BACKGROUND:To investigate the association between apolipoprotein E (APOE) gene polymorphisms and coronary heart disease (CHD) risk within a localized Mongolian clinical cohort. METHODS:This hospital-based case–control study recruited 63 patients with angiographically confirmed CHD and 61 sex-matched healthy controls. Anthropometric measurements and lipid profiles and pathways for APOE genotypes were strictly assessed. This exploratory hospital-based case–control study was not designed as a nationally representative population-based survey, and participant recruitment was limited to a single tertiary referral center in Mongolia. RESULTS:High-density lipoprotein cholesterol levels were significantly higher in the case group than in the control group (1.56 ± 0.14 vs. 1.33 ± 0.18 mmol/L, P < .001), while total cholesterol was significantly lower in cases than in controls (3.91 ± 0.60 vs. 5.34 ± 0.80 mmol/L, P < .001). The distribution of APOE genotypes (ε2/ε3, ε3/ε3, ε3/ε4, and ε4/ε4) differed significantly between the case and control groups (P = .009). Both systolic and diastolic blood pressure significantly correlated with waist circumference (P = .026). Multivariable logistic regression revealed that the ε2/ε3 genotype was associated with significantly lower odds of disease (odds ratio [OR] = 0.29, P = .007, 95% CI: 0.12-0.71), whereas ε4-related findings were highly imprecise due to sparse genotype counts and lacked statistical significance (OR = 1.07, P = .930, 95% CI: 0.23-5.02). CONCLUSION:This study showed a significant association between the APOE genotype and CHD in a Mongolian population. These findings highlight the importance of considering qualitative aspects of lipid metabolism, rather than total cholesterol alone, and suggest that genetic factors, including APOE polymorphisms, may contribute to CHD risk independently of absolute cholesterol levels, underscoring the need for population-specific cardiovascular risk assessment.
BACKGROUND:Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired acute kidney injury, and oxidative stress is thought to play a crucial role in its pathogenesis. Evidence regarding DNA damage after contrast exposure remains limited. This study aimed to evaluate oxidative stress and DNA damage in patients develop-ng CIN by assessing total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels as well as clinical factors associated with CIN. METHODS:A total of 191 patients undergoing coronary angiography were prospectively evaluated. Blood samples were obtained before the procedure and at 72 hours afterward. CIN was defined as ≥25% or ≥0.5 mg/dL increase in serum creatinine. Patients were classified into CIN (n = 85) and control groups (n = 106). RESULTS:Advanced age and heart failure were the strongest predictors of CIN. Hypertension, anemia, chronic kidney disease, and hyperuricemia were also more frequent in the CIN group. After angiography, TAS increased and TOS decreased in both groups; however, the reduction in TOS reached significance only in controls. Post-procedure TAS levels were higher in the CIN group (P = .033). Baseline 8-OHdG levels were higher in patients who later developed CIN, whereas the post-procedure decline in 8-OHdG was significant only in controls (P = .02). No significant differences in TOS, OSI, or post-procedure 8-OHdG were observed between groups. CONCLUSION:This study is among the first to investigate DNA damage in CIN using 8-OHdG levels. The higher baseline DNA damage in CIN patients and the greater reduction in controls suggest a possible link between DNA injury and CIN. Oxidative stress markers did not differ significantly, which may reflect the use of modern low-toxicity contrast agents or the involvement of multifactorial mechanisms. Further studies are needed to clarify the role of oxidative stress and DNA damage in CIN.
