The FoxO3 gene and cause-specific mortality.
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ABSTRACT:
SUBMITTER: Willcox BJ
PROVIDER: S-EPMC4933667 | biostudies-literature | 2016 Aug
REPOSITORIES: biostudies-literature
Publications
The FoxO3 gene and cause-specific mortality.
Willcox Bradley J BJ Tranah Gregory J GJ Chen Randi R Morris Brian J BJ Masaki Kamal H KH He Qimei Q Willcox D Craig DC Allsopp Richard C RC Moisyadi Stefan S Poon Leonard W LW Rodriguez Beatriz B Newman Anne B AB Harris Tamara B TB Cummings Steven R SR Liu Yongmei Y Parimi Neeta N Evans Daniel S DS Davy Phil P Gerschenson Mariana M Donlon Timothy A TA
Aging cell 20160413 4
The G allele of the FOXO3 single nucleotide polymorphism (SNP) rs2802292 exhibits a consistently replicated genetic association with longevity in multiple populations worldwide. The aims of this study were to quantify the mortality risk for the longevity-associated genotype and to discover the particular cause(s) of death associated with this allele in older Americans of diverse ancestry. It involved a 17-year prospective cohort study of 3584 older American men of Japanese ancestry from the Hono ...[more]
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Project description:BackgroundIncreasing mortality among men from drugs, alcohol and suicides is a growing public health concern in many countries. Collectively known as "deaths of despair", they are seen to stem from unprecedented economic pressures and a breakdown in social support structures.MethodsWe use high-quality population wide Scottish data to calculate directly age-standardized mortality rates for men aged 15-44 between 1980 and 2018 for 15 leading causes of mortality. Absolute and relative inequalities in mortality by cause are calculated using small-area deprivation and the slope and relative indices of inequality (SII and RIIL) for the years 2001-2018.ResultsSince 1980 there have been only small reductions in mortality among men aged 15-44 in Scotland. In that period drug-related deaths have increased from 1.2 (95% CI 0.7-1.4) to 44.9 (95% CI 42.5-47.4) deaths per 100,000 and are now the leading cause of mortality. Between 2001 and 2018 there have been small reductions in absolute but not in relative inequalities in all-cause mortality. However, absolute inequalities in mortality from drugs have doubled from SII = 66.6 (95% CI 61.5-70.9) in 2001-2003 to SII = 120.0 (95% CI 113.3-126.8) in 2016-2018. Drugs are the main contributor to inequalities in mortality, and together with alcohol harm and suicides make up 65% of absolute inequalities in mortality.ConclusionsContrary to the substantial reductions in mortality across all ages in the past decades, deaths among young men are increasing from preventable causes. Attempts to reduce external causes of mortality have focused on a single cause of death and not been effective in reducing mortality or inequalities in mortality from external causes in the long-run. To reduce deaths of despair, action should be taken to address social determinants of health and reduce socioeconomic inequalities.
