李乐
中国医学科学院阜外医院 心内科
BACKGROUND:Substantial focus has been placed on atrial fibrillation (AF) treatment and associated stroke prevention rather than preventing AF itself. We employed Mendelian randomization (MR) approach to examine the causal relationships between 50 modifiable risk factors (RFs) and AF.METHODS:Instrumental variables for genetically predicted exposures were derived from corresponding genome-wide association studies (GWASs). Summary-level statistical data for AF were obtained from a GWAS meta-analysis (discovery dataset, N = 1,030,836) and FinnGen (validation dataset, N = 208,594). Univariable and multivariable MR analyses were performed, primarily using inverse variance weighted method with a series of robust sensitivity analyses.RESULTS:Genetic predisposition to insomnia, daytime naps, apnea, smoking initiation, moderate to vigorous physical activity and obesity traits, including body mass index, waist-hip ratio, central and peripheral fat/fat-free mass, exhibited significant associations with an increased risk of AF. Coffee consumption and ApoB had suggestive increased risks. Hypertension (odds ratio (OR) 95% confidence interval (CI): 5.26 (4.42, 6.24)), heart failure (HF) (OR 95% CI, 4.77 (2.43, 9.37)) and coronary artery disease (CAD) (OR 95% CI: 1.20 (1.16, 1.24)) were strongly associated with AF, while college degree, higher education attachment and HDL levels were associated with a decreased AF risk. Reverse MR found a bidirectional relationship between genetically predicted AF and CAD, HF and ischemic stroke. Multivariable analysis further indicated that obesity-related traits, systolic blood pressure and lower HDL levels independently contributed to the development of AF.CONCLUSIONS:This study identified several lifestyles and cardiometabolic factors that might be causally related to AF, underscoring the importance of a holistic approach to AF management and prevention.
European journal of clinical investigation 2024
BACKGROUND:The stress hyperglycemia ratio (SHR) has been demonstrated as an independent risk factor for acute kidney injury (AKI) in certain populations. However, this relationship in patients with congestive heart failure (CHF) remains unclear. Our study sought to elucidate the relationship between SHR and AKI in patients with CHF.METHODS:A total of 8268 patients with CHF were included in this study. We categorized SHR into distinct groups and evaluated its association with mortality through logistic or Cox regression analyses. Additionally, we applied the restricted cubic spline (RCS) analysis to explore the relationship between SHR as a continuous variable and the occurrence of AKI. The primary outcome of interest in this investigation was the incidence of AKI during hospitalization.RESULTS:Within this patient cohort, a total of 5,221 (63.1%) patients experienced AKI during their hospital stay. Upon adjusting for potential confounding variables, we identified a U-shaped correlation between SHR and the occurrence of AKI, with an inflection point at 0.98. When the SHR exceeded 0.98, for each standard deviation (SD) increase, the risk of AKI was augmented by 1.32-fold (odds ratio [OR]: 1.32, 95% CI: 1.22 to 1.46). Conversely, when SHR was below 0.98, each SD decrease was associated with a pronounced increase in the risk of AKI.CONCLUSION:Our study reveals a U-shaped relationship between SHR and AKI in patients with CHF. Notably, we identified an inflection point at an SHR value of 0.98, signifying a critical threshold for evaluating AKI in this population.
