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1.
Front Cardiovasc Med ; 9: 821068, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35548428

RESUMO

Background: Observational studies have shown an association between early age at menarche (AAM) and myocardial infarction (MI) with recorded cases. In this Mendelian randomization (MR) study, we used large amounts of summary data from genome-wide association studies (GWASs) to further estimate the association of genetically predicted AAM with genetically predicated risk of MI and investigate to what extent this association is mediated by genetically determined lifestyles, cardiometabolic factors, and estrogen exposure. Methods: A two-step, two-sample MR study was performed by mediation analysis. Genetic variants identified by GWAS meta-analysis of reproductive genetics consortium (n = 182,416) were selected for genetically predicted AAM. Genetic variants identified by the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis plus The Coronary Artery Disease Genetics Consortium (n = 184,305) were selected for genetically predicted risk of MI. Genetic variants from other international GWAS summary data were selected for genetically determined mediators. Results: This MR study showed that increase in genetically predicted AAM was associated with lower risk of genetically predicted MI (odds ratio 0.91, 95% confidence interval 0.84-0.98). Inverse variance weighted (IVW) MR analysis also showed that decrease in genetically predicted AAM was associated with higher genetically predicted alcohol intake frequency, current smoking behavior, higher waist-to-hip ratio, and higher levels of systolic blood pressure (SBP), fasting blood glucose, hemoglobin A1c (HbA1c), and triglycerides (TGs). Furthermore, increase in genetically predicted AAM was associated with genetically predicted longer sleep duration, higher levels of high-density lipoproteins, and older age at which hormone replacement therapy was started. The most essential mediators identified were genetically predicted current smoking behavior and levels of HbA1c, SBP, and TGs, which were estimated to genetically mediate 13.9, 12.2, 10.5, and 9.2%, respectively, with a combined mediation proportion of 37.5% in the association of genetically predicted AAM with genetically predicted increased risk of MI in an MR framework. Conclusion: Our MR analysis showed that increase in genetically predicted AAM was associated with lower genetically predicted risk of MI, which was substantially mediated by genetically determined current smoking behavior and levels of HbA1c, SBP, and TGs. Intervening on the above mediators may reduce the risk of MI.

2.
Front Pharmacol ; 13: 845689, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35418863

RESUMO

Background: For anaphylaxis, a life-threatening allergic reaction, the incidence rate was presented to have increased from the beginning of the 21st century. Underdiagnosis and undertreatment of anaphylaxis are public health concerns. Objective: This guideline aimed to provide high-quality and evidence-based recommendations for the emergency management of anaphylaxis. Method: The panel of health professionals from fifteen medical areas selected twenty-five clinical questions and formulated the recommendations with the supervision of four methodologists. We collected evidence by conducting systematic literature retrieval and using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: This guideline made twenty-five recommendations that covered the diagnosis, preparation, emergency treatment, and post-emergency management of anaphylaxis. We recommended the use of a set of adapted diagnostic criteria from the American National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network (NIAID/FAAN), and developed a severity grading system that classified anaphylaxis into four grades. We recommended epinephrine as the first-line treatment, with specific doses and routes of administration for different severity of anaphylaxis or different conditions. Proper dosage is critical in the administration of epinephrine, and the monitor is important in the IV administration. Though there was only very low or low-quality evidence supported the use of glucocorticoids and H1 antagonists, we still weakly recommended them as second-line medications. We could not make a well-directed recommendation regarding premedication for preventing anaphylaxis since it is difficult to weigh the concerns and potential effects. Conclusion: For the emergency management of anaphylaxis we conclude that: • NIAID/FAAN diagnostic criteria and the four-tier grading system should be used for the diagnosis • Prompt and proper administration of epinephrine is critical.

3.
Front Cardiovasc Med ; 9: 755376, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360040

RESUMO

Introduction and Objectives: The risk of ventricular arrhythmia and heart failure in patients with hypertrophic obstructive cardiomyopathy (HOCM) is much higher than that in the general population. More and more pieces of evidence showed that HOCM is the leading cause of sudden cardiac death in young people. We reported our experience in a study, comparing surgical myectomy, alcohol septal ablation (ASA), and medical therapy. Methods: The original cohort included 965 consecutive patients with HOCM. The patients were divided into three groups according to treatment strategies: myectomy group (n = 502), ASA group (n = 138), and medical treatment group (n = 325). The median follow-up duration was 42.99 ± 18.32 months, and the primary endpoints were all-cause mortality and heart transplantation. Results: Both in short- and long-term observations, surgical myectomy reduced the left ventricular outflow tract (LVOT) gradients more effectively (7 days, 16.15 ± 12.07 mmHg vs. 42.33 ± 27.76 mmHg, p < 0.05; 1 year, 14.65 ± 13.18 mmHg vs. 41.17 ± 30.76 mmHg, p < 0.05). Among the three groups, the patients in the medical treatment group were at a higher risk of mortality and cardiac transplantation (vs. the myectomy group, p < 0.001 by log-rank test; vs. the alcohol septal ablation group, p = 0.017 by log-rank test), and the myectomy group shows a lower risk of reaching the primary endpoint than the two other groups. In the multivariate Cox regression analysis, previous atrial fibrillation (AF), N terminal pro B type natriuretic peptide (NT-pro-BNP), and surgical myectomy predicted an HOCM prognosis. However, the impact of surgical myectomy on HOCM prognosis seems to be limited to the <56 years group. Conclusions: The patients with medical treatments seemed to suffer from the highest risk of achieving an all-cause mortality and the endpoint of heart transplantation. In the long-term survival and clinical outcome, myectomy seemed better than alcohol septal ablation, especially the younger patients. Due to the less-controllable degree, periprocedural complication frequency after alcohol septal ablation was higher, compared with myectomy. Furthermore, gradients after myectomy are lower at late follow-up. To sum up, when selecting treatment strategies, the patients should be individually evaluated by a multidisciplinary team of cardiologists and surgeons.

