Hazard Of All-cause Mortality Research Articles

Leisure-time physical activity and all-cause mortality and cardiovascular disease in adults with type 2 diabetes: Cross-country comparison of cohort studies

PurposeThis study aimed to quantify the dose–response association and the minimal effective dose of leisure-time physical activity (PA) to prevent mortality and cardiovascular disease in adults with type 2 diabetes. MethodsCross-country comparison of 2 prospective cohort studies including 14,913 and 17,457 population-based adults with type 2 diabetes from the UK and China. Baseline leisure-time PA was self-reported and categorized by metabolic equivalent hours per week (MET-h/week) according to World Health Organization recommendations: none, below recommendation (>0–7.49 MET-h/week); at recommended level (7.5–14.9 MET-h/week); above recommendation (≥15 MET-h/week). Mortality and cardiovascular disease data were obtained from national registries. ResultsDuring a median follow-up of 12.4 and 9.7 years, in the UK and China cohorts, repectively, higher levels of leisure-time PA were inversely associated with all-cause (1571 and 2351 events) and cardiovascular mortality (392 and 1060 events), mostly consistent with a linear dose–response relationship. PA below, at, and above recommendations, compared with no activity, yielded all-cause mortality hazard ratios of 0.94 (95% confidence interval (95%CI): 0.79–1.12), 0.90 (95%CI: 0.74–1.10), and 0.85 (95%CI: 0.70–1.02) in British adults and 0.87 (95%CI: 0.68–1.10), 0.88 (95%CI: 0.74–1.03), and 0.77 (95%CI: 0.70–0.85) in Chinese adults. Associations with cardiovascular mortality were more pronounced in British adults (0.80 (95%CI: 0.58–1.11), 0.75 (95%CI: 0.52–1.09), and 0.69 (95%CI: 0.48–0.97)) but less pronounced in Chinese adults (1.06 (95%CI: 0.76–1.47), 1.01 (95%CI: 0.80–1.28), and 0.79 (95%CI: 0.69–0.92)). PA at recommended levels was not associated with lower rates of major adverse cardiovascular events (2345 and 4458 events). ConclusionLeisure-time PA at the recommended levels was not convincingly associated with lower mortality and had no association with risk of major adverse cardiovascular events in British or Chinese adults with type 2 diabetes. Leisure-time PA above current recommendations may be needed to prevent cardiovascular disease and premature mortality in adults with type 2 diabetes.

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.

Individual-level home values and cancer mortality in a statewide registry.

Prior work assessing disparities in cancer outcomes has relied on regional socioeconomic metrics. These metrics average data across many individuals, resulting in a loss of granularity and confounding with other regional factors. Using patients' addresses at the time of diagnosis from the Ohio Cancer Incidence Surveillance System, we retrieved individual home price estimates from an online real estate marketplace. This individual-level estimate was compared with the Area Deprivation Index (ADI) at the census block group level. Multivariable Cox proportional hazards models were used to determine the relationship between home price estimates and all-cause and cancer-specific mortality. A total of 667 277 patients in Ohio Cancer Incidence Surveillance System were linked to individual home prices across 16 cancers. Increasing home prices, adjusted for age, stage at diagnosis, and ADI, were associated with a decrease in the hazard of all-cause and cancer-specific mortality (hazard ratio [HR] = 0.92, 95% confidence interval [CI] = 0.92 to 0.93, and HR = 0.95, 95% CI = 0.94 to 0.95, respectively). Following a cancer diagnosis, individuals with home prices 2 standard deviations above the mean had an estimated 10-year survival probability (7.8%, 95% CI = 7.2% to 8.3%) higher than those with home prices 2 standard deviations below the mean. The association between home price and mortality was substantially more prominent for patients living in less deprived census block groups (Pinteraction < .001) than for those living in more deprived census block groups. Higher individual home prices were associated with improved all-cause and cancer-specific mortality, even after accounting for regional measures of deprivation.

Thigh-hip ratio is significantly associated with all-cause mortality among Japanese community-dwelling men.

