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- Identifying Factors for Low-Risk Participation in Alternative Cardiac
Rehabilitation Models for Patients with Coronary Heart Disease Using
MI’S SCOREPAD
Abstract: Introduction. Although a recent joint society scientific statement (the American Association of Cardiovascular Pulmonary Rehabilitation, the American Heart Association, and the American College of Cardiology) suggests home-based cardiac rehab (CR) is appropriate for low- and moderate-risk patients, there are no paradigms to define such individuals with coronary heart disease. Methods. We reviewed a decade of data from all patients with coronary heart disease enrolled in a single CR center (University of Michigan) to identify the prevalence of low-risk factors, which may inform on consideration for participation in alternative models of CR. Low-risk factors included not having any of the following: metabolic syndrome, presence of implantable cardioverter defibrillator or permanent pacemaker, active smoking, prior stroke, congestive heart failure, obesity, advanced renal disease, poor exercise capacity, peripheral arterial disease, angina, or clinical depression (MI’S SCOREPAD). We report on the proportion of participants with these risk factors and the proportion with all of these low-risk factors. Results. The mean age of CR participants () was 63 years; 25% were women, and 82% were non-Hispanic White. The mean number of low-risk factors was 8.5, which was similar in the 2011-2012 and 2018-2019 cohorts (8.5 vs. 8.3, respectively, ). Additionally, 9.3% of the 2011-2012 cohort and 7.6% of the 2018-2019 cohort had all 11 of the low-risk factors. Conclusion. In this observational study, we provide a first paradigm of identifying factors among coronary heart disease patients that may be considered low-risk and likely high-gain for participation in alternative models of CR. Further work is needed to track clinical outcomes in patients with these factors to determine thresholds for enrolling participants in alternative forms of CR.
PubDate: Fri, 08 Sep 2023 09:50:00 +000
- Elevated Serum Total Bilirubin Might Indicate Poor Coronary Conditions for
Unstable Angina Pectoris Patients beyond as a Cardiovascular Protector
Abstract: Backgrounds. Serum total bilirubin (STB) is recently more regarded as an antioxidant with vascular protective effects. However, we noticed that elevated STB appeared in unstable angina pectoris (UAP) patients with diffused coronary lesions. We aimed to explore STB’s roles in UAP patients, which have not been reported by articles. Methods and Results. 1120 UAP patients were retrospectively screened, and 296 patients were finally enrolled. They were grouped by Canadian Cardiovascular Society (CCS) angina grades. The synergy between PCI with TAXUS stent and cardiac surgery score (SYNTAX score) and corrected thrombolysis in myocardial infarction flow count (CTFC) were adopted to profile coronary features. The results showed that STB, mean platelet volume (MPV), hs-CRP, fasting blood glucose (FBG), red blood cell width (RDW), and CTFC elevated significantly in the CCS high-risk group. STB (, 95% CI: 0.39-0.74, ) and MPV (, 95% CI: 0.42-1.31, ) could indicate SYNTAX score changes for these patients. STB (≥21.7 μmol/L) could even indicate a coronary slow flow condition (AUC: 0.88, 95% CI: 0.84-0.93, ). Moreover, UAP patients with elevated STB had a lower event-free survival rate by the Kaplan-Meier curve. STB ≥21.7 μmol/L could reflect a poor coronary flow status and indicate 1-year poor outcomes for these patients (HR: 2.01, 95% CI: 1.06-3.84, ).Conclusion. Elevated STB in UAP patients has a close relationship with changes in SYNTAX score. STB (over 21.7 μmol/L) could even indicate a coronary slow flow condition and poor outcomes for the UAP patients.
PubDate: Tue, 05 Sep 2023 05:50:00 +000
- Left Bundle Branch Area Pacing versus Right Ventricular Pacing in Patients
with Atrioventricular Block: An Observational Cohort Study
Abstract: Objective. We aim to conduct a comparison of the safety and effectiveness performance between left bundle branch area pacing (LBBAP) and right ventricular pacing (RVP) regimens for patients with atrioventricular block (AVB). Methods. This observational cohort study included patients who underwent pacemaker implantations with LBBAP or RVP for AVB indications from the 1st of January 2018 to the 18th of November 2021 at West China Hospital. The primary composite outcome included all-cause mortality, lead failure, or heart failure hospitalization (HFH). The secondary outcome included periprocedure complication, cardiac death, or recurrent unexplained syncope. A 1 : 1 propensity score–matched cohort was conducted for left ventricular (LV) function analysis. Results. A total of 903 patients met the inclusion criteria and completed clinical follow-up. After adjusting for the possible confounders, LBBAP was independently associated with a lower risk of the primary outcome (OR 0.48, 95% CI 0.28 to 0.83, ), including a lower risk of all-cause mortality and HFH. No significant difference in the secondary outcome was detected between the groups except that LBBAP was independently associated with a lower risk of recurrent unexplained syncope. In the propensity-score matching cohort of echocardiographic analysis, the LV systolic dyssynchrony index was lower in LBBAP compared with that in RVP ( vs. %, ).Conclusions. Compared to conventional RVP, LBBAP is a feasible novel pacing model associated with a significant reduction in the primary composite outcome. Moreover, LBBAP significantly reduces the risk of recurrent unexplained syncope and improves LV systolic synchrony. This study is registered with ClinicalTrials.gov NCT05722379.
