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Objectives:Previous studies using objective parameters have shown that irregular sleep is associated with the disease incidence, progression, or mortality. This study aimed to determine the association between subjective sleep duration and sleep regularity, with mortality in a large population., Methods:Participants were from the Japan Multi-Institutional Collaborative Cohort study. We obtained information from each participant on sleep duration, sleep regularity, and demographics and overall lifestyle using self-administered questionnaires. We defined sleep regularity according to participants' subjective assessment of sleep/wake time regularity. Participants (n = 81,382, mean age: 58.1 ± 9.1years, males: 44.2%) were classified into 6 groups according to sleep duration and sleep regularity. Hazard ratios (HR) for time-to-event of death were calculated using the Cox proportional hazards model., Results:The mean follow-up period was 9.1 years and the mean sleep duration was 6.6 h/day. Irregular sleep significantly increased the risk of all-cause mortality in all models compared with regular sleep (HR 1.30, 95% confidence interval; CI, 1.18-1.44), regardless of sleep duration. Multivariable analysis of the 6 groups by sleep pattern (sleep regularity and duration) showed irregular sleep and sleep durations of, Conclusions:Our study shows an association between sleep irregularity and all-cause mortality in a large Japanese population. Our findings provide further confirmation of the need to consider not only sleep duration, but also the regularity aspect of sleep schedules.

Objective: To examine the association between surgical waiting times (SWTs) and all-cause mortality (ACM) in non-metastatic patients with RCC, in relation to tumour stage. Patients and methods: This nation-wide population-based cohort study included 9,918 M0 RCC patients registered in the National Swedish Kidney Cancer Register, between 2009 and 2021, followed-up for ACM until 9 December 2021, and having measured SWTs. The associations between primarily SWTs from date of radiological diagnosis to date of surgery (WRS) and secondarily SWTs from date of radiological diagnosis to date of treatment decision (WRT) and date of treatment decision to date of surgery (WTS), in relation to ACM, were analysed using Cox regression analysis, adjusted for clinical and demographic characteristics, stratified and unstratified according to T-stage. Results: During a mean follow-up time of 5 years (49,873 person-years), 23% (n = 2291) of the patients died. The adjusted hazard ratio (AHR) for WRS (months) for all patients was 1.03 (95% confidence interval [CI] = 1.02–1.04; p < 0.001). When subdividing WRS on T-stage, the AHRs were 1.03 (95% CI = 1.01–1.04; p < 0.001) and 1.05 (95% CI = 1.02–1.08; p = 0.003) for stages T1 and T3, respectively, while non-significant for T2 (p = 0.079) and T4 (p = 0.807). Similar results were obtained for WRT and WTS. Conclusions: Prolonged SWTs significantly increased the risk of early overall death among patients with RCC. The increased risk of early death from any cause show the importance of shortening SWTs in clinical work of patients with this malignant disease.

Purpose Epidemiological studies have indicated a higher prevalence of hypothyroidism in breast cancer patients, possibly related to shared risk factors and breast cancer treatments. However, few studies have evaluated how hypothyroidism impacts survival outcomes in breast cancer patients. We aimed to determine the association between hypothyroidism and breast cancer-specific and all-cause mortality. Methods We conducted a population-based study using the Scottish Cancer Registry to identify women diagnosed with breast cancer between 2010 and 2017. A matched comparison cohort of breast cancer-free women was also identified. Using hospital diagnoses and dispensed prescriptions for levothyroxine, we identified hypothyroidism diagnosed before and after breast cancer diagnosis and determined associations with breast cancer-specific and all-cause mortality. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for potential confounders. Results A total of 33,500 breast cancer patients were identified, of which 3,802 had hypothyroidism before breast cancer diagnosis and 565 patients went on to develop hypothyroidism after. Breast cancer patients had higher rates of hypothyroidism compared with cancer-free controls (HR 1.14, 95% CI 1.01–1.30). Among breast cancer patients, we found no association between hypothyroidism (diagnosed before or after) and cancer-specific mortality (before: HR 0.99, 95% CI 0.88–1.12, after: HR 0.97, 95% CI 0.63–1.49). Similar associations were seen for all-cause mortality. Conclusion In a large contemporary breast cancer cohort, there was little evidence that hypothyroidism, either at diagnosis or diagnosed after breast cancer, was associated with cancer-specific or all-cause mortality.

Background The effects of left atrial appendage (LAA) occlusion compared to non-vitamin K antagonist oral anticoagulant (NOAC) therapy in patients with atrial fibrillation (AF) remain unknown. Aims We aimed to evaluate the outcomes in patients with AF who received LAA occlusion vs. NOAC therapy. Methods We utilised data from TriNetX which is a global federated health research network currently containing data for 88.5 million patients. ICD-10 codes were employed to identify AF patients treated with either LAA occlusion or NOAC between 1st December 2010 and 17th January 2019. Clinical outcomes of interest were analysed up to 2 years. Results 108,697 patients were included. Patients who underwent LAA occlusion were younger, more likely to be white Caucasian and male, had a greater incidence of comorbidities, and were less likely to be prescribed other cardiovascular medications. Using propensity score matching, the risk of all-cause mortality was significantly lower among patients who received LAA occlusion compared to NOAC therapy [1.51% vs. 5.60%, RR 0.27 (95% CI 0.14–0.54)], but there were no statistical differences in the composite thrombotic or thromboembolic events [8.17% vs. 7.72%, RR 1.06 (95% CI 0.73–1.53)], ischaemic stroke or TIA [4.69% vs. 5.45%, RR 0.86 (95% CI 0.54–1.38)], venous thromboembolism [1.66% vs. 1.51%, RR 1.10 (95% CI 0.47–2.57)] and intracranial haemorrhage [1.51% vs. 1.51%, RR 1.00 (95% CI 0.42–2.39)]. Conclusion Overall, LAA occlusion might be a suitable alternative to NOAC therapy for stroke prevention in patients with AF. Graphical abstract

Supplemental Digital Content is available in the text., It remains debated whether pulse pressure is associated with left ventricular traits and adverse outcomes over and beyond mean arterial pressure (MAP) in patients with heart failure (HF) with preserved ejection fraction. We investigated these associations in 3428 patients with HF with preserved ejection fraction (51.5% women; mean age, 68.6 years) enrolled in the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist). We computed association sizes and hazards ratios with 1-SD increase in MAP and pulse pressure. In multivariable-adjusted analyses, association sizes (P≤0.039) for MAP were 0.016 cm and 0.014 cm for septal and posterior wall thickness, −0.15 for E/A ratio, −0.66 for E/e′, and −0.64% for ejection fraction, independent of pulse pressure. With adjustment additionally applied for MAP, E/A ratio and longitudinal strain increased with higher pulse pressure with association sizes amounting to 0.067 (P=0.026) and 0.40% (P=0.023). In multivariable-adjusted analyses of both placebo and spironolactone groups, lower MAP and higher pulse pressure predicted the primary composite end point (P≤0.028) and hospitalized HF (P≤0.002), whereas MAP was also significantly associated with total mortality (P≤0.007). Sensitivity analyses stratified by sex, median age, and region generated confirmatory results with exception for the association of adverse outcomes with pulse pressure in patients with age ≥69 years. In conclusion, the clinical application of MAP and pulse pressure may refine risk estimates in patients with HF with preserved ejection fraction. This finding may help further investigation for the development of HF with preserved ejection fraction preventive strategies targeting pulsatility and blood pressure control.

Arterial stiffness is a progressive aging process that predicts cardiovascular disease. Pulse wave velocity (PWV) has emerged as a noninvasive, valid, and reliable measure of arterial stiffness and an independent risk predictor for adverse outcomes. However, up to now, PWV measurement has mostly been used as a tool for risk prediction and has not been widely used in clinical practice. This consensus paper aims to discuss multiple PWV measurements currently available in Asia and to provide evidence-based assessment together with recommendations on the clinical use of PWV. For the methodology, PWV measurement including the central elastic artery is essential and measurements including both the central elastic and peripheral muscular arteries, such as brachial-ankle PWV and cardio-ankle vascular index, can be a good alternative. As Asian populations are rapidly aging, timely detection and intervention of “early vascular aging” in terms of abnormally high PWV values are recommended. More evidence is needed to determine if a PWV-guided therapeutic approach will be beneficial to the prevention of cardiovascular diseases beyond current strategies. Large-scale randomized controlled intervention studies are needed to guide clinicians.

Chenbo Xu,1 Lizhe Sun,1 Mengya Dong,2 Habib Ullah,3 Hameed Ullah,1 Juan Zhou,1,4 Zuyi Yuan1,5 1Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Cardiovascular Medicine, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, People’s Republic of China; 3Department of Cardiology, Dow University of Health and Sciences, Karachi, Pakistan; 4Key Laboratory of Molecular Cardiology of Shaanxi Province, Xi’an, Shaanxi, People’s Republic of China; 5Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Zuyi Yuan; Hameed UllahDepartment of Cardiovascular Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xi’an, Shaanxi, 710061, People’s Republic of ChinaTel +86 29 8532 3819; +86 29 8532 3524Email zuyiyuan@mail.xjtu.edu.cn; 807287144@qq.comPurpose: Anion gap (AG) is a valuable and easily obtained clinical tool for differentially diagnosis of acid-base disorders. Current understanding of the prognostic impact of AG on mortality after acute myocardial infarction (AMI) is limited. We aimed to investigate whether AG is a predictor of short-term and long-term all-cause mortality after AMI.Patients and Methods: We examined 1806 patients diagnosed with AMI in intensive care unit from the Medical Information Mart for Intensive Care III (MIMIC-III) database. We analyzed the association of AG with 30-day, 180-day and 1-year all-cause mortality on a continuous scale and in categories, using multivariable Cox regression. We utilized restricted cubic splines to evaluate the linearity between hazard ratio (HR) and AG concentrations.Results: AG was associated with a higher risk of 30-day, 180-day and 1-year all-cause mortality, with adjusted HRs of 1.083 (95% CI 1.051 to 1.117), 1.077 (95% CI 1.049 to 1.105), and 1.074 (95% CI 1.047 to 1.101), respectively. The results were consistent in subgroup analyses. The association between AG and all-cause mortality was linear for 180-day and 1-year mortality, and near linear for 30-day mortality, as higher concentrations were associated with high all-cause mortality. When stratified according to quartiles, AG was associated with 30-day mortality (HR[95% CI]: second quartile, 2.243[1.273, 3.955]; third quartile, 3.026[1.763, 5.194]; top quartile, 4.402[2.573, 7.531]), 180-day mortality (HR[95% CI]: second quartile, 1.719[1.118, 2.645]; third quartile, 2.362[1.575, 3.542]; top quartile, 3.116[2.077, 4.676]), and 1-year mortality (HR[95% CI]: second quartile, 1.700[1.143, 2.528]; third quartile, 2.239[1.536, 3.264]; top quartile, 2.876[1.969, 4.201]) using bottom quartile as reference.Conclusion: We firstly demonstrated that higher AG was significantly associated with increased 30-day, 180-day and 1-year all-cause mortality in AMI patients. AG as an easily obtained marker is of strong and reliable predictive value for AMI mortality during follow-up.Keywords: acute myocardial infarction, anion gap, all-cause mortality

BackgroundContinued expansion of indications for sodium-glucose cotransporter-2 inhibitors increases importance of evaluating cardiovascular and kidney efficacy and safety of empagliflozin in patients with type 2 diabetes compared to similar therapies.MethodsThe EMPRISE Europe and Asia study is a non-interventional cohort study using data from 2014–2019 in seven European (Denmark, Finland, Germany, Norway, Spain, Sweden, United Kingdom) and four Asian (Israel, Japan, South Korea, Taiwan) countries. Patients with type 2 diabetes initiating empagliflozin were 1:1 propensity score matched to patients initiating dipeptidyl peptidase-4 inhibitors. Primary endpoints included hospitalization for heart failure, all-cause mortality, myocardial infarction and stroke. Other cardiovascular, renal, and safety outcomes were examined.FindingsAmong 83,946 matched patient pairs, (0·7 years overall mean follow-up time), initiation of empagliflozin was associated with lower risk of hospitalization for heart failure compared to dipeptidyl peptidase-4 inhibitors (Hazard Ratio 0·70; 95% CI 0.60 to 0.83). Risks of all-cause mortality (0·55; 0·48 to 0·63), stroke (0·82; 0·71 to 0·96), and end-stage renal disease (0·43; 0·30 to 0·63) were lower and risk for myocardial infarction, bone fracture, severe hypoglycemia, and lower-limb amputation were similar between initiators of empagliflozin and dipeptidyl peptidase-4 inhibitors. Initiation of empagliflozin was associated with higher risk for diabetic ketoacidosis (1·97; 1·28 to 3·03) compared to dipeptidyl peptidase-4 inhibitors. Results were consistent across continents and regions.InterpretationResults from this EMPRISE Europe and Asia study complements previous clinical trials and real-world studies by providing further evidence of the beneficial cardiorenal effects and overall safety of empagliflozin compared to dipeptidyl peptidase-4 inhibitors. Background: Continued expansion of indications for sodium-glucose cotransporter-2 inhibitors increases importance of evaluating cardiovascular and kidney efficacy and safety of empagliflozin in patients with type 2 diabetes compared to similar therapies. Methods: The EMPRISE Europe and Asia study is a non-interventional cohort study using data from 2014–2019 in seven European (Denmark, Finland, Germany, Norway, Spain, Sweden, United Kingdom) and four Asian (Israel, Japan, South Korea, Taiwan) countries. Patients with type 2 diabetes initiating empagliflozin were 1:1 propensity score matched to patients initiating dipeptidyl peptidase-4 inhibitors. Primary endpoints included hospitalization for heart failure, all-cause mortality, myocardial infarction and stroke. Other cardiovascular, renal, and safety outcomes were examined. Findings: Among 83,946 matched patient pairs, (0·7 years overall mean follow-up time), initiation of empagliflozin was associated with lower risk of hospitalization for heart failure compared to dipeptidyl peptidase-4 inhibitors (Hazard Ratio 0·70; 95% CI 0.60 to 0.83). Risks of all-cause mortality (0·55; 0·48 to 0·63), stroke (0·82; 0·71 to 0·96), and end-stage renal disease (0·43; 0·30 to 0·63) were lower and risk for myocardial infarction, bone fracture, severe hypoglycemia, and lower-limb amputation were similar between initiators of empagliflozin and dipeptidyl peptidase-4 inhibitors. Initiation of empagliflozin was associated with higher risk for diabetic ketoacidosis (1·97; 1·28 to 3·03) compared to dipeptidyl peptidase-4 inhibitors. Results were consistent across continents and regions. Interpretation: Results from this EMPRISE Europe and Asia study complements previous clinical trials and real-world studies by providing further evidence of the beneficial cardiorenal effects and overall safety of empagliflozin compared to dipeptidyl peptidase-4 inhibitors.

Background Debate over “social distancing” as a response to the pandemic includes the claim that disrupting clinical and public health programming dependent on human-to-human contact increased non-COVID-19 deaths. This claim warrants testing because novel pathogens will continue to emerge. Tests, however, appear frustrated by lack of a convention for estimating non-COVID-19 deaths that would have occurred had clinical and public health programming during the pre-vaccine pandemic remained as efficacious as in the pre-pandemic era. Intending to hasten the emergence of such a convention, we describe and demonstrate “new-signal, prior-response expectations” suggested by research and methods at the intersection of epidemiology and process control engineering. Methods Using German data, we estimate pre-pandemic public health efficacy by applying Box-Jenkins methods to 271 weekly counts of all-cause deaths from December 29 2014 through March 8 2020. We devise new-signal, prior-response expectations by applying the model to weekly non-COVID-19 deaths from March 9 2020 through December 26 2020. Results The COVID-19 pandemic did not coincide with more non-COVID-19 deaths than expected from the efficacy of responses to pre-pandemic all-cause deaths. Conclusions New-signal, prior-response estimates can contribute to evaluating the efficacy of public health programming in reducing non-COVID-19 deaths during the pre-vaccine pandemic.

Aims To determine if medium- and long-term blood glucose control as well as glycemic variability, which are known to be strong predictors of vascular complications, are associated with underlying cerebral small vessel disease (cSVD) in neurologically asymptomatic individuals with type 1 diabetes. Methods A total of 189 individuals (47.1% men; median age 40.0, IQR 33.0–45.2 years) with type 1 diabetes (median diabetes duration of 21.7, IQR 18.3–30.7 years) were enrolled in a cross-sectional retrospective study, as part of the Finnish Diabetic Nephropathy (FinnDiane) Study. Glycated hemoglobin (HbA1c) values were collected over the course of ten years before the visit including a clinical examination, biochemical sampling, and brain magnetic resonance imaging. Markers of glycemic control, measured during the visit, included HbA1c, fructosamine, and glycated albumin. Results Signs of cSVD were present in 66 (34.9%) individuals. Medium- and long-term glucose control and glycemic variability did not differ in individuals with signs of cSVD compared to those without. Further, no difference in any of the blood glucose variables and cSVD stratified for cerebral microbleeds (CMBs) or white matter hyperintensities were detected. Neither were numbers of CMBs associated with the studied glucose variables. Additionally, after dividing the studied variables into quartiles, no association with cSVD was observed. Conclusions We observed no association between glycemic control and cSVD in neurologically asymptomatic individuals with type 1 diabetes. This finding was unexpected considering the large number of signs of cerebrovascular pathology in these people after two decades of chronic hyperglycemia and warrants further studies searching for underlying factors of cSVD.

Sixty-four percent of adults in America drink coffee daily, and caffeine is the main reason people tend to drink coffee habitually. Few studies have examined the association between caffeine and all-cause and cause-specific mortality. The objective of this study was to examine the association between caffeine and all-cause and cause-specific mortality using the National Health and Nutrition Examination Survey (NHANES) 1999–2014 database. The multivariate Cox proportional hazards regression model was used to examine 23,878 individuals 20 years and older. Daily caffeine intake was measured once at baseline. A total of 2206 deaths occurred, including 394 cardiovascular (CVD) deaths and 525 cancer deaths. Compared to those with a caffeine intake of &lt, 100 mg/day, the hazard ratios (HRs) for CVD mortality were significantly lower in the participants with a caffeine intake of 100–200 mg/day (HR, 0.63, 95% confidence interval [CI], 0.45–0.88), and those with a caffeine intake of &gt, 200 mg/day (HR, 0.67, 95% CI, 0.50–0.88) after adjusting for potential confounders. The HRs for all-cause mortality were significantly lower in the participants with a caffeine intake of 100–200 mg/day (HR, 0.78, 95% CI, 0.67–0.91), and those with a caffeine intake of &gt, 200 mg/day (HR, 0.68, 95% CI, 0.60–0.78). Subgroup analyses showed that caffeine may have different effects on all-cause mortality among different age and body mass index (BMI) groups. In conclusion, higher caffeine intake was associated with lower all-cause and CVD mortality.

Backgrounds:. Physical activity (PA) and sedentary behavior (SB) have been associated with mortality, while the joint association with mortality is rarely reported among Chinese population. We aimed to examine the independent and joint association of PA and SB with all-cause mortality in southern China. Methods:. A cohort of 12,608 China Hypertension Survey participants aged ≥35 years were enrolled in 2013 to 2014, with a follow-up period of 5.4 years. Baseline self-reported PA and SB were collected via the questionnaire. Kaplan–Meier curves (log-rank test) and Cox proportional hazards regression were performed to evaluate the associations of PA and SB on all-cause mortality. Results:. A total of 11,744 eligible participants were included in the analysis. Over an average of 5.4 years of follow-up, 796 deaths occurred. The risk of all-cause mortality was lower among participants with high PA than those with low to moderate level (5.2% vs. 8.9%; hazards ratio [HR]: 0.75, 95% confidence interval [CI]: 0.61–0.87). Participants with SB ≥ 6 h had a higher risk of all-cause mortality than those with SB

Purpose: Living alone, an indicator of social isolation, has been increasing in the United States; 28% of households in 2019 were one-person households, compared with 13% in 1960. The working-age population is particularly vulnerable to adverse social conditions such as low social support. Although previous research has shown that social isolation and loneliness lead to poorer health and decreased longevity, few studies have focused on the working-age population and heart disease mortality in the United States using longitudinal data. Methods: This study examines social isolation as a risk factor for all-cause and heart disease mortality among U.S. adults aged 18–64 years using the pooled 1998–2014 data from the National Health Interview Survey (NHIS) linked to National Death Index (NDI) (n=388,973). Cox proportional hazards regression was used to model survival time as a function of social isolation, measured by “living alone,” and sociodemographic, behavioral, and health characteristics. Results: In Cox regression models with 17 years of mortality follow-up, the age-adjusted all-cause mortality risk was 45% higher (hazard ratio [HR]=1.45; 95% confidence interval [CI]=1.40–1.50) and the heart disease mortality risk was 83% higher (HR=1.83; 95% CI=1.67–2.00) among adults aged 18–64 years living alone at the baseline, compared with adults living with others. In the full model, the relative risk associated with social isolation was 16% higher (HR=1.16; 95% CI=1.11–1.20) for all-cause mortality and 33% higher (HR=1.33; 95% CI=1.21–1.47) for heart disease mortality after controlling for sociodemographic, behavioral-risk, and health status characteristics. Conclusion: In this national study, adults experiencing social isolation had statistically significantly higher relative risks of all-cause and heart disease mortality in the United States than adults living with others.

BackgroundHigh alcohol intake is associated with increased mortality. We aimed to identify factors affecting mortality in people drinking extreme amounts of alcohol.MethodsWe obtained information from the UK Biobank on approximately 500,000 participants aged 40-70 years at baseline assessment in 2006-2010. Habitual alcohol intake, lifestyle and physiological data, laboratory test results, and hospital diagnoses and death certificate data (to June 2020) for 5136 men (2.20% of male participants) and 1504 women (0.60%) who reported consuming ≥80 or ≥50 g/day, respectively, were used in survival analysis.ResultsMortality hazard ratios for these excessive drinkers, compared to all other participants, were 2.02 (95% CI 1.89-2.17) for all causes, 1.89 (1.69-2.12) for any cancer, 1.87 (1.61-2.17) for any circulatory disease, and 9.40 (7.00-12.64) for any liver disease. Liver disease diagnosis or abnormal liver function tests predicted not only deaths attributed to liver disease but also those from cancers or circulatory diseases. Mortality among excessive drinkers was also associated with quantitative alcohol intake; diagnosed alcohol dependence, harmful use, or withdrawal syndrome; and current smoking at assessment.ConclusionsPeople with chronic excessive alcohol intake experience decreased average survival, but there is substantial variation in their mortality, with liver abnormality and alcohol dependence or other alcohol use disorders associated with a worse prognosis. Clinically, patients with these risk factors and high alcohol intake should be considered for early or intensive management. Research can usefully focus on the factors predisposing to dependence or liver abnormality.

AimsCatheter ablation (CA) for ventricular tachycardia (VT) can improve outcomes in patients with ischemic cardiomyopathy. Data on patients with non-ischemic cardiomyopathy are scarce. The purpose of this systematic review and meta-analysis is to compare early CA for VT to deferred or no ablation in patients with ischemic or non-ischemic cardiomyopathy.Methods and resultsStudies were selected according to the following PICOS criteria: patients with structural heart disease and an implantable cardioverter-defibrillator (ICD) for VT, regardless of the antiarrhythmic drug treatment; intervention–early CA; comparison–no or deferred CA; outcomes–any appropriate ICD therapy, appropriate ICD shocks, all-cause mortality, VT storm, cardiovascular mortality, cardiovascular hospitalizations, complications, quality of life; published randomized trials with follow-up ≥12 months. Random-effect meta-analysis was performed. Outcomes were assessed using aggregate study-level data and reported as odds ratio (OR) or mean difference with 95% confidence intervals (CIs). Stratification by left ventricular ejection fraction (LVEF) was also done. Eight trials (n = 1,076) met the criteria. Early ablation was associated with reduced incidence of ICD therapy (OR 0.53, 95% CI 0.33–0.83, p = 0.005), shocks (OR 0.52, 95% CI 0.35–0.77, p = 0.001), VT storm (OR 0.58, 95% CI 0.39–0.85, p = 0.006), and cardiovascular hospitalizations (OR 0.67, 95% CI 0.49–0.92, p = 0.01). All-cause and cardiovascular mortality, complications, and quality of life were not different. Stratification by LVEF showed a reduction of ICD therapy only with higher EF (high EF OR 0.40, 95% CI 0.20–0.80, p = 0.01 vs. low EF OR 0.62, 95% CI 0.34–1.12, p = 0.11), while ICD shocks (high EF OR 0.54, 95% CI 0.25–1.15, p = 0.11 vs. low EF OR 0.50, 95% CI 0.30–0.83, p = 0.008) and hospitalizations (high EF OR 0.95, 95% CI 0.58–1.58, p = 0.85 vs. low EF OR 0.58, 95% CI 0.40–0.82, p = 0.002) were reduced only in patients with lower EF.ConclusionEarly CA for VT in patients with structural heart disease is associated with reduced incidence of ICD therapy and shocks, VT storm, and hospitalizations. There is no impact on mortality, complications, and quality of life. (The review protocol was registered with INPLASY on June 19, 2022, #202260080).Systematic review registration[https://inplasy.com/], identifier [202260080].

BackgroundChronic heart failure (CHF) affects the health care system with high social and economic costs due to recurrent hospital admissions or frequent ambulatory reassessments. Subclinical hypothyroidism (SCH) is commonly observed in patients with CHF and negatively affects myocardial function and remodeling and, ultimately, increases the risk of hospitalizations and all-cause and cardiovascular (CV) mortality. The role of levothyroxine replacement on relevant CV outcomes in patients with SCH and CHF is unclear.ObjectiveTo assess the effect of levothyroxine (compared to placebo or no treatment) on the incidence of all-cause and CV mortality, major adverse CV events, and heart failure in patients with SCH and CHF.MethodsPubMed/MEDLINE, Cochrane Library, and ClinicalTrial.gov were searched for randomized clinical trials, non-randomized observational, multicentric, and comparative studies. No language restrictions were included. After duplicate removal, articles were screened and extracted for the synthesis according to a hierarchical strategy that included title, abstract, and full-text appraisal. The risk of bias was assessed by RoB2 and ROBIN-I tools. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied to rate the quality of evidence and grade the strength of recommendations.ResultsTwo trials were included in the systematic review with considerable indirectness and inaccuracy that down-graded the level of evidence.DiscussionNo evidence supports the use of levothyroxine for treating SCH in CHF due to the lack of reliable and well-designed clinical trials.ConclusionCV outcome and dose-response trials are needed to understand better the role of levothyroxine replacement treatment for a safer prescription in this clinical setting.

Aims/hypothesis In our current society sedentary behaviour predominates in most people and is associated with the risk of developing type 2 diabetes. It has been suggested that replacing sitting time by standing and walking could be beneficial for individuals with type 2 diabetes but the underlying mechanisms are unknown and direct comparisons with exercise are lacking. Our objective was to directly compare metabolic responses of either sitting less or exercising, relative to being sedentary. Methods We performed a randomised, crossover intervention study in 12 overweight women who performed three well-controlled 4 day activity regimens: (1) sitting regimen (sitting 14 h/day); (2) exercise regimen (sitting 13 h/day, exercise 1 h/day); and (3) sitting less regimen (sitting 9 h/day, standing 4 h/day and walking 3 h/day). The primary outcome was insulin sensitivity measured by a two-step hyperinsulinaemic–euglycaemic clamp. We additionally performed metabolomics on muscle biopsies taken before the clamp to identify changes at the molecular level. Results Replacing sitting time by standing and walking over 4 days resulted in improved peripheral insulin sensitivity, comparable with the improvement achieved by moderate-to-vigorous exercise. Specifically, we report a significant improvement in peripheral insulin sensitivity in the sitting less (~13%) and the exercise regimen (~20%), compared with the sitting regimen. Furthermore, sitting less shifted the underlying muscle metabolome towards that seen with moderate-to-vigorous exercise, compared with the sitting regimen. Conclusions/interpretations Replacing sitting time by standing and walking is an attractive alternative to moderate-to-vigorous exercise for improving metabolic health. Trial registration ClinicalTrials.gov NCT03912922. Graphical abstract

Objective: High body mass index (BMI) is an important predictor of mortality but estimating underlying causality is hampered by confounding and pre-existing disease. Here, we use information from the offspring to approximate parental BMIs, with an aim to avoid biased estimation of mortality risk caused by reverse causality. Methods: The analyses were based on information on 9674 offspring–mother and 9096 offspring–father pairs obtained from the 1958 British birth cohort. Parental BMI–mortality associations were analysed using conventional methods and using offspring BMIas a proxy, or instrument, for their parents’ BMI. Results: In the conventional analysis, associations between parental BMI and all-cause mortality were U-shaped (Pcurvature < 0.001),while offspring BMI had linear associations with parental mortality (Ptrend < 0.001, Pcurvature > 0.46). Curvature was particularly pronounced for mortality from respiratory diseases and from lung cancer. Instrumental variable analyses suggested a positive association between BMI and mortality from all causes [mothers: HR per SD of BMI 1.43 (95% CI 1.21–1.69), fathers: HR 1.17(1.00–1.36)] and from coronary heart disease [mothers: HR 1.65 (1.15–2.36), fathers: HR 1.51 (1.17–1.97)]. These were larger than HR from the equivalent conventional analyses, despite some attenuation by adjustment for social indicators and smoking. Conclusions: Analyses using offspring BMI as a proxy for parental BMI suggest that the apparent adverse consequences of low BMI are considerably overestimated and adverse consequences of overweight are underestimated in conventional epidemiological studies. Refereed/Peer-reviewed

Background The red blood cell distribution width (RDW)–albumin ratio (RA) is a new biomarker, which is d-efined as RDW divided by albumin. This study aimed at determining the prognostic values of RA for diabetic ketoacidosis (DKA). Methods Data were obtained from Medical Information Mart for Intensive Care Database III V1.4 (MIMIC-III) and the RA calculated. Multivariate Cox regression analysis was performed to determine the correlation between RA and 90-day mortality or 365-day mortality. To further investigate the association with RA and mortality, the patients were divided into two groups. The second outcome was the association between the incidence of DKA-related infections and RA. Results For DKA patients in the ICU, RA was significantly correlated with 90-day mortality (HR: 2.1, 95% CI: 1.5, 3.0, p

Yu Hong,1,2,&ast; Xian-Hui Wang,3,&ast; Yi-Tong Xiong,2 Jie Li,2 Chun-Feng Liu1 1Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215004, People’s Republic of China; 2Department of Neurology, Affiliated Yixing People’s Hospital of Jiangsu University, Yixing, Jiangsu, 214200, People’s Republic of China; 3Department of Neurology, Taicang First People’s Hospital, Taicang, Jiangsu, 215400, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie LiDepartment of Neurology, Yixing People’s Hospital, No. 75 Tongzhenguan Road, Yicheng Street, Yixing, Jiangsu, 214200, People’s Republic of ChinaEmail jielee1983@163.comChun-Feng LiuDepartment of Neurology, The Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Suzhou, Jiangsu, 215004, People’s Republic of ChinaEmail liuchunfeng@suda.edu.cnBackground: Hypophosphatemia was reported to frequently occur in patients with nontraumatic intracranial hemorrhage (ICH); however, the correlation between hypophosphatemia and outcomes of ICH remains unclear. This study aimed to examine the association between admission serum phosphate and all-cause mortality among patients with mild–moderate spontaneous ICH (sICH).Methods: A total of 851 patients with sICH were enrolled. Serum phosphate was acquired within 24 hours on admission, and participants were divided according to phosphate quartiles. The primary outcome was all-cause mortality within 90 days, and univariate and multivariate models were employed to estimate the mortality risk.Results: There were significant differences among sICH patients with different phosphate quartiles in terms of age, diastolic blood pressure (DBP), activated partial thromboplastin time (APTT), platelet count, and incidence of respiratory failure events on admission (P < 0.05). Log rank test showed a significant difference in the mortality risk among sICH patients with each phosphate quartile. Univariate Cox regression analysis revealed that age, smoking, DBP, APTT, NIH stroke scale (NIHSS) score, hematoma volume and serum phosphate might be associated with the 90-day all-cause mortality in patients with sICH (P < 0.05). Multivariable Cox regression analysis showed that the crude mortality was 4.3-fold greater in sICH patients with serum phosphate Q1 than those with Q4 (P < 0.001), and remained 3.18-fold higher after adjusting for age, smoking, DBP, APTT, NIHSS score, hematoma volume and early withdrawal of life-sustaining therapy (P = 0.011). Representative operating curve (ROC) analysis showed that admission serum phosphate was predictable for all-cause mortality within 90 days in patients with sICH (area under the ROC = 0.628, P < 0.001).Conclusion: Low admission serum phosphate is strongly associated with a high risk of mortality in patients with mild–moderate sICH, and hypophosphatemia may be a prognostic marker for all-cause mortality in patients with mild–moderate sICH.Keywords: spontaneous intracerebral hemorrhage, serum phosphate level, risk factor, all-cause mortality

Background We previously reported that, among asymptomatic patients with type 2 diabetes mellitus (T2DM) without a history of cardiovascular disease (CVD), up to 19% of the patients with myocardial ischemia were detected by annual cardiovascular screening tests (ACVSTs). Thus, the present study assessed the long-term clinical outcomes of ACVSTs in those patients. Methods Six hundred and fifty-seven outpatients with T2DM who received ACVSTs at least once or not at all from April 2014 to March 2018 were defined as the S and NS groups, respectively. The data were compared between these two groups. Results This study revealed that, among outpatients with T2DM in our hospital over those four years, with the increasing frequency of receiving ACVSTs, 1) the frequency of the internal use of statins, anti-platelets, and renin-angiotensin system inhibitors, which are well-known as medications for preventing CVD, significantly increased; 2) low-density lipoprotein-cholesterol and triglyceride levels significantly improved; 3) levels of highly sensitive C-protein, a strong predictors of CVD, were significantly suppressed; 4) the progression of renal dysfunction was significantly suppressed; 5) the cumulative of four-point major adverse cardiovascular events and admissions due to heart failure significantly decreased; and 6) the cumulative of all-cause mortality was significantly suppressed. Conclusions Given the above, it may be important to continue ACVSTs in outpatients with T2DM without a history of CVD for several years.

Peter Ascanius Jacobsen,1,2 Kristian Hay Kragholm,2,3 Christian Torp-Pedersen,4 Daisy JA Janssen,5,6 Martijn A Spruit,5,7,8 Ulla Møller Weinreich1,2 1Department of Respiratory Diseases, Aalborg University Hospital, Aalborg, Denmark; 2The Clinical Institute, Aalborg University, Aalborg, Denmark; 3Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark; 4Department of Clinical Research, Hillerød Hospital, Hillerød, Denmark; 5Department of Research and Development, Ciro, Horn, the Netherland; 6Department of Health Services Research, Care and Public Health Research Institute, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands; 7Nutrim School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands; 8Department of Respiratory Medicine, Maastricht University Medical Centre (MUMC+), Maastricht, the NetherlandsCorrespondence: Peter Ascanius JacobsenDepartment of Respiratory Diseases, Aalborg University Hospital, Aalborg, DenmarkTel +45 97 66 48 00Email peter.jacobsen@rn.dkIntroduction: The understanding of whether and to what extent employment status affects readmission and mortality is limited in patients with COPD.Aim: To explore how employment status affects readmission and mortality after first admission to the hospital with acute exacerbation of COPD (AECOPD).Methods: This study used Danish national registry-based data. All patients admitted for the first time to the hospital between 1999 and 2014 with a diagnosis of AECOPD, age 35– 59, without a previous asthma diagnosis were included in the study. Employment status effect on 30-, 90-, and 365-day readmission and mortality was examined using logistic regression, adjusting for relevant confounders.Results: A total of 11,850 COPD patients were included in the study of which 3563 (30%) were working, 1368 (12%) unemployed, 840 (7%) on sick leave, and 6079 (51%) receiving early retirement. Patients receiving early retirement had, compared to patients working, an adjusted increased likelihood of readmission at 30, 90, and 365 days (odds ratio (OR) 1.26 (CI95% (1.06– 1.49)), 1.33 (CI95% (1.16– 1.53)), and 1.48 (CI95% (1.33– 1.66)), respectively). An increased likelihood was also seen in unemployed at 365 days follow-up (OR 1.44 (CI95% (1.22– 1.68))). Early retirement was associated with an increased mortality at 30, 90, and 365 days (OR 1.39 (CI95% (1.07– 1.80)) 1.37 (CI95% (1.09– 1.79)) and 1.48 (CI95% (1.25– 1.75)), respectively). An increased likelihood was also seen in patients receiving sick leave (OR 1.57 (CI95% (1.21– 2.04))).Conclusion: Patients with COPD who are not working at the time of first admission have a higher likelihood of readmission and mortality.Keywords: chronic obstructive pulmonary disease, employment, mortality, readmission

Bin Hu,1 Jinxia Cao,1 Yangyang Hu,2 Zuoan Qin,3 Jun Wang1 1Department of Hematology, First People’s Hospital of Changde City, Changde, Hunan, People’s Republic of China; 2Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 3Department of Cardiovascular Medicine, First People’s Hospital of Changde City, Changde, Hunan, People’s Republic of ChinaCorrespondence: Jun WangDepartment of Hematology, First People’s Hospital of Changde City, 818 Renmin Road, Changde, 415000, Hunan, People’s Republic of ChinaTel +86 736-7788720Email xueyeke2020@sina.comPurpose: Studies regarding death risk factors of disseminated intravascular coagulation (DIC) patients were limited. Therefore, we conducted this study to investigate whether the serum anion gap (AG) was independently related to all-cause mortality of DIC patients.Methods: We used the data from Medical Information Mart for Intensive Care III version 1.4 (MIMIC-III v1.4). A total of 2,654 DIC patients were included. The main outcomes were in-hospital, 30-day, and 90-day all-cause mortality. The AG was measured upon ICU admission and its association with mortality was evaluated using the Cox proportional-hazards regression model. The generalized additive model and the smooth curve fitting were introduced to examine the non-linear association.Results: After adjusting for potential covariates, the in-hospital, 30-day, and 90-day all-cause mortality were positively correlated with AG. The hazard ratio (HR), confidence intervals (CI), and P were 1.05 (1.04– 1.07) < 0.0001, 1.06 (1.04– 1.07) < 0.0001, and 1.05 (1.03– 1.07) < 0.0001, respectively. We did not find an obvious non-linear relationship between AG and in-hospital, 30-day, and 90-day mortality, which indicated that the association between AG and all-cause mortality of DIC patients was nearly linear.Conclusion: Serum AG is positively related with all-cause mortality in DIC patients.Keywords: anion gap, disseminated intravascular coagulation, all-cause mortality, MIMIC-III, retrospective study

Background: Obesity is associated with increased mortality as a significant risk factor for chronic diseases, including cardiovascular diseases and cancer. Several people believe that weight gain is harmful, and weight loss helps maintain health. However, some studies have shown that weight loss, particularly among older adults, is more likely to increase the risk of mortality than weight gain.Methods: We used data for the cohort of the Korean Longitudinal Study of Aging, which is a nationwide stratified multi-stage sample of adults aged 45 years. The all-cause mortality risk was assessed using the survival status and the number of months of survival calculated from 2006 (baseline year) to 2016. Cox proportional hazard regression were used to study the causal link between weight change and all-cause mortality risk.Results: The results showed interactive associations between weight loss and mortality among middle-aged and older adults. The hazard ratio was 1.62 (95% confidence interval [CI], 1.10–2.40) for the participants aged 45–65 years with weight losses greater than 5 kg and 1.56 (95% CI, 1.29–1.89) for those older than 65 years with weight losses greater than 5 kg. The results for the group with weight gain above 5 kg were not significant. Middle-aged and older men showed an increase in all-cause mortality associated with weight loss of more than 5 kg, but only the older women showed significant results.Conclusion: This large-scale cohort study in Korea showed a relationship between weight loss and all-cause mortality in middle-aged and older individuals.

IntroductionHospital length of stay (LoS) and hospital readmissions are metrics of healthcare performance. We examined the association between these two metrics in older patients hospitalized with decompensated heart failure (HF).Material and methodsEight thousand and forty-nine patients hospitalized for HF in 106 U.S. hospitals had a median LoS of 5 days; among them, 3777 had a LoS > 5 days. Using propensity scores for LoS > 5 days, we assembled 2723 pairs of patients with LoS 1–5 vs. > 5 days. The matched cohort of 5446 patients was balanced on 40 baseline characteristics. We repeated the above process in 7045 patients after excluding those with LoS > 10 days, thus assembling a second matched cohort of 2399 pairs of patients with LoS 1–5 vs. 6–10 days. Hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with longer LoS were estimated in matched cohorts.ResultsIn the primary matched cohort (n = 5446), LoS > 5 days was associated with a higher risk of all-cause readmission at 30 days (HR = 1.16; 95% CI: 1.04–1.31; p = 0.010), but not during longer follow-up. A longer LoS was also associated with a higher risk of mortality during 8.8 years of follow-up (HR = 1.13; 95% CI: 1.06–1.21; p < 0.001). LoS had no association with HF readmission. Similar associations were observed among the matched sensitivity cohort (n = 4798) that excluded patients with LoS > 10 days.ConclusionsIn propensity score-matched balanced cohorts of patients with HF, a longer LoS was independently associated with poor outcomes, which persisted when LoS > 10 days were excluded.

Office pulse pressure (PP) is a predictor for cardiovascular (CV) events and mortality. Our aim was to evaluate ambulatory PP as a long‐term risk factor in a random cohort of middle‐aged participants. The Opera study took place in years 1991–1993, with a 24‐h ambulatory blood pressure measurement (ABPM) performed to 900 participants. The end‐points were non‐fatal and fatal CV events, and deaths of all‐causes. Follow‐up period, until the first event or until the end of the year 2014, was 21.1 years (mean). Of 900 participants, 22.6% died (29.6% of men/15.6% of women, p

Background Population-based studies generally show neutral associations between dairy consumption and ischemic heart disease (IHD) mortality, whereas weak inverse associations were found for cardiovascular disease (CVD) and stroke mortality. Whether dairy consumption affects long-term survival after myocardial infarction (MI) is unknown. Objectives We studied types of dairy and long-term mortality risk in drug-treated post-MI patients. Methods We included 4365 Dutch patients from the Alpha Omega Cohort aged 60–80 y (21% women) with an MI ≤10 y before enrollment. Dietary data were collected at baseline (2002–2006) using a 203-item FFQ and patients were followed for cause-specific mortality through December 2018. HRs of CVD, IHD, stroke, and all-cause mortality for types of dairy were obtained from Cox models, adjusting for age, sex, energy intake, physical activity, smoking, alcohol intake, diabetes, obesity, and dietary factors. Results Most patients were Dutch, 24% were obese, 20% had diabetes, and 97% used cardiovascular medication. Median intakes were 39 g/d for plain yogurt, 88 g/d for total nonfermented milk, and 17 g/d for hard cheeses. Of the cohort, 10% consumed high-fat milk. During ∼12 y of follow-up (48,473 person-years) 2035 deaths occurred, including 903 from CVD, 558 from IHD, and 170 from stroke. Yogurt was linearly inversely associated with CVD mortality (HR: 0.96; 95% CI: 0.93, 0.99; per 25 g/d) and nonlinearly inversely associated with all-cause mortality. Milk was not associated with any of the outcomes (HRs: ∼1.0 per 100 g/d), except for a higher mortality risk in high-fat milk consumers (HR: 1.30; 95% CI: 1.13, 1.49). Other dairy groups were not associated with mortality risk. Conclusions In Dutch post-MI patients, yogurt consumption was inversely associated with CVD mortality and all-cause mortality. Associations for milk and other dairy products were neutral or inconsistent. This trial was registered at clinicaltrials.gov as NCT03192410.

Na Zhao,1 WanHua Hu,1 Zhimin Wu,1 Xujie Wu,1 Wei Li,1 Yiru Wang,1 Han Zhao2 1Department of Neurology, Wenzhou Hospital of Traditional Chinese Medicine, Zhejiang, Wenzhou, 325000, People’s Republic of China; 2Department of Neurology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Zhejiang, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Han Zhao Email zhaohan0577@sina.comObjective: Within this study we attempt to express a correlation between the mortality of stroke and stroke related infection to a novel biomarker represented by the red blood cell width–albumin levels ratio within the patient. We hypothesize that this novel biomarker could be utilized as better predictive tool for stroke associated infections.Methods: Patient data sets were obtained via the Medical Information Mart for Intensive Care Database iii V1.4 (MIMIC-iii). Data from 1480 patients were obtained to serve the testing for the RA biomarker tests. Clinical endpoints of 30-, 60-, and 365-day all-cause mortality in stroke patients were used as subgroups within the analyzed population. Estimation of hazard ratios (HR) were obtained from Cox regression models for stroke-associated infection and all-cause mortality in relation to RA values.Results: A high-RA was associated with increased mortality in ICU patients suffering from a stroke. After adjusting for age and sex, compared to the reference group (the first quartile), the high-RA group had the highest 30-day (HR, 95% CI: 1.88 (1.36, 2.58)), 90-day (HR, 95% CI: 2.12 (1.59, 2.82)), and one-year (HR, 95% CI: 2.15 (1.65, 2.80)) all-cause mortality. The RA values were independently associated with an increased risk of stroke-associated infection when adjusting for confounders.Conclusions: Our data suggest RA may be an easily accessible, reproducible, and low-cost biomarker for predicting stroke-associated infections and mortality in patients who have suffered from a stroke.Keywords: red blood cell distribution width–albumin ratio, stroke-associated infection, stroke, all-cause mortality

To investigate the effects of glucose-lowering agents on all-cause mortality, and cardiovascular and renal outcomes in adults with type 2 diabetes.A MEDLINE and EMBASE search was performed to identify randomized controlled trials, published up to 28 February 2022, with a follow-up ≥52 weeks, in which glucose-lowering drugs were compared with either placebo or active comparators. We included only trials reporting formal external adjudication of events. All-cause mortality, 3-point MACE (major cardiovascular events), and hospitalization for heart failure (HHF) were considered as principal outcomes. Doubling of serum creatinine, worsening albuminuria, and renal death were considered as secondary endpoints.We included randomized controlled trials performed on metformin (n = 17), pioglitazone (n = 20), alpha-glucosidase inhibitors (n = 9), insulin secretagogues (n = 42), dipeptidyl-peptidase-4 inhibitors (n = 67), glucagon-like peptide-1 receptor agonists (n = 45) or sodium-glucose co-transporter-2 inhibitors (SGLT-2i; n = 42) and insulin (n = 18). Glucagon-like peptide-1 receptor agonist and SGLT-2i were associated with a significant reduction in all-cause mortality [Mantel-Haenszel odds ratio (MH-OR), 95% confidence interval: 0.88 (0.83; 0.95) and 0.85 (0.79; 0.91), respectively] and MACE [MH-OR, 95% confidence interval: 0.89 (0.84; 0.94) and 0.90 (0.84; 0.96), respectively]. SGLT-2i was associated with a reduced risk of HHF [MH-OR 0.68 (0.62; 0.75)], worsening albuminuria [MH-OR 0.67 (0.55; 0.80)] and doubling of serum creatinine [MH-OR 0.58 (0.44; 0.79)]. Metformin and pioglitazone were associated with a significantly lower risk of MACE [MH-OR 0.60 (0.47; 0.80) and 0.85 (0.74; 0.97), respectively] and pioglitazone with a higher risk of HHF [MH-OR 1.30 (1.04; 1.62)]. Insulin secretagogues were associated with increased risk of all-cause mortality [MH-OR 1.12 (1.01; 1.24)] and MACE [MH-OR 1.19 (1.02; 1.39)].The results of this updated meta-analysis need to be considered in the choice of drug treatment for type 2 diabetes mellitus, which cannot be merely based on the effect of glucose-lowering drugs on long-term glycaemic control.

As research documenting disparate impacts of COVID-19 by race and ethnicity grows, little attention has been given to dynamics in mortality disparities during the pandemic and whether changes in disparities persist. We estimate age-standardized monthly all-cause mortality in the United States from January 2018 through February 2022 for seven racial/ethnic populations. Using joinpoint regression, we quantify trends in race-specific rate ratios relative to non-Hispanic White mortality to examine the magnitude of pandemic-related shifts in mortality disparities. Prepandemic disparities were stable from January 2018 through February 2020. With the start of the pandemic, relative mortality disadvantages increased for American Indian or Alaska Native (AIAN), Native Hawaiian or other Pacific Islander (NHOPI), and Black individuals, and relative mortality advantages decreased for Asian and Hispanic groups. Rate ratios generally increased during COVID-19 surges, with different patterns in the summer 2021 and winter 2021/2022 surges, when disparities approached prepandemic levels for Asian and Black individuals. However, two populations below age 65 fared worse than White individuals during these surges. For AIAN people, the observed rate ratio reached 2.25 (95% CI = 2.14, 2.37) in October 2021 vs. a prepandemic mean of 1.74 (95% CI = 1.62, 1.86), and for NHOPI people, the observed rate ratio reached 2.12 (95% CI = 1.92, 2.33) in August 2021 vs. a prepandemic mean of 1.31 (95% CI = 1.13, 1.49). Our results highlight the dynamic nature of racial/ethnic disparities in mortality and raise alarm about the exacerbation of mortality inequities for Indigenous groups due to the pandemic.

Background and objectives:Cholinesterase inhibitors (ChEIs) have cardiovascular effects in addition to their neurological activity and might alter mortality. We wanted to know if treatment with ChEIs modifies mortality in patients with dementia.Methods:We searched PubMed, EMBASE, Cochrane CENTRAL, ClinicalTrials.gov and ICRTP, from their inception to November 2021, and screened bibliographies of reviews, guidelines and included studies. We included randomized controlled trials (RCTs) and non-randomized controlled studies at lower risk of bias comparing ChEI treatment with placebo or usual treatment, for 6 months or longer, in patients with dementia of any type. Two investigators independently assessed studies for inclusion, assessed their risk of bias and extracted data, using predefined forms. Any discordance between investigators was solved by discussion and consensus. Data on all-cause and cardiovascular mortality, measured as either crude death rates or multivariate adjusted hazard ratios (HR), was pooled using a random-effect model. Information size achieved was assessed using trial sequential analysis (TSA). We followed PRISMA guidelines.Results:24 studies (12 RCTs, 12 cohorts, mean follow-up 6 to 120 months), cumulating 79 153 patients with Alzheimer’s (13 studies), Parkinson’s (1), vascular (1) or any type (9) dementia, fulfilled inclusion criteria. Pooled all-cause mortality in control patients was 15.1 per 100 person-years. Treatment with ChEIs was associated with lower all-cause mortality (unadjusted RR 0.74, 95%CI 0.66 – 0.84; adjusted HR 0.77, 95%CI 0.70 – 0.84, moderate to high quality evidence). This result was consistent between randomized and non-randomized studies and in several sensitivity analyses. No difference appeared between subgroups by type of dementia, age, individual drug or dementia severity. Less data was available for cardiovascular mortality (3 RCTs, 2 cohorts, 9 182 patients, low to moderate quality evidence), which was also lower in patients treated with ChEIs (unadjusted RR 0.61, 95%CI 0.40 – 0.93, adjusted HR 0.47, 95%CI 0.32 – 0.68). In TSA analysis, results for all-cause mortality were conclusive, but not those for cardiovascular mortality.Discussion:There is moderate to high quality evidence of a consistent association between long-term treatment with ChEIs and a reduction in all-cause mortality in patients with dementia. These findings may influence decisions to prescribe ChEIs in those patients.Trial Registration Information:This systematic review was registered in the PROSPERO international prospective register of systematic reviews with the number CRD42021254458 (11/06/2021).

Aim: To investigate the association between periodontitis and edentulism with cardiovascular disease (CVD) and all-cause mortality. Methods: Baseline data of 506 subjects including 256 angiographically verified coronary artery disease patients and 250 matched participants in cardiovascular health from the Kuopio Oral Health and Heart study were collected from 1995–1996. Mortality data were accrued until May 31, 2015, and related to baseline periodontal health and edentulism, assessed as exposure and collected by means of clinical and radiographic examination by a single examiner. Cox proportional hazards regression models were fit using covariates such as age, gender, smoking, BMI, and education. The final sample size for the periodontitis models ranged from 358 to 376, while the edentate models included 413 to 503 subjects for CVD and all-cause mortality, respectively with no missing values in the predictor, confounders, and outcome. Results: The strongest association was found between edentulism and CVD and allcause mortality (HR: 1.9 CVD, HR: 1.6all-cause; p< .01). Conclusions: Edentulism considered as a poor oral health marker was associated strongly with CVD mortality while periodontitis was not.

Protocol, PRISMA checklist, template data collection forms and data extracted from included studies in this systematic review

We aim to determine the gender-sensitive risks of psychosocial factors for the incidence of IHD outcomes in the general population, as well as for adverse outcomes in patients with IHD. This meta-analysis is funded by ZonMw and the Dutch Heart Foundation (de Hartstichting), grant number #849100001

Background: Following acute pulmonary embolism (PE), a relevant number of patients experience decreased exercise capacity which can be associated with disturbed pulmonary perfusion. Cardiopulmonary exercise testing (CPET) shows several patterns typical for disturbed pulmonary perfusion. Research question: We aimed to examine whether CPET can also provide prognostic information in chronic thromboembolic pulmonary hypertension (CTEPH). Study Design and Methods: We performed a multicenter retrospective chart review in Germany between 2002 and 2020. Patients with CTEPH were included if they had ≥6 months of follow-up and complete CPET and hemodynamic data. Symptom-limited CPET was performed using a cycle ergometer (ramp or Jones protocol). The association of anthropometric data, comorbidities, symptoms, lung function, and echocardiographic, hemodynamic, and CPET parameters with survival was examined. Mortality prediction models were calculated by Cox regression with backward selection. Results: 345 patients (1532 person-years) were included; 138 underwent surgical treatment (pulmonary endarterectomy or balloon pulmonary angioplasty) and 207 received only non-surgical treatment. During follow-up (median 3.5 years), 78 patients died. The death rate per 1000 person-years was 24.9 and 74.2 in the surgical and non-surgical groups, respectively (p < 0.001). In age- and sex-adjusted Cox regression analyses, CPET parameters including peak oxygen uptake (VO2peak, reflecting cardiopulmonary exercise capacity) were prognostic in the non-surgical group but not in the surgical group. In mortality prediction models, age, sex, VO2peak (% predicted), and carbon monoxide transfer coefficient (% predicted) showed significant prognostic relevance in both the overall cohort and the non-surgical group. In the non-surgical group, Kaplan–Meier analysis showed that patients with VO2peak below 53.4% predicted (threshold identified by receiver operating characteristic analysis) had increased mortality (p = 0.007). Interpretation: The additional measurement of cardiopulmonary exercise capacity by CPET allows a more precise prognostic evaluation in patients with CTEPH. CPET might therefore be helpful for risk-adapted treatment of CTEPH.

AimThis observational study aimed to examine the association between the A Body Shape Index (ABSI) and/or sarcopenia and total, cardiovascular, and cancer mortality.MethodsThe associations of sarcopenia and ABSI with all-cause, cardiovascular, and cancer mortality were assessed in 4,488 participants from the 1999–2004 National Health and Nutrition Examination Survey (NHANES) who were followed up until December 31, 2015. Models were analyzed separately for men and women and adjusted for age, race, and other confounding factors. ABSI was assessed as a continuous measurement by quartile for men and women. Population attributable fractions (PAFs) were calculated to assess mortality caused by sarcopenia and/or ABSI in the study population.ResultsWhen ABSI was assessed as a continuous variable, the ABSI quartile showed a linear trend for total (p = 0.0001), cardiovascular (p = 0.04), and cancer (p = 0.02) mortality in men and for total (p = 0.06) and cardiovascular (p = 0.06) mortality in women. The hazard ratios (HRs) of the fourth ABSI quartile were 1.51 [95% confidence interval (CI): 1.20–1.89] in men and 1.23 (95% CI: 0.93–1.64) in women, compared with those in the first quartile. When ABSI was assessed by quartile, the appendicular skeletal mass index (ASMI) was lower in the groups with high ABSI. When high ABSI was combined with sarcopenia, the HRs of all-cause mortality were 2.05 (95% CI: 1.60–2.62) in men and 1.51 (95% CI: 1.19–1.92) in women. In the subpopulation (sarcopenia group or higher ABSI), the PAFs of mortality due to sarcopenia were 26.16% (95% CI: 12.68–37.56) in men and 21.89% (95% CI: 5.64–35.35) in women, and the PAF of mortality due to higher ABSI was 23.70% (95% CI: 12.11–33.77) in men.ConclusionThe ABSI value was significantly associated with all-cause and cardiovascular mortality, and the co-existence of higher ABSI values and sarcopenia can contribute to a more significant death risk in comparison with high ABSI values or sarcopenia. Moreover, the ABSI values in combination with the ASMI can be used to preliminarily evaluate the content and distribution of fat and muscle and to predict the risk of death in obese and sarcopenic populations.

Aims Patients with a pacemaker or implantable cardioverter-defibrillator are often considered for cardiac resynchronization therapy (CRT). However, limited comprehensive data are available regarding their long-term outcomes. Methods and results Our retrospective registry included 2524 patients [1977 (78%) de novo, 547 (22%) upgrade patients] with mild to severe symptoms, left ventricular ejection fraction ≤35%, and QRS ≥ 130ms. The primary outcome was the composite of all-cause mortality, heart transplantation (HTX), or left ventricular assist device (LVAD) implantation; secondary endpoints were death from any cause and post-procedural complications. In our cohort, upgrade patients were older [71 (65–77) vs. 67 (59–73) years; P Conclusion In our retrospective analysis, upgrade patients had a higher risk of all-cause mortality than de novo patients, which might be attributable to their more significant comorbidity burden. The occurrence of lead dysfunction and pocket infections was more frequent in the upgrade group.

Aims CVD is the main cause of morbidity and mortality in individuals with diabetes. It is currently unclear whether daily glucose variability contributes to CVD. Therefore, we investigated whether glucose variability is associated with arterial measures that are considered important in CVD pathogenesis. Methods We included participants of The Maastricht Study, an observational population-based cohort, who underwent at least 48 h of continuous glucose monitoring (CGM) (n = 853; age: 59.9 ± 8.6 years; 49% women, 23% type 2 diabetes). We studied the cross-sectional associations of two glucose variability indices (CGM-assessed SD [SDCGM] and CGM-assessed CV [CVCGM]) and time in range (TIRCGM) with carotid–femoral pulse wave velocity (cf-PWV), carotid distensibility coefficient, carotid intima–media thickness, ankle–brachial index and circumferential wall stress via multiple linear regression. Results Higher SDCGM was associated with higher cf-PWV after adjusting for demographics, cardiovascular risk factors and lifestyle factors (regression coefficient [B] per 1 mmol/l SDCGM [and corresponding 95% CI]: 0.413 m/s [0.147, 0.679], p = 0.002). In the model additionally adjusted for CGM-assessed mean sensor glucose (MSGCGM), SDCGM and MSGCGM contributed similarly to cf-PWV (respective standardised regression coefficients [st.βs] and 95% CIs of 0.065 [−0.018, 0.167], p = 0.160; and 0.059 [−0.043, 0.164], p = 0.272). In the fully adjusted models, both higher CVCGM (B [95% CI] per 10% CVCGM: 0.303 m/s [0.046, 0.559], p = 0.021) and lower TIRCGM (B [95% CI] per 10% TIRCGM: −0.145 m/s [−0.252, −0.038] p = 0.008) were statistically significantly associated with higher cf-PWV. Such consistent associations were not observed for the other arterial measures. Conclusions Our findings show that greater daily glucose variability and lower TIRCGM are associated with greater aortic stiffness (cf-PWV) but not with other arterial measures. If corroborated in prospective studies, these results support the development of therapeutic agents that target both daily glucose variability and TIRCGM to prevent CVD. Graphical abstract

Prehypertension is a risk factor for cardiovascular disease (CVD) and all‐cause mortality. However, it is unclear whether prehypertension combined with diabetes associate with a higher risk for cardiovascular disease and all‐cause mortality. The purpose of this study was to explore the relationship between prehypertension and the risk of CVD and all‐cause mortality was different among individuals with or without diabetes. In the prospective community‐based Kailuan study, 67 344 participants without hypertension or a history of CVD at baseline (2006) were included. Prehypertension was defined as systolic blood pressure of 120–139 mmHg or diastolic blood pressure of 80–89 mmHg. The outcomes were CVD and all‐cause mortality were followed up through December 31, 2017. We performed Cox proportional hazards models to evaluate the relationships between prehypertension and CVD and all‐cause mortality by diabetes status. During a median follow‐up of 11.03 years, 2981 CVD events and 4655 all‐cause mortality occurred. After adjusting age, sex, and other factors, the associations of prehypertension with risk of CVD and all‐cause mortality were significant in participants without diabetes (hazard ratio and 95% confidence interval: 1.54 [1.38–1.71] and 1.27 [1.17–1.38]), but not in participants with diabetes (1.20 [0.93–1.56] and 0.88 [0.73–1.07]). The interactions between prehypertension and diabetes for the risk of CVD and all‐cause mortality were all significant (all p

BackgroundElectrocardiographic T-wave morphology is used in drug safety studies as an adjunct to the QT c interval, but few measurements of T-wave morphology can be interpreted in clinical practice. Morphology combination score (MCS) is a combination of T-wave flatness/peakedness, asymmetry, and notching, enabling easy visual assessment of T-wave morphology. We aimed to test the association between T-wave morphology, quantified by MCS, and mortality.MethodsWe included electrocardiograms recorded in 2001–2011 from 342,294 primary care patients. Using Cox regression, we evaluated the association between MCS, cardiovascular death, and all-cause mortality, adjusting for heart rate, QT c, QT-prolonging drugs, diabetes, ischemic heart disease, hypertension, and congestive heart failure.Results270,039 individuals (44% men, median age 55 [inter-quartile range: 42–67 years]) were included and followed for a median of 9.3 years, during which time 13,489 (5.0%) died from cardiovascular causes and 50,481 (18.7%) from any cause. High values of MCS (i.e. asymmetric, flattened, and/or notched T waves) were associated with an adjusted mortality Hazard Ratio of 1.75 (95% CI 1.62–1.89) and 1.61 (1.43–1.92) for women and men, respectively. Low values of MCS (i.e. peaked and symmetric T waves) were associated with a Hazard Ratio of 1.18 (1.08–1.28) and 1.71 (1.48–1.98) for women and men, respectively.ConclusionsIn a large primary care population, we found that T-wave asymmetry, flatness, and notching provided prognostic information on mortality independent of heart rate, QTc, and baseline comorbidities.

Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates insulin-like growth factor-I (IGF-I) bioactivity, and is a central player in normal growth, metabolism, and stroke recovery. However, the role of serum IGFBP-1 (s-IGFBP-1) after ischemic stroke is unclear. We determined whether s-IGFBP-1 is predictive of poststroke outcome. The study population comprised patients (n = 470) and controls (n = 471) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months, 2, and 7 years using the modified Rankin Scale (mRS). Survival was followed for a minimum of 7 years or until death. S-IGFBP-1 was increased after 3 months (p < 0.01), but not in the acute phase after stroke, compared with the controls. Higher acute s-IGFBP-1 was associated with poor functional outcome (mRS score > 2) after 7 years [fully adjusted odds ratio (OR) per log increase 2.9, 95% confidence interval (CI): 1.4-5.9]. Moreover, higher s-IGFBP-1 after 3 months was associated with a risk of poor functional outcome after 2 and 7 years (fully adjusted: OR 3.4, 95% CI: 1.4–8.5 and OR 5.7, 95% CI: 2.5–12.8, respectively) and with increased mortality risk (fully adjusted: HR 2.0, 95% CI: 1.1–3.7). Thus, high acute s-IGFBP-1 was only associated with poor functional outcome after 7 years, whereas s-IGFBP-1 after 3 months was an independent predictor of poor long-term functional outcome and poststroke mortality.

Background: The impact of vitamin D supplementation on cardiovascular outcomes and mortality risk reduction remains unclear due to conflicting study findings. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), published between 1983 and 2022, that reported the effect of vitamin D supplementation in adults versus placebo or no treatment on all-cause mortality (ACM), cardiovascular mortality (CVM), non-cardiovascular mortality (non-CVM), and cardiovascular morbidities. Only studies with a follow-up period longer than one year were included. The primary outcomes were ACM and CVM. Secondary outcomes were non-CVM, myocardial infarction, stroke, heart failure, and major or extended adverse cardiovascular events. Subgroup analyses were performed according to low-, fair- and good-quality RCTs. Results: Eighty RCTs were assessed, including 82,210 participants receiving vitamin D supplementation and 80,921 receiving placebo or no treatment. The participants’ mean (SD) age was 66.1 (11.2) years, and 68.6% were female. Vitamin D supplementation was associated with a lower risk of ACM (OR: 0.95 [95%CI 0.91–0.99] p = 0.013), was close to statistical significance for a lower risk of non-CVM (OR: 0.94 [95%CI 0.87–1.00] p = 0.055), and was not statistically associated with a lower risk of any cardiovascular morbi-mortality outcome. Meta-analysis of low-quality RCTs showed no association with cardiovascular or non-cardiovascular morbi-mortality outcomes. Conclusions: The emerging results of our meta-analysis present evidence that vitamin D supplementation appears to decrease the risk of ACM (especially convincing in the fair- and good-quality RCTs), while not showing a decrease in the specific cardiovascular morbidity and mortality risk. Thus, we conclude that further research is warranted in this area, with well-planned and executed studies as the basis for more robust recommendations.

Background: Short and long sleep durations are associated with mortality outcomes. The association between sleep duration and mortality outcomes may differ according to sex and age. Methods: Participants of the Japan Public Health Center-based prospective study (JPHC Study) were aged 40–69 years and had completed a detailed questionnaire on lifestyle factors. Sex- and age-stratified analyses on the association between habitual sleep duration and mortality from all-causes, cardiovascular diseases (CVD), cancer and other causes included 46,152 men and 53,708 women without a history of CVD or cancer. Cox proportional hazards regression models, adjusted for potential confounders, were used to determine hazard ratios and 95% confidence intervals. Results: Mean follow-up time was 19.9 years for men and 21.0 years for women. In the multivariable sex-stratified models, some categories of sleep durations ≥8 hours were positively associated with mortality from all-causes, CVD, and other causes in men and women compared with 7 hours. The sex- and age-stratified analyses did not reveal any major differences in the association between sleep duration and mortality outcomes in groups younger and older than 50 years of age. The only exception was the significant interaction between sleep duration and age in women for mortality from other causes. Conclusions: Sleep durations ≥8 hours are associated with mortality outcomes in men and women. Age may be an effect modifier for the association between sleep duration and mortality from other causes in women.

Fang Gong,1 Quan Zhou,2 Chunmei Gui,1 Shaohua Huang,1 Zuoan Qin3 1Department of Intensive Care Unit, The First People’s Hospital of Changde, Changde City, Hunan Province, 415000, People’s Republic of China; 2Department of Science and Education Section, The First People’s Hospital of Changde, Changde City, Hunan Province, 415000, People’s Republic of China; 3Cardiovascular Medicine Department, The First People’s Hospital of Changde, Changde City, Hunan Province, 415000, People’s Republic of ChinaCorrespondence: Fang GongDepartment of Intensive Care Unit, The First People’s Hospital of Changde, 818 Renmin Road, Changde City, Hunan Province, 415000, People’s Republic of ChinaTel +86-0736-7788035Email gficu2009@163.comPurpose: We aimed to investigate the relationship between the serum anion gap (AG) and all-cause mortality in patients with acute pancreatitis (AP) in intensive care units (ICUs).Patients and Methods: In this retrospective cohort analysis, data of patients with AP were extracted from the Medical Information Mart for Intensive Care database (version III). We collected the maximum serum AG value within the first 24 hours of ICU admission. The main outcome was 90-day all-cause mortality. A multivariate Cox proportional hazard regression model was used to examine the association between the serum AG and mortality. The restricted cubic spline curve was used to confirm a non-linear relationship between serum AG values and mortality.Results: Of the 279 patients included in the study, 87 (31.18%) died. The serum AG value was positively associated with 90-day all-cause mortality (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.02– 1.14), after adjusting for age, sex, alcohol consumption, congestive heart failure, diabetes mellitus, hypertension, eGFR, albumin, and the SOFA score. There was a non-linear relationship between serum AG values and mortality after adjusting for potential confounders. We used a two-piecewise regression model to obtain a threshold inflection point value of 13.8 mmol/L. The HR and the 95% CI on the left inflection point were 0. 82 (0.61– 1.09; p = 0.1719), and on the right inflection point were 1.15 (1.08– 1.23; p < 0.0001).Conclusion: The relationship between all-cause mortality in patients with acute pancreatitis and serum AG values was non-linear. All-cause mortality and serum AG values were positively correlated when the serum AG value was > 13.8 mmol/L.Keywords: anion gap, all-cause mortality, acute pancreatitis, MIMIC III database

Objective: To compare cancer-specific mortality (CSM) and all-cause mortality (ACM) between patients with and without sarcopenia who underwent radical cystectomy for bladder cancer. Materials and methods: We performed a systematic review and meta-analysis of original articles published from October 2010 to March 2019 evaluating the effect of sarcopenia on CSM and ACM. We extracted hazard ratios (HRs) and 95% confidence intervals (CIs) for CSM and ACM from the included studies. Heterogeneity amongst studies was measured using the Q-statistic and the I2 index. Meta-analysis was performed using a random-effects model if heterogeneity was high and fixed-effects models if heterogeneity was low. Results: We identified 145 publications, of which five were included in the meta-analysis. These five studies represented 1447 patients of which 453 were classified as sarcopenic and 534 were non-sarcopenic. CSM and ACM were increased in sarcopenic vs non-sarcopenic patients (HR 1.64, 95% CI 1.30–2.08, P

Jinbo Yu,1– 3 Xiaohong Chen,1– 3 Yang Li,1– 3 Yaqiong Wang,1– 3 Zhonghua Liu,1– 3 Bo Shen,1– 3 Jie Teng,1– 3 Jianzhou Zou,1– 3 Xiaoqiang Ding1– 3 1Division of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Institute of Kidney Disease and Dialysis, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, People’s Republic of ChinaCorrespondence: Xiaoqiang DingDivision of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of ChinaTel +86-2164041990Email ding.xiaoqiang@zs-hospital.sh.cnBackground: A greater interdialytic weight gain (IDWG) implies a greater ultrafiltration rate, which might lead to hemodynamic instability and intradialytic blood pressure (BP) change in hemodialysis patients. However, current studies have not explicated the impact of IDWG on the association between intradialytic BP changes and prognosis, especially in patients without cardiac dysfunction and diabetes. In this study, we aimed to explore the relationship between absolute intradialytic BP changes and mortality with different IDWG levels.Methods: A total of 204 hemodialysis patients (without cardiac dysfunction and diabetes) were included in this prospective observation study, with a mean follow-up of 55.32± 20.99 months. Initially, we collected IDWG, IDWG% (percentages according to dry weight), and pre-/post-BPs of 36 consecutive dialysis sessions during three months enrollment. And the average value of them was defined as baseline value. Patients were divided into 3 cohorts according to IDWG% tertiles (< 3.3%, 3.3%– 4.6%, ≥ 4.6%). Comparisons between different tertiles were analyzed.Results: Compared to the low IDWG% group (tertile 1, T1), patients of high IDWG% group (tertile 3, T3) were younger, had higher ultrafiltration rate, less residual kidney function, lower BMI and dry weight, longer dialysis vintage and higher N terminal pro B type natriuretic peptide levels (P< 0.05). Correlations were found between IDWG% and intradialytic BP changes. Kaplan–Meier analysis and multivariate Cox regression model adjusted for demographic data, dialysis information and predialysis BPs indicated that greater absolute intradialytic BP changes were associated with worse prognosis in T1 group (P< 0.05). While in T3 group, less absolute intradialytic BP changes were associated with higher mortality (P< 0.05).Conclusion: There is a paradoxical association between absolute intradialytic BP changes and long-term mortality with different IDWG levels. Both BP stability and volume balance are crucial to patients’ prognosis.Keywords: all-cause mortality, hemodialysis, interdialytic weight gain, intradialytic blood pressure

The most fundamental function of vitamin K is to activate the blood coagulation factors in the liver. Despite the recent recognition of its extra-hepatic actions, the current Dietary Reference Intakes for vitamin K is based on the amount necessary for maintaining the normal blood coagulation in many countries. To define the Dietary Reference Intake for vitamin K, appropriate biomarkers well-reflecting the vitamin K status are essential. Unfortunately, however, no markers are currently available with properties enabling us to properly define the vitamin K status; i.g., no interference by other factors and the presence of widely approved cut-off values. Thus, Adequate Intake is determined, which is an index based on the representative dietary intake data from healthy individuals. Recently, epidemiological studies have been reported regarding the relationship between vitamin K and noncommunicable diseases including osteoporotic fracture. Furthermore, studies focusing on the relationship between vitamin K intake and metabolic syndrome, physical function, depression, cognition, and all-cause mortality have become available, although limited in number. This review summarizes the recent findings in favor of the novel functions of vitamin K. More epidemiological studies are needed to define the appropriate vitamin K intake value based on the prevention of various disorders.

Introduction: Since December 2019, the humanity is constantly under affection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite global dissemination, neither the treatment or the specific predictive factors have been found or strictly defined yet. Aim: Aim of this study was to assess the long-term (1 year) predictive value of high-sensitive Troponin T (hsTnT) in COVID-19 affected, hospitalised patients. Methods: Between 5 March 2020 and 31 March 2020, 87 consecutive patients hospitalised at University Clinical Centre of the Republic of Srpska due to SARS-CoV2caused pneumonia, in whom hsTnT was measured, were included. The Kaplan-Meier analysis was used to assess differences in all-cause mortality between the groups. Independent predictors of all-cause mortality were identified through univariateand multivariate Cox regression analysis. Results: Compared with patients who had normal hsTnT levels, patients with raised hsTnT were significantly older (70.7 ± 13.23 vs 49 ± 15.29; p < 0.001). Glucose values were significantly increased in patients with raised hsTnT (9.29 ± 5.14 vs 6.76 ± 2.46 [4.1-5.9] mmol/L; p = 0.005), as well as serum creatinine (179.07 ± 225.58 vs 87.53 ± 18.16 µmol/L; p = 0.01), hsTnT (187.43 ± 387.29 vs 7.58 ± 3.40 pg/mL; p = 0.003), D-dimer (5.94 ± 13.78 vs 1.04 ± 1.26 [0-0.50] mg/L; p = 0.024), C-reactive protein (125.92 ± 116.82 vs 69.97 ± 73.09) [< 5.0] mg/L; p = 0.009) and calcium (1.32 ± 0.46 vs 1.03 ± 0.173 [2.20-2.65] mmol/L; p = 0.001). Kaplan-Meier analysis revealed that the number of all-cause deaths at 1 year was 19 of whom 18 were presented with elevated hsTnT (log-rank p < 0.001). When univariate Cox regression was applied, multiple predictors of all-cause mortality have been identified ie age, haemoglobin, haematocrit, urea, CK-MB as well as hsTnT. In a multiple regression model, hsTnT remained an independent predictor of poor outcome. Conclusion: Results from this study showed that the value of hsTnT during hospitalisation is possibly associated with long-term poor outcome of COVID-19 patients. Therefore, hsTnT may appear as a surrogate factor to differentiate between patients at high risk who need more intensive follow-ups.

HIGHLIGHTS • D-dimer levels can discriminate between COVID 19 patients with and without worse clinical outcomes (all-cause mortality, ICU admission or ARDS) • Elevated D-dimer levels are associated with increased risk of adverse clinical outcomes in patients hospitalized with COVID 19 infection • Patients who died had higher D-dimer levels than patients who survived • A substantial elevation in D-dimers may be an indicator of progressive disease, Aim To determine if D-dimers are elevated in individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who have adverse clinical outcomes including all-cause mortality, intensive care unit (ICU) admission or acute respiratory distress syndrome (ARDS). Methods We conducted a systematic review and meta-analysis of the published literature in PubMed, Embase and Cochrane databases through April 9, 2020 for studies evaluating D-dimer levels in SARS-COV-2 infected patients with and without a composite clinical endpoint, defined as the presence of all-cause of mortality, Intensive care unit (ICU) admission or acute respiratory distress syndrome (ARDS). A total of six studies were included in the meta-analysis. Results D-dimers were significantly increased in patients with the composite clinical end point than in those without (SMD, 1.67 ug/ml (95% CI, 0.72-2.62 ug/ml). The SMD of the studies (Tang et al, Zhou et al, Chen et al), which used only mortality as an outcome measure was 2.5 ug/mL (95% CI, 0.62-4.41 ug/ml). Conclusion We conclude that SARS-CoV-2 infected patients with elevated D-dimers have worse clinical outcomes (all-cause mortality, ICU admission or ARDS) and thus measurement of D-dimers can guide in clinical decision making.

Aims: The 2019 and 2021 European Society of Cardiology (ESC) classifications stratified patients with type 2 diabetes into three categories according to the 10-year risk of death from atherosclerotic cardiovascular disease (ASCVD). The very high-risk category included individuals with established ASCVD, target organ damage (TOD), and/or, in the 2019 classification only, ≥ 3 additional ASCVD risk factors. We assessed risk of all-cause mortality according to the two ESC classifications in the Renal Insufficiency And Cardiovascular Events cohort. Methods: Participants (n = 15,773) were stratified based on the presence of ASCVD, TOD, and ASCVD risk factors at baseline (2006–2008). Vital status was retrieved in 2015. Results: Less than 1% of participants fell in the moderate-risk category. According to the 2019 classification, ~ 1/3 fell in the high-risk and ~ 2/3 in the very high-risk category, whereas the opposite occurred with the 2021 classification. Mortality risk increased across categories according to both classifications. Among very high-risk patients, mortality was much lower in those with ≥ 3 additional ASCVD risk factors and almost equal in those with TOD and ASCVD ± TOD, using the 2019 classification, whereas it was much higher in those with ASCVD + TOD and, to a lesser extent, TOD only than in those with ASCVD only, using the 2021 classification. Conclusions: The negligible number of moderate-risk patients suggests that these classifications might overestimate risk of ASCVD death. Downgrading patients with ≥ 3 additional ASCVD risk factors to the high-risk category is consistent with mortality data. Risk of death is very high in the presence of TOD irrespective of established ASCVD. Trial registration: ClinicalTrials.gov, NCT00715481.