Anthropometric evaluation is a simple yet essential indicator of muscle and fat mass when studying life prognosis in aging. This study aimed to investigate the contributions of anthropometric measurements, independent of body mass index, to measures of all-cause mortality. We examined data for 1,704 participants from the 2014 Nomura Cohort Study who attended follow-ups for the subsequent eight years (follow-up rate: 93.0%). Of these, 765 were male (aged 69 ± 11 years) and 939 were female (aged 69 ± 9 years). The Japanese Basic Resident Registry provided data on adjusted relative hazards for all-cause mortality. The data were subjected to a Cox regression analysis, wherein the time variable was age and the risk factors were gender, age, anthropometric index, smoking habits, drinking habits, exercise habits, cardiovascular history, hypertension, lipid levels, diabetes, renal function, and serum uric acid. Of the total number of participants, 158 (9.3%) were confirmed to have died, and of these, 92 were male (12.0% of all male participants) and 66 were female (7.0% of all female participants). The multivariable Cox regression analysis revealed that a smaller thigh-hip ratio predicted eight-year all-cause mortality in male participants, but only baseline body mass index was associated with all-cause mortality in female participants. Thigh-hip ratio is a useful predictor of death in Japanese community-dwelling men.

Long-term Outcomes of Robot-assisted Versus Laparoscopic Surgery for Colon Cancer: A Nationwide Register-based Cohort Study.

To determine long-term survival in patients undergoing robot-assisted surgery (RAS) or laparoscopic surgery (LAS) for colon cancer. The potential long-term benefits of RAS compared with LAS for colon cancer are not well examined. Using a register-based approach, we aimed to compare these 2 surgical platforms in an analysis of long-term outcomes, including recurrence-free survival and all-cause- and colon cancer-specific mortality. A nationwide register-based cohort study of patients with Union for International Cancer Control stage I-III colon cancer undergoing planned RAS or LAS from 2010 through 2018. Patient demographic, clinical, and pathological data were retrieved from Danish national registers. Survival and recurrence rates were estimated by Cox proportional hazard multivariate regression analysis adjusting for baseline covariates. A total of 7565 patients [LAS=6905 (91%) and RAS=660 (9%)] were included in the complete case survival analysis. Patients undergoing LAS had a significantly increased risk of cancer recurrence [LAS=1178 (17.1%), RAS=82 (12.4%), P =0.002] with a mean follow-up time of 4.93 years (standard deviation 2.47). The survival analysis of recurrence-free survival favored RAS [hazard ratio adjusted =0.80, 95% CI (0.64-1.00), P =0.049]. No associations between the 2 surgical platforms were evident regarding all-cause [hazard ratio adjusted =0.98, 95% CI (0.82-1.17), P =0.783] or colon cancer-specific mortality [hazard ratio adjusted =0.89, 95% CI (0.67-1.18), P =0.405]. Adopting RAS for colon cancer was associated with improved recurrence-free survival. However, it did not cause a lower all-cause- or colon cancer-specific mortality.

Waist to height ratio as a simple tool for predicting mortality: a systematic review and meta-analysis.

The association of central obesity with higher rates of mortality is not well studied. This study evaluates the association between waist-to-height ratio (WHtR), as a measure of central obesity, with mortality. Documents were retrieved from PubMed, Web of Science, Scopus, and Google Scholar databases until May 2022. Data were extracted from cohort studies reporting effect size (hazard ratio (HR)) regarding the association between WHtR as a continuous (per 1 SD increment) or categorical (highest/lowest) measure and all-cause and cause-specific mortality. Screening of included studies was performed independently by two authors. Moreover, the quality assessment of included studies was performed based on the Newcastle-Ottawa assessment scale. Finally, random effect meta-analysis was performed to pool the data, and the outcomes' certainty level was assess based on the GRADE criteria. Of the 815 initial studies, 20 were included in the meta-analysis. Random effect meta-analysis showed that in the general population, the all-cause mortality HRs for categorical and continuous measurements of WHtR increased significantly by 23% (HR:1.23; 95% CI: 1.04-1.41) and 16% (HR:1.16; 95% CI: 1.07-1.25), respectively. Moreover, the hazard of cardiovascular (CVD) mortality increased significantly for categorical and continuous measurements of WHtR by 39% (HR:1.39; 95% CI: 1.18-1.59) and 19% (HR:1.19; 95% CI: 1.07-1.31). The quality assessment score of all included studies was high. Higher levels of WHtR, indicating central obesity, were associated with an increased hazard of CVD and all-cause mortality. This measure can be used in the clinical setting as a simple tool for predicting mortality.

