Education and cardiovascular diseases: a Mendelian randomization study.

Background: Observational studies have indicated a potential association between education and cardiovascular diseases (CVDs). However, uncertainties regarding the causal relationship persist. Therefore, this study aimed to investigate whether higher levels of education causally reduce the risks of CVDs. Methods: Employing a two-sample Mendelian randomization (MR) design, our study examined the relationship between education and ten different CVDs. Utilizing data from the IEU Open GWAS database, relevant single nucleotide polymorphisms (SNPs) were identified through stringent screening criteria. Causality was assessed using the inverse-variance weighted (IVW), ME-Egger regression, and weighted median methods. Sensitivity analyses, including heterogeneity and pleiotropy tests, were conducted to ensure the robustness of our findings. Results: Our study identified a genetic predisposition associated with an additional 3.6 years of education, which significantly reduced the risk of various CVDs. Specifically, this genetic factor was found to lower the risk of type 2 diabetes by 46.5%, coronary heart disease by 37.5%, ischemic stroke by 35.4%, cardiac-related mortality by 28.6%, heart failure by 28.2%, transient ischemic attack by 24%, atrial fibrillation by 15.2%, peripheral artery disease by 0.3%, and hypertension by 0.3%. However, no significant evidence revealed a causal relationship between education and pulmonary embolism. Conclusion: Our study provides robust evidence supporting the role of higher educational attainment in reducing the incidence of various cardiovascular diseases, including type 2 diabetes, coronary heart disease, ischemic stroke, cardiac-related mortality, heart failure, transient ischemic attack, atrial fibrillation, peripheral artery disease, and hypertension. However, the impact of education on pulmonary embolism remains inconclusive.

Panax quinquefolium L. and Salvia miltiorrhiza Bunge. Enhances Angiogenesis by Regulating the miR-155-5p/HIF-1α/VEGF Axis in Acute Myocardial Infarction.

Background: Combination of Panax quinquefolium L and Salvia miltiorrhiza Bunge. (PS) has been widely used in the clinical treatment of ischemic heart disease. The purpose of this study was to explore the therapeutic effect and mechanism of PS on angiogenesis in rats after acute myocardial infarction (AMI). Methods: A rat model of AMI was established by ligating the left anterior descending (LAD) artery. The grouping and administration scheme were as follows: sham group, model group, PS low-dose (PS-L) group, PS high-dose (PS-H) group, PX-478 group and angiotensin converting enzyme inhibitor (ACEI) group. After 28 days of treatment, echocardiography, myocardial infarct size, some angiogenesis markers and the miR-155-5p/HIF-1α/VEGF axis were measured. Results: PS improved cardiac structure and function, reduced infarct size, and alleviated myocardial fibrosis and inflammatory cell infiltration in AMI rats. Mechanistically, PS enhanced the expression of HGF and bFGF in serum, increased the levels of MVD and CD31 in myocardial tissues, and inhibited the activation of the miR-155-5p/HIF-1α/VEGF pathway, which ultimately promoted angiogenesis. In addition, the regulatory effect of PS on angiogenesis was partly abolished by PX-478. Conclusion: PS increased the expression of MVD and CD31 in the myocardium and stimulated angiogenesis. The above effects of PS may be associated with the inhibition of the miR-155-5p/HIF-1α/VEGF axis.

A Systematic Review and Meta-Analysis of Phytoestrogen Protects Against Myocardial Ischemia/Reperfusion Injury: Pre-Clinical Evidence From Small Animal Studies.

