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OBJECTIVES: Serum matrix metalloproteinase (MMP) levels are associated with cardiovascular diseases. However, the causal associations between serum levels of specific MMPs and venous thromboembolism (VTE) remain unclear. The present study sought to explore the causal relationship between serum MMP levels and VTE by using the Mendelian randomization (MR) method. METHODS: In this study 2-sample MR study, the exposure data on serum MMP levels were derived from genome-wide association studies involving 21,758 individuals from 13 cohorts of European descent. The outcome data on VTE, including deep vein thrombosis and pulmonary embolism, were derived from the FinnGen research project. The primary method used was the inverse-variance weighting method. The MR-Egger intercept test and the Cochran Q test were used to evaluate pleiotropy and heterogeneity. RESULTS: Using the inverse-variance weighting method, higher serum MMP-12 levels were found to be associated with an increased risk of VTE (odds ratio, 1.04; 95% confidence interval, 1.01 to 1.07; p=0.001). Moreover, there was a weak association between the levels of certain MMPs and VTE. Sensitivity analyses revealed no significant heterogeneity and pleiotropy in our study, and the Steiger directionality test did not reveal a significant reverse causation association. CONCLUSIONS: There is a causal association between MMP-12 levels and VTE, which may have substantial implications for the diagnostic and therapeutic strategies used for VTE.
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Estudo de Associação Genômica Ampla , Metaloproteinases da Matriz , Análise da Randomização Mendeliana , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/sangue , Metaloproteinases da Matriz/sangue , Causalidade , Metaloproteinase 12 da Matriz/sangue , Metaloproteinase 12 da Matriz/genéticaRESUMO
Cardiovascular aging is a progressive remodeling process constituting a variety of cellular and molecular alterations that are closely linked to mitochondrial dysfunction. Therefore, gaining a deeper understanding of the changes in mitochondrial function during cardiovascular aging is crucial for preventing cardiovascular diseases. Cardiac aging is accompanied by fibrosis, cardiomyocyte hypertrophy, metabolic changes, and infiltration of immune cells, collectively contributing to the overall remodeling of the heart. Similarly, during vascular aging, there is a profound remodeling of blood vessel structure. These remodeling present damage to endothelial cells, increased vascular stiffness, impaired formation of new blood vessels (angiogenesis), the development of arteriosclerosis, and chronic vascular inflammation. This review underscores the role of mitochondrial dysfunction in cardiac aging, exploring its impact on fibrosis and myocardial alterations, metabolic remodeling, immune response remodeling, as well as in vascular aging in the heart. Additionally, we emphasize the significance of mitochondria-targeted therapies in preventing cardiovascular diseases in the elderly.
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BACKGROUND: The latest information regarding the awareness of atrial fibrillation (AF) remains limited in China. OBJECTIVES: The present study aimed to understand the variation and disparity in awareness of AF in China. METHODS: The cross-sectional study used data from the 2020 nationwide epidemiology survey on AF among adults aged 18 years or older in mainland China to assess the prevalence of AF awareness. The awareness of AF diagnostic methods and outcomes was also assessed using an interviewer-administered questionnaire. RESULTS: Of the 114,039 adults responding to the survey, 1463 (age-standardized prevalence, 55.3% (95% confidence interval [CI], 47.7-62.9%) and 10,202 (8.2%, 95%CI 5.4-10.9%) were aware of AF in participants with and without AF, respectively. Of these, 36.4% (95%CI 30.0-42.9%) and 6.3% (95%CI 3.6-9.1%) considered electrocardiogram as a method of diagnosing AF, and 30.0% (95% CI 3.2-8.2%) and 5.2% (95%CI 2.7-7.6%) considered stroke as an outcome of AF. The proportion of participants who being aware of AF varied significantly across sociodemographic and cardiovascular disease subgroups, and was almost consistently lower in rural areas than those in urban areas. Overall, lack of AF awareness was associated with rural areas, geographical region, lower education levels, and without history and had no risk factors of cardiovascular disease. CONCLUSIONS: Nearly half of adults with AF, and >90% non-AF population are unaware of AF in China, with significant variation and disparity. Focused public health initiatives are needed to improve awareness and knowledge of AF among high-risk populations.
