The ASPREE Healthy Ageing Biobank: Methodology and participant characteristics.

ASPirin in Reducing Events in the Elderly (ASPREE), a placebo-controlled prevention trial of low dose aspirin, provided the opportunity to establish a biospecimen biobank from initially healthy persons aged 70+ years for future research. The ASPREE Healthy Ageing Biobank (ASPREE Biobank) collected, processed and stored blood and urine samples at -80degC or under nitrogen vapour at two timepoints, three years apart, from a willing subset of Australian ASPREE participants. Written informed consent included separate opt-in questions for biomarker and genetic testing. Fractionated blood and urine were aliquoted into multiple low-volume, barcoded cryotubes for frozen storage within 4 hours of collection. Specially designed and outfitted mobile laboratories provided opportunities for participation by people in regional and rural areas. Detailed, high quality demographic, physiological and clinical data were collected annually through the ASPREE trial. 12,219 participants contributed blood/urine at the first timepoint, 10,617 of these older adults provided 3-year follow-up samples, and an additional 1,712 provided saliva for DNA. The mean participant age was 74 years, 54% were female and 46% lived outside major cities. Despite geographical and logistical challenges, nearly 100% of blood/urine specimens were processed and frozen within 4 hours of collection into >1.4 million aliquots. After a median of 4.7 years, major clinical events among ASPREE Biobank participants included 332 with dementia, 613 with cardiovascular disease events, 1259 with cancer, 357 with major bleeds and 615 had died. The ASPREE Biobank houses and curates a large number of biospecimens collected prior to the clinical manifestations of major disease, and 3-year follow-up samples, all linked to high quality, extensive phenotypic information. This provides the opportunity to identify or validate diagnostic, prognostic and predictive biomarkers, and potentially study biological effectors, of ageing-related diseases or maintenance of older-age good health.

Daily low-dose aspirin and incident type 2 diabetes in community-dwelling healthy older adults: a post-hoc analysis of efficacy and safety in the ASPREE randomised placebo-controlled trial.

BACKGROUND: Inflammation has been implicated in the pathogenesis of diabetes. This study investigated the randomised treatment effect of low-dose aspirin on incident type 2 diabetes and fasting plasma glucose (FPG) concentrations among older adults. METHODS: ASPREE was a double-blind, placebo-controlled trial of daily oral low-dose aspirin. The study population included community-dwelling individuals aged 70 years or older (≥65 years for US minority ethnic groups) in the USA and Australia who were free of cardiovascular disease, independence-limiting physical disability, or dementia. For the post-hoc analysis, we excluded participants with diabetes at baseline or with incomplete or missing incident diabetes data during follow-up. Participants were randomly assigned 1:1 to oral 100 mg daily enteric-coated aspirin or placebo. Incident diabetes was defined as self-reported diabetes, commencement of glucose-lowering medication, or a FPG concentration of 7·0 mmol/L or more assessed at annual follow-up visits among participants with no diabetes at baseline. We used Cox proportional hazards models and mixed-model repeated measures to assess the effect of aspirin on incident diabetes and FPG concentrations in the intention-to-treat population. We assessed major bleeding in participants who had taken at least one dose of study medication. FINDINGS: Between March 10, 2010, and Dec 24, 2014, a total of 16 209 participants were included (8086 [49·9%] randomly assigned to aspirin and 8123 [50·1%] randomly assigned to placebo). During a median follow-up of 4·7 years (IQR 3·6-5·7), 995 (in 6·1% individuals) incident cases of type 2 diabetes were recorded (459 in the aspirin group and 536 in the placebo group). Compared with placebo, the aspirin group had a 15% reduction in risk of incident diabetes (hazard ratio 0·85 [95% CI 0·75 to 0·97]; p=0·013) and a slower rate of increase in FPG concentration at year 5 (between-group difference estimate -0·048 mmol/L [95% CI -0·079 to -0·018]; p=0·0017). Major bleeding (major gastrointestinal bleeding, intracranial bleeding, and clinically significant bleeding at other sites) occurred in 510 (3·2%) of 16 104 participants (300 [3·7%] in the aspirin group and 210 [2·6%] in the placebo group). Compared with placebo, the aspirin group had a 44% increase in risk of major bleeding (hazard ratio 1·44 [95% CI 1·21 to 1·72]; p<0·0001). INTERPRETATION: Aspirin treatment reduced the incidence of type 2 diabetes and slowed the increase in FPG concentration but increased major bleeding among community-dwelling older adults. Given the increasing prevalence of type 2 diabetes among older adults, the potential for anti-inflammatory agents such as aspirin to prevent type 2 diabetes or improve glucose levels warrants further study with a comprehensive assessment of all potential safety events of interest. FUNDING: US National Institute on Aging, US National Cancer Institute, National Health and Medical Research Council of Australia, Monash University, and the Victorian Cancer Agency.

