Circulating bile acids concentration is predictive of coronary artery disease in human.
Ontology highlight
ABSTRACT:
SUBMITTER: Chong Nguyen C
PROVIDER: S-EPMC8608912 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
Publications
Circulating bile acids concentration is predictive of coronary artery disease in human.
Chong Nguyen Caroline C Duboc Denis D Rainteau Dominique D Sokol Harry H Humbert Lydie L Seksik Philippe P Bellino Adèle A Abdoul Hendy H Bouazza Naïm N Treluyer Jean-Marc JM Saadi Malika M Wahbi Karim K Soliman Heithem H Coffin Benoit B Bado André A Le Gall Maude M Varenne Olivier O Duboc Henri H
Scientific reports 20211122 1
Synthetized by the liver and metabolized by the gut microbiota, BA are involved in metabolic liver diseases that are associated with cardiovascular disorders. Animal models of atheroma documented a powerful anti-atherosclerotic effect of bile acids (BA). This prospective study examined whether variations in circulating BA are predictive of coronary artery disease (CAD) in human. Consecutive patients undergoing coronary angiography were enrolled. Circulating and fecal BA were measured by high pre ...[more]
Similar Datasets
Project description:BackgroundVascular calcification is common among patients with chronic kidney disease (CKD), and it is associated with all-cause and cardiovascular disease mortality. Deoxycholic acid, a metabolite of circulating bile acids, is elevated in CKD and induces vascular mineralization and osteogenic differentiation in animal models.Study designCohort analysis of clinical trial participants.Setting & participants112 patients with moderate to severe CKD (estimated glomerular filtration rate, 20-45mL/min/1.73m2) who participated in a randomized controlled study to examine the effects of phosphate binders on vascular calcification.PredictorSerum deoxycholic acid concentration.OutcomesBaseline coronary artery calcification (CAC) volume score and bone mineral density (BMD) and change in CAC volume score and BMD after 9 months.MeasurementsDeoxycholic acid was assayed in stored baseline serum samples using liquid chromatography-tandem mass spectrometry, CAC was measured using a GE-Imitron C150 scanner, and BMD was determined using computed tomographic scans of the abdomen with calibrated phantom of known density.ResultsHigher serum deoxycholic acid concentrations were significantly correlated with greater baseline CAC volume and lower baseline BMD. After adjusting for demographics, coexisting illness, body mass index, estimated glomerular filtration rate, and concentrations of circulating markers of mineral metabolism, including serum calcium, phosphorus, vitamin D, parathyroid hormone, and fibroblast growth factor 23, a serum deoxycholic acid concentration > 58ng/mL (the median) was positively associated with baseline CAC volume (β=0.71; 95% CI, 0.26-1.16; P=0.003) and negatively associated with baseline BMD (β = -20.3; 95% CI, -1.5 to -39.1; P=0.04). Serum deoxycholic acid concentration > 58ng/mL was not significantly associated with change in CAC volume score after 9 months (β=0.06; 95% CI, -0.09 to 0.21; P=0.4). The analysis for the relationship between baseline deoxycholic acid concentrations and change in BMD after 9 months was not statistically significant, but was underpowered.LimitationsThe use of nonfasting serum samples is a limitation because deoxycholic acid concentrations may vary based on time of day and dietary intake. Few trial participants with complete data to evaluate the change in CAC volume score (n=75) and BMD (n=59). No data for changes in deoxycholic acid concentrations over time.ConclusionsAmong patients with moderate to severe CKD, higher serum deoxycholic acid concentrations were independently associated with greater baseline CAC volume score and lower baseline BMD.
| S-EPMC5742074 | biostudies-literature
Project description:The role of fatty acids (FAs) in primary prevention of coronary artery disease (CAD) is highly debated, and the modification effect by genetic risk profiles remains unclear. Here, we report the prospective associations of circulating FAs and genetic predisposition with CAD development in 101,367 U.K. Biobank participants. A total of 3719 CAD cases occurred during a mean follow-up of 11.5 years. Plasma monounsaturated FAs (MUFAs) were positively associated with risk of CAD, whereas the risk was significantly lower with higher n-3 polyunsaturated FAs (PUFAs) and more reductions in risk were detected among TT carriers of rs174547. Furthermore, increased plasma saturated FAs (SFAs) and linoleic acid were related to a significant increase in CAD risk among participants with high genetic risk (genetic risk score > 90%). These findings suggest that individuals with high genetic risk need to reduce plasma SFAs levels for CAD prevention. Supplementation of n-3 PUFAs for CAD prevention may consider individuals' genetic makeup.