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Fibrilação Atrial , Acidente Vascular Cerebral , Adulto , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Estudos Transversais , Acidente Vascular Cerebral/epidemiologia , Fatores de Risco , China/epidemiologia , PrevalênciaRESUMO
Aim: To evaluate the costs and consequences of two front-line atrial fibrillation (AF) treatments from Chinese healthcare system perspective: radiofrequency catheter ablation (RFCA) using ThermoCool SmartTouch Catheter guided by Ablation Index (STAI), in comparison to antiarrhythmic drugs (AADs). Patients & methods: We simulated clinical and economic consequences for AF patients initially receiving STAI or AADs using a short-term decision tree model leading to a 10-year long-term Markov model. The model projected both clinical consequences and costs associated with, among others, AF, heart failure (HF), strokes, and deaths due to AF or AF related complications. Data informing the models included combination of a local real-world study and published clinical studies. Results: STAI was advantageous versus AADs on all 4 main clinical outcomes evaluated; AF: 25.83% lower (12.84% vs 38.67%), HF: 2.22% lower (1.33% vs 3.55%), stroke or post stroke: 1.82% lower (10.00% vs 11.82%) and deaths due to AF or AF related complications: 0.64% lower (4.11% vs 4.75%). The average total cost per patient in STAI group was ¥16,682 lower (¥123,124 vs ¥139,806). The one-way sensitivity analysis indicated that the difference in total cost was most sensitive to annual AF recurrence probability in AADs-treated patients. Probabilistic sensitivity analysis indicated a 98.5% probability that RFCA treatment would result in cost savings by the end of the 10th year. Conclusion: Radiofrequency catheter ablation using SmartTouch catheter guided by Ablation Index was superior to AADs as the first-line AF treatment in Chinese setting with better clinical outcomes and at lower costs over a 10-year time horizon.
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Fibrilação Atrial , Ablação por Cateter , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/cirurgia , Fibrilação Atrial/tratamento farmacológico , Antiarrítmicos/efeitos adversos , Resultado do Tratamento , Análise Custo-Benefício , CatéteresRESUMO
Doxorubicin (Dox) is a widely used antitumor agent with dose-dependent and cumulative cardiotoxic effects. Resveratrol (Res) is a natural non-flavonoid polyphenol that can potentially provide cardiovascular benefits. We aimed to estimate the protective effect of Res on Dox-induced cardiotoxicity (DIC) and explore whether it was related to attenuating ferroptosis. We established DIC models in C57BL/6 J mice, H9C2 cardiomyoblasts, and neonatal rat cardiomyocytes (NRCMs). We further treated H9C2 cells with RSL3, a ferroptosis agonist, to investigate whether Res exerted protective effects through inhibiting ferroptosis. Ferrostatin-1 (Fer-1) was applied to suppress ferroptosis. Dox treatment caused cardiac dysfunction and resulted in apparent ferroptotic damage in cardiac tissue, involving increased iron accumulation, glutathione depletion, increased expression of ferroptosis-related proteins, and decreased expression of glutathione peroxidase 4, which were alleviated by Fer-1 and Res administration. These findings were also confirmed in Dox-treated H9C2 cells and NRCMs, with Fer-1 and Res effectively attenuating Dox-induced cytotoxicity and ferroptosis. Furthermore, Res protected H9C2 cells from RSL3-induced ferroptotic cell death, and the protective effect was similar to that of Fer-1. Both Dox and RSL3 treatment increased the phosphorylation levels of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinases; however, these changes were hindered by Res. This study demonstrates that Res effectively alleviates DIC by suppressing ferroptosis possibly through modulating the MAPK signaling pathway. Our results highlight that targeting ferroptosis can be a potential cardioprotective strategy for DIC.
