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.

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 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.

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.

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.

Impact of Blood Lipids on 10-Year Cardiovascular Risk in Individuals Without Dyslipidemia and With Low Risk Factor Burden.

OBJECTIVE: To determine the association of plasma lipids with the prevalence of subclinical atherosclerosis and 10-year risk of incident cardiovascular (CV) events among healthy individuals without dyslipidemia and with low risk factor burden. PATIENTS AND METHODS: The analysis (June 24, 2020, through June 12, 2021) included 1204 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) study who were current nonsmokers and did not have CV disease, hypertension (blood pressure ≥130/80 mm Hg or antihypertensive use), diabetes (fasting glucose ≥126 mg/dL or glucose-lowering medication use), and dyslipidemia (low-density-lipoprotein-cholesterol [LDL-C] ≥160 mg/dL, high-density-lipoprotein-cholesterol [HDL-C] <40 mg/dL, total cholesterol [TC] ≥240 mg/dL, triglycerides [TGs] ≥150 mg/dL, or lipid-lowering medication use) at baseline. Associations of lipids with baseline atherosclerosis (presence of carotid plaque and/or coronary calcification) and incident CV events over 10 years were examined using multivariable relative risk regression and Cox regression, respectively. RESULTS: At baseline, participants' median age was 54 (IQR, 49 to 62) years, and 10-year CV risk was 2.7% (IQR, 1.0% to 6.6%); 43.4% had subclinical atherosclerosis. A 1-SD higher LDL-C (23.4 mg/dL), TC (24.7 mg/dL), non-HDL-C (25.3 mg/dL), TC/HDL-C (0.75), and LDL-C/HDL-C (0.66) was associated with a higher prevalence of atherosclerosis of between 6% and 9% (P<.05). For every 1-SD higher LDL-C, non-HDL-C, TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C (0.49), the 10-year incidence of CV events was significantly increased by 40%, 44%, 51%, 49%, and 39%, respectively. For every 1-SD lower HDL-C (13.5 mg/dL), CV risk was increased by 37%. Triglycerides had no association with either outcome. CONCLUSION: Except for TGs, all lipid variables were associated with atherosclerosis and future risk of CV disease among persons without dyslipidemia and with low risk factor burden.

Antihypertensive drug class in combination with lipid lowering treatment for primary prevention of cardiovascular disease in the elderly.

BACKGROUND: Antihypertensives and lipid-lowering therapy (LLT) are often used concurrently. OBJECTIVES: To determine whether there was a difference in clinical outcomes when older patients with LLT were prescribed angiotensin-converting-enzyme-inhibitors (ACE-Is) compared with diuretics. METHODS: This analysis included 648 LLT older users free of cardiovascular disease (CVD) from a trial comparing ACE-I versus diuretic-based therapy. Comparisons were made between LLT+ACE-I (n = 335) and LLT+diuretic groups (n = 313) using multivariable Cox proportional-hazard models. Primary endpoints were all-cause and CVD mortality (in-trial [4.1-year]+post-trial [6.9-year]) and secondary endpoints (in-trial) were the composite of all-cause mortality and first CVD events and its components, CVD mortality and incident diabetes. RESULTS: There were no significant differences between the two groups for the primary endpoints over the in-trial plus post-trial follow-up, nor was there a difference for any secondary outcomes over the in-trial follow-up. CONCLUSIONS: The LLT+ACE-I and LLT+diuretic combinations showed similar effects in CVD-free older individuals. Randomised trials are needed to provide conclusive evidence.

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.

Effect of Statin Therapy on Cognitive Decline and Incident Dementia in Older Adults.

BACKGROUND: The neurocognitive effect of statins in older adults remain uncertain. OBJECTIVES: The aim of this study was to investigate the associations of statin use with cognitive decline and incident dementia among older adults. METHODS: This analysis included 18,846 participants ≥65 years of age in a randomized trial of aspirin, who had no prior cardiovascular events, major physical disability, or dementia initially and were followed for 4.7 years. Outcome measures included incident dementia and its subclassifications (probable Alzheimer's disease, mixed presentations); mild cognitive impairment (MCI) and its subclassifications (MCI consistent with Alzheimer's disease, other MCI); and changes in domain-specific cognition, including global cognition, memory, language and executive function, psychomotor speed, and the composite of these domains. Associations of baseline statin use versus nonuse with dementia and MCI outcomes were examined using Cox proportional hazards models and with cognitive change using linear mixed-effects models, adjusting for potential confounders. The impact of statin lipophilicity on these associations was further examined, and effect modifiers were identified. RESULTS: Statin use versus nonuse was not associated with dementia, MCI, or their subclassifications or with changes in cognitive function scores over time (p > 0.05 for all). No differences were found in any outcomes between hydrophilic and lipophilic statin users. Baseline neurocognitive ability was an effect modifier for the associations of statins with dementia (p for interaction < 0.001) and memory change (p for interaction = 0.02). CONCLUSIONS: In adults ≥65 years of age, statin therapy was not associated with incident dementia, MCI, or declines in individual cognition domains. These findings await confirmation from ongoing randomized trials.

