Cardiovascular Therapeutics最新文献

Coronary artery disease (CAD) is a complex condition influenced by genetic factors, lifestyle, and other risk factors that contribute to increased mortality. This study is aimed at evaluating the diagnostic potential of genes associated with cuproptosis, ferroptosis, and pyroptosis (CFP) using network modularization and machine learning methods. CAD-related datasets GSE42148, GSE20680, and GSE20681 were sourced from the GEO database, and genes related to CFP genes were gathered from MsigDB and FerrDb datasets and literature. To identify diagnostic genes linked to these pathways, weighted gene coexpression network analysis (WGCNA) was used to isolate CAD-related modules. The diagnostic accuracy of key genes in these modules was then assessed using LASSO, SVM, and random forest models. Immunity and drug sensitivity correlation analyses were subsequently performed to investigate possible underlying mechanisms. The function of a potential gene, STK17B, was analyzed through western blot and transwell assays. Two CAD-related modules with strong correlations were identified and validated. The SVM model outperformed LASSO and random forest models, demonstrating superior discriminative power (AUC = 0.997 in the blue module and AUC = 1.000 in the turquoise module), with nine key genes identified: CTDSP2, DHRS7, NLRP1, MARCKS, PELI1, RILPL2, JUNB, STK17B, and SLC40A1. Knockdown of STK17B inhibited cell migration and invasion in human umbilical vein endothelial cells. In summary, our findings suggest that CFP genes hold potential as diagnostic biomarkers and therapeutic targets, with STK17B playing a role in CAD progression.

Purpose: This study is aimed at identifying clinical and echocardiographic factors associated with all-cause mortality or heart transplantation (HTx) in young patients with dilated cardiomyopathy (DCM).

Methods: We conducted a retrospective analysis of hospitalized patients (aged 18–45 years) diagnosed with DCM between January 2012 and December 2022. All patients underwent a 2-year medical therapy for heart failure, followed by at least 1 year of follow-up. Clinical and echocardiographic data were collected at baseline and after the 2-year treatment period. Multivariate Cox proportional hazards regression with a backward stepwise method was used to identify risk factors for all-cause mortality or HTx.

Results: The study cohort comprised 67 patients. Over a median follow-up of 38 months (range 18–50), 15 patients died and 24 underwent HTx. Significant risk factors for all-cause mortality/HTx included smoking, digoxin use, elevated N-terminal pro-brain natriuretic peptide (NT-proBNP, ≥ 5678 pg/mL), higher C-reactive protein (CRP, ≥ 3.0 mg/L), higher uric acid (UA, ≥ 570 μmol/L), lower left ventricular ejection fraction (LVEF, ≤25%), and enlarged end-diastolic left ventricular diameter (LVD, ≥ 65 mm). Among these, elevated CRP (hazard ratio, HR = 6.727, p < 0.001) and enlarged LVD (HR = 3.038, p = 0.007) were the strongest independent risk factors, irrespective of other risk factors. Moreover, each 5 mm annual increase in end-systolic left atrial diameter (LAD, HR = 3.641, p < 0.001) and each unit annual increase in Ln(NT-proBNP) (HR = 4.069, p < 0.001) were the strongest predictors of all-cause mortality/HTx, even after accounting for the effects of body mass index, duration of treatment, and baseline CRP level.

Conclusions: Intensive monitoring and medical care may be beneficial for young adult DCM patients with defined risk factors such as smoking, elevated NT-proBNP and CRP, lower LVEF, and enlarged LV diameter. Our findings suggest that personalized intensive monitoring and medical care based on identified risk factors may improve outcomes in young adult DCM patients.

Background: With the progression of chronic kidney disease (CKD), we can often observe cardiac remodeling, fibrosis, and cardiac failure in patients. Cysteine-rich protein 61 (CCN1) is an extracellular matrix protein that plays a reuse role in cardiac remodeling. However, whether CCN1 participates in the crosslink between the heart and kidney in CKD and the potential mechanism remains unknown.

Methods: We constructed a mouse model of CKD by 5/6 nephrectomy (5/6 Nx). Hematoxylin–eosin staining (H&E), Masson’s trichrome staining, and Sirius red staining were used to observe cardiac morphology and fibrosis. H9c2 cells were treated with si-CCN1 or si-NC or mitogen-activated protein kinase (MAPK)–related inhibitors or agonist before being cultured with 5/6 Nx mouse serum. The relative protein level was detected by Western blotting.

