Development and validation of a machine learning-based model to predict isolated post-challenge hyperglycemia in middle-aged and elder adults: Analysis from a multicentric study.

INTRODUCTION: Due to the high cost and complexity, the oral glucose tolerance test is not adopted as the screening method for identifying diabetes patients, which leads to the misdiagnosis of patients with isolated post-challenge hyperglycemia (IPH), that is., patients with normal fasting plasma glucose (<7.0 mmoL/L) and abnormal 2-h postprandial blood glucose (≥11.1 mmoL/L). We aimed to develop a model to differentiate individuals with IPH from the normal population. METHODS: Data from 54301 eligible participants were obtained from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a longitudinal (REACTION) study in China. Data from 37740 participants were used to develop the diagnostic system. External validation was performed among 16561 participants. Three machine learning algorithms were used to create the predictive models, which were further evaluated by various classification algorithms to establish the best predictive model. RESULTS: Ten features were selected to develop an IPH diagnosis system (IPHDS) based on an artificial neural network. In external validation, the AUC of the IPHDS was 0.823 (95% CI 0.811-0.836), which was significantly higher than the AUC of the Taiwan model [0.799 (0.786-0.813)] and that of the Chinese Diabetes Risk Score model [0.648 (0.635-0.662)]. The IPHDS model had a sensitivity of 75.6% and a specificity of 74.6%. This model outperformed the Taiwan and CDRS models in subgroup analyses. An online site with instant predictions was deployed at https://app-iphds-e1fc405c8a69.herokuapp.com/. CONCLUSIONS: The proposed IPHDS could be a convenient and user-friendly screening tool for diabetes during health examinations in a large general population.

Bidirectional Two-Sample Mendelian Randomization Study of Immunoglobulin G N-Glycosylation and Senescence-Associated Secretory Phenotype.

Observational studies revealed changes in Immunoglobulin G (IgG) N-glycosylation during the aging process. However, it lacks causal insights and remains unclear in which direction causal relationships exist. The two-sample bidirectional Mendelian randomization (MR) design was adopted to explore causal associations between IgG N-glycans and the senescence-associated secretory phenotype (SASP). Inverse variance weighted (IVW) and Wald ratio methods were used as the main analyses, supplemented by sensitivity analyses. Forward MR analyses revealed causal associations between the glycan peak (GP) and SASP, including GP6 (odds ratio [OR] = 0.428, 95% confidence interval [CI] = 0.189-0.969) and GP17 (OR = 0.709, 95%CI = 0.504-0.995) with growth/differentiation factor 15 (GDF15), GP19 with an advanced glycosylation end-product-specific receptor (RAGE) (OR = 2.142, 95% CI = 1.384-3.316), and GP15 with matrix metalloproteinase 2 (MMP2) (OR = 1.136, 95% CI =1.008-1.282). The reverse MR indicated that genetic liability to RAGE was associated with increased levels of GP17 (OR = 1.125, 95% CI = 1.003-1.261) and GP24 (OR = 1.222, 95% CI = 1.046-1.428), while pulmonary and activation-regulated chemokines (PARC) exhibited causal associations with GP10 (OR = 1.269, 95% CI = 1.048-1.537) and GP15 (OR = 1.297, 95% CI = 1.072-1.570). The findings provided suggested evidence on the bidirectional causality between IgG N-glycans and SASP, which might reveal potential regulatory mechanisms.

Genetic association of glycemic traits and antihyperglycemic agent target genes with the risk of lung cancer: A Mendelian randomization study.

