Association of dietary selenium intake and all-cause mortality of Parkinson's disease and its interaction with blood cadmium level: a retrospective cohort study.

BACKGROUND: Parkinson's disease (PD) is a slowly progressive neurodegenerating disease that may eventually lead to disabling condition and pose a threat to the health of aging populations. This study aimed to explore the association of two potential risk factors, selenium and cadmium, with the prognosis of Parkinson's disease as well as their interaction effect. METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 to 2015-2016 and National Death Index (NDI). Participants were classified as Parkinson's patients by self-reported anti-Parkinson medications usage. Cox regression models and restricted cubic spline models were applied to evaluate the association between PD mortality and selenium intake level as well as blood cadmium level. Subgroup analysis was also conducted to explore the interaction between them. RESULTS: A total of 184 individuals were included. In full adjusted cox regression model (adjusted for age, gender, race, hypertension, pesticide exposure, smoking status and caffeine intake), compared with participants with low selenium intake, those with normal selenium intake level were significantly associated with less risk of death (95%CI: 0.18-0.76, P = 0.005) while no significant association was found between low selenium intake group and high selenium group (95%CI: 0.16-1.20, P = 0.112). Restricted cubic spline model indicated a nonlinear relationship between selenium intake and PD mortality (P for nonlinearity = 0.050). The association between PD mortality and blood cadmium level was not significant (95%CI: 0.19-5.57, P = 0.112). However, the interaction term of selenium intake and blood cadmium showed significance in the cox model (P for interaction = 0.048). Subgroup analysis showed that the significant protective effect of selenium intake existed in populations with high blood cadmium but not in populations with low blood cadmium. CONCLUSION: Moderate increase of selenium intake had a protective effect on PD mortality especially in high blood cadmium populations.

Causes and attributable fraction of death from ARDS in inflammatory phenotypes of sepsis.

BACKGROUND: Hypoinflammatory and hyperinflammatory phenotypes have been identified in both Acute Respiratory Distress Syndrome (ARDS) and sepsis. Attributable mortality of ARDS in each phenotype of sepsis is yet to be determined. We aimed to estimate the population attributable fraction of death from ARDS (PAFARDS) in hypoinflammatory and hyperinflammatory sepsis, and to determine the primary cause of death within each phenotype. METHODS: We studied 1737 patients with sepsis from two prospective cohorts. Patients were previously assigned to the hyperinflammatory or hypoinflammatory phenotype using latent class analysis. The PAFARDS in patients with sepsis was estimated separately in the hypo and hyperinflammatory phenotypes. Organ dysfunction, severe comorbidities, and withdrawal of life support were abstracted from the medical record in a subset of patients from the EARLI cohort who died (n = 130/179). Primary cause of death was defined as the organ system that most directly contributed to death or withdrawal of life support. RESULTS: The PAFARDS was 19% (95%CI 10,28%) in hypoinflammatory sepsis and, 14% (95%CI 6,20%) in hyperinflammatory sepsis. Cause of death differed between the two phenotypes (p < 0.001). Respiratory failure was the most common cause of death in hypoinflammatory sepsis, whereas circulatory shock was the most common cause in hyperinflammatory sepsis. Death with severe underlying comorbidities was more frequent in hypoinflammatory sepsis (81% vs. 67%, p = 0.004). CONCLUSIONS: The PAFARDS is modest in both phenotypes whereas primary cause of death among patients with sepsis differed substantially by phenotype. This study identifies challenges in powering future clinical trials to detect changes in mortality outcomes among patients with sepsis and ARDS.

Deaths Among Ambulance Patients Released from the Emergency Department Within the First 24 Hours With Nonspecific Diagnoses - Expected or Not?

BACKGROUND: Emergency patients are frequently assigned nonspecific diagnoses. Nonspecific diagnoses describe observations or symptoms and are found in chapters R and Z of the International Classification of Diseases, 10th edition (ICD-10). Patients with such diagnoses have relatively low mortality, but due to patient volume, the absolute number of deaths is substantial. However, information on cause of short-term mortality is limited. OBJECTIVES: To investigate whether death could be expected for ambulance patients brought to the emergency department (ED) after a 1-1-2 call, released with a nonspecific ICD-10 diagnosis within 24 h, and who subsequently died within 30 days. METHODS: Retrospective medical record review of adult 1-1-2 emergency ambulance patients brought to an ED in the North Denmark Region during 2017-2021. Patients were divided into three categories: unexpected death, expected death (terminal illness), and miscellaneous. Charlson Comorbidity Index (CCI) was assessed. RESULTS: We included 492 patients. Mortality was distributed as follows: Unexpected death 59.2% (n = 291), expected death (terminal illness) 25.8% (n = 127), and miscellaneous 15.0% (n = 74). Patients who died unexpectedly were old (median age of 82 years) and had CCI 1-2 (58.1%); 43.0% used at least five daily prescription drugs, and they were severely acutely ill upon arrival (24.7% with red triage, 60.1% died within 24 h). CONCLUSIONS: More than half of ambulance patients released within 24 h from the ED with nonspecific diagnoses, and who subsequently died within 30 days, died unexpectedly. One-fourth died from a pre-existing terminal illness. Patients dying unexpectedly were old, treated with polypharmacy, and often life-threateningly sick at arrival.

