• Association of Paraoxonase-1 (p.L55M) and Paraoxonase-2 (p.S311C) polymorphisms with coronary artery disease in North Indian Punjabi population.
    3 weeks ago
    Paraoxonases (PONs) are a unique family of calcium-dependent enzymes which are tightly associated with the high-density lipoprotein cholesterol (HDL-C), plays a crucial role in protecting the low-density lipoprotein cholesterol (LDL-C) from oxidation, thereby providing protection against atherosclerosis-a key factor for the pathogenesis of coronary artery disease (CAD). The activity of PON enzymes is influenced by genetic polymorphisms in the PON genes. The present case-control study was performed to investigate the association of PON1 (p.L55M, rs854560) and PON2 (p.S311C, rs7493) polymorphisms with CAD in the North Indian Punjabi population.

    The present study included 211 CAD patients and 260 healthy controls genotyped using the polymerase chain reaction-reaction fragment length polymorphism (PCR-RFLP) technique. Binary logistic regression analysis revealed that the SC and CC genotypes of the PON2 (p.S311C) conferred 2-and 3.5-folds increased risk for CAD (OR: 2.03, 95%CI: 1.36-3.01, p=0.001; OR: 3.49, 95%CI: 1.86-6.55, p=0.001, respectively). Moreover, the dominant (OR: 2.29, 95%CI: 1.58-3.32, p=0.0001), co-dominant (OR: 1.62, 95%CI: 1.11-2.36, p=0.012), recessive (OR: 2.58, 95%CI: 1.41-4.72, p=0.001), and log-additive (OR: 1.92, 95%CI: 1.46-2.54, p=0.0001) are the best-fit inheritance models to predict the susceptible gene effects. Furthermore, the LC haplotype (PON1 and PON2) was found to be significantly and independently associated with the increased risk of CAD (OR: 2.34, 95%CI: 1.65-3.32, p=0.0001).

    Our results indicate a significant and independent association of PON2 (p.S311C) polymorphism with CAD even after gender stratification in North Indian Punjabi population.
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  • Impact of serum uric acid to high-density lipoprotein cholesterol ratio on short-term outcomes in acute decompensated heart failure: a cohort study in Jiangxi Province, China.
    3 weeks ago
    Accumulating evidence suggests that both serum uric acid (UA) and high-density lipoprotein cholesterol(HDL-C) play critical roles in the pathogenesis of heart failure. This study aimed to investigate the association between the UA-to-HDL-C ratio(UHR) and short-term all-cause and cardiovascular mortality in patients with acute decompensated heart failure(ADHF).

    A total of 2,404 ADHF patients admitted to Jiangxi Provincial People's Hospital from 2018 to 2024 were included in this study. The association between the UHR and 30-day all-cause and cardiovascular-specific mortality in patients with ADHF was systematically evaluated using Kaplan-Meier analysis, Cox regression, restricted cubic spline models, and stratified analysis. The robustness of the findings was further validated through multi-faceted sensitivity analyses.

    During the 30-day follow-up period, 156 patients(6.49%) died in the entire cohort, with 120 deaths attributed to cardiovascular causes. The all-cause mortality rates across UHR quartiles were as follows: Q1: 3.83%, Q2: 4.16%, Q3: 6.82%, Q4: 11.15%, while cardiovascular mortality rates were Q1: 2.33%, Q2: 3.49%, Q3: 5.32%, Q4: 8.82%. Multivariable Cox regression analysis revealed that each 1-unit increase in UHR was associated with a 30% increased risk of both all-cause and cardiovascular mortality in ADHF patients. Furthermore, compared with patients in the lowest UHR quartile, those in the highest quartile had an 88% increased risk of 30-day all-cause mortality and a 113% increased risk of cardiovascular mortality. Further restricted cubic spline regression analysis demonstrated a linear positive association between UHR and the 30-day risks of all-cause and cardiovascular mortality in ADHF patients. Stratified analysis revealed that the association between UHR and mortality in ADHF patients was not modified by age, gender, New York Heart Association classification, left ventricular ejection fraction, or comorbidities. Finally, multiple sensitivity analyses conducted across four dimensions-population heterogeneity, causal temporality, model adjustment, and data integrity-confirmed the robustness of the primary findings.