4.
J Healthc Eng ; 2022: 1350673, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295178

RESUMO

We evaluate the effect of extracorporeal membrane oxygenation combined with intraaortic balloon pump mechanical circulatory support for patients with cardiogenic shock complicating acute myocardial infarction during the PCI process. Extracorporeal membrane oxygenation combined with intraaortic balloon pump hemodynamic support during the percutaneous coronary intervention process for patients with cardiac shock complicating acute myocardial infarction might play a complementary role. Yet, evidence of application of both devices at the same time remains unclear. Patients with cardiogenic shock complicating myocardial infarction who underwent PCI in our hospital from January 2015 to January 2018 were screened. Those who were under hemodynamic support of extracorporeal membrane oxygenation combined with intraaortic balloon pump were enrolled as the ECMO&IABP group, and the patients only under support of intraaortic balloon pump were enrolled as the IABP group. The differences of clinical prognosis between the two groups were compared. A total of 39 patients were enrolled into the study: 10 were in the ECMO&IABP group and 29 in the IABP group. Compared with the IABP group, more patients were complicated with old myocardial infarction (5/10 vs. 2/29, p=0.002), more patients were diagnosed as non-ST elevated myocardial infarction (8/10 vs. 11/29, p=0.002) and left ventricular ejecting fraction was lower (41.1 ± 9.86 vs. 48.55 ± 8.86, p=0.03) in the ECMO&IABP group. Mechanical complications were higher in the ECMO&IABP group (5/10 vs. 5/29, p=0.048), The survive rate in the ECMO&IABP group is higher than that in the IABP group (90.00% vs. 47.83%, p=0.042) at one-year follow-up. Compared with only IABP, ECMO combined with IABP hemodynamic support during the PCI process for patients with cardiogenic shock complicating acute myocardial infarction enjoys better mortality outcome.


Assuntos
Oxigenação por Membrana Extracorpórea , Infarto do Miocárdio , Intervenção Coronária Percutânea , Oxigenação por Membrana Extracorpórea/efeitos adversos , Hemodinâmica , Humanos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/efeitos adversos , Choque Cardiogênico/terapia , Resultado do Tratamento
5.
Front Cardiovasc Med ; 9: 813208, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35282373

RESUMO

Objective: The objective of this study is to investigate the roles of cardiometabolic factors (including blood pressure, blood lipids, thyroid function, body mass, and insulin sensitivity) in mediating the causal effect of type 2 diabetes (T2DM) on cardiovascular disease (CVD) outcomes. Design: Two-step, two-sample multivariable Mendelian randomization (MVMR) study. Setting: International genome-wide association study (GWAS) consortia data. Exposure: Type 2 diabetes, blood pressure: systolic blood pressure (SBP), diastolic blood pressure (DBP); blood lipids: low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), triglycerides (TG); thyroid function: hyperthyroidism, hypothyroidism; body mass index (BMI), waist-hip-ratio (WHR), and insulin sensitivity. Main Outcomes: Cardiovascular disease includes coronary heart disease (CHD), myocardial infarction (MI), and stroke. Methods: Summary-level data for exposures and main outcomes were extracted from GWAS consortia. We used two-sample MR to illustrate the causal effect of T2DM on CVD subtypes and regression-based MVMR to quantify the possible mediation effects of cardiometabolic factors on CVD. Results: Each additional unit of log odds of T2DM increased 16% risk of CHD [odds ratio (OR): 1.16, 95% CI: 1.12-1.21], 15% risk of myocardial infarction (MI) (OR: 1.15, 95% CI: 1.10-1.20), and 10% risk of stroke (OR: 1.10, 95% CI: 1.06-1.13). In mediation analysis, SBP, DBP, and TG were found as main mediators, while the mediation effects of other cardiometabolic factors were not significant. The proportion of total effect of T2DM on CHD mediated by SBP, DBP, and TG was 16% (95% CI: 8-24%), 7% (95% CI: 1-13%) and 10% (95% CI: 2-18%), respectively. Mediation effect of SBP and DBP on MI and stroke, TG on MI was also prominent, while mediation effect of TG on stroke was not significant. The combined mediation effect of all the three mediators accounted for 29%, 26%, and 13% of the total effect of T2DM on CHD, MI, and stroke, respectively. Conclusion: Systolic blood pressure, DBP, and TG mediate a substantial proportion of the causal effect of T2DM on CVD and thus interventions on these factors might reduce the considerable excess risk of CVD among patients with T2DM.

