BMC Cardiovascular Disorders[JOURNAL]
Sun
200 papers
Temporal changes of oxidative stress and ferroptosis-associated biomarkers in STEMI patients undergoing primary PCI and their correlation with myocardial reperfusion injury.
Sharifikia M, Mehrpooya M, Ranjbar A … +4 more , Naghdi S, Familmotaghi A, Talebi SS, Hosseini SK
BMC Cardiovasc Disord · 2026 Jun · PMID 42304213 · Full text
BACKGROUND: Myocardial ischemia-reperfusion injury in ST-elevation myocardial infarction (STEMI) involves complex mechanisms, including oxidative stress and ferroptosis, but the timing and relationship of these processes...
BACKGROUND: Myocardial ischemia-reperfusion injury in ST-elevation myocardial infarction (STEMI) involves complex mechanisms, including oxidative stress and ferroptosis, but the timing and relationship of these processes with cardiac injury markers remain unclear. This study investigated how oxidative stress and ferroptosis-associated biomarkers change over time and their correlations with cardiac injury markers in STEMI patients undergoing primary percutaneous coronary intervention (PCI). METHODS: A prospective cohort of 25 STEMI patients undergoing primary PCI was studied. Serum levels of cardiac injury biomarkers (Troponin I, CK-MB) and oxidative stress/ferroptosis markers (superoxide dismutase [SOD], total antioxidant capacity [TAC], glutathione peroxidase [GPx], lipid peroxidation products [LPO], serum iron, and ferritin) were measured at pre-PCI, and at 6, 12, 24, and 48 h post-PCI. Temporal trends and Pearson correlations between these biomarkers were analyzed. RESULTS: Markers of oxidative stress and ferroptosis-associated biomarkers demonstrated distinct time-dependent patterns post-reperfusion: SOD and TAC peaked early (6-12 h), while GPx initially decreased. LPO levels peaked at 6 h. Serum iron transiently declined, and ferritin showed a temporary increase at 6-12 h. Activities of antioxidant enzymes (SOD, GPx, TAC) showed inverse correlations with peak and cumulative cardiac injury markers in this pilot cohort, whereas higher LPO and iron showed positive correlations with greater myocardial damage observed here. CK-MB associations were stronger than those with Troponin I in this pilot cohort. CONCLUSION: In this pilot cohort, oxidative stress and ferroptosis-associated biomarkers showed rapid early changes after reperfusion in STEMI patients undergoing primary PCI, correlating with myocardial injury extent (stronger correlations with CK-MB than troponin I). These findings suggest early oxidative stress and iron dysregulation as potential therapeutic targets for reperfusion injury, warranting confirmation in larger studies.
Circulating angiopoietin-2 and TEK receptor tyrosine kinase-2 protein provide prognostic value in patients with acute myocardial infarction.
Tan S, Hao X, Peng Y … +6 more , Zhu W, Yin Z, Hu Z, Zheng Z, Peng J, Tang Y
BMC Cardiovasc Disord · 2026 Jun · PMID 42298430 · Full text
BACKGROUND: Acute myocardial infarction (AMI) is an acute heart disease that can result in high rates of disability and mortality. Biomarkers can reflect the pathophysiological progress of AMI, such as myocardial ischemi...
BACKGROUND: Acute myocardial infarction (AMI) is an acute heart disease that can result in high rates of disability and mortality. Biomarkers can reflect the pathophysiological progress of AMI, such as myocardial ischemia injury, ventricular remodelling and oxidative stress, and provide advantages in the prognostic evaluation of AMI. Finding novel biomarkers can help improve the risk stratification of AMI. METHOD: A total of 180 patients who were diagnosed with AMI in the Department of Cardiovascular Medicine of Hunan Provincial People's Hospital from July 2020 to March 2021 were included in this study. Baseline circulating ANGPT-2 and TIE-2 levels were measured, and patients underwent a regular follow-up to record the occurrence of major adverse cardiovascular events (MACE) after discharge. RESULTS: During the entire follow-up period with an average of 444 (356-586) days, 55 patients developed MACE. Multivariate Cox regression analysis revealed that ANGPT-2 (HR: 2.400; 95% CI: 1.380-4.523; P = 0.002) and TIE-2 (HR: 2.004; 95% CI: 1.127-3.562; P = 0.018) were independent predictors of MACE in patients with AMI. The area under the curve (AUC) of circulating ANGPT-2 for predicting MACE was 0.756 (95% CI: 0.682-0.785; P < 0.001), and the AUC of circulating TIE-2 for predicting MACE was 0.664 (95% CI: 0.572-0.755; P < 0.001).The Kaplan-Meier survival curve revealed that patients with an ANGPT-2 level ≥ 1.896 ng/mL had a greater risk of MACE than those with an ANGPT-2 level < 1.896 ng/mL (HR = 3.189; 95% CI: 1.856-5.481; P < 0.001), and patients with a TIE-2 level ≥ 21.886 ng/mL had a greater risk of MACE than those with a TIE-2 level < 21.886 ng/mL (HR = 2.912; 95% CI: 1.681-5.042; P < 0.001). CONCLUSION: ANGPT-2 and TIE-2 are significantly correlated with the prognosis of AMI, which suggests that they might be potential biomarkers for predicting prognosis.
Intravascular imaging-guided versus angiography-guided percutaneous coronary intervention in multivessel coronary artery disease: a systematic review, meta-analysis, and trial sequential analysis of randomized controlled trials.
Mohamed AA, Elhefnawy AM, Shehata AS … +6 more , Khalid S, Mostafa A, Ali A, Ibrahim B, Saeed TZ, Dibas M
BMC Cardiovasc Disord · 2026 Jun · PMID 42298423 · Full text
BACKGROUND: Percutaneous coronary intervention (PCI) in patients with multivessel coronary artery disease is associated with increased anatomical complexity and adverse cardiovascular outcomes. Conventional angiography p...