    In this cohort study conducted in Jiangxi, China, we demonstrated for the first time that the UHR could serve as a tool for early prognostic assessment of short-term all-cause and cardiovascular mortality risk in ADHF patients, and elevated UHR levels were independently associated with an increased risk of both outcomes.
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  • Novel adiposity indices and their associations with all-cause and cardiovascular mortality in individuals with cardiovascular-kidney-metabolic syndrome stages 0-3: findings from a nationwide prospective cohort study.
    3 weeks ago
    Excess visceral fat drives CKM syndrome. This study assessed how newer obesity measures relate to death risk in early CKM (stages 0-3).

    This study included 26,899 participants with CKM stages 0-3 from the NHANES conducted between 2001 and 2018. Participants were grouped according to their baseline measurements of the adiposity indices (WWI, ABSI, WHtR, C-index, BRI, and BMI), which served as the exposure variables. Cox models, RCS curves, and two-stage Cox analyses were used to assess how novel obesity indices relate to mortality in this population. Subgroup analyses and sensitivity analyses evaluated risk differences across demographic groups and the robustness of the results. AUC, continuous NRI and IDI were used to compare the predictive performance of the novel indices and BMI for mortality.

    The final analysis included a total of 26,899 participants. At the baseline, the gender distribution was 51.08% male, with an average age of 45.39 years. Compared with the lowest quartile group, the mortality rate was higher in the higher levels of the new obesity index groups.Novel indices significantly increased the risk of mortality. WWI showed the strongest link to all-cause death (HR:1.41, 95%CI:1.31 - 1.51) and cardiovascular death (HR 1.66,95%CI:1.39 - 1.99). ABSI, WWI, WHtR, and C-index had linear positive relationships with mortality. In contrast, BMI, BRI, and WHtR showed U-shaped associations with all-cause death (higher risk at both low and high values). The increased death risk linked to the new indices was greater in people aged 20-59 than in those ≥60. The incorporation of novel obesity biomarkers into the fully adjusted model significantly improved the predictive performance for adverse outcomes, as demonstrated by WWI, ABSI, and C-index. The continuous NRI values for these indices were 0.1831 (95% CI: 0.1289-0.1992), 0.2191 (0.1644-0.2877), and 0.1805 (0.1173-0.2398), with corresponding IDI values of 0.0356 (0.0193-0.0569), 0.0572 (0.0365-0.0839), and 0.0245 (0.0118-0.0432), respectively.

    Novel obesity index is closely associated with mortality risk in the early CKM population. Novel indices offer superior obesity assessment and mortality prediction in early CKM compared to BMI.
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  • Endovenous Laser Ablation of Insufficient Superficial Veins in Patients After Deep Vein Thrombosis Recanalisation.
    3 weeks ago
    This study is aimed at investigating the safety of endovenous laser ablation treatment in the superficial venous system and perforator venous system in patients with previous deep vein thrombosis.

    From February 2017 to January 2023, 28 patients (20 women) with an average age of 41.5 ± 8.6 years, insufficient great saphenous vein and previous deep vein thrombosis were treated. All patients were diagnosed based on previous ultrasound examinations. In this retrospective study, patients were indeed included if they met specific criteria. Preoperative evaluations and thrombophilia assessments were conducted.

    Most patients had previous thrombosis in the popliteal vein (36.4%), while 31.8% had thrombosis in both the femoral and calf veins. Technical success was achieved in all patients, with concomitant procedures (closure of incompetent perforators and phlebectomies), and during follow-up (20 ± 16 months, range: 2-168 months), there were no signs of recanalisation of previously treated superficial veins. Patients were followed up at 1-month, 3-month, 6-month and 12-month intervals postprocedure. Recurrent deep vein thrombosis occurred in two (7%) patients after 26 and 31 months after treatment. Early complications included one (3.5%) case of endovenous heat-induced thrombosis Type II.