AIMS: To evaluate the potential causal effect of glycemic traits on lung cancer and investigate the impact of antihyperglycemic agent-target genes on lung cancer risk. METHODS: Genetic variants associated with glycemic traits, antihyperglycemic agent-target genes, and lung cancer were extracted from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), expression quantitative trait loci (eQTLs), protein quantitative trait loci (pQTLs), and the International Lung Cancer Consortium (ILCCO), respectively. Mendelian randomization (MR) analyses were performed to examine the associations of glycemic traits and antihyperglycemic agent-target genes with lung cancer. Mediation analysis was conducted to explore whether overweight operated as a mediator between antihyperglycemic agents and lung cancer outcomes. RESULTS: Genetically determined glycated hemoglobin A1c levels were associated with squamous cell lung cancer (OR = 1.78; 95 % CI, 1.08-2.92; p = 0.023). The PRKAB1 gene (the target of metformin) was associated with a lower risk of developing lung adenocarcinoma (OR = 0.85; 95 % CI, 0.76-0.96; p = 0.006). Further mediation analyses did not support overweight as a mediator between PRKAB1 activation and lung adenocarcinoma. CONCLUSION: Our analyses suggest an association of genetically determined abnormal glycemic traits with squamous cell lung cancer. The potential association between PRKAB1 activation and a reduced risk of developing lung adenocarcinoma appears to be independent of the anti-obesity effects of metformin, suggesting that PRKAB1 activation may have a direct protective effect on lung adenocarcinoma development.

Metabolic Traits and Risk of Ischemic Stroke in Japanese and European Populations: A Two-Sample Mendelian Randomization Study.

The role of metabolic traits in ischemic stroke (IS) has been explored through observational studies and a few Mendelian randomization (MR) studies employing limited methods in European populations. This study aimed to investigate the causal effects of metabolic traits on IS in both East Asian and European populations utilizing multiple MR methods based on genetic insights. Two-sample and multivariable MR were performed, and MR estimates were calculated as inverse-variance weighted (IVW), weighted median, and penalized weighted median. Pleiotropy was assessed by MR-Egger and Mendelian randomization pleiotropy residual sum and outlier tests. Systolic blood pressure (SBP) was associated with an increased risk of IS by IVW in both European (ORIVW: 1.032, 95% CI: 1.026-1.038, p < 0.001) and Japanese populations (ORIVW: 1.870, 95% CI: 1.122-3.116, p = 0.016), which was further confirmed by other methods. Unlike the European population, the evidence for the association of diastolic blood pressure (DBP) with IS in the Japanese population was not stable. No evidence supported an association between the other traits and IS (all Ps > 0.05) in both races. A positive association was found between SBP and IS in two races, while the results of DBP were only robust in Europeans.

Assessment of prolonged proteasome inhibition through ixazomib-based oral regimen on newly diagnosed and first-relapsed multiple myeloma: A real-world Chinese cohort study.

OBJECTIVE: To evaluate the effectiveness, safety, and convenience of in-class transition (iCT) from intravenous bortezomib-based induction to ixazomib-based oral regimens. METHODS: This retrospective real-world study was conducted in 16 Chinese hospitals between October 2017 and April 2023 and analyzed newly diagnosed (NDMM) and first-line relapsed multiple myeloma (FRMM) patients who attained at least a partial response from bortezomib-based induction therapy, followed by an ixazomib-based oral regimen for 2 year or until disease progression or intolerable toxicity. RESULTS: The study enrolled 199 patients, median age: 63 years old, male 55.4%, 53% as high risk (HR), and 47% as standard risk. Cytogenetic risk stratification by metaphase fluorescence in situ hybridization (M-FISH), based on the Mayo Clinic risk stratification system. The median duration of total PI therapy was 11 months, with ixazomib-based treatment spanning 6 months. At the 20-month median follow-up, 53% of patients remained on therapy. The 24-month PFS rate was 84.3% from the initiation of bortezomib-based induction and 83.4% from the start of ixazomib-based treatment. Overall response rate (ORR) was 100% post-bortezomib induction and 90% following 6 cycles of the ixazomib-based regimen. Based on the Sankey diagrams, 89.51% of patients maintained or improved their disease response after 2 cycles of iCT, 6 cycles (90.14%), and 12 cycles (80%). The HR level of Mayo was found to be a significant independent factor in a worse remission (hazard ratio (HR) 2.55; p = 0.033). Ixazomib's safety profile aligned with previous clinical trial data, with 49% of patients experiencing at least one AE of any grade. The most common AEs included peripheral neuropathy, nausea and vomiting, diarrhea, thrombocytopenia, and granulocytopenia. CONCLUSION: In the real-world Chinese MM population, NDMM and FRMM patients responded favorably to PI-based continuous therapy, demonstrating substantial response rates. The ixazomib-based iCT allows for sustained PI-based treatment, offering promising efficacy and tolerable AEs.

