Uric acid levels are associated with endothelial dysfunction and severity of coronary atherosclerosis during a first episode of acute coronary syndrome.
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ABSTRACT:
SUBMITTER: Gaubert M
PROVIDER: S-EPMC5940631 | biostudies-literature | 2018 Jun
REPOSITORIES: biostudies-literature
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Uric acid levels are associated with endothelial dysfunction and severity of coronary atherosclerosis during a first episode of acute coronary syndrome.
Gaubert Mélanie M Marlinge Marion M Alessandrini Marine M Laine Marc M Bonello Laurent L Fromonot Julien J Cautela Jennifer J Thuny Franck F Barraud Jeremie J Mottola Giovanna G Rossi Pascal P Fenouillet Emmanuel E Ruf Jean J Guieu Régis R Paganelli Franck F
Purinergic signalling 20180406 2
The role of serum uric acid in coronary artery disease has been extensively investigated. It was suggested that serum uric acid level (SUA) is an independent predictor of endothelial dysfunction and related to coronary artery lesions. However, the relationship between SUA and severity of coronary atherosclerosis evaluated via endothelial dysfunction using peripheral arterial tone (PAT) and the reactive hyperhemia index (RHI) has not been investigated during a first episode of acute coronary synd ...[more]
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Project description:Background Elevated plasma ceramides are independent predictors of cardiovascular disease and mortality in patients with advanced epicardial coronary artery disease. Our understanding of plasma ceramides in early epicardial coronary artery disease, however, remains limited. We examined the role of plasma ceramides in early coronary atherosclerosis characterized by coronary endothelial dysfunction. Methods and Results Participants presenting with chest pain and nonobstructive epicardial coronary artery disease underwent coronary endothelial function. Patients (n=90) demonstrated abnormal coronary endothelial function with acetylcholine (≥20% decrease in coronary artery diameter or ≤50% increase in coronary blood flow). A total of 30 controls had normal coronary endothelial function. Concentrations of plasma ceramide 18:0 (P=0.038), 16:0 (P=0.021), and 24:0 (P=0.019) differed between participants with normal and abnormal coronary endothelial function. Ceramide 24:0 (odds ratio [OR], 2.23 [95% CI, 1.07-4.66]; P=0.033) and 16:0 (OR, 1.91×106 [95% CI, 11.93-3.07×1011]; P=0.018) were independently associated with coronary endothelial dysfunction. Among participants with endothelium-dependent coronary dysfunction (n=78), ceramides 16:0 (OR, 5.17×105 [95% CI, 2.83-9.44×1010]; P=0.033), 24:0 (OR, 2.98 [95% CI, 1.27-7.00]; P=0.012), and 24:1/24:0 (OR, 4.39×10-4 [95% CI, 4×10-7-0.48]; P=0.030) were more likely to be elevated. Conclusions The current study demonstrated an association between increased circulating ceramide levels and coronary endothelial dysfunction in the absence of epicardial coronary artery disease. This study supports the role of plasma ceramides as a potential biomarker or a therapeutic target for early coronary atherosclerosis in humans.
| S-EPMC9075496 | biostudies-literature
Project description:BackgroundWe investigated the role of ANGPTL3 and ANGPTL4 in atherosclerosis development and determined whether plasma concentrations of ANGPTL3 and ANGPTL4 are related to the degree of coronary stenosis.MethodsA total of 305 consecutive patients with angina who underwent diagnostic coronary angiography were enrolled in the study between August 2017 and August 2018. The levels of ANGPTL3 and ANGPTL4 were measured by using competitive ELISA kits.ResultsAccording to the degree of coronary artery stenosis, patients were classified into four types: coronary artery stenosis of < 10%, 10-50%, 50-75, and > 75%. The plasma ANGPTL3 level was higher (51.71 ± 52.67 vs. 24.65 ± 10.32 ng/mL, P < 0.001) and that of ANGPTL4 was lower (454.66 ± 269.05 vs. 875.49 ± 961.15 ng/mL, P < 0.001) in the coronary artery stenosis ≥ 10% group than in the < 10% group. ANGPTL3 and ANGPTL4 levels were significantly associated with the severity of coronary vascular stenosis. ROC curve analyses indicated that ANGPTL3 concentrations above 30.5 ng/mL can predict atherosclerosis with a sensitivity of 71.2% and specificity of 75.3%, and that ANGPTL4 levels below 497.5 ng/mL can predict atherosclerosis with a sensitivity of 63.9% and specificity of 74.5%. ANGPTL3 and ANGPTL4 were determined to be independent risk factors for coronary atherosclerosis with odds ratios (ORs) of 0.189 (95% CI 0.097-0.368, P < 0.001) and 3.625 (95% CI 1.873-7.016, P < 0.001), respectively.ConclusionsIncreased ANGPTL3 or decreased ANGPTL4 shows an association with coronary atherosclerosis and, may become a predictor of coronary atherosclerosis in the future.
