A multi-omics approach unveils an association between subclinical atherosclerosis and epigenetic age acceleration mediated by systemic inflammation
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ORGANISM(S): Homo sapiens
PROVIDER: GSE224624 | GEO | 2023/06/21
REPOSITORIES: GEO
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Project description:Whole blood methylomics, transcriptomics and plasma proteomics were obtained for 391 participants of the Progression of Early Subclinical Atherosclerosis (PESA) study. Epigenetic age was calculated from methylomics data for each participant. Its divergence from chronological age is termed epigenetic age acceleration. Subclinical atherosclerosis burden was estimated by multi-territory 2D/3D vascular ultrasound and by coronary artery calcification.
2023-06-21 | GSE220622 | GEO
Project description:Whole blood methylomics, transcriptomics and plasma proteomics were obtained for 391 participants of the Progression of Early Subclinical Atherosclerosis (PESA) study. Epigenetic age was calculated from methylomics data for each participant. Its divergence from chronological age is termed epigenetic age acceleration. Subclinical atherosclerosis burden was estimated by multi-territory 2D/3D vascular ultrasound and by coronary artery calcification.
2023-06-21 | GSE221615 | GEO
Project description:BackgroundSleep disordered breathing (SDB) is a common disorder that results in oxidative stress and inflammation and is associated with multiple age-related health outcomes. Epigenetic age acceleration is a DNA methylation (DNAm)-based marker of fast biological aging. We examined the associations of SDB traits with epigenetic age acceleration.MethodsA sample of 622 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) had blood DNAm measured and underwent Type 2 in-home polysomnography that assessed apnea-hypopnea index (AHI), percentage of sleep time with oxygen saturation lower than 90% (Per90), and arousal index. DNAm data provided measures of DNAm-Age acceleration and DNAm-PhenoAge acceleration. The association of each SDB trait with age acceleration was estimated using linear regression, controlling for covariates. In secondary analyses, we studied the associations of SDB traits with epigenetic age acceleration 2-10 years after sleep study in 530 individuals from the Framingham Heart Study (FHS).FindingsIn MESA, AHI was associated with greater DNAm-PhenoAge acceleration (? = 0.03; 95% CI [0.001, 0.06]). Arousal index was associated with greater DNAm-Age acceleration (? = 0.04; 95% CI [0.01, 0.07]). Both associations were stronger in women than men. In the secondary FHS analyses, Per90 was associated with greater DNAm-Age acceleration and this association was stronger in men.InterpretationMore severe SDB was associated with epigenetic age acceleration in both cohorts. Future work should prospectively study short- and long-term effects of SDB, and whether treatment reduces epigenetic age acceleration among those individuals with SBD.FundingNational Institutes of Health.
| S-EPMC6921369 | biostudies-literature
Project description:OBJECTIVE:We previously reported a statistically significant association of SCARB1 intronic single nucleotide polymorphism (SNP) rs10846744 with common carotid intimal-medial artery thickness in each of the 4 Multi-Ethnic Study of Atherosclerosis racial/ethnic groups (white, Chinese, black, and Hispanic). METHODS AND RESULTS:Using an expanded sample of 7936 Multi-Ethnic Study of Atherosclerosis participants, phenotyped for measures of subclinical atherosclerosis, incident myocardial infarction, and cardiovascular disease, and genotyped through the SNP Health Association Resource project, we have now examined the genetic association of these phenotypes with 126 genotyped and imputed SCARB1 SNPs. We also performed stratified analyses to examine whether SCARB1 SNP effects differed by sex. Our analysis of the full Multi-Ethnic Study of Atherosclerosis cohort provides strong evidence for the association of rs10846744 with common carotid intimal-medial thickness (P=1.04E-4 in combined analysis of all 4 Multi-Ethnic Study of Atherosclerosis racial/ethnic groups). In sex-stratified analysis, we observed statistically significant association of rs10846744 with incident cardiovascular disease events in males (P=0.01). Examining analytical results from the Myocardial Infarction Genetics Consortium for replication, we observed further support for the association of rs10846744 with myocardial infarction. CONCLUSIONS:The SCARB1 SNP, rs10846744, exerts a major effect on subclinical atherosclerosis and incident cardiovascular disease in humans.
