Impact of economic factors, social health and stressful life events on physical health-related quality of life trajectories in older Australians.

PURPOSE: Physical health-related quality of life (HRQoL) is associated with adverse health outcomes, including hospitalizations and all-cause mortality. However, little is known about how physical HRQoL changes over time in older people and the predictors of this trajectory. This study (a) identified trajectories of physical HRQoL among older people and (b) explored whether economic factors, social health or stressful life events impact physical HRQoL trajectories. METHOD: A cohort of 12,506 relatively 'healthy' community-dwelling Australians aged ≥ 70 years (54.4% females), enrolled in the ASPREE Longitudinal Study of Older Persons (ALSOP) study and was followed for six years. Economic factors, social health and life events in the last 12 months were assessed through a questionnaire at baseline. Physical HRQoL was measured by using the 12-item short form at baseline and annual follow-ups. Growth mixture and structural equation modelling were used to identify physical HRQoL trajectories and their predictors. RESULTS: Four physical HRQoL trajectories were identified-stable low (7.1%), declining (9.0%), stable intermediate (17.9%) and stable high (66.0%). Living in more disadvantaged areas, having a lower household income, no paid work, no voluntary work, loneliness and stressful life events (i.e. spousal illness, friend/family illness, financial problem) were associated with a 10%-152% higher likelihood of being in the stable low or declining physical HRQoL trajectory than the stable high group. CONCLUSION: Specific stressful life events had a greater impact on adverse physical HRQoL trajectories in older people than other factors. Volunteering may prevent physical HRQoL decline and requires further investigation.

Dispositional Optimism and All-Cause Mortality in Older Adults: A Cohort Study.

OBJECTIVE: Optimism is modifiable and may be associated with healthy aging. We aim to investigate whether dispositional optimism is associated with all-cause mortality in adults 70 years and older. METHODS: Between 2010 and 2014, older adults free of serious cardiovascular disease and dementia were recruited through primary care physicians and enrolled in the Aspirin Reducing Events in the Elderly (ASPREE) clinical trial. Australian ASPREE participants were invited to participate in the ASPREE Longitudinal Study of Older Persons (ALSOP) that was running in parallel to ASPREE. Optimism was assessed at baseline using the Life Orientation Test-Revised. The association between optimism, divided into quartiles, and all-cause mortality was assessed using Cox proportional hazards models. RESULTS: A total of 11,701 participants (mean [standard deviation] age = 75.1 [4.24] years; 46.6% men) returned the ALSOP Social questionnaire and completed the Life Orientation Test-Revised. During a median follow-up of 4.7 years, 469 deaths occurred. The fully adjusted model was not significant (hazard ratio = 0.78, 95% confidence interval = 0.58-1.06). There was evidence that age was an effect modifier of the association between optimism and longevity. Higher optimism was associated with lower mortality risk in the oldest individuals only (77+ years; hazard ratio = 0.61, 95% confidence interval = 0.39-0.96). CONCLUSIONS: We observed no independent relationship between optimism and all-cause mortality in the total sample, although optimism seemed to be associated with lower risk among the oldest old (adults 77 years and older).

Social isolation, social support, and loneliness and their relationship with cognitive health and dementia.

BACKGROUND: Poor social health is prevalent in older adults and may be associated with worse cognition, and increased dementia risk. The aim of this study was to determine whether social isolation, social support and loneliness are independently associated with cognitive function and incident dementia over 5 years in older adults, and to investigate potential gender differences. METHODS: Participants were 11,498 community-dwelling relatively healthy Australians aged 70-94, in the ASPREE Longitudinal Study of Older Persons (ALSOP). Social isolation, social support, loneliness and cognitive function were assessed through self-report. Outcomes examined were cognitive decline (>1.5 SD decline in cognitive performance since baseline) and incident dementia (adjudicated according to DSM-IV criteria). RESULTS: Most participants self-reported good social health (92%) with very few socially isolated (2%), with low social support (2%) or lonely (5%). Among women, social isolation and low social support were consistently associated with lower cognitive function (e.g., social support and cognition ß = -1.17, p < 0.001). No consistent longitudinal associations were observed between baseline social health and cognitive decline (over median 3.1 years) or incident dementia (over median 4.4 years; social isolation: HR = 1.00, p = 0.99; low social support: HR = 1.79, p = 0.11; loneliness: HR = 0.72, p = 0.34 among women and men). CONCLUSION: Our study provides evidence that social isolation and a low social support are associated with worse cognitive function in women, but not men. Social health did not predict incident cognitive decline or dementia, but we lacked power to stratify dementia analyses by gender.

