All-cause Mortality In Relation Research Articles

The incidence of death and risk factors for mortality following major bleeding in patients anticoagulated with factor Xa inhibitors: an observational study in the UK clinical setting (AXIOM UK)

Abstract Background Major bleeding (MB) in association with anticoagulant use results in significant mortality. Mortality can be directly attributed to bleeding, or may follow bleeding complications such acute kidney injury, myocardial infarction, stroke and other cardiovascular events. Most real-world data relating to bleeding mortality is derived from cohorts receiving vitamin-K antagonists. We investigated all-cause mortality (ACM) after MB in a large cohort anticoagulated with Factor Xa inhibitors (FXai), e.g. direct oral anticoagulants (DOAC) rivaroxaban, apixaban and low-molecular-weight heparins (LMWH). Purpose To describe incidence rates of and risk factors for ACM following MB in patients receiving FXai. To investigate MB related ACM by bleeding site, treatment indication, treatment subgroups and individual and cumulative time periods. Methods Retrospective cohort analysis of new users of FXai, between 2012-2020, for therapeutic indications including atrial fibrillation (AF), venous thromboembolism, bioprosthetic cardiac valves or adult congenital heart disease was conducted. MB was defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria. Incidence rates were reported per 100 person-years. Sub-distribution hazard ratios with 95% confidence intervals (95% CI) were estimated from Fine and Gray regression models accounting for competing risks. Results In 240,357 new users of FXai, 88% used an oral FXai. The most common FXai indication was AF (72%). There were 10,163 patients (4.2%) hospitalised for bleeding events during FXai use. Of these, 3,873 MB events (38%) fulfilled the ISTH definition of MB and 1312 died during 3,542 person years of follow-up (Table 1). ACM incidence rates varied by time, indication, bleeding subtype, and drug type. ACM occurred in 926 patients (23.9%) in the first month. Mortality rates were highest in the first month 607 (95% CI 568-647) per 100 person years, the rates then decreased over the year but remained elevated throughout the first year compared with subsequent years. Those receiving LMWH had higher ACM than those receiving a DOAC, but this was not significant in the adjusted risk factor analysis. Risk factors for ACM following bleeding included age ≥80, and a history of current smoking, myocardial infarction, congestive heart failure, peripheral artery disease, Stage 4 or 5 kidney disease, metastatic cancer, and intracranial haemorrhage. Age<60, bleeding following major trauma, and a history of anaemia were associated with lower risk of ACM (Table 2). Conclusions There is a significant incidence of ACM following MB among FXai users. The incidence rate of ACM in patients treated with FXai was highest in the first month after FXai initiation, declined during the first year and then plateaued. Multiple risk factors associated with ACM have been recognised and these could guide urgent therapies such as antidotes.

The Association of Metformin, Other Antidiabetic Medications, and Statins with the Prognosis of Hepatocellular Carcinoma in Patients with Type 2 Diabetes: A Retrospective Cohort Study.

This study aimed to explore whether the prediagnostic use of metformin and statins is associated with the prognosis of patients with hepatocellular carcinoma (HCC) and type 2 diabetes. We identified 1383 eligible individuals who had both type 2 diabetes and HCC diagnosed between 1998 and 2017 from several Finnish registers. Cox models were fitted for cause-specific and all-cause mortality in relation to the use of antidiabetic medications and statins prior to the HCC diagnosis. Prediagnostic metformin use was associated with decreased overall mortality (hazard ratio 0.84, 95% confidence interval 0.74-0.94) compared with nonuse in patients with type 2 diabetes. Similarly, slightly decreased HCC mortality and other-cause mortality were observed among metformin users. The results were inconclusive regarding metformin use and both overall and HCC mortality among patients with localized HCC. No discernible contrast between statin users and nonusers was found in overall mortality nor HCC mortality in either the whole cohort or patients with localized cancer.

Geospatial disparities in survival of patients with breast cancer in sub-Saharan Africa from the African Breast Cancer-Disparities in Outcomes cohort (ABC-DO): a prospective cohort study