6.
Int J Cardiol ; 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35306031

RESUMO

AIMS: Although accumulating evidence demonstrated that virtual fractional flow reserve (FFR) based on coronary computed tomography angiography (CCTA) (CT-FFR) or invasive coronary angiogram (ICA) (CA-FFR) are promising alternatives to wire based FFR, which method has better diagnostic accuracy was still unclear. In our study, we aim to directly compare the diagnostic performance of CT-FFR and CA-FFR. METHODS: During the period of September 2019 to December 2020, patients with at least one 30%-90% coronary artery stenosis were enrolled and received invasive FFR. Then, virtual FFR values were calculated based on both CCTA and ICA, and then compared with the invasive FFR value. RESULTS: Invasive FFR measurements were successfully performed in 114 vessels of 96 patients. Both CT-FFR and CA-FFR showed good correlation with wire-based FFR, with r values of 0.84 and 0.71 respectively. In paired t-test, the deviation of CT-FFR and CA-FFR was not significantly different (t = -1.9083, p = 0.05889). In Bland-Altman analysis, the coefficients of variation were 8.4% and 13.2% for CT-FFR and CA-FFR respectively. In ROC curve analysis, the per-vessel diagnostic accuracy of CT-FFR and CA-FFR was 94.7% and 92.1% respectively. The area under the curve of CT-FFR was slightly higher than that of CA-FFR (0.986 and 0.916 respectively, the difference between areas = 0.070, 95% CI 0.003-0.137, p = 0.0227). CONCLUSION: Both CT-FFR and CA-FFR had good diagnostic concordance with wire-based FFR. In ROC Curve analysis, CT-FFR demonstrated slightly higher diagnostic accuracy than CA-FFR. CLINICAL TRIAL REGISTRATION: URL: https://www.chictr.org.cn/showproj.aspx?proj=44719. Unique Identifier: ChiCTR1900026971.

7.
J Geriatr Cardiol ; 19(1): 61-70, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35233224

RESUMO

BACKGROUND: Growing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular metabolism. However, the causal relationship of thyroid function and cardiometabolic health remains partly unknown. METHODS: The Mendelian randomization (MR) was used to test genetic, potentially causal relationships between instrumental variables and cardiometabolic traits. Genetic variants of free thyroxine (FT4) and thyrotropin (TSH) levels within the reference range were used as instrumental variables. Data for genetic associations with cardiometabolic diseases were acquired from the genome-wide association studies of the FinnGen, CARDIoGRAM and CARDIoGRAMplusC4D, CHARGE, and MEGASTROKE. This study was conducted using summary statistic data from large, previously described cohorts. Association between thyroid function and essential hypertension (EHTN), secondary hypertension (SHTN), hyperlipidemia (HPL), type 2 diabetes mellitus (T2DM), ischemic heart disease (IHD), myocardial infarction (MI), heart failure (HF), pulmonary heart disease (PHD), stroke, and non-rheumatic valve disease (NRVD) were examined. RESULTS: Genetically predicted FT4 levels were associated with SHTN (odds ratio = 0.48; 95% CI = 0.04-0.82,P = 0.027), HPL (odds ratio = 0.67; 95% CI = 0.18-0.88,P = 0.023), T2DM (odds ratio = 0.80; 95% CI = 0.42-0.86,P = 0.005), IHD (odds ratio = 0.85; 95% CI = 0.49-0.98,P = 0.039), NRVD (odds ratio = 0.75; 95% CI = 0.27-0.97,P = 0.039). Additionally, genetically predicted TSH levels were associated with HF (odds ratio = 0.82; 95% CI = 0.68-0.99,P = 0.042), PHD (odds ratio = 0.75; 95% CI = 0.32-0.82,P = 0.006), stroke (odds ratio = 0.95; 95% CI = 0.81-0.97,P = 0.007). However, genetically predicted thyroid function traits were not associated with EHTN and MI. CONCLUSIONS: Our study suggests FT4 and TSH are associated with cardiometabolic diseases, underscoring the importance of the pituitary-thyroid-cardiac axis in cardiometabolic health susceptibility.

