Prediabetes, diabetes and loss of disability-free survival in a community-based older cohort: a post-hoc analysis of the ASPirin in Reducing Events in the Elderly trial.

BACKGROUND: Evidence for the prognostic implications of hyperglycaemia in older adults is inconsistent. OBJECTIVE: To evaluate disability-free survival (DFS) in older individuals by glycaemic status. METHODS: This analysis used data from a randomised trial recruiting 19,114 community-based participants aged ≥70 years, who had no prior cardiovascular events, dementia and physical disability. Participants with sufficient information to ascertain their baseline diabetes status were categorised as having normoglycaemia (fasting plasma glucose [FPG] < 5.6 mmol/l, 64%), prediabetes (FPG 5.6 to <7.0 mmol/l, 26%) and diabetes (self-report or FPG ≥ 7.0 mmol/l or use of glucose-lowering agents, 11%). The primary outcome was loss of disability-free survival (DFS), a composite of all-cause mortality, persistent physical disability or dementia. Other outcomes included the three individual components of the DFS loss, as well as cognitive impairment-no dementia (CIND), major adverse cardiovascular events (MACE) and any cardiovascular event. Cox models were used for outcome analyses, with covariate adjustment using inverse-probability weighting. RESULTS: We included 18,816 participants (median follow-up: 6.9 years). Compared to normoglycaemia, participants with diabetes had greater risks of DFS loss (weighted HR: 1.39, 95% CI 1.21-1.60), all-cause mortality (1.45, 1.23-1.72), persistent physical disability (1.73, 1.35-2.22), CIND (1.22, 1.08-1.38), MACE (1.30, 1.04-1.63) and cardiovascular events (1.25, 1.02-1.54) but not dementia (1.13, 0.87-1.47). The prediabetes group did not have an excess risk for DFS loss (1.02, 0.93-1.12) or other outcomes. CONCLUSIONS: Among older people, diabetes was associated with reduced DFS, and higher risk of CIND and cardiovascular outcomes, whereas prediabetes was not. The impact of preventing or treating diabetes in this age group deserves closer attention.

The Effects of Statins on Cardiovascular and Inflammatory Biomarkers in Primary Prevention: A Systematic Review and Meta-Analysis.

BACKGROUND: Statins are well-established for their treatment of cardiovascular disease (CVD) due to their cholesterol-lowering effects and potential anti-inflammatory properties. Although previous systematic reviews demonstrate that statins reduce inflammatory biomarkers in the secondary prevention of CVD, none examine their effects on cardiac and inflammatory biomarkers in a primary prevention setting. METHODS: We conducted a systematic review and meta-analysis to examine the effects of statins on cardiovascular and inflammatory biomarkers among individuals without established CVD. The biomarkers included are: cardiac troponin, N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM), soluble E-selectin (sE-selectin) and endothelin-1 (ET-1). A literature search was performed through Ovid MEDLINE, Embase and CINAHL Plus for randomised controlled trials (RCTs) published up to June 2021. RESULTS: Overall, 35 RCTs with 26,521 participants were included in our meta-analysis. Data was pooled using random effects models presented as standardised mean differences (SMD) with 95% confidence intervals (CI). Combining 36 effect sizes from 29 RCTs, statin use resulted in a significant reduction in CRP levels (SMD -0.61; 95% CI -0.91, -0.32; P<0.001). This reduction was observed for both hydrophilic (SMD -0.39; 95% CI -0.62, -0.16; P<0.001) and lipophilic statins (SMD -0.65; 95% CI -1.01, -0.29; P<0.001). There were no significant changes in serum concentrations of cardiac troponin, NT-proBNP, TNF-α, IL-6, sVCAM, sICAM, sE-selectin and ET-1. CONCLUSION: This meta-analysis demonstrates that statin use reduces serum CRP levels in a primary prevention setting for CVD, with no clear effect on the other eight biomarkers studied.

Comparison of statins for primary prevention of cardiovascular disease and persistent physical disability in older adults.

