Background: Patients undergoing routine non-gated chest computed tomography (CT) for health checkups or atypical chest discomfort often present with a coronary artery calcium (CAC) score of zero on standard 5.0 mm reconstructions. We hypothesized that these thick slices obscure mild calcification due to partial volume effects (PVEs), which could be recovered by retrospective analysis of native thin-slice images. This study aimed to quantify the rate of unrecognized coronary calcification on standard thick-slice CT by comparing paired thin- and thick-slice reconstructions. Methods: We analyzed data of 2,914 patients across four datasets: Stanford Coronary Calcium and chest CT's (COCA) (n=651) for reference validation; an internal cohort evaluated by invasive angiography for early-onset coronary artery disease (CAD) (n=766) and National Lung Screening Trial (NLST) (n=852) with paired thin (1.0-2.0 mm) vs. standard (5.0 mm) scans; and TotalSegmentator (n=645) for robustness. A validated deep learning algorithm quantified CAC. The primary outcome was the "RESCUE" rate: patients reclassified from CAC =0 on 5.0 mm to CAC >0 on thinner slices. Results: In the internal cohort, 19.0% were reclassified from CAC =0 on 5.0 mm scans to CAC >0 on 1.0 mm scans. Similarly, 10.2% of NLST participants were reclassified using 2.0 mm scans. Most reclassified patients (91-99%) fell into the mild risk category (Agatston 1-99). Crucially, 31% of symptomatic patients with CAC =0 on standard scans had obstructive CAD (>50% stenosis); many were "rescued" to a positive CAC status by thin-slice analysis. Risk categorization showed strong agreement (weighted kappa 0.705-0.816). Artificial intelligence (AI) correlated strongly with expert annotations (r=0.956). Conclusions: Standard 5 mm reconstructions cause significant false negative CAC assessments. Analyzing routinely available thin slice reconstructions improves sensitivity for early subclinical atherosclerosis without additional radiation, supporting their use in opportunistic screening.

BACKGROUND:Treatments for heart failure with preserved ejection fraction (HFpEF) remain inconclusive. AIMS:We aim to explore in this prospective and observational cohort study how combined therapy with sodium-dependent glucose transporter 2 inhibitor (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP-1RA), angiotensin receptor-neprilysin inhibitor (ARNI), or mineralocorticoid receptor antagonists (MRA) impact clinical outcomes in HFpEF patients with type 2 diabetes mellitus (T2DM). METHODS:We enrolled 1445 HFpEF patients with T2DM from a prospective cohort between October 2018 and October 2022. The patients were divided into five groups based on their medications at 3 months after discharge: defined as a combination of SGLT2i, GLP-1RA, ARNI, and MRA. The primary outcome is major adverse cardiovascular (CV) events (MACEs), corresponding to the CV mortality and/or HF rehospitalization. The secondary outcome is CV mortality as well as left ventricular ejection fraction (LVEF) change or HF category transition. RESULTS:During a median follow-up period of 54 (27-75) months, participants with quadruple combination showed the most benefits, corresponding to MACEs (79/174; P <0.001), CV mortality (46/174; P = 0.03), LVEF change, or HF transitions. Quadruple combination was a protective factor for MACEs, while higher N-terminal pro-B-type natriuretic peptide level was an independent risk factor. For participants with LVEF less than 60%, quadruple combination reduced the incidence of composite endpoint events compared to those with LVEF over 60%. CONCLUSIONS:Quadruple combination therapy with SGLT2i, GLP-1RA, ARNI, and MRA in HFpEF patients with T2DM was associated with favorable clinical outcomes, especially in participants with LVEF less than 60%.