The association of allopurinol with persistent physical disability and frailty in a large community based older cohort.

BACKGROUND: The protective effects of allopurinol on physical function in older adults are not well understood, despite its potential to improve functional gains and reduce sarcopenia. This study aims to determine the association between allopurinol, persistent physical disability, and frailty in older gout patients. METHODS: This analysis used data from a randomized trial in an older cohort, ASPirin in Reducing Events in the Elderly (ASPREE). ASPREE recruited 19,114 participants aged ≥65 years without prior cardiovascular events, dementia, or independence-limiting physical disability at trial enrolment. This analysis examined the association of baseline and time-varying allopurinol use with persistent physical disability and new-onset frailty in participants with gout at baseline (self-report or use of any anti-gout medications). Frailty was measured using the Fried frailty phenotype (score ≥3/5) and a deficit accumulation frailty index (FI) (score >0.21/1.0). Multivariable Cox proportional-hazards models were used for main analyses. RESULTS: This analysis included 1155 gout participants, with 630 taking allopurinol at baseline and 525 not. During a median follow-up of 5.7 years, 113 new allopurinol users were identified. Compared with nonusers, baseline allopurinol use was associated with a significant risk reduction of persistent physical disability (Adjusted HR 0.46, 95% CI 0.23-0.92, p = 0.03). The strength of the association was modestly attenuated in the time-varying analysis (Adjusted HR 0.56, 0.29-1.08, p = 0.08). No significant associations with frailty measures were observed for either baseline allopurinol use (Fried frailty: Adjusted HR 0.83, 0.62-1.12; FI: Adjusted HR 0.96, 0.74-1.24) or time-varying allopurinol use (Fried frailty: Adjusted HR 0.92, 0.69-1.24; FI: Adjusted HR 1.02, 0.78-1.33). CONCLUSIONS: Allopurinol use in older adults with gout is associated with a reduced risk of persistent physical disability but not associated with risk of frailty.

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.

Dietary supplement and complementary and alternative medicine use among older adults in Australia and the United States.

BACKGROUND: Dietary supplement and complementary and alternative medication (CAM) use can contribute to drug interactions, polypharmacy, nonadherence with prescription medications, and healthcare expenses, whereas evidence supporting benefits of using these products is sparse. There is a lack of current published literature describing the patterns or predictors of their use in community-dwelling older adults. MATERIALS AND METHODS: We performed a cross-sectional analysis of community-dwelling adults from Australia and the US, aged 70 years and older (65 years for US minorities), enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) study. At study enrollment, eligible participants were required to be without concurrent 5-year life-limiting illness and free of documented evidence of cardiovascular disease, dementia, or significant physical disability. During the final study visit, a questionnaire was administered to collect information about supplement/CAM use. Data from 15,729 participants who completed this questionnaire between January 2017 and January 2018 were analyzed. Descriptive statistics were used to report the prevalence and types of products used. Factors associated with use were determined using multivariate regression. RESULTS: Mean age of respondents was 79.6 years; 56.4% were female, 88.8% were from Australia, 56.5% reported 12 years of education or less, and 98.7% were living at home. Two-thirds (66.2%) of participants reported use of one or more supplement/CAM in the previous month. Products most commonly used included vitamin D (33.8% of participants), fish oil (22.7%), calcium (20.6%), glucosamine (14.8%), and multivitamin (12.9%). Female sex, US residency, higher education, polypharmacy (prescription medications), and frailty (in women) were significantly associated with higher use of supplements/CAMs. CONCLUSIONS: Dietary supplement and CAM use is common among community-dwelling older adults in the United States and Australia. Given the high prevalence of use, collaboration between healthcare providers and older adult patients is important to insure safe and optimal use of these products.