PURPOSE: Recent epidemiological evidence has suggested that use of lipid-lowering medications, particularly statins, was associated with reduced cardiovascular disease (CVD) events and persistent physical disability in healthy older adults. However, the comparative efficacy of different statins in this group remains unclear. This study aimed to compare different forms of statins in their associations with CVD and physical disability in healthy older adults. METHODS: This post hoc analysis included data from 5981 participants aged ≥ 70 years (≥ 65 if US minorities; median age:74.0) followed for a median of 4.7 years, who had no prior CVD events or physical disability and reported using a statin at baseline. The incidence of the composite and components of major adverse cardiovascular events and persistent physical disability were compared across different statins according to their type, potency, and lipophilicity using multivariable Cox proportional-hazards models. RESULTS: Atorvastatin was the most used statin type at baseline (37.9%), followed by simvastatin (29.6%), rosuvastatin (25.5%), and other statins (7.0%, predominantly pravastatin). In comparisons of specific statins according to type and lipophilicity (lipophilic vs. hydrophilic statin), observed differences in all outcomes were small and not statistically significant (all p values > 0.05). High-potency statin use (atorvastatin and rosuvastatin) was marginally associated with lower risk of fatal CVD events compared with low-/moderate-potency statin use (hazard ratio: 0.59; 95% confidence interval: 0.35, 1.00). CONCLUSION: There were minimal differences in CVD outcomes and no significant difference in persistent physical disability between various forms of statins in healthy older adults. Future investigations are needed to confirm our results.

Impact of age at type 2 diabetes mellitus diagnosis on mortality and vascular complications: systematic review and meta-analyses.

AIMS/HYPOTHESIS: Few studies examine the association between age at diagnosis and subsequent complications from type 2 diabetes. This paper aims to summarise the risk of mortality, macrovascular complications and microvascular complications associated with age at diagnosis of type 2 diabetes. METHODS: Data were sourced from MEDLINE and All EBM (Evidence Based Medicine) databases from inception to July 2018. Observational studies, investigating the effect of age at diabetes diagnosis on macrovascular and microvascular diabetes complications in adults with type 2 diabetes were selected according to pre-specified criteria. Two investigators independently extracted data and evaluated all studies. If data were not reported in a comparable format, data were obtained from authors, presented as minimally adjusted ORs (and 95% CIs) per 1 year increase in age at diabetes diagnosis, adjusted for current age for each outcome of interest. The study protocol was recorded with PROSPERO International Prospective Register of Systematic Reviews (CRD42016043593). RESULTS: Data from 26 observational studies comprising 1,325,493 individuals from 30 countries were included. Random-effects meta-analyses with inverse variance weighting were used to obtain the pooled ORs. Age at diabetes diagnosis was inversely associated with risk of all-cause mortality and macrovascular and microvascular disease (all p < 0.001). Each 1 year increase in age at diabetes diagnosis was associated with a 4%, 3% and 5% decreased risk of all-cause mortality, macrovascular disease and microvascular disease, respectively, adjusted for current age. The effects were consistent for the individual components of the composite outcomes (all p < 0.001). CONCLUSIONS/INTERPRETATION: Younger, rather than older, age at diabetes diagnosis was associated with higher risk of mortality and vascular disease. Early and sustained interventions to delay type 2 diabetes onset and improve blood glucose levels and cardiovascular risk profiles of those already diagnosed are essential to reduce morbidity and mortality. Graphical abstract.

Older participant perspectives on permanent study drug discontinuation in an ongoing primary prevention trial of statins.

PURPOSE: Study drug discontinuation is commonplace in clinical trials of older populations. Little is known about why older participants discontinue the study drug. This qualitative study aimed to understand factors contributing to permanent study drug discontinuation among participants aged ≥ 70 years within an ongoing primary prevention trial of statins by exploring their experiences and perceptions. METHODS: Trial participants who had permanently discontinued the study drug within 2 years of randomisation were purposively sampled by age (< 75 and ≥ 75 years) and sex to participate in semi-structured phone interviews between March 2019 and February 2020. Interviews were audio-recorded, transcribed and analysed thematically. RESULTS: Thirty participants were interviewed (21 females; mean age, 77 years), and three themes were identified from the data. Perceived adverse events (AEs) and their effect on daily living (mobility, functional capacity, quality of life) were identified as the major factors leading to the participants permanently discontinuing their study drug, despite an ambiguity about the cause of the AE. For some, concurrent challenging life circumstances further lowered their tolerance to perceived AEs thus making discontinuation more likely. A few discontinuations were attributed to other factors (e.g. GP advice, unrelated illness). CONCLUSION: Among healthy older participants enrolled in a statin trial, perceived AEs and their related impact were key factors contributing to the permanent study drug discontinuation. Addressing anticipated participant-reported AEs and their concerns about drug-related side effects at trial entry, as well as offering timely medical assistance and support when AEs occur, may be useful to reduce drug discontinuation rates.