Results: We observed that CCN1 expression was markedly enhanced in the serum and heart tissues, accompanied by disordered myocardial arrangement, obvious cardiac fibrosis, hypertrophy, and decreased cardiac systolic function reflected by echocardiography. The relative markers collagen 1 (COL-1), transforming growth factor-β (TGF-β), heavy-chain cardiac myosin (MyHC), and atrial natriuretic peptide (ANP) presented an increase in expression. In vivo and in vitro, after the knockdown of CCN1, the above results in the CKD group or CKD serum group were reversed; in addition, the MAPK signaling pathway was obviously activated due to 5/6 Nx, which was abolished by CCN1 inhibition. CCN1 silencing or MAPK pathway inhibition also decreased the expression of myocardial fibrosis and hypertrophy markers in H9c2 cells, while MAPK-related agonist partly reversed the effect of CCN1 inhibition.

Conclusion: Our in vivo and in vitro study showed that specific CCN1 deficiency markedly alleviated cardiac remodeling in 5/6 Nx mice through the inhibition of the MAPK pathway.

Background: Identifying high-risk patients with acute pulmonary embolism is vital for improving disease prognosis. However, current guidelines and research on risk factors are insufficient to meet clinical needs. This study was aimed at exploring novel risk factors to predict in-hospital mortality.

Methods: We utilized a patient cohort from the Medical Information Mart for Intensive Care Version IV (MIMIC-IV) database as training cohort. Major analyses included screening risk factors for in-hospital mortality, correlation analysis via smooth curve fitting, multivariate Cox regression, and subgroup analysis. The findings were further validated with our own institute patient cohort.

Results: Among 1463 adult patients with acute pulmonary embolism in the MIMIC-IV database, the overall in-hospital mortality rate was 17.8%. A nonlinear correlation was observed between urine output and in-hospital mortality. A urine discharge less than 0.85 mL/kg/h was used as the threshold and was negatively associated with the risk for in-hospital death. Compared to patients with urine value < 0.5 mL/kg/h, the risk for in-hospital mortality reduced by 36% and 48% in patients with urine values of 0.5–0.85 mL/kg/h and > 0.85 mL/kg/h, with the hazard ratios of 0.64 (0.47, 0.87) and 0.52 (0.38, 0.72), respectively. This association remained significant in the subgroup analysis after adjusting for age, gender, hypotension, and low oxygen saturation. Our validation patient cohort (n = 151) further confirmed the strong association of the urine value with in-hospital mortality and consistent cutoff value.

Conclusion: Our study revealed a negative association of urine output with in-hospital mortality in acute pulmonary embolism patients, with the optimal urine output being significantly higher than the value of other critical illnesses.

Background: Recent studies have indicated that cluster of differentiation 36 (CD36) is closely linked to dyslipidemia and early-onset coronary artery disease (EOCAD). This study is aimed at investigating the impacts of CD36 gene variants on lipid profiles and EOCAD risk.

Methods: PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until June 15, 2024.

Results: In total, 25 studies (11,494 individuals) were included for the analysis. The A allele carriers of the rs1761667 variant had higher high-density lipoprotein cholesterol (HDL-C) levels and higher EOCAD risk than noncarriers. In contrast, the G allele carriers of the rs1049673 and rs3211956 variants had lower low-density lipoprotein cholesterol (LDL-C) levels and lower EOCAD risk than noncarriers. Subgroup analysis indicated that the antiatherosclerotic impact and reduced EOCAD risk were primarily observed in Chinese with rs1049673 and rs3211956.

Conclusions: The rs1761667, rs1049673, and rs3211956 variants of the CD36 gene have significant impacts on lipid levels and may serve as genetic markers for the risk of EOCAD primarily in Chinese. The impacts of CD36 variants on EOCAD risk are mediated, at least partly, by dyslipidemia. Genetic screening of CD36 gene variants may be helpful for early intervention or prevention of EOCAD in individuals with high risk factors.

