This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Diabetes mellitus (DM) is a leading cause of cardiovascular (CV) disease and related complications, particularly in minority communities. Patients with DM and microalbuminuria are at increased risk for developing progressive deterioration in renal function, premature CV disease, and stroke. Treating DM at an early stage may reduce or halt disease progression. The objective of this study is to determine whether an aggressive treatment with inhibition of the renin-angiotensin-aldosterone system (RAAS) in initial stages of diabetic nephropathy (DM and microalbuminuria) will slow the progression of vascular disease in diabetic minority populations. Strict glucose and blood pressure (BP) control are key, but are often difficult to achieve, especially in diverse ethnic minority populations. Some studies have shown that pharmacotherapy with RAAS inhibition improves clinical outcomes in patients with diabetes via a blood pressure independent effect. However, few of these studies have included racial/ethnic minorities. Frequently, the standard of care in the community for patients with DM and microalbuminuria is administration of low doses of RAAS inhibition as part of a multi-pharmacologic regimen. Increased doses of RAAS inhibition therapy is usually reserved for patients with gross proteinuria or overt CV complications. No well- controlled randomized prospective studies exist to demonstrate that aggressive titration with RAAS inhibition is superior to standard therapy in order to slow the progression of vascular disease in patients with DM and microalbuminuria. The hypothesis for this study is that aggressive RAAS inhibition is superior to standard RAAS inhibition in retarding the progression of vascular disease among patients with DM and microalbuminuria. This hypothesis will be tested through the following specific aims: 1) Assess the effect of standard-versus-aggressive RAAS inhibition on progression of atherosclerotic disease on a primary outcome of structural vascular changes as assessed by carotid intima media thickness, 2) Assess the effect of standard-versus-aggressive RAAS inhibition on progression of atherosclerotic disease on a secondary outcome of functional vascular changes as assessed by brachial artery reactivity, and 3) Examine the relationship of vascular changes to both baseline and change in urinary protein excretion rates. Please see attached Project.
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