Beta blockers are associated with lower all-cause mortality among HFpEF patients.

BACKGROUND: The evidence regarding beta blocker (BB) benefit in heart failure with preserved ejection fraction (HFpEF) remains inconclusive, leading to consideration of BB withdrawal in this population. OBJECTIVES: In this study, we retrospectively analyzed the association of BB on all-cause mortality in HFpEF patients. METHODS: This is a single-center retrospective cohort study of 20,206 patients with left ventricular ejection fraction (EF) ≥ 50% who were hospitalized with decompensated HF between January 2011 and March 2020. Survival is reported at 30 days, 1 year, and 3 years. A secondary analysis comparing mortality for patients on BB with additional indications including hypertension (HTN), coronary artery disease (CAD), and atrial fibrillation (AF) was completed. Mortality was compared between patients on BB and additional therapies of spironolactone or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs). RESULTS: BB showed lower all-cause mortality at 30 days, 1 year, and 3 years (p < 0.0001). This association with lower all-cause mortality was validated by a supplementary propensity score-matched analysis. At 3 years, there was significant mortality reduction with addition of BB to either spironolactone (p = 0.0359) or ACEi/ARBs (p < 0.0001). CONCLUSION: In a large single-center retrospective registry, BB use was associated with lower mortality in HFpEF patients with a recent decompensated HF hospitalization. The mortality benefit persisted in those treated with spironolactone or ACEi/ARBs, and in those with AF. This provocative data further highlights the uncertainty of the benefit of BB use in this cohort and calls for re-consideration of BB withdrawal, especially in those tolerating it well, without conclusive, large, and randomized trials showing lack of benefit or harm.

Five-Year Cumulative Cardiovascular Health and Clinical Events in Patients With Chronic Kidney Disease: The CRIC Study.

BACKGROUND: Higher cardiovascular health (CVH) score is associated with lower risks of cardiovascular disease (CVD) and mortality in the general population. However, it is unclear whether cumulative CVH is associated with CVD, end-stage kidney disease (ESKD), and death in patients with chronic kidney disease. METHODS AND RESULTS: Among individuals from the prospective CRIC (Chronic Renal Insufficiency Cohort) Study, we used the percentage of the maximum possible CVH score attained from baseline to the year 5 visit to calculate cumulative CVH score. Multivariable-adjusted Cox proportional hazards regression was used to investigate the associations of cumulative CVH with risks of adjudicated CVD (myocardial infarction, stroke, and heart failure), ESKD, and all-cause mortality. A total of 3939 participants (mean age, 57.7 years; 54.9% men) were included. The mean (SD) cumulative CVH score attained during 5 years was 55.5% (12.3%). Over a subsequent median 10.2-year follow-up, 597 participants developed CVD, 656 had ESKD, and 1324 died. A higher cumulative CVH score was significantly associated with lower risks of CVD, ESKD, and mortality, independent of the CVH score at year 5. Multivariable-adjusted hazard ratios and 95% CIs per 10% higher cumulative CVH score during 5 years were 0.81 (0.69-0.95) for CVD, 0.82 (0.70-0.97) for ESKD, and 0.80 (0.72-0.89) for mortality. CONCLUSIONS: Among patients with chronic kidney disease stages 2 to 4, a better CVH status maintained throughout 5 years is associated with lower risks of CVD, ESKD, and all-cause mortality. The findings support the need for interventions to maintain ideal CVH status for prevention of adverse outcomes in the population with chronic kidney disease.

Trends in Survival After First Myocardial Infarction in People With Diabetes.

BACKGROUND: The aim of this study was to investigate temporal trends in survival and subsequent cardiovascular events in a nationwide myocardial infarction population with and without diabetes. METHODS AND RESULTS: Between 2006 and 2020, we identified 2527 individuals with type 1 diabetes, 48 321 individuals with type 2 diabetes and 243 170 individuals without diabetes with first myocardial infarction in national health care registries. Outcomes were trends in all-cause death after 30 and 365 days, cardiovascular death and major adverse cardiovascular events (ie, nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, and heart failure hospitalization). Pseudo-observations were used to estimate the mortality risk, with 95% CIs, using linear regression, adjusted for age and sex. Individuals with type 1 diabetes were younger (62±12.2 years) and more often women (43.6%) compared with individuals with type 2 diabetes (75±10.8 years; women, 38.1%), and individuals without diabetes (73±13.2 years; women, 38.4%). Early death decreased in people without diabetes from 23.1% to 17.5%, (annual change -0.48% [95% CI, -0.52% to -0.44%]) and in people with type 2 diabetes from 22.6% to 19.3% (annual change, -0.33% [95% CI, -0.43% to -0.24%]), with no such significant trend in people with type 1 diabetes from 23.8% to 21.7% (annual change, -0.18% [95% CI, -0.53% to 0.17%]). Similar trends were observed with regard to 1-year death, cardiovascular death, and major adverse cardiovascular events. CONCLUSIONS: During the past 15 years, the trend in survival and major adverse cardiovascular events in people with first myocardial infarction without diabetes and with type 2 diabetes have improved significantly. In contrast, a similar improvement was not seen in people with type 1 diabetes.

