Prognostic impact of admission high-sensitivity C-reactive protein in acute myocardial infarction patients with and without diabetes mellitus

Abstract

Background: High-sensitivity C-reactive protein (hs-CRP) elevation frequently occurs in acute myocardial infarction (AMI) and is associated with adverse outcomes. Since diabetes mellitus (DM) is characterized by an underlying chronic inflammation, hs-CRP may have a different prognostic power in AMI patients with and without DM.

Methods: We prospectively included 2064 AMI patients; hs-CRP was measured at hospital admission. Patients were grouped according to hs-CRP quartiles and DM status. The primary endpoint was a composite of in-hospital mortality, cardiogenic shock, and acute pulmonary edema. Two-year all-cause mortality was the secondary endpoint.

Results: Twenty-six percent (n = 548) of patients had DM and they had higher hs-CRP levels than non-DM patients (5.32 vs. 3.24 mg/L; P < 0.0001). The primary endpoint incidence in the overall population (7%, 9%, 13%, 22%; P for trend < 0.0001), in DM (14%, 9%, 21%, 27%; P = 0.0001), and non-DM (5%, 8%, 10%, 19%; P < 0.0001) patients increased in parallel with hs-CRP quartiles. The adjusted risk of the primary endpoint increased in parallel with hs-CRP quartiles in DM and non-DM patients but this relationship was less evident in DM patients. In the overall population, the adjusted OR of the primary endpoint associated with an hs-CRP value ≥ 2 mg/L was 2.10 (95% CI 1.46-3.00). For the same risk, hs-CRP was 7 and 2 mg/L in patients with and without DM. A similar behavior was observed for the secondary endpoint when the HR associated with an hs-CRP value ≥ 2 mg/L found in the overall population was 2.25 (95% CI 1.57-3.22). For the same risk, hs-CRP was 8 and 1.5 mg/L in DM and non-DM patients.

Conclusions: This study shows that hs-CRP predicts in-hospital outcome and two-year mortality in AMI patients with and without DM. However, in DM patients, the same risk of developing events as in non-DM patients is associated to higher hs-CRP levels.

Keywords: Acute myocardial infarction; Diabetes mellitus; High-sensitivity C-reactive protein; Inflammation.

Fig. 1

Panel A: incidence of the in-hospital combined clinical endpoint (death, cardiogenic shock, and acute pulmonary edema) in patients with and without diabetes mellitus (DM) and adjusted odds ratio (OR) and 95% confidence interval (CI) associated with DM. Panel B: Kaplan–Meier survival curves stratified by DM status and adjusted hazard ratio (HR) and 95% CI associated with DM. Panel C: incidence of the in-hospital combined clinical endpoint (death, cardiogenic shock, and acute pulmonary edema) in patients with high-sensitivity C-reactive protein (hs-CRP) ≥ and < 2 mg/L and adjusted OR and 95% CI associated with a hs-CRP value ≥ 2 mg/L. Panel D: Kaplan–Meier survival curves stratified by hs-CRP cut-off value (2 mg/L) and adjusted HR and 95% CI associated with a hs-CRP value ≥ 2 mg/L. All analyses were adjusted for left ventricular ejection fraction (≤ or > 40%), estimated glomerular filtration rate (≤ or > 60 ml/min/1.73 m²), type of acute myocardial infarction (STEMI vs. NSTEMI) and prior statin use

Fig. 2

Adjusted odds ratios (OR) and 95% confidence intervals for the primary endpoint according to high-sensitivity C-reactive protein (hs-CRP) level quartiles in the overall study population (Panel A), in patients with diabetes mellitus (DM) (Panel B), and in those without DM (Panel C). Odd ratios and P for trend were adjusted for left ventricular ejection fraction (≤ or > 40%), estimated glomerular filtration rate (≤ or > 60 ml/min/1.73 m²), type of acute myocardial infarction (STEMI vs. NSTEMI), and prior statin use. P for interaction between DM status and hs-CRP = 0.36

Fig. 3

Adjusted hazard ratios (HR) and 95% confidence intervals for the secondary endpoint according to high-sensitivity C-reactive protein (hs-CRP) level quartiles in the overall study population (Panel A), in patients with diabetes mellitus (DM) (Panel B), and in those without DM (Panel C). Hazard ratios and P for trend were adjusted for left ventricular ejection fraction (≤ or > 40%), estimated glomerular filtration rate (≤ or > 60 ml/min/1.73 m²), type of acute myocardial infarction (STEMI vs. NSTEMI), and prior statin use. P for interaction between DM status and hs-CRP = 0.02

Fig. 4

Threshold values of high-sensitivity C-reactive protein (hs-CRP) in patients with and without diabetes mellitus (DM) considered separately, corresponding to the adjusted risk of the primary and secondary endpoints associated with an hs-CRP value ≥ 2 mg/L found in the overall population. OR Odds ratio, HR Hazard ratio, CI Confidence interval

Fig. 5

Relative risks and 95% confidence interval (CI) of two-year mortality associated with different high-sensitivity C-reactive protein (hs-CRP) cut-offs in patients with diabetes mellitus (DM) (blue) and in those without DM (red). Relative risk was adjusted for left ventricular ejection fraction (≤ or > 40%), estimated glomerular filtration rate (≤ or > 60 ml/min/1.73 m²), type of acute myocardial infarction (STEMI vs. NSTEMI) and and prior statin use. The vertical dotted line refers to hs-CRP value of 2 mg/L. The horizontal dotted line refers to the RR associated with hs-CRP value of 2 mg/L in non-DM patients