There is an urgent need to improve breast cancer survival in sub-Saharan Africa. Geospatial barriers delay diagnosis and treatment, but their effect on survival in these settings is not well understood. We examined geospatial disparities in 4-year survival in the African Breast Cancer-Disparities in Outcomes cohort. In this prospective cohort study, women (aged ≥18 years) newly diagnosed with breast cancer were recruited from eight hospitals in Namibia, Nigeria, South Africa, Uganda, and Zambia. They reported sociodemographic information in interviewer-administered questionnaires, and their clinical and treatment data were collected from medical records. Vital status was ascertained by contacting participants or their next of kin every 3 months. The primary outcome was all-cause mortality in relation to rural versus urban residence, straight-line distance, and modelled travel time to hospital, analysed using restricted mean survival time, Cox proportional hazards, and flexible parametric survival models. 2228 women with breast cancer were recruited between Sept 8, 2014, and Dec 31, 2017. 127 were excluded from analysis (58 had potentially recurrent cancer, had previously received treatment, or had no follow-up; 14 from minority ethnic groups with small sample sizes; and 55 with missing geocoded home addresses). Among the 2101 women included in analysis, 928 (44%) lived in a rural area. 1042 patients had died within 4 years of diagnosis; 4-year survival was 39% (95% CI 36-42) in women in rural areas versus 49% (46-52) in urban areas (unadjusted hazard ratio [HR] 1·24 [95% CI 1·09-1·40]). Among the 734 women living more than 1 h from the hospital, the crude 4-year survival was 37% (95% CI 32-42) in women in rural areas versus 54% (46-62) in women in urban areas (HR 1·35 [95% CI 1·07-1·71] after adjustment for age, stage, and treatment status). Among women in rural areas, mortality rates increased with distance (adjusted HR per 50 km 1·04, 1·01-1·07) and travel time (adjusted HR per h 1·06, 1·02-1·10). Among women with early-stage breast cancer receiving treatment, women in rural areas had a strong survival disadvantage (overall HR 1·54, 1·14-2·07 adjusted for age and stage; >1 h distance adjusted HR 2·14, 1·21-3·78). Geospatial barriers reduce survival of patients with breast cancer in sub-Saharan Africa. Specific attention is needed to support patients with early-stage breast cancer living in rural areas far from cancer treatment facilities. US National Institutes of Health (National Cancer Institute), Susan G Komen for the Cure, and the International Agency for Research on Cancer.

Association of lifestyles and multimorbidity with mortality among individuals aged 60 years or older: Two prospective cohort studies

Lifestyles are associated with all-cause mortality, yet limited research has explored the association in the elderly population with multimorbidity. We aim to investigate the impact of adopting a healthy lifestyle on reducing the risk of all-cause mortality in older individuals with or without multimorbidity in both China and UK. This prospective study included 29,451 and 173,503 older adults aged 60 and over from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and UK Biobank. Lifestyles and multimorbidity were categorized into three groups, respectively. Cox proportional hazards regression was used to estimate the Hazard Ratios (HRs), 95% confidence intervals (95% CIs), and dose-response for all-cause mortality in relation to lifestyles and multimorbidity, as well as the combination of both factors. During a mean follow-up period of 4.7 years in CLHLS and 12.14 years in UK Biobank, we observed 21,540 and 20,720 deaths, respectively. For participants with two or more conditions, compared to those with an unhealthy lifestyle, adopting a healthy lifestyle was associated with a 27%–41% and 22%–42% reduction in mortality risk in the CLHLS and UK Biobank, respectively; Similarly, for individuals without multimorbidity, this reduction ranged from 18% to 41%. Among participants with multimorbidity, individuals with an unhealthy lifestyle had a higher mortality risk compared to those maintaining a healthy lifestyle, with HRs of 1.15 (95% CI: 1.00, 1.32) and 1.27 (95% CI: 1.16, 1.39) for two conditions, and 1.24 (95% CI: 1.06, 1.45) and 1.73 (95% CI: 1.56, 1.91) for three or more conditions in CLHLS and UK Biobank, respectively. Adherence to a healthy lifestyle can yield comparable mortality benefits for older individuals, regardless of their multimorbidity status. Furthermore, maintaining a healthy lifestyle can alleviate the mortality risks linked to a higher number of diseases.

Number of medically prescribed pharmaceutical agents as predictor of mortality risk: a longitudinal, time-variable analysis in the EPIC-Heidelberg cohort

The number of prescribed medications might be used as proxy indicator for general health status, in models to predict mortality risk. To estimate the time-varying association between active pharmaceutical ingredient (API) count and all-cause mortality, we analyzed data from a population cohort in Heidelberg (Germany), including 25,546 participants with information on medication use collected at 3-yearly intervals from baseline recruitment (1994–1998) until end of 2014. A total of 4548 deaths were recorded until May 2019. Time-dependent modeling was used to estimate hazard ratios (HR) and their 95% confidence intervals (CI) for all-cause mortality in relation to number of APIs used, within three strata of age (≤ 60, > 60 to ≤ 70 and > 70 years) and adjusting for lifestyle-related risk factors. For participants reporting commonly used APIs only (i.e., API types accounting for up to 80% of medication time in the population) total API counts showed no association with mortality risk within any age stratum. However, when at least one of the APIs was less common, the total API count showed a strong relationship with all-cause mortality especially up to age ≤ 60, with HR up to 3.70 (95% CI 2.30–5.94) with 5 or 6 medications and 8.19 (5.61–11.97) for 7 or more APIs (versus none). Between > 60 and 70 years of age this risk association was weaker, with HR up to 3.96 (3.14–4.98) for 7 or more APIs, and above 70 years it was weakened further (HR up to 1.54 (1.34–1.79)). Multiple API-use may predict mortality risk in middle-aged and women and men ≤ 70 years, but only if it includes at least one less frequently used API type. With advancing age, and multiple medication becomes increasingly prevalent, the association of API count with risk of death progressively attenuates, suggesting an increasing complexity with age of underlying mortality determinants.

