Dataset Information

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness.

ABSTRACT: Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta = -0.0264, p value = 3.5 × 10^-8) in the discovery panel and was replicated in replication panel (beta = -0.07, p value = 0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value = 1.4 × 10^-13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

SUBMITTER: Portilla-Fernandez E

PROVIDER: S-EPMC8629903 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Meta-analysis of epigenome-wide association studies of carotid intima-media thickness.

Portilla-Fernández Eliana E Hwang Shih-Jen SJ Wilson Rory R Maddock Jane J Hill W David WD Teumer Alexander A Mishra Pashupati P PP Brody Jennifer A JA Joehanes Roby R Ligthart Symen S Ghanbari Mohsen M Kavousi Maryam M Roks Anton J M AJM Danser A H Jan AHJ Levy Daniel D Peters Annette A Ghasemi Sahar S Schminke Ulf U Dörr Marcus M Grabe Hans J HJ Lehtimäki Terho T Kähönen Mika M Hurme Mikko A MA Bartz Traci M TM Sotoodehnia Nona N Bis Joshua C JC Thiery Joachim J Koenig Wolfgang W Ong Ken K KK Bell Jordana T JT Meisinger Christine C Wardlaw Joanna M JM Starr John M JM Seissler Jochen J Then Cornelia C Rathmann Wolfgang W Ikram M Arfan MA Psaty Bruce M BM Raitakari Olli T OT Völzke Henry H Deary Ian J IJ Wong Andrew A Waldenberger Melanie M O'Donnell Christopher J CJ Dehghan Abbas A

European journal of epidemiology 20210606 11

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG sit ...[more]

PMID: 34091768

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Project description:Background The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and Results We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.

Project description:BackgroundIntima-media thickness of the walls of the common carotid artery and internal carotid artery may add to the Framingham risk score for predicting cardiovascular events.MethodsWe measured the mean intima-media thickness of the common carotid artery and the maximum intima-media thickness of the internal carotid artery in 2965 members of the Framingham Offspring Study cohort. Cardiovascular-disease outcomes were evaluated for an average follow-up of 7.2 years. Multivariable Cox proportional-hazards models were generated for intima-media thickness and risk factors. We evaluated the reclassification of cardiovascular disease on the basis of the 8-year Framingham risk score category (low, intermediate, or high) after adding intima-media thickness values.ResultsA total of 296 participants had a cardiovascular event. The risk factors of the Framingham risk score predicted these events, with a C statistic of 0.748 (95% confidence interval [CI], 0.719 to 0.776). The adjusted hazard ratio for cardiovascular disease with a 1-SD increase in the mean intima-media thickness of the common carotid artery was 1.13 (95% CI, 1.02 to 1.24), with a nonsignificant change in the C statistic of 0.003 (95% CI, 0.000 to 0.007); the corresponding hazard ratio for the maximum intima-media thickness of the internal carotid artery was 1.21 (95% CI, 1.13 to 1.29), with a modest increase in the C statistic of 0.009 (95% CI, 0.003 to 0.016). The net reclassification index increased significantly after addition of intima-media thickness of the internal carotid artery (7.6%, P<0.001) but not intima-media thickness of the common carotid artery (0.0%, P=0.99). With the presence of plaque, defined as intima-media thickness of the internal carotid artery of more than 1.5 mm, the net reclassification index was 7.3% (P=0.01), with an increase in the C statistic of 0.014 (95% CI, 0.003 to 0.025).ConclusionsThe maximum internal and mean common carotid-artery intima-media thicknesses both predict cardiovascular outcomes, but only the maximum intima-media thickness of (and presence of plaque in) the internal carotid artery significantly (albeit modestly) improves the classification of risk of cardiovascular disease in the Framingham Offspring Study cohort. (Funded by the National Heart, Lung, and Blood Institute.).

Project description:ObjectiveRecently, increasing epidemiological evidence has shown that there is a correlation between serum uric acid level (SUA) and carotid intima-media thickness (CIMT). This paper explored the relationship between them through meta-analysis.MethodsPubMed, Cochrane Library, EMBASE, Web of Science and Google Scholar were searched to obtain literature. The keywords used to retrieve the literature were carotid intima thickness, intima-media thickness, carotid atherosclerosis, carotid stenosis, carotid artery, uric acid, blood uric acid, and hyperuricaemia. The retrieval time was from the establishment of the database through July 2020. Stata15.0 and RevMan5.3 software were used for statistical analysis. The standardized mean difference (SMD) and 95% confidence interval (95% CI) were calculated by a random effect model to estimate the correlation. Publication bias was assessed using the Begg and Egger tests. The stability of these results was evaluated using sensitivity analyses.ResultsFifteen studies were included with a total sample size of 11382, including 7597 participants in the high uric acid group and 3785 in the control group, on the basis of the inclusion and exclusion criteria. According to the evaluation of the JBI scale, the literature was of high quality. The average age ranged from 42 to 74. Meta-analysis showed that CIMT in the high uric acid group was significantly higher than that in the control group (SMD = 0.53, 95% CI: [0.38, 0.68]), and the difference was significant (z = 6.98, P < 0.00001). The heterogeneity among the 15 articles was obvious (I2 = 89%, P < 0.00001). Subgroup analysis by disease status illustrated a positive relationship between SUA and CIMT in healthy people and people with diseases. SUA was shown to be positively correlated with CIMT in people aged 45-60 years and ≥60 years by subgroup analysis by age. SUA was also found to be positively correlated with CIMT in a population with BMI>24 kg/m2 by subgroup analysis by BMI. In addition, subgroup analysis of other risk factors for CIMT, including TC, SBP, DBP, triglycerides, and LDL-C, all showed a positive correlation between SUA and CIMT.ConclusionsThere is a significant correlation between serum uric acid level and carotid intima-media thickness, and a high concentration of serum uric acid is related to carotid artery intima-media thickness.

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Meta-analysis of epigenome-wide association studies of carotid intima-media thickness.

Publications

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness.

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