8.
Cardiovasc Diabetol ; 21(1): 29, 2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35193553

RESUMO

BACKGROUND: Non-diabetic coronary artery disease (CAD) patients are thought to encounter metabolic dysfunction and while these changes may be imperceptible to the patient they probably influence outcomes. At present, there is no system to support patients sensing these subtle changes, nor is there an established model for prognoses. The Atherogenic Index of Plasma (AIP) index has already proven useful for atherosclerosis although further research is needed, especially for those without hyperglycemia. METHODS: This is a prospective study of 5538 non-diabetic CAD patients who had received percutaneous coronary intervention (PCI). Participants were assigned to one of three groups according to their AIP index. High AIP index cases were then compared to low index patients according to major adverse cardiac events (MACE). Restricted cubic spline (RCS) analysis was also conducted to investigate interrelations between AIP index levels and hazard ratios (HR) for MACEs. RESULTS: Patients with a high AIP index encountered metabolic dysfunction compared to those with a low AIP index i.e., higher Body Mass Index (BMI), Total Cholesterol (TC), Triglycerides (TG), and uric acid as well as lower HDL-C. Each of the aforementioned interrelations were significant with p values of less than 0.001. There was also a significant increase in the number of MACEs in the high AIP index group compared to the low AIP index group (HR: 1.37, 95% CI 1.04-1.81; p = 0.025). A J-shaped RCS curve highlighted a change in the HR after the 0.18 juncture (HR per SD: 1.20, 95% CI 0.96-1.50). Further subgroup analysis supported the main findings, all with HRs greater than one. CONCLUSION: The AIP index could be used in prognostics for non-diabetic CAD patients 2 years after PCI. The relationship between hazard ratio and the AIP index appears to be J-shaped. Although, further multi-center studies designed for non-diabetic patients with potential metabolic dysfunction should be conducted to determine the value of the AIP index.


Assuntos
Doença da Artéria Coronariana , Intervenção Coronária Percutânea , China/epidemiologia , HDL-Colesterol , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Fatores de Risco , Triglicerídeos
9.
Diabetes Care ; 45(4): 947-956, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35045167

RESUMO

OBJECTIVE: In recent years, some studies have indicated that a novel marker described as the stress hyperglycemia ratio (SHR) can reflect true acute hyperglycemic status and is associated with the short-term poor prognosis in patients with acute myocardial infarction. In the current study we evaluated the association of SHR with adverse cardiovascular events among patients with acute coronary syndrome (ACS). RESEARCH DESIGN AND METHODS: We consecutively enrolled 5,562 ACS patients who underwent drug-eluting stent (DES) implantation. All subjects were divided into five groups according to SHR, which was determined by the following formula: ABG / [(28.7 × HbA1c %) - 46.7], where ABG is admission blood glucose level. The primary end point was major adverse cardiovascular and cerebrovascular events (MACCE) at the 2-year follow-up, and the secondary end point included major adverse cardiovascular events (MACE) at 2-year follow-up, cardiac death, and nonfatal myocardial infarction (MI) at 2-year follow-up and in-hospital cardiac death and nonfatal MI. RESULTS: A total of 643 MACCE were recorded during a median follow-up of 28.3 months. Kaplan-Meier survival analysis showed the lowest MACCE incidence in quintile 3 (P < 0.001). Moreover, the outcomes of restricted cubic spline analysis suggested that there was a U-shaped or J-shaped association between the SHR and early and late cardiovascular outcomes even after adjustment for other confounding factors. CONCLUSIONS: There were U-shaped associations of SHR with MACCE rate and MACE rate at 2-year follow-ups and J-shaped associations of SHR with in-hospital cardiac death and MI and that at 2-year follow-up in ACS patients who underwent DES implantation, and the inflection point of SHR for poor prognosis was 0.78.


Assuntos
Síndrome Coronariana Aguda , Stents Farmacológicos , Hiperglicemia , Infarto do Miocárdio , Intervenção Coronária Percutânea , Estudos de Coortes , Morte , Humanos , Hiperglicemia/epidemiologia , Infarto do Miocárdio/epidemiologia , Prognóstico , Resultado do Tratamento
10.
J Cardiovasc Pharmacol ; 79(2): 217-228, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34983914

RESUMO

ABSTRACT: Over the past decade, histone deacetylases (HDACs) has been proven to manipulate development and exacerbation of cardiovascular diseases, including myocardial ischemia/reperfusion injury, cardiac hypertrophy, ventricular remodeling, and myocardial fibrosis. Inhibition of HDACs, especially class-I HDACs, is potent to the protection of ischemic myocardium after ischemia/reperfusion (I/R). Herein, we examine whether mocetinostat (MGCD0103, MOCE), a class-I selective HDAC inhibitor in phase-II clinical trial, shows cardioprotection under I/R in vivo and in vitro, if so, reveal its potential pharmacological mechanism to provide an experimental and theoretical basis for mocetinostat usage in a clinical setting. Human cardiac myocytes (HCMs) were exposed to hypoxia and reoxygenation (H/R), with or without mocetinostat treatment. H/R reduced mitochondrial membrane potential and induced HCMs apoptosis. Mocetinostat pretreatment reversed these H/R-induced mitochondrial damage and cellular apoptosis and upregulated CREB, p-CREB, and PGC-1α in HCMs during H/R. Transfection with small interfering RNA against PGC-1α or CREB abolished the protective effects of mocetinostat on cardiomyocytes undergoing H/R. In vivo, mocetinostat was demonstrated to protect myocardial injury posed by myocardial I/R via the activation of CREB and upregulation of PGC-1α. Mocetinostat (MGCD0103) can protect myocardium from I/R injury through mitochondrial protection mediated by CREB/PGC-1α pathway. Therefore, activation of the CREB/PGC-1α signaling pathway via the inhibition of Class-I HDACs may be a promising new therapeutic strategy for alleviating myocardial reperfusion injury.


