Anti-Cardiolipin Antibodies and Risk of Myocardial Infarction in a Prospective Cohort of Middle-Aged Men

Vaarala, Outi; Mänttäri, Matti; Manninen, Vesa; Tenkanen, Leena; Puurunen, Marja; Aho, Kimmo; Palosuo, Timo

doi:10.1161/01.cir.91.1.23

Cited by 327 publications

(163 citation statements)

References 23 publications

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“…A number of studies have previously demonstrated that aPL can increase the risk of thrombotic events, suggesting an important role for these autoantibodies in the pathogenesis of APS (28,29). However, their role in the development of lupus has largely remained unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Lupus patients who develop aPL have an increased risk of developing thrombocytopenia (range 11-40%, versus ϳ4-17% in aPL-negative SLE), hemolytic anemia (range 5-16% versus 2-8%), and symptoms traditionally thought of as being associated with APS rather than SLE, such as arterial or venous thrombosis and recurrent fetal loss (6)(7)(8)(9)(10)(28)(29)(30)(31). In our study, thrombocytopenia and hemolytic anemia were found to be significantly more common among aPL-positive patients, as was the risk of thrombotic events usually associated with APS.…”

Section: Discussionmentioning

confidence: 99%

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The prevalence, onset, and clinical significance of antiphospholipid antibodies prior to diagnosis of systemic lupus erythematosus

McClain¹,

Arbuckle²,

Heinlen³

et al. 2004

Arthritis & Rheumatism

171

126

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Objective. To determine whether antiphospholipid antibodies (aPL) occur before the diagnosis of systemic lupus erythematosus (SLE) and before initial clotting events, and whether their presence early in the disease course influences clinical outcome.Methods. Serum samples obtained from 130 lupus patients before and after SLE diagnosis were screened for IgG and IgM aPL using an anticardiolipin (aCL) enzyme-linked immunosorbent assay. Medical records of all patients were carefully reviewed for data on the time of onset of SLE features meeting clinical criteria and on disease manifestations.Results. Twenty-four patients (18.5%) were positive for IgG and/or IgM aCL prior to SLE diagnosis. Anticardiolipin antibodies appeared from 7.6 years prior to SLE diagnosis to within the same month as SLE diagnosis, with a mean onset occurring 3.0 years before SLE diagnosis. Additionally, aCL presence early in the disease process seemed to predict a more severe clinical outcome; these patients eventually met an average of 6.1 of the 11 classification criteria for SLE, compared with 4.9 criteria for other patients (P < 0.001). The early aCL-positive population also had more frequent renal disease, central nervous system disease, thrombocytopenia, and clotting events. In this population, aCL preceded initial thrombotic events by a mean of 3.1 years.Conclusion. Anticardiolipin antibodies in SLE patients tend to precede initial clotting events by several years. Furthermore, the presence of early, prediagnosis aPL seems to herald a more varied, severe clinical course with earlier onset in patients with SLE.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The prevalence, onset, and clinical significance of antiphospholipid antibodies prior to diagnosis of systemic lupus erythematosus

McClain¹,

Arbuckle²,

Heinlen³

et al. 2004

Arthritis & Rheumatism

171

126

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“…In stroke patients, 18% of young patients (mean age, 38 years) were positive for antiphospholipid antibodies (LA and aCL) and 9.7% of patients who developed stroke for the first time were positive for aCL according to the Antiphospholipid Antibodies in Stroke Study Group (APASS) [8,9]. In patients with myocardial infarction, the prevalence of aCL is reported to be between 5% and 15% [10]. In 543 blood donors under 65 years of age, 2% were positive for aCL [11].…”

Section: Introductionmentioning

confidence: 99%

High prevalence of anti‐prothrombin antibody in patients with deep vein thrombosis