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.

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.

Association of Statin Use With Disability-Free Survival and Cardiovascular Disease Among Healthy Older Adults.

BACKGROUND: There is clinical uncertainty regarding the benefits and harms of prescribing statins in healthy subjects ≥70 years of age. OBJECTIVES: The aim of this study was to examine the association among statins, dementia-free and disability-free survival, and cardiovascular disease (CVD) among healthy older adults using data from the ASPREE (Aspirin in Reducing Events in the Elderly) trial. METHODS: ASPREE was a randomized trial of 19,114 community-dwelling persons in Australia and the United States ≥65 years of age and free of documented CVD, dementia, and disability. Data were collected for those ≥70 years of age, and participants who took statins at baseline were compared with those who did not using Cox proportional hazards regression with inverse probability weighting. The primary outcome, referred to as "disability-free survival," was a composite of all-cause mortality, dementia, or persistent physical disability. Other outcomes included the individual components of the composite outcome, major adverse cardiovascular events, fatal CVD, myocardial infarction, and stroke. RESULTS: Of the 18,096 included participants (median age 74.2 years, 56.0% women), 5,629 took statins at baseline. Over a median follow-up period of 4.7 years, baseline statin use was not associated with disability-free survival or with the risk for all-cause mortality or dementia. However, it was associated with lower risks for physical disability and all cardiovascular outcomes. CONCLUSIONS: Among healthy community-dwelling adults ≥70 years of age, statin use may be beneficial for preventing physical disability and CVD but not beneficial for prolonging disability-free survival or avoiding death or dementia. Future clinical trials are needed to confirm these findings.

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.

The Safety and Tolerability of Statin Therapy in Primary Prevention in Older Adults: A Systematic Review and Meta-analysis.

PURPOSE: The use of statins in the primary prevention of cardiovascular disease (CVD) is increasing in older adults. Nonetheless, good clinical evidence for the safety and tolerability of statins in this population is limited. OBJECTIVE: We aimed to evaluate the safety and tolerability of statins in older adults without overt CVD, focusing on statin-related muscle symptoms. METHODS: Double-blinded randomised controlled trials (RCTs) of statins published before January 2012 were identified from a Cochrane review updated to 2012. Trials published between January 2012 and July 2018 were identified through the CENTRAL, MEDLINE and EMBASE databases. Eligible trials were limited to those including individuals aged ≥ 65 years without overt CVD, who were followed for at least 1 year. Trials had to have reported at least one of the outcomes of interest. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using random-effects models. RESULTS: We identified 11 trials, including 18,192 participants (mean age 73.7 years; 43% females). Compared with placebo, statins neither increased the risks of muscle-related symptoms (RR 1.01; 95% CI 0.90-1.12), total adverse events (AEs) and serious AEs nor led to more total permanent treatment discontinuations and discontinuations due to AEs or specifically due to muscle-related symptoms. No evidence of heterogeneity was observed in any of these outcomes. CONCLUSIONS: This meta-analysis of RCTs found no excess incidence of muscle-related symptoms, total AEs, serious AEs and treatment discontinuations attributable to statin treatment compared with placebo among older adults without CVD.

Association between Dietary Intake and Lipid-Lowering Therapy: Prospective Analysis of Data from Australian Diabetes, Obesity, and Lifestyle Study (AusDiab) Using a Quantile Regression Approach.