BACKGROUND: Percutaneous coronary intervention (PCI) in patients with multivessel coronary artery disease is associated with increased anatomical complexity and adverse cardiovascular outcomes. Conventional angiography provides limited assessment of vessel structure and plaque characteristics, whereas intravascular imaging with intravascular ultrasound (IVUS) or optical coherence tomography (OCT) may improve procedural guidance. However, the clinical impact of imaging-guided PCI in this population remains uncertain. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials comparing intravascular imaging-guided versus angiography-guided PCI in patients with multivessel coronary artery disease regarding major adverse cardiovascular events (MACE). Major databases were searched through December 2025. Outcomes were pooled as risk ratios (RRs) with 95% confidence intervals (CIs) using random-effects models. Trial sequential analysis (TSA) and an exploratory network meta-analysis (NMA) were performed. RESULTS: Five randomized trials, including 3,023 patients, were analyzed. Imaging-guided PCI was associated with a significant reduction in MACE compared with angiography-guided PCI (RR 0.58, 95% CI 0.46 to 0.74; p < 0.0001; I = 9.8%). In subgroup analyses by imaging modality, IVUS-guided PCI was associated with a reduction in MACE (RR 0.53, 95% CI 0.39 to 0.73; p < 0.0001; I = 0%), as was OCT-guided PCI (RR 0.49, 95% CI 0.28 to 0.87; p = 0.014; I = 24.3%). TSA provided supportive evidence for a beneficial effect of imaging-guided PCI. NMA suggested that both IVUS and OCT were associated with improved outcomes compared with angiography, with no significant difference between the two imaging modalities. CONCLUSION: Intravascular imaging-guided PCI is associated with a reduction in MACE in patients with multivessel coronary artery disease. These findings support the clinical value of intravascular imaging in this population, with similar effects observed across imaging modalities.
Prevalence and risk factors of echocardiographically suspected pulmonary hypertension in maintenance hemodialysis patients: a retrospective study.
Jiang Y, Liu Z, Su C … +2 more , Chen Y, Liu X
BMC Cardiovasc Disord · 2026 Jun · PMID 42298407 · Full text
BACKGROUND: Pulmonary hypertension (PH) is a prevalent complication in maintenance hemodialysis (MHD) patients, contributing to increased cardiovascular morbidity. This study aimed to determine the prevalence and indepen...
BACKGROUND: Pulmonary hypertension (PH) is a prevalent complication in maintenance hemodialysis (MHD) patients, contributing to increased cardiovascular morbidity. This study aimed to determine the prevalence and independent risk factors for echocardiographically suspected PH in a Chinese MHD cohort. METHODS: This single-center retrospective cross-sectional study reviewed 948 MHD patients who underwent transthoracic echocardiography between January 2023 and December 2024. Suspected PH was consistently defined using standardized objective echocardiographic criteria (estimated pulmonary artery systolic pressure > 35 mmHg), with qualitative right-heart markers serving as supportive criteria only when tricuspid regurgitant jets were unmeasurable. Following rigorous data cleaning to remove extreme outliers, a prespecified multivariable logistic regression model-adjusted for core clinical confounders-was used to identify independent predictors. RESULTS: The prevalence of echocardiographically suspected PH was 29.7% (282/948). Patients with suspected PH had significantly lower hemoglobin (107.48 ± 23.70 vs. 113.10 ± 23.93 g/L, p = 0.001) and serum albumin (41.79 ± 5.22 vs. 43.03 ± 4.40 g/L, p < 0.001), alongside markedly higher median brain natriuretic peptide levels (414.30 [IQR: 132.46-1466.23] vs. 124.25 [IQR: 50.30-338.54] pg/mL, p < 0.001). After multivariable adjustment for age, sex, diabetes, hypertension, and dialysis vintage, independent predictors included larger left atrial diameter (OR 1.292, 95% CI 1.223-1.364, p < 0.001), lower left ventricular ejection fraction (OR 0.954, 95% CI 0.927-0.981, p = 0.001), history of thrombectomy (OR 2.450, 95% CI 1.249-4.807, p = 0.009), and history of percutaneous transluminal angioplasty (PTA) (OR 1.511, 95% CI 1.014-2.250, p = 0.042). CONCLUSION: Echocardiographically suspected PH affects approximately 30% of Chinese MHD patients. It is significantly and independently associated with left-sided cardiac remodeling and a history of severe vascular access interventions.
Helicobacter pylori infection is associated with elevated insulin resistance and cardiovascular risk, particularly in otherwise low-risk individuals: the Tongren health care study.
Zhao MM, Cui J, Liu W … +5 more , Li Y, Xie RR, Chen DN, Yang JK, Zhang XL
BMC Cardiovasc Disord · 2026 Jun · PMID 42298404 · Full text
BACKGROUND AND OBJECTIVES: Helicobacter pylori (H. pylori) has been increasingly linked to extragastric conditions. However, the relationship between H. pylori infection and cardiovascular diseases (CVD) remains controve...
BACKGROUND AND OBJECTIVES: Helicobacter pylori (H. pylori) has been increasingly linked to extragastric conditions. However, the relationship between H. pylori infection and cardiovascular diseases (CVD) remains controversial. This study aims to investigate the association between H. pylori infection and 10-year cardiovascular risk. METHODS: A total of 1,398 subjects who underwent health examinations at Beijing Tongren Hospital were included in this study. H. pylori infection was determined using C-breath test. The 10-year cardiovascular risk was assessed using the Framingham score. Insulin resistance was evaluated through the triglyceride-glucose (TyG) index and its derivatives. Logistic regression and subgroup analyses were performed to evaluate associations. RESULTS: Individuals with H. pylori infection exhibited significantly higher TyG index and its derivatives (all P < 0.001), indicating increased insulin resistance. All TyG-related indices were strongly correlated with 10-year CVD risk, with TyG-WHR showing the strongest association (R = 0.745, P < 0.001). The estimated 10-year CVD risk was significantly higher in the H. pylori-infected group (P = 0.003). After adjusting for potential confounders, H. pylori infection remained independently associated with high cardiovascular risk (OR = 2.552, 95% CI: 1.312-4.963, P = 0.006). Notably, this association was more pronounced in females, individuals younger than 50 years, non-smokers, non-diabetics, and those without hypertension. CONCLUSIONS: H. pylori infection is associated with increased insulin resistance and elevated 10-year cardiovascular risk, particularly among individuals without traditional risk factors. These findings suggest that H. pylori infection may represent a non-traditional contributor to cardiovascular risk and warrants further investigation.
Comparable survival over an extended follow-up after on-pump versus off-pump coronary artery bypass grafting: a propensity score-matched cohort.
Pikkujämsä A, Rinne P, Wistbacka JO … +1 more , Hilska M
BMC Cardiovasc Disord · 2026 Jun · PMID 42288779 · Full text
BACKGROUND: Long-term survival following off-pump coronary artery bypass grafting (OPCAB) compared with conventional on-pump coronary artery bypass grafting (ONCAB) remains uncertain. Randomised trials and meta-analyses...