Predictors of first-year nonadherence and discontinuation of statins among older adults: a retrospective cohort study.

AIMS: The aim of this study was to examine the level of and predictors of statin nonadherence and discontinuation among older adults. METHODS: Among 22 340 Australians aged ≥65 years who initiated statin therapy from January 2014 to December 2015, we estimated the first-year nonadherence (proportion of days covered [PDC] <0.80) and discontinuation (≥90 days without statin coverage) rates. Predictors of nonadherence and discontinuation were examined via multivariable logistic regression. Analyses were performed separately for general beneficiaries (with a higher co-payment; n = 4841) and concessional beneficiaries (with a lower co-payment; n = 17 499). RESULTS: During the one-year follow-up, 55.1% were nonadherent (concessional 52.6%; general beneficiaries 64.2%) and 44.7% discontinued statins (concessional 43.1%; general beneficiaries 50.4%). Among concessional beneficiaries, those aged 75-84 years and ≥85 years were more likely to discontinue than people aged 65-74 years (odds ratio 1.11, 95% confidence interval 1.04-1.19 and 1.38, 1.23-1.54, respectively). Diabetes was associated with an increased likelihood of nonadherence and discontinuation, while hypertension, angina and congestive heart failure were associated with a lower likelihood of nonadherence and discontinuation. Anxiety was associated with an increased likelihood of discontinuation, but polypharmacy (concurrent use of five or more drugs) was associated with a lower likelihood of nonadherence and discontinuation. Statin initiation by a general medical practitioner was associated with both increased likelihood of nonadherence and discontinuation. Similar predictors of nonadherence and discontinuation were identified for the general beneficiaries. CONCLUSIONS: Among older adults prescribed statins, first-year nonadherence and discontinuation are high. Specific population subgroups such as people aged ≥85 years, those with diabetes or anxiety may require additional attention to improve statin adherence.

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.

The Effects of Statins on Physical Activity or Physical Fitness Among Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This review examines the effects of statins on physical activity and/or fitness, as statins can have adverse muscle effects. A search was done of MEDLINE, Embase, and EBMR databases up to July 2018 for randomized controlled trials comparing statin with placebo or control, measuring physical activity and/or fitness in adults. Sixteen randomized controlled trials (total participants [N] = 2,944) were included, 6 randomized controlled trials contributed data for meta-analysis. Random effects meta-analysis examined differences in physical fitness, maximal exercise time (in seconds) in exercise testing, and maximal heart rate (in beats per minute) between statins and control. No significant difference between statin and control for maximal heart rate (mean difference = 2.8 beats per minute, 95% confidence interval [-7.4, 13.0]; p = .59) nor exercise time (mean difference = 82.8 s, 95% confidence interval [-31.9, 197.4]; p = .516) were seen. There were insufficient studies reporting habitual physical activity to perform a meta-analysis. This review found no evidence for an effect of statins on physical activity or fitness, but data availability is limited.

A 10-Year Trend in Statin Use Among Older Adults in Australia: an Analysis Using National Pharmacy Claims Data.