Breath and brain activity have been integral to daily life since time immemorial. Cognition and cardiorespiratory responses are closely interlinked, necessitating further investigation into their dynamics. The potential benefits of combining motor imagery (MI) and action observation (AO) based breathing exercises in rehabilitation have not been fully explored. This study was aimed at assessing the acute effects of MI combined with AO on cognitive function and cardiorespiratory responses. Thirty-three healthy adults were randomized into MI combined with AO breathing (MI+AO), active respiratory exercise (ARE), and control groups, with equal distribution across groups. Electroencephalography (EEG) data were collected using a Muse EEG headband, and cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) while imagining activities were measured via the Kinesthetic and Visual Imagery Questionnaire (KVIQ). Significant improvements in the Timed Up and Go (TUG) test and systolic blood pressure were observed in the ARE group (p < 0.05), alongside improvements in MoCA and KVIQ scores (p < 0.05). EEG data revealed significant decreases in delta and theta power at the temporoparietal (TP) location in the ARE group (p < 0.05). These findings suggest that MI and AO, when combined with respiratory exercises, may serve as effective passive strategies to support cognition and cardiorespiratory function, particularly in individuals who struggle to actively participate in pulmonary rehabilitation.

Trial Registration: ClinicalTrials.gov identifier: NCT06099483

Background: Cardiovascular diseases (CVDs) encompass a group of diseases that affect the heart and/or blood vessels, making them the leading cause of global mortality. In our study, we performed proteome-wide Mendelian randomization (MR) and colocalization analyses to identify novel therapeutic protein targets for CVDs and evaluate the potential drug-related protein side effects.

Methods: We conducted a comprehensive proteome-wide MR study to assess the causal relationship between plasma proteins and the risk of CVDs. Summary-level data for 4907 circulating protein levels were extracted from a large-scale protein quantitative trait loci (pQTL) study involving 35,559 individuals. Additionally, genome-wide association study (GWAS) data for CVDs were extracted from the UK Biobank and the Finnish database. Colocalization analysis was utilized to identify causal variants shared between plasma proteins and CVDs. Finally, we conducted a comprehensive phenome-wide association study (PheWAS) using the R10 version of the Finnish database. This study was aimed at examining the potential drug-related protein side effects in the treatment of CVDs. A total of 2408 phenotypes were included in the analysis, categorized into 44 groups.

Results: The research findings indicate the following associations: (1) In coronary artery disease (CAD), the plasma proteins A4GNT, COL6A3, KLC1, CALB2, KPNA2, MSMP, and ADH1B showed a positive causal relationship (p-fdr < 0.05). LAYN and GCKR exhibited a negative causal relationship (p-fdr < 0.05). (2) In chronic heart failure (CHF), PLG demonstrated a positive causal relationship (p-fdr < 0.05), while AZGP1 displayed a negative causal relationship (p-fdr < 0.05). (3) In ischemic stroke (IS), ALDH2 exhibited a positive causal relationship (p-fdr < 0.05), while PELO showed a negative causal relationship (p-fdr < 0.05). (4) In Type 2 diabetes (T2DM), the plasma proteins MCL1, SVEP1, PIP4K2A, RFK, HEXIM2, ALDH2, RAB1A, APOE, ANGPTL4, JAG1, FGFR1, and MLN demonstrated a positive causal relationship (p-fdr < 0.05). PTPN9, SNUPN, VAT1, COMT, CCL27, BMP7, and MSMP displayed a negative causal relationship (p-fdr < 0.05). Colocalization analysis conclusively identified that AZGP1, ALDH2, APOE, JAG1, MCL1, PTPN9, PIP4K2A, SNUPN, and RAB1A share a single causal variant with CVDs (PPH3 + PPH4 > 0.8). Further phenotype-wide association studies have shown some potential side effects of these nine targets (p-fdr < 0.05).

Conclusions: This study identifies plasma proteins with significant causal associations with CVDs, providing a more comprehensive understanding of potential therapeutic targets. These findings contribute to our knowledge of the underlying mechanisms and offer insights into potential avenues for treatment.