Periodic Repolarization Dynamics (PRD) identifies patients who profit from ICD implantation, A meta-analysis of the predictive value of PRD

Abstract Background Periodic repolarization dynamics (PRD) is an electrocardiographic marker that quantifies sympathetic-activity associated instabilities of cardiac repolarization. PRD is a strong predictor of mortality in patients with ischemic (ICM) and non-ischemic cardiomyopathy (NICM) and has been proposed to identify patients who benefit from prophylactic ICD implantation. Purpose To conduct a systematic review and meta-analysis concerning the prognostic value of PRD for predicting all-cause mortality in relation to prophylactic ICD-implantation. Methods This meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A total of 25 articles were screened and 7 randomized and non-randomized controlled trials identified. Finally, a total of 5 could be included in the analysis (Fig.1). Patients were stratified into patients with or without prophylactic ICD-implantation (Fig.2). The prognostic value of PRD for predicting all-cause mortality was extracted from published data as hazard ratio (HR) per 1 deg2 increase in PRD. We used inverse-variance-weighted average meta-analysis to calculate fixed and random effect models to estimate the overall predictive value of PRD in both groups. The interaction between PRD and prophylactic ICD-implantation for predicting mortality was calculated using meta-regression analysis. All analyses were performed using CRAN R v. 4.1.2 and the meta-package v 5.2.0. Results We included 4,338 patients in this meta-analysis, of whom 3,167 (73%) suffered from ICM and 1,171 (27%) from NICM. 1,906 (44%) patients were treated with an ICD. During an estimated mean follow-up time of 3.2 years, 604 (14%) patients died. Fig. 2 (left) shows patients without ICD treatment (N = 2,432, 56%). In these patients, a 1 deg2 increase in PRD was significantly associated with an overall 8% increase in mortality (fixed effect HR 1.08; 95% CI 1.06-1.10; p< 0.001, random effect HR 1.08; 95% CI 1.06-1.11; p < 0.001). Fig. 2 (right) displays the prognostic value of PRD in patients treated by ICD (N = 1,906). In these patients, a 1 deg2 increase in PRD was significantly associated with an overall 3% increase in mortality (fixed-effect HR 1.03; 95% CI 1.01-1.05; p< 0.001, random-effect HR 1.03; 95% CI 1.00-1.06; p < 0.001). An increase in PRD was not significantly associated with an increase in mortality in patients from the EU-CERT-ICD and DANISH trial. There was a significant interaction between PRD and prophylactic ICD-implantation for predicting all-cause mortality (p = 0.008). Conclusion In patients with ICM and NICM, PRD is a strong predictor of all-cause mortality in patients with and without prophylactic ICD. The significant interaction between PRD and prophylactic ICD-implantation most probably implies a reduction in the risk identified by PRD through ICD implantation. Consequently, PRD could prove a useful tool for identifying patients that might benefit from ICD treatment.Figure 1Figure 2

Associations of blood cadmium and lead concentrations with all-cause mortality in US adults with chronic obstructive pulmonary disease

BackgroundSome literature indicates an association between exposure to cadmium and lead and the presence of emphysema and chronic bronchitis, which are the two primary components of COPD. Understanding whether there is a potential association between cadmium and lead exposure and higher mortality rates in individuals with COPD could provide profound insights into the long-term effects of these two metal exposures on human health. MethodsThis study included 2024 patients with COPD in the US from the NHANES from 1999 through 2016 who were followed up to 2019. Multivariable Cox regression models were used to calculate HRs and 95 % CIs for all-cause mortality in relation to blood cadmium and lead concentrations. Plotting Kaplan-Meier curves and Restricted cubic spline curves to visualize results. Furthermore, stratified and sensitivity analyses were conducted. ResultsAfter multivariate adjustment, blood cadmium and blood lead concentrations were independently associated with an increased risk of all-cause mortality. Compared with the first tertile, the HRs of all-cause mortality associated with the blood cadmium concentration were 1.74 (95 % CI, 1.22–2.49) in the second tertile and 1.89 (95 % CI, 1.31–2.72) in the third tertile. The HRs of all-cause mortality associated with the blood lead concentration were 1.13 (95 % CI, 0.84–1.51) in the second tertile and 1.43 (95 % CI, 1.05–1.93) in the third tertile. ConclusionThis study found that increased blood cadmium and blood lead concentrations were associated with increased all-cause mortality in COPD patients. Reducing cadmium and lead exposure could potentially mitigate mortality risk in these individuals. More prospective studies are needed in the future to demonstrate our findings.