| S-EPMC7716282 | biostudies-literature
Project description:ImportanceHypochondriasis, also known as health anxiety disorder, is a prevalent, yet underdiagnosed psychiatric disorder characterized by persistent preoccupation about having serious and progressive physical disorders. The risk of mortality among individuals with hypochondriasis is unknown.ObjectiveTo investigate all-cause and cause-specific mortality among a large cohort of individuals with hypochondriasis.Design, setting, and participantsThis Swedish nationwide matched-cohort study included 4129 individuals with a validated International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis of hypochondriasis assigned between January 1, 1997, and December 31, 2020, and 41 290 demographically matched individuals without hypochondriasis. Individuals with diagnoses of dysmorphophobia (body dysmorphic disorder) assigned during the same period were excluded from the cohort. Statistical analyses were conducted between May 5 and September 27, 2023.ExposureValidated ICD-10 diagnoses of hypochondriasis in the National Patient Register.Main outcome and measuresAll-cause and cause-specific mortality in the Cause of Death Register. Covariates included birth year, sex, county of residence, country of birth (Sweden vs abroad), latest recorded education, civil status, family income, and lifetime psychiatric comorbidities. Stratified Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% CIs of all-cause and cause-specific mortality.ResultsOf the 4129 individuals with hypochondriasis (2342 women [56.7%]; median age at first diagnosis, 34.5 years [IQR, 26.3-46.1 years]) and 41 290 demographically matched individuals without hypochondriasis (23 420 women [56.7%]; median age at matching, 34.5 years [IQR, 26.4-46.2 years]) in the study, 268 individuals with hypochondriasis and 1761 individuals without hypochondriasis died during the study period, corresponding to crude mortality rates of 8.5 and 5.5 per 1000 person-years, respectively. In models adjusted for sociodemographic variables, an increased rate of all-cause mortality was observed among individuals with hypochondriasis compared with individuals without hypochondriasis (HR, 1.69; 95% CI, 1.47-1.93). An increased rate was observed for both natural (HR, 1.60; 95% CI, 1.38-1.85) and unnatural (HR, 2.43; 95% CI, 1.61-3.68) causes of death. Most deaths from unnatural causes were attributed to suicide (HR, 4.14; 95% CI, 2.44-7.03). The results were generally robust to additional adjustment for lifetime psychiatric disorders.Conclusions and relevanceThis cohort study suggests that individuals with hypochondriasis have an increased risk of death from both natural and unnatural causes, particularly suicide, compared with individuals from the general population without hypochondriasis. Improved detection and access to evidence-based care should be prioritized.
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Project description:To assess whether women with a history of hypertensive disease of pregnancy have increased risk for early adult mortality.In this retrospective cohort study, women with one or more singleton pregnancies (1939-2012) with birth certificate information in the Utah Population Database were included. Diagnoses were categorized into gestational hypertension; preeclampsia; hemolysis, elevated liver enzymes, and low platelet count syndrome; and eclampsia. Women with more than one pregnancy with hypertensive disease (exposed) were included only once, assigned to the most severe category. Exposed women were matched one to two to unexposed women by age, year of childbirth, and parity at the time of the index pregnancy. The causes of death were ascertained using Utah death certificates and the fact of death was supplemented with the Social Security Death Index. Hazard ratios for cause-specific mortality among exposed women compared with unexposed women were estimated using Cox regressions adjusting for neonatal sex, parental education, preterm delivery, race-ethnicity, and maternal marital status.A total of 60,580 exposed women were matched to 123,140 unexposed women; 4,520 (7.46%) exposed and 6,776 (5.50%) unexposed women had died by 2012. All-cause mortality was significantly higher among women with hypertensive disease of pregnancy (adjusted hazard ratio [HR] 1.65, 95% confidence interval [CI] 1.57-1.73). Exposed women's greatest excess mortality risks were from Alzheimer disease (adjusted HR 3.44, 95% CI 1.00-11.82), diabetes (adjusted HR 2.80, 95% CI 2.20-3.55), ischemic heart disease (adjusted HR 2.23, 95% CI 1.90-2.63), and stroke (adjusted HR 1.88, 95% CI 1.53-2.32).Women with hypertensive disease of pregnancy have increased mortality risk, particularly for Alzheimer disease, diabetes, ischemic heart disease, and stroke.
| S-EPMC4961555 | biostudies-literature
Project description:BACKGROUND: Diabetes is the most common risk factor for end-stage renal disease (ESRD) and has been associated with increased risk of death. In order to better understand the influence of diabetes on outcomes in hemodialysis, we examine the risk of death of diabetic participants in the HEMODIALYSIS (HEMO) study. METHODS: In the HEMO study, 823 (44.6%) participants were classified as diabetic. Using the Schoenfeld residual test, we found that diabetes violated the proportional hazards assumption. Based on this result, we fit two non-proportional hazard models: Cox's time varying covariate model (Cox-TVC) that allows the hazard for diabetes to change linearly with time and Gray's time-varying coefficient model. RESULTS: Using the Cox-TVC, the hazard ratio (HR) for diabetes increased with each year of follow up (p?=?0.02) for all cause mortality. Using Gray's model, the HR for diabetes ranged from 1.41 to 2.21 (p <0.01). The HR for diabetes using Gray's model exhibited a different pattern, being relatively stable at 1.5 for the first 3?years in the study and increasing afterwards. CONCLUSION: Risk of death associated with diabetes in ESRD increases over time and suggests that an increasing risk of death among diabetes may be underappreciated when using conventional survival models.
