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1.
Crit Care ; 25(1): 158, 2021 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-33902676

RESUMEN

BACKGROUND: COVID-19 has resulted in high mortality worldwide. Information regarding cardiac markers for precise risk-stratification is limited. We aim to discover sensitive and reliable early-warning biomarkers for optimizing management and improving the prognosis of COVID-19 patients. METHODS: A total of 2954 consecutive COVID-19 patients who were receiving treatment from the Wuhan Huoshenshan Hospital in China from February 4 to April 10 were included in this retrospective cohort. Serum levels of cardiac markers were collected after admission. Coronary artery disease diagnosis and survival status were recorded. Single-cell RNA-sequencing and bulk RNA-sequencing from different cohorts of non-COVID-19 were performed to analyze SARS-CoV-2 receptor expression. RESULTS: Among 2954 COVID-19 patients in the analysis, the median age was 60 years (50-68 years), 1461 (49.5%) were female, and 1515 (51.3%) were severe/critical. Compared to mild/moderate (1439, 48.7%) patients, severe/critical patients showed significantly higher levels of cardiac markers within the first week after admission. In severe/critical COVID-19 patients, those with abnormal serum levels of BNP (42 [24.6%] vs 7 [1.1%]), hs-TNI (38 [48.1%] vs 6 [1.0%]), α- HBDH (55 [10.4%] vs 2 [0.2%]), CK-MB (45 [36.3%] vs 12 [0.9%]), and LDH (56 [12.5%] vs 1 [0.1%]) had a significantly higher mortality rate compared to patients with normal levels. The same trend was observed in the ICU admission rate. Severe/critical COVID-19 patients with pre-existing coronary artery disease (165/1,155 [10.9%]) had more cases of BNP (52 [46.5%] vs 119 [16.5%]), hs-TNI (24 [26.7%] vs 9.6 [%], α- HBDH (86 [55.5%] vs 443 [34.4%]), CK-MB (27 [17.4%] vs 97 [7.5%]), and LDH (65 [41.9%] vs 382 [29.7%]), when compared with those without coronary artery disease. There was enhanced SARS-CoV-2 receptor expression in coronary artery disease compared with healthy controls. From regression analysis, patients with five elevated cardiac markers were at a higher risk of death (hazards ratio 3.4 [95% CI 2.4-4.8]). CONCLUSIONS: COVID-19 patients with pre-existing coronary artery disease represented a higher abnormal percentage of cardiac markers, accompanied by high mortality and ICU admission rate. BNP together with hs-TNI, α- HBDH, CK-MB and LDH act as a prognostic biomarker in COVID-19 patients with or without pre-existing coronary artery disease.


Asunto(s)
Biomarcadores/sangre , /terapia , Enfermedad de la Arteria Coronaria/sangre , Anciano , China/epidemiología , Enfermedad de la Arteria Coronaria/epidemiología , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo/métodos
2.
Nutr Metab Cardiovasc Dis ; 31(4): 1137-1147, 2021 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-33712363

RESUMEN

BACKGROUND AND AIMS: In-stent restenosis (ISR) remains the most daunting challenge of current treatments of coronary artery disease (CAD). MicroRNAs (miRNAs) are prominent regulators of key pathological processes leading to restenosis and used as diagnostic tools in different studies. miR-152 and miR-148a are implicated to contribute in the putative intracellular mechanisms of ISR. The aim of present study is to investigate the potential early-stage diagnostic role of miR-152 and miR-148a expression levels for ISR in peripheral blood mononuclear cells (PBMCs) of patients who underwent stent implantation. METHODS AND RESULTS: The miRNAs that are supposed to be involved in the ISR were nominated by bioinformatics approach mainly using miRWalk3. Then by quantitative real-time PCR, we determined the relative expression of miR-152 and miR-148a of PBMCs from ISR patients with their age/sex-matched controls. RESULTS: The presence of ISR significantly coincided with a decrease in the relative expression of miR-152. The area under the curve (AUC) for miR-152 receiver operating characteristic (ROC) curve was 0.717 (95% CI; 0.60-0.83) with a sensitivity of 70% and a specificity of 67%, suggesting that the miRNA expression level might be employed to identify patients at risk of ISR. CONCLUSIONS: To the best of our knowledge, this is the first work to show that the miR-152 expression level can possibly be applied to predict CAD patients at risk of ISR. The results suggest that the expression levels of miR-152 in PBMCs may serve as a biomarker for ISR. Our finding suggests the importance of miRNA levels in PBMCs as a novel biological tool to detect diseases in their early clinical stages.


