Abstract:Cardiac rehabilitation is a core comprehensive intervention system for the full-cycle management and secondary prevention of cardiovascular diseases. Evidence-based medicine has demonstrated that this system can effectively improve patients' cardiopulmonary function, exercise endurance, and quality of life, reduce readmission rates and the risk of cardiovascular adverse events. Currently, it has been listed as a Class I recommended plan by multiple authoritative guidelines at home and abroad. At present, there are a large number of cardiovascular disease patients in China. Although the cardiac rehabilitation industry is steadily developing, there are still problems such as low patient participation rate, insufficient standardization, single evaluation system, homogeneous intervention plans, and weak management of special populations. This article combines five studies in this column to explore prognostic markers, construct non-exercise cardiopulmonary function prediction models, analyze traditional exercise rehabilitation mechanisms, and review cutting-edge achievements in the field of perioperative rehabilitation in cardiac surgery. It objectively evaluates the clinical value, application advantages, and limitations of various technologies and plans, and looks forward to future development directions, aiming to provide evidence-based reference and theoretical support for clinical practice, scientific research innovation, and disciplinary construction of cardiac rehabilitation in China.

Abstract:Aim To investigate the predictive value of peak rate-pressure product (RPP peak) derived from cardiopulmonary exercise testing (CPET) for the risk of heart failure after acute myocardial infarction (AMI), and to evaluate its role in risk stratification. Methods This retrospective cohort study included AMI patients who underwent early standardized symptom-limited cycle ergometer-based CPET between January 2018 and December 2023 at the Second Affiliated Hospital of Harbin Medical University, Guangdong Provincial People's Hospital, and Hegang People's Hospital. Patients were classified into heart failure after acute myocardial infarction (Post-MI HF) and non-Post-MI HF groups based on the occurrence of Post-MI HF. Cox proportional hazards regression was used to assess the association between RPP peak and the risk of Post-MI HF. Restricted cubic spline (RCS) analysis was applied to examine the dose-response relationship between RPP peak and post-MI HF risk. Time-dependent receiver operating characteristic (ROC) curves were used to evaluate the predictive performance of RPP peak. For risk stratification, patients were categorized into tertiles (T1, T2 and T3) according to RPP peak levels. Kaplan-Meier survival curves were constructed to compare cumulative event-free survival across tertiles, and Cox regression analysis was further performed to quantify risk differences among groups. Results After applying inclusion and exclusion criteria, 2 221 AMI patients were included, among whom 237 developed post-MI HF. Cox regression analysis demonstrated that elevated RPP peak was an independent protective factor for Post-MI HF, with each one-unit increase in RPP peak associated with a 9% reduction in Post-MI HF risk (HR＝0.4,5%CI:0.883~0.944, P＜0.001). RCS analysis indicated a linear association between RPP peak and Post-MI HF risk (P_nonlinear＝0.978). ROC curves analysis showed that RPP peak achieved higher area under the curve (AUC) values for predicting 1-, 3-, and 5-year Post-MI HF compared with peak heart rate (HR peak) and peak systolic blood pressure (SBP peak) alone. Kaplan-Meier analysis revealed a significant graded relationship between RPP peak tertiles and Post-MI HF risk (Log-rank P＜0.001), with higher RPP peak levels associated with improved survival. Further Cox regression analysis showed that, compared with the lowest tertile (T1), the risk of post-MI HF was significantly lower in T2 (HR＝0.8,5%CI:0.363~0.657, P＜0.001) and T3 (HR＝0.8,5%CI:0.219~0.434, P＜0.001). Conclusions RPP peak is an independent predictor of Post-MI HF and is linearly and inversely associated with Post-MI HF risk. These findings highlight the clinical value of RPP peak for early risk assessment, prevention, and risk stratification in AMI patients.

