Metabolic Impairment in Coronary Artery Disease: Elevated Serum Acylcarnitines Under the Spotlights.
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ABSTRACT:
SUBMITTER: Gander J
PROVIDER: S-EPMC8716394 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Recent studies support that acylcarnitines exert a significant role in cardiovascular disease development and progression. The aim of this metabolomics-based study was to investigate the association of serum acylcarnitine levels with coronary artery disease (CAD) severity, as assessed via SYNTAX Score. Within the context of the prospective CorLipid trial (NCT04580173), the levels of 13 circulating acylcarnitines were accurately determined through a newly developed HILIC-MS/MS method in 958 patients undergoing coronary angiography in the AHEPA University Hospital of Thessaloniki, Greece. Patients presenting with acute coronary syndrome had significantly lower median acylcarnitine C8, C10, C16, C18:1 and C18:2 values, compared to patients with chronic coronary syndrome (p = 0.012, 0.007, 0.018, 0.011 and <0.001, respectively). Among CAD subgroups, median C5 levels were significantly decreased in unstable angina compared to STEMI (p = 0.026), while median C10, C16, C18:1 and C18:2 levels were higher in stable angina compared to STEMI (p = 0.019 p = 0.012, p = 0.013 and p < 0.001, respectively). Moreover, median C2, C3, C4 and C8 levels were significantly elevated in patients with diabetes mellitus (p < 0.001, <0.001, 0.029 and 0.011, respectively). Moreover, short-chain acylcarnitine C2, C4, C5 and C6 levels were elevated in patients with heavier calcification and lower left ventricular ejection fraction (LVEF) % (all p-values less than 0.05). With regard to CAD severity, median C4 and C5 levels were elevated and C16 and C18:2 levels were reduced in the high CAD complexity group with SYNTAX Score > 22 (p = 0.002, 0.024, 0.044 and 0.012, respectively), indicating a potential prognostic capability of those metabolites and of the ratio C4/C18:2 for the prediction of CAD severity. In conclusion, serum acylcarnitines could serve as clinically useful biomarkers leading to a more individualized management of patients with CAD, once further clinically oriented metabolomics-based studies provide similar evidence.
| S-EPMC8945505 | biostudies-literature
Project description:BackgroundLipoprotein(a)[Lp(a)] has been considered as an independent risk factor for coronary artery disease (CAD). The present study aimed to evaluate the association between baseline serum Lp(a) and CAD progression determined by angiographic score.MethodsA total of 814 patients who had undergone two or more coronary computed tomography angiography at least 6 months apart were consecutively enrolled and the coronary severity was determined by the Gensini score system. Patients were stratified into two groups according to Lp(a)>300 mg/L and Lp(a) ≤ 300 mg/L or classified as "progressors" and "non-progressors" based on the Gensini score rate of change per year. The association of continuous Lp(a) and Lp(a)>300 mg/L with CAD progression were respectively assessed by logistic regression analysis. Moreover, further evaluation of those association was performed in subgroups of the study population.ResultsPatients in the "progressors" group had significant higher Lp(a) levels. Furthermore, the multivariate logistic regression analysis showed that elevated Lp(a) (odds ratio [OR]: 1.451, 95% confidence interval [CI]: 1.177-1.789, p<.001) and Lp(a)>300 mg/L (OR:1.642, 95% CI:1.018-2.649, p = .042) were positively associated with CAD progression after adjusting for confounding factors. In addition, those relation seemed to be more prominent in subjects with lower body mass index (OR: 1.880, 95% CI: 1.224-2.888, p for interaction = .060).ConclusionsElevated baseline serum Lp(a) is positively and independently associated with angiographic progression of CAD, particularly in participants with relatively low body mass index. Therefore, Lp(a) could be a potent risk factor for CAD progression, assisting in early risk stratification in cardiovascular patients.
