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Proteinuria strongly associated with CHD risk

PLoS Medicine 2008; 5: e207

Proteinuria is strongly and continuously associated with the risk for coronary heart disease (CHD), and should be incorporated into individual cardiovascular (CV) risk assessments, say researchers.

Markers of early kidney dysfunction such as albuminuria and proteinuria have previously been linked to CHD risk, but both the direction and strength of reported associations have been inconsistent.

To investigate further, Vlado Perkovic (University of Sydney, New South Wales, Australia) and colleagues conducted a systematic review and meta-analysis of studies that provided estimates of the association between CHD risk and proteinuria and albuminuria. Studies were excluded if they involved patients with known glomerular disease or who had undergone renal transplant.

As reported in the journal PLoS Medicine, the team identified a total of 26 studies, involving 169,949 individuals and a total of 7117 coronary events.

The meta-analysis revealed that proteinuria (total urinary protein >300 mg/dl or dipstick 1+ or more) was associated with an approximately 50% increased risk for CHD, at a risk ratio of 1.47 after adjusting for established CHD risk factors.

There appeared to be a dose-response relationship between albuminuria and CHD risk. Individuals with microalbuminuria (urinary albumin 30-300mg/dl) were 50% more likely to develop CHD than those with lower levels, while those with macroalbuminuria (urinary albumin >300 m/dl) were more than twice as likely to develop CHD as those without albuminuria.

The association between proteinuria and CHD did not differ substantially between subgroups such as those with and without diabetes.

PLoS Medicine editors caution that the observed 50% increase in risk for CHD associated with proteinuria may be an overestimate owing to publication bias towards studies that do rather than do not show an association.

Nevertheless, given that the study includes several large, population-based studies done across the world, they say the findings are likely to be “generalizable.”

Perkovic and co-authors conclude: “The findings of this study therefore strongly support a role for the evaluation of proteinuria in the prediction of CHD risk. They suggest that the use of strategies to reduce proteinuria, and better targeting of other cardioprotective therapies, may help to reduce the overall burden of CHD. Studies to assess the impact of these strategies are warranted.”

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