Long-term exposure to low-level air pollution and greenness and mortality in Northern Europe. The Life-GAP project

BackgroundAir pollution has been linked to mortality, but there are few studies examining the association with different exposure time windows spanning across several decades. The evidence for the effects of green space and mortality is contradictory. ObjectiveWe investigated all-cause mortality in relation to exposure to particulate matter (PM2.5 and PM10), black carbon (BC), nitrogen dioxide (NO2), ozone (O3) and greenness (normalized difference vegetation index - NDVI) across different exposure time windows. MethodsThe exposure assessment was based on a combination of the Danish Eulerian Hemispheric Model and the Urban Background Model for the years 1990, 2000 and 2010. The analysis included a complete case dataset with 9,135 participants from the third Respiratory Health in Northern Europe study (RHINE III), aged 40–65 years in 2010, with mortality follow-up to 2021. We performed Cox proportional hazard models, adjusting for potential confounders. ResultsAltogether, 327 (3.6 %) persons died in the period 2010–2021. Increased exposures in 1990 of PM2.5, PM10, BC and NO2 were associated with increased all-cause mortality hazard ratios of 1.40 (95 % CI1.04–1.87 per 5 μg/m3), 1.33 (95 % CI: 1.02–1.74 per 10 μg/m3), 1.16 (95 % CI: 0.98–1.38 per 0.4 μg/m3) and 1.17 (95 % CI: 0.92–1.50 per 10 μg/m3), respectively. No statistically significant associations were observed between air pollution and mortality in other time windows. O3 showed an inverse association with mortality, while no association was observed between greenness and mortality. Adjusting for NDVI increased the hazard ratios for PM2.5, PM10, BC and NO2 exposures in 1990. We did not find significant interactions between greenness and air pollution metrics. ConclusionLong term exposure to even low levels of air pollution is associated with mortality. Opening up for a long latency period, our findings indicate that air pollution exposures over time may be even more harmful than anticipated.

Associations of urinary and blood cadmium concentrations with all-cause mortality in US adults with chronic kidney disease: a prospective cohort study.

Epidemiological evidence for the relationship between cadmium exposure and mortality in specific chronic kidney disease (CKD) populations remains scarce. We aimed to explore the relationships between cadmium concentrations in urine and blood and all-cause mortality among CKD patients in the USA. This cohort study was composed of 1825 CKD participants from the National Health and Nutrition Examination Survey (NHANES) (1999-2014) who were followed up to December 31, 2015. All-cause mortality was ascertained by matching the National Death Index (NDI) records. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality in relation to urinary and blood cadmium concentrations by Cox regression models. During an average follow-up period of 82 months, 576 CKD participants died. Compared with the lowest quartiles, HRs (95% CIs) for all-cause mortality associated with the fourth weighted quartiles of urinary and blood cadmium concentrations were 1.75 (1.28 to 2.39) and 1.59 (1.17 to 2.15), respectively. Furthermore, the HRs (95% CIs) for all-cause mortality per ln-transformed IQR increment in cadmium concentrations in urine (1.15 μg/g UCr) and blood (0.95 μg/L) were 1.40 (1.21 to 1.63) and 1.22 (1.07 to 1.40), respectively. Linear concentration-response relationships between urinary and blood cadmium concentrations and all-cause mortality were also found. Our findings suggested that increased cadmium concentrations in both urine and blood significantly contributed to enhanced mortality risk in CKD patients, thus highlighting that efforts to reduce cadmium exposure may reduce mortality risk in high-risk populations with CKD.

Device-evaluated autonomic nervous function for predicting ventricular arrhythmias and all-cause mortality in patients who underwent cardiac resynchronization therapy-defibrillator.