Abstract:Aim To develop a peak oxygen uptake (VO₂ peak) prediction equation applicable to Chinese cardiovascular disease (CVD) patients. Methods This study was a retrospective multicenter study that included 21 402 CVD patients who underwent cardiopulmonary exercise testing (CPET) from 20 hospitals between January 2018 and December 2024, and randomly divided into a development group (n＝14 981) and a verification group (n＝6 421) at a ratio of 7∶3. Multiple forward stepwise regression analysis method was used to establish a VO₂ peak prediction equation suitable for Chinese CVD patients, which was compared with prediction equations established from other cohorts. Results This study incorporated age, sex, height, body weight and CVD diagnosis as key influencing factors into the predictive equation, resulting in the final predictive model:VO₂ peak (mL/min)＝246.206－ (9.858×age (years)＋(187.643×sex (male＝1, female＝0)＋(4.500×height (cm)＋(10.250×weight (kg)＋(94.969×SA (yes＝1, no＝0)－(39.293×PCI (yes＝1, no＝0)－(110.124× MI (yes＝1, no＝0)－(208.447×HF (yes＝1, no＝0). Adjusted R²＝0.51, SE＝264.0 mL/min. The validation group analysis showed that the Wasserman prediction equation (152%), Friend healthy population prediction equation (197%), Friend CVD prediction equation (117%), Chinese healthy population PUTH prediction equation (292%), and Chinese healthy population X-ET prediction equation (109%) all overestimated the VO₂ peak of Chinese CVD patients, while the prediction results of the Chinese CVD prediction equation (104%) developed in this study were closer to the measured values. Conclusion This study developed a VO₂ peak prediction equation suitable for Chinese CVD patients, which has smaller prediction errors compared to existing equations and is more suitable for the Chinese population.

Abstract:Aim To investigate the prognostic value of the endothelial activation and stress index (EASIX) in patients with cardiovascular-kidney-metabolic syndrome (CKM) and acute myocardial infarction (AMI), and to evaluate its association with the risks of all-cause and cardiovascular mortality. Methods This study enrolled a total of 3 996 patients hospitalized for AMI who met the diagnostic criteria for CKM stage 4 between December 2017 and September 2019.Using the optimal cutoff value of log₂(EASIX) as the grouping basis, we evaluated its association with the risk of all-cause and cardiovascular mortality. Furthermore, propensity score matching (PSM), Fine-Gray competing risk models, and subgroup analysis were performed to verify the robustness of the study's conclusions. Results Restricted cubic spline regression revealed a J-shaped nonlinear relationship between log₂(EASIX) and the risks of all-cause and cardiovascular mortality. Kaplan-Meier survival curves demonstrated that patients in the high-EASIX group experienced significantly elevated risks of mortality from the early follow-up period (P＜0.001), and this trend remained robust after PSM. Fine-Gray competing risk models confirmed that EASIX was a potent independent predictor of cardiovascular death, regardless of matching or multivariable adjustment (fully adjusted SHR of 4.799 and 5.741, respectively, both P＜0.05). In Cox regression analysis, each 1-unit increase in log₂(EASIX) as a continuous variable was associated with a 1.665-fold increase in the risk of all-cause mortality (95%CI:1.363～2.034, P＜0.001); this association remained significant after full adjustment for all confounders (HR 1.4,5%CI:1.293～1.966, P＜0.001), with an even higher risk observed for cardiovascular mortality. Intergroup comparisons showed that the risk of all-cause mortality in the high-EASIX group was approximately 4.718 times that of the low-EASIX group (95%CI:2.849～7.813, P＜0.001). Furthermore, time-dependent receiver operating characteristic curve analysis indicated that EASIX exhibited superior predictive performance in short-term prognostic assessment. Conclusions In the CKM-AMI population, the EASIX score demonstrates a robust and independent association with mortality risk. As a simple and efficient predictive tool, EASIX holds significant potential to assist clinicians in the early identification of high-risk patients and the optimization of prognostic management strategies.