Cardiovascular diabetology 2024
BACKGROUND:Autoimmune myocarditis, with increasing incidence and limited therapeutic strategies, is in urgent need to explore its underlying mechanisms and effective drugs. Pyroptosis is a programmed cell death that may contribute to the pathogenesis of myocarditis. Nonetheless, no direct evidence validated the role of pyroptosis in autoimmune myocarditis. Lupeol (Lup), a pentacyclic triterpene, possesses various biological activities such as antidiabetic properties. However, the effects of Lup on autoimmune myocarditis and pyroptosis remain unelucidated.PURPOSE:This study aimed to reveal the role of pyroptosis in autoimmune myocarditis and explore the protective effects of Lup, and its engaged mechanisms.METHODS:The experimental autoimmune myocarditis (EAM) mouse model was established by immunization with a fragment of cardiac myosin in Balb/c mice. Lup and MCC950 were administered after EAM induction. The protective effects were assessed by inflammation score, cardiac injury, chronic fibrosis, and cardiac function. Mechanistically, the effects of Lup on the M1 polarization and pyroptosis of macrophages were evaluated. Transcriptome sequencing and molecular docking were subsequently employed, and the underlying mechanisms of Lup were further explored in vitro with small interfering RNA and adenovirus.RESULTS:Administration of Lup and MCC950 alleviated EAM progression. Western blotting and immunofluorescence staining identified macrophages as the primary cells undergoing pyroptosis. Lup inhibited the expression of pyroptosis-associated proteins in macrophages during EAM in a dose-dependent manner. Furthermore, Lup suppressed pyroptosis in both bone marrow-derived macrophages (BMDMs) and THP-1-derived macrophages in vitro. In addition, Lup inhibited the M1 polarization of macrophages both in vivo and in vitro. Mechanistically, the protective effects of Lup were demonstrated via the suppression of the nuclear factor-κΒ (NF-κB) signaling pathway. Transcriptome sequencing and molecular docking revealed the potential involvement of peroxisome proliferator-associated receptor α (PPARα). Subsequently, we demonstrated that Lup activated PPARα to reduce the expression level of LACC1, thereby inhibiting the NF-κB pathway and pyroptosis.CONCLUSION:Our findings indicated the crucial role of macrophage pyroptosis in the pathogenesis of EAM. Lup ameliorated EAM by inhibiting the M1 polarization and pyroptosis of macrophages through the PPARα/LACC1/NF-κB signaling pathway. Thus, our results provided a novel therapeutic target and agent for myocarditis.
Phytomedicine : international journal of phytotherapy and phytopharmacology 2024
BACKGROUND:Stress hyperglycemia has been associated with poor prognosis in patients admitted to the cardiac intensive care unit (ICU). Recently, the stress hyperglycemia ratio (SHR) has been proposed to reflect true acute hyperglycemic. This study aimed to investigate the relationship between SHR and prognosis of patients in the cardiac ICU.METHODS:A retrospective analysis was conducted on a cohort of 5,564 patients admitted to the cardiac ICU. The participants were divided into seven groups based on their SHR levels. SHR was calculated as admission blood glucose/[(28.7 × HbA1c %) - 46.7]. The primary outcomes of this study were 28-day all-cause mortality.RESULTS:During the follow-up period, 349 (6.3%) patients succumbed within 28 days. A U-shaped correlation between SHR and mortality persisted, even after adjusting for other confounding variables, with a discernible inflection point at 0.95. When SHR surpassed 0.95, each standard deviation (SD) increase corresponded to a 1.41-fold elevation in the risk of mortality (odds ratio [OR]: 1.41, 95% CI: 1.25 to 1.59). In contrast, when SHR fell below 0.95, each SD increment correlated with a significantly reduced risk of mortality (OR: 0.56, 95% CI: 0.34 to 0.91).CONCLUSION:There was a U-shaped association between SHR and short -term mortality in patients in the cardiac ICU. The inflection point of SHR for poor prognosis was identified at an SHR value of 0.95.
Diabetes & metabolic syndrome 2024
AIMS:The aim of this study was to investigate the outcomes of catheter ablation (CA) in preventing arrhythmic events among patients with symptomatic Brugada syndrome (BrS) who declined implantable cardioverter defibrillator (ICD) implantation.METHODS AND RESULTS:A total of 40 patients with symptomatic BrS were included in the study, of which 18 refused ICD implantation and underwent CA, while 22 patients received ICD implantation. The study employed substrate modification (including endocardial and epicardial approaches) and ventricular fibrillation (VF)-triggering pre-mature ventricular contraction (PVC) ablation strategies. The primary outcomes were a composite endpoint consisting of episodes of VF and sudden cardiac death during the follow-up period. The study population had a mean age of 43.8 ± 9.6 years, with 36 (90.0%) of them being male. All patients exhibited the typical Type 1 BrS electrocardiogram pattern, and 16 (40.0%) were carriers of an SCN5A mutation. The Shanghai risk scores were comparable between the CA and the ICD groups (7.05 ± 0.80 vs. 6.71 ± 0.86, P = 0.351). Ventricular fibrillation-triggering PVCs were ablated in 3 patients (16.7%), while VF substrates were ablated in 15 patients (83.3%). Epicardial ablation was performed in 12 patients (66.7%). During a median follow-up of 46.2 (17.5-73.7) months, the primary outcomes occurred more frequently in the ICD group than in the CA group (5.6 vs. 54.5%, Log-rank P = 0.012).CONCLUSION:Catheter ablation is an effective alternative therapy for improving arrhythmic outcomes in patients with symptomatic BrS who decline ICD implantation. Our findings support the consideration of CA as an alternative treatment option in this population.
