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Open Access Highly Accessed Research article

Low levels of IgM antibodies to oxidized cardiolipin increase and high levels decrease risk of cardiovascular disease among 60-year olds: a prospective study

Jun Su1, Xiang Hua1, Max Vikström2, Karin Leander2, Bruna Gigante2, Mai-Lis Hellenius3, Ulf de Faire24 and Johan Frostegård1*

Author Affiliations

1 Institute of Environmental Medicine, Unit of Immunology and Chronic Disease, Karolinska Institutet, 17177 Stockholm, Stockholm, Sweden

2 Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

3 Department of Medicine, Karolinska University Hospital, Solna, Sweden

4 Department of Cardiology, Karolinska University Hospital, Solna, Sweden

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BMC Cardiovascular Disorders 2013, 13:1  doi:10.1186/1471-2261-13-1

Published: 7 January 2013

Abstract

Background

Antibodies against cardiolipin (aCL) are associated with increased risk of cardiovascular disease (CVD). We here determine the role of antibodies against oxidized CL (aOxCL).

Methods

One third of sixty-year olds from the Stockholm County were screened (2039 men, 2193 women), where 211 incident CVD-cases and 633 age- and sex-matched controls were identified (5–7 year follow-up). Antibodies were determined by ELISA and uptake of oxLDL in macrophages by FACScan.

Results

IgM aOxCL was lower among CVD cases than controls (p=0.024). aOxCL-levels were divided in quartiles with the highest quartile set as the reference group. After adjustment for smoking, BMI, type II diabetes, hypercholesterolaemia and hypertension, an increased risk was determined in the lowest quartile of IgM aOxCL (OR: 1.80, CI: 1.12–2.91, p=0.0159); OR for men in the lowest quartile was 2.46 (CI 1.34–4.53, p=0.0037) for CVD and for stroke: 12.28 (CI: 1.48-101.77, p=0.02). IgG aOxCL levels did not differ between quartiles in CVD-risk. High levels of IgM aOxCL (reaching significance above 86th) and IgG aOxCL (above 95th percentile) were associated with decreased risk of CVD (OR: 0.485, CI: 0.283-0.829; p=0.0082 and OR: 0.23, CI: 0.07-0.69; p=0.0091). aCL were not associated with CVD. oxCL but not CL competed out uptake of OxLDL in macrophages, and aOxLDL recognized oxCL but not CL. In contrast to aCL, aOxCL was not dependent on co-factor Beta2-glycoprotein-I.

Conclusions

aOxCL is a novel risk/protection marker for CVD, with therapeutic implications. OxCL competes with oxLDL for uptake in macrophages and the possibility that aOxCL inhibits such uptake by interfering with same or similar epitopes in oxCL and oxLDL should be further studied.

Keywords:
Cardiovascular disease; Cardiolipin; Oxidation; Antibodies