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

J Thromb Thrombolysis. 2014 Apr;37(3):310-6. doi: 10.1007/s11239-013-0968-y.

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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acute Coronary Syndrome* / blood
  • Acute Coronary Syndrome* / complications
  • Acute Coronary Syndrome* / 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
  • Myocardial Infarction* / etiology
  • Myocardial Infarction* / prevention & control
  • Phosphorylcholine*
  • Rivaroxaban
  • Stroke* / blood
  • Stroke* / etiology
  • Stroke* / prevention & control
  • Thiophenes / administration & dosage*

Substances

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