Mortality Benefits of Cardiac Rehabilitation in Coronary Artery Disease Are Mediated by Comprehensive Risk Factor Modification: A Retrospective Cohort Study.

BACKGROUND: Cardiac rehabilitation (CR) is a multicomponent intervention to reduce adverse outcomes from coronary artery disease, but its mechanisms are not fully understood. The aims of this study were to examine the impact of CR on survival and cardiovascular risk factors, and to determine potential mediators between CR attendance and reduced mortality. METHODS AND RESULTS: A retrospective mediation analysis was conducted among 11 196 patients referred to a 12-week CR program following an acute coronary syndrome event between 2009 and 2019. A panel of cardiovascular risk factors was assessed at a CR intake visit and repeated on CR completion. All-cause and cardiovascular mortality were ascertained via health care administrative data sets at mean 4.2-year follow-up (SD, 2.81 years). CR completion was associated with reduced all-cause (adjusted hazard ratio [HR], 0.67 [95% CI, 0.54-0.83]) and cardiovascular (adjusted HR, 0.57 [95% CI, 0.40-0.81]) mortality, as well as improved cardiorespiratory fitness, lipid profile, body composition, psychological distress, and smoking rates (P<0.001). CR attendance had an indirect effect on all-cause mortality via improved cardiorespiratory fitness (ab=-0.006 [95% CI, -0.008 to -0.003]) and via low-density lipoprotein cholesterol (ab=-0.002 [95% CI, -0.003 to -0.0003]) and had an indirect effect on cardiovascular mortality via cardiorespiratory fitness (ab=-0.007 [95% CI, -0.012 to -0.003]). CONCLUSIONS: Cardiorespiratory fitness and lipid control partly explain the mortality benefits of CR and represent important secondary prevention targets.

Age-specific and cause-specific mortality contributions to the socioeconomic gap in life expectancy in Germany, 2003-21: an ecological study.

BACKGROUND: Earlier death among people in socioeconomically deprived circumstances has been found internationally and for various causes of death, resulting in a considerable life-expectancy gap between socioeconomic groups. We examined how age-specific and cause-specific mortality contributions to the socioeconomic gap in life expectancy have changed at the area level in Germany over time. METHODS: In this ecological study, official German population and cause-of-death statistics provided by the Federal Statistical Office of Germany for the period Jan 1, 2003, to Dec 31, 2021, were linked to district-level data of the German Index of Socioeconomic Deprivation. Life-table and decomposition methods were applied to calculate life expectancy by area-level deprivation quintile and decompose the life-expectancy gap between the most and least deprived quintiles into age-specific and cause-specific mortality contributions. FINDINGS: Over the study period, population numbers varied between 80 million and 83 million people per year, with the number of deaths ranging from 818 000 to 1 024 000, covering the entire German population. Between Jan 1, 2003, and Dec 31, 2019, the gap in life expectancy between the most and least deprived quintiles of districts increased by 0·7 years among females (from 1·1 to 1·8 years) and by 0·1 years among males (from 3·0 to 3·1 years). Thereafter, during the COVID-19 pandemic, the gap increased more rapidly to 2·2 years in females and 3·5 years in males in 2021. Between 2003 and 2021, the causes of death that contributed the most to the life-expectancy gap were cardiovascular diseases and cancer, with declining contributions of cardiovascular disease deaths among those aged 70 years and older and increasing contributions of cancer deaths among those aged 40-74 years over this period. COVID-19 mortality among individuals aged 45 years and older was the strongest contributor to the increase in life-expectancy gap after 2019. INTERPRETATION: To reduce the socioeconomic gap in life expectancy, effective efforts are needed to prevent early deaths from cardiovascular disease and cancer in socioeconomically deprived populations, with cancer prevention and control becoming an increasingly important field of action in this respect. FUNDING: German Cancer Aid and European Research Council.

Predictors of Unfavorable Prognosis in Patients with Heart Failure After Cardioverter-Defibrillator Implantation According to the Prospective Part of the Kuzbass Registry.