PubDate: Mon, 21 Aug 2023 07:35:00 +000
- Comparison of Different Chronic Maintenance Antithrombotic Strategies in
Patients with Coronary Artery Disease: A Systematic Review and Network
Meta-Analysis
Abstract: Background. Optimal antithrombotic therapy during the chronic maintenance period in patients with coronary artery disease (CAD) is unknown. We compared five kinds of mainstream chronic maintenance antithrombotic strategies at least one year after the acute phase: aspirin alone, clopidogrel alone, ticagrelor alone, continued dual antiplatelet therapy (DAPT) for a period of time, and maintenance with aspirin combined with a low-dose anticoagulant such as rivaroxaban. Methods. Ten randomized, controlled trials were selected using PubMed, Ovid MEDLINE, Embase, and Cochrane library through February 2023. The primary outcome was main adverse cardiac events (MACEs), and secondary outcomes include net adverse clinical events (NACEs), cardiac death, all-cause death, ischemic stroke, stent thrombosis, total bleeding, and major bleeding. A network meta-analysis was conducted with a random-effects model. Data extraction was performed by three independent reviewers. Results. Our search identified ten eligible randomized controlled trials enrolling a total of 82,084 patients comparing different chronic maintenance antithrombotic strategies. As for the primary endpoint, there was no statistical difference in MACE outcomes between any two of the five methods. As for the secondary endpoint, there was no statistical difference in NACE, major bleeding, all-cause death, cardiac death, and stent thrombosis between any two methods. The aspirin plus low-dose rivaroxaban group had a lower incidence of ischemic stroke compared to the aspirin group (, 95% CrI 0.26-0.91). And the prolonged DAPT group had a higher total bleeding rate compared to aspirin group (, 95% CrI 1.1-5.9). Conclusions. In terms of MACE, NACE, all-cause death, cardiac death, stent thrombosis, and major bleeding, there were no significant differences between using aspirin alone, clopidogrel alone, and ticagrelor alone; extending DAPT duration; and using aspirin combined with low-dose rivaroxaban for chronic maintenance antithrombotic regimens. However, choosing aspirin combined with low-dose rivaroxaban can reduce the incidence of ischemic stroke, and prolonged DAPT may have a higher rate of total bleeding. However, it is important to note that this study is based on indirect comparisons, and there is currently a lack of direct evidence comparing various maintenance antiplatelet therapy regimens. Further high-quality studies are needed to address this gap and provide more conclusive evidence on the comparative effectiveness of different maintenance antiplatelet strategies.
PubDate: Thu, 17 Aug 2023 10:20:01 +000
- Drug-Coated Balloon-Only Strategy for De Novo Coronary Artery Disease: A
Meta-analysis of Randomized Clinical Trials
Abstract: Backgrounds. Many clinical trials have demonstrated the value of drug-coated balloons (DCB) for in-stent restenosis. However, their role in de novo lesions is not well documented. The aim of this study is to evaluate the safety and efficacy of the DCB-only strategy compared to other percutaneous coronary intervention strategies for de novo coronary lesions. Methods. The PubMed, Embase, Web of Science, and Cochrane Library Central Register of Controlled Trials (CENTRAL) electronic databases were searched for randomized controlled trials published up to May 6, 2023. The primary outcomes were major adverse cardiac events and late lumen loss. Results. A total of eighteen trials with 3336 participants were included. Compared with drug-eluting stents, the DCB-only strategy was associated with a similar risk of major adverse cardiac events (risk ratio ; 95% confidence interval (CI): 0.59 to 1.37, ) and a significant decrease in late lumen loss (standardized mean difference , 95% CI: −0.53 to −0.04, ). This effect was consistent in subgroup analysis regardless of indication, follow-up time, drug-eluting stent type, and dual antiplatelet therapy duration. However, DCBs were inferior to DESs for minimum lumen diameter and percentage diameter stenosis. The DCB-only strategy showed significantly better outcomes for most endpoints compared to plain-old balloon angioplasty or bare metal stents. Conclusions. Interventions with a DCB-only strategy are comparable to those of drug-eluting stents and superior to plain-old balloon angioplasty or bare metal stents for the treatment of selected de novo coronary lesions. Additional evidence is still warranted to confirm the value of DCB before widespread clinical utilization can be recommended.
PubDate: Tue, 08 Aug 2023 10:05:01 +000
- Heart Failure with Preserved Left Ventricular Ejection Fraction: A Complex
Conundrum Simply Not Limited to Diastolic Dysfunction
Abstract: Over the last two decades, the changing paradigm of heart failure with preserved ejection fraction (HFpEF) has transformed our understanding not only of the pathophysiology of this clinical entity but also the diagnostic and therapeutic approaches aimed at treating this complex patient population. No longer HFpEF should be seen as simply left ventricular diastolic dysfunction but as a group of that in addition of having small and thick left ventricles with abnormal diastolic filling patterns as their main pathophysiologic abnormality; they also have whole host of different abnormalities. In fact, this heterogeneous clinical entity embodies numerous mechanisms and is linked to multiorgan dysfunction, with hypertension and obesity playing a major role. Although we have gained an enormous amount of understanding not only on the causes but also the downstream effects of HFpEF, there is still much to be learned before we can fully comprehend this complex clinical entity. It is the main intention of this review to synthesize the most recent attributes, mechanism, diagnostic tools, and most useful therapeutic alternatives to be considered when evaluating patients either complaining of dyspnea on exertion as well as exercise intolerance or those recently admitted with HF symptoms but with normal LVEF in the absence of any other valvular abnormalities
PubDate: Tue, 18 Jul 2023 09:20:00 +000
- Water-Based Exercises on Peak Oxygen Consumption, Exercise Time, and
Muscle Strength in Patients with Coronary Artery Disease: A Systematic
Review with Meta-Analysis
Abstract: Background. There is a growing use of water-based exercises in cardiac rehabilitation programs. However, there is little data concerning the effects of water-based exercise on the exercise capacity of coronary artery disease (CAD) patients. Objective. To perform a systematic review to investigate the effects of water-based exercise on peak oxygen consumption, exercise time, and muscle strength in patients with CAD. Methods. Five databases were searched to find randomized controlled trials that evaluated the effects of water-based exercise for coronary artery disease patients. Mean differences (MD) and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed using the test. Results. Eight studies were included. Water-based exercise resulted in an improvement in peak VO2 of 3.4 mL/kg/min (95% CI, 2.3 to 4.5; %; 5 studies, ), exercise time of 0.6 (95% CI, 0.1 to 1.1; %; 3 studies, ), and total body strength of 32.2 kg (95% CI, 23.9 to 40.7; %; 3 studies, ) when compared to no exercising controls. Water-based exercise resulted in an improvement in peak VO2 of 3.1 mL/kg/min (95% CI, 1.4 to 4.7; %; 2 studies, ), when compared to the plus land exercise group. No significant difference in peak VO2 was found for participants in the water-based exercise plus land exercise group compared with the land exercise group. Conclusions. Water-based exercise may improve exercise capacity and should be considered as an alternative method in the rehabilitation of patients with CAD.