BACKGROUND:Primary (non-ischemic) cardiomyopathy poses diagnostic challenges due to phenotypic heterogeneity and non-specific clinical presentation, and commonly used circulating biomarkers have limited disease specificity. The aim was to prioritize mechanism-informed plasma biomarkers and evaluate their diagnostic discrimination in a clinical cohort. METHODS:pQTL data from 8 proteomic studies covering 5,034 proteins were integrated, and Mendelian randomization was performed across 3 cardiomyopathy GWAS datasets. Top MR candidates were clinically validated by enzyme-linked immunosorbent assays quantification in a prospective case-control cohort of 81 subjects (48 cardiomyopathy patients and 33 healthy controls). Echocardiography evaluated cardiac function and remodeling, correlating with plasma biomarker levels. RESULTS:Proteome-wide MR prioritized 27 proteins linked to cardiomyopathy risk. Clinical validation confirmed significant differences in plasma levels of 5 selected biomarkers (CD163, LGALS3BP, FABP5, FSTL3, VCAM1). CD163 (odds ratio (OR) = 1.019, P < .0001) was positively associated with CM, while LGALS3BP (OR = 0.390, P < .0001), FABP5, FSTL3, and VCAM1 showed inverse associations. Multivariate analysis revealed CD163 and LGALS3BP as independent CM predictors, strongly correlating with echocardiographic indices of cardiac dysfunction. Receiver operating characteristic analyses showed individual area under the curve (AUC) ranging from 0.632 (VCAM1) to 0.917 (CD163). Given the modest discrimination of VCAM1, 5- versus 4-protein combined models were compared, and a parsimonious 4-protein panel was selected (CD163, LGALS3BP, FABP5, FSTL3). The 4-protein panel achieved an apparent AUC of 0.993, with optimism-corrected and repeated cross-validated AUCs of 0.988 and 0.980. CONCLUSION:This integrative genetic-to-clinical approach supports a 4-protein plasma panel with promising diagnostic discrimination for primary cardiomyopathy, warranting external validation. CD163 and LGALS3BP emerged as particularly informative markers for further evaluation.
BACKGROUND:Comparative data on ultrasound-assisted catheter-directed thromboly-sis (USAT) and systemic low-dose tissue-type plasminogen activator (tPA) for intermediate-high-risk (IHR) pulmonary embolism (PE) remain limited. The efficacy and safety outcomes of USAT vs. intravenous (IV) low-dose tPA were evaluated in this population. METHODS:This study enrolled 329 IHR PE patients treated with USAT (n = 205) or IV low-dose tPA (n = 124). Post-treatment changes in clot burden (Qanadli score), right ventricular (RV) strain, and long-term mortality (median follow-up 95.8 months) were assessed. Propensity score analysis with inverse probability weighting (IPW) was employed to adjust for confounders. RESULTS:Ultrasound-assisted catheter-directed thrombolysis was predominantly bilateral (82.9%), with a mean tPA dose of 38.5 ± 13.6 mg. In the IV tPA cohort, 58.9% required a second infusion to achieve stabilization. While IV tPA was associated with more pronounced early reductions in heart rate and RV/LV (left ventricle) ratio, USAT provided significantly greater thrombus resolution (all P < .005). After IPW adjustment, USAT demonstrated clear superiority over IV tPA in reducing residual clot burden (P < .001). However, improvements in oxygen saturation, tricuspid annular plane systolic excursion , and pulmonary artery systolic pressure (PASP) were comparable. No significant differences were observed in in-hospital mortality, PE recurrence, or long-term survival between cohorts. Higher PE severity indexes scores independently predicted in-hospital adverse events, whereas older age, male sex, and higher discharge PASP were predictors of shortened long-term survival. CONCLUSIONS:In IHR PE, IV low-dose tPA relates to more pronounced early hemodynamic and RV diameter improvements, whereas USAT achieves superior thrombus resolution. Despite these divergent surrogate responses, both strategies yield comparable early and long-term clinical outcomes, supporting their roles as viable reperfusion options.
