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Vitamin K deficiency is common among kidney transplant recipients (KTRs) and likely contributes to progressive vascular calcification and stiffness. In this single-center, randomized, double-blind, placebo-controlled trial, we aimed to investigate the effects of vitamin K supplementation on the primary end point, serum calcification propensity (calciprotein particle maturation time, T50), and secondary end points arterial stiffness (pulse wave velocity [PWV]) and vitamin K status in 40 vitamin K-deficient KTRs (plasma dephosphorylated uncarboxylated matrix Gla protein [dp-ucMGP] ≥500 pmol/L). Participants (35% female; age, 57 ± 13 years) were randomized 1:1 to vitamin K2 (menaquinone-7, 360 μg/day) or placebo for 12 weeks. Vitamin K supplementation had no effect on calcification propensity (change in T50 vs baseline +2.3 ± 27.4 minutes) compared with placebo (+0.8 ± 34.4 minutes; Pbetween group = .88) but prevented progression of PWV (change vs baseline -0.06 ± 0.26 m/s) compared with placebo (+0.27 ± 0.43 m/s; Pbetween group = .010). Vitamin K supplementation strongly improved vitamin K status (change in dp-ucMGP vs baseline -385 [-631 to -269] pmol/L) compared with placebo (+39 [-188 to +183] pmol/L; Pbetween group < .001), although most patients remained vitamin K-deficient. In conclusion, vitamin K supplementation did not alter serum calcification propensity but prevented progression of arterial stiffness, suggesting that vitamin K has vascular effects independent of calciprotein particles. These results set the stage for longer-term intervention studies with vitamin K supplementation in KTRs.TRIAL REGISTRY: EU Clinical Trials Register (EudraCT Number: 2019-004906-88) and the Dutch Trial Register (NTR number: NL7687).

Objective Type D personality, a joint tendency toward negative affectivity and social inhibition, has been linked to adverse events in patients with heart disease, although with inconsistent findings. Here, we apply an individual patient-data meta-analysis to data from 19 prospective cohort studies (N = 11,151) to investigate the prediction of adverse outcomes by type D personality in patients with acquired cardiovascular disease. Method For each outcome (all-cause mortality, cardiac mortality, myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, major adverse cardiac event, any adverse event), we estimated type D's prognostic influence and the moderation by age, sex, and disease type. Results In patients with cardiovascular disease, evidence for a type D effect in terms of the Bayes factor (BF) was strong for major adverse cardiac event (BF = 42.5; odds ratio [OR] = 1.14) and any adverse event (BF = 129.4; OR = 1.15). Evidence for the null hypothesis was found for all-cause mortality (BF = 45.9; OR = 1.03), cardiac mortality (BF = 23.7; OR = 0.99), and myocardial infarction (BF = 16.9; OR = 1.12), suggesting that type D had no effect on these outcomes. This evidence was similar in the subset of patients with coronary artery disease (CAD), but inconclusive for patients with heart failure (HF). Positive effects were found for negative affectivity on cardiac and all-cause mortality, with the latter being more pronounced in male than female patients. Conclusion Across 19 prospective cohort studies, type D predicts adverse events in patients with CAD, whereas evidence in patients with HF was inconclusive. In both patients with CAD and HF, we found evidence for a null effect of type D on cardiac and all-cause mortality.

Background: Sleep is fragmented by brief arousals, and excessive arousal burden has been linked to increased cardiovascular (CV) risk, but mechanisms are poorly understood. Research Question: Do arousals trigger cardiac ventricular repolarization lability that may predispose people to long-term cardiovascular mortality? Study Design and Methods: This study analyzed 407,541 arousals in the overnight polysomnograms of 2,558 older men in the Osteoporotic Fractures in Men sleep study. QT and RR intervals were measured beat-to-beat starting 15 s prior to arousal onset until 15 s past onset. Ventricular repolarization lability was quantified by using the QT variability index (QTVi). Results: During 10.1 ± 2.5 years of follow-up, 1,000 men died of any cause, including 348 CV deaths. During arousals, QT and RR variability increased on average by 5 and 55 ms, respectively, resulting in a paradoxical transient decrease in QTVi from 0.07 ± 1.68 to –1.00 ± 1.68. Multivariable Cox proportional hazards analysis adjusted for age, BMI, cardiovascular and respiratory risk factors, sleep-disordered breathing and arousal, diabetes, and Parkinson disease indicated that excessive QTVi during arousal was independently associated with all-cause and CV mortality (all-cause hazard ratio, 1.20 [95% CI, 1.04-1.38; P = .012]; CV hazard ratio, 1.29 [95% CI, 1.01 -1.65; P = .043]). Interpretation: Arousals affect ventricular repolarization. A disproportionate increase in QT variability during arousal is associated with an increased all-cause and CV mortality and may reflect ventricular repolarization maladaptation to the arousal stimulus. Whether arousal-related QTVi can be used for more tailored risk stratification warrants further study, including evaluating whether arousal suppression attenuates ventricular repolarization lability and reduces subsequent mortality. Clinical Trial Registration: ClinicalTrials.gov; No.: NCT00070681; URL: www.clinicaltrials.gov

ObjectivesA European League Against Rheumatism taskforce was convened to review the literature and develop recommendations on lifestyle behaviours for rheumatic and musculoskeletal diseases (RMDs).MethodsSix lifestyle exposures (exercise, diet, weight, alcohol, smoking, work participation) and seven RMDs (osteoarthritis, rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, systemic lupus erythematosus, systemic sclerosis, gout) were considered. The taskforce included health professionals in rheumatology, geriatricians, epidemiologists, public health experts, people with RMDs and exposure domain experts. Systematic reviews were conducted to gather available evidence, from which recommendations were developed.ResultsFive overarching principles and 18 specific recommendations were defined based on available evidence. The overarching principles define the importance of a healthy lifestyle, how lifestyle modifications should be implemented, and their role in relation to medical treatments. Exercise recommendations highlight the safety and benefits of exercise on pain and disability, particularly among people with osteoarthritis and axial spondyloarthritis. The diet recommendations emphasise the importance of a healthy, balanced diet for people with RMDs. People with RMDs and health professionals should work together to achieve and maintain a healthy weight. Small amounts of alcohol are unlikely to negatively affect the outcomes of people with RMDs, although people with rheumatoid arthritis and gout may be at risk of flares after moderate alcohol consumption. Smokers should be supported to quit. Work participation may have benefits on RMD outcomes and should be discussed in consultations.ConclusionsThese recommendations cover a range of lifestyle behaviours and can guide shared decision making between people with RMDs and health professionals when developing and monitoring treatment plans.

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.

Background: The aim of this systematic review was to synthesise the current literature on all-cause and cause-specific mortality in individuals with autism spectrum disorders (ASD) to identify whether they experience an increased risk of mortality compared to the general population and to establish which specific causes of death are most prevalent in ASD individuals.Method: Medline, Embase, CINAHL and PsycINFO databases were searched. The review was registered with PROSPERO (CRD42021219582).Results: 26 of the 8,505 retrieved papers were included. All 26 studies reported an increased risk of mortality for individuals with ASD. The highest standardised mortality ratio for people with ASD was 5.6 (95% CI= 2.5-10.5). Five studies suggested that females with ASD were at an even greater risk of death when compared to their male counterparts. The most common causes of deaths were from external causes (particularly suicide) and neurological diseases.Conclusions: Recognising the increased mortality experienced by individuals with ASD is an important factor in how clinicians, support workers and healthcare systems in general should plan and approach care for this population. Although a significant portion of deaths in this group occur due to intentional or unintentional external causes, the reviewed literature also indicates that many people with ASD die from underlying health conditions. As the increased mortality risk seems to be partially mediated by the co-occurrence of other conditions, it is of great importance to provide an increased level of support and care for this population.