| S-EPMC10881029 | biostudies-literature
Project description:Monocytes and T-cells play an important role in the development of atherosclerotic coronary artery disease (CAD). Differences in transcriptional activity of these cells might reflect the individual's atherosclerotic burden. Transcriptome analysis of circulating mononuclear cells from carefully matched atherosclerotic and control patients will potentially provide insights into the pathophysiology of atherosclerosis and supply biomarkers for diagnostic purposes. From patients undergoing coronary angiography because of anginal symptoms, we carefully matched 18 patients with severe triple-vessel CAD to 13 control patients without signs of CAD on angiography. All patients were on statin and aspirin treatment. RNA from circulating CD4+ T-cells, CD14+ monocytes, lipopolysaccharide-stimulated monocytes, macrophages and CD34+ progenitor cells was subjected to genome-wide expression analysis. Only CD14+ monocytes demonstrated that a small number of genes involved in activation was overexpressed in control patients, which was verified by real-time polymerase-chain reaction. In this pilot study, cautious matching of patients with severe atherosclerotic CAD with control patients without angiographic signs of coronary atherosclerosis did not reveal differences in transcriptional activity in four out of five different mononuclear cell types. In resting monocytes from patients without overt CAD some inflammatory genes were overexpressed as compared to patients with severe CAD. Large inter-individual variability prevented the use of single differentially expressed genes as biomarkers. Keywords: disease-state analysis In total 153 arrays were analyzed with 6 technical replicates (147 biological samples). CD34+ stem cells, CD4+ T-cells, resting CD14+ monocytes, stimulated monocytes and macrophages were analyzed, all from patient with severe coronary atherosclerosis or controls that had no coronary atherosclerosis as determined angiographically, and which were carefully matched for age and gender.
2008-12-01 | E-GEOD-9820 | biostudies-arrayexpress
Project description:Our previous study reckons that the impact of the rs1801133 variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) on coronary artery disease (CAD) is possibly mediated by cardiometabolic disorder. This study is performed to verify this hypothesis. Four hundred and thirty CAD patients and 216 CAD-free individuals were enrolled in this case-control study. The rs1801133 variant was genotyped by PCR-RFLP. Severity of coronary lesions was evaluated by number of stenotic coronary vessels and extent of coronary stenosis. The rs1801133 T allele significantly increased homocysteine levels in patients with CAD and CAD-free individuals. Individuals with the T allele of rs1801133 had an increased risk of developing CAD. In contrast, individuals with the TT genotype of rs1801133 were at high risk of multiple vessel lesions. The carriers of CT genotype had higher levels of systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP), and lower levels of apolipoprotein A1 (APOA1) than those with CC genotype in male patients with CAD. The receiver operating characteristic (ROC) curve and precision-recall (PR) curve indicated that hyperhomocysteinemia was sensitive to predict the severity of CAD. Multivariate logistic regression revealed that homocysteine, rs1801133, age, smoking, weight, body mass index (BMI), lipoprotein(a) [Lp(a)], and hs-CRP were independent risk factors for CAD. The increased risk of CAD and severity of coronary lesions associated with rs1801133 in the Chinese Han population were attributed, at least partly, to high homocysteine levels. Hyperhomocysteinemia had a high predictive value for severe CAD or multiple vessel lesions.
| S-EPMC11187881 | biostudies-literature
Project description:BACKGROUND:Patients with high-risk coronary artery disease (CAD) may be difficult to identify. METHODS:Using the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) cohort randomized to coronary computed tomographic angiography (n=4589), 2 predictive models were developed for high-risk CAD, defined as left main stenosis (≥50% stenosis) or either (1) ≥50% stenosis [50] or (2) ≥70% stenosis [70] of 3 vessels or 2-vessel CAD involving the proximal left anterior descending artery. Pretest predictors were examined using stepwise logistic regression and assessed for discrimination and calibration. RESULTS:High-risk CAD was identified in 6.6% [50] and 2.4% [70] of patients. Models developed to predict high-risk CAD discriminated well: [50], bias-corrected C statistic=0.73 (95% CI, 0.71-0.76); [70], bias-corrected C statistic=0.73 (95% CI, 0.68-0.77). Variables predictive of CAD in both models included family history of premature CAD, age, male sex, lower glomerular filtration rate, diabetes mellitus, elevated systolic blood pressure, and angina. Additionally, smoking history was predictive of [50] CAD and sedentary lifestyle of [70] CAD. Both models characterized high-risk CAD better than the Pooled Cohort Equation (area under the curve=0.70 and 0.71 for [50] and [70], respectively) and Diamond-Forrester risk scores (area under the curve=0.68 and 0.71, respectively). Both [50] and [70] CAD was associated with more frequent invasive interventions and adverse events than non-high-risk CAD (all P<0.0001). CONCLUSIONS:In contemporary practice, 2.4% to 6.6% of stable, symptomatic patients requiring noninvasive testing have high-risk CAD. A simple combination of pretest clinical variables improves prediction of high-risk CAD over traditional risk assessments. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov . Unique identifier: NCT01174550.