| S-EPMC6637944 | biostudies-literature
Project description:Background/objectivesA cluster of metabolic abnormalities termed metabolic syndrome (MetS) is associated with vascular endothelial dysfunction and oxidative internal milieu. We examined whether the association of MetS with subclinical atherosclerosis is explained by biomarkers of endothelial damage and oxidative stress.Subjects/methodsMulti-Ethnic Study of Atherosclerosis (MESA) is a population-based study of 45- to 84-year-old individuals of four US ethnicities without clinical cardiovascular disease. A random sample of 997 MESA participants had data on the following biomarkers: von Willebrand factor, soluble intercellular adhesion molecule-1 (sICAM-1), CD40 ligand (CD40L), soluble thrombomodulin, E-selectin and oxidized LDL (oxLDL). We examined whether the associations of MetS with B-mode ultrasound-defined common and internal carotid intimal-medial thickness (IMT) and coronary artery calcium (CAC) measured using computerized tomography were explained by the biomarkers using multiple regression methods.ResultsMetS was associated with higher levels of each of the biomarkers (P<0.001, CD40L-suggestive association P=0.004), with greater IMT (P<0.001), and with greater extent of CAC in those in whom CAC was detectable (P=0.01). The association of MetS with measures of subclinical atherosclerosis remained unchanged after adjustment for the biomarkers. After adjusting for MetS, oxLDL was suggestively associated with greater prevalence of detectable CAC (P=0.005) and thicker internal carotid IMT (P=0.002), whereas sICAM-1 was significantly associated with greater prevalence of detectable CAC (P=0.001).ConclusionsThe association of MetS with subclinical atherosclerosis was independent of its association with biomarkers of endothelial damage and oxidative stress, suggesting that metabolic abnormalities and oxidative endothelial damage may lead to atherosclerotic disease through distinct mechanisms.
| S-EPMC3130805 | biostudies-literature
Project description:Few adults have ideal cardiovascular health (CVH). We studied associations of an overall CVH score with subclinical cardiovascular disease and events. We assessed whether associations varied by race/ethnicity.Among 5961 participants in the Multi-Ethnic Study of Atherosclerosis, components of CVH were measured at baseline, 2000-2002: systolic blood pressure, total cholesterol, fasting glucose, smoking, physical activity, diet, and body mass index. Levels were classified as ideal (2 points), intermediate (1 point), and poor (0 points) according to American Heart Association definitions. Points were summed to produce a CVH score (0-7 low, 8-11 moderate, 12-14 high). Coronary artery calcium, carotid intima-media thickness, and left ventricular mass were measured at baseline. Cardiovascular disease was defined as myocardial infarction, coronary heart disease death, resuscitated cardiac arrest, stroke, heart failure, or peripheral artery disease. Follow-up was 10.3 years. Regression models were used to examine associations of the CVH score with subclinical disease and events, adjusting for age, sex, and education. Analyses were stratified by race/ethnicity. Adults with high or moderate CVH scores had significantly lower odds of coronary artery calcium and lower carotid intima-media thickness and left ventricular mass than adults with low CVH scores. Adults with high or moderate CVH scores were 67% (95%CI 41% to 82%) and 37% (95%CI 22% to 49%) less likely, respectively, to experience a cardiovascular disease event than adults with low scores. There was no interaction with race/ethnicity.There is a graded inverse association between CVH scores and measures of subclinical and overt cardiovascular disease that is similar across race/ethnic groups.
| S-EPMC5524019 | biostudies-other
Project description:Little is known about the association of scavenger receptor class B type I (SCARB1) single-nucleotide polymorphisms (SNPs) and subclinical atherosclerosis, particularly in subjects of different racial/ethnic backgrounds. We examined this relationship in the Multi-Ethnic Study of Atherosclerosis.Forty-three SCARB1-tagging SNPs were genotyped. Baseline examinations included fasting lipids and subclinical atherosclerosis phenotypes (coronary artery calcification, common carotid intimal-medial artery thickness [CCIMT], and internal carotid intimal-medial artery thickness). Examining SNP associations with different subclinical atherosclerosis phenotypes across multiple racial/ethnic groups with adjustment for multiple covariates, we found that the C allele of SNP rs10846744 was associated with higher CCIMT in African American (P=0.03), Chinese (P=0.02), European American (P=0.05), and Hispanic participants (P=0.03) and was strongly associated in pooled analyses (P=0.0002). The results also showed that the association of this SNP with CCIMT was independent of lipids and other well-established cardiovascular risk factors. Stratifying by sex, there seemed to be a strong association of rs10846744 with CCIMT in women, but no genotype-sex interactions were observed.Variation in SCARB1 at rs10846744 was significantly associated with CCIMT across racial/ethnic groups in Multi-Ethnic Study of Atherosclerosis.