Social isolation, social support, loneliness and cardiovascular disease risk factors: A cross-sectional study among older adults.

BACKGROUND: Social health reflects one's ability to form interpersonal relationships. Poor social health is a risk factor for cardiovascular disease (CVD), however an in-depth exploration of the link through CVD risk factors is lacking. AIM: To examine the relationship between social health (social isolation, social support, loneliness) and CVD risk factors among healthy older women and men. METHODS: Data were from 11,498 healthy community-dwelling Australians aged ≥70 years from the ASPirin in Reducing Events in the Elderly (ASPREE) trial and the ASPREE Longitudinal Study of Older Persons sub-study. Ten-year CVD risk was estimated using the Atherosclerotic CVD Risk Scale (ASCVDRS) and the Framingham Risk Score (FRS). RESULTS: Physical inactivity and experiencing depressive symptoms were the only CVD risk factors that consistently differed by all three social health constructs. Loneliness was associated with greater ASCVDRS (women: ß = 0.01, p < 0.05; men: ß = 0.03, p < 0.001), social isolation with greater FRS (women: ß = 0.02, p < 0.01; men: ß = 0.03, p < 0.01) and the social health composite of being lonely (regardless of social isolation and/or social support status) with greater ASCVDRS (women: ß = 0.01, p = 0.02; men: ß = 0.03, p < 0.001). Among men, loneliness was also associated with greater FRS (ß = 0.03, p < 0.001) and social support with greater ASCVDRS (ß = 0.02, p = 0.01). Men were more socially isolated, less socially supported and less lonely than women. CONCLUSION: Social isolation, social support and loneliness displayed diverse relationships with CVD risk factors and risk scores, emphasising the importance of distinguishing between these constructs. These findings inform on potential avenues to manage poor social health and CVD risk among older adults.

Social isolation, social support and loneliness as predictors of cardiovascular disease incidence and mortality.

BACKGROUND: Poor social health is associated with increased risk of cardiovascular disease (CVD). Recent research suggests that different social health domains should be considered separately as the implications for health and possible interventions may differ. AIM: To assess social isolation, low social support and loneliness as predictors of CVD. METHODS: Secondary analysis of 11,486 community-dwelling, Australians, aged 70 years and over, free of CVD, dementia, or significant physical disability, from the ASPirin in Reducing Events in the Elderly (ASPREE) trial. Social isolation, social support (Revised Lubben Social Network Scale), and loneliness were assessed as predictors of CVD using Cox proportional-hazard regression. CVD events included fatal CVD, heart failure hospitalization, myocardial infarction and stroke. Analyses were adjusted for established CVD risk factors. RESULTS: Individuals with poor social health were 42 % more likely to develop CVD (p = 0.01) and twice as likely to die from CVD (p = 0.02) over a median 4.5 years follow-up. Interaction effects indicated that poorer social health more strongly predicted CVD in smokers (HR 4.83, p = 0.001, p-interaction = 0.01), major city dwellers (HR 1.94, p < 0.001, p-interaction=0.03), and younger older adults (70-75 years; HR 2.12, p < 0.001, p-interaction = 0.01). Social isolation (HR 1.66, p = 0.04) and low social support (HR 2.05, p = 0.002), but not loneliness (HR 1.4, p = 0.1), predicted incident CVD. All measures of poor social health predicted ischemic stroke (HR 1.73 to 3.16). CONCLUSIONS: Among healthy older adults, social isolation and low social support may be more important than loneliness as cardiovascular risk factors. Social health domains should be considered in future CVD risk prediction models.

Mental health trajectories among women in Australia as they age.