PubDate: Mon, 26 Jun 2023 11:20:01 +000
- The Regulation Network of Glycerolipid Metabolism as Coregulators of
Immunotherapy-Related Myocarditis
Abstract: Background. To date, immunotherapy for patients with malignant tumors has shown a significant association with myocarditis. However, the mechanism of metabolic reprogramming changes for immunotherapy-related cardiotoxicity is still not well understood. Methods. The CD45+ single-cell RNA sequencing (scRNA-seq) of the Pdcd1-/-Ctla4+/- and wild-type mouse heart in GSE213486 was downloaded to demonstrate the heterogeneity of immunocyte atlas in immunotherapy-related myocarditis. The liquid chromatography–tandem mass spectrometry (LC-MS/MS) spectrum metabolomics analysis detects the metabolic network differences. The drug prediction, organelle level interaction, mitochondrial level regulatory network, and phosphorylation site prediction for key regulators have also been screened via multibioinformatics analysis methods. Results. The scRNA analysis shows that the T cell is the main regulatory cell subpopulation in the pathological progress of immunotherapy-related myocarditis. Mitochondrial regulation pathway significantly participated in pseudotime trajectory- (PTT-) related differential expressed genes (DEGs) in the T cell subpopulation. Additionally, both the gene set enrichment analysis (GSEA) of PTT-related DEGs and LC-MS/MS metabolomics analysis showed that mitochondrial-regulated glycerolipid metabolism plays a central role in metabolic reprogramming changes for immunotherapy-related cardiotoxicity. Finally, the hub-regulated protease of diacylglycerol kinase zeta (Dgkz) was significantly identified and widely played various roles in glycerolipid metabolism, oxidative phosphorylation, and lipid kinase activation. Conclusion. Mitochondrial-regulated glycerolipid metabolism, especially the DGKZ protein, plays a key role in the metabolic reprogramming of immunotherapy-related myocarditis.
PubDate: Wed, 21 Jun 2023 04:50:15 +000
- Statin Eligibility according to 2013 ACC/AHA and USPSTF Guidelines among
Abstract: The objectives of this study were to evaluate statin eligibility among Middle Eastern patients admitted with acute myocardial infarction (AMI) who had no prior use of statin therapy, according to 2013 ACC/AHA and 2016 USPSTF guidelines, and to compare statin eligibility between men and women. This was a retrospective multicenter observational study of all adult patients admitted to five tertiary care centers in Jordan with a first-time AMI, no prior cardiovascular disease, and no prior statin use between April 2018 and June 2019. Ten-year atherosclerotic cardiovascular disease (ASCVD) risk score was estimated based on ACC/AHA risk score. A total of 774 patients met the inclusion criteria. The mean age was 55 years (), 120 (15.5%) were women, and 688 (88.9%) had at least one risk factor of cardiovascular disease. Compared to men, women were more likely to be older; had a history of diabetes, hypertension, and hypercholesterolemia; and had higher body mass index, systolic blood pressure, total cholesterol, and high-density lipoproteins. Compared to women, men were more likely to have a higher 10-year ASCVD risk score (14.0% vs. 17.8%, ), and more men had a 10-year ASCVD risk score of ≥7.5% and ≥10%. The proportion of patients eligible for statin therapy was 80.2% based on the 2013 ACC/AHA guidelines and 59.5% based on the USPSTF guidelines. A higher proportion of men were eligible for statin therapy compared to women, based on both the 2013 ACC/AHA (81.4% vs. 73.5%, ) and USPSTF guidelines (62.0% vs. 45.2%, ). Among Middle Easterners, over half of patients with AMI would have been eligible for statin therapy prior to admission based on the 2013 ACC/AHA and USPSTF guidelines, with the presence of gender gap. Adopting these guidelines in clinical practice might positively impact primary cardiovascular preventive strategies in this region.