Objectively regular sleep patterns and mortality in a prospective cohort: The Multi-Ethnic Study of Atherosclerosis.

Irregular sleep and non-optimal sleep duration separately have been shown to be associated with increased disease and mortality risk. We used data from the prospective cohort Multi-Ethnic Study of Atherosclerosis sleep study (2010-2013) to investigate: do aging adults whose sleep is objectively high in regularity in timing and duration, and of sufficient duration tend to have increased survival compared with those whose sleep is lower in regularity and duration, in a diverse US sample? At baseline, sleep was measured by 7-day wrist actigraphy, concurrent with at-home polysomnography and questionnaires. Objective metrics of sleep regularity and duration from actigraphy were used for statistical clustering using sparse k-means clustering. Two sleep patterns were identified: "regular-optimal" (average duration: 7.0 ± 1.0 hr obtained regularly) and "irregular-insufficient" (duration: 5.8 ± 1.4 hr obtained with twice the irregularity). Using proportional hazard models with multivariate adjustment, we estimated all-cause mortality hazard ratios. Among 1759 participants followed for a median of 7.0 years (Q1-Q3, 6.4-7.4 years), 176 deaths were recorded. The "regular-optimal" group had a 39% lower mortality hazard than did the "irregular-insufficient" sleep group (hazard ratio [95% confidence interval]: 0.61 [0.45, 0.83]) after adjusting for socio-demographics, lifestyle, medical comorbidities and sleep disorders. In conclusion, a "regular-optimal" sleep pattern was significantly associated with a lower hazard of all-cause mortality. The regular-optimal phenotype maps behaviourally to regular bed and wake times, suggesting sleep benefits of adherence to recommended healthy sleep practices, with further potential benefits for longevity.

Disease trajectories following myocardial infarction: insights from process mining of 145 million hospitalisation episodes

Knowledge of post-myocardial infarction (MI) disease risk to date is limited-yet the number of survivors of MI has increased dramatically in recent decades. We investigated temporally ordered sequences of all conditions following MI in nationwide electronic health record data through the application of process mining. We conducted a national retrospective cohort study of all hospitalisations (145,670,448 episodes; 34,083,204 individuals) admitted to NHS hospitals in England (1st January 2008-31st January 2017, final follow-up 27th March 2017). Through process mining, we identified trajectories of all major disease diagnoses following MI and compared their relative risk (RR) and all-cause mortality hazard ratios (HR) to a risk-set matched non-MI control cohort using Cox proportional hazards and flexible parametric survival models. Among a total of 375,669 MI patients (130,758 females; 34.8%) and 1,878,345 matched non-MI patients (653,790 females; 34.8%), we identified 28,799 unique disease trajectories. The accrual of multiple circulatory diagnoses was more common amongst MI patients (RR 4.32, 95% CI 3.96-4.72) and conferred an increased risk of death (HR 1.32, 1.13-1.53) compared with matched controls. Trajectories featuring neuro-psychiatric diagnoses (including anxiety and depression) following circulatory disorders were markedly more common and had increased mortality post MI (HR ranging from 1.11 to 1.73) compared with non-MI individuals. These results provide an opportunity for early intervention targets for survivors of MI-such as increased focus on the psychological and behavioural pathways-to mitigate ongoing adverse disease trajectories, multimorbidity, and premature mortality. British Heart Foundation; Alan Turing Institute.