Background: The role of euthyroid hormone levels in clinical outcomes after drug-coated balloon (DCB) angioplasty in patients with coronary heart disease (CHD) remains unclear. Thus, this study aimed to explore the relationship between thyroid function and the risk of restenosis at one year, as well as the prognosis over five years in euthyroid patients with CHD following DCB angioplasty. Methods: This prospective study evaluated 189 euthyroid CHD patients who underwent successful DCB angioplasty. Coronary angiographic follow-up was performed 9–12 months post-procedure to assess the status of target lesions, with restenosis defined as ≥50% reduction in luminal diameter. All patients underwent five-year clinical follow-ups, during which major adverse cardiovascular events (MACEs) were recorded. Results: Following angiographic follow-ups, patients were categorized into two groups: those with restenosis (n = 66) and those without (n = 123). At baseline and during the follow-up, the restenosis group demonstrated significantly higher levels of thyroid-stimulating hormone (TSH), lymphocytes, hemoglobin A1c (HbA1c), lipoprotein(a), and platelet count, along with lower free triiodothyronine (FT3) levels. Multivariable logistic regression analysis revealed that the TSH levels both at the baseline (odds ratio (OR) 1.607, 95% confidence interval (CI) 1.238–2.085, p < 0.001) and angiographic follow-up (OR 2.970, 95% CI 2.000–4.411, p < 0.001) were independently associated with an increased risk of post-DCB restenosis. Furthermore, patients in the high TSH tertile had a 90% increased risk of MACEs during the 5-year follow-up period (hazard ratio (HR) 1.922, 95% CI 1.343–2.750, p < 0.001) compared with those in the low TSH tertile. Conclusions: A high-normal TSH level within the euthyroid range was strongly associated with an increased 1-year restenosis risk and decreased 5-year MACE-free survival following DCB angioplasty in CHD patients.

With advancing age and the development of risk factors such as hypertension, type 2 diabetes, obesity, and atrial fibrillation, the incidence of heart failure with preserved ejection fraction (HFpEF) has shown a year-on-year increase and is projected to become the most common form of heart failure in the near future. Uric acid (UA) is the end product of purine metabolism in the body and is closely associated with metabolic syndrome. Studies indicate that elevated serum uric acid levels constitute an independent risk factor for the onset, progression, and prognosis of HFpEF. UA can directly participate in the pathophysiological process of HFpEF by inducing oxidative stress, activating the inflammasome and pro-inflammatory signaling pathways, and impairing both cardiomyocyte function and microvascular endothelial integrity. This systematic review examines the epidemiological association between UA and HFpEF, the underlying mechanisms of UA involvement in HFpEF, and the potential benefits of urate-lowering therapy, including xanthine oxidase inhibitors and sodium-glucose cotransporter 2 inhibitors, for patients with HFpEF. It aims to enhance awareness of serum uric acid management in HFpEF patients and promote further exploration of pharmacological interventions in this field.

Introduction: Cardiovascular disease (CVD) and neoplasms are the two leading causes of death worldwide. Previous research has predominantly addressed these conditions separately or focused on specific regions. We aimed to characterize the global co-occurrence pattern of CVD and neoplasms from spatial and temporal perspectives and identify corresponding risk factors across different epidemiological contexts. Material and methods: Using GBD 2021 data, we extracted age-standardized disability-adjusted life year (DALY) rates of CVD and neoplasms and modifiable risk factor exposure from 204 countries and territories (1990-2021). We identified four epidemiological patterns: low-burden, neoplasm-dominant, CVD-dominant, and dual-burden regions. We calculated population attributable fractions (PAF) and integrated machine learning with SHAP values to distinguish intervention priorities. Average annual percentage changes (AAPC) were used to evaluate temporal trends. Results: Each pattern comprised 50-52 countries. Spatial distribution overlapped with socioeconomic development stages and risk factor exposure. Temporal analysis revealed widening global inequality: low-burden regions achieved 3-4% annual reductions while dual-burden regions experienced an increasing burden, creating a 5.8 percentage point gap. High systolic blood pressure was the universal dominant CVD risk factor, accounting for 49.7% of the global burden (49.2-52.4% across patterns). For neoplasms, smoking contributed 18.5% globally but varied dramatically by pattern (10.4-23.4%). Modifiable risk factors' specific combinations greatly influenced global disparities. Conclusions: The co-occurrence of CVD and neoplasms represents interconnected manifestations of different epidemiological transition stages, with concerning divergence between regions. Interventions targeting hypertension control and tobacco cessation, combined with pattern-specific strategies, can fundamentally reduce the global disease burden.