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Cardiotoxicidade , Ferroptose , Camundongos , Ratos , Animais , Resveratrol/farmacologia , Cardiotoxicidade/patologia , Apoptose , Linhagem Celular , Camundongos Endogâmicos C57BL , Transdução de Sinais , Doxorrubicina/farmacologia , Miócitos Cardíacos , Estresse OxidativoRESUMO
Background: Limited studies have explored the association between sexual factors [age at first sexual intercourse (AFS) and lifetime number of sexual partners (LNSP)] and cardiovascular diseases (CVDs), leaving the causality inconclusive. Methods: We performed a bi-directional Mendelian randomization (MR) study to investigate the causality between sexual factors and CVDs, including coronary artery disease, myocardial infarction, atrial fibrillation (AF), heart failure (HF), and ischemic stroke (IS). Single-nucleotide polymorphisms (SNPs) for sexual factors were extracted from the UK Biobank. Statistics for each CVD were derived from two different databases. MR estimates were calculated per outcome database and were combined through meta-analysis. Several complementary sensitivity analyses were also performed. Results: The primary analysis suggested that AFS was causally associated with the risk of CVDs; the odds ratios (ORs) ranged from 0.686 [95% confidence interval (CI), 0.611-0.770] for HF to 0.798 (95% CI, 0.719-0.886) for AF. However, the association between AFS and IS (OR, 0.844; 95% CI, 0.632-1.126) was not consistent in the meta-analysis after excluding SNPs related to confounders. Moreover, non-significant associations were found between LNSP and CVDs. Reverse direction MR analysis showed that CVDs were not associated with sexual factors. Conclusions: Genetic evidence suggested that AFS was causally associated with the risk of CVDs except for IS, whereas non-significant association of LNSP with CVDs was detected. Further investigation into AFS could be warranted in preventing the progression of CVDs.
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Circular RNAs (circRNAs) play a role in sepsis-related autophagy. However, the role of circRNAs in autophagy after sepsis-induced cardiomyopathy (SICM) is unknown, so we explored the circRNA expression profiles associated with autophagy in an acute sepsis mouse model. At a dose of 10 mg/kg, mice were intraperitoneally administered with lipopolysaccharides. The myocardial tissue was harvested after 6 h for microarray analysis, qRT-PCR, and western blotting. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analysis were evaluated, and a competing endogenous RNA network was constructed, to evaluate the role of circRNAs related to autophagy in SICM. In total, 1,735 differently expressed circRNAs were identified in the LPS-treated group, including 990 upregulated and 745 downregulated circRNAs. The expression level of the autophagy-specific protein p62 decreased, while the ratio of LC3 II to LC3 I increased. Additionally, 309 mRNAs and 187 circRNAs were correlated with autophagy in myocardial tissue after SICM. Of these, 179 circRNAs were predicted to function as "miRNA sponges". Some distinctive circRNAs and mRNAs found by ceRNA analysis might be involved in autophagy in SICM. These findings provide insights into circRNAs and identified new research targets that may be used to further explore the pathogenesis of SICM.
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Cardiomiopatias , MicroRNAs , Sepse , Animais , Camundongos , RNA Circular/genética , Cardiomiopatias/genética , Sepse/complicações , Sepse/genética , Autofagia/genética , Lipopolissacarídeos , MicroRNAs/genética , RNA MensageiroRESUMO
BACKGROUND: Numerous studies have linked visceral adipose tissue (VAT) to gastrointestinal diseases. However, it remains unclear whether these associations reflect causal relationships. METHODS: We used a two-sample Mendelian randomization (MR) approach to elucidate the causal effect of VAT on nine non-tumour gastrointestinal diseases. The inverse-variance weighted method was used to perform the MR analyses. Complementary and multivariable MR analyses were performed to confirm the results. RESULTS: Genetically predicted higher VAT was associated with an increased risk of gastro-oesophageal reflux disease (GORD) (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.09-1.34; P = 3.06 × 10-4), duodenal ulcer (DU) (OR, 1.40; 95% CI, 1.10-1.77; P = 0.005), cholelithiasis (OR, 1.75; 95% CI, 1.53-2.00; P = 1.14 × 10-16), and non-alcoholic fatty liver disease (NAFLD) (OR, 2.68; 95% CI, 1.87-3.82; P = 6.26 × 10-8). There were suggestive associations between VAT and gastric ulcer (GU) (OR, 1.22; 95% CI, 1.01-1.48; P = 0.035) and acute pancreatitis (AP) (OR, 1.26; 95% CI, 1.05-1.52; P = 0.013). However, there was little evidence to support the associations between VAT and inflammatory bowel disease, irritable bowel syndrome, or chronic pancreatitis. The associations with GORD, GU, and NAFLD remained in the multivariable MR analyses with adjustment for body mass index (BMI). CONCLUSIONS: This study provided evidence in support of causal associations between VAT and GORD, GU, DU, cholelithiasis, AP, and NAFLD. Moreover, the associations between GORD, GU, and NAFLD were independent of the effect of BMI.
