BACKGROUND:In 2012, the randomised trial IABP SHOCK II demonstrated that IABP did not reduce 30-day mortality in patients with acute myocardial infarction complicating cardiogenic shock (CS). However, SCAI proposed a new standardised classification of cardiogenic shock in 2019. It is reasonably hypothesised that the use of IABP may have different benefits for patients in different stages of CS. METHODS:AMI patients ≥18 years who had received treatment of implantation of IABP during emergency setting in Beijing Chaoyang Hospital between December 2010 and July 2021 were enrolled in this study. CS stages were classified at admission for all eligible cases. During the same period, AMI patients without implantation of IABP were matched with each stage of CS above using propensity score matching (PSM). Data were as follows: Stage B (n = 302), Stage C (n = 290), Stage D (n = 68), and Stage E (n = 32). In-hospital mortality was compared between using and without using IABP at each stage. RESULTS:In stage C, the in-hospital mortality was significantly lower in the IABP group (31/145, 21.4%) than in the group without IABP (47/145, 32.4%) (OR 0.567, 95% CI, p = .034). In-hospital mortality had no significant difference between use and no-use of IABP in stage B (16.6% vs 14.6%, p = .634), stage D (47.1% vs 38.2%, p = .462), and in stage E (81.3%vs 68.8%, p = .414). CONCLUSIONS:For patients with acute myocardial infarction complicating cardiogenic shock, IABP has no effect on in-hospital mortality in SCAI stages B, D, and E. However, in SCAI stage C, IABP can reduce in-hospital mortality.

Telomere length (TL) has been linked to mortality risk across various populations. However, its predictive value for mortality risk specifically in hypertensive adults remains unclear. This cohort study utilized data from the 1999–2000 and 2001–2002 cycles of the National Health and Nutrition Examination Survey (NHANES). TL was assessed using DNA methylation (DNAmTL) and quantitative polymerase chain reaction (qPCRTL). Cox proportional hazards models were employed to examine the relationship between TL and mortality risk. This study included 1601 participants, with 988 deaths occurring during a median follow-up of 184 months, including 279 from cardiovascular disease (CVD). Deceased participants exhibited significantly lower levels of DNAmTL (6.45 ± 0.30 vs. 6.70 ± 0.28, P < 0.001) and qPCRTL (0.89 ± 0.22 vs. 0.99 ± 0.24, P < 0.001) compared to survivors. After full adjustment, each 1-kb decrement in DNAmTL and qPCRTL was associated with a 52

Aims The prediction of atrial fibrillation (AF) progression and post-ablation recurrence is currently based on empirical estimates, leading to suboptimal predictive accuracy. This study investigates whether atrial remodelling, a key factor in the severity of atrial cardiomyopathy, could serve as a shared substrate influencing both AF progression and recurrence. We aimed to identify circular RNAs (circRNAs) associated with atrial remodelling and to evaluate their ability to predict AF progression and recurrence. Methods and results We assessed the differential expression of plasma circRNAs between paroxysmal (PAF) and persistent AF (PsAF) patients using microarray analysis. Selected candidate circRNAs were validated through qPCR following rigorous statistical and bioinformatics analysis. circDGCR8 was consistently found to be up-regulated in PsAF compared with PAF patients. Additionally, circDGCR8 was significantly up-regulated in human atrial fibroblasts treated with angiotensin II (AngII). Gain- and loss-of-function studies suggested that circDGCR8 could promote atrial remodelling at cellular level by enhancing collagen production and fibroblast proliferation. Overexpression of circDGCR8 in human cardiac fibroblasts significantly altered the gene expression spectrum, impacting pathways including IL-17 signalling and TNF signalling. Moreover, circDGCR8 levels were positively correlated with atrial fibrosis, as indicated by increased percentages of low voltage zones. The predictive value of circDGCR8 was evaluated in two cohorts: (i) PAF patients monitored for 36 months with progression to PsAF as the endpoint, and (ii) AF patients who underwent radiofrequency ablation followed for 12 months to assess recurrence. In both cohorts, higher level of circDGCR8 was associated with increased risks of AF progression and post-ablation recurrence. Conclusion Our results suggest that circDGCR8, associated with atrial remodelling, holds potential as a predictive biomarker for both AF progression and post-ablation recurrence.