Asunto(s)
Enfermedad de la Arteria Coronaria/terapia , Reestenosis Coronaria/sangre , Leucocitos Mononucleares/metabolismo , MicroARNs/sangre , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/instrumentación , Stents , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Casos y Controles , Biología Computacional , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Reestenosis Coronaria/diagnóstico por imagen , Reestenosis Coronaria/etiología , Diagnóstico Precoz , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de Tiempo , Resultado del Tratamiento
3.
Mol Med Rep ; 23(5)2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33760184

RESUMEN

It has previously been shown that the number of endothelial progenitor cells (EPCs) is negatively correlated with Syntax score in patients with coronary artery disease (CAD). However, the association between alterations in EPC function and Syntax score is still unknown. The present study evaluated the association between the activity of EPCs as well as endothelial function and Syntax score in patients with CAD and investigated the underlying mechanisms. A total of 60 patients with CAD were enrolled in 3 groups according to Syntax score, and 20 healthy subjects were recruited as the control group. The number and migratory, proliferative and adhesive activities of circulating EPCs were studied. The endothelial function was measured by flow­mediated dilatation (FMD) and the levels of nitric oxide (NO) in plasma or secreted by EPCs were detected. The number and activity of circulating EPCs were lower in patients with a high Syntax score, which was similar to the alteration in FMD. The level of NO in plasma or secreted by EPCs also decreased as Syntax score increased. There was a negative association between FMD or circulating EPCs and Syntax score. A similar association was observed between the levels of NO in plasma or secreted by EPCs and Syntax score. Patients with CAD who had a higher Syntax score exhibited lower EPC numbers or activity and weaker endothelial function, which may be associated with attenuated NO production. These findings provide novel surrogate parameters for evaluation of the severity and complexity of CAD.


Asunto(s)
Enfermedad de la Arteria Coronaria/sangre , Células Progenitoras Endoteliales/metabolismo , Óxido Nítrico/sangre , Anciano , Movimiento Celular/genética , Proliferación Celular/genética , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/patología , Endotelio Vascular/crecimiento & desarrollo , Endotelio Vascular/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Vasodilatación/genética
4.
Int Heart J ; 62(2): 396-406, 2021 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-33731537

RESUMEN

Endothelial injury and inflammation have been found to be essential in the pathogenesis of coronary artery disease (CAD). Circulating exosomes are of great value as novel biomarkers for CAD. However, the role of circulating exosomes in the pathogenesis of CAD remains unclear. Thus, in this study, we aimed to examine whether circulating exosomes from CAD are involved in the endothelial injury and inflammation. The serum-derived exosomes were isolated from CAD and controls using an ExoQuick reagent, and these were then quantified by measuring the protein levels using BCA methods. The uptake of exosomes by human umbilical vein endothelial cells (HUVECs) was observed by laser scanning microscope and analyzed via flow cytometry. Then, HUVECs were treated with vehicle, exosomes from CAD (CAD-exo), and controls (ctrl-exo) in the absence and presence of vascular endothelial growth factor (VEGF). Cell viability, migration, and angiogenesis were evaluated using CCK-8 assay, scratch assay, and tube formation assay. Inflammatory factors including IL-1ß, IL-6, TNF-α, ICAM-1, and VCAM-1 levels were detected via qPCR. As per our findings, no significant differences were noted in uptake of ctrl-exo and CAD-exo by HUVECs. CAD-exo suppressed cell viability in a dose-dependent manner. Compared with ctrl-exo, CAD-exo-treated HUVECs significantly suppressed migration and angiogenesis. However, CAD-exo had a stronger inhibitory effect on VEGF-induced migration and angiogenesis compared with ctrl-exo. Moreover, IL-1ß, TNF-α, and ICAM-1 were determined to be significantly upregulated in HUVECs treated with CAD-exo, but IL-6 and VCAM-1 expressions were not affected. Overall, our results suggest that CAD-exo are involved in endothelial injury and inflammation, which may, in turn, cause endothelial dysfunction and potentially promote the development of CAD.


Asunto(s)
Enfermedad de la Arteria Coronaria/sangre , Exosomas/metabolismo , Movimiento Celular , Proliferación Celular , Células Cultivadas , Enfermedad de la Arteria Coronaria/patología , Femenino , Citometría de Flujo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/patología , Humanos , Inflamación/metabolismo , Inflamación/patología , Masculino , Persona de Mediana Edad
5.
Molecules ; 26(4)2021 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-33670057

RESUMEN

The prevention and diagnosis of sudden cardiac death (SCD) are among the most important keystones and challenges in clinical and forensic practice. However, the diagnostic value of the current biomarkers remains unresolved issues. Therefore, novel diagnostic biomarkers are urgently required to identify patients with early-stage cardiovascular diseases (CVD), and to assist in the postmortem diagnosis of SCD cases without typical cardiac damage. An increasing number of studies show that circular RNAs (circRNAs) have stable expressions in myocardial tissue, and their time- and tissue-specific expression levels might reflect the pathophysiological status of the heart, which makes them potential CVD biomarkers. In this article, we briefly introduced the biogenesis and functional characteristics of circRNAs. Moreover, we described the roles of circRNAs in multiple SCD-related diseases, including coronary artery disease (CAD), myocardial ischemia or infarction, arrhythmia, cardiomyopathy, and myocarditis, and discussed the application prospects and challenges of circRNAs as a novel biomarker in the clinical and forensic diagnosis of SCD.


