Mario Negri Institute for Pharmacological Research, Centro Anna Maria Astori Science and Technology Park, Kilometro Rosso Via Stezzano 87, Bergamo, Italy.
J Am Soc Nephrol. 2012 Oct;23(10):1717-24. doi: 10.1681/ASN.2012030252. Epub 2012 Aug 30.
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.
微量白蛋白尿或大量白蛋白尿与 2 型糖尿病患者心血管危险因素增加相关，但正常范围内的白蛋白尿是否预示着长期心血管风险尚不清楚。我们评估了来自 Bergamo 肾内科糖尿病并发症试验（BENEDICT）的 1208 例高血压、正常白蛋白尿 2 型糖尿病患者的白蛋白尿与心血管事件之间的关系，所有患者在试验结束时均接受血管紧张素转换酶抑制剂（ACEI）治疗，并中位随访 9.2 年。主要结局为致命或非致命性心肌梗死、卒中等首次事件的时间；冠状动脉、颈动脉或外周动脉血运重建；或因心力衰竭住院。共有 189 例（15.6%）患者发生主要结局事件（2.14 例/100 患者-年）；24 例事件为致命性。白蛋白尿独立预测事件（风险比[HR]，1.05；95%置信区间[CI]，1.02-1.08）。二阶多项式多变量分析显示白蛋白尿与事件之间存在连续非线性关系，无阈值。考虑整个研究人群，即使白蛋白尿为 1-2μg/min 与白蛋白尿<1μg/min 相比，风险显著增加（HR，1.04；95%CI，1.02-1.07）。在最初随机分配至非 ACEI 治疗的亚组中，这种关系相似。然而，在最初接受 ACEI 治疗的患者中，事件发生率始终较低，与白蛋白尿无关。综上，在 2 型糖尿病正常白蛋白尿患者中，任何程度的可测量白蛋白尿均存在显著的心血管风险。与风险的相关性是连续的，但在早期接受 ACEI 治疗后则消失。
