Effects of genetically proxied lipid-lowering drugs on acute myocardial infarction: a drug-target mendelian randomization study.

OBJECTIVE: High low-density-lipoprotein (LDL) cholesterol has been associated with an increased risk of coronary artery diseases (CAD) including acute myocardial infarction (AMI). However, whether lipids lowering drug treatment is causally associated with decreased risk of AMI remains largely unknown. We used Mendelian randomization (MR) to evaluate the influence of genetic variation affecting the function of lipid-lowering drug targets on AMI. METHODS: Single-nucleotide polymorphisms (SNPs) associated with lipids as instruments were extracted from the Global Lipids Genetics Consortium (GLGC). The genome-wide association study (GWAS) data for AMI were obtained from UK Biobank. Two sample MR analysis was used to study the associations between high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides (TG) with AMI (n = 3,927). Genetic variants associated with LDL cholesterol at or near drug target gene were used to mimic drug effects on the AMI events in drug target MR. RESULTS: Genetically predicted higher LDL-C (per one SD increase in LDL-C of 38.67 mg/dL, OR 1.006, 95% CI 1.004-1.007) and TG (per one SD increase in TG of 90.72 mg/dL, 1.004, 1.002-1.006) was associated with increased risk of AMI, but decreased risk for higher HDL-C (per one SD increase in HDL-C of 15.51 mg/dL, 0.997, 0.995-0.999) in univariable MR. Association remained significant for LDL-C, but attenuated toward the null for HDL-C and TG in multivariable MR. Genetically proxied lower LDL-C with genetic variants at or near the PCSK9 region (drug target of evolocumab) and NPC1L1 (drug target of ezetimibe) were associated with decreased risk of AMI (0.997, 0.994-0.999 and 0.986, 0.975-0.998, respectively), whereas genetic variants at HMGCR region (drug target of statin) showed marginal association with AMI (0.995, 0.990-1.000). After excluding drug target-related SNPs, LDL-C related SNPs outside the drug target region remained a causal effect on AMI (0.994, 0.993-0.996). CONCLUSIONS: The findings suggest that genetically predicted LDL-C may play a predominant role in the development of AMI. The drug MR results imply that ezetimibe and evolocumab may decrease the risk of AMI due to their LDL-C lowering effect, and there are other non-drug related lipid lowering pathways that may be causally linked to AMI.

Genetically determined blood pressure, antihypertensive drug classes, and frailty: A Mendelian randomization study.

Observational studies have suggested that the use of antihypertensive drugs was associated with the risk of frailty; however, these findings may be biased by confounding and reverse causality. This study aimed to explore the effect of genetically predicted lifelong lowering blood pressure (BP) through different antihypertensive medications on frailty. One-sample Mendelian randomization (MR) and summary data-based MR (SMR) were applied. We utilized two kinds of genetic instruments to proxy the antihypertensive medications, including genetic variants within or nearby drugs target genes associated with systolic/diastolic BP, and expression level of the corresponding gene. Among 298,618 UK Biobank participants, one-sample MR analysis observed that genetically proxied BB use (relative risk ratios, 0.76; 95% CI, 0.65-0.90; p = 0.001) and CCB use (0.83; 0.72-0.95; p = 0.007), equivalent to a 10-mm Hg reduction in systolic BP, was significantly associated with lower risk of pre-frailty. In addition, although not statistically significant, the effect directions of systolic BP through ACEi variants (0.72; 0.39-1.33; p = 0.296) or thiazides variants (0.74; 0.53-1.03; p = 0.072) on pre-frailty were also protective. Similar results were obtained in analyses for diastolic BP. SMR of expression in artery showed that decreased expression level of KCNH2, a target gene of BBs, was associated with lower frailty index (beta -0.02, p = 2.87 × 10-4). This MR analysis found evidence that the use of BBs and CCBs was potentially associated with reduced frailty risk in the general population, and identified KCNH2 as a promising target for further clinical trials to prevent manifestations of frailty.

Women's reproductive risk score and healthy lifestyle modification in cardiovascular disease: Findings from the UK Biobank.