Asunto(s)
Enfermedad de la Arteria Coronaria/diagnóstico , Muerte Súbita Cardíaca/patología , Medicina Legal , ARN Circular/sangre , Biomarcadores/sangre , Biomarcadores/metabolismo , Enfermedad de la Arteria Coronaria/sangre , Humanos , ARN Circular/genética , ARN Circular/metabolismo
6.
Medicine (Baltimore) ; 100(13): e25209, 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33787603

RESUMEN

ABSTRACT: Cardiovascular disease (CAD) is a devastating illness, but to date there are limited means of predicting a person's coronary stenosis severity and their prognosis. The study was performed to investigate the relationship between dipeptidyl peptidase 4(DPP4) gene polymorphisms and serum lipid profiles, as well as the severity of coronary artery stenosis in patients with CAD and type 2 diabetes (T2DM) for the first time.Herein, 201 patients with CAD and T2DM were enrolled in the Department of Cardiology, Shandong Provincial Qianfoshan Hospital. DPP4 rs3788979 and rs7608798 single nucleotide polymorphisms (SNPs) were genotyped. The general information of all patients was collected, and the associations between DPP4 SNPs and lipid profiles were detected. At the same time, association between SNP polymorphisms and the degree of coronary artery stenosis were analyzed.There was a significant difference in apolipoprotein B (ApoB) levels (P = .011) for the rs3788979 polymorphism, while no difference was identified in other blood lipids or with other mutations. SNP mutation of A to G in rs3788979 was associated with a reduced percentage of severe coronary artery stenosis in female patients (P = .023) as well as those with nosmoking (P = .030), nodrinking (P = 0.007), and nocardiovascular family history (P = 0.015).G allele of rs3788979 is associated with a reduced ApoB level. Besides, we suggest that G allele in rs3788979 may have a cardioprotective effect and prove to be a useful and specific measure when predicting a patient's coronary stenosis severity if diagnosed with CAD and T2DM.


Asunto(s)
Enfermedad de la Arteria Coronaria/genética , Estenosis Coronaria/genética , Diabetes Mellitus Tipo 2/genética , Dipeptidil Peptidasa 4/genética , Lípidos/sangre , Alelos , Apolipoproteínas B/sangre , Enfermedad de la Arteria Coronaria/sangre , Estenosis Coronaria/sangre , Diabetes Mellitus Tipo 2/sangre , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Pronóstico , Índice de Severidad de la Enfermedad
7.
Medicine (Baltimore) ; 100(8): e24932, 2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33663130

RESUMEN

BACKGROUND: Exercise test (ET) may have adverse effects on platelet function and induce acute thrombotic events in patients with coronary artery disease (CAD). The aim of this study is to investigate the platelet function and evaluate the risk of thrombotic events in CAD patients during ET. METHODS: Pubmed, Embase, Cochrane Library, and Web of Science were searched for a systematic review from initiation to October 2019. The inclusion criteria were controlled clinical trails as study design; investigating platelet function in CAD patients during ET; with ET carried out by treadmill or bicycle ergometer; written in English. Included articles were screened based on title/abstract and full-text review by 2 independent reviewers. Platelet aggregation (PA), platelet surface expression of CD62p and PAC-1, plasma levels of platelet factor 4 (PF4) and beta-thromboglobulin (ß-TG) were evaluated before and after ET. RESULTS: Eighteen articles were included out of the 427 references initially identified. In most of the studies included ET was terminated because of limited symptoms. Prior to ET, no difference in platelet aggregation was observed in CAD patients compared with healthy controls in majority of the studies, with or without the treatment with Aspirin. Dual anti-platelet therapy suppressed adenosine diphosphate (ADP)-induced platelet aggregation at rest. After ET, platelet aggregation, the serum levels of ß-thromboglobulin were found unchanged in majority of studies and platelet factor-4 were found unchanged in half of studies. The expression of platelet surface markers were elevated by ET in a few study. CONCLUSION: Symptom-limited exercise test did not affect platelet function in patients with coronary artery disease; however exercise to higher intensity may induce platelet activation.


Asunto(s)
Enfermedad de la Arteria Coronaria/sangre , Prueba de Esfuerzo/efectos adversos , Agregación Plaquetaria , Rehabilitación Cardiaca , Enfermedad de la Arteria Coronaria/terapia , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pruebas de Función Plaquetaria
8.
Medicine (Baltimore) ; 100(9): e24962, 2021 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-33655963