Assuntos
Traumatismo por Reperfusão Miocárdica , Animais , Apoptose , Benzamidas , Inibidores de Histona Desacetilases/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Histona Desacetilases/metabolismo , Histona Desacetilases/farmacologia , Histona Desacetilases/uso terapêutico , Humanos , Isquemia/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/farmacologia , Isoformas de Proteínas/uso terapêutico , Pirimidinas , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
11.
Heart Vessels ; 37(1): 152-160, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34236463

RESUMO

Growing evidences have revealed that a histone deacetylase inhibitor (HDACi), suberoylanilide hydroxamic acid (SAHA) has anti-fibrotic effect in different diseases. In this study, we first evaluated whether SAHA could suppress cardiac fibrosis. Mice with MI-induced cardiac fibrosis were treated with SAHA by intraperitoneal injection and their cardiac function was improved after SAHA treatment. Results of western blotting and qRT-PCR in heart tissues suggested that TGFß1/P38 pathway was activated in MI mice, and this effect was reversed by SAHA. Cell proliferation assay suggested that SAHA could suppress TGF-ß1-induced cardiac fibroblasts proliferation. Furthermore, results of western blotting and qRT-PCR in cardiac fibroblasts depicted that SAHA may exert its anti-fibrotic effect through inhibiting TGF-ß1-induced P38 phosphorylation by promoting DUSP4 expression. Our findings may substantiate SAHA as a promising treatment for MI-induced cardiac fibrosis.


Assuntos
Cardiopatias , Animais , Fibroblastos , Fibrose , Inibidores de Histona Desacetilases/farmacologia , Sistema de Sinalização das MAP Quinases , Camundongos , Proteínas Tirosina Fosfatases , Fator de Crescimento Transformador beta1/genética , Vorinostat/farmacologia
12.
J Clin Endocrinol Metab ; 107(4): e1518-e1527, 2022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-34850013

RESUMO

CONTEXT: Observational studies have suggested that higher resting heart rate (RHR) may be associated with increased cardiometabolic risk. However, causal associations are not fully understood. OBJECTIVE: We aimed to examine the direction, strength, and causality of the associations of RHR with cardiometabolic traits. METHODS: We assessed the strength of associations between measured RHR and cardiometabolic traits in 506 211 and 372 452 participants from China Kadoorie Biobank (CKB) and UK Biobank (UKB). Mendelian randomization (MR) analyses were used to make causal inferences in 99 228 and 371 508 participants from CKB and UKB, respectively. RESULTS: We identified significant directionally concordant observational associations between RHR and higher total cholesterol, triglycerides (TG), low-density lipoprotein, C-reactive protein (CRP), glucose, body mass index, waist-hip ratio (WHR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) after the Bonferroni correction. MR analyses showed that 10 beat/min higher genetically predicted RHR was trans-ethnically associated with a higher DBP (beta 2.059 [95% CI 1.544, 2.574] mmHg in CKB; 2.037 [1.845, 2.229] mmHg in UKB), higher CRP (0.180 [0.057, 0.303] log mg/L in CKB; 0.154 [0.134, 0.174] log mg/L in UKB), higher TG (0.052 [-0.009, 0.113] log mmol/L in CKB; 0.020 [0.010, 0.030] log mmol/L in UKB) and higher WHR (0.218 [-0.033, 0.469] % in CKB; 0.225 [0.111, 0.339] % in UKB). In the opposite direction, higher genetically predicted SBP, TG, glucose, and WHR, and lower high-density lipoprotein, were associated with elevated RHR. CONCLUSION: Our large-scale analyses provide causal evidence for associations between RHR and cardiometabolic traits, highlighting the importance of monitoring heat rate as a means of alleviating the adverse effects of metabolic disorders.


Assuntos
Doenças Cardiovasculares , Análise da Randomização Mendeliana , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/genética , Glucose , Frequência Cardíaca/genética , Humanos , Triglicerídeos , Relação Cintura-Quadril
13.
J Clin Endocrinol Metab ; 107(4): 986-997, 2022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-34850030

