ASPirin In Reducing Events In The Elderly Research Articles

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

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

The association between frailty and incident cardiovascular disease events in community-dwelling healthy older adults

Study objectiveThis study examined the association between frailty and incident cardiovascular disease (CVD) events, major adverse cardiovascular events (MACE), and CVD-related mortality. DesignLongitudinal cohort study. SettingThe ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial in Australia and the United States. Participants19,114 community-dwelling older adults (median age 74.0 years; 56.4 % females). InterventionsPre-frailty and frailty were assessed using a modified Fried phenotype and a deficit accumulation Frailty Index (FI) at baseline. Main outcome measuresCVD was defined as a composite of CVD death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for heart failure; MACE included all except heart failure. Cox proportional hazards regression was used to analyze the association between frailty and CVD outcomes over a median follow-up of 4.7 years. ResultsBaseline pre-frail and frail groups had a higher risk of incident CVD events (Hazard Ratio (HR): 1.31; 95 % Confidence Interval (CI): 1.14–1.50 for pre-frail and HR: 1.63; 95 % CI: 1.15–2.32 for frail) and MACE (pre-frail HR: 1.26; 95 % CI: 1.08–1.47 and frail HR: 1.51; 95 % CI: 1.00–2.29) than non-frail participants according to Fried phenotype after adjusting for traditional CVD risk factors. Effect sizes were similar or larger when frailty was assessed with FI; similar results for men and women. ConclusionFrailty increases the likelihood of developing CVD, including MACE, in community-dwelling older men and women without prior CVD events. Screening for frailty using Fried or FI method could help identify community-dwelling older adults without prior CVD events who are more likely to develop CVD, including MACE, and may facilitate targeted preventive measures to reduce their risk.

Associations of body size with all-cause and cause-specific mortality in healthy older adults

In the general population, body mass index (BMI) and waist circumference are recognized risk factors for several chronic diseases and all-cause mortality. However, whether these associations are the same for older adults is less clear. The association of baseline BMI and waist circumference with all-cause and cause-specific mortality was investigated in 18,209 Australian and US participants (mean age: 75.1 ± 4.5 years) from the ASPirin in Reducing Events in the Elderly (ASPREE) study, followed up for a median of 6.9 years (IQR: 5.7, 8.0). There were substantially different relationships observed in men and women. In men, the lowest risk of all-cause and cardiovascular mortality was observed with a BMI in the range 25.0–29.9 kg/m2 [HR25-29.9 vs 21–24.9 kg/m2: 0.85; 95% CI, 0.73–1.00] while the highest risk was in those who were underweight [HRBMI <21 kg/m2 vs BMI 21–24.9 kg/m2: 1.82; 95% CI 1.30–2.55], leading to a clear U-shaped relationship. In women, all-cause mortality was highest in those with the lowest BMI leading to a J-shaped relationship (HRBMI <21 kg/m2 vs BMI 21–24.9 kg/m2: 1.64; 95% CI 1.26–2.14). Waist circumference showed a weaker relationship with all-cause mortality in both men and women. There was little evidence of a relationship between either index of body size and subsequent cancer mortality in men or women, while non-cardiovascular non-cancer mortality was higher in underweight participants. For older men, being overweight was found to be associated with a lower risk of all-cause mortality, while among both men and women, a BMI in the underweight category was associated with a higher risk. Waist circumference alone had little association with all-cause or cause-specific mortality risk.Trial registration ASPREE https://ClinicalTrials.gov number NCT01038583.

In Memoriam: Richard H. Grimm, Jr, MD, MPH, PhD (August 22, 1946-September 8, 2022).

In Memoriam: Richard H. Grimm, Jr, MD, MPH, PhD (August 22, 1946-September 8, 2022).

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

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. 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. 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. 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.

Cancer Treatment Patterns and Factors Affecting Receipt of Treatment in Older Adults: Results from the ASPREE Cancer Treatment Substudy (ACTS).

Cancer treatment planning in older adults is complex and requires careful balancing of survival, quality of life benefits, and risk of treatment-related morbidity and toxicity. As a result, treatment selection in this cohort tends to differ from that for younger patients. However, there are very few studies describing cancer treatment patterns in older cohorts. We used data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial and the ASPREE Cancer Treatment Substudy (ACTS) to describe cancer treatment patterns in older adults. We used a multivariate logistic regression model to identify factors affecting receipt of treatment. Of 1893 eligible Australian and United States (US) participants with incident cancer, 1569 (81%) received some form of cancer treatment. Non-metastatic breast cancers most frequently received treatment (98%), while haematological malignancy received the lowest rates of treatment (60%). Factors associated with not receiving treatment were older age (OR 0.94, 95% CI 0.91-0.96), residence in the US (OR 0.34, 95% CI 0.22-0.54), smoking (OR 0.57, 95% CI 0.40-0.81), and diabetes (OR 0.56, 95% CI 0.39-0.80). After adjustment for treatment patterns in sex-specific cancers, sex did not impact receipt of treatment. This study is one of the first describing cancer treatment patterns and factors affecting receipt of treatment across common cancer types in older adults. We found that most older adults with cancer received some form of cancer treatment, typically surgery or systemic therapy, although this varied by factors such as cancer type, age, sex, and country of residence.