BACKGROUND AND AIMS: Reproductive risk factors are associated with increased risk of cardiovascular disease (CVD) in women. However, the combined effects of the composite reproductive risk factors on CVD are unknown. This study was performed to construct a reproductive risk score (RRS) to measure reproductive status, examine the association between RRS and CVD, and explore the modification effect of healthy lifestyle on the association in women in the UK Biobank cohort. METHODS: The RRS was constructed in 74,141 female participants with data about the items derived for the RRS in the UK Biobank. The RRS was derived from 17 baseline variables, all of which indicated women's reproductive health status. We defined four categories of RRS status: low-risk group (score 0-1); low-intermediate group (score 2-3); high-intermediate group (score 4-5); and high-risk group (score 6-13). We also constructed a healthy lifestyle score (HLS) with five related factors, and categorized into unhealthy lifestyle group (score: 0-1), intermediate lifestyle group (score: 2-3) and healthy lifestyle group (score: 4-5). RESULTS: Each point increase in the RRS was associated with a 22 % higher risk of CVD (adjusted hazard ratio (aHR): 1.22; 95 % confidence interval (CI): 1.16 to 1.28), 23 % higher risk of IHD (1.23; 1.17 to 1.31) and 19 % higher risk of stroke (1.19; 1.07 to 1.32). The percentage population-attribution risks (PAR%) were 16 % (95 % CI: 8 to 24) for CVD, 15 % (95 % CI: 6 to 24) for IHD and 18 % (95 % CI: 1 to 33) for stroke. A healthy lifestyle significantly attenuated RRS associations with the incidence of CVD and IHD. The attributable proportions due to additive interaction (p < 0.001) between RRS and HLS were 0.14 (95 % CI: 0.07 to 0.22) for CVD and 0.15 (95 % CI: 0.09 to 0.23) for IHD, respectively. CONCLUSIONS: High RRS was associated with increased risks of CVD, IHD and stroke in female participants in the UK Biobank. The early-stage identification of women with reproductive risk using synthesised indicators and appropriate healthy lifestyle interventions could be useful for the prevention of early CVD and the extension of healthy active life expectancy.

Associations of birth weight, plasma metabolome in adulthood and risk of type 2 diabetes.

AIMS: We aimed to examine the longitudinal associations of birth weight with plasma metabolites in adulthood, and further quantify the proportions of the links between birth weight and incident adult type 2 diabetes (T2D) that were mediated by plasma metabolites. MATERIALS AND METHODS: A total of 62,033 participants with complete nuclear magnetic resonance metabolomics and birth weight data from the UK Biobank were included in this study. Linear regression was used to assess the associations between birth weight and metabolites. Cox regression was used to estimate hazard ratios for T2D associated with metabolites. We further performed mediation analyses to estimate the extent to which metabolites might mediate the association between birth weight and T2D risk. RESULTS: Low birth weight was associated with the adverse metabolic responses across multiple metabolic pathways, including lipoprotein subclasses, amino acids, fatty acids (FA), and inflammation. Metabolites associated with higher birth weight tended to be associated with a lower risk of T2D (Pearson correlation coefficient: -0.85). A total of 62 metabolites showed statistically significant mediation effects in the protective association of higher birth weight and T2D risk, including large-sized very low-density lipoprotein particles and triglyceride concentrations as well as saturated, and monounsaturated FA and glycoprotein acetyls. CONCLUSIONS: We identified a range of metabolites that reflect the adult metabolic response to birth weight, some of which might lie on the pathway between birth weight and adult T2D risk.

The long-term efficacy of imatinib with hepatic resection or other local treatment for gastrointestinal stromal tumours liver metastases: a retrospective cohort study.