Introduction: Autonomic nervous system (ANS) function quantified by heart rate variability (HRV) was associated with long-term prognosis, but it was rarely used in the evaluation of patients with heart failure, especially those with cardiac resynchronization therapy-defibrillator (CRT-D) implantation. This study aimed to describe the changes in ANS function among patients who underwent CRT-D with remote home monitoring function, and explore predictive value of HRV for ventricular tachyarrhythmias (VTAs) and all-cause mortality. Method: Patients who underwent CRT-D implantation were included. Device-measured all-day HR, night-time HR, and HRV (measured by the standard deviation of the atrial-atrial sensed intervals) were used to quantify ANS function. Multivariate Cox proportional hazards models were fitted to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of VTAs or all-cause mortality in relation to ANS function at baseline and 6months post-implantation. The cutoff value was determined using restrictive cubic splines. Multivariable logistic regression was further established to determine factors influencing postoperative HRV. Results: A total of 170 patients treated with CRT-D were eligible for analysis. During a median follow-up period of 50.8months, 61 patients died and 69 patients experienced at least one spontaneous episode of VTAs. At 6months after CRT implantation, 114 patients showed improvement in HRV, increasing from 66.4 ± 19.4ms to 76.7 ± 21.2ms. The postoperative HRV was associated with both all-cause mortality (HRs: 0.983; 95% CI: 0.968 to 0.998, p = 0.012) and VTAs (HRs: 0.973; 95% CI: 0.954 to 0.993, p = 0.008), and the relative risk would significantly increase when the postoperative HRV lower than 75ms. After adjusting for basic ANS function and possible influencing factors, patients without diabetes (p = 0.018) and with higher daily physical activity (p = 0.041) could maintain higher postoperative HRV after CRT implantation. Conclusion: More than two-thirds of heart failure patients showed improvement in ANS function following CRT treatment. However, patients with diabetes and low daily physical activity levels have difficulty maintaining a higher postoperative HRV, which is associated with a worse clinical outcome.

Prognostic importance of obstructive sleep apnea and CPAP treatment for cardiovascular and mortality outcomes in patients with resistant hypertension: a prospective cohort study.

The prognostic importance of obstructive sleep apnea (OSA) severity and other polysomnographic parameters in patients with resistant hypertension (RHT) has never been evaluated. We aimed to assess it in a prospective cohort of 422 individuals with RHT. OSA presence/severity was ascertained by complete polysomnography (PSG) at baseline. Multivariable Cox regressions assessed the risks associated with OSA severity and other PSG parameters (apnea-hypopnea index, sleep duration, nocturnal hypoxemia and periodic limb movements) for the primary (total cardiovascular events [CVEs] and all-cause mortality) and secondary outcomes (major CVEs). In the subgroup of patients with moderate/severe OSA, the risks associated with CPAP treatment were also estimated in relation to untreated individuals. One-hundred and eighty-six participants (44%) had no/mild OSA and 236 (56%) had moderate/severe OSA, and 67 of them were CPAP-treated. Over a mean follow-up of 5 years, there were 46 CVEs (37 major ones) and 44 all-cause deaths. Neither the presence of moderate/severe or severe OSA, nor being untreated during follow-up, was associated with significant excess risks for any outcome in relation to the subgroup with no/mild OSA. Similarly, no other PSG-derived parameter predicted any adverse outcome. Otherwise, CPAP treatment was associated with non-significant risk reductions of 37% for total CVEs, 49% for major CVEs and 63% for all-cause mortality in relation to those who remained untreated during follow-up. In conclusion, the presence/severity of OSA and its related PSG parameters were not associated with worse cardiovascular/mortality prognosis in patients with RHT. However, CPAP treatment might be protective in individuals with moderate/severe OSA.

Transvalvular Pressure Gradients andAll-Cause Mortality Following TAVR: AMulticenter Echocardiographic and Invasive Registry.

Low ejection fraction (EF) and low flow as determined by an echocardiographic stroke volume index(SVi)<35mL/m2 are associated with low transvalvular gradients and increased mortality in both severe aorticstenosis (AS) and post-transcatheter aortic valve replacement (TAVR). Absence of an elevated echocardiographic transaorticgradient post-TAVR is considered a marker of procedural success despite the absence of data on its impactonmortality. The authors sought to examine the association of invasive and echocardiographic gradients post-TAVR with all-cause mortality in relation to flow and EF. In a multicenter retrospective registry of patients undergoing TAVR, Cox models with regression splines explored the relationship between invasive and echocardiographic gradients post-TAVR with 2-year mortality. An invasive gradient<5mmHg was considered low, between≥5 and<10mmHg was considered intermediate, and≥10mmHg was considered high. An echocardiographic gradient<10mmHg was considered low,≥10 and<20mmHg was considered intermediate, and≥20mmHg was considered high. Higher mortality occurred in low echocardiographic gradients at discharge relative to intermediate gradients (P< 0.001), and low gradient was associated with lower EF and echocardiographic SVi (P< 0.001 and P< 0.008, respectively). Lower mortality occurred in low invasive gradients relative to intermediate gradients (P=0.012) with no difference in EF and echocardiographic SVi between groups (P = 0.089 and P=0.947, respectively). There were insufficient observations to determine the impact of high echocardiographic and invasive gradients on mortality. In this large retrospective analysis, the impact of transaortic gradients on mortality after TAVR wasnot linear and complex, showing opposite results among echocardiographic and invasive measurements in low-gradient patients.

