Dataset Information

Relationship of Autoantibodies to MDA-LDL and ApoB-Immune Complexes to Sex, Ethnicity, Subclinical Atherosclerosis, and Cardiovascular Events.

ABSTRACT: OBJECTIVE:Modifications of lipid constituents within atherosclerotic lesions generate neoepitopes that activate innate and adaptive immune responses. We aimed to define the prevalence, distribution, and relationship of autoantibody titers of oxidized lipoproteins to subclinical atherosclerosis and major adverse cardiovascular events (MACE) in different ethnic groups. APPROACH AND RESULTS:IgG and IgM autoantibodies to malondialdehyde-modified low-density lipoprotein (MDA-LDL) and apolipoprotein B-100-immune complexes were measured in 3509 individuals (1814 blacks, 1031 whites, 589 Hispanics, and 85 no race identifier) from the Dallas Heart Study with median 10.5-year follow-up. Coronary artery calcium score, abdominal aortic plaque by magnetic resonance imaging, and MACE were quantified. IgG MDA-LDL and IgG and IgM apolipoprotein B-100-immune complexes were significantly different between groups, with blacks having the highest levels of IgG MDA-LDL and IgG apolipoprotein B-100-immune complexes and Hispanics having the highest levels of IgM apolipoprotein B-100-immune complexes (P<0.001 for all). IgGs tended to be higher and IgMs lower with age for all markers. In multivariable-adjusted binary logistic regression analysis, a doubling of IgG MDA-LDL levels was associated with prevalent coronary artery calcium score >10 Agatston units (odds ratio [95% confidence interval], 1.21 [1.07-1.36]; P=0.002). Multivariable-adjusted Cox regression analysis revealed that IgG MDA-LDL was independently associated with time to incident MACE in the entire group (hazard ratio [95% confidence interval], 1.76 [1.16-2.72]; P=0.009 for fourth versus first quartile). This effect was particularly prominent in black subjects (hazard ratio [95% confidence interval], 2.52 [1.39-4.57]; P=0.002). CONCLUSIONS:Autoantibodies to oxidized lipoproteins and immune complexes with apoB-100 lipoproteins vary significantly by sex, age, and ethnicity. Higher baseline IgG MDA-LDL titers independently associate with new MACE. These findings may contribute to the understanding of differences in ethnic-specific MACE events.

SUBMITTER: Prasad A

PROVIDER: S-EPMC5500201 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Relationship of Autoantibodies to MDA-LDL and ApoB-Immune Complexes to Sex, Ethnicity, Subclinical Atherosclerosis, and Cardiovascular Events.

Prasad Anand A Clopton Paul P Ayers Colby C Khera Amit A de Lemos James A JA Witztum Joseph L JL Tsimikas Sotirios S

Arteriosclerosis, thrombosis, and vascular biology 20170504 6

<h4>Objective</h4>Modifications of lipid constituents within atherosclerotic lesions generate neoepitopes that activate innate and adaptive immune responses. We aimed to define the prevalence, distribution, and relationship of autoantibody titers of oxidized lipoproteins to subclinical atherosclerosis and major adverse cardiovascular events (MACE) in different ethnic groups.<h4>Approach and results</h4>IgG and IgM autoantibodies to malondialdehyde-modified low-density lipoprotein (MDA-LDL) and a ...[more]