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Gastroenteropatias , Hepatopatia Gordurosa não Alcoólica , Pancreatite , Humanos , Doença Aguda , Gordura Intra-Abdominal , Análise da Randomização Mendeliana , Gastroenteropatias/epidemiologia , Gastroenteropatias/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Atrial tachycardias (ATs) frequently develop after a surgical Maze procedure. We aimed to elucidate the electrophysiologic mechanisms and their arrhythmogenic substrates of these ATs. METHODS AND RESULTS: We retrospectively reviewed 20 patients (14 females, mean age of 55.5 ± 8.6 years) with post-Maze ATs who underwent high-resolution mapping at three institutions. The slow conduction areas, reentry circuits, voltage signals, complex electrograms, and their correlation with the surgical incisions and lesions placed in the surgical Maze procedures were analyzed. Thirty-six ATs with a mean cycle length of 260.0 ± 67.6 ms were mapped in these patients. Among them, 22 (61.1%) were anatomical macro-reentrant ATs (AMAT), 12 (33.3%) non-AMATs (localized ATs), and 2 (5.6%) focal ATs, respectively. Epicardial conduction bridges were observed in 6/20 (30.0%) patients and 7/36 (19.4%) ATs. Different arrhythmogenic substrates were identified in these ATs, including slow conduction regions within the previous lesion areas or between the incisions and anatomical structures, the prolonged activation pathways caused by the short lesions connecting the tricuspid annulus, and the circuits around the long incisions and/or lesions. CONCLUSIONS: Reentry is the main mechanism of the post-Maze ATs. The pro-arrhythmic substrates are most likely caused by surgical incisions and lesions. The slow conduction regions and the protected channels yielded from these areas are the major arrhythmogenic factors.
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Fibrilação Atrial , Ablação por Cateter , Ferida Cirúrgica , Taquicardia Supraventricular , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/etiologia , Taquicardia Supraventricular/cirurgia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/complicaçõesRESUMO
AIMS: We aimed to investigate the effect and mechanism of pleiotropic chemokine CCL24 in heart failure. METHODS AND RESULTS: Compared with normal donators, the expression of CCL24 and number of cardiac M2 macrophages in heart were higher in heart failure patients, the same as plasma CCL24. Treatment with CCL24 antibody hindered Ang II (1500 ng/kg/min)-induced cardiac adverse remodeling through preventing cardiac hypertrophy and fibrosis. RNA-seq showed that CCL24/CCR3 axis was involved in immune and inflammatory responses. Single-cell analysis of cytometry by time of flight (CyTOF) revealed that CCL24 antibody decreased the M2 macrophage and monocyte polarization during Ang II stimulation. Immunofluorescence co-localization analysis confirmed the expression of CCR3 in macrophage and fibroblasts. Then, in vitro experiments confirmed that CCL24/CCR3 axis was also involved in cardiac primary fibroblast activation through its G protein-coupled receptor function. CONCLUSION: CCL24/CCR3 axis plays a crucial part in cardiac remodeling by stimulating M2 macrophage polarization and cardiac fibroblast activation. Cardiac M2 macrophages, CCL24 and circulation CCL24 increased in heart failure patients. Treatment with CCL24 Ab hindered Ang II induced cardiac structural dysfunction and electrical remodeling. In CCL24 Ab group RNA-seq found that it was related to immune responses and hypertrophic cardiomyopathy, CytoF revealed M2 macrophages and monocytes decreased obviously. In vitro,CCL24 promoted activation and migration of cardiac fibroblast.
