Interactive and joint associations of C-reactive protein-triglyceride glucose index and body roundness index on incident cardiovascular diseases: a nationwide prospective cohort study.

Sex differences in cardiovascular-kidney-metabolic syndrome and new onset cardiovascular outcomes.

The metabolic roles in arterial calcification remain largely unclear. We aimed to elucidate the associations between nuclear magnetic resonance (NMR) metabolic biomarkers with site- and sex-specific arterial calcification as well as their causal nature. This study included participants from the Rotterdam Study (RS, N=1062), Leiden Longevity Study (LLS, N=272), and UK Biobank (UKBB, N=271,793). In RS and LLS, we applied linear regression (both overall and sex-stratified) to assess the association between NMR metabolic biomarkers and arterial calcification at coronary artery (CAC), aortic arch (AAC), and aortic valve (AVC). Two-sample Mendelian randomization (MR) was employed using genome-wide association study of NMR biomarkers (N=115,082) and CAC (N=26,909) to infer their genetic causality. Biomarkers with consistent observational and causal associations were further examined for associations with coronary heart disease (CHD) in UKBB. From multiple-testing correction (P-value < 4.39×10-4), three fatty acids ratio biomarkers were associated with decreased CAC burden: Omega_6_pct (Beta: -0.10, SE: 0.03, P-value: 2.94×10-4), PUFA_by_MUFA (Beta: -0.10, SE: 0.03, P-value: 3.08×10-4), and PUFA_pct (Beta: -0.10, SE: 0.03, P-value: 3.33×10-4). Sex-stratification revealed glycoprotein acetyls (GlycA) associated with CAC in males only (Beta: 0.13, SE: 0.04, P-value: 3.10×10-4). MR identified 17 biomarkers causally associated with CAC, 14 of which were subsequently associated with CHD in UKBB. We identified NMR-based metabolic biomarkers, particularly fatty acid ratios, that were significantly and causally associated with CAC burden. GlycA was associated with CAC in males only. Replication in UKBB further underscores their clinical relevance with CHD.

Wendan tablet and its active component isocurcumenol protect against myocardial ischemia via targeting ALOX15 and inhibiting lipid peroxidation.

Introduction. Modern advances in the development of reconstructive urology show high efficacy in treating urethral stricture (US) in men and maintaining an acceptable quality of life. An urgent task in the treatment of this category of patients is not only the restoration of physiological urination and relief of symptoms of emptying, but also the preservation and restoration of erectile function (EF). The purpose of the study. To evaluate the effect of preoperative risk factors for erectile dysfunction (ED) in men with stricture disease of the urethra on erectile function and hemodynamic parameters of penile blood flow. Material and methods. The study included 153 sexually active patients with US, who underwent reconstructive and reconstructive surgery on the urethra. The EF assessment was carried out using the IIEF-5 questionnaire. The study patients were divided into 2 groups, depending on the presence of risk factors for erectile dysfunction (hypertension, coronary heart disease, type 2 diabetes mellitus, tobacco smoking). Control points of assessment: initially (before surgery), 3, 12 months after urethroplasty. Penile hemodynamics in patients was assessed during preoperative preparation based on the results of pharmacodopplerography of penile vessels using alprostadil 10 micrograms. Results. The age of the study patients ranged from 18 to 80 years (Me = 53.00, Q1 – Q3 =38.00 – 64.00). Before urethroplasty, signs of ED were noted in 55.6% (n=85) of patients (median IIEF-5 - 19,0 [13,0- 22,0]). A significant progression of ED signs was noted 3 months after urethroplasty, the presence of ED signs was recorded in 75.8% (n=116) of patients (median IIEF-5: 13,0 [5,0; 20,0], p=0.001). According to the results of the EF examination for the 12th month of the postoperative period, a significant improvement in EF indicators was confirmed (median IIEF-5: 21,0 [18,0; 23,0], p &lt;0.001). The presence of ED risk factors was noted in 52.9% (n=81) of patients with US. With an increase in the World Health Organization (WHO) age group, there is an increase in the prevalence of ED risk factors. In the age group of patients from 18 to 45, risk factors for ED were identified in 29.6% (n=16), and in the group from 60 to 74 - 72.3% (n=34). According to the result of comparing groups of patients, depending on the presence of ED risk factors, during the preparation for urethroplasty, the EF indicators of the studied groups did not significantly differ. 3 and 12 months after urethroplasty, the EF scores of the group without ED risk factors were significantly better (median IIEF-5 - 16.0 [10.75-21.0] versus 10.0 [5.0-16.0], p&lt;0.001; 22.0 [21.00-24.0] versus 18.0 [15.0-22.0], p&lt;0.001). In the group of patients with risk factors for ED, there was a higher incidence of severe ED, reaching 56.8% (n=46) 3 months after urethroplasty, and a higher incidence of signs of ED during the 12th month of the postoperative period (50.6%, n=41). The presence of risk factors in patients with US is associated with poorer indicators of penile hemodynamics. According to the results of pharmacodopplerography of the vessels of the penis before surgery, in the group of patients with ED risk factors, higher values of the end diastolic velocity (EDV) and lower resistance index (RI) were recorded compared with the group without ED risk factors (EDV: 9.38 [6.46; 13.90] vs. 3.29 [0.10; 5.68], p&lt;0.001; RI: 0.70 [0.63; 0.73] vs. 0.84 [0.78; 1.00], p=0.001). According to the results of a multifactorial analysis, the predictors of ED development 3 months after surgery are age (AOR 1.082; 95% CO 1.038 – 1.127; p &lt; 0.001), hypertension (AOR 4.608; 95% CO - 1.089 – 19.511; p = 0.038) and baseline status of erectile function (AOR 0.046; 95% CO - 0.013 – 0.160; p &lt; 0.001). However, the examination after 12 months confirmed a decrease in the effect of concomitant pathology and age on the negative dynamics in EF indicators. Conclusion. The presence of modifiable and unmodifiable ED risk factors is associated with more pronounced EF changes in patients with US after urethroplasty. The predictors of the development of ED after urethroplasty are age, concomitant pathology (arterial hypertension) and the initial level of EF of the patient, followed by a decrease in the effect of predictors on EF by the 12th month of the postoperative period. Keywords: urethral stricture; urethral plastic surgery, erectile dysfunction, risk factors for erectile dysfunction.