Objectively Assessed Weight Change and All-Cause Mortality among Community-Dwelling Older People.

Later life changes in body weight may be associated with an increased risk of mortality in older adults. The objective of this study was to examine whether weight change over four years was associated with a 17-year mortality risk in older adults. Participants were 1664 community-dwelling adults aged ≥65 years in the longitudinal Enquete de Sante' Psychologique-Risques, Incidence et Traitement (ESPRIT) study. Outcomes were all-cause mortality, cardiovascular disease (CVD) and cancer mortality. Weight change was defined as difference between weight at baseline and 4 years, categorised into: weight stable (±<5% weight change), weight loss (≥5%) and weight gain (≥5%). Association between weight change and mortality risk was evaluated using Cox proportional hazards models. Over 17 years of follow-up (median 15 years), 565 participants died. Compared to stable weight participants, those with ≥ 5% weight loss had an increased risk of all-cause mortality (HR: 1.24, 95% CI: 1.00−1.56, p = 0.05) and CVD mortality (HR: 1.53, 95% CI: 1.10−2.14, p = 0.01), but not cancer mortality (HR: 0.83, 95% CI: 0.50−1.39, p = 0.49). Weight gain of ≥5% was not associated with increased mortality (HR: 1.05, 95% CI: 0.76−1.45, p = 0.74). Weight monitoring in older adults could help identify weight loss at its early stages to better target interventions to maintain nutritional reserve and prevent premature mortality.

Quality of life and associations with health-related behaviours among older adults with increased cardiovascular risk.

BACKGROUND AND AIMS: A better understanding of the relationship between cardiovascular disease risk factors and quality of life (QoL) in older age is needed to inform development of risk reduction strategies. This cross-sectional study investigated the association of QoL with health-related behaviours in older adults at risk of heart failure. METHODS AND RESULTS: Older adults (N = 328) at risk of heart failure residing in Melbourne, Australia, provided data on QoL and health-related behaviours including physical activity, diet, smoking and alcohol consumption. Multiple linear regression modelling was used to examine associations between health-related behaviours, QoL and its constituent domains. After adjustment for age, gender, body mass index and comorbidities, current smoking was found to have a negative association with the mental component score (MCS) of QoL (ß = -0.174, p ≤ 0.01), with a positive association seen between MCS and physical activity (ß = 0.130, p = 0.01). Current alcohol use had a positive association with the physical component score (PCS) (ß = 0.120, p = 0.02) and saturated fat intake consumption had a negative association with the physical functioning domain of QoL (ß = -0.105, p = 0.03) but was not associated with either PCS or MCS. CONCLUSION: Engagement of older adults at increased cardiovascular risk with behavioural risk factor modification using QoL as a driver of change may offer new opportunities to promote healthy ageing. Development of such strategies should consider that for some behaviours which are cardiovascular risk factors (alcohol intake, in particular), the positive association to QoL is complicated and needs further deliberation.

Anticholinergic medication burden and cognitive function in participants of the ASPREE study.

STUDY OBJECTIVE: What is the association between anticholinergic burden and specific domains of cognitive function in older adults who are initially without major cognitive impairment? DESIGN: Post-hoc analysis of longitudinal observational data from the ASPirin in Reducing Events in the Elderly (ASPREE) study. PATIENTS: 19,114 participants from Australia and the United States aged 70 years and older (65 years and older for US minorities) were recruited and followed for a median of 4.7 years. At enrollment, participants were free of known cardiovascular disease, major physical disability, or dementia. MEASUREMENTS: Cognitive assessments administered at baseline and biennially at follow-up visits included the Modified Mini-Mental State examination (3MS), Hopkins Verbal Learning Test-Revised (HVLT-R) delayed recall, Controlled Oral Word Association Test (COWAT), and Symbol Digit Modalities Test (SDMT). Anticholinergic burden was calculated at baseline using the Anticholinergic Cognitive Burden (ACB) scale and grouped as scores of 0 (no burden), 1-2 (low to moderate), or 3+ (high). MAIN RESULTS: Linear mixed effects models were used to assess the relationship between ACB score and cognition over time. After adjusting for sex, age, education, minority status, smoking status, hypertension, diabetes, depression, chronic kidney disease, country, and frailty, participants with a high ACB score had worse performance over time for 3MS (Adjusted [Adj] B=-0.092, P=0.034), HVLT-R delayed recall (Adj B=-0.104, P<0.001), COWAT (Adj B=-0.151, P<0.001), and SDMT (Adj B=-0.129, P=0.026), than participants with an ACB score of 0. A low to moderate ACB score was also associated with worse performance over time for HVLT-R delayed recall (Adj B=-0.037, P=0.007) and COWAT (Adj B=-0.065, P=0.003), compared to those with no ACB. CONCLUSIONS: Anticholinergic burden predicts worse cognitive function over time in initially dementia-free older adults, particularly for executive function (COWAT) and episodic memory (HVLT-R).