Perceived Fatigability, Fatigue, and Mortality in Mid-to-Late Life in the Baltimore Longitudinal Study of Aging.

Fatigue is an established prognostic indicator of mortality risk. It remains unknown whether fatigability anchored to a physical task is a more sensitive prognostic indicator and whether sensitivity differs by prevalent chronic conditions. A total of 1076 physically well-functioning participants 50 yr or older in the Baltimore Longitudinal Study of Aging self-reported fatigue (unusual tiredness or low energy) and had perceived fatigability assessed after a standardized treadmill walk. All-cause mortality was ascertained by proxy contact and National Death Index linkage. Cox proportional hazards models estimated associations of perceived fatigability and fatigue with all-cause mortality, adjusting for demographic and clinical covariates. Interactions by chronic conditions were also examined. Each 1 SD higher in perceived fatigability, unusual tiredness, or low energy was associated with a higher relative hazard of all-cause mortality after covariate adjustment (fatigability: hazard ratio (HR), 1.18 (95% confidence interval (CI), 1.03-1.36); unusual tiredness: HR, 1.25 (95% CI, 1.08-1.44); low energy: HR, 1.27 (95% CI, 1.10-1.46)). Models had similar discrimination ( P > 0.14 for all). Perceived fatigability was associated with mortality risk among participants free of arthritis or osteoarthritis who otherwise appeared healthy (no arthritis: HR, 1.45 (95% CI, 1.15-1.84); arthritis: HR, 1.09 (95% CI, 0.92-1.30); P -interaction = 0.031). Unusual tiredness was associated with mortality among those with a history of diabetes (no diabetes: HR, 1.16 (95% CI, 0.97-1.38); diabetes: HR, 1.65 (95% CI, 1.22-2.23); P -interaction = 0.045) or pulmonary disease (no pulmonary disease: HR, 1.22 (95% CI, 1.05-1.43); pulmonary disease: HR, 2.15 (95% CI, 1.15-4.03); P -interaction = 0.034). Higher perceived fatigability and fatigue symptoms were similarly associated with higher all-cause mortality, but utility differed by chronic condition. Perceived fatigability might be useful for health screening and long-term mortality risk assessment for well-functioning adults. Alternatively, self-reported fatigue seems more disease-specific with regard to mortality risk.

Risky health behaviors and subsequent late mortality after blood or marrow transplantation: a BMTSS report

AbstractWe examined the association between risky health behaviors (smoking, heavy alcohol consumption, and lack of vigorous physical activity) and all-cause and cause-specific late mortality after blood or marrow transplantation (BMT) to understand the role played by potentially modifiable risk factors. Study participants were drawn from the BMT Survivor Study (BMTSS) and included patients who received transplantation between 1974 and 2014, had survived ≥2 years after BMT, and were aged ≥18 years at study entry. Survivors provided information on sociodemographic characteristics, chronic health conditions, and health behaviors. National Death Index was used to determine survival and cause of death. Multivariable regression analyses determined the association between risky health behaviors and all-cause mortality (Cox regression) and nonrecurrence-related mortality (NRM; subdistribution hazard regression), after adjusting for relevant sociodemographic, clinical variables and therapeutic exposures. Overall, 3866 participants completed the BMTSS survey and were followed for a median of 5 years to death or 31 December 2021; and 856 participants (22.1%) died after survey completion. Risky health behaviors were associated with increased hazard of all-cause mortality (adjusted hazard ratio [aHR] former smoker, 1.2; aHR current smoker, 1.7; reference, nonsmoker; aHR heavy drinker, 1.4; reference, nonheavy drinker; and aHR no vigorous activity, 1.2; reference, vigorous activity) and NRM (aHR former smoker, 1.3; aHR current smoker, 1.6; reference, nonsmoker; aHR heavy drinker, 1.4; reference: nonheavy drinker; and aHR no vigorous activity, 1.2; reference, vigorous activity). The association between potentially modifiable risky health behaviors and late mortality offers opportunities for development of interventions to improve both the quality and quantity of life after BMT.