Associations of muscle mass, strength, and quality with all-cause mortality in China: a population-based cohort study.

BackgroundIt remains unclear about the association of muscle mass, strength, and quality with death in the general Chinese population of diverse economical and geographical backgrounds. The present study aimed to comprehensively examine such associations across different regions in China.MethodsBased on the China Kadoorie Biobank study, the present study included 23,290 participants who were aged 38 to 88 years and had no prevalent cardiovascular diseases or cancer. Muscle mass and grip strength were measured using calibrated instruments. Arm muscle quality was defined as the ratio of grip strength to arm muscle mass. Low muscle mass, grip strength, and arm muscle quality were defined as the sex-specific lowest quintiles of muscle mass index, grip strength, and arm muscle quality, respectively. Cox proportional hazards models yielded hazard ratios (HRs) and 95% confidence intervals (CIs) for risks of all-cause mortality in relation to muscle mass, strength, and quality.ResultsDuring a median follow-up of 3.98 years, 739 participants died. The HR (95% CI) of all-cause mortality risk was 1.28 (1.08–1.51) for low appendicular muscle mass index, 1.38 (1.16–1.62) for low total muscle mass index, 1.68 (1.41–2.00) for low grip strength, and 1.41 (1.20–1.66) for low arm muscle quality in models adjusted for sociodemographic characteristics, lifestyle factors, and medical histories.ConclusionLow muscle mass, grip strength, and arm muscle quality are all associated with short-term increased risks of mortality, indicating the importance of maintaining normal muscle mass, strength, and quality for general Chinese adults.

Impacts of depression subcase and case on all-cause mortality in older people: The findings from the multi-centre community-based cohort study in China.

It is unclear whether and to what extent depression subcases and cases in older age were associated with all-cause mortality. Little is known about gender differences in the associations. We assess these in older Chinese. We examined a random sample of 6124 participants aged ≥60 years across five provinces in China. They were interviewed using a standard method of the GMS-AGECAT to diagnose depression subcase and case and record sociodemographic and disease risk factors at baseline, and to follow up their vital status. We employed Cox regression models to determine all-cause mortality in relation to depression subcases and cases, with adjustment for important variables, including social support and co-morbidities. Over the 10-year follow-up, 928 deaths occurred. Compared to those without depression at baseline, participants with depression subcase (n=196) and case (n=264) had increased risk of mortality; adjusted hazard ratios (HRs) were 1.46 (95% CI 1.07-2.00) and 1.45 (1.10-1.91). The adjusted HRs in men were 1.15 (0.72-1.81) and 1.85 (1.22-2.81), and in women 1.87 (1.22-2.87) and 1.22 (0.83-1.77) respectively. In participants aged ≥65 years, the adjusted HRs were 1.12 (0.68-1.84) and 1.99 (1.28-3.10) in men, and 2.06 (1.32-2.24) and 1.41 (0.94-2.10) in women. Increased HR in depression subcases was higher in women than man (ratio of HRs was 1.84, p=0.034). Older people with depression subcase could have increased all-cause mortality to a similar extent to those with depression case. More attention should be paid to subcases of depression in women to tackle gender inequalities and improve survival.

Sugar-sweetened beverage, artificially sweetened beverage and sugar intake and colorectal cancer survival.

The influence of a high sugar diet on colorectal cancer (CRC) survival is unclear. Among 1463 stage I-III CRC patients from the Nurses' Health Study and Health Professionals Follow-up Study, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC-specific and all-cause mortality in relation to intake of post-diagnosis sugar-sweetened beverages (SSB), artificially sweetened beverages (ASB), fruit juice, fructose and other sugars. Over a median 8.0 years, 781 cases died (173 CRC-specific deaths). Multivariable-adjusted HRs for post-diagnosis intake and CRC-specific mortality were 1.21 (95% CI: 0.87-1.68) per 1 serving SSBs per day (serving/day) and 1.24 (95% CI: 0.95-1.63) per 20 grams fructose per day. Significant positive associations for CRC-specific mortality were primarily observed ≤5 years from diagnosis (HR per 1 serving/day of SSBs = 1.59, 95% CI: 1.06-2.38). Significant inverse associations were observed between ASBs and CRC-specific and all-cause mortality (HR for ≥5 versus <1 serving/week = 0.44, 95% CI: 0.26-0.75 and 0.70, 95% CI: 0.55-0.89, respectively). Higher post-diagnosis intake of SSBs and sugars may be associated with higher CRC-specific mortality, but only up to 5 years from diagnosis, when more deaths were due to CRC. The inverse association between ASBs and CRC-specific mortality warrants further examination.

