Dataset Information

ABO blood group associations with markers of endothelial dysfunction in the Multi-Ethnic Study of Atherosclerosis.

ABSTRACT: ABO blood type is associated with cardiovascular disease, although the underlying mechanisms are presumed to be complex. While the relationship between non-O blood types and von Willebrand Factor (vWF) is well-established, associations with cellular adhesion molecules (CAMs) across diverse populations are understudied.We genetically inferred ABO alleles for N = 6202 participants from the Multi-Ethnic Study of Atherosclerosis. Linear regression was used to evaluate associations between major ABO allele dosages and log-transformed measurements of vWF (N = 924), soluble E-selectin (sE-selectin, N = 925), soluble P-selectin (sP-selectin, N = 2392), and soluble ICAM-1 (sICAM-1, N = 2236) by race/ethnicity.For the selectins, the A1 allele was associated with significantly lower levels for all races/ethnicities, with each additional allele resulting in a 28-39% decrease in sE-selectin and 10-18% decrease in sP-selectin relative to Type O subjects. However, the A2 allele demonstrated effect heterogeneity across race/ethnicity for sE-selectin, with lower levels for non-Hispanic whites (p = 0.0011) but higher levels for Hispanics (p = 0.0021). We also identified elevated sP-selectin levels for B-allele carriers solely in Hispanic participants (p = 1.0E-04). ABO-by-race/ethnicity interactions were significant for both selectins (p < 0.0125). More modest associations were observed between A1 allele dosage and levels of sICAM-1, with ABO alleles explaining 0.8-1.1% of the total phenotypic variation within race/ethnicity. ABO associations with vWF activity were consistent across race/ethnicity, with B allele carriers corresponding to the highest vWF activity levels.ABO blood type demonstrates complex associations with endothelial markers that are largely generalizable across diverse populations.

SUBMITTER: Larson NB

PROVIDER: S-EPMC4983247 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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ABO blood group associations with markers of endothelial dysfunction in the Multi-Ethnic Study of Atherosclerosis.

Larson Nicholas B NB Bell Elizabeth J EJ Decker Paul A PA Pike Mindy M Wassel Christina L CL Tsai Michael Y MY Pankow James S JS Tang Weihong W Hanson Naomi Q NQ Alexander Kristine K Zakai Neil A NA Cushman Mary M Bielinski Suzette J SJ

Atherosclerosis 20160607

<h4>Background and aims</h4>ABO blood type is associated with cardiovascular disease, although the underlying mechanisms are presumed to be complex. While the relationship between non-O blood types and von Willebrand Factor (vWF) is well-established, associations with cellular adhesion molecules (CAMs) across diverse populations are understudied.<h4>Methods</h4>We genetically inferred ABO alleles for N = 6202 participants from the Multi-Ethnic Study of Atherosclerosis. Linear regression was used ...[more]

PMID: 27298014

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Project description:AimsWe aimed to investigate the association between endothelial dysfunction, assessed by brachial flow-mediated dilation (FMD), and the incidence of heart failure (HF) in the community-based Multi-Ethnic Study of Atherosclerosis.Methods and resultsBrachial artery FMD was measured in a nested case-cohort sample including 3496 of 6814 Multi-Ethnic Study of Atherosclerosis participants without prevalent cardiovascular disease (mean age 61 years, 50% women). Multivariable probability-weighted Cox proportional hazards analysis was used to examine the association between FMD and incident HF. We also investigated the association between FMD and HF with reduced vs. preserved ejection fraction [HFrEF (left ventricular ejection fraction <45%) vs. HFpEF (left ventricular ejection fraction ?45%)]. During follow-up (median 12 years), 149 participants developed incident HF (incidence rate 3.7 events per 1000 person years). There were 56 HFrEF and 69 HFpEF events (incidence rates 1.4 and 1.7 events per 1000 person years, respectively). In multivariable models adjusted for established HF risk factors (age, sex, race/ethnicity, body mass index, systolic blood pressure, antihypertensive treatment, heart rate, diabetes mellitus, history of myocardial infarction, current smoker, and former smoker status), individuals in the highest quartile of FMD (reflecting better endothelial function) had a lower HF risk compared with individuals in the lowest quartile [hazard ratio 0.53, 95% confidence interval (CI) 0.31-0.95]. Lower risk according to higher FMD was particularly evident for HFrEF, but not for HFpEF (hazard ratio per standard deviation increase 0.79, 95% CI 0.64-0.97 vs. 0.99, 95% CI 0.78-1.26, respectively). Results remained similar after adjustment for baseline natriuretic peptide levels. The addition of FMD to established HF risk factors generally rendered no or only modest improvement in C-statistics [C-statistics for model with established HF risk factors: 0.774, and with the addition of FMD: 0.776 (delta C 0.002, 95% confidence interval -0.002 to 0.006)].ConclusionsEndothelial dysfunction was independently associated with HF in this community cohort, suggesting a pathophysiological contribution of endothelial function to the development of HF, in particular HFrEF. However, the value of FMD measurements for HF risk prediction seems limited.

Dataset Information

ABO blood group associations with markers of endothelial dysfunction in the Multi-Ethnic Study of Atherosclerosis.

Publications

ABO blood group associations with markers of endothelial dysfunction in the Multi-Ethnic Study of Atherosclerosis.

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