| S-EPMC3519533 | biostudies-other
Project description:BACKGROUND:Most large, prospective studies of the effects of diabetes on mortality have focused on high-income countries where patients have access to reasonably good medical care and can receive treatments to establish and maintain good glycemic control. In those countries, diabetes less than doubles the rate of death from any cause. Few large, prospective studies have been conducted in middle-income countries where obesity and diabetes have become common and glycemic control may be poor. METHODS:From 1998 through 2004, we recruited approximately 50,000 men and 100,000 women 35 years of age or older into a prospective study in Mexico City, Mexico. We recorded the presence or absence of previously diagnosed diabetes, obtained and stored blood samples, and tracked 12-year disease-specific deaths through January 1, 2014. We accepted diabetes as the underlying cause of death only for deaths that were due to acute diabetic crises. We estimated rate ratios for death among participants who had diabetes at recruitment versus those who did not have diabetes at recruitment; data from participants who had chronic diseases other than diabetes were excluded from the main analysis. RESULTS:At the time of recruitment, obesity was common and the prevalence of diabetes rose steeply with age (3% at 35 to 39 years of age and >20% by 60 years of age). Participants who had diabetes had poor glycemic control (mean [±SD] glycated hemoglobin level, 9.0±2.4%), and the rates of use of other vasoprotective medications were low (e.g., 30% of participants with diabetes were receiving antihypertensive medication at recruitment and 1% were receiving lipid-lowering medication). Previously diagnosed diabetes was associated with rate ratios for death from any cause of 5.4 (95% confidence interval [CI], 5.0 to 6.0) at 35 to 59 years of age, 3.1 (95% CI, 2.9 to 3.3) at 60 to 74 years of age, and 1.9 (95% CI, 1.8 to 2.1) at 75 to 84 years of age. Between 35 and 74 years of age, the excess mortality associated with previously diagnosed diabetes accounted for one third of all deaths; the largest absolute excess risks of death were from renal disease (rate ratio, 20.1; 95% CI, 17.2 to 23.4), cardiac disease (rate ratio, 3.7; 95% CI, 3.2 to 4.2), infection (rate ratio, 4.7; 95% CI, 4.0 to 5.5), acute diabetic crises (8% of all deaths among participants who had previously diagnosed diabetes), and other vascular disease (mainly stroke). Little association was observed between diabetes and mortality from cirrhosis, cancer, or chronic obstructive pulmonary disease. CONCLUSIONS:In this study in Mexico, a middle-income country with high levels of obesity, diabetes was common, glycemic control was poor, and diabetes was associated with a far worse prognosis than that seen in high-income countries; it accounted for at least one third of all deaths between 35 and 74 years of age. (Funded by the Wellcome Trust and others.).
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Project description:This study explores whether there is a short-term relationship between intragenerational social mobility and mortality while individuals are working and whether it is widespread across different causes of death. Net of accumulated advantages and disadvantages, social mobility may influence mortality through health selection or changes in well-being. Men and women working in 1996 up to age 65 are observed annually until 2012 in Swedish register data. Time-varying covariates and origin and destination status are controlled for in discrete time event-history analyses. Results show that when men were upwardly mobile, mortality was lower due to cancer, CVD, IHD, and suicide. Upward mobility was only associated with lower odds of suicide for women. When downwardly mobile, cancer mortality was higher for both men and women and smoking-related cancer mortality was higher for men. Social mobility was not linked to deaths related to accidents and poisoning or alcohol-related mortality. The results may support a relationship between social mobility and mortality characterized by health selection: Only in the case of a chronic illness (cancer) was downward mobility associated with higher mortality. The widespread relationship between upward mobility and lower mortality for men may also indicate positive health selection into attaining a higher class and that individuals with poor health may be less likely to search for better positions or receive promotions.
