Xiaoping Li

Background: Metabolic syndrome substantially elevates venous thromboembolism (VTE) risk, increasing health care burdens. The Metabolic Score for Visceral Fat (METS‐VF) offers a novel, simplified approach to assess visceral fat. This study evaluates METS‐VF's association with VTE risk and its utility for risk stratification in patients with metabolic syndrome. Methods: Using UK Biobank data, we included 118 619 participants with metabolic syndrome free of VTE at baseline. Time‐dependent area under the curve analysis with bootstrap validation identified the strongest VTE predictor. Multivariable Cox models assessed associations of METS‐VF, a VTE‐specific polygenic risk score, and their combination with incident VTE. Mediation analysis evaluated potential mediators. Robustness was assessed through subgroup and sensitivity analyses, including competing risk of death. Results: Over a median 12‐year follow‐up, 5162 participants developed VTE. METS‐VF demonstrated stronger association with VTE than traditional metabolic indicators. Highest quartile participants showed significantly increased risks of VTE (hazard ratio [HR], 1.46 [95% CI, 1.33–1.61]), pulmonary embolism (HR, 1.50 [95% CI, 1.33–1.70]), deep vein thrombosis (HR, 1.52 [95% CI, 1.34–1.73]), and lower‐extremity deep vein thrombosis (HR, 1.59 [95% CI, 1.38–1.82]). Stratified analysis revealed synergistic interaction between METS‐VF and genetic susceptibility. CRP (C‐reactive protein) and estimated glomerular filtration rate significantly mediated the METS‐VF–VTE association. Conclusions: METS‐VF is a significant, independent risk indicator for VTE in patients with metabolic syndrome, demonstrating synergistic effects with genetic risk. The CRP‐ and estimated glomerular filtration rate–mediated association supports METS‐VF's clinical utility in VTE risk stratification.

Aims: Biallelic variants in Popeye domain containing 1 ( POPDC1 ) classically cause limb-girdle muscular dystrophy, but their impact on cardiac system remains unclear. We investigated the functional consequence of a POPDC1 frameshift variant (c.448delT), first identified in a consanguineous family with arrhythmogenic cardiomyopathy (ACM) and sudden death. Methods and results: Comprehensive clinical and genetic evaluation was followed by mechanistic studies in an orthologous Popdc1 knock-in rat model. Functional characterization included biotelemetry and programed electrical stimulation, optical mapping, patch clamp, intracellular Ca ²⁺ imaging, proteomics, and oxidative stress assays. Homozygous mutants ( Popdc1 ^fs/fs ) exhibited a shortened QTc interval and high incidence of ventricular tachycardia compared to wild-type ( Popdc1 ^+/+ ). Urethane anesthesia provoked second-degree AV block in all 10 Popdc1 ^fs/fs rats but in only 1 of 9 Popdc1 ^+/+ littermates. Optical mapping demonstrated abbreviated action potentials, slowed conduction velocity, and inducible polymorphic VT. Patch clamp confirmed accelerated repolarization, with upregulated transient outward potassium currents ( I _to ) and L-type calcium currents ( I _{Ca, L} ), but downregulated peak sodium currents ( I _Na ). Multi-omics and ultrastructural analyses revealed a post-translational collapse of intercalated disc: POPDC1 loss destabilized Ankyrin-G and its membrane-anchored cargo, Nav1.5, coinciding with enhanced Kv4.3 and Cav1.2 protein levels. These disruptions create a convergence of delayed conduction and shortened refractoriness, forming substrate for malignant re-entry. Conclusion: We defined a recessive short-QT ACM leading to potentially fatal arrhythmias caused by biallelic POPDC1 truncation driving Ankyrin-G disruption, manifesting as a triad: (1) bradycardia/AV block, (2) accelerated repolarization as short-QT pattern/diffuse T-wave flattening or inversion, and (3) progressive cardiomyopathy and sudden death. What’s new?: We define a novel diagnostic triad for recessive short-QT arrhythmogenic cardiomyopathy (rSQT-ACM) in a loss-of-function POPDC1 truncation: (1) early-onset bradyarrhythmia (sinus bradycardia or AV block); (2) a paradoxical short-QT interval with maladaptive rate response/diffuse T-wave flattening or inversion; and (3) progressive cardiomyopathy accompanied accompanied by with SCD. Mechanistically, biallelic POPDC1 truncation induces collapse of the POPDC1-AnkG hub, which triggers a unique “opposing remodeling” phenotype (severe I _Na reduction coupled with paradoxical upregulation of Kv4.3-mediated I _to ), and established a unified “slow-conduction, short-wavelength” substrate that underpins malignant re-entry. Implications for safety and device therapy: Nav1.5 deficiency indicates that sodium channel blockers may be contraindicated, and early ICD implantation may be preferable to bradycardia pacing. Mechanism-directed treatments: POPDC1’s recessive inheritance and small gene size make it a strong candidate for AAV-mediated gene supplementation aimed at restoring the intercalated disc architecture and ion-channel anchoring. Abstract Figure: Graphical