The association between high blood pressure and fracture showed obvious discrepancies and were mostly between hypertension with future fracture, but rarely between fracture and incident hypertension. The present study aims to investigate the associations of hypertension with future fracture, and fracture with incident hypertension. We included adult participants from the China Health and Nutrition Survey (CHNS) prospective cohort in 1997–2015 (N = 10,227), 2000–2015 (N = 10,547), 2004–2015 (N = 10,909), and 2006–2015 (N = 11,121) (baseline in 1997, 2000, 2004, 2006 respectively and outcome in 2015). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. In the analysis of the association between hypertension and future fracture, the adjusted HRs (95% CIs) were 1.34 (0.95–1.90) in 1997–2015, 1.40 (1.04–1.88) in 2000–2015, 1.32 (0.98–1.78) in 2004–2015, and 1.38 (1.01–1.88) in 2006–2015. In the analysis of the association between fracture and incident hypertension, the adjusted HRs (95% CIs) were 1.28 (0.96–1.72) in 1997–2015, 1.18 (0.94–1.49) in 2000–2015, 1.12 (0.89–1.40) in 2004–2015, and 1.09 (0.85–1.38) in 2006–2015. The present study showed that hypertension history was associated with increased risk of future fracture, but not vice versa.

Abstract Background The association between bone fracture and cardiovascular diseases is examined in this study. While basic research has established a connection between fractures and heart attacks through the linkage between bones and arteries, population studies have not provided clear evidence. The aim of the present study is to investigate the association between bone fracture and the occurrence of myocardial infarction in a natural population during long-term follow-up. Methods A total of 13,196 adult participants with bone fracture history at baseline from the China Health and Nutrition Survey (CHNS) prospective cohort were included in this study. Baseline investigation was performed in 1997–2009 and the outcome was followed up till 2015. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Results From 1997 to 2015, a total of 329 incident myocardial infarction cases were identified. In univariate and multivariate Cox regression analysis, a history of bone fracture was associated with an increased risk of myocardial infarction incidence in the total population (for the crude model: HR = 2.56, 95% CI 1.83–3.53, P < 0.001; for the multivariate model: HR = 1.43, 95% CI 1.02–1.99, P = 0.036). In the stratified analysis, bone fracture was not associated with an increased risk of incident myocardial infarction in subjects with age < 50 years (HR = 0.71, 95% CI 0.34–1.47, P = 0.356), but significantly associated with an increased risk of incident myocardial infarction in subjects with age ≥ 50 years (HR = 1.80, 95% CI 1.23–2.63, P = 0.003). Conclusions It is suggested by the present study that bone fracture may be associated with an increased risk of incident myocardial infarction in the elderly population during long-term follow-up.

This study aimed at exploring how using different kinds of sheaths will affect the very first ablation procedure of apprentices. 15 patients with paroxysmal atrial fibrillation were randomized to used fixed-curve, conventional steerable or visualized steerable sheath, and received complete isolation of pulmonary veins. All ablations were the very first procedure performed by 15 ablation apprentices. The use of fluoroscopy and catheter stability during the PVI were analyzed. Procedure duration was much longer in the fixed-curve group (116.8 ± 27 vs. 62.2 ± 17 vs. 60.4 ± 17, p < 0.001). X-ray exposure was lowest with visualized sheath (17.6 ± 5 vs. 18.6 ± 6 vs. 5.2 ± 6, p < 0.001). CF SD differed significantly, especially at the anterior aspect of LSPV (7.90 ± 2.90 vs. 5.04 ± 2.18 vs. 4.52 ± 2.40, p < 0.001) and posterior aspect of RSPV (6.84 ± 2.79 vs. 3.42 ± 2.04 vs. 3.50 ± 2.30, p < 0.001) in the fixed-curve group. Impedance drop was significantly smaller in the fixed-curve group at the anterior aspect of LSPV (8.74 ± 3.02 vs. 11.49 ± 5.48 vs. 12.57 ± 5.96, p = 0.005). Even for the very first ablation procedure of an ablation apprentice, the use of steerable sheaths will significantly reduce the procedure duration and improve the catheter stability, but only visualized steerable sheath can reduce fluoroscopic time.