Background and Aims:Arrhythmias and major adverse cardiac events remain significant complications following ST-segment elevation myocardial infarction (STEMI). Shenfu injection, a traditional Chinese medicine formulation, has shown cardioprotective effects in preclinical studies. This trial is aimed at investigating whether Shenfu injection as an adjunctive therapy to standard treatment could reduce arrhythmias and improve clinical outcomes in patients with STEMI undergoing percutaneous coronary intervention (PCI). Methods:A single-center, prospective, randomized, controlled trial was conducted at Shanghai Ninth People's Hospital among 245 patients with STEMI undergoing PCI. Participants were randomized to receive either standard therapy plus Shenfu injection (50 mL, administered intravenously twice daily for five consecutive days) (n = 123) or standard therapy alone (n = 122). The primary endpoint was the incidence of in-hospital arrhythmias. Secondary endpoints included major adverse cardiac events (MACEs) during the 12-month follow-up period and cardiac magnetic resonance imaging parameters. Results:A total of 245 patients underwent randomization (123 assigned to Shenfu injection group and 122 assigned to control group). During hospitalization, patients assigned to Shenfu injection had a significantly lower incidence of arrhythmias compared with the control group (24.4% vs. 38.5%, p = 0.017), with the most pronounced effect on frequent ventricular premature contractions (7.3% vs. 15.5%, p = 0.042). After adjustment for key baseline covariates including age, coronary artery disease extent, myocardial injury markers (CK-MB max and TNI max), left ventricular ejection fraction, B-type natriuretic peptide, door-to-balloon time, hypertension, and diabetes mellitus, Shenfu injection remained independently associated with reduced risk of in-hospital arrhythmias (adjusted OR 0.454, 95% CI: 0.249-0.827, p = 0.010). Cardiac magnetic resonance imaging performed in 174 patients revealed significantly smaller infarct size (16.1 ± 9.1 vs. 20.8 ± 13.1 g, p = 0.007) and lower incidence of microvascular obstruction (45.0% vs. 65.0%, p = 0.008) in the Shenfu group, with both parameters showing significant positive correlations with arrhythmia occurrence. During the 12-month follow-up, patients receiving Shenfu injection had a higher event-free rate from MACEs compared with the control group (12-month Kaplan-Meier event-free rate estimates, 84.6% vs. 73.0%, respectively; p = 0.028). Conclusions:Treatment with Shenfu injection as an adjunctive therapy to standard treatment in patients with STEMI undergoing PCI significantly reduced in-hospital arrhythmias, infarct size, microvascular obstruction, and major adverse cardiac events during a 12-month follow-up period. The independent effect on arrhythmias after comprehensive statistical adjustment and the demonstrated correlation between reduced myocardial damage and arrhythmia prevention suggest the potential therapeutic value of Shenfu injection in improving both short-term and long-term outcomes in STEMI patients. Trial Registration:Chinese Clinical Trial Registry Identifier: ChiCTR2200066918.

Fail to reach the bilioenteric anastomosis is the main cause of treatment failure during single-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (SBE-assisted ERCP) in patients after bilioenteric Roux-en-Y anastomosis. We aim to evaluate factors influencing the endoscopic insertion failure. We retrospectively reviewed the clinical data of 231 cases undergoing SBE-assisted ERCP from January 2016 to December 2021. Treatment details and outcomes were studied to analyze the factors involved in endoscopic insertion failure. The enteroscopy success rate and procedural success rate were 88.3

Shorter leukocyte telomere length (LTL) is associated with aging-related cardiovascular diseases, but its relationship with heart failure with preserved ejection fraction (HFpEF) in high-risk Chinese patients with hypertension under 65 years remains unclear. In this observational prospective study, we investigated 646 patients with hypertension aged < 65 years with diabetes, coronary heart disease (CHD), or ≥ 3 cardiovascular risk factors. Baseline assessments included clinical evaluation, measurement of aging markers (LTL and mitochondrial DNA copy number) and echocardiography. Participants underwent scheduled quarterly follow-up for 5 years, with documentation of major adverse cardiovascular events (MACEs), including cardiovascular mortality, myocardial infarction, ischemia-driven revascularization, stroke and heart failure hospitalization. At the final follow-up visit, the evaluation for HFpEF was performed through echocardiography and plasma B-type natriuretic peptide (BNP) measurement. Participants were stratified by LTL tertiles: long (> 79.89; n = 216), mid (58.49–79.89; n = 214), and short (< 58.49; n = 216). Compared with the long and mid LTL groups, the short LTL group had a higher prevalence of male, smoking, hyperlipidemia, diabetes, and CHD, along with elevated blood pressure and fasting blood glucose, but lower mitochondrial DNA copy number (all P < 0.05). At 5-year follow-up, HFpEF prevalence increased with shorter LTL (15.7