BACKGROUND: Statins have become standard of care in the prevention and treatment of atherosclerotic cardiovascular disease. The objective of this study was to examine the trends in statin use among Australians aged ≥ 65 years for the period 2007-2016. METHODS: Data from the Pharmaceutical Benefits Scheme covering a 10% random sample of the Australian population were analysed. The 1-year prevalence and incidence of statin use were determined for each year, as were the percentage of statin dispensations according to statin type or intensity and the percentage of new users prescribed each statin type or intensity. To describe relative changes, age-sex adjusted rate ratios (RRs) and 95% confidence intervals (CIs) were determined via Poisson regression modelling using 2007 as the reference year. RESULTS: The 1-year prevalence of statin use increased consistently each year from 34.2% in 2007 to 44.1% in 2016 (RR 1.29, 95% CI 1.28-1.31). The 1-year incidence was 68.5 per 1000 in 2007 and 59.0 per 1000 in 2016 (RR 0.87, 95% CI 0.84-0.90). Women were 18% (age-adjusted rate ratio [aRR] 0.82, 95% CI 0.79-0.83) less likely than men to initiate statins across all years. The incidence of statin use was also highest among individuals aged 65-74 years, who were about 15% (sex-adjusted rate ratio [sRR] 1.15, 95% CI 1.13-1.16) and 45% (sRR 1.45, 95% CI 1.44-1.47) more likely to initiate statins than those aged 75-84 and ≥ 85 years, respectively. Atorvastatin was the most commonly dispensed statin across all years. The proportion of new users dispensed high-intensity statins increased year-on-year from 23.6% in 2007 to 30.5% in 2016 (RR 1.26, 95% CI 1.21-1.31). CONCLUSION: The proportion of older adults in Australia using statins has increased over the last decade, although the incidence has declined. Atorvastatin is the most commonly dispensed statin and the use of high intensity statin has increased.

Comparing two methods for delivering clinical trial informed consent information to older adults: singular versus stepped approach.

BACKGROUND: Adapting the informed consent process to the needs of older adults may enhance engagement and willingness to participate in a clinical trial. A key aspect of the process is being provided with written clinical trial information and consent documents and having an opportunity to discuss the information with the researcher. However, there are no guidelines on the most appropriate method for delivering this information to older adults and it is not known whether the delivery method is a facilitator or barrier towards clinical trial participation. AIMS: To compare two delivery methods of informed consent on recruitment, refusal to continue and randomisation rates in a general practice-based clinical trial involving older adults. METHODS: In a matched cohort sub-study as part of the STAtins in Reducing Events in the Elderly clinical trial, 520 participants were allocated into two groups by age, gender and attending general practice location, to receive the trial information and consent form in the mail (Method 1) prior to the first baseline visit or in person (Method 2) at the visit where a comprehensive informed consent process took place. RESULTS: Compared with Method 1, potential participants assigned to Method 2 were more likely to agree to attend the first baseline screening visit (refusal rate 20% vs 13.5%, respectively, p = 0.05). However, there was no significant difference in the proportion of participants recruited into the trial by providing written informed consent at the first baseline screening visit. For each informed consent delivery method, similar proportions of participants refused to take part in the trial by the end of the screening phase. Randomisation rates in the two groups were also similar. Time to conduct the informed consent procedure took significantly longer with Method 2 compared with Method 1 (median time 20 vs 15 min, respectively, p < 0.01). Interest in the research trial topic was the main reason cited (33.4%) for considering trial participation. CONCLUSION: Later delivery of informed consent documents to potential participants in this trial was associated with a small increase in attendance at the first, in person, screening visit. However, the randomisation rate of participants into the trial was not affected by the method and timing of delivery of informed consent information. Similar randomisation rates occurred whether potential participants were mailed informed consent documents prior to the first in person screening visit or were given the information at the screening visit.

Improvements in life expectancy among Australians due to reductions in smoking: Results from a risk percentiles approach.

