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

Diabetes Obes Metab. 2018 Mar;20(3):654-659. doi: 10.1111/dom.13136. Epub 2017 Nov 21.

Abstract

Aims: 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.

Materials and methods: Study participants enrolled in the EXAMINE trial (Clinical trials registration number: NCT00968708) and were stratified by baseline hsCRP levels (<1, 1-3 and >3 mg/L). They 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 5380 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 to 3 and >3 mg/L, respectively (P < .001). In patients with hsCRP >3 mg/L, the adjusted hazard ratio (95% confidence interval) was 1.42 (1.13, 1.78; P = .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 < .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.

Keywords: LDL cholesterol; acute coronary syndromes; cardiovascular outcomes; high-sensitivity C-reactive protein; type 2 diabetes.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome
  • C-Reactive Protein / metabolism*
  • Cholesterol, LDL / metabolism*
  • Diabetes Mellitus, Type 2 / mortality*
  • Diabetic Angiopathies / drug therapy*
  • Double-Blind Method
  • Female
  • Heart Failure / mortality
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Myocardial Infarction / mortality
  • Myocardial Revascularization / mortality
  • Piperidines / therapeutic use*
  • Standard of Care
  • Treatment Outcome
  • Uracil / analogs & derivatives*
  • Uracil / therapeutic use

Substances

  • Cholesterol, LDL
  • Hypoglycemic Agents
  • Piperidines
  • Uracil
  • C-Reactive Protein
  • alogliptin

Associated data

  • ClinicalTrials.gov/NCT00968708