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Angiotensina II , Insuficiência Cardíaca , Humanos , Animais , Camundongos , Quimiocina CCL24/metabolismo , Angiotensina II/farmacologia , Angiotensina II/metabolismo , Macrófagos/metabolismo , Insuficiência Cardíaca/metabolismo , Fibroblastos , Camundongos Endogâmicos C57BL , Receptores CCR3/metabolismoRESUMO
Under certain conditions, cardiovascular implantable electronic devices can be directly involved in initiating and sustaining pacemaker-mediated arrhythmias (PMA), of which repetitive reentrant ventriculoatrial synchrony (RRVAS) is the most well-known and common type. RRVAS, also known as pacemaker-mediated tachycardia, was commonly secondary to atrioventricular (AV) dissociation and subsequent ventriculoatrial (VA) conduction. RRVAS in a biventricular system is rare due to its less predisposition to the appearance of AV dissociation and subsequent VA conduction, but urgent in its adverse impact on cardiac resynchronization therapy (CRT), which may predispose to exacerbated heart failure. We present a rare case of recurrent PMA manifested as a right bundle branch block pattern in a patient with a CRT device. Notably, most episodes of PMA were triggered by a premature atrial contraction accompanied by the appearance of VA conduction with no prolongation of AV delay. In this study, we have demonstrated the impact of the appearance of VA conduction due to the loss of capture of right ventricular lead and its potential risk for inducing RRVAS in a CRT device.
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Terapia de Ressincronização Cardíaca , Marca-Passo Artificial , Humanos , Bloqueio de Ramo/complicações , Bloqueio de Ramo/terapia , Dispositivos de Terapia de Ressincronização Cardíaca , Eletrocardiografia , Marca-Passo Artificial/efeitos adversos , Arritmias Cardíacas/etiologia , Terapia de Ressincronização Cardíaca/efeitos adversosRESUMO
OBJECTIVES: Spinal cord stimulation (SCS) is an established neuromodulation method that regulates the cardiac autonomic system. However, the biological mechanisms of the therapeutic effects of SCS after myocardial infarction (MI) remain unclear. MATERIALS AND METHODS: Twenty-five rabbits were divided into five groups: SCS-MI (voltage: 0.5 v; pulse width: 0.2 ms; 50 Hz; ten minutes on and 30 minutes off; two weeks; n = 5), MI (n = 5), sham SCS-MI (voltage: 0 v; two weeks; n = 5), sham MI (n = 5), and blank control (n = 5) groups. MI was induced by permanent left anterior descending artery ligation. SCS-MI and sham SCS-MI rabbits received the corresponding interventions 24 hours after MI. Autonomic remodeling was evaluated using enzyme-linked immunosorbent assay and immunohistochemistry. Inflammation and myocardial fibrosis were assessed using immunohistochemistry, quantitative polymerase chain reaction, hematoxylin and eosin staining, Masson staining, and Western blot. RESULTS: SCS improved the abnormal systemic autonomic activity. Cardiac norepinephrine decreased after MI (p < 0.01) and did not improve with SCS. Cardiac acetylcholine increased with SCS compared with the MI group (p < 0.05). However, no difference was observed between the MI and blank control groups. Growth-associated protein 43 (p < 0.001) and tyrosine hydroxylase (p < 0.001) increased whereas choline acetyltransferase (p < 0.05) decreased in the MI group compared with the blank control group. These changes were attenuated with SCS. SCS inhibited inflammation, decreased the ratio of phosphorylated-Erk to Erk (p < 0.001), and increased the ratio of phosphorylated-STAT3 to STAT3 (p < 0.001) compared with the MI group. Myocardial fibrosis was also attenuated by SCS. CONCLUSIONS: SCS improved abnormal autonomic activity after MI, leading to reduced inflammation, reactivation of STAT3, and inhibition of Erk. Additionally, SCS attenuated myocardial fibrosis. Our results warrant future studies of biological mechanisms of the therapeutic effects of SCS after MI.
