Inflammatory biomarkers and risk of cardiovascular events in patients undergoing coronary angiography

Abstract

Background: Inflammation, measured by traditional biomarkers such as C-reactive protein, has been linked to cardiovascular (CV) events. Recent technological advancement has allowed for measuring larger numbers of inflammatory biomarkers. A contemporary evaluation with established and novel biomarkers of inflammation is needed.

Methods: 1,090 individuals who underwent coronary angiography were enrolled. Twenty-four inflammatory biomarkers were collected prior to angiography. Unsupervised machine learning cluster analyses determined unique patterns of inflammatory biomarkers. Cox proportional hazard regression assessed both association of inflammatory biomarker clusters and individual biomarker associations with major adverse cardiovascular events (MACE; non-fatal myocardial infarction or stroke, and CV death) during a median follow-up of 3.67 years.

Results: Four distinct clusters were recognized. Incremental increases in inflammatory biomarkers were observed from cluster 1 to cluster 4. During follow-up, 263 MACE were ascertained. Considering cluster 1 as a reference, study participants with inflammatory cluster 2 (Hazard ratio [HR] 1.55, 95% confidence interval [CI]: 1.01-2.37), cluster 3 (HR 1.89, CI: 1.25-2.85), and cluster 4 (HR 2.93, CI: 1.95-4.42) were at increased risk of MACE. Interleukin (IL)-1α IL-6, IL-8, IL-10, IL-12, Adhesion molecule-1 high-sensitivity C-reactive protein, ferritin, myeloperoxidase, macrophage inflammatory protein (MIP)-1a, MIP 3, and macrophage colony-stimulating factor-1 were independently associated with MACE.

Conclusions: Among persons undergoing coronary angiography procedures, distinct clusters of inflammatory biomarker distributions with significant prognostic meaning may be identified. These results may identify unique targets for anti-inflammatory treatments aimed at CV disease.

Graphical abstract

Figure 1

Association of inflammatory cluster groupings with cardiovascular outcomes. Models were adjusted for age, sex, history of diabetes mellitus, hypertension, chronic kidney disease, coronary artery disease, acute coronary syndrome as well as statin use and concentrations of low density and high-density lipoprotein cholesterol. MACE: major adverse cardiovascular outcome (MI, stroke, and CV mortality), MI: myocardial infarction, CV: cardiovascular, HR: hazard ratio, CI: confidence interval.

Figure 2

Event rate based on Kaplan-Meier curve across the clusters. Patients in cluster 4 had higher rate of adverse events; A) Major adverse cardiovascular events, B) myocardial infarction C) cardiovascular death D) all-cause death.

Figure 3

Most influential factors associated with major adverse cardiovascular events according to LASSO regression IL: interleukin, MCSF-1: macrophage colony-stimulating factor-1, hxdm2: history of diabetes mellitus.