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.

Colorectal cancer (CRC) is increasingly recognized as a heterogeneous disease. No studies have prospectively examined associations of blood metabolite concentrations with all-cause mortality in patients with colon and rectal cancer separately. Targeted metabolomics (Biocrates AbsoluteIDQ p180) and pathway analyses (MetaboAnalyst 4.0) were performed on pre-surgery collected plasma from 674 patients with non-metastasized (stage I–III) colon (n = 394) or rectal cancer (n = 283). Metabolomics data and covariate information were received from the international cohort consortium MetaboCCC. Cox proportional hazards models were computed to investigate associations of 148 metabolite levels with all-cause mortality adjusted for age, sex, tumor stage, tumor site (whenever applicable), and cohort; the false discovery rate (FDR) was used to account for multiple testing. A total of 93 patients (14%) were deceased after an average follow-up time of 4.4 years (60 patients with colon cancer and 33 patients with rectal cancer). After FDR adjustment, higher plasma creatinine was associated with a 39% increase in all-cause mortality in patients with rectal cancer. HR: 1.39, 95% CI 1.23–1.72, pFDR = 0.03; but not colon cancer: pFDR = 0.96. Creatinine is a breakdown product of creatine phosphate in muscle and may reflect changes in skeletal muscle mass. The starch and sucrose metabolisms were associated with increased all-cause mortality in colon cancer but not in rectal cancer. Genes in the starch and sucrose metabolism pathways were previously linked to worse clinical outcomes in CRC. In summary, our findings support the hypothesis that colon and rectal cancer have different etiological and clinical outcomes that need to be considered for targeted treatments.

Although recent evidence has revealed that a body shape index (ABSI) is correlated with the incidence of death among different ethnicities, there remains a paucity of studies investigating the impact of ABSI on mortality within the Chinese elderly. Our objective was to ascertain the link between ABSI, as well as its alterations over time, and all-cause mortality among Chinese aged 65 y and above. A total of 3789 participants were enrolled from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Cox regressions and restricted cubic splines were employed to assess the association of ABSI and relative changes with all-cause mortality. When nonlinearity was detected, a restricted cubic spline regression was subsequently conducted to compute hazard ratios and 95% confidence intervals. The median survival time was 46 months, and 1342 individuals (35.4%) were reported to have died. ABSI contributed independently to rising death rates among Chinese old populations according to univariate and multivariate Cox regressions. Statistically significant associations were also found stratified by age, sex, and lifestyle. A U-shaped association of ABSI changes with all-cause mortality (p = 0.027) was observed, indicating that old adults with stable ABSI during the follow-up period experienced the lowest risk of mortality. After multivariable adjustment, participants with a 10% reduction in ABSI changes had an increased 9.4% risk of death, while participants with a 10% rise in ABSI changes had an increased 1.9% risk. ABSI and its changes are predictors for all-cause mortality among the elderly Chinese population, which emphasizes the clinical importance of monitoring ABSI and keeping it stable over time.

BackgroundWhile educational gradients in longevity have been observed consistently in adult Europeans, these inequalities have been understudied within the context of family- and country-level influences. We utilized population-based multi-generational multi-country data to assess the role (1) of parental and individual education in shaping intergenerational inequalities in longevity, and (2) of country-level social net expenditure in mitigating these inequalities.MethodsWe analyzed data from 52,271 adults born before 1965 who participated in the Survey of Health, Ageing and Retirement in Europe, comprising 14 countries. Mortality from all causes (outcome) was ascertained between 2013 and 2020. Educational trajectories (exposure) were High-High (reference), Low-High, High-Low, and Low-Low, corresponding to the sequence of parental-individual educational attainment. We quantified inequalities as years of life lost (YLL) between the ages of 50 and 90 estimated via differences in the area under standardized survival curves. We assessed the association between country-level social net expenditure and YLL via meta-regression.ResultsInequalities in longevity due to educational trajectories were associated with low individual education regardless of parental education. Compared to High-High, having High-Low and Low-Low led to 2.2 (95% confidence intervals: 1.0 to 3.5) and 2.9 (2.2 to 3.6) YLL, while YLL for Low-High were 0.4 (−0.2 to 0.9). A 1% increase in social net expenditure led to an increase of 0.01 (−0.3 to 0.3) YLL for Low-High, 0.007 (−0.1 to 0.2) YLL for High-Low, and a decrease of 0.02 (−0.1 to 0.2) YLL for Low-Low.ConclusionIn European countries, individual education could be the main driver of inequalities in longevity for adults older than 50 years of age and born before 1965. Further, higher social expenditure is not associated with smaller educational inequalities in longevity.

The average UPFD consumption was 181 (SD 88) g per 1000 kcal. High UPF consumption was statistically significantly inversely associated with all environmental impact indicators (Q4vsQ1: -13.6% to -3.0%) whereas high UPD consumption was, except for land use, statistically significant positively associated with all environmental impact indicators (Q4vsQ1: 5.9% to 1.2%). High UPFD consumption was heterogeneously associated with environmental impacts (Q4vsQ1: 2.6% to -4.0% ). After multivariable adjustment, the highest quartiles of UPFD and UPD consumption were significantly associated with all-cause mortality (HRQ4vsQ1 1.20, 95%CI 1.10,1.30 and HRQ4vsQ1 1.19, 95%CI 1.09,1.29, respectively). UPF consumption of Q2 and Q3 were associated with a borderline significant lower risk of all-cause mortality (HRQ2vsQ1 0.93, 95% CI 0.85,1.00; HRQ3vsQ1 0.91, 95% CI 0.84,0.99), while Q4 was not statistically significant (HRQ4vsQ1 1.05, 95% CI 0.96,1.15).

The average UPFD consumption was 181 (SD 88) g per 1000 kcal. High UPF consumption was statistically significantly inversely associated with all environmental impact indicators (Q4vsQ1: -13.6% to -3.0%) whereas high UPD consumption was, except for land use, statistically significant positively associated with all environmental impact indicators (Q4vsQ1: 5.9% to 1.2%). High UPFD consumption was heterogeneously associated with environmental impacts (Q4vsQ1: 2.6% to -4.0% ). After multivariable adjustment, the highest quartiles of UPFD and UPD consumption were significantly associated with all-cause mortality (HRQ4vsQ1 1.20, 95%CI 1.10,1.30 and HRQ4vsQ1 1.19, 95%CI 1.09,1.29, respectively). UPF consumption of Q2 and Q3 were associated with a borderline significant lower risk of all-cause mortality (HRQ2vsQ1 0.93, 95% CI 0.85,1.00; HRQ3vsQ1 0.91, 95% CI 0.84,0.99), while Q4 was not statistically significant (HRQ4vsQ1 1.05, 95% CI 0.96,1.15).