AbstractAimsThe molecular signatures in epicardial adipose tissue (EAT) that contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF) are poorly characterized. In this study, we sought to elucidate molecular signatures including genetic transcripts and long non‐coding RNAs (lncRNAs) in EAT that might modulate HFpEF development.MethodsRNA sequencing (RNA‐seq) was performed to identify differentially expressed lncRNAs and mRNAs in EAT samples from patients with HFpEF (n = 5) and without HF (control, n = 5) who underwent coronary artery bypass grafting. The sequencing results were validated using quantitative real‐time PCR (qRT‐PCR). Bioinformatics analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) of differentially expressed RNAs was performed to predict enriched functions.ResultsHFpEF patients had higher EAT thickness and NT‐proBNP levels than the control group. A total of 64 471 transcripts were detected including 35 395 protein‐coding sequences, corresponding to 16 854 genes in EAT. RNA‐seq identified a total of 741 dysregulated mRNA transcripts (394 up‐regulated and 347 down‐regulated) and 334 differentially expressed lncRNA transcripts (222 up‐regulated and 112 down‐regulated) in the HFpEF group compared with the control group (P < 0.05). qRT‐PCR analysis confirmed that two lncRNAs ENST00000561775 (P = 0.0194) and ENST00000519093 (P = 0.027) and an mRNA POSTN (P = 0.003) were differentially expressed. Functional enrichment analysis of the differentially expressed mRNAs suggested their potential roles in immune response involving cytokine interaction and chemokine signalling.ConclusionsWe are the first group to report on the lncRNA and mRNA landscape in EAT in HFpEF patients. Our study suggests the possible role of lncRNAs in EAT.

Telomere length (TL) serves as a pivotal gauge of cellular aging, with shorter TL linked to various age-related ailments. Recently, a DNA methylation-based TL estimator, known as DNAmTL, has emerged as a novel TL measurement tool. Our current investigation scrutinized the correlation between DNAmTL and the risks of cardiovascular disease (CVD) and enduring mortality among middle-aged and elderly individuals. We enrolled a nationwide, population-based cohort of subjects from the National Health and Nutrition Examination Survey spanning 1999 to 2002, possessing data on both DNAmTL and quantitative polymerase chain reaction-based TL (qPCRTL). Logistic regression models and Cox proportional hazards models were employed to evaluate the associations of DNAmTL with CVD risk and mortality, respectively. The cohort comprised 2532 participants, with a weighted CVD prevalence of 19.06

Background: Reperfusion injury often persists even with successful primary percutaneous catheterization intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI). Therefore, we developed volume-controlled reperfusion (VCR), a method combined with accurate gentle reperfusion for active protection against unstable plaque formation. This study aimed to investigate the feasibility, safety, and efficacy of VCR as an adjunct for PPCI in patients with STEMI.Methods: The STEMI VCR trial (http://www.chictr.org.cn; Unique identifier: ChiCTR2100052856) was a single-center prospective, interventional, randomized controlled trial. Sixty patients were randomized to the VCR (n = 30, VCR + routine PCI) or control (n = 30, routine PCI only) groups. In-hospital late gadolinium enhancement-cardiac magnetic resonance imaging (LGE-cMRI) was subsequently performed, with follow-up patient evaluation after 12 months.Results: No differences were observed in the occurrence of major adverse cardiac events (MACE) between the two groups. Similarly, there was no procedure failure in the VCR group. In-hospital echocardiographic left ventricular ejection fraction (LVEF) revealed significant differences between the VCR and control groups, with similar results observed in the anterior subgroups. However, LGE-cMRI and CMR-LVEF revealed no significant differences in infarct size, microvascular obstruction (MVO) mass, or MVO mass/infarct mass ratio in the anterior subgroup. Follow-up echocardiographic LVEF revealed significant differences between the two groups and the anterior subgroups.Conclusions: VCR was feasible and clinically safe in patients with STEMI undergoing PPCI, indicating that this adjunctive therapy might attenuate reperfusion injury.Trial Registration: ChiCTR2100052856.Funding: The trial was sponsored by the Clinical Research Incubation Fund (CYFH202204), Beijing Chao-Yang Hospital, Capital Medical University.Declaration of Interest: None.Ethical Approval: The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Beijing Chao-Yang Hospital, Capital Medical University (CYFH202204).

