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

Viazzi, Francescaa; Muiesan, Maria L.b; Schillaci, Giuseppec,d; Salvetti, Massimob; Pucci, Giacomoc,d; Bonino, Barbaraa; Signori, Alessioe; Pontremoli, Robertoa

doi: 10.1097/HJH.0000000000000991

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, R2 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.

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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

Correspondence to Roberto Pontremoli, MD, PhD, Department of Internal Medicine, University of Genova and IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Genoa, Italy. E-mail:

Abbreviations: CI, confidence interval; CV, cardiovascular; CVE, cardiovascular events; GFR, glomerular filtration rate; MI, myocardial infarction; RR, relative risks; UAE, urine albumin excretion

Received 19 February, 2016

Revised 19 April, 2016

Accepted 4 May, 2016

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