We evaluated the association between chronic kidney disease and the current and background conditions of adults with spina bifida.

Patients with spina bifida (group A, n = 34) and patients with a history of pediatric encephalitis or spinal cord injury (group B, n = 23) who were older than 18 years between January 2013 and August 2022 were retrospectively analyzed. The chronic kidney disease-free survival was compared between groups. In each group, the congenital or pediatric background conditions (gender, disease type, history of febrile urinary tract infection, bladder augmentation, vesico-ureteral reflux, or detrusor overactivity) and current background conditions (age at last follow-up, ambulatory status, hypertension, and albuminuria) were compared between patients with or without chronic kidney disease.

The median age was 37 years (range 20-67 years). The median chronic kidney disease-free survival was younger in group A than group B (48.0 vs. 65.0 years, p = 0.0027). In group A, chronic kidney disease was associated with pediatric febrile urinary tract infection (p = 0.0018) and vesico-ureteral reflux (p = 0.0090), current hypertension (p < 0.001), and albuminuria (p = 0.0053). Multivariate analysis showed only hypertension was significantly associated with chronic kidney disease.

Young to middle-aged adults with spina bifida with a history of pediatric febrile urinary tract infection or vesico-ureteral reflux and those with current hypertension or albuminuria have an increased risk of chronic kidney disease, suggesting the need for renal function monitoring.

Coronary microvascular dysfunction (CMD) was frequently encountered in patients with angina in the absence of epicardial coronary stenosis. CMD was associated with adverse outcomes while the etiology was unclear.

In this study, we aimed to investigate the association between lipidomic abnormalities, biological aging and CMD.

We consecutively enrolled 43 patients with angina exhibiting no epicardial coronary stenosis on angiography. CMD was defined by a coronary angiography-derived index of microvascular resistance (caIMR) >25. Targeted lipidomic profiling quantified 781 lipids. PhenoAge was calculated from clinical parameters. Using machine learning, lipidomic data and clinical characteristics were screened to identify candidate biomarkers.

There were 25 patients having CMD with the mean caIMR of 34.0 (Interquartile range [IQR], 31.0-36.5), in contrast to 23.0 (IQR, 19.0-24.5) in the control group. Patients with CMD had substantially older PhenoAge (61 vs 52, p = 0.002). Forty-eight lipid species were dysregulated in patients with CMD, which predominantly belonged to triacylglycerol (TAG). PhenoAge, triglyceride glucose index, hypertension, TAG47:2-FA14:0, TAG48:4-FA18:1 and phosphatidylcholine (18:1/20:3) were independent risk factors of CMD. Incorporating dysregulated lipids significantly improved CMD prediction compared to traditional clinical factors alone (area under the curve, 0.94 vs 0.86, p < 0.05).

PhenoAge acceleration and dysregulated lipidome were associated with CMD. Larger-scale studies and external validation are needed in the future.

Overt hyperthyroidism is associated with increased cardiovascular morbidity, including tachyarrhythmias and heart failure. Although standard electrocardiographic abnormalities are well recognized, data regarding advanced markers of ventricular repolarization heterogeneity remain limited. We aimed to evaluate electrocardiographic dispersion parameters as markers of altered ventricular repolarization in patients with overt hyperthyroidism.

This single-centre retrospective case-control study included 97 adults: 55 patients with overt hyperthyroidism and 42 healthy euthyroid controls. Six ventricular repolarization dispersion parameters were assessed from standard 12-lead ECG recordings: QT dispersion (QTd), Bazett-corrected QT dispersion (QTcBd), Fridericia-corrected QT dispersion (QTcFd), JT dispersion (JTd), Fridericia-corrected JT dispersion (JTcFd), and Tpeak-Tend dispersion (Tp-ed). Group comparisons, correlation analyses, receiver operating characteristic (ROC) analyses, and internally validated multivariable modelling were performed.

All six parameters were significantly higher in overt hyperthyroidism than in controls (all p < 0.001). The best discriminatory performance was observed for JTcFd (AUC 0.813) and QTcBd (AUC 0.804). In multivariable analysis, Tp-ed remained independently associated with overt hyperthyroidism. Correlations between thyroid hormone levels and dispersion indices were weak and non-significant.