The impact of recipient and donor gender-match and mismatch on the post-liver transplant outcomes of patients with primary biliary cholangitis.

In this study, we evaluate the effects of donor gender on post-liver transplant (LT) prognosis. We specifically consider patients with primary biliary cholangitis (PBC). The 2005 to 2019 UNOS transplant registry was used to select patients with PBC. The study cohort was stratified by donor gender. All-cause mortality and graft failure hazards were compared using iterative Cox regression analysis. Subanalyses were performed to evaluate gender mismatch on post-LT prognosis. There were 1885 patients with PBC. Of these cases, 965 entries had male donors and 920 had female donors. Median follow-up was 4.82 (25-75% IQR 1.83-8.93) years. Having a male donor was associated with higher all-cause mortality (aHR 1.28 95%CI 1.03-1.58) and graft failure (aHR 1.70 95%CI 1.02-2.82). Corresponding incidence rates were also relatively increased. In the sub-analysis of female recipients (n=1581), those with gender-mismatch (male donors, n=769) were associated with higher all-cause mortality (aHR 1.41 95%CI 1.11-1.78) but not graft failure. In the male recipient subanalysis (n=304), no associations were found between gender-mismatch (female donors, n=108) and all-cause mortality or graft failure. This study shows that recipients who have male donors experienced higher rates of all-cause mortality following LT. This finding was consistent in the female recipient-male donor mismatch cohort.

Catheter ablation and lower risk of incident dementia and mortality in older adults with atrial fibrillation.

Atrial fibrillation (AF) has consistently been associated with a higher risk of incident dementia. Observational evidence has suggested catheter ablation may be associated with a lower risk of dementia in patients with AF, but further research is needed. The objectives of this study were to use a global health research network to examine associations between catheter ablation, incident dementia and mortality in older adults with AF, and amongst subgroups by age, sex, co-morbidity status, and oral anticoagulant use. The research network primarily included healthcare organizations in the United States. This network was searched on 28th September 2022 for patients aged ≥65 years with a diagnosis of AF received at least 5 years prior to the search date. Cox proportional hazard models were run on propensity-score matched cohorts. After propensity score matching, 20,746 participants (mean age 68 years; 59% male) were included in each cohort with and without catheter ablation. The cohorts were well balanced for age, sex, ethnicity, co-morbidities, and cardiovascular medications received. The risk of dementia was significantly lower in the catheter ablation cohort (Hazard Ratio 0.52, 95% confidence interval: 0.45-0.61). The catheter ablation cohort also had a lower risk of all-cause mortality (Hazard Ratio 0.58, 95% confidence interval: 0.55-0.61). These associations remained in subgroup analyses in individuals aged 65-79 years, ≥80 years, males, females, participants who received OACs during follow-up, participants with paroxysmal and non-paroxysmal AF, and participants with and without hypertension, diabetes mellitus, ischemic stroke, chronic kidney disease and heart failure, including heart failure with preserved ejection fraction and heart failure with reduced ejection fraction. The observed lower risk of dementia and mortality with catheter ablation could be an important consideration when determining appropriate patient-centered rhythm control strategies for patients with AF. Further studies including data on the success of ablation are required.

The association between all-cause mortality and HIV acquisition risk groups in the United States, 2001-2014.

