Baseline characteristics and age-related macular degeneration in participants of the 'ASPirin in Reducing Events in the Elderly' (ASPREE)-AMD trial

Purpose: To describe the baseline participant characteristics in the ASPREE-AMD study, investigating the effect of aspirin on AMD incidence and progression.Methods: Australian participants from the ASPirin in Reducing Events in the Elderly (ASPREE) trial, randomized to 100 mg aspirin daily or placebo, had non-mydriatic, digital color fundus images graded according to the Beckman AMD classification. Associations with AMD were determined for baseline characteristics and genetic risk variants.Results: ASPREE-AMD sub-study enrolled 4993 participants with gradable macular images. Median age was 73.4 years (IQR, 71.5, 76.6), 52% were female, 10% had diabetes mellitus, 73% had hypertension, and 44% were former/current smokers. Early, intermediate and late AMD (detected in 20.6%, 16.1%, 1.1%, respectively), significantly associated with age, were also associated with increasing HDL levels: OR = 1.52 (95%CI, 1.26, 1.84), OR = 1.43 (1.17, 1.77) and OR = 1.96 (1.02, 3.76), respectively. Female sex was associated with early [OR = 1.37 (1.16, 1.62)], and intermediate [OR = 1.35 (1.12, 1.63)] AMD, as was previous regular use of aspirin, with OR = 1.46 (1.11, 1.92) and OR = 1.37 (1.01, 1.85), respectively. Current smoking had increased odds for late AMD, OR = 4.02 (1.42, 11.36). Genetic risk variant rs3750846 (ARMS2/HTRA1) was associated with each AMD stage (p CFH) with intermediate and late AMD (p C3) with late AMD (p Conclusions: Observed associations are typical of AMD. The ASPREE-AMD clinical trial provides a unique opportunity to determine the risks and benefits of low-dose aspirin for AMD incidence and progression in elderly population

Recruiting general practice patients for large clinical trials: lessons from the Aspirin in Reducing Events in the Elderly (ASPREE) study

Objective: To assess the factors that contributed to the successful completion of recruitment for the largest clinical trial ever conducted in Australia, the Aspirin in Reducing Events in the Elderly (ASPREE) study.Design: Enrolment of GPs; identification of potential participants in general practice databases; screening of participants.Setting, Participants: Selected general practices across southeast Australia (Tasmania, Victoria, Australian Capital Territory, New South Wales, South Australia).Major Outcomes: Numbers of patients per GP screened and randomised to participation; geographic and demographic factors that influenced screening and randomising of patients.Results: 2717 of 5833 GPs approached (47%) enrolled to recruit patients for the study; 2053 (76%) recruited at least one randomised participant. The highest randomised participant rate per GP was for Tasmania (median, 5; IQR, 1-11), driven by the high rate of participant inclusion at phone screening. GPs in inner regional (adjusted odds ratio [aOR], 1.45; 95% CI, 1.14-1.84) and outer regional areas (aOR, 1.86; 95% CI, 1.19-2.88) were more likely than GPs in major cities to recruit at least one randomised participant. GPs in areas with a high proportion of people aged 70 years or more were more likely to randomise at least one participant (per percentage point increase: aOR, 1.10; 95% CI, 1.05-1.15). The number of randomised patients declined with time from GP enrolment to first randomisation.Conclusion: General practice can be a rich environment for research when barriers to recruitment are overcome. Including regional GPs and focusing efforts in areas with the highest proportions of potentially eligible participants improves recruitment. The success of ASPREE attests to the clinical importance of its research question for Australian GPs

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

Factors associated with treatment and control of hypertension in a healthy elderly population free of cardiovascular disease: a cross-sectional study

Published: 06 December 2019BACKGROUND: Despite readily available treatments, control of blood pressure (BP) with population ageing remains suboptimal. Further, there are gaps in the understanding of the management of high BP in the aged. We explored antihypertensive treatment and control among elderly hypertensive participants free from overt cardiovascular disease (CVD), and identified factors related to both 'untreated' and 'treated but uncontrolled' high BP. METHODS: We analyzed baseline data from 19,114 individuals aged ≥65-years enrolled from Australia and US in the ASPirin in Reducing Events in the Elderly (ASPREE) study. Hypertension was defined as an average systolic/diastolic BP ≥140/90mmHg and/or the use of any BP lowering medication. 'Controlled hypertension' was defined if participants were receiving antihypertensive medication and BP <140&90mmHg. Descriptive analyses were used to summarize hypertension control rates; logistic regression was used to investigate relationships with treatment and BP control. RESULTS: Overall, 74% (14,213/19,114) of participants were hypertensive; and of these 29% (4,151/14,213) were untreated. Among those treated participants, 53% (5,330/10,062) had BP≥140/90 mmHg. Participants who were untreated were more likely to be men, have higher educational status, and be in good physical health, and less likely to have significant comorbidities. The factors related to 'treated but uncontrolled' BP included older age, male, Black race (versus White), using antihypertensive monotherapy (versus multiple) and residing in Australia (versus US). CONCLUSION: High levels of 'untreated' and 'treated but uncontrolled' BP occur in healthy elderly people without CVD , suggesting there are opportunities for better BP control in the primary prevention of CVD in this population.Enayet K. Chowdhury, Mark R. Nelson, Michael E. Ernst, Karen L. Margolis ... Walter P Abhayaratna, Nigel P Stocks ... at al

Effect of aspirin on all-cause mortality in the healthy elderly

Background: 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. Methods: 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. Results: 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). Conclusions: 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

Effect of aspirin on cardiovascular events and bleeding in the healthy elderly

Background: 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. Methods: 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). Results: 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&lt;0.001). Conclusions: 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