BACKGROUND: Cancer-targeted therapies are progressively pivotal in oncological care. Observational studies underscore the emergence of cancer therapy-related cardiovascular toxicity (CTR-CVT), impacting patient outcomes. We aimed to investigate the causal relationship between different types of cancer-targeted therapies and cardiovascular disease (CVD) outcomes through a two-sample Mendelian randomization (MR) study.; METHODS: This genome-wide association study was conducted using a two-sample Mendelian randomization framework. Genetic instruments for drug target gene expression were extracted from the eQTLGen consortium (31684 individuals, 37 cohorts). Genome-wide association study (GWAS) summary statistics for 19 cardiovascular diseases were derived from the FinnGen database. Primary analysis was carried out using the summary-data-based MR (SMR) method, with sensitivity analysis for validation. Colocalization analysis identifies shared causal variants between exposure eQTLs and CVD-associated single-nucleotide polymorphisms (SNPs).; RESULTS: Among the 39 drug target genes, 8 were identified with detectable cis-eQTLs and were subsequently validated through positive control analysis for further investigation. In the SMR and sensitivity analyses, genetically proxied VEGFA inhibition showed significantly strong association with stroke (odds ratio [OR]=1.17, 95% confidence interval [CI]=1.09-1.26, p=1.33*10-5). Additionally, the inhibition of FGFR1, FLT1, and MAP2K2 exhibited suggestive association with corresponding cardiovascular disease outcomes. Nevertheless, only VEGFA expression and stroke shared a causal variant (93.6%), whereas FGFR1, MAP2K2, and FLT1 did not share causal variants with corresponding cardiovascular diseases in the colocalization analysis.; CONCLUSIONS: This genetic association study revealed evidence supporting the genetic association between the use of VEGFA inhibitors and increased stroke risk, highlighting the need for enhanced pharmacovigilance. These findings underscore the delicate balance between cardiovascular toxicity risk and the benefits of cancer-targeted therapy. © 2024. The Author(s).

Introduction: Worsening renal function poses a significant health risk to elderly individuals. This study aimed to construct a simple risk prediction model for new-onset chronic kidney disease (CKD) among elderly populations. Methods: In this retrospective cohort study, 5,416 elderly residents (aged >= 65 years) who underwent physical examinations as part of the National Basic Public Health Service project at least twice between January 2017 and July 2021 were included. The endpoint was new-onset CKD, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) during the follow-up period. Predictors of new-onset CKD were selected using multivariable Cox regression and a stepwise approach. A risk prediction model based on the selected predictors was constructed and evaluated using the concordance index (C-index) and area under curve (AUC). External validation was conducted to verify the model's performance. Results: During the median follow-up period of 2.3 years, the incident of new-onset CKD was 20.1% (n = 1,088). Age, female gender, diabetes, elevated triglyceride levels, and baseline eGFR were selected as predictors. The model demonstrated good predictive performance across the cohort, with a C-index of 0.802. The AUCs for 2-year, 3-year, and 4-year predictions were 0.831, 0.829, and 0.839, respectively. External validation confirmed the model's efficacy, with a 2-year AUC of 0.735. Conclusion: This study developed a simple yet effective risk prediction model for new-onset CKD among elderly populations. The model facilitates prompt identification of elderly individuals at risk of renal function decline in primary care, enabling timely interventions.

ObjectiveThe Klotho protein is a well-documented anti-aging protein known for its diverse biological functions. Hyperlipidemia is an established independent risk factor for various chronic diseases. However, there is limited understanding of the connection between Klotho and hyperlipidemia. The aim was to assess the association between serum Klotho levels and hyperlipidemia among adults.MethodsThe study included 11,618 individuals from the NHANES database from 2006 to 2017. Hyperlipidemia was diagnosed following the National Cholesterol Education Program guidelines. Serum Klotho concentration was measured by an enzyme-linked immunosorbent assay kit, and the association between Klotho and hyperlipidemia was assessed by a multivariable logistic regression model. Fitted smoothing curves and threshold-effect analysis were employed to describe nonlinear relationships.ResultsIn our multiple logistic regression models, serum Klotho concentration was significantly associated with hyperlipidemia after adjusting for comprehensive confounders (per SD increment odds ratio (OR): 0.91; 95% confidence interval (CI): 0.86-0.97). Compared to individuals in the lowest Klotho quartile, those in the highest quartile exhibited a substantially decreased prevalence of hyperlipidemia (OR: 0.72; 95% CI: 0.58-0.90). Using a two-segment logistic regression model, we identified a U-shaped relationship between serum Klotho concentration and hyperlipidemia, with an inflection point at 1,365.5 pg/mL. Subgroup analysis did not reveal any potential moderating effects.ConclusionThis study revealed an inverse relationship between Klotho levels and hyperlipidemia. Further investigation is warranted to explore the underlying mechanism between serum Klotho and hyperlipidemia.