et al. 2004

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The present study was designed to determine the prevalence of lupus anticoagulant (LA) antibody and several antibodies for antiphospholipid syndrome (APS) in patients with deep vein thrombosis (DVT)/pulmonary embolism (PE) (n = 48), cerebral thrombosis (CT, n = 30), systemic lupus erythematosus (SLE, n = 22), and idiopathic thrombocytopenic purpura (ITP, n = 30). The presence of antibodies was examined by using the respective ELISA kits. LA was positive in 38.6% of patients with DVT/PE, suggesting that LA is one of the most important risk factors in DVT/PE. The highest prevalence of anti-b 2 glycoprotein I (b 2 GPI) IgG was in CT and SLE, followed by DVT, and none in ITP and healthy volunteers (control, n = 40), suggesting that it is related to thrombosis, particularly arterial thrombosis. The highest prevalence of anti-prothrombin (aPT) IgG antibody was in DVT, followed by CT and SLE, and none in ITP and the control, suggesting that it is related to thrombosis, especially venous thrombosis. The highest prevalence of antiphospholipid (aPL) IgG was in DVT, CT, and SLE, but 0% in ITP and control. On the other hand, aPL IgM, anti-annexin V IgG, and anti-annexin V IgM were positive in patients both with and without thrombosis, suggesting that they are not related to thrombosis. Our results indicated that among the anti-phospholipid antibodies, LA is the most sensitive marker for APS while anti-b 2 GPI IgG, aPT IgG, and aPL IgG are risk factors for thrombosis. In particular, aPT IgG is a significant marker for DVT/PE. Am.

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“…Correlation between the levels of anticardiolipin antibodies and antibodies to oxidized LDL was also found in a prospective study of healthy men in whom the presence of increased levels of both antibodies predicted myocardial infarction [12,13]. However, the effect was additive, suggesting that their biological functions, despite the cross-reaction, may differ in vivo [13].…”

Section: Introductionmentioning

confidence: 65%

“…However, the effect was additive, suggesting that their biological functions, despite the cross-reaction, may differ in vivo [13].…”

Section: Introductionmentioning

confidence: 99%

Affinity-purified cardiolipin-binding antibodies show heterogeneity in their binding to oxidized low-density lipoprotein

Vaarala¹,

Puurunen²,

Lukka³

et al. 1996

Clinical and Experimental Immunology

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SUMMARYAntiphospholipid antibodies in autoimmune sera have been shown to react with a complex of phospholipids (cardiolipin) and a plasma phospholipid-binding protein, 2 -glycoprotein I (apolipoprotein H). The binding of these antibodies was inhibited by oxidized low-density lipoprotein (LDL) in sera from patients with systemic lupus erythematosus (SLE), suggesting cross-reactivity between antiphospholipid antibodies and antibodies binding to oxidized LDL. We purified antiphospholipid antibodies by cardiolipin-polyacrylamide column from seven SLE sera and studied the reactivity of eluted fractions with cardiolipin-2 -glycoprotein I complex and oxidized LDL (malondialdehydeconjugated LDL) in solid-phase enzyme immunoassay. In four sera the binding of IgG antibodies to cardiolipin-2 -glycoprotein I complex and to oxidized LDL appeared in the same fractions, whereas in three sera reactivities against cardiolipin and oxidized LDL were observed, at least in part, in separate fractions. The binding to solid-phase cardiolipin was dependent on the presence of exogenous 2 -glycoprotein I in all fractions. Our findings show that antiphospholipid antibodies are heterogeneous in their binding to oxidized LDL, indicating that these two antibodies may have different subspecificities. Some eluted fractions reacted only with oxidized LDL, and did not show binding to cardiolipin-2 -glycoprotein I complex, suggesting that the lipid part in the antigenic complex might be responsible for the cross-reactivity of these antibodies. Accordingly, the biological functions of antibodies against phospholipid-2 -glycoprotein I complex and antibodies against oxidized LDL may also be different.Keywords anticardiolipin antibodies oxidized low-density lipoprotein systemic lupus erythematosus antiphospholipid antibodies 2

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Anti-Cardiolipin Antibodies and Risk of Myocardial Infarction in a Prospective Cohort of Middle-Aged Men

Abstract: In a prospective cohort of healthy middle-aged men, the presence of a high aCL antibody level is an independent risk factor for myocardial infarction or cardiac death. Antibodies to cardiolipin and oxidized LDL may, at least in part, represent cross-reactive antibody populations.

Cited by 327 publications

References 23 publications

The prevalence, onset, and clinical significance of antiphospholipid antibodies prior to diagnosis of systemic lupus erythematosus

The prevalence, onset, and clinical significance of antiphospholipid antibodies prior to diagnosis of systemic lupus erythematosus

High prevalence of anti‐prothrombin antibody in patients with deep vein thrombosis

Affinity-purified cardiolipin-binding antibodies show heterogeneity in their binding to oxidized low-density lipoprotein

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