RESUMEN
Background: Identification of the unknown pathogenic factor driving atherosclerosis not only enhances the development of disease biomarkers but also facilitates the discovery of new therapeutic targets, thus contributing to the improved management of coronary artery disease (CAD). We aimed to identify causative protein biomarkers in CAD etiology based on proteomics and 2-sample Mendelian randomization (MR) design. Methods: Serum samples from 33 first-onset CAD patients and 31 non-CAD controls were collected and detected using protein array. Differentially expressed analyses were used to identify candidate proteins for causal inference. We used 2-sample MR to detect the causal associations between the candidate proteins and CAD. Network MR was performed to explore whether metabolic risk factors for CAD mediated the risk of identified protein. Vascular expression of candidate protein in situ was also detected. Results: Among the differentially expressed proteins identified utilizing proteomics, we found that circulating Golgi protein 73 (GP73) was causally associated with incident CAD and other atherosclerotic events sharing similar etiology. Network MR approach showed low-density lipoprotein cholesterol and glycated hemoglobin serve as mediators in the causal pathway, transmitting 42.1% and 8.7% effects from GP73 to CAD, respectively. Apart from the circulating form of GP73, both mouse model and human specimens imply that vascular GP73 expression was also upregulated in atherosclerotic lesions and concomitant with markers of macrophage and phenotypic switching of vascular smooth muscle cells (VSMCs). Conclusions: Our study supported GP73 as a biomarker and causative for CAD. GP73 may involve in CAD pathogenesis mainly via dyslipidemia and hyperglycemia, which may enrich the etiological information and suggest future research direction on CAD.
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Biomarcadores , Enfermedad de la Arteria Coronaria , Proteínas de la Membrana , Análisis de la Aleatorización Mendeliana , Proteómica , Humanos , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/patología , Ratones , Animales , Proteínas de la Membrana/genética , Proteínas de la Membrana/sangre , Masculino , Femenino , Biomarcadores/sangre , Persona de Mediana Edad , LDL-Colesterol/sangre , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Estudios de Casos y Controles , Aterosclerosis/sangre , Aterosclerosis/genéticaAsunto(s)
Glucemia , Enfermedad de la Arteria Coronaria , Insuficiencia Renal Crónica , Triglicéridos , Humanos , Triglicéridos/sangre , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/sangre , Insuficiencia Renal Crónica/complicaciones , Glucemia/análisis , Glucemia/metabolismo , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/complicaciones , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
Background: Natural killer (NK) cells are proposed to participate in coronary artery disease (CAD) development. However, little is known about how CAD patients' NK cells respond to different stimulatory factors in terms of proliferation capability. Methods and results: Twenty-nine CAD patients' peripheral blood NK cells were isolated and individually treated with IL-2, IL-12, IL-15, IL-18, IL-21, cortisone acetate, hydrocortisone, or ascorbic acid for 36 hours, followed by cell cycle analysis using flow cytometry. The ratio of S and G2/M phase cell number to total cell number was defined as a proliferation index (PrI) and used for proliferative capability indication. The results showed that these eight factors resulted in different life cycle changes in the 29 NK cell samples. Remarkably, 28 out of 29 NK cell samples showed an obvious increase in PrI upon ascorbic acid treatment. The serum lactate dehydrogenase (LDH) level of the 29 CAD patients was measured. The results showed a negative correlation between serum LDH level and the CAD patients' NK cell PrI upon stimulation of interleukins, but not the non-interleukin stimulators. Consistently, a retrospective analysis of 46 CAD patients and 32 healthy donors showed that the circulating NK cell number negatively correlated with the serum LDH level in CAD patients. Unexpectedly, addition of LDH to NK cells significantly enhanced the production of IFN-γ, IL-10 and TNF-α, suggesting a strong regulatory role on NK cell's function. Conclusion: Ascorbic acid could promote the proliferation of the CAD patients' NK cells; LDH serum level may function as an indicator for NK cell proliferation capability and an immune-regulatory factor.
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Proliferación Celular , Enfermedad de la Arteria Coronaria , Citocinas , Células Asesinas Naturales , L-Lactato Deshidrogenasa , Humanos , Células Asesinas Naturales/inmunología , Enfermedad de la Arteria Coronaria/inmunología , Enfermedad de la Arteria Coronaria/sangre , Masculino , Femenino , Persona de Mediana Edad , L-Lactato Deshidrogenasa/sangre , Anciano , Células CultivadasRESUMEN
The correlation between diabetes and coronary artery disease (CAD) is well established. Insulin resistance (IR) is considered a primary contributor to elevated CAD risk in diabetic individuals. The triglyceride-glucose (TyG) index serves as a straightforward surrogate marker for insulin resistance. However, few studies have explored their correlations with myocardial infarction and CAD severity. Therefore, our study aimed to investigate the association between the TyG index and the occurrence of myocardial infarction, as well as the severity of coronary artery disease. We conducted a retrospective study involving 3865 consecutive patients who underwent coronary angiography at the First Affiliated Hospital of Zhejiang University, School of Medicine. Of these, 1724 patients were diagnosed with coronary artery disease. Demographic, biochemical, clinical, and angiographic data were gathered. A robust correlation exists between the TyG index and CAD subtypes, suggesting its potential as an independent clinical diagnostic marker. Moreover, the TyG index exhibited a significant positive correlation with disease severity, as assessed by the Gensini score. Elevated TyG index was associated with an increased predisposition to severe CAD, as indicated by the Gensini score, and myocardial infarction, even after adjusting for well-established cardiovascular risk factors.
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Glucemia , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Índice de Severidad de la Enfermedad , Triglicéridos , Humanos , Masculino , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Triglicéridos/sangre , Persona de Mediana Edad , Glucemia/análisis , Glucemia/metabolismo , Estudios Retrospectivos , Anciano , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Biomarcadores/sangre , Resistencia a la Insulina , Factores de RiesgoRESUMEN
OBJECTIVE: The aim of this study was to investigate the relationship between circulating levels of B cell activating factor (BAFF) and the presence and severity of coronary artery disease (CAD) and acute myocardial infarction (AMI) in humans, as its biological functions in this context remain unclear. METHODS: Serum BAFF levels were measured in a cohort of 723 patients undergoing angiography, including 204 patients without CAD (control group), 220 patients with stable CAD (CAD group), and 299 patients with AMI (AMI group). Logistic regression analyses were used to assess the association between BAFF and CAD or AMI. RESULTS: Significantly elevated levels of BAFF were observed in patients with CAD and AMI compared to the control group. Furthermore, BAFF levels exhibited a positive correlation with the SYNTAX score (r = 0.3002, P < 0.0001) and the GRACE score (r = 0.5684, P < 0.0001). Logistic regression analysis demonstrated that increased BAFF levels were an independent risk factor for CAD (adjusted OR 1.305, 95% CI 1.078-1.580) and AMI (adjusted OR 2.874, 95% CI 1.708-4.838) after adjusting for confounding variables. Additionally, elevated BAFF levels were significantly associated with a high GRACE score (GRACE score 155 to 319, adjusted OR 4.297, 95% CI 1.841-10.030). BAFF exhibited a sensitivity of 75.0% and specificity of 71.4% in differentiating CAD patients with a high SYNTAX score, and a sensitivity of 75.5% and specificity of 72.8% in identifying AMI patients with a high GRACE score. CONCLUSION: Circulating BAFF levels serve as a valuable diagnostic marker for CAD and AMI. Elevated BAFF levels are associated with the presence and severity of these conditions, suggesting its potential as a clinically relevant biomarker in cardiovascular disease.
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Factor Activador de Células B , Biomarcadores , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Regulación hacia Arriba , Humanos , Masculino , Factor Activador de Células B/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnóstico , Femenino , Persona de Mediana Edad , Biomarcadores/sangre , Anciano , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Estudios de Casos y Controles , Factores de Riesgo , Medición de Riesgo , PronósticoRESUMEN
Bilirubin is widely recognized to possess antioxidant and anti-inflammatory characteristics. However, the relationship between bilirubin and coronary artery disease (CAD) remains controversial, particularly in individuals receiving Percutaneous Coronary Intervention (PCI). Given that statins may enhance the production of heme oxygenase-1 (HO-1) and bilirubin, we investigated the long-term cardiovascular prognostic role of bilirubin levels elevated by statin use in patients undergoing PCI. Data of 6945 subjects undergoing PCI were enrolled in this study. We divided the patients into two groups based on serum total bilirubin (TB) levels detected prior to PCI. The high TB group consisted of patients with serum TB values > 8.4 µmmol/L, while the low TB group consisted of patients with serum TB values ≤ 8.4 µmmol/L. The median follow-up time was 836 days. Cox proportional hazards models were performed to evaluate the hazard ratios (HRs) and 95% confidence interval (CI) for the incidence of major adverse cardiovascular event (MACE) associated with bilirubin levels. The association between TB levels and risk of MACE was significant [adjusted HR = 0.557, 95% CI (0.59-0.96), p = 0.020). Linear analysis was performed to determine the association between preadmission usage of statin and bilirubin level. The preadmission usage of statin independently linearly increases TB [adjusted-ß = 0.371, 95% CI (0.134-0.608), p = 0.002] and direct bilirubin (DB) [adjusted-ß = 0.411, 95% CI (0.300-0.522), p < 0.001). Mediation analysis demonstrated a direct protective role of preadmission statins treatment (ß = - 0.024, p < 0.01), TB (ß = - 0.003, p < 0.05) and DB (ß = - 0.009, p < 0.05). Furthermore, it was found that TB (4.0%) and DB (12.0%) mediated the relationship between preadmission statins therapy and MACE. Bilirubin has a protective effect against MACE. In patients with normal bilirubin level undergoing elective PCI, preadmission statin use elevated bilirubin levels, which were independently associated with a lower incidence of MACE over the long-term follow-up period.
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Bilirrubina , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Intervención Coronaria Percutánea , Humanos , Bilirrubina/sangre , Masculino , Femenino , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Anciano , Pronóstico , Persona de Mediana Edad , Enfermedad de la Arteria Coronaria/sangre , Factores de RiesgoRESUMEN
OBJECTIVE: Coronary artery disease (CAD) is frequent, but coronary slow flow (CSF) is a less common cardiovascular disease with a significant risk of mortality and morbidity. Endocan is a proinflammatory glycopeptide that has been investigated in cardiovascular diseases as well as some inflammatory diseases in recent years. We planned to compare the levels of endocan in both CAD and CSF in a similar population and examine the relationship of endocan with additional clinical variables. MATERIALS AND METHODS: In the trial, we included 169 consecutive subjects having a coronary angiography indication. According to the results of coronary angiography, 58 people were included in the CAD group, 52 were in the CSF group, and 59 people were in the control group. The control group includes those who did not have any lesions in their epicardial coronary arteries. Thrombolysis in myocardial infarction (TIMI)-frame counts (TFC) were calculated for all patients. RESULTS: Notably, 2.6% of the population in our study had CSF. Both the CAD (555±223 pg/mL) and CSF (559±234 pg/mL) groups had higher endocan levels than the control group (331±252 pg/mL) (p<0.001). There were similar endocan levels between the CAD and CSF groups. Endocan levels were shown to be favorably associated with mean TFC (r=0.267; p0.001). Serum endocan levels (particularly those above 450 pg/mL) and the presence of hyperlipidemia were the most important predictors of both CAD and CSF. CONCLUSION: Endocan levels are higher in CAD and CSF patients than in those with normal coronary arteries.
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Biomarcadores , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Proteínas de Neoplasias , Proteoglicanos , Humanos , Proteoglicanos/sangre , Proteoglicanos/líquido cefalorraquídeo , Masculino , Femenino , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/líquido cefalorraquídeo , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/fisiopatología , Persona de Mediana Edad , Proteínas de Neoplasias/sangre , Proteínas de Neoplasias/líquido cefalorraquídeo , Proteínas de Neoplasias/análisis , Estudios de Casos y Controles , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Anciano , Circulación Coronaria/fisiología , Valor Predictivo de las Pruebas , Factores de RiesgoRESUMEN
BACKGROUND: Lipoprotein(a) [Lp(a)] plasma level is a well-known risk factor for coronary artery disease (CAD). Existing data regarding the influence of sex on the Lp(a)-CAD relationship are inconsistent. OBJECTIVE: To investigate the relationship between Lp(a) and CAD in men and women and to elucidate any sex-specific differences that may exist. METHODS: Data of patients with Lp(a) measurements who were admitted to a tertiary university hospital, Koc University Hospital, were analyzed. The relationship between Lp(a) levels and CAD was explored in all patients and in subgroups created by sex. Two commonly accepted Lp(a) thresholds ≥ 30 and ≥ 50 mg/dL were analyzed. RESULTS: A total of 1858 patients (mean age 54 ± 17 years; 53.33% females) were included in the analysis. Lp(a) was an independent predictor of CAD according to the multivariate regression model for the entire cohort. In all cohort, both cut-off values (≥ 30 and ≥ 50 mg/dL) were detected as independent predictors of CAD (p < 0.001). In sex-specific analysis, an Lp(a) ≥ 30 mg/dL was an independent predictor of CAD only in women (p < 0.001), but Lp(a) ≥ 50 mg/dL was a CAD predictor both in men and women (men, p = 0.004; women, p = 0.047). CONCLUSION: The findings of this study may suggest that different thresholds of Lp(a) level can be employed for risk stratification in women compared to men.
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Biomarcadores , Enfermedad de la Arteria Coronaria , Lipoproteína(a) , Humanos , Femenino , Masculino , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/epidemiología , Lipoproteína(a)/sangre , Persona de Mediana Edad , Medición de Riesgo/métodos , Factores Sexuales , Biomarcadores/sangre , Anciano , Factores de Riesgo , Estudios Retrospectivos , República de Corea/epidemiología , Adulto , Análisis Multivariante , Valor Predictivo de las Pruebas , Factores de Riesgo de Enfermedad Cardiaca , PronósticoRESUMEN
BACKGROUND: Evidence is scarce on the effect of free fatty acid (FFA) level in the prognosis of coronary artery disease (CAD) patients with hypertension. This study. METHODS: A large prospective cohort study with a follow-up period of average 2 years was conducted at Xinjiang Medical University Affiliated First Hospital from December 2016 to October 2021. A total of 10,395 CAD participants were divided into groups based on FFA concentration and hypertension status, and then primary outcome mortality and secondary endpoint ischemic events were assessed in the different groups. RESULTS: A total of 222 all-cause mortality (ACMs), 164 cardiac mortality (CMs), 718 major adverse cardiovascular events (MACEs) and 803 major adverse cardiovascular and cerebrovascular events (MACCEs) were recorded during follow-up period. A nonlinear relationship between FFA and adverse outcomes was observed only in CAD patients with hypertension. Namely, a "U -shape" relationship between FFA levels and long-term outcomes was found in CAD patients with hypertension. Lower FFA level (< 310 µmol/L), or higher FFA level (≥ 580 µmol/L) at baseline is independent risk factors for adverse outcomes. After adjustment for confounders, excess FFA increases mortality (ACM, HR = 1.957, 95%CI(1.240-3.087), P = 0.004; CM, HR = 2.704, 95%CI(1.495-4.890, P = 0.001) and MACE (HR = 1.411, 95%CI(1.077-1.848), P = 0.012), MACCE (HR = 1.299, 95%CI (1.013-1.666), P = 0.040) prevalence. Low levels of FFA at baseline can also increase the incidence of MACE (HR = 1.567,95%CI (1.187-2.069), P = 0.002) and MACCE (HR = 1.387, 95%CI (1.070-1.798), P = 0.013). CONCLUSIONS: Baseline FFA concentrations significantly associated with long-term mortality and ischemic events could be a better and novel risk biomarker for prognosis prediction in CAD patients with hypertension. TRIAL REGISTRATION: The details of the design were registered on https://www.chictr.org.cn/ (Identifier NCT05174143).
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Enfermedad de la Arteria Coronaria , Ácidos Grasos no Esterificados , Hipertensión , Humanos , Hipertensión/complicaciones , Hipertensión/sangre , Masculino , Femenino , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/sangre , Persona de Mediana Edad , Estudios Prospectivos , Ácidos Grasos no Esterificados/sangre , Anciano , Factores de Riesgo , PronósticoRESUMEN
High-sensitivity C-reactive protein (hsCRP) to high-density lipoprotein cholesterol (HDL-C) ratio (CHR) is associated with coronary artery disease (CAD), but its predictive value for long-term adverse outcomes in patients with CAD following percutaneous coronary intervention (PCI) remains unexplored and is the subject of this study. Patients with CAD who underwent PCI at the Korea University Guro Hospital-Percutaneous Coronary Intervention (KUGH-PCI) Registry since 2004 were included. Patients were categorized into tertiles according to their CHR. The end points were all-cause mortality (ACM), cardiac mortality (CM) and major adverse cardiac events (MACEs). Kaplan-Meier analysis, multivariate Cox regression, restricted cubic spline (RCS) and sensitivity analyses were performed. A total of 3260 patients were included and divided into Group 1 (CHR <0.830, N = 1089), Group 2 (CHR = 0.830-3.782, N = 1085) and Group 3 (CHR >3.782, N = 1086). Higher CHR tertiles were associated with progressively greater risks of ACM, CM and MACEs (log-rank, p < 0.001). Multivariate Cox regression showed that patients in the highest tertile had greater risks of ACM (HR: 2.127 [1.452-3.117]), CM (HR: 3.575 [1.938-6.593]) and MACEs (HR: 1.337 [1.089-1.641]) than those in the lowest tertile. RCS analyses did not reveal a significant non-linear relationship between CHR and ACM, CM or MACEs. The significant associations remained significant in the sensitivity analyses, RCS analyses with or without extreme values, subgroup analyses and multiple imputations for missing data. Elevated CHR is a novel, independent risk factor for long-term ACM, CM and MACEs in CAD patients following PCI.
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Proteína C-Reactiva , HDL-Colesterol , Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Humanos , Intervención Coronaria Percutánea/efectos adversos , Masculino , Femenino , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Estudios Prospectivos , Persona de Mediana Edad , HDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/mortalidad , Anciano , Resultado del Tratamiento , Valor Predictivo de las Pruebas , Factores de RiesgoRESUMEN
Objective: The level of mitochondrial DNA copy number (mtDNA-CN) in peripheral blood cells had been identified to be involved in several immune and cardiovascular diseases. Thus, the aim of this study is to evaluate the levels of mtDNA-CN in Kawasaki disease (KD) and to construct a nomogram prediction for coronary artery lesions in children with KD. Methods: One hundred and forty-four children with KD diagnosed from March 2020 to March 2022 were involved in the study. The clinical features and laboratory test parameters of these children were assessed between the KD and normal groups. Univariable and multivariable analyses were performed sequentially to identify the essential risk factors. Subsequently, a nomogram prediction was constructed. Results: A total of 274 children were included in the analysis. Of these, 144 (52.6%) represented the KD group. Peripheral blood DNA mtDNA qPCR showed that the -log value of mtDNA-CN in the KD group (6.67 ± 0.34) was significantly higher than that in the healthy group (6.40 ± 0.18) (P<0.001). The area under the ROC curve for mtDNA-CN in distinguishing KD was 0.757. MtDNA-CN (OR = 13.203, P = 0.009, 95% CI 1.888-92.305), RBC (OR = 5.135, P = 0.014, 95% CI 1.394-18.919), and PA (OR = 0.959, P = 0.014, 95% CI 0.927-0.991) were identified as independent risk factors for coronary artery dilation in children with KD. Finally, the nomogram predictive was established based on the results of multivariable analysis, demonstrating the satisfied prediction and calibration values. Conclusion: The results of this study revealed that mtDNA-CN could be used as a biomarker in predicting the development of KD. Furthermore, the higher the mtDNA-CN was significantly associated with coronary artery dilation in KD.
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Variaciones en el Número de Copia de ADN , ADN Mitocondrial , Síndrome Mucocutáneo Linfonodular , Nomogramas , Humanos , Síndrome Mucocutáneo Linfonodular/genética , Síndrome Mucocutáneo Linfonodular/diagnóstico , Masculino , ADN Mitocondrial/genética , Femenino , Preescolar , Lactante , Vasos Coronarios/patología , Niño , Factores de Riesgo , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/sangre , Curva ROC , Biomarcadores/sangreRESUMEN
There is evidence to support a link between abnormal lipid metabolism and Alzheimer's disease (AD) risk. Similarly, observational studies suggest a comorbid relationship between AD and coronary artery disease (CAD). However, the intricate biological mechanisms of AD are poorly understood, and its relationship with lipids and CAD traits remains unresolved. Conflicting evidence further underscores the ongoing investigation into this research area. Here, we systematically assess the cross-trait genetic overlap of AD with 13 representative lipids (from eight classes) and seven CAD traits, leveraging robust analytical methods, well-powered large-scale genetic data, and rigorous replication testing. Our main analysis demonstrates a significant positive global genetic correlation of AD with triglycerides and all seven CAD traits assessed-angina pectoris, cardiac dysrhythmias, coronary arteriosclerosis, ischemic heart disease, myocardial infarction, non-specific chest pain, and coronary artery disease. Gene-level analyses largely reinforce these findings and highlight the genetic overlap between AD and three additional lipids: high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), and total cholesterol. Moreover, we identify genome-wide significant genes (Fisher's combined p value [FCPgene] < 2.60 × 10-6) shared across AD, several lipids, and CAD traits, including WDR12, BAG6, HLA-DRA, PHB, ZNF652, APOE, APOC4, PVRL2, and TOMM40. Mendelian randomisation analysis found no evidence of a significant causal relationship between AD, lipids, and CAD traits. However, local genetic correlation analysis identifies several local pleiotropic hotspots contributing to the relationship of AD with lipids and CAD traits across chromosomes 6, 8, 17, and 19. Completing a three-way analysis, we confirm a strong genetic correlation between lipids and CAD traits-HDL and sphingomyelin demonstrate negative correlations, while LDL, triglycerides, and total cholesterol show positive correlations. These findings support genetic overlap between AD, specific lipids, and CAD traits, implicating shared but non-causal genetic susceptibility. The identified shared genes and pleiotropic hotspots are valuable targets for further investigation into AD and, potentially, its comorbidity with CAD traits.
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Enfermedad de Alzheimer , Enfermedad de la Arteria Coronaria , Estudio de Asociación del Genoma Completo , Humanos , Enfermedad de Alzheimer/genética , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/sangre , Predisposición Genética a la Enfermedad , Lípidos/sangre , Metabolismo de los Lípidos/genética , Sitios de Carácter Cuantitativo , Polimorfismo de Nucleótido Simple , Triglicéridos/sangreRESUMEN
BACKGROUND/OBJECTIVES: The hemoglobin glycation index (HGI) has been demonstrated to serve as a substitute for the individual bias in glycosylated hemoglobin A1c (HbA1c). Our objective was to assess the correlation between HGI and cardiovascular (CV) outcomes in patients with diabetes and coronary artery disease (CAD). SUBJECTS/METHODS: We sequentially recruited 11921 patients with diabetes and CAD at Fuwai Hospital. The patients were categorized into five groups based on their HGI quintiles, ranging from Q1 to Q5. The primary endpoint was the occurrence of major adverse cardiac events (MACEs), which included CV death and nonfatal myocardial infarction. RESULTS: During the median 3-year follow-up, 327 (2.7%) MACEs were observed. A U-shaped relationship between HGI and 3-year MACEs was demonstrated by restricted cubic spline (RCS) after multivariable adjustment (nonlinear P = 0.014). The Kaplan-Meier curves demonstrated that the Q2 group had the lowest risk of MACE (P = 0.006). When comparing the HGI Q2 group, multivariable Cox regression models showed that both low (Q1) and high (Q4 or Q5) HGI were linked to a higher risk of MACEs (all P < 0.05). Patients with a low HGI (Q1) had a significantly increased risk of all-cause and CV death, with a 1.70-fold increase in both cases (both P < 0.05). CONCLUSIONS: In individuals with diabetes and established CAD, HGI levels were found to have a U-shaped relationship with the occurrence of MACEs over a period of three years. Significantly, those with low HGI had an increased risk of CV death.
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Enfermedad de la Arteria Coronaria , Hemoglobina Glucada , Humanos , Enfermedad de la Arteria Coronaria/sangre , Masculino , Femenino , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Persona de Mediana Edad , Anciano , Estudios de Cohortes , Factores de Riesgo , Diabetes Mellitus/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/mortalidad , Infarto del Miocardio/sangre , Modelos de Riesgos Proporcionales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Estudios de SeguimientoRESUMEN
BACKGROUND: Clotting, leading to thrombosis, requires interactions of coagulation factors with the membrane aminophospholipids (aPLs) phosphatidylserine and phosphatidylethanolamine. Atherosclerotic cardiovascular disease (ASCVD) is associated with elevated thrombotic risk, which is not fully preventable using current therapies. Currently, the contribution of aPL to thrombotic risk in ASCVD is not known. Here, the aPL composition of circulating membranes in ASCVD of varying severity will be characterized along with the contribution of external facing aPL to plasma thrombin generation in patient samples. METHODS: Thrombin generation was measured using a purified factor assay on platelet, leukocyte, and extracellular vesicles (EVs) from patients with acute coronary syndrome (n=24), stable coronary artery disease (n=18), and positive risk factor (n=23) and compared with healthy controls (n=24). aPL composition of resting/activated platelet and leukocytes and EV membranes was determined using lipidomics. RESULTS: External facing aPLs were detected on EVs, platelets, and leukocytes, elevating significantly following cell activation. Thrombin generation was higher on the surface of EVs from patients with acute coronary syndrome than healthy controls, along with increased circulating EV counts. Thrombin generation correlated significantly with externalized EV phosphatidylserine, plasma EV counts, and total EV membrane surface area. In contrast, aPL levels and thrombin generation from leukocytes and platelets were not impacted by disease, although circulating leukocyte counts were higher in patients. CONCLUSIONS: The aPL membrane of EV supports an elevated level of thrombin generation in patient plasma in ASCVD. Leukocytes may also play a role although the platelet membrane did not seem to contribute. Targeting EV formation/clearance and developing strategies to prevent the aPL surface of EV interacting with coagulation factors represents a novel antithrombotic target in ASCVD.
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Plaquetas , Enfermedad de la Arteria Coronaria , Vesículas Extracelulares , Leucocitos , Trombina , Humanos , Trombina/metabolismo , Vesículas Extracelulares/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Anciano , Plaquetas/metabolismo , Leucocitos/metabolismo , Enfermedad de la Arteria Coronaria/sangre , Estudios de Casos y Controles , Aterosclerosis/sangre , Lípidos de la Membrana/sangre , Lípidos de la Membrana/metabolismo , Fosfatidilserinas/sangre , Síndrome Coronario Agudo/sangre , Coagulación Sanguínea , LipidómicaRESUMEN
BACKGROUND: Guidelines recommend the use of risk scores to select patients for further investigation after myocardial infarction has been ruled out but their utility to identify those with coronary artery disease is uncertain. METHODS: In a prospective cohort study, patients with intermediate high-sensitivity cardiac troponin I concentrations (5 ng/L to sex-specific 99th percentile) in whom myocardial infarction was ruled out were enrolled and underwent coronary CT angiography (CCTA) after hospital discharge. History, ECG, Age, Risk factors, Troponin (HEART), Emergency Department Assessment of Chest Pain Score (EDACS), Global Registry of Acute Coronary Event (GRACE), Thrombolysis In Myocardial Infarction (TIMI), Systematic COronary Risk Evaluation 2 and Pooled Cohort Equation risk scores were calculated and the odds ratio (OR) and diagnostic performance for obstructive coronary artery disease were determined using established thresholds. RESULTS: Of 167 patients enrolled (64±12 years, 28% female), 29.9% (50/167) had obstructive coronary artery disease. The odds of having obstructive disease were increased for all scores with the lowest and highest increase observed for an EDACS score ≥16 (OR 2.2 (1.1-4.6)) and a TIMI risk score ≥1 (OR 12.9 (3.0-56.0)), respectively. The positive predictive value (PPV) was low for all scores but was highest for a GRACE score >88 identifying 39% as high risk with a PPV of 41.9% (30.4-54.2%). The negative predictive value (NPV) varied from 77.3% to 95.2% but was highest for a TIMI score of 0 identifying 26% as low risk with an NPV of 95.2% (87.2-100%). CONCLUSIONS: In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been excluded, clinical risk scores can help identify patients with and without coronary artery disease, although the performance of established risk thresholds is suboptimal for utilisation in clinical practice. TRIAL REGISTRATION NUMBER: NCT04549805.
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Síndrome Coronario Agudo , Biomarcadores , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Troponina I , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Medición de Riesgo/métodos , Biomarcadores/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/epidemiología , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/epidemiología , Anciano , Troponina I/sangre , Factores de Riesgo , Angiografía por Tomografía Computarizada , Valor Predictivo de las Pruebas , PronósticoRESUMEN
Coagulation disorders are common in Kawasaki disease (KD). The main objectives of the present study were to probe the associations of coagulation profiles with clinical classification, IVIG responsiveness, coronary artery abnormalities (CAAs) in the acute episode of KD. A total of 313 KD children were recruited and divided into six subgroups, including complete KD (n = 217), incomplete KD (n = 96), IVIG-responsive KD (n = 293), IVIG-nonresponsive KD (n = 20), coronary artery noninvolvement KD (n = 284) and coronary artery involvement KD (n = 29). Blood samples were collected within 24-h pre-IVIG therapy and 48-h post-IVIG therapy. Coagulation profiles, conventional inflammatory mediators and blood cell counts were detected. Echocardiography was performed during the period from 2- to 14-day post-IVIG infusion. In addition, 315 sex- and age-matched healthy children were enrolled as the controls. (1) Before IVIG therapy, coagulation disorders were more prone to appear in KD patients than in healthy controls, and could be overcome by IVIG therapy. FIB and DD significantly increased in the acute phase of KD, whereas reduced to normal levels after IVIG therapy. (2) PT and APTT were significantly longer in patients with complete KD when compared with their incomplete counterparts after IVIG therapy. (3) The larger δDD, δFDP and the smaller δPT, δINR predicted IVIG nonresponsiveness. (4) The higher δDD and δFDP correlated with a higher risk for CAAs (DD: r = -0.72, FDP: r = -0.54). Coagulation disorders are correlated with complete phenotype, IVIG nonresponsiveness and CAA occurrence in the acute episode of KD, and can be rectified by synergistic effects of IVIG and aspirin.
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Inmunoglobulinas Intravenosas , Síndrome Mucocutáneo Linfonodular , Humanos , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Síndrome Mucocutáneo Linfonodular/sangre , Síndrome Mucocutáneo Linfonodular/complicaciones , Inmunoglobulinas Intravenosas/uso terapéutico , Masculino , Femenino , Preescolar , Lactante , Niño , Vasos Coronarios/patología , Vasos Coronarios/diagnóstico por imagen , Ecocardiografía , Coagulación Sanguínea/efectos de los fármacos , Resultado del Tratamiento , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Trastornos de la Coagulación Sanguínea/etiología , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/tratamiento farmacológicoRESUMEN
OBJECTIVE: Coronary artery ectasia (CAE) is a condition characterized by the localized or widespread dilation of one or more coronary arteries. The majority of CAE patients do not present with clinical symptoms, and the exact cause of CAE remains unclear. Therefore, a retrospective analysis was conducted to explore the potential causes of CAE. METHODS: This study was a retrospective analysis of patients who underwent coronary angiography at Guangdong Provincial People's Hospital between January 2017 and July 2022, of whom 679 patients were ultimately enrolled in the study. Among them, 260 patients were diagnosed with CAE, whereas 419 patients with normal coronary results composed the control group. Remnant cholesterol (RC) was calculated as total cholesterol (TC) minus high-density lipoprotein cholesterol (HDL-C) minus low-density lipoprotein cholesterol (LDL-C). The association between RC levels and the risk of CAE was assessed via multivariable logistic models. RESULTS: Out of the 679 patients who participated in this study, with an average age of 59.9 years, 38.3% were diagnosed with CAE. Patients with CAE had higher RC levels than did those without CAE (P = 0.001). A significant positive association was observed between RC levels and the risk of CAE, with a multivariable adjusted odds ratio (OR) of 1.950 (95% confidence interval [CI]: 1.163-3.270). There was a significant positive association between RC levels and the risk of CAE in both single-vessel and multivessel dilation cases, as well as in isolated CAE and dilation secondary to coronary atherosclerosis. According to the subgroup analyses, RC levels were positively associated with the risk of CAE in participants with hypertension (OR, 1.065; 95% CI, 1.034-1.098). CONCLUSION: RC levels are positively correlated with CAE, implying that a focus on RC could be beneficial in CAE research.
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HDL-Colesterol , LDL-Colesterol , Colesterol , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Vasos Coronarios , Humanos , Persona de Mediana Edad , Masculino , Femenino , Estudios Transversales , Colesterol/sangre , Dilatación Patológica/sangre , Estudios Retrospectivos , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/patología , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Anciano , LDL-Colesterol/sangre , Vasos Coronarios/patología , Vasos Coronarios/diagnóstico por imagen , HDL-Colesterol/sangre , Factores de Riesgo , Triglicéridos/sangre , Oportunidad RelativaRESUMEN
Background: Glycosylated hemoglobin (HbA1c) variability is a risk factor for cardiovascular complications in patients with Type 2 diabetes mellitus (T2DM), but its relationship with the severity of coronary artery disease (CAD) is unclear. Methods: Patients with T2DM who underwent coronary angiography due to angina were enrolled. HbA1c variability was expressed as coefficient of variation (CV), standard deviation (SD), variability independent of mean (VIM), and time in range (TIR). The severity of CAD was expressed by the number of involved vessels and Gensini score. Multivariate regression models were constructed to test the relationship between HbA1c variability, number of involved vessels, and the Gensini score, followed by linear regression analysis. Results: A total of 147 patients were included. In multivariate analysis, VIM-HbA1c (OR = 2.604; IQR: 1.15, 5.90; r = 0.026) and HbA1cTIR (OR = 0.13; IQR: 0.04, 0.41; r < 0.001) were independent risk factors for the number of involved vessels. After adjustment, HbA1cTIR (OR = 0.01; IQR: 0.002, 0.04; r < 0.001), SD-HbA1c (OR = 4.12, IQR: 1.64, 10.35; r = 0.001), CV-HbA1c (OR = 1.41, IQR: 1.04, 1.92; r = 0.007), and VIM-HbA1c (OR = 3.26; IQR: 1.43, 7.47; r = 0.003) were independent risk factors for the Gensini score. In the linear analysis, the Gensini score was negatively correlated with HbA1cTIR (ß = -0.629; r < 0.001) and positively correlated with SD-HbA1c (ß = 0.271; r = 0.001) and CV-HbA1c (ß = 0.176; r = 0.033). After subgroup analysis, HbA1cTIR was a risk factor for the number of involved vessels. The Gensini score was negatively correlated with HbA1cTIR and positively correlated with SD-HbA1c at subgroups of subjects with a mean HbA1c ≤ 7%. Conclusions: Our analysis indicates that HbA1c variability, especially HbA1cTIR, plays a role for the severity of CAD in patients with T2DM. HbA1c variability may provide additional information and require management even at the glycemic target. Translational Aspects: Studies have shown that HbA1c variability is related to cardiovascular complications. Further, we explore the correlation between HbA1c variability and the severity of CAD. HbA1c variability is a risk factor for coronary stenosis in T2DM. It may be a potential indicator reflecting glycemic control for the prevention and treatment of cardiovascular complications.
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Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Diabetes Mellitus Tipo 2 , Hemoglobina Glucada , Índice de Severidad de la Enfermedad , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Hemoglobina Glucada/metabolismo , Hemoglobina Glucada/análisis , Masculino , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/epidemiología , Femenino , Persona de Mediana Edad , Anciano , Factores de Riesgo , Análisis MultivarianteRESUMEN
BACKGROUND: Kawasaki Disease (KD) involves arterial inflammation, primarily affecting the coronary arteries and leading to coronary artery lesions. Recent advancements in understanding the immunomodulatory roles of vitamin D have prompted investigations into the potential correlation between serum vitamin D levels and the risk of coronary artery lesions (CAL) in KD. This review aims to explore this association. METHODS: A systematic search utilizing relevant keywords related to Kawasaki disease and coronary artery lesions was conducted across four databases (PubMed, Embase, Scopus, and Web of Science). The quality of the incorporated studies was assessed utilizing the Newcastle-Ottawa Scale. The study protocol is registered in PROSPERO under the registry code CRD42024493204. RESULTS: In a review of five studies involving 442 KD patients and 594 healthy controls, KD patients generally had lower serum vitamin D levels compared to controls, with mixed findings on the association with coronary artery lesions and IVIG resistance. While three studies supported lower vitamin D in KD, one showed no significant difference. Regarding CAL, one study found lower vitamin D, another found higher levels associated with CAL, and two found no significant difference. CONCLUSIONS: Overall, the evidence is inconclusive, but there's a trend suggesting potential benefits of sufficient vitamin D levels in Kawasaki disease rather than evidence refuting any association with clinical outcomes.
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Enfermedad de la Arteria Coronaria , Síndrome Mucocutáneo Linfonodular , Vitamina D , Síndrome Mucocutáneo Linfonodular/sangre , Síndrome Mucocutáneo Linfonodular/complicaciones , Humanos , Vitamina D/sangre , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/sangreRESUMEN
BACKGROUND: The impact of rosuvastatin versus atorvastatin on new-onset diabetes mellitus (NODM) among patients treated with high-intensity statin therapy for coronary artery disease (CAD) remains to be clarified. This study aimed to evaluate the risk of NODM in patients with CAD treated with rosuvastatin compared to atorvastatin in the randomized LODESTAR trial. METHODS: In the LODESTAR trial, patients with CAD were randomly assigned to receive either rosuvastatin or atorvastatin using a 2-by-2 factorial randomization. In this post-hoc analysis, the 3-year incidence of NODM was compared between rosuvastatin and atorvastatin treatment in the as-treated population with high-intensity statin therapy as the principal population of interest. RESULTS: Among 2932 patients without diabetes mellitus at baseline, 2377 were included in the as-treated population analysis. In the as-treated population with high-intensity statin therapy, the incidence of NODM was not significantly different between the rosuvastatin and atorvastatin groups (11.4% [106/948] versus 8.8% [73/856], hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 0.98 to 1.77, P = 0.071). When the risk of NODM with rosuvastatin versus atorvastatin was assessed according to the achieved low-density lipoprotein cholesterol (LDL-C) level, the risk of NODM began to increase at a LDL-C level below 70 mg/dL. The incidence of NODM was significantly greater in the rosuvastatin group than it was in the atorvastatin group when the achieved LDL-C level was < 70 mg/dL (13.9% versus 8.0%; HR = 1.79, 95% CI 1.18 to 2.73, P = 0.007). CONCLUSIONS: Among CAD patients receiving high-intensity statin therapy, the incidence of NODM was not significantly different between rosuvastatin and atorvastatin. However, a drug effect of the statin type on NODM was observed when the achieved LDL-C level was < 70 mg/dL. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02579499.