| S-EPMC6368397 | biostudies-literature
Project description:BackgroundThe 5-hydroxymethylcytosine (5hmC) DNA modification is an epigenetic marker involved in a range of biological processes. Its function has been studied extensively in tumors, neurodegenerative diseases, and atherosclerosis. Studies have reported that 5hmC modification is closely related to the phenotype transformation of vascular smooth muscle cells and endothelial dysfunction. However, its role in coronary artery disease (CAD) has not been fully studied.ResultsTo investigate whether 5hmC modification correlates with CAD pathogenesis and whether 5hmC can be used as a biomarker, we used a low-input whole-genome sequencing technology based on selective chemical capture (hmC-Seal) to firstly generate the 5hmC profiles in the circulating cell-free DNA(cfDNA) of CAD patients, including stable coronary artery disease (sCAD) patients and acute myocardial infarction (AMI) patients. We detected a significant difference of 5hmC enrichment in gene bodies from CAD patients compared with normal coronary artery (NCA) individuals. Our results showed that CAD patients can be well separated from NCA individuals by 5hmC markers. The prediction performance of the model established by differentially regulated 5hmc modified genes were superior to common clinical indicators for the diagnosis of CAD (AUC = 0.93) and sCAD (AUC = 0.93). Specially, we found that 5hmC markers in cfDNA showed prediction potential for AMI (AUC = 0.95), which was superior to that of cardiac troponin I, muscle/brain creatine kinase, and myoglobin.ConclusionsOur results suggest that 5hmC markers derived from cfDNA can serve as effective epigenetic biomarkers for minimally noninvasive diagnosis and prediction of CAD.
| S-EPMC6974971 | biostudies-literature
Project description:Monocytes and T-cells play an important role in the development of atherosclerotic coronary artery disease (CAD). Differences in transcriptional activity of these cells might reflect the individual's atherosclerotic burden. Transcriptome analysis of circulating mononuclear cells from carefully matched atherosclerotic and control patients will potentially provide insights into the pathophysiology of atherosclerosis and supply biomarkers for diagnostic purposes. From patients undergoing coronary angiography because of anginal symptoms, we carefully matched 18 patients with severe triple-vessel CAD to 13 control patients without signs of CAD on angiography. All patients were on statin and aspirin treatment. RNA from circulating CD4+ T-cells, CD14+ monocytes, lipopolysaccharide-stimulated monocytes, macrophages and CD34+ progenitor cells was subjected to genome-wide expression analysis. Only CD14+ monocytes demonstrated that a small number of genes involved in activation was overexpressed in control patients, which was verified by real-time polymerase-chain reaction. In this pilot study, cautious matching of patients with severe atherosclerotic CAD with control patients without angiographic signs of coronary atherosclerosis did not reveal differences in transcriptional activity in four out of five different mononuclear cell types. In resting monocytes from patients without overt CAD some inflammatory genes were overexpressed as compared to patients with severe CAD. Large inter-individual variability prevented the use of single differentially expressed genes as biomarkers. Keywords: disease-state analysis
2008-12-01 | GSE9820 | GEO
Project description:Recent clinical studies have revealed that the serum levels of toxic hydrophobic bile acids (deoxy cholic acid, lithocholic acid [LCA], and glycoursodeoxycholic acid) are significantly higher in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) when compared to control subjects. The elevated serum bile acids may be the result of hepatic peroxisomal dysfunction. Circulating hydrophobic bile acids are able to disrupt the blood-brain barrier and promote the formation of amyloid-β plaques through enhancing the oxidation of docosahexaenoic acid. Hydrophobic bile acid may find their ways into the neurons via the apical sodium-dependent bile acid transporter. It has been shown that hydrophobic bile acids impose their pathological effects by activating farnesoid X receptor and suppressing bile acid synthesis in the brain, blocking NMDA receptors, lowering brain oxysterol levels, and interfering with 17β-estradiol actions such as LCA by binding to E2 receptors (molecular modelling data exclusive to this paper). Hydrophobic bile acids may interfere with the sonic hedgehog signaling through alteration of cell membrane rafts and reducing brain 24(S)-hydroxycholesterol. This article will 1) analyze the pathological roles of circulating hydrophobic bile acids in the brain, 2) propose therapeutic approaches, and 3) conclude that consideration be given to reducing/monitoring toxic bile acid levels in patients with AD or aMCI, prior/in combination with other treatments.