Impacts of Depression Case and Subcase on All-Cause Mortality Among Older People in China: Are There Gender Differences?

Background: Depression cases and subcases have increased in older communities. It is unclear whether and to what extent they were associated with all-cause mortality in older people. Little is known about gender differences in the association. Methods: We examined a random sample of 6,124 participants aged ≥60 years across five provinces in China. They were interviewed using a standard method of the GMS-AGECAT to diagnose depression case and subcase and record sociodemographic and disease risk factors at baseline, and to follow up their vital status. We employed Cox regression models to determine all-cause mortality in relation to depression cases and subcases, with adjustment for important variables, including co-morbidities and social support. Results: Over the 10 years follow-up, 928 deaths occurred. Compared to those without depression, participants with depression subcase (n=196) and case (n=264) had increased risk of all-cause mortality; adjusted hazard ratios (HR) were 1.46 (95% CI 1.07-2.00) and 1.45 (1.10-1.91). The adjusted HRs in men were 1.15 (0.72-1.81) and 1.85 (1.22-2.81), and in women 1.87 (1.22-2.87) and 1.22 (0.83-1.77) respectively. In participants aged ≥65 years, the adjusted HRs were 1.12 (0.68-1.84) and 1.99 (1.28-3.10) in men, and 2.06 (1.32-2.24) and 1.41 (0.94-2.10) in women. Increased HR in depression subcases was higher in women than man (ratio of HRs was 1.84, p=0.034). Conclusions: Older people with subcase depression could have increased all-cause mortality to a similar extent to those with case depression. More attention should be paid to subcases of depression in women to tackle gender inequalities and improve survival. Funding Statement: The data collection of the two cohort studies were funded by the Royal Society of UK, the BUPA Foundation (Grants Nos. 45NOV06, and TBF-M09-05) and Alzheimer’s Research UK (Grant No. ART/PPG2007B/2). Declaration of Interests: Non declared. Adam Spira received honoraria from Springer Nature Switzerland AG for Guest Editing special issues of Current Sleep Medicine Reports. Ethics Approval Statement: Informed consent was obtained from each participant. If an individual was unable to provide informed consent due to disability or limited educational level, their next of kin or care givers were invited to provide assent for participation.Ethical approvals for the Anhui cohort study and the 4-province study were obtained from the Ethics Committees of University College London, and School of Health and Wellbeing at University of Wolverhampton, UK and the Research Ethics Committee of Anhui Medical University.

Age-dependency in mortality of Finnish family caregivers: a nationwide register-based study

Abstract Purpose Mortality appears to be lower in family caregivers than in the general population. However, there is lack of knowledge whether the difference in mortality between family caregivers and the general population is dependent on age. The purpose of this study was to analyze all-cause mortality in relation to age in family caregivers and to study their cause-specific mortality using data from multiple Finnish national registers. Methods The data included all individuals, who received family caregiver's allowance in Finland in 2012 (n = 42 256, mean age 67 years, 71% women) and a control population matched for age, sex, and municipality of residence (n = 83 618). Information on dates and causes of death between 2012 and 2017 were obtained from the Finnish Causes of Death Register. Flexible parametric survival modeling and competing risk regression adjusted for socioeconomic status were used. Results The total follow-up time was 717 877 person-years. Family caregivers had lower all-cause mortality than the controls over the follow-up (8.1% vs. 11.6%) both among women (hazard ratio [HR]: 0.64, 95% CI: 0.61-0.68) and men (HR: 0.73, 95% CI: 0.70-0.77). Younger adult caregivers had equal or only slightly lower mortality than their controls, but after age 60, the difference increased markedly resulting in over 10% lower mortality in favor of the caregivers in the oldest age groups. Caregivers had lower mortality for all the causes of death studied, namely cardiovascular, cancer, neurological, external, respiratory, gastrointestinal and dementia than the controls. Of these, the lowest was the risk for dementia (subhazard ratio=0.29, 95%CI: 0.25-0.34). Conclusions Older family caregivers have lower mortality than the age-matched controls from the general population while younger caregivers have similar mortality to their peers. This age-dependent advantage in mortality is likely to reflect selection of healthier individuals into the family caregiver role. Key messages The difference in mortality between family caregivers and the age-matched general population varies considerably with age. Advantage in mortality observed in family caregiver studies is likely to reflect the selection of healthier individuals into the caregiver role, which underestimates the adverse effects of caregiving.

Prognostic Significance of Long-term HbA1c Variability for All-Cause Mortality in the ACCORD Trial.

