Age, growth and size interact with stress to determine life span and mortality

Individuals in a large experimental field population, of the short-lived perennial species Plantago lanceolata, were followed to determine the sources of variation that influence mortality and life span. The design included multiple age groups with initially similar genetic structure, which made it possible to separate age effects from period effects and to identify the genetic component to variation in life span. During a period of stress, individuals of all ages showed parallel increases in mortality but different cohorts experienced this period of high mortality at different ages. This then influenced the distribution of life spans across cohorts. Age and size-age interactions influenced mortality during the period of stress. Smaller individuals died but only if they were old. Additionally, growth and age interacted with stress such that older individuals had negative growth and high mortality whereas younger individuals had positive growth and relatively lower mortality during stress. The results of this study show that it is not simply the environment that can have a major impact on demography in natural populations; rather, age, size and growth can interact with the environment to influence mortality and life span when the environment is stressful.     

Trends in alcohol-related mortality in Sweden 1969-2002: an age-period-cohort analysis

AIM: To study the effects of age, period and cohorts on alcohol-related mortality trends in Sweden. DESIGN: The study comprises an age-period-cohort analysis. SETTING AND PARTICIPANTS: The analysis was based on all deaths in the Swedish population between 1969 and 2002. MEASUREMENTS: Data on alcohol-related deaths in Sweden from 1969 to 2002 excluding accidental injury and homicide were used. The analysis covered 43 021 deaths. FINDINGS: Time period and birth cohort both influenced alcohol-related mortality. Male cohorts born in the 1930-40s exhibited the highest alcohol-related mortality, while for females those born in the 1940-50s had the highest alcohol-related mortality. For both men and women, those born in the 1960-70s had the lowest age-adjusted alcohol-related mortality. High-risk cohorts were young or in early adulthood during the periods that alcohol became more available in Sweden. The low-risk cohorts of the 1960-70s were brought up during a period when society was concerned with increasing alcohol problems and more emphasis was placed on issuing alcohol awareness information in schools. CONCLUSIONS: Cohort effects were found suggesting that the link between alcohol consumption and non-accident alcohol-related mortality at the population level is dependent on other factors that may change over time. One such factor may be that restrictive alcohol policies have a greater effect on drinking in those who are younger at the time they are put into effect.     

Slowing of age-specific mortality rates in Drosophila melanogaster

We have studied age-dependent mortality in large cohorts of male and female D. melanogaster from four inbred lines. Average longevity varies substantially between genotypes (broad-sense heritability = 22%). Contrary to the predictions of the Gompertz model, mortality rates tend to decelerate at the most advanced ages. Fitting Gompertz, Weibull, Logistic, and Two-stage Gompertz mortality models to the data, we find that the best fit is obtained with the two-stage model, with exponentially increasing mortality at early ages, and zero or nearly zero increase at older ages. There is little microenvironmental effect from cage to cage. There is a sex-dependent mortality crossover: males and females differ in initial mortality rate and degree of acceleration of mortality rate, but the ordering of the sexes according to mortality parameters depends on genotype. Model fitting can be affected by gaps between deaths in the tail of the survivorship distribution. The observations are inconsistent with the limited life-span paradigm, which predicts sudden and well-defined drops in survivorship and corresponding sharp increases in mortality at advanced ages for large cohorts of genetically identical individuals.     

Adult height and risk of death from all-cause,cardiovascular, and cancer-specific disease: The Rural Chinese Cohort Study

Background and aimsWe aimed to evaluate the sex-specific association of height and all-cause and cause-specific mortality in rural Chinese adults.Methods and resultsA total of 17,263 participants (10,448 women) ≥18 years old were randomly enrolled during 2007–2008 and followed up during 2013–2014. Sex-specific hazard ratios (HRs) for the height–mortality association, assessed in quintiles or 5 cm increments, were calculated by Cox proportional-hazards models. For both men and women, tall participants showed a baseline prevalence of high levels of socioeconomic factors including income and education but low systolic blood pressure and total cholesterol level. During a median of 6.01 years of follow-up, 620 men (in 39,993.45 person-years) and 490 women (in 61,590.10 person-years) died. With increasing height, the risk of all-cause mortality decreased in a curvilinear trend after adjustment for baseline age, socioeconomic and behavioral factors, and anthropometric and laboratory measurements. For men, height was inversely associated with all-cause mortality (HR per 5 cm increase: 0.89, 95% CI: 0.83–0.96) and cardiovascular mortality (HR per 5 cm increase: 0.81, 95% CI: 0.72–0.91). For women, height was inversely associated with all-cause mortality (HR per 5 cm increase: 0.88, 95% CI: 0.81–0.96) and other mortality (HR per 5 cm increase: 0.82, 95% CI: 0.71–0.96).ConclusionsOur study demonstrated a sex-specific inverse effect of height on mortality from different major causes in rural Chinese adults.     

