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Abstract: TH-PO682

Proteinuria as an Independent Predictor of Stroke: Systematic Review and Meta-Analysis

Session Information

Category: Hypertension and CVD

  • 1401 Hypertension and CVD: Epidemiology, Risk Factors, and Prevention


  • Kelly, Dearbhla, University of Oxford, Oxford, United Kingdom
  • Rothwell, Peter M., University of Oxford, Oxford, United Kingdom

Proteinuria has emerged as an important vascular risk factor for adverse cardiovascular events including stroke. Hypertension has been proposed as the principal confounder of this relationship but its role has not been systematically examined. We aimed to determine if proteinuria remains an independent predictor of stroke after more complete adjustment for blood pressure (BP).


We performed a systematic review, searching MEDLINE and EMBASE (to February 2018) for cohort studies or randomized controlled trials that reported stroke incidence in adults according to baseline proteinuria +/- glomerular filtration rate (eGFR). Study and participant characteristics and relative risks (RR) were extracted. Estimates were combined using a random effects model. Heterogeneity was assessed by x2 statistics and I2, and by subgroup strata and meta-regression, with a particular focus on the impact of more complete adjustment for blood pressure (BP) on the association. The quality of cohort studies and posthoc analyses was assessed using the Newcastle–Ottawa Scale.


We identified 38 studies comprising 1,735,390 participants with 26,405 stroke events. Overall, the presence of any level of proteinuria was associated with greater stroke risk (18 studies; Pooled crude RR 2.00, 95%CI 1.63-2.46; p<0.001) even after adjustment for established cardiovascular risk factors (33 studies; Pooled adjusted RR 1.72, 1.51-1.95; p<0.001), albeit with considerable heterogeneity between studies (p< 0.001; I2=77.3%). Moreover, the association did not substantially attenuate with more thorough adjustment for hypertension: single baseline BP measure (10 studies; Pooled adjusted RR=1.92, 1.39-2.66; p<0.001); history or treated hypertension (4 studies; Pooled adjusted RR=1.76, 1.13-2.75, p=0.013); multiple BP measurements over months to years (4 studies; RR=1.68, 1.33-2.14; p<0.001).


Even after extensive adjustment, proteinuria is strongly and independently associated with incident stroke risk, possibly indicating a shared renal and cerebral susceptibility to vascular injury that is not fully explained by traditional vascular risk factors.