Dataset Information

Association between ADAMTS7 polymorphism and carotid artery plaque vulnerability.

ABSTRACT: Recent genome-wide association studies (GWAS) indicated that polymorphisms in ADAMTS7 were associated with artery disease caused by atherosclerosis. However, the correlation between the ADAMTS7 polymorphism and plaque stability remains unclear. The objective of this study was to evaluate the association between 2 ADAMTS7 variants rs3825807 and rs7173743 and ischemic stroke or atherosclerotic plaque vulnerability.This research is an observational study. Patients with ischemic stroke and normal control individuals admitted to Beijing Tiantan Hospital from May 2014 to October 2017 were enrolled. High-resolution magnetic resonance imaging was used to distinguish vulnerable and stable carotid plaques. The ADAMTS7 SNPs were genotyped using TaqMan assays on real-time PCR system. The multivariate logistic regression analyses were used to adjust for multiple risk factors between groups.Three hundred twenty-six patients with ischemic stroke (189 patients with vulnerable plaque and 81 patients with stable plaque) and 432 normal controls were included. ADAMTS7 polymorphisms of both rs7173743 and rs3825807 were associated with carotid plaque vulnerability but not the prevalence of ischemic stroke. The T/T genotype of rs7173743 [odds ratio (OR) = 1.885, 95% confidence interval (CI) = 1.067-3.328, P?=?.028] and A/A genotype of rs3825807 (OR?=?2.146, 95% CI?=?1.163-3.961, P?=?.013) were considered as risk genotypes for vulnerable plaque susceptibility.In conclusion, ADAMTS7 variants rs3825807 and rs7173743 are associated with the risk for carotid plaque vulnerability.

SUBMITTER: Li HW

PROVIDER: S-EPMC6824807 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Association between ADAMTS7 polymorphism and carotid artery plaque vulnerability.

Li Hao-Wen HW Shen Mi M Gao Pei-Yi PY Li Zi-Rui ZR Cao Jing-Li JL Zhang Wen-Li WL Sui Bin-Bin BB Wang Yu-Xin YX Wang Ya-Jie YJ

Medicine 20191001 43

Recent genome-wide association studies (GWAS) indicated that polymorphisms in ADAMTS7 were associated with artery disease caused by atherosclerosis. However, the correlation between the ADAMTS7 polymorphism and plaque stability remains unclear. The objective of this study was to evaluate the association between 2 ADAMTS7 variants rs3825807 and rs7173743 and ischemic stroke or atherosclerotic plaque vulnerability.This research is an observational study. Patients with ischemic stroke and normal co ...[more]

PMID: 31651847

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Project description:BackgroundResearch has shown that carotid intima-media thickness (CIMT) could help to predict carotid plaque (CP) progression in patients with mild carotid stenosis. However, the debate continues as to the value of carotid intima thickness (CIT) in monitoring the development of CP in patients with severe carotid stenosis. This study sought to evaluate the relationships between CIT and the ultrasonic characteristics of CP and to analyze the value of CIT and the ultrasonic parameters of CP in assessing plaque vulnerability in advanced human carotid atherosclerosis.MethodsA total of 55 individuals who underwent carotid endarterectomy (CEA) were included in the study (mean age: 65±7 years; female: 9.1%). CIMT and CIT were examined at the common carotid artery (CCA). Plaque textural features, such as the gray-scale median (GSM), superb microvascular imaging (SMI) level, and total plaque area (TPA), were also identified. A Spearman correlation coefficient analysis was performed to examine the relationship between CIT and the ultrasonic parameters of CP. The CIT of various plaque types was compared. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic values of the ultrasound characteristics to evaluate CP vulnerability.ResultsThe mean CIT of all the participants was 0.382±0.095 mm, the mean CIT of the participants with stable plaques was 0.328±0.031 mm, and the mean CIT of participants with vulnerable plaques was 0.424±0.106 mm (P<0.001). CIT was associated with the SMI level (Spearman's correlation coefficient: r=0.392, P=0.005), TPA (Spearman's correlation coefficient: r=0.337, P=0.012). Patients with thicker CIT had larger lipid cores, higher levels of plaque vulnerability, and more intraplaque hemorrhages (IPHs). The areas under the ROCs (AUCs) with 95% confidence interval (CI) for CIMT, CIT, the SMI level, the GSM, the TPA, and the combined model for identifying vulnerable plaques were 0.673 (0.533-0.793), 0.849 (0.727-0.932), 0.771 (0.629-0.879), 0.669 (0.529-0.790), 0.858 (0.738-0.938), and 0.949 (0.854-0.990), respectively.ConclusionsCIT was associated with both the histology and ultrasonic features of CP. CIT may be helpful in the detection of severe CP development.

Project description:ImportanceIt remains unknown whether in an asymptomatic community-based cohort magnetic resonance imaging (MRI) measures of plaque characteristics are independently associated with incident cardiovascular disease (CVD) events when adjusted for carotid artery (CA) wall thickness, a measure of plaque burden.ObjectiveTo assess associations of CA MRI plaque characteristics with incident CVD events.Design, setting, and participantsThe Atherosclerosis Risk in Communities (ARIC) study is a prospective epidemiologic study of the incidence of CVD in 15 792 adults of which 2066 women and men were enrolled in the ARIC Carotid MRI substudy. ARIC participants were enrolled from 1987 to 1989, and the substudy was conducted between January 2004 and December 2005. Analysis began January 2017 and ended August 2020.ExposuresIncident CVD events during a median (interquartile range [IQR]) follow-up time of 10.5 (8.1-10.9) years were assessed.Main outcomes and measuresProportional hazards Cox analyses were performed to ascertain associations between MRI variables of CA plaque burden and plaque characteristics.ResultsOf 15 792 ARIC participants, 2066 were enrolled in the substudy, of whom 1256 (701 women [55.8%]) had complete data and were eligible for incident CVD analyses. Carotid artery plaques in participants with incident CVD events (172 [13.7%]) compared with those without (1084 [86.3%]) had a higher normalized wall index (median [IQR], 0.48 [0.36-0.62] vs 0.43 [0.34-0.55]; P = .001), maximum CA wall thickness (median [IQR], 2.22 [1.37-3.52] mm vs 1.96 [1.29-2.85] mm; P = .01), maximum CA stenosis (median [IQR], 5% [0%-22%] vs 0% [0%-13%]; P < .001), and when present, a larger lipid core volume (median [IQR], 0.05 [0.02-0.11] mL vs 0.03 [0.01-0.07] mL; P = .03), respectively. The presence of a lipid core was independently associated with incident CVD events when adjusted for traditional CVD risk factors and maximum CA wall thickness (hazard ratio, 2.48 [95% CI, 1.36-4.51]; P = .003), whereas the presence of calcification was not. The frequency of intraplaque hemorrhage presence in this population of individuals free of CVD at baseline who were not recruited for carotid stenosis was too small to draw any meaningful conclusions (intraplaque hemorrhage presence: 68 of 1256 participants [5.4%]). Carotid artery lumen area and maximum stenosis, which were overall low, were independently associated with incident CVD events when adjusted for traditional CVD risk factors, as anticipated.Conclusions and relevanceThe presence of a CA lipid core on MRI is associated with incident CVD events independent of maximum CA wall thickness in asymptomatic participants.

Project description:BackgroundIL-6 (interleukin-6) has important roles in atherosclerosis pathophysiology. To determine if anti-IL-6 therapy warrants evaluation as an adjuvant stroke prevention strategy in patients with carotid atherosclerosis, we tested whether circulating IL-6 levels predict carotid plaque severity, vulnerability, and progression in the prospective population-based CHS (Cardiovascular Health Study).MethodsDuplex carotid ultrasound was performed at baseline and 5 years. Baseline plaque severity was scored 0 to 5 based on North American Symptomatic Carotid Endarterectomy Trial grade of stenosis. Plaque vulnerability at baseline was the presence of markedly irregular, ulcerated, or echolucent plaques. Plaque progression at 5 years was a ≥1 point increase in stenosis severity. The relationship of baseline plasma IL-6 levels with plaque characteristics was modeled using multivariable linear (severity) or logistic (vulnerability and progression) regression. Risk factors of atherosclerosis were included as independent variables. Stepwise backward elimination was used with P>0.05 for variable removal. To assess model stability, we computed the E-value or minimum strength of association (odds ratio scale) that unmeasured confounders must have with log IL-6 and the outcome to suppress the association. We performed internal validation with 100 bootstrap samples.ResultsThere were 4334 participants with complete data (58.9% women, mean age: 72.7±5.1 years), including 1267 (29.2%) with vulnerable plaque and 1474 (34.0%) with plaque progression. Log IL-6 predicted plaque severity (β=0.09, P=1.3×10-3), vulnerability (OR, 1.21 [95% CI, 1.05-1.40]; P=7.4×10-3, E-value=1.71), and progression (OR, 1.44 [95% CI, 1.23-1.69], P=9.1×10-6, E-value 2.24). In participants with >50% predicted probability of progression, mean log IL-6 was 0.54 corresponding to 2.0 pg/mL. Dichotomizing IL-6 levels did not affect the performance of prediction models.ConclusionsCirculating IL-6 predicts carotid plaque severity, vulnerability, and progression. The 2.0 pg/mL cutoff could facilitate the selection of individuals that would benefit from anti-IL-6 drugs for stroke prevention.

Dataset Information

Association between ADAMTS7 polymorphism and carotid artery plaque vulnerability.

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Association between ADAMTS7 polymorphism and carotid artery plaque vulnerability.

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