The NACHT, leucine-rich repeat, and pyrin domain–containing protein 3 (NLRP3) inflammasome plays an essential role in myocardial infarction (MI) development. Up to now, no bibliometric analyses of NLRP3 in MI have been performed. Publications related to NLRP3 in MI from 1 January 2013 to 20 August 2024 were extracted from the Web of Science Core Collection (WoSCC). HistCite Pro, CiteSpace, VOSviewer, Scimago Graphica, and bibliometric online analysis program were used for bibliometric analysis and visualization. The impact of publications was assessed using the total global citation score (TGCS). A total of 324 articles (284 articles and 40 reviews) were included. China has published the most in this field, followed by the United States. Harbin Medical University was the leading institution for research related to NLRP3 in MI. Professor Abbate A. from the United States has made significant achievements in this field. International Immunopharmacology was the most active journal and Journal of Cardiovascular Pharmacology was the most cited journal. This study systematically summarizes the research results of NLRP3 in MI over the past 12 years. NLRP3 in myocardial ischemia–reperfusion injury (MIRI) will become a hot research topic, and translational research on NLRP3 inhibitors in MIRI will benefit a greater number of patients.

Background: Atrial fibrillation (AF) complicates cardiac surgery, including valve replacements, increasing perioperative risk and impacting long-term outcomes. Concomitant radiofrequency ablation (RFA) during cardiac surgeries shows promise for managing AF. This study investigates the safety, early efficacy, and predictors of atrial arrhythmia recurrence (AAR) following AF RFA during total thoracoscopic valve replacement (TTVR).

Methods: This retrospective observational study included 625 patients who underwent TTVR with concomitant AF RFA from January 2017 to May 2023. Demographic data, preoperative characteristics, operative details, and postoperative outcomes were collected. The primary outcome was AAR within 3 months postoperatively.

Results: Of the 625 patients, AAR was observed in 21.6% (135 patients), with a median time to recurrence of 45 days. Independent predictors of early AAR included age, AF duration, body mass index (BMI), AF type, left atrial diameter, and ablation extent. Notably, persistent and long-standing persistent AF, a larger left atrial diameter, and ablation of the left atrium alone were associated with higher recurrence risks. The in-hospital mortality rate was 1.6%, with no significant differences in early complications between the recurrence and nonrecurrence groups.

Conclusions: Concomitant AF RFA during TTVR is a safe and effective strategy for managing AF in minimally invasive valve surgery. Early predictors of AAR include age, AF duration, BMI, AF type, left atrial diameter, and ablation extent. Future multicenter studies with longer follow-ups are needed to validate these findings and provide robust evidence on long-term outcomes.

Background: In cardiovascular pathology, both direct bilirubin (DBIL) and high-density lipoprotein cholesterol (HDLC) have been associated with adverse clinical outcomes. However, the prognostic significance of these biomarkers in the context of dilated cardiomyopathy (DCM) remains unclear. To address this gap, this study conducted a retrospective analysis to evaluate the prognostic value of the DBIL/HDLC ratio in patients diagnosed with DCM.

Methods and Results: A total of 986 consecutive DCM patients were retrospectively enrolled from January 2010 to December 2019 and divided into two groups based on the DBIL/HDLC ratio cut-off value: ≤ 4.45 (n = 483) and > 4.45 (n = 503). Patients with lower DBIL/HDLC (≤ 4.45) experienced lower in-hospital mortality, long-term mortality, and major adverse clinical events (MACEs) (0.8%, 32.9%, and 12.2%, respectively) compared to those with higher DBIL/HDLC (> 4.45) (6.4%, 59.1%, and 16.7%, respectively). Multivariate analysis identified DBIL/HDLC as an independent risk factor for long-term mortality (odds ratio: 1.026; 95% confidence interval (CI): 1.005–1.048; p = 0.016) and all-cause mortality over a median follow-up of 67 ± 1.8 months (hazard ratio: 1.011; 95% CI: 1.005–1.018; p < 0.001). The receiver operating characteristic curve showed good discrimination for long-term mortality (area under the curve (AUC): 0.675; 95% CI: 0.692–0.708; p < 0.001). The Kaplan–Meier survival analysis demonstrated a better prognosis for patients with DBIL/HDLC ≤ 4.45 (log-rank χ² = 40.356, p < 0.001). Furthermore, the impact of additional variables on the results was investigated by a subgroup analysis.

Conclusion: The DBIL/HDLC ratio could serve as a simple and cost-effective tool for evaluating prognosis in DCM.