AIM: Identification of clinical and instrumental predictors for non-arrhythmic death in patients with heart failure (HF) and implantable cardioverter-defibrillator (ICD). MATERIAL AND METHODS: Through a telephone survey and examination of medical records from hospital and polyclinic databases, data were obtained on the alive/dead status and causes of death for 260 patients with heart failure (HF) and ICD included in the Kuzbass Registry of Patients with ICD. The follow-up period was 1.5 years. Clinical and instrumental parameters entered into the registry before the ICD implantation were included in a univariate and multivariate step-by-step analysis using the logistic (for qualitative variables) and linear (for quantitative variables) regression with calculation of regression coefficients and construction of a prognostic regression model. The quality of the created model was assessed using a ROC analysis. RESULTS: During the observation period, 54 (20.8%) patients died. In 21 (38.8%) patients, death occurred in the hospital and was caused by acute decompensated heart failure in 15 (71.4%) patients, myocardial infarction in 3 (14.3%) patients, stroke in 1 (4.7%) patient, and pneumonia in 2 (9.5%) patients. 33 (61.2%) patients died outside the hospital; the cause of death was stated as the underlying disease associated with acute decompensated heart failure: in 9 (27.2%) patients, dilated cardiomyopathy; in 1 (3.0%) patient, rheumatic mitral disease; and in 23 (69.7%) patients, ischemic cardiomyopathy. According to the univariate regression model, the risk of death in the long-term period was increased by the QT interval prolongation (U 2.41, p = 0.0161); elevated pulmonary artery systolic pressure (U 4.30, p=0.0000) and increased left atrial size according to echocardiography (U 2.98, p=0.0029); stage IIB HF (OR 2.41; 95% CI: 1.26-4.6), NYHA III-IV (OR 3.03; 95% CI: 1.58-5.81); chronic obstructive pulmonary disease (OR 5.24; 95% CI: 2.04-13.45); and lack of optimal drug therapy (ODT) for HF before ICD implantation (OR 2.41; 95% CI: 1.29-4.49). The multivariate analysis identified the most significant factors included in the prognostic regression model: pulmonary artery systolic pressure above 45 mm Hg, social status, chronic obstructive pulmonary disease, and lack of ODT for HF. CONCLUSION: To ensure a maximum benefit from ICD, the factors that increase the likelihood of non-arrhythmic death should be considered before making a decision on ICD implantation. Particular attention should be paid to mandatory ODT for HF as the main modifiable risk factor for unfavorable prognosis.

Salud cardiovascular en España basada en el Life's Essential 8 y su asociación con mortalidad general y cardiovascular: la cohorte ENRICA / Cardiovascular health in Spain based on the Life's Essential 8 and its association with all-cause and cardiovascular mortality: the ENRICA cohort

Introducción y objetivos: La American Heart Association ha desarrollado el índice Life's Essential 8 (LE8) para promover la prevención de la enfermedad cardiovascular (ECV). Este estudio examinó la distribución del LE8 en la población adulta española y su asociación con la mortalidad general y por ECV.MétodosSe analizaron datos de 11.616 personas de edad≥ años (el 50,5% mujeres) del estudio ENRICA, reclutadas en 2008-2010 y seguidas hasta 2020-2022. El LE8 incluye 8 parámetros (dieta, actividad física, exposición a la nicotina, sueño, índice de masa corporal, lípidos y glucosa en sangre y presión arterial) y se puntúa de 0 a 100. La asociación entre LE8 y mortalidad se resumió mediante hazardratio obtenidas de modelos de Cox.ResultadosEl 13,2% de los participantes (del 6,1 al 16,9% según la comunidad autónoma) mostraron mala salud cardiovascular (LE8≤49). Tras una mediana de 12,9 años de seguimiento, ocurrieron 908 muertes totales y, durante una mediana de 11,8 años de seguimiento, 207 muertes por ECV. Tras ajustar por los principales factores de confusión y comparados con el cuartil más bajo (menos saludable) de LE8, los HR (IC 95%) de mortalidad general en el segundo, el tercer y el cuarto cuartil fueron, respectivamente, 0,68 (0,56-0,83), 0,63 (0,51-0,78) y 0,53 (0,39-0,72). Los resultados correspondientes a la mortalidad cardiovascular, considerando riesgos competitivos de muerte, fueron 0,62 (0,39-0,97), 0,55 (0,32-0,93) y 0,38 (0,16-0,89).ConclusionesUna proporción sustancial de los españoles mostraron mala salud cardiovascular. Una mayor puntación de LE8, desde el segundo cuartil, se asocia con menores mortalidad general y cardiovascular. (AU)

Introduction and objectives: The American Heart Association has recently developed the Life's Essential 8 (LE8) score to encourage prevention of cardiovascular disease (CVD). This study assessed the distribution of LE8 in the Spanish adult population and its association with all-cause and CVD death.MethodsWe used data from 11 616 individuals aged 18 years and older (50.5% women) from the ENRICA study, recruited between 2008 and 2010 and followed up until 2020 to 2022. The LE8 score includes 8 metrics (diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids and glucose, and blood pressure) and ranges from 0 to 100. The association of LE8 score with mortality was summarized with hazard ratios (HR), obtained from Cox regression.ResultsIn total, 13.2% of participants (range, 6.1%-16.9% across regions) had low cardiovascular health (LE8≤49). During a median follow-up of 12.9 years, 908 total deaths occurred, and, during a median follow-up of 11.8 years, 207 CVD deaths were ascertained. After adjustment for the main potential confounders and compared with being in the least healthy (lowest) quartile of LE8, the HR (95%CI) of all-cause mortality for the second, third and fourth quartiles were 0.68 (0.56-0.83), 0.63 (0.51-0.78), and 0.53 (0.39-0.72), respectively. The corresponding figures for CVD mortality, after accounting for competing mortality risks, were 0.62 (0.39-0.97), 0.55 (0.32-0.93), and 0.38 (0.16-0.89).ConclusionsA substantial proportion of the Spanish population showed low cardiovascular health. A higher LE8 score, starting from the second quartile, was associated with lower all-cause and CVD mortality. (AU)

[Direct and indirect impact of COVID-19 on life expectancy at birth in Chile in 2020]. / Impacto directo e indirecto del COVID-19 en la esperanza de vida al nacer de Chile en el año 2020.