| S-EPMC8571829 | biostudies-literature
Project description:AimsRecent genome-wide association studies (GWAS) have identified that the JCAD locus is associated with risk of coronary artery disease (CAD) and myocardial infarction (MI). However, the mechanisms whereby candidate gene JCAD confers disease risk remain unclear. We addressed whether and how JCAD affects the development of atherosclerosis, the common cause of CAD.Methods and resultsBy mining data in the Genotype-Tissue Expression (GTEx) database, we found that CAD-associated risk variants at the JCAD locus are linked to increased JCAD gene expression in human arteries, implicating JCAD as a candidate causal CAD gene. We therefore generated global and endothelial cell (EC) specific-JCAD knockout mice, and observed that JCAD deficiency attenuated high fat diet-induced atherosclerosis in ApoE-deficient mice. JCAD-deficiency in mice also improved endothelium-dependent relaxation. Genome-wide transcriptional profiling of JCAD-depleted human coronary artery ECs showed that JCAD depletion inhibited the activation of YAP/TAZ pathway, and the expression of downstream pro-atherogenic genes, including CTGF and Cyr61. As a result, JCAD-deficient ECs attracted fewer monocytes in response to lipopolysaccharide (LPS) stimulation. Moreover, JCAD expression in ECs was decreased under unidirectional laminar flow in vitro and in vivo. Proteomics studies suggest that JCAD regulates YAP/TAZ activation by interacting with actin-binding protein TRIOBP, thereby stabilizing stress fiber formation. Finally, we observed that endothelial JCAD expression was increased in mouse and human atherosclerotic plaques.ConclusionThe present study demonstrates that the GWAS-identified CAD risk gene JCAD promotes endothelial dysfunction and atherosclerosis, thus highlighting the possibility of new therapeutic strategies for CAD by targeting JCAD.
| S-EPMC6698662 | biostudies-literature
Project description:ObjectiveThe impact of serum uric acid (sUA) levels on the clinical prognosis and severity of coronary artery disease in patients with acute coronary syndrome (ACS) and hypertension after percutaneous coronary intervention (PCI) is not fully clear. This study aimed to assess the association among sUA levels, clinical prognosis and severity of coronary artery disease in patients with ACS and hypertension after PCI.DesignIn this prospective cohort study, we followed-up patients with ACS and hypertension after PCI for 1 year to explore the risk factors for 1 year total major adverse cardiovascular events (MACEs) and multivessel coronary artery disease, the dose-effect relationship among sUA levels, MACEs and severity of coronary artery disease and correlation between sUA levels and severity of coronary artery disease (Gensini score).Setting/patientsSeveral Chinese internists followed-up 422 patients who were diagnosed with ACS and hypertension after PCI in a large tertiary hospital of Qingdao during the period from 1 June 2019 to 1 December 2019.Outcome measuresOne-year follow-up MACEs results and coronary angiography results.ResultsIn the coronary angiography results, multivessel coronary artery disease (28.5% vs 21.4%, p=0.006) and non-culprit lesion vascular occlusion (11.7% vs 5.3%, p=0.042) were more common in the hyperuricaemia group, and the Gensini score (26.69±13.46 vs 17.66±10.57, p<0.001) was also higher. In the results of 1-year MACEs, the incidence of all-cause mortality (3.5% vs 2.5%, p=0.037), PCI or coronary artery bypass grafting therapy due to myocardial infarction or angina pectoris (15.1% vs 7.6%, p=0.027), medication conservative therapy in hospital due to myocardial infarction or angina pectoris (12.9% vs 6.7%, p=0.041) and total MACEs (31.8% vs 16.9%, p=0.001) were higher in patients with hyperuricaemia. Univariate and multivariate logistic regression analysis models showed that hyperuricaemia was still an independent risk factor for total MACEs within 1 year (OR=2.618, 95% CI 1.656 to 4.139, p<0.001; OR=1.920, 95% CI 1.158 to 3.183, p=0.011, respectively) and multivessel coronary artery disease (OR=2.140, 95% CI 1.371 to 3.342, p=0.001; OR=1.688, 95% CI 1.051 to 2.710, p=0.030, respectively) after adjusting for confounding factors. The severity of coronary artery disease (non-culprit lesion vascular occlusion (4.7% vs 8.4% vs 9.6% vs 16.2%, p=0.041); multivessel coronary artery disease (17.9% vs 22.4% vs 29.8% vs 35.2%, p=0.022); Gensini score (16.96±10.35 vs 19.31±10.63 vs 26.12±11.48 vs 33.33±14.01, p<0.001)) and the incidence of total MACEs (13.2% vs 14.2% vs 34.6% vs 41%, p<0.001) increased significantly with the sUA levels increasing. Further, the Gensini score was positively correlated with uric acid levels (r=0.515, p<0.001).ConclusionsHyperuricaemia is an independent risk factor for 1-year total MACEs and multivessel coronary artery disease in patients with ACS and hypertension after PCI.
| S-EPMC8756275 | biostudies-literature
Project description:BackgroundEndothelial lipase (EL), a new member of the lipase family, has been shown to modulate high-density lipoprotein (HDL-C) metabolism and atherosclerosis in mouse models. We hypothesized that EL concentrations would be associated with decreased HDL-C and increased atherosclerosis in humans.Methods and findingsHealthy individuals with a family history of premature coronary heart disease (n = 858) were recruited as part of the Study of the Inherited Risk of Atherosclerosis. Blood was drawn in the fasting state before and, in a subgroup (n = 510), after administration of a single dose of intravenous heparin. Plasma lipids were measured enzymatically, lipoprotein subclasses were assessed by nuclear magnetic resonance, and coronary artery calcification (CAC) was quantified by electron beam computed tomography. Plasma EL mass was measured using a newly developed enzyme-linked immunosorbent assay. Median EL mass in pre-heparin plasma was 442 (interquartile range = 324-617) ng/ml. Median post-heparin mass was approximately 3-fold higher, 1,313 (888-1,927) ng/ml. The correlation between pre-heparin EL mass and post-heparin EL mass was 0.46 (p < 0.001). EL mass concentrations in both pre- and post-heparin plasma significantly correlated with all NCEP ATPIII-defined metabolic syndrome factors: waist circumference (r = 0.28 and 0.22, respectively, p < 0.001 for each), blood pressure (r = 0.18 and 0.24, p < 0.001 for each), triglycerides (r = 0.22, p < 0.001; and 0.13, p = 0.004), HDL cholesterol (r = -0.11, p = 0.002; and -0.18, p < 0.001), and fasting glucose (r = 0.11 and 0.16, p = 0.001 for both). EL mass in both routine (odds ratio [OR] = 1.67, p = 0.01) and post-heparin (OR = 2.42, p = 0.003) plasma was associated with CAC as determined by ordinal regression after adjustment for age, gender, waist circumference, vasoactive medications, hormone replacement therapy (women), and established cardiovascular risk factors.ConclusionsWe report, to our knowledge for the first time, that human plasma EL concentrations, in both post-heparin and routine pre-heparin plasma, are significantly associated with metabolic syndrome features and with subclinical atherosclerosis. EL may be a pro-atherogenic factor in humans, especially in overweight individuals and those with metabolic syndrome.