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Infarto do Miocárdio , Estimulação da Medula Espinal , Animais , Coelhos , Modelos Animais de Doenças , Fibrose , Inflamação/terapia , Infarto do Miocárdio/tratamento farmacológico , Estimulação da Medula Espinal/métodosRESUMO
PURPOSE: This study compared the effectiveness of sacubitril/valsartan (SV) vs. valsartan (V) for treating persistent atrial fibrillation (AF) after radio-frequency catheter ablation (RFCA). METHODS: Patients with persistent AF who received RFCA were randomly assigned to the SV or V treatment group with the intervention lasting for 12 months. The primary outcome included any atrial arrhythmia episode lasting ≥ 30 s after a 3-month blanking period. The secondary outcome included any atrial arrhythmia episode lasting ≥ 24 h or requiring cardioversion after a 3-month blanking period. The H2FPEF score was used to assess the possibility of patients suffering from heart failure with preserved ejection fraction. RESULTS: A total of 143 patients with persistent AF who received RFCA were randomized for the study, with 5 patients failing to follow-up. Among them, 29 (42%) out of 69 patients receiving V and 15 (21.7%) out of 69 patients receiving SV reached the primary endpoint (P < 0.001). A total of 26 (37.7%) out of 69 patients receiving V and 7 (10.1%) out of 69 patients receiving SV reached the secondary endpoint (P < 0.001). A decrease in the H2FPEF score after a 1-year follow-up seemed to be related to the recurrence of AF (OR, 0.065; 95% CI: 0.018-0.238, P < 0.001). CONCLUSIONS: SV can decrease AF recurrence after catheter ablation in patients with persistent AF at the 1-year follow-up. The mechanism for this process may be related to the reduction in the H2FPEF score in patients with preserved ejection fraction heart failure.
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Fibrilação Atrial , Ablação por Cateter , Insuficiência Cardíaca , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Recidiva , Ablação por Cateter/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Valsartana/efeitos adversos , Resultado do TratamentoRESUMO
Background: Coronavirus Disease 2019 (COVID-19) has rapidly evolved as a global pandemic. Observational studies found that visceral adipose tissue (VAT) increased the likelihood of worse clinical outcomes in COVID-19 patients. Whereas, whether VAT is causally associated with the susceptibility, hospitalization, or severity of COVID-19 remains unconfirmed. We aimed to investigate the causal associations between VAT and susceptibility, hospitalization, and severity of COVID-19. Methods: We applied a two-sample Mendelian randomization (MR) study to infer causal associations between VAT and COVID-19 outcomes. Single-nucleotide polymorphisms significantly associated with VAT were derived from a large-scale genome-wide association study. The random-effects inverse-variance weighted method was used as the main MR approach, complemented by three other MR methods. Additional sensitivity analyses were also performed. Results: Genetically predicted higher VAT mass was causally associated with higher risks of COVID-19 susceptibility [odds ratios (ORs) = 1.13; 95% confidence interval (CI), 1.09-1.17; P = 4.37 × 10-12], hospitalization (OR = 1.51; 95% CI = 1.38-1.65; P = 4.14 × 10-20), and severity (OR = 1.58; 95% CI = 1.38-1.82; P = 7.34 × 10-11). Conclusion: This study provided genetic evidence that higher VAT mass was causally associated with higher risks of susceptibility, hospitalization, and severity of COVID-19. VAT can be a useful tool for risk assessment in the general population and COVID-19 patients, as well as an important prevention target.