Background: Phytoestrogens are a class of natural compounds that have structural similarities to estrogens. They have been identified to confer potent cardioprotective effects in experimental myocardial ischemia-reperfusion injury (MIRI) animal models. We aimed to investigate the effect of PE on MIRI and its intrinsic mechanisms. Methods: A systematic search was conducted to identify PEs that have been validated in animal studies or clinical studies as effective against MIRI. Then, we collected studies that met inclusion and exclusion criteria from January 2016 to September 2021. The SYRCLE's RoB tool was used to evaluate the quality. Data were analyzed by STATA 16.0 software. Results: The search yielded 18 phytoestrogens effective against heart disease. They are genistein, quercetin, biochanin A, formononetin, daidzein, kaempferol, icariin, puerarin, rutin, notoginsenoside R1, tanshinone IIA, ginsenoside Rb1, ginsenoside Rb3, ginsenoside Rg1, ginsenoside Re, resveratrol, polydatin, and bakuchiol. Then, a total of 20 studies from 17 articles with a total of 355 animals were included in this meta-analysis. The results show that PE significantly reduced the myocardial infarct size in MIRI animals compared with the control group (p < 0.001). PE treatment significantly reduced the creatine kinase level (p < 0.001) and cTnI level (p < 0.001), increased left ventricular ejection fraction (p < 0.001) and left ventricular fractional shortening (p < 0.001) in MIRI animals. In addition, PE also exerts a significant heart rate lowering effect (p < 0.001). Conclusion: Preclinical evidence suggests that PE can be multi-targeted for cardioprotective effects in MIRI. More large animal studies and clinical research are still needed in the future to further confirm its role in MIRI.

Trimethylamine N-Oxide in Heart Failure: A Meta-Analysis of Prognostic Value.

OBJECTIVE: The present study aimed to explore the prognostic value of trimethylamine N-oxide (TMAO) in heart failure (HF). METHODS: PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, Web of Science, Wanfang Database, SINOMED, China Science and Technology Journal Database (VIP), and China National Knowledge Infrastructure (CNKI) were searched up to June 1, 2021. Studies recording the major adverse cardiovascular events (MACEs) or all-cause mortality in HF patients and their circulating TMAO concentrations were included. Meta-analysis was performed using Stata 13.0. RESULTS: Ten articles (12 studies) involving 13,425 participants from 2014 to 2021 were considered. Compared to low-level TMAO, elevated TMAO was correlated with MACEs and all-cause mortality in HF (RR: 1.28, 95% CI: 1.17, 1.39, P < 0.0001, random-effects model and RR: 1.35, 95% CI: 1.28, 1.42, P < 0.0001, random-effects model, respectively). Consistent results were obtained in all examined subgroups as well as in the sensitivity analysis. CONCLUSION: Elevated TMAO may be an adverse prognostic indicator in patients with HF. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=267208.

Relationships Between Obstructive Sleep Apnea and Cardiovascular Disease: A Bibliometric Analysis (2010-2021).

BACKGROUND Obstructive sleep apnea (OSA) is a common disease that can lead to intermittent hypoxia, increased sympathetic overdrive, and excessive oxidative stress, and eventually lead to cardiovascular/cerebrovascular diseases and metabolic disorders. The prevalence of OSA is reported to be higher in people with certain cardiovascular diseases (CVD). Therefore, the relationship between OSA and CVD has been gradually favored by researchers. MATERIAL AND METHODS Data were downloaded from the Web of Science Core Collection database. Citespace was used to remove duplicated data and construct knowledge visual maps. RESULTS A total of 7047 publications were obtained. The USA was the largest contributor as well as an important player in the cooperation network between nations. The leading institution was the Mayo Clinic. Our study ultimately identified the top 5 hotspots and 4 research frontiers in this field. Top 5 hotspots were: the specific types of obstructive sleep apnea-related cardiovascular and metabolic co-morbidities, the curative effects of CPAP on these co-morbidities, the specific mechanisms of co-morbidities, the importance of polysomnography on OSA and its co-morbidities with CVD, and the prevalence of OSA and its co-morbidities with CVD in particular populations. The top 4 frontiers were: the relationship between OSA and resistant hypertension, the molecular mechanisms of OSA and its co-morbidities with CVD, specific medications and treatment guidelines for the co-morbidities, and the mainstream research methods in this field. CONCLUSIONS This study provides insight and valuable information for researchers and helps to identify new perspectives concerning potential collaborators and cooperative institutions, hot topics, and research frontiers in this field.

Qishen Taohong Granule () as Adjuvant Therapy for Improving Cardiac Function and Quality of Life in Patients with Chronic Heart Failure: A Randomized Controlled Trial.