BACKGROUND: The liver is the most common site of metastasis from gastrointestinal stromal tumors (GISTs). The authors aimed to evaluate imatinib (IM) combined with hepatic resection (HR) or other local treatments such as radiofrequency ablation (RFA) and transarterial chemoembolization (TACE), compared to IM monotherapy in long-term survival benefits in patients suffering from GIST liver metastases. METHODS: Our research encompassed 238 patients diagnosed with liver metastases of GISTs from January 2002 to April 2022 at the First Affiliated Hospital of Sun Yat-Sen University. The oncological outcomes of concern included overall survival (OS), progression-free survival (PFS), and liver-specific PFS. RESULTS: Of all 238 patients, 126 were treated with IM alone (IM group), 81 with IM combined with HR (IM+HR group), and 31 with IM combined with RFA/TACE (IM+RFA/TACE group). The median follow-up time was 44.83 months. The median OS in the IM group was 132.60 months and was not reached in either the IM+HR group or the IM+RFA/TACE group. The 10-year OS rate in the IM+HR group was significantly superior to the IM group and the IM+RFA/TACE group (91.9% vs. 61.1% vs. 55.2%, respectively, P =0.015), and the liver-specific PFS ( P =0.642) and PFS ( P =0.369) in the three groups showed a beneficial trend in the combined treatment group. Multivariate analyses showed that age less than or equal to 60 years (HR 0.280, P< 0.001) and IM+HR (HR 0.361, P =0.047) were independently associated with better OS. Achieving no evidence of disease through surgical intervention was independently correlated with enhanced OS (HR 0.099, P =0.034), liver-specific PFS (HR 0.388, P =0.014), and PFS (HR 0.402, P =0.004). CONCLUSIONS: In patients with GIST liver metastases, IM combined with HR might improve OS in selected patients compared with IM alone and IM combined with RFA/TACE. Achieving no evidence of disease status with surgical treatment of patients results in significant prolonging of OS, liver-specific PFS, and PFS.

Elevated blood remnant cholesterol and triglycerides are causally related to the risks of cardiometabolic multimorbidity.

The connection between triglyceride-rich lipoproteins and cardiometabolic multimorbidity, characterized by the concurrence of at least two of type 2 diabetes, ischemic heart disease, and stroke, has not been definitively established. We aim to examine the prospective associations between serum remnant cholesterol, triglycerides, and the risks of progression from first cardiometabolic disease to multimorbidity via multistate modeling in the UK Biobank. We also evaluate the causality of these associations via Mendelian randomization using 13 biologically relevant SNPs as the genetic instruments. Here we show that elevated remnant cholesterol and triglycerides are significantly associated with gradually higher risks of cardiometabolic multimorbidity, particularly the progression of ischemic heart disease to the multimorbidity of ischemic heart disease and type 2 diabetes. These results advocate for effective management of remnant cholesterol and triglycerides as a potential strategy in mitigating the risks of cardiometabolic multimorbidity.

Sleep patterns, genetic predisposition, and risk of chronic liver disease: A prospective study of 408,560 UK Biobank participants.

BACKGROUND: Little is known about the role that combined sleep behaviors play in the association with chronic liver disease (CLD) risk. METHODS: We included 408,560 participants initially free of CLD from the UK Biobank. A healthy sleep pattern was defined by early chronotype, sleep duration of 7-8 h/day, no insomnia, no snoring, and no excessive daytime sleepiness. Cox regression models were used to examine the association of healthy sleep pattern with incident CLD and their interaction with PNPLA3 genetic risk. RESULTS: During a median 12.5 years of follow-up, we documented 10,915 incident all-cause CLD cases, including 388 viral hepatitis, 4782 non-alcoholic fatty liver disease (NAFLD), 1356 cirrhosis, 973 alcoholic liver disease, and 725 liver cancer cases. Compared to participants with a healthy sleep score of 0-1, the hazard ratio (HR) (95 % confidence interval [CI]) for those with a sleep score of 5 was 0.54 (0.49, 0.60) for CLD, 0.52 (0.30, 0.90) for viral hepatitis, 0.47 (0.41, 0.55) for NAFLD, 0.57 (0.43, 0.75) for cirrhosis, 0.32 (0.23, 0.44) for alcoholic liver disease, and 0.53 (0.37, 0.77) for liver cancer. Healthy sleep pattern and PNPLA3 genetic risk exerted significant additive effects on CLD risk (relative excess risk due to the interaction: 0.05; attributable proportion due to the interaction: 13 %). LIMITATIONS: Measurement error was unavoidable for self-reported data on sleep behaviors. CONCLUSIONS: Our analyses provide evidence that healthy sleep pattern was inversely associated with the development of CLD, and participants with higher genetic risk were more likely to develop CLD when exposed to the unhealthy sleep pattern.