Background: The diagnostic potential of circular RNAs (circRNAs) in circulating exosomes for acute myocardial infarction (AMI) is not well understood, despite existing research indicating their role in cardiovascular diseases. This study aimed to clarify the significance of exosomal circular RNAs as indicators for AMI. Methods: We examined 120 individuals diagnosed with AMI and 83 individuals with non-cardiogenic chest pain (NCCP), all previously enrolled in a conducted study. High-throughput sequencing to identify differentially expressed circRNAs in the circulating exosomes of AMI patients. To validate, we employed Real-Time polymerase chain reaction (RT-PCR) targeting five circRNAs that exhibited notable increase. Results: The sequencing identified 893 exosomal circRNAs with altered expression in AMI patients, including 118 up-regulated and 775 down-regulated circRNAs. Genes linked to these circRNAs were enriched in crucial Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, highlighting their direct relevance to AMI pathophysiology. Three exosomal circRNAs (hsa_circ_0001558, hsa_circ_0001535, and hsa_circ_0000972) showed significant up-regulation in AMI patients during the initial validation cohort. The corresponding area under the curve (AUC) values were 0.79, 0.685, and 0.683, respectively. Further validation of hsa_circ_0001558 in a second cohort showed a 4.45-fold increase in AMI patients, with AUC = 0.793. The rise was particularly noticeable in patients with non-ST-elevation myocardial infarction (NSTEMI) (2.80 times, AUC = 0.72) and patients with ST-elevation myocardial infarction (STEMI) (5.27 times, AUC = 0.831) compared to patients with NCCP. Conclusions: Our findings demonstrate significant differences in the expression patterns of circRNAs in plasma exosomes between AMI patients and NCCP patients. Specifically, hsa_circ_0001558 appears as a promising indicator for AMI diagnosis. Further research is necessary to fully evaluate the diagnostic potential of exosomal circRNAs in the context of AMI, emphasizing the importance of these findings.

Abstract Background Atrial fibrillation (AF) is associated with circulating inflammation. Short-chain fatty acids (SCFAs) derived from gut microbiota (GM) regulate leukocyte function and inhibit the release of inflammatory cytokines, which are partly mediated by the G-protein-coupled receptor 43 (GPR43) signaling. This study aimed to investigate the expression of GPR43/NOD-like receptors family pyrin domain containing 3 (NLRP3) in leukocytes and the interaction with intestinal SCFAs levels in AF patients. Methods Expressions of GPR43 and NLRP3 mRNA in peripheral blood leukocytes from 23 AF patients and 25 non-AF controls were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Expressions of leukocyte GPR43 and NLRP3 protein were evaluated by western blot analysis. The levels of plasma IL-1β were measured by enzyme-linked immunosorbent assay (ELISA). The fecal SCFAs levels based on GC/MS metabolome of corresponding 21 controls and 14 AF patients were acquired from our published dataset. To evaluate the expression of NLRP3 and GPR43 and the release of IL-1β, human THP-1 cells were stimulated with or without SCFAs (acetate, propionate, and butyrate), lipopolysaccharide (LPS), and nigericin in vitro, respectively. Results Compared to the controls, the mRNA expression in peripheral leukocytes was significantly reduced in AF patients (P = 0.011) coupled with the increase in downstream leukocyte NLRP3 mRNA expression (P = 0.007) and plasma IL-1β levels (P < 0.001), consistent with changes in GPR43 and NLRP3 protein expression. Furthermore, leukocyte GPR43 mRNA levels were positively correlated with fecal GM-derived acetic acid (P = 0.046) and negatively correlated with NLRP3 mRNA expression (P = 0.024). In contrast to the negative correlation between left atrial diameter (LAD) and GPR43 (P = 0.008), LAD was positively correlated with the leukocyte NLRP3 mRNA levels (P = 0.024). Subsequent mediation analysis showed that 68.88% of the total effect of intestinal acetic acid on AF might be mediated by leukocyte GPR43/NLRP3. The constructed GPR43–NLRP3 score might have a predictive potential for AF detection (AUC = 0.81, P < 0.001). Moreover, SCFAs treatment increased GPR43 expression and remarkably reduced LPS/nigericin-induced NLRP3 expression and IL-1β release in human THP-1 cells in vitro. Conclusions Disrupted interactions between GPR43 and NLRP3 expression in peripheral blood leukocytes, associated with reduced intestinal GM-derived SCFAs, especially acetic acid, may be involved in AF development and left atrial enlargement by enhancing circulating inflammation.