OBJECTIVE: To confirm the improvement of cardiac function and quality of life (QOL) in patients with chronic heart failure (CHF) via Chinese medicine (CM) Qishen Taohong Granule (, QTG). METHODS: This study was a single-center, prospective, randomized, controlled clinical trial. Seventy-six patients from 27 to 84 years old diagnosed with CHF New York Heart Association (NYHA) class II or III in stage C were enrolled and randomly assigned at a 1:1 ratio to receive QTG or trimetazidine (TMZ), in addition to their standard medications for the treatment of CHF. The study period was 4 weeks. The primary outcomes included cardiac function evaluated by NYHA classification and left ventricular ejection fraction (LVEF), as well as QOL evaluated by CHF Integrated Chinese and Western Medicine Survival Scale (CHFQLS). The secondary outcomes included 6-min walking test (6MWT), CM syndrome score, symptom and sign scores and N-terminal pro-B-type natriuretic peptide (NT-proBNP). All indices were measured at baseline and the end of the trial. RESULTS: At the 4-week follow-up period, the effective rate according to NYHA classification in the QTG group was better than that in the TMZ group (74.29% vs. 54.29%, P<0.05). But there was no significant difference in post-treatment level of LVEF between the two groups (P>0.05). The CHFQLS scores improved by 13.82±6.04 vs. 7.49±2.28 in the QTG and TMZ groups, respectively (P<0.05). Subgroup analysis of the CHFQLS results showed that physiological function, role limitation and vitality were significantly higher in the QTG group than in the TMZ group (15.76±7.85 vs. 7.40±3.36, P<0.05; 16.00±8.35 vs. 10.53±4.64, P<0.05; 15.31±8.09 vs. 7.89±4.60, P<0.05). Compared with TMZ group, treatment with QTG also demonstrated superior performance with respect to 6MWT, CM syndrome, shortness of breath, fatigue, gasping, general edema and NT-proBNP level. No significant adverse reactions or adverse cardiac events occurred during treatment in either group. CONCLUSION: In addition to conventional treatments, the use of QTG as an adjuvant therapy significantly improved cardiac function and QOL in patients with CHF class II or III in stage C. [Registration No. ChiCTR1900022036 (retrospectively registered)].

Antiplatelet Therapy with Integrated Traditional Chinese and Western Medicine for Use in Myocardial Ischemia-Reperfusion Injury: A Review of Clinical Applications and Mechanisms.

Myocardial ischemia-reperfusion injury (MIRI) is common in patients with acute coronary syndrome (ACS) after PCI treatment, which seriously affects the efficacy of revascularization and hinders the postoperative recovery of patients; therefore, the current study is focused on determining effective methods in the treatment of MIRI. Antiplatelet therapy is a routine treatment for ACS, and its benefits for treating MIRI have been previously verified. With the development of traditional Chinese medicine (TCM), many TCM preparations are widely used in the clinic. Many basic and clinical studies have shown that TCM can be used together with antiplatelet drugs, and the safety and efficacy when TCM is included in the treatment are better than when antiplatelet drugs are used alone. This paper summarizes the current research progress of traditional Chinese medicine and Western medicine in the treatment of MIRI to provide a theoretical basis for further research and clinical treatment.

Cardiac rehabilitation of Baduanjin exercise in coronary heart disease after PCI: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Percutaneous coronary intervention (PCI) is an effective revascularization strategy in patients with coronary heart disease (CHD). However, recent studies had indicated that postPCI patients usually suffer from a low-quality life. Cardiac rehabilitation (CR) has been recommended by numerous guidelines in the clinic for these patients. And Baduanjin exercise can significantly benefit patients with CHD. Regrettably, the effect of Baduanjin exercise on postPCI patients is still not clear. Therefore, this systematic review and meta-analysis protocol is planned to explore the effect of Baduanjin exercise in patients with CHD who have undergone PCI. METHODS: PubMed, Excerpta Medica Database, Cochrane Library, Web of Science, Wanfang Database, SINOMED, China Science and Technology Journal Database, and China National Knowledge Infrastructure will be searched for appropriate articles from respective inceptions until December 1th, 2020. Two reviewers will independently conduct article selection, data collection, and risk of bias evaluation. Disagreements will be resolved first by discussion and then by consulting a third author for arbitration. The primary outcome will include left ventricular ejection fraction. And the change in the scores on the Seattle Angina Questionnaire, SF-36 health survey scale, Zung Self-rating Anxiety scale and self-rating depression scale will be used as the secondary outcomes. RevMan 5.3 will be used for meta-analysis. RESULTS: This systematic review and meta-analysis will explore whether Baduanjin exercise is an effective intervention in postPCI patients. CONCLUSION: This systematic review and meta-analysis will provide convincing evidence of Baduanjin exercise that specifically focuses on CR of Baduanjin exercise on CHD after PCI. REGISTRATION NUMBER: INPLASY202130065.

