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Malondialdehyde (MDA) is generated in oxidized LDL. It forms covalent protein adducts, and is recognized by antibodies (anti-MDA). We previously studied IgM anti-MDA, and here we focus on IgG, IgG1 and IgG2 anti-MDA in predicting cardiovascular disease (CVD). We determined, by ELISA, anti-MDA in a 7-year follow-up of 60-year-old men and women from Stockholm County (2039 men, 2193 women). We identified 210 incident CVD cases (defined as new events of myocardial infarction (MI), and hospitalization for angina pectoris) and ischemic stroke, and 620 age- and sex-matched controls. IgG anti-MDA was not associated with CVD. Median values only differed significantly for IgG1 anti-MDA among men, with lower levels among cases than controls (p = 0.039). High IgG1 anti-MDA (above 75th percentile) was inversely associated with CVD risk after adjustment for smoking, body mass index, type 2 diabetes, hyperlipidemia, and hypertension, (OR and 95% CI: 0.59; 0.40–0.89). After stratification by sex, this association emerged in men (OR and 95% CI: 0.46; 0.27–0.77), but not in women. IgG2 anti-MDA were associated with protection in the whole group and among men though weaker than IgG1 anti-MDA. IgG2 anti-MDA above the 75th percentile was associated with an increased risk of MI/angina in women (OR and 95% CI: 2.57; (1.08–6.16)). IgG1 and less so IgG2 anti-MDA are protection markers for CVD and MI/angina in the whole group and among men. However, IgG2 anti-MDA was a risk marker for MI/angina among women. These findings could have implications for both prediction and therapy. [ABSTRACT FROM AUTHOR]