Individual and joint effects of borderline ankle-brachial index and high plasma total homocysteine on all-cause death in hypertensive adults

BACKGROUND The cardiovascular hazards of total homocysteine(tHcy)are long known.In addition,despite the acknow-ledgment on the importance of low ankle-brachial index(ABI)(<0.9),borderline ABI(0.91-0.99)was once commonly overlooked.This study aims to explore the independent and joint effect of tHcy level and borderline ABI on all-cause death in hypertensive population.METHODS This study included 10,538 participants from China H-type Hypertension Registry Study.ABI was described into two groups:normal ABI(1.00-1.40)and borderline ABI.tHcy level was also divided into two groups:<15.02 and≥15.02μmo/L.Four groups were analyzed,using COX proportional hazard regression model,separately and pairwise to observe the independ-ent and joint effect on all-cause death.RESULTS A total of 126(1.2%)deaths were observed in the 1.7 years follow-up time.Borderline ABI has a higher predicted risk of death than normal ABI(HR=1.87,95%CI:1.17-3.00)after adjusting for potential covariates.Compare with tHcy level<15.02μmo/L(low tHcy),those with tHcy≥15.02μmo/L(high tHcy)had higher risk to event outcome(HR=1.99,95%CI:1.30-3.05).According to the cumulative hazard curve,group with borderline ABI and high tHcy level has significantly higher altitude and larger increasing rate over follow-up period compare to other groups.Among those with borderline ABI,participants with high tHcy had higher death risk than those with low tHcy,nevertheless,no significant different between borderline and normal ABI among those with low tHcy levels.CONCLUSIONS Borderline ABI and tHcy level both have independent predictive value on all-cause death.The combined group of borderline ABI and high tHcy has highest risk factor of outcomes,which suggested the mutual additive value of border-line ABI and tHcy.More attention should be given to the importance of borderline ABI in hypertensive population,especially with elevated tHcy level.

Relationship between pulmonary hypertension and cardiovascular events, all-cause death in maintenance hemodialysis patients

Objective: To determine the impact of pulmonary hypertension (PH) on maintenance hemodialysis (MHD) patients' cardiovascular events and all-cause mortality. Methods: We included 90 MHD patients, divided into group with PH and group without PH. All patients had been followed up for 4 years, and the primary endpoints were all cause mortality and cardiovascular events. We compared the clinical data and the endpoint events between the two groups. Results: We found PH in 37 patients (41.11%). The incidence of previous cardiovascular disease in group with PH was significantly higher than that in group without PH (χ2=2.034, P < 0.05). The left atrial diameter in group with PH was significantly higher than that in group without PH (t = 7.265, P < 0.01). Logistic regression analysis revealed that previous cardiovascular disease and left atrial diameter were the independent determinants of PH. The rate of new cardiovascular events in group with PH(59.5%) was significantly higher than that in group without PH(34%) (χ2=9.203, P < 0.05). The associated variables of cardiovascular events were:systolic pulmonary arterial pressure, age, history cardiovascular disease, hs-CRP, ejection fraction, left ventricular diastolic dysfunction. In a multivariate model, the PH maintained its independent association. The mortality rate in group with PH (48.6%) was significantly higher than that in group without PH (26.4%) (χ2=5.049, P <0.05). In the Cox survival analysis, we found an association between mortality and systolic pulmonary arterial pressure, age, previous cardiovascular disease, Alb, ejection fraction. In a multivariate model the PH remains as independent predictor of mortality. Conclusion:Pulmonary hypertension is common in HD patients and a valuable predictor of mortality and cardiovascular events.

Relationship of body fat and left ventricular hypertrophy with the risk of all-cause death in patients with coronary artery disease