PMID: 28473443

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Project description:ObjectivesIn this study, we aimed to establish whether age-sex-specific percentiles of coronary artery calcium (CAC) predict cardiovascular outcomes better than the actual (absolute) CAC score.BackgroundThe presence and extent of CAC correlates with the overall magnitude of coronary atherosclerotic plaque burden and with the development of subsequent coronary events.MethodsMESA (Multi-Ethnic Study of Atherosclerosis) is a prospective cohort study of 6,814 asymptomatic participants followed for coronary heart disease (CHD) events including myocardial infarction, angina, resuscitated cardiac arrest, or CHD death. Time to incident CHD was modeled with Cox regression, and we compared models with percentiles based on age, sex, and/or race/ethnicity to categories commonly used (0, 1 to 100, 101 to 400, 400+ Agatston units).ResultsThere were 163 (2.4%) incident CHD events (median follow-up 3.75 years). Expressing CAC in terms of age- and sex-specific percentiles had significantly lower area under the receiver-operating characteristic curve (AUC) than when using absolute scores (women: AUC 0.73 versus 0.76, p = 0.044; men: AUC 0.73 versus 0.77, p < 0.001). Akaike's information criterion indicated better model fit with the overall score. Both methods robustly predicted events (>90th percentile associated with a hazard ratio [HR] of 16.4, 95% confidence interval [CI]: 9.30 to 28.9, and score >400 associated with HR of 20.6, 95% CI: 11.8 to 36.0). Within groups based on age-, sex-, and race/ethnicity-specific percentiles there remains a clear trend of increasing risk across levels of the absolute CAC groups. In contrast, once absolute CAC category is fixed, there is no increasing trend across levels of age-, sex-, and race/ethnicity-specific categories. Patients with low absolute scores are low-risk, regardless of age-, sex-, and race/ethnicity-specific percentile rank. Persons with an absolute CAC score of >400 are high risk, regardless of percentile rank.ConclusionsUsing absolute CAC in standard groups performed better than age-, sex-, and race/ethnicity-specific percentiles in terms of model fit and discrimination. We recommend using cut points based on the absolute CAC amount, and the common CAC cut points of 100 and 400 seem to perform well.

Project description:OBJECTIVES:To examine the contemporary effect of smoking in a multiethnic sample, and to explore the respective contributions of inflammation and subclinical atherosclerosis to the cardiovascular consequences of smoking. APPROACH AND RESULTS:We studied 6814 participants free of cardiovascular disease and coronary heart disease (CHD) from the Multiethnic Study of Atherosclerosis. Smoking status and cumulative exposure were determined by self-report and confirmed by urinary cotinine. Multivariable Cox regression was used to estimate the association between smoking parameters and all-cause cardiovascular disease, all-cause CHD, and hard CHD events. We further adjusted for high-sensitivity C-reactive protein and coronary artery calcium (CAC) in hierarchical Cox models. We identified 3218 never smokers, 2607 former smokers, and 971 current smokers. Median follow-up was 10.2 years. Compared with never smokers, adjusted hazard ratios in current smokers were 1.7 (95% confidence interval, 1.3-2.2) for all-cause cardiovascular disease, 1.6 (1.1-2.1) for all-cause CHD, and 1.7 (1.2-2.4) for hard CHD. Similarly, among current smokers, hazard ratios were higher in the 4th versus 1st quartile of pack-years (eg, all-cause CHD hazard ratio=2.7 [1.1-6.6]). Both CAC>100 and high-sensitivity C-reactive protein ?3 mg/L identified higher relative risk among current smokers (eg, all-cause CHD hazard ratio of 3.0 [1.5-6.0, compared with CAC=0] and 2.6 [1.4-4.8, compared with high-sensitivity C-reactive protein <2 mg/L], respectively). However, CAC was a stronger mediator of events and adversely modified the effect of smoking on events (eg, P-interaction=0.02 for hard CHD). Compared with never smokers, former smokers (median cessation interval=22 years) had similar adjusted hazard for events. CONCLUSIONS:In this multiethnic cohort, current smoking and cumulative exposure remain important modifiable determinants of cardiovascular disease. Both high-sensitivity C-reactive protein ?3 mg/L and, particularly, CAC>100 identified high-risk smokers who may benefit from more intensive smoking-cessation efforts.

Dataset Information

Relationship of Autoantibodies to MDA-LDL and ApoB-Immune Complexes to Sex, Ethnicity, Subclinical Atherosclerosis, and Cardiovascular Events.

Publications

Relationship of Autoantibodies to MDA-LDL and ApoB-Immune Complexes to Sex, Ethnicity, Subclinical Atherosclerosis, and Cardiovascular Events.

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