BACKGROUND:Long-term durability data for early-generation balloon-expandable transcatheter aortic valve implantation (TAVI) in Turkish populations remain limited. The authors evaluated 7-year clinical outcomes and valve durability according to the Valve Academic Research Consortium (VARC-3) criteria. METHODS:In this single-center registry, 270 consecutive patients with symptomatic severe aortic stenosis treated with the early-generation balloon-expandable SAPIEN XT valve (January 2012-March 2017) were included. Clinical and echocardiographic outcomes were assessed up to 7 years. The primary endpoint was all-cause mortality. Structural valve deterioration (SVD) and bioprosthetic valve failure (BVF) were defined according to the VARC-3 criteria. Cumulative incidence was estimated using competing-risk analysis, with death from any cause treated as a competing event. Predictors of mortality were evaluated using Cox regression. RESULTS:At 7 years, cumulative survival was 29.6%. Cardiovascular and non-cardiovascular mortality occurred at comparable rates. In multivariable analysis, higher Katz index, reflecting better functional status, and higher body mass index were inversely associated with all-cause mortality, whereas eGFR <30 mL/min/1.73 m² was associated with increased mortality risk. The 5- and 7-year cumulative incidences of combined Stage 2-3 SVD were 0.74% and 3.72%, respectively; BVF rates were 1.11% and 2.23%, respectively. CONCLUSION:In this Turkish single-center cohort treated during the early TAVI era, long-term outcomes reflected the advanced age and comorbidity burden of the study population. Using a competing-risk framework, the observed cumulative incidence of SVD and BVF was low at 5 and 7 years; however, these findings should be interpreted in the context of substantial competing mortality.
BACKGROUND:With evolving risk factors, the frequency of right-sided infective endocarditis (RSIE) is increasing. Despite its distinct clinical features, data on RSIE remain limited, and no dedicated cohort has been reported from Türkiye. This study aimed to describe the epidemiological and clinical characteristics of RSIE and identify factors associated with mortality in a tertiary-care center. METHODS:This retrospective cohort study evaluated 65 adult patients diagnosed with definite RSIE between January 2018 and January 2024. Demographic data, risk factors, echocardiographic findings, causative microorganisms, and outcomes were analyzed. Statistical comparisons were performed between intravenous drug use (IVDU) and non-IVDU groups. RESULTS:The cohort was predominantly male (76.9%) with a median age of 36 years. Intravenous drug use was the primary risk factor (55.4%), followed by central venous catheters (24.6%) and hemodialysis (23.1%). Staphylococcus aureus was the leading causative agent (79%). Septic pulmonary embolism was detected in 81.6% of patients. The overall in-hospital mortality rate was 26.2%. Mortality was significantly lower in IVDU patients than in non-IVDU patients (17.4% vs. 44%; P = .036); however, multiple regression analysis identified hemodialysis as an independent predictor of mortality (OR = 6.72, 95% CI: 1.27-35.42; P = .025). Multiple Cox regression analysis further demonstrated that hemoglobin level and age were independent predictors of mortality. CONCLUSION:Although IVDU patients demonstrated higher survival rates-likely attributable to a younger age profile and fewer comorbidities-RSIE remains a critical condition requiring high clinical suspicion and early intervention. RSIE in this region is strongly associated with IVDU and typically presents with respiratory symptoms due to septic pulmonary emboli.
BACKGROUND:Atrial fibrillation (AF) is frequently encountered in patients with cancer and poses challenges for anticoagulant management. The present study was conducted to compare clinical outcomes associated with direct oral anticoagulants (DOACs) and low-molecular-weight heparin (LMWH) in individuals with active malignancy and nonvalvular AF (NVAF). METHODS:Data from patients with active cancer who received LMWH or DOACs for NVAF were retrospectively screened. Efficacy, safety, and survival outcomes were analyzed. RESULTS:The study enrolled 222 patients, of whom 25.7% received LMWH and 74.3% received DOACs. Cancer stage, type, and treatment were comparable between groups. The DOAC group had higher CHA2DS2-VA (3.13 ± 1.21 vs. 2.42 ± 1.33; P < .001) and HAS-BLED scores (2.13 ± 0.83 vs. 1.84 ± 0.79; P = .022). The primary composite endpoint occurred more frequently in the LMWH group (17.5% vs. 12.1%; log-rank P = .036). Myocardial infarction was significantly higher in the LMWH group (8.8% vs. 1.8%; log-rank P = .003), while rates of ischemic stroke (3.5% vs. 6.7%; log-rank P = .927) and venous thromboembolism (5.3% vs. 4.8%; P = .537) were similar. Any bleeding (17.5% vs. 13.3%; log-rank P = .039) and major bleeding (7.0% vs. 1.8%; log-rank P = .010) were more frequent with LMWH, whereas clinically relevant non-major bleeding was comparable (10.5% vs. 11.5%; log-rank P = .359). All-cause mortality was significantly higher in the LMWH group (75.4% vs. 49.1%; log-rank P < .001), and LMWH use independently predicted mortality (hazard ratio = 2.14, P < .001, 95%CI: 1.45-3.17). CONCLUSION:Although unmeasured confounders such as drug adherence and selection bias cannot be excluded due to the retrospective design, DOACs appear to be more effective and safer than LMWH in cancer patients with AF.