| S-EPMC8571555 | biostudies-literature
Project description:Chronic kidney disease (CKD) is associated with increased coronary artery disease (CAD) and coronary artery calcification. We hypothesized that the osteogenic factor, bone morphogenetic protein-4 (sBMP-4), is elevated in subjects with both CKD and CAD. Serum was collected from 79 subjects undergoing diagnostic angiography and stratified according to CAD and CKD status. Subjects with both CAD and CKD had significantly elevated sBMP-4 compared to those with only one or no disease. sBMP-4 continued to be associated with the presence of both diseases after adjustment for other risk factors. To determine if sBMP-4 is associated with coronary artery calcification, we compared coronary artery calcium scores (CAC) to sBMP-4 in 22 subjects. A positive correlation between CAC and sBMP-4 was seen. In conclusion, sBMP-4 is elevated in patients with both CAD and CKD and positively correlates with CAC, suggesting a role for sBMP-4 in the increased CAD seen in CKD patients.
| S-EPMC3594471 | biostudies-literature
Project description:IntroductionIndividuals with metabolic syndrome (MetS) are at increasing risk of coronary artery disease (CAD). We investigated the common metabolic perturbations of CAD and MetS via serum metabolomics to provide insight into potential associations.MethodsNon-targeted serum metabolomics analyses were performed using ultra high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) in samples from 492 participants (272 CAD vs. 121 healthy controls (HCs) as cohort 1, 55 MetS vs. 44 HCs as cohort 2). Cross-sectional data were obtained when the participants were recruited from the First Affiliated Hospital of Zhengzhou University. Multivariate statistics and Student's t test were applied to obtain the significant metabolites [with variable importance in the projection (VIP) values >1.0 and p values <0.05] for CAD and MetS. Logistic regression was performed to investigate the association of identified metabolites with clinical cardiac risk factors, and the association of significant metabolic perturbations between CAD and MetS was visualized by Cytoscape software 3.6.1. Finally, the receiver operating characteristic (ROC) analysis was evaluated for the risk prediction values of common changed metabolites.ResultsThirty metabolites were identified for CAD, mainly including amino acids, lipid, fatty acids, pseudouridine, niacinamide; 26 metabolites were identified for MetS, mainly including amino acids, lipid, fatty acids, steroid hormone, and paraxanthine. The logistic regression results showed that all of the 30 metabolites for CAD, and 15 metabolites for MetS remained significant after adjustments of clinical risk factors. In the common metabolic signature association analysis between CAD and MetS, 11 serum metabolites were significant and common to CAD and MetS outcomes. Out of this, nine followed similar trends while two had differing directionalities. The nine common metabolites exhibiting same change trend improved risk prediction for CAD (86.4%) and MetS (90.9%) using the ROC analysis.ConclusionSerum metabolomics analysis might provide a new insight into the potential mechanisms underlying the common metabolic perturbations of CAD and MetS.
| S-EPMC8498335 | biostudies-literature
Project description:Background Elevated levels of serum homocysteine, via impaired nitric oxide production, and coronary microvascular dysfunction are associated with increased risk of major adverse cardiovascular events. However, whether serum homocysteine levels and coronary microvascular endothelial dysfunction (CMED) are linked remains unknown. Methods and Results This study included 1418 patients with chest pain or an abnormal functional stress test and with nonobstructive coronary artery disease (<40% angiographic stenosis), who underwent CMED evaluation with functional angiography and had serum homocysteine levels measured. Patients were classified as having normal microvascular function versus CMED. Patients in the CMED group (n=743; 52%) had higher mean age (52.1±12.2 versus 50.0±12.4 years; P<0.0001), higher body mass index (29.1 [25.0-32.8] versus 27.5 [24.2-32.4]; P=0.001), diabetes mellitus (12.5% versus 9.4%; P=0.03), and fewer women (63.5% versus 68.7%; P=0.04) compared with patients in the normal microvascular function group. However, they had lower rates of smoking history, and mildly lower low-density lipoprotein cholesterol levels. Serum homocysteine levels were significantly higher in patients with CMED, and the highest quartile of serum homocysteine level (>9 µmol/L) was an independent predictor of CMED (odds ratio, 1.34 [95% CI, 1.03-1.75]; P=0.03) after adjustment for age; sex; body mass index; chronic kidney disease (CKD); diabetes mellitus; smoking exposure; low-density lipoprotein cholesterol; high-density lipoprotein cholesterol and triglycerides; and aspirin, statin, and B vitamin use. Conclusions Patients with CMED have significantly higher levels of serum homocysteine. Elevated serum homocysteine levels were associated with a significantly increased odds of an invasive diagnosis of CMED. The current study supports a potential role for homocysteine for diagnosis and target treatment in the patients with early coronary atherosclerosis.