This study aimed to investigate the role of the gut microbiota (GM)-bile acid (BA)-fibroblast growth factor (FGF) 19 axis in patients with atrial fibrillation (AF). Gut bacterial metabolisms of BAs were determined in an AF metagenomic dataset. The composition of faecal BAs pools was characterized by targeted metabolomics in an independent AF cross-sectional cohort. Circulating levels of FGF19 were measured by ELISA. In vitro cell experiments were conducted to validate the regulatory role of FGF19 in atrial cardiomyocytes stimulated with palmitic acid. First, metagenomic profiling revealed that gut microbial biotransformation from primary to secondary BAs was dysregulated in AF patients. Second, the proportion of secondary BAs decreased in the faeces of patients with AF. Also, eight BAs were identified as AF-associated BAs, including seven AF-enriched BAs (ursodeoxycholic acid, chenodeoxycholic acid, etc.), and AF-decreased dehydrolithocholic acid. Third, reduced levels of circulating FGF19 were observed in patients with AF. Subsequently, FGF19 was found to protect against palmitic acid-induced lipid accumulation and dysregulated signalling in atrial cardiomyocytes, including attenuated phosphorylation of YAP and Ca2+ /calmodulin-dependent protein kinases II and secretion of interleukin-1β, mediated via peroxisome proliferator-activated receptor α. Our data found decreased levels of secondary BAs and circulating FGF19, resulting in the impaired protective function of FGF19 against lipid accumulation in atrial cardiomyocytes.

Background: The purpose of this study was to explore whether consideration of FIB levels might improve the predictive value of the ACEF score in patients with ACS. Methods: A total of 290 patients with ACS were enrolled in this study. The clinical characteristics and MACE were recorded. Results: Multivariate logistic regression analysis revealed that the FIB level (odds ratio=7.798, 95%CI, 3.44–17.676, P<0.001) and SYNTAX score (odds ratio=1.034, 95%CI, 1.001–1.069, P=0.041) were independent predictors of MACE. On the basis of the regression coefficient for FIB, the ACEF-FIB was developed. The area under the ROC of the ACEF-FIB scoring system in predicting MACE after PCI was 0.753 (95%CI 0.688–0.817, P<0.001), a value greater than those for the ACEF score, SYNTAX score and Grace score (0.627, 0.637 and 0.570, respectively). Conclusion: ACEF-FIB had better discrimination ability than the other risk scores, according to ROC curve analysis, net reclassification improvement and integrated discrimination improvement.

Emerging evidence suggests an association of dysbiotic gut microbiota (GM) with atrial fibrillation (AF). The current study aimed to determine whether aberrant GM promotes AF development. A fecal microbiota transplantation (FMT) mouse model demonstrated that dysbiotic GM is sufficient to enhance AF susceptibility assessed by transesophageal burst pacing. Compared with recipients transplanted with GM obtained from healthy subjects (FMT-CH), the prolonged P wave duration and an enlarging tendency for the left atrium were detected in recipients transplanted with AF GM (FMT-AF). Meanwhile, the disrupted localizations of connexin 43 and N-cadherin and increased expression levels of phospho-CaMKII and phospho-RyR2, were observed in the atrium of FMT-AF, which indicated aggravated electrical remodeling caused by the altered gut flora. Specifically, exacerbated fibrosis disarray, collagen deposition, α-SMA expression, and inflammation in the atrium were also confirmed to be transmissible by the GM. Furthermore, deteriorated intestinal epithelial barrier and intestinal permeability, accompanied by disturbing metabolomic features in both feces and plasma, especially decreased linoleic acid (LA), were identified in FMT-AF mice. Subsequently, the anti-inflammatory role of LA among the imbalanced SIRT1 signaling discovered in the atrium of FMT-AF was confirmed in mouse HL-1 cells treated with LPS/nigericin, LA, and SIRT1 knockdown. This study provides preliminary insights into the causal role of aberrant GM in the pathophysiology of AF, suggesting the GM-intestinal barrier-atrium axis might participate in the vulnerable substrates for AF development, and the GM could be utilized as an environmental target in AF management.