The Association between Frailty and Dementia-Free and Physical Disability-Free Survival in Community-Dwelling Older Adults

Introduction: Frailty is a common geriatric syndrome that adversely impacts health outcomes. This study examined correlates of physical frailty in healthy community-dwelling older adults and studied the effect of frailty on disability-free survival (DFS), defined as survival free of independence-limiting physical disability or dementia. Methods: This is a post hoc analysis of 19,114 community-dwelling older adults (median age: 74.0 years, interquartile range or IQR: 6.1 years) from Australia and the USA enrolled in the “ASPirin in Reducing Events in the Elderly (ASPREE)” clinical trial. Frailty was assessed using a modified Fried phenotype and a deficit accumulation frailty index (FI) utilizing a ratio score derived from 66 items. Multinomial logistic regression was used to examine the correlates of frailty and Cox regression to analyze the association between frailty and DFS (and its components). Results: At study enrollment, 39.0% were prefrail, and 2.2% of participants were frail, according to Fried phenotype. Older age, higher waist circumference, lower education, ethnoracial origin, current smoking, depression, and polypharmacy were associated with prefrailty and frailty according to Fried phenotype and FI. Fried phenotype defined prefrailty and frailty predicted reduced DFS (prefrail: HR: 1.67; 95% CI: 1.50–1.86 and frail: HR: 2.80; 95% CI: 2.27–3.46), affecting each component of DFS including dementia, physical disability, and mortality. Effect sizes were larger, according to FI. Conclusion: Our study showed that prefrailty is common in community-dwelling older adults initially free of cardiovascular disease, dementia, or independence-limiting physical disability. Prefrailty and frailty significantly reduced disability-free survival. Addressing modifiable correlates, like depression and polypharmacy, might reduce the adverse impact of frailty on dementia-free and physical disability-free survival.

Health-related heterogeneity in brain aging and associations with longitudinal change in cognitive function.

Neuroimaging-based 'brain age' can identify individuals with 'advanced' or 'resilient' brain aging. Brain-predicted age difference (brain-PAD) is predictive of cognitive and physical health outcomes. However, it is unknown how individual health and lifestyle factors may modify the relationship between brain-PAD and future cognitive or functional performance. We aimed to identify health-related subgroups of older individuals with resilient or advanced brain-PAD, and determine if membership in these subgroups is differentially associated with changes in cognition and frailty over three to five years. Brain-PAD was predicted from T1-weighted images acquired from 326 community-dwelling older adults (73.8 ± 3.6 years, 42.3% female), recruited from the larger ASPREE (ASPirin in Reducing Events in the Elderly) trial. Participants were grouped as having resilient (n=159) or advanced (n=167) brain-PAD, and latent class analysis (LCA) was performed using a set of cognitive, lifestyle, and health measures. We examined associations of class membership with longitudinal change in cognitive function and frailty deficit accumulation index (FI) using linear mixed models adjusted for age, sex and education. Subgroups of resilient and advanced brain aging were comparable in all characteristics before LCA. Two typically similar latent classes were identified for both subgroups of brain agers: class 1 were characterized by low prevalence of obesity and better physical health and class 2 by poor cardiometabolic, physical and cognitive health. Among resilient brain agers, class 1 was associated with a decrease in cognition, and class 2 with an increase over 5 years, though was a small effect that was equivalent to a 0.04 standard deviation difference per year. No significant class distinctions were evident with FI. For advanced brain agers, there was no evidence of an association between class membership and changes in cognition or FI. These results demonstrate that the relationship between brain age and cognitive trajectories may be influenced by other health-related factors. In particular, people with age-resilient brains had different trajectories of cognitive change depending on their cognitive and physical health status at baseline. Future predictive models of aging outcomes will likely be aided by considering the mediating or synergistic influence of multiple lifestyle and health indices alongside brain age.

