrated for eGFR<jats:sub>Cr-Cys</jats:sub>, but not eGFR<jats:sub>Cr</jats:sub>. eGFR<jats:sub>Cys</jats:sub> and eGFR<jats:sub>Cr-Cys</jats:sub> were more strongly associated with major bleeding and all-cause mortality than eGFR<jats:sub>Cr</jats:sub> in both men and women. Event numbers were small for haemorrhagic stroke. </jats:p></jats:sec><jats:sec><jats:title>Discussion:</jats:title><jats:p> To a greater degree than is seen in men, eGFR<jats:sub>Cr</jats:sub> underestimates risk of ischaemic stroke and major bleeding in women compared to eGFR<jats:sub>Cys</jats:sub>. The difference between measures is likely explained by non-GFR biology of creatinine and cystatin C. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> 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. </jats:p></jats:sec>},

keywords = {Cardiology and Cardiovascular Medicine, Neurology (clinical), SHE-ROCKS},

pubstate = {published},

tppubtype = {article}

}