Measurable Urinary Albumin Predicts Cardiovascular Risk among Normoalbuminuric Patients with Type 2 Diabetes

Micro- or macroalbuminuria is associated with increased cardiovascular risk factors among patients with type 2 diabetes, but whether albuminuria within the normal range predicts long-term cardiovascular risk is unknown. We evaluated the relationships between albuminuria and cardiovascular events in 1208 hypertensive, normoalbuminuric patients with type 2 diabetes from the BErgamo NEphrologic Diabetes Complication Trial (BENEDICT), all of whom received angiotensin-converting enzyme inhibitor (ACEI) therapy at the end of the trial and were followed for a median of 9.2 years. The main outcome was time to the first of fatal or nonfatal myocardial infarction; stroke; coronary, carotid, or peripheral artery revascularization; or hospitalization for heart failure. Overall, 189 (15.6%) of the patients experienced a main outcome event (2.14 events/100 patient-years); 24 events were fatal. Albuminuria independently predicted events (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.02-1.08). Second-degree polynomial multivariable analysis showed a continuous nonlinear relationship between albuminuria and events without thresholds. Considering the entire study population, even albuminuria at 1-2 μg/min was significantly associated with increased risk compared with albuminuria <1 μg/min (HR, 1.04; 95% CI, 1.02-1.07). This relationship was similar in the subgroup originally randomly assigned to non-ACEI therapy. Among those originally receiving ACEI therapy, however, the event rate was uniformly low and was not significantly associated with albuminuria. Taken together, among normoalbuminuric patients with type 2 diabetes, any degree of measurable albuminuria bears significant cardiovascular risk. The association with risk is continuous but is lost with early ACEI therapy.