PubDate: Mon, 05 Jun 2023 12:05:01 +000
- E-Selectin/AAV Gene Therapy Promotes Myogenesis and Skeletal Muscle
Recovery in a Mouse Hindlimb Ischemia Model
Abstract: The response to ischemia in peripheral artery disease (PAD) depends on compensatory neovascularization and coordination of tissue regeneration. Identifying novel mechanisms regulating these processes is critical to the development of nonsurgical treatments for PAD. E-selectin is an adhesion molecule that mediates cell recruitment during neovascularization. Therapeutic priming of ischemic limb tissues with intramuscular E-selectin gene therapy promotes angiogenesis and reduces tissue loss in a murine hindlimb gangrene model. In this study, we evaluated the effects of E-selectin gene therapy on skeletal muscle recovery, specifically focusing on exercise performance and myofiber regeneration. C57BL/6J mice were treated with intramuscular E-selectin/adeno-associated virus serotype 2/2 gene therapy (E-sel/AAV) or LacZ/AAV2/2 (LacZ/AAV) as control and then subjected to femoral artery coagulation. Recovery of hindlimb perfusion was assessed by laser Doppler perfusion imaging and muscle function by treadmill exhaustion and grip strength testing. After three postoperative weeks, hindlimb muscle was harvested for immunofluorescence analysis. At all postoperative time points, mice treated with E-sel/AAV had improved hindlimb perfusion and exercise capacity. E-sel/AAV gene therapy also increased the coexpression of MyoD and Ki-67 in skeletal muscle progenitors and the proportion of Myh7+ myofibers. Altogether, our findings demonstrate that in addition to improving reperfusion, intramuscular E-sel/AAV gene therapy enhances the regeneration of ischemic skeletal muscle with a corresponding benefit on exercise performance. These results suggest a potential role for E-sel/AAV gene therapy as a nonsurgical adjunct in patients with life-limiting PAD.
PubDate: Fri, 19 May 2023 09:50:00 +000
- Analysis of the Efficacy and Safety of Coronary Catheterization through
Distal Transradial Access: A Single-Center Data
Abstract: Background and Aims. The distal transradial access (dTRA) is a new puncture site for coronary catheterization. We sought to evaluate the feasibility, safety, and complication rates of using the dTRA for cardiac catheterization in Chinese patients. Methods. A total of 263 consecutive patients who underwent catheterization through the dTRA were enrolled. The primary endpoint of the study was the rate of conversion to another access site due to the impossibility of successful artery puncture or intubation. Secondary safety endpoints were the rates of bleeding-related complications and nerve disorders. Results. Among 263 patients, the puncture success rate was 96.2% (253/263). Eleven patients were successfully punctured, but the guide wire was difficult to advance. One patient had intubation failure, and the success rate of intubation was 91.6% (241/263). Two hundred thirty-three patients underwent puncture via the right dTRA, 5 patients underwent puncture via the left dTRA, and 3 patients underwent puncture via the bilateral dTRA. A total of 158 (65.6%) patients underwent coronary angiography, and 83 (34.4%) patients underwent percutaneous coronary intervention. After the procedure, only 2 (0.8%) patients had mild bleeding at the puncture site, 2 (0.8%) had a forearm hematoma, and no patient had a nerve disorder. Conclusions. DTRA has a low incidence of complications, making it a safe and effective technique for cardiac catheterization.
PubDate: Tue, 16 May 2023 15:35:01 +000
- Pulegone Prevents Hypertension through Activation of Muscarinic Receptors
and Cyclooxygenase Pathway in L-NAME-Induced Hypertensive Rats
Abstract: The current study was designed to determine pulegone’s antihypertensive and vasoprotective activity in L-NAME-induced hypertensive rats. Firstly, the hypotensive dose-response relationship of pulegone was evaluated in normotensive anesthetized rats using the invasive method. Secondly, the mechanism involved in hypotensive activity was determined in the presence of pharmacological drugs such as atropine/muscarinic receptor blocker (1 mg/kg), L-NAME/NOS inhibitor (20 mg/kg), and indomethacin/COX inhibitor (5 mg/kg) in anesthetized rats. Furthermore, studies were carried out to assess the preventive effect of pulegone in L-NAME-induced hypertensive rats. Hypertension was induced in rats by administering L-NAME (40 mg/kg) orally for 28 days. Rats were divided into six groups which were treated orally with tween 80 (placebo), captopril (10 mg/kg), and different doses of pulegone (20 mg/kg, 40 mg/kg, and 80 mg/kg). Blood pressure, urine volume, sodium, and body weight were monitored weekly. After 28 days, the effect of pulegone on lipid profile, hepatic markers, antioxidant enzymes, and nitric oxide was estimated from the serum of treated rats. Moreover, plasma mRNA expression of eNOS, ACE, ICAM1, and EDN1 was measured using real-time PCR. Results show that pulegone dose-dependently decreased blood pressure and heart rate in normotensive rats, with the highest effect at 30 mg/kg/i.v. The hypotensive effect of pulegone was reduced in the presence of atropine and indomethacin, whereas L-NAME did not change its hypotensive effect. Concurrent treatment with pulegone for four weeks in L-NAME-treated rats caused a reduction in both systolic blood pressure and heart rate, reversed the reduced levels of serum nitric oxide (NO), and ameliorated lipid profile and oxidative stress markers. Treatment with pulegone also improved the vascular response to acetylcholine. Plasma mRNA expression of eNOS was reduced, whereas ACE, ICAM1, and EDN1 levels were high in the L-NAME group, which was facilitated by pulegone treatment. To conclude, pulegone prevented L-NAME-induced hypertension by demonstrating a hypotensive effect through muscarinic receptors and cyclooxygenase pathway, indicating its use as a potential candidate in managing hypertension.