BACKGROUND: Visceral adiposity index (VAI) and lipid accumulation product (LAP) are comprehensive indicators to evaluate visceral fat and determine the metabolic health of individuals. Carotenoids are a group of naturally occurring antioxidants associated with several diseases. The purpose of this investigation was to explore the association between serum carotenoid concentration and VAI or LAP.; METHODS: The data were obtained from the National Health and Nutrition Examination Survey between 2001 and 2006. The levels of serum carotenoids were evaluated using high-performance liquid chromatography. Multivariate linear regression models were employed to investigate the relationship between levels of serum carotenoids and VAI or LAP. The potential non-linear relationship was determined using threshold effect analysis and fitted smoothing curves. Stratification analysis was performed to investigate the potential modifying factors.; RESULTS: In total, 5,084 participants were included in this population-based investigation. In the multivariate linear regressions, compared to the lowest quartiles of serum carotenoids, the highest quartiles were significantly associated with VAI, and the effect size (beta) and 95% CI was -0.98 (-1.34, -0.62) for alpha-carotene, -1.39 (-1.77, -1.00) for beta-carotene, -0.79 (-1.18, -0.41) for beta-cryptoxanthin, -0.68 (-0.96, -0.39) for lutein/zeaxanthin, and -0.88 (-1.50, -0.27) for trans-lycopene. Using piece-wise linear regression models, non-linear relationships were found between beta-carotene and trans-lycopene and VAI with an inflection point of 2.44 (log2-transformed, ug/dL) and 3.80 (log2-transformed, ug/dL), respectively. The results indicated that alpha-carotene, beta-cryptoxanthin, and lutein/zeaxanthin were linearly associated with VAI. An inverse association was also found between serum carotenoids and LAP after complete adjustments.; CONCLUSION: This study revealed that several serum carotenoids were associated with VAI or LAP among the general American population. Further large prospective investigations are warranted to support this finding. © 2023. The Author(s).

Background To develop a reliable model to predict rapid kidney function decline (RKFD) among population at risk of cardiovascular disease. Methods In this retrospective study, key monitoring residents including the elderly, and patients with hypertension or diabetes of China National Basic Public Health Service who underwent community annual physical examinations from January 2015 to December 2020 were included. Healthy records were extracted from regional chronic disease management platform. RKFD was defined as the reduction of estimated glomerular filtration rate (eGFR) >= 40% during follow-up period. The entire cohort were randomly assigned to a development cohort and a validation cohort in a 2:1 ratio. Cox regression analysis was used to identify the independent predictors. A nomogram was established based on the development cohort. The concordance index (C-index) and calibration plots were calculated. Decision curve analysis was applied to evaluate the clinical utility. Results A total of 8455 subjects were included. During the median follow-up period of 3.72 years, the incidence of RKFD was 11.96% (n = 1011), 11.98% (n = 676) and 11.92% (n = 335) in the entire cohort, development cohort and validation cohort, respectively. Age, eGFR, hemoglobin, systolic blood pressure, and diabetes were identified as predictors for RKFD. Good discriminating performance was observed in both the development (C-index, 0.73) and the validation (C-index, 0.71) cohorts, and the AUCs for predicting 5-years RKFD was 0.763 and 0.740 in the development and the validation cohort, respectively. Decision curve analysis further confirmed the clinical utility of the nomogram. Conclusions Our nomogram based on five readily accessible variables (age, eGFR, hemoglobin, systolic blood pressure, and diabetes) is a useful tool to identify high risk patients for RKFD among population at risk of cardiovascular disease in primary care. Whereas, further external validations are needed before clinical generalization.