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce incidence of cardiovascular events in type 2 diabetes (T2D) patients. Yet, the impact of GLP-1RAs on coronary lesion progression and cardiovascular outcomes after coronary stent implantation remains unclear. We aimed to investigate the effects of GLP-1RAs on coronary lesion progression and major adverse cardiovascular events (MACEs) after percutaneous coronary intervention (PCI). This prospective cohort study enrolled 1664 patients with T2D who underwent PCI from January 2020 to March 2024. Matched GLP-1RAs-treated and non-treated cohorts were formed using the propensity score matching method. The primary endpoint was the incidence of MACEs (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure). Secondary endpoints included in-stent restenosis and non-target lesion progression. Two 131-patient cohorts with balanced baseline characteristics were formed by propensity score matching. During the median follow-up period of 20 months (ranging from 6 to 48 months), the incidence of MACEs was significantly lower in the GLP-1RA group (7.63%)compared to the control group (19.85%) (HR 0.444; 95%CI, 0.215-0.918; P = 0.024). During a median follow-up period of 12 months, 79.39% (104/131) of patients in the control group and 82.44% (108/131) of patients in the GLP-1RA group successfully underwent coronary angiography follow-up. The incidence of in-stent restenosis was 2.78% (3/108) in the GLP-1RA group and 11.54% (12/104) in the control group (P = 0.028). Non-target lesion progression was found in 10.19% (11/108) patient of the GLP-1RA group and 22.12% (23/104) in the control group (P = 0.037). Notable disparities were observed between the two groups regarding improvements of BMI, SBP, HbA1c, LDL-C, CRP. GLP-1RAs significantly reduced the incidence of MACEs and coronary lesion progression in patients with T2D after coronary stent implantation. These findings suggest that GLP-1RAs may have beneficial effects on cardiovascular outcomes and coronary artery disease progression in this population.

Backgrounds The use of guideline-directed medical therapy (GDMT) in heart failure (HF) has been shown to decrease hospitalization and mortality risks. However, the implementation of GDMT remains suboptimal. This study aimed to evaluate the challenges of GDMT intolerance in a real-world setting. Methods The study initially screened 263 patients diagnosed with acute HF. All patients attempted to initiate quadruple GDMT before discharge; patients who failed to initiate quadruple GDMT were classified in the GDMT Intolerant Group, while those who successfully initiated GDMT were classified in the GDMT Group. The primary endpoint was the time to first worsening HF events or death due to HF within 180 days. Results Nearly half of the study patients cannot tolerate quadruple therapy at discharge and the main intolerance reasons of GDMT were renal insufficiency and hypotension. Patients who tolerated quadruple GDMT at discharge were more likely to use quadruple at the endpoint GDMT (92.4 % vs 27.8 %). Only 13.4 % of overall patients ultimately used the maximum dose of all four GDMTs at endpoint, patients with de novo HF had better prognosis than ADCHF (Acute Decompensated Chronic HF) patients, and GDMT Initiation at discharge was associated with a reduced risk of worsening HF in both HF patients, and the more types of medication initiated at discharge, the better the prognosis of the patients. Conclusions Real-world implementation of GDMT and dose up-titration remains challenging, with a high proportion of patients unable to tolerate quadruple GDMT, with renal insufficiency and hypotension being the most challenging factors.

BACKGROUND:The prevalence of diabetic cardiomyopathy (DiabCM) is increasing in parallel with diabetes mellitus, with no consensus on targeted treatment. AIMS:This study aims to investigate the cardiovascular benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) alone and combination on symptomatic DiabCM participants. MATERIAL AND METHODS:This was a single-center prospective cohort study focusing on patients with symptomatic DiabCM. The study comprised 587 participants: 154 in the SGLT2is group, 105 in the GLP-1RAs group, 93 in the SGLT2is combined with GLP-1RAs group (SGLT2is + GLP-1RAs), and 235 in the control group (without SGLT2is or GLP-1RAs). All participants were followed for 36 months. The primary outcome was a composite of all-cause death and hospitalization for heart failure. RESULTS:The incidence of endpoint event was lowest in the SGLT2is + GLP-1RAs group (23.7%), followed by the SGLT2is group (32.5%), GLP-1RAs group (39.0%), and control group (53.6%). Multivariable Cox regression analysis showed that SGLT2is (P <0.001), GLP-1RAs (P = 0.02) or SGLT2is + GLP-1RAs prescription (P <0.001) were independent protective factors for the occurrence of primary outcome. In subgroup analysis, SGLT2is or SGLT2is + GLP-1RAs treatment remained the independent factors for freedom from primary outcome in both heart failure with reduced ejection fraction + heart failure with mildly reduced ejection fraction and heart failure with preserved ejection fraction patients. However, GLP-1RAs alone did not exert clinical benefits in subgroup analysis. CONCLUSIONS:SGLT2is and GLP-1RAs might reduce the incidence of all-cause mortality and heart failure hospitalization in patients with symptomatic DiabCM, and the combination of these two agents may further improve clinical outcomes.

