Prognostic value of vascular inflammation biomarkers over clinical risk factors for cardiovascular risk : a meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background Measurement of vascular inflammation biomarkers is supported for estimation of residual inflammatory risk and cardiovascular risk stratification, but to date there is no systematic assessment of the added value of such biomarkers in predicting cardiovascular events and their comparative performance. Methods We systematically searched in MEDLINE published literature before Apr 14, 2020 for prospective cohort studies assessing the prognostic value of common biomarkers of vascular inflammation in stable patients with or without cardiovascular disease. The primary outcome was the difference in the c-index (Δ[c-index]) of the best clinical model with the use of inflammatory biomarkers for the prediction of the composite endpoint of major adverse cardiovascular events (MACEs) and mortality. The secondary outcome was the Δ[c-index] for MACEs only. We calculated I² to test heterogeneity. We used random-effects modelling for the meta-analyses to assess the primary and secondary outcome. Results We identified 92,507 studies in MEDLINE after duplicates were removed, of which 90,882 (96%) studies were excluded after screening the titles and abstracts, and 1,507 (93%) of the 1,625 remaining studies were excluded after assessment of the full texts. We included 93 (6%) studies in our quantitative evaluation, in which 351,628 individuals participated. The combination of high-risk plaque features and Fat attenuation Index (FAI) by CCTA was associated with the highest prognostic value i.e. Δ[c-index] for the composite endpoint per biomarker type (A). In meta-analysis, both plasma and imaging biomarkers of vascular inflammation offered incremental prognostic value for the primary outcome (pooled estimate for Δ[c-index]% 2.9, 95%CI 2.1-3.6, B) and for MACEs only (pooled estimate for Δ[c-index]% 2.9, 95%CI 2.1-3.8). The prognostic value of imaging biomarkers significantly surpassed that of plasma biomarkers for the primary outcome (Δ[c-index]% 11.3, 95%CI 8.3-14.3 vs. 1.4, 95%CI 0.9-1.8 respectively, p = 1.7x10-10, C). Notably, biomarkers of vascular inflammation offered higher incremental prognostic value in studies with a shorter duration of follow-up (i.e. <5 years), in primary CHD prevention setting and lower cardiovascular risk populations i.e. (studies with <5% cumulative event incidence, D) Conclusions The combination of HRP features and FAI by CCTA imaging had the highest prognostic value for cardiovascular events among plasma or imaging biomarkers of vascular inflammation. CCTA imaging to detect residual inflammatory risk and the vulnerable patient at risk for events is a rational approach to improve risk stratification and prognostication. Abstract Figure.