Associations of healthy aging index and all-cause and cause-specific mortality: a prospective cohort study of UK Biobank participants.

The healthy aging index (HAI) has been recently developed as a surrogate measure of biological age. However, to what extent the HAI is associated with all-cause and cause-specific mortality and whether this association differs in younger and older adults remains unknown. We aimed to quantify the association between the HAI and mortality in a population of UK adults. In the prospective cohort study, data are obtained from the UK Biobank. Five HAI components (systolic blood pressure, reaction time, cystatin C, serum glucose, forced vital capacity) were scored 0 (healthiest), 1, and 2 (unhealthiest) according to sex-specific tertiles or clinically relevant cut-points and summed to construct the HAI (range 0-10). Cox proportional hazard regression models were used to estimate the associations of the HAI with the risk of all-cause and cause-specific mortality. 387,794 middle-aged and older participants were followed up for a median of 8.9 years (IQR 8.3-9.5). A total of 14,112 all-cause deaths were documented. After adjustments, each 1-point increase in the HAI was related to a higher risk of all-cause mortality (hazards ratio [HR], 1.17; 95%CI, 1.15-1.18). Such association was stronger among adults younger than 60 years (1.19, 1.17-1.21) than that among those 60 years and older (1.15, 1.14-1.17) (P interaction < 0.001). For each unit increment of the HAI, the multivariate-adjusted HRs for risk of death were 1.28 (1.25-1.31) for cardiovascular diseases, 1.09 (1.07-1.10) for cancer, 1.36 (1.29-1.44) for digestive disease, 1.42 (1.35-1.48) for respiratory disease, 1.42 (1.33-1.51) for infectious diseases, and 1.15 (1.09-1.21) for neurodegenerative disease, respectively. Our findings indicate that the HAI is positively associated with all-cause and cause-specific mortality independent of chronological age. Our results further underscore the importance of effective early-life interventions to slow aging and prevent premature death.

Identifying Potential Causal Effects of Telomere Length on Health Outcomes: A Phenome-Wide Investigation and Mendelian Randomization Study.

BACKGROUND: Telomere length has been linked to various health outcomes. To comprehensively investigate the causal effects of telomere length throughout the human disease spectrum, we conducted a phenome-wide Mendelian randomization study (MR-PheWAS) and a systematic review of MR studies. METHODS: We conducted a PheWAS to screen for associations between telomere length and 1 035 phenotypes in the UK Biobank (n = 408 354). The exposure of interest was the genetic risk score (GRS) of telomere length. Observed associations passing multiple testing corrections were assessed for causality by 2-sample MR analysis. A systematic review of MR studies on telomere length was performed to harmonize the published evidence and complement our findings. RESULTS: Of the 1 035 phenotypes tested, PheWAS identified 29 and 78 associations of telomere length GRS at a Bonferroni- and false discovery rate-corrected threshold; 24 and 66 distinct health outcomes were causal in the following principal MR analysis. The replication MR using data from the FinnGen study provided evidence of causal effects of genetically instrumented telomere length on 28 out of 66 outcomes, including decreased risks of 5 diseases in respiratory diseases, digestive diseases, and myocardial infarction, and increased risks of 23 diseases, mainly comprised neoplasms, diseases of the genitourinary system, and essential hypertension. A systematic review of 53 MR studies found evidence to support 16 out of the 66 outcomes. CONCLUSIONS: This large-scale MR-PheWAS identified a wide range of health outcomes that were possibly affected by telomere length, and suggested that susceptibility to telomere length may vary across disease categories.

Observational and genetic associations of adiposity with cardiopulmonary multimorbidity: Linear and nonlinear Mendelian randomization analysis.

