Associations between blood sex steroid concentrations and risk of major adverse cardiovascular events in healthy older women in Australia: a prospective cohort substudy of the ASPREE trial.

BACKGROUND: Blood testosterone concentrations in women decline during the reproductive years and reach a nadir in the seventh decade, after which concentrations increase and are restored to those of reproductive-aged women early in the eighth decade. We aimed to establish the association between the concentration of testosterone in the blood and risk of major adverse cardiovascular events (MACE) and all-cause mortality in healthy older women. METHODS: SHOW was a prospective cohort substudy of the longitudinal randomised ASPREE trial. Eligible participants were women aged at least 70 years from Australia with unimpaired cognition, no previous MACE, and a life expectancy of at least 5 years. Participants who were receiving hormonal or steroid therapy were ineligible for inclusion. We measured serum concentrations of sex steroids with liquid chromatography-tandem mass spectrometry and of SHBG with immunoassay. We compared lower concentrations of sex hormones with higher concentrations using four quartiles. Primary endpoints were risk of MACE and all-cause mortality, the associations of which with sex steroid concentrations were assessed using Cox proportional hazards regression that included age, body-mass index, smoking status, alcohol consumption, diabetes, hypertension, dyslipidaemia, impaired renal function, and treatment allocation in the ASPREE trial (aspirin vs placebo). ASPREE is registered with ClinicalTrials.gov, NCT01038583. FINDINGS: Of the 9180 women recruited to the ASPREE trial between March 10, 2010, and Dec 31 2014, 6358 participants provided sufficient biobank samples at baseline and 5535 were included in the final analysis. Median age at entry was 74·0 years (IQR 71·7-77·7). During a median 4·4 years of follow-up (24 553 person-years), 144 (2·6%) women had a first MACE (incidence 5·9 per 1000 person-years). During a median 4·6 years of follow-up (3·8-5·6), 200 women died (7·9 per 1000 person-years). In the fully adjusted models, higher concentrations of testosterone were associated with a lower incidence of MACE (quartile 4 vs quartile 1: hazard ratio 0·57 [95% CI 0·36-0·91]; p=0·02), as were higher concentrations of DHEA (quartile 4 vs quartile 1: 0·61 [0·38-0·97]; p=0·04). For oestrone, a lower risk of MACE was seen for concentrations in quartile 2 only, compared with quartile 1 (0·55 [0·33-0·92]; p=0·02). In fully adjusted models, no association was seen between SHBG and MACE, or between any hormone or SHBG and all-cause mortality. INTERPRETATION: Blood concentrations of testosterone and DHEA above the lowest quartile in older women were associated with a reduced risk of a first-ever MACE. Given that the physiological effects of DHEA are mediated through its steroid metabolites, if the current findings were to be replicated, trials investigating testosterone therapy for the primary prevention of ischaemic cardiovascular disease events in older women would be warranted. FUNDING: The National Health and Medical Research Council of Australia, US National Institute on Aging, the Victorian Cancer Agency, the Commonwealth Scientific and Industrial Research Organisation, and Monash University.

Testosterone and Estrone Increase From the Age of 70 Years: Findings From the Sex Hormones in Older Women Study.