This article shows the direct and indirect impacts of COVID-19 on life expectancy in Chile in 2020, based on mortality statistics published in March 2023. To this end, a counterfactual mortality was estimated for 2020 without COVID-19; based on the pattern of mortality by cause of death from 1997 to 2019, mortality charts were created to calculate life expectancy from 2015 to 2020 and an estimation for 2020, and the difference between expected and observed life expectancy in 2020 was then separated by age group and cause of death. Life expectancy in 2020 interrupted the upward trend from 2015 to 2019, showing a decline of 1.32 years in men and 0.75 years in women compared to 2019. Compared to the estimated 2020, life expectancy was 1.51 years lower in men and 0.92 years lower in women, but the direct impact of COVID-19 on the decrease in life expectancy was greater (1.89 for men and 1.5 for women) in the 60-84 age group in men and the 60-89 age group in women. The direct negative impact of COVID-19 on life expectancy was partially mitigated by significant positive indirect impacts on two groups of causes of death: diseases of the respiratory system and infectious and parasitic diseases. This study shows the need to differentiate direct and indirect impacts of COVID-19, due to the implications for public health when the intensity of COVID-19 decreases and mobility restrictions are suspended.

El artículo muestra el impacto directo e indirecto del COVID-19 en la esperanza de vida de Chile durante el año 2020, utilizando las estadísticas de defunciones definitivas publicadas en marzo del año 2023. Para ello, se estimó una mortalidad contrafactual para año 2020 sin el COVID-19, siguiendo el patrón de mortalidad según causas de muerte desde 1997 a 2019, se elaboraron tablas de mortalidad para calcular la esperanza de vida para los años 2015 a 2020 y para el año 2020 estimado, y luego se descompuso la diferencia entre la esperanza de vida esperada y observada del año 2020 según grupos de edad y causas de muerte. La esperanza de vida del año 2020 quiebra la tendencia a su aumento entre 2015 y 2019, mostrando un retroceso, en hombres y en mujeres, con respecto al año 2019, de 1,32 y 0,75 años respectivamente. Con respecto al año 2020 estimado, la esperanza de vida del 2020 observado es 1,51 años menor en hombres y 0,92 en mujeres, pero el impacto directo del COVID-19 en pérdida de esperanza de vida fue mayor, 1,89 para los hombres y 1,5 para las mujeres, concentrándose en las edades entre los 60 y 84 años en hombres y entre 60 y 89 años en mujeres. El impacto directo negativo del COVID-19 a la esperanza de vida en parte fue contrarrestado por impactos indirectos positivos significativos en dos grupos de causas de muerte, las enfermedades del sistema respiratorio y las enfermedades infecciosas y parasitarias. El estudio muestra la necesidad de distinguir los impactos directos e indirectos del COVID-19, por la incidencia que pueden tener en la salud pública cuando el COVID-19 baje su intensidad y se eliminen las restricciones de movilidad.

Este artigo apresenta os impactos direto e indireto da COVID-19 na expectativa de vida no Chile em 2020 a partir de estatísticas de mortalidade publicadas em março de 2023. Para tanto, foi estimada uma mortalidade contrafactual para 2020 sem a COVID-19; a partir do padrão de mortalidade por causa de morte de 1997 a 2019, foram criadas tabelas de mortalidade para calcular a expectativa de vida para o período de 2015 a 2020 e para o ano estimado de 2020 e, em seguida, a diferença entre a expectativa de vida esperada e observada em 2020 foi separada por faixa etária e causa de morte. A expectativa de vida em 2020 interrompe a tendência de aumento entre 2015 e 2019, mostrando um declínio com relação a 2019 de 1,32 ano nos homens e 0,75 ano nas mulheres. Com relação ao ano estimado de 2020, a expectativa de vida observada é 1,51 ano menor nos homens e 0,92 nas mulheres, mas o impacto direto da COVID-19 na diminuição da expectativa de vida foi maior (1,89 para homens e 1,5 para mulheres), concentrando-se nas idades entre 60 e 84 anos nos homens e entre 60 e 89 anos nas mulheres. O impacto direto negativo da COVID-19 na expectativa de vida foi parcialmente atenuado por impactos indiretos positivos significativos em dois grupos de causas de morte: doenças do sistema respiratório e doenças infecciosas e parasitárias. Este estudo mostra a necessidade de diferenciar impactos diretos e indiretos da COVID-19, devido às implicações para a saúde pública quando a intensidade da COVID-19 diminuir e as restrições de mobilidade forem suspensas.