To investigate associations between all-cause mortality and human immunodeficiency virus (HIV) acquisition risk groups among people without HIV in the United States. We used data from 23,657 (NHANES) participants (2001-2014) and the Linked Mortality File to classify individuals without known HIV into HIV acquisition risk groups: people who ever injected drugs (ever-PWID); men who have sex with men (MSM); heterosexually active people at increased risk for HIV (HIH), using low income as a proxy for increased risk. We used Cox proportional hazards models to estimate adjusted and unadjusted all-cause mortality hazard ratios (HR) with 95% confidence intervals (CI). Compared with sex-specific heterosexually active people at average risk for HIV (HAH), the adjusted HR (95% CI) were: male ever-PWID 1.67 (1.14, 2.46), female ever-PWID 3.50 (2.04, 6.01), MSM 1.51 (1.00, 2.27), male HIH 1.68 (1.04, 2.06), female HIH 2.35 (1.87, 2.95), and male ever-PWID 1.67 (1.14, 2.46). Most people at increased risk for HIV in the US experience higher all-cause mortality than people at average risk. Strategies addressing social determinants that increase HIV risk should be incorporated into HIV prevention and other health promotion programs.

Long-term influence of air pollutants on morbidity and all-cause mortality of cardiometabolic multi-morbidity: A cohort analysis of the UK Biobank participants

BackgroundThe effects of air pollutants on cardiometabolic diseases (CMDs) have been widely explored, whereas their influences on cardiometabolic multi-morbidity (CMM) were not clear. MethodsWe employed the UK Biobank cohort (N = 317,160) to study the association between six air pollutants (PM2.5, PM10, PM2.5-10, PM2.5abs, NO2, and NOx) and four CMDs including type II diabetes (T2D), coronary artery disease (CAD), stroke and hypertension. CMM was defined as occurrence of two or more of the four diseases. Multi-state Cox models were performed to estimate hazard ratio (HR) and its 95% confidence interval (95%CI). ResultsDuring a median follow-up of 12.8 years, 52,211 participants developed only one CMD, 15,446 further developed CMM, and 16,861 ultimately died. It was demonstrated that per interquartile range increase (IQR) increases in PM2.5, PM10, PM2.5-10, PM2.5abs, NO2, and NOx would increase 12% (9%–15%), 4% (1%–7%), 3% (1%–6%), 7% (4%–10%), 11% (8%–15%) and 10% (7%–13%) higher risk of developing one CMD from health baseline; 7% (2%–12%), 8% (3%–13%), 6% (2%–11%), 10% (5%–15%), 13% (7%–18%) and 10% (5%–15%) greater risk of occurring CMM from one CMD baseline; and 11% (−2%∼26%), 22% (7%–38%), 17% (3%–32%), 31% (16%–49%), 33% (17%–51%) and 32% (17%–50%) larger risk of causing death from CMM baseline, respectively. ConclusionsWe revealed that people living in areas with high air pollution suffered from higher hazard of CMD, CMM and all-cause mortality; our findings implied keeping clean air was an effective approach to prevent or mitigate initiation, progression, and death from healthy to CMDs and from CMDs to CMM.

Association between hospital competition and quality of prostate cancer care

BackgroundHospitals account for approximately 6% of United States’ gross domestic product. We examined the association between hospital competition and outcomes in elderly with localized prostate cancer (PCa). We also assessed if race moderated this association.MethodsRetrospective study using Surveillance, Epidemiology, and End Results (SEER) – Medicare database. Cohort included fee-for-service, African American and white men aged ≥ 66, diagnosed with localized PCa between 1998 and 2011 and their claims between 1997 and 2016.We used Hirschman-Herfindahl index (HHI) to measure of hospital competition. Outcomes were emergency room (ER) visits, hospitalizations, Medicare expenditure and mortality assessed in acute survivorship phase (two years post-PCa diagnosis), and long-term mortality. We used Generalized Linear Models for analyzing expenditure, Poisson models for ER visits and hospitalizations, and Cox models for mortality. We used propensity score to minimize bias.ResultsAmong 253,176 patients, percent change in incident rate of ER visit was 17% higher for one unit increase in HHI (IRR: 1.17, 95% CI: 1.15–1.19). Incident rate of ER was 24% higher for whites and 48% higher for African Americans. For one unit increase in HHI, hazard of short-term all-cause mortality was 7% higher for whites and 11% lower for African Americans. The hazard of long-term all-cause mortality was 10% higher for whites and 13% higher for African Americans.ConclusionsLower hospital competition was associated with impaired outcomes of localized PCa care. Magnitude of impairment was higher for African Americans, compared to whites. Future research will explore process through which competition affects outcomes and racial disparity.