Risk factors for asymptomatic echocardiographic abnormalities that predict symptomatic heart failure.

AIMS: Risk factors for asymptomatic echocardiographic abnormalities that predict symptomatic heart failure (HF) may provide insight into early mechanisms of HF pathogenesis. We examined risk factors associated with asymptomatic echocardiographic structural, systolic, and diastolic abnormalities, separately and in combination, and interactions between risk factors, in the prospective community-based SCReening Evaluation of the Evolution of New HF (SCREEN-HF) Study cohort of 3190 participants at increased risk of cardiovascular disease. METHODS AND RESULTS: Inclusion criteria were age ≥ 60 years with one or more of hypertension, diabetes, ischaemic heart disease, valvular heart disease, abnormal heart rhythm, cerebrovascular disease, or renal impairment. Exclusion criteria were known HF, ejection fraction < 50%, or >mild valve abnormality. Structural, systolic, and diastolic echocardiographic abnormalities were defined according to the Atherosclerosis Risk in Communities study criteria, and risk factors for asymptomatic structural, systolic, and diastolic abnormalities were identified using logistic regression analysis. In multivariable analysis, increased body mass index (BMI), non-steroidal anti-inflammatory drug therapy, and alcohol intake were risk factors for isolated structural abnormality, whereas male gender, increased heart rate, atrial fibrillation (AF), angiotensin-converting enzyme inhibitor therapy, and obstructive sleep apnoea were associated with a lower risk. Moreover, male gender, smoking, increased systolic blood pressure, and physical inactivity were risk factors for isolated systolic abnormality, whereas increased pulse pressure and antihypertensive therapy were associated with a lower risk. Furthermore, increased age, blood pressure, amino-terminal pro-B-type natriuretic peptide level, and warfarin therapy (associated with AF) were risk factors for isolated diastolic abnormality, whereas increased heart rate and triglyceride level (associated with BMI) were associated with a lower risk. The association of increased heart rate with lower risk of structural and diastolic abnormalities was independent of ß-blocker therapy. Interactions between risk factors differed for structural, systolic, and diastolic abnormalities. CONCLUSIONS: The different risk factors for asymptomatic structural, systolic, and diastolic abnormalities that predict symptomatic HF, and the interactions between risk factors, illustrate how these structural, systolic, and diastolic abnormalities represent unique trajectories that lead to symptomatic HF. Improved understanding of these trajectories may assist in the design of HF prevention strategies.

Mis-reporting of energy intake among older Australian adults: Prevalence, characteristics, and associations with quality of life.

OBJECTIVES: Mis-reporting is common in dietary assessment, leading to misinterpretation of disease risk and could be important in older adults with increased chronic disease risk. This study investigated the prevalence and characteristics of mis-reporting among older adults and its association with health outcomes including quality of life (QoL). METHODS: The study was conducted in 335 community-dwelling older adults at increased risk for cardiovascular disease, participating in the SCReening Evaluation of the Evolution of New Heart Failure Study dietary substudy. Diet was assessed using 4-day weighed food diaries, QoL measured through Short Form 36, and physical activity assessed using the European Prospective Investigation into Cancer and Nutrition physical activity questionnaire. Dietary mis-reporting was defined based on Goldberg cutoffs, using individual physical activity levels. Odds ratios were determined to establish associations between mis-reporting and health outcomes. RESULTS: The prevalence of mis-reporting among older adults was 49.3%, with 44.5% of women mis-reporting their energy intake. The study found under-reporting of energy to be associated with body mass index, specifically being overweight (odds ratio: 3.08; 95% confidence interval [CI], 1.54-6.15) and obese (odds ratio: 6.60; 95% CI, 3.05-4.26), as well as physical inactivity (odds ratio: 0.24; 95% CI, 0.14-0.43). Only physical inactivity predicted over-reporting of dietary intake (odds ratio: 7.52; 95% CI, 1.57-36.0). CONCLUSIONS: Dietary under-reporting was associated with being overweight, obese, and physically inactive in addition to the absence of comorbidities, reinforcing the need for further research in older adults to factor in dietary mis-reporting for meaningful diet-disease relationship analyses.