OBJECTIVES: To ascertain the trajectories of mental health among women in Australia assessed in repeat waves from their early 70 s to the end of their lives or their mid 80 s. METHOD: Secondary analysis of data contributed by the 1921-26 cohort of the Australian Longitudinal Study of Women's Health Waves 1-6. Primary outcome was the 4-item SF-36 Vitality Subscale, which assesses mental health as life satisfaction, social participation, energy and enthusiasm. Structural, individual and intermediary factors were assessed using study-specific and standardised measures. Trajectories were identified using Growth Mixture Modelling and associations with baseline characteristics with Structural Equation Modelling. RESULTS: 12,432 women completed Survey One. Three mental health trajectories: stable high (77%); stable low (18.2%) and declining from high to low (4.8%) were identified. Compared to the stable high group, women in the stable low group were significantly less physically active, had more nutritional risks, more recent adverse life events, fewer social interactions and less social support, reported more stress and were more likely to have a serious illness or disability at Survey One. The declining group had similar characteristics to the stable high group, but were significantly more likely to report at baseline that they had experienced recent financial, physical and emotional elder abuse. These interact, but not directly with socioeconomic position and marital status. CONCLUSION: Mental health among older women is related to social relationships, general health, access to physical activity and healthy nutrition, coincidental adverse life events and experiences of interpersonal violence, in particular elder abuse.

Gender-specific aspects of socialisation and risk of cardiovascular disease among community-dwelling older adults: a prospective cohort study using machine learning algorithms and a conventional method.

BACKGROUND: Gender influences cardiovascular disease (CVD) through norms, social relations, roles and behaviours. This study identified gender-specific aspects of socialisation associated with CVD. METHODS: A longitudinal study was conducted, involving 9936 (5,231 women and 4705 men) initially healthy, community-dwelling Australians aged 70 years or more from the ASPirin in Reducing Events in the Elderly (ASPREE) study and ASPREE Longitudinal Study of Older Persons, with a median follow-up time of 6.4 years. Variable categorisation, variable selection (using machine learning (ML) models; Elastic Net and extreme gradient boosting) and Cox-regression were employed separately by binary gender to identity socialisation factors (n=25 considered) associated with CVD. RESULTS: Different socialisation factors were identified using the ML models. In the Cox model, for both genders, being married/partnered was associated with a reduced risk of CVD (men: HR 0.76, 95% CI 0.60 to 0.96; women: HR 0.67, 95% CI 0.58 to 0.95). For men, having 3-8 relatives they felt close to and could call on for help (HR 0.76, 95% CI 0.58 to 0.99; reference <3 relatives), having 3-8 relatives they felt at ease talking with about private matters (HR 0.70, 95% CI 0.55 to 0.90; reference <3 relatives) or playing games such as chess or cards (HR 0.82, 95% CI 0.67 to 1.00) was associated with reduced risk of CVD. For women, living with others (HR 0.71, 95% CI 0.55 to 0.91) or having ≥3 friends they felt at ease talking with about private matters (HR 0.74, 95% CI 0.58 to 0.95; reference <3 friends) was associated with a lower risk of CVD. CONCLUSIONS: This study demonstrates the need to prioritise gender-specific social factors to improve cardiovascular health in older adults.

Socioeconomic, Behavioural, and Social Health Correlates of Optimism and Pessimism in Older Men and Women: A Cross-Sectional Study.

BACKGROUND: Optimism is a disposition characterised by positive future expectancies, while pessimism is characterised by expecting the worst. High optimism and low pessimism promote the health of older adults and may potentiate full engagement in life. We identified socioeconomic, behavioural, and social factors associated with optimism and pessimism in older adults. METHODS: Participants included 10,146 community-dwelling, apparently healthy Australian adults aged 70 years and over from the ASPREE Longitudinal Study of Older Persons (ALSOP). Optimism and pessimism were measured using the revised Life Orientation Test. Cross-sectional ordinal logistic regression was used to determine the socioeconomic, behavioural, and social health factors associated with optimism and pessimism. RESULTS: Higher education, greater physical activity, lower loneliness, and volunteering were associated with higher optimism and lower pessimism. Low social support was associated with higher pessimism. Higher socioeconomic advantage, greater income, and living alone were associated with lower pessimism. Women were more optimistic and less pessimistic than men. The association of age, smoking status, and alcohol consumption with optimism and pessimism differed for men and women. CONCLUSIONS: Factors associated with higher optimism and lower pessimism were also those demonstrated to support healthy ageing. Health-promotion action at the individual level (e.g., smoking cessation or regular physical activity), health professional level (e.g., social prescribing or improving access and quality of care for all older adults), and community level (e.g., opportunities for volunteer work or low-cost social activities for older adults) may improve optimism and reduce pessimism, possibly also promoting healthy ageing.