Case report of variant origin and course of the middle colic artery

To provide a descriptive analysis of the overall health and well-being of older adults of Pacific Peoples ethnicity using the interRAI-Home Care assessments, compared with NZ Europeans. A cross-sectional retrospective analysis was conducted of interRAI-Home Care assessments assessed between 5 July 2016 and 31 December 2020. Basic descriptive information was gathered from Pacific Peoples and NZ Europeans separately. The frequency and percentage of the health conditions of interest were reported. Binary and multinomial logistic regression models adjusted for age and sex were used to investigate any differences between the prevalence of health conditions. A total of 123,023 interRAI-HC assessments were examined, of which 5390 (4%) were Pacific Peoples and 117,633 (96%) NZ Europeans. The mean age of Pacific Peoples was 75.8 years (SD 8.4) and NZ Europeans 82.6 years (SD 7.5). After adjusting for age and sex, Pacific Peoples were less likely to smoke, consume alcohol, have coronary heart disease, fall, report loneliness or have difficulty hearing than NZ Europeans. In contrast, Pacific Peoples were more likely to have diabetes, cognitive impairment, congestive heart failure, require a mobility aid or be bed bound, experience bladder incontinence, have difficulty understanding others or have poorer vision than NZ Europeans. Older Pacific Peoples who were assessed for home support and aged residential care have more complex needs and require services at an earlier age than NZ Europeans. There is a need for improvements in equity in the health system and underlying social determinants of health to raise the earlier age and lower the high burden of chronic diseases that Pacific Peoples face.

Ferroptosis-driven coronary plaque vulnerability: A tandem mechanism involving endothelial cells, macrophages, and smooth muscle cells.

A significant residual risk of myocardial infarction (MI) persists in hypertensive patients treated with angiotensin receptor blockers (ARBs). Conventional risk models often fail to capture the complex, nonlinear interactions among clinical phenotypes, comorbidities, and pharmacogenetic factors. This retrospective cohort study included 1229 hospitalized hypertensive patients treated with ARBs. We analyzed 26 clinical variables and two key genetic polymorphisms: AGTR1 rs5186 and CYP2C9 rs1057910. A hybrid downsampling technique was employed to address severe class imbalance. Ten machine learning models were developed, with a focus on the interpretable deep learning model, TabNet. The TabNet model demonstrated superior predictive performance, achieving an area under the receiver operating characteristic curve (AUC) of 0.887 and a recall of 0.795 in the validation cohort. Model interpretation using Shapley Additive Explanations (SHAP) identified pre-existing coronary heart disease, hypertension stage, chronic heart failure, sex, hyperlipidemia, and the AGTR1 rs5186 polymorphism as the most significant predictors of MI. The CYP2C9 rs1057910 variant showed a risk-modifying interaction effect in patients with pre-existing coronary heart disease. An interpretable deep learning model integrating clinical and pharmacogenetic data effectively predicts MI risk in ARB-treated hypertensive patients. The AGTR1 rs5186 polymorphism is an independent predictor of MI, highlighting its potential as a prognostic biomarker. This clinico-pharmacogenetic approach offers a powerful tool for personalized risk stratification and may guide more targeted preventive interventions.