Mortality, Hospitalization, and Cardiac Interventions in Patients With Atrial Fibrillation Aged <65 Years.

BACKGROUND: The risk factor (RF) burden, clinical course, and long-term outcome among patients with atrial fibrillation (AF) aged <65 years is unclear. METHODS: Adult (n=67 221; mean age, 72.4±12.3 years; and 45% women) patients with AF evaluated at the University of Pittsburgh Medical Center between January 2010 and December 2019 were studied. Hospital system-wide electronic health records and administrative data were utilized to ascertain RFs, comorbidities, and subsequent hospitalization and cardiac interventions. The association of AF with all-cause mortality among those aged <65 years was analyzed using an internal contemporary cohort of patients without AF (n=918 073). RESULTS: Nearly one-quarter (n=17 335) of the cohort was aged <65 years (32% women) with considerable cardiovascular RFs (current smoker, 16%; mean body mass index, 33.0±8.3; hypertension, 55%; diabetes, 21%; heart failure, 20%; coronary artery disease, 19%; and prior ischemic stroke, 6%) and comorbidity burden (chronic obstructive pulmonary disease, 11%; obstructive sleep apnea, 18%; and chronic kidney disease, 1.3%). Over mean follow-up of >5 years, 2084 (6.7%, <50 years; 13%, 50-65 years) patients died. The proportion of patients with >1 hospitalization for myocardial infarction, heart failure, and stroke was 1.3%, 4.8%, and 1.1% for those aged <50 years and 2.2%, 7.4%, and 1.1% for the 50- to 65-year subgroup, respectively. Multiple cardiac and noncardiac RFs were associated with increased mortality in younger patients with AF with heart failure and hypertension demonstrating significant age-related interaction (P=0.007 and P=0.013, respectively). Patients with AF aged <65 years experienced significantly worse survival compared with comorbidity-adjusted patients without AF (men aged <50 years and hazard ratio, 1.5 [95% CI, 1.24-1.79]; 50-65 years and hazard ratio, 1.3 [95% CI, 1.26-1.43]; women aged <50 years and hazard ratio, 2.4 [95% CI, 1.82-3.16]; 50-65 years and hazard ratio, 1.7 [95% CI, 1.6-1.92]). CONCLUSIONS: Patients with AF aged <65 years have significant comorbidity burden and considerable long-term mortality. They are also at a significantly increased risk of hospitalization for heart failure, stroke, and myocardial infarction. These patients warrant an aggressive focus on RF and comorbidity evaluation and management.

[Mortality trends in Germany in an international context]. / Sterblichkeitsentwicklung in Deutschland im internationalen Kontext.

BACKGROUND AND AIM: Due to its strong economy and a well-developed healthcare system, Germany is well positioned to achieve above-average reductions in mortality. Nevertheless, in terms of life expectancy, Germany is increasingly falling behind Western Europe. We compare mortality trends in Germany with other Western European countries, covering the period from 1960 to 2019. The focus is on long-term trends in Germany's ranking in international mortality trends. In addition, we conduct a detailed mortality analysis by age. METHODS: Our analysis is mostly based on mortality data from the Human Mortality Database (HMD). Cause-specific mortality data originate from the database of the World Health Organization (WHO). For the international comparison of mortality trends, we use conventional mortality indicators (age-standardized mortality rate, period life expectancy). RESULTS: Compared to other Western European countries, Germany has higher mortality in the middle and older age groups. Germany's life expectancy gap compared to Western Europe has grown during the past 20 years. In 2000, Germany was 0.73 years behind for men and 0.74 years behind for women. By 2019, these figures had risen to 1.43 and 1.34 years, respectively. This is mainly due to mortality from non-communicable diseases. CONCLUSION: For Germany to catch up with other Western European countries, a stronger focus on further reducing mortality at ages 50+ is crucial. This also requires further research to understand the factors behind Germany's disadvantageous position.

Association of platelet distribution width with all-cause and cause-specific mortality in US adults.

