hsCRP levels predict CV outcomes in type 2 diabetic patients post-ACS

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

Literature - Hwang YC, Morrow DA, Cannon CP, et al. - Diabetes Obes Metab. 2017; published online ahead of print


CRP concentrations predict CV risk in primary and in secondary prevention. The predictive value of CRP levels is comparable with that of SBP, TC, and non-HDL-c in primary prevention, whereas in the setting of secondary prevention, higher high-sensitivity (hs)CRP concentrations during the first 72 hours of an ACS have been associated with a higher long-term risk of recurrent CV events [1-3].

In this analysis of the multicenter, randomized, double-blind EXAMINE trial [4], the predictive value of baseline hsCRP in regard to MACE was evaluated in type 2 diabetes (T2DM) patients at high CV risk with a recent ACS, but well treated with statins and good glycemic control. Moreover, it was assessed whether the association of hsCRP levels and CV outcomes was independent of LDL-c levels.

EXAMINE evaluated the efficacy and safety of the DPP-4 inhibitor alogliptin in 5380 T2DM patients who suffered an ACS within 15 to 90 days before randomization. The primary MACE endpoint consisted of CV death, non-fatal MI, and stroke.

Main results

  • During a median duration of 18 months of follow-up, the cumulative incidences of MACE were as follows (P<0.001): 11.5% in patients with baseline hsCRP <1 mg/l, 14.6% in patients with baseline hsCRP: 1-3 mg/l, 18.4% in patients with baseline hsCRP >3 mg/l.
  • Compared to patients with baseline hsCRP <1 mg/l, in patients with a baseline hsCRP >3 mg/l, the following adjusted HRs were calculated: 1.42 (95%CI:1.13-1.78; P=0.002) for MACE, 1.40 (95%CI:1.04-1.89; P=0.025) for non-fatal MI, 2.04 (95%CI:1.34-3.11; P<0.001) for HF hospitalization, 1.77 (95%CI:1.29-2.42; P<0.001) for all-cause death.
  • The results were independent of treatment group, age, gender, BMI, current smoking, TC, estimated GFR, BP, glycated hemoglobin, and duration of DM.
  • The baseline hsCRP concentrations were not independently associated with the individual endpoints of CV death, non-fatal stroke, or urgent revascularization due to unstable angina.
  • Patients with average concentrations of hsCRP (1–3 mg/l) had a CV risk comparable to patients with hsCRP concentrations <1 mg/l.
  • The cumulative incidences of MACE were (P<0.001): 11.0% in patients with low LDL-c and low hsCRP concentrations, 14.4% in patients with low LDL-c and high hsCRP concentrations, 15.6% in patients with high LDL-c and low hsCRP concentrations, 21.3% in patients with high LDL-c and high hsCRP concentrations.


In T2DM patients at high CV risk with a recent ACS, there is a significant association between baseline hsCRP values and future CV outcomes, independent and additive to the achieved LDL-c level. These results suggest that the measurement of hsCRP levels, in addition to LDL-c, in these patients may be useful to assess their residual CV risk.


1. Soedamah-Muthu SS, Livingstone SJ, Charlton-Menys V, et al. Effect of atorvastatin on C-reactive protein and benefits for cardiovascular disease in patients with type 2 diabetes: analyses from the Collaborative Atorvastatin Diabetes Trial. Diabetologia. 2015;58:1494-1502.

2. Lowe G, Woodward M, Hillis G, et al. Circulating inflammatory markers and the risk of vascular complications and mortality in people with type 2 diabetes and cardiovascular disease or risk factors: the ADVANCE study. Diabetes. 2014;63:1115-1123.

3. Biasucci LM, Liuzzo G, Della Bona R, et al. Different apparent prognostic value of hsCRP in type 2 diabetic and nondiabetic patients with acute coronary syndromes. Clin Chem. 2009;55:365-368.

4. White WB, Bakris GL, Bergenstal RM, et al. EXamination of cArdiovascular outcoMes with alogliptIN versus standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome (EXAMINE): a cardiovascular safety study of the dipeptidyl peptidase 4 inhibitor alogliptin in patients with type 2 diabetes with acute coronary syndrome. Am Heart J. 2011;162:620-626.e621.

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