BACKGROUND: Long-term survival following off-pump coronary artery bypass grafting (OPCAB) compared with conventional on-pump coronary artery bypass grafting (ONCAB) remains uncertain. Randomised trials and meta-analyses up to 5-10 years after procedures have demonstrated either no significant differences or modest disadvantages of OPCAB, particularly regarding completeness of revascularisation and late mortality. However, comparative data extending up to 20 years after procedure are scarce. Thus, very-long-term outcomes after ONCAB versus OPCAB in a propensity score-matched cohort were evaluated. METHODS: Consecutive adults undergoing isolated primary coronary artery bypass grafting between 1999 and 2016 at a single cardiac surgery centre were retrospectively identified. Patients undergoing isolated OPCAB or ONCAB procedures were included and matched in a 1:2 ratio using clinically relevant preoperative variables. The primary outcome was overall survival in the matched cohort analysed using Cox proportional hazards regression. RESULTS: During the study period, 2,935 patients underwent isolated primary coronary artery bypass grafting (CABG), of whom 2,496 (85.0%) underwent ONCAB and 439 (15.0%) OPCAB procedures. Median survival time was 13.7 years (95% CI 13.2-14.2) and median follow-up was 12.3 years (interquartile range 8.0-17.1, maximum 23.9 years). The matched cohort consisted of 402 OPCAB patients matched to 804 ONCAB patients. Median survival time was 12.4 years (95% CI 11.9-13.2) in ONCAB and 12.6 years (95% CI 11.5-13.8) in OPCAB patients. Overall survival did not differ significantly between the groups (HR 0.95, 95% CI 0.82-1.11; ONCAB as reference). No significant differences were observed in the cumulative incidence of cardiovascular mortality. CONCLUSION: In this propensity score-matched cohort with follow-up extending up to 20 years, ONCAB and OPCAB were associated with comparable long-term survival and cardiovascular mortality. These findings support an individualised approach to operative technique selection based on patient characteristics and surgical expertise.
Epicardial fat is associated with prevalent heart failure and adverse cardiac remodeling in atrial fibrillation.
Hamel AP, Orwig T, Tran BN … +9 more , Vogt B, Senser E, Hegde S, Kovell L, Lee JA, Parker MW, Fitzgibbons T, McManus DD, Tran KT
BMC Cardiovasc Disord · 2026 Jun · PMID 42288762 · Full text
BACKGROUND: Atrial fibrillation (AF) frequently coexists with cardiometabolic conditions such as diabetes and heart failure (HF), which increase morbidity and mortality. While body mass index (BMI) is widely used for ris...
BACKGROUND: Atrial fibrillation (AF) frequently coexists with cardiometabolic conditions such as diabetes and heart failure (HF), which increase morbidity and mortality. While body mass index (BMI) is widely used for risk stratification, regional adiposity measures including epicardial adipose tissue (EAT) and EAT indexed to body surface area (iEAT) may better reflect local cardiac fat burden and its association with conditions of adverse cardiac remodeling. METHODS: We identified 348 participants from an AF registry with EAT area quantified from a pre-ablation CT scan. Echocardiographic parameters and clinical covariates were collected from the electronic medical record. Adiposity measures were analyzed in tertiles. Multivariable logistic regression models adjusted for age, sex, and race assessed associations between adiposity and outcomes. ROC curves were used to compare predictive performance. Multivariable linear regression analysis assessed echocardiographic parameters, including left ventricular (LV) ejection fraction, LV dimensions, LV mass, left atrial anteroposterior diameter, and pulmonary artery systolic pressure. RESULTS: Among 348 participants, higher BMI, EAT and iEAT were each associated with older age and increased prevalence of cardiometabolic comorbidity. In multivariable models, the highest tertiles of EAT and iEAT were each independently associated with heart failure [EAT OR 4.83 (95% CI 1.82-12.84); iEAT OR 4.40 (95% CI 1.70-11.43)]. ROC analysis showed that iEAT best discriminated heart failure (AUC = 0.74), while BMI best discriminated diabetes (AUC = 0.69). In adjusted models, all three adiposity metrics were significantly associated with higher LV mass; EAT and iEAT were additionally linked to higher pulmonary artery systolic pressure. CONCLUSION: In patients with atrial fibrillation, epicardial adiposity measures were more strongly associated with prevalent heart failure than BMI, possibly due to its association with adverse cardiac remodeling. In contrast, BMI remains a stronger predictor of diabetes. Incorporating epicardial fat may enhance risk stratification for heart failure in patients with atrial fibrillation beyond BMI alone.
Association of left ventricular end-systolic volume with peri-echocardiographic acute kidney injury proxy beyond ejection fraction: a retrospective linked echocardiographic cohort study.
Isleyen HB, Tugrul Yavuz S, Bulut S … +5 more , Kizkapan F, Alioglu C, Eren NZ, Sozen AA, Khanmohammadi M
BMC Cardiovasc Disord · 2026 Jun · PMID 42288761 · Full text
BACKGROUND: Left ventricular ejection fraction (LVEF) remains the default echocardiographic summary of systolic performance, yet its ratio structure makes it sensitive to geometry and loading conditions. Left ventricular...
BACKGROUND: Left ventricular ejection fraction (LVEF) remains the default echocardiographic summary of systolic performance, yet its ratio structure makes it sensitive to geometry and loading conditions. Left ventricular end-systolic volume (LVESV) may capture adverse remodeling more directly. The relation of LVESV to peri-echocardiographic renal dysfunction in hospitalized patients remains uncertain. METHODS: This retrospective linked echocardiographic cohort study analyzed 1,022 complete biplane studies from 784 patients in the credentialed PhysioNet MIMIC-IV-ECHO-Ext-LVVOLUMES-A4C-ROI resource linked to MIMIC-IV v3.1 clinical tables. The primary endpoint was an acute kidney injury (AKI) proxy defined as maximum serum creatinine ≥ 2.0 mg/dL within a ± 24-hour peri-echocardiographic window. Hierarchical logistic regression with patient-level cluster-robust standard errors included age, sex, first-day SOFA score, and vasopressor exposure; 5 chained-equation imputations addressed missing SOFA. Temporal analysis compared echocardiography time with the first creatinine value meeting the endpoint threshold. RESULTS: AKI proxy was present in 80 of 1,022 studies (7.8%). Among these 80 studies, 73 (91.3%) reached the creatinine threshold before echocardiography and 7 (8.8%) after echocardiography. For AKI proxy, LVESV showed modestly higher discrimination than LVEF (AUC 0.572 vs. 0.548; ΔAUC 0.024; p = 0.253). In the fully adjusted hierarchical model, LVESV remained associated with AKI proxy (OR 1.40 per SD increase, 95% CI 1.10-1.78; p = 0.006), whereas LVEF did not (OR 0.83 per SD decrease, 95% CI 0.62-1.10; p = 0.188). Model 3 yielded the highest C-statistic (0.727) and the lowest AIC (517.0), but BIC was not improved and reclassification gains were modest. CONCLUSIONS: LVESV was associated with peri-echocardiographic AKI proxy after severity adjustment, but the temporal analysis indicates that the signal predominantly reflected concurrent renal illness rather than prospective prediction. Any incremental value beyond LVEF was modest and should be interpreted within the limits of a non-KDIGO creatinine-based proxy endpoint.