RESUMO

CONTEXT: Limited studies have focused on the impact of subclinical hyperthyroidism (SHyper) on poor prognosis in patients with known coronary artery disease (CAD). OBJECTIVE: We implemented the present study to explore the association between SHyper and adverse cardiovascular events in CAD patients who underwent drug-eluting stent implantation. METHODS: We consecutively recruited 8283 CAD patients undergoing percutaneous coronary intervention (PCI). All subjects were divided into 2 groups according to their thyroid function: group 1 (euthyroidism group, n = 7942) and group 2 (SHyper group, n = 341). After 1:4 propensity score (PS) matching, 1603 patients (332 SHyper group and 1271 euthyroidism group) were selected. The primary endpoint was major adverse cardiovascular events (MACEs), a composite of cardiac mortality, nonfatal myocardial infarction (MI), and target vessel revascularization (TVR). RESULTS: Kaplan-Meier (K-M) survival analyses suggested that there was no significant difference in the primary endpoint and secondary endpoints (MACE: 11.4% vs 8.8%, log-rank P = .124; cardiac death: 1.2% vs 0.9%, log-rank P = .540; nonfatal MI: 5.7% vs 4%, log-rank P = .177; and TVR: 6% vs 4.7%, log-rank P = .303) in the PS-matched population. Cox regression analysis indicated that SHyper was not an independent risk factor for MACEs (HR 1.33, 95% CI 0.92-1.92, P = .127). CONCLUSION: SHyper is not independently associated with adverse cardiovascular events in CAD patients undergoing PCI. More studies should be implemented in the future to assess the long-term predictive value of SHyper with thyrotropin levels <0.1 mIU/L for CAD patients undergoing PCI.


Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Hipertireoidismo , Infarto do Miocárdio , Intervenção Coronária Percutânea , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Stents Farmacológicos/efeitos adversos , Humanos , Hipertireoidismo/complicações , Hipertireoidismo/epidemiologia , Hipertireoidismo/cirurgia , Infarto do Miocárdio/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Prognóstico , Fatores de Risco , Resultado do Tratamento
14.
Cardiovasc Diabetol ; 20(1): 239, 2021 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-34922553

RESUMO

BACKGROUND: Evidence is limited regarding the association of healthy lifestyle including sleep pattern with the risk of complicated type 2 diabetes mellitus (T2DM) among patients with hypertension. We aimed to investigate the associations of an overall healthy lifestyle including a healthy sleep pattern with subsequent development of T2DM among participants with hypertension compared to normotension, and to estimate how much of that risk could be prevented. METHODS: This study examined six lifestyle factors with T2DM cases among hypertension (227,966) and normotension (203,005) and their interaction in the UK Biobank. Low-risk lifestyle factors were defined as standard body mass index (BMI), drinking alcohol in moderation, nonsmoking, engaging in moderate- to vigorous-intensity physical activity, eating a high-quality diet, and maintaining a healthy sleep pattern. RESULTS: There were 12,403 incident T2DM cases during an average of 8.63 years of follow-up. Compared to those with 0 low-risk lifestyle factors, HRs for those with 5-6 were 0.14 (95% CI 0.10 to 0.19) for hypertensive participants, 0.13 (95% CI 0.08 to 0.19) for normotensive participants, respectively (ptrend < 0.001). 76.93% of hypertensive participants were considerably less likely to develop T2DM if they adhered to five healthy lifestyle practices, increased to 81.14% if they followed 6-factors (with a healthy sleep pattern). Compared with hypertension adults, normotensive people gain more benefits if they stick to six healthy lifestyles [Population attributable risk (PAR%) 83.66%, 95% CI 79.45 to 87.00%, p for interaction = 0.0011]. CONCLUSIONS: Adherence to a healthy lifestyle pattern including a healthy sleep pattern is associated with lower risk of T2DM in hypertensives, and this benefit is even further in normotensives.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Estilo de Vida Saudável , Hipertensão/terapia , Comportamento de Redução do Risco , Sono , Adulto , Idoso , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Dieta Saudável , Exercício Físico , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Proteção , Medição de Risco , Fatores de Risco , Reino Unido/epidemiologia
15.
ACS Nano ; 15(12): 20164-20180, 2021 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-34898184

RESUMO

Nanomaterials that combine multimodality imaging and therapeutic functions within a single nanoplatform have drawn extensive attention for molecular medicines and biological applications. Herein, we report a theranostic nanoplatform based on a relatively smaller (<20 nm) iron oxide loaded porphyrin-grafted lipid nanoparticles (Fe3O4@PGL NPs). The amphiphilic PGL easily self-assembled on the hydrophobic exterior surface of ultrasmall Fe3O4 NPs, resulting in a final ultrasmall Fe3O4@PGL NPs with diameter of ∼10 nm. The excellent self-assembling nature of the as-synthesized PGL NPs facilitated a higher loading of porphyrins, showed a negligible dark toxicity, and demonstrated an excellent photodynamic effect against HT-29 cancer cells in vitro. The in vivo experimental results further confirmed that Fe3O4@PGL NPs were ideally qualified for both the fluorescence and magnetic resonance (MR) imaging guided nanoplatforms to track the biodistribution and therapeutic responses of NPs as well as to simultaneously trigger the generation of highly cytotoxic reactive oxygen species (ROS) necessary for excellent photodynamic therapy (PDT). After recording convincing therapeutic responses, we further evaluated the ability of Fe3O4@PGL NPs/Fe3O4@Lipid NPs for ferroptosis therapy (FT) via tumor microenvironment (TME) modulation for improved anticancer activity. We hypothesized that tumor-associated macrophages (TAMs) could significantly improve the efficacy of FT by accelerating the Fenton reaction in vitro. In our results, the Fe ions released in vitro directly contributed to the Fenton reaction, whereas the presence of RAW 264.7 macrophages further accelerated the ROS generation as observed by the fluorescence imaging. The significant increase in the ROS during the coincubation of NPs, endocytosed by HT-29 cells and RAW264.7 cells, further induced increased cellular toxicity of cancer cells.