Cause of death in individuals with chronic HBV and/or HCV infection, a nationwide community-based register study

Summary.  Studies on chronic viral hepatitis and mortality have often been made on selected populations or in high-endemic countries. The aim of this study was to investigate the causes of death and the mortality rates in the nationwide cohorts of people chronically infected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) in Sweden, a low-endemic country. All notifications on chronic HBV infection and HCV infection 1990–2003 were linked to the Cause of Death Register. A total of 9517 people with chronic HBV infection, 34 235 people with HCV infection and 1601 with chronic HBV–HCV co-infection were included, and the mean observation times were 6.4, 6.3 and 7.9 years, respectively. The mortality in the cohorts was compared with age- and gender-specific mortality in the general population and standardized mortality ratios (SMR) were calculated. All-cause mortality was significantly increased, SMR 2.3 (HBV), 5.8 (HCV) and 8.5 (HBV–HCV), with a great excess liver-related mortality in all cohorts, SMR 21.7, 35.5 and 46.2, respectively. In HCV and HBV–HCV infected there was an increased mortality due to drug-related psychiatric diagnoses (SMR: 20.7 and 27.6) and external causes (SMR: 12.4 and 11.4), predominantly at younger age. To conclude, this study demonstrated an increased all-cause mortality, with a great excess mortality from liver disease, in all cohorts. In people with HCV infection the highest excess mortality in younger ages was from drug-related and external reasons.     

Mortality in rheumatoid arthritis: have we made an impact in 4 decades?

OBJECTIVE: To evaluate trends in survival among patients with rheumatoid arthritis (RA) over the past 4 decades. METHODS: Three population based prevalence cohorts of all Rochester, Minnesota, residents age > or =35 years with RA (1987 American College of Rheumatology criteria) on January 1, 1965, January 1, 1975, and January 1, 1985; and an incidence cohort of all new cases of RA occurring in the same population between January 1, 1955 and January 1, 1985, were followed longitudinally through their entire medical records (including all inpatient and outpatient care by any provider) until death or migration from the county. Mortality was described using the Kaplan-Meier method and the influence of age, sex, rheumatoid factor (RF) positivity, and comorbidity (using the Charlson Comorbidity Index) on mortality was analyzed using Cox proportional hazards models. RESULTS: Mortality was statistically significantly worse than expected for each of the cohorts (overall p<0.0001). A trend toward increased mortality in the 1975 and 1985 prevalence cohorts compared to the 1965 prevalence cohort was present, even after adjusting for significant predictors of mortality (age, RF positivity, and comorbidity). Survival for the general population of Rochester residents of similar age and sex improved in 1975 compared to 1965, and in 1985 compared to 1975. CONCLUSION: The excess mortality associated with RA has not changed in 4 decades. Moreover, people with RA have not enjoyed the same improvements in survival experienced by their non-RA peers. More attention should be paid to mortality as an outcome measure in RA.     

Changes in clinical characteristics, course, and prognosis of inflammatory bowel disease during the last 5 decades: a population-based study from Copenhagen, Denmark

BACKGROUND: It remains uncertain whether the increasing incidence of inflammatory bowel disease (IBD) during the last decades has been accompanied by an alteration in the presentation, course, and prognosis of the disease. To answer this question, 3 consecutive population-based IBD cohorts from Copenhagen, Denmark (1962-2005), were assessed and evaluated. METHODS: Phenotype, initial disease course, use of medications, cumulative surgery rate, standardized incidence ratio of colorectal cancer (CRC), and standardized mortality ratio (SMR) were compared in the 3 cohorts, which had a total of 641 patients with Crohn's disease (CD) and 1575 patients with ulcerative colitis (UC). RESULTS: From 1962 to 2005, the proportion of IBD patients suffering from CD increased (P < 0.001), time from onset of symptoms to diagnosis of CD decreased (P = 0.001), and median age at diagnosis of UC increased (P < 0.01). The prevalence of upper gastrointestinal involvement and pure colonic CD varied significantly between cohorts. UC patients diagnosed in the 1990s had a higher prevalence of proctitis, received more medications, and had a milder initial disease course than did previous patients. The surgery rate decreased significantly in CD but not in UC. The risk of CRC in IBD was close to expected over the entire period, whereas the mortality of patients with CD increased (overall SMR, 1.31; 95% CI, 1.07-1.60). CONCLUSIONS: Despite variations in the presentation and initial course of IBD during the last 5 decades, its long-term prognosis remained fairly stable. Treatment of IBD changed recently, and future studies should address the effect of these changes on long-term prognosis.     