Background:Coronary artery disease (CAD) is a leading cause of global mortality, primarily due to the accumulation of atheromatous plaques in coronary arteries. The current diagnostic standards include X-ray coronary angiography, which evaluates morphological features of the coronary arteries. The primary goal of this modality is to quantify stenosis severity, but variability and complexities in the resultant images make consistent interpretation challenging. This study developed a deep learning-based approach for segmenting and grading vessel stenosis via X-ray coronary angiography. Methods:Based on 383 angiographic images from 168 patients, we developed a dual-output deep convolutional neural network (CNN) to automatically diagnose stenosis. For clinical relevance, we manually annotated stenosis severity into five distinct levels: nonobstructive lesion (1-49%), intermediate lesion (50-70%), severe lesion (71-95%), sub-total occlusion (96-99%), and total occlusion (100%). Results:We built a coronary stenosis segmentation and grading method based on X-ray coronary angiography. The model achieved an average intersection over union (IoU) of 0.92, a Dice score of 0.95, a precision of 0.93, and a sensitivity of 0.96. Conclusions:We introduce an image-based vascular analysis method that localizes and grades stenosis in X-ray coronary angiography. This method can automatically identify clinically critical grades, especially within the 71-100% range. Deep learning methods can potentially facilitate the diagnosis of CAD and patient-centric treatment planning.

Background:Cardiovascular adverse events represent critical complications of antineoplastic therapy with profound implications for cancer survivorship and treatment outcomes. Despite the clinical significance, comprehensive pharmacovigilance data characterizing distinctive cardiotoxicity profiles across modern cancer therapeutics remain limited. Objectives:This investigation systematically analyzes cardiotoxicity patterns associated with antineoplastic agents using the FDA Adverse Event Reporting System (FAERS) database to inform evidence-based cardiovascular monitoring strategies. Design:A retrospective pharmacovigilance study utilizing disproportionality analysis and time-to-onset evaluation. Methods:We conducted a comprehensive analysis of FAERS data spanning 2004-2024, employing validated disproportionality metrics including reporting odds ratio (ROR) and proportional reporting ratio (PRR) to detect significant drug-event associations. Advanced time-to-onset analysis revealed temporal patterns of cardiotoxicity development across therapeutic classes. Statistical significance was defined as ROR >1 with 95% confidence intervals excluding 1.0, and PRR >2 with chi-square >4. Results:Analysis of 18,289,374 reports identified 51,402 cases of antineoplastic-related cardiovascular toxicity, demonstrating distinct class-specific patterns. Anthracyclines exhibited profound associations with structural cardiac damage (doxorubicin-cardiomyopathy: ROR = 20.64, 95% CI: 19.87-21.45). Immune checkpoint inhibitors demonstrated unprecedented immune-mediated cardiac inflammation (pembrolizumab-myocarditis: ROR = 245.36, 95% CI: 218.42-275.88). Fluoropyrimidines showed distinctive vasospastic effects (5-fluorouracil-Prinzmetal angina: ROR = 18.27, 95% CI: 14.72-22.69). Critical temporal patterns emerged: fluoropyrimidines caused early-onset cardiotoxicity (median: 11 days, IQR: 4-28), anthracyclines showed intermediate onset (doxorubicin median: 64 days, IQR: 21-156; epirubicin median: 72 days, IQR: 28-168), while mitoxantrone demonstrated delayed effects (median: 457 days, IQR: 182-891). Cardiogenic shock emerged as the most lethal manifestation with a 43.08% mortality rate (95% CI: 40.12-46.14). Conclusion:This landmark pharmacovigilance study reveals previously uncharacterized temporal and mechanistic patterns of antineoplastic cardiotoxicity, providing an essential evidence-based framework for cardiovascular monitoring strategies. The findings highlight critical intervention windows: immediate monitoring for fluoropyrimidines, intermediate surveillance for anthracyclines (2-6 months), and extended follow-up for agents like mitoxantrone (>12 months). These insights support the development of risk-stratified cardio-oncology protocols tailored to specific therapeutic classes.

