Cardiovascular

Sex-specific clinical profiles in patients with acute ischemic stroke and chronic kidney disease.

Holden-Kapshuck S, Pham D, et al. • Frontiers in neurology • 2026

PubMed 42890522 DOI 10.3389/fneur.2026.1959768
TL;DR

Patients with acute ischemic stroke demonstrated distinct sex-associated clinical profiles according to CKD status, with associations of male sex with sleep apnea, smoking, and diastolic blood pressure ≥80 mmHg being numerically stronger in the CKD group, though formal interaction testing did not establish statistically significant effect modification.

Key Findings

Results

Among 5,469 AIS patients, 8.2% had documented CKD.

  • Total cohort included 5,469 patients with acute ischemic stroke.
  • 447 patients (8.2%) had documented CKD.
  • Data were drawn from a retrospective analysis of the PRISMA Health Stroke Registry.
  • Baseline characteristics were compared between patients with and without documented CKD in the overall cohort and after stratification by sex.
Results

Prosthetic heart valve was the strongest independent characteristic associated with documented CKD among AIS patients.

  • Prosthetic heart valve was associated with documented CKD with an OR of 3.73.
  • Elevated serum creatinine was associated with CKD with an OR of 2.79.
  • Obesity was associated with CKD with an OR of 2.51.
  • Heart failure was associated with CKD with an OR of 2.21.
  • Multivariable logistic regression with backward likelihood-ratio selection was used to identify independent characteristics.
Results

Hypertension, African American race, and depression were independently associated with documented CKD in AIS patients.

  • Hypertension was associated with CKD with an OR of 2.20.
  • African American race was associated with CKD with an OR of 2.11.
  • Depression was associated with CKD with an OR of 1.97.
  • Adjusted odds ratios and 95% confidence intervals were calculated for all independent predictors.
  • Internal stability was assessed using bootstrap resampling.
Results

The association of male sex with sleep apnea was numerically stronger among AIS patients with CKD than those without CKD.

  • In the CKD subgroup, the OR for male sex associated with sleep apnea was 4.62.
  • In the non-CKD subgroup, the OR for male sex associated with sleep apnea was 2.38.
  • These estimates were derived from stratified multivariable logistic regression models.
  • Formal interaction testing did not demonstrate statistically significant effect modification by CKD status.
Results

The association of male sex with smoking was numerically stronger among AIS patients with CKD than those without CKD.

  • In the CKD subgroup, the OR for male sex associated with smoking was 3.19.
  • In the non-CKD subgroup, the OR for male sex associated with smoking was 1.31.
  • Despite the numerical difference, formal interaction testing did not establish statistically significant effect modification by CKD status.
  • Analyses were conducted within stratified sex-association models.
Results

The association of male sex with diastolic blood pressure ≥80 mmHg was numerically stronger in the CKD subgroup than the non-CKD subgroup.

  • In the CKD subgroup, the OR for male sex associated with diastolic blood pressure ≥80 mmHg was 2.58.
  • In the non-CKD subgroup, the corresponding OR was 1.43.
  • Formal interaction testing did not demonstrate statistically significant effect modification by CKD status.
  • This finding was part of stratified analyses comparing sex-associated clinical profiles across CKD subgroups.
Results

The sex-association model among AIS patients with CKD demonstrated greater apparent discrimination than the corresponding non-CKD model.

  • The AUC for the sex-association model in the CKD subgroup was 0.785.
  • The AUC for the sex-association model in the non-CKD subgroup was 0.630.
  • This difference in model discrimination suggests greater clinical heterogeneity between men and women in the CKD population.
  • Internal stability of models was assessed using bootstrap resampling.
Results

Formal interaction testing did not establish statistically significant effect modification by CKD status for the sex-associated clinical characteristics examined.

  • Despite numerically stronger associations of male sex with sleep apnea, smoking, and diastolic blood pressure ≥80 mmHg in the CKD group, no statistically significant interaction was detected.
  • The authors note these findings 'warrant further investigation to determine whether these profiles have implications for treatment or outcomes.'
  • The absence of significant interaction testing limits causal conclusions about CKD as an effect modifier of sex-associated clinical profiles.

What This Means

This research examined whether men and women who have both a stroke and chronic kidney disease (CKD) present with different clinical characteristics compared to stroke patients without CKD. Using a registry of 5,469 stroke patients, the researchers found that about 8% had documented CKD. Several conditions were strongly linked to having CKD among stroke patients, including prosthetic heart valves, elevated kidney function markers in the blood, obesity, heart failure, high blood pressure, African American race, and depression. When the researchers looked at differences between men and women separately within the CKD and non-CKD groups, they found that certain characteristics associated with being male — specifically sleep apnea, smoking history, and having a diastolic blood pressure of 80 mmHg or higher — showed numerically larger differences in the CKD group than in the non-CKD group. For example, male stroke patients with CKD were about 4.6 times more likely to have sleep apnea compared to female CKD stroke patients, whereas male stroke patients without CKD were only about 2.4 times more likely. The model predicting sex among CKD patients also performed better than the one for non-CKD patients, suggesting the two groups are clinically more distinct from each other. However, formal statistical tests did not confirm that CKD status significantly changed these sex-related associations. This research suggests that men and women experiencing strokes may present with different clinical patterns depending on whether they also have CKD, particularly regarding sleep apnea, smoking, and blood pressure. While the differences were not statistically confirmed as being driven by CKD status itself, the findings highlight clinical complexity in this population and point to the need for further study to understand whether these sex-specific profiles affect treatment decisions or patient outcomes.

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Citation

Holden-Kapshuck S, Pham D, Holler G, Roper G, Nathaniel S, Dang A, et al.. (2026). Sex-specific clinical profiles in patients with acute ischemic stroke and chronic kidney disease.. Frontiers in neurology. https://doi.org/10.3389/fneur.2026.1959768