| S-EPMC7792413 | biostudies-literature
Project description:Coronary artery disease is a potentially treatable comorbidity observed frequently in both chronic obstructive pulmonary disease and interstitial lung disease. The prevalence of angiographically proven coronary artery disease in advanced lung disease is not well described. We sought to characterize the treatment patterns of coronary artery disease complicating advanced lung disease and to describe the frequency of occult coronary artery disease in this population.We performed a 2-center, retrospective cross-sectional study of patients with either chronic obstructive pulmonary disease or interstitial lung disease evaluated for lung transplantation. Medications and diagnoses before the transplant evaluation were recorded in conjunction with left heart catheterization results.Of 473 subjects, 351 had chronic obstructive pulmonary disease, and 122 had interstitial lung disease. In subjects diagnosed clinically with coronary artery disease, medical regimens included a statin in 78%, antiplatelet therapy in 62%, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in 42%, and a beta-blocker in 37%. Ten percent were on no medication from these 4 classes. Fifty-seven percent of these subjects were on an antiplatelet agent as well as a statin, and 13% were on neither. Beta-blockers were less frequently prescribed in chronic obstructive pulmonary disease than interstitial lung disease (23% vs 58%, P=.007). Coronary angiography was available in 322 subjects. It demonstrated coronary artery disease in 60% of subjects, and severe coronary artery disease in 16%. Occult coronary artery disease and severe occult coronary artery disease were found in 53% and 9%, respectively. There were no significant differences in angiographic results between chronic obstructive pulmonary disease and interstitial lung disease, despite imbalanced risk factors.Coronary artery disease is common in patients with advanced lung disease attributable to chronic obstructive pulmonary disease or interstitial lung disease and is under-diagnosed. Guideline-recommended cardioprotective medications are suboptimally utilized in this population.
| S-EPMC3732035 | biostudies-literature
Project description:Being activated by endogenous and exogenous ligands, nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) enhances insulin sensitivity, promotes adipocyte differentiation, stimulates adipogenesis, and has the properties of anti-atherosclerosis, anti-inflammation, and anti-oxidation. The Human PPARγ gene (PPARG) contains thousands of polymorphic loci, among them two polymorphisms (rs10865710 and rs7649970) in the promoter region and two polymorphisms (rs1801282 and rs3856806) in the exonic region were widely reported to be significantly associated with coronary artery disease (CAD). Mechanistically, PPARG polymorphisms lead to abnormal expression of PPARG gene and/or dysfunction of PPARγ protein, causing metabolic disorders such as hypercholesterolemia and hypertriglyceridemia, and thereby increasing susceptibility to CAD.
| S-EPMC8984027 | biostudies-literature
Project description:AIM: Omentin-1, a novel adipokine expressed in visceral adipose tissue, is negatively correlated with insulin resistance and obesity. Decreased omentin-1 expression has been found in many chronic inflammatory diseases. However, the role of omentin-1 in coronary artery disease (CAD) has not been elucidated. The aim of the present study was to determine whether serum concentration of omentin-1 was independently associated with CAD. METHODS: One hundred and fifty five patients with CAD were divided into two groups: acute coronary syndrome (ACS) and stable angina pectoris (SAP). A total of 52 healthy participants served as controls. Serum concentrations of omentin-1 and interleukin-6 (IL-6) were measured using ELISA. The association of omentin-1 with CAD and cardiovascular disease risk factors was evaluated. RESULTS: Serum omentin-1 levels were lower in patients with ACS or SAP compared with controls (ACS, 113.08±61.43 ng/mL; SAP, 155.41±66.89 ng/mL; control, 254.00±72.9 ng/mL; P<0.01). Patients with ACS also had lower serum concentrations of omentin-1 compared with patients with SAP (P<0.01). Serum concentration of omentin-1 was negatively correlated with body mass index (r=-0.17, P<0.05) and serum IL-6 concentration (r=-0.19, P<0.05). Furthermore, multiple logistic regression analysis showed that serum omentin-1 concentrations were independently correlated with CAD. CONCLUSION: The findings suggest that serum concentrations of omentin-1 are related to CAD.