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Project description:This study aimed to examine differences in all-cause mortality and main causes of death across different migrant and local-born populations living in six European countries. We used data from population and mortality registers from Denmark, England & Wales, France, Netherlands, Scotland, and Spain. We calculated age-standardized mortality rates for men and women aged 0-69 years. Country-specific data were pooled to assess weighted mortality rate ratios (MRRs) using Poisson regression. Analyses were stratified by age group, country of destination, and main cause of death. In six countries combined, all-cause mortality was lower for men and women from East Asia (MRRs 0.66; 95 % confidence interval 0.62-0.71 and 0.76; 0.69-0.82, respectively), and Other Latin America (0.44; 0.42-0.46 and 0.56; 0.54-0.59, respectively) than local-born populations. Mortality rates were similar for those from Turkey. All-cause mortality was higher in men and women from North Africa (1.09; 1.08-1.11 and 1.19; 1.17-1.22, respectively) and Eastern Europe (1.30; 1.27-1.33 and 1.05; 1.01-1.08, respectively), and women from Sub-Saharan Africa (1.34; 1.30-1.38). The pattern differed by age group and country of destination. Most migrants had higher mortality due to infectious diseases and homicide while cancer mortality and suicide were lower. CVD mortality differed by migrant population. To conclude, mortality patterns varied across migrant populations in European countries. Future research should focus both on migrant populations with favourable and less favourable mortality pattern, in order to understand this heterogeneity and to drive policy at the European level.
| S-EPMC4977342 | biostudies-literature
Project description:IMPORTANCE:Previous studies have shown distinct associations between specific dietary fat and cardiovascular disease. However, evidence on specific dietary fat and mortality remains limited and inconsistent. OBJECTIVE:To examine the associations of specific dietary fats with total and cause-specific mortality in 2 large ongoing cohort studies. DESIGN, SETTING, AND PARTICIPANTS:This cohort study investigated 83?349 women from the Nurses' Health Study (July 1, 1980, to June 30, 2012) and 42?884 men from the Health Professionals Follow-up Study (February 1, 1986, to January 31, 2012) who were free of cardiovascular disease, cancer, and types 1 and 2 diabetes at baseline. Dietary fat intake was assessed at baseline and updated every 2 to 4 years. Information on mortality was obtained from systematic searches of the vital records of states and the National Death Index, supplemented by reports from family members or postal authorities. Data were analyzed from September 18, 2014, to March 27, 2016. MAIN OUTCOMES AND MEASURES:Total and cause-specific mortality. RESULTS:During 3?439?954 person-years of follow-up, 33?304 deaths were documented. After adjustment for known and suspected risk factors, dietary total fat compared with total carbohydrates was inversely associated with total mortality (hazard ratio [HR] comparing extreme quintiles, 0.84; 95% CI, 0.81-0.88; P?<?.001 for trend). The HRs of total mortality comparing extreme quintiles of specific dietary fats were 1.08 (95% CI, 1.03-1.14) for saturated fat, 0.81 (95% CI, 0.78-0.84) for polyunsaturated fatty acid (PUFA), 0.89 (95% CI, 0.84-0.94) for monounsaturated fatty acid (MUFA), and 1.13 (95% CI, 1.07-1.18) for trans-fat (P?<?.001 for trend for all). Replacing 5% of energy from saturated fats with equivalent energy from PUFA and MUFA was associated with estimated reductions in total mortality of 27% (HR, 0.73; 95% CI, 0.70-0.77) and 13% (HR, 0.87; 95% CI, 0.82-0.93), respectively. The HR for total mortality comparing extreme quintiles of ?-6 PUFA intake was 0.85 (95% CI, 0.81-0.89; P?<?.001 for trend). Intake of ?-6 PUFA, especially linoleic acid, was inversely associated with mortality owing to most major causes, whereas marine ?-3 PUFA intake was associated with a modestly lower total mortality (HR comparing extreme quintiles, 0.96; 95% CI, 0.93-1.00; P?=?.002 for trend). CONCLUSIONS AND RELEVANCE:Different types of dietary fats have divergent associations with total and cause-specific mortality. These findings support current dietary recommendations to replace saturated fat and trans-fat with unsaturated fats.