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2023
BACKGROUND:Life-threatening ventricular arrhythmias (LTVAs) are main causes of sudden cardiac arrest and are highly associated with an increased risk of mortality. A prediction model that enables early identification of the high-risk individuals is still lacking.OBJECTIVE:We aimed to build machine learning (ML)-based models to predict in-hospital mortality in patients with LTVA.METHODS:A total of 3140 patients with LTVA were randomly divided into training (n=2512, 80%) and internal validation (n=628, 20%) sets. Moreover, data of 2851 patients from another database were collected as the external validation set. The primary output was the probability of in-hospital mortality. The discriminatory ability was evaluated by the area under the receiver operating characteristic curve (AUC). The prediction performances of 5 ML algorithms were compared with 2 conventional scoring systems, namely, the simplified acute physiology score (SAPS-II) and the logistic organ dysfunction system (LODS).RESULTS:The prediction performance of the 5 ML algorithms significantly outperformed the traditional models in predicting in-hospital mortality. CatBoost showed the highest AUC of 90.5% (95% CI 87.5%-93.5%), followed by LightGBM with an AUC of 90.1% (95% CI 86.8%-93.4%). Conversely, the predictive values of SAPS-II and LODS were unsatisfactory, with AUCs of 78.0% (95% CI 71.7%-84.3%) and 74.9% (95% CI 67.2%-82.6%), respectively. The superiority of ML-based models was also shown in the external validation set.CONCLUSIONS:ML-based models could improve the predictive values of in-hospital mortality prediction for patients with LTVA compared with traditional scoring systems.
Journal of medical Internet research 2023
BACKGROUND:High-sensitivity C-reaction protein (hsCRP), a biomarker of residual inflammatory risk, has been demonstrated with poor cardiovascular outcomes. We aimed to investigate the prognostic value of hsCRP in patients undergoing percutaneous coronary intervention (PCI) with or without diabetes mellitus (DM).METHODS:In this large-scale, prospective cohort study, we enrolled 8050 consecutive patients who underwent PCI for coronary artery stenosis. All subjects were stratified as high hsCRP (> 3 mg/L) and low hsCRP (≤ 3 mg/L) and were divided into four groups (hsCRP-L/non-DM, hsCRP-H/non-DM, hsCRP-L/DM, hsCRP-H/DM). The primary endpoint of the study was major adverse cardiovascular events (MACEs), including all-cause mortality, myocardial infarction, stroke, and unplanned vessel revascularization, evaluated at a 3 year follow-up.RESULTS:After 35.7 months (interquartile range: 33.2 to 36.0 months) of median follow-up time, 674 patients suffered from MACEs. We found elevated hsCRP was highly associated with an increased risk of MACEs in both diabetic (hazard ratio [HR] = 1.68, 95% confidence interval CI 1.29-2.19, P < 0.001) and non-diabetic patients (HR = 1.31, 95% CI: 1.05-1.62, P = 0.007) after adjustment for other confounding factors. Kaplan-Meier survival analysis showed the highest incidence of MACEs in hsCRP-H/DM (P < 0.001). In addition, the results of the restricted cubic spline analysis suggested a positive linear relationship between hsCRP and MACEs.CONCLUSION:Elevated hsCRP is an independent risk factors of MACEs in patients undergoing PCI irrespective of glycemic metabolism status.
Cardiovascular diabetology 2023
BACKGROUND:Renal denervation (RDN) is a promising treatment based on catheter intervention for patients with refractory hypertension. However, the effect in patients with isolated systolic hypertension (ISH) remains controversial. The aim of this meta-analysis was to determine the blood pressure lowing effect of RDN in patients with ISH compared with combined systolic/diastolic hypertension (CH) patients.METHODS:PubMed, Embase, Cochrane and ClinicalTrials.gov were searched for prospective clinical studies that included RDN. The outcomes of interest were the change of 24-hour ambulatory systolic blood pressure (SBP) from baseline. We used the fixed effects model to calculate weighted mean difference (WMD) with 95% confidence interval (CI).RESULTS:Six trials were included, with 1405 participants, including 597 patients with ISH and 808 patients with CH. Mean follow-up was five months. The reduction of 24-hour ambulatory SBP was significantly greater for the CH patients than the ISH patients (WMD = 3.89, 95% CI: 2.32-5.45, P < 0.0001). RDN also showed a greater reduction in office SBP in the CH patients compared to the ISH patients (WMD = 10.24, 95% CI: 4.24-15.74, P = 0.0003). And the effect was independent of age, length of follow-up, and ablation device.CONCLUSIONS:RDN provides superior blood pressure control in the CH patients compared with the ISH patients, and the CH patients may be the best suitable population for which RDN is indicated.
