Francesca Viazzi1, Maria L Muiesan, Giuseppe Schillaci, Massimo Salvetti, Giacomo Pucci, Barbara Bonino, Alessio Signori, Roberto Pontremoli. 1. aDepartment of Internal Medicine, University of Genova and IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Genoa bDepartment of Clinical and Experimental Sciences, University of Brescia, Brescia cDipartimento di Medicina, Università di Perugia, Perugia dThe Struttura Complessa di Medicina Interna, Azienda Ospedaliero-Universitaria di Terni, Terni eBiostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy.
Abstract
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.
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 hypertensivepatients, 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.