Estimating the Productivity Impact of Acute Myeloid Leukemia in Australia Between 2020 and 2029, Using a Novel Work Utility Measure: The Productivity-Adjusted Life Year (PALY).

PURPOSE: Acute myeloid leukemia (AML) is a rare hematologic malignancy accounting for 0.8% of new cancer diagnoses in Australia. High mortality and morbidity affect work productivity through workforce dropout and premature death. This study sought to estimate the productivity loss attributable to AML in the Australian population over 10 years and to estimate the costs of this productivity loss. Productivity was measured using productivity-adjusted life years (PALYs), a similar concept to quality-adjusted life years, but adjusts for the productivity loss attributable to disease, rather than impaired health. MATERIALS AND METHODS: Dynamic life tables modeled the Australian working population (age 15-65 years) between 2020 and 2029. The model population had two cohorts: those with and without AML. Differences in life years, PALYs, and costs represented the health and productivity impact of AML. Secondary analyses evaluated the impact of different scenarios. RESULTS: Over the next 10 years, there will be 7,600 years of life lost and 7,337 PALYs lost because of AML, amounting to Australian dollars (AU$) 1.43 billion in lost gross domestic product ($971 million in US dollars). Secondary analyses highlight potential savings of approximately AU$52 million if survival rates were improved by 20% and almost AU$118 million in savings if the return-to-work rates increased by 20% on the current estimates. CONCLUSION: Our study demonstrates that even in low-incidence cancer, high mortality and morbidity translate to profound impacts on years of life, productivity, and the broader economy. Better treatment strategies are likely to result in significant economic gains. This highlights the value of investing in research for improved therapies.

Development, Relative Validity and Reproducibility of the Aus-SDS (Australian Short Dietary Screener) in Adults Aged 70 Years and Above.

The aim of this study was to assess the relative validity and reproducibility of a six-item Australian Short Dietary Screener (Aus-SDS). The Aus-SDS assessed the daily intake of core food groups (vegetables, fruits, legumes and beans, cereals, protein sources and dairy sources) in 100 Australians (52 males and 48 females) aged ≥70 years. Relative validity was assessed by comparing intakes from the Aus-SDS1 with an average of three 24-hour recalls (24-HRs), and reproducibility using two administrations of the Aus-SDS (Aus-SDS1 and Aus-SDS2). Cohen's kappa statistic between the Aus-SDS1 and 24-HRs showed moderate to good agreement, ranging from 0.44 for fruits and dairy to 0.64 for protein. There was poor agreement for legume intake (0.12). Bland-Altman plots demonstrated acceptable limits of agreement between the Aus-SDS1 and 24-HRs for all food groups. Median intakes obtained from Aus-SDS1 and Aus-SDS2 did not differ. For all food groups, Cohen's kappa statistic ranged from 0.68 to 0.89, indicating acceptable agreement between the Aus-SDS1 and Aus-SDS2. Spearman's correlation coefficient between Aus-SDS1 and 24-HRs across all food groups ranged from 0.64 for fruit to 0.83 for protein. We found the Aus-SDS to be a useful tool in assessing daily intake of core food groups in this population.

Recommended Intake of Key Food Groups and Cardiovascular Risk Factors in Australian Older, Rural-Dwelling Adults.

