Research Article: IgM antibodies against phosphorylcholine measured early after acute ST-elevation myocardial infarction in relation to atherosclerotic disease burden and long-term clinical outcome

Date Published: April 19, 2019

Publisher: Public Library of Science

Author(s): Eva Cecilie Knudsen, Ingebjørg Seljeflot, Tonje Amb Aksnes, Jan Eritsland, Harald Arnesen, Geir Øystein Andersen, Tohru Minamino.

http://doi.org/10.1371/journal.pone.0215640

Abstract

Studies have reported an association between low levels of natural immunoglobulin M antibodies against phosphorylcholine(IgM anti-PC) and worse prognosis in patients with coronary artery disease (CAD). The aims of the present study were, in patients with ST-elevation myocardial infarction (STEMI); 1) to compare serum levels of IgM anti-PC measured acutely and after 3 months; 2) to study an association between levels of IgM anti-PC and the severity ofCAD, and; 3) to investigate whether IgM anti-PC levels are associated with long-term clinical outcome.

A total of 213 patients without known diabetes (median age 59 years) with a PCI treated STEMI were enrolled. IgM anti-PC was measured in-hospital and after 3 months. Median follow-up time was 6.5 years (all-cause mortality, non-fatal myocardial re-infarction, recurrent ischemia causing hospital admission, heart failure and stroke). The severity of CAD was evaluated by coronary angiograms and patients were classified as having single- or multi-vessel disease and by SYNTAX score (SXscore).

IgM anti-PC levels were stable over time when measured acutely and after 3 months. Patients with multi-vessel disease and high SXscore had significantly lower levels of IgM anti-PC in the acute phase of STEMI. Low levels of IgM anti-PC (the 25 percentile) measured acutely were associated with a 2-fold increase in the odds of having multi-vessel disease (adjusted OR 2.28 (95% CI 1.17, 4.44), p = 0.016), but not with high SXscore (Crude OR 2.20 (95% CI 0.96, 5.07), p = 0.06). Fifty-three patients experienced a new clinical event during long-term follow-up. Low levels of IgM anti PC were not associated with worse prognosis, (crude HR 1.54 (0.87–2.76), p = 0.14).

STEMI patients with multi-vessel disease or high SXscore had significantly lower levels of IgM anti-PC in the acute phase and low levels were associated with multi-vessel disease, but not with worse clinical outcome during long-term follow-up.

Partial Text

The atherosclerotic process leading to plaque rupture and coronary occlusion is the leading underlying cause of myocardial infarction and sudden cardiac death, and atherosclerosis is considered at least partly to be an inflammatory disease [1–3]. Autoantibodies directed towards a variety of oxidation-specific epitopes or self—antigens have been identified as mediators in this complex inflammatory environment [4]. Oxidation-specific epitopes belong to a class of danger-associated molecular patterns (DAMPS), and DAMPs are recognized by pattern recognition receptors (PRR) on macrophages, natural antibodies and other effector proteins from the innate immune system [5]. Phosphorylcholine (PC) is a known oxidation-specific epitope on oxidized low-density lipoprotein (OxLDL) and natural immunoglobulin M (IgM) antibodies against PC (IgM anti-PC) may have atheroprotective properties in response to oxidative stress [4]. Low levels of IgM anti-PC have been shown, in some studies, to be associated with worse prognosis in patients with acute coronary syndrome [6]. However, little is known about the levels of IgM anti-PC during an acute ST-elevation myocardial infarction (STEMI), how levels change in patients post-MI, or a possible association between levels of IgM anti-PC measured acutely and the extent of coronary artery disease, or new clinical events after STEMI. The aims of the present study were therefore; in patients with STEMI 1) to compare serum levels of IgM anti-PC measured acutely with measurements after 3 months; 2) to study a possible association between levels of IgM anti-PC and the severity of coronary artery disease, and; 3) to investigate whether IgM anti-PC levels are associated with long-term clinical outcome.

In this cohort of STEMI patients the levels of IgM anti-PC were stable over time when measured during acute illness in-hospital and again in a stable condition after 3 months. Patients with advanced coronary heart disease defined as multi-vessel disease or high SxScore had significantly lower levels of IgM anti-PC during the acute STEMI. There was a significant association between low levels of IgM anti-PC and multi-vessel disease, but not with high SXscore or long-term clinical outcome.

The levels of IgM anti-PC were stable over time when measured acutely and again after 3 months in this cohort of STEMI patients. Patients with multi-vessel disease or high SXscore had significantly lower levels of IgM anti-PC in the acute phase of STEMI. Low levels of IgM anti-PC were also associated with multi-vessel disease after adjustment in multivariate analyses, indicating that IgM anti-PC are a marker of patients with advanced atherosclerotic disease burden. Low levels of IgM anti-PC were not associated with worse clinical outcome during long-term follow-up, although the study may lack statistical power to detect an increased risk due to the excellent clinical outcome.

 

Source:

http://doi.org/10.1371/journal.pone.0215640

 

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