BACKGROUND Left ventricular hypertrophy(LVH)is prevalent in obese individuals.Besides,both of LVH and obesity is as-sociated with subclinical LV dysfunction.The study aims to investigate the interplay between body fat and LVH in relation to all-cause death in patients with coronary artery disease(CAD).METHODS In this retrospective cohort study,a total of 2243 patients with angiographically proven CAD were included.Body fat and LV mass were calculated using established formulas.Patients were grouped according to body fat percentage and pres-ence or absence of LVH.Cox-proportional hazard models were used to observe the interaction effect of body fat and LVH on all-cause death.RESULTS Of 2243 patients enrolled,560(25%)had a higher body fat percentage,and 1045(46.6%)had LVH.After a median follow-up of 2.2 years,the cumulative mortality rate was 8.2%in the group with higher body fat and LVH,2.5%in those with lower body fat and no LVH,5.4%in those with higher body fat and no LVH,and 7.8%in those with lower body fat and LVH(log-rank P<0.001).There was a statistically significant interaction between body fat percentage and LVH(P interaction was 0.003).After correcting for confounding factors,patients with higher body fat and LVH had the highest risk of all-cause death(HR=3.49,95%CI:1.40-8.69,P=0.007)compared with those with lower body fat and no LVH;in contrast,patients with higher body fat and no LVH had no statistically significant difference in risk of death compared with those with lower body fat and no LVH(HR=2.03,95%CI:0.70-5.92,P=0.195).CONCLUSION A higher body fat percentage was associated with a different risk of all-cause death in patients with CAD,strat-ified by coexistence of LVH or not.Higher body fat was significantly associated with a greater risk of mortality among patients with LVH but not among those without LVH.

Proton pump inhibitors and all-cause mortality risk among cancer patients

BACKGROUND Proton pump inhibitors(PPIs)are widely used,including among cancer patients,to manage gastroesophageal reflux and other gastric acid-related disorders.Recent evidence suggests associations between long-term PPI use and higher risks for various adverse health outcomes,including greater mortality.AIM To investigate the association between PPI use and all-cause mortality among cancer patients by a comprehensive analysis after adjustment for various confounders and a robust methodological approach to minimize bias.METHODS This retrospective cohort study used data from the TriNetX research network,with electronic health records from multiple healthcare organizations.The study employed a new-user,active comparator design,which compared newly treated PPI users with non-users and newly treated histamine2 receptor antagonists(H2RA)users among adult cancer patients.Newly prescribed PPIs(esomeprazole,lansoprazole,omeprazole,pantoprazole,or rabeprazole)users were compared to non-users or newly prescribed H2RAs(cimetidine,famotidine,nizatidine,or ranitidine)users.The primary outcome was all-cause mortality.Each patient in the main group was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects.Multivariable Cox regression models were used to estimate hazard ratios(HRs)and 95% confidence interval(CI).RESULTS During the follow-up period(median 5.4±1.8 years for PPI users and 6.5±1.0 years for non-users),PPI users demonstrated a higher all-cause mortality rate than non-users after 1 year,2 years,and at the end of follow up(HRs:2.34-2.72).Compared with H2RA users,PPI users demonstrated a higher rate of all-cause mortality HR:1.51(95%CI:1.41-1.69).Similar results were observed across sensitivity analyses by excluding deaths from the first 9 months and 1-year post-exposure,confirming the robustness of these findings.In a sensitivity analysis,we analyzed all-cause mortality outcomes between former PPI users and individuals who have never used PPIs,providing insights into the long-term effects of past PPI use.In addition,at 1-year follow-up,the analysis revealed a significant difference in mortality rates between former PPI users and non-users(HR:1.84;95%CI:1.82-1.96).CONCLUSION PPI use among cancer patients was associated with a higher risk of all-cause mortality compared to non-users or H2RA users.These findings emphasize the need for cautious use of PPIs in cancer patients and suggest that alternative treatments should be considered when clinically feasible.However,further studies are needed to corroborate our findings,given the significant adverse outcomes in cancer patients.

Prognostic factors affecting the all-cause death and sudden cardiac death rates of post myocardial infarction patients with low left ventricular ejection fraction

Background Post myocardial infarction （post-MI） patients with low left ventricular ejection fraction （LVEF） have been candidates for an implantable cardioverter-defibrillator （ICD） since the Multicenter Automatic Defibrillator Implantation Trail Ⅱ （MADIT Ⅱ）. However, due to the high costs of ICDs, widespread usage has not been accepted. Therefore, further risk stratification for post-MI patients with low LVEF may aid in the selection of patients that will benefit most from ICD treatment. Methods Four hundred and seventeen post-MI patients with low LVEF （≤35%） were enrolled in the study. All the patients received standard examination and proper treatment and were followed up to observe the all-cause death rate and sudden cardiac death （SCD） rate. Then COX proportional-hazards regression model was used to investigate the clinical factors which affect the all-cause death rate and SCD rate. Results Of 55 patients who died during （32±24） months of follow-up, 37 （67%） died suddenly. After adjusting for baseline clinical characteristics, multivariate COX proportional-hazards regression model identified the following variables associated with death from all causes： New York Heart Association （NYHA） heart failure class ≥Ⅲ （Hazard ratio： 2.361）, LVEF ≤20% （Hazard ratio： 2.514）, sustained ventricular tachycardia （Hazard ratio： 6.453）, and age 〉70 years （Hazard ratio： 3.116）. The presence of sustained ventricular tachycardia （Hazard ratio： 6.491） and age ≥70 years （Hazard ratio： 2.694） were specifically associated with SCD. Conclusions In the post-MI patients with low LVEF, factors as LVEF ≤20%, age ≥70 years, presence of ventricular tachycardia, and NYHA heart failure class ≥111 predict an adverse outcome. The presence of sustained ventricular tachycardia and age ≥70 years was associated with occurrence of SCD in these patients.

Dietary oleic acid intake,olive oil consumption,and risk of cardiovascular and all-cause mortality

Objective:Oleic acid,a subtype of monounsaturated fatty acid(MUFA),is present in abundance in certain edible oils,particularly olive oils.Epidemiological evidence concerning dietary oleic acid intake and the long-term risk of mortality is lacking.This study aimed to evaluate the associations of the dietary intake of oleic acid and other specific subtypes of MUFAs,olive oil,and other vegetable oils with cardiovascular disease(CVD)and all-cause mortality.Methods:This prospective cohort study included adults aged 40 years or older who participated in the included U.S.adults National Health and Nutrition Examination Survey(NHANES).Dietary MUFA intake was assessed via 24-h dietary recall interviews in NHANES 1999–2018,and the consumption of olive oil and other vegetable oils was assessed via a food frequency questionnaire in NHANES 2003–2006.Deaths and underlying causes of death were ascertained by linkage to the National Death Index through December 31,2019.Weighted Cox proportional hazards regression models were used to estimate the hazard ratio(HR)and 95%CIs.Results:Dietary intake of total MUFAs and oleic acid was associated with a lower risk of CVD mortality,with HRs(95%CI)of 0.62(0.39–0.99)and 0.61(0.39–0.97),respectively.Total MUFA and oleic acid intake were inversely associated with all-cause mortality;the multivariable-adjusted HRs were 0.77(95%CI:0.60–0.99)and 0.78(95%CI:0.62–0.99),respectively.There was no significant association between palmitoleic acid intake and all-cause mortality.The habitual consumption of olive oil,but not the consumption of other vegetable oils,was inversely associated with the risk of cardiovascular mortality.In the joint association analysis,the HRs(95%CI)of cardiovascular mortality were 0.36(0.19–0.69)for people who exclusively consumed olive oil,0.59(0.27–1.32)for people who consumed both olive oil and other vegetable oils,and 0.73(0.46–1.14)for people who exclusively consumed other vegetable oils compared with people who never consumed vegetable oils.Conclusions:In a U.S.nationally representative prospective cohort,higher dietary oleic acid intake and olive oil consumption were associated with a lower risk of cardiovascular mortality.

Association between inflammatory bowel disease and all-cause dementia:A two-sample Mendelian randomization study

BACKGROUND Numerous observational studies have documented a correlation between inflammatory bowel disease(IBD)and an increased risk of dementia.However,the causality of their associations remains elusive.AIM To assess the causal relationship between IBD and the occurrence of all-cause dementia using the two-sample Mendelian randomization(MR)method.METHODS Genetic variants extracted from the large genome-wide association study(GWAS)for IBD(the International IBD Genetics Consortium,n=34652)were used to identify the causal link between IBD and dementia(FinnGen,n=306102).The results of the study were validated via another IBD GWAS(United Kingdom Biobank,n=463372).Moreover,MR egger intercept,MR pleiotropy residual sum and outlier,and Cochran's Q test were employed to evaluate pleiotropy and heterogeneity.Finally,multiple MR methods were performed to estimate the effects of genetically predicted IBD on dementia,with the inverse variance weighted approach adopted as the primary analysis.RESULTS The results of the pleiotropy and heterogeneity tests revealed an absence of significant pleiotropic effects or heterogeneity across all genetic variants in outcome GWAS.No evidence of a causal effect between IBD and the risk of dementia was identified in the inverse variance weighted[odds ratio(OR)=0.980,95%CI:0.942-1.020,P value=0.325],weighted median(OR=0.964,95%CI:0.914-1.017,P value=0.180),and MR-Egger(OR=0.963,95%CI:0.867-1.070,P value=0.492)approaches.Consistent results were observed in validation analyses.Reverse MR analysis also showed no effect of dementia on the development of IBD.Furthermore,MR analysis suggested that IBD and its subtypes did not causally affect allcause dementia and its four subtypes,including dementia in Alzheimer's disease,vascular dementia,dementia in other diseases classified elsewhere,and unspecified dementia.CONCLUSION Taken together,our MR study signaled that IBD and its subentities were not genetically associated with all-cause dementia or its subtypes.Further large prospective studies are warranted to elucidate the impact of intestinal inflammation on the development of dementia.

Triceps skinfold thickness trajectories and the risk of all-cause mortality:A prospective cohort study

BACKGROUND The measurement of triceps skinfold(TSF)thickness serves as a noninvasive metric for evaluating subcutaneous fat distribution.Despite its clinical utility,the TSF thickness trajectories and their correlation with overall mortality have not been thoroughly investigated.AIM To explore TSF thickness trajectories of Chinese adults and to examine their associations with all-cause mortality.METHODS This study encompassed a cohort of 14747 adults sourced from the China Health and Nutrition Survey.Latent class trajectory modeling was employed to identify distinct trajectories of TSF thickness.Subjects were classified into subgroups reflective of their respective TSF thickness trajectory.We utilized multivariate Cox regression analyses and mediation examinations to explore the link between TSF thickness trajectory and overall mortality,including contributory factors.RESULTS Upon adjustment for multiple confounding factors,we discerned that males in the‘Class 2:Thin-stable’and‘Class 3:Thin-moderate’TSF thickness trajectories exhibited a markedly reduced risk of mortality from all causes in comparison to the‘Class 1:Extremely thin’subgroup.In the mediation analyses,the Geriatric Nutritional Risk Index was found to be a partial intermediary in the relationship between TSF thickness trajectories and mortality.For females,a lower TSF thickness pattern was significantly predictive of elevated all-cause mortality risk exclusively within the non-elderly cohort.CONCLUSION In males and non-elderly females,lower TSF thickness trajectories are significantly predictive of heightened mortality risk,independent of single-point TSF thickness,body mass index,and waist circumference.

The association of serum manganese concentrations with all-cause,cardiovascular disease and cancer mortality:A cohort study based on the 2011–2014 National Health and Nutrition Examination Survey(NHANES)

Objectives:There is a debate on the association between the circulating manganese(Mn)levels and mortality.The aim of this study was to explore the nonlinear association between the serum Mn levels and all-cause or cause-specific mortality.Methods:We included 8,145 adults from the United States(US)and their serum Mn concentrations obtained from the National Health and Nutrition Examination Survey(NHANES 2011–2014).We retrieved their survival information from baseline until 2019 using the national death index.Multivariable Cox proportional hazards models were used to show the risk of all-cause or cause-specific mortality according to the baseline serum Mn concentrations.Smooth curve fitting and threshold effect analyses were used to clarify the potential nonlinearity.Results:During a median follow-up of 6.2 years,there were 716 deaths from all causes,224 of which were due to cardiovascular dis-ease(CVD)and 165 due to cancer.The serum Mn levels exhibited a U-shaped relationship with all-cause or CVD-associated mortality.Serum Mn levels lower than the threshold value(7.32μg/L)were negatively associated with all-cause(fully adjusted HR:0.86,95%CI:0.80–0.94)and CVD(fully adjusted HR:0.82,95%CI:0.71–0.94)mortality.In contrast,serum Mn levels higher than the threshold value(7.32μg/L)were positively associated with all-cause(fully adjusted HR:1.04,95%CI:1.02–1.06)and CVD(fully adjusted HR:1.05,95%CI:1.02–1.08)mortality.Conclusions:The serum Mn concentrations showed a U-shaped relationship with all-cause and CVD-associated mortality among NHANES participants.

Maternal and fetal death associated with acute pancreatitis during pregnancy:A case report

BACKGROUND Acute pancreatitis in pregnancy is a rare but serious condition that can lead to high maternal mortality and fetal loss.Instances of pregnancy complicated by severe acute pancreatitis,particularly with subsequent respiratory and cardiac arrest,are rarely reported.CASE SUMMARY We present the case of a 35-year-old woman,at 36+5 weeks of gestation,who presented with paroxysmal epigastric pain accompanied by low back pain,nausea,and vomiting.According to the clinical symptoms,B-ultrasound imaging and biochemical indicators,the patient was diagnosed with acute pancreatitis and initially managed conservatively.However,3 hours after admission,the patient experienced respiratory and cardiac arrest,and the fetus died.In this case,the adverse outcomes occurred due to the lack of aggressive fluid resuscitation and an active surgical intervention.CONCLUSION Implementing aggressive fluid resuscitation to sustain tissue perfusion,alongside the proactive evaluation of pharmacological agents that suppress gastric acid secretion and inhibit pancreatic enzyme activity,may be beneficial in mitigating the risk of a severely adverse prognosis.Effective management of acute pancreatitis during pregnancy requires careful timing of surgical intervention,a thorough evaluation of the risks and benefits regarding the continuation or termination of pregnancy,and a focus on safeguarding both maternal and fetal health.

Programmed cell death 1 inhibitor sintilimab plus S-1 and gemcitabine for liver metastatic pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.

Interleukin-17A facilitates tumor progression via upregulating programmed death ligand-1 expression in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.

Glaucomatous retinal ganglion cells:death and protection

Glaucoma is a group of diseases characterized by progressive optic nerve degeneration,with the characteristic pathological change being death of retinal ganglion cells(RGCs),which ultimately causes visual field loss and irreversible blindness.Elevated intraocular pressure(IOP)remains the most important risk factor for glaucoma,but the exact mechanism responsible for the death of RGCs is currently unknown.Neurotrophic factor deficiency,impaired mitochondrial structure and function,disrupted axonal transport,disturbed Ca2+homeostasis,and activation of apoptotic and autophagic pathways play important roles in RGC death in glaucoma.This review was conducted using Web of Science,PubMed,Project,and other databases to summarize the relevant mechanisms of death of RGCs in glaucoma,in addition to outlining protective treatments to improve the degradation of RGCs.

Programmed cell death receptor 1 inhibitor Pembrolizumab in the treatment of advanced gastric cancer

This editorial discusses Christodoulidis et al's article,which appeared in the most recent edition.The clinical trials have demonstrated the programmed cell death receptor 1(PD-1)inhibitor Pembrolizumab involved combination therapy can improve the efficacy of advanced gastric cancer(AGC).Pembrolizumab combined with chemotherapy can enhance its sensitivity,and further eliminate tumor cells that develop resistance to chemotherapy.The combination of Pembrolizumab and Trastuzumab targeting human epidermal growth factor receptor 2 showed improved prognosis.The overall toxic effects of Pembrolizumab are significantly lower than traditional chemotherapy,and the safety is controllable.PD-1 inhibitor Pembrolizumab sheds a light on the treatment of AGC and brings new hope to the clinical practice.

The serum anion gap is associated with disease severity and all-cause mortality in coronary artery disease

Objective To evaluate the associations between the serum anion gap （AG） with the severity and prognosis of coronary artery disease （CAD）. Methods We measured serum electrolytes in 18,115 CAD patients indicated by coronary angiography. The serum AG was calculated according to the equation： AG = Na^＋ [（mmol/L） ＋ K^＋ （mmol/L）] - [Cl^- （mmol/L） ＋ HCO3^- （mmol/L）]. Results A total of 4510 （24.9%） participants had their AG levels greater than 16 mmol/L. The serum AG was independently associated with measures of CAD severity, including more severe clinical types of CAD （P 〈 0.001） and worse cardiac function （P = 0.004）. Patients in the 4th quartile of serum AG （≥ 15.92 mmol/L） had a 5.171-fold increased risk of 30 days all-cause death （P 〈 0.001）. This association was robust, even after adjustment for age, sex, evaluated glomerular filtration rate [hazard ratio （HR）： 4.861, 95% confidence interval （CI）： 2.150–10.993, P 〈 0.001], clinical diagnosis, severity of coronary artery stenosis, cardiac function grades, and other confounders （HR： 3.318, 95% CI： 1.76–2.27, P = 0.009）. Conclusion In this large population-based study, our findings reveal a high percentage of increased serum AG in CAD. Higher AG is associated with more severe clinical types of CAD and worse cardiac function. Furthermore, the increased serum AG is an independent, significant, and strong predictor of all-cause mortality. These findings support a role for the serum AG in the risk-stratification of CAD.

Fatty liver disease:Disparate predictive ability for cardiometabolic risk and all-cause mortality

AIM: To assess the association of a surrogate of fatty liver disease(FLD) with incident type-2 diabetes, coronary heart disease, and all-cause mortality.METHODS: In a prospective population-based study on 1822 middle-aged adults, stratified to gender, we used an algorithm of fatty liver index(FLI) to identify associations with outcomes. An index ≥ 60 indicated the presence of FLD. In Cox regression models, adjusted for age, smoking status, high-density lipoprotein cholesterol, and systolic blood pressure, we assessed the predictive value of FLI for incident diabetes, coronary heart disease(CHD), and all-cause mortality.RESULTS: At a mean 8 year follow-up, 218 and 285 incident cases of diabetes and CHD, respectively, and 193 deaths were recorded. FLD was significantly associated in each gender with blood pressure, total cholesterol, apolipoprotein B, uric acid, and C-reactive protein; weakly with fasting glucose; and inversely with high-density lipoprotein-cholesterol and sex hormonebinding globulin. In adjusted Cox models, FLD was(with a 5-fold HR) the major determinant of diabetes development. Analyses further disclosed significant independent prediction of CHD by FLD in combined gender [hazard ratio(HR) = 1.72, 95% confidence interval(CI): 1.17-2.53] and men(HR = 2.35, 95%CI: 1.25-4.43). Similarly-adjusted models for all-cause mortality proved, however, not to confer risk, except for a tendency in prediabetics and diabetic women.CONCLUSION: A surrogate of FLD conferred significant high risk of diabetes and coronary heart disease, independent of some metabolic syndrome traits. Allcause mortality was not associated with FLD, except likely in the prediabetic state. Such a FLI may reliably be used in epidemiologic studies.

The relationships between step count and all-cause mortality and cardiovascular events:A doseresponse meta-analysis

Background:A goal of 10,000 steps per day is widely advocated,but there is little evidence to support that goal.Our purpose was to examine the doseresponse relationships between step count and all-cause mortality and cardiovascular disease risk.Methods:Cochrane Central Register of Controlled Trials,EMBASE,OVID,PubMed,Scopus,and Web of Science databases were systematically searched for studies published before July 9,2021,that evaluated the association between daily steps and at least 1 outcome.Results:Sixteen publications(12 related to all-cause mortality,5 related to cardiovascular disease;and 1 article contained 2 outcomes:both allcause death and cardiovascular events)were eligible for inclusion in the meta-analysis.There was evidence of a nonlinear doseresponse relationship between step count and risk of all-cause mortality or cardiovascular disease(p=0.002 and p=0.014 for nonlinearity,respectively).When we restricted the analyses to accelerometer-based studies,the third quartile had a 40.36%lower risk of all-cause mortality and a 35.05%lower risk of cardiovascular event than the first quartile(all-cause mortality:Q1=4183 steps/day,Q3=8959 steps/day;cardiovascular event:Q1=3500 steps/day,Q3=9500 steps/day;respectively).Conclusion:Our meta-analysis suggests inverse associations between higher step count and risk of premature death and cardiovascular events in middle-aged and older adults,with nonlinear doseresponse patterns.

Effect of Body Mass Index on All-cause Mortality and Incidence of Cardiovascular Diseases─Report for Meta-Analysis of Prospective Studies on Optimal Cut-off Points of Body Mass Index in Chinese Adults

Objective To verify the optimal cut-off points for overweight and obesity in Chinese adults based on the relationship of baseline body mass index (BMI) to all-cause mortality, and incidence of cardiovascular diseases from pooled data of Chinese cohorts. Methods The prospective study data of existing cohort studies in China were collected, and the age-adjusted all-cause mortality stratified by BMI were estimated. The similar analysis was repeated after excluding deaths within the first three years of follow-up and after excluding smokers. The incidence of age-adjusted coronary heart disease (CHD) and stroke stratified by BMI were also analyzed. Multiple Cox regression coefficients of BMI for the incidence of CHD and stroke after controlling other risk factors were pooled utilizing the methods of weighting by inverse of variance to reveal whether BMI had independent effect and its strength on the incidence of CHD and stroke. Results The data of 4 cohorts including 76 227 persons, with 745 346 person-years of follow-up were collected and analyzed. The age-adjusted all-cause mortality stratified by BMI showed a U-shaped curve, even after excluding deaths within the first three years of follow-up and excluding smokers. Age-adjusted all-cause mortality increased when BMI was lower than 18.5 and higher than 28. The incidence of CHD and stroke, especially ishemic stroke increased with increasing BMI, this was consistent with parallel increasing of risk factors. Cox regression analysis showed that BMI was an independent risk factor for both CHD and stroke. Each amount of 2 kg/m2 increase in baseline BMI might cause 15.4%, 6.1% and 18.8 % increase in relative risk of CHD, total stroke and ischemic stroke. Reduction of BMI to under 24 might prevent the incidence of CHD by 11% and that of stroke by 15 % for men, and 22 % of both diseases for women. Conclusion BMI ≤18.5, 24-27.9 and ≥28 (kg/m2) is the appropriate cut-off points for underweight, overweight and obesity in Chinese adults.

