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BACKGROUND: Insulin resistance (IR) is linked to both the complexity of coronary artery lesions and the prognosis of acute coronary syndrome (ACS). However, the precise extent of this correlation and its impact on adverse cardiovascular outcomes in ACS patients remain unclear. Therefore, this study aims to investigate the intricate relationship between IR, coronary artery lesion complexity, and the prognosis of ACS through a cohort design analysis. METHOD: A total of 986 patients with ACS who underwent percutaneous coronary intervention (PCI) were included in this analysis. IR was assessed using the triglyceride-glucose (TyG) index, while coronary artery lesion complexity was evaluated using the SYNTAX score. Pearson's correlation coefficients were utilized to analyze the correlations between variables. The association of the TyG index and SYNTAX score with major adverse cardiovascular events (MACEs) in ACS was investigated using the Kaplan-Meier method, restricted cubic splines (RCS), and adjusted Cox regression. Additionally, a novel 2-stage regression method for survival data was employed in mediation analysis to explore the mediating impact of the SYNTAX score on the association between the TyG index and adverse cardiovascular outcomes, including MACEs and unplanned revascularization. RESULTS: During a median follow-up of 30.72 months, 167 cases of MACEs were documented, including 66 all-cause deaths (6.69%), 26 nonfatal myocardial infarctions (MIs) (2.64%), and 99 unplanned revascularizations (10.04%). The incidence of MACEs, all-cause death, and unplanned revascularization increased with elevated TyG index and SYNTAX score. Both the TyG index (non-linear, P = 0.119) and SYNTAX score (non-linear, P = 0.004) displayed a positive dose-response relationship with MACEs, as illustrated by the RCS curve. Following adjustment for multiple factors, both the TyG index and SYNTAX score emerged as significant predictors of MACEs across the total population and various subgroups. Mediation analysis indicated that the SYNTAX score mediated 25.03%, 18.00%, 14.93%, and 11.53% of the correlation between the TyG index and MACEs in different adjusted models, respectively. Similar mediating effects were observed when endpoint was defined as unplanned revascularization. CONCLUSION: Elevated baseline TyG index and SYNTAX score were associated with a higher risk of MACEs in ACS. Furthermore, the SYNTAX score partially mediated the relationship between the TyG index and adverse cardiovascular outcomes.
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Síndrome Coronariana Aguda , Biomarcadores , Glicemia , Doença da Artéria Coronariana , Resistência à Insulina , Intervenção Coronária Percutânea , Humanos , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Glicemia/metabolismo , Fatores de Tempo , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico , Triglicerídeos/sangue , Estudos Retrospectivos , Valor Preditivo dos TestesRESUMO
BACKGROUND: Atrial fibrillation (AF) is acknowledged as a disease continuum. Despite catheter ablation being recommended as a primary therapy for AF, the high recurrence rates have tempered the initial enthusiasm. Insulin resistance (IR) has been established as an independent predictor for the onset of AF. However, the correlation between non-insulin-based IR indices and late AF recurrence in patients undergoing radiofrequency catheter ablation remains unknown. METHODS: A retrospective cohort of 910 AF patients who underwent radiofrequency catheter ablation was included in the analysis. The primary endpoint was late AF recurrence during the follow-up period after a defined blank period. The relationship between non-insulin-based IR indices and the primary endpoint was assessed using multivariate Cox hazards regression models and restricted cubic splines (RCS). Additionally, the net reclassification improvement and integrated discrimination improvement index were calculated to further evaluate the additional predictive value of the four IR indices beyond established risk factors for the primary outcome. RESULTS: During a median follow-up period of 12.00 months, 189 patients (20.77%) experienced late AF recurrence, which was more prevalent among patients with higher levels of IR. The multivariate Cox hazards regression analysis revealed a significant association between these IR indices and late AF recurrence. Among the four indices, METS-IR provided the most significant incremental effect on the basic model for predicting late AF recurrence. Multivariable-adjusted RCS curves illustrated a nonlinear correlation between METS-IR and late AF recurrence. In subgroup analysis, METS-IR exhibited a significant correlation with late AF recurrence in patients with diabetes mellitus (HR: 1.697, 95% CI 1.397 - 2.063, P < 0.001). CONCLUSION: All the four non-insulin-based IR indices were significantly associated with late AF recurrence in patients undergoing radiofrequency catheter ablation. Addressing IR could potentially serve as a viable strategy for reducing the late AF recurrence rate.