Our findings suggest an association between overt hyperthyroidism and increased ventricular repolarization heterogeneity, as reflected by alterations in ECG-derived repolarization parameters. These results support the presence of electrophysiological changes in overt hyperthyroidism; however, the clinical implications regarding arrhythmic risk remain uncertain, as no clinical arrhythmic outcomes were assessed.

Establishing clear links between different Turner syndrome (TS) karyotypes and phenotypes would help inform discussions around likely disease trajectories. Here we explored associations between karyotype, clinical features, and growth hormone (GH) responses in individuals with TS.

This was a retrospective observational study of 86 patients diagnosed with TS attending three endocrine centers in Abu Dhabi, UAE. Clinical and genetic data were retrieved from the medical records. Changes in height standard deviation score (SDS) over time were assessed with repeated measured ANOVA with Tukey's post hoc test.

The median (IQR) age of participants at diagnosis was 9.3 (6.5, 13.4) years. 44.2% were classical monosomies, 18.6% were mosaic, and 37.2% were structural X-chromosome abnormalities (isochromosome Xq, deletions, ring chromosome). GH treatment was started at a mean (SD) of 8.7 (4.0) years, which resulted in a significant increase in mean (SD) height SDS, with a greater increase in the first year [0.59 (0.13)] than between years 1 and 3 [0.22 (0.13)]. Spontaneous menarche occurred in 1/23 (4.3%) of evaluable 45, X individuals, compared with 6/12 (50.0%) of mosaic and 10/22 (45.5%) of structural X-chromosome abnormality cases (p=0.002), and autoimmune hypothyroidism was significantly more common in individuals with structural X-chromosome abnormalities (15/32, 46.9%, vs 5/37, 13.5%, and 1/16, 6.2%, in monosomy and mosaic cases, respectively; p<0.001; adjusted OR 5.22 [95% CI 1.55-17.53] after adjustment for current age). No detectable association was observed between karyotype and one-year GH response in the available analyses.

TS remains challenging to recognize and manage, and early detection and management are crucial to optimize growth, pubertal development, and quality of life. Knowledge of karyotype-phenotype associations helps to manage patient and family expectations and plan likely future management.

Kallikrein-related peptidase 7 (KLK7) is a protease implicated in metabolic disease and obesity. Patients with chronic kidney disease (CKD) exhibit several cardio-metabolic comorbidities and increased mortality. The goal of this study was to investigate the associations of KLK7 levels with renal function and clinical outcomes in patients with CKD.

Baseline KLK7 serum levels were cross-sectionally related to renal and cardiometabolic markers in the Leipzig-CKD cohort (n=542). Longitudinal Cox Regression analyses (n=472) were performed to associate baseline circulating KLK7 concentrations and risk of major adverse renal (MARE) and cardiovascular (MACE) events, as well as all-cause mortality. Additionally, mRNA expression of Klk7 and related genes was examined in CKD versus control mice using bulk RNA sequencing.

KLK7 levels were inversely associated with markers of renal function, i.e. estimated glomerular filtration rate (eGFR), and inflammation, i.e. C-reactive protein, in multivariable regression. Longitudinal analyses associated higher baseline KLK7 with lower all-cause (adjusted HR [95% CI]: 0.65 [0.49-0.86], p=0.003) and non-cardiovascular (adjusted HR [95% CI]: 0.56 [0.40-0.78], p=0.001) mortality over a median follow-up of 7.6 years. A KLK7 threshold of 1383.6 pg/ml stratified patients into low- and high-risk groups for mortality. No associations were found for MARE or MACE. In tissues of CKD and control mice, no significant changes in Klk7 mRNA expression were found.