Background:Hyperuricemia is associated with poor clinical outcomes in several cardiovascular diseases, including heart failure (HF). However, whether lowering serum uric acid (SUA) levels improves the prognosis of HF remains insufficiently studied. Aims:To evaluate whether urate-lowering therapy (ULT) with febuxostat confers clinical benefits in patients with HF and concomitant hyperuricemia. Study Design:Prospective, observational cohort study. Methods:Patients with chronic HF and hyperuricemia were enrolled and assigned either to a febuxostat group or to a non-ULT group and were followed prospectively for 5 years. The primary endpoint was all-cause mortality or rehospitalization for HF. Results:Among 2005 patients, those with higher SUA levels experienced more endpoint events. After propensity score matching, we found that febuxostat therapy significantly reduced the incidence of primary endpoints in patients with HF with preserved ejection fraction (HFpEF) [p = 0.012; hazard ratios (HR), 0.744; 95% confidence intervals (CI), 0.589-0.939], but not in those with HF with reduced ejection fraction (HFrEF) or mildly reduced ejection fraction (HFmrEF) (p = 0.234; HR, 0.894; 95% CI, 0.742-1.077). The benefits of febuxostat in HFpEF were most evident in patients within the highest tertiles of B-type natriuretic peptide (BNP) (p = 0.021; HR, 0.647; 95% CI, 0.436-0.960) and SUA (p = 0.025; HR, 0.651; 95% CI, 0.441-0.963). Conclusion:High SUA levels are associated with increased all-cause mortality and rehospitalization for HF. Febuxostat-mediated SUA reduction significantly improved clinical outcomes in patients with HFpEF, particularly those with elevated SUA and BNP levels.

IMPORTANCE:Lower extremity peripheral arterial disease (PAD) is a significant health concern among older adults globally, affecting both mortality and quality of life. OBJECTIVE:To evaluate the temporospatial trends and its risk factors in lower extremity PAD-related burden among adults aged 60 years and older from 1990 to 2021. DESIGN, SETTING, AND PARTICIPANTS:This repeated cross-sectional study utilized data from the Global Burden of Disease Study 2021, encompassing 204 countries and territories. The study population included adults aged 60 years and older. EXPOSURE:Lower extremity PAD among older adults from January 1990 to December 2021. MAIN OUTCOMES AND MEASURES:Primary outcomes included age-standardized prevalence rates (ASPR), mortality rates (ASMR), disability-adjusted life-years (DALYs), and average annual percentage changes (AAPCs). Trends were analyzed by age, sex, and sociodemographic index (SDI). Joinpoint regression analysis was used to identify significant trend changes. RESULTS:From 1990 to 2021, global trends showed decreases in lower extremity PAD-related prevalence, mortality, and DALYs. Significant geographical disparities were observed: high-SDI regions had the highest prevalence (11,171.66 per 100,000 in 2021) but showed declining trends (AAPC, -0.74; 95% CI, -0.80 to -0.68), while low-SDI regions had the lowest prevalence (4,842.40 per 100,000) but demonstrated increasing trends (AAPC, 0.22; 95% CI, 0.21 to 0.24). Regionally, although lower extremity PAD-related prevalence showed a decreasing trend in most regions from 1990 to 2021, there were still some regions with an increasing trend (North Africa and Middle East AAPC, 0.57; 95% CI, 0.55 to 0.59). Temporal analysis showed sex-specific divergent trends in recent years, with males exhibiting an upward trend since 2015 (APC, 0.15; 95% CI, 0.07 to 0.24), while females showed a slowed decline since 2014 (APC, -0.06; 95% CI, -0.12 to -0.01). Decomposition analysis identified population growth as the primary driver of PAD burden increase, with epidemiological changes showing contrasting effects across SDI regions. Among risk factors, high fasting glucose emerged as the leading contributor, while smoking's contribution decreased. CONCLUSIONS AND RELEVANCE:This study revealed significant disparities in lower extremity PAD burden across different SDI levels and regions, with low-SDI countries facing an increasing burden. The contrasting trends between high- and low-SDI regions, coupled with varying risk factor patterns (particularly the rise in high fasting glucose and decline in smoking), suggest the need for targeted interventions in resource-limited settings to address this growing health challenge among older adults.