The association between high glycemic variability and all-cause mortality has been widely investigated in epidemiological studies but rarely validated in glucose-lowering clinical trials. We aimed to identify the prognostic significance of visit-to-visit HbA1c variability in treated patients in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial population. We studied the risk of all-cause mortality in relation to long-term visit-to-visit HbA1c variability, expressed as coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV), from the 8th month to the transition from intensive to standard glycemic therapy. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (HR) and 95% CI. Compared with the standard therapy group (n = 4,728), the intensive therapy group (n = 4,755) had significantly lower mean HbA1c (6.6% [49 mmol/mol] vs. 7.7% [61 mmol/mol], P < 0.0001) and lower CV, VIM, and ARV (P < 0.0001). In multivariate adjusted analysis, all three HbA1c variability indices were significantly associated with total mortality in all patients as well as in the standard- and intensive-therapy groups analyzed separately. The hazard ratios for a 1-SD increase in HbA1c variability indices for all-cause mortality were 1.19 and 1.23 in intensive and standard therapy, respectively. Cross-tabulation analysis showed the third tertile of HbA1c mean and VIM had significantly higher all-cause mortality (HR 2.05; 95% CI 1.17-3.61; P < 0.01) only in the intensive-therapy group. Long-term visit-to-visit HbA1c variability was a strong predictor of all-cause mortality. HbA1c VIM combined with HbA1c mean conferred an increased risk for all-cause mortality in the intensive-therapy group.

Education inequalities in adult all-cause mortality: first national data for Australia using linked census and mortality data.

BackgroundNational linked mortality and census data have not previously been available for Australia. We estimated education-based mortality inequalities from linked census and mortality data that are suitable for international comparisons.MethodsWe used the Australian Bureau of Statistics Death Registrations to Census file, with data on deaths (2011–2012) linked probabilistically to census data (linkage rate 81%). To assess validity, we compared mortality rates by age group (25–44, 45–64, 65–84 years), sex and area-inequality measures to those based on complete death registration data. We used negative binomial regression to quantify inequalities in all-cause mortality in relation to five levels of education [‘Bachelor degree or higher’ (highest) to ‘no Year 12 and no post-secondary qualification’ (lowest)], separately by sex and age group, adjusting for single year of age and correcting for linkage bias and missing education data.ResultsMortality rates and area-based inequality estimates were comparable to published national estimates. Men aged 25–84 years with the lowest education had age-adjusted mortality rates 2.20 [95% confidence interval (CI): 2.08‒2.33] times those of men with the highest education. Among women, the rate ratio was 1.64 (1.55‒1.74). Rate ratios were 3.87 (3.38‒4.44) in men and 2.57 (2.15‒3.07) in women aged 25–44 years, decreasing to 1.68 (1.60‒1.76) in men and 1.44 (1.36‒1.53) in women aged 65–84 years. Absolute education inequalities increased with age. One in three to four deaths (31%) was associated with less than Bachelor level education.ConclusionsThese linked national data enabled valid estimates of education inequality in mortality suitable for international comparisons. The magnitude of relative inequality is substantial and similar to that reported for other high-income countries.

Left atrial diameter, left ventricle filling indices, and association with all-cause mortality: Results from the population-based Tromsø Study.

To examine the associations between diastolic dysfunction indices and long-term risk of all-cause mortality in adults over 23-year follow-up. Participants (n=2734) of the population-based Tromsø Study of Norway had echocardiography in 1994-1995. Of these 67% were repeated in 2001 and/or 2007-2008. Mortality between 1994 and 2016 was determined by linkage to the national death registry. Cox regression was used to model the hazard of all-cause mortality in relation to left atrial parameters (treated as time-dependent using repeated measurements) adjusted for traditional risk factors and cardiovascular disease. During the follow-up, 1399 participants died. Indexed left atrial diameter, mitral peak E deceleration time, and mitral peak E to peak A ratio showed an U-shaped association with all-cause mortality. Combining left atrial diameter with mitral peak E deceleration time increased the prognostic accuracy for all-cause mortality whereas adding mitral peak E to peak A ratio did not increase prognostic value. We estimated new optimal cutoff values of left atrial diameter, mitral peak E deceleration time, and mitral peak E to peak A ratio for all-cause mortality outcome. E/e' had a cubic relation to mortality. Both enlarged and small left atrial diameters were associated with increased all-cause mortality risk. A combination of Doppler-based left ventricle filling parameters had an incremental effect on all-cause mortality risk. The cutoff values of diastolic dysfunction indices we determined had similar all-cause mortality prediction ability as those recommended by American Association of Echocardiography and European Association of Cardiovascular Imaging.