Aims To develop a nomogram for incident chronic kidney disease (CKD) risk evaluation among community residents with high cardiovascular disease (CVD) risk. Methods In this retrospective cohort study, 5730 non-CKD residents with high CVD risk participating the National Basic Public Health Service between January 2015 and December 2020 in Guangzhou were included. Endpoint was incident CKD defined as an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m(2) during the follow-up period. The entire cohorts were randomly (2:1) assigned to a development cohort and a validation cohort. Predictors of incident CKD were selected by multivariable Cox regression and stepwise approach. A nomogram based on these predictors was developed and evaluated with concordance index (C-index) and area under curve (AUC). Results During the median follow-up period of 4.22 years, the incidence of CKD was 19.09% (n=1094) in the entire cohort, 19.03% (727 patients) in the development cohort and 19.21% (367 patients) in the validation cohort. Age, body mass index, eGFR 60-89 mL/min/1.73 m(2), diabetes and hypertension were selected as predictors. The nomogram demonstrated a good discriminative power with C-index of 0.778 and 0.785 in the development and validation cohort. The 3-year, 4-year and 5-year AUCs were 0.817, 0.814 and 0.834 in the development cohort, and 0.830, 0.847 and 0.839 in the validation cohort. Conclusion Our nomogram based on five readily available predictors is a reliable tool to identify high-CVD risk patients at risk of incident CKD. This prediction model may help improving the healthcare strategies in primary care.

Mitochondrial reactive oxygen species (mtROS)-induced apoptosis has been suggested to contribute to myocardial ischemia/reperfusion injury. Interleukin 35 (IL-35), a novel anti-inflammatory cytokine, has been shown to protect the myocardium and inhibit mtROS production. However, its effect on cardiomyocytes upon exposure to hypoxia/reoxygenation (H/R) damage has not yet been elucidated. The present study aimed to investigate the potential protective role and underlying mechanisms of IL-35 in H/R-induced mouse neonatal cardiomyocyte injury. Mouse neonatal cardiomyocytes were challenged to H/R in the presence of IL-35, and we found that IL-35 dose dependently promotes cell viability, diminishes mtROS, maintains mitochondrial membrane potential, and decreases the number of apoptotic cardiomyocytes. Meanwhile, IL-35 remarkably activates mitochondrial STAT3 (mitoSTAT3) signaling, inhibits cytochrome c release, and reduces apoptosis signaling. Furthermore, co-treatment of the cardiomyocytes with the STAT3 inhibitor AG490 abrogates the IL-35-induced cardioprotective effects. Our study identified the protective role of IL-35 in cardiomyocytes following H/R damage and revealed that IL-35 protects cardiomyocytes against mtROS-induced apoptosis through the mitoSTAT3 signaling pathway during H/R.

本课题针对我国高发、危害重大的冠心病和脑卒中两大心脑血管慢病，在前期研究结果的基础上，聚焦于“互联网+”运行模式，采用移动互联网、智能传感、云计算、大数据等现代信息化技术手段进行规范化采集，形成多尺度心脑血管专病数据平台，建设并完善冠心病、脑卒中等重大心脑血管疾病“协防共管”的管理网络，推广互联网+在心脑血管“协防共管”中的应用。从“协防共管”的管理流程角度出发分为健康数据采集、健康状态评估、健康干预执行、健康效果跟踪四个阶段，解决目前心脑血管疾病管理工作中监测与干预相脱节的问题，实现心脑疾病“协防同管”管理流程的最优化。建立互联网+心脑血管疾病防控技术示范基地，在示范区进行互联网+运行模式与效果的经济学评价，将基于互联网+的心脑“协防共管”创新模式在更大范围内推广。 Aiming at the two major cardiovascular and cerebrovascular diseases with high incidence and serious harm in China,this project focuses on the operation mode of"Internet plus"based on the previous researches.The standardized collection is carried out by means of modern information technology,such as mobile Internet,intelligent sensing,cloud computing,big data and so on,to form a multi-scale cardio-cerebrovascular data platform.We will build and improve the management network of"co-prevention and co-management"for major cardiovascular and cerebrovascular diseases such as coronary heart disease and stroke,and promote the application of Internet plus in this field.According to the process of"co-prevention and co-management",the management can be divided into four stages:health data collection,health status assessment,health intervention implementation and health effect tracking to solve the problem of disconnection between monitoring and intervention in the management of cardiovascular and cerebrovascular diseases.To realize the optimization of the management process of"co-prevention and co-management".Establish Internet plus prevention and control technology demonstration base of cardiovascular and cerebrovascular disease,carry on the economic evaluation of Internet plus operation mode and effect in the demonstration area,and popularize the innovative mode in a larger scope.