Adverse events in older adults and the risk of dementia and cognitive decline.

Background: Increasing evidence suggests that stress could be a risk factor for dementia but this might vary by gender. This study investigated whether adverse life events were associated with cognitive decline and dementia in later-life, separately in men and women. Methods: Participants were 12,789 community-dwelling Australians aged ≥ 70 years. Ten common adverse events in later-life were self-reported. Cognitive decline was defined as a 1.5 SD decline from participants' baseline score in tests of global cognition, psychomotor speed, episodic memory, and executive functioning, which were assessed regularly over a maximum of 10.3 years. Dementia was diagnosed according to DSM-IV criteria. Results: An increased risk of dementia was observed in participants who experienced the death of a spouse/partner (HR: 1.72, 95% CI: 1.17 - 2.52) and for individuals who experienced major financial problems (HR: 1.53, 95% CI: 1.05 - 2.23). The latter also increased the risk of cognitive decline in men specifically (HR: 1.43, 95% CI: 1.10 - 1.86). In contrast, some events for women were associated with a reduced risk of dementia (e.g. close family or friends lost their job/retired (HR: 0.62, 95% CI: 0.40-0.95)). Limitations: Events including major money problems may result from prodromal dementia symptoms, thus reverse causation needs to be considered. Conclusions: Adverse life events may influence dementia risk in older adults, but associations vary depending on the nature of the event, and across genders. These findings support the need for early interventions in older people who have experienced adversities, particularly for the death of a loved one.

Normative Data for Single-Letter Controlled Oral Word Association Test in Older White Australians and Americans, African-Americans, and Hispanic/Latinos.

Background: The Controlled Oral Word Association Test (COWAT) is a commonly used measure of verbal fluency. While a normal decline in verbal fluency occurs in late adulthood, significant impairments may indicate brain injury or diseases such as Alzheimer's disease. Normative data is essential to identify when test performance falls below expected levels based on age, gender, and education level. Objective: This study aimed to establish normative performance data on single-letter COWAT for older community-dwelling adults. Methods: Over 19,000 healthy men and women, without a diagnosis of dementia or a Modified Mini-Mental State Examination score below 77/100, were recruited for the ASPREE trial. Neuropsychological assessments, including the COWAT with letter F, were administered at study entry. Results: Median participant age was 75 years (range 65-98), with 56.5% being women. The majority of participants had 9-11 years of education in Australia and over 12 years in the U.S. The COWAT performance varied across ethno-racial groups and normative data were thus presented separately for 16,335 white Australians, 1,084 white Americans, 896 African-Americans, and 316 Hispanic/Latinos. Women generally outperformed men in the COWAT, except for Hispanic/Latinos. Higher education levels consistently correlated with better COWAT performance across all groups, while the negative association with age was weaker. Conclusions: This study provides comprehensive normative data for the COWAT stratified by ethno-racial groups in Australia and the U.S., considering age, gender, and education level. These norms can serve as reference standards for screening cognitive impairments in older adults in both clinical and research settings.

The Association of Dispositional Optimism and Pessimism With Cardiovascular Disease Events in Older Adults: A Prospective Cohort Study.

Objective: Positive psychosocial factors may protect against cardiovascular disease (CVD). We aimed to determine the association of optimism and pessimism with CVD events in community-dwelling older adults. Methods: 11,651 adults aged 70 years and over, participants of the ASPREE Longitudinal Study of Older Persons (ALSOP), were followed-up for 4.7 years (median). The association of optimism and pessimism (assessed as separate constructs by revised Life Orientation Test) and incident CVD events (composite and components) was assessed by Cox regression adjusted for demographic, socioeconomic and health factors. Results: No association was observed between optimism and pessimism with composite CVD events. Being more pessimistic was associated with a greater risk of fatal coronary heart disease, while being more optimistic was associated with a lower risk of non-fatal myocardial infarction. Conclusions: Optimism and pessimism may shape cardiovascular health of older adults; and we argue these psychosocial factors should be researched as separate constructs.

Musculoskeletal Pain Experienced on Most Days is a Common Accompaniment of Ageing amongst Community-Dwelling Older Australians: A Questionnaire-Based Study.