This study examined the relationship between diet quality scores and cardiometabolic risk factors in regionally-dwelling older Australian adults with increased cardiovascular risk. This study was a cross-sectional analysis of demographic, anthropometric, and cardiometabolic risk factor data from 458 participants of the Cardiovascular Stream of the Hazelwood Health Study. Participants completed a 120 item semi-quantitative food frequency questionnaire. Multivariable linear regression adjusting for age, sex, smoking, physical activity, education, diabetes, and body mass index was used to examine the relationship between diet and cardiometabolic risk factors. Mean (SD) age of participants was 71 (8) years, and 55% were male. More than half of men and women did not meet recommended intakes of fibre, while 60% of men and 42% of women exceeded recommended dietary sodium intakes. Higher diet quality in terms of intake of vegetables, grains, and non-processed meat, as well as intake of non-fried fish, was associated with more favourable cardiometabolic risk profiles, while sugar-sweetened soft drink intake was strongly associated with adverse cardiometabolic risk factor levels. In older, regionally-dwelling adults, dietary public health strategies that address whole grain products, vegetable and fish consumption, and sugar-sweetened soft-drink intake may be of benefit in reducing cardiometabolic risk.

Impact of tobacco use on health and work productivity in Malaysia.

BACKGROUND: The loss of productivity arising from tobacco use in low/middle-income countries has not been well described. We sought to examine the impact of cigarette smoking on population health and work productivity in Malaysia using a recently published measure, the productivity-adjusted life year (PALY). METHODS: A life table model was constructed using published Malaysian demographic and mortality data. Our analysis was limited to male smokers due to the low smoking prevalence in females (1.1%). Male smokers aged 15-64 years were followed up until 65 years or until death. The population attributable risk, health-related quality of life decrements and relative reduction in productivity due to smoking were sourced from published data. The analysis was repeated assuming the cohorts were never smokers, and the differences in outcomes represented the health and productivity burden conferred by smoking. The cost of productivity loss was estimated based on the gross domestic product per equivalent full-time worker in Malaysia. RESULTS: Tobacco use is highly prevalent among working-age males in Malaysia, with 4.2 million (37.5%) daily smokers among men aged between 15 and 64 years. Overall, our model estimated that smoking resulted in the loss of over 2.1 million life years (2.9%), 5.5 million (8.2%) quality-adjusted life years (QALYs) and 3.0 million (4.8%) PALYs. Smoking was estimated to incur RM275.3 billion (US$69.4 billion) in loss of productivity. CONCLUSION: Tobacco use imposes a significant public health and economic burden among working-age males in Malaysia. This study highlights the need of effective public health interventions to reduce tobacco use.

Physical activity participation and the risk of chronic diseases among South Asian adults: a systematic review and meta-analysis.

South Asia specific reviews on the role of physical activity (PA) domains on chronic disease prevention are lacking. This study aimed to systematically review published literature to identify the association between PA domains and chronic diseases and to provide summary estimates of the strength of association. Nine electronic databases were searched using the predefined inclusion criteria which included population (South Asian adults 40 years or older), exposure (PA or sedentary behaviour) and outcome (type 2 diabetes mellitus, breast cancer, colorectal cancer, coronary heart disease, stroke, vascular disease and musculoskeletal diseases and their markers). A random-effects meta-analysis was carried out for cardiometabolic outcomes whereas narrative synthesis was completed for other outcome variables. Inactive or less active South Asian adults were at 31% higher risk of being hypertensive. Likewise, the risk of cardiometabolic outcomes was 1.34 times higher among inactive adults. Household PA was found to have a protective effect  on breast cancer risk. Total and leisure time PA had a protective effect on osteoporosis among males and females respectively. Contemporary studies with a longitudinal design, representative samples, valid and reliable assessment of different domains are needed to establish the role of PA in chronic disease prevention in the region.

Productivity burden of smoking in Australia: a life table modelling study.