BackgroundAcute coronary syndrome (ACS) is a leading cause of morbidity and mortality worldwide. In recent years, ACS has been reported to be associated with age, and the incidence has become more common in younger patients. Previous studies have identified various risk factors that contribute to the stratification of ACS patients. However, it remains unclear whether these risk factors, along with proteomic and clinical characteristics, are applicable to young ACS patients, as they are for middle-aged and elderly patients. This study aimed to investigate the proteomics, risk factors, and clinical characteristics of young ACS patients, as well as the differences between them and middle-aged and elderly ACS patients. By comparing these findings with those of middle-aged and elderly patients, we aimed to identify any discrepancies and these findings possibly may have implications for future management strategies of this specific population.MethodsThis observational study included a total of 187 participants diagnosed with ACS and 17 young healthy individuals as the control group. ACS patients were divided into three age groups: <45 years old, 45–60 years old, and 61–75 years old. The control group consisted of healthy individuals under the age of 45 who underwent coronary angiography and were excluded from CAD. We collected clinical characteristics, laboratory data, and echocardiographic results from each participant. Additionally, blood samples were collected for further analysis of relevant proteomic and arteriosclerosis marker data using proteomics analysis.ResultsOur findings revealed that the presence of certain key factors was associated with a significantly difference in patients with ACS aged younger than 45 years, and this association differed from that of traditional cardiovascular risk factors in patients older than 45 years. Specifically, a higher body mass index and hyperlipidemia were found to be associated with an increased risk of ACS morbidity in young adults (<45 years old) compared to middle-aged and elderly individuals. Furthermore, our findings indicated that the expression levels of growth differentiation factor 15, osteopontin, and NT-proBNP were significantly different among the groups.ConclusionIn summary, our study revealed that the main pathogenic factors of ACS patients under 45 years of age differed from those of middle-aged and elderly patients. These findings may contribute to the prevention and treatment strategies for young patients with ACS.

Diabetic cardiomyopathy (DbCM) is characterized by diastolic dysfunction, which progresses into heart failure and aberrant electrophysiology in diabetic patients. Dyslipidemia in type 2 diabetic patients leads to the accumulation of lipid droplets (LDs) in cardiomyocytes and results in lipid toxicity which has been suggested to drive DbCM. It is aimed to explore potential pathways that may boost LDs degradation in DbCM and restore cardiac function. LDs accumulation resulted in an increase in lipid toxicity in DbCM hearts is confirmed. Microlipophagy pathway, rather than traditional macrolipophagy, is activated in DbCM hearts. RNA-Seq data and Rab7-CKO mice implicate that Rab7 is a major modulator of the microlipophagy pathway. Mechanistically, Rab7 is phosphorylated at Tyrosine 183, which allows the recruitment of Rab-interacting lysosome protein (Rilp) to proceed LDs degradation by lysosome. Treating DbCM mice with Rab7 activator ML-098 enhanced Rilp level and rescued the observed cardiac dysfunction. Overall, Rab7-Rilp-mediated microlipophagy may be a promising target in the treatment of lipid toxicity in DbCM is suggested.

Abdominal aortic aneurysm (AAA) is characterized by localized structural deterioration of the aortic wall, leading to progressive dilatation and rupture. Protease activated receptor 2 (PAR2) dependent signaling has been implicated in the pathophysiology of atherosclerosis through the regulation of smooth muscle cell function. However, its role in AAA remains unclear. This study investigates the function and potential mechanism of PAR2 in AAA progression. Angiotensin II (Ang II) and β-aminopropionitrile (BAPN) were administered to wild type (WT) mice to induce AAA. Increased PAR2 expression was observed in the aneurysmal tissues of these mice and in Ang II-treated vascular smooth muscle cells (VSMCs). We demonstrated that PAR2 deficiency markedly inhibited aorta dilatation and vascular remodeling in the AAA model relative to WT mice. Immunohistochemical staining showed significant upregulation of contractile markers and a reduction in synthetic markers in PAR2 knockout mice. Consistent with in vivo results, PAR2 knockdown diminished the effects of Ang II on VSMCs phenotypic switching, resulting in reduced proliferation and migration. Conversely, a PAR2 agonist (SLIGRL) induced the opposite effect, which was partially mitigated by pretreatment with an extracellular signal-regulated kinase (ERK) inhibitor (PD98059). This study suggests that PAR2 deficiency restrains aortic expansion and mitigates adverse vascular remodeling in AAA models, mediated in part by the ERK signaling pathway, indicating that PAR2 could be a potential therapeutic target for mitigating AAA development or progression.