AIMS:Intensive systolic blood pressure (SBP) lowering has been increasingly used; however, data is missing on patients who had target-achieved (TA). This study aims to show the cardiovascular effect of maintaining SBP at intensive levels. METHODS:The Strategy of Blood Pressure Intervention in Elderly Hypertensive Patients (STEP) trial was a multicentre, randomized, controlled trial which enrolled 8511 young-older (60-80 years) hypertensive patients without prior stroke to compare the cardiovascular prognosis of the intensive treatment (SBP target, 110 to <130 mmHg) vs. the standard treatment (130 to <150 mmHg). This secondary analysis assessed data in patients who achieved a mean SBP within target values. The association of mean achieved SBP and cardiovascular events was examined using a cubic spline function. RESULTS:In total, 3053 patients (72.0%) in the intensive-treatment group and 3427 (80.3%) in the standard-treatment group had an SBP target achieved, with mean follow-up SBP values of 124.2 mmHg and 137.4 mmHg, respectively. Throughout the median 3.38-year follow-up, the cardiovascular risk was significantly lower in the TA intensive-treatment group than in the TA standard-treatment group [adjusted hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.46-0.80; P < 0.001]. In the intensive-treatment group, patients failing to achieve SBP targets presented higher cardiovascular risk than those TA patients (HR 2.04, 95% CI 1.44-2.88; P < 0.001). A J-shaped relationship was observed between the mean achieved SBP and risk of cardiovascular events, with the lowest risk at an SBP of 126.9 mmHg. CONCLUSIONS:Maintaining SBP at <130 mmHg offers additional cardiovascular benefits among young-older patients with hypertension. REGISTRATION:ClinicalTrials.gov: NCT03015311.

OBJECTIVE:To analyze the factors related to pregnancy of endometriosis and whether Chinese herbal medicines (CHMs) can improve pregnancy outcomes in patients with endometriosis in long-term management. METHODS:This multicenter cohort study retrospectively analyzed the clinical data of endometriosis patients with fertility needs from January 2019 to November 2019. A total of 252 patients with endometriosis from 5 level-III Grade A hospitals in Beijing were included in this study. Univariate and multivariate logistic regression analysis were performed for the relevant factors. The propensity score matching (PSM) function of SPSS software was used to match the CHMs group with the non-CHMs group. The pregnancy rate and live birth rate were analyzed. RESULTS:The results of univariate analysis showed that age, disease course, presence of infertility, presence of adenomyosis, time after surgery or use of gonadotropin-releasing hormone agonist (GnRH-a), use of CHMs and follow-up time were influencing factors of pregnancy in endometriosis patients (P<0.05). The results of multivariate analysis showed that age, presence of adenomyosis, time after surgery or use of GnRH-a, use of CHMs and follow-up time were independent factors affecting pregnancy in endometriosis patients, among which, age ⩾35 years old, presence of adenomyosis and follow-up time >6 months were independent risk factors (OR=0.445, 0.348, 0.140, respectively, P<0.05), time after surgery or use of GnRH-a ⩽6 months and use of CHMs were independent protective factors (OR=3.839, 3.842, respectively, P<0.05). After PSM, 99 pairs of two groups were matched successfully. The pregnancy rate of the CHMs group was higher than that of the non-CHMs group [55.56% (55/99) vs. 36.36% (36/99), P<0.05]. The live birth rate of the CHMs group was higher than that of the non-CHMs group [49.49% (49/99) vs. 35.35% (35/99), P<0.05]. CONCLUSION:CHMs can effectively improve clinical pregnancy rate and live birth rate of patients with endometriosis in the chronic disease management.

