Immune-related biochemical markers and 20-year incidence of atherosclerotic cardiovascular disease: the ATTICA study (2002–2022)

Abstract

Background and aims

Inflammation has been associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. We evaluated immune-related biomarkers regarding their ability, individually and as a composite score, to predict 20-year ASCVD incidence in an apparently healthy adult population.

Methods

A cohort of 1270 adults, who were free of ASCVD at baseline, with a 20-year follow-up from the prospective ATTICA study, were included in this analysis. Immune-related biochemical markers independently predictive of 20-year ASCVD risk were identified, and an aggregate biomarker score was developed. The incremental predictive value of this score beyond the SCORE2 was assessed using area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI).

Results

Three immune-related biomarkers -interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and fibrinogen-showed the best predictive ability of 20-year ASCVD risk and were subsequently integrated into an aggregate biomarker score (ImmActScore), exhibiting a range from 0 (6 % absolute risk) to 4 (63 % absolute risk). Individual ImmActScore was independently associated with 20-year ASCVD risk (multi-adjusted HR per 1-unit:1.24, 95 %CI:1.05–1.46, p = 0.011). The 38.5 % of the 20-year incident ASCVD could be attributed to ImmActScores of ≥1. Integrating ImmActScore into the SCORE2 model yielded a continuous NRI of 0.603 and a categorical NRI of 18.4 % in the 40–50 year age group.

Conclusions

Assessing immune-related pathways may offer additional potential for long-term ASCVD risk stratification. A combined measure of IL-6, TNF-α and fibrinogen levels was associated with ASCVD events over a 20-year period. Further validation in independent cohorts is warranted.