Abstract:Aim To investigate the effects of the traditional Chinese exercise Baduanjin on gut microbiota and metabolomic profiles of patients with chronic heart failure, elucidating its potential therapeutic benefits by characterizing microbiome and metabolomic features. Methods Thirty-two patients with chronic heart failure were enrolled and divided into two groups:the control group received conventional treatment, while the Baduanjin group practiced Baduanjin in addition to conventional therapy. After 12 weeks of intervention, fecal and serum samples were collected from both groups of patients for gut microbiota and serum metabolomics analysis. Results At baseline, Baduanjin group and control group showed no significant differences in demographic characteristics, vital signs, heart failure classification, or comorbidities (P＞0.05). After 12 weeks of Baduanjin exercise, compared with the control group, the Baduanjin group showed a significant increase in the 6-minute walking distance (P＝0.026); meanwhile, the improvement in peak oxygen uptake exceeded the minimum clinically significant difference, but the intergroup difference did not reach statistical significance (P＝0.323). Analysis of gut microbiota showed that compared with the control group, the Baduanjin group had relatively higher alpha diversity, but there was no statistically significant difference in alpha diversity and beta diversity between the two groups (P＞0.05); 14 discriminative taxa were identified (7 related to the Baduanjin group and 7 related to the control group), at the genus level, the relative abundance of the Dialister was highest in the Baduanjin group (P＝0.021), while the relative abundance of the Haemophilus was highest in the control group (P＝0.037). Metabolite profile analysis showed that non-targeted metabolomics results indicated that the metabolite profile characteristics of the two groups were distinguishable; 39 differential metabolites were identified, with enriched pathways including cancer-related choline metabolism, primary bile acid biosynthesis, glycerophospholipid metabolism, and niacin/nicotinamide metabolism. The analysis of gut microbiota combined with serum metabolites showed a positive correlation between the genus Dialister and lysophosphatidylcholine (20∶1(11Z)/0∶0) in the Baduanjin group (r＝0.55, P＝0.001), and there was a positive correlation between Haemophilus and N1-methyl-2-pyridone-5-carboxamide in the control group (r＝0.56, P＝0.001). Conclusion Baduanjin exercise can improve exercise endurance in patients with chronic heart failure, and may also improve the intestinal metabolic environment and skeletal muscle mitochondrial energy metabolism by increasing the production of short chain fatty acid related bacteria and raising the level of lysophosphatidylcholine.

Abstract:As the prevalence of coronary heart disease continues to rise, the application of coronary artery bypass grafting (CABG) has become increasingly widespread. Perioperative management of CABG patients is of critical importance, and early perioperative enhanced recovery after surgery (ERAS), particularly exercise training, has emerged as a key factor in improving outcomes for these patients. Existing evidence indicates that early exercise training significantly improves patients' cardiopulmonary function, exercise tolerance, and psychological status, while reducing complication rates, shortening hospital stays, and lowering medical costs. This article summarizes evidence from rehabilitation studies published in the past five years, providing a systematic introduction to perioperative ERAS for CABG patients, with a focus on the implementation, clinical value, innovative models, and precautions of exercise training. The aim is to provide evidence-based support for optimizing exercise rehabilitation protocols. Future efforts should further explore individualized rehabilitation strategies based on minimally invasive techniques and mobile health.

Abstract:Aim To investigate the mechanism by which hawthorn-derived exosome-like nanovesicles (HDELN) on inhibiting the activation of rat cardiac fibroblasts (RCF) induced by angiotensinⅡ(AngⅡ) and transforming growth factor-β (TGF-β). Methods Primary RCF was extracted and cultured in vitro. RCF activation was induced by AngⅡ and TGF-β, and the cell viability was detected by CCK-8 assay. Western blot was used to detect protein expression levels. RT-qPCR was used to detect the mRNA expression levels. Cell scratch assay was used to detect cell migration ability. siRNA was transfected into RCF to construct a cell model with low expression of SRY-box transcription factor 9 (SOX9) low expression cell model. Results CCK-8 results showed that AngⅡ and TGF-β could enhance the cell viability of RCF (P＜0.05). RT-qPCR results showed that AngⅡ and TGF-β upregulated the mRNA expression of typeⅠcollagen α1 (COL1A1), type Ⅲ collagen α1 (COL3A1), α-smooth muscle actin (α-SMA), periostin (Postn), Runt-related transcription factor 2 (RUNX2) in RCF (P＜0.05). Western blot results showed that AngⅡ and TGF-β upregulated the protein expression levels of COL1A1, COL3A1, and α-SMA in RCF (P＜0.05). The results of cell scratch assay showed that AngⅡ and TGF-β markedly promoted the migration ability of RCF (P＜0.05). HDELN was extracted by differential centrifugation and sucrose gradient density centrifugation. The activation of RCF induced by AngⅡ and TGF-β was reversed by the addition of HDELN (P＜0.05). Western blot and RT-qPCR results showed that AngⅡ and TGF-β upregulated the expression levels of SOX9 in RCF, while HDELN downregulated its expression (P＜0.05). After constructing a cell model with low expression of SOX9, the experimental results showed that the activation level of RCF with low expression of SOX9 was significantly lower than that of normal RCF (P＜0.05). Conclusion HDELN can inhibit the activation of RCF induced by AngⅡ and TGF-β via suppressing the SOX9 signaling pathway.