Cardiovascular risk factors and obesity: are baseline levels of blood pressure, glucose, cholesterol and uric acid elevated prior to weight gain?

The increased risk of cardiovascular morbidity and mortality experienced by the obese may be partially mediated through alterations induced in other associated risk factors. The attribution of this cardiovascular risk to obesity presumes that levels of those risk factors are not elevated independently of, or prior to, weight gain. We therefore examined baseline levels of blood pressure, glucose, cholesterol, and uric acid within age and sex specific strata of a population of 4015 individuals followed an average of 15 years to determine if an increasing level of fatness (weight/height 2) at follow-up was associated with elevation of other risk factors at baseline. After controlling for baseline fatness we were unable to demonstrate any consistent relationship between future fatness and baseline elevation of any of the factors. The magnitude of the partial correlation coefficients for those age 6-24 or 25-65 years at baseline were less than 0.11 for all of the risk factors. While a metabolic predisposition may link obesity to alterations of other risk factors it appears unlikely that their elevation commonly precedes weight gain. A pre-existing elevation of risk factors has not resulted in the misattribution of cardiovascular risk to obesity.     

Siblings of Okinawan centenarians share lifelong mortality advantages

Okinawa, an isolated island prefecture of Japan, has among the highest prevalence of exceptionally long-lived individuals in the world; therefore, we hypothesized that, within this population, genes that confer a familial survival advantage might have clustered. We analyzed the pedigrees of 348 centenarian families with 1142 siblings and compared sibling survival with that of the 1890 Okinawan general population cohort. Both male and female centenarian siblings experienced approximately half the mortality of their birth cohort-matched counterparts. This mortality advantage was sustained and did not diminish with age in contrast to many environmentally based mortality gradients, such as education and income. Cumulative survival advantages for this centenarian sibling cohort increased over the life span such that female centenarian siblings had a 2.58-fold likelihood, and male siblings a 5.43-fold likelihood, versus their birth cohorts, of reaching the age of 90 years. These data support a significant familial component to exceptional human longevity.     

Epidemiology of cardiovascular disease in systemic lupus erythematosus

Awareness of the impact of cardiovascular disease on the late morbidity and mortality in patients with Systemic Lupus Erythematosus (SLE) is increasing. Clinical events secondary to accelerated atherosclerosis have been documented in lupus cohorts across the globe. We review the history and epidemiology of cardiovascular disease in patients with SLE.     

Cohort change in images of older adults, 1974-1981.

This study examines images of older people held by adults of all ages at two points in time. The two surveys, 7 years apart (1974 and 1981), permit the examination of cohort changes in such perceptions over time. Multivariate analysis indicated that social class and health status evaluations of older adults declined between the two surveys, principally because of the assessments by more recent cohorts. With regard to media portrayals of older adults, more recent cohorts felt that the media portrayals of older adults were distorted by presenting a more positive picture than what older people actually experienced.     

Cohort Size and Maximum Likelihood Estimation of Mortality Parameters

The purpose of this study was to investigate the effects of cohort size on maximum likelihood estimates of mortality parameters. Recent experimental investigations have stressed the importance of large cohorts for detecting leveling off of mortality rates at older ages. In the present study, emphasis was placed on evaluation of relatively small cohorts (about 150–300 individuals). Deaths were simulated under the assumption of the frailty mortality model. Two different parameter sets that resulted in differences in mean life span of more than twofold were used for simulations. Our smallest cohorts yielded parameter estimates that had generally good statistical properties, but relatively large standard errors. For tests of hypotheses concerning equality of parameters among populations or experimental treatments, empirical standard errors (obtained from several cohorts) were preferable to asymptotic standard errors (obtained for single cohorts). In particular, empirical standard errors yielded reliable type I error rates.     