| S-EPMC4003121 | biostudies-other
Project description:Any combination of metabolic abnormalities may constitute the metabolic syndrome (MetS), conferring coronary artery disease (CAD) risk, but the independent effect of different combinations on CAD onset remains unknown. RESEARCH DESIGN AND METHODS" Healthy adult siblings (n = 987) of premature CAD (<60 years) case subjects were followed for 9.8 +/- 3.8 years. Baseline MetS variables (insulin sensitivity index, waist circumference, systolic blood pressure, HDL cholesterol, and triglycerides) were recombined into five principal components (PC1-5), and risk factor-adjusted proportional hazards for CAD onset of median-dichotomized PCs were estimated.The significant hazard ratios were as follows: for PC1 (all abnormalities except blood pressure) 1.66 (P = 0.036), PC2 (high blood pressure levels, high HDL cholesterol) 1.71 (P = 0.016), and PC4 (low HDL cholesterol, high insulin sensitivity, low triglycerides) 2.0 (P = 0.001). Traditionally defined MetS had a hazard ratio of 1.32 (P = 0.18).Independent MetS variants identified by PC analysis may explain metabolic mechanisms that increase CAD risk better than the presence of traditional MetS.
| S-EPMC2875458 | biostudies-other
Project description:BackgroundMore than a million diagnostic cardiac catheterizations are performed annually in the US for evaluation of coronary artery anatomy and the presence of atherosclerosis. Nearly half of these patients have no significant coronary lesions or do not require mechanical or surgical revascularization. Consequently, the ability to rule out clinically significant coronary artery disease (CAD) using low cost, low risk tests of serum biomarkers in even a small percentage of patients with normal coronary arteries could be highly beneficial.MethodsSerum from 359 symptomatic subjects referred for catheterization was interrogated for proteins involved in atherogenesis, atherosclerosis, and plaque vulnerability. Coronary angiography classified 150 patients without flow-limiting CAD who did not require percutaneous intervention (PCI) while 209 required coronary revascularization (stents, angioplasty, or coronary artery bypass graft surgery). Continuous variables were compared across the two patient groups for each analyte including calculation of false discovery rate (FDR ≤ 1%) and Q value (P value for statistical significance adjusted to ≤ 0.01).ResultsSignificant differences were detected in circulating proteins from patients requiring revascularization including increased apolipoprotein B100 (APO-B100), C-reactive protein (CRP), fibrinogen, vascular cell adhesion molecule 1 (VCAM-1), myeloperoxidase (MPO), resistin, osteopontin, interleukin (IL)-1β, IL-6, IL-10 and N-terminal fragment protein precursor brain natriuretic peptide (NT-pBNP) and decreased apolipoprotein A1 (APO-A1). Biomarker classification signatures comprising up to 5 analytes were identified using a tunable scoring function trained against 239 samples and validated with 120 additional samples. A total of 14 overlapping signatures classified patients without significant coronary disease (38% to 59% specificity) while maintaining 95% sensitivity for patients requiring revascularization. Osteopontin (14 times) and resistin (10 times) were most frequently represented among these diagnostic signatures. The most efficacious protein signature in validation studies comprised osteopontin (OPN), resistin, matrix metalloproteinase 7 (MMP7) and interferon γ (IFNγ) as a four-marker panel while the addition of either CRP or adiponectin (ACRP-30) yielded comparable results in five protein signatures.ConclusionsProteins in the serum of CAD patients predominantly reflected (1) a positive acute phase, inflammatory response and (2) alterations in lipid metabolism, transport, peroxidation and accumulation. There were surprisingly few indicators of growth factor activation or extracellular matrix remodeling in the serum of CAD patients except for elevated OPN. These data suggest that many symptomatic patients without significant CAD could be identified by a targeted multiplex serum protein test without cardiac catheterization thereby eliminating exposure to ionizing radiation and decreasing the economic burden of angiographic testing for these patients.
| S-EPMC3566965 | biostudies-literature