Inonotus obliquus (Ach. ex Pers.) Pilát aqueous extract alleviates acute cold exposure/rewarming-induced myocardial injury by regulating mitochondrial dynamics via liver kinase B1/adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator-1 alpha signaling pathway activation.

Ischemic stroke (IS) accounts for 87% of all strokes and is a leading cause of disability worldwide. Women face higher lifetime IS risk and worse functional outcomes, yet predictive biomarkers remain limited. Moreover, inflammation is increasingly recognized as a contributor to IS pathogenesis, with inflammatory markers such as C-reactive protein (CRP) positively associated with IS. Yet, the metabolic pathways linking chronic inflammation to IS risk are poorly understood. We aimed to identify a metabolomic signature reflecting systemic inflammation and evaluate its association with incident IS in women. This study used nested case-control designs within the Nurses' Health Study (NHS), a prospective cohort of US female registered nurses aged 30-55 at enrollment. Using elastic net regression in a derivation cohort with inflammatory biomarker (high-sensitive CRP, interleukin 6, tumor necrosis factor receptor 2, adiponectin) and metabolomic data, we developed a metabolomic signature index of inflammation (i-MSI). The i-MSI's association with incident IS was examined in an independent NHS nested case-control study using conditional logistic regression, adjusting for cardiovascular risk factors. Generalizability to atherosclerotic disease was evaluated in a coronary heart disease (CHD) nested case-control study from the Women's Health Initiative (WHI). The derivation cohort included 1,699 women (mean age 58 years, 94% White). The i-MSI comprised 102 metabolites, with lysophosphatidylcholine species-promoters of endothelial activation, vascular inflammation, and plaque instability-contributing most significantly. In the independent IS case-control study (454 cases, 454 controls; mean age 66 years), women in the highest compared with lowest i-MSI quartile had a multivariable-adjusted odds ratio (OR) of 1.76 (95% CI 1.02-3.03) for IS, whereas each 1-SD increase in the i-MSI was associated with an OR of 1.35 (95% CI 1.09-1.67). In the WHI study (793 cases, 795 controls; mean age 67 years), each SD increase in the i-MSI was associated with an OR of 1.20 (95% CI 1.05-1.37) for CHD. An inflammatory metabolomic signature was associated with higher IS risk, independent of traditional cardiovascular disease risk factors, with consistent findings for CHD. Future studies should replicate these findings in other populations and evaluate whether these metabolites can improve risk stratification and serve as biomarkers for atherosclerotic cardiovascular diseases.

Orthostatic hypotension is thought to be associated with coronary heart disease, falls, and syncope due to low blood pressure (BP) upon standing. The ARIC study (Atherosclerosis Risk in Communities) measured supine and standing BP among adult participants aged 45 to 64 years once at baseline and followed them for over 35 years. We evaluated higher and lower supine and standing systolic BP, diastolic BP, mean arterial pressure, pulse pressure, absolute and relative orthostatic changes in BP after standing, and mean BP across positions. Associations with adjudicated coronary heart disease and mortality events, as well as hospitalizations and medical claims-based falls and syncope, were assessed via adjusted Cox models in strata of antihypertensive treatment. Among 11 386 participants (mean age, 54 years [SD, 5.7 years]; 56% female; 25% Black adults), drops in systolic BP upon standing (absolute or relative) were associated with coronary heart disease, syncope, and mortality. Higher supine systolic BP and mean arterial pressure were associated with syncope among untreated participants. Increases in systolic BP ≥20 mm Hg upon standing were associated with falls (hazard ratio, 1.52 [95% CI, 1.14-2.02]) and syncope (hazard ratio, 1.40 [95% CI, 1.03-1.92]), particularly among untreated participants. Lower standing systolic BP was associated with a higher risk of syncope among treated participants (hazard ratio, 1.55 [95% CI, 1.14-2.12]). Regardless of treatment status, a higher pulse pressure was associated with coronary heart disease and mortality, but this was not observed for falls or syncope. Higher BP, rather than lower standing BP alone, may be an important risk factor for both cardiovascular and hypotension-related events, especially among untreated adults.