    Endovenous laser ablation is safe and effective in patients with resolved deep vein thrombosis when combined with appropriate anticoagulant therapy.
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  • Burden of Valvular Heart Disease Diagnosed on Protocolised Echocardiography for Waitlist Placement in End-Stage Kidney Patients.
    3 weeks ago
    The burden of valvular heart disease (VHD), which is high amongst end-stage kidney disease patients (ESKD), is less well defined in those referred to the transplant waitlist. We aimed to determine the prevalence, incidence, impact on survival and risk factors of VHD in ESKD patients who are referred for deceased donor kidney transplant (DDKT).

    This is a single-centre retrospective cohort analysis of ESKD patients who were referred for waitlist placement between 2009 and 2017 and underwent at least 1 transthoracic echocardiogram (TTE), then followed up until death or transplantation. Significant VHD was defined as VHD that was moderate or worse in severity as assessed on echocardiography.

    Of the 512 patients included, 89 (17.4%) had significant baseline VHD. Over a median follow-up of 6.6 years, severe VHD (adjusted HR (aHR) 2.73, 95% CI 1.28-5.83, p = 0.009), severe tricuspid regurgitation (aHR 3.04, 95% CI 1.20-7.69, p = 0.02), significant aortic stenosis (aHR 2.93, 95% CI 1.15-7.45, p = 0.02), MS (aHR 3.83, 95% CI 1.54-9.50, p = 0.004) and AR (aHR 1.76, 95% CI 1.05-2.97, p = 0.03) were independently associated with all-cause mortality. In 350 patients with repeat TTEs, 53 (15.1%) developed de novo significant VHD or progression of pre-existing VHD, which was independently associated with all-cause mortality (aHR 2.02, 95% CI 1.14-3.61, p = 0.02). Age, time on dialysis, and mineral bone disease were associated with baseline VHD and de novo or progression of pre-existing VHD.

    VHD is common amongst ESKD patients referred for DDKT waitlist. Both baseline and progressive VHD predict worse survival.
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  • Hybrid Health IT and Telehealth-Delivered Behavioral Weight Loss Services for Primary Care Patients With Cardiovascular Risk Factors: Intervention Component Design and Pragmatic Randomized Feasibility Trial.
    3 weeks ago
    Intensive lifestyle interventions (ILI) improve weight loss and cardiovascular risk factors, but health care systems face challenges in implementing them. We engaged stakeholders to cocreate and evaluate primary care implementation strategies for ILI components.

    This study aimed to describe the design of intervention components and implementation strategies and to evaluate the feasibility of pragmatic trial enrollment and randomization procedures, as well as the acceptability and preliminary effectiveness of the interventions.

    The study setting was a single, urban primary care office. Patients with a BMI ≥27 kg/m² and ≥1 cardiovascular risk factor were sent a single electronic health record (EHR) message between December 2019 and January 2020 offering services to support a weight loss goal of 10 pounds in 10 weeks. All patients who affirmed interest were pragmatically enrolled in a trial offering basic lifestyle support (BLS), which provided a scale that transmits weight data to the EHR using cellular networks, a coupon to enroll in lifestyle coaching resources through a partnering fitness organization, and periodic EHR messages encouraging use of those resources. About half (n=42) of participants were randomized by an EHR algorithm to also receive customized lifestyle support (CLS), including weekly email messages adaptive to weight loss progress and telephonic coaching by a nurse for those facing challenges. Interventions and assessments spanned from January to July 2020, with disruption by the COVID-19 pandemic. Weight data were collected from administrative sources. Qualitative analysis of stakeholder recommendations and patient interviews assessed intervention acceptability, appropriateness, and sustainability.