The Causality between Human Immunoglobulin G (IgG) N-Glycosylation and Aging: A Mendelian Randomization Study.

BACKGROUND: Immunoglobulin G (IgG) N-glycosylation is considered a potential biomarker for aging and various pathological conditions. However, whether these changes in IgG N-glycosylation are a consequence or a contributor to the aging process remains unclear. This study aims to investigate the causality between IgG N-glycosylation and aging using Mendelian randomization (MR) analysis. METHODS: We utilized genetic variants associated with IgG N-glycosylation traits, the frailty index (FI), and leukocyte telomere length (LTL) from a previous genome-wide association study (GWAS) on individuals of European ancestry. Two-sample and multivariable MR analyses were conducted, employing the inverse-variance weighted (IVW) method. Sensitivity analyses were performed to assess potential confounding factors. RESULTS: Using the IVW method, we found suggestive evidence of a causal association between GP14 and FI (ß 0.026, 95% CI 0.003 to 0.050, p = 0.027) and LTL (ß -0.020, 95% CI -0.037 to -0.002, p = 0.029) in the two-sample MR analysis. In the multivariable MR analysis, suggestive evidence was found for GP23 and FI (ß -0.119, 95% CI -0.219 to -0.019, p = 0.019) and GP2 and LTL (ß 0.140, 95% CI 0.020 to 0.260, p = 0.023). CONCLUSIONS: In conclusion, our results supported a potentially causal effect of lower GP23 levels on an advanced aging state. Additional verification is required to further substantiate the causal relationship between glycosylation and aging.

Frailty mediating the causality between leucocyte telomere length and mortality: a cohort study of 440,551 UK Biobank participants.

Introduction: Previous studies reported leucocyte telomere length (LTL) and frailty were associated with mortality, but it remains unclear whether frailty serves as a mediator in the relationship between leucocyte telomere length and mortality risk. This study aimed to evaluate how measuring LTL and frailty can support early monitoring and prevention of risk of mortality from the prospective of predictive, preventive, and personalized medicine (PPPM/3PM). Methods: We included 440,551 participants from the UK Biobank between the baseline visit (2006-2010) and November 30, 2022. The time-dependent Cox proportional hazards model was conducted to assess the association between LTL and frailty index with the risk of mortality. Furthermore, we conducted causal mediation analyses to examine the extent to which frailty mediated the association between LTL and mortality. Results: During a median follow-up of 13.74 years, each SD increase in LTL significantly decreased the risk of all-cause [hazard ratio (HR): 0.94, 95% confidence interval (CI): 0.93-0.95] and CVD-specific mortality (HR: 0.92, 95% CI: 0.90-0.95). The SD increase in FI elevated the risk of all-cause (HR: 1.35, 95% CI: 1.34-1.36), CVD-specific (HR: 1.47, 95% CI: 1.44-1.50), and cancer-specific mortality (HR: 1.22, 95% CI: 1.20-1.24). Frailty mediated approximately 10% of the association between LTL and all-cause and CVD-specific mortality. Conclusions: Our results indicate that frailty mediates the effect of LTL on all-cause and CVD-specific mortality. There findings might be valuable to predict, prevent, and reduce mortality through primary prevention and healthcare in context of PPPM. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00355-7.

Revealing genes associated with cervical cancer in distinct immune cells: A comprehensive Mendelian randomization analysis.

Human papillomavirus can be contracted by sexually active women. However, only a small proportion of these infections persist and have the potential to progress into cervical cancers, indicating a significant involvement of the immune system in cervical cancer development. Despite this, our understanding of the precise contributions of genes from different immune cell types in cervical cancers remains limited. Therefore, the primary objective of our study was to investigate the potential causal relationships between specific immune cell genes and the development of cervical cancers. By accessing expression quantitative trait loci datasets of 14 distinct immune cell types and genome wide association study of cervical cancers, we employed the summary data-based Mendelian randomization (SMR) along with multi-single nucleotide polymorphism (SNP)-based SMR to identify significant genes associated with cervical cancers. Colocalization analysis was further conducted to explore the shared genetic causality. A total of 10 genes across 11 immune cell types (26 significant gene-trait associations) were found to be associated with cervical cancers after false discovery rate correction. Notably, the ORMDL3, BRK1 and HMGN1 gene expression levels showed significant association with cervical cancer in specific immune cell types, respectively. These associations were supported by strong evidence of colocalization analyses. Our study has identified several genes in different immune cells that were associated with cervical cancer. However, further research is necessary to confirm these findings and provide more comprehensive insights into the association between these gene expressions and cervical cancer risk.