| S-EPMC3359098 | biostudies-literature
Project description:Previously identified single nucleotide polymorphisms (SNPs) in genome wide association studies (GWAS) of cardiovascular disease (CVD) in participants of mostly European descent were tested for association with subclinical cardiovascular disease (sCVD), coronary artery calcium score (CAC) and carotid intima media thickness (CIMT) in the Multi-Ethnic Study of Atherosclerosis (MESA). The data in this data in brief article correspond to the article Common Genetic Variants and Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis [1]. This article includes the demographic information of the participants analyzed in the article as well as graphical displays and data tables of the association of the selected SNPs with CAC and of the meta-analysis across ethnicities of the association of CIMT-c (common carotid), CIMT-I (internal carotid), CAC-d (CAC as dichotomous variable with CAC>0) and CAC-c (CAC as continuous variable, the log of the raw CAC score plus one) and CVD. The data tables corresponding to the 9p21 fine mapping experiment as well as the power calculations referenced in the article are also included.
| S-EPMC4773483 | biostudies-literature
Project description:BackgroundGestational diabetes mellitus (GDM) is associated with an elevated risk of adverse health outcomes such as type 2 diabetes and cardiovascular diseases. Carotid intima-media thickness (cIMT) is increasingly used as a noninvasive marker for subclinical atherosclerosis. Whether there is a direct correlation between GDM and elevated cIMT is still controversial.MethodsPubMed, Embase and reference lists of relevant papers were reviewed. Studies assessing the relationship between GDM and cIMT were included. Weighted Mean Difference (WMD) of cIMT was calculated using random-effect models.ResultsFifteen studies with a total of 2247 subjects were included in our analysis, giving a pooled WMD of 0.05 (95% confidence interval [CI] 0.03 -0.07). Furthermore, meta regression and subgroup analysis found that the association between GDM and larger cIMT already existed during pregnancy, and this relation was stronger in obese GDM patients.ConclusionsGDM in and after pregnancy is associated with subclinical atherosclerosis. Weight control may be helpful to prevent cardiovascular diseases for GDM patients.
| S-EPMC4192280 | biostudies-literature
Project description:ImportanceCross-sectional measures of cardiovascular health (CVH) have been associated with cardiovascular disease in older age, but little is known about longitudinal trajectories in CVH and their association with subclinical atherosclerosis in middle age.ObjectivesTo model long-term patterns in CVH starting in childhood and to assess their association with subclinical atherosclerosis in middle age.Design, setting, and participantsThis cohort study used data from 5 prospective cardiovascular cohort studies from the United States and Finland from 1973 to 2015. A total of 9388 participants aged 8 to 55 years had at least 3 examinations and were eligible for this study. Statistical analysis was performed from December 1, 2015, to June 1, 2019.ExposuresClinical CVH factors (body mass index, total cholesterol level, blood pressure, and glucose level) were classified as ideal, intermediate, or poor, and were summed as a clinical CVH score. Group-based latent class modeling identified trajectories in this score over time.Main outcomes and measuresCarotid intima-media thickness (cIMT) was measured for participants in 3 cohorts, and high cIMT was defined as a value at or above the 90th percentile. The association between CVH trajectory and cIMT was modeled using both linear and logistic regression adjusted for demographics, baseline health behaviors, and baseline (or proximal) CVH score.ResultsAmong 9388 participants (5146 [55%] female; 6228 [66%] white; baseline mean [SD] age, 17.5 [7.5] years), 5 distinct trajectory groups were identified: high-late decline (1518 participants [16%]), high-moderate decline (2403 [26%]), high-early decline (3066 [32%]), intermediate-late decline (1475 [16%]), and intermediate-early decline (926 [10%]). The high-late decline group had significantly lower adjusted cIMT vs other trajectory groups (high-late decline: 0.64 mm [95% CI, 0.63-0.65 mm] vs intermediate-early decline: 0.72 mm [95% CI, 0.69-0.75 mm] when adjusted for demographics and baseline smoking, diet, and physical activity; P?<?.01). The intermediate-early declining group had higher odds of high cIMT (odds ratio, 2.4; 95% CI, 1.3-4.5) compared with the high-late decline group, even after adjustment for baseline or proximal CVH score.Conclusions and relevanceIn this study, CVH declined from childhood into adulthood. Promoting and preserving ideal CVH from early life onward may be associated with reduced CVD risk later in life.
| S-EPMC7066520 | biostudies-literature