Astragaloside IV protects human cardiomyocytes from hypoxia/reoxygenation injury by regulating miR-101a.

Astragaloside IV (AS/IV) is one of the extracted components from the traditional Chinese medicine Astragalus which has been demonstrated to have potential capacity for anti-inflammation activity and for treating cardiovascular disease. Our purpose was to determine the function and underlying molecular mechanism of AS/IV in hypoxia/reoxygenation (H/R) injured in cardiomyocytes. Differentially expressed genes (DEGs) were screened using bioinformatic analysis, and the molecular targeting relationship was verified by the dual-luciferase report system. H/R injured cardiomyocytes were employed to explore the effect of AS/IV. QRT-PCR and Western blot analysis were applied to detect the expression of mRNA and proteins, respectively. Additionally, superoxide dismutase (SOD), lactic dehydrogenase (LDH) and MDA (malondialdehyde) levels were detected to determine the oxidative damage. Cell viability was assessed by CCK-8, and flow cytometry was used to evaluate cell apoptosis ratio. TGFBR1 and TLR2 were selected as DEGs. Additionally, AS/IV could enhance cell proliferation and upregulated miR-101a expression, which suppressed TGFBR1 and TLR2 expression in H/R injured cardiomyocytes. Moreover, the results of Western blot exhibited that the downstream genes (p-ERK and p-p38) in the MAPK signaling pathway were suppressed, which meant AS/IV could inhibit this pathway in H/R injured cardiomyocytes. Overall, this study demonstrated AS/IV could attenuate H/R injury in human cardiomyocytes via the miR-101a/TGFBR1/TLR2/MAPK signaling pathway axis, which means that it could serve as a possible alternate for H/R treatment.

Astragalus polysaccharide protects human cardiac microvascular endothelial cells from hypoxia/reoxygenation injury: The role of PI3K/AKT, Bax/Bcl-2 and caspase-3.

In the present study, the mechanisms associated with the Astragalus polysaccharide (APS)-mediated protection of human cardiac microvascular endothelial cells (HCMEC) against hypoxia/reoxygenation (HR) injury were investigated. Pretreatment of HCMECs with APS at various concentrations was performed prior to Na2S2O4-induced HR injury. Subsequently, cell viability and apoptosis were measured by MTT and Hoechst assays, respectively. The viability of HCMECs was reduced by Na2S2O4 and apoptosis was enhanced; however, cell viability was observed to be increased by APS via inhibition of apoptosis. Additionally, intracellular reactive oxygen species (ROS), Ca2+, nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT), B­cell lymphoma­2 (Bcl­2), Bcl­2 associated X protein (Bax) and caspase­3 were measured using detection kits or western blot analysis. In HCMECs with HR injury, the levels of ROS and Ca2+, MDA and Bax expression levels, and the activity of caspase­3 were elevated. By contrast, the level of NO, the protein expression levels of SOD, Bcl­2 and PI3K, and the phosphorylation of AKT were decreased. However, compared with the HR group, the effects of HR injury were significantly reduced by APS, with APS providing a protective effect on HCMECs, particularly at higher doses. The current study concluded that APS protects HCMECs from Na2S2O4­induced HR injury by reducing the levels of ROS, Ca2+, MDA and Bax, inhibiting the activity of caspase­3, and enhancing the levels of NO, SOD, Bcl­2, PI3K and phosphorylated AKT. These results may provide an insight into the clinical application of APS and novel therapeutic strategies for HR injury.