The psychosocial and health consequences of ocular conditions that cause visual impairment (VI) are extensive and include impaired daily activities, social isolation, cognitive impairment, impaired functional status and functional decline, increased reliance on others, increased risk of motor vehicle accidents, falls and fractures, poor self-rated health, and depression. We aimed to determine whether VI increases the likelihood of a poor prognosis, including mental illness, suicide, and mortality over time. In this large, location, population-based, nested, cohort study, we used data from 2000 to 2015 in the Taiwan National Health Insurance Research Database (NHIRD), which includes diagnoses of all the patients with VI. Baseline features, comorbidities, and prognostic variables were evaluated using a 1:4-matched cohort analysis. Furthermore, comparisons were performed using Cox regression and Bonferroni-correction (for multiple comparisons) to study the association between VI and poor prognosis (mental illness, suicide). The study outcome was the cumulative incidence of poor prognosis among the visually impaired and controls. A two-tailed Bonferroni-corrected p < 0.001 was considered statistically significant. Among the 1,949,101 patients enlisted in the NHIRD, 271 had been diagnosed with VI. Risk factors for poor prognosis and the crude hazard ratio was 3.004 (95% confidence interval 2.135–4.121, p < 0.001). Participants with VI had an increased risk of poor prognosis according to the sensitivity analysis, with a poor prognosis within the first year and first five years. VI was associated with suicide and mental health risks. This study revealed that patients with VI have a nearly 3-fold higher risk of psychiatric disorders, including anxiety, depression, bipolar, and sleep disorders, than the general population. Early detection through comprehensive examinations based on increased awareness in the clinical context may help maintain visual function and avoid additional complications.

BackgroundHigher baseline intakes of flavonoid-rich foods and beverages are associated with a lower risk of chronic disease and mortality in observational studies. However, associations between changes in intakes and mortality remain unclear. We aimed to evaluate associations between 8-year changes in intakes of (1) individual flavonoid-rich foods and (2) a composite measure (termed the ‘flavodiet’) of foods and beverages that are known to be main contributors to flavonoid intake and subsequent total and cause-specific mortality.MethodsWe evaluated associations between 8-year changes in intakes of (1) individual flavonoid-rich foods and (2) a novel ‘flavodiet’ score and total and cause-specific mortality. We included 55,786 females from the Nurses’ Health Study (NHS) and 29,800 males from the Health Professionals Follow-up Study (HPFS), without chronic disease at baseline in our analyses. Using multivariable-adjusted Cox proportional hazard models, we examined associations of 8-year changes in intakes of (1) flavonoid-rich foods and (2) the flavodiet score with subsequent 2-year lagged 6-year risk of mortality adjusting for baseline intakes. Data were pooled using fixed-effects meta-analyses.ResultsWe documented 15,293 deaths in the NHS and 8988 deaths in HPFS between 1986 and 2018. For blueberries, red wine and peppers, a 5%, 4% and 9% lower risk of mortality, respectively, was seen for each 3.5 servings/week increase in intakes while for tea, a 3% lower risk was seen for each 7 servings/week increase [Pooled HR (95% CI) for blueberries; 0.95 (0.91, 0.99); red wine: 0.96 (0.93, 0.99); peppers: 0.91 (0.88, 0.95); and tea: 0.97 (0.95, 0.98)]. Conversely, a 3.5 servings/week increase in intakes of onions and grapefruit plus grapefruit juice was associated with a 5% and 6% higher risk of total mortality, respectively. An increase of 3 servings per day in the flavodiet score was associated with an 8% lower risk of total mortality [Pooled HR: 0.92 (0.89, 0.96)], and a 13% lower risk of neurological mortality [Pooled HR: 0.87 (0.79, 0.97)], after multivariable adjustments.ConclusionsEncouraging an increased intake of specific flavonoid-rich foods and beverages, namely tea, blueberries, red wine, and peppers, even in middle age, may lower early mortality risk.

A substantial part of mortality during the COVID-19-pandemic occurred among nursing home residents which caused alarm in many countries. We investigate nursing home mortality in relation to the expected mortality prior to the pandemic. This nationwide register-based study included all 135,501 Danish nursing home residents between 2015 until October 6, 2021. All-cause mortality rates were calculated using a standardization method on sex and age distribution of 2020. Survival probability and lifetime lost for 180 days was calculated using Kaplan Meier estimates. Of 3,587 COVID-19 related deaths, 1137 (32%) occurred among nursing home residents. The yearly all-cause mortality rates per 100,000 person-years in 2015, 2016, and 2017 were 35,301 (95% CI: 34,671–35,943), 34,801 (95% CI: 34,180–35,432), and 35,708 (95% CI: 35,085–36,343), respectively. Slightly elevated mortality rates per 100,000 person-years were seen in 2018, 2019, 2020, and 2021 of 38,268 (95% CI: 37,620–38,929), 36,956 (95% CI: 36,323–37,600), 37,475 (95% CI: 36,838–38,122), and 38,536 (95% CI: 37,798–39,287), respectively. For SARS-CoV-2-infected nursing home residents, lifetime lost difference was 42 days (95% CI: 38–46) in 2020 versus non-infected in 2018. Among vaccinated in 2021, lifetime lost difference was 25 days (95% CI: 18–32) for SARS-CoV-2-infected versus non-infected. Even though a high proportion of COVID-19 fatalities took place in nursing homes and SARS-CoV-2-infection increased the risk of individual death, the annual mortality was only slightly elevated. For future epidemics or pandemics reporting numbers of fatal cases in relation to expected mortality is critical. A substantial part of mortality during the COVID-19-pandemic occurred among nursing home residents which caused alarm in many countries. We investigate nursing home mortality in relation to the expected mortality prior to the pandemic. This nationwide register-based study included all 135,501 Danish nursing home residents between 2015 until October 6, 2021. All-cause mortality rates were calculated using a standardization method on sex and age distribution of 2020. Survival probability and lifetime lost for 180 days was calculated using Kaplan Meier estimates. Of 3,587 COVID-19 related deaths, 1137 (32%) occurred among nursing home residents. The yearly all-cause mortality rates per 100,000 person-years in 2015, 2016, and 2017 were 35,301 (95% CI: 34,671–35,943), 34,801 (95% CI: 34,180–35,432), and 35,708 (95% CI: 35,085–36,343), respectively. Slightly elevated mortality rates per 100,000 person-years were seen in 2018, 2019, 2020, and 2021 of 38,268 (95% CI: 37,620–38,929), 36,956 (95% CI: 36,323–37,600), 37,475 (95% CI: 36,838–38,122), and 38,536 (95% CI: 37,798–39,287), respectively. For SARS-CoV-2-infected nursing home residents, lifetime lost difference was 42 days (95% CI: 38–46) in 2020 versus non-infected in 2018. Among vaccinated in 2021, lifetime lost difference was 25 days (95% CI: 18–32) for SARS-CoV-2-infected versus non-infected. Even though a high proportion of COVID-19 fatalities took place in nursing homes and SARS-CoV-2-infection increased the risk of individual death, the annual mortality was only slightly elevated. For future epidemics or pandemics reporting numbers of fatal cases in relation to expected mortality is critical.