Background:It has been well acknowledged that disordered intestinal microflora and their fermented products play crucial role during the development of hypertension (HTN). Aberrant profiles of fecal bacteria have been documented in subjects with isolated systolic HTN (ISH) and isolated diastolic HTN (IDH) previously. Nevertheless, evidence regarding the association of metabolic products in the bloodstream with ISH, IDH and combined systolic and diastolic HTN (SDH) remains scarce.Methods:We performed a cross-sectional study and conducted untargeted liquid chromatography-mass spectrometry (LC/MS) analysis on serum samples of 119 participants, including 13 subjects with normotension (SBP < 120/DBP < 80 mm Hg), 11 individuals with ISH (SBP ≥ 130/DBP < 80 mm Hg), 27 patients with IDH (SBP < 130/DBP ≥ 80 mm Hg), and 68 SDH patients (SBP ≥ 130, DBP ≥ 80 mm Hg).Results:Here, the results showed clearly separated clusters in PLS-DA and OPLS-DA score plots for patients suffering from ISH, IDH and SDH when compared with normotension controls. The ISH group was characterized by elevated levels of 3,5-tetradecadien carnitine and notable reduction of maleic acid. While IDH patients were enriched with metabolites in L-lactic acid and depleted in citric acid. Stearoylcarnitine was identified to be specifically enriched in SDH group. The differentially abundant metabolites between ISH and controls were involved in tyrosine metabolism pathways, and in biosynthesis of phenylalanine for those between SDH and controls. Potential linkages between the gut microbial and serum metabolic signatures were detected within ISH, IDH and SDH groups. Furthermore, we found the association of discriminatory metabolites with the characteristics of patients.Conclusion:Our findings demonstrate disparate blood metabolomics signatures across ISH, IDH and SDH, with differentially enriched metabolites and potential functional pathways identified, reveal the underlying microbiome and metabolome network in HTN subtypes, and provide potential targets for disease classification and therapeutic strategy in clinical practice.

BACKGROUND Reperfusion injury is associated with larger infarct size and drawback of long-term outcome in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Volume-Controlled Reperfusion (VCR) is our original reperfusion method combined with accurate gentle reperfusion and active protection for unstable plaque. A single center, prospective, randomized clinical trial was conducted to demonstrate the feasibility, clinical safety, and potential effects of VCR in STEMI patients during PPCI. METHODS AND RESULTS A total of 60 patients with STEMI presenting within 12 h of symptom onset undergoing PPCI were randomized enrolled to VCR group (n=30) or control group (n=30). Patients in VCR group recanalized with VCR followed by routine PCI. Patients in control group recanalized with routine PCI procedure only. The primary endpoint was all-cause death and major adverse cardiac events (MACE) during hospitalization and followed up, the main second endpoints were MVO extent measured 5-7 days post PPCI and left ventricular function. Baseline characteristics were well matched between two groups. No MACE from in-hospital to 1 year followed up in VCR group. In-hospital echocardiography based left ventricular eject fraction (LVEF) in VCR group compared with control group was (57.6 ± 6.2) % vs (52.9 ± 8.5) %, p = 0.018; especially in anterior STEMI VCR subgroup (55.1 ± 6.3) % v (s 48.6 ± 6.4) %, p = 0.003. There was no significant difference in infarct size, MVO mass or MVO mass/infarct mass ratio by late gadolinium enhancement-cardiac magnetic resonance imaging (LGE-CMR). In hospital CMR based LVEF in anterior STEMI VCR subgroup was (50.55 ± 7.55) % vs (40.53 ± 7.39) %, p = 0.002. Follow up echocardiography based LVEF were (64.12 ± 6.35) % vs (59.44 ± 8.20) %, p = 0.025 between two groups and (62.07 ± 7.06) % vs (55.94 ± 6.70) %, p = 0.016 between anterior STEMI subgroups. CONCLUSIONS This is the pilot RCT study demonstrated that VCR method was feasibility and clinical safe among patients with acute STEMI during PPCI to 12-month follow-up, indicated potential attenuate effect in reperfusion injury as well. Staged II RCT is needed to verify clinical benefit. REGISTRATION URL: . Unique identifier: ChiCTR00052856 ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial REGISTRATION: URL: . Unique identifier: ChiCTR00052856 ### Funding Statement This research project is funded by the Clinical Incubation Program of Beijing Chaoyang Hospital (CYFH202204) and Beijing Municipal Administration of Hospitals (XXZ0607). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was conducted in accordance with the Declaration of Helsinki and the protocol was approved by the ethics committee in Beijing Chao-Yang Hospital, Capital Medical University. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All the data mentioned in the manuscript are available to public.