The triglyceride-glucose index and C-reactive protein-triglyceride-glucose index as surrogate markers of vascular stiffness in prediabetes: a cross-sectional study.
Qiu G, Li X, Jiang L … +5 more , Zhou Y, Liu J, Chen K, Zhu X, Wang Y
BMC Cardiovasc Disord · 2026 Jun · PMID 42288731 · Full text
BACKGROUND: Prediabetes accelerates arterial stiffening, yet the optimal metabolic biomarker for vascular assessment remains undetermined. This study investigated the associations of the homeostasis model assessment of i...
BACKGROUND: Prediabetes accelerates arterial stiffening, yet the optimal metabolic biomarker for vascular assessment remains undetermined. This study investigated the associations of the homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride-glucose (TyG) index, and C-reactive protein-triglyceride-glucose index (CTI) with arterial stiffness in a prediabetic population. METHODS: This cross-sectional study enrolled 2,008 prediabetic adults. Arterial stiffness was defined by brachial-ankle pulse wave velocity (baPWV). Multivariable logistic regression, restricted cubic spline (RCS) modeling, and ROC curve analyses were employed to evaluate and compare the discriminatory performance of HOMA-IR, TyG, and CTI. RESULTS: All three indices were independently associated with arterial stiffness. Fully adjusted odds ratios (ORs) per one-unit increment were 1.12 (1.04-1.21) for HOMA-IR, 1.49 (1.24-1.80) for TyG, and 1.52 (1.25-1.85) for CTI. Comparing the highest to the lowest quartiles, the ORs for arterial stiffness were 1.84 ( 1.31-2.59) for HOMA-IR, 2.02 (1.44-2.82) for TyG, and 1.72 (1.23-2.39) for CTI, respectively. RCS analysis revealed a nonlinear relationship for HOMA-IR, whereas TyG and CTI exhibited linear dose-response patterns. ROC analyses based on adjusted prediction models showed that CTI had the numerically highest discriminatory performance (AUC = 0.790), followed closely by TyG (AUC = 0.784), whereas HOMA-IR showed lower discrimination (AUC = 0.737). Pairwise DeLong tests showed that CTI provided a modest but statistically significant improvement over TyG (P = 0.041), while both CTI and TyG significantly outperformed HOMA-IR (both P < 0.001). Findings remained robust across subgroup and sensitivity analyses. CONCLUSIONS: HOMA-IR, TyG, and CTI are independent risk indicators for arterial stiffness in prediabetes. Notably, TyG and CTI exhibit stronger associations and superior discriminatory utility compared to HOMA-IR. These simple, accessible metabolic indices-particularly TyG and CTI-serve as robust practical surrogate markers for identifying prevalent arterial stiffness in individuals with prediabetes.
Estimated pulse wave velocity and risk of cardiometabolic multimorbidity in middle-aged and older adults: a cohort study.
Zhang J, Li Y, Wu J … +5 more , Sun Z, Juan W, Liu W, Huang M, Yao K
BMC Cardiovasc Disord · 2026 Jun · PMID 42288723 · Full text
BACKGROUND: Cardiometabolic multimorbidity (CMM) is a growing global public health challenge. Early identification of CMM is crucial for preventive management and reducing disease burden. OBJECTIVE: The aim of this study...
BACKGROUND: Cardiometabolic multimorbidity (CMM) is a growing global public health challenge. Early identification of CMM is crucial for preventive management and reducing disease burden. OBJECTIVE: The aim of this study was to investigate the association between estimated pulse wave velocity (ePWV), a convenient measure derived from age and blood pressure, and risk of incident CMM in middle-aged and older adults. METHODS: This study used data from Health and Retirement Study (HRS). Cox proportional hazards regression models and restricted cubic spline (RCS) regression models were used to explore the association between ePWV and incident CMM. RESULTS: A total of 6551 participants were included in the analysis. The median age of the participants at baseline was 66 years [IQR: 58-73 years], and 2396 (36.57%) were men. Participants were stratified into three groups according to tertiles of ePWV, with median (IQR) values of 8.69 (8.01-9.19), 10.58 (10.11-11.08), and 12.82 (12.18-13.89) m/s, respectively. After multivariate adjustment, compared with the lowest tertile, the middle and highest tertiles were associated with a 80% (HR: 1.80, 95% CI: 1.38-2.34) and 89% (HR: 1.89, 95% CI: 1.35-2.64) increased risk of CMM. The RCS regression model revealed a significant positive association between ePWV and the incidence of CMM (P = 0.0004). Subgroup analyses and competing risk analysis confirmed the robustness of the main results. CONCLUSIONS: A positive association was observed between ePWV and incident CMM in middle-aged and older adults. This simplified approach holds notable value in resource-limited settings, highlighting the potential of integrating ePWV into routine screenings for early CMM identification.
Prognostic factors in patients with Marfan syndrome referred to a cardiac surgery center: a retrospective cohort study.
Cheng YM, Chen YJ, Wang CQ … +3 more , Mo SY, Lai DF, Chen GX
BMC Cardiovasc Disord · 2026 Jun · PMID 42288721 · Full text
BACKGROUND: Marfan syndrome (MFS) is associated with a high risk of aortic complications and premature mortality. This study aimed to evaluate long-term outcomes and identify clinical predictors of mortality in patients...