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COVID-19 , Humanos , COVID-19/epidemiologia , Gordura Intra-Abdominal , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , HospitalizaçãoRESUMO
Atherosclerosis, characterized as the chronic inflammation of the arterial wall, is one of the leading causes of coronary artery disease (CAD), and macrophages are found to play essential roles in the initiation and progression of inflammation in atherosclerosis. N6-methyladenosine (m6A) modification, as the most abundant epi-transcriptomic modification in mRNA, is found to mediate the atherogenic inflammatory cascades in vascular endothelium. The detailed molecular mechanism of m6A methylation regulating inflammatory response during atherosclerosis is still not fully known. In this study, we find oxidized low-density lipoprotein (oxLDL) stimulation increases methyltransferases Mettl3 and Mettl14 expressions in macrophages, whereas the total m6A modification level in macrophages decreases under oxLDL stimulation. Matrin-3 (Matr3), an RNA binding protein, is identified to play a suppressive role on oxLDL-mediated macrophage inflammatory responses through inhibiting activation of pro-inflammatory signaling, mitogen-activated protein kinase (Mapk) by m6A-mediated mRNA decay via regulating the formation of Mettl3-Mettl14 complex. Moreover, we find that Matr3 expression decreases in the oxLDL-stimulated macrophages, and the peripheral blood-derived monocytes from patients with CAD, and overexpression of Matr3 significantly alleviates atherosclerosis development in vivo. Our study for the first time clarifies the role of Matr3 on macrophage inflammatory responses during atherosclerotic development, and supplies deep understanding on the relationship of m6A modification and inflammatory responses in atherosclerosis.
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Aterosclerose , Metiltransferases , Humanos , Metiltransferases/genética , Metiltransferases/metabolismo , Proteínas de Ligação a RNA , Inflamação , Macrófagos/metabolismo , Aterosclerose/genética , Proteínas Associadas à Matriz Nuclear/metabolismoRESUMO
Background: Numerous studies have been conducted to investigate the relationship between tea consumption and the risk of cardiovascular diseases (CVD); however, no conclusive results have been achieved. We conducted a Mendelian randomization (MR) study to elucidate the causal associations between tea consumption and several CVD outcomes, including coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), and heart failure (HF). Methods: Independent single-nucleotide polymorphisms (SNPs) genome-wide significantly associated with tea consumption were used as instrumental variables (IVs). Summary statistics for CVD outcomes were obtained from the corresponding genetic consortia and the FinnGen consortium. The inverse-variance weighted (IVW) method was the primary analytical method, and MR estimates from different data sources were combined using fixed-effects meta-analysis. Supplementary MR analyses, including the weighted median, MR-Egger, and the MR pleiotropy residual sum and outlier methods, were conducted to evaluate the robustness of the results. Further MR analyses were repeated by including more genetic variants at a higher P-value threshold. Results: We found that genetically predicted tea consumption was not causally associated with any CVD outcomes in the IVW method using data from large genetic consortia [CAD: odds ratio (OR) = 1.00, 95% confidence interval (CI), 0.91, 1.10, P = 0.997; MI: OR = 0.98, 95% CI, 0.90, 1.08, P = 0.751; AF: OR = 0.97, 95% CI, 0.92, 1.03, P = 0.350; HF: OR = 0.96, 95% CI, 0.88, 1.05, P = 0.401] or the FinnGen consortium (CAD: OR = 1.06, 95% CI, 0.96, 1.17, P = 0.225; MI: OR = 1.01, 95% CI, 0.89, 1.15, P = 0.882; AF: OR = 1.00, 95% CI, 0.88, 1.14, P = 0.994; HF: OR = 0.96, 95% CI, 0.88, 1.04, P = 0.362). The results were robust and consistent across meta-analysis, supplementary MR analyses, and analyses with more IVs included. Conclusion: This MR study revealed no causal association between tea consumption and four CVD outcomes, suggesting that tea consumption may not be beneficial for the primary prevention of CVD.