Association of sex-specific body mass index and waist circumference trajectories with non-alcoholic fatty liver disease incidence based on growth mixture modeling.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease. The relationship between the trajectories of obesity indicators and incident NAFLD is unknown. Therefore, this study aims to explore the sex-specific association between the trajectories of obesity indicators and the incidence of NAFLD. METHODS AND RESULTS: In total, 9067 participants were recruited for this longitudinal study. Obesity indicators use body mass index (BMI) and waist circumference (WC). The trajectory of obesity indicators was analyzed using the growth mixture modeling. The multivariate logistic regression model was used to analyze the association between obesity indicators' trajectories and incident NAFLD. Over a median follow-up of 1.82 years, 1013 (11.74%) participants developed NAFLD. We identified BMI and WC change trajectories as the stable group, increasing group, and decreasing group. After adjusting for baseline level and other confounders, multivariate logistic regression analysis showed that compared with stable group of BMI, the increasing group, and decreasing group odds ratio and 95% confidence interval of NAFLD were 2.10 (1.06-4.15), and 0.25 (0.09-0.67) in men, and 1.82 (1.08-3.04) and 0.32 (0.16-0.64) in women. Compared with stable group of WC, the increasing group was 2.57 (1.39-4.74) in men, the increasing group, and decreasing group were 2.29 (1.70-3.10) and 0.28 (0.12-0.64) in women. Sensitivity analysis showed that the results were stable. CONCLUSION: The BMI and WC changing trajectories are significantly associated with the incidence of NAFLD in men and women. Populations of real-world health examinations can be categorized based on obesity indicator changes to prevent NAFLD.

Temporal relationship between elevated serum uric acid levels and dyslipidemia: A 5-year cohort study using cross-lagged panel analysis.

BACKGROUND AND AIM: Previous studies have demonstrated an association between SUA and dyslipidemia. This study aims to explore the temporal relationship between SUA and dyslipidemia. METHODS AND RESULTS: Based on the Beijing Health Management Cohort conducted from 2013 to 2018, the data of a physical examination population was collected, including a total of 6630 study subjects. Cross-lagged panel analysis was employed to examine the temporal relationship between elevated SUA levels and dyslipidemia, indicated by either elevated TG or decreased HDL-C. The path coefficient and the 95 % CI from baseline TG to follow-up SUA were as follows: in the general population, men, women, and people with BMI ≥25 kg/m2were 0.027 (0.008-0.045), 0.024 (0.001-0.048), 0.032 (0.001-0.063) and 0.033 (0.006-0.059) (P < 0.05); however, the path coefficient from baseline SUA to follow-up TG and the 95 % CI were not statistically significant. Furthermore, the path coefficients and 95 % CIs between elevated SUA and decreased HDL-C were not statistically significant, both in the general population and in populations stratified by gender and BMI. CONCLUSIONS: We found a temporal relationship from elevated TG to elevated SUA in the general population and the populations stratified by gender and BMI (≥25 kg/m2). However, we did not observe a reverse relationship from elevated SUA to elevated TG. Additionally, we did not find a temporal relationship between decreased HDL-C and elevated SUA in both the general population and the stratified populations.

The Association Between Serum Uric Acid and Cognitive Function Among Middle-Aged and Older Adults Without Hyperuricemia: The Mediating Role of Depressive Symptoms.