BACKGROUND: Marfan syndrome (MFS) is associated with a high risk of aortic complications and premature mortality. This study aimed to evaluate long-term outcomes and identify clinical predictors of mortality in patients with MFS. METHODS: We conducted a retrospective cohort study of consecutive patients diagnosed with MFS according to the revised Ghent criteria who presented between February 2000 and June 2022. Kaplan-Meier analysis was used to estimate overall survival, and survival was compared according to preoperative left ventricular end-diastolic dimension (LVEDD). Univariable and multivariable Cox regression analyses were performed to identify predictors of all-cause mortality. A time-dependent Cox regression model was additionally used to account for surgery as a time-varying covariate and reduce potential immortal time bias. RESULTS: A total of 67 patients were included, with a mean age of 32 ± 10 years and a mean maximum ascending aortic diameter of 58.0 ± 11.7 mm. During a median follow-up of 53 months, the 1-, 5-, 10-, and 15-year overall survival rates were 74.6% (95% CI: 64.2-85.0), 62.8% (95% CI: 50.8-74.8), 48.7% (95% CI: 34.2-63.2), and 43.3% (95% CI: 27.0-59.6), respectively. Patients with preoperative LVEDD ≥ 65 mm had significantly worse survival (P = 0.024). In multivariable Cox regression analysis, preoperative LVEDD ≥65 mm (HR 2.39; 95% CI 1.06-5.38; P = 0.035) and emergent intubation (HR 6.43; 95% CI 1.54-26.88; P = 0.011) were independently associated with increased mortality, whereas surgical intervention was associated with lower mortality (HR 0.44; 95% CI 0.20-0.99; P = 0.046). In time-dependent Cox analysis, surgery remained significantly associated with lower mortality after adjustment (HR 0.31; 95% CI 0.13-0.70; P = 0.005). CONCLUSION: In patients with MFS, larger LV dimensions, particularly LVEDD ≥65 mm, were associated with poorer long-term outcomes and may provide complementary information for exploratory risk stratification beyond aortic diameter. Surgical intervention was associated with lower mortality after accounting for time-dependent bias. These findings suggest that LVEDD may help identify high-risk patients and support its potential role as a complementary marker for risk stratification.
Differential expression of metabolic genes distinguishes physiological from pathological cardiac hypertrophy.
Cai X, Lin S, Chen J … +3 more , Dai Q, Diao Y, Zheng L
BMC Cardiovasc Disord · 2026 Jun · PMID 42288718 · Full text
BACKGROUND: Cardiac hypertrophy is an adaptive or maladaptive response to physiological or pathological stimuli, with distinct functional outcomes. Metabolic reprogramming plays a key role in this process; however, the m...
BACKGROUND: Cardiac hypertrophy is an adaptive or maladaptive response to physiological or pathological stimuli, with distinct functional outcomes. Metabolic reprogramming plays a key role in this process; however, the metabolism-associated genes underlying different remodeling patterns remain unclear. METHODS: Transcriptomic microarray data related to cardiac hypertrophy (GSE776) were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified by comparing physiological (exercise-induced) and pathological (high-salt diet-induced) hypertrophy models with controls. Metabolism-associated genes were retrieved from the Molecular Signatures Database (MSigDB) and intersected with physiological hypertrophy-specific DEGs to identify candidate metabolic genes. Protein-protein interaction (PPI) analysis was performed to identify hub genes. Experimental validation was performed using mouse models of pregnancy-induced physiological hypertrophy and isoproterenol-induced pathological hypertrophy, isoproterenol-treated neonatal rat cardiomyocytes, and human myocardial tissue samples. RESULTS: Transcriptomic analysis identified 48 genes specifically associated with physiological cardiac hypertrophy, which were predominantly enriched in metabolic pathways. Intersection of these genes with metabolism-related gene sets revealed 22 physiological hypertrophy-related metabolic genes. PPI analysis identified HADHA, ACOX1 and GOT2 as key hub genes. In vivo and in vitro experiments demonstrated that these genes were significantly upregulated in physiological cardiac hypertrophy but markedly downregulated in pathological hypertrophy. Immunohistochemical analysis of human myocardial tissues confirmed reduced expression of HADHA, ACOX1 and GOT2 in pathological hypertrophic myocardium compared with non-hypertrophic controls. CONCLUSION: Differential expression of HADHA, ACOX1, and GOT2 highlights altered fatty acid oxidation and mitochondrial energy metabolism as key features distinguishing physiological and pathological cardiac hypertrophy.
Sex-stratified polygenic risk scores for coronary artery disease incidence: Insights from a 20-year cohort study.
Najd-Hassan-Bonab L, Moazzam-Jazi M, Khalili D … +3 more , Mahdavi M, Khalili M, Daneshpour MS
BMC Cardiovasc Disord · 2026 Jun · PMID 42288717 · Full text
BACKGROUND: Polygenic risk scores (PRS) utilize genetic variants to evaluate susceptibility to diseases. While the performance of PRS has been extensively studied in European populations, its accuracy and validation in t...
BACKGROUND: Polygenic risk scores (PRS) utilize genetic variants to evaluate susceptibility to diseases. While the performance of PRS has been extensively studied in European populations, its accuracy and validation in the Middle East, particularly in Iran, remain underexplored. We aimed to assess whether PRSs improve coronary artery disease (CAD) prediction beyond clinical risk factors using sex-stratified analyses. METHODS: This longitudinal study leveraged data from the Tehran cardiometabolic genetic study (TCGS) cohort (N = 16,226), a long-term population-based study in Iran, including participants free of baseline CAD. We evaluated three established CAD-PRSs (PRS241, PRS175, PRS161) derived from GWAS of European cohorts, alongside a meta-PRS and multi-ancestry data. Multivariable Cox proportional hazards regression models were employed to assess the association between each PRS and CAD incidence, adjusting for established clinical covariates. Sensitivity analyses were conducted by sequentially adjusting for clinical risk factors to evaluate the independent effect of the PRS. Incremental predictive value beyond clinical factors was evaluated using net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA).The association of clinical risk factors associated with PRS was also investigated. RESULTS: Over a median follow-up of 15 years in 4,594 individuals, 991 CAD events occured. PRS241 demonstrated consistent sex-stratified associations, with a 70% increased risk in females (HR = 1.70, 95% CI: 1.28-2.25) and 54% in males (HR = 1.54, 95% CI: 1.22-1.93) comparing highest versus lowest quartiles. In sensitivity analyses, adjustment for HDL, LDL, hypertension, and diabetes resulted in only modest attenuation of these associations, with PRS241 maintaining significant independent risk. PRS161 was significantly associated with CAD only in males (38% increased risk), while PRS175 showed no significant associations in either sex. Integrating PRS241 into clinical risk models yielded small improvements in CAD prediction, indicated by enhanced discrimination (female: ΔC = 0.004; male: ΔC = 0.004) and reclassification (males: relative IDI = 0.0255). DCA further confirmed small net benefit for PRS241. Also, PRS241 and PRS161 were linked to adverse HDL levels in both sexes (PRS161: β = - 0.0068, FDR P-value = 0.002 in females ; β = - 0.006, FDR P-value = 0.010 in males. PRS241: β = - 0.005, FDR P-value = 0.007 in females ; β = - 0.005, FDR P-value = 0.012 in males). Notably, PRS241 also showed sex-stratified associations with hypertension (OR = 1.11, FDR P-value = 0.04) and diabetes (OR = 1.66, FDR P-value = 0.008) exclusively in females. CONCLUSION: These findings demonstrate that incorporation of PRS241 into established clinical risk factors provides small but complementary value for CAD risk prediction. This may facilitate improved risk stratification and support more targeted primary prevention strategies in both sexes.
