Low-Dose Aspirin and Progression of Age-Related Hearing Loss: A Secondary Analysis of the ASPREE Randomized Clinical Trial.

Importance: Age-related hearing loss is common in an aging population, affecting communication and contributing to a worsened quality of life. It occurs as a result of cochlear degeneration and may be further exacerbated by inflammation and microvascular changes, as observed in animal models. Objective: To compare the effect of daily low-dose aspirin vs placebo on the progression of age-related hearing loss in healthy older adults. Design, Setting, and Participants: A prespecified secondary analysis was conducted of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial. Participants were 279 healthy community-dwelling individuals living in Australia who were aged 70 years or older and free of overt cardiovascular diseases, dementia, and life-limiting illnesses. Participants were recruited between January 1, 2010, and December 31, 2014, and followed up over 3 years. Statistical analysis was completed from June to December 2023. Intervention: A 100-mg daily dose of enteric-coated aspirin or matching placebo. Main Outcomes and Measures: Hearing measures were air conduction audiometry and binaural speech perception in noise. Assessments were conducted at baseline, 18 months, and 3 years. The change from baseline hearing measures were analyzed using an intention to treat approach. Aspirin and placebo were compared using mixed linear regression models adjusting for age, sex, diabetes, and smoking. Results: Of 279 participants, 154 (55%) were male, and the median age at baseline was 73.1 years (IQR, 71.5-76.2 years). A total of 98 of 138 participants (71%) in the aspirin group and 94 of 141 participants (67%) in the placebo group reported experiencing hearing loss at baseline. Compared with placebo, aspirin did not affect the changes in mean (SD) 4-frequency average hearing threshold from baseline to year 3 (aspirin: baseline, 27.8 [13.3] dB; year 3, 30.7 [13.7] dB; difference, 3.3 [3.9] dB; placebo: baseline, 27.5 [12.6] dB; year 3, 30.9 [13.8] dB; difference, 3.0 [4.8] dB; P = .55) nor any other tested frequencies. An increase in air conduction threshold indicates a deterioration in hearing. Similarly, for the mean (SD) speech reception threshold, there was no significant difference observed between the aspirin and placebo group at the year 3 follow-up assessment (aspirin: baseline, -9.9 [3.8] dB; year 3, -9.1 [3.8] dB; difference, 0.9 [2.9] dB; placebo: baseline, -10.5 [7.1] dB; year 3, -9.6 [4.1] dB; difference, 0.9 [5.9] dB; P = .86). The findings were consistent across sex, age groups, diabetic and smoking status. Conclusions and Relevance: In this secondary analysis of the ASPREE randomized clinical trial, low-dose aspirin did not affect the progression of age-related hearing loss. More investigation is warranted on whether a longer follow-up or the use of a more powerful anti-inflammatory agent might prove beneficial. Trial Registration: anzctr.org.au Identifier: ACTRN12614000496617.

Testosterone and the risk of incident atrial fibrillation in older men: further analysis of the ASPREE study.

Background: A cardiovascular safety trial of testosterone in men with cardiovascular risk factors or disease found no difference in rates of major adverse cardiovascular events (MACE) or death but noted more atrial fibrillation (AF) events in testosterone-treated men. We investigated the relationship between endogenous testosterone concentrations with risk of developing AF in healthy older men. Methods: Post-hoc analysis of 4570 male participants in the ASPirin in Reducing Events in the Elderly (ASPREE) study. Men were aged ≥ 70 years, had no history of cardiovascular disease (including AF), thyroid disease, prostate cancer, dementia, or life-threatening illnesses. Risk of AF was modelled using Cox proportional hazards regression. Findings: Median (IQR) age was 73.7 (71.6-77.1) years and median (IQR) follow-up 4.4 (3.3-5.5) years, during which 286 men developed AF (15.3 per 1000 participant-years). Baseline testosterone was higher in men who developed incident AF compared men who did not [17.0 (12.4-21.2) vs 15.7 (12.2-20.0) nmol/L]. There was a non-linear association of baseline testosterone with incident AF. The risk for AF was higher in men with testosterone in quintiles (Q) 4&5 (Q4:Q3, HR = 1.91; 95%CI = 1.29-2.83 and Q5:Q3HR = 1.98; 95%CI = 1.33-2.94). Results were similar after excluding men who experienced MACE or heart failure during follow-up. Interpretation: Circulating testosterone concentrations within the high-normal range are independently associated with an increased risk of incident AF amongst healthy older men. This suggests that AF may be an adverse consequence of high-normal total testosterone concentrations. Funding: National Institute on Aging and National Cancer Institute at the National Institutes of Health; Australian Government (NHMRC, CSIRO); Monash University; and AlfredHealth.

Sex-dependent associations of plasma high-density lipoprotein cholesterol and mortality risk in healthy older men and women: two prospective cohort studies.