Lipid-lowering therapy (LLT) should be accompanied by dietary guidance for cardiovascular risk reduction; however, current evidence suggests sub-optimal dietary behaviors in those on LLT. We examined the associations between the dietary intake of key food groups (vegetables, fruit, cereal, protein, and dairy) and LLT use in Australian adults using quantile regression. We used data from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab), a prospective population-based study of adults aged ≥25 years, conducted over 5 years (1999-2005). Measurements included a 121-item food frequency questionnaire and LLT use. LLT use was categorized as: LLT users (n = 446), commenced LLT (n = 565), ceased LLT (n = 71), and non-users (n = 4813). Less than 1% of the cohort met recommended intakes of all food groups at the baseline and follow up. The median daily dietary intake at the follow up among LLT users was 2.2 serves of vegetables, 1.4 serves of fruit, 2.8 serves of cereal, 2.0 serves of protein, and 1.4 serves of dairy. Adjusted analysis showed no differences across the quantiles of intake of key food groups in LLT users and commenced LLT compared to non-users. The LLT medication status is not associated with any difference in meeting recommended intakes of key foods.

Prevalence and impact of non-cardiovascular comorbidities among older adults hospitalized for non-ST segment elevation acute coronary syndrome.

BACKGROUND: There is a paucity of information on the prognostic importance of non-cardiovascular comorbidities (NCCs) among patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). This study examined the prevalence and impact of NCCs on the length of stay (LOS) and mortality among older adults hospitalized for NSTE-ACS. METHODS: Among 1,488 older adults (mean age 79.4±8.4 years; 62.0% male) hospitalized for NSTE-ACS at a tertiary hospital in Melbourne, Australia, during 2013-2015, we collected data on comorbidities, LOS, and discharge outcomes. Thirteen NCCs were studied. Negative binomial and Cox proportional regression models were applied to examine the association between NCCs and LOS and in-hospital death, respectively. RESULTS: Approximately 53% of the patients had ≥1 NCCs. Diabetes and renal disease as well as anemia and renal disease co-existed more frequently than expected. Compared to having no NCCs, having one NCC was not associated with a significant increase in the likelihood of longer LOS [incidence rate ratio (IRR) 1.07; 95% CI: 0.99-1.15; P=0.085] or in-hospital death [hazard ratio (HR) 1.11; 95% CI: 0.65-1.90; P=0.707]. However, having ≥2 NCCs was associated with 22% and 79% increased likelihood of longer LOS (IRR 1.22, 95% CI: 1.11-1.33; P<0.001) and in-hospital death (HR 1.79, 95% CI: 1.06-3.03; P=0.029), respectively, compared to not having any NCC. Certain NCC dyads [e.g., chronic pulmonary disease (CPD) + renal disease] exhibited multiplicative effect such that their impact on patients' LOS or survival exceeded the sum of the individual effects of the component NCCs. CONCLUSIONS: Over half of older patients hospitalized with NSTE-ACS had NCCs. A higher burden of NCCs correlated with increased LOS and lower survival. Contemporary ACS management guidelines need to recognize and incorporate protocols for the treatment of individuals with multiple chronic conditions to reduce the occurrence of adverse outcomes.

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.

Recent Patterns of Multimorbidity Among Older Adults in High-Income Countries.

Population aging along with the rising burden of chronic medical conditions (CMCs) is challenging the sustainability of health care systems globally. The authors sought to characterize contemporary patterns of multimorbidity among older adults (aged ≥65 years) in high-income countries (HICs). Medline, EMBASE, CINAHL, PsycINFO, and Web of Science were searched in January 2018 for English-language articles that reported the prevalence of multimorbidity (defined as co-occurrence of ≥2 CMCs in an individual without defining an index disease) among older adults in HICs, or the proportions with ≥3 or ≥5 CMCs. Only studies that utilized data collected during January 2007-December 2017 were included. A total of 52 articles (45 studies) that reported data among >60 million older adults in 30 HICs were included. The overall prevalence of multimorbidity was 66.1% (interquartile range [IQR] 54.4-76.6). The multimorbidity prevalence increased with age as well as with the number of CMCs included in the assessment. The prevalence of ≥3 or ≥5 CMCs was 44.2% (IQR 34.0-70.3) and 12.3% (IQR 8.7-19.1), respectively. The multimorbidity prevalence was also higher among females as well as among studies using care-based data rather than self-reported data. The prevalence of hypertension, dyslipidemia, diabetes, pain disorders, depression, heart failure, cancer, and dementia among the older adults was 60.6%, 51.2%, 25.2%, 34.0%, 12.0%, 14.0%, 8.6%, and 8.4%, respectively. The available data suggest a high prevalence of multimorbidity among older adults. There is a need for increased research into understanding the causal mechanisms that underlie multimorbidity toward supporting the development of cost-effective interventions. In addition, the study results reiterate the need for preventive health care to move beyond targeting single diseases in favor of directing efforts toward reducing overall morbidity among this population.