BACKGROUND: The association between serum uric acid (SUA) and cognitive function remains unclear, especially among individuals without hyperuricemia. We examined the cross-sectional and longitudinal bidirectional associations between SUA and cognition, as well as the mediating effect of depressive symptoms among Chinese adults. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS). SUA (continuous) and cognitive function (based on mental intactness and episodic memory) were measured at Wave 1 and Wave 3. Depressive symptoms (Center for Epidemiologic Studies Depression scale) were assessed at Wave 1. Bivariate latent change score models and mediation analysis were used to investigate these possible associations. RESULTS: A total of 6 236 participants free of hyperuricemia (aged 58.3 ±â€…8.5 years) were included. After controlling for potential confounders, the SUA level was associated with cognition at baseline (standardized r = 0.042; p = .001). Higher baseline SUA level was associated with slower subsequent cognitive decline (standardized ß = 0.026; p = .027), whereas baseline cognition was not significantly associated with subsequent change in SUA (standardized ß = 0.003; p = .817). In mediation analysis, baseline SUA was indirectly associated with subsequent cognition via baseline depressive symptoms (mediation effect 13.3%; p < .001). CONCLUSIONS: Higher baseline SUA level is associated with better baseline cognition and less subsequent cognitive decline among Chinese adults without hyperuricemia. Baseline depressive symptoms may partially mediate the association between baseline SUA and later cognition. Continued research is warranted to verify these findings and elucidate the causality and underlying mechanisms.

Environmental factors affecting the risk of generalization for ocular-onset myasthenia gravis: a nationwide cohort study.

BACKGROUND: The environmental effects on the prognosis of ocular myasthenia gravis (OMG) remain largely unexplored. AIM: To investigate the association between specific environmental factors and the generalization of OMG. DESIGN: The cohort study was conducted in China based on a nationwide multicenter database. METHODS: Adult patients with OMG at onset, who were followed up for at least 2 years until May 2022, were included. We collected data on demographic and clinical factors, as well as environmental factors, including latitude, socioeconomic status (per capita disposable income [PDI] at provincial level and education) and smoking. The study outcome was the time to the development of generalized myasthenia gravis (GMG). Cox models were employed to examine the association between environmental exposures and generalization. Restricted cubic spline was used to model the association of latitude with generalization risk. RESULTS: A total of 1396 participants were included. During a median follow-up of 5.15 (interquartile range [IQR] 3.37-9.03) years, 735 patients developed GMG within a median of 5.69 (IQR 1.10-15.66) years. Latitude of 20-50°N showed a U-shaped relation with generalization risk, with the lowest risk at around 30°N; both higher and lower latitudes were associated with the increased risk (P for non-linearity <0.001). Living in areas with lower PDI had 1.28-2.11 times higher risk of generalization. No significant association was observed with education or smoking. CONCLUSIONS: Latitude and provincial-level PDI were associated with the generalization of OMG in China. Further studies are warranted to validate our findings and investigate their potential applications in clinical practice and health policy.

Parapapillary ßBM and γ Zones Played Different Roles in Axial Elongation Among Young Adolescents Using Optical Coherence Tomography.

Purpose: To evaluate the influencing factors of parapapillary ßBM and γ zones incidence in young adolescents and to explore their associations with axial length progression. Methods: In this prospective cohort study, 976 seventh-grade students from nine secondary schools in Beijing, China, were enrolled and followed up 1 year later. Parapapillary ßBM zone was defined as retinal pigment epithelium loss while Bruch's membrane was present. Parapapillary γ zone was defined as the absence of retinal pigment epithelium and Bruch's membrane. Logistic regression model was used to analyze the influencing factors of ßBM and γ zone incidence. A linear mixed model was used to analyze the associations between parapapillary zones and axial elongation. Results: Of the 976 participants, 139 (14.2%) had only ßBM zone, 398 (40.8%) had only γ zone, and 171 (17.5%) had both. At follow-up, the incidence of ßBM zone was 11.5% (76/659), and the incidence of γ zone was 9.7% (39/404). Optic disc tilt, thinner subfoveal choroid, and longer axial length at baseline showed a higher risk of γ zone incidence. The absence of γ zone at baseline showed a faster axial length progression. When the baseline axial length was 25 mm or longer, the ßBM zone was also related to the axial elongation. Conclusions: The γ zone was associated with axial length progression, and the ßBM zone was also associated with the axial length progression when the axial length exceeded 25 mm, which was consistent with the notion that excessive axial length growth not only is the extension of the eyeball but also has its own pathologic changes.

