Circulation. 2002 Aug 6;106(6):672-8. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect. (MARVAL) Viberti G， Wheeldon NM; MicroAlbuminuria Reduction With VALsartan (MARVAL) Study Investigators. Department of Diabetes， Endocrinology， and Internal Medicine， GKT School of Medicine， Guy’s Hospital， King’s College London， London， UK. giancarlo.viberti@kcl.ac.uk

BACKGROUND: Elevated urine albumin excretion (UAER) is a modifiable risk factor for renal and cardiovascular disease in type 2 diabetes. Blockade of the renin-angiotensin system lowers UAER， but whether this effect is independent of blood pressure (BP) reduction remains controversial. The MicroAlbuminuria Reduction With VALsartan (MARVAL) study was designed to evaluate the BP-independent effect of valsartan on UAER in type 2 diabetic patients with microalbuminuria.

METHODS AND RESULTS: Three hundred thirty-two patients with type 2 diabetes and microalbuminuria， with or without hypertension， were randomly assigned to 80 mg/d valsartan or 5 mg/d amlodipine for 24 weeks. A target BP of 135/85 mm Hg was aimed for by dose-doubling followed by addition of bendrofluazide and doxazosin whenever needed. The primary end point was the percent change in UAER from baseline to 24 weeks. The UAER at 24 weeks was 56% (95% CI， 49.6 to 63.0) of baseline with valsartan and 92% (95% CI， 81.7 to 103.7) of baseline with amlodipine， a highly significant between-group effect (P<0.001). Valsartan lowered UAER similarly in both the hypertensive and normotensive subgroups. More patients reversed to normoalbuminuria with valsartan (29.9% versus 14.5%; P=0.001). Over the study period， BP reductions were similar between the two treatments (systolic/diastolic 11.2/6.6 mm Hg for valsartan， 11.6/6.5 mm Hg for amlodipine) and at no time point was there a between-group significant difference in BP values in either the hypertensive or the normotensive subgroup.

CONCLUSIONS: For the same level of attained BP and the same degree of BP reduction， valsartan lowered UAER more effectively than amlodipine in patients with type 2 diabetes and microalbuminuria， including the subgroup with baseline normotension. This indicates a BP-independent antiproteinuric effect of valsartan.