OBJECTIVE: Whether adiposity traits are causal risk factors for cardiopulmonary multimorbidity (CP-MM) remains largely unknown. The aim of this study was to examine the causal role of adiposity traits in the development of CP-MM. METHODS: This study involved 408,886 participants from the UK Biobank who had complete phenotypic and genetic data. Cox regression and Mendelian randomization (MR) analyses were conducted separately for observational and causal associations. RESULTS: During a median follow-up of 8.7 years, 1492 incident CP-MM were ascertained. In observational analysis, individuals with obesity had a hazard ratio (HR) of 1.51 (95% confidence intervals [CI]: 1.30-1.75) for developing CP-MM, compared with those with normal body mass index (BMI). Restricted cubic spline analyses showed a U-shaped relationship between continuous BMI and CP-MM (p < 0.001), whereas WHRadjBMI exhibited a linear relationship (p = 0.828). Joint analysis revealed that maintaining ideal waist-hip ratio (WHR) in adults with overweight is still effective in preventing CP-MM. In linear MR analysis, 1 kg/m2 increase in genetically predicted BMI and per 1% higher in genetically predicted WHRadjBMI was associated with 9% and 10% higher risk for incident CP-MM, respectively. Nonlinear MR analyses demonstrated linearity between genetically predicted BMI or WHRadjBMI and CP-MM. CONCLUSIONS: Adiposity may play a causal role in CP-MM development and represent a promising approach for multimorbidity prevention.

Polysocial and Polygenic Risk Scores and All-Cause Dementia, Alzheimer's Disease, and Vascular Dementia.

BACKGROUND: To establish a polysocial risk score (PsRS) incorporating various social factors for capturing the dementia risk and investigate the benefits of favorable social conditions across different genetic backgrounds. METHODS: This prospective cohort study comprised 345 439 participants initially free of dementia from the UK Biobank. A total of 10 social factors were summed to create a PsRS. A polygenic risk score (PRS) was constructed based on genome-wide significant variants. RESULTS: During a median follow-up of 12.5 years, we documented 4 595 incident all-cause dementia events including 2 067 Alzheimer's disease (AD) events and 1 028 vascular dementia (VD) events. Each additional PsRS was associated with a 19% increased risk of all-cause dementia (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.17 to 1.21), a 13% increased risk of AD (1.13; 1.10 to 1.16), and a 24% increased risk of VD (1.24; 1.19 to 1.29). 29% (24% to 33%) of dementia cases, 22% (14% to 29%) of AD cases, and 39% (28% to 48%) of VD cases were associated with a disadvantageous social environment. In addition, among participants at a high genetic risk, the low social risk was linked to a lower incidence rate of all-cause dementia, AD, and VD compared to those who had a high social risk, with reductions of 67.8%, 64.5%, and 84.2%, respectively. CONCLUSIONS: The PsRS could be effectively used in discriminating individuals at high risk of dementia. Around a quarter of dementia events could have a connection with a disadvantageous social environment, especially for those genetically susceptible to dementia.

Frequency of Adding Salt to Foods, Genetic Susceptibility, and Incident Type 2 Diabetes: A Prospective Cohort Study.

CONTEXT: Excessive salt consumption is known to increase the risk of hypertension and cardiovascular disease, but the association between salt intake and incident type 2 diabetes has not been extensively researched. OBJECTIVE: In this study, we aimed to investigate the relationships between the frequency of adding salt to foods and incident type 2 diabetes, as well as any potential interactions with genetic predisposition. METHODS: We included 368 137 eligible participants, aged 37 to 73 years, from the UK Biobank. The frequency of adding salt to foods was assessed via a food frequency questionnaire. RESULTS: During a median follow-up of 12.6 years, we documented 10 981 incident type 2 diabetes cases. After adjustment for major confounders, participants who sometimes, usually, and always added salt to foods had 7% (hazard ratio [HR]: 1.07; 95% CI, 1.03-1.12), 9% (HR: 1.09; 95% CI, 1.03-1.16), 28% (HR: 1.28; 95% CI, 1.19-1.38) higher risks of developing type 2 diabetes, respectively, than those that never/rarely added salt to foods (P for trend < .001). We found these associations to be consistent across stratified and sensitivity analyses. However, we did not observe any statistically significant multiplicative or additive interactions between the frequency of adding salt to foods and genetic predisposition regarding incident type 2 diabetes. CONCLUSION: Our findings suggest that consuming salt regularly, regardless of genetic susceptibility, may increase the risk of type 2 diabetes. Therefore, public health interventions aimed at reducing excessive salt consumption may help prevent the onset of type 2 diabetes.