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Background and Aims: Epidemiological studies have suggested positive associations between asthma and the risk of cardiovascular diseases (CVDs). However, causality remains inconclusive. We aim to explore the causal associations between asthma and CVDs risk using the Mendelian Randomization (MR) approach. Methods: We obtained summary-level data for eight CVDs [including atrial fibrillation (AF), coronary artery disease (CAD), heart failure (HF), stroke, ischemic stroke, large artery stroke, small vessel stroke, and cardioembolic stroke] from several large genome-wide association studies (GWASs) and the FinnGen consortium. Nine lead single-nucleotide polymorphisms associated with asthma (p < 5 × 10-8) were identified from the GWAS conducted by the Trans-National Asthma Genetic Consortium. MR analyses were performed using the inverse variance weighted method, supplemented by the weighted median and MR-Egger methods. Results: Inverse variance weighted method showed suggestive effects of genetically determined asthma on AF (odds ratio (OR), 1.08; 95% confidence interval (CI), 1.02, 1.14; p = 0.009) and HF (OR, 1.05; 95% CI, 1.01, 1.09; p = 0.029). We found no causal associations between asthma and other CVDs. No horizontal pleiotropy was observed. Conclusion: This MR study provides genetic evidence suggesting a causal association between asthma and the risk of AF and HF, although not at the level of significance after multiple testing correction. Programs aimed at treating asthma among asthmatics might help prevent the adverse health effects inflicted by CVDs.
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BACKGROUND: Benefits of adjunctive ablation strategies beyond circumferential pulmonary vein isolation (CPVI) are uncertain in patients with persistent atrial fibrillation (PeAF). OBJECTIVES: This study sought to compare clinical outcomes of CPVI plus low-voltage area (LVA) modification during STABLE-SR (SubsTrate ABlation in the LEft Atrium during Sinus Rhythm) vs circumferential pulmonary vein isolation (CPVI) alone in patients with PeAF. METHODS: From March 2018 to August 2019, 300 patients with PeAF who underwent de novo ablation were recruited and prospectively randomized to either STABLE-SR group (n = 150) or CPVI alone (n = 150) group. In the STABLE-SR group, after CPVI, high-density voltage mapping of left atrium (LA) was performed during sinus rhythm, and additive ablation targeted LVA and complex electrograms, if any were present. All the ablations were titrated by ablation index. The primary endpoint was freedom from documented atrial arrhythmias lasting for ≥30 s without the use of antiarrhythmic drugs, after a single ablation procedure and blanking period of 3 months. RESULTS: After 18 months, atrial-arrhythmia-free survival did not differ significantly between STABLE-SR group and CPVI alone group (67.2% vs 67.4%; HR: 0.89; 95% CI: 0.55-1.36; P = 0.52). Only around one-half of the patients (50.2%) had abnormal LA substrate with a medium LVA burden of 4.6% (2.1%-9.5%). However, the success rate differs dramatically between patients with normal vs abnormal LA substrate (84.8% vs 60.9%; P < 0.001). CONCLUSIONS: Additional LVA ablation did not improve successful rates of CPVI in this PeAF cohort, of whom one-half had normal LA substrate. Voltage map could identify patients with PeAF with normal LA substrate who can achieve excellent rhythm control with CPVI alone. (CPVI Alone Versus CPVI Plus Electrophysiological Substrate Ablation in the LA During SR for the Treatment of Non-PAF [STABLE-SR_II]; NCT03448562).
Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Humanos , Veias Pulmonares/cirurgia , Fatores de Tempo , Resultado do TratamentoRESUMO
Objective: This study focused on mood regulations and their association with sociodemographic status, exercise pattern, and physical conditions of adults and older adults in China who did not undergo interventions. Method: Data were based on the 2016 to 2018 Guangdong National Physique Monitoring data, in which 5242 participants aged 20-69 years were recruited. Multiple statistical analysis methods, such as descriptive and logistic regression analyses, were used to study each exercise motivation and its association with influencing factors, including sociodemographic characteristics, exercise measurements, and physical conditions. An exercise index for mental health was also used to investigate the number and types of people who were more likely to meet the index. Results: We observed that 44.9% (2355/5242) of participants did not engage in physical exercise in this study. Only older participants (40 to 69 years old) and those with an average level of education (high school/technical secondary school) showed a significant association with exercising for mood regulation. Few people met the index that is good for mental health (16.64% [872/5242] met index 1, and 2.84% (149/5242) met index 2), and higher education showed a significant association with a reduction in the mental health burden and the prevention of depression. Conclusion: This study found that motivating people to be more active and educating them on the potential mental health benefits of exercise could help them to exercise more.