| S-EPMC10041467 | biostudies-literature
Project description:AimThe modest added predictive value of the existing genetic risk scores (GRSs) for coronary artery disease (CAD) could be partly due to missing genetic components, hidden in the genetic architecture of intermediate phenotypes such as coronary artery calcification (CAC). In this study, we investigated the predictive ability of CAC GRS for CAD.Materials and methodsWe investigated the association of CAC GRSs with CAD and coronary calcification among the participants in the Ludwigshafen Risk and Cardiovascular Health study (LURIC) (n = 2742), the Tampere Vascular Study (TVS) (n = 133), and the Tampere Sudden Death Study (TSDS) (n = 660) using summary data from the largest multi-ancestry GWAS meta-analysis of CAC to date. Added predictive value of the CAC GRS over the traditional CVD risk factors as well as metaGRS, a GRS for CAD constructed with 1.7 million genetic variants, was tested with standard train-test machine learning approach using the LURIC data, which had the largest sample size.ResultsCAC GRS was significantly associated with CAD in LURIC (OR=1.41, 95 % CI [1.28-1.55]), TVS (OR=1.79, 95 % CI [1.05-3.21]) as well as in TSDS (OR=4.20, 95 % CI [1.74-10.52]). CAC GRS showed strong association with calcification areas in left (OR=1.78, 95 % CI [1.16-2.74]) and right (OR=1.71, 95 % CI [1.98-2.67]) coronary arteries. There was statistically significant added predictive value of the CAC GRS for CAD over the used traditional CVD risk factors (AUC 0.734 vs 0.717, p-value = 0.02). Furthermore, CAC GRS improved the prediction accuracy for CAD when combined with metaGRS.ConclusionsThis study showed that CAC GRS is a new risk marker for CAD in three European cohorts, with added predictive value over the traditional CVD risk factors.
| S-EPMC11525111 | biostudies-literature
Project description:BackgroundResistant starch (RS) type 4 (RS4) is a type of RS, a class of non-digestible prebiotic dietary fibers with a range of demonstrated metabolic health benefits to the host. On the other hand, bile acids (BA) have recently emerged as an important class of metabolic function mediators that involve host-microbiota interactions. RS consumption alters fecal and cecal BA in humans and rodents, respectively. The effect of RS intake on circulating BA concentrations remains unexplored in humans.Methods and resultsUsing available plasma and stool samples from our previously reported double-blind, controlled, 2-arm crossover nutrition intervention trial (Clinicaltrials.gov: NCT01887964), a liquid-chromatography/mass-spectrometry-based targeted multiple reaction monitoring, and absolute quantifications, we assessed BA changes after 12 weeks of an average 12 g/day RS4-intake. Stool BA concentrations were lower post RS4 compared to the control, the two groups consuming similar macronutrients (n = 14/group). Partial least squares-discriminant analysis revealed distinct BA signatures in stool and plasma post interventions. The increased circulating BA concentrations were further investigated using linear mixed-effect modeling that controlled for potential confounders. A higher plasma abundance of several BA species post RS4 was observed (fold increase compared to control in parenthesis): taurocholic acid (1.92), taurodeoxycholic acid (1.60), glycochenodeoxycholic acid (1.58), glycodeoxycholic acid (1.79), and deoxycholic acid (1.77) (all, p < 0.05). Distinct microbiome ortholog-signatures were observed between RS4 and control groups (95% CI), derived using the Piphillin function-prediction algorithm and principal component analysis (PCA) of pre-existing 16S rRNA gene sequences. Association of Bifidobacterium adolescentis with secondary BA such as, deoxycholic acid (rho = 0.55, p = 0.05), glycodeoxycholic acid (rho = 0.65, p = 0.02), and taurodeoxycholic acid (rho = 0.56, p = 0.04) were observed in the RS4-group, but not in the control group (all, p > 0.05).ConclusionOur observations indicate a previously unknown in humans- RS4-associated systemic alteration of microbiota-derived secondary BA. Follow-up investigations of BA biosynthesis in the context of RS4 may provide molecular targets to understand and manipulate microbiome-host interactions.
| S-EPMC9631925 | biostudies-literature