Serum Inflammatory Markers Used in Cardiovascular Disease Risk Prediction Models: A Systematic Review

The aim of this review was to perform a critical appraisal of serum inflammatory biomarkers used for the prediction of cardiovascular disease (CVD) risk. We conducted a systematic review of studies listed on MEDLINE and Scopus from January 2000 to December 2023, focused on the prognostic value of serum inflammatory biomarkers [i.e., C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)] in individuals without known CVD. Eligible studies used a multivariate prediction model and included discrimination or risk reclassification analysis. The Quality in Prognostic Studies (QUIPS) tool was used to evaluate study quality and potential bias. Thirty-five studies (i.e., total 208,897 participants) that evaluated the added prognostic value of CRP, IL-6, TNF-α on CVD risk prediction were retrieved. Significant improvements in CVD risk model's predictive ability were observed in 7 out of 32 studies relating CRP and 1 out of 8 studies relating IL-6 with CVD risk. The single study found no added prognostic value of TNF-α use in CVD risk model. The integration of serum inflammatory biomarkers into CVD risk prediction models does not appear to improve risk discrimination models, suggesting that these biomarkers may act as surrogate markers, but not as predictors of atherosclerotic CVD.