BACKGROUND: Platelet distribution width (PDW) indicates heterogeneity in circulating platelet sizes. Studies reporting PDW association with mortality were limited by small sample sizes. Therefore, we examined the relationship between PDW and all-cause and cause-specific mortality in a large representative cohort. METHODS: The NHANES III data were linked to mortality files to examine the association between PDW and mortality. We excluded participants <18 years old and had a history of myocardial infarction. Since the hazards violated the proportionality assumption, we used piece-wise spline with 5-year time intervals in Cox models without and with adjustment for age, gender, race, smoking history, diabetes mellitus, hypertension, eGFR and total cholesterol. RESULTS: Of 15,688 participants, 53.2% were females, 36.2% had a history of hypertension, and 6368(40.6%) died during follow-up (range 0 to 31 years). The mean (SD) age of the participants was 47(20) years, platelet count was 275.0(71.7) 109/L, and PDW 16.5(0.5). In multivariable analyses, PDW was associated with all-cause mortality at 0-5 years (HR = 1.44; 95%CI = 1.21, 1.72; P < 0.001) and at 5-10 years (HR = 1.23; 95%CI =1.03, 1.46; P = 0.02). Similarly, PDW association was significant for the first 0-5 years in cardiovascular mortality (HR = 1.58, 95%CI = 1.10, 2.25; P = 0.013) and for cancer mortality (HR = 1.48 (1.15, 95%CI = 1.15, 1.91, P = 0.003). For other-cause mortality, PDW remained significantly associated for 0-5 years (HR = 1.35, 95%CI =1.05, 1.74; P = 0.02) and for 5-10 years (HR = 1.38, 95%CI = 1.05, 1.83; P = 0.023). CONCLUSIONS: PDW is an independent, but time-dependent, predictor of all-cause, cardiovascular, cancer and other-cause mortality up to 5 years. The mechanisms underlying this association need further study.

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021.

BACKGROUND: Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS: The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION: Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING: Bill & Melinda Gates Foundation.

The impact of triglyceride glucose-body mass index on all-cause and cardiovascular mortality in elderly patients with diabetes mellitus: evidence from NHANES 2007-2016.

BACKGROUND: The relationship between triglyceride glucose-body mass index (TyG-BMI) index and mortality in elderly patients with diabetes mellitus (DM) are still unclear. This study aimed to investigate the association between TyG-BMI with all-cause and cardiovascular mortality among elderly DM patients in the United States (US). METHODS: Patients aged over 60 years with DM from the National Health and Nutrition Examination Survey (2007-2016) were included in this study. The study endpoints were all-cause and cardiovascular mortality and the morality data were extracted from the National Death Index (NDI) which records up to December 31, 2019. Multivariate Cox proportional hazards regression model was used to explore the association between TyG-BMI index with mortality. Restricted cubic spline was used to model nonlinear relationships. RESULTS: A total of 1363 elderly diabetic patients were included, and were categorized into four quartiles. The mean age was 70.0 ± 6.8 years, and 48.6% of them were female. Overall, there were 429 all-cause deaths and 123 cardiovascular deaths were recorded during a median follow-up of 77.3 months. Multivariate Cox regression analyses indicated that compared to the 1st quartile (used as the reference), the 3rd quartile demonstrated a significant association with all-cause mortality (model 2: HR = 0.64, 95% CI 0.46-0.89, P = 0.009; model 3: HR = 0.65, 95% CI 0.43-0.96, P = 0.030). Additionally, the 4th quartile was significantly associated with cardiovascular mortality (model 2: HR = 1.83, 95% CI 1.01-3.30, P = 0.047; model 3: HR = 2.45, 95% CI 1.07-5.57, P = 0.033). The restricted cubic spline revealed a U-shaped association between TyG-BMI index with all-cause mortality and a linear association with cardiovascular mortality, after adjustment for possible confounding factors. CONCLUSIONS: A U-shaped association was observed between the TyG-BMI index with all-cause mortality and a linear association was observed between the TyG-BMI index with cardiovascular mortality in elderly patients with DM in the US population.

Heart Failure-Related Death in Subjects With Atrial Fibrillation in the United States, 1999 to 2020.

BACKGROUND: Population-based data on heart failure (HF)-related death in patients with atrial fibrillation (AF) are lacking. We assessed HF-related death in people with AF in the United States over the past 21 years and examined differences by age, sex, race, ethnicity, urbanization, and census region. METHODS AND RESULTS: Data were extracted from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research to determine trends in age-adjusted mortality rates per 100 000 people, due to HF-related death among subjects with AF aged ≥15 years. To calculate nationwide annual trends, we assessed the average annual percent change (AAPC) and annual percent change with relative 95% CIs using joinpoint regression. Between 1999 and 2020, 916 685 HF-related deaths (396 205 men and 520 480 women) occurred among US adults having a concomitant AF. The overall age-adjusted mortality rates increased (AAPC: +4.1% [95% CI, 3.8-4.4]; P<0.001), especially after 2011 (annual percent change, +6.8% [95% CI, 6.2-7.4]; P<0.001) in men (AAPC, +4.8% [95% CI, 4.4-5.1]; P<0.001), in White subjects (AAPC: +4.2% [95% CI, 3.9 to 4.6]; P<0.001) and in subjects aged <65 years (AAPC: +7.5% [95% CI, 6.7-8.4]; P<0.001). The higher percentage of deaths were registered in the South (32.8%). During the first year of the COVID-19 pandemic, a significant excess in HF-related deaths among patients with AF aged >65 years was observed. CONCLUSIONS: A worrying increase in the HF-related mortality rate among patients with AF has been observed in the United States over the past 2 decades.

Predictors of heart failure readmission and all-cause mortality in patients with acute heart failure.

