Interleukin-6 modifies Lipoprotein(a) and oxidized phospholipids associated cardiovascular disease risk in a secondary prevention cohort

Background and aims: There is a need for effective tools to stratify and modify cardiovascular risk associated with elevated lipoprotein(a) [Lp(a)] and oxidized phospholipids (OxPL). The objective of this analysis was to explore the modifying effects of low-grade inflammation on Lp(a)- and OxPL-associated risk in a secondary prevention cohort. Methods: Levels of Lp(a), OxPL associated with apolipoprotein(a) (OxPL-apo[a]) and apolipoprotein B (OxPL-apoB) were determined in the placebo-arm of the low-dose colchicine 2 trial. Patients were between 35 and 82 years, had established chronic coronary syndrome (CCS), and were clinically stable for at least six months prior to randomization. The outcome was the incidence of the composite endpoint of spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization stratified by biomarker levels using a Cox regression model. Results: There was a significant interaction between Lp(a) and IL-6 <3.2 ng/L (median) and IL-6 ≥3.2 ng/L for the composite endpoint (HR 0.90; 95 %CI 0.78–1.03 vs HR 1.18; 95 %CI 1.01–1.39, P_interaction = 0.01). No interaction was found for Lp(a) levels in participants with hsCRP <2 mg/L (HR 1.00; 95 %CI 0.89–1.14) versus those with hsCRP ≥2 mg/L (HR 1.04; 95 %CI 0.86–1.25, P_interaction = 0.79). In line with Lp(a) levels, significant interaction was observed between OxPL-apo(a) as well as OxPL-apoB levels for the composite endpoint with IL-6 (P_interaction<0.01 and 0.03, respectively), but not for hsCRP. Conclusions: In patients with CCS, Lp(a), OxPL-apo(a) and OxPL-apoB associated cardiovascular risk was only pertinent in those with elevated IL-6 but not hsCRP levels.