PubDate: Thu, 11 May 2023 13:20:00 +000
- miR-135a Regulates Atrial Fibrillation by Targeting Smad3
Abstract: Background. Atrial fibrillation (AF) is the most common arrhythmia in clinical. Atrial fibrosis is a hallmark feature of atrial structural remodeling in AF, which is regulated by the TGF-β1/Smad3 pathway. Recent studies have implicated that miRNAs are involved in the process of AF. However, the regulatory mechanisms of miRNAs remain largely unknown. This study is aimed at investigating the function and regulatory network of miR-135a in AF. Methods. In vivo, the plasma was collected from patients with AF and non-AF subjects. Adult SD rats were induced by acetylcholine (ACh) (66 μg/ml)-CaCl2 (10 mg/ml) to establish an AF rat model. In vitro, atrial fibroblasts (AFs), isolated from adult SD rats, were treated with high-frequency electrical stimulation (HES) (12 h) and hypoxia (24 h) to mimic the AF and atrial fibrosis, respectively. miR-135a expression was detected through quantitative real-time polymerase chain reaction (qRT-PCR). The association between miR-135a and Smad3 was speculated by the TargetScan database and confirmed by the luciferase reporter assay. Fibrosis-related genes, Smad3, and TRPM7 were all assessed. Results. The expression of miR-135a was markedly decreased in the plasma of AF patients and AF rats, which was consistent with that in HES-treated and hypoxia-treated AFs. Smad3 was identified as a target of miR-135a. the downregulation of miR-135a was associated with the enhancement of Smad3/TRPM7 expressions in AFs. Additionally, the knockdown of Smad3 significantly reduced the expression of TRPM7 and further inhibited atrial fibrosis. Conclusions. Our study demonstrates that miR-135a regulates AF via Smad3/TRPM7, which is a potential therapeutic target for AF.
PubDate: Fri, 05 May 2023 09:35:00 +000
- Cardioprotection of mAb2G4/ODN/lip on Myocardial Ischemia-Reperfusion
Injury via Inhibiting the NF-κB Signaling Pathway
Abstract: Substantial evidence suggests that the interventions of NF-κB would likely effectively prevent inflammatory response and reduce myocardial damage in the ischemic myocardium. And the NF-кB decoy ODN is a specific inhibitor that suppresses the expression of NF-κB. Herein, we revealed the effect and possible mechanism of mAb2G4/ODN/lip on myocardial ischemia-reperfusion injury (MI/RI). As shown in the results, post-treatment with mAb2G4/ODN/lip improved the impaired histological morphology in the MI/RI model and elevated cell viability in the H/R model. The mAb2G4/ODN/lip complex inhibited the NLRP3 signaling pathway and decreased the expression of LDH, IL-1β, TNF-α, IL-6, and MDA. Mechanistically, we demonstrated that post-treatment with mAb2G4/ODN/lip exerted protective effects against I/R injuries by inhibiting the NF-кB-related inflammatory response. In summary, the present study may offer a novel therapeutic strategy for treating MI/RI.
PubDate: Thu, 27 Apr 2023 13:05:01 +000
- Effect of Statins on Major Adverse Cardiovascular Events in Patients with
Coronary Artery Spasm: A Meta-Analysis of the Asia Region
Abstract: Background. Whether statins can reduce major cardiovascular adverse events (MACE) in patients with coronary artery spasm (CAS) is controversial. And most of the relevant research to date has been conducted in Asia. Methods. We systematically searched electronic databases for studies on the effect of statins on MACE in patients with CAS in Asia and published up to September 2022. We included data on MACE in a statin therapy patient group and a no-statin therapy control group. We then evaluated the effect of statin therapy on MACE in patients with CAS in Asia by meta-analysis and trial sequential analysis (TSA). All statistical analyses were performed using Stata 16.0 software and TSA software. Results. A total of 10 studies ( patients) were included in the final analysis. Meta-analysis showed that the use of statins had a significant effect on MACE in CAS patients (with RR, 0.70; 95% CI, 0.49-0.99), and the sensitivity analysis further confirmed this finding. Subgroup analysis suggested that the correlation between statin therapy and reduced MACE endpoint was stronger in Japanese patients and patients followed up for more than 4 years. But our TSA results indicated that the available samples were insufficient and further research is needed. Conclusions. Our meta-analysis suggests that statin therapy can reduce MACE in patients with CAS in Asia, and the correlation between the two was stronger in Japanese patients and patients followed up for more than 4 years.
PubDate: Thu, 27 Apr 2023 11:05:01 +000
- Efficacy of Acupuncture in the Treatment of Essential Hypertension: An
Overview of Systematic Reviews and Meta-Analyses
Abstract: Background. Acupuncture is widely used in the clinical treatment of essential hypertension (EH). This overview is aimed at summarizing current systematic reviews of acupuncture for EH and assessing the methodological bias and quality of evidence. Methods. Two researchers searched and extracted 7 databases for systematic reviews (SRs)/meta-analyses (MAs) and independently assessed the methodological quality, risk of bias, reporting quality, and quality of evidence of randomized controlled trials (RCTs) included in the SRs/MAs. Tools used included the measurement tool to assess systematic reviews 2 (AMSTAR-2), the risk of bias in systematic (ROBIS) scale, the checklist of preferred reporting items for systematic reviews and meta-analyses (PRISMA), and the grading of recommendations assessment, development, and evaluation (GRADE) system. Results. This overview included 14 SRs/MAs that use quantitative calculations to comprehensively assess the various effects of acupuncture in essential hypertension interventions. The methodological quality, reporting quality, risk of bias, and quality of evidence for outcome measures of SRs/MAs were all unsatisfactory. According to the results of the AMSTAR-2 assessment, all SRs/MAs were of low or very low quality. According to the results of the ROBIS evaluation, a few SRs/MAs were assessed as low risk of bias. According to the results of the PRISMA checklist assessment, SRs/MAs that were not fully reported on the checklist accounted for the majority. According to the GRADE system, 86 outcomes were assessed under different interventions in SRs/MAs, and 2 were rated as moderate-quality evidence, 23 as low-quality evidence, and 61 as very low-quality evidence. Limitations of the included SRs/MAs included the lack of necessary items, such as not being registered in the protocol, not providing a list of excluded studies, and not analyzing and addressing the risk of bias. Conclusion. Currently, acupuncture may be an effective and safe treatment for EH, but the quality of evidence is low, and caution should be exercised when applying this evidence in clinical practice.