Development and validation of a real-time mortality risk calculator before,during and after hepatectomy: an analysis of the ACS NSQIP database

BackgroundAlthough most conventional risk prediction models have been based on preoperative information, intra- and post-operative events may be more relevant to mortality after surgery. We sought to develop a mortality risk calculator based on real time characteristics associated with hepatectomy.MethodsPatients who underwent hepatectomy between 2014 and 2017 were identified in the ACS-NSQIP dataset. Three prediction models (pre-, intra-, post-operative) were developed and validated using perioperative data.ResultsAmong 14,720 patients, 197 (1.3%) experienced 30-day mortality. The predictive ability of the real-time mortality risk calculator was very good based on only preoperative factors (AUC; training cohort: 0.813, validation cohort: 0.731). Incorporating intra-operative variables into the model increased the AUC (training: 0.838, validation: 0.777), while the post-operative model achieved an AUC of 0.922 in the training and 0.885 in the validation cohorts, respectively. While patients with low preoperative risk had only very small fluctuations in the estimated 30-day mortality risk during the intraoperative (Δ0.4%) and postoperative (Δ0.6%) phases, patients who were already deemed high risk preoperatively had additional increased mortality risk based on factors that occurred in the intraoperative (Δ5.4%) and postoperative (Δ9.3%) periods.ConclusionA real-time mortality risk calculator may better help clinicians identify patients at risk of death at the different stages of the surgical episode.     

Height, health, and development

Adult height is determined by genetic potential and by net nutrition, the balance between food intake and the demands on it, including the demands of disease, most importantly during early childhood. Historians have made effective use of recorded heights to indicate living standards, in both health and income, for periods where there are few other data. Understanding the determinants of height is also important for understanding health; taller people earn more on average, do better on cognitive tests, and live longer. This paper investigates the environmental determinants of height across 43 developing countries. Unlike in rich countries, where adult height is well predicted by mortality in infancy, there is no consistent relationship across and within countries between adult height on the one hand and childhood mortality or living conditions on the other. In particular, adult African women are taller than is warranted by their low incomes and high childhood mortality, not to mention their mothers' educational level and reported nutrition. High childhood mortality in Africa is associated with taller adults, which suggests that mortality selection dominates scarring, the opposite of what is found in the rest of the world. The relationship between population heights and income is inconsistent and unreliable, as is the relationship between income and health more generally.     

Diabetes, prediabetes and cancer mortality

Aims/hypothesis

We aimed to investigate the risk of cancer mortality in relation to the glucose tolerance status classified according to the 2 h OGTT.

Methods

Data from 17 European population-based or occupational cohorts involved in the DECODE study comprising 26,460 men and 18,195 women aged 25–90 years were collaboratively analysed. The cohorts were recruited between 1966 and 2004 and followed for 5.9 to 36.8 years. Cox proportional hazards analysis with adjustment for cohort, age, BMI, total cholesterol, blood pressure and smoking status was used to estimate HRs for cancer mortality.

Results

Compared with people in the normal glucose category, multivariable adjusted HRs (95% CI) for cancer mortality were 1.13 (1.00, 1.28), 1.27 (1.02, 1.57) and 1.71 (1.35, 2.17) in men with prediabetes, previously undiagnosed diabetes and known diabetes, respectively; in women they were 1.11 (0.94, 1.30), 1.31 (1.00, 1.70) and 1.43 (1.01, 2.02), respectively. Significant increases in deaths from cancer of the stomach, colon–rectum and liver in men with prediabetes and diabetes, and deaths from cancers of the liver and pancreas in women with diabetes were also observed. In individuals without known diabetes, the HR (95% CI) for cancer mortality corresponding to a one standard deviation increase in fasting plasma glucose was 1.06 (1.02, 1.09) and in 2 h plasma glucose was 1.07 (1.03, 1.11).

Conclusions/interpretation

Diabetes and prediabetes were associated with an increased risk of cancer death, particularly death from liver cancer. Mortality from all cancers rose linearly with increasing glucose concentrations.     

Physical Activity, Weight Loss, and Cardiac Rehabilitation to Reduce Recurrent Cardiovascular Events

Contemporary studies now suggest that multifactorial risk factor modification—especially smoking cessation, more intensive dietary modifications, pharmacotherapies to control hyperlipidemia, antihypertensive regimens, weight reduction, and regular moderate-to-vigorous physical activity—may reduce the risk of recurrent cardiovascular events. Although better outcomes for cardiovascular and all-cause mortality have been reported in some overweight and moderately obese cohorts of patients with cardiovascular disease (the “obesity paradox”), numerous reports now support purposeful weight reduction in this escalating patient population. Moreover, cardiorespiratory fitness is one of the strongest prognostic indicators in persons with coronary disease, irrespective of traditional risk factors, body habitus, and left ventricular function. Accordingly, sedentary patients should be counseled to become more physically active and/or fit by starting an exercise program, increasing lifestyle activity, or both. Despite the effectiveness and safety of cardiac rehabilitation, these services remain vastly underutilized. Cardiac rehabilitation has been shown to markedly improve the cardiovascular risk factor profile and is associated with significant reductions in all-cause and cardiac mortality.     

