Inflammation
IL-6, not hsCRP, unmasks Lp(a)- and oxidised-phospholipid-associated cardiovascular risk in the LoDoCo2 placebo arm (Atherosclerosis 2025)
Original title: Interleukin-6 modifies Lipoprotein(a) and oxidized phospholipids associated cardiovascular disease risk in a secondary prevention cohort
This analysis used the placebo arm of the low-dose colchicine 2 (LoDoCo2) trial, in patients with chronic coronary syndrome stable for at least six months, to test whether low-grade inflammation modifies cardiovascular risk associated with Lp(a) and oxidised phospholipids (OxPL) on apo(a) and apoB. A significant interaction was found between Lp(a) and IL-6 for the composite endpoint of myocardial infarction, ischaemic stroke or ischaemia-driven revascularisation: risk was not elevated with Lp(a) when IL-6 was below the 3.2 ng/L median (HR 0.90) but was elevated when IL-6 was at or above it (HR 1.18, P for interaction = 0.01). No such interaction was seen with hsCRP (P for interaction = 0.79). The same pattern held for OxPL-apo(a) and OxPL-apoB, both showing significant interaction with IL-6 but not hsCRP. The authors conclude that in chronic coronary syndrome, Lp(a)- and OxPL-associated risk is only apparent with elevated IL-6, not hsCRP, pointing to IL-6 as the more relevant marker for identifying at-risk Lp(a) patients.
Original abstract
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, Pinteraction = 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, Pinteraction = 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 (Pinteraction<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.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.