The relationship between high plasma high-density lipoprotein cholesterol (HDL-C) and cause and mortality are not well established in healthy older people. This study examined the associations between HDL-C levels and mortality in initially healthy older men and women. This analysis included participants from the Aspirin in Reducing Events in the Elderly (ASPREE; n=18,668) trial and a matched cohort from the UK Biobank (UKB; n=62,849 ≥65 years). Cox regression was used to examine hazard ratios between HDL-C categories <1.03 mmol/L, 1.03-1.55 mmol/L (referent category), 1.55-2.07 mmol/L, and >2.07 mmol/L and all-cause, cancer, cardiovascular disease (CVD), and "non-cancer non-CVD" mortality. Genetic contributions were assessed using a polygenic score for HDL-C. Among ASPREE participants (aged 75±5 years), 1836 deaths occurred over a mean follow-up of 6.3±1.8 years. In men, the highest category of HDL-C levels was associated with increased risk of all-cause (HR 1.60, 95% CI 1.26-2.03), cancer (HR 1.37, 95% CI 0.96-2.00), and "non-cancer non-CVD" mortality (HR 2.35, 95% CI 1.41-3.42) but not CVD mortality (HR 1.08, 95% CI 0.60-1.94). The associations were replicated among UKB participants (aged 66.9±1.5 years), including 8739 deaths over a mean follow-up of 12.7±0.8 years. There was a non-linear association between HDL-C levels and all-cause and cause-specific mortality. The association between HDL-C levels and mortality was unrelated to variations in the HDL-C polygenic score. No significant association was found between HDL-C levels and mortality in women. Higher HDL-C levels are associated with increased risk from cancer and "non-cancer non-CVD" mortality in healthy older men but no such relationship was observed in women.

Self-rated eyesight among healthy older Australians: Baseline results of the ASPREE Longitudinal Study of Older Persons.

BACKGROUND: We aimed to describe the self-reported level of eyesight amongst a cohort of relatively healthy older Australian adults, and to investigate associations between poorer self-rated eyesight and demographic, health, and functional characteristics METHODS: The ASPirin in Reducing Events in the Elderly (ASPREE) Longitudinal Study of Older Persons (ALSOP) study was embedded in a multisite trial which recruited independently living Australians from general practices (2010-2014). Self-rated eyesight was recorded on a paper-based questionnaire as Excellent, Good, Fair, Poor, Very poor, or Completely blind at the baseline study wave RESULTS: Data from 14 592 participants (aged 70-95 years, 54.61% female) were included in this cross-sectional analysis. Eighty percent of participants reported excellent or good eyesight (n = 11 677). People with complete blindness were precluded from enrolling but 299 participants (2.0%) reported poor or very poor eyesight, and 2616 rated their eyesight as fair (17.9%). Lower levels of eyesight were associated with being older, female, fewer years of formal education, a primary language other than English, smoking, and self-reported macular degeneration, glaucoma, retinopathy, cataracts, and hearing problems (each p ≤ 0.021). People with lower levels of eyesight had a higher number of falls, frailty characteristics, and depressive symptoms, and lower mental and physical health functioning scores (each p < 0.001) CONCLUSIONS: Whilst most of these healthy older Australians reported good or excellent eyesight, a notable minority reported poor or very poor eyesight, and this was associated with a range of poorer health measures. These findings support the need for additional resources to prevent vision loss and associated sequelae.

Associations of Change in Body Size With All-Cause and Cause-Specific Mortality Among Healthy Older Adults.

Importance: The association between weight change and subsequent cause-specific mortality among older adults is not well described. The significance of changes in waist circumference (WC) has also not been compared with weight change for this purpose. Objective: To examine the associations of changes in body weight and WC with all-cause and cause-specific mortality. Design, Setting, and Participants: This cohort study is a post hoc analysis of data from the Aspirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial, which recruited participants between March 1, 2010, and December 31, 2014. The study included community-based older adults (16 703 Australian participants aged ≥70 years and 2411 US participants aged ≥65 years) without evident cardiovascular disease (CVD), dementia, physical disability, or life-limiting chronic illness. Data analysis was performed from April to September 2022. Exposures: Body weight and WC were measured at baseline and at annual visit 2. Analysis models were adjusted for baseline body mass index because height and weight were measured at baseline, allowing for calculation of body mass index and other variables. Both body weight and WC changes were categorized as change within 5% (stable), decrease by 5% to 10%, decrease by more than 10%, increase by 5% to 10%, and increase by more than 10%. Main Outcomes and Measures: All-cause, cancer-specific, CVD-specific, and noncancer non-CVD-specific mortality. Mortality events were adjudicated by an expert review panel. Cox proportional hazards regression and competing risk analyses were used to calculate hazard ratios (HRs) and 95% CIs. Results: Among 16 523 participants (mean [SD] age, 75.0 [4.3] years; 9193 women [55.6%]), 1256 deaths were observed over a mean (SD) of 4.4 (1.7) years. Compared with men with stable weight, those with a 5% to 10% weight loss had a 33% higher (HR, 1.33; 95% CI, 1.07-1.66) risk of all-cause mortality, and those with more than a 10% decrease in body weight had a 289% higher (HR, 3.89; 95% CI, 2.93-5.18) risk. Compared with women with stable weight, those with a 5% to 10% weight loss had a 26% higher (HR, 1.26; 95% CI, 1.00-1.60) risk of all-cause mortality, and those with more than a 10% decrease in body weight had a 114% higher (HR, 2.14; 95% CI, 1.58-2.91) risk. Weight loss was associated with a higher cancer-specific mortality (>10% decrease among men: HR, 3.49; 95% CI, 2.26-5.40; 5%-10% decrease among women: HR, 1.44; 95% CI, 1.46-2.04; >10% decrease among women: HR, 2.78; 95% CI, 1.82-4.26), CVD-specific mortality (>10% decrease among men: HR, 3.14; 95% CI, 1.63-6.04; >10% decrease among women: HR, 1.92; 95% CI, 1.05-3.51), and noncancer non-CVD-specific mortality (>10% decrease among men: HR, 4.98; 95% CI, 3.14-7.91). A decrease in WC was also associated with mortality. Conclusions and Relevance: This cohort study of healthy older adults suggests that weight loss was associated with an increase in all-cause and cause-specific mortality, including an increased risk of cancer, CVD, and other life-limiting conditions. Physicians should be aware of the significance of weight loss, especially among older men.