Aspirin is a well-established therapy for the secondary prevention of cardiovascular events. However, its role in the primary prevention of cardiovascular disease is unclear, especially in older persons, who have an increased risk. From 2010 through 2014, we enrolled community-dwelling men and women in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. The primary end point was a composite of death, dementia, or persistent physical disability; results for this end point are reported in another article in the Journal. Secondary end points included major hemorrhage and cardiovascular disease (defined as fatal coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal stroke, or hospitalization for heart failure). Of the 19,114 persons who were enrolled in the trial, 9525 were assigned to receive aspirin and 9589 to receive placebo. After a median of 4.7 years of follow-up, the rate of cardiovascular disease was 10.7 events per 1000 person-years in the aspirin group and 11.3 events per 1000 person-years in the placebo group (hazard ratio, 0.95; 95% confidence interval [CI], 0.83 to 1.08). The rate of major hemorrhage was 8.6 events per 1000 person-years and 6.2 events per 1000 person-years, respectively (hazard ratio, 1.38; 95% CI, 1.18 to 1.62; P<0.001). The use of low-dose aspirin as a primary prevention strategy in older adults resulted in a significantly higher risk of major hemorrhage and did not result in a significantly lower risk of cardiovascular disease than placebo. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583.)

In the primary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, now published in the Journal, we report that the daily use of aspirin did not provide a benefit with regard to the primary end point of disability-free survival among older adults. A numerically higher rate of the secondary end point of death from any cause was observed with aspirin than with placebo. From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. Deaths were classified according to the underlying cause by adjudicators who were unaware of trial-group assignments. Hazard ratios were calculated to compare mortality between the aspirin group and the placebo group, and post hoc exploratory analyses of specific causes of death were performed. Of the 19,114 persons who were enrolled, 9525 were assigned to receive aspirin and 9589 to receive placebo. A total of 1052 deaths occurred during a median of 4.7 years of follow-up. The risk of death from any cause was 12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group (hazard ratio, 1.14; 95% confidence interval [CI], 1.01 to 1.29). Cancer was the major contributor to the higher mortality in the aspirin group, accounting for 1.6 excess deaths per 1000 person-years. Cancer-related death occurred in 3.1% of the participants in the aspirin group and in 2.3% of those in the placebo group (hazard ratio, 1.31; 95% CI, 1.10 to 1.56). Higher all-cause mortality was observed among apparently healthy older adults who received daily aspirin than among those who received placebo and was attributed primarily to cancer-related death. In the context of previous studies, this result was unexpected and should be interpreted with caution. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583.)

Information on the use of aspirin to increase healthy independent life span in older persons is limited. Whether 5 years of daily low-dose aspirin therapy would extend disability-free life in healthy seniors is unclear. From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or physical disability. Participants were randomly assigned to receive 100 mg per day of enteric-coated aspirin or placebo orally. The primary end point was a composite of death, dementia, or persistent physical disability. Secondary end points reported in this article included the individual components of the primary end point and major hemorrhage. A total of 19,114 persons with a median age of 74 years were enrolled, of whom 9525 were randomly assigned to receive aspirin and 9589 to receive placebo. A total of 56.4% of the participants were women, 8.7% were nonwhite, and 11.0% reported previous regular aspirin use. The trial was terminated at a median of 4.7 years of follow-up after a determination was made that there would be no benefit with continued aspirin use with regard to the primary end point. The rate of the composite of death, dementia, or persistent physical disability was 21.5 events per 1000 person-years in the aspirin group and 21.2 per 1000 person-years in the placebo group (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11; P=0.79). The rate of adherence to the assigned intervention was 62.1% in the aspirin group and 64.1% in the placebo group in the final year of trial participation. Differences between the aspirin group and the placebo group were not substantial with regard to the secondary individual end points of death from any cause (12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group), dementia, or persistent physical disability. The rate of major hemorrhage was higher in the aspirin group than in the placebo group (3.8% vs. 2.8%; hazard ratio, 1.38; 95% CI, 1.18 to 1.62; P<0.001). Aspirin use in healthy elderly persons did not prolong disability-free survival over a period of 5 years but led to a higher rate of major hemorrhage than placebo. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583.)

Ageing is one of the principal risk factors for many chronic diseases. However, there is considerable between-person variation in the rate of ageing and individual differences in their susceptibility to disease and death. Epigenetic mechanisms may play a role in human ageing, and DNA methylation age biomarkers may be good predictors of age-related diseases and mortality risk. The aims of this systematic review were to identify and synthesise the evidence for an association between peripherally measured DNA methylation age and longevity, age-related disease, and mortality risk. A systematic search was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using relevant search terms, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and PsychINFO databases were searched to identify articles meeting the inclusion criteria. Studies were assessed for bias using Joanna Briggs Institute critical appraisal checklists. Data was extracted from studies measuring age acceleration as a predictor of age-related diseases, mortality or longevity, and the findings for similar outcomes compared. Using Review Manager 5.3 software, two meta-analyses (one per epigenetic clock) were conducted on studies measuring all-cause mortality. Twenty-three relevant articles were identified, including a total of 41,607 participants. Four studies focused on ageing and longevity, 11 on age-related disease (cancer, cardiovascular disease, and dementia), and 11 on mortality. There was some, although inconsistent, evidence for an association between increased DNA methylation age and risk of disease. Meta-analyses indicated that each 5-year increase in DNA methylation age was associated an 8 to 15% increased risk of mortality. Due to the small number of studies and heterogeneity in study design and outcomes, the association between DNA methylation age and age-related disease and longevity is inconclusive. Increased epigenetic age was associated with mortality risk, but positive publication bias needs to be considered. Further research is needed to determine the extent to which DNA methylation age can be used as a clinical biomarker.

Background: Quality of life (QoL) is multi-dimensional concept of an individual’ general well-being status in relation to their value, environment, cultural and social context in which they live. This study aimed to quantitatively synthesise available evidence on the association between QoL and mortality in the general population.Methods: An electronic search was conducted using three bibliographic databases, MEDLINE, EMBASE and PsycINFO. Inclusion criteria were studies that assessed QoL using standardized tools and examined mortality risk in a non-patient population. Qualitative data synthesis and meta-analyses using a random-effects model were performed.Results: Of 4184 articles identified, 47 were eligible for inclusion, involving approximately 1,200,000 participants. Studies were highly heterogeneous in terms of QoL measures, population characteristics and data analysis. In total, 43 studies (91.5%) reported that better QoL was associated with lower mortality risk. The results of four meta-analyses indicated that higher health-related QoL (HRQoL) is associated with lower mortality risk, which was consistent for overall HRQoL (HR 0.633, 95% CI: 0.514 to 0.780), physical function (HR 0.987, 95% CI: 0.982 to 0.992), physical component score (OR 0.950, 95% CI: 0.935 to 0.965), and mental component score (OR 0.980, 95% CI: 0.969 to 0.992).Conclusion: These findings provide evidence that better QoL/HRQoL was associated with lower mortality risk. The utility of these measures in predicting mortality risk indicates that they should be considered further as potential screening tools in general clinical practice, beyond the traditional objective measures such as body mass index and the results of laboratory tests.