BACKGROUND: Predischarge risk stratification of patients with acute heart failure (AHF) could facilitate tailored treatment and follow-up, however, simple scores to predict short-term risk for HF readmission or death are lacking. METHODS: We sought to develop a congestion-focused risk score using data from a prospective, two-center observational study in adults hospitalized for AHF. Laboratory data were collected on admission. Patients underwent physical examination, 4-zone, and in a subset 8-zone, lung ultrasound (LUS), and echocardiography at baseline. A second LUS was performed before discharge in a subset of patients. The primary endpoint was the composite of HF hospitalization or all-cause death. RESULTS: Among 350 patients (median age 75 years, 43% women), 88 participants (25%) were hospitalized or died within 90 days after discharge. A stepwise Cox regression model selected four significant independent predictors of the composite outcome, and each was assigned points proportional to its regression coefficient: NT-proBNP ≥2000 pg/mL (admission) (3 points), systolic blood pressure < 120 mmHg (baseline) (2 points), left atrial volume index ≥60 mL/m2 (baseline) (1 point) and ≥ 9 B-lines on predischarge 4-zone LUS (3 points). This risk score provided adequate risk discrimination for the composite outcome (HR 1.48 per 1 point increase, 95% confidence interval: 1.32-1.67, p < 0.001, C-statistic: 0.70). In a subset of patients with 8-zone LUS data (n = 176), results were similar (C-statistic: 0.72). CONCLUSIONS: A four-variable risk score integrating clinical, laboratory and ultrasound data may provide a simple approach for risk discrimination for 90-day adverse outcomes in patients with AHF if validated in future investigations.

Mortality trend of ischemic heart disease (2008-2022): A retrospective analysis of epidemiological data.

BACKGROUND: Age-sex specific trend analyses of ischemic heart disease (IHD)-related mortality and prevalent risk factors can improve our understanding and approach to the disease. METHODS: We performed a 15-year retrospective epidemiological analysis of acute and chronic IHD-related mortality and prevalent cardiovascular risk factors using administrative data from Veneto, a socio-economically homogeneous Italian region. Standard mortality statistics using the underlying cause of death (UCOD) and deaths with any mention of IHD in death certificates (MCOD) from ICD-10 codes I20-I25 was performed between 2008 and 2022. RESULTS: A total of 134,327 death certificates reported IHD-related deaths, representing 18.6% of all deaths. Proportional mortality decreased from 14.6% in 2008 to 7.8% in 2022 for deaths with IHD as the UCOD and from 23.5% to 14.6% for deaths with IHD among the MCOD. A more pronounced decline of proportionate and case-specific mortality rate was seen in women. The decline in mortality over the whole study period was larger for acute (vs. chronic) IHD. The COVID-19 pandemic led to a marked increase in mortality in 2020 (+12.2%) with a subsequent further decline. IHD-related deaths displayed a typical seasonal pattern with more deaths during winter. The prevalence of cardiovascular risk factors was higher in IHD (vs. no IHD) deaths: this association appeared more pronounced in younger adults. CONCLUSIONS: We provided an analysis of epidemiological trends in IHD-related mortality and prevalence of risk factors. Our findings indicate a change in the pattern of cardiovascular deaths and may suggest a switch in death from acute to chronic conditions.

Risk of death, thrombotic and hemorrhagic events in anticoagulated patients with atrial fibrillation and systemic autoimmune diseases: an analysis from a global federated dataset.

BACKGROUND: Growing evidence showing that systemic autoimmune diseases (SADs) are associated with a high risk of atrial fibrillation (AF). However, the impact of SAD on the clinical course of AF patients is largely unknown. METHODS: Retrospective cohort study within a federated healthcare network (TriNetX). Using ICD codes, AF patients on anticoagulant therapy were categorized according to the presence of SAD (M32: Systemic Lupus Erythematosus (SLE); M33: Dermato-polymyositis (DMP); M34: Systemic Sclerosis (SSc); M35: Sjogren syndrome). The primary outcomes were the 5-year risks of (1) all-cause death, (2) thrombotic events (ischemic stroke, acute myocardial infarction, deep vein thrombosis, and pulmonary embolism), and (3) bleeding (intracranial (ICH) and gastrointestinal (GI)). Secondary outcomes were each component of the primary outcomes. Cox regression analysis after propensity score matching (PSM) was used to estimate hazard ratio (HR) and 95% confidence interval (95%CI). RESULTS: We identified 16,098 AF patients with SAD (68.2 ± 13.4 years; 71.0% female) and 828,772 AF controls (70.7 ± 12.9 years, 41.1% females). After PSM, AF patients with SAD were associated with a higher risk of all-cause death (HR 1.13, 95%CI 1.09-1.71), thrombotic events (HR 1.37, 95%CI 1.32-1.43), and hemorrhagic events (HR 1.41, 95%CI 1.33-1.50) compared to AF controls without SAD. The highest risk of all-cause death and GI bleeding was associated with SSc, while the highest risk of thrombotic events and ICH was associated with SLE. CONCLUSION: AF patients with SAD are associated with a high risk of all-cause death, thrombotic, and hemorrhagic events. These patients merit careful follow-up and integrated care management to improve their prognosis.