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Project description:COVID-19 prematurely ended many lives, particularly among the oldest Americans, but the pandemic also had an indirect effect on health and non-COVID mortality among the working-age population, who suffered the brunt of the economic consequences. This analysis investigates whether monthly excess mortality in the US during 2020 varied by age and cause of death. Based on national-level death counts and population estimates for 1999-2020, negative binomial regression models-fit separately by sex-were used to estimate monthly cause-specific excess mortality by age group during 2020. Among males, 71% non-COVID excess deaths occurred at working ages (25-64), but those ages accounted for only 36% of non-COVID excess deaths in females. The results revealed substantial numbers of excess deaths from external causes (particularly among males), heart disease, diabetes, Alzheimer's disease (particularly among women), and cerebrovascular disease. For males, the largest share of non-COVID excess deaths resulted from external causes, nearly 80% of which occurred at working ages. Although incorrectly classified COVID-19 deaths may explain some excess non-COVID mortality, misclassification is unlikely to explain the increase in external causes of mortality. Auxiliary analyses suggested that drug-related mortality may be driving the rise in external mortality, but drug overdoses were already increasing for a full year prior to the pandemic. The oldest Americans bore the brunt of COVID-19 mortality, but working-age Americans, particularly men, suffered substantial numbers of excess non-COVID deaths, most commonly from external causes and heart disease.
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Project description:Data on the long-term association between low-carbohydrate diets and mortality are sparse.To examine the association of low-carbohydrate diets with mortality during 26 years of follow-up in women and 20 years in men.Prospective cohort study of women and men who were followed from 1980 (women) or 1986 (men) until 2006. Low-carbohydrate diets, either animal-based (emphasizing animal sources of fat and protein) or vegetable-based (emphasizing vegetable sources of fat and protein), were computed from several validated food-frequency questionnaires assessed during follow-up.Nurses' Health Study and Health Professionals' Follow-up Study.85 168 women (aged 34 to 59 years at baseline) and 44 548 men (aged 40 to 75 years at baseline) without heart disease, cancer, or diabetes.Investigators documented 12 555 deaths (2458 cardiovascular-related and 5780 cancer-related) in women and 8678 deaths (2746 cardiovascular-related and 2960 cancer-related) in men.The overall low-carbohydrate score was associated with a modest increase in overall mortality in a pooled analysis (hazard ratio [HR] comparing extreme deciles, 1.12 [95% CI, 1.01 to 1.24]; P for trend = 0.136). The animal low-carbohydrate score was associated with higher all-cause mortality (pooled HR comparing extreme deciles, 1.23 [CI, 1.11 to 1.37]; P for trend = 0.051), cardiovascular mortality (corresponding HR, 1.14 [CI, 1.01 to 1.29]; P for trend = 0.029), and cancer mortality (corresponding HR, 1.28 [CI, 1.02 to 1.60]; P for trend = 0.089). In contrast, a higher vegetable low-carbohydrate score was associated with lower all-cause mortality (HR, 0.80 [CI, 0.75 to 0.85]; P for trend </= 0.001) and cardiovascular mortality (HR, 0.77 [CI, 0.68 to 0.87]; P for trend < 0.001).Diet and lifestyle characteristics were assessed with some degree of error. Sensitivity analyses indicated that results were probably not substantively affected by residual confounding or an unmeasured confounder. Participants were not a representative sample of the U.S. population.A low-carbohydrate diet based on animal sources was associated with higher all-cause mortality in both men and women, whereas a vegetable-based low-carbohydrate diet was associated with lower all-cause and cardiovascular disease mortality rates.National Institutes of Health.
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