RESUMEN

ABSTRACT: Lipoprotein a (Lp (a)) and coronary artery calcification (CAC) are markers of coronary artery and cardiovascular diseases. However, the association between Lp (a) and CAC in asymptomatic individuals remains unclear. In this study, we aimed to determine the influence of Lp (a) on CAC in asymptomatic individuals.We included 2019 asymptomatic Korean adults who underwent testing for a coronary artery calcium score (CACS) and Lp (a) at the Gangnam Severance Hospital Health Checkup Center in Korea from January 2017 to August 2019. Participants were divided into 2 groups: CACS = 0 and CACS > 0. Factors affecting the CACS were analyzed by sex. Because age is a major risk factor for atherosclerosis, ≥45 years in men and ≥55 years in women, we further divided participants into 4 subgroups (≥45 and <45 in men, ≥55 and <55 in women). Factors affecting the CACS in the 4 groups were analyzed.There was a positive correlation between the CACS and traditional cardiovascular risk factors. Lp (a) positively correlated with the CACS in men (P < .01) and remained significant after multivariable logistic regression (P < .01). The same result was observed in men aged ≥45 years (P < .01).Lp (a) is an independently associated factor of CAC and a marker of coronary atherosclerosis in asymptomatic men aged ≥45 years. In asymptomatic men aged ≥45 years, Lp (a) should be measured, and intensive Lp (a)-lowering treatment should be considered.


Asunto(s)
Enfermedad de la Arteria Coronaria/sangre , Vasos Coronarios/diagnóstico por imagen , Lipoproteína(a)/sangre , Tamizaje Masivo/métodos , Calcificación Vascular/sangre , Enfermedades Asintomáticas , Biomarcadores/sangre , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/epidemiología , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , República de Corea/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Calcificación Vascular/epidemiología
9.
Medicine (Baltimore) ; 100(9): e25025, 2021 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-33655974

RESUMEN

ABSTRACT: This study aimed to investigate the correlation between triglyceride glucose (TyG) index and coronary artery disease (CAD) with type 2 diabetes mellitus (T2DM) and identify the risk associated TyG index in different subgroups.A total of 1665 eligible inpatients (CAD with T2DM group [n = 680], non-coronary artery disease without T2DM [n = 985]) were consecutively enrolled in this study. They were assigned into 4 subgroups: middle-aged, elderly, male, and female subgroups. Receiver operating characteristic curve diagnostic test and a logistic regression model was established to analyze the risk factors for CAD with T2DM.TyG index is an independent risk factor for patients with CAD with T2DM. The risk of increased TyG index is greater in the middle-aged and male subgroups than in the elderly and female subgroups, respectively (all P < .05). The specificity and the positive predictive value of the TyG index is greater than the sensitivity and the negative predictive value, respectively (all P < .05).Increased TyG index is a new independent risk factor for CAD with T2DM, and its risk is higher in the middle-aged and male subgroups than in the elderly and female subgroups, respectively. TyG index may be used as a clinical predictor of CAD with T2DM.


Asunto(s)
Glucemia/metabolismo , Enfermedad de la Arteria Coronaria/sangre , Diabetes Mellitus Tipo 2/sangre , Medición de Riesgo/métodos , Triglicéridos/sangre , Anciano , Biomarcadores/sangre , China/epidemiología , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Estudios Retrospectivos , Factores de Riesgo
10.
Am J Cardiol ; 146: 1-7, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33539858

RESUMEN

Comparisons of the outcomes of patients with myocardial infarction with nonobstructive coronary artery disease (MINOCA) and patients with nonobstructive coronary artery disease (CAD) without myocardial infarction (MI) are limited. Here we compare the outcomes of patients with MINOCA and patients with nonobstructive CAD without MI and assess the influence of medical therapy on outcomes in these patients. Veterans who underwent coronary angiography between 2008 to 2017 with nonobstructive CAD were divided into those with or without pre-procedural troponin elevation. Patients with prior revascularization, heart failure, or who presented with cardiogenic shock, STEMI, or unstable angina were excluded. After propensity matching, outcomes were compared between groups. The primary outcome was major adverse cardiovascular events (MACE: mortality, myocardial infarction, and revascularization) within one year: 3,924 patients with nonobstructive CAD and a troponin obtained prior to angiography were identified (n=1,986 with elevated troponin) and restricted to 1,904 patients after propensity-matching. There was a significantly higher risk of MACE among troponin-positive patients compared with those with a negative troponin (HR 2.37; 95% CI, 1.67 to 3.34). Statin (HR 0.32; 95% CI, 0.22 to 0.49) and ACE inhibitor (HR 0.49; 95% CI, 0.32 to 0.75) therapy after angiography was associated with decreased MACE, while P2Y12 inhibitor, calcium-channel and beta-blocker therapy were not associated with outcomes. In conclusion, Veterans with MINOCA are at increased risk for MACE compared with those with nonobstructive CAD and negative troponin at the time of angiography. Specific medications were associated with a reduction in MACE, suggesting an opportunity to explore novel approaches for secondary prevention in this population.