The development of chronic disease is a long-term process involving multiple endpoints. Although multi-state Cox models can estimate state-specific survival risks over time, they are not well suited for comparing the effectiveness of treatment regimes. A discrete-time split-state framework has been proposed, which divides disease states into substates by conditioning on past history. As this framework is both "memoryless" and "memorable," the transition rates can be synthesized into summary measures, multimorbidity-adjusted life year (MALY) and substate-specific life year (SSLY). Building on this framework, we propose to investigate the causal effects of static and dynamic treatment regimes over the disease course under the assumptions of constant baseline confounders and instantaneous effects of interventions on transition rates. We identify the optimal treatment regime as the one that maximizes MALY and use SSLY to elucidate the mechanisms of how treatments influence disease progression. In the application, we identified the optimal weight targets in the ARIC study by modeling the disease course in healthy, at-metabolic-risk, coronary heart disease, heart failure, and mortality states. The estimated MALY was 1.80 years higher (95% CI: 0.62, 2.78) under regime "Normal weight initially and change to overweight if age >65 y" compared to regime "Normal weight across all states." SSLY decomposition indicates that this gain arises from increased life year in all substates except the healthy state. In summary, our method provides a framework to evaluate the health benefits of treatment regimes over the disease course and has the potential to improve the precision prevention of chronic diseases.

Although dietary pulses are recognized by major clinical practice guidelines to reduce cholesterol and coronary heart disease risk, intake is low. There are no health claims for any pulse for cholesterol reduction, which could support uptake. We therefore conducted a systematic review and dose-response meta-analysis of randomized trials of the effect of different types of whole dietary pulses on lipid targets. MEDLINE, Embase, and the Cochrane Library were searched through March 2025 for trials ≥3 weeks. The primary outcome was low-density lipoprotein-cholesterol. Secondary outcomes were other lipid targets. Independent reviewers extracted data and assessed risk of bias. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. Thirty-eight trials (52 trial comparisons, n=2095) with a median of 6 weeks and dose of 130 g/d (0.5-0.67 cup/d) showed that whole dietary pulses decreased low-density lipoprotein-cholesterol (mean difference, -0.14 mmol/L [95% CI, -0.19 to -0.08]), non-high-density lipoprotein-cholesterol (-0.22 mmol/L [95% CI, -0.30 to -0.14]), apoB (apolipoprotein B) (-0.08 g/L [95% CI, -0.13 to -0.03]) and high-density lipoprotein-cholesterol (-0.03 mmol/L [95% CI, -0.05 to -0.01]) with no effects on other lipids. Analyses by pulse type showed similar results. A linear inverse relationship was shown for beans up to 1 cup/d for low-density lipoprotein-cholesterol (coefficient, -0.25 mmol/L/0.5 cup [95% CI, -0.48 to -0.02]) and non-high-density lipoprotein-cholesterol (-0.45 mmol/L/0.5 cup [95% CI, -0.71 to -0.18]). Grading of Recommendations Assessment, Development, and Evaluation was moderate-to-high for all outcomes, except apoB (very low). Whole dietary pulses likely result in small important-to-moderate reductions in lipid targets and trivial reductions in high-density lipoprotein-cholesterol. Similar effects were observed across pulse types with an inverse dose-response gradient for beans up to 1 cup/d. Future studies on chickpeas, dried peas, and lentils are warranted. URL: https://www.crd.york.ac.uk/PROSPERO/view/CRD42023432826; Unique identifier: CRD42023432826.