PubDate: Tue, 18 Apr 2023 14:05:01 +000
- KCa3.1 Promotes Proinflammatory Exosome Secretion by Activating AKT/Rab27a
in Atrial Myocytes during Rapid Pacing
Abstract: Purpose. The aim of this study was to investigate the role of the medium-conductance calcium-activated potassium channel (KCNN4, KCa3.1) in the secretion of proinflammatory exosomes by atrial myocytes. Methods. Eighteen beagles were randomly divided into the sham group (), pacing group (), and pacing+TRAM-34 group (). Electrophysiological data, such as the effective refractory period, atrial fibrillation (AF) induction, and AF duration, were collected by programmed stimulation. Atrial tissues were subjected to hematoxylin and eosin, Masson’s trichrome, and immunofluorescence staining. The expression of KCa3.1 and Rab27a was assessed by immunohistochemistry and western blotting. The downstream signaling pathways involved in KCa3.1 were examined by rapid pacing or overexpressing KCNN4 in HL-1 cells. Results. Atrial rapid pacing significantly induced electrical remodeling, inflammation, fibrosis, and exosome secretion in the canine atrium, while TRAM-34 (KCa3.1 blocker) inhibited these changes. Compared with those in control HL-1 cells, the levels of exosome markers and inflammatory factors were increased in pacing HL-1 cells. Furthermore, the levels of CD68 and iNOS in macrophages incubated with exosomes derived from HL-1 cells were higher in the pacing-exo group than in the control group. More importantly, KCa3.1 regulated exosome secretion through the AKT/Rab27a signaling pathway. Similarly, inhibiting the downstream signaling pathway of KCa3.1 significantly inhibited exosome secretion. Conclusions. KCa3.1 promotes proinflammatory exosome secretion through the AKT/Rab27a signaling pathway. Inhibiting the KCa3.1/AKT/Rab27a signaling pathway reduces myocardial tissue structural remodeling in AF.
PubDate: Thu, 30 Mar 2023 08:50:00 +000
- Mass Cytometry Reveals the Imbalanced Immune State in the Peripheral Blood
of Patients with Essential Hypertension
Abstract: Mounting evidence has confirmed that essential hypertension (EH) is closely related to low-grade inflammation, but there is still a lack of in-depth understanding of the state of immune cells in the circulating blood of patients with EH. We analyzed whether hypertensive peripheral blood immune cell balance was destroyed. The peripheral blood mononuclear cells (PBMCs) of all subjects were analyzed using time-of-flight cytometry (CyTOF) based on 42 kinds of metal-binding antibodies. CD45+ cells were categorized into 32 kinds of subsets. Compared with the health control (HC) group, the percentage of total dendritic cells, two kinds of myeloid dendritic cell subsets, one intermediate/nonclassical monocyte subset and one CD4+ central memory T cell subset in the EH group, was significantly higher; the percentage of low-density neutrophils, four kinds of classical monocyte subsets, one CD14lowCD16- monocyte subset, one naive CD4+ and one naive CD8+ T cell subsets, one CD4+ effector and one CD4+ central memory T cell subsets, one CD8+ effector memory T cell subset, and one terminally differentiated γδ T cell subset, decreased significantly in EH. What is more, the expression of many important antigens was enhanced in CD45+ immune cells, granulocytes, and B cells in patients with EH. In conclusion, the altered number and antigen expression of immune cells reflect the imbalanced immune state of the peripheral blood in patients with EH.
PubDate: Mon, 27 Feb 2023 12:50:01 +000
- Pharmacological Activation of Rev-erbα Attenuates Doxorubicin-Induced
Cardiotoxicity by PGC-1α Signaling Pathway
Abstract: Background. Doxorubicin-induced cardiotoxicity has been closely concerned in clinical practice. Rev-erbα is a transcriptional repressor that emerges as a drug target for heart diseases recently. This study is aimed at investigating the role and mechanism of Rev-erbα in doxorubicin-induced cardiotoxicity. Methods. H9c2 cells were treated with 1.5 μM doxorubicin, and C57BL/6 mice were treated with a 20 mg/kg cumulative dose of doxorubicin to construct doxorubicin-induced cardiotoxicity models in vitro and in vivo. Agonist SR9009 was used to activate Rev-erbα. PGC-1α expression level was downregulated by specific siRNA in H9c2 cells. Cell apoptosis, cardiomyocyte morphology, mitochondrial function, oxidative stress, and signaling pathways were measured. Results. SR9009 alleviated doxorubicin-induced cell apoptosis, morphological disorder, mitochondrial dysfunction, and oxidative stress in H9c2 cells and C57BL/6 mice. Meanwhile, PGC-1α and downstream signaling NRF1, TAFM, and UCP2 expression levels were preserved by SR9009 in doxorubicin-treated cardiomyocytes in vitro and in vivo. When downregulating PGC-1α expression level by specific siRNA, the protective role of SR9009 in doxorubicin-treated cardiomyocytes was attenuated with increased cell apoptosis, mitochondrial dysfunction, and oxidative stress. Conclusion. Pharmacological activation of Rev-erbα by SR9009 could attenuate doxorubicin-induced cardiotoxicity through preservation of mitochondrial function and alleviation of apoptosis and oxidative stress. The mechanism is associated with the activation of PGC-1α signaling pathways, suggesting that PGC-1α signaling is a mechanism for the protective effect of Rev-erbα against doxorubicin-induced cardiotoxicity.