Asunto(s)
Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico , Infarto del Miocardio/etiología , Sistema de Registros , Anciano , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Troponina/sangre
11.
Nutr Metab Cardiovasc Dis ; 31(4): 1276-1285, 2021 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-33549433

RESUMEN

BACKGROUND AND AIMS: Dual antiplatelet therapy (DAPT) and Renin-angiotensin system inhibitors (RASi) represent the cornerstone in the treatment of patients undergoing percutaneous coronary interventions (PCI), mainly after an acute ischemic event. However, high-on treatment residual platelet reactivity (HRPR), is not infrequent despite optimal medical treatment. Homocysteine (Hcy) is a metabolite of methionine catabolism linked to atherothrombosis. Recently, a potential crosstalk between RAS and Hcy has been suggested, potentially favouring platelet aggregation and cardiovascular disease.Therefore, we aimed to investigate the impact of RASi on Hcy levels and platelet aggregation in patients on DAPT after PCI. METHODS AND RESULTS: Patients undergoing PCI on DAPT with ASA plus an ADP-antagonist (clopidogrel, ticagrelor or prasugrel), were included. RASi comprised angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB). Aggregation tests were performed by Multiple Electrode Aggregometry. We included 1210 patients, of whom 862 (71.2%) were on treatment with RASi. Overall, DAPT composition was ASA+clopidogrel in 566 (46.8%) patients, ASA+ticagrelor in 428 (35.4%) and ASA+prasugrel in 216 (17.9%). Median values of Hcy were higher in RASi patients (p = 0.006), who displayed a higher percentage of Hcy above the median value (52.4% vs. 44.8%, p = 0.019, adjustedOR [95%CI] = 1.40 [1.04-1.88], p = 0.027). No differences in HRPR rate were found according to RASi use for ASPI test (3.6% vs. 3.3%, p = 0.88) and ADP test (25.6% vs. 24.3%,p = 0.62; adjustedOR [95%CI] = 1.23 [0.89-1.70], p = 0.220) and according to ADP-antagonist type. A direct linear relationship was observed between platelet reactivity and Hcy in both patients receiving RASi and untreated ones, with higher values of platelet aggregation being observed in patients with Hcy above the median, independently from RASi administration and DAPT strategy. CONCLUSION: In patients on DAPT after PCI, RASi treatment did not emerge as an independent predictor of HRPR. However, the levels of Hcy were significantly elevated in patients on RASi and related to higher values of platelet reactivity, independently from the DAPT strategy.


Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Plaquetas/efectos de los fármacos , Enfermedad de la Arteria Coronaria/terapia , Terapia Antiplaquetaria Doble , Homocisteína/sangre , Intervención Coronaria Percutánea , Agregación Plaquetaria/efectos de los fármacos , Anciano , Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Biomarcadores/sangre , Plaquetas/metabolismo , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Terapia Antiplaquetaria Doble/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia Arriba
12.
Nutr Metab Cardiovasc Dis ; 31(4): 1166-1176, 2021 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-33579580

RESUMEN

BACKGROUND AND AIMS: Developing laboratory assays to evaluate HDL functions and improve cardiovascular disease (CVD) risk assessment has recently emerged as a challenge. The present study was conducted to help predict the risk of coronary artery disease (CAD) by investigating new cardiometabolic risk factors based on substituting paraoxonase 1 (PON1) as a critical enzyme in the functionality of HDL for that of HDL-C. METHODS AND RESULTS: The present study recruited 274 subjects undergoing diagnostic coronary angiography, 92 without significant CAD (non-CAD), and 182 with a severe CAD. The diagnostic accuracy of the new biomarkers in non-CAD versus multi-vessel disease was obtained in descending order of AUC as 0.72 (P < 0.001) for log (TG/PON1), 0.70 (P < 0.001) for nonHDL-C/PON1, and 0.67 (P < 0.001) for LDL-C/PON1. After performing a multivariate adjustment for age, gender, BMI, statin therapy, and diabetes mellitus, the increased odds of CAD remained significant for the new cardiometabolic ratios as independent variables [adjusted OR = 1.47 (1.15-1.88), p = 0.002 for LDL-C/PON1; adjusted OR = 2.15 (1.41-3.5), p = 0.009 for nonHDL-C/PON1; adjusted OR = 5.03 (2.14-13.02), p = 0.004 for log (TG/PON1)]. CAD was diagnosed with an optimal discriminating cutoff of 1.84 for LDL-C/PON1, 2.8 for nonHDL-C/PON1, and 0.48 for log (TG/PON1). CONCLUSIONS: To improve CAD's risk assessment, the PON1 activity was proposed as an alternative to HDL-C in the commonly used atherogenic lipid ratios. Substituting the PON1 activity for the HDL-C concentration can provide an index of the HDL activity. The present study sought to exploit the lipoprotein-related risk factors of CAD from a more effective perspective.