While the efficacy of the newly developed mRNA and vector vaccines against SARS-CoV-2 have been widely advertised, their harm-to-benefit ratio still remains widely ignored. Though, reports of possible side effects are piling up. The most severe of those side effects is a sudden and unexpected death, with liability issues inducing strong incentives to communicate potentially associated mortalities always aligned with the particular motives and interests. Accordingly, reliable estimates of how many deaths might have been actually caused by the vaccination are still missing up to date, to the best of our knowledge, in Germany at least. Here, we fill this void and provide such an estimate for Germany during the course of 2021. Thereto, the number of deaths reported by the Paul-Ehrlich-Institut to have occurred within the group of people suspectedly struck by a vaccine-induced adverse event is scaled by the factor of under-reporting, based on health insurance reports, and finally corrected by known all-cause mortality. Our point estimate for the year 2021 alone reaches a total of 16,817 (short-term) deaths caused by SARS-CoV-2 vaccination. Taking independent autopsy reports into account, the estimate of 11,194 deaths is the lower bound. This report may serve as a pivot for further investigations in this matter. &nbsp

Relative abundance of fibroblast growth factor-23 (FGF23) measured by the C-terminal (cFGF23, which measures both intact FGF23 and C-terminal fragments) versus intact (iFGF23, measures only intact hormone) assays varies by kidney function in humans. Differential kidney clearance may explain this finding. We measured cFGF23 and iFGF23 in the aorta and bilateral renal veins of 162 patients with essential hypertension undergoing renal angiography. Using multivariable linear regression, we examined factors associated with aorta to renal vein reduction of FGF23 using both assays. Similar parameters and with addition of urine concentrations of cFGF23 and iFGF23 were measured in six Wistar rats. Mean ± standard deviation (SD) age was 54± 12 years, 54% were women, and mean creatinine clearance was 72 ± 48 mL/min/100 g. The human kidney reduced the concentrations of both cFGF23 (16% ± 12%) and iFGF23 (21% ± 16%), but reduction was higher for iFGF23. Greater kidney creatinine and PTH reductions were each independently associated with greater reductions of both cFGF23 and iFGF23. The greater kidney reduction of iFGF23 compared to cFGF23 appeared stable and consistent across the range of creatinine clearance evaluated. Kidney clearance was similar, and urine concentrations of both assays were low in the rat models, suggesting kidney metabolism of both cFGF23 and iFGF23. Renal reduction of iFGF23 is higher than that of creatinine and cFGF23. Our data suggest that FGF23 is metabolized by the kidney. However, the major cell types involved in metabolization of FGF23 requires future study. Kidney clearance of FGF23 does not explain differences in C-terminal and intact moieties across the range of kidney function. © 2022 American Society for Bone and Mineral Research (ASBMR).

Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with waist circumference and waist-to-hip ratio adjusted for body mass index (WCadjBMI, WHRadjBMI), but it remains unclear whether these SNPs relate to change in WCadjBMI or WHRadjBMI with lifestyle intervention. We hypothesized that polygenic scores (PS) comprised of 59 SNPs previously associated with central adiposity would predict less of a reduction in WCadjBMI or WHRadjBMI at eight-to-ten weeks in two lifestyle intervention trials, NUGENOB and DiOGenes, and at one year in 5 lifestyle intervention trials, Look AHEAD, Diabetes Prevention Program, Diabetes Prevention Study, DIETFITS, and PREDIMED-Plus. One standard deviation higher PS related to smaller one-year change in WCadjBMI in the lifestyle intervention arms at year 1, and thus predicted poorer response (beta=0.007, SE=0.003, p=0.03) among White participants overall and in White men (beta=0.01, SE=0.004, p=0.01). At average weight loss, this amounted to 0.20-0.28 cm per standard deviation. No significant findings emerged in White women, African American men, for the 8-10 week outcomes or for WHRadjBMI. Findings were heterogeneous in African American women. These results indicate that polygenic risk relates to change in WCadjBMI with lifestyle intervention but the effects are small and not of sufficient magnitude to be clinically significant.

Zuoan Qin,1,2 Nuohan Liao,3 Xuelin Lu,4 Xiangjie Duan,5 Quan Zhou,6 Liangqing Ge1,2 1Jinan University, Guangzhou, 510632, People’s Republic of China; 2Department of Cardiology, The First People’s Hospital of Changde City, Changde, 415003, People’s Republic of China; 3University of South China, Hengyang, Hunan, 421002, People’s Republic of China; 4Department of Pathology, The First People’s Hospital of Changde City, Changde, 415003, People’s Republic of China; 5Department of Infectious Diseases, The First People’s Hospital of Changde City, Changde, 415003, People’s Republic of China; 6Department of Science and Education, The First People’s Hospital of Changde City, Changde, 415003, People’s Republic of ChinaCorrespondence: Liangqing Ge, Email geliangqing@163.comAim: To investigate the association between the hemoglobin-to-red cell distribution width (RDW) ratio (HRR) and all-cause mortality in ischemic stroke patients with atrial fibrillation (AF).Design: This study was a retrospective cohort analysis. In total, 1018 ischemic stroke patients with AF were enrolled using the Medical Information Mart for Intensive Care database, (MIMIC)-IV. The patients were divided into four groups according to the HRR values. The primary outcome was 180-day all-cause mortality.Methods: Multivariate Cox proportional risk regression models were used to examine the association between HRR and all-cause mortality. The non-linear relationship between HRR and all-cause mortality was confirmed using a Cox proportional risk regression model fitted by cubic spline function and smooth curve fitting.Results: A total of 246/1018 patients (24.17%) died. The serum HRR values were negatively associated with 180-day all-cause mortality (hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.68– 0.94). A two-piecewise regression model was used to obtain a threshold inflection point value of 9.74. The HR and the 95% CI on the left inflection point were 0.73 and 0.61– 0.87 (p = 0.0005); on the right inflection point they were 1.06 and 0.82– 1.38 (p = 0.6383).Conclusion: The relationship between all-cause mortality and the HRR values was non-linear in ischemic stroke patients with AF. All-cause mortality and HRR values were negatively correlated when the HRR value was ≤ 9.74.Keywords: ischemic stroke, atrial fibrillation, all-cause mortality, MIMIC-IV

Zesong Hu, Jie Wang, Yangjing Xue, Qianqian Zhang, Qianqian Xu, Kangting Ji, Ripeng Yin Department of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of ChinaCorrespondence: Kangting Ji; Ripeng YinDepartment of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Xueyuanxi Road, No. 109, Wenzhou, 325000, Zhejiang, People’s Republic of China, Tel/Fax +86-577-88002216, Email jikt@wmu.edu.cn; 15948657@qq.comBackground: Neutrophils and albumin had been shown to be independent predictors of mortality from various diseases. Purpose of this study was to investigate the effect of neutrophil-to-albumin ratio (NPAR) as an independent predictor of mortality in heart failure (HF) patients.Methods: Data were extracted from Medical Information Mart for Intensive Care-III database. Primary outcome was 30-day mortality, secondary outcomes were in-hospital, 90-day, 365-day mortality, length of stay (LOS) in hospital. Cox proportional hazards regression model and receiver operating characteristic (ROC) curve analysis and Pearson correlation analysis were used.Results: The HR (95% CI) values of the mid-tertile and the upper tertile were 1.27 (1.01 to 1.59) and 2.29 (1.87 to 2.81) in 30-day mortality compared with the reference. The trend continued after adjusted for demographic and clinical variables. In the secondary outcomes were the same trends. The data of the Second Affiliated Hospital of Wenzhou Medical University showed the correlation coefficient between hospital LOS with NPAR.Conclusion: NPAR was an independent factor of mortality in HF patients, which was correlated with hospital LOS. Our results need to be verified by prospective studies.Keywords: neutrophils, albumin, neutrophil-to-albumin ratio, all-cause mortality, heart failure

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

Aims The aim of this prospective study was to examine CVD risk reduction in type 1 diabetes (1) for people with favourable cardiovascular health metrics and (2) by clustering of these metrics. Methods Data from 2313 participants from the EURODIAB Prospective Complications Study were analysed. All had type 1 diabetes (51% men, mean ± SD age 32 ± 9 years). Seven cardiovascular health metrics were studied—smoking, BMI, physical activity, a diet score, total cholesterol/HDL-cholesterol ratio, combined systolic and diastolic BP and HbA1c—divided into favourable/less favourable categories. Cox proportional hazards models were used to calculate HRs (95% CIs) of incident CVD for each metric. Clusters were made by scoring each individual by the number of favourable metrics. Results A total of 163 people developed incident CVD during a mean ± SD follow-up of 7.2 ± 1.3 years. Participants with more favourable HbA1c levels of 1c (HR [95% CI] 0.63 [0.44, 0.91]), and participants with a more favourable BP (systolic BP Conclusions/interpretation Low HbA1c and low BP were protective cardiovascular health metrics in our study of people with type 1 diabetes. Targeting all cardiovascular health metrics could be more effective in preventing CVD than targeting single metrics. Graphical abstract

Purpose: Cardiorespiratory fitness (CRF) plays an essential role in health outcomes and quality of life. However, it is often not assessed nor estimated. Objective CRF assessment is costly, labour intensive and not widely available. Patient-reported outcome measures estimate CRF more cost-efficiently, but current questionnaires lack accuracy. The aim of this study is to develop a new self-reported questionnaire to estimate CRF.Materials and Methods: The FitMáx©-questionnaire, consisting of only three questions assessing walking, stair climbing, and cycling capacity, was compared with the commonly used Duke Activity Status Index (DASI) and Veterans Specific Activity Questionnaire (VSAQ). These questionnaires were compared to peak oxygen uptake (VO2peak) as measured with cardiopulmonary exercise testing. This study included 759 cardiac, pulmonary and oncologic patients and healthy persons aged 18‒90.Results: FitMáx© strongly correlated (r = 0.94 (0.92‒0.95) SEE = 4.14 mL∙kg-1∙min-1) with measured VO2peak. Bias between predicted and measured VO2peak was -0.24 (-9.23‒8.75; 95% limits of agreement) mL·kg-1·min-1. The FitMáx© scored superiorly on correlation and SEE compared with the DASI and VSAQ, r = 0.75 (0.68‒0.80) SEE = 4.62 mL∙kg-1∙min-1 and r = 0.87 (0.83‒0.90) SEE = 6.75 mL∙kg-1∙min-1, respectively.Conclusion: FitMáx© is a valid and accessible questionnaire to estimate CRF expressed as VO2peak in clinical practice and shows substantial improvement compared to currently used questionnaires.

The prevalence and public health burden of chronic heart failure (CHF) in Europe is steadily increasing mainly caused by the ageing population and prolonged survival of patients with CHF. Frequent hospitalizations, high morbidity and mortality rates, and enormous healthcare costs contribute to the health-related burden. However, multidisciplinary frameworks that emphasize effective long-term management and the psychological needs of the patients are sparse. The present position paper endorsed by the European Association of Preventive Cardiology (EAPC) provides a comprehensive overview on the scientific evidence of psychosocial aspects of heart failure (HF). In order to synthesize newly available information and reinforce best medical practice, information was gathered via literature reviews and consultations of experts. It covers the evidence for aetiological and prospective psychosocial risk factors and major underlying psycho-biological mechanisms. The paper elucidates the need to include psychosocial aspects in self-care concepts and critically reviews the current shortcomings of psychotherapeutic and psycho-pharmacological interventions. It also highlights the need for involvement of psychological support in device therapy for patients with HF and finally calls for better palliative care in the final stage of HF progression.

Background Body mass index (BMI) and physical activity (PA) has been documented to be associated with cardiovascular disease (CVD). However, the evidences regarding joint phenotypes of BMI and PA trajectories with risk for CVD and all-cause mortality are still limited. Methods Participants from the Kailuan Study, followed up during 2006–2019 were included, with primary outcomes of CVDs (myocardial infarction or stroke) and all-cause mortality. BMI and PA were repeatedly measured at least three times, and thus joint phenotypes trajectory groups were identified by group-based trajectory modeling. Cox proportional hazards models were used to examine the associations between trajectory groups and CVDs and all-cause mortality. Results Totally 88,141 (6 trajectories) and 89,736 participants (5 trajectories) were included in the final analyses relating trajectories to CVDs and all-cause mortality, respectively. Compared with persistent normal-weight with moderate PA group, participants were associated with increased risk of CVD in persistent overweight with moderate PA trajectory group (adjusted hazard ratio [aHR]: 1.31, 95% confidence interval [CI]: 1.22–1.41) and persistent obesity with moderate PA trajectory group (aHR: 1.55, 95% CI: 1.41–1.69). While the rising to overweight with moderate PA in normal-weight status with active PA (aHR: 0.72, 95% CI: 0.65–0.79), persistent overweight with moderate PA (aHR: 0.92, 95% CI: 0.87–0.97) and decline to normal-weight in overweight status with moderate PA (aHR: 0.73, 95% CI: 0.67–0.80) trajectories group were significantly associated with decreased all-cause mortality risk. The associations remained robust among stratifying by age and sex individuals and sensitive analysis. Conclusions The long-term trajectories analysis showed that moderate PA may not decrease the risk of CVD in persistently overweight and obesity adults.

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

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

The purpose of this study is to evaluate the very basic numerical skills of health professionals and the general public, to correctly understand the health information that comes to them routinely. The importance of mathematical and statistical literacy cannot be overstated so that informed consent can take place and adequate joint decision-making between doctor and patient can happen. The goal is todecrease the number of interventions and increase the quality of the services provided, reducing healthcare spending as a result. The competences measured in this study encompasses basic but fundamental concepts related to risk, such as the comparison of risks for its correct assessment, the estimation of the reduction of unwanted effects in a group from the reduction in the number of unwanted effects in another group of a different size (absolute risk reduction), the recognition that the bases are necessary to be able to compare absolute frequencies between two groups, and the knowledge and perception that lowering all-cause mortality provides better evidence of benefit than lowering single-cause mortality. The results indicate a need to strengthen the numerical and statistical education of the general community, specifically physicians and nurses, {"references":["G. Gigerenzer, W.Gaissmaier, E.Kurz-Milcke, L.M.Schwartz, and S. Woloshin, Helping Doctors and Patients Make Sense of Health Statistics,Psychological Science in the Public Interest, 8(2), 2007, 53-96.","C. Ferreira, T. Abreu, and M. Basto, Perception of transmitted risk in healthcare, Journal of Public Health: From Theory to Practice, 30, 2022, 1245–1249.","] D.Sarfati, P.Howden-Chapman, A.Woodward, andC. Salmond, Does the frame affect the picture? A study into how attitudes to screening for cancer are affected by the way benefits are expressed, Journal of Medical Screening, 5, 1998,137–140.","L.M.Schwartz, S. Woloshin, andH.G. Welch, Can patients interpret health information? An assessment of the medical data interpretation test,Medical Decision Making, 25,2005, 290–300.","V.F.Reyna, andC.J. Brainerd, The importance of mathematics in health and human judgment: Numeracy, risk communication, and medical decision making,Learning and Individual Differences, 17,2007, 147–159.","G.Gigerenzer, S. Krauss, andO. Vitouch, The Null Ritual: What You Always Wanted to Know About Significance Testing but Were Afraid to Ask, in: D. Kaplan (Ed.),Sage handbook of quantitative methodology for the social sciences,(2004) 391–408.","IBM Corp. Released. IBM SPSS statistics for windows, version 25.0. Armonk (NY): IBM Corp; 2017","Tableau Desktop. [Computer software]. (www.tableau.com/products/desktop); 2018"]}

Purpose: The importance of body composition on cancer outcomes is of great clinical interest. Measures of body composition that differentiate fat mass from skeletal muscle mass can help redefine our understanding of body composition for cancer survival. We investigated whether the risk of all-cause and cancer-specific mortality differ by levels of total fat mass and sarcopenia status in cancer survivors. Our secondary aim was a subgroup analysis assessing the role of race within these associations. Methods: Participants included 1682 adult cancer survivors who had undergone a dual-energy X-ray absorptiometry (DXA) examination to measure body composition, from the 1999–2006 and 2011–2018 National Health and Nutrition Examination Survey (NHANES). Total fat mass was categorized into tertiles (we assessed high vs. low tertiles), and sarcopenia was considered as having an appendicular skeletal muscle mass index less than 7.26 kg/m2 for males and less than 5.45 kg/m2 for females. Multivariable Cox proportional hazard models estimated the adjusted hazard ratio (aHR) and 95% confidence interval (CI). Results: The mean age of study participants was 61.9 years, and they were followed up for an average of 9.67 years. The prevalence of sarcopenia was 25.0% (N = 304), and 33.4% (N = 561) had a high total fat mass. Participants with a higher fat mass (aHR = 1.30, 95% CI = 1.06–1.61) and with sarcopenia (aHR = 1.51, 95% CI = 1.22–1.88) had a 30% and 51% increased risk of all-cause mortality compared to participants with a low fat mass and with no sarcopenia, respectively. Further, sarcopenia (aHR = 1.74, 95% CI = 1.23–2.29) was associated with a higher risk of cancer-specific mortality in cancer survivors. The association between sarcopenia and all-cause mortality was twice as strong in Black people (aHR = 2.99, 95% CI = 1.39–6.06) compared to White people (aHR = 1.53, 95% CI = 1.19–1.95). Conclusions: Our findings show the opposing relations of fat mass and appendicular skeletal muscle mass index with mortality in a national sample of cancer survivors, and that the relationships may differ by race. These results emphasize the importance of maintaining a healthy body composition among cancer survivors.

Measures of cardiovascular health (CVH) assessed by a combination of behavioral and biological factors has shown protective associations with all-cause mortality. The mechanisms underlying these associations have not been fully elucidated. In this study, we characterized the plasma proteomics profile of CVH and tested whether specific proteins mediated the associations between CVH and all-cause mortality in participants of the InCHIANTI study. Of the 1301 proteins tested, 92 proteins were associated with CVH (22 positively, 70 negatively). Proteins most strongly associated with CVH included leptin (LEP), fatty acid binding protein 3 (FABP3), Angiopoietin-2 (ANGPT2), and growth-differential factor 15 (GDF15). Of the 92 CVH-associated proteins, 33 proteins significantly mediated the associations between CVH and all-cause mortality, with percent mediation ranging from 5 to 30%. The most significant mediating proteins were GDF15 and insulin-like growth factor 2 (IGFBP2). Proteins associated with better CVH were enriched for proteins that reflect the suppression of the complement coagulation and GH/IGF pathways.

In the general population, there is little evidence of a link between blood urea nitrogen (BUN) and long-term mortality. The goal of this study was to explore whether higher BUN concentration is a predictor of cardiovascular disease (CVD) and all-cause mortality. From 1999 to 2006, the National Health and Nutrition Examination Survey (NHANES) included 17,719 adult individuals. Death outcomes were ascertained by linkage to the database records through 31 December 2015. The Cox proportional hazard regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD and all-cause mortality in individuals. We also performed stratified analyses based on age, gender, drinking, smoking, history of hypertension and diabetes. During a mean follow-up 11.65 years, a total of 3628 deaths were documented, of which 859 were due to CVD. Participants with higher BUN had a higher risk of CVD and all-cause death compared to those with lower BUN. After multifactor adjustment for demographics, major lifestyle factors, and hypertension and diabetes history, higher BUN levels compared with lower levels were significantly associated with higher risk of CVD (HR: 1.48 [1.08, 2.02], P-trend < 0.001) and all-cause mortality (HR: 1.48 [1.28, 1.72], P-trend < 0.001). In subgroup analyses, we found that the trend in the association of BUN with the risk of death remained strong in female subjects. Greater BUN levels were linked to higher CVD and all-cause mortality in the NHANES of American adults. The importance of BUN in predicting death is supported by our research.

The association between socioeconomic status (SES) and alcohol-related diseases has been widely explored. Less is known, however, on whether the association of moderate drinking with all-cause mortality is modified by educational level (EL). Using harmonized data from 16 cohorts in the MORGAM Project (N = 142,066) the association of pattern of alcohol intake with hazard of all-cause mortality across EL (lower = primary-school; middle = secondary-school; higher = university/college degree) was assessed using multivariable Cox-regression and spline curves. A total of 16,695 deaths occurred in 11.8 years (median). In comparison with life-long abstainers, participants drinking 0.1–10 g/d of ethanol had 13% (HR = 0.87; 95%CI: 0.74–1.02), 11% (HR = 0.89; 0.84–0.95) and 5% (HR = 0.95; 0.89–1.02) lower rate of death in higher, middle and lower EL, respectively. Conversely, drinkers > 20 g/d had 1% (HR = 1.01; 0.82–1.25), 10% (HR = 1.10; 1.02–1.19) and 17% (HR = 1.17; 1.09–1.26) higher rate of death. The association of alcohol consumption with all-cause mortality was nonlinear, with a different J-shape by EL levels. It was consistent across both sexes and in various approaches of measuring alcohol consumption, including combining quantity and frequency and it was more evident when the beverage of preference was wine. We observed that drinking in moderation (≤ 10 g/d) is associated with lower mortality rate more evidently in individuals with higher EL than in people with lower EL, while heavy drinking is associated with higher mortality rate more evidently in individuals with lower EL than in people with higher EL, suggesting that advice on reducing alcohol intake should especially target individuals of low EL.

There is increasing evidence linking long-term fine particulate matter (PM2.5) exposure to negative health effects. However, the relative influence of each component of PM2.5 on health risk is poorly understood. In a cohort study in the contiguous United States between 2000 and 2017, we examined the effect of long-term exposure to PM2.5 main components and all-cause mortality in older adults who had to be at least 65 years old and enrolled in Medicare. We estimated the yearly mean concentrations of six key PM2.5 compounds, including black carbon (BC), organic matter (OM), soil dust (DUST), nitrate (NO3–), sulfate (SO42–), and ammonium (NH4+), using two independently sourced well-validated prediction models. We applied Cox proportional hazard models to evaluate the hazard ratios for mortality and penalized splines for assessing potential nonlinear concentration–response associations. Results suggested that increased exposure to PM2.5 mass and its six main constituents were significantly linked to elevated all-cause mortality. All components showed linear concentration–response relationships in the low exposure concentration ranges. Our research indicates that long-term exposure to PM2.5 mass and its essential compounds are strongly connected to increased mortality risk. Reductions of fossil fuel burning may yield significant air quality and public health benefit. There is increasing evidence linking long-term fine particulate matter (PM2.5) exposure to negative health effects. However, the relative influence of each component of PM2.5 on health risk is poorly understood. In a cohort study in the contiguous United States between 2000 and 2017, we examined the effect of long-term exposure to PM2.5 main components and allcause mortality in older adults who had to be at least 65 years old and enrolled in Medicare. We estimated the yearly mean concentrations of six key PM2.5 compounds, including black carbon (BC), organic matter (OM), soil dust (DUST), nitrate (NO3-), sulfate (SO42-), and ammonium (NH4+), using two independently sourced well-validated prediction models. We applied Cox proportional hazard models to evaluate the hazard ratios for mortality and penalized splines for assessing potential nonlinear concentration-response associations. Results suggested that increased exposure to PM2.5 mass and its six main constituents were significantly linked to elevated all-cause mortality. All components showed linear concentration-response relationships in the low exposure concentration ranges. Our research indicates that long-term exposure to PM2.5 mass and its essential compounds are strongly connected to increased mortality risk. Reductions of fossil fuel burning may yield significant air quality and public health benefit.

Dysbiosis and impaired gastrointestinal barrier function have emerged as potential chronic kidney disease (CKD) modulators. Accumulation of gut-derived uremic toxins, a subsequent shift in the gut microbiome, and modified expression levels of intestinal tight junction proteins are all contributing factors to hyperpermeability and endotoxemia in CKD. Experimental studies in animals provide evidence that renal decline is linked to gastrointestinal health and that pharmacological or dietary intervention might attenuate this process. In this review, we will highlight the current knowledge on CKD-induced changes in the gut microbiome and the resulting consequences regarding gastrointestinal health with a focus on animal studies. Furthermore, we will explore possible disease management options linking to evidence in humans, if available.

BackgroundThe adverse cardiovascular effects of benzodiazepines and Z-drugs (jointly referred as BZDRs) have been of concern. Yet, little is known about the use of BZDRs in relation to mortality risk among older adults with myocardial infarction history (post-MI).MethodsThis study is a secondary analysis of the Alpha Omega Cohort study, comprising post-MI patients aged 40–60 years. Self-reported information on the use of BZDRs, including types and dose, was collected at baseline. Four categories of mortality were examined, namely all-cause mortality, cardiovascular (CVD) mortality, cancer mortality, and non-CVD/non-cancer mortality. Associations between BZDRs use, by types and doses, and mortality were estimated with Cox regression models, adjusted for demographic and classic cardiovascular risk factors.ResultsA total of 433 (8.9%) out of 4837 (21.8% females) patients reported BZDRs use at baseline. During a median follow-up of 12.4 years, 2287 deaths were documented, of which 825 (36.1%) were due to CVD. BZDRs use was related to a statistically significantly higher risk of all-cause and CVD mortality; adjusted hazard ratios [95% CI] were (1.31 [1.41, 1.52]) and (1.43 [1.14, 1.81]), respectively. These relationships were dose-dependent—patients using BZDRs on an as-needed basis had similar risks compared to the non-uses, whereas patients with a daily use schedule and increasing doses had higher risks (p-value for trend: ConclusionBZDRs use was independently associated with a higher risk of all-cause and cardiovascular mortality in older post-MI patients, and there was evidence for a dose-dependent relationship.Clinical trial registrationNCT00127452 (www.ClinicalTrials.gov).

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.

End-stage renal disease (ESRD) patients receiving hemodialysis (HD) continue to have a low quality of life and face severe mortality. Biomarkers involved in deterioration and predicting the clinical outcome in ESRD patients on HD are needed. Abnormal angiogenesis has been noted in kidney diseases, characterized by a disruption of balance in the expression of pro-angiogenic and anti-angiogenic factors. The most dominant pro-angiogenic factor, vascular endothelial growth factor, has shown a critical effect in the pathogenesis of kidney diseases in past studies. Moreover, Angiopoietin-2 (Ang-2), as one of the most well-characterized vascular growth factors, its circulating level is increased in HD patients and has been reported to have a prognostic significance for mortality in patients with chronic kidney disease. Together with previous evidence of sexual dimorphism in endothelial cell-derived growth factors, this study evaluated the prognostic value of Ang-2 in HD patients and its sexual difference. Prevalent HD patients were recruited and followed up for five years for all-cause mortality. Circulating Ang-2 concentrations were assessed by validated ELISA. Survival analysis was performed using Kaplan-Meier analysis and Cox proportional hazards regression analysis. There were 157 deaths among 313 participants during the follow-up. The median level of Ang-2 was 91.20 pmol/l (interquartile range 63.35, 140.65 pmol/l). Ang-2 concentration was significantly lower in survivors than in non-survivors (p, Patienten mit terminaler Niereninsuffizienz, die eine Hämodialyse (HD) erhalten, haben nach wie vor eine geringe Lebensqualität und eine hohe Mortalität. Es werden Biomarker benötigt, die an der Verschlechterung der Lebensqualität beteiligt sind und das klinische Ergebnis bei Patienten mit terminaler Niereninsuffizienz vorhersagen. Bei Nierenerkrankungen wurde eine abnorme Angiogenese festgestellt, die durch eine ausgewogene Störung der Expression von pro- und anti-angiogenen Faktoren gekennzeichnet ist. Angiopoietin-2 (Ang-2), einer der am besten charakterisierten vaskulären Wachstumsfaktoren, ist im Blutkreislauf von HD-Patienten in erhöhter Konzentration vorhanden und hat Berichten zufolge eine prognostische Bedeutung für die Mortalität von Patienten mit chronischen Nierenerkrankungen. Zusammen mit früheren Hinweisen auf Geschlechtsunterschiede bei den aus Endothelzellen hergestellten Wachstumsfaktoren untersuchte diese Studie den prognostischen Wert von Ang-2 bei HD-Patienten und dessen Geschlechtsunterschiede. Prävalente HD-Patienten wurden rekrutiert und fünf Jahre lang nachbeobachtet, um die Gesamtmortalität zu untersuchen. Zu Beginn wurden demografische und medizinische Daten erhoben, und die zirkulierenden Ang-2-Konzentrationen wurden mit einem validierten ELISA bestimmt. Während der Nachbeobachtungszeit starben 157 der 313 Teilnehmer. Der Medianwert von Ang-2 betrug 91,20 pmol/l (Interquartilsbereich 63,35 bis 140,65 pmol/l). Die Ang-2-Konzentration war bei den Überlebenden signifikant niedriger als bei den Nicht-Überlebenden (p

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.

We aimed (1) to evaluate the agreement between two methods (equation and bio-impedance analysis [BIA]) to estimate skeletal muscle mass (SMM), and (2) to assess if SMM was associated with all-cause mortality risk in individuals across different geographical sites in Peru.We used data from the CRONICAS Cohort Study (2010-2018), a population-based longitudinal study in Peru to assess cardiopulmonary risk factors from different geographical settings. SMM was computed as a function of weight, height, sex and age (Lee equation) and by BIA. All-cause mortality was retrieved from national vital records. Cox proportional-hazard models were developed and results presented as hazard ratios (HR) with 95% confidence intervals (95% CI).At baseline, 3216 subjects, 51.5% women, mean age 55.7 years, were analyzed. The mean SMM was 23.1 kg (standard deviation [SD]: 6.0) by Lee equation, and 22.7 (SD: 5.6) by BIA. Correlation between SMM estimations was strong (Pearson's ρ coefficient = 0.89, p0.001); whereas Bland-Altman analysis showed a small mean difference. Mean follow-up was 7.0 (SD: 1.0) years, and there were 172 deaths. In the multivariable model, each additional kg in SMM was associated with a 19% reduction in mortality risk (HR=0.81; 95% CI: 0.75-0.88) using the Lee equation, but such an estimate was not significant when using BIA (HR=0.98; 95% CI: 0.94-1.03). Compared to the lowest tertile, subjects at the highest SMM tertile had a 56% reduction in risk of mortality using the Lee equation, but there was no such association when using BIA estimations.There is a strong correlation and agreement between SMM estimates obtained by the Lee equation and BIA. Howevers, an association between SMM and all-cause mortality exists only when the Lee equation is used. Our findings call for appropriate use of approaches to estimate SMM, and there should be a focus on muscle mass in promoting healthier ageing. This article is protected by copyright. All rights reserved.

Background: Recent evidence suggests that prolonged sitting and its adverse impact on glycaemic indicators appear to be proportional to the degree of insulin resistance. To investigate this finding in a free-living context, we aimed to examine associations of device-measured 24-hour time-use compositions of sitting, standing, stepping, and sleeping with fasting glucose (FPG) and 2h post-load glucose (2hPLG) levels, and to examine separately the associations with time-use compositions among those at lower and at higher risk of developing type 2 diabetes. Methods: Cross-sectional analyses examined thigh-worn inclinometer data (activPAL, 7 day, 24h/day protocol) from 648 participants (aged 36-80 years) at either lower (, The Health & Fitness Journal of Canada, Vol. 14 No. 3 (2021): Proceedings from the 8th International Society for Physical Activity and Health Congress

Background: This study investigates the predictive value of the systemic immune-inflammation index (SII), which was calculated as platelet × neutrophil/lymphocyte ratio, for all-cause mortality in patients with hypertrophic cardiomyopathy (HCM). Methods: A total of 360 HCM patients were enrolled. They were divided into three groups based on the tertiles of baseline SII. The association between SII and all-cause mortality was analyzed. Results: There were 53 HCM patients who died during a mean follow-up time of 4.8 years (min: 6 days and max: 10.8 years), and the mortality rate was 3.0 per 100 person years. The cumulative mortality rate was significantly different among the three tertiles of SII (P = 0.004), and the mortality rate in tertile 3 was much higher than that in the first two tertiles. In reference to tertile 1, the fully adjusted hazard ratios of all-cause mortality were 1.02 for the tertile 2 (95% confidence interval [CI]: 0.45–2.31, P = 0.966) and 2.31 for tertile 3 (95% CI: 1.10–4.87, P = 0.027). No significant interactions between SII and other variables were observed during subgroup analysis. The discriminative power was better for mid-term outcome than that for short-term or long-term outcomes. Sensitivity analyses including patients with normal platelet and white blood cell count have revealed similar results. Conclusion: SII was a significant risk factor for all-cause mortality in HCM patients. However, the discriminative power was poor to moderate. It could be used in combination with other risk factors in mortality risk stratification in HCM.

The association between pulse pressure and long‐term mortality was investigated among acute coronary syndrome (ACS) patients who received percutaneous coronary intervention (PCI). The study population included 5055 ACS patients in the Department of Cardiology of Beijing Friendship Hospital who were enrolled from January 2013 to July 2019. The median duration of follow‐up was 24 months. Multivariate Cox regression was used to analyze the relationships between PP on inpatient admission and mortalities. Non‐linear associations were studied by restricted cubic splines. Considering the heart function, the analyses were performed in the whole cohort and the LVEF > = 0.5 cohort separately. Subgroup analyses were performed according to the different diagnosis (the myocardial infarction subgroup and the unstable angina pectoris subgroup). When PP was used as categorical variable, the high PP group (≥61 mm Hg) significantly increased the risk of death compared with the intermediate PP group (50–60 mm Hg) in the both cohorts. When PP was used as continuous variable, a U‐shape relationship were found between PP and mortalities in the whole cohort (p (for nonlinearity) = .005 and .003, respectively), with reference PP level of 55 mm Hg. However, this U‐shape relationship disappeared in the LVEF > 0.5 cohort (p (for nonlinearity) = .111 and .117, respectively). The similar results were obtained in MI subgroup. From this study, the U‐shape relationships between PP level and all‐cause and cardiac mortalities were found in ACS patients who underwent PCI. The U‐shape relationships disappeared in the LVEF > 0.5 cohort. The reference PP level was 55 mm Hg.

Kai Jin, Shu-Yuan Zhang, Li-Wen Li, Yang-Fan Zou, Bin Wu, Liang Xia, Cai-Xing Sun Department of Neurosurgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Cai-Xing SunDepartment of Neurosurgery, Zhejiang Cancer Hospital, 11th Floor, Building 2, Hangzhou City, Zhejiang Province, People’s Republic of ChinaTel +86 572-88128082Email 18744016937@163.comPurpose: Glioma may affect patients of any age. So far, only a limited number of big data studies have been conducted concerning oligodendroglioma (OG) in diverse age groups. This study evaluated the risk factors for OG in different age groups using the Surveillance, Epidemiology, and End Results (SEER) database built by the National Cancer Institute, which is part of the National Institutes of Health.Patients and Methods: A total of 5437 cases within the SEER database were included. These patients were divided into seven age groups. The Kaplan-Meier method was employed for survival analysis. The independent risk factors for the survival of OG patients were identified using the Cox regression model. A nomogram was drawn with R software based on the independent risk factors. The X-tile software was adopted to find the optimal age group at diagnosis.Results: The all-cause mortality and the tumor-specific mortality increased with age. The univariate analysis showed that the patients’ age, gender, primary lesion location, side affected by the primary lesion (left or right), surgery for the primary lesion, and tumor size were correlated with survival (P< 0.05). Multivariate Cox regression analysis showed that age was an independent risk factor for the survival of OG patients (P< 0.05). The optimal cutoff value of age in terms of overall survival (OS) and cause-specific survival (CSS) were identified as 48 and 61 years and 48 and 59 years, respectively.Conclusion: The older the age, the worse the survival would be. That’s, the mortality increased with age. In the clinic, healthcare professionals should be fully aware of the variability in the prognosis of OG patients in different age groups. Therefore, individualized treatments are recommended to OG patients in different age groups to optimize the prognosis.Keywords: oligodendroglioma, SEER, age, prognosis, all-cause mortality, tumor-specific mortality

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.

Yingbei Weng, Ripeng Yin, Lala Qian, Zhi Chen, Jie Wang, Huaqiang Xiang, Yangjing Xue, Kangting Ji, Xueqiang Guan Department of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of ChinaCorrespondence: Kangting Ji; Xueqiang GuanDepartment of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Xueyuanxi Road, No. 109, Wenzhou, 325000, Zhejiang, People’s Republic of ChinaEmail jikt@wzmc.edu.cn; wzsgxq@163.comObjective: The aims of this study were to investigate the relationship between low-density lipoprotein cholesterol (LDL-C) levels and all-cause mortality in coronary care unit (CCU) patients, adjusting for a wide range of potential confounding factors, to examine the potential of LDL-C in predicting the prognostic value of CCU patients.Methods: Clinical data were extracted from Medical Information Mart for Intensive Care-III database (MIMIC-III database version v.1.4). Baseline data were collected within 24 hours after the patient was first admitted to the hospital. The primary endpoint of our study is 30-day all-cause mortality. The secondary endpoints are 90-day and one-year all-cause mortality and infections. Cox proportional hazard regression and propensity score-matched (PSM) analysis were used to analyze the association between LDL-C levels and prognostic value of CCU patients.Results: We included a total of 1476 patients with an average age of 66.7 ± 14.1 years (66% male). For 30-day all-cause mortality, the hazard ratio (95% confidence interval) of high LDL-C level group (≥ 55 mg/dl) was 0.42 (0.29, 0.62), which was compared with low LDL-C level group (< 55 mg/dl) in unadjusted model. After adjusting for age, gender and race, the association still existed (P < 0.05), and the HR (95% CI) was 0.49 (0.33, 0.72). Further adjustment of possible covariates showed similar correlation (P < 0.05), and HR (95% CI) was 0.65 (0.43, 0.97). Similar correlations were observed for 90-day and one-year all-cause mortality. The relationship between all-cause mortality and LDL-C levels in CCU patients was further verified by propensity score-matched (PSM) analysis. In addition, the higher the LDL-C level, the lower the risk of infection, odds ratio (OR) values in the three models were less than 1 (P < 0.05).Conclusion: Our data suggest that high LDL-C level is associated with a reduced risk of 30-day, 90-day, and one-year mortality of patients in the CCU. And this result is still stable in the PSM model. The results need to be verified in prospective trials.Keywords: low-density lipoprotein cholesterol, coronary care unit, all-cause mortality, cardiovascular disease

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