PubDate: Wed, 22 Feb 2023 15:35:01 +000
- Bardoxolone Methyl Ameliorates Myocardial Ischemia/Reperfusion Injury by
Activating the Nrf2/HO-1 Signaling Pathway
Abstract: Background. Myocardial ischemia/reperfusion (I/R) injury is a severe heart problem resulting from restoring coronary blood flow to the myocardium after ischemia. This study is aimed at ascertaining the therapeutic efficiency and action mechanism of bardoxolone methyl (BARD) in myocardial I/R injury. Methods. In male rats, myocardial ischemia was performed for 0.5 h, and then, reperfusion lasted for 24 h. BARD was administrated in the treatment group. The animal’s cardiac function was measured. Myocardial I/R injury serum markers were detected via ELISA. The 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to estimate the infarction. H&E staining was used to evaluate the cardiomyocyte damage, and Masson trichrome staining was used to observe the proliferation of collagen fiber. The apoptotic level was assessed via the caspase-3 immunochemistry and TUNEL staining. Oxidative stress was measured through malondialdehyde, 8-hydroxy-2-deoxyguanosine, superoxide dismutase, and inducible nitric oxide synthases. The alteration of the Nrf2/HO-1 pathway was confirmed via western blot, immunochemistry, and PCR analysis. Results. The protective effect of BARD on myocardial I/R injury was observed. In detail, BARD decreased cardiac injuries, reduced cardiomyocyte apoptosis, and inhibited oxidative stress. For mechanisms, BARD treatment significantly activates the Nrf2/HO-1 pathway. Conclusion. BARD ameliorates myocardial I/R injury by inhibiting oxidative stress and cardiomyocyte apoptosis via activating the Nrf2/HO-1 pathway.
PubDate: Wed, 22 Feb 2023 14:50:01 +000
- DT-010 Exerts Cardioprotective Effects by Regulating the Crosstalk between
the AMPK/PGC-1α Pathway and ERp57
Abstract: The AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) pathway performs a crucial role in energy metabolism and mitochondrial network. Our previous study found that DT-010, a novel danshensu (DSS) and tetramethylpyrazine (TMP) conjugate, had significant cardioprotective properties in vitro and in vivo. We also reported that ERp57 served as a major target of DSS using the chemical proteomics approach. In this article, we focus on exploring the interrelationship between the regulation of the AMPK/PGC-1α pathway and promoting ERp57 expression induced by DT-010 in tert-butylhydroperoxide- (t-BHP-) induced H9c2 cell injury. The results showed that DT-010 activated the AMPK/PGC-1α pathway and increased ERp57 protein expression. Importantly, the above phenomenon as well as the mitochondrial function can be partially reversed by siRNA-mediated ERp57 suppression. Meanwhile, silencing AMPK significantly inhibited the ERp57 expression induced by DT-010. In addition, molecular docking and kinase assay in vitro revealed that DT-010 had no direct regulation effects on AMPK activity. Taken together, DT-010 exerted cardioprotective effects by regulating the crosstalk of AMPK/PGC-1α pathway and ERp57, representing a potential therapeutic agent for ischemic heart disease.
PubDate: Fri, 10 Feb 2023 12:20:01 +000
- Identification of Potential Biomarkers for Coronary Artery Disease Based
on Cuproptosis
Abstract: Identifying peripheral biomarkers is an important noninvasive diagnosis method for coronary artery disease (CAD) which has aroused the strong interest of researchers. Cuproptosis, a newly reported kind of programmed cell death, is closely related to mitochondrial respiration, adenosine triphosphate (ATP) production, and the TCA cycle. Currently, no studies have been published about the effects of cuproptosis-related genes (CRGs) on diagnosing CAD. To screen marker genes for CAD from CRGs, we downloaded the whole blood cell gene expression profile of CAD patients and normal samples, i.e., the GSE20680 dataset, from the GEO database. By differential expression analysis, we obtained 10 differentially expressed CRGs (DE-CRGs), which were associated with copper ion response, immune response, and material metabolism. Based on the 10 DE-CRGs, we furtherly performed LASSO analysis and SVM-RFE analysis and identified 5 DE-CRGs as marker genes, including F5, MT4, RNF7, S100A12, and SORD, which had an excellent diagnostic performance. Moreover, the expression of the marker genes was validated in the GSE20681 and GSE42148 datasets, and consistent results were obtained. In mechanism, we conducted gene set enrichment analyses (GSEA) based on the marker genes, and the results implied that they might participate in the regulation of immune response. Therefore, we calculated the relative contents of 22 kinds of immune cells in CAD and normal samples using the CIBERSORT algorithm, followed by differential analysis and correlation analysis of the immune microenvironment, and found that regulatory T cell (Treg) significantly decreased and was negatively correlated with marker gene S100A12. To further reveal the regulation mechanisms, a lncRNA-miRNA-mRNA ceRNA network based on the marker genes was established. Finally, 13 potential therapeutic drugs targeting 2 marker genes (S100A12 and F5) were identified using the Drug Gene Interaction Database (DGIdb). In summary, our findings indicated that some CRGs may be diagnostic biomarkers and treatment targets for CAD and provided new ideas for further scientific research.