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Fibrilação Atrial , Ablação por Cateter , Resistência à Insulina , Recidiva , Humanos , Fibrilação Atrial/cirurgia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Masculino , Feminino , Ablação por Cateter/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Idoso , Fatores de Tempo , Medição de Risco , Resultado do Tratamento , Biomarcadores/sangue , Valor Preditivo dos Testes , Glicemia/metabolismoRESUMO
BACKGROUND: Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 1 diabetes mellitus (T1DM), which still lacks adequate therapy. Irisin, a cleavage peptide off fibronectin type III domain-containing 5, has been shown to preserve cardiac function in cardiac ischemia-reperfusion injury. Whether or not irisin plays a cardioprotective role in DCM is not known. METHODS AND RESULTS: T1DM was induced by multiple low-dose intraperitoneal injections of streptozotocin (STZ). Our current study showed that irisin expression/level was lower in the heart and serum of mice with STZ-induced TIDM. Irisin supplementation by intraperitoneal injection improved the impaired cardiac function in mice with DCM, which was ascribed to the inhibition of ferroptosis, because the increased ferroptosis, associated with increased cardiac malondialdehyde (MDA), decreased reduced glutathione (GSH) and protein expressions of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), was ameliorated by irisin. In the presence of erastin, a ferroptosis inducer, the irisin-mediated protective effects were blocked. Mechanistically, irisin treatment increased Sirtuin 1 (SIRT1) and decreased p53 K382 acetylation, which decreased p53 protein expression by increasing its degradation, consequently upregulated SLC7A11 and GPX4 expressions. Thus, irisin-mediated reduction in p53 decreases ferroptosis and protects cardiomyocytes against injury due to high glucose. CONCLUSION: This study demonstrated that irisin could improve cardiac function by suppressing ferroptosis in T1DM via the SIRT1-p53-SLC7A11/GPX4 pathway. Irisin may be a therapeutic approach in the management of T1DM-induced cardiomyopathy.
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Diabetes Mellitus Tipo 1 , Cardiomiopatias Diabéticas , Ferroptose , Humanos , Animais , Camundongos , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/prevenção & controle , Sirtuína 1 , Fibronectinas , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Proteína Supressora de Tumor p53 , Miócitos CardíacosRESUMO
OBJECTIVE: Sepsis can have severe implications on lung function, leading to acute lung injury (ALI), a major contributor to sepsis-related mortality. Anisodamine hydrobromide (Ani HBr), a bioactive constituent derived from the root of Scopolia tangutica Maxim, a plant endemic to China, has demonstrated efficacy in treating septic shock. We aim to explore whether Ani HBr can alleviate sepsis-triggered ALI and elucidate the fundamental mechanisms involved. MATERIALS AND METHOD: The protective effects of Ani HBr were assessed in two models: in vitro, lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and in vivo, cecal ligation puncture (CLP)-induced sepsis. To measure the cell viability of RAW264.7 cells after Ani HBr treatment, we used the CCK-8 assay. We quantified the levels of pro-inflammatory cytokines expression using ELISA. We also measured the expression of pyrotosis indicators by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence. RESULTS: Our study demonstrates that Ani HBr can alleviate pulmonary edema, bleeding, and excessive inflammation induced by CLP. Additionally, it exhibits protective effects against cytotoxicity induced by LPS in RAW264.7 macrophage cells. Furthermore, Ani HBr downregulates the mRNA and protein levels of NLRP3, Caspase-1, GSDMD, IL-18, and IL-1ß in both animal models and cell cultures, thereby inhibiting pyroptosis in a similar mechanism to AC-YVAD-CMK (AYC)'s blockade of Caspase-1. Moreover, Ani HBr suppresses the production and release of proinflammatory cytokines. CONCLUSION: These findings suggest that Ani HBr could serve as a protective agent against sepsis-induced ALI by suppressing pyroptosis.
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BACKGROUND: The Triglyceride-glucose (TyG) index, as a surrogate marker of insulin resistance, is independently associated with the severity of coronary artery lesions and the prognosis of coronary heart disease. The investigation aimed to explore the relationship between the TyG index and recurrent revascularization in individuals with type 2 diabetes mellitus (T2DM) resulting from the progression of lesions or in-stent restenosis (ISR) after percutaneous coronary intervention (PCI). METHOD: A total of 633 patients who met the inclusion and exclusion criteria were enrolled and divided into three groups based on the tertiles of the TyG index. The primary endpoint was recurrent revascularization resulting from the progression of lesions or ISR. All-cause death was considered as the competing risk event. Competing risk analysis and Cox regression analysis for predicting recurrent revascularization after PCI were conducted stepwise. Variables were standardized to make the hazard ratio (HR), subdistribution hazard ratio (SHR) and corresponding 95% CI more consistent prior to being used for fitting the multivariate risk model. The predictive ability of the TyG index was evaluated using several measures, including the ROC curve, likelihood ratio test, Akaike's information criteria, category-free continuous net reclassification improvement (cNRI > 0), and integrated discrimination improvement (IDI). Internal validation was conducted through bootstrapping with 1000 resamples. RESULTS: During a median follow-up period of 18.33 months, a total of 64 (10.11%) patients experienced recurrent revascularization, including 55 cases of lesion progression and 9 cases of in-stent restenosis. After controlling for competitive risk events, the TyG index was independently associated with a higher risk of recurrent revascularization [SHR:1.4345, (95% CI 1.1458-1.7959), P = 0.002]. The likelihood ratio test and Akaike's information criteria showed that the TyG index significantly improves the prognostic ability. Additionally, adding the TyG index improved the ability of the established risk model in predicting recurrent revascularization, indicated by a C-index of 0.759 (95% CI 0.724-0.792, P < 0.01), with a cNRI > 0 of 0.170 (95% CI 0.023-0.287, P < 0.05), and an IDI of 0.024 (95% CI 0.009-0.039, P = 0.002). These results remained consistent when the models containing TyG index were confirmed using an internal bootstrap validation method. CONCLUSION: The findings highlight the potential of the TyG index as a predictor of recurrent revascularization. Lesion progression emerged as the primary contributor to recurrent revascularization instead of in-stent restenosis. The incorporation of the TyG index into risk prediction models is likely to be beneficial for accurate risk stratification in order to improve prognosis.
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Reestenose Coronária , Diabetes Mellitus Tipo 2 , Intervenção Coronária Percutânea , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Glucose , Triglicerídeos , Fatores de Risco , Intervenção Coronária Percutânea/efeitos adversos , Reestenose Coronária/etiologia , Reestenose Coronária/terapia , Glicemia/metabolismo , Medição de Risco , BiomarcadoresRESUMO
AIM: The triglyceride-glucose (TyG) index has been shown to be an independent predictor for the progression and prognosis of coronary artery disease (CAD). Whether the TyG index predicts the severity of CAD in patients presenting with acute coronary syndrome (ACS) remains unknown. METHODS: A total of 1,007 individuals presenting with ACS undergoing coronary angiography were stratified according to the tertiles of the TyG index and The Synergy Between Percutaneous Coronary Intervention (SYNTAX) score (SYNTAX score ≤ 22 versus SYNTAX score > 22). CAD complexity was determined by the SYNTAX score. RESULTS: After adjusting for multiple confounding factors, the TyG index was still an independent risk factor for mid/high SYNTAX scores (SYNTAX score > 22, OR 2.6452, 95% CI 1.9020-3.6786, P < 0.0001). Compared with the lowest tertile of the TyG (T1) group, the risk for a mid/high SYNTAX score in the T2 and T3 groups was 2.574-fold higher (OR, 2.574; 95% CI 1.610-4.112; P < 0.001) and 3.732-fold higher (OR, 3.732; 95% CI 2.330-5.975; P < 0.001), respectively. Furthermore, there was a doseâresponse relationship between the TyG index and the risk of complicated CAD (SYNTAX score > 22; nonlinear P = 0.200). The risk for a mid/high SYNTAX score in the T2 and T3 groups was significantly higher in normoglycemia, prediabetes mellitus, and diabetes mellitus subgroups. CONCLUSIONS: A higher TyG index was associated with the presence of a higher coronary anatomical complexity (SYNTAX score > 22) in ACS patients, irrespective of diabetes mellitus status. The TyG index might serve as a noninvasive predictor of CAD complexity in ACS patients and could potentially influence the management and therapeutic approach.
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Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Diabetes Mellitus , Humanos , Glucose , Síndrome Coronariana Aguda/terapia , Triglicerídeos , Fatores de Risco , Glicemia , Medição de Risco , BiomarcadoresRESUMO
Background: As a classical biomarker associated with hypertension, the prognostic value of homocysteine (Hcy) in the intermediate-term outcome of acute coronary syndrome (ACS) remains controversial. This study aimed to investigate the role of homocysteine in ACS patients with different blood pressure statuses. Methods: A total of 1288 ACS patients from 11 general hospitals in Chengdu, China, from June 2015 to December 2019 were consecutively included in this observational study. The primary endpoint was defined as all-cause death. Secondary endpoints included cardiac death, nonfatal myocardial infarction (MI), unplanned revascularization and nonfatal stroke. The patients in the hypertension group (n = 788) were further stratified into hyperhomocysteinemia (H-Hcy, n = 245) and normal homocysteinaemia subgroups (N-Hcy, n = 543) around the cut-off value of 16.81 µmol/L. Similarly, the nonhypertensive patients were stratified into H-Hcy (n = 200) and N-Hcy subgroups (n = 300) around the optimal cut-off value of 14.00 µmol/L. The outcomes were compared between groups. Results: The median follow-up duration was 18 months. During this period, 78 (6.05%) deaths were recorded. KaplanâMeier curves illustrated that H-Hcy had a lower survival probability than N-Hcy in both hypertension and nonhypertension groups (p < 0.01). Multivariate Cox regression analysis revealed that H-Hcy was a predictor of intermediate-term mortality in ACS, regardless of blood pressure status. Conclusions: Elevated Hcy levels predict intermediate-term all-cause mortality in ACS regardless of blood pressure status. This association could be conducive to risk stratification of ACS. Clinical Trial Registration: The study was registered in the Chinese Clinical Trials Registry in China (ChiCTR1900025138).
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The clinical risk factors associated with late recurrence in patients with non-valvular atrial fibrillation (AF) (NVAF) undergoing radiofrequency catheter ablation (RFCA) remain unknown. Furthermore, the current prognostic risk score system is commonly used in such patients as a noninvasive method to assess late AF recurrence. According to recent research, the Age, creatinine, and ejection fraction (ACEF) score is a useful risk score for cardiovascular morbidity and mortality. As a result, we hypothesized that pre-ablation ACEF score could be used to assess late recurrence in patients with NVAF. We included 325 NVAF patients undergoing RFCA. During a median follow-up period of 12 months, patients with late AF recurrence had higher ACEF scores (P < .001). The pre-ablation ACEF score was a risk factor for late AF recurrence after RFCA (P = .027). The ACEF score was a predictor of late AF recurrence after RFCA, with an AUC of 0.624 (P = .001). Moreover, the AUC of left atrial diameter (LAD) was 0.7 (P < .001), which was higher than the ACEF score, but no significant difference was found (P = .104). The ACEF score was positively correlated with LAD, advanced age, and B-type natriuretic peptide. In patients with NVAF, the pre-ablation ACEF score is a valuable risk score for assessing late AF recurrence after RFCA, as with LAD.
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Fibrilação Atrial , Ablação por Radiofrequência , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Creatinina , Volume Sistólico , Átrios do CoraçãoRESUMO
BACKGROUND: The Global Registry of Acute Coronary Events (GRACE) score derived from clinical parameters at the time of hospital discharge is a powerful predictor of long-term mortality and reinfarction after acute coronary syndrome (ACS). The triglyceride glucose (TyG) index, which is a simple and reliable surrogate marker of insulin resistance, has been demonstrated to be an independent predictor of long-term adverse major adverse cardiac events, irrespective of diabetes mellitus. We investigate whether the addition of the TyG index improves the predictive ability of the GRACE score after percutaneous coronary intervention (PCI) in ACS patients regardless of diabetes mellitus. METHOD: A retrospective cohort of 986 ACS patients undergoing PCI was enrolled in the present analyses. The GRACE score for discharge to 6 months and the TyG index were calculated. The primary endpoint was the composite of MACEs, including all-cause death and nonfatal myocardial infarction. Patients were stratified according to the primary endpoint and the tertiles of the TyG index. Cumulative curves were calculated using the Kaplan-Meier method. Multivariate Cox regression was adopted to identify predictors of MACEs. The predictive value of the GRACE score alone and combined with the TyG index or fasting blood glucose (FBG) was estimated by the area under the receiveroperating characteristic curve, likelihood ratio test, Akaike's information criteria, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Internal validation was assessed using the means of bootstrap method with 1000 bootstrapped samples. RESULTS: During a median follow-up of 30.72 months ((interquartile range, 26.13 to 35.07 months), 90 patients developed MACEs, more frequently in the patients with a higher TyG index. Multivariate Cox hazards regression analysis found that the TyG index, but not FBG was an independent predictor of MACEs (hazard ratio 1.6542; 95% CI 1.1555-2.3681; P = 0.006) in all types of ACS regardless of diabetes mellitus when included in the same model as GRACE score. Furthermore, Kaplan-Meier analysis revealed that the incidence of the primary endpoint rose with increasing TyG index tertiles (log-rank, P < 0.01). Adjustment the GRACE score by the TyG index improved the predictive ability for MACEs (increase in C-statistic value from 0.735 to 0.744; NRI, 0.282, 95% CI 0.028-0.426, P = 0.02; IDI, 0.019, 95% CI 0.004-0.046, P = 0.01). Likelihood ratio test showed that the TyG index significantly improved the prognostic ability of the GRACE score (χ2 = 12.37, 1 df; P < 0.001). The results remained consistent when the models were confirmed by internal bootstrap validation method. CONCLUSION: The TyG index, but not FBG is an independent predictor of long-term MACEs after PCI in all types of ACS patients regardless of diabetes mellitus after adjusting for the GRACE score, and improves the ability of the GRACE score to stratify risk and predict prognosis of ACS patients undergoing PCI.
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Síndrome Coronariana Aguda , Diabetes Mellitus , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/terapia , Biomarcadores , Diabetes Mellitus/etiologia , Glucose , Humanos , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , TriglicerídeosRESUMO
BACKGROUND: The residual SYNTAX score (rSS), a quantitative measure of angiographic completeness of revascularization after percutaneous coronary intervention (PCI), and the triglyceride-glucose index (TyG index), a reliable surrogate marker of insulin resistance, have been regarded as independent predictors of major adverse cardiac events (MACEs) after PCI. Whether a combination of the rSS and the TyG index improves the predictive ability for MACEs in patients with type 2 diabetes mellitus (T2DM) undergoing PCI remains unknown. METHODS: A total of 633 consecutive patients with T2DM who underwent PCI were included in the present analyses. Patients were stratified according to the optimal cutoff point value of the TyG index, or the rSS determined by receiveroperating characteristic (ROC) curve analysis. The primary endpoint was the composite of MACEs, including all-cause death, nonfatal myocardial infarction, and unplanned repeat revascularization. Cumulative curves were calculated using the Kaplan-Meier method. Multivariate Cox regression was used to identify predictors of MACEs. The predictive value of the TyG index combined with the rSS was estimated by the area under the ROC curve, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: During a median follow-up of 18.83 months, 99 patients developed MACEs, more frequently in the patients with a higher TyG index or rSS. Multivariate Cox hazards regression analysis revealed that both the TyG index and rSS were independent predictors of MACEs (hazard ratio 1.8004; 95% CI 1.2603-2.5718; P = 0.0012; 1.0423; 95% CI 1.0088-1.0769; P = 0.0129, respectively). Furthermore, Kaplan-Meier analysis demonstrated that both the TyG index and the rSS were significantly associated with an increased risk of MACEs (log-rank, all P < 0.01). The addition of the rSS and the TyG index to the baseline risk model had an incremental effect on the predictive value for MACE (increase in C-statistic value from 0.660 to 0.732; IDI 0.018; NRI 0.274; all P < 0.01). CONCLUSIONS: The TyG index predicts intermediate-term MACE after PCI in patients with T2DM independent of known cardiovascular risk factors. Adjustment of the rSS by the TyG index further improves the predictive ability for MACEs in patients with T2DM undergoing PCI.
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Síndrome Coronariana Aguda , Diabetes Mellitus Tipo 2 , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Progressão da Doença , Glucose , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Medição de Risco , Fatores de Risco , TriglicerídeosRESUMO
We report a case in which real-time remote interrogation and reprogramming of the parameters of a dual-chamber pacemaker was performed during the COVID-19 pandemic. The described case demonstrated the safety and effectiveness of CIED remote programming based on the 5G cloud technology support platform (5G-CTP), and showed that the application of real-time remote programming would help in reducing the risk of cross-infection between doctors and patients.
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COVID-19 , Marca-Passo Artificial , Humanos , PandemiasRESUMO
BACKGROUND: A cluster of acute respiratory illness, now known as Corona Virus Disease 2019 (COVID-19) caused by 2019 novel coronavirus (SARS-CoV-2), has become a global pandemic. Aged population with cardiovascular diseases are more likely be to infected with SARS-CoV-2 and result in more severe outcomes and elevated case-fatality rate. Meanwhile, cardiovascular diseases have a high prevalence in the middle-aged and elderly population. However, despite of several researches in COVID-19, cardiovascular implications related to it still remains largely unclear. Therefore, a specific analysis in regard to cardiovascular implications of COVID-19 patients is in great need. METHODS: In this single-centered, retrospective, observational study, 116 patients with laboratory-confirmed COVID-19 were enrolled, who admitted to the General Hospital of Central Theater Command (Wuhan, China) from January 20 to March 8, 2020. The demographic data, underlying comorbidities, clinical symptoms and signs, laboratory findings, chest computed tomography, treatment measures, and outcome data were collected from electronic medical records. Data were compared between non-severe and severe cases. RESULTS: Of 116 hospitalized patients with COVID-19, the median age was 58.5 years (IQR, 47.0-69.0), and 36 (31.0%) were female. Hypertension (45 [38.8%]), diabetes (19 [16.4%]), and coronary heart disease (17 [14.7%]) were the most common coexisting conditions. Common symptoms included fever [99 (85.3%)], dry cough (61 [52.6%]), fatigue (60 [51.7%]), dyspnea (52 [44.8%]), anorexia (50 [43.1%]), and chest discomfort (50 [43.1%]). Local and/or bilateral patchy shadowing were the typical radiological findings on chest computed tomography. Lymphopenia (lymphocyte count, 1.0 × 109/L [IQR, 0.7-1.3]) was observed in 66 patients (56.9%), and elevated lactate dehydrogenase (245.5 U/L [IQR, 194.3-319.8]) in 69 patients (59.5%). Hypokalemia occurred in 24 (20.7%) patients. Compared with non-severe cases, severe cases were older (64.0 years [IQR, 53.0-76.0] vs 56.0 years [IQR, 37.0-64.0]), more likely to have comorbidities (35 [63.6%] vs 24 [39.3%]), and more likely to develop acute cardiac injury (19 [34.5%] vs 4 [6.6%]), acute heart failure (18 [32.7%] vs 3 [4.9%]), and ARDS (20 [36.4%] vs 0 [0%]). During hospitalization, the prevalence of new onset hypertension was significantly higher in severe patients (55.2% vs 19.0%) than in non-severe ones. CONCLUSIONS: In this single-centered, retrospective, observational study, we found that the infection of SARS-CoV-2 was more likely to occur in middle and aged population with cardiovascular comorbidities. Cardiovascular complications, including new onset hypertension and heart injury were common in severe patients with COVID-19. More detailed researches in cardiovascular involvement in COVID-19 are urgently needed to further understand the disease.
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Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Hospitalização/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Idoso , Betacoronavirus , COVID-19 , China/epidemiologia , Infecções por Coronavirus/patologia , Tosse/epidemiologia , Feminino , Febre/epidemiologia , Humanos , Linfopenia/epidemiologia , Linfopenia/patologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia , Estudos Retrospectivos , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/epidemiologiaRESUMO
BACKGROUND/AIMS: Obesity and high salt intake are major risk factors for hypertension and cardiometabolic diseases. Obese individuals often consume more dietary salt. We aim to examine the neurophysiologic effects underlying obesity-related high salt intake. METHODS: A multi-center, random-order, double-blind taste study, SATIETY-1, was conducted in the communities of four cities in China; and an interventional study was also performed in the local community of Chongqing, using brain positron emission tomography/computed tomography (PET/CT) scanning. RESULTS: We showed that overweight/obese individuals were prone to consume a higher daily salt intake (2.0 g/day higher compared with normal weight individuals after multivariable adjustment, 95% CI, 1.2-2.8 g/day, P < 0.001), furthermore they exhibited reduced salt sensitivity and a higher salt preference. The altered salty taste and salty preference in the overweight/obese individuals was related to increased activity in brain regions that included the orbitofrontal cortex (OFC, r = 0.44, P= 0.01), insula (r = 0.38, P= 0.03), and parahippocampus (r = 0.37, P= 0.04). CONCLUSION: Increased salt intake among overweight/obese individuals is associated with altered salt sensitivity and preference that related to the abnormal activity of gustatory cortex. This study provides insights for reducing salt intake by modifying neural processing of salty preference in obesity.
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Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Cloreto de Sódio na Dieta/efeitos adversos , Paladar/fisiologia , Adolescente , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
Hypertension-induced renal fibrosis contributes to the progression of chronic kidney disease, and apigenin, an anti-hypertensive flavone that is abundant in celery, acts as an agonist of transient receptor potential vanilloid 4 (TRPV4). However, whether apigenin reduces hypertension-induced renal fibrosis, as well as the underlying mechanism, remains elusive. In the present study, the deoxycorticosterone acetate (DOCA)-salt hypertension model was established in male Sprague-Dawley rats that were treated with apigenin or vehicle for 4 weeks. Apigenin significantly attenuated the DOCA-salt-induced structural and functional damage to the kidney, which was accompanied by reduced expression of transforming growth factor-ß1 (TGF-ß1)/Smad2/3 signaling pathway and extracellular matrix proteins. Immunochemistry, cell-attached patch clamp and fluorescent Ca2+ imaging results indicated that TRPV4 was expressed and activated by apigenin in both the kidney and renal cells. Importantly, knockout of TRPV4 in mice abolished the beneficial effects of apigenin that were observed in the DOCA-salt hypertensive rats. Additionally, apigenin directly inhibited activation of the TGF-ß1/Smad2/3 signaling pathway in different renal tissues through activation of TRPV4 regardless of the type of pro-fibrotic stimulus. Moreover, the TRPV4-mediated intracellular Ca2+ influx activated the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway, which inhibited the TGF-ß1/Smad2/3 signaling pathway. In summary, dietary apigenin has beneficial effects on hypertension-induced renal fibrosis through the TRPV4-mediated activation of AMPK/SIRT1 and inhibition of the TGF-ß1/Smad2/3 signaling pathway. This work suggests that dietary apigenin may represent a promising lifestyle modification for the prevention of hypertension-induced renal damage in populations that consume a high-sodium diet.
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Apigenina/uso terapêutico , Suplementos Nutricionais , Hipertensão Renal/dietoterapia , Rim/patologia , Canais de Cátion TRPV/fisiologia , Proteínas Quinases Ativadas por AMP/fisiologia , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Apigenina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Cálcio/metabolismo , Acetato de Desoxicorticosterona , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Fibrose , Hipertensão Renal/induzido quimicamente , Hipertensão Renal/metabolismo , Hipertensão Renal/fisiopatologia , Rim/metabolismo , Rim/fisiopatologia , Masculino , Ratos Sprague-Dawley , Sirtuína 1/fisiologia , Cloreto de Sódio na Dieta , Canais de Cátion TRPV/metabolismoRESUMO
The pathogenesis of hypertension remains elusive. Current treatments on hypertension have only achieved modest reductions. Facilitating theoretical research and looking for new therapeutic strategy are urgently needed. Besides food digestion and nutrients absorption, the gastrointestinal tract (GI) has been shown to influence the status of the central nervous system, immune system, metabolism, and cardiovascular homeostasis. Emerging findings demonstrate that endogenous factors derived from GI including gut hormones, autonomic nerve, and gut microbiota play important roles in the regulation of vascular function and/or blood pressure. Meanwhile, evidences from clinical practice and experimental study have found that intervention in GI through metabolic surgery, probiotics consumption, and dietary modification can efficiently ameliorate or even remit hypertension and related cardiometabolic diseases. Thus, we propose that GI might be an initiating organ of hypertension and a promising target for the management of hypertension. Further, illuminating this concept may aid to understand the pathogenesis and control of hypertension.
Assuntos
Trato Gastrointestinal , Hipertensão , Animais , Cirurgia Bariátrica , Pressão Sanguínea , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Humanos , Hipertensão/metabolismo , ProbióticosRESUMO
Hypertension is an important global public-health challenge because of its high prevalence and concomitant risks for cardiovascular and kidney diseases. More than 60% of the risk factors for hypertension are associated with metabolic disorders. Furthermore, many metabolic risk factors can directly cause the vascular dysfunction and the elevated blood pressure. Metabolic disorders not only increase the risk for hypertension but also participate in the development of hypertension. Thus, some types of hypertension induced by metabolic disturbances can be defined as metabolic hypertension. However, the pathogenesis of metabolic hypertension remains largely unknown. The gastrointestinal tract is a unique gate through which external food, metabolites, and microbes enter the human body. Thus, metabolism-related risk factors may affect blood pressure through the gastrointestinal tract and alter processes such as taste perception, mucosal absorption, gut hormone homeostasis, GI nerve activity, and gut microbiota. Meanwhile, gastrointestinal intervention through dietary approaches, gut microbiota modification, and metabolic surgery could profoundly improve or remit the vascular dysfunction and metabolic hypertension. It suggests that the GI tract could be an initial organ of metabolic hypertension. However, more clinical and basic studies are necessary to further validate this novel concept.
Assuntos
Trato Gastrointestinal/metabolismo , Hipertensão/patologia , Trato Gastrointestinal/microbiologia , Humanos , Hipertensão/etiologia , Doenças Metabólicas/complicações , Microbiota , Sistema Nervoso/metabolismo , Fatores de Risco , Percepção GustatóriaRESUMO
NEW FINDINGS: What is the topic of this review? Transient receptor potential (TRP) channels are highly implicated in the pathogenesis of hypertension and the regulation of metabolism. What advances does it highlight? Dysfunction of TRP channels leads to hypertension and metabolic disorders. Elucidating the role of TRP channels in hypertension and metabolic vascular damage would facilitate the design of novel target therapeutics for these intractable diseases. Intracellular Ca2+ homeostasis is critical for vascular function and the regulation of metabolism. Metabolic disorders are major risk factors for hypertension. A family of transient receptor potential (TRP) channels plays an important role in the regulation of cellular calcium signalling and cardiometabolic function. Emerging evidence indicates that TRP channels are highly implicated in the pathogenesis of hypertension and metabolic disorders. Dysfunction of TRP channels leads to hypertension and metabolic dysfunction. Activation of certain subtypes of TRP channels could attenuate metabolic vascular damage and alleviate hypertension. Therefore, elucidating the role of TRP channels in the physiological state and in cardiometabolic diseases will facilitate the design of novel targeted therapeutics for these intractable diseases.
Assuntos
Hipertensão/metabolismo , Doenças Metabólicas/metabolismo , Canais de Potencial de Receptor Transitório/metabolismo , Animais , Sinalização do Cálcio/fisiologia , Homeostase/fisiologia , HumanosRESUMO
BACKGROUND: There is sufficient evidence that women with atrial fibrillation (AF) have a greater symptom burden than men with AF and are more likely to experience recurrence after catheter ablation. However, the mechanisms underlying these sex differences are unclear. METHODS: We prospectively enrolled 125 consecutive patients, including 40 non-AF patients and 85 AF patients, who underwent high-density voltage mapping during sinus rhythm and AF patients who underwent first ablation. RESULTS: Overall, 37 (44%) female patients with AF and 24 (60%) female non-AF patients with a mean age of 61.7 ± 11.6 years and 53.6 ± 16.7 years, respectively, were enrolled in this study. The results showed that the atrial voltage of female AF patients was significantly lower than that of male AF patients (1.11 ± 0.58 mV vs. 1.53 ± 0.65 mV; P = 0.003), while there were no significant sex differences in non-AF patients (3.02 ± 0.86 mV vs. 3.21 ± 0.84 mV; P = 0.498). Multiple linear regression analysis revealed that female sex (- 0.29, 95% confidence interval [CI] - 0.64 to - 0.13, P = 0.004) and AF type (- 0.32, 95% CI - 0.69 to - 0.13, P = 0.004) were the only factors independently associated with voltage. Compared with men, women in the paroxysmal AF group had a 3.5-fold greater incidence of recurrence (adjusted hazard ratio 4.49; 95% CI 1.101-18.332, P = 0.036). Both globally and regionally, the results showed that sex-related differences in voltage values occurred prominently in paroxysmal AF patients but not in nonparoxysmal AF patients. CONCLUSION: Sex-related differences in atrial substrates and arrhythmia-free survival were found in paroxysmal AF patients, suggesting the existence of sex-related pathophysiological factors.
Assuntos
Fibrilação Atrial , Átrios do Coração , Humanos , Fibrilação Atrial/fisiopatologia , Feminino , Masculino , Pessoa de Meia-Idade , Átrios do Coração/fisiopatologia , Idoso , Estudos Prospectivos , Ablação por Cateter/métodos , Fatores Sexuais , Adulto , Caracteres Sexuais , RecidivaRESUMO
OBJECTIVE: The benefits of rhythm control in early atrial fibrillation (AF) are increasingly recognized. This study aimed to investigate whether early AF ablation contributes to long-term sinus rhythm maintenance and to identify a suitable predictive score. METHODS: According to diagnosis-to-ablation time, this study prospectively enrolled 245 patients with very early AF, 262 with early AF, and 588 with late AF for radiofrequency ablation from June 2017 to December 2022. Clinical data, risk scores, and follow-up results were collected and analyzed. RESULTS: Baseline characteristics were similar among the three cohorts. During a median follow-up period of 26 months, AF recurrence was observed in 61 (24.9%), 66 (25.2%), and 216 (36.7%) patients in the very early, early, and late AF cohorts, respectively. In the multivariable-adjusted model, very early and early AF were associated with a reduced risk of AF recurrence, with hazard ratios of 0.72 (95% confidence interval [CI] 0.52-0.99) and 0.57 (95% CI 0.41-0.78), respectively. The APPLE score demonstrated the highest predictive power for very early AF, with an area under the curve (AUC) of 0.74. However, its predictive power decreased with time from diagnosis, showing low predictive power for late AF (AUC = 0.58). In addition, the time-dependent concordance index showed consistent results. For very early AF, the Akaike information criterion and decision curve analysis showed that APPLE had the highest predictive value. CONCLUSION: Very early AF ablation was associated with a lower recurrence rate, and the APPLE score provided a higher predictive value for these patients. (URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR-OIN-17013021).
RESUMO
BACKGROUND: The renal proximal tubule (RPT) plays a pivotal role in regulating sodium reabsorption and thus blood pressure (BP). Transient receptor potential ankyrin 1 (TRPA1) has been reported to protect against renal injury by modulating mitochondrial function. We hypothesize that the activation of TRPA1 by its agonist cinnamaldehyde may mitigate high-salt intake-induced hypertension by inhibiting urinary sodium reabsorption through restoration of renal tubular epithelial mitochondrial function. METHODS: Trpa1-deficient (Trpa1-/-) mice and wild-type (WT) mice were fed standard laboratory chow [normal diet (ND) group, 0.4% salt], standard laboratory chow with 8% salt [high-salt diet (HS) group], or standard laboratory chow with 8% salt plus 0.015% cinnamaldehyde [high-salt plus cinnamaldehyde diet (HSC) group] for 6 months. Urinary sodium excretion, reactive oxygen species (ROS) production, mitochondrial function, and the expression of sodium hydrogen exchanger isoform 3 (NHE3) and Na+/K+-ATPase of RPTs were determined. RESULTS: Chronic dietary cinnamaldehyde supplementation reduced tail systolic BP and 24-hour ambulatory arterial pressure in HS-fed WT mice. Compared with the mice fed HS, cinnamaldehyde supplementation significantly increased urinary sodium excretion, inhibited excess ROS production, and alleviated mitochondrial dysfunction of RPTs in WT mice. However, these effects of cinnamaldehyde were absent in Trpa1-/- mice. Furthermore, chronic dietary cinnamaldehyde supplementation blunted HS-induced upregulation of NHE3 and Na+/K+-ATPase in WT mice but not Trpa1-/- mice. CONCLUSIONS: The present study demonstrated that chronic activation of Trpa1 attenuates HS-induced hypertension by inhibiting urinary sodium reabsorption through restoring renal tubular epithelial mitochondrial function. Renal TRPA1 may be a potential target for the management of excessive dietary salt intake-associated hypertension.