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

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.

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Division of Endocrinology and Metabolism, Department of Medicine, Kyung Hee University School of Medicine, Kyung Hee University Hospital at Gangdong, Seoul, South Korea.
Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
Baim Institute for Clinical Research, Boston, Massachusetts.
International Diabetes Center, Park-Nicollet Clinic, Minneapolis, Minnesota.
University of Sheffield, Sheffield, UK.
Harvard School of Public Health, Boston, Massachusetts.
University of Tennessee College of Medicine, Memphis, Tennessee.
University of Chicago Med, Chicago, Illinois.
Universite de Lorraine, Nancy, France.
University of Connecticut School of Medicine, Farmington, Connecticut.



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.


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.


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).


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.


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

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