Association between nonalcoholic fatty liver disease and type 2 diabetes: A bidirectional two-sample mendelian randomization study.

OBJECTIVE: The aim of this study was to explore the mutually causal relationship between NAFLD and type 2 diabetes. METHODS: Based on the data obtained from GWAS, this study employed bidirectional two-sample MR analysis to investigate the causal relationship between NAFLD and type 2 diabetes, and also examined the causal relationship between liver fat accumulation and type 2 diabetes as well as the relationship between NAFLD and FPG, IR. RESULTS: In MR analysis of NAFLD and type 2 diabetes, when NAFLD as an exposure and type 2 diabetes as a result, the OR (95 % CI) was 1.10890 (1.00135-1.22801); in the reverse analysis, the OR value was not statistically significant. In MR analysis of NAFLD, FPG and IR, there was no statistical significance in both directions. In MR analysis of liver fat accumulation and type 2 diabetes, when liver fat as an exposure and type 2 diabetes as a result, the OR (95 % CI) was 1.17516 (1.02054-1.35321); in the reverse analysis, the OR value (95 % CI) was 1.06283 (1.02879-1.09799). CONCLUSION: There is a unidirectional causal relationship between NAFLD and type 2 diabetes. Furthermore, a bidirectional causal relationship exists between liver fat accumulation and type 2 diabetes.

Bidirectional relationship between nonalcoholic fatty liver disease and serum creatinine-to-body weight ratio as a proxy for skeletal muscle mass index.

BACKGROUND AND AIM: Although an association between skeletal muscle mass index and nonalcoholic fatty liver disease (NAFLD) has previously been demonstrated, the causal direction remains unclear. Herein, we investigated the directional association between NAFLD and the serum creatinine-to-body weight ratio (sCr/bw), a surrogate marker of the muscle mass index, using longitudinal data. METHODS: We recruited 9662 participants in 2017 and performed follow-up over 4 years. We evaluated whether sCr/bw was related to NAFLD development (Analysis I) and whether NAFLD was associated with a low sCr/bw incidence (Analysis II) using logistic regression models. Furthermore, a random intercept cross-lagged panel model was applied to evaluate the bidirectional association between sCr/bw ratio and NAFLD (Analysis III). RESULTS: Analysis I demonstrated an association between sCr/bw and incident NAFLD (odds ratio [OR] = 0.160, 95% confidence interval [CI]:0.107-0.232). Analysis II indicated a relationship between NAFLD and subsequent low sCr/bw ratio (OR = 1.524, 95% CI: 1.258-1.846). Analysis III indicated that the standard regression coefficient from sCr/bw to subsequent hepatic steatosis (HS) was -0.053 for ßsCr/bw2017 â†’ HS2019 and -0.060 for ßsCr/bw2019 â†’ HS2021 and the coefficient from HS to subsequent sCr/bw was -0.093 for ßHS2017 â†’ sCr/bw2019 and -0.112 for ßHS2019 â†’ sCr/bw2021 (all P < 0.05). CONCLUSIONS: This study indicated mutual causality between sCr/bw and NAFLD. Considering that sCr/bw is a surrogate marker of muscle mass index, the findings emphasize that NAFLD and low muscle mass form a vicious cycle, which should be taken seriously in clinical practice.

Causality assessment of circulating Vitamin D level on venous thromboembolism: A Mendelian randomization study.

BACKGROUND AND AIMS: The associations of vitamin D level with venous thromboembolism (VTE) reported in observational studies, whereas these causal associations were uncertain in European population. Therefore, we used Mendelian randomization (MR) method to explore the causal associations between 25-hydroxyvitamin D (25(OH)D) concentrations and the risk of VTE and its subtypes [including deep vein thrombosis (DVT) and pulmonary embolism (PE)]. METHODS AND RESULTS: We used three kinds of genetic instruments to proxy the exposure of 25(OH)D, including genetic variants significantly associated with 25(OH)D, expression quantitative trait loci of 25(OH)D target genes, and genetic variants within or nearby 25(OH)D target genes. MR analyses did not provide any evidence for the associations of 25(OH)D levels with VTE and its subtypes (p > 0.05). The summary-data-based MR (SMR) analyses indicated that elevated expression of VDR was associated with decreased risk of VTE (OR = 0.81; 95% CI, 0.65-0.998; p = 0.047) and PE (OR = 0.67; 95% CI, 0.50-0.91; p = 0.011), and expression of AMDHD1 was associated with PE (OR = 0.93; 95% CI, 0.88-0.99; p = 0.027). MR analysis provided a significant causal effect of 25(OH)D level mediated by gene AMDHD1 on PE risk (OR = 0.09; 95% CI, 0.01-0.60; p = 0.012). CONCLUSION: Our MR analysis did not support causal association of 25(OH)D level with the risk of VTE and its subtypes. In addition, the expression of VDR and AMDHD1 involved in vitamin D metabolism showed a strong association with VTE or PE and might represent targets for these conditions.