The clinical benefit of intensive LDL-C-lowering with evolocumab in patients with prior percutaneous coronary intervention (PCI) but without a prior myocardial infarction (MI) is not established. VESALIUS-CV randomized patients with atherosclerosis or high-risk diabetes but without prior MI or stroke and with LDL-C ≥90 mg≥dL to evolocumab vs placebo. The median follow-up was 4.6 years. The dual primary endpoints were: coronary heart disease death, MI, or ischemic stroke (3-point MACE); and the same composite plus ischemia-driven arterial revascularization (4-point MACE). For this pre-specified subgroup analysis, patients were categorized by whether they had undergone PCI at any time prior to trial enrollment. Among 12,257 randomized patients, 3,627 (29.6≥) had undergone prior PCI with a median time between PCI and enrollment of 4 years. Their median age was 66 years and 30.7≥ were women. The median LDL-C at 48 weeks was 41.5 (26.0-67.0) mg/dL vs. 107.0 (84.0-135.0) mg/dL in the evolocumab vs. placebo arms (p<0.0001). Evolocumab reduced the risk of 3-point MACE by 30% (5yr KM 7.0% vs 9.5%; HR 0.70; 95%CI 0.56-0.89; P=0.004) and 4-point MACE by 18% (17.9% vs 21.7%HR 0.82; 95%CI 0.71-0.96; P=0.012), and reduced the risk of MI by 50% (3.0%vs 6.1%; HR 0.50; 95%CI 0.36-0.70; P<0.001), with the effect apparent as soon as 6 months after randomization, and of urgent coronary revascularization by 39% (HR 0.61; 95%CI 0.46-0.80; P<0.001). There were nominally lower rates of CV death (2.6% vs 3.7%; HR 0.66; 95%CI 0.45-0.96; P=0.030) and all-cause death (8.2% vs 10.2%; HR 0.76; 95%CI 0.60-0.95; P=0.016) with evolocumab. Evolocumab reduced the risk of major CV events in stable patients with prior PCI but no MI. These findings support intensive LDL-C-lowering in patients who have undergone PCI even in the absence of prior MI.

Coronary heart disease (CHD) is a leading global cause of death, with established links to various risk factors. Recent evidence suggests an association between impaired masticatory function and CHD, but the causal nature of this relationship remains unclear. To investigate the causal relationship between masticatory function and CHD, we propose a novel hybrid approach that combined constraint-based and score-based methods to learn causal Bayesian network (CBN) structures from observational data. The proposed method is compared against PC, TAN, Naive Bayes, Chow-Liu, and HillClimb algorithms using BIC, K2, BDeu, and BDs scores. A cross-sectional study was conducted in Shanghai, China, from January to May 2023. Data were collected via structured questionnaires, yielding a sample of 179,141 individuals. For analysis, 10,817 healthy individuals (free of any chronic diseases) and 3,382 individuals with CHD are selected. A total of 15 variables covering sociodemographic, functional, cognitive, and health-related aspects are included in the CBN modeling to capture relevant confounders and mediators. The proposed method outperforms several baseline algorithms while maintaining model interpretability. The learned CBN identifies age, motor function, medical constipation, and sleep as direct causes of CHD. Masticatory function is found to influence CHD indirectly through its effects on motor function and medical constipation. Probabilistic inference indicates that sleep, muscle force, cognitive function and education level are key confounders, with decreasing levels of confounding impact. Causal inference using do-calculus reveals that abnormal masticatory function increases CHD risk by 23% points after adjusting for confounding impact, compared to 39% points without adjustment. This hybrid CBN approach effectively uncovers interpretable causal pathways, emphasizing the role of oral health in cardiovascular risk and demonstrating the utility of causal models in informing public health strategies.

The platelet-to-high-density lipoprotein cholesterol ratio (PHR) integrates platelet count and HDL-C concentration and may reflect thrombo-inflammatory and lipid-related cardiovascular risk. However, its association with incident coronary heart disease (CHD) and its incremental value beyond its individual components remain uncertain. We included 326,803 UK Biobank participants without baseline CHD. PHR was calculated as platelet count (×109 cells/L) divided by HDL-C concentration (mmol/L) and analyzed in quartiles and as a log-transformed continuous variable. Incident CHD was defined as the first occurrence of angina pectoris, acute myocardial infarction (AMI), or chronic ischemic heart disease. Cox proportional hazards models were used to estimate hazard ratios (HRs) after adjustment for demographic, socioeconomic, lifestyle, and clinical covariates. Restricted cubic spline models were applied to examine non-linearity. Discriminatory performance and incremental model information were evaluated using ROC/C-index analyses and likelihood ratio tests. Exploratory mediation-oriented analyses examined hs-CRP, HbA1c, and neutrophil count. During a median follow-up of 13.0 years, 20,340 incident CHD events occurred. Compared with participants in the lowest PHR quartile, those in the highest quartile had a higher hazard of incident CHD in the fully adjusted model (HR 1.36, 95% CI 1.31-1.42; P < 0.01). The association was also observed for CHD subtypes and appeared stronger for AMI (Q4 vs. Q1: HR 1.68, 95% CI 1.56-1.81) than for chronic ischemic heart disease (Q4 vs. Q1: HR 1.38, 95% CI 1.32-1.45). Restricted cubic spline analysis suggested a non-linear association between log-transformed PHR and incident CHD (P for non-linearity < 0.001), with a relatively flat association at lower values and a steeper increase at higher values. PHR showed moderate discrimination for incident CHD (AUC 0.716, 95% CI 0.713-0.720), and adding PHR to the fully adjusted clinical model produced a small increase in C-index (0.714 to 0.720), larger than that observed when platelet count or HDL-C was added separately. Exploratory analyses suggested that hs-CRP, HbA1c, and neutrophil count statistically accounted for part of the observed association, although these findings may reflect shared inflammatory and metabolic background rather than causal mediation. Higher PHR was associated with increased risk of incident CHD in this large prospective cohort, particularly for AMI. PHR may serve as a simple adjunctive marker for CHD risk stratification when interpreted alongside established clinical risk factors.