Abstract:Aim To establish the first m⁶A methylation profile for calcific aortic valve disease (CAVD) and elucidate the epigenetic regulatory mechanism of m⁶A modification during the process of valve calcification. Methods The m⁶A methylation profile of the valve tissues from CAVD patients was obtained through RNA methylation sequencing (MeRIP-seq). Differential methylation analysis, GO functional annotation, and KEGG pathway enrichment analysis were performed using bioinformatics methods to identify key signaling pathways, with the transforming growth factor-β (TGF-β) pathway showing the most significant enrichment. An in vitro calcification model using aortic valve interstitial cells (AVIC) was established, and RT-qPCR and Western blot analysis were employed to detect key m⁶A methylation enzymes, including Wilms' tumor 1-associating protein (WTAP), methyltransferase-like 3 (METTL3), fat mass and obesity-associated protein (FTO), alkylated base repair protein homolog 5 (ALKBH5), and YTH domain family proteins 1/2 (YTHDF1/2), to identify core regulatory factors. siRNA technology was used to knock down ALKBH5, and the effects of ALKBH5 deficiency on AVIC calcification and the TGF-β signaling pathway were detected. The results were further verified through ALKBH5 overexpression experiments, clearly demonstrating the role of ALKBH5. The methylation of specific pathway target gene mothers against decapentaplegic homolog 2 (SMAD2) was verified through MeRIP-RT-qPCR. Results The first m⁶A methylation profile of CAVD was successfully obtained through MeRIP-seq. It was found that the m⁶A methylation modification level in calcified valve tissues was significantly increased (P＜0.01), and 7 412 m⁶A differentially methylated peaks and a large number of key signaling pathways related to calcification, such as TGF-β, mitogen-activated protein kinase (MAPK), and autophagy, were identified. In vitro experiments on AVIC calcification, ALKBH5 knockdown, and overexpression confirmed that the expression of the demethylase ALKBH5 was downregulated in calcified AVIC (P＜0.05). ALKBH5 knockdown promoted AVIC calcification, while overexpression inhibited it. Further mechanism studies revealed that after ALKBH5 knockdown, the expression of TGF-β type Ⅱ receptor (TGFBR2) protein and the phosphorylation level of SMAD2 (p-SMAD2) in calcified AVIC were both upregulated (both P＜0.05), and the TGF-β signaling pathway was activated. Additionally, after ALKBH5 knockdown, the m⁶A methylation level of the SMAD2 gene increased (P＜0.05). Conclusions The m⁶A methylation modification is involved in the calcification process of CAVD valve. The downregulation of the demethylase ALKBH5 may promote the calcification of valve interstitial cells by activating the TGF-β signaling pathway.

Abstract:Aim To investigate the effect of omentin-1 on the expression of ATP-binding cassette transporter A1 (ABCA1) in macrophages and its mediated cholesterol efflux, as well as to elucidate its regulatory mechanism. Methods After THP-1-derived macrophages incubated with omentin-1 for 24 h, phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) were inhibited and silenced, respectively. Western blot was used to detect protein levels of ABCA1 and liver X receptor α (LXRα), high performance liquid chromatography was adopted to detect total cholesterol (TC), free cholesterol (FC) and cholesterol ester (CE) content, a liquid scintillation counter was applied to determine cholesterol efflux, and intracellular lipid droplets were observed via oil red O staining. In order to explore its mechanism of action in depth, ABCA1-specific siRNA silencing technique was used to observe the effect of omentin-1 on cholesterol efflux. Results Omentin-1 increased the expression of ABCA1 in macrophages in a concentration-dependent manner, promoted cholesterol efflux, reduced the contents of TC, FC and CE in cells, reduced lipid accumulation and inhibited the formation of foam cells. After specifically silencing the expression of ABCA1, the effect of omentin-1 on cholesterol efflux was significantly weakened, the intracellular lipid accumulation was increased, and the formation of foam cells was significantly increased. After inhibiting or silencing PI3K and Akt, the expression of LXR α and ABCA1 was significantly downregulated, the cholesterol efflux effect of omentin-1 was inhibited, the intracellular lipid accumulation increased, and the formation of foam cells increased. Conclusion Omentin-1 can upregulate the expression of ABCA1 in macrophages through PI3K/Akt pathway, enhance cholesterol efflux, thereby reducing lipid accumulation and inhibiting the formation of foam cells.