Time spent in a better cardiovascular health and risk of cardiovascular diseases and mortality: a prospective cohort study.

BACKGROUND: The protective effect of a higher ideal cardiovascular health (CVH) score on cardiovascular diseases (CVDs) and mortality is well recognized. However, little is known regarding the length of favorable CVH status associated with CVDs and mortality. This study aimed to examined whether the duration of better (ideal or intermediate) CVH is associated with risk of developing CVDs and mortality. METHODS: This prospective cohort study used data from 83,536 individuals from 2006 to 2020 who were enrolled in the Kailuan Study. The CVH scores of individuals were assessed at visits 1, 2, 3, and 4, respectively. The years spent in better CVH were estimated for each individual as the number of examination cycles (0-4) in which the participant was in that CVH score ≥ 8 multiplied by 2 (the mean year interval of each visit). The primary outcomes are CVD events and all-cause mortality. RESULTS: After a median follow-up period of 7.48 years, 5486 (7.07%) cases of incident CVD events and 7669 (9.18%) deaths occurred. Compared with participants in " ≤ 4 years" group, those who maintained for > 4 years had less likely to develop adverse outcomes (CVD events: hazard ratio (HR): 0.60, 95% confidence interval (CI 0.56-0.63; all-cause mortality: HR: 0.77, 95% CI 0.74-0.81). The number of years spent in better CVH was nonlinearly correlated with CVD events or mortality (all Ps for nonlinear < 0.05). The results indicated that maintaining more than 6 years in a better CVH status was associated with a decreased risk of CVD events or mortality. CONCLUSION: Our study indicates that individuals maintaining more than 6 years in better CVH could increase cardiometabolic benefits and a lower risk of all-cause mortality.

Externalizing traits: Shared causalities for COVID-19 and Alzheimer's dementia using Mendelian randomization analysis.

Externalizing traits have been related with the outcomes of coronavirus disease 2019 (COVID-19) and Alzheimer's dementia (AD); however, whether these associations are causal remains unknown. We used the two-sample Mendelian randomization (MR) approach with more than 200 single-nucleotide polymorphisms (SNPs) for externalizing traits to explore the causal associations of externalizing traits with the risk of COVID-19 (infected COVID-19, hospitalized COVID-19, and severe COVID-19) or AD based on the summary data. The inverse variance-weighted method (IVW) was used to estimate the main effect, followed by several sensitivity analyses. IVW analysis showed significant associations of externalizing traits with COVID-19 infection (odds ratio [OR] = 1.456, 95% confidence interval [95% CI] = 1.224-1.731), hospitalized COVID-19 (OR = 1.970, 95% CI = 1.374-2.826), and AD (OR = 1.077, 95% CI = 1.037-1.119). The results were consistent using weighted median (WM), penalized weighted median (PWM), MR-robust adjusted profile score (MR-RAPS), and leave-one-out sensitivity analyses. Our findings assist in exploring the causal effect of externalizing traits on the pathophysiology of infection and severe infection of COVID-19 and AD. Furthermore, our study provides evidence that shared externalizing traits underpin the two diseases.

Serum uric acid to creatinine ratio and metabolic syndrome in middle-aged and elderly population: Based on the 2015 CHARLS.

