Volume 405, June 2025, 119211Author links open overlay panel, , , , , , , , , , , , Highlights•

We assessed whether biomarkers of inflammation modify Lp(a) and OxPL-associated cardiovascular risk.

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In a secondary analysis of the LoDoCo2 trial, elevated IL-6 but not hsCRP levels modified Lp(a) and OxPL-associated risk.

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This suggest that in patients with elevated Lp(a) levels, IL-6 may identify those with the highest cardiovascular risk.

AbstractBackground 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.

Graphical abstractThe figure shows that Lp(a), OxPL-apo(a) and OxPL-apoB associated cardiovascular risk was only pertinent in those with elevated IL-6 but not hsCRP levels in a secondary prevention cohort. Lp(a) = Lipoprotein (a); OxPL-apo(a) = Oxidized phospholipids on apolipoprotein(a); OxPL-apoB = Oxidized phospholipids on apolipoprotein B-100; CAD = Coronary artery disease; IL-6 = Interleukin-6; hsCRP = High sensitivity C-reactive protein.Download: Download high-res image (372KB)Download: Download full-size image

© 2025 The Authors. Published by Elsevier B.V.