Cohort analysis of retirement preparation, 1974-1981

Extending Easterlin's (1987) thesis regarding cohort size and personal welfare, this study was designed to examine cohort differences and changes in preparation for retirement. The data on which the study is based came from two cross-sectional surveys commissioned by the National Council on the Aging and conducted in 1974 and 1981. Major research questions included: (a) Which cohorts are most active in taking steps to prepare for retirement? and (b) Did Americans increase their retirement preparation activities during the time period studied? Results indicate that retirement preparation is influenced by cohort effects, especially among the more recent cohorts, and that earlier cohorts generally prepare more. Most respondents, especially the earlier cohorts, experienced a decrease in retirement preparation between 1974 and 1981 (i.e., a period effect). Analysis of the separate indicators of a retirement preparation index show that most activities, for instance, savings, decreased during this time while others either increased (will preparation) or remained stable (home ownership). The findings suggest that retirement preparation is influenced by economic climate and provide partial support for this application of Easterlin's thesis. Retirement preparation is also strongly related to education and race.     

Period effects,generation effects and age effects in peptic ulcer mortality

The interpretation of secular trends in terms of period, age and cohorts is illustrated by data on peptic ulcer mortality for England and Wales from 1900 to 1977. Approaches to the external validation of the inferences made from such analyses are also illustrated. These data conform with predictions from a cohort analysis of some 20 years ago that peptic ulcer mortality and morbidity would decline.     

Declining trend in mortality after myocardial infarction.

All patients under 60 years of age who were discharged from hospital after a first myocardial infarction between 1968 and 1977 in Göteborg were followed for a minimum of 24 months. The patients were unselected, and treatment was standardised. The patients were divided into five two yearly cohorts, and the prognostic comparability and mortality of these cohorts were assessed. There was a reduction in the two year mortality rate after discharge during the 10 year period. Small baseline differences between the cohorts were controlled by multivariate methods, and a subsequent analysis showed that there was a declining trend in mortality between 1968 and 1977. A higher tendency among smokers to give up smoking and a lower prevalence of angina pectoris could explain only part of the reduction in mortality. A small number of patients underwent a coronary bypass operation; the slight increase in the number of operations during the period cannot, however, account for the reduced mortality. Most of the patients in the later cohorts were treated with beta blockers, and this is the most likely explanation for the majority of the decline in mortality.     

The relation between pulse pressure and cardiovascular mortality in 12,763 middle-aged men from various parts of the world: a 25-year follow-up of the seven countries study

BACKGROUND: Hypertension is a dominant characteristic in the prediction of cardiovascular diseases (CVDs). We aimed to evaluate the association of blood pressure measurements with CVD mortality among different populations of the world. METHODS: A total of 12 763 men, aged 40 to 59 years, from 7 countries (United States, Japan, Italy, Greece, former Yugoslavia, Finland, and the Netherlands) were surveyed from 1958 to 1964. Follow-up for vital status and causes of death was carried out over 25 years. RESULTS: All baseline blood pressure measurements were the best predictors of CVD mortality, compared with age, physical activity, total serum cholesterol level, body mass index or height, and smoking. Moreover, pulse pressure and diastolic and systolic blood pressures were the best predictors for CVD death, followed by mean and mid blood pressures. The age-adjusted hazard ratio per 10-mm Hg increase in pulse pressure varied among cohorts from 1.19 in the United States (P = .04) to 1.29 in southern Europe (P = .01). Differences among cohorts were not significant. In the pooled cohorts, pulse pressure measurements were also a significant predictor for coronary heart disease (hazard ratio per 10-mm Hg increase, 1.15; P = .04) as well as stroke death (hazard ratio per 10-mm Hg increase, 1.32; P = .01). CONCLUSIONS: Pulse pressure followed by diastolic and systolic blood pressures were the best predictors for CVD mortality among other blood pressures, as well as age, physical activity, total serum cholesterol level, anthropometric indexes, and smoking habits. No significant differences were observed among the different populations studied.