Healthy soils and clean water are essential for human survival, yet, both are increasingly compromised by chemical and plastic pollution. This preventable crisis causes an estimated 9 million premature deaths each year, including about 0.9 million linked to soil pollution and 1.3 million to water pollution. In 2019 alone, pollution contributed to 5.5 million cardiovascular deaths, underscoring its role in the global burden of non-communicable disease. A key underrecognized driver is the rapid rise in plastic production and plastic-associated chemicals. Global plastic output has increased more than 250-fold since 1950 and is projected to nearly triple by 2060, while less than 10% is effectively recycled. As highlighted by the Lancet Countdown on health and plastics, plastics threaten human health across their lifecycle, from fossil fuel extraction to waste, fragmentation, and environmental persistence. Soils and water systems are increasingly contaminated by heavy metals, pesticides, persistent synthetic chemicals, and micro- and nanoplastics. These pollutants degrade soil, reduce agricultural productivity, contaminate food chains, and spread through aquatic ecosystems, thereby amplifying disease risk. Micro- and nanoplastics have been detected in human blood, placenta, brain, and cardiovascular tissues, raising concern about biological effects. These exposures are drivers of cardiovascular disease. Despite their chemical diversity, they converge on shared mechanisms, including oxidative stress, inflammation, endocrine disruption, and circadian dysregulation. Their persistence reflects policy failure. Reducing soil, water, and plastic pollution must become a central pillar of cardiovascular prevention through enforceable, lifecycle-based policies that protect human health. #These authors contributed equally and should be considered as joint first and joint last authors.
BACKGROUND:Frailty is common yet underdiagnosed in elderly patients with atrial fibrillation (AF), worsening outcomes and complicating treatment. Traditional assessments are time-consuming and subjective, while physiological monitoring offers potential for automated detection. Combining machine learning (ML) with multimodal data, especially electrocardiogram (ECG) and clinical features, may improve frailty identification, even in noisy real-world conditions. To develop a noise-resilient ML framework for identifying frailty status in elderly patients with AF using multimodal clinical and ECG data and to compare traditional and deep learning models under varying signal conditions. METHODS:This retrospective study included 110 patients aged ≥65 with documented AF. Frailty was assessed via a composite of the Fried Phenotype and Clinical Frailty Scale. Electrocardiogram data (resting 12-lead and Holter) were processed through a denoising and segmentation pipeline. Over 180 ECG features and clinical parameters were used as inputs. Five models (Random Forest, Extreme Gradient Boosting, 1-dimensional convolutional neural network, bidirectional long short-term memory-attention, SiamAF) were trained and evaluated using an 80:20 split. Performance metrics included accuracy, F1-score, receiver operating characteristic-area under the curve (ROC-AUC), and Brier score; robustness was tested with synthetic noise. RESULTS:Frailty and pre-frailty prevalence were 41.82% and 34.55%. The SiamAF achieved the best performance (accuracy 90.00%, F1-score 89.75%, ROC-AUC 93.00%, Brier score 0.084), maintaining robustness under noise. Deep learning models also showed strong performance (ROC-AUC > 90%). Key predictors included standard deviation of normal-to-normal (NN) intervals, corrected QT interval, N-terminal pro-brain natriuretic peptide, and grip strength. CONCLUSION:Multimodal ML effectively identifies frailty status in elderly patients with AF. The SiamAF model demonstrated strong discriminatory performance and noise robustness in this single-center cohort; however, these findings should be considered hypothesis-generating and require external validation in larger, multicenter AF populations before clinical adoption. Given the limited sample size relative to the high-dimensional feature space, these results should be interpreted as exploratory and hypothesis-generating. The present framework primarily leverages predefined ECG-derived features rather than fully end-to-end raw-signal learning.