Assuntos
Ferroptose , Nanopartículas , Neoplasias , Fotoquimioterapia , Porfirinas , Linhagem Celular Tumoral , Compostos Férricos , Humanos , Lipossomos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/farmacologia , Porfirinas/uso terapêutico , Distribuição Tecidual , Microambiente Tumoral
16.
Ann Transl Med ; 9(17): 1390, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733942

RESUMO

BACKGROUND: Computed tomography-derived fractional flow reserve (CT-FFR) has emerged as a promising non-invasive substitute for fractional flow reserve (FFR) measurement. Normally, CT-FFR providing functional significance of coronary artery disease (CAD) by using a simplified total coronary resistance index (TCRI) model. Yet the error or discrepancy caused by this simplified model remains unclear. METHODS: A total of 20 consecutive patients with suspected CAD who underwent CTA and invasive FFR measurement were retrospectively analyzed. CT-FFR and CT-(Pd/Pa)rest values derived from the coronary CTA images. The diagnostic performance of CT-FFR and CT-(Pd/Pa)rest were evaluated on a per-vessel level using C statistics with invasive FFR<0.80 as the reference standard. RESULTS: Of the 25 vessels eventually analyzed, the prevalence of functionally significant CAD were 64%. The Youden index of the ROC curve indicated that the best cutoff value of invasive resting Pd/Pa was 0.945 for identifying functionally significant lesions. Sensitivity, specificity, negative predictive value, positive predictive value and accuracy were 85%, 91%, 92%, 83% and 88% for CT-(Pd/Pa)rest and 85%, 58% 69%, 78% and 72% for CT-FFR. Area under the receiver-operating characteristic curve (AUC) to detect functionally significant stenoses of CT-(Pd/Pa)rest and CT-FFR were 0.87 and 0.90. CONCLUSIONS: In this study, the results suggest CT-derived resting Pd/Pa has a potential advantage over CT-FFR in triaging patients for revascularization.

17.
J Control Release ; 339: 506-520, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34655677

RESUMO

The combination of nitric oxide (NO) and siRNA is highly desirable for cancer therapy. Here, the furoxans-grafted PEI polymer (FDP) with caspase-3 responsive cleavable DEVD linker was synthesized, and used to bind siRNAs via electrostatic interaction and self-assembled into FDP/siRNA nanoplexes by hydrophobic force. After cellular uptake and lysosomal escape, the FDP/siRNA nanoplexes could achieve GSH-triggered NO release, and then increase the activity of caspase-3. The activated caspase-3 could specifically cleave the DEVD peptide sequence and enhance cell apoptosis. With the cleavage of DEVD peptide sequence, the disassembly of FDP/siRNA nanoplexes was further promoted, thereby resulting in increased siRNAs of ~40% were released at 48 h compared with the caspase-3 non-responsive FDnP/siRNA nanoplexes. By this way, cell apoptosis promotion and cell proliferation inhibition was achieved by siRNA-based downregulation of EGFR protein and the upregulated activity of caspase-3, followed by the enhanced cascade release of NO from FDP/siRNA nanoplexes. Furthermore, in vivo results demonstrated the improved anti-cancer efficiency of FDP/siEGFR nanoplexes without any detectable side effects. Therefore, it is believed that the caspase-3 responsive cleavable furoxans-grafted PEI polymers could provide a potential and efficient enhancement for cancer therapeutic efficiency by the co-delivery of nitric oxide and siRNA.


Assuntos
Neoplasias , Polímeros , Caspase 3 , Humanos , Óxido Nítrico , RNA Interferente Pequeno
18.
Anatol J Cardiol ; 25(10): 691-698, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34622783