CONTEXT: There is a lack of understanding of what is normal in terms of sex steroid levels in older women. OBJECTIVE: To determine whether sex steroid levels vary with age in and establish reference ranges for women >70 years of age. DESIGN AND SETTING: Cross-sectional, community-based study. PARTICIPANTS: Included 6392 women ≥70 years of age. MAIN OUTCOME MEASURES: Sex steroids measured by liquid chromatography-tandem mass spectrometry. A reference group, to establish sex steroid age-specific reference ranges, excluded women using systemic or topical sex steroid, antiandrogen or glucocorticoid therapy, or an antiglycemic agent. RESULTS: The reference group of 5326 women had a mean age of 75.1 (±4.2) years, range of 70 to 94.7 years. Median values (range) were 181.2 pmol/L (3.7 to 5768.9) for estrone (E1), 0.38 nmol/L (0.035 to 8.56) for testosterone (T), 2.60 nmol/L (0.07 to 46.85) for dehydroepiandrosterone (DHEA), and 41.6 nmol/L (2.4 to 176.6) for SHBG. Estradiol and DHT were below method sensitivity in 66.1% and 72.7% of the samples, respectively. Compared with women aged 70 to 74 years, women aged ≥85 years had higher median levels of E1 (11.7%, P = 0.01), T (11.3%, P = 0.02), and SHBG (22.7%, P < 0.001) and lower DHEA (30% less, P < 0.001). Women with overweight and obesity had higher E1 (P < 0.001) and T (P < 0.03) and lower SHBG (P < 0.001) than did women with normal body mass index. Smokers had 17.2% higher median T levels (P = 0.005). CONCLUSION: From the age of 70 years, T and E1 increase with age, despite a steady decline in DHEA. Whether E1 and T are biomarkers for longevity or contribute to healthy aging merits investigation.

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.

Quality of Life for 19,114 participants in the ASPREE (ASPirin in Reducing Events in the Elderly) study and their association with sociodemographic and modifiable lifestyle risk factors.

PURPOSE: To explore the relationship between sociodemographic and lifestyle variables with health-related quality of life (HRQoL) of a large cohort of 'healthy' older individuals. METHODS: The sample included individuals aged 65+ years from Australia (N = 16,703) and the USA (N = 2411) enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) multicentre placebo-controlled trial study and free of cardiovascular disease, dementia, serious physical disabilities or 'fatal' illnesses. The associations with the physical (PCS) and mental component scores (MCS) of HRQoL (SF-12 questionnaire) were explored using multiple linear regression models from data collected at baseline (2010-2014). RESULTS: The adjusted PCS mean was slightly higher in the USA (49.5 ± 9.1) than Australia (48.2 ± 11.6; p < 0.001), but MCS was similar in both samples (55.7 ± 7.5 and 55.7 ± 9.6, respectively; p = 0.603). Males, younger participants, better educated, more active individuals, or those currently drinking 1-2 alcoholic drinks/day showed a better HRQoL (results more evident for PCS than MCS), while current heavy smokers had the lowest physical HRQoL in both countries. Neither age, walking time, nor alcohol intake was associated with MCS in either cohort. CONCLUSIONS: Baseline HRQoL of ASPREE participants was higher than that reported in population-based studies of older individuals, but the associations between sociodemographic and lifestyle variables were consistent with the published literature. As the cohort ages and develops chronic diseases, ASPREE will be able to document HRQoL changes.

Baseline Characteristics of Participants in the ASPREE (ASPirin in Reducing Events in the Elderly) Study.

BACKGROUND: There are no primary prevention trials of aspirin with relevant geriatric outcomes in elderly people. ASPirin in Reducing Events in the Elderly (ASPREE) is a placebo-controlled trial of low-dose aspirin that will determine whether 5 years of daily 100-mg enteric-coated aspirin extends disability-free and dementia-free life in a healthy elderly population and whether these benefits outweigh the risks. METHODS: Set in primary care, this randomized double-blind placebo-controlled trial has a composite primary endpoint of death, incident dementia or persistent physical disability. Participants aged 70+ years (non-minorities) or 65+ years (U.S. minorities) were free of cardiovascular disease, dementia, or physical disability and without a contraindication to, or indication for, aspirin. Baseline data include physical and lifestyle, personal and family medical history, hemoglobin, fasting glucose, creatinine, lipid panel, urinary albumin:creatinine ratio, cognition (3MS, HVLT-R, COWAT, SDMT), mood (CES-D-10), physical function (gait speed, grip strength), Katz activities of daily living and quality of life (SF-12). RESULTS: Recruitment ended in December 2014 with 16,703 Australian and 2,411 U.S. participants, a median age of 74 (range 65-98) years and 56% women. Approximately 55% of the U.S. cohort were from minority groups; 9% of the total cohort. Proportions with hypertension, overweight, and chronic kidney disease were similar to age-matched populations from both countries although lower percentages had diabetes, dyslipidemia, and osteoarthritis. DISCUSSION: Findings from ASPREE will be generalizable to a healthier older population in both countries and will assess whether the broad benefits of daily low-dose aspirin in prolonging independent life outweigh the risks.