    Over 6 weeks, 426 patients were sent the EHR invitation message, and 80 (18.8%) patients affirmed interest in the weight loss goal and were enrolled. Overall, 48 of 80 (60%) trial participants lost weight at 6 months; 12 (15%) exhibited weight loss ≥5%, with no significant difference between CLS and BLS arms (P=.85). During the 12 weeks of adaptive MyChart (Epic Systems) messaging, 18 (43%) CLS patients and 8 (21%) BLS patients performed daily self-weighing (P=.06), and 22 (52%) CLS patients and 14 (37%) BLS patients enrolled in referral-based lifestyle resources (P=.18).

    Pragmatic enrollment, randomization, and data collection procedures proved feasible, and interventions showed preliminary effectiveness warranting further study in a larger trial.
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  • Methylome-driven regulation of miRNA expression and its relationship to cardiac dysfunction in idiopathic dilated cardiomyopathy.
    3 weeks ago
    Idiopathic dilated cardiomyopathy (iDCM) is a multifactorial disease with a complex pathogenesis involving diverse molecular mechanisms. Among these, epigenetic mechanisms, including both DNA methylation and microRNAs (miRNAs)-mediated regulation, play an important role in determining the disease phenotype. However, the interplay between the DNA methylome and the miRNA transcriptome in iDCM remains largely unexplored.

    We conducted a cross-cohort multiomic integrative analysis of left ventricular (LV) tissue samples from iDCM patients and control (CNT) donors. DNA methylation profiling was performed using the Infinium MethylationEPIC BeadChip, whereas ncRNA-seq was used to assess transcriptomic changes.

    We identified a subset of three miRNAs exhibiting both differential methylation in their promoter regions and differential expression in their primary and mature forms. Notably, the miRNA hsa-miR-433-3p (r = 0.671, p < 0.01), which is involved in fibrotic pathways, appear to be significantly correlated with the left ventricular ejection fraction (LVEF), an established echocardiographic marker of cardiac function.

    This study enhances our understanding of the epigenetic mechanisms shaping the miRNA transcriptomic landscape in iDCM, suggesting potential roles for these miRNAs in cardiac dysfunction and myocardial fibrosis.
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  • Triglyceride-glucose (TyG) index combined with C-reactive protein outperforms the TyG index alone in predicting stroke in arthritis patients: a nationwide prospective cohort study.
    3 weeks ago
    Arthritis patients exhibit a higher stroke risk, but effective predictive biomarkers are scarce. This research sought to examine and compare the associations between the triglyceride-glucose (TyG) index, its integration with C-reactive protein (CRP) (TyG-CRP), and stroke risk in these patients.

    This research examined data from 3,419 arthritis patients participating in the China Health and Retirement Longitudinal Study (CHARLS), focusing on the occurrence of new stroke events as the main outcome. Examination of the association between the TyG index, TyG-CRP and stroke risk relied on Kaplan-Meier, Cox regression, and restricted cubic splines (RCS) analyses.

    During the 9-year follow-up period, 339 arthritis patients (9.9%) had their initial stroke. Stroke incidence increased steadily from the lowest to highest tertile categories as determined by both TyG index and TyG-CRP (P < 0.05). After full covariate adjustment, each 1-unit increment in TyG-CRP raised stroke risk by 18% (HR, 1.18; 95% CI, 1.01-1.39), and individuals in the top TyG-CRP tertile were 1.4 times more likely to experience a stroke versus those in the bottom tertile (HR, 1.40; 95% CI, 1.03-1.92). There was no significant link between the TyG index and stroke risk, whether it was assessed continuously or by tertiles (P > 0.05) in the fully adjusted models. TyG-CRP was significantly linearly related to stroke incidence (P-overall: 0.047; P-nonlinear: 0.725), whereas the TyG index, although linear, also demonstrated an insignificance (P-overall: 0.165; P-nonlinear: 0.557). In sensitivity analyses conducted among complete cases, TyG-CRP demonstrated borderline statistical significance for stroke risk in the model with comprehensive covariate adjustment (P = 0.058 for the continuous variable analysis; P = 0.064 for tertile-based comparisons).

    TyG-CRP is a standalone predictor of stroke in arthritis individuals, whereas the TyG index does not significantly predict stroke risk.
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  • Augmented reality-assisted infraclavicular first rib resection for arterial and venous thoracic outlet syndrome: a case series.
    3 weeks ago
    The infraclavicular approach is a surgical approach for vascular thoracic outlet syndrome (TOS). However, difficulty in accessing the posterior aspect of the first rib may cause insufficient decompression. To address this problem, we used augmented reality (AR) technology to intraoperatively visualize and determine the extent of rib resection. This study aimed to introduce AR-assisted infraclavicular first rib resection for arterial or venous TOS and report its clinical outcomes.

    AR-assisted rib resection was introduced in our unit in 2022. Using an infraclavicular approach, we performed first rib resection and scalenectomy with the assistance of endoscopy. We compared the edge of the intraoperatively resected rib with the resection area of the preoperative simulation displayed in the AR to determine the extent of the resection.

    Six patients who underwent AR-assisted rib resection for arterial or venous TOS had excellent or good Derkash scores at 1 year postoperatively. Postoperative angiography revealed no subclavian vessel stenosis.

    AR technology enables intraoperative three-dimensional assessment of the location of major vessels and the extent of resection, which may contribute to improved outcomes.
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  • Association of estimated glucose disposition rate with aging acceleration and mortality risk in individuals with cardiovascular-kidney-metabolic syndrome: evidence from two large national population-based studies.
    3 weeks ago
    This study investigated the relationship between estimated glucose disposal rate (eGDR), aging acceleration (AgeAccel), and mortality in adults diagnosed with cardiovascular-kidney-metabolic (CKM) stages 1 to 4.

    The study utilized data from 4,826 adults with CKM syndrome stages 1 to 4, collected from the National Health and Nutrition Examination Survey (NHANES) conducted during the 2005-2010 survey cycles. The assessment of AgeAccel was performed using two complementary measures: phenotypic AgeAccel (PhenoAgeAccel) and biological AgeAccel (BioAgeAccel). Survey-weighted logistic regression and Cox proportional hazards models were used to assess the associations of eGDR with AgeAccel and mortality risk, respectively. To assess the prognostic value of eGDR for mortality risk, we implemented a suite of nine distinct machine learning models. Additionally, a nomogram was developed to enhance the clinical applicability of our findings. Furthermore, we performed causal mediation analysis to quantify the proportion of the total effect of eGDR on mortality that was mediated through AgeAccel. To ensure the robustness of the results, we replicated our primary analyses using data from the nationally representative China Health and Retirement Longitudinal Study (CHARLS) cohort.

    Our analysis included 4,826 NHANES participants, among whom we documented 831 all-cause mortality events and 208 cardiovascular disease (CVD)-specific deaths during follow-up. In multivariable-adjusted Cox regression models, each unit increase in eGDR was significantly associated with a 10% reduction in all-cause mortality risk (Hazard ratio [HR] = 0.90, 95% Confidence interval [CI] 0.86-0.93) and a 13% decrease in CVD mortality risk (HR = 0.87, 95% CI 0.81-0.93). Additionally, eGDR showed a negative association with AgeAccel, including both BioAgeAccel (odds ratio [OR] = 0.85, 95% CI 0.82-0.87) and PhenoAgeAccel (OR = 0.78, 95% CI 0.75-0.80). For predicting all-cause mortality from eGDR, the K-Nearest Neighbors (KNN) showed superior discrimination (Area Under the Curve [AUC]: 0.926), exceeding the performance of other machine learning algorithms in a comparative evaluation. Mediation analysis revealed that the protective effect of higher eGDR was partially explained by slower PhenoAgeAccel, with mediation effects accounting for 23.53% and 15.73% of the total impact on all-cause and CVD mortality, respectively.

    In the CKM population, lower eGDR levels may be associated with both AgeAccel and an increased risk of mortality, with AgeAccel potentially mediating the relationship between eGDR and mortality. These findings suggested that eGDR could serve as a potential predictor and intervention target for delaying aging and reducing mortality risk.
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