RESUMO

OBJECTIVE: Presently, an effective model to predict long-term cardiac mortality in patients with hypertrophic obstructive cardiomyopathy (HOCM) is lacking. Therefore, the objective of this study was to evaluate the predictive value of the modified Age, Creatinine clearance, and Ejection Fraction (mACEF) score for long-term cardiac mortality in patients with HOCM. METHODS: Two hundred and ninety two patients with HOCM treated non-invasively were enrolled in this study, all of whom had intact medical information. RESULTS: Over a median follow-up period of 41.9 months, 28 cardiac deaths occurred. In univariate Cox regression analysis, the mACEF score was associated with long-term cardiac death [hazard ratio (HR)=1.795, 95% confidence interval (CI) 1.518-2.124, p<0.001]. Multiple Cox regression analysis identified the mACEF score as an independent risk factor for long-term cardiac death (adjusted HR=1.372, 95% CI 1.076-1.749, p=0.011). Analysis of the receiver operating characteristic (ROC) for long-term cardiac death showed that the mACEF score had a considerable predictive value (area under ROC 0.844, sensitivity 89.29%, specificity 75.00%) with an optimum cut-off value of 0.96. The study population was divided into high-risk (mACEF score ≥0.96, n=91) and low-risk (mACEF score <0.96, n=201) groups according to the optimum cut-off value. Kaplan-Meier survival analysis was performed and showed a dramatic higher rate of long-term cardiac mortality in the high-risk group than in the low-risk group (27.4% vs. 1.7%, p<0.001 by log-rank test). CONCLUSION: The mACEF score has a considerable predictive value for long-term cardiac mortality in patients with HOCM treated non-invasively. A mACEF score ≥0.96 could be considered as a sign of poor prognosis in patients with HOCM.


Assuntos
Cardiomiopatia Hipertrófica , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Creatinina , Humanos , Prognóstico , Estudos Retrospectivos , Volume Sistólico
19.
Front Endocrinol (Lausanne) ; 12: 710240, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489866

RESUMO

Background: The triglyceride-glucose index (TyG index) is a valuable marker for predicting adverse cardiovascular events in diabetic patients. However, for nondiabetic patients, whether the TyG index is independently related to poor prognosis remains unclear. This cohort study assessed the association of the TyG index with future cardiovascular risk in nondiabetic subjects who received percutaneous coronary intervention (PCI). Methods: We consecutively enrolled 5,489 nondiabetic patients who underwent PCI. All experimental subjects were divided into three groups based on their TyG index, which was determined by the equation ln (fasting triglyceride (mg/dl) × fasting blood glucose (mg/dl)/2). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, and target vessel revascularization (TVR). Results: A total of 386 MACCE were documented during a median 29-month follow-up. The Kaplan-Meier survival results indicated that among the three groups, there was no obvious difference in any endpoints. Further Cox regression analyses suggested that the TyG index was not independently related to adverse cardiovascular outcomes for nondiabetic patients who underwent PCI (HR: 0.77, 95% CI 0.56-1.16, P = 0.210 for MACCE). Subgroup analysis suggested that the TyG index was independently relevant to MACCE for patients with low-density lipoprotein cholesterol (LDL-C) lower than 1.8 mmol/L. Conclusion: The TyG index is not an effective predictive factor for adverse cardiovascular prognosis in nondiabetic patients who underwent PCI. However, in subjects with LDL-C lower than 1.8mmol/L, it may predict future cardiovascular risk.


Assuntos
Biomarcadores/sangue , Glicemia/análise , Doenças Cardiovasculares/diagnóstico , Transtornos Cerebrovasculares/diagnóstico , Doença da Artéria Coronariana/terapia , Intervenção Coronária Percutânea/efeitos adversos , Triglicerídeos/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Transtornos Cerebrovasculares/sangue , Transtornos Cerebrovasculares/etiologia , Doença da Artéria Coronariana/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco , Taxa de Sobrevida
20.
Ann Transl Med ; 9(13): 1066, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34422978

RESUMO

BACKGROUND: The prognostic value of the CYP2C19 genotype in post-percutaneous coronary intervention (PCI) patients remains controversial. The recently-published, limited-sample PHARMCLO trial indicates a personalized pharmacogenomic approach may reduce adverse events. This study aimed to determine the prognostic value of CYP2C19 genotypes. METHODS: The original cohort consisted of 10,724 PCI patients in 2013. 756 patients with genotyped CYP2C19 were included in our analysis. The CYP2C19 genotype prognostic value was tested based on different clinical factors. The primary endpoint was major adverse cardio- and cerebro-vascular event (MACCE). RESULTS: MACCE 2-years post-PCI occurred in 19 patients (17.4%) in poor metabolizers (PM, CYP2C19 *2/*2, *2/*3, *3/*3), 43 patients (12.2%) in intermediate metabolizers (IM, CYP2C19 *1/*2 or *1/*3) and 27 patients (9.2%) in extensive metabolizers (EM, CYP2C19 *1/*1). PM was an independent MACCE predictor compared with EM (HR: 1.960, 95% CI: 1.139-3.372), but the difference between IM and PM was not significant (HR: 1.314, 95% CI: 0.843-2.048). Major bleeding (BARC grade ≥3) was not significantly different between the three groups (2.5% vs. 2.1% vs. 0.8%, P=0.133). Subgroup analysis showed that the CYP2C19 genotype prognostic value was present in the following subgroups: male, age >60 years, body mass index (BMI) >24 kg/m2, SYNTAX score >15, current smokers, and patients without chronic kidney disease. CONCLUSIONS: Utilizing CYP2C19 genotype to guide post-PCI antiplatelet therapy might be appropriate in patients with the following characteristics: male, age >60 years, BMI >24 kg/m2, SYNTAX score >15, current smokers, and non-chronic kidney disease (CKD) patients.

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