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Project description:Background:Whether serum uric acid (UA) is associated with all-cause mortality in patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI) remains unclear. Methods:We performed a retrospective cohort study of 2296 patients with ACS. Curve-fitting and Cox proportional-hazard regression models with a hazard ratio (HR) and 95% confidence interval (CI) were used. Results:During a mean follow-up of 246.31?±?49.16?days, 168 (7.32%) patients died from all causes. Patients were divided into two groups [the high-UA group (n = 566) and the low-UA group (n = 1730)] based on the serum UA threshold value (5.6?mg/dl) identified through curve fitting. Fifty-three (9.36%) patients died in the high-UA group, and 115 (6.65%) patients died in the low-UA group. The difference between groups was statistically significant (P = 0.031). Univariate analysis showed that the risk of all-cause mortality in the high-UA group was significantly greater than that in the low-UA group (HR?=?1.45, 95% CI: 1.03 to 2.04). This difference persisted after adjustment for baseline characteristics, medical history, and medication history (HR?=?1.42, 95% CI: 1.05 to 1.87). Conclusions:Our study demonstrated that elevated serum UA (>5.6?mg/dl) is associated with all-cause mortality in ASC patients after PCI.
| S-EPMC6311730 | biostudies-other
Project description:Multiterritorial atherosclerosis has dramatically increased annual risk of adverse cardiovascular events than atherosclerotic disease with single-artery affected. Serum uric acid (SUA) is an important predictor of stroke and atherosclerosis; however, which is supported by few direct evidence based on cohort studies. A prospective cohort study including 2644 North Chinese adults aged ≥40 years was performed in 2010-2012 to investigate the association between SUA and multiterritorial vascular stenosis. Hyperuricaemia was defined as SUA levels >6 and >7 mg/dL for males and females, respectively. All participants underwent twice transcranial Doppler (TCD) and bilateral carotid duplex ultrasound to evaluate intracranial artery stenosis (ICAS) and extracranial arterial stenosis (ECAS) and peripheral arterial disease (PAD) was determined by ankle-brachial index (ABI) on January 2010 and January 2012 based on regular health check-ups. The cumulative incidence of vascular stenosis was significantly higher in subjects with hyperuricaemia than in those without hyperuricaemia (54.1% vs. 34.7%, P < 0.001). The adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for new on-set vascular stenosis due to hyperuricaemia and a 1-mg/dL change in SUA level were 1.75 (1.32-2.31) and 1.29 (1.21-1.38), respectively. Furthermore, in the gender-stratified analysis, the association between SUA levels and ICAS was statistically significant in males (OR: 2.02; 95% CI: 1.18-3.46), but not females (OR: 0.85, 95% CI: 0.41-1.76, P for interaction: 0.026).
| S-EPMC6652300 | biostudies-literature
Project description:Endothelial dysfunction is an early manifestation of atherosclerosis. Inflammation and vasa vasorum play a pivotal role in the pathophysiology of plaque initiation, development, and complications. Optical coherence tomography allows high-resolution imaging of tissue microstructure. Therefore, the aim of this study was to test the hypothesis that segments with endothelial dysfunction show macrophages and vasa vasorum in patients with early coronary artery disease.Optical coherence tomography images were obtained from 40 patients with mild coronary atherosclerosis who underwent coronary endothelial function assessment. Optical coherence tomography findings, including macrophages and microchannels, were evaluated in 76 coronary segments corresponding to those in endothelial response to acetylcholine. Coronary artery diameter change in response to acetylcholine was more severe in segments showing macrophages (-17.7±14.7% versus -6.3±13.9%; P<0.01) and microchannels (-15.9±15.9% versus -6.4±13.5%; P<0.01) than those without. There were increasing trends of the prevalence of macrophages and microchannels with endothelial dysfunction as stratified by quartiles of coronary artery diameter change (P<0.01 and P=0.02 for trend, respectively). In particular, segments with both macrophages and microchannels (n=12) tended to have worse endothelial function than those with macrophages alone (n=15) and microchannels alone (n=15; -22.1±14.6% versus -10.9±15.6% and -10.9±15.6%; P=0.07 and P=0.06, respectively).Epicardial endothelial dysfunction was associated with optical coherence tomography -identified macrophages and microchannels in mild coronary atherosclerosis. The current study further supports the role of inflammation and vasa vasorum proliferation in the early stage of coronary atherosclerosis.