Association between birth weight/joint exposure to ambient air pollutants and type 2 diabetes: a cohort study in the UK Biobank.

Early life events and environmental factors are associated with type 2 diabetes (T2D) development. We assessed the combined effect of birth weight andambient air pollutants, and effect of their interaction on T2D risk. Totally, 6,474 T2D incidents were recorded over an 8.7-year follow-up period. The adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were 1.31 (1.26, 1.36) for each kilogram decrease in birth weight, and 1.08 (1.05, 1.11) for each standard deviation increase in air pollution score (APS). Birth weight<3000 g amplified the T2D risk associated with high APS. A combination of the lowest birth weight (<2500 g) and the highest quintile of APS led to over two-fold increase in T2D risk (aHR: 2.17; 95% CI: 1.79-2.64). There was a significant additive interaction between them. In conclusion, ambient air pollutants increase the risk for T2D, particularly in populations with low birth weight.

Potential Common Molecular Mechanisms Between Periodontitis and Hepatocellular Carcinoma: A Bioinformatic Analysis and Validation.

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has a poor prognosis. Periodontitis, or tooth loss, is considered to be related to hepatocarcinogenesis and its poor prognosis. This study aimed to explore potential associations and cross-talk mechanisms between periodontitis and HCC. MATERIALS AND METHODS: Periodontitis and HCC microarray datasets were acquired from the Gene Expression Omnibus (GEO) database and were analyzed to obtain differentially expressed (DE) lncRNAs, miRNAs and mRNAs. Functional enrichment analysis was used to detect the functions of these mRNAs. Then, a ceRNA network of periodontitis-related HCC was constructed. Least absolute shrinkage and selection operator (LASSO) regression, random forest algorithm, and support vector machine-recursive feature elimination (SVM-RFE) were performed to explore the diagnostic significance of mRNAs in periodontitis-related HCC. Cox regression analyses were conducted to screen mRNAs with prognostic significance in HCC. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were conducted to validate the expression of these mRNAs in HCC tissues. RESULTS: A ceRNA network was constructed. Functional enrichment analysis indicated that the network is associated with immune and inflammatory responses, the cell cycle and liver metabolic function. LASSO, random forest algorithm and SVM-RFE showed the diagnostic significance of DE mRNAs in HCC. Cox regression analyses revealed that MSH2, GRAMD1C and CTHRC1 have prognostic significance for HCC, and qRT-PCR and IHC validated this finding. CONCLUSION: Periodontitis may affect the occurrence of HCC by changing the immune and inflammatory response, the cell cycle and liver metabolic function. MSH2, GRAMD1C and CTHRC1 are potential prognostic biomarkers for HCC.

Daily stair climbing, disease susceptibility, and risk of atherosclerotic cardiovascular disease: A prospective cohort study.

