Mortality In General Population Research Articles

Abstract 4137689: Artificial Intelligence Assessment of Diastolic Dysfunction by Electrocardiogram: Outcomes in Cardiac Intensive Care Unit Patients

Background: Left ventricular diastolic dysfunction (LVDD) predicts mortality in cardiac intensive care unit (CICU) patients. A novel artificial intelligence enhanced electrocardiogram (AIECG) algorithm can predict LVDD and mortality in general populations but has not been examined in the cardiac intensive care unit (CICU). We aim to assess if LVDD by AI-ECG is associated with in-hospital and one-year mortality in CICU patients. Methods: In this retrospective cohort study, we included consecutive unique adults admitted to the Mayo Clinic CICU from 2007 to 2018 with an admission AIECG, which AI assigned LVDD grade (0 to 3). Medial mitral E/e’ ratio >15 on transthoracic echocardiogram (TTE) defined elevated filling pressures. AIECG and TTE assessment of LVDD were used to assign patients to four groups based on TTE as gold standard: true and false negative, and true and false positive. In-hospital mortality was evaluated using multivariable logistic regression. One-year survival was evaluated using Kaplan-Meier curves and multivariable Cox proportional-hazards. Results: We included 11,868 patients (median age 69.5 years, 37.7% females); 48% had heart failure and 44% had acute coronary syndromes. AIECG LVDD grades were: grade 0 (normal), 33%; grade 1, 7%; grade 2, 39%; grade 3, 21%. In-hospital (adjusted OR) and one-year (adjusted HR) mortality increased in each higher AIECG LVDD grade (Figure A/B), before and after adjustment including TTE measurements. Patients with grade 2-3 LVDD by AIECG and medial mitral E/e’ ratio >15 by TTE (true positive) had the highest in-hospital (adjusted OR 2.5 [1.7-3.9]) and one-year (adjusted HR 1.9 [1.5-2.5]) mortality (Figure C/D), and mortality was elevated similarly in patients with either grade 2-3 LVDD by AIECG (false positive) or medial mitral E/e’ ratio >15 by TTE (false negative). Conclusions: The AIECG LVDD grade was strongly associated with in-hospital and one-year mortality in CICU patients, even after adjusting for clinical variables and TTE measurements. Patients with concordant AIECG and TTE for elevated filling pressures (true positive) were at highest risk.

Cost-effectiveness analysis of transcatheter aortic valve implantation versus surgical aortic valve replacement in patients with severe aortic stenosis at low risk of surgical mortality in Sweden

Background: Transcatheter aortic valve implantation (TAVI) has shown similar or improved clinical outcomes compared with surgical aortic valve replacement (SAVR) in patients with symptomatic severe aortic stenosis at low risk for surgical mortality. This cost-utility analysis compared TAVI with SAPIEN 3 versus SAVR in symptomatic severe aortic stenosis patients at low risk of surgical mortality from the perspective of the Swedish healthcare system. Methods: A published, two-stage, Markov-based cost-utility model that captured clinical outcomes from the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated according to Recommended Therapies (SWEDEHEART) registry (2018–2020) was adapted from the perspective of the Swedish healthcare system using local general population mortality, utility and costs data. The model had a lifetime horizon. Model outputs included changes in direct healthcare costs and health-related quality of life from using TAVI as compared with SAVR. Results: TAVI with SAPIEN 3 resulted in lifetime costs per patient of 940,541 Swedish krona (SEK) and lifetime quality-adjusted life years (QALYs) per patient of 7.16, whilst SAVR resulted in lifetime costs and QALYs per patient of 821,380 SEK and 6.81 QALYs, respectively. Compared with SAVR, TAVI offered an incremental improvement of +0.35 QALY per patient at an increased cost of +119,161 SEK per patient over a lifetime horizon, resulting in an incremental cost-effectiveness ratio of 343,918 SEK per QALY gained. Conclusion: TAVI with SAPIEN 3 is a cost-effective option versus SAVR for patients with symptomatic severe aortic stenosis at low risk for surgical mortality treated in the Swedish healthcare setting. These findings may inform policy decisions in Sweden for the management of this patient group.

Mortality and causes of death of traumatic spinal cord injury in Finland.

Prospective cohort study. To study the mortality rates of TSCI patients compared to matched controls and to examine possible TSCI-related mortality risk factors and causes of death. Oulu and Tampere University Hospital, Finland. All consecutive patients with a new TSCI were included in a prospective study (n = 344, 2012-16). All patients were followed until death or the end of 2019. Patients were compared to a control group formed by randomly choosing gender, age, municipality, and calendar time-matched controls (5 controls/TSCI patient). Standardized mortality ratios (SMR) were calculated using general population mortality rates. Mortality information was extracted from the Statistics of Finland (Helsinki, Finland). TSCI patients had an increased mortality (SMR = 2.9) compared with the Finnish population. During the observation period, 26% of TSCI patients and 12% of the matched controls died. Of the TSCI patient deaths, 51% occurred within the first two years postinjury. Increased age, severity of TSCI (as per International SCI Core Data Set) and fall were related to mortality (p < 0.05). The two most common etiologies of death were: circulatory (30%), and pulmonary diseases (28%). Pneumonia was the single most frequent disease leading to death among TSCI patients. During the first years after injury, the mortality of the patients with TSCI is double compared to the controls. Most deaths occur within two years postinjury. Elderly patients with more severe fall-related injury have the highest mortality risk. Circulatory diseases and pulmonary diseases, especially pneumonia, are the foremost causes of death after TSCI.

Associations between neutrophil-percentage-to-albumin ratio level and all-cause mortality and cardiovascular disease-cause mortality in general population: evidence from nhanes 1999-2010

Abstract Introduction Chronic inflammation is a recognized independent risk factor for cardiovascular disease (CVD), highlighting the need for reliable inflammatory indicators to predict CVD(1). As an inflammatory indicator which has been proved to have predictive value for the prognosis of CVDs, neutrophil percentage-to-albumin ratio (NPAR) has obtained increasing attention(2,3), but further research is needed to confirm the relationship with mortality in general population. Purpose To explore whether NPAR can serve as a predictive inflammatory indicator for CVD-cause and all-cause mortality in general population. Methods This prospective cohort study included 21317 individuals who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. The baseline NPAR level was calculated as Neutrophil percentage (%) * 100/Albumin (g/dl). Data for CVD and all-cause mortality were acquired by linking the cohort database with the National Death Index through December 31, 2019.Weighted Kaplan–Meier curves with log-rank tests were conducted to access cumulative survival differences across different NPAR results. Restricted cubic spline analyses were employed to examine the nonlinear association. Multivariable Cox proportional hazards regression models were used to compute hazard ratios and 95% CIs. Receiver Operating Characteristic (ROC) curves were used to compare predictive value of NPAR with systemic immune inflammation index (SII) and neutrophils percent. Results In this cohort study, during 270014 person-years of follow-up, 4074 all-cause deaths and 1116 CVD-cause deaths were documented. We found significant associations between elevated NPAR and both CVD-cause and all-cause mortality in Kaplan–Meier curves (both P for log-rank test&amp;lt;0.001). Restricted cubic splines revealed non-linear associations between NPAR level and both CVD-cause (P=0.018 for nonlinearity) and all-cause mortality (P&amp;lt;0.001 for nonlinearity) (Figure 1A and 1B). After adjusting for confounding factors, participants in the highest NPAR tertile had a significantly increased risk of all-cause mortality (HR: 1.46, 95% CI: 1.33-1.61) and CVD-cause mortality (HR: 1.54, 95% CI: 1.32-1.80) compared to those in the lowest tertile, while no association was detected for individuals in the middle tertile (Figure 2). The effect of NPAR was consistent across most subgroups, with no significant interaction with most covariates except for high cholesterol (CVD-cause mortality: P=0.014, all-cause mortality: P=0.022). Further ROC analysis confirmed that NPAR had higher predictive value than neutrophil percent and SII. Conclusions Elevated NPAR level was significantly associated with an increased risk of all-cause and CVD-cause mortality in general population.Given its easy-to-calculate nature and high predictive value, NPAR index, with implications in public health, deserves greater attention in inflammatory assessment and cardiovascular prevention.Figure 1 Nonlinear associationFigure 2 Cox regression table

The association between remnant cholesterol and all-cause mortality and cardiovascular mortality was modified by aged in American adults: a retrospective cohort study

Abstract Background Limited evidence exists regarding the association between remnant cholesterol (RC) and both all-cause and cardiovascular mortality. Also, the effect of age on the association between RC and the risk of mortality in general population has not been studied comprehensively. Therefore, the aim of this study is to investigate how age modifies the relationship between RC and the risk of all-cause and cardiovascular mortality. Methods A total of 21722 participants aged over 18 years were obtained from the National Health and Nutrition Examination Survey (1999–2018) , with follow-up mortality outcomes records linked to the National Death Index (NDI) until December 31, 2019 and divided into two groups (&amp;lt;65 years old and ≥65 years old).Weighted multivariable cox proportional hazards models and weighted restricted cubic spline (RCS) were used to estimate the relationship of RC with the risk of all-cause mortality and cardiovascular mortality among American adults. The age interaction between RC and all-cause mortality and cardiovascular mortality was assessed. Restricted cubic spline (RCS) and sensitivity analysis were also used. Results During a median 110-month follow-up, a total of 3176 (10.77%) all-cause deaths and 1002 (3.22%) cardiovascular related deaths were recorded. A significant age interaction between RC and all-cause or cardiovascular mortality was found. After adjusting for multiple potential confounding factors, higher RC was associated with an increased risk of all-cause mortality[RC per unit increase Hazard Ratio (HR) 1.45, 95% Confidence Interval (CI) 1.16–1.81, p=0.001] and cardiovascular mortality (RC per unit increase HR 1.80, 95% CI 1.15–2.84, p=0.010) specifically in the younger age group but not in the older age group. Consistent findings were observed in restricted cubic spline analyses and sensitivity analyses. Conclusion In our study, we observed that the association between serum RC and all-cause mortality and cardiovascular mortality was modified by age. Specifically, higher RC levels were found to be significantly associated with an increased risk of all-cause mortality and cardiovascular mortality exclusively in patients below 65 years old. This novel finding warrants further confirmation through randomized controlled trials to provide robust evidence.

Small Left Ventricular Chamber Size and Mortality in a Large General Population

Enlargement of the left ventricle (LV) is an important marker of adverse cardiac remodeling and poor prognosis. Previous studies demonstrated increased cardiovascular risk in small subsets of patients with small LV chamber size, however, the prognostic implications of small chamber size in a general population remains unclear. The objective of this study was to examine the prognosis of a small LV chamber in a large general cohort. All consecutive subjects that underwent echocardiography examinations from 2011 to 2023 were retrieved for analysis. Small chamber size was defined as end-diastolic diameter less than 42 mm for men and 37.8 mm for women as per ASE guidelines. The primary endpoint for the study was all-cause mortality. 46,529 subjects (mean age 60 ± 19 years, 56% males) were included of whom 3,787 had small LV chamber size. Clinical variables associated with small chamber included increasing age and lower BSA. Echocardiographic variables included higher relative wall thickness, and E/e' ratio. On multivariable analysis, the presence of a small LV was significantly associated with mortality (HR 1.34 with 95% CI 1.22-1.46; p <0.001). This finding was significant in both older (over 65 years) (HR 1.30 95% CI 1.19-1.41; p <0.001) and younger (HR 2.09 95% CI 1.81-2.41; p <0.001) subjects and in both males and females. In conclusion, in this retrospective large cohort study, small LV chamber size was significantly associated with mortality in a broad range of patients. Further study is necessary to elucidate mechanisms and design preventive strategies.

Transcatheter aortic valve implantation with SAPIEN 3 versus surgical aortic valve replacement in patients with symptomatic severe aortic stenosis at low risk of surgical mortality: a cost-utility analysis for Switzerland.

The 2021 European Society of Cardiology Guidelines on valvular heart disease recommend transcatheter aortic valve implantation (TAVI) for patients with symptomatic severe aortic stenosis at low surgical risk and age ≥75 years who are suitable for a transfemoral approach (recommendation class IA) based on two large randomised controlled trials (PARTNER 3 and Evolut Low Risk) comparing transcatheter aortic valve implantation with surgical aortic valve replacement (SAVR). Whether such an approach is cost-effective in Switzerland remains unclear. The aim of this cost-utility analysis was to compare transcatheter aortic valve implantation with SAPIEN 3 versus surgical aortic valve replacement in symptomatic severe aortic stenosis patients at low risk of surgical mortality from the perspective of Swiss compulsory health insurance using data from the PARTNER 3 trial (reflecting specifically the safety and efficacy of the SAPIEN 3 TAVI device). A previously published two-stage Markov-based model that captured clinical outcomes from the PARTNER 3 trial was adapted from the perspective of the Swiss compulsory health insurance system, using local or geographically close general population mortality and utility data, unit costs and medical resource use from publicly available sources and based on expert opinion. The model had a lifetime horizon with a 3% yearly discounting factor. The cost-utility analysis estimated changes in both direct healthcare costs and health-related quality-adjusted life years for transcatheter aortic valve implantation compared with surgical aortic valve replacement in patients with symptomatic severe aortic stenosis at low risk of surgical mortality. Overall, transcatheter aortic valve implantation with SAPIEN 3 resulted in lifetime costs per patient of CHF 79,534 and quality-adjusted life years per patient of 9.64, compared with surgical aortic valve replacement lifetime costs and quality-adjusted life years per patient of CHF 76,891 and 8.96, respectively. Compared with surgical aortic valve replacement, transcatheter aortic valve implantation was estimated to offer an incremental improvement of +0.68 quality-adjusted life years per patient at an increased cost of +CHF 2643 per patient over a lifetime horizon. The incremental cost-effectiveness ratio was CHF 3866 per quality-adjusted life year gained and remained below CHF 50,000 per quality-adjusted life year gained across several sensitivity analyses. This analysis suggests that transcatheter aortic valve implantation using the SAPIEN 3 device is likely to be a highly cost-effective alternative for symptomatic severe aortic stenosis patients at a low risk of surgical mortality, treated in the contemporary Swiss setting. These findings may help to inform a holistic approach when making policy decisions for the management of this patient group.

Risk of Suicide and Suicidality in Patients with Moderate to Severe Psoriasis: results from the British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR).

Psoriasis is associated with poor mental health and reduced quality of life. Although the high risk for depression in patients with psoriasis is well-established, their suicidality risk is uncertain. Previous studies provide contrasting results and have not included patients with clinically-confirmed severe disease. Our aim was to determine risk of suicide among patients with moderate to severe psoriasis compared with the general population, and investigate if psychiatric comorbidity or history of suicidality increases future suicidality risk in psoriasis. We further estimated the incidence of suicidal and self-injurious behaviours in patients. Analysis was performed using the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR). As controls, general population mortality and suicide data were used. There were 9 suicides in BADBIR. The incidence rate of suicide was 12.5 per 100,000 person-years (95% CI 6.53, 24.11) in BADBIR versus 11.0 per 100,000 person-years (95% CI 10.7, 11.3) in the general population in England and Wales. Among patients, psychiatric comorbidity or past suicidality was associated with higher risk for suicidal ideation, suicide attempts and self-injurious behaviours. Suicide rates among patients with moderate to severe psoriasis were not significantly higher compared with the general population. Suicide is a rare event and our results are limited by the uncertainty in the estimate reliability. However, considering the high depression prevalence in psoriasis, our findings support the need for prompt assessment of patients for psychiatric comorbidities and suicidality history. Further research is required on suicidal behaviours and the role of psoriasis severity.

Associations between neutrophil-percentage-to-albumin ratio level and all-cause mortality and cardiovascular disease-cause mortality in general population: evidence from NHANES 1999-2010.

Chronic inflammation is a recognized independent risk factor for cardiovascular disease (CVD), highlighting the need for reliable inflammatory indicator to predict CVDs. As an inflammatory indicator which has been proved to have predictive value for prognosis of CVDs, neutrophil percentage-to-albumin ratio (NPAR) has obtained increasing attention, but further research is needed to confirm the relationship with mortality in the general population. This prospective cohort study included 21,317 individuals who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010, where baseline characteristics and NPAR level were extracted. Data for CVD and all-cause mortality were acquired by linking the cohort database with the National Death Index through December 31, 2019. We employed restricted cubic spline analyses to examine the nonlinear association. Weighted Kaplan-Meier curves with log-rank tests were conducted to access cumulative survival differences across different NPAR results. Multivariable Cox proportional hazards regression models were used to compute hazard ratios and 95% CIs. Receiver Operating Characteristic (ROC) curves were used to compare predictive value of NPAR with systemic immune inflammation index (SII) and neutrophils percent. In this cohort study, during 270,014 person-years of follow-up, 4,074 all-cause deaths and 1,116 CVD-cause deaths were documented. NPAR levels exhibited significant nonlinear associations with both CVD-cause (P = 0.018 for nonlinearity) and all-cause mortality (P < 0.001 for nonlinearity). Participants in the highest NPAR tertile had a significantly increased risk of all-cause mortality (HR: 1.46, 95% CI: 1.33-1.61) and CVD-cause mortality (HR: 1.54, 95% CI: 1.32-1.80) compared to those in the lowest tertile in the fully adjusted model, while no association was detected for individuals in the middle tertile. Further ROC analysis confirmed that NPAR had higher predictive value than neutrophil percent segment and SII. Elevated NPAR level was significantly associated with an increased risk of all-cause and CVD-cause mortality in general population. The high predictive value of NPAR, combined with the easy-to-calculate property, suggests that its potential as a novel inflammatory indicator is worthy of further investigation.

The Impact of the Approach to Accounting for Age and Sex in Economic Models on Predicted Quality-Adjusted Life-Years.

The method used to model general population mortality estimates in cohort models can make a meaningful difference in appraisals; particularly in scenarios involving potentially curative treatments where a prior National Institute for Health and Care Excellence (NICE) appraisal demonstrated that this assumption alone could make a difference of ~£10,000 to the incremental cost-effectiveness ratio. Our objective was to evaluate the impact of different methods for calculating general population mortality estimates on the predicted total quality-adjusted life expectancy (QALE) as well as absolute and proportional quality-adjusted life year (QALY) shortfall calculations. We employed three distinct methods for deriving general population mortality estimates: firstly, utilizing the population mean age at baseline; secondly, modelling the distribution of mean age at baseline by fitting a parametric distribution to patient-level data sourced from the Health Survey for England (HSE); and thirdly, modelling the empirical age distribution. Subsequently, we simulated patient age distributions to explore the effects of mean starting age and variance levels on the predicted QALE and applicable severity modifiers. Provided sample code in R and Visual Basic for Applications (VBA) facilitates the utilization of individual patient age and sex data to generate weighted average survival and health-related quality of life (utility) outputs. We observed differences of up to 10.4% (equivalent to a difference of 1.01 QALYs in quality-adjusted life-expectancy) between methods using the HSE dataset. In our simulation study, increasing variance in baseline age diminished the accuracy of predictions relying solely on mean age estimation. Differences of -0.30 to 2.24 QALYs were found at a standard deviation of 20%; commonly observed in trials. For potentially curative treatments this would represent a difference in economically justifiable price of -£4,500-+£33,600 at a cost-effectiveness threshold of £30,000 per QALY for a treatment with a 50% cure rate. For lower baseline ages, the population mean method tended to overestimate QALE, whereas for higher baseline ages, it tended to underestimate QALE compared with individual patient age-based approaches. The severity modifier assigned did not vary, however, apart from simulations with means at the extremes of the age distribution or with very high variance. Our analysis underscores the necessity of accounting for the distribution of mean age at baseline, as failure to do so can lead to inaccurate QALE estimates, thereby affecting calculations of incremental costs and QALYs in models, which base survival and quality of life predictions on general population expectations. We would recommend that patient age and sex distribution should be accounted for when incorporating general population mortality in economic models. Provided sufficient sample size, utilizing the observed empirical distribution for the expected population in clinical practice is likely to yield the most accurate results. However, in the absence of patient-level data, selecting a suitable parametric distribution is recommended.

General Population Mortality Adjustment in Survival Extrapolation of Cancer Trials: Exploring Plausibility and Implications for Cost-Effectiveness Analyses in HER2-Positive Breast Cancer in Sweden.

In economic evaluations of novel therapies, assessing lifetime effects based on trial data often necessitates survival extrapolation, with the choice of model affecting outcomes. The aim of this study was to assess accuracy and variability between alternative approaches to survival extrapolation. Data on HER2-positive breast cancer patients from the Swedish National Breast Cancer Register were used to fit standard parametric distribution (SPD) models and excess hazard (EH) models adjusting the survival projections based on general population mortality (GPM). Models were fitted using 6-y data for stage I and II, 4-y data for stage III, and 2-y data for stage IV cancer reflecting an early data cutoff while maintaining sufficient events for comparison of model estimates with actual long-term outcomes. We compared model projections of 15-y survival and restricted mean survival time (RMST) to 15-y registry data and explored the variability between models in extrapolations of long-term survival. Among 11,224 patients compared with the observed registry 15-y RMST estimates across the disease stages, EH cure models provided the most accurate estimates in patients with stage I to III cancer, whereas EH models without cure most closely matched survival in patients with stage IV cancer, in which cure assumption was less plausible. The Akaike information criterion-averaged model projections varied as follows: -8.2% to +5.3% for SPD models, -4.9% to +5.2% for the EH model without a cure assumption, and -19.3% to -0.2% for the EH model with a cure assumption. EH models significantly reduced between-model variance in the predicted RMSTs over a 50-y time horizon compared with SPD models. EH models may be considered as alternatives to SPD models to produce more accurate and plausible survival extrapolation that accounts for general population mortality. Excess hazard (EH) methods have been suggested as an approach to incorporate background mortality rates in economic evaluation using survival extrapolation.We highlight that EH models with or without a cure assumption can produce more accurate survival projections and significantly reduce between-model variability in comparison with standard parametric distribution models across cancer stages.EH models may be a preferred modeling method to reduce model uncertainty in health economic modeling since models that would otherwise have produced implausible extrapolations are constrained by the EH framework.Reduced uncertainty in economic evaluations will enhance the application of evidence-based health care decision making.

Long-term survival analysis of patients with primary Sjögren's syndrome in China: A multicenter retrospective cohort study.

This study aimed to evaluate the long-term survival, causes of death, and prognostic factors in Chinese patients with primary Sjögren syndrome (pSS). We included patients with pSS registered in the Chinese Rheumatism Data Centre between May 2016 and December 2021, and collected baseline clinical, laboratory, and treatment data. Survival and standard mortality rates were calculated using general population mortality data. Factors related to mortality were identified using Cox proportional hazards regression. Among the 8588 patients included, 274 died during a median follow-up of 4.0 years. The overall standardized mortality ratio was 1.61 (95% CI: 1.43-1.81). Overall survival rates were 98.2% at 5 years and 93.8% at 10 years. The predominant causes of death were comorbidities, including cardiovascular diseases, tumors, and infections, while the most frequent pSS-related causes of death were interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). Male sex, older age, ILD, PAH, and high EULAR Sjögren's syndromedisease activity index (ESSDAI), thrombocytopenia, anemia, high immunoglobulin A (IgA) level, and glucocorticoid treatment independently increased the mortality risk, while using hydroxychloroquine was a protective factor. Mortality rates have significantly increased in Chinese patients with pSS. Comorbidities, rather than pSS-related organ damage, were the main causes of death. All-cause mortality was associated with male sex, older age, ILD, PAH, high ESSDAI, thrombocytopenia, anemia, high IgA level, and glucocorticoid treatment, whereas hydroxychloroquine use might improve the long-term survival.

Randomized Controlled Trial Based US Commercial Payor Cost-Effectiveness Analysis of Endoscopic Sleeve Gastroplasty Versus Lifestyle Modification Alone for Adults With Class I/II Obesity.

Endoscopic sleeve gastroplasty (ESG) is a minimally invasive day procedure that the MERIT randomized controlled trial (RCT) has demonstrated to be an effective and safe method of weight loss versus lifestyle modification alone. We sought to evaluate the cost-effectiveness of ESG from the perspective of a US commercial payer in a cohort of adults with class II and class I obesity with diabetes based on this RCT. We used a Markov modelling approach with BMI group health states and an absorbing death state. Baseline characteristics, utilities, BMI group transition probabilities, and adverse events (AEs) were informed by patient-level data from the MERIT RCT. Mortality was estimated by applying BMI-specific hazard ratios to US general population mortality rates. We used BMI-based health state utilities to reflect the impact of obesity comorbidities and applied disutilities due to ESG AEs. Costs included intervention costs, AE costs, and BMI-based annual direct healthcare costs to account for costs associated with obesity comorbidities. A willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY) was assumed. In our base-case analysis over a 5-year time horizon, ESG was cost-effective versus lifestyle modification alone with an incremental cost-effectiveness ratio of $23,432/QALY. ESG remained cost-effective in all sensitivity analyses we conducted and was dominant in analyses with longer time horizons. ESG is a cost-effective treatment option for people living with obesity and should be considered in commercial health plans as an additional treatment option for clinically eligible patients.

Association between serum folate concentrations and all-cause mortality in U.S. adults: a cohort study based on National Health and Nutrition Examination Survey III.

The association between serum folate and all-cause mortality in general population remains unclear. The objective of this study was to investigate the potential association between serum folate concentrations and all-cause mortality in a large, prospective, long-term U.S. cohort. Our study included adults from the National Health and Nutrition Examination Survey (NHANES) III, and mortality data was obtained by linking with the National Death Index (NDI) until December 31, 2019. Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) to assess the association between serum folate concentrations and all-cause mortality. A total of 12,862 participants were included in this cohort study. After a median follow-up of 26.4 years [interquartile range (IQR), 15.4-28.7 years], a total of 5,299 deaths were recorded. The risk of death was lower by 12% per 1.0 g/L increase in log-transformed serum folate concentrations (HR, 0.88; 95% CI, 0.83-0.94). Compared with the lowest quartiles of serum folate level, the risk of death was lower in the second (HR, 0.84; 95% CI, 0.72-0.97), third (HR, 0.78; 95% CI, 0.68-0.91) and the highest quartiles (HR, 0.78; 95% CI, 0.69-0.88) in multivariable-adjusted model. In subgroup analyses, the inverse association between serum folate and all-cause mortality remained statistically significant for women, men and non-Hispanic White people. Higher serum folate levels were found to be significantly associated with reduced risk of all-cause mortality. However, further studies are needed to verify these findings and explore the underlying mechanism.

#1778 Effects of comorbidities, social deprivation and sex on the excess mortality of French ESKD patients on dialysis

Abstract Background and Aims Inequalities in access to care may affect End-stage Kidney Disease (ESKD) patient's overall mortality, i.e. mortality directly or indirectly related to ESRD (excess mortality) as well as mortality related to other causes of death. Previous studies in France have identified sex and comorbidities, especially diabetes and cardiovascular diseases, as factors influencing the overall mortality of ESKD patients, whereas social deprivation was not associated with overall mortality. However, no study has yet examined the impact of these factors on excess mortality in dialysis patients. This study thus aims to quantify the effects of social deprivation, sex and comorbidities on the excess mortality of ESKD patients on dialysis in France. Method This retrospective observational study included adults aged 18-85 years who started dialysis in France between 2017 and 2019, and were followed up until 31 December 2022. Dialysis patients receiving a transplant were censored. Analyses were based on the excess hazard approach: the overall mortality rate was decomposed into the sum of a mortality rate associated with ESKD (the excess rate) and a mortality rate associated with other causes of death (the expected rate). The latter is usually drawn from mortality tables for the general population stratified by demographic covariates. A model is then fitted in order to estimate the excess mortality hazard: the impact of covariates on this hazard is quantified in terms of excess hazard ratios. In France, mortality tables are provided by the “Institut National de la Statistique et des Études Économiques” and stratified by age, calendar year, sex, and “départements” of residence. However, stratification by level of social deprivation or levels of the Charlson Comorbidity Index is not available, which may bias the excess mortality hazard estimates. To assess the impact of using inadequately stratified life tables on estimating excess hazard, we compared the following models using Akaike's Information Criterion: (i) an excess hazard model using the standard life tables and accounting for the hierarchical structure of the data by including a random intercept for the “département” (M0), (ii) an excess hazard model with a model-based life table correction and with (M1) or without (M2) the random intercept at the “département” level, and (iv) an excess hazard model in which the life table correction is achieved by using an individual frailty term (M3). Results 29148 dialysis patients were included in the study, 65% of whom were men. Compared to the other regression models, the excess hazard model (M2) was the best model (AIC: M0 = 58936.69; M1 = 58966.94, M2 = 58870.41, M3 = 58908.59). There were no differences in excess mortality by deprivation status {EHR (Q5 versus others) 1.054 [0.992; 1.120]; p value = 0.088}. Excess mortality was higher for women than for men {HER (women versus men) = 1.083 [1.017; 1.154]; P-value = .012}. Excess mortality was higher in patients with comorbidities than in those without, and in those who started dialysis in emergency compared with those who started on a planned basis. Elderly patients on dialysis had a higher excess hazard than younger patients. The ratio between the other cause mortality of French dialysis patients and general population was equal to 2.18[1.95; 2.45]. This means that the other cause mortality of French dialysis patients is 2.18 higher than that of the general population with the same characteristics (Table 1, Fig. 1). Conclusion Using a methodology allowing to account for the insufficient stratification of population mortality tables, we identified several factors other than sex that might be targeted by public health interventions. For example, improved referral to nephrologists could reduce the impact of emergency dialysis. The extent of these inequalities will be better understood by comparison of these results with those of ESKD patients on dialysis in European countries.

ALBUMINURIA IS AN IMPORTANT PREDICTOR FOR ALL CAUSE MORTALITY IN GENERAL RURAL POPULATION

Objective: Albuminuria stands as a robust predictor of both cardiovascular and all-cause mortality, despite that there remains a notable gap in understanding how albuminuria's association with mortality varies across subgroups defined by sex, comorbidities and estimated glomerular filtration rate (eGFR). The aim of this study was to determine whether the association between albuminuria and mortality differs according to eGFR, sex, and comorbidities. Design and method: This prospective observational study includes 857 adult subjects from the ENAH rural study in Croatia. Albuminuria, the ratio of urinary albumin to creatinine (ACR) was subsequently categorized into two levels as &gt;30mg/g (group A) and &lt;30mg/g (group B). Results: Subjects from the group A were older (70.5 vs. 49.0 years), had a higher BMI (29.7 vs. 27.4 kg/m2), and lower eGFR (69.3 vs. 85.2 ml/min/1.73m2). They had higher prevalence of arterial hypertension (AH) (78.2% vs. 53.3%) and diabetes (DM) (30.8% vs. 11.9%) (p&lt;0.001 for both). A significantly higher mortality rate (64.1% vs. 27.3%, p&lt;0.001) was observed in Group 1 compared to the group 2. In logistic regression analysis the highest odds of mortality were observed for ACR&gt;30mg/g (OR=2.43, 95%CI=1.40-4.19, p=0.002), followed with male gender (OR=1.79, 95%CI=1.28-2.49, p&lt;0.001), DM (OR=1.71, 95%CI=1.10-2.67, p=0.018), eGFR &lt; 60 (OR=1.71, 95%CI 1.00-2.94 and AH (OR=1.55, 95%CI=1.06-2.27, p=0.025). Conclusions: Our study underscores the significant impact of albuminuria on all-cause mortality in general rural population indicating that this diagnostic tool should be included in everyday clinical work.

Cardiorespiratory fitness is a strong and consistent predictor of morbidity and mortality among adults: an overview of meta-analyses representing over 20.9 million observations from 199 unique cohort studies

ObjectiveTo examine and summarise evidence from meta-analyses of cohort studies that evaluated the predictive associations between baseline cardiorespiratory fitness (CRF) and health outcomes among adults.DesignOverview of systematic reviews.Data sourceFive bibliographic...

Inter-leg systolic blood pressure difference has been associated with all-cause and cardiovascular mortality: analysis of NHANES 1999–2004

BackgroundInter-leg systolic blood pressure difference (ILSBPD) has emerged as a novel cardiovascular risk factor. This study aims to investigate the predictive value of ILSBPD on all-cause and cardiovascular mortality in general population.MethodsWe combined three cycles (1999–2004) of the National Health and Nutrition Examination Survey (NHANES) data. Levels of ILSBPD were calculated and divided into four groups based on three cut-off values of 5, 10 and 15mmHg. Time-to-event curves were estimated with the use of the Kaplan-Meier method, and two multivariable Cox proportional hazards regression models were conducted to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause and cardiovascular mortality associated with ILSBPD.ResultsA total of 6 842 subjects were included, with the mean (SD) age of 59.5 (12.8) years. By December 31, 2019, 2 544 and 648 participants were identified all-cause and cardiovascular mortality respectively during a median follow-up of 16.6 years. Time-to-event analyses suggested that higher ILSBPD was associated with increased all-cause and cardiovascular mortality (logrank, p < 0.001). Every 5mmHg increment of ILSBPD brings about 5% and 7% increased risk of all-cause and cardiovascular mortality, and individuals with an ILSBPD ≥ 15mmHg were significantly associated with higher incidence of all-cause mortality (HR 1.43, 95%CI 1.18–1.52, p < 0.001) and cardiovascular mortality (HR 1.73, 95%CI 1.36–2.20, p < 0.001) when multiple confounding factors were adjusted. Subgroup and sensitivity analysis confirmed the relationship.ConclusionsOur findings suggest that the increment of ILSBPD was significantly associated with higher risk of all-cause and cardiovascular mortality in general population.

Non-linear associations of HOMA2-IR with all-cause mortality in general populations: insights from NHANES 1999-2006.

The association between homeostatic model assessment (HOMA2-IR) and mortality in obese and non-obese populations has not been clearly explained. A total of 7,085 individuals aged ≥ 20 years from the 1999-2006 National Health and Nutrition Examination Survey were included in the study. Study endpoints were all-cause and cardiovascular mortality. Multivariate Cox proportional hazards regression models with restricted cubic spline analysis were used for analysis. In the study populations, a total of 1666 all-cause deaths and 555 cardiovascular (CV) deaths were recorded during a mean follow-up of 195.53 months. Notably, a significant difference in obesity was observed in the association between HOMA2-IR and mortality. After adjustment for multiple variables, HOMA2-IR was positively associated with all-cause mortality in all participants, in those with normal BMI, and in those with obesity. Conversely, tertile 2 of HOMA2-IR was associated with a lower risk of all-cause mortality in participants with obesity compared with tertile 1 (adjusted hazard ratio, 0.68; 95% confidence interval, 0.52-0.89; P = 0.005). Results from restricted cubic spline analysis showed a J-shaped association between HOMA2-IR and all-cause and CV mortality. In addition, a nonlinear U-shaped correlation with all-cause (P for nonlinear < 0.001) and CV (P for nonlinear = 0.002) mortality was observed in the population with obesity, with inflection points of HOMA2-IR identified at 1.85 and 1.75. Below the inflection point of 1.85, a negative relationship between HOMA2-IR and all-cause mortality was observed. Elevated HOMA2-IR showed a notable correlation with increased risk of all-cause mortality. It was noteworthy that excessively reduced levels of insulin resistance showed a distinct association with increased mortality in individuals with obesity.

Associations of sleep disorders with all-cause and cause-specific mortality in cancer survivors: a cross-sectional analysis of the NHANES 2005–2016

BackgroundThe circadian clock and endoplasmic reticulum stress signaling play important roles in oncogenesis and development of cancer. Sleep disorders have been linked to an elevated risk of mortality in general populations. Nonetheless, the evidence for the sleep disorders-mortality association among cancer patients is limited. We aimed to prospectively investigate the association of sleep disorders with all-cause, cancer, and cardiovascular disease (CVD) mortality among cancer individuals.MethodsWe assessed 3187 participants with cancer from the National Health and Nutrition Examination Survey 2005–2016 cohorts with a median follow-up time of 83.0 months. Multivariable Cox proportional hazards models estimated the adjusted hazard ratio (HR) and 95% confidence interval (CI).ResultsMultivariable Cox proportional hazards models showed that sleep disorders were associated with a higher risk of all-cause mortality (HR 1.23, 95%CI: 1.06,1.42), cancer mortality (HR 1.30, 95%CI: 1.02, 1.66), and cardiovascular disease mortality (HR 1.35, 95%CI: 1.02, 1.80). After the total group was stratified by gender, the high HRs were observed in men (P < 0.05), not in women. The correlation between sleep disorders and higher long-term mortality was also significant after individuals who died within 2 years of follow-up were excluded, with HR 1.24 (95%CI: 1.07, 1.45) in model I, HR 1.20 (95%CI: 1.02, 1.42) in model II for long-term all-cause mortality, HR (95%CI: 1.00, 1.74) in model I for long-term cancer mortality, and HR 1.5 (95%CI:1.12, 2.02) in model I, HR 1.45 (95%CI: 1.06, 1.99) in model II for long-term CVD mortality.ConclusionsSleep disorders were associated with a higher risk of all-cause mortality, cancer mortality, and CVD mortality, as well as long-term mortality in cancer patients. Our finding underlies the importance of screening for sleep disorders for all cancer survivors and the urge to integrate sleep health as an important part of cancer care more effectively. Male individuals may be particularly vulnerable and could benefit from more frequent screening.