Objective: To describe the prevalence, location and impact of moderate to severe pain experienced on most days in community-dwelling older (≥70 years) adults who were ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial participants. Methods: Cross-sectional ASPREE Longitudinal Study of Older Persons (ALSOP) data were collected from self-reported questionnaires administered to 16,439 ASPREE participants. Results: Of 14,155 respondents, 41% of males (n = 2651/6475) and 50% of females (n = 3803/7680) reported experiencing pain on most days. One quarter of respondents reported experiencing pain on most days that was moderate or severe in intensity (n = 3560/14,155), commonly located in the lower back, knees and upper back. Of those reporting moderate or severe pain, 51% reported taking analgesic medication on most days (n = 1812/3560), almost one-third also reported regular interference with sleep (29%, n = 1024/3560), walking (35%, n = 1239/3560) and daily activities (41%, n = 1467/3560). Discussion: Lower back, knee or upper back pain is a common accompaniment of ageing.

Normative performance of older individuals on the Hopkins Verbal Learning Test-Revised (HVLT-R) according to ethno-racial group, gender, age and education level.

OBJECTIVE: The Hopkins Verbal Learning Test-Revised (HVLT-R) provides a measure of verbal learning and memory. The aim of this study was to provide normative performance data on the HVLT-R for community-dwelling older individuals according to ethno-racial group, age, gender, and years of completed education, in Australia and the U.S. METHOD: The ASPirin in Reducing Events in the Elderly (ASPREE) study recruited 19,114 generally healthy community dwelling individuals aged 70 years and over (65 years and over for U.S minorities), who were without a diagnosis of dementia and scored above 77 on the modified Mini-Mental State (3MS) examination. Included in the analysis presented here were 16,251 white Australians, and in the U.S. 1,082 white, 894 African American and 314 Hispanic/Latino individuals at baseline. RESULTS: Performance on each of the components of the HVLT-R (trials 1-3, total, learning, delayed recall, delayed recognition, percentage retention and recognition discrimination index [RDI]) differed by demographic variables. In country and ethno-racial stratified analyses, female gender, younger age and higher education were significantly associated with better total recall, delayed recall and RDI. Among white Australians these characteristics were also associated with better retention. Age, education and gender-specific reference values across ethno-racial categories were determined. CONCLUSIONS: Ethno-racial, age, gender and education-stratified normative data from this large cohort of community-dwelling older individuals will serve as important reference standards in Australia and the U.S. to assess cognition in older individuals.

Normative Data for the Symbol Digit Modalities Test in Older White Australians and Americans, African-Americans, and Hispanic/Latinos.

BACKGROUND: Processing speed, which can be assessed using the Symbol Digit Modalities Test (SDMT), is central to many brain functions. Processing speed declines with advanced age but substantial impairments are indicative of brain injury or disease. OBJECTIVE: The purpose of this study was to provide SDMT normative data for older community-dwelling individuals in the U.S. and Australia. METHODS: The ASPREE trial recruited 19,114 relatively healthy older men and women in Australia and the U.S. from the general community. All participants were without a diagnosis of dementia and with a Modified Mini-Mental State examination score of 78 or more at enrolment. The SDMT was administered at baseline as part of a neuropsychological test battery. RESULTS: The median age of participants was 74 years (range 65-99), and 56% were women. The median years of education was 12. Ethno-racial differences in SDMT performance were observed and normative data were thus presented separately for 16,289 white Australians, 1,082 white Americans, 891 African-Americans, and 316 Hispanic/Latinos. There were consistent positive associations found between SDMT and education level, and negative associations between SDMT and age. Mean scores for women were consistently higher than men with the exception of Hispanic/Latinos aged ≥70 years. CONCLUSION: This study provides comprehensive SDMT normative data for whites (Australian and U.S.), Hispanic/Latinos, and African-Americans, according to gender, age, and education level. These norms can be used clinically as reference standards to screen for cognitive impairments in older individuals.

Moderate or severe low back pain is associated with body mass index amongst community-dwelling older Australians.