PubDate: Wed, 25 Jan 2023 08:20:01 +000
- Social App to Improve Warfarin Therapy in Post-MHVR Chinese Patients: A
Randomized Controlled Trial
Abstract: Background. Poor anticoagulation quality was a major problem among warfarin-treated patients, which called for innovative and effective methods to improve it. Objective. To investigate whether social app could be used to reduce warfarin-associated adverse events among post-MHVR Chinese patients. Method. 735 warfarin-treated patients (, 59.9% female) were enrolled and randomized to a social app care group (warfarin therapy was guided by experienced clinicians via a social app) or a routine care group (warfarin therapy was managed through traditional in-office visits) at a 1 : 1 ratio. Ending points (bleeding and thrombotic events) were recorded during an 18-month follow-up period. Results. A total of 718 patients were included in analysis. 57 of them suffered warfarin-associated adverse events, including 30 major bleedings and 27 thrombotic events. The time in the therapeutic range (TTR, Rosendaal method) in the social app group was 71.5%, which was significantly better than 52.6% in the routine care group (difference: 18.8%, 95% CI: 16.8-20.8). Compared with the patients from the social app group, patients under routine care experienced more bleeding (hazard ratio (HR): 2.31, 95% CI: 1.13-4.72). The social app care group had lower variation (0.55 vs. 0.70) in the international normalized ratio (INR) values and fewer incidents of extremely high INR (e.g., , 0.87% vs. 3.42%) than the routine care group. Conclusions. Social app management could significantly improve warfarin control and was associated with a reduction in bleeding risk. This trial was registered with NCT03264937.
PubDate: Sat, 14 Jan 2023 09:50:00 +000
- The Effect of Clinically Indicated Liraglutide on Pericoronary Adipose
Tissue in Type 2 Diabetic Patients
Abstract: Vascular inflammation can be detected in the pericoronary adipose tissue (PCAT) by coronary computed tomography angiography (CCTA) attenuation. Treatment with liraglutide is associated with anti-inflammatory effects and reduces cardiovascular risk in diabetic patients. This study is aimed at examining the effect of clinically indicated liraglutide on PCAT attenuation. Asymptomatic patients with type 2 diabetes mellitus (T2DM) and without known ischemic heart disease underwent clinical examination, blood analysis, and CCTA. The main coronary arteries were outlined and PCAT attenuation was measured on the proximal 40 mm. Patients treated with liraglutide on a clinical indication were compared to patients not receiving liraglutide. The study included 190 patients; 53 (28%) received liraglutide (Lira+) and 137 (72%) did not (Lira-). There were no significant differences in PCAT attenuation between the two groups in either artery. However, PCAT attenuation measured around the left anterior descending artery (LAD) was lower in the Lira+ group after adjustment for age, sex, body mass index, and T2DM duration ( coefficient -2.4, ). In a population of cardiac asymptomatic T2DM patients, treatment with clinically indicated liraglutide was not associated with differences in PCAT attenuation compared to nonliraglutide treatment in the unadjusted model. An association was seen in the adjusted model for the left anterior descending artery, possibly indicating an anti-inflammatory effect.
PubDate: Sat, 14 Jan 2023 07:35:01 +000
- Effect of TRIB1 Variant on Lipid Profile and Coronary Artery Disease: A
Systematic Review and Meta-Analysis
Abstract: Background. Emerging evidence indicates tribbles homolog 1 (Trib1) protein may be involved in lipid metabolism regulation and coronary artery disease (CAD) pathogenesis. However, whether TRIB1 gene variants affect lipid levels and CAD remains elusive, this study is aimed at clarifying the effect of TRIB1 variants on lipid profile and CAD. Methods. By searching PubMed and Cochrane databases for studies published before December 18, 2022, a total of 108,831 individuals were included for the analysis. Results. The outcomes of the analysis on all individuals showed that the A allele carriers of rs17321515 and rs2954029 variants had higher low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels than the noncarriers. Consistently, a higher CAD risk was observed in the A allele carriers. Subgroup analysis indicated that increased LDL-C, TC, and CAD risk were observed in Asian population. Conclusions. Variants of TRIB1 (i.e., rs17321515 and rs2954029) may serve as causal genetic markers for dyslipidemia and CAD in Asian population.
PubDate: Mon, 09 Jan 2023 02:05:00 +000
- An Updated Meta-Analysis for Safety Evaluation of Alirocumab and
Evolocumab as PCSK9 Inhibitors
Abstract: Background. Alirocumab and evolocumab, as protein convertase subtilisin kexin type 9 (PCSK9) inhibitors, have been reported to reduce cardiovascular risk. This meta-analysis is aimed at updating the safety data of PCSK9 inhibitors. Methods. We assessed the relative risk for all treatment-related adverse events, serious adverse events, diabetes-related adverse events, and neurocognitive and neurologic adverse events with PCSK9 inhibitors compared to controls (placebo or ezetimibe). In addition, we conducted a meta-analysis to quantitatively integrate and estimate the adverse event rates in long-term studies. Results. There were no significant differences between PCSK9 inhibitors and controls in the relative risk analysis. In a subgroup analysis of each PCSK9 inhibitor, alirocumab treatment significantly reduced the risk of serious adverse events compared to control treatment (; 95% confidence interval (CI), 0.896–0.980), but no significant difference was observed with evolocumab treatment (; 95% CI, 0.963–1.054). Moreover, alirocumab treatment afforded a significant reduction in the risk of diabetes-related adverse events compared to control treatment (; 95% CI, 0.845–0.987). The overall incidence (event rate) of long-term adverse events was 75.1% (95% CI, 71.2%–78.7%), and the incidence of serious long-term event rate was 16.2% (95% CI, 11.6%–22.3%). Conclusions. We suggest that alirocumab and evolocumab are generally safe and well tolerated and that their addition to background lipid-lowering therapy is not associated with an increased risk of adverse events or toxicity.
PubDate: Wed, 04 Jan 2023 13:50:02 +000
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