Even though nirmatrelvir–ritonavir can improve the short-term morbidity and mortality in COVID-19 patients, the effects of this treatment on long-term major adverse cardiovascular events (MACEs), especially myocardial injury, remains undetermined. This prospective cohort study identified hospitalized adult patients with COVID-19 between April 19, 2022, and June 9, 2022, amid the omicron wave of the pandemic. Matched nirmatrelvir–ritonavir-treated and non-treated cohorts were formed using the propensity score matching method. The primary outcome of this study was the incidence of MACEs (cardiovascular death, myocardial infarction, stroke, new-onset heart failure or heart failure hospitalization or ventricular arrhythmia) from 30 days to 16 months after the diagnosis of COVID-19. Two 949-patient cohorts with balanced baseline characteristics were formed by propensity score matching. Patients with nirmatrelvir–ritonavir, compared to those untreated, had a lower level of troponin I peak as well as the incidence of troponin I elevation. During the follow-up period, 59 patients in the nirmatrelvir–ritonavir group and 86 patients in the control group developed MACEs (P = 0.020). Regarding specific constituents of MACEs, the differences are mainly reflected in new-onset heart failure or heart failure hospitalization. COVID-19 clinical severity and troponin I peak were the independent predictors, while nirmatrelvir–ritonavir was the independent protective factor for the occurrence of MACEs in this population. Nirmatrelvir–ritonavir was effective in reducing myocardial injury as well as long-term adverse cardiovascular outcomes among hospitalized patients with COVID-19 amid the omicron wave of the pandemic.

Background: Lipid profiles differ naturally between individuals and between populations. So far, the data relating to non-fasting lipid profiles has been derived predominantly from studies on Western population. The characteristics and clinical significance of non-fasting lipids in Chinese patients with coronary heart disease (CHD) in response to traditional Chinese diets remain poorly understood. Methods: A total of 1022 Chinese CHD patients with coronary artery luminal stenosis >40% as diagnosed by coronary artery angiography were enrolled in the study. All patients received standard treatment for CHD, including statins. They were divided into an intermediate stenosis group (luminal stenosis 40–70%, n = 486) or a severe stenosis group (luminal stenosis >70%, n = 536). Their blood lipid profiles were measured in the fasting state, and 4 hours after normal breakfast. All participants were followed up for five years. Major adverse cardiovascular events (MACE) including all-cause death, cardiac death, myocardial infarction, unscheduled coronary revascularization and stroke were recorded. Results: After normal breakfast intake, patients with intermediate or severe stenosis showed an apparent increase in the levels of triglyceride (TG), remnant cholesterol (RC) and Apo (apolipoprotein) A1 compared to the fasting state, but a significant reduction in the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), Apo B and Apo E. In addition to the traditional risk factors (older age, male, diabetes and smoking) and coronary artery stenosis, the fasting levels of LDL-C and Apo B, as well as non-fasting levels of HDL-C and Apo A1, were identified as independent predictors of 5-year MACE occurrence by multivariate Cox proportional hazards analysis. Patients in the 1st tertile of the non-fasting HDL-C group (<0.86 mmol/L) showed a significantly higher risk of MACE than 3rd tertile (>1.07 mmol/L) (1st tertile: 2.786, 95% CI (confidence intervals) [1.808, 4.293], p < 0.001). Conclusions: This prospective observational study found that lipid profiles in either the fasting or non-fasting states were associated with the long-term risk of MACE in Chinese CHD patients. In addition to the fasting LDL-C level, a low non-fasting HDL-C level may also be an independent risk factors for cardiovascular events. Measurement of lipid profiles during the non-fasting state may be feasible for the management of CHD patients in routine clinical practice in China.