Associations between dual‐decline in cognition and gait speed with risk of dementia – results from the ASPREE trial cohort

AbstractBackgroundDual decline in gait speed and cognition is associated with an increased risk of dementia. However, it is unclear if risks are conferred by decline in domain‐specific cognition and gait. We aimed to examine associations between dual decline in gait speed and cognition (global cognition, memory, processing speed and verbal fluency) with risk of dementia.MethodsProspective cohort study. Participants were from the ASPREE (ASPirin in Reducing Events in the Elderly) study, a double‐blind, randomized, placebo‐controlled trial of low dose aspirin in older adults (≥70 years; ≥65 if US minority). Of 19,114 randomized participants, 16,855 (88%) had longitudinal gait and cognitive data. Gait speed was measured at 0, 2, 4, 6 years and close‐out. Cognitive measures included Modified Mini‐Mental State examination (3MS, global cognition), Hopkins Verbal Learning Test‐Revised (HVLT‐R, memory), Symbol Digit Modalities (SDMT, processing speed) and Controlled Oral Word Association Test (COWAT‐F, verbal fluency), assessed at years 0, 1, 3, 5, and close‐out. Participants were classified into four groups: 1) dual decline in gait and cognition; 2) gait decline only; 3) cognitive decline only and 4) non‐decliners. Cognitive decline was defined as membership of the lowest tertile of annual change. Gait decline was defined as decline in gait speed ≥0.05 m/s per year across the study. Dementia (DSM‐IV criteria) was adjudicated by an expert panel using cognitive tests, functional status and clinical records. Cox proportional hazard models were used to estimate risk of dementia adjusting for covariates with death as competing risk.ResultsThe mean age of participants was 75.0 (SD4.4) years. Compared with non‐decliners, risk of dementia was highest in the gait+HVLT‐R decliners (HR 24.7; 95% CI 16.3‐37.3), followed by the gait+3MS (HR 22.2; 95% CI 15.0‐32.9), gait+COWAT‐F (HR 4.66 95%; CI 3.5‐6.3) and gait+SDMT (HR 4.3 95% CI 3.2‐5.8) groups. Dual decliners also had higher risk of dementia than those with either gait or cognitive decline alone for 3MS and HVLT‐R.ConclusionThe combination of decline in gait speed and memory may be the best suited to predict future dementia risk.

The Effect of Clonal Hematopoiesis of Indeterminate Potential (CHIP) and Aspirin on Clinical Outcomes in the Healthy Elderly: A Sub-Study of the Aspirin in Reducing Events in the Elderly (ASPREE) Randomized Controlled Trial

Background Clonal hematopoiesis of indeterminate potential (CHIP) increases with age and is a risk factor for blood cancer, cardiovascular disease (CVD) and other diseases. Recent experimental evidence suggests a causal link between CHIP and CVD, however it is not known whether individuals with CHIP are more likely to benefit from preventive interventions for CVD, such as low-dose aspirin. ASPREE was a double-blind, randomized, placebo-controlled trial comparing 100mg aspirin with placebo on disability-free survival (DFS, composed of death, dementia and physical disability) in initially healthy participants aged ≥70y (≥65y for US minorities of Black and Hispanic background). We measured CHIP in serial blood samples of 11,298 ASPREE participants at baseline and/or year 3 (Y3), and assessed incidence of CHIP and its association with various clinical outcomes. We also examined whether randomization to aspirin had a differential effect on clinical outcomes according to the presence of CHIP at study entry. Methods CHIP was measured in 19 CHIP-associated genes using a custom targeted amplicon-based NGS assay, designed to have a sensitivity of 0.5-2% variant allele fraction (VAF). CHIP was defined as a VAF ≥ 2%. We evaluated the association of CHIP at baseline and Y3, defined as a categorical variable (VAF< 2%, VAF 2-10%, VAF >10%), with clinical outcomes, including DFS, all-cause mortality, cancer and major adverse cardiovascular events (MACE, composed of fatal coronary heart disease, non-fatal myocardial infarction and ischemic stroke) using Y3-landmark Cox proportional hazards models. Risk factors for incident CHIP at Y3 were identified using multivariable logistic regression. Treatment heterogeneity of aspirin was assessed in CHIP subgroups overall and by the most common genes. Results CHIP was present in 3,345/9,926 (34%) participants at baseline and in 3,685/9,812 (39%) at Y3. Of the 5,612 participants without CHIP at baseline who had a Y3 sample, 1,195 (25%) developed CHIP by Y3 (incidence 7% per year). Risk factors for incident CHIP included cancer history (odds ratio [OR] (95% CI) 1.20 [1.02-1.41] P=0.031), and family history of blood cancer (OR 1.50 [1.16-1.93] P=0.002). With regards to clinical outcomes, the presence of CHIP at >10% VAF at baseline (but not VAF 2-10%) was associated with increased all-cause mortality (adjusted [aHR] [95% