title: 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.affiliation: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 350 Longwood Avenue, First Floor, Boston, MA, USA, bgeller@partners.org.
authors.forename: Bram J
authors.initials: BJ
authors.lastname: Geller
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Mega
authors.forename: David A
authors.initials: DA
authors.lastname: Morrow
authors.forename: Jianping
authors.initials: J
authors.lastname: Guo
authors.forename: Elaine B
authors.initials: EB
authors.lastname: Hoffman
authors.forename: C Michael
authors.initials: CM
authors.lastname: Gibson
authors.forename: Christian T
authors.initials: CT
authors.lastname: Ruff
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy; D000368:Aged; D017152:Antibodies, Antiphospholipid / Q000097:blood*; D065427:Factor Xa Inhibitors / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage*; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D010767:Phosphorylcholine; D000069552:Rivaroxaban; D020521:Stroke / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D013876:Thiophenes / Q000008:administration & dosage*
chemical_list: D017152:Antibodies, Antiphospholipid; D065427:Factor Xa Inhibitors; D007075:Immunoglobulin M; D009025:Morpholines; D013876:Thiophenes; D010767:Phosphorylcholine; D000069552:Rivaroxaban