Abstract
BackgroundProteinuria 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.AimWe aimed to determine if proteinuria remains an independent predictor of stroke after more complete adjustment for blood pressure.Summary of reviewWe 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. Study and participant characteristics and relative risks were extracted. Estimates were combined using a random effects model. Heterogeneity was assessed by χ2 statistics and I2, and by subgroup strata and meta-regression, with a particular focus on the impact of more complete adjustment for blood pressure on the association. The quality of cohort studies and post hoc 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 relative risk 2.00, 95%CI 1.63–2.46; p < 0.001) even after adjustment for established cardiovascular risk factors (33 studies; pooled adjusted relative risk 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 blood pressure measure (10 studies; pooled adjusted relative risk = 1.92, 1.39–2.66; p < 0.001); history or treated hypertension (four studies; pooled adjusted relative risk = 1.76, 1.13–2.75, p = 0.013); multiple blood pressure measurements over months to years (four studies; relative risk = 1.68, 1.33–2.14; p < 0.001).ConclusionsEven after extensive adjustment for hypertension, 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.
Highlights
Proteinuria has emerged as an important vascular risk factor for adverse cardiovascular events across a range of populations.[1,2,3] It has been suggested that proteinuria reflects glomerular damage, and is a sensitive indicator of generalized endothelial dysfunction and capillary vasculopathy that allows penetration of atherosclerotic lipoproteins into vessel walls.[4]There appears to be a strong association between proteinuria and stroke
In our recently published systematic review and meta-analysis of low glomerular filtration rate (GFR) and stroke risk,[7] we showed that this risk association was greatly attenuated by adjustment for long-term blood pressure (BP) burden, suggesting that hypertension might confound the association
Using a systematic review and meta-analysis, we aimed to assess the impact of proteinuria on stroke risk and whether any association present remained after more complete adjustment for BP
Summary
Proteinuria has emerged as an important vascular risk factor for adverse cardiovascular events across a range of populations.[1,2,3] It has been suggested that proteinuria reflects glomerular damage, and is a sensitive indicator of generalized endothelial dysfunction and capillary vasculopathy that allows penetration of atherosclerotic lipoproteins into vessel walls.[4]There appears to be a strong association between proteinuria and stroke. Proteinuria has emerged as an important vascular risk factor for adverse cardiovascular events across a range of populations.[1,2,3] It has been suggested that proteinuria reflects glomerular damage, and is a sensitive indicator of generalized endothelial dysfunction and capillary vasculopathy that allows penetration of atherosclerotic lipoproteins into vessel walls.[4]. In a larger metaanalysis of 83 studies (over two million participants), a 25 mg/mmol increase in albumin–creatinine ratio was associated with a 10% increased risk of stroke.[6] Stroke risk increased linearly and additively with declining glomerular filtration rate (GFR) and increasing albuminuria. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