Abstract Background Microfibrillar-associated protein (MFAP4), initially identified as an extracellular matrix protein, has been demonstrated in multiple human disorders, but it is yet to be discovered following acute coronary syndrome (ACS) in clinical practice. Therefore, this study aimed to investigate the relationship between circulating MFAP4 levels and coronary stenosis in ACS. Methods We performed the study in 148 ACS subjects, including 75 ST-segment elevation myocardial infarction (STEMI), 27 non-ST-segment elevation myocardial infarction (non-STEMI) and 46 unstable angina (UA). Clinical variables were collected and Gensini and Syntax stenosis scoring systems were applied to assess the severity of coronary stenosis. Kaplan–Meier and logistic regression analysis were used to analyze the relationship between MFAP4 and the severity of coronary stenosis or ACS outcomes. Spearman analysis was used to describe the correlation between MFAP4 and clinical parameters. Results Circulating MFAP4 levels were significantly decreased in the STEMI group (0.008 ng/ml) compared with the non-STEMI group (0.014 ng/ml) and UA group (0.019 ng/ml) (p < 0.001). After adjusting for confounding factors, we found that MFAP4 was an independent risk factor for STEMI (odds ratio = 0.395, 95% CI 0.174–0.895, p = 0.026). MFAP4 level was negatively correlated with Gensini score and Syntax score (r = − 0.311 and − 0.211, p < 0.001 and 0.01, respectively). Based on the MFAP4 level of 0.117 ng/ml, ACS patients were divided into two groups: the low-MFAP4 group (< 0.117 ng/ml, n = 60) and the high-MFAP4 group (≥ 0.117 ng/ml, n = 88). After the median follow-up of 165 days, Kaplan–Meier survival analysis revealed that the MACE-free rate was significantly lower in ACS patients with lower MFAP4 levels (p = 0.009). Conclusions MFAP4 has a potential as a biomarker for the degree of coronary stenosis in ACS. Confirmation of observations in larger cohorts and longer follow-up periods is warranted.

OBJECTIVE:Heart failure with preserved ejection fraction (HFpEF) is a complex cardiovascular syndrome. Along with pro-inflammatory and metabolic factors, epicardial adipose tissue (EAT) is believed to play a key role in the pathogenesis of HFpEF. Studies have increasingly shown a critical role of circRNAs in the development of cardiovascular diseases; however, their role in the pathogenetic mechanism of HFpEF is not well characterized. The objective of this study was to investigate the expression profiles of circRNAs in EAT of HFpEF patients.METHODS:Samples of epicardial adipose tissue were obtained from patients with HFpEF (n=5) and patients without heart failure (non-HF; n=5). CircRNA expression profiles were screened using RNA sequencing method. RNA-sequencing results were confirmed by qRT-PCR analysis. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed on the differentially expressed circRNAs.RESULTS:A total of 131 circRNAs were differentially expressed between HFpEF and non-HF groups (77 upregulated and 54 downregulated). Among these, hsa_circ_0118464 corresponding to HECW2 gene which showed the highest fold-change was assessed by qRT-PCR, and the outcome was consistent with RNA-sequencing results. The differentially expressed circRNAs corresponded to genes mainly involved in regulation of cellular and metabolic processes.CONCLUSION:This study provides the expression profile of circRNAs in EAT of HFpEF patients and the associated molecular mechanism. Our findings may provide insight into diagnostic markers and therapeutic targets in the context of HFpEF.