Adverse associations of sedentary behavior with cancer incidence and all-cause mortality:A prospective cohort study

Background:Inconsistent results have been reported in developed countries for relationships between sedentary behavior and cancer incidence and mortality,and evidence from the Chinese population is scarce.This study aimed to investigate such relationships in large Chinese population-based prospective cohorts and to explore the joint effect and interaction of sedentary behavior and moderate-to-vigorous physical activity(MVPA)on these relationships.Methods:We included 95,319 Chinese adults without cancer from 3 large cohorts and assessed their sedentary behavior and physical activity with a unified questionnaire.Cancer incidence and mortality were confirmed by interviewing participants or their proxies and checking hospital records and death certificates.Hazard ratios(HRs)and 95%confidence intervals(95%CIs)for cancer and mortality were estimated using Cox proportional hazards regression models.Results:During 559,002 person-years of follow-up,2388 cancer events,1571 cancer deaths,and 4562 all-cause deaths were recorded.Sedentary behavior was associated with increased risk of developing cancer and deaths in a doseresponse manner.The multivariable-adjusted HRs(95%CIs)were the following:HR=1.16,95%CI:1.01-1.33;HR=1.24,95%CI:1.04-1.48;and HR=1.15,95%CI:1.04-1.28 for cancer incidence,cancer mortality,and all-cause mortality,respectively,for those having≥10 h/day of sedentary time compared with those having<6 h/day of sedentary time.Sedentary populations(≥10 h/day)developed cancer or died 4.09 years and 2.79 years earlier,respectively,at the index age of 50 years.Failure to achieve the recommended level of MVPA may further aggravate the adverse associations,with the highest cancer and mortality risks being observed among participants with both≥10 h/day of sedentary time and<150 min/week of MVPA.Limitations of this study include the fact that physical activity information was obtained via questionnaire instead of objective measurement and that there were insufficient incident cases for the analysis of associations between sedentary behavior and site-specific cancers.Conclusion:Sedentary behavior was associated with an increased risk of cancer and all-cause mortality among Chinese adults,especially for those with≥10 h/day of sedentary time.It is necessary to reduce sedentary time,in addition to increasing MVPA levels,for the prevention of cancer and premature death.

BMI and BMI Changes to All-cause Mortality among the Elderly in Beijing： a 20-year Cohort Study

Objective To explore the association between body mass index （BMI） and all-cause mortality among the elderly in Beijing. Methods This analysis was based on the Beijing multidimensional longitudinal study of aging （BLSA）, which included 2,090 subjects over 55 years old and was followed-up from 1992 to 2012. BMI-mortality curves were drawn to find the optimal BMI range with the lowest mortality. Cox proportional hazard models were used to obtain the hazard ratios （HRs） for BMI and BMI changes in the overall population and in specific stratified populations. Results During follow-up, 2,264 deaths were recorded; BMI-mortality curve was U-shaped, with the lowest mortality at a BMI of approximately 25 kg/m2. After adjusting for gender, age, smoking, drinking and some pre-existing diseases, HRs for underweight, overweight and obesity compared with normal weight were 2.372 （95% C/： 2.254-2.632）, 0.767 （95% CI： 0.666-0.884） and 0.872 （95% CI： 0.830-1.246）, respectively. HR for BMI drop was 3.245 （95% CI： 0.824-22.772） in the underweight group and 1.892 （95% C/： 0.830-1.246） in the normal weight group, HR for BMI rise was 1.795 （95% CI： 1.243-2.591） in normal weight group and 2.962 （95% CI： 2.202-3.203） in the overweight group. Conclusion Keeping BMI in an overweight status and stable is related to a reduced mortality