| S-EPMC4212523 | biostudies-literature
Project description:Schizophrenia is associated with widespread cortical and subcortical abnormalities. Studies examining cognitive deficits in schizophrenia have historically focused on cortical deficits; however, many subcortical areas also support cognition. We sought to determine whether deficits in subcortical gray matter are linked to neurocognitive dysfunction in patients with first-episode schizophrenia. This study included 170 patients with first-episode schizophrenia and 88 healthy controls. Clinical symptoms, neurocognitive function, and structural images were assessed. Subcortical volumes were recorded. Patients had significant deficits in all cognitive domains, including processing speed, attention, memory, executive function and social cognition. Patients also demonstrated significantly smaller volumes in the amygdala, hippocampus, thalamus, and total cortical gray matter than did controls after Bonferroni correction for multiple comparisons. Reasoning/problem solving was significantly and positively correlated with the volume of the amygdala and nucleus accumbens in patients. Positive symptoms of psychosis were positively correlated with the volume of the amygdala and nucleus accumbens. In addition, the dose of antipsychotic medication was positively correlated with the volume of the amygdala, nucleus accumbens, caudate, putamen, and pallidum. In conclusion, schizophrenia is associated with profound cognitive deficits. Our findings suggest that subcortical structures contribute to specific domains of cognitive dysfunction in first-episode schizophrenia.
| S-EPMC6475899 | biostudies-literature
Project description:AimsHyperuricemia has attracted increasing attention. However, limited concern has been paid to the potential dangers of lowering serum uric acid (SUA). We observed lower levels of SUA in patients with COVID-19. Therefore, we aim to explore whether patients with COVID-19 had SUA lower than normal and the relationship of SUA and the severity of COVID-19.MethodsThis was a case-control study based on 91 cases with COVID-19 and 273 age- and sex-matched healthy control subjects. We first compared SUA levels and uric acid/creatinine (UA/Cr) ratio between patients with COVID-19 and the healthy controls. Then, we examined the association of SUA levels and UA/Cr ratios with COVID-19 severity in COVID-19 cases only, defined according to the fifth edition of China's Diagnosis and Treatment Guidelines of COVID-19.ResultsSUA levels in patients with COVID-19 were 2.59% lower, UA/Cr ratios 6.06% lower at admission compared with healthy controls. In sex stratified analysis, levels of SUA and UA/Cr were lower in male patients with COVID-19 while only level of SUA was lower in female patients with COVID-19. Moreover, SUA and UA/Cr values were 4.27 and 8.23% lower in the severe group than that in the moderate group among male COVID-19 patients. Bivariate and partial correlations analysis showed negative correlations between SUA or UA/Cr ratio and COVID-19 after adjusting for age, sex, BMI and eGFR. A multiple linear regression analysis showed that SARS-CoV-2 infection and male sex were independent risk factors associated with lower SUA levels. Male patients with COVID-19 accompanied by low SUA levels had higher risk of developing severe symptoms than those with high SUA levels (incidence rate ratio: 4.05; 95% CI:1.11, 14.72) at admission. Comparing SUA and UA/Cr ratio at three time points (admission, discharge, and follow-up), we found that male patients experienced severe symptoms had lower SUA and UA/Cr ratio levels comparing to moderate patients, but no significant difference between three time points. On the contrary, female patients had lower SUA and UA/Cr ratio at discharge than those at admission, but no significant difference of SUA and UA/Cr ratio between moderate and severe group.ConclusionPatients with COVID-19 had SUA and UA/Cr values lower than normal at admission. Male COVID-19 patients with low SUA levels had a significantly higher crude risk of developing severe symptoms than those with high SUA levels. During disease aggravation, the level of SUA gradually decreased until discharge. At the follow-up exam, the level of SUA was similar to the levels at admission.
| S-EPMC8106517 | biostudies-literature