BACKGROUND: Tobacco smoking is a major burden on the Australian population in terms of health, social and economic costs. Because of this, in 2008, all Australian Governments agreed to set targets to reduce prevalence of smoking to 10 % by 2018 and subsequently introduced several very strong anti-smoking measures. On this backdrop, we estimated in 2012-13 the impact of several scenarios related to reduction of smoking prevalence to 10 % across the entire Australian population and for below specific ages, on improving life expectancy. METHODS: Using the risk percentiles method the Australian Diabetes, Obesity and Lifestyle (AUSDIAB) baseline survey and the Australian Bureau of Statistics (ABS) age-sex specific death counts were analyzed. RESULTS: Amongst men the gains in life expectancy associated with 10 % smoking prevalence are generally greater than those of women with average life expectancy for men increasing by 0.11 to 0.41 years, and for women by 0.12 to 0.29 years. These are at best 54 % and 49 % for men and women of the gains achieved by complete smoking cessation. The gains plateau for interventions targeting those <70 and <80 years. Amongst smokers the potential gains are much greater, with an increase in average life expectancy amongst men smokers of 0.43 to 2.08 years, and 0.73 to 2.05 years amongst women smokers. These are at best 46 % and 38 % for men and women smokers of the gains achieved by complete smoking cessation. CONCLUSION: The estimated optimum gain in life expectancy is consistent with potentially moderate gains which occur when both men and women below 60 years are targeted to reduce smoking prevalence to 10 %.

Statins in the elderly: an answered question?

PURPOSE OF REVIEW: A strong potential exists for greater promotion of statin therapy among the over-70 age group on the basis of their high absolute cardiovascular risk. However, the evidence for this approach is currently unclear. RECENT FINDINGS: Meta-analysis of trials highlights the uncertainty about the efficacy of statins in the prevention of major vascular events and all-cause mortality in the elderly. This stems from inadequate numbers of participants from this age group included in previous randomized clinical trials. Adverse effects of statins are likely to be greater in the elderly, but their frequency is uncertain and their contribution to frailty and loss of independence in the elderly has been little studied. SUMMARY: Real world trials examining the impact of statin therapy in the elderly are now called for.

Vitamin E supplementation and mortality in healthy people: a meta-analysis of randomised controlled trials.

PURPOSE: To evaluate the effect of oral vitamin E supplementation on all-cause mortality in apparently healthy people. METHODS: A systematic review and meta-analysis was conducted on randomised controlled trials (RCTs) with ≥ 6 months of follow up investigating the effect of vitamin E supplementation on healthy adults in developed countries. Electronic databases (MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials) and reference lists of trial reports were searched for RCTs published between 1966 and June 2012. Three investigators assessed eligibility of identified trials. Disagreements were resolved by consensus. Two investigators independently extracted data according to the criteria. RESULTS: There were 18 RCTs identified with 142,219 apparently healthy participants (71,116 in vitamin E intervention groups and 71,103 in control groups) that were included in the final analysis. Fixed effect and random effects analysis of the 18 trials revealed that supplementation with vitamin E was not associated with all-cause mortality (relative risk 1.01, 95% confidence interval 0.97 - 1.05, p = 0.65). Subgroup analyses by type of vitamin E (natural or synthetic), dose or duration of exposure, study design or quality, and pre-specified mortality outcome showed no association with all-cause mortality. CONCLUSIONS: The evidence from pooled analysis of 18 randomised controlled trials undertaken in apparently healthy people shows no effect of vitamin E supplementation at a dose of 23-800 IU/day on all-cause mortality.

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.

Low-Density-Lipoprotein Cholesterol and Mortality Outcomes Among Healthy Older Adults: A Post Hoc Analysis of ASPREE Trial.

BACKGROUND: The prognostic implication of cholesterol levels in older adults remains uncertain. This study aimed to examine the relationship between low-density-lipoprotein cholesterol (LDL-c) and mortality outcomes in older individuals. METHODS: This post hoc analysis examined the associations of LDL-c levels with mortality risks from all-cause, cardiovascular disease (CVD), cancer, and combined non-CVD/noncancer conditions in a cohort of individuals aged ≥65 years from the ASPirin in Reducing Events in the Elderly trial (NCT01038583). At baseline, participants had no diagnosed dementia, physical disability, or CVD, and were not taking lipid-lowering agents. Outcome analyses were performed using multivariable Cox models. RESULTS: We analyzed 12 334 participants (mean age: 75.2 years). Over a median 7-year follow-up, 1 250 died. Restricted cubic splines found a U-shaped relation for LDL-c and all-cause mortality, cancer mortality, and noncancer/non-CVE mortality (nadir: 3.3-3.4 mmol/L); the risk of CVD mortality was similar at LDL-c below 3.3 mmol/L and increased above 3.3 mmol/L. Similar trends were observed in analyses modeling LDL-c by quartiles. When modeling LDL-c as a continuous variable, the risk of all-cause mortality, cancer mortality, and noncancer/non-CVD mortality was decreased by 9%, 16%, and 18%, respectively, per 1-mmol/L higher LDL-c, and the risk of CVD mortality was increased by 19% per 1-mmol/L higher LDL-c. Reduced all-cause and non-CVD/noncancer mortality risks were only significant in males but not females (pinteraction < .05). CONCLUSIONS: There were U-shaped relationships between LDL-c and all-cause mortality, cancer mortality, and noncancer/non-CVD mortality in healthy older adults. Higher LDL-c levels were associated with an increased risk of CVD mortality. Future studies are warranted to confirm our results.

