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American Heart Association, Circulation, Suppl_1(148), 2023

DOI: 10.1161/circ.148.suppl_1.17748

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Abstract 17748: Lipoprotein(a) and Oxidized Phospholipids on Lipoproteins and Cardiovascular Outcomes in Patients With Chronic Coronary Syndrome Treated With Colchicine

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

Introduction: Lipoproteins carrying pro-inflammatory oxidized phospholipids (OxPL), exemplified by lipoprotein(a) [Lp(a)], contribute to residual risk for major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome (CCS) despite optimal medical treatment. Hypothesis: Anti-inflammatory colchicine therapy modifies MACE in patients with elevated Lp(a), OxPL on apo(a) [OxPL-apo(a)], and OxPL on apoB containing lipoproteins (OxPL-apoB). Aims To study the relationship of Lp(a), OxPL-apo(a) and OxPL-apoB with MACE in 1777 LoDoCo2 trial participants with CCS randomized to colchicine or placebo. Methods: End of study but not baseline samples were available. Because Lp(a), OxPL-apo(a) and OxPL-apoB levels are strongly genetically determined, we assumed that end of study values would reflect baseline values. The primary endpoint was a composite of MI, ischemic CVA or ischemia driven coronary revascularization. Cox regression was used to compare the incidence of the primary endpoint by Lp(a) dichotomized at 125 nmol/L and OxPL-apo(a) and OxPL-apoB in tertiles. Results: At study end, median (IQR) on-colchicine Lp(a), OxPL-apo(a), and OxPL-apoB levels in nmol/L were 22.4 (7.2-102.7), 7.8 (2.0-34.5) and 3.1 (1.3-6.3), similar to on-placebo levels of 23.9 (9.9-95.7), 8.8 (2.7-34.0), and 3.1 (1.4-5.9), respectively (p = 0.20, 0.98 and 0.18). MACE reduction with colchicine was independent of Lp(a) and OxPL-apo(a) (P interaction = 0.92 and 0.66 respectively). However, the largest MACE reduction was present in the highest vs lowest OxPL-apoB tertile ( Figure , P interaction < 0.05). Conclusions: The benefit of colchicine in reducing MACE was highest in subjects with elevated OxPL-apoB, suggesting colchicine may be most effective in subjects with heightened oxidation-driven inflammation. These findings may be hypothesis-generating and require validation in larger trials with baseline biomarker assessment including CRP and IL-6.