GRACE score predicts systemic inflammation in patients with acute coronary syndrome
Authors: Ortega-Hernandez J A , Sanchez-Munoz F , Amezcua-Guerra L M , Arana-Martinez J C , Arias-Mendoza A , Gonzalez-Pacheco H , Bojalil R , Springall R 
Published: October 2021

Abstract

Background
New insights of inflammation CANTOS (1) and COLCOT (2) demonstrated the importance of blocking inflammation in CAD for major outcomes, but only in patients with systemic inflammation. The GRACE score is a readily available tool that uses a variety of items none related to inflammation per se. Many studies have emphasised the importance of inflammation, however, most markers are not readily available in the clinic setting.

Purpose
Determine if GRACE score may reflect systemic inflammation measured by WBC, hsCRP, albumin, IL-1β, IL-6, IL-8, and IL-10.

Methods
77 patients with NSTEMI/STEMI were enrolled at time of hospital admission, all patients had &lt;24 h of the initial symptom, were &gt;18 years old and received no therapy before the samples were obtained. Patients with pregnancy or in postpartum period, infectious, autoimmune, hepatic, or neoplastic diseases were excluded; as well as patients with current or previous dialysis, transplant, episodes of acute or chronic heart failure, and previous ACS.
WBC, hsCRP and troponin I, IL-1β, IL-6, IL-8, IL-10, were measured. Low rank regression splines, a predefined analysis of IL-1β + hsCRP/ IL-1β + IL-6 / IL-6 + hsCRP vs GRACE score was performed, adjusted by sex, type of ACS, hypertension, and diabetes. A p&lt;0,05 was set as significant.

Results
GRACE score significantly correlated with IL-1β (ρ=0.352), IL-6 (ρ=0.465), IL-8 (ρ=0.325), IL-10 (ρ=0.31), WBC (ρ=0.428), hsCRP (ρ=0.46), and albumin (ρ=−0.538). In low rank regression splines WBC had a positive correlation with GRACE score (F=45.52 p&lt;0.001; fig 1B) with inflection in scores &gt;150. hsCRP also significant (F=21.54 p&lt;0.001; fig 1C). IL-1β, IL-6 and IL-10 had a positive linear regression (F=7.32; F=8.36; F=5.32 p&lt;0.02; respectively; fig 1 D,E,G); and IL-8, had a positive non-linear association (F=6.54 p=0.003; fig 1F). Finally, albumin had a negative relationship (F=29.68 p&lt;0.001; fIg 1A), with inflection point in GRACE&gt;125.
Analysis of log-IL-1 β + log-hsCRP vs GRACE (df= 2.07 and 4.9, F=12.84 and 23.23; p&lt;0.001; fig 2A) and log- IL-1β + log-IL-6 vs GRACE (df= 2.23 and 6.53, F= 12.98 and 16.87, p&lt;0.001; fig 2B) showed that the presence of a proportional increase in the variables correlates with higher GRACE scores. Lastly, log-hsCRP + log-IL-6 vs GRACE the F=18.18 and 2.8 with a p&lt;0.001 and 0.07, respectively (fig 2C).

Conclusion
Our data suggest that a higher GRACE score reflect higher systemic inflammation and correlates with various cytokines that could be inferred non directly, IL-1, IL-6, IL-8 and IL-10. This open new avenues for personalized cardiology based in practical tools, possibly identifying patients that get the most benefit of the new anti-cytokine or anti-inflammatory interventions.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): Instituto Nacional de Cardiología Ignacio Chávez Figure A. Low rank regression splinesFigure B. Low rank regression splines