Mechanism of Shanhu Qishiwei pills in regulating endoplasmic reticulum stress through GRP78/CHOP signaling pathway for the treatment of cerebral ischemia.

The effect of childhood body weight status on cardiovascular disease risk in adulthood: A narrative review.

To compare the multidimensional clinical characteristics of patients with Wagner grade 4-5 diabetic foot (DF) according to the severity of lower extremity atherosclerotic occlusive disease and gender, and to provide clinical evidence for DF wound repair and comprehensive management. Patients with DF who were admitted between January 2021 and June 2025 were enrolled. Eligible patients were included according to predefined inclusion and exclusion criteria. Data collected included general information (demographic characteristics, diabetes-related conditions, comorbidities, and risk factors), clinical indicators (laboratory results obtained within 48 hours of admission), and immune-inflammatory indices. The immune-inflammatory indices were calculated from ratios or weighted relationships among blood cell subsets based on laboratory findings within 48 hours after admission, and were used to reflect inflammatory status, immune profile, and nutritional status. According to lower extremity CT angiography findings, patients were divided into a non-significant stenosis group (patent trunk arteries or luminal stenosis <99%) and a diffuse occlusion group (multisegment trunk artery occlusion or luminal stenosis ≥99%). Univariate analysis was first performed, and variables (general information and clinical indicators) with significant differences were further assessed using logistic regression. In addition, the above indicators were compared between male and female patients. A total of 522 patients with DF were initially enrolled, and 104 patients were finally included in the analysis according to the selection criteria, including 73 males and 31 females. Based on lower extremity blood flow status, 44 patients were assigned to the non-significant stenosis group and 60 to the diffuse occlusion group. Among the 104 patients, 68 underwent amputation (65.38%), including 30 cases (44.1%) in the non-significant stenosis group and 38 cases (55.9%) in the diffuse occlusion group; the difference in amputation rate between the two groups was not significant ( χ 2=0.264, P=0.608). Univariate analysis showed that, compared with the non-significant stenosis group, the diffuse occlusion group had a higher proportion of female patients, older age, lower body mass index (BMI), and a higher prevalence of coronary heart disease. Laboratory examination showed lower neutrophil count, fasting blood glucose, and glycated hemoglobin, but higher hemoglobin and albumin levels in the diffuse occlusion group. Among the immune-inflammatory indices, only the prognostic nutritional index was significantly higher. All of the above differences were significant ( P<0.05). logistic regression analysis further showed that older age, female, coexisting coronary heart disease, higher neutrophil count, lower BMI, and higher hemoglobin level were independently associated with diffuse occlusion ( P<0.05). Compared with female patients, male patients were younger and had a higher proportion of smokers. In laboratory examination, male patients had lower absolute lymphocyte counts but higher hemoglobin, total bilirubin, indirect bilirubin, and procalcitonin levels. Among the immune-inflammatory indices, the platelet-to-lymphocyte ratio and monocyte-to-lymphocyte ratio were significantly higher. These differences were all significant ( P≤0.05). Patients with Wagner grade 4-5 DF with different lower extremity blood flow status exhibit significant differences in cardiovascular comorbidities, nutritional status, and inflammatory profiles. In addition, gender-related differences are also observed in vascular lesion characteristics, nutritional status, and inflammatory response. Therefore, comprehensive evaluation incorporating blood flow status, laboratory indicators, and gender-specific characteristics is warranted to develop more individualized treatment strategies, improve limb salvage, and optimize overall prognosis.