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

You-Cheol Hwang, David A Morrow, Christopher P Cannon, Yuyin Liu, Richard Bergenstal, Simon Heller, Cyrus Mehta, William Cushman, George L Bakris, Faiez Zannad, William B White, You-Cheol Hwang, David A Morrow, Christopher P Cannon, Yuyin Liu, Richard Bergenstal, Simon Heller, Cyrus Mehta, William Cushman, George L Bakris, Faiez Zannad, William B White

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.

Conflict of interest statement

W. B. W. is chair of the EXAMINE steering committee and has received personal fees from Takeda Development Center, Deerfield, Illinois. F. Z. is a member of the EXAMINE steering committee and has received personal fees from Takeda Development Center, Deerfield, Illinois. C. R. M. is a member of the EXAMINE steering committee has received personal fees from Takeda Development Center, Deerfield Illinois. Y. L. is an employee of Baim Clinical Research Group, Boston, Massachsetts. G. L. B. is a member of the EXAMINE steering committee and has received personal fees from Takeda Development Center, Deerfield, Illinois. W. C. C. is a member of the EXAMINE steering committee and has received personal fees from Takeda Development Center, Deerfield, Illinois. S. R. H. is a member of the EXAMINE steering committee and has received personal fees from Takeda Development Center, Deerfield, Illinois. R. M. B. is a member of the EXAMINE steering committee and has received personal fees from Takeda Development Center, Deerfield, Illinois. C. P. C. is an employee of the Baim Clinical Research Institute, Boston, Massachusetts.

© 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Time to the primary endpoint (major adverse cardiovascular events) according to baseline high‐sensitivity C‐reactive protein (hs‐CRP) in the EXAMINE trial
Figure 2
Figure 2
Time to the primary endpoint (major adverse cardiovascular events) according to baseline high‐sensitivity C‐reactive protein (hs‐CRP) and low‐density lipoprotein (LDL) cholesterol in the EXAMINE trial

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