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Association of the platelet GPIIb/IIIa polymorphism with atherosclerotic plaque morphology: the Atherosclerosis Risk in Communities (ARIC) Study.

ABSTRACT: OBJECTIVES:Platelet activation and aggregation play an important role in the pathogenesis of cardiovascular disease. We examined the association of a single nucleotide polymorphism (SNP) in the GPIIIa platelet glycoprotein (Leu33Pro) with carotid artery plaque morphology and with expression of platelet markers using data from the Atherosclerosis Risk in Communities (ARIC) Carotid MRI study. METHODS:The study sample consisted of 1202 Caucasian members of the ARIC study cohort recruited in 2004-2005 to participate in the Carotid MRI Substudy under stratified sampling based on maximum carotid artery wall thickness. The Leu33Pro polymorphism was identified as SNP rs5918 in the ITGB3 gene. Plaque visualization was accomplished with contrast enhanced MRI examination of the thickest segment of the carotid artery. Expression of platelet markers was measured using fasting whole blood flow cytometry. RESULTS:This cross-sectional analysis based on age and gender adjusted weighted linear regression models suggests that those homozygous for the Leu33Pro risk allele (C) have decreased mean and minimum fibrous cap thickness. We did not observe differences in plaque lipid volume or maximum carotid artery wall thickness across SNP rs5918 genotypes. Carriers of the Leu33Pro polymorphism, as compared to major allele homozygotes, had greater percent of platelets expressing P-selectin, a platelet glycoprotein indicating activation status. Prevalent coronary heart disease did not affect estimates of fibrous cap thickness or of platelet activation. CONCLUSION:Our results suggest that individuals with Leu33Pro polymorphism of the GPIIIa glycoprotein may be predisposed to increased risk of atherosclerotic plaque rupture.

SUBMITTER: Kucharska-Newton AM

PROVIDER: S-EPMC3089705 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Association of the platelet GPIIb/IIIa polymorphism with atherosclerotic plaque morphology: the Atherosclerosis Risk in Communities (ARIC) Study.

Kucharska-Newton Anna M AM Monda Keri L KL Campbell Stephen S Bradshaw Patrick T PT Wagenknecht Lynne E LE Boerwinkle Eric E Wasserman Bruce A BA Heiss Gerardo G

Atherosclerosis 20110202 1

<h4>Objectives</h4>Platelet activation and aggregation play an important role in the pathogenesis of cardiovascular disease. We examined the association of a single nucleotide polymorphism (SNP) in the GPIIIa platelet glycoprotein (Leu33Pro) with carotid artery plaque morphology and with expression of platelet markers using data from the Atherosclerosis Risk in Communities (ARIC) Carotid MRI study.<h4>Methods</h4>The study sample consisted of 1202 Caucasian members of the ARIC study cohort recru ...[more]

PMID: 21353223

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Project description:<p>The Atherosclerosis Risk in Communities (ARIC) Study, sponsored by the National Heart, Lung and Blood Institute (NHLBI), is a prospective epidemiologic study conducted in four U.S. communities. The four communities are Forsyth County, NC; Jackson, MS; the northwest suburbs of Minneapolis, MN; and Washington County, MD. ARIC is designed to investigate the etiology and natural history of atherosclerosis, the etiology of clinical atherosclerotic diseases, and variation in cardiovascular risk factors, medical care and disease by race, gender, location, and date.</p> <p>ARIC includes two parts: the Cohort Component and the Community Surveillance Component. The Cohort Component began in 1987, and each ARIC field center randomly selected and recruited a cohort sample of approximately 4,000 individuals aged 45-64 from a defined population in their community. A total of 15,792 participants received an extensive examination, including medical, social, and demographic data. These participants were reexamined every three years with the first screen (baseline) occurring in 1987-89, the second in 1990-92, the third in 1993-95, and the fourth and last exam was in 1996-98. Follow-up occurs yearly by telephone to maintain contact with participants and to assess health status of the cohort.</p> <p>In the Community Surveillance Component, currently ongoing, these four communities are investigated to determine the community-wide occurrence of hospitalized myocardial infarction and coronary heart disease deaths in men and women aged 35-84 years. Hospitalized stroke is investigated in cohort participants only. Starting in 2006, the study conducts community surveillance of inpatient (ages 55 years and older) and outpatient heart failure (ages 65 years and older) for heart failure events beginning in 2005.</p> <p>ARIC is currently funded through January 31, 2012.</p> <p>This study is part of the Gene Environment Association Studies initiative (GENEVA, <a href="http://www.genevastudy.org" target="_blank">http://www.genevastudy.org</a>) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to atherosclerosis and cardiovascular disease through large-scale genome-wide association studies of well-characterized cohorts of adults in four defined populations. Genotyping was performed at the Broad Institute of MIT and Harvard, a GENEVA genotyping center. Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.</p>

Project description:BACKGROUND:Previous studies suggest that heart failure (HF) is an independent risk factor for cognitive decline. A better understanding of the relationship between HF, cognitive status, and cognitive decline in a community-based sample may help clinicians understand disease risk. OBJECTIVE:To examine whether persons with HF have a higher prevalence of cognitive impairment and whether persons developing HF have more rapid cognitive decline. DESIGN:This observational cohort study of American adults in the Atherosclerosis Risk in Communities (ARIC) study has two components: cross-sectional analysis examining the association between prevalent HF and cognition using multinomial logistic regression, and change over time analysis detailing the association between incident HF and change in cognition over 15 years. PARTICIPANTS:Among visit 5 (2011-2013) participants (median age 75 years), 6495 had neurocognitive information available for cross-sectional analysis. Change over time analysis examined the 5414 participants who had cognitive scores and no prevalent HF at visit 4 (1996-1998). MEASUREMENTS:The primary outcome was cognitive status, classified as normal, mild cognitive impairment [MCI], and dementia on the basis of standardized cognitive tests (delayed word recall, word fluency, and digit symbol substitution). Cognitive change was examined over a 15-year period. Control variables included socio-demographic, vascular, and smoking/drinking measures. RESULTS:At visit 5, participants with HF had a higher prevalence of dementia (adjusted relative risk ratio [RRR] = 1.60 [95% CI 1.13, 2.25]) and MCI (RRR = 1.36 [1.12, 1.64]) than those without HF. A decline in cognition between visits 4 and 5 was - 0.07 standard deviation units [- 0.13, - 0.01] greater among persons who developed HF compared to those who did not. Results did not differ by ejection fraction. CONCLUSION:HF is associated with neurocognitive dysfunction and decline independent of other co-morbid conditions. Further study is needed to determine the underlying pathophysiology.

Dataset Information

Association of the platelet GPIIb/IIIa polymorphism with atherosclerotic plaque morphology: the Atherosclerosis Risk in Communities (ARIC) Study.

Publications

Association of the platelet GPIIb/IIIa polymorphism with atherosclerotic plaque morphology: the Atherosclerosis Risk in Communities (ARIC) Study.

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