BACKGROUND AND AIMS: The associations between intensity of stair climbing and atherosclerotic cardiovascular disease (ASCVD) and how these vary by underlying disease susceptibility are not fully understood. We aim to evaluate the intensity of stair climbing and risk of ASCVD types and whether these vary with the presence of ASCVD risk factors. METHODS: This prospective study used data of 458,860 adult participants from the UK Biobank. Information about stair climbing, sociodemographic, and lifestyle factors was collected at baseline and a resurvey 5 years after baseline. ASCVD was defined as coronary artery disease (CAD), ischemic stroke (IS), or acute complications. Associations between flights of stair climbing and ASCVD were examined as hazard ratios (HRs) from Cox proportional hazards models. The modification role of disease susceptibility on such associations was assessed by analyses stratified by levels of genetic risk score (GRS), 10-year risks of ASCVD, and self-reported family history of ASCVD. RESULTS: During a median of 12.5 years of follow-up, 39,043 ASCVD, 30,718 CAD, and 10,521 IS cases were recorded. Compared with the reference group (reported climbing stairs 0 times/day at baseline), the multivariable-adjusted HRs for ASCVD were 0.97 (95% CI, 0.93-1.01), 0.84 (0.82-0.87), 0.78 (0.75-0.81), 0.77 (0.73-0.80) and 0.81 (0.77-0.85) for stair climbing of 1-5, 6-10, 11-15, 16-20 and ≥21 times/day, respectively. Comparable results were obtained for CAD and IS. When stratified by different disease susceptibility based on the GRS for CAD/IS, 10-year risk, and family history of ASCVD, the protection association of stair climbing was attenuated by increasing levels of disease susceptibility. Furthermore, compared with people who reported no stair climbing (<5 times/d) at two examinations, those who climbed stairs at baseline and then stopped at resurvey experienced a 32% higher risk of ASCVD (HR 1.32, 95% CI:1.06-1.65). CONCLUSIONS: Climbing more than five flights of stairs (approx 50 steps) daily was associated with a lower risk of ASCVD types independent of disease susceptibility. Participants who stopped stair climbing between baseline and resurvey had a higher risk of ASCVD compared with those who never climbed stairs.

Association of TyG index with hypertension in Chinese adults: the China Health Examination Collaborative Study (CHEC Study).

BACKGROUND AND OBJECTIVES: We aimed to investigate the association of triglyceride-glucose (TyG) index with hypertension and compare the discriminative power of the TyG index, lipid, glycemic parameters for hypertension using the China Health Examination Collaborative study (CHEC Study). METHODS AND STUDY DESIGN: Data were collected at Ningbo Mingzhou Hospital and Beijing physical examination center from the CHEC Study during 2014 and 2021. Participants with ≥2 medical check-up times were included. The TyG index is the logarithmized product of fasting triglyceride and glucose. Generalised estimation equation (GEE) model was used to evaluate the association between the TyG index, lipid parameters, glycemic parameters and hypertension. Receiver operating characteristic (ROC) analysis was performed to explore the predictive ability of TyG index on hypertension at different years of medical check-up. RESULTS: 112,902 participants with an average age of 42.8 years were recruited in the study, 36,839 participants developed hypertension over the 8-year period. GEE model analysis showed that the ORs with 95% CI of hypertension were 3.35 (3.15-3.57), 1.86 (1.76-1.95), 1.67 (1.58-1.78), 1.45 (1.33-1.58), 1.24 (1.19-1.29), 0.92 (0.86-0.99), and 1.90 (1.83-1.97) in the highest versus lowest quintiles of TyG index, TG/HDL-C ratio, TG, TC, LDL-C, HDL-C and FPG in model 2. The area under the ROC curve of the overall years of medical check-up was signifi-cantly higher than a particular year in predicting hypertension (AUC: 0.883, p < 0.05). CONCLUSIONS: TyG index is associated with hypertension and shows the superior discriminative ability for hypertension compared with lipid and glycemic parameters.

Leisure-Time Television Viewing and Computer Use, Family History, and Incidence of Dementia.

