The Effects of Colchicine on Lipoprotein(a) and Oxidized Phospholipid Associated Cardiovascular Disease Risk

Niekbachsh Mohammadnia; Amber van Broekhoven; Willem A Bax; John W Eikelboom; Arend Mosterd; Aernoud T L Fiolet; Jan G P Tijssen; Peter L Thompson; Dominique P V de Kleijn; Sotirios Tsimikas; Jan H Cornel; Calvin Yeang; Saloua El Messaoudi

doi:10.1093/eurjpc/zwae355

The Effects of Colchicine on Lipoprotein(a) and Oxidized Phospholipid Associated Cardiovascular Disease Risk

Eur J Prev Cardiol. 2024 Oct 30:zwae355. doi: 10.1093/eurjpc/zwae355. Online ahead of print.

Authors

Niekbachsh Mohammadnia¹, Amber van Broekhoven¹, Willem A Bax², John W Eikelboom³, Arend Mosterd^{4

5}, Aernoud T L Fiolet^{4

6}, Jan G P Tijssen⁷, Peter L Thompson^{8

9

10}, Dominique P V de Kleijn^{11

12}, Sotirios Tsimikas¹³, Jan H Cornel¹⁴, Calvin Yeang¹³, Saloua El Messaoudi¹

Affiliations

¹ Department of Cardiology, Radboud University Medical Center, Nijmegen, The Netherlands.
² Department of Internal Medicine, Northwest Clinics, Alkmaar, The Netherlands.
³ Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
⁴ Dutch Network for Cardiovascular Research (WCN), Utrecht, The Netherlands.
⁵ Department of Cardiology, Meander Medical Center, Amersfoort, The Netherlands.
⁶ Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
⁷ Department of Cardiology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
⁸ Heart and Vascular Research Institute of Western Australia, Perth, Australia.
⁹ School of Medicine, University of Western Australia, Perth, Australia.
¹⁰ Sir Charles Gairdner Hospital, Perth, Australia.
¹¹ The Netherlands Heart Institute, Utrecht, The Netherlands.
¹² Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
¹³ Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
¹⁴ Department of Cardiology, Northwest Clinics, Alkmaar, The Netherlands.

PMID: 39478683
DOI: 10.1093/eurjpc/zwae355

Abstract

Aims: Inflammatory lipoprotein(a) [Lp(a)] and oxidized phospholipids (OxPLs) on lipoproteins convey residual cardiovascular disease risk. The LoDoCo2 (low-dose colchicine 2) trial showed that colchicine reduced the risk for cardiovascular events occurring on standard therapies in patients with chronic coronary disease (CCS). We explored the effects of colchicine on Lp(a) and oxidized lipoprotein associated risk in a LoDoCo2 biomarker subpopulation.

Methods: Lp(a), OxPLs on apolipoprotein(a) [OxPL-apo(a)] and apolipoprotein B (OxPL-apoB) levels were determined in the biomarker population of the LoDoCo2 trial (n = 1777). Cox regression analysis was used to compare the risk for the primary endpoint, consisting of myocardial infarction, ischemic stroke, or ischemia-driven revascularization by biomarker levels. Interactions between treatment, Lp(a) and OxPL levels were evaluated.

Results: Lp(a), OxPL-apo(a) and OxPL-apoB levels were similar between the colchicine and placebo groups. Consistent risk reduction by colchicine was observed in those with Lp(a) <125 nmol/L and ≥125 nmol/L, and the highest OxPL-apo(a) tertile compared to the lowest (Pinteraction=0.92 and 0.66). The absolute risk reduction for those with Lp(a) ≥125 nmol/L appeared higher compared to those with Lp(a) <125 nmol/L (4.4% vs 2.4%). A treatment interaction for colchicine was found in those with the highest OxPL-apoB tertile vs the lowest (Pinteraction=0.04).

Conclusion: In patients with CCS, colchicine reduces cardiovascular disease risk in those with and without elevated Lp(a) but absolute benefits appeared higher in those with Lp(a) ≥125 nmol/L. Patients with higher levels of OxPL-apoB experienced greater benefit of colchicine, suggesting colchicine may be more effective in subjects with heightened oxidation-driven inflammation.

Keywords: Colchicine; Inflammation; Lipoprotein(a); Lipoproteins; Oxidized Phospholipids; Secondary Prevention.

Plain language summary

Oxidized circulating particles containing lipids and proteins (lipoproteins), including lipoprotein(a), are inflammatory and increase the risk for heart disease. Colchicine, an anti-inflammatory agent, reduces heart disease risk in patients with elevated levels of lipoprotein(a).Colchicine was more effective at reducing heart disease risk in patients with high levels of oxidized apoB containing lipoproteins compared to those with lower levels.

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