Impact of residual cholesterol and inflammation risk on non-culprit plaque progression in patients with acute coronary syndrome: a serial optical coherence tomography study.
Zhang D, He L, Yi B … +14 more , Xu Y, Zhao C, Zeng M, Qin Y, Weng Z, Wang N, Feng X, Li L, Wang Y, Hou J, Mintz GS, Hu S, Jia H, Yu B
BMC Cardiovasc Disord · 2026 Jun · PMID 42286493 · Full text
BACKGROUND: Acute Coronary Syndrome (ACS) patients face recurrent cardiovascular events due to non-culprit plaque progression despite optimal secondary prevention, but the differential impacts of residual cholesterol ris...
BACKGROUND: Acute Coronary Syndrome (ACS) patients face recurrent cardiovascular events due to non-culprit plaque progression despite optimal secondary prevention, but the differential impacts of residual cholesterol risk (RCR, on-treatment LDL-C ≥ 1.8mmol/L) and residual inflammation risk (RIR, on-treatment hs-CRP ≥2 mg/L) on plaque microstructure dynamics remain undefined. This study aimed to clarify how residual cholesterol and inflammatory risk factors differentially modulate the progression of non-culprit plaques in patients with ACS using serial optical coherence tomography (OCT). METHODS: A retrospective cohort of 243 ACS patients underwent baseline and 1-year (9-15 months) follow-up OCT. Patients were stratified into four groups (RCR, RIR, combined residual cholesterol-inflammation risk [RCIR], no residual risk). OCT assessed plaque morphology (e.g., thin-cap fibroatheroma [TCFA]) and quantitative parameters (lumen area, fibrous cap thickness [FCT], lipid arc). Multivariate logistic regression identified factors associated with plaque progression (defined as a decrease in minimal lumen area > 0.5 mm² from baseline to follow-up) and TCFA persistent. RESULTS: Of 583 evaluable non-culprit lesions, RIR was independently associated with patient-level plaque progression (odds ratio [OR]: 2.915, 95% confidence interval [CI]: 1.005-9.212, P = 0.046) and was linked to significant reductions in reference, mean, and minimal lumen area (all P < 0.05) vs. the no-risk group. RCR was associated with attenuated lipid plaque regression compared with the no residual risk group, as evidenced by smaller min-FCT increases (20.0 [-13.3, 73.3] µm vs. 50.0 [18.3, 86.7] µm, P = 0.014) and attenuated mean lipid arc reductions (-8.8 ± 27.1° vs. -17.7 ± 23.6°, P = 0.027). RCR (OR: 4.462, 95%CI: 1.723-12.521, P = 0.003) and RCIR (OR: 4.892, 95%CI: 1.623-15.467, P = 0.005) were independently associated with follow-up TCFA persistent. CONCLUSIONS: This study demonstrated distinct associations of RIR and RCR with non-culprit plaque progression: RIR was linked to luminal narrowing, while RCR attenuated lipid plaque stabilization. These findings provide imaging-based insights into plaque dynamics and may inform future risk stratification and residual risk management strategies in ACS patients.
Association of adipokines with major adverse cardiovascular events following acute myocardial infarction: a systematic review and meta-analysis.
Nadira A, Sunita S, Alparisi BD … +5 more , Fayza AC, Rahmatika NS, Karisa P, Sylviana N, Syamsunarno MRAA
BMC Cardiovasc Disord · 2026 Jun · PMID 42286472 · Full text
BACKGROUND: Major adverse cardiovascular events (MACEs) remain a leading cause of poor prognosis following acute myocardial infarction (AMI). Emerging evidence suggests that adipose tissue-derived adipokines may provide...
BACKGROUND: Major adverse cardiovascular events (MACEs) remain a leading cause of poor prognosis following acute myocardial infarction (AMI). Emerging evidence suggests that adipose tissue-derived adipokines may provide additional information on cardiometabolic risk beyond conventional anthropometric measures. This systematic review and meta-analysis aimed to evaluate the association between circulating adipokines, specifically adiponectin and visfatin, and the occurrence of MACE among patients with AMI. METHODS: A systematic search of PubMed/MEDLINE, Scopus, and Cochrane Library was performed from inception to identify cohort studies reporting adiponectin or visfatin levels in adult AMI patients with and without MACE during follow-up. Pooled mean differences (MD) with 95% confidence intervals (CI) were calculated. RESULTS: Five cohort studies (n = 707 AMI patients) conducted across China, Taiwan, Japan, and Poland, with follow-up durations ranging from 2 to 43 months, were included. Adiponectin levels were lower in MACE patients (MD=-2.85 [95% CI -5.42 to -0.27, p = 0.03]; I = 94%), while visfatin levels were significantly higher in the MACE group (MD = 2.99 [95% CI 1.51 to 4.47, p < 0.0001]; I0%). CONCLUSION: Lower adiponectin and higher visfatin levels are associated with MACE occurrences in AMI patients, whereas BMI did not demonstrate significant discriminatory value.
Trends in cardiovascular mortality (1999-2023) in the United States: an analysis of underlying causes of death using the CDC WONDER database.
Jiang J, Qi L, Mao Y … +1 more , Ding S
BMC Cardiovasc Disord · 2026 Jun · PMID 42286468 · Full text
OBJECTIVES: National statistics on mortality due to cardiovascular disease (CVD) in the United States remain insufficiently characterized. This study aimed to analyze the long-term trends and subgroup disparities in CVD-...
