Kinetics and Prognosis Value of CCL5/RANTES at the Acute Phase of ST-Segment-Elevation Myocardial Infarction

Abstract

Background: RANTES (regulated upon activation, normal T cell expressed, and secreted) or CCL5 (CC chemokine ligand 5) is a chemokine that mediates chemotaxis and activation of T cells, monocytes, mast cells, and dendritic cells. It is involved in the pathogenesis of several diseases, including atherosclerosis, but its role at the acute phase of myocardial infarction (MI) is unclear. Our objective is to determine whether the serum level of RANTES is a marker of the severity of acute MI.

Methods and results: The study included 250 consecutive patients with ST-segment-elevation MI who underwent percutaneous coronary intervention in a prospective cohort. Peripheral venous blood samples were taken at 5 time points and ELISA was performed. Major adverse cardiovascular events were prospectively recorded over the 12-month follow-up. Serum RANTES level raised from 12.9 (8.0-20.7) ng/mL at H0 to 13.9 (7.4-22.4) ng/mL at H4 and decreased gradually until 1 month at 9.7 (5.4-13.6) ng/mL (P<0.0001). RANTES area under the curve (AUC) level was not correlated with infarct size (r=-0.03, P=0.70) or left ventricular ejection fraction assessed by magnetic resonance imaging (r=0.02, P=0.80). Patients with a RANTES AUC serum level below the first tertile value of the population (411.0 ng.h.mL^-1) were more likely to have a major adverse cardiovascular event during the first 12 months after ST-segment-elevation MI (hazard ratio [HR], 2.9 [1.3-6.6], P=0.01). In a multivariable Cox regression analysis, serum level below the first tertile remained associated with an increased risk of experiencing major adverse cardiovascular event during the follow-up (adjusted HR, 2.6 [1.2-5.8], P=0.02).

Conclusions: A low level of circulating RANTES post ST-segment-elevation MI was associated with an increased risk of experiencing major adverse cardiovascular event and might be a valuable prognostic marker in patients with ST-segment-elevation MI.

Keywords: ELISA; biomarker; myocardial infarction; systemic inflammation.

Figure 1. Design of the HIBISCUS STEMI prospective cohort (NCT03070496).

Blood samples were collected at 5 time points: at hospital admission (at the time of percutaneous coronary intervention), and then at 4, 24, and 48 hours and 1 month after admission for each patient. HIBISCUS indicates Cohort of Patients to Identify Biological and Imaging Markers of Cardiovascular Outcomes; LVEF, left ventricular ejection fraction; and STEMI, ST‐segment–elevation myocardial infarction.

Figure 2. RANTES serum release kinetics and correlative analysis.

A, RANTES release kinetics in a cohort of patients with (STEMI). B, Serum RANTES level according to infarct size (IS). C, Serum RANTES level according to (LVEF). D, Serum RANTES level according to coronarographic TIMI () score. IS indicates infarct size; LVEF, left ventricular ejection fraction; RANTES, regulated upon activation, normal T cell expressed, and secreted; STEMI, ST‐segment–elevation myocardial infarction; and TIMI, thrombolysis in myocardial infarction.

Figure 3. Correlation of RANTES levels with clinical outcome.

A, Serum RANTES levels according to MACE (all‐cause mortality, hospitalization for heart failure, relapse MI, or stroke). B, Wilcoxon matched‐pairs signed rank test was used to compare RANTES levels at the different time points. A comparison of survival curves was made using the log‐rank (Mantel‐Cox) test. A P value <0.05 was considered statistically significant. C, HR for composite end point at 12 months (all‐cause death, hospitalization for heart failure, myocardial infarction, and stroke). AUC indicates area under the curve; CRP, C‐reactive protein; HR, hazard ratio; MACE, major adverse cardiac events; MI, myocardial infarction; RANTES, regulated upon activation, normal T cell expressed, and secreted; and STEMI, ST‐segment–elevation myocardial infarction.