OBJECTIVE: Low back pain is prevalent in older populations and modifiable risk factors may include being overweight or obese. This study aimed to describe the prevalence and impact of moderate or severe low back pain in community-dwelling older adults and its association with body mass index (BMI). METHODS: Cross-sectional study involving 16,439 Australians aged ≥70 years. Logistic regression was used to describe associations between the presence or absence of moderate or severe low back pain experienced on most days with BMI. Analyses were conducted separately for males and females, and controlled for age and depression at baseline. RESULTS: Of 14,155 pain question respondents, 11 % of males (n = 710/6475) and 18 % of females (n = 1391/7680) reported moderate or severe low back pain (total 15 %, n = 2101/14,155). Of those reporting moderate or severe low back pain (n = 2101), 55 % reported taking pain-relieving medication regularly, and 29 % reported that the pain regularly interfered with sleep, 37 % with walking, and 47 % with day to day activities. When age and depression were controlled for, there was a statistically significant (p < 0.001) association between moderate or severe low back pain and being overweight (females: odds ratio OR = 1.50, 95 % confidence interval CI = 1.27-1.76) or obese (males: OR = 2.23, 95 %CI = 1.77-2.80 and females: OR = 2.91, 95 %CI = 2.48-3.42). CONCLUSION: Moderate or severe low back pain is common, has a significant impact, and is associated with either an overweight or obese BMI among community-dwelling Australians aged ≥70 years.

Normative performance of healthy older individuals on the Modified Mini-Mental State (3MS) examination according to ethno-racial group, gender, age, and education level.

OBJECTIVE: To present normative performance data on the Modified Mini-Mental State (3MS) examination for healthy community-dwelling older individuals according to gender, age, education level, and ethno-racial group. METHOD: More than 19,000 generally healthy older men and women without a diagnosis of dementia were recruited from the general population in Australia and the U.S. for the ASPirin in Reducing Events in the Elderly (ASPREE) study. The 3MS exam was administered as part of the baseline screening and individuals scoring above 77 were eligible to participate. RESULTS: The sample comprised 16,360 Australian whites, 1080 U.S. whites, 895 African-Americans and 316 Hispanic/Latinos. The median age of participants was 74 years (range 65-98), with an average of 12 years of education and 56% were female. Increasing age and fewer years of completed education were associated with lower scores on the 3MS. Women scored higher than men in most age and education categories. Differences across ethno-racial groups were found. With factor analysis, four factors were identified which accounted for 35% of the between-person variance in 3MS scores for white Australians. CONCLUSIONS: This large cohort of older individuals provides some of the most comprehensive 3MS normative data to be generated for whites (Australian and U.S.), Hispanic/Latinos and African-Americans, by age, gender, and educational attainment. These findings will serve as important reference standards for monitoring cognitive function in generally healthy older individuals, becoming increasingly important as this fraction of the population increases.

Development of a standardized definition for clinically significant bleeding in the ASPirin in Reducing Events in the Elderly (ASPREE) trial.

BACKGROUND: Bleeding is the major risk of aspirin treatment, especially in the elderly. A consensus definition for clinically significant bleeding (CSB) in aspirin primary prevention trials is lacking in the literature. METHODS: This paper details the development, modification, application, and quality control of a definition for clinically significant bleeding in the ASPirin in Reducing Events in the Elderly (ASPREE) trial, a primary prevention trial of aspirin in 19,114 community-dwelling elderly men and women. In ASPREE a confirmed bleeding event needed to meet criteria both for substantiated bleeding and clinical significance. Substantiated bleeding was defined as: 1) observed bleeding, 2) a reasonable report of symptoms of bleeding, 3) medical, nursing or paramedical report, or 4) imaging evidence. Bleeding was defined as clinically significant if it: 1) required transfusion of red blood cells, 2) required admission to the hospital for >24 h, or prolonged a hospitalization, with bleeding as the principal reason, 3) required surgery to stop the bleeding, or 4) resulted in death. Bleeding sites were subclassified as upper gastrointestinal, lower gastrointestinal, intracranial (hemorrhagic stroke, subarachnoid hemorrhage, subdural hematoma, extradural hematoma, or other), or other sites. Potential events were retrieved from medical records, self-report or notification from treating doctors. Two reviewers adjudicated each event using electronic adjudication software, and discordant cases were reviewed by a third reviewer. Adjudication rules evolved to become more strictly defined as the trial progressed and decision rules were added to assist with frequent scenarios such as post-operative bleeding. CONCLUSIONS: This paper provides a detailed methodologic description of the development of a standardized definition for clinically significant bleeding and provides a benchmark for development of a consensus definition for future aspirin primary prevention trials. TRIAL REGISTRATION: ASPREE is registered on the International Standard Randomized Controlled Trial Number Register (ISRCTN83772183) and on clinicaltrials.gov (NCT01038583).