BACKGROUND AND AIMS: Serum uric acid to creatinine ratio (SUA/Cr) may be associated with metabolic syndrome (MS). Here, we investigated the correlation between SUA/Cr and MS in Chinese residents aged ≥ 45 years. METHODS AND RESULTS: Data were obtained from the 2015 China Health and Retirement Longitudinal Study (CHARLS) database. MS was diagnosed using the Chinese Diabetes Society 2017 criteria. We grouped the population according to SUA/Cr quartiles and compared the index differences between groups. We used spearman correlation analysis and binary logistic regression. The possible dose-response association of SUA/Cr with MS were analyzed using restricted cubic spline model. Of 12,946 included participants, 3370 (26.0%) had MS, and 1900 (56.4%) were female. After adjusting for multiple confounders, binary logistic regression analysis showed that compared with Quartile 1, the odds ratio (95% confidence interval) of the MS risk was 1.29 (1.09-1.52), 1.47 (1.25-1.74), and 1.80 (1.53-2.12) in Quartiles 2, 3, and 4, respectively. The restricted cubic spline model indicated a significant nonlinear dose-response association (Poverall < 0.001, Pnon-linearity = 0.029) between SUA/Cr and strength of MS prevalence association; MS risk began increasing when SUA/Cr > 6.22. CONCLUSIONS: A significant positive correlation existed between SUA/Cr and MS risk in Chinese individuals aged ≥ 45 years, which may be a new predictive marker for MS risk.

The Bidirectional Association Between Cognitive Function and Gait Speed in Chinese Older Adults: Longitudinal Observational Study.

BACKGROUND: Cognitive and gait speed decline are common conditions in older adults and are often associated with future adverse consequences. Although an association between cognitive function and gait speed has been demonstrated, its temporal sequence remains unclear, especially in older Chinese adults. Clarifying this could help identify interventions to improve public health in older adults. OBJECTIVE: This study aims to examine the longitudinal reciprocal association between gait speed and cognitive function and the possible temporal sequence of changes in both factors in a national longitudinal cohort. METHODS: Data were derived from 2 waves (2011 baseline and 2015 follow-up) of the China Health and Retirement Longitudinal Study (CHARLS). Participants 60 years or older, without dementia or Parkinson disease at baseline, and with completed data on gait speed and cognition at both baseline and follow-up were included. Usual gait speed was measured over two 2.5-m walks. Mental intactness and episodic memory were used to assess global cognitive function. Cross-lagged panel models and linear mixed-effects models were used to examine the association between cognition and gait speed over time. Standardized coefficients were reported. RESULTS: A total of 3009 participants (mean age 66.4 years, SD 5.4 years; 1422/3009, 47.26%, female participants) were eligible for inclusion in our analyses. Cross-lagged panel analyses revealed that after accounting for baseline gait speed, cognition, and potential confounders, baseline global cognition (ß=.117, 95% CI 0.082-0.152; P<.001), mental intactness (ß=.082, 95% CI 0.047-0.118; P<.001), and episodic memory (ß=.102, 95% CI 0.067-0.137; P<.001) were associated with subsequent gait speed. Simultaneously, baseline gait speed was also associated with subsequent global cognition (ß=.056, 95% CI 0.024-0.087; P=.001), mental intactness (ß=.039, 95% CI 0.008-0.069; P=.01), and episodic memory (ß=.057, 95% CI 0.023-0.092; P=.001). The comparison of standardized cross-lagged coefficients suggested that the effect size of baseline global cognition on subsequent gait speed was significantly larger than the reverse effect (χ12=6.50, P for difference=.01). However, the effects of both mental intactness and episodic memory on subsequent gait speed were not significantly stronger than those of the reverse pathway (χ12=3.33, P for difference=.07 and χ12=3.21, P for difference=.07). Linear mixed-effects analyses further supported these bidirectional relationships, revealing that lower baseline cognitive scores predicted steeper declines in gait speed trajectory, and slower baseline gait speed predicted more declines in cognitive trajectory over time. CONCLUSIONS: There is a longitudinal bidirectional association between usual gait speed and both global cognitive function and specific domains of mental intactness and episodic memory among Chinese older adults. Baseline global cognition is likely to have a stronger association with subsequent gait speed than the reverse pathway. This interlinkage is noteworthy and may have implications for public health. Maintaining normal cognitive function may be an important interventional strategy for mitigating age-related gait speed reduction.