Inflammatory and anti-inflammatory variable clusters and risk prediction in acute coronary syndrome patients: a
Dimitrios N Tziakas1, Georgios K Chalikias, Juan Carlos Kaski
1University Cardiology Department, Democritus University of Thrace, Voulgaroktonou 23, 68100 Alexandroupolis, Greece. dtziakas@med.duth.gr
Insights
Anti-inflammatory markers, including interleukin-10 (IL-10) and HDL cholesterol, better predict recurrent cardiac events in acute coronary syndrome (ACS) patients than pro-inflammatory markers. This finding highlights the prognostic value of anti-inflammatory mechanisms in ACS risk stratification.
Area of Science:
- Cardiology
- Biomarkers
- Inflammation
Background:
- Acute coronary syndrome (ACS) involves numerous inflammatory mediators, complicating risk stratification.
- Interactions among markers like C-reactive protein (CRP), fibrinogen, IL-18, and ICAM-1 hinder accurate risk assessment.
- Factor analysis offers a method to identify underlying physiological relationships among correlated inflammatory markers.
Purpose of the Study:
- To investigate the clustering of pro-inflammatory and anti-inflammatory markers in ACS patients using factor analysis.
- To determine the role of these marker clusters in predicting recurrent coronary events.
- To assess the prognostic value of anti-inflammatory markers compared to pro-inflammatory markers in ACS.
Main Methods:
- 320 ACS patients (mean age 67) were assessed for serum levels of CRP, fibrinogen, HDL cholesterol, IL-10, IL-18, and ICAM-1 at study entry.
- A composite endpoint of cardiac death, non-fatal myocardial infarction, or unstable angina within 1 year was used.
- Factor analysis identified marker clusters, and logistic regression assessed predictors of the endpoint.
Main Results:
- Factor analysis revealed three distinct clusters: "systemic inflammation" (CRP, fibrinogen), "local inflammation-endothelial dysfunction" (IL-18, ICAM-1), and "anti-inflammation" (IL-10, HDL cholesterol).
- The "anti-inflammation" cluster was a significant predictor of adverse cardiac events (OR 0.66).
- This association remained significant in a multivariate model including all identified factors (OR 0.65).
Conclusions:
- While inflammatory markers like CRP are known predictors, anti-inflammatory markers offer superior prognostic value in ACS.
- The "anti-inflammation" cluster, comprising IL-10 and HDL cholesterol, is a key indicator of future cardiovascular risk in ACS patients.
- These findings emphasize the importance of assessing anti-inflammatory mechanisms for improved risk stratification in ACS management.
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.
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