OBJECTIVES: National statistics on mortality due to cardiovascular disease (CVD) in the United States remain insufficiently characterized. This study aimed to analyze the long-term trends and subgroup disparities in CVD-related mortality across the US from 1999 to 2023. METHODS: We utilized the CDC WONDER database to identify all US residents with CVD recorded as the only underlying cause of death from 1999 to 2023 (ICD-10 codes: I00-I99). Age-adjusted mortality rates (AAMRs) per 100,000 population and average annual percent changes (AAPCs) with 95% confidence intervals (CIs) were calculated via Joinpoint regression analysis (version 5.3.0). RESULTS: In the United States, the number of cardiovascular-related deaths decreased from 954,339 in 1999 to 915,973 in 2023. Concurrently, the overall AAMR fell from 350.76 (95% CI: 350.06 to 351.47) in 1999 to 218.32 (95% CI: 217.87 to 218.77) in 2023, reflecting an AAPC of -1.95 (95% CI: -2.36 to -1.55). Notably, AAMR was consistently higher in men compared to women (2023: 263.04 vs. 180.16). An analysis by race indicated that non-Hispanic blacks experienced the highest mortality in 2023 (290.03 (95% CI: 288.35 to 291.72)), followed by whites (223.73 (95% CI: 223.19 to 224.27)), Hispanics (156.65 (95% CI: 155.42 to 157.88)), and individuals from other racial backgrounds (124.21 (95% CI: 122.92 to 125.49)). Regionally, the South exhibited the highest AAMR in 2023 (234.53 (95% CI: 233.77 to 235.30)), succeeded by the Midwest (231.41 (95% CI: 230.39 to 232.42)), the West (197.25 (95% CI: 196.35 to 198.16)), and the Northeast (194.97 (95% CI: 193.99 to 195.96)). Furthermore, the AAMR was most pronounced among individuals aged over 85 years. Between 1999 and 2020, AAMR was notably higher in rural regions compared to urban areas, with a widening gap after 2011. CONCLUSION: The age-adjusted mortality rate of CVD in the United States continued to decrease from 1999 to 2023, with the highest burden among men, non-Hispanic black, rural areas, and individuals over 85 years of age.
Impact of RAS inhibitors on 2-year mortality and disease progression in chronic mitral regurgitation.
Li C, Ye Y, Wang C … +9 more , Hu X, Lv J, Zhou Z, Liu Z, Lei L, Xu H, Wu Y, Zhang E, CHINA-VHD collaborators
BMC Cardiovasc Disord · 2026 Jun · PMID 42286466 · Full text
BACKGROUND: Chronic mitral regurgitation (MR) is associated with adverse clinical outcomes, and the role of renin-angiotensin system inhibitors (RASI) in patients with MR remains uncertain. This study evaluated the assoc...
BACKGROUND: Chronic mitral regurgitation (MR) is associated with adverse clinical outcomes, and the role of renin-angiotensin system inhibitors (RASI) in patients with MR remains uncertain. This study evaluated the association between RASI use patterns and 2-year all-cause mortality and disease progression in patients with primary MR (PMR) and secondary MR (SMR). METHODS: This registry-based study included 3,297 patients with moderate-to-severe chronic MR from the China Valvular Heart Disease registry, including 955 with PMR and 2,342 with SMR. RASI use was assessed at baseline and during follow-up, and patients were categorized as always users, never users, or inconsistent users. The primary endpoint was 2-year all-cause mortality. The secondary endpoint was change in MR severity. Associations between RASI use and outcomes were assessed using multivariable Cox regression, propensity-score matching, and time-varying Cox analyses. RESULTS: Consistent RASI use was associated with lower 2-year all-cause mortality in both PMR and SMR. In multivariable Cox regression, never users had higher mortality risk than always users in both cohorts (PMR: HR 5.40, 95% CI 1.58-18.47, P = 0.007; SMR: HR 5.09, 95% CI 2.85-9.09, P < 0.001). Inconsistent users also had higher mortality risk than always users (PMR: HR 7.56, 95% CI 2.25-25.37, P = 0.001; SMR: HR 3.29, 95% CI 1.85-5.84, P < 0.001). Propensity-score-matched analyses showed broadly consistent results. Time-varying Cox analyses demonstrated directionally consistent associations in the overall cohort and SMR during selected follow-up intervals, whereas in PMR the interval-specific estimates were less stable and did not reach statistical significance. Consistent RASI use was also associated with improvement in MR severity, particularly in SMR and in patients without guideline-based indications for valvular intervention. CONCLUSIONS: In patients with moderate-to-severe chronic MR, consistent RASI use was associated with lower 2-year all-cause mortality and improvement in MR severity. These findings suggest that RASI therapy may have a role in optimized medical management for selected patients with chronic MR, particularly those with SMR or impaired/borderline LV function. Further prospective studies are needed to confirm whether RASI directly improves survival or delays MR progression. TRIAL REGISTRATION: This study utilized data from the China Valvular Heart Disease (China-VHD) registry (NCT03484806).
Long-term metabolic-adiposity burden and cardiovascular risk: the cumTyG-WHtR in Chinese adults.
Xu H, Huang S, Xia Y … +3 more , Niu H, Li J, He P
BMC Cardiovasc Disord · 2026 Jun · PMID 42277710 · Full text
BACKGROUND: Evidence on the relationship between a long-term cumulative metric that couples the triglyceride-glucose index (TyG) with the waist‒to-height ratio (WHtR) (cumTyG‒WHtR) and incident cardiovascular disease (CV...