OBJECTIVES: This study aimed to examine the impact of smoking on productivity in Australia, in terms of years of life lost, quality-adjusted life years (QALYs) lost and the novel measure of productivity-adjusted life years (PALYs) lost. METHODS: Life table modelling using contemporary Australian data simulated follow-up of current smokers aged 20-69 years until age 70 years. Excess mortality, health-related quality of life decrements and relative reduction in productivity attributable to smoking were sourced from published data. The gross domestic product (GDP) per equivalent full-time (EFT) worker in Australia in 2016 was used to estimate the cost of productivity loss attributable to smoking at a population level. RESULTS: At present, approximately 2.5 million Australians (17.4%) aged between 20 and 69 years are smokers. Assuming follow-up of this population until the age of 70 years, more than 3.1 million years of life would be lost to smoking, as well as 6.0 million QALYs and 2.5 million PALYs. This equates to 4.2% of years of life, 9.4% QALYs and 6.0% PALYs lost among Australian working-age smokers. At an individual level, this is equivalent to 1.2 years of life, 2.4 QALYs and 1.0 PALY lost per smoker. Assuming (conservatively) that each PALY in Australia is equivalent to $A157 000 (GDP per EFT worker in 2016), the economic impact of lost productivity would amount to $A388 billion. CONCLUSIONS: This study highlights the potential health and productivity gains that may be achieved from further tobacco control measures in Australia via application of PALYs, which are a novel, and readily estimable, measure of the impact of health and health risk factors on work productivity.

Physical activity participation and the risk of chronic diseases among South Asian adults: protocol for a systematic review and meta-analysis.

BACKGROUND: Chronic diseases contribute to about half of the adult disease burden in the South Asian region. Meanwhile, physical activity levels are declining despite the global evidence of its role in the prevention of chronic diseases. While there are a plethora of systematic reviews on the effects of physical activity on chronic diseases, there has not yet been a synthesis of the evidence concerning the nature of this relationship among people living in South Asian countries incorporating multiple chronic diseases and a focus on physical activity domains. The aim of this protocol is to describe the rationale and methods for a systematic review of published research to identify the association between physical activity and selected chronic diseases and their markers and analysis of the strength of association with a focus on physical activity domains among South Asian adults 40 years and older. METHODS: Nine electronic databases including Medline, PsycINFO, Embase, CENTRAL, CINAHL Plus, AgeLine, SPORTDiscus, Scopus and Web of Science will be systematically searched for papers reporting the association between physical activity and selected chronic diseases (type 2 diabetes mellitus, breast cancer, colorectal cancer, coronary heart disease, stroke, vascular diseases and musculoskeletal diseases (osteoarthritis, osteoporosis, back and neck pain)) and their markers using predefined search terms. Searches will be limited to peer-reviewed, English language papers with a quantitative design. In addition, a manual search of references of relevant systematic reviews as well as citations and references of eligible studies will also be carried out. The methodological appraisal will be performed using the National Institutes of Health quality assessment checklist for observational studies and the Effective Public Health Practice Project quality assessment tool for intervention studies. The overall quality of evidence for the study outcomes across the study designs will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. The review results will be presented in the form of narrative synthesis, and a random effects meta-analysis is planned depending on the nature of included studies and available data. DISCUSSION: This review will summarise the strength of the association between physical activity and selected chronic diseases and their markers among South Asian adults 40 years or older. The findings will provide an evidence base to guide public health policy and interventions in the South Asian region and to inform future research to address the rising burden of chronic diseases. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018096505.

Risk factors for incident heart failure with preserved or reduced ejection fraction, and valvular heart failure, in a community-based cohort.

Background: The lack of effective therapies for heart failure with preserved ejection fraction (HFpEF) reflects an incomplete understanding of its pathogenesis. Design: We analysed baseline risk factors for incident HFpEF, heart failure with reduced ejection fraction (HFrEF) and valvular heart failure (VHF) in a community-based cohort. Methods: We recruited 2101 men and 1746 women ≥60 years of age with hypertension, diabetes, ischaemic heart disease (IHD), abnormal heart rhythm, cerebrovascular disease or renal impairment. Exclusion criteria were known heart failure, left ventricular ejection fraction <50% or valve abnormality >mild in severity. Median follow-up was 5.6 (IQR 4.6-6.3) years. Results: Median time to heart failure diagnosis in 162 participants was 4.5 (IQR 2.7-5.4) years, 73 with HFpEF, 53 with HFrEF and 36 with VHF. Baseline age and amino-terminal pro-B-type natriuretic peptide levels were associated with HFpEF, HFrEF and VHF. Pulse pressure, IHD, waist circumference, obstructive sleep apnoea and pacemaker were associated with HFpEF and HFrEF; atrial fibrillation (AF) and warfarin therapy were associated with HFpEF and VHF and peripheral vascular disease and low platelet count were associated with HFrEF and VHF. Additional risk factors for HFpEF were body mass index (BMI), hypertension, diabetes, renal dysfunction, low haemoglobin, white cell count and ß-blocker, statin, loop diuretic, non-steroidal anti-inflammatory and clopidogrel therapies, for HFrEF were male gender and cigarette smoking and for VHF were low diastolic blood pressure and alcohol intake. BMI, diabetes, low haemoglobin, white cell count and warfarin therapy were more strongly associated with HFpEF than HFrEF, whereas male gender and low platelet count were more strongly associated with HFrEF than HFpEF. Conclusions: Our data suggest a major role for BMI, hypertension, diabetes, renal dysfunction, and inflammation in HFpEF pathogenesis; strategies directed to prevention of these risk factors may prevent a sizeable proportion of HFpEF in the community. Trial registration number: NCT00400257, NCT00604006 and NCT01581827.