Journal of geriatric cardiology : JGC 2023
BACKGROUND:The stress hyperglycemia ratio (SHR) has demonstrated a noteworthy association with unfavorable cardiovascular clinical outcomes and heightened in-hospital mortality. Nonetheless, this relationship in critically ill patients remains uncertain. This study aims to elucidate the correlation between SHR and patient prognosis within the critical care setting.METHODS:A total of 8978 patients admitted in intensive care unit (ICU) were included in this study. We categorized SHR into uniform groups and assessed its relationship with mortality using logistic or Cox regression analysis. Additionally, we employed the restricted cubic spline (RCS) analysis method to further evaluate the correlation between SHR as a continuous variable and mortality. The outcomes of interest in this study were in-hospital and 1-year all-cause mortality.RESULTS:In this investigation, a total of 825 (9.2%) patients experienced in-hospital mortality, while 3,130 (34.9%) individuals died within the 1-year follow-up period. After adjusting for confounding variables, we identified a U-shaped correlation between SHR and both in-hospital and 1-year mortality. Specifically, within the SHR range of 0.75-0.99, the incidence of adverse events was minimized. For each 0.25 increase in the SHR level within this range, the risk of in-hospital mortality rose by 1.34-fold (odds ratio [OR]: 1.34, 95% CI: 1.25-1.44), while a 0.25 decrease in SHR within 0.75-0.99 range increased risk by 1.38-fold (OR: 1.38, 95% CI: 1.10-1.75).CONCLUSION:There was a U-shaped association between SHR and short- and long-term mortality in critical ill patients, and the inflection point of SHR for poor prognosis was identified at an SHR value of 0.96.
Cardiovascular diabetology 2023
BACKGROUND AND AIMS:Non-alcoholic fatty liver disease (NAFLD) is prevalent in hypertensive people, but the causal effect remains unclear. We employed Mendelian randomization (MR) approach to assess the causality between NAFLD and different blood pressure (BP) parameters.METHOD AND RESULTS:Instrumental variables for genetically predicted NAFLD, including chronically elevated serum alanine aminotransferase levels (cALT) and imaging and biopsy-confirmed NAFLD, were obtained from a genome-wide association study (N = 164,197). Multiple MR methods were implemented, including Inverse variance weighted, MR-Egger, Maximum likelihood, Weighted median, Simple median, Penalised weighted median, MR-RAPS, and cML-MA. Outliers were detected using MR-PRESSO, and pleiotropy was assessed using MR-Egger intercept and Phenoscanner. Heterogeneity was quantified using Cochran's Q and Rucker's Q' tests. Potential shared risk factors were analyzed to reveal the mediating effect. A higher genetic predisposition to cALT was causally associated with an increased risk of elevated BP levels, resulting in 0.65 mmHg (95% CI, 0.42-0.87), 0.38 mmHg (95% CI, 0.25-0.50) and 0.33 mmHg (95% CI, 0.22-0.44) higher for systolic BP, diastolic BP and pulse pressure, respectively. When more stringent criteria were used, imaging and biopsy-confirmed NAFLD showed a 1.12 mmHg (95% CI, 0.94-1.30) increase in SBP and a 0.55 mmHg (95% CI, 0.39-0.70) increase in DBP. Risk factor and mediation analyses suggested type 2 diabetes and fasting insulin levels might mediate the causal relationship between NAFLD and BP.CONCLUSION:The two-sample MR analyses showed robust causal effects of genetically predicted NAFLD on 3 different BP indices. The shared genetic profile between NAFLD and BP may suggest important therapeutic targets and early interventions for cardiometabolic risk factors.
Nutrition, metabolism, and cardiovascular diseases : NMCD 2023
