Etiological Subtypes of Transient Ischemic Attack and Ischemic Stroke in Chronic Kidney Disease Population-Based Study

Background and Purpose: Chronic kidney disease (CKD) is strongly associated with stroke risk, but the mechanisms underlying this association are unclear and might be informed by subtype-specific analyses. However, few studies have reported stroke subtypes in CKD according to established classification systems, such as the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria. We, therefore, aimed to determine which transient ischemic attack and ischemic stroke subtypes using the TOAST classification occur most frequently in patients with CKD. Methods: In a population-based study of all transient ischemic attack and stroke (OXVASC [Oxford Vascular Study]; 2002-2017), all ischemic events were classified by TOAST subtypes (cardioembolism, large artery disease, small vessel disease, undetermined, multiple, other etiology, or incompletely investigated). Logistic regression was used to determine the relationship between CKD (defined as an estimated glomerular filtration rate <60 mL/min per 1.73 m2) and transient ischemic attack/stroke subtypes adjusted for age, sex, and hypertension and then stratified by age and estimated glomerular filtration rate category. Results: Among 3178 patients with transient ischemic attack (n=1167), ischemic stroke (n=1802), and intracerebral hemorrhage (n=209), 1267 (40%) had CKD. Although there was a greater prevalence of cardioembolic events (31.8% versus 21.2%;P<0.001) in patients with CKD, this association was lost after adjustment for age, sex, and hypertension (adjusted odds ratio=1.20 [95% CI, 0.99-1.45];P=0.07). Similarly, although patients with CKD had a lower prevalence of small vessel disease (8.8% versus 13.6%;P<0.001), undetermined (26.1% versus 39.4%;P<0.001), and other etiology (1.0% versus 3.6%;P<0.001) subtypes, these associations were also lost after adjustment (adjusted odds ratio=0.86 [0.65-1.13];P=0.27 and 0.73 [0.36-1.43];P=0.37 for small vessel disease and other defined etiology, respectively) for all but undetermined (adjusted odds ratio=0.81 [0.67-0.98];P=0.03). Conclusions: There were no independent positive associations between CKD and specific TOAST subtypes, which suggest that renal-specific risk factors are unlikely to play an important role in the etiology of particular subtypes. Future studies of stroke and CKD should report subtype-specific analyses to gain further insights into potential mechanisms.