Proteinuria and Stroke: A Meta-analysis of Cohort Studies
Received 30 April 2008; accepted 29 August 2008. published online 15 December 2008.
Background
The associations between decreased kidney function and cardiovascular disease recently have been established. However, there is uncertainty about the consistency between the independent associations of proteinuria as a risk factor across all cardiovascular end points. We undertook a meta-analysis of published cohort studies to provide a reliable estimate of the strength of association between proteinuria and risk of stroke.
Study Design
Meta-analysis of observational cohort studies.
Setting & Population
General population of participants with diabetes. Studies were excluded if participants had known glomerular disease or had undergone dialysis or transplantation.
Selection Criteria for Studies
MEDLINE, EMBASE, and CINAHL databases were searched for studies that reported age- or multivariate-adjusted risk ratio with some estimate of the variance of the association between proteinuria and risk of stroke, without language restriction.
Factor
Proteinuria or albuminuria.
Outcomes
Fatal or nonfatal stroke.
Results
Data from 10 published studies involving 140,231 participants and 3,266 strokes were eligible for inclusion. Participants with proteinuria had a 71% greater risk of stroke compared with those without proteinuria (95% confidence interval, 1.39 to 2.10). There was evidence of significant quantitative heterogeneity in the magnitude of the association across studies (I2 = 60%; P for heterogeneity = 0.008), which was partially explained by differences in methods for measuring proteinuria. The risk of stroke remained significant after adjustment for other vascular risk factors.
Limitations
Because individual patient data were unavailable, we were unable to fully examine the impact of adjustment for known cardiovascular risk factors on the strength of the association between proteinuria and stroke risk. It is possible that the pooled estimate was affected by regression dilution bias.
Conclusions
These findings support the independent relationship between proteinuria and stroke. Additional studies are warranted to determine whether interventions to reduce proteinuria are effective at reducing rates of stroke.
1The George Institute for International Health, The University of Sydney, Sydney, Australia
2School of Public Health, The University of Sydney, Sydney, Australia
Address correspondence to Vlado Perkovic, MD, PhD, The George Institute for International Health, The University of Sydney, Level 10, King George V Bldg, Royal Prince Alfred Hospital, Camperdown, Sydney NSW 2050, Australia
ABSTRACT