Statins for extension of disability-free survival and primary prevention of cardiovascular events among older people: protocol for a randomised controlled trial in primary care (STAREE trial).

INTRODUCTION: The world is undergoing a demographic transition to an older population. Preventive healthcare has reduced the burden of chronic illness at younger ages but there is limited evidence that these advances can improve health at older ages. Statins are one class of drug with the potential to prevent or delay the onset of several causes of incapacity in older age, particularly major cardiovascular disease (CVD). This paper presents the protocol for the STAtins in Reducing Events in the Elderly (STAREE) trial, a randomised double-blind placebo-controlled trial examining the effects of statins in community dwelling older people without CVD, diabetes or dementia. METHODS AND ANALYSIS: We will conduct a double-blind, randomised placebo-controlled trial among people aged 70 years and over, recruited through Australian general practice and with no history of clinical CVD, diabetes or dementia. Participants will be randomly assigned to oral atorvastatin (40 mg daily) or matching placebo (1:1 ratio). The co-primary endpoints are disability-free survival defined as survival-free of dementia and persistent physical disability, and major cardiovascular events (cardiovascular death or non-fatal myocardial infarction or stroke). Secondary endpoints are all-cause death, dementia and other cognitive decline, persistent physical disability, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, heart failure, atrial fibrillation, fatal and non-fatal cancer, all-cause hospitalisation, need for permanent residential care and quality of life. Comparisons between assigned treatment arms will be on an intention-to-treat basis with each of the co-primary endpoints analysed separately in time-to-first-event analyses using Cox proportional hazards regression models. ETHICS AND DISSEMINATION: STAREE will address uncertainties about the preventive effects of statins on a range of clinical outcomes important to older people. Institutional ethics approval has been obtained. All research outputs will be disseminated to general practitioner co-investigators and participants, published in peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER: NCT02099123.

Demand at the emergency department front door: 10-year trends in presentations.

OBJECTIVES: To measure the increase in volume and age-specific rates of presentations to public hospital emergency departments (EDs), as well as any changes in ED length of stay (LOS); and to describe trends in ED utilisation. DESIGN, PATIENTS AND SETTING: Population-based retrospective analysis of Department of Health public hospital ED data for metropolitan Melbourne for 1999-00 to 2008-09. MAIN OUTCOME MEASURES: Presentation numbers; presentation rates per 1000 person-years; ED LOS. RESULTS: ED presentations increased from 550,662 in 1999-00 to 853,940 in 2008-09. This corresponded to a 32% rise in rate of presentation (95% CI, 29%-35%), an average annual increase of 3.6% (95% CI, 3.4%-3.8%) after adjustment for population changes. Almost 40% of all patients remained in the ED for ≥4 hours in 2008-09, with LOS increasing over time for patients who were more acutely unwell. The likelihood of presentation rose with increasing age, with people aged≥85 years being 3.9 times as likely to present as those aged 35-59 years (95% CI, 3.8-4.0). The volume of older people presenting more than doubled over the decade. They were more likely to arrive by emergency ambulance and were more acutely unwell than 35-59 year olds, with 75% having an LOS≥4 hours and 61% requiring admission in 2008-09. CONCLUSION: The rise in presentation numbers and presentation rates per 1000 person-years over 10 years was beyond that expected from demographic changes. Current models of emergency and primary care are failing to meet community needs at times of acute illness. Given these trends, the proposed 4-hour targets in 2012 may be unachievable unless there is significant redesign of the whole system.