Asunto(s)
Arildialquilfosfatasa/sangre , HDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Adulto , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/enzimología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Medición de Riesgo , Índice de Severidad de la Enfermedad
13.
Clin Appl Thromb Hemost ; 27: 1076029621989813, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33523719

RESUMEN

Brain-derived neurotrophic factor (BDNF) plays a functional role in vascular endothelium homeostasis and the alleviation of atherosclerosis. Matrix gla protein (MGP) and Nε-(1-carboxymethyl)-l-lysine (CML) are both confirmed to be VC predictors. This study investigated the association between BDNF, MGP, CML and coronary artery calcification (CAC). Plasma BDNF, MGP, and CML levels were measured in 274 patients who underwent computed tomography to determine the CAC score (Agatston score). It was found that patients with CAC exhibited lower BDNF and MGP and higher CML levels than those without CAC. Plasma BDNF levels in patients with diabetes or hypertension were lower compared with the control groups. In logistic regression analysis, age, hypertension, BDNF, and MGP were independent predictors of CAC. Plasma BDNF and MGP levels were both correlated with the Agatston score even after adjustment for age, total cholesterol level, triglycerides, low-density lipoprotein level, creatinine clearance rate, and the presence of hypertension and diabetes mellitus. In 167 patients with CAC, circulating BDNF level was inversely associated with CML level and positively related to MGP level. In the receiver operating characteristic analysis for CAC, the areas under the curves for BDNF, MGP, and CML were 0.757, 0.777 and 0.653, respectively. In summary, plasma BDNF levels are associated with the Agatston score, and BDNF further predicts the occurrence of CAC.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/sangre , Enfermedad de la Arteria Coronaria/sangre , Calcificación Vascular/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Proteínas de Unión al Calcio/sangre , Estudios de Casos y Controles , Angiografía por Tomografía Computarizada , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estudios Transversales , Proteínas de la Matriz Extracelular/sangre , Femenino , Humanos , Lisina/análogos & derivados , Lisina/sangre , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Calcificación Vascular/diagnóstico por imagen
14.
Int Heart J ; 62(1): 9-15, 2021 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-33390563

RESUMEN

Cathepsin L (CatL) is a potent collagenase involved in atherosclerotic vascular remodeling and dysfunction in animals and humans. This study investigated the hypothesis that plasma CatL is associated with the prevalence of coronary artery disease (CAD). Between February May 2011 and January 2013, 206 consecutive subjects were enrolled from among patients who underwent coronary angiography and percutaneous coronary intervention treatment. Age-matched subjects (n = 215) served as controls. Plasma CatL and high-sensitive C-reactive protein (hs-CRP) and high-density lipoprotein cholesterol were measured. The patients with CAD had significantly higher plasma CatL levels compared to the controls (1.4 ± 0.4 versus 0.4 ± 0.2 ng/mL, P < 0.001), and the patients with acute coronary syndrome had significantly higher plasma CatL levels compared to those with stable angina pectoris (1.7 ± 0.7 versus 0.8 ± 0.4 ng/mL, P < 0.01). Linear regression analysis showed that overall, the plasma CatL levels were inversely correlated with the high-density lipoprotein levels (r = -0.32, P < 0.01) and positively with hs-CRP levels (r = 0.35, P < 0.01). Multiple logistic regression analyses shows that cathepsin L levels were independent predictors of CAD (add ratio, 1.8; 95% CI, 1.2 to 2.1; P < 0.01). These data demonstrated that increased levels of plasma CatL are closely associated with the presence of CAD and that circulating CatL serves as a useful biomarker for CAD.


Asunto(s)
Aterosclerosis/sangre , Biomarcadores/sangre , Catepsina L/metabolismo , Enfermedad de la Arteria Coronaria/sangre , Síndrome Coronario Agudo/sangre , Adulto , Anciano , Angina Estable/sangre , Aterosclerosis/fisiopatología , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , China/epidemiología , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/cirugía , Femenino , Humanos , Lipoproteínas HDL/sangre , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/métodos , Prevalencia
15.
Clin Appl Thromb Hemost ; 27: 1076029620984546, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33448867

RESUMEN

In patients with von Willebrand disease (vWD) the interest in age-related comorbidities has grown, because the life expectancy of these patients has increased. The research question of this study was whether patients with vWD show a different endothelial function compared to the general population. A total of 37 patients with type 1 (n = 23), type 2 (n = 10) and type 3 (n = 4) vWD, 14 controls and 38 patients with coronary artery disease (CAD) were included in this study. Five markers of endothelial dysfunction (MOED) were determined. Moreover, the endothelial function was examined using the Itamar Endo-PAT. The reactive hyperemia index (RHI) was calculated from the results. The markers soluble intercellular adhesion molecule-1 (p = 0.171), P-Selectin (p = 0.512), interleukin-6 (p = 0.734) and monocyte chemoattractant protein-1 (p = 0.761) showed higher levels in patients with vWD, but were not significantly different compared to the control group. RHI was impaired in CAD-patients (1.855), whereas vWD patients had mean results of 1.870 and controls 2.112 (p = 0.367). In this study, the endothelial function measurements of patients with von Willebrand disease were not significantly different compared to healthy controls.


Asunto(s)
Endotelio Vascular/fisiopatología , Enfermedades de von Willebrand/fisiopatología , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Quimiocina CCL2/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/fisiopatología , Femenino , Humanos , Hiperemia/sangre , Hiperemia/fisiopatología , Molécula 1 de Adhesión Intercelular/sangre , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Selectina-P/sangre , Enfermedad de von Willebrand Tipo 1/sangre , Enfermedad de von Willebrand Tipo 1/fisiopatología , Enfermedad de von Willebrand Tipo 2/sangre , Enfermedad de von Willebrand Tipo 2/fisiopatología , Enfermedad de von Willebrand Tipo 3/sangre , Enfermedad de von Willebrand Tipo 3/fisiopatología , Enfermedades de von Willebrand/sangre
16.
Nat Commun ; 12(1): 547, 2021 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-33483510

RESUMEN

Elevated plasma cholesterol and type 2 diabetes (T2D) are associated with coronary artery disease (CAD). Individuals treated with cholesterol-lowering statins have increased T2D risk, while individuals with hypercholesterolemia have reduced T2D risk. We explore the relationship between lipid and glucose control by constructing network models from the STARNET study with sequencing data from seven cardiometabolic tissues obtained from CAD patients during coronary artery by-pass grafting surgery. By integrating gene expression, genotype, metabolomic, and clinical data, we identify a glucose and lipid determining (GLD) regulatory network showing inverse relationships with lipid and glucose traits. Master regulators of the GLD network also impact lipid and glucose levels in inverse directions. Experimental inhibition of one of the GLD network master regulators, lanosterol synthase (LSS), in mice confirms the inverse relationships to glucose and lipid levels as predicted by our model and provides mechanistic insights.


Asunto(s)
Glucemia/metabolismo , Enfermedad de la Arteria Coronaria/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Glucosa/metabolismo , Metabolismo de los Lípidos , Modelos Biológicos , Animales , Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/genética , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/genética , Femenino , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo/métodos , Humanos , Hipercolesterolemia/sangre , Hipercolesterolemia/genética , Hipercolesterolemia/metabolismo , Ratones Endogámicos C57BL , Polimorfismo de Nucleótido Simple
17.
Angiology ; 72(5): 451-458, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33401931

RESUMEN

We investigated the association between plasma microRNA (miR)-204 and coronary artery calcification (CAC) in patients with type 2 diabetes mellitus (T2DM). We consecutively enrolled 179 individuals with T2DM who underwent coronary computed tomography at Anzhen Hospital from January 2015 to September 2016. The CAC score (CACS) was expressed in Agatston units and >10 Hounsfield units were defined as CAC-positive status. Significant CAC was observed in 98 (54.7%) patients. Plasma miR-204 levels (relative expression) were significantly lower in patients with significant CAC than controls (1.001 ± 0.100 vs 0.634 ± 0.211, P < .001). Plasma miR-204 levels were also negatively correlated with the glycosylated hemoglobin A1c (HbA1c) level (r = -0.702, P < .001), CACS (r = -0.710, P < .001), and the United Kingdom Prospective Diabetes Study (UKPDS) score (r = -0.355, P < .001). After multivariate logistic analyses, plasma miR-204 levels were still significantly and independently associated with the presence of CAC (odds ratio = 0.103, CI = 0.018-0.583, P < .001) after adjustment for conventional risk factors. Receiver operating characteristic curve analysis showed that plasma miR-204 levels can predict the severity and extent of CAC, and the specificity was higher than that of the traditional risk factors UKPDS score and HbA1c. In conclusion, the downregulation of miR-204 was independently associated with CAC in patients with T2DM.


Asunto(s)
MicroARN Circulante/sangre , Enfermedad de la Arteria Coronaria/sangre , Diabetes Mellitus Tipo 2/sangre , MicroARNs/sangre , Calcificación Vascular/sangre , Anciano , Beijing , Biomarcadores/sangre , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Regulación hacia Abajo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Calcificación Vascular/complicaciones , Calcificación Vascular/diagnóstico por imagen
18.
Angiology ; 72(5): 442-450, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33467865

RESUMEN

Epicardial adipose tissue has a paracrine effect, enhancing coronary artery atherosclerotic plaque development. This study evaluated epicardial fat volume (EFV), adipokines, coronary atherosclerosis, and adverse cardiovascular events in a cohort of asymptomatic patients with type 2 diabetes mellitus (T2DM). Epicardial fat volume was calculated using data from computed tomography coronary angiograms. Adipokines and inflammatory cytokines were also assayed and correlated with EFV. Epicardial fat volume was also assessed as a predictor of coronary artery calcium (CAC) score, number of coronary artery plaques, and significant plaque (>50% luminal stenosis). Data from the EFV analysis were available for 221 (85.7%) participants. Median EFV was 97.4 cm3, mean body mass index was 28.1 kg/m2, and mean duration of T2DM was 13 years. Statistically significant, but weak, correlations were observed between several adipokines, inflammatory cytokines, and EFV. Epicardial fat volume was a significant univariate (P = .01), but not multivariate, predictor of the number of coronary plaques, but not of CAC score or significant plaque. After a mean follow-up of 22.8 months, 12 adverse cardiovascular events were reported, exclusively in participants with EFV >97.4 cm3. Epicardial fat volume has limited utility as a marker of coronary artery plaque in patients with T2DM and is weakly correlated with adipokine expression.


Asunto(s)
Tejido Adiposo/diagnóstico por imagen , Angiografía por Tomografía Computarizada , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Diabetes Mellitus Tipo 2/complicaciones , Pericardio/diagnóstico por imagen , Adipoquinas/sangre , Tejido Adiposo/metabolismo , Adulto , Anciano , Enfermedades Asintomáticas , Biomarcadores/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/complicaciones , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Humanos , Mediadores de Inflamación/sangre , Londres , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo
19.
Metabolism ; 116: 154706, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33421505

RESUMEN

BACKGROUND: Elevated plasma lipoprotein (a) [Lp(a)] and coronary artery calcification (CAC) are established cardiovascular risk factors that correlate with each other. We hypothesized that other cardiovascular risk factors could affect their relationship. METHODS: We tested for interactions of 24 study variables related to dyslipidemia, diabetes, insulin resistance, hypertension, inflammation and coagulation with baseline Lp(a) on change in CAC volume and density over 9.5 years in 5975 Multi-Ethnic Study of Atherosclerosis (MESA) participants, free of apparent cardiovascular disease at baseline. RESULTS: Elevated Lp(a) was associated with larger absolute increase in CAC volume (3.21 and 4.45 mm3/year higher for Lp(a) ≥30 versus <30 mg/dL, and Lp(a) ≥50 versus <50 mg/dL, respectively), but not relative change in CAC volume. No association was found with change in CAC density when assessing continuous ln-transformed Lp(a). The association between elevated Lp(a) (≥30 mg/dL) and absolute change in CAC volume was greater in participants with higher circulating levels of interleukin-2 soluble receptor α, soluble tumor necrosis factor alpha receptor 1 and fibrinogen (15.33, 11.81 and 7.02 mm3/year in quartile 4, compared to -3.44, -0.59 and 1.91 mm3/year in quartile 1, respectively). No significant interaction was found for other study variables. Similar interactions were seen when assessing Lp(a) levels ≥50 mg/dL. CONCLUSIONS: Elevated Lp(a) was associated with an absolute increase in CAC volume, especially in participants with higher levels of selected markers of inflammation and coagulation. These results suggest Lp(a) as a potential biomarker for CAC volume progression.


Asunto(s)
Enfermedad de la Arteria Coronaria/sangre , Lipoproteína(a)/sangre , Calcificación Vascular/sangre , Anciano , Anciano de 80 o más Años , Aterosclerosis/sangre , Aterosclerosis/epidemiología , Aterosclerosis/etiología , Biomarcadores/sangre , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/etiología , Vasos Coronarios/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Estados Unidos/epidemiología , Calcificación Vascular/epidemiología , Calcificación Vascular/etiología
20.
Nutr Metab Cardiovasc Dis ; 31(1): 145-152, 2021 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-33500103

RESUMEN

BACKGROUND AND AIMS: Healed plaque is a hallmark of previous regional plaque rupture or erosion. We hypothesized that the plasma level of trimethylamine N-oxide (TMAO) is related to healed culprit plaque in ST-segment elevation myocardial infarction (STEMI) patients. METHODS AND RESULTS: A prospective cohort of 206 patients with STEMI, who were examined by optical coherence tomography (OCT) was enrolled in our study. After exclusion, 156 patients were categorized into healed plaque (n = 54) and nonhealed plaque (n = 102) groups. Plasma TMAO levels were detected by stable isotope dilution liquid chromatography tandem mass spectrometry in these two groups. Increased age and low BMI were more common in patients with healed plaques than in those without healed plaques. Through OCT observation, plaque rupture (81.5% vs. 45.1%, p < 0.001), thin cap fibroatheroma (TCFA) and macrophages (42.6% vs. 20.6%, p = 0.004, 70.4% vs. 26.5%, p < 0.001, respectively) were more frequently seen in patients with healed plaques than in those without healed plaques. The TMAO level in patients with healed plaques was significantly higher than that in patients with nonhealed plaques (3.9 µM [2.6-5.1] vs. 1.8 µM [1.0-2.7], p < 0.001). Furthermore, the receiver operating characteristic curve showed that TMAO can be used as a potential biomarker to predict healed plaque presence with a cutoff value of 2.9 µM (AUC = 0.810, sensitivity: 72.2%, specificity: 81.4%). CONCLUSIONS: Healed plaque in STEMI patients is associated with a high level of plaque vulnerability and inflammation. A high level of plasma TMAO can be a useful biomarker to differentiate STEMI patients with healed culprit plaques.


Asunto(s)
Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Metilaminas/sangre , Placa Aterosclerótica , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Tomografía de Coherencia Óptica , Cicatrización de Heridas , Anciano , Biomarcadores/sangre , Cromatografía Liquida , Enfermedad de la Arteria Coronaria/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los Resultados , Rotura Espontánea , Infarto del Miocardio con Elevación del ST/sangre , Espectrometría de Masas en Tándem
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