Risk of atrial fibrillation in individuals with dysglycemia and diabetes

ObjectiveDiabetes is a risk factor for atrial fibrillation (AF), and increases the risk of thromboembolic events in persons with AF. However, the link between the two conditions is not fully elucidated. Few studies have investigated the association of dysglycemia and incident AF. We investigated the risk of incident AF and prognosis according to diabetes status. Research design and methodsThe Copenhagen Primary Care Laboratory Database was merged with data on medical prescriptions, in- and outpatient contacts and vital status. The risk of AF according to diabetes status was investigated by use of Cox regression models. ResultsOf 354.807 individuals with a hemoglobin A1c (HbA1c) measurement, 28.541 (8 %) had known diabetes, 13.038 (4 %) had new onset diabetes and 27.754 (8 %) had prediabetes (HbA1c 42-47 mmol/mol). Persons with dysglycemia (HbA1c > 42 mmol/mol) and diabetes were older, more were men, they had lower level of education and were more likely to be living alone. We observed a gradual increase in risk of developing AF from HbA1c levels of 40 to 60 mmol/mol. In adjusted analyses we found a stepwise increase in hazard of AF from normoglycemia over prediabetes to persons with diabetes (no diabetes: 1.00 [ref.]; prediabetes: 1.12 [1.08–1.16]; new-onset diabetes: 1.16 [1.10–1.22]; known diabetes: 1.15 [1.11–1.20]). Persons with known diabetes had a significant higher hazard of stroke, cardiovascular and all-cause mortality. ConclusionIncreasing levels of HbA1c were associated with an increased hazard of developing AF. Persons with new onset of diabetes and those with known diabetes had similar hazard of developing AF, however persons with known diabetes had a significant higher hazard of stroke, cardiovascular- and all-cause mortality.

A prospective cohort study of long-term fasting blood glucose variability and risk of mortality in patients with type 2 diabetes

Objective: To investigate the association between long-term fasting blood glucose (FPG) variability and all-cause mortality in patients with type 2 diabetes. Methods: A total of 7 174 type 2 diabetic patients included in National Basic Public Health Service Program in Changshu of Jiangsu Province were recruited as participants. Long-term glucose variability was assessed using standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variability independent of the mean (VIM) across FPG measurements at the more than three visits. Death information were mainly obtained from the death registry system in Jiangsu. Then Cox proportional hazards regression models were used to estimate the associations of four variability indicators and all-cause mortality's hazard ratios (HRs) and their 95%CIs. Results: Among 55 058.50 person-years of the follow-up, the mean follow-up time was 7.67 years, and 898 deaths occurred during the follow-up period. After adjustment, compared with T1 group, the Cox regression model showed that HRs of T3 group in SD, CV, ARV and VIM were 1.24 (95%CI: 1.03-1.49), 1.20 (95%CI: 1.01-1.43), 1.28 (95%CI: 1.07-1.55) and 1.20 (95%CI:1.01-1.41), respectively. HRs of per 1 SD higher SD, CV, ARV and VIM were 1.13 (95%CI: 1.06-1.21), 1.08 (95%CI: 1.01-1.15), 1.05 (95%CI: 1.00-1.12) and 1.09 (95%CI: 1.02-1.16) for all-cause mortality, respectively. In the stratified analysis, age, gender, hypoglycemic agent and insulin uses had no effect on the above associations (all P for interaction >0.05). Conclusion: Long-term FPG glycemic variability was positively associated with the risk of all-cause mortality in type 2 diabetes patients.