Circulating KLK7 associates inversely with renal function and inflammation, likely reflecting reduced renal clearance. Higher circulating KLK7 independently predicts lower all-cause mortality, whereas baseline KLK7 was not related to composite renal and CV outcomes.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with coronary heart disease (CHD), but convenient and effective biomarkers for identifying CHD risk in patients with MASLD remain limited. The C-reactive protein-triglyceride-glucose index (CTI) reflects both systemic inflammation and insulin resistance, and may add value to cardiovascular risk stratification. This study examined the association of CTI with the presence and severity of CHD in patients with MASLD and developed a nomogram for individualized CHD assessment.

This study included 611 patients with MASLD who underwent coronary angiography. Participants were classified according to coronary angiography findings. Logistic regression was first performed to assess the association between CTI and CHD, followed by subgroup and restricted cubic spline (RCS) analyses. Among patients with CHD, the association between CTI and coronary lesion severity was assessed. Receiver operating characteristic (ROC) analysis and DeLong's test were applied to compare the discriminative performance of CTI with other simple insulin resistance-related indices. Independent predictors of CHD were identified using the least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression, and a nomogram model was subsequently established and internally validated.

Among the 611 patients with MASLD, 387 (63.3%) had CHD. CTI was independently associated with odds of CHD (OR 2.48, 95% CI 1.69-3.63, P < 0.001) and higher CTI levels corresponded to greater coronary stenosis severity. The association between CTI and CHD was generally stable across common subgroups, but it was stronger in patients aged ≥55 years. CTI showed significantly better discriminative ability for CHD than other simple indices of insulin resistance. Smoking status, age, neutrophils (NEUT), non-high-density lipoprotein cholesterol (non-HDL-C), serum albumin (ALB), CTI, and subclinical carotid atherosclerosis (SCAS) were included in the final nomogram. The AUC was 0.845 (95% CI 0.815-0.876), indicating good discrimination for CHD.

Higher CTI was associated with CHD presence and greater coronary lesion burden among MASLD patients. The nomogram may help identify patients who warrant further cardiovascular evaluation.

Cardiovascular-kidney-metabolic (CKM) syndrome emphasizes the interplay between metabolic dysfunction, kidney injury, and cardiovascular abnormalities. The triglyceride-glucose (TyG) and its obesity-related derivatives have emerged as simple biomarkers for insulin resistance, yet their association with aortic stenosis (AS) risk in CKM syndrome stages 0-3 remains unclear.

This prospective cohort study included 363,907 participants with CKM stages 0-3 from the UK Biobank. We calculated six TyG-related indices (TyG, TyG-BMI, TyG-Waist, TyG-WHR, TyG-WHtR, and TyG-ABSI) and evaluated their associations with incident AS using Cox proportional hazards and competing risk models. Mediation analysis assessed the role of systolic blood pressure (SBP), and incremental predictive value was evaluated using C-index and net reclassification index (NRI).

During 15.25 years of follow-up, 3,326 AS cases occurred. After full adjustment, each 1-SD increment in TyG-related indices was associated with 8-24% increased AS risk. Compared with the lowest tertile, the highest tertile showed 1.13-1.77-fold increased risk. All indices demonstrated linear dose-response relationships with AS. SBP mediated 12.1-18.1% of these associations. TyG-WHtR showed the greatest predictive improvement (C-index: 0.806; NRI: 0.308).

TyG-related indices, particularly TyG-WHtR, are independently associated with AS risk in CKM syndrome stages 0-3, offering potential for early risk stratification and targeted prevention strategies.

Occupational noise exposure is prevalent, but its cardiovascular effects are under recognized. Most studies are cross-sectional, focus on single endpoints, and rarely account for the healthy worker effect (HWE). This study aimed to identify risk factors for cardiovascular composite events in noise-exposed workers and further assess this effect.

This retrospective cohort study enrolled 1,381 noise-exposed workers with normal blood pressure and normal electrocardiogram at baseline in 2020. All participants were followed annually through 2023. The primary endpoint was a composite cardiovascular event (hypertension or electrocardiographic abnormality). Cox proportional hazards models were used to identify associated factors. Restriction analysis, restricted cubic spline analysis, and sensitivity analyses were performed to assess robustness.

