Changes in albuminuria and cardiovascular risk under antihypertensive treatment: a systematic review and meta-regression analysis.

Background: Increased urine albumin excretion (UAE) is a well known predictor of cardiovascular events in patients with primary hypertension. Whether a reduction in UAE is associated to an improvement in cardiovascular risk is at present unclear. We performed a systematic review and meta-regression analysis of available trials to investigate whether treatment-induced changes in UAE are related to cardiovascular outcome.

Methods: We searched MEDLINE, ISIWeb of Science, Cochrane Database and Scopus for studies including hypertensive patients, which reported cardiovascular events and UAE at baseline and at end of follow-up.

Results: In trials reporting pairwise comparisons between antihypertensive treatment for cardiovascular outcome (16 randomized controlled trials and 48 580 patients, mean follow-up 45 months, 5867 cardiovascular events) after adjustment for differences in achieved blood pressure, a relationship between changes in albuminuria and risk was evident in the presence of a relevant between-arms difference in albuminuria [relative risks (RR) pooled 0.45, confidence interval (CI) 0.23-0.85] but not when no improvement in UAE was found between randomized arms (RR pooled 1.04, 95% CI 0.86-1.26, P for difference between subgroups <0.001). Meta-regression analysis showed a relationship between changes in albuminuria and risk after adjustment for blood pressure variation under treatment (adj. coeff. 0.005, 95% CI 0.0005-0.0096, P = 0.033, R 34.8%). In studies reporting changes in cardiovascular events on the basis of UAE variations (six trials and 36 325 patients, mean follow-up 60 months, 3741 cardiovascular events), the overall adjusted RR of total cardiovascular events was 0.51 (95% CI 0.38-0.59, P = 0.000) for albuminuria regression/stable vs increase.

Conclusion: Reduction in UAE under antihypertensive treatment is associated with reduced risk of clinical cardiovascular events. Our findings suggest that UAE changes may represent a valuable intermediate end point for cardiovascular events in primary hypertension.