title: Measurable urinary albumin predicts cardiovascular risk among normoalbuminuric patients with type 2 diabetes.
abstract: 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.
authors.affiliation: Mario Negri Institute for Pharmacological Research, Centro Anna Maria Astori Science and Technology Park, Kilometro Rosso Via Stezzano 87, Bergamo, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
authors.forename: Esteban
authors.initials: E
authors.lastname: Porrini
authors.forename: Nicola
authors.initials: N
authors.lastname: Motterlini
authors.forename: Annalisa
authors.initials: A
authors.lastname: Perna
authors.forename: Aneliya Parvanova
authors.initials: AP
authors.lastname: Ilieva
authors.forename: Ilian Petrov
authors.initials: IP
authors.lastname: Iliev
authors.forename: Alessandro Roberto
authors.initials: AR
authors.lastname: Dodesini
authors.forename: Roberto
authors.initials: R
authors.lastname: Trevisan
authors.forename: Antonio
authors.initials: A
authors.lastname: Bossi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sampietro
authors.forename: Enrica
authors.initials: E
authors.lastname: Capitoni
authors.forename: Flavio
authors.initials: F
authors.lastname: Gaspari
authors.forename: Nadia
authors.initials: N
authors.lastname: Rubis
authors.forename: Bogdan
authors.initials: B
authors.lastname: Ene-Iordache
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000150:complications* / Q000652:urine; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D015415:Biomarkers / Q000652:urine; D002316:Cardiotonic Agents / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014700:Verapamil / Q000627:therapeutic use
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D002316:Cardiotonic Agents; D007211:Indoles; C052035:trandolapril; D014700:Verapamil