Prognostic Relevance of Left Ventricular Global Longitudinal Strain in Patients With Heart Failure and Reduced Ejection Fraction

Patients with heart failure (HF) and reduced ejection fraction (HFrEF) are complex patients who often have a high prevalence of co-morbidities and risk factors. In the present study, we investigated the prognostic significance of left ventricular (LV) global longitudinal strain (GLS) along with importantclinical and echocardiographic variables in patients with HFrEF. Patients who had a first echocardiographic diagnosis of LV systolic dysfunction, defined as LV ejection fraction ≤45%, were selected. The study population was subdivided into 2 groups based on a spline curve analysis derived optimal threshold value of LV GLS (≤10%). The primary end point was occurrence of worsening HF, whereas the composite of worsening HF and all-cause death was chosen for the secondary end point. A total of 1,873 patients (mean age 63±12years, 75% men) were analyzed. During a median follow-up of 60months (interquartile range 27 to 60months), 256 patients (14%) experienced worsening HF and the composite end point of worsening HF and all-cause mortality occurred in 573 patients (31%). The 5-year event-free survival rates for the primary and secondary end point were significantly lower in the LV GLS ≤10% group compared with the LV GLS >10% group. After adjustment for important clinical and echocardiographic variables, baseline LV GLS remained independently associated with a higher risk of worsening HF (hazard ratio0.95, 95% confidence interval 0.90 to 0.99, p=0.032) and the composite of worsening HF and all-cause mortality (hazard ratio0.94, 95% confidence interval 0.90 to 0.97, p=0.001). In conclusion, baseline LV GLS is associated with long-term prognosis in patients with HFrEF, independent of various clinical and echocardiographic predictors.

Drinking alcohol in moderation is associated with lower rate of all-cause mortality in individuals with higher rather than lower educational level: findings from the MORGAM project.

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 11.8years (median). In comparison with life-long abstainers, participants drinking 0.1-10g/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 > 20g/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 (≤ 10g/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.

Clinical characteristics and outcomes of infection with human T-lymphotropic virus in a non-endemic area: a single institution study.

Understanding of human T-lymphotropic virus (HTLV) remains largely based on epidemiologic and clinical data from endemic areas. Globalization has resulted in migration of persons living with HTLV (PLHTLV) from endemic to non-endemic areas, and a rise of HTLV infection in the United States. Yet, due to the historical rarity of this disease, affected patients are often under- and mis-diagnosed. Thus, we sought to characterize the epidemiology, clinical features, comorbidities, and survival of HTLV-1- or HTLV-2-positive individuals identified in a non-endemic area. Our study was a single institution, retrospective case-control analysis of HTLV-1 or HTLV-2 patients between 1998 and 2020. We utilized two HTLV-negative controls, matched for age, sex, and ethnicity, for each HTLV-positive case. We evaluated associations between HTLV infection and several hematologic, neurologic, infectious, and rheumatologic covariates. Finally, clinical factors predictive of overall survival (OS) were assessed. We identified 38 cases of HTLV infection, of whom 23 were HTLV-1 and 15 were HTLV-2 positive. The majority (~54%) of patients in our control group received HTLV testing for transplant evaluation, compared to ~24% of HTLV-seropositive patients. Co-morbidities associated with HTLV, hepatitis C seropositivity were higher in HTLV-seropositive patients compared to controls (OR 10.7, 95% CI = 3.2-59.0, p < 0.001). Hepatitis C and HTLV co-infection resulted in decreased OS, compared to no infection, hepatitis C infection alone, or HTLV infection alone. Patients with any cancer diagnosis and HTLV infection had worse OS compared to patients with cancer or HTLV alone. HTLV-1 positive patients had lower median OS compared to HTLV-2 patients (47.7 months vs. 77.4 months). In univariate analysis, the hazard for 1-year all-cause mortality was increased among patients with HTLV-seropositivity, adult T-cell leukemia, acute myelogenous leukemia, and hepatitis C infection. When corrected, multivariate analysis showed that HTLV seropositivity was no longer associated with 1 year all-cause mortality; however association with AML and hepatitis C infection remained significant. HTLV-seropositivity was not associated with increased 1 year mortality in multivariate analysis. However, our study is limited by our small patient sample size, as well as the biased patient control population due to selection factors for HTLV testing.