Prediction of 10-year Risk of Incident Heart Failure in Elderly Hypertensive Population: The ANBP2 Study.

BACKGROUND: Multivariable risk prediction models consisting of routinely collected measurements can facilitate early detection and slowing of disease progression through pharmacological and nonpharmacological risk factor modifications. This study aims to develop a multivariable risk prediction model for predicting 10-year risk of incident heart failure diagnosis in elderly hypertensive population. METHODS: The derivation cohort included 6083 participants aged 65 to 84 years at baseline (1995-2001) followed for a median of 10.8 years during and following the Second Australian National Blood Pressure Study (ANBP2). Cox proportional hazards models were used to develop the risk prediction models. Variables were selected using bootstrap resampling method, and Akaike and Bayesian Information Criterion and C-statistics were used to select the parsimonious model. The final model was internally validated using a bootstrapping, and its discrimination and calibration were assessed. RESULTS: Incident heart failure was diagnosed in 319 (5.2%) participants. The final multivariable model included age, male sex, obesity (body mass index > 30kg/m2), pre-existing cardiovascular disease, average visit-to-visit systolic blood pressure variation, current or past smoking. The model has C-statistics of 0.719 (95% CI: 0.705-0.748) in the derivation cohort, and 0.716 (95% CI: 0.701-0.731) after internal validation (optimism corrected). The goodness-of-fit test showed the model has good overall calibration (χ 2 = 1.78, P = 0.94). CONCLUSION: The risk equation, consisting of variables readily accessible in primary and community care settings, allows reliable prediction of 10-year incident heart failure in elderly hypertensive population. Its application for the prediction of heart failure needs to be studied in the community setting to determine its utility for improving patient management and disease prevention.

Incidence of heart failure in 6083 elderly hypertensive patients: the Second Australian National Blood Pressure Study (ANBP2).

AIMS: Hypertension is a known risk factor for the development of heart failure (HF); however, few data are available on the magnitude of short- and long-term progression from hypertension to HF. The present study aims to determine the short- and long-term incidence of HF, and identify factors associated with onset of HF in elderly hypertensive patients. METHODS AND RESULTS: The incidence of HF was measured in 6083 hypertensive patients, in the Second Australian National Blood Pressure Study (ANBP2), followed for a median of 10.8 years (4.1 years during the trial and 6.7 years during post-trial follow-up). A total of 373 cases of HF were identified over 59 581 person-years of follow-up (PY). The overall cumulative incidence of HF was 6.26 per 1000 PY; 5.33 per 1000 PY during the ANBP2 clinical trial and 7.04 per 1000 PY during the post-trial follow-up. HF was 63% higher among men [incidence rate ratios (IRR) 1.63, P < 0.01]. Older age, male sex, obesity, and history of cardiovascular disease independently predicted HF during both the short- and long-term follow-up. In addition, diabetes and smoking were associated with onset of HF in the short-term follow-up, and higher systolic blood pressure in the long-term follow-up. Median survival following diagnosis with HF was 3.94 years, and women (6.06 years) had a survival advantage over men (3.32 years). CONCLUSION: Heart failure is a frequent long-term outcome in treated elderly hypertensive patients. Development of HF was predicted by patient characteristics and co-morbidities, with the effect of some predictors varying over the short- and long-term follow-up.