Abstract:Ventricular remodeling after myocardial infarction (MI) is a critical pathological process in cardiovascular diseases, in which macrophages serve as essential regulators. Advances in single-cell and spatial transcriptomic technologies have revealed the heterogeneity, origins, and spatiotemporal dynamics of cardiac macrophages following injury. Distinct macrophage subsets exhibit stage-specific functional switching during inflammation, tissue repair, and fibrosis:Ly6C^hi/CCR2＋ pro-inflammatory macrophages dominate the early inflammatory response; TREM2^hi reparative macrophages facilitate inflammation resolution and scar maturation; BHLHE41＋ macrophages restrict excessive collagen deposition; and spleen-derived CD169＋TIM4＋ macrophages help maintain local cardic immune homeostasis. This review summarizes the distribution, functional roles, and interaction networks of these macrophage populations during ventricular remodeling, elaborates their regulatory effects on myocardial repair and fibrotic progression, and proposes precision intervention strategies that may offer new therapeutic targets for post-MI remodeling.

Abstract:Atherosclerosis (As) is a chronic vascular disorder characterized by the accumulation of lipids and the hyperplasia of fibrous tissue within the arterial wall. Exosomes, nanoscale extracellular vesicles, serve as a major conduit for intercellular communication, ferrying bioactive cargoes (e.g., proteins and nucleic acids) that modulate pivotal pathological events in As, including lipid deposition, inflammatory response, and plaque stabilization. Endothelial-to-mesenchymal transition (EndoMT) denotes a phenotypic conversion in which endothelial cells downregulate vascular-specific markers, acquire a mesenchymal signature, and thereby potentiate arterial fibrosis and plaque rupture. Emerging evidence indicates that exosomes orchestrate EndoMT by transmitting activating signals through canonical axes such as transforming growth factor-β (TGF-β ) and Wnt/β-catenin, as well as by delivering transcriptional regulators (e.g., Snail, Twist) that repress endothelial identity genes and activate mesenchymal programs. This article systematically reviews the molecular mechanisms by which exosomes regulate As via modulating EndoMT, focuss on how bioactive molecules carried by exosomes derived from different cell types mediate EndoMT and further affect As. This review is expected to provide new strategies for targed intervention and treatment of atherosclerosis.

Abstract:Peripheral arterial disease (PAD) is a kind of high burden disease caused by atherosclerosis and affecting the peripheral arteries of the whole body. The precise risk stratification of adverse events (amputation, reintervention, death, etc.) is crucial to clinical decision-making. Machine learning models provide a new means for personalized risk prediction of PAD patients, which can compensate for the shortcomings of traditional statistical methods in capturing complex nonlinear relationships. This article systematically reviews the application of machine learning methods including Logistic regression, XGBoost, random forest and neural networks in the risk prediction of adverse events of PAD, and the predictive performance and applicable scenarios of different models were compared. And further explored key challenges such as model interpretability, data privacy, and ethics, aiming to provide methodological references for accurate risk prediction of adverse events in PAD and indicate directions for future research.

Abstract:Panvascular disease (PVD) represents a category of systemic vascular disorders characterized by atherosclerosis as a common pathological foundation. Elevated lipid variability (LV) is not only an independent risk factor for cardiovascular disease (CVD), cerebrovascular disease, and diabetic vascular complications but is also significantly associated with increased all-cause mortality and poor prognosis. Therefore, alongside intensive lipid-lowering therapy, maintaining stable and target lipid levels is of great significance for achieving precise prevention and treatment of PVD. This article reviews the recent research progress on the correlation between LV and PVD.