Autoantibodies to phosphorylcholine and cardiovascular outcomes in patients with acute coronary syndromes in the ATLAS ACS-TIMI 46 trial.

Abstract

Atherogenesis is a complex inflammatory process stemming from the accumulation and oxidation of low density lipoproteins (LDL). IgM autoantibodies against phosphorylcholine (anti-PC) bind to the PC epitope on oxidized LDL (OxLDL), inhibiting the uptake of oxLDL by macrophages in atherosclerotic lesions. Anti-PC autoantibodies have been reported to be protective against atherothrombosis. We investigated the relationship of anti-PC concentrations with cardiovascular outcomes in patients with acute coronary syndromes (ACS). We measured anti-PC levels within 7 days of an ACS in 3,356 patients enrolled in the ATLAS ACS-TIMI 46 trial, a randomized dose ranging study of rivaroxaban versus placebo. The primary endpoint was death, myocardial infarction (MI), stroke, or severe recurrent ischemia (SRI) requiring revascularization during 6 months. The median baseline anti-PC concentration was 40.9 U/mL (25th, 75th percentiles: 25.4, 67.4). There was no significant association between anti-PC levels and the primary endpoint (Q1: 6.8 %, Q2: 4.2 %, Q3: 7.8 %, Q4: 5.4 %, p-trend = 0.87), all-cause mortality (Q1: 1.4 %, Q2: 0.7 %, Q3: 2.4 %, Q4: 0.9 %, p-trend = 0. 96), or any of the other individual endpoint components (MI: p-trend = 0.87, Stroke: p-trend = 0.43, SRI: p-trend = 0.66). Using the previously reported anti-PC cutpoint of 17 U/mL did not reveal a significant relationship between anti-PC concentrations and cardiovascular outcomes (<17 U/mL: 8.1 % vs. ≥17 U/mL: 5.8 %; p = 0.11). Similarly, evaluation of anti-PC as a continuous variable did not reveal a significant association (p = 0.30). In this study of patients early after ACS undergoing intensive secondary preventive therapy, IgM anti-PC titers did not exhibit a significant relationship with cardiovascular outcomes.

• Authors: Bram J Geller, Jessica L Mega, David A Morrow, Jianping Guo, Elaine B Hoffman, C Michael Gibson, Christian T Ruff
• Journal: Journal of thrombosis and thrombolysis (J Thromb Thrombolysis) Vol. 37 Issue 3 Pg. 310-6 (Apr 2014) ISSN: 1573-742X [Electronic] Netherlands
• PMID: 23860881 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Antibodies, Antiphospholipid
• Factor Xa Inhibitors
• Immunoglobulin M
• Morpholines
• Thiophenes
• Phosphorylcholine
• Rivaroxaban

Topics

• Acute Coronary Syndrome (blood, complications, drug therapy)
• Aged
• Antibodies, Antiphospholipid (blood)
• Factor Xa Inhibitors (administration & dosage)
• Female
• Humans
• Immunoglobulin M (blood)
• Male
• Middle Aged
• Morpholines (administration & dosage)
• Myocardial Infarction (blood, etiology, prevention & control)
• Phosphorylcholine
• Rivaroxaban
• Stroke (blood, etiology, prevention & control)
• Thiophenes (administration & dosage)