BACKGROUND: Evidence on the relationship between a long-term cumulative metric that couples the triglyceride-glucose index (TyG) with the waist‒to-height ratio (WHtR) (cumTyG‒WHtR) and incident cardiovascular disease (CVD), particularly when integrated with obesity phenotypes, remains limited. METHODS: We analyzed 4,254 middle-aged and older adults from the China Health and Retirement Longitudinal Study (CHARLS), with a median follow-up of approximately 3 years. Covariates were selected via the Boruta algorithm. Cox proportional hazards models were used to assess the associations between the cumTyG-WHtR and incident CVD. Restricted cubic splines (RCSs) were used to evaluate nonlinearity and dose-response. Effect modification was examined via interaction terms and stratified analyses, and robustness was assessed via multiple sensitivity analyses. Exploratory associational decomposition using nonparametric percentile bootstrap resampling (1,000 iterations) was performed to estimate the proportion of the total association between cumTyG-WHtR and CVD that was statistically accounted for by mean arterial pressure (MAP). RESULTS: During follow-up, 587 incident CVD events occurred (cumulative incidence 13.80%), with the incidence increasing across quartiles of cumTyG-WHtR (Q1-Q4: 9.21%, 13.26%, 14.29%, 18.44%). In fully adjusted models, each 1-unit increase in cumTyG-WHtR (continuous) was associated with a 5.2% higher CVD risk (hazard ratio 1.052, 95% confidence interval 1.011-1.094). RCS revealed no evidence of nonlinearity (P for nonlinearity = 0.790), indicating a near-linear, monotonic dose-response. A significant age interaction was observed (P for interaction = 0.025), with stronger associations in participants aged 45-59 years. The findings were consistent across the sensitivity analyses. In an exploratory associational decomposition (not a causal mediation analysis), MAP statistically accounted for a significant proportion of the total association, with an indirect association estimate of 0.005 (95% CI, 0.002-0.008; p < 0.001)-a small absolute effect but in this decomposition accounting for 20.3% of the total association. CONCLUSIONS: In this cohort of middle-aged and elderly individuals, a higher cumulative TyG - WHtR was positively associated with the incidence of CVD. This association showed an approximately linear trend, and it was more significant in the population aged 45 to 59. In an exploratory associational decomposition, MAP statistically accounted for a portion of the total association. This hypothesis-generating finding requires confirmation in future studies with stronger causal designs.
Trends in characteristics and outcomes following primary percutaneous coronary intervention: insights from a nationwide analysis.
Arabi A, AlQahtani A, Arafa S … +15 more , Tamimi OA, Abujalala S, Khani MA, Ali M, Abdelghani MS, Habib MB, Altermanini M, Singh R, Dros RS, Rafie I, Qintar M, Tamimi HA, Hamid T, AlHijji M, AlSuwaidi J
BMC Cardiovasc Disord · 2026 Jun · PMID 42277699 · Full text
BACKGROUND: Primary percutaneous coronary intervention (PPCI) is the standard of care for ST-segment elevation myocardial infarction (STEMI). Yet, data from the Middle East on long-term national trends in procedural char...
BACKGROUND: Primary percutaneous coronary intervention (PPCI) is the standard of care for ST-segment elevation myocardial infarction (STEMI). Yet, data from the Middle East on long-term national trends in procedural characteristics and outcomes remain limited. This study aimed to evaluate nationwide trends in PPCI for STEMI in Qatar over nine years (2015-2023), analyzing trends of cardiovascular risk factors, presentation management, and in-hospital outcomes of STEMI cases treated with PPCI in Qatar. METHODS: We examined 7,959 STEMI patients who underwent PPCI at Qatar Heart Hospital between 2015 and 2023. Descriptive statistics were presented as mean ± SD or proportions. One-way ANOVA and chi-square tests were used to assess temporal trends. Multivariate logistic regression identified risk factors associated with in-hospital mortality. A p-value ≤ 0.05 was considered significant. RESULTS: Annual PPCI volume increased > 50% from 820 cases in 2015 to 1,264 in 2023. The mean age was 49 years, predominantly male and non-Qatari. Cardiovascular risk factors increased significantly throughout the study, while EMS utilization rose from 63% to 77%. Radial access use increased from 57% to 84%, and intravascular ultrasound from 1.4% to 10%. Door-to-balloon time at the PPCI center declined from 60 to 45 min (p = 0.001). In-hospital mortality decreased from 4.4% in 2016 to 1.5% in 2023 (p < 0.001). Predictors of in-hospital mortality included older age (OR 1.03, 95% CI 1.01-1.04), prolonged door-to-balloon time 71-80 min: OR 3.49, 95% CI 1.35-9.05; 81-90 min: OR 3.01, 95% CI 1.06-8.60; ≥91 min: OR 3.31, 95% CI 1.36-8.08), cardiogenic shock requiring IABP (OR 12.08, 95% CI 8.30-17.60), and cardiac arrest (OR 4.76, 95% CI 3.04-7.49). CONCLUSIONS: This nine-year national PPCI registry demonstrates substantial improvements in access, procedural practice, and efficiency of STEMI care in Qatar, with marked decline in in-hospital mortality.
Combined impact of inflammation score and depression on clinical outcomes in patients after percutaneous coronary intervention: a retrospective cohort study.
Zhu J, Liu Y, Song Q … +6 more , Zhou H, Bai B, Chang J, Zhao W, Lei L, Ma H
BMC Cardiovasc Disord · 2026 Jun · PMID 42277697 · Full text
BACKGROUND: Systemic inflammation and depressive symptoms are both associated with adverse cardiovascular prognosis, but their combined prognostic value after percutaneous coronary intervention (PCI) remains uncertain. T...
BACKGROUND: Systemic inflammation and depressive symptoms are both associated with adverse cardiovascular prognosis, but their combined prognostic value after percutaneous coronary intervention (PCI) remains uncertain. This study examined the individual and joint associations of inflammatory score (IS) and clinically relevant depressive symptoms with traditional major adverse cardiovascular events (MACE). METHODS: A total of 487 patients with angiographically confirmed coronary artery disease were included. Depressive symptoms were assessed using the 9-item Patient Health Questionnaire (PHQ-9), with PHQ-9 ≥ 10 used as the primary definition of clinically relevant depressive symptoms. IS was calculated from z-scores of C-reactive protein and white blood cell count and dichotomized using the original cohort-specific median cutoff (-0.78). The primary outcome was traditional MACE. Cox regression, restricted cubic spline, additive interaction, and exploratory discrimination analyses were performed. RESULTS: During follow-up, 134 patients (27.5%) experienced MACE. After extensive cardiovascular adjustment, PHQ-9 ≥ 10 remained independently associated with MACE (HR 1.91, 95% CI 1.08-3.39, P = 0.027), whereas high IS alone was not significant (HR 1.34, 95% CI 0.89-2.00, P = 0.159). Patients with both high IS and PHQ-9 ≥ 10 had the highest MACE risk compared with those with low IS and PHQ-9 < 10 (HR 3.50, 95% CI 1.58-7.76, P = 0.002). hs-CRP threshold analyses were less consistent, and additive interaction estimates were imprecise. CONCLUSIONS: PHQ-9 ≥ 10 was independently associated with traditional MACE. Coexistence of high IS and PHQ-9 ≥ 10 identified a high-risk subgroup, although IS and additive interaction findings require cautious interpretation.
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