Abstract 17748: Lipoprotein(a) and Oxidized Phospholipids on Lipoproteins and Cardiovascular Outcomes in Patients With Chronic Coronary Syndrome Treated With Colchicine
Niekbachsh Mohammadnia, Amber van Broekhoven, Willem A Bax, John W Eikelboom, Arend Mosterd, Xiaohong Yang, Jan G Tijssen, Peter L Thompson, Dominique de Kleijn, Saloua El Messaoudi, Sotirios Tsimikas, Calvin Yeang, Jan H Cornel- Physiology (medical)
- Cardiology and Cardiovascular Medicine
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.