High-sensitivity C-reactive Protein, Low-Density Lipoprotein Cholesterol, and Cardiovascular Outcomes in Patients with Type 2 Diabetes in the EXAMINE (Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care) Trial

OBJECTIVE: We sought to assess the risk of major adverse cardiovascular events (MACE) by utilizing high-sensitivity C-reactive protein (hsCRP) level and low-density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes and recent acute coronary syndrome. RESEARCH DESIGN AND METHODS: Study participants enrolled in the EXAMINE trial, were stratified by baseline hsCRP levels (<1, 1-3, and >3 mg/l) and were also sub-divided into 4 groups according to baseline hsCRP (≤3 or >3 mg/l) and achieved LDL-C (<70 or ≥70 mg/dl) levels. Among 5,380 patients, the MACE rate, a composite of cardiovascular death, non-fatal acute myocardial infarction, and non-fatal stroke, was evaluated during the 30 months of follow-up. RESULTS: Cumulative incidence of MACE was 11.5% (119 events), 14.6% (209 events), and 18.4% (287 events) in patients with hsCRP levels of <1, 1-3, and >3 mg/l, respectively (P<0.001). In patients with hsCRP >3 mg/l, the adjusted hazard ratio (95% confidence interval) was 1.42 (1.13, 1.78; P=0.002) for MACE compared with patients with hsCRP <1 mg/l. MACE cumulative incidences were 11.0% (128 events), 14.4% (100 events), 15.6% (194 events), and 21.3% (182 events) in patients with low LDL-C and low hsCRP, low LDL-C and high hsCRP, high LDL-C and low hsCRP, and high LDL-C and high hsCRP levels, respectively (P<0.001). CONCLUSIONS: Levels of hsCRP were associated with recurrent cardiovascular events in patients with type 2 diabetes and recent acute coronary syndrome, and this association appears to be independent of and additive to the achieved LDL-C level. Clinical trials registration number: NCT00968708.