Mobile telephone use is associated with changes in cognitive function in young adolescents.

As part of the Mobile Radiofrequency Phone Exposed Users' Study (MoRPhEUS), a cross-sectional epidemiological study examined cognitive function in secondary school students. We recruited 317, 7th grade students (144 boys, 173 girls, median age 13 years) from 20 schools around Melbourne, Australia. Participants completed an exposure questionnaire based on the Interphone study, a computerised cognitive test battery, and the Stroop colour-word test. The principal exposure metric was the total number of reported mobile phone voice calls per week. Linear regression models were fitted to cognitive test response times and accuracies. Age, gender, ethnicity, socio-economic status and handedness were fitted as covariates and standard errors were adjusted for clustering by school. The accuracy of working memory was poorer, reaction time for a simple learning task shorter, associative learning response time shorter and accuracy poorer in children reporting more mobile phone voice calls. There were no significant relationships between exposure and signal detection, movement monitoring or estimation. The completion time for Stroop word naming tasks was longer for those reporting more mobile phone voice calls. The findings were similar for total short message service (SMS, also known as text) messages per week, suggesting these cognitive changes were unlikely due to radiofrequency (RF) exposure. Overall, mobile phone use was associated with faster and less accurate responding to higher level cognitive tasks. These behaviours may have been learned through frequent use of a mobile phone.

Analysis of complaints lodged by patients attending Victorian hospitals, 1997-2001.

OBJECTIVE: To describe complaints by patients and compare rates of complaint in demographic subgroups of patients and hospital departments. DESIGN AND SETTING: Retrospective analysis of complaints made by patients attending 67 hospitals (metropolitan, 25; rural, 42) in Victoria, and lodged with the Victorian Health Complaint Information Program (January 1997 - December 2001). MAIN OUTCOME MEASURES: Demographic characteristics of patients lodging complaints and the hospital department involved; nature and outcome of complaints. RESULTS: From a total of over 13 million patients presenting to hospital during the study period, 19 156 patients or their representatives (mostly their parents, children or spouses) lodged 26 785 "issues" of complaint (overall complaint rate, 1.42 complaints/1000 patients). Significantly more complaints (P < 0.001) were lodged by (or on behalf of) female patients (complaint rate ratio, 1.3; 95% CI, 1.2-1.3), public patients (rate ratio, 2.1; 95% CI, 2.0-2.2) and Australian-born patients (rate ratio, 8.9; 95% CI, 8.3-9.6). The complaint rate for general wards was 6.2/1000 patients (95% CI, 6.1-6.3). Intensive care units had a similar rate of 5.9/1000 (95% CI, 5.4-6.5), but aged-care departments had a significantly higher rate of 45.2/1000 (95% CI, 39.5-51.7), while emergency departments (1.9/1000; 95% CI, 1.8-2.0), operating theatres (1.0/1000; 95% CI, 1.0-1.1), day-procedure units (0.5/1000; 95% CI, 0.5-0.6) and outpatient departments (0.4/1000; 95% CI, 0.4-0.4) had significantly lower rates. Complaints relating to communication (poor attention, discourtesy, rudeness), access to healthcare (no/inadequate service, treatment delays) and treatment (inadequate treatment and nursing care) accounted for 29.2%, 28.5% and 22.5% of complaints, respectively. Most (84.5%) complaints were resolved. Apologies or explanations resolved 27.8% and 27.5% of complaints, respectively. CONCLUSION: Interventions to decrease the number of complaints in the areas of communication and access to healthcare need to be implemented. The active use of complaint data for quality-improvement activities is recommended.