Multivariable Cox regression identified systolic blood pressure (SBP) (HR = 1.012, 95% CI 1.005-1.020, p < 0.001) and smoking (HR = 1.191, 95% CI 1.029-1.377, p = 0.019) as independent risk factors. Work duration >120 months showed an apparent protective effect (HR = 0.621, 95% CI 0.466-0.826, p = 0.001). After excluding pre-employment workers, the reduced risk for >120 months persisted (HR = 0.787, 95% CI 0.638-0.969, p = 0.024). Forcing age into the multivariable model did not materially change the effect estimates. Sensitivity analysis showed that baseline SBP ≥ 130 mmHg was associated with a 66.3% increased risk of composite events (HR = 1.663, 95% CI 1.327-2.085, p < 0.001). For the hypertension endpoint, combined exposure to noise and dust (HR = 1.896, 95% CI 1.219-2.949, p = 0.005) and combined exposure to noise and chemical agents (HR = 1.580, 95% CI 1.013-2.463, p = 0.044) significantly increased risk.

Smoking and elevated SBP are independent risk factors for cardiovascular composite events in noise-exposed workers. The apparent protective effect of work duration is consistent with the HWE. Combined exposure to noise with dust or chemical agents significantly increases the risk of hypertension.

The escalating prevalence of cardiometabolic risk factors (CRFs) contributes to increased risks of cardiometabolic diseases. Micronutrients, essential for nearly all physiological functions, have been widely linked to CRFs. However, the joint associations of micronutrient mixtures with CRFs, as well as the potential biological pathways remain incompletely understood. To address this gap, this protocol describes the rationale and design of a longitudinal panel study, which included 205 adults with four repeated seasonal visits in Hefeng County, Enshi Prefecture, Hubei province, China. This project aimed to (1) evaluate the individual and joint associations of biomarker-based micronutrient profiles with CRFs; (2) characterize biological samples using multi-omics approaches to explore candidate biomarkers and potential pathways linking micronutrient profiles with cardiometabolic risk. The planned analyses are expected to help identify relationship of micronutrient profiles with altered biological effects and cardiometabolic diseases risk, and provide a framework for future validation studies and precision nutrition research.

Older adults in rural settings often show overlapping cardiovascular, renal, and metabolic abnormalities, yet the meaning of routine-recorded physical activity in health-examination data remains uncertain.

To examine the association between routine-recorded physical activity and screening-defined cardio-renal-metabolic (CRM) vulnerability amongst older adults in Wangkui County, China.

This community-based cross-sectional study used data from the 2025 annual health examination programme for adults aged ≥65 years. Physical activity was derived from a routine health-examination item and treated as a coarse activity-status indicator, not as a validated measure of exercise dose, intensity, energy expenditure, or activity domain. The primary exposure was inactive versus active; the three-category classification was retained for secondary analysis. The primary outcome was high screening-defined CRM vulnerability, defined as involvement of at least two cardiovascular, metabolic, and broad renal-urinary domains; this was an operational screening construct, not a clinically validated disease phenotype. Modified Poisson regression with robust standard errors estimated prevalence ratios (PRs), with multiple imputation for primary analyses.

Amongst participants with non-missing activity data, 852 were inactive and 1,363 were active. In the fully adjusted multiply imputed model, active routine-recorded activity was associated with higher prevalence of high CRM vulnerability than inactivity (PR = 1.121, 95% CI: 1.051-1.197). Similar patterns were observed for severe and subclinical high CRM vulnerability. Domain-specific analyses showed that the positive pattern was observed mainly for cardiovascular burden and broad renal-urinary screening signals, whereas metabolic and stricter renal indicators were weaker or less consistent.

Being recorded as active in the routine health-examination activity item co-occurred with greater screening-defined CRM vulnerability. This finding should be interpreted as a context-sensitive screening association, not evidence that physical activity causes CRM vulnerability or that structured physical activity is harmful. The renal-urinary signal should be interpreted conservatively because UACR was unavailable and the broader renal-urinary pattern was observed primarily in relation to urine occult blood positivity.