INTRODUCTION: Time spent on screen-based sedentary activities is significantly associated with dementia risk, however, whether the associations vary by family history (FHx) of dementia is currently unknown. We aimed to examine independent associations of two prevalent types of screen-based sedentary activities (television [TV] viewing and computer use) with dementia and assess the modifying effect of FHx. METHODS: We included 415,048 individuals free of dementia from the UK Biobank. Associations of TV viewing, computer use, and FHx with dementia risk were determined using Cox regression models. We estimated both multiplicative- and additive-scale interactions between TV viewing and computer use and FHx. RESULTS: During a median follow-up of 12.6 years, 5,549 participants developed dementia. After adjusting for potential confounding factors, we observed that moderate (2-3 h/day; hazard ratio [HR] 1.13, 95% confidence interval 0.03-1.23) and high (>3 h/day; 1.33, 1.21-1.46) TV viewing was associated with a higher dementia risk, compared with low (0-1 h/day) TV viewing. Using restricted cubic spline models, the relationship of TV viewing with dementia was nonlinear (relative to 0 h/day; p for nonlinear = 0.005). We found that >3 h/day of TV viewing was associated with a 42% (1.42, 1.18-1.71) higher dementia risk in participants with FHx while a 30% (1.30, 1.17-1.45) in those without FHx. For computer use, both low (0 h/day; 1.41, 1.33-1.50) and high (>2 h/day; 1.17, 1.05-1.29) computer use were associated with elevated dementia risk, compared with moderate (1-2 h/day) computer use. We observed a J-shaped relationship with dementia (relative to 2 h/day; p for nonlinear <0.001). Compared with 1-2 h/day of computer use, the HRs of dementia were 1.46 (1.29-1.65) and 1.10 (0.90-1.36) for 0 h/day and >2 h/day of computer use in participants with FHx, respectively, while the corresponding HRs were 1.40 (1.30-1.50) and 1.19 (1.06-1.33) in those without FHx. We observed a positive additive interaction (RERI 0.29, 0.06-0.53) between computer use and FHx, while little evidence of interaction between TV viewing and FHx. CONCLUSIONS: The time spent on TV viewing and computer use were independent risk factors for dementia, and the adverse effects of computer use and FHx were additive. Our findings point to new behavioral targets for intervention on preventing an early onset of dementia, especially for those with FHx.

A novel nomogram based on preoperative parameters to predict posthepatectomy liver failure in patients with hepatocellular carcinoma.

BACKGROUND: Posthepatectomy liver failure is one of the main causes of death in patients after hepatectomy. This study intends to establish a prediction model to predict the risk of posthepatectomy liver failure and provide a scientific basis for further reducing the incidence of posthepatectomy liver failure. METHODS: This was a retrospective analysis of 1,172 patients with hepatocellular carcinoma undergoing partial hepatectomy. Using univariate and multivariate logistic regression analyses and stepwise regression, a prediction model for posthepatectomy liver failure was established based on the independent risk factors for posthepatectomy liver failure and validated by bootstrapping with 100 resamples, and the receiver operating characteristic curve was used to evaluate the predictive value of the prediction model. RESULTS: The incidence rate of posthepatectomy liver failure was 22.7% (266/1172). The results showed that the indocyanine green retention rate at 15 minutes (odds ratio = 1.05, P = .002), alanine transaminase (odds ratio = 1.02, P < .001), albumin rate (odds ratio = 0.92, P < .001), total bilirubin (odds ratio = 1.04, P < .001), prothrombin time (odds ratio = 2.44, P < .001), aspartate aminotransferase-neutrophil ratio (odds ratio = 0.95, P < .001), and liver fibrosis index (odds ratio = 1.35, P < .001) were associated with posthepatectomy liver failure. These 7 independent risk factors for posthepatectomy liver failure were integrated into a nomogram prediction model, the predictive efficiency for posthepatectomy liver failure (area under the curve = 0.818, 95% confidence interval 0.789-0.848) was significantly higher than in other predictive models with a liver fibrosis index (area under the curve = 0.651), indocyanine green R15 (area under the curve = 0.669), albumin-bilirubin score (area under the curve = 0.709), albumin-indocyanine green evaluation score (area under the curve = 0.706), model for end-stage liver disease score (area under the curve = 0.636), and Child‒Pugh (area under the curve = 0.551) (all P < .001). The risk of posthepatectomy liver failure in the high-risk posthepatectomy liver failure group (score ≥152) was higher than that in the posthepatectomy liver failure low-risk group (score <152). CONCLUSION: This study developed and validated a nomogram model to predict the risk of posthepatectomy liver failure before surgery that can effectively predict the risk of posthepatectomy liver failure in patients with hepatocellular carcinoma.