Inflammatory and anti-inflammatory variable clusters and risk prediction in acute coronary syndrome patients: A factor analysis approach

Abstract

Background Numerous inflammatory mediators such as C-reactive protein (CRP), fibrinogen, interleukin-18 (IL-18), and inter-cellular adhesion molecule-1 (ICAM-1) have been proposed for risk stratification in acute coronary syndrome (ACS) patients. However, interactions between these markers have made it difficult to assess their true role in risk prediction. Factor analysis is a multivariable statistical technique that reduces a large number of intercorrelated variables to a smaller set of independent clusters, underlining physiological relationships. The aim of this study was to investigate, using factor analysis, a clustering of pro-inflammatory markers, anti-inflammatory cytokines such as interleukin-10 (IL-10) and HDL cholesterol, and to determine their role in prediction of risk of recurrent coronary events in ACS patients. Methods We assessed 320 consecutive patients (236 men; 67 years; IQ 58–74 years) admitted with ACS. The composite of cardiac death and re-hospitalization with non-fatal myocardial infarction, or unstable angina, was the pre-specified study end-point. Serum CRP, fibrinogen, HDL cholesterol, IL-10, IL-18 and ICAM-1 levels were measured at study entry. We assessed independent predictors of the combined end-point during a 1-year follow-up using multiple logistic regression analysis. Results Factor analysis identified three clusters which were arbitrarily interpreted as (1) a “systemic inflammation” cluster with positive loadings of CRP and fibrinogen, (2) a “local inflammation–endothelial dysfunction” cluster with positive loadings of IL-18 and ICAM-1 and (3) an “anti-inflammation” cluster comprising IL-10 and HDL cholesterol. Only the “anti-inflammation” cluster was a significant predictor (OR 0.66, 95% CI: 0.49–0.89) of adverse cardiac events during a 1-year follow-up and remained significant (OR 0.65, 95% CI: 0.48–0.88) in a multivariate model that included all three factors. Conclusions Although inflammatory markers such as CRP predict future cardiovascular events in ACS patients, when all inflammatory mediators are taken into account in a prospective analysis of risk, markers reflecting anti-inflammatory mechanisms are better prognostic markers.