The Anatolian Journal of Cardiology - Peer-reviewed cardiology journal publishing original research, reviews, case reports. Impact Factor 1.5. The Anatolian Journal of Cardiology - Leading international cardiology journal with Impact Factor 1.5. Publishing original research, reviews, and case reports in cardiovascular medicine. Indexed in PubMed, Scopus, and Web of Science.

The Anatolian Journal of Cardiology - Peer-reviewed cardiology journal publishing original research, reviews, case reports. Impact Factor 1.5. The Anatolian Journal of Cardiology - Leading international cardiology journal with Impact Factor 1.5. Publishing original research, reviews, and case reports in cardiovascular medicine. Indexed in PubMed, Scopus, and Web of Science.

The Anatolian Journal of Cardiology - Peer-reviewed cardiology journal publishing original research, reviews, case reports. Impact Factor 1.5. The Anatolian Journal of Cardiology - Leading international cardiology journal with Impact Factor 1.5. Publishing original research, reviews, and case reports in cardiovascular medicine. Indexed in PubMed, Scopus, and Web of Science.

Calcium/calmodulin-dependent protein kinase II (CAMKII) is a critical regulator of cardiac electrophysiology. However, the role of the four bases deletion polymorphism in Camk2d which codes delta subunit of CAMKII, particularly those involving intron sequences, remains poorly understood. This study aimed to investigate the impact of Camk2d c.1044+125_128delGTTT missing polymorphism on cardiac morphology and arrhythmogenesis in normal adult Sprague-Dawley (SD) rats. A total of 85 SD rats were genotyped by Sanger sequencing, revealing a distribution of 25.9% wild-type (WT), 48.2% heterozygous, and 25.9% homozygous variants. Echocardiography, Hematoxylin-Eosin staining, Masson’s trichrome staining and transmission electron microscopy indicated no significant differences in cardiac structure or baseline function among the three groups. In freely moving rats, premature atrial arrhythmias were detected in 2 of 9 WT rats, 1 of 9 heterozygous rats, and 1 of 9 homozygous rats. Premature ventricular contractions (PVCs) were observed in none of 9 WT or homozygous rats, 3 of 9 heterozygous rats, with one heterozygous rat exhibiting frequent PVCs. Electrical programmed stimulation revealed a higher incidence of inducible atrial fibrillation in homozygous rats compared to WT rats and a higher incidence of inducible ventricular tachycardia in heterozygous rats compared to WT rats. These findings suggest that deletion polymorphism in the intron sequences of Camk2d are unexpectedly common in normal SD rat populations and that such polymorphism predispose to ventricular arrhythmias without overt structural heart disease. Our study highlights the potential arrhythmogenic risk associated with non-coding DNA sequence alterations in Camk2d and underscores the importance of genetic screening in experimental animal models.

Background: Digital therapeutics represents a promising approach to support the management of hypertension. Rural regions in China face substantial challenges in hypertension prevention and management. Given the rapid growth in use of the internet and mobile technologies, particularly smartphones, we developed a user-friendly WeChat mini-program “E-controlled pressure (eKongya)” to assist village physicians in managing patients with hypertension. Objective: This trial aimed to investigate the efficacy of digital interventions for blood pressure (BP) control in patients with hypertension. Methods: This open-label cluster-randomized controlled study was conducted in 8 villages in China. Individuals with systolic BP (SBP) ≥140 mm Hg or diastolic BP (DBP) ≥90 mm Hg were recruited. Eight villages were randomly assigned in a 1:1 ratio to the digital intervention group or control group. The primary end point was the hypertension control rate at 24 weeks among the study participants. The secondary end points were the changes in mean SBP and DBP from baseline to 24 weeks. All analyses were performed using the full analysis set. Results: Between June and July 2024, a total of 95 participants were enrolled and allocated to the digital intervention group (n=48, 51%) or the control group (n=47, 49%). After 24 weeks, data were available from 87 (92%) participants, and the mean age was 63.8 (SD 9.7) years, with 48% (n=42) being female participants. The digital intervention group (25/44, 57%) had a higher percentage of participants with controlled BP compared to the control group (21/43, 49%), although this difference was not statistically significant ( P =.60). Logistic regression analysis showed that the digital interventions did not significantly increase the hypertension control rate (odds ratio 0.73, 95% CI 0.31‐1.69; P =.46). In the intervention group, SBP decreased from 158.0 (SD 18.4) mm Hg at baseline to 137.5 (SD 13.0) mm Hg at 24 weeks and DBP decreased from 93.8 (SD 10.3) mm Hg to 85.3 (SD 11.6) mm Hg. In the control group during that same period, SBP decreased from 161.1 (SD 18.2) mm Hg to 139.6 (SD 13.2) mm Hg, and DBP decreased from 99.2 (SD 9.2) mm Hg to 83.4 (SD 12.1) mm Hg. After adjusting for baseline SBP or DBP, the mean change from baseline to 24 weeks was comparable between the digital intervention and control groups for both SBP (between-group difference −1.6, 95% CI −7.2 to 3.9; P =.56) and DBP (between-group difference 3.3, 95% CI −1.8 to 8.5; P =.21). No major program-related safety events occurred up to 24 weeks. Conclusions: Our study demonstrated that the digital interventions increased the hypertension control rate in rural areas, although this improvement was not statistically significant. Nevertheless, providing convenient BP measurements and health education to these patients notably enhanced hypertension control rates.

BACKGROUND: The estimated glucose disposal rate (eGDR) is a validated surrogate marker of insulin resistance. However, its association with stroke and dementia in nondiabetic populations remains insufficiently investigated. METHODS: This prospective cohort study included nondiabetic participants from the UK Biobank. The outcomes in this study were stroke, ischemic stroke, hemorrhagic stroke, all-cause dementia, vascular dementia, and Alzheimer disease. Multivariable Cox regression and restricted cubic splines were used to examine the associations between eGDR and outcomes. Polygenic risk score analyses were applied to investigate interactions between eGDR and genetic risk. RESULTS: Overall, 430 093 participants were included. During a follow-up of around 13.5 years, 10 307 stroke cases and 11 137 all-cause dementia cases were recorded. Restricted cubic splines analyses indicated nonlinear associations between eGDR and the risks of stroke and vascular dementia. Below specific thresholds (P =0.012). In contrast, above these thresholds, higher eGDR levels were associated with significantly reduced risks of stroke (HR, 0.80 [95% CI, 0.78–0.82]; P P P P <0.001). A linear inverse relationship was observed between eGDR and all-cause dementia and Alzheimer disease. The HR in the highest versus lowest quartile was 0.81 (95% CI, 0.75–0.88) for all-cause dementia and 0.73 (95% CI, 0.64–0.84) for Alzheimer disease. Stratified polygenic risk score analyses revealed a synergistic interaction between reduced eGDR and elevated genetic susceptibility. CONCLUSIONS: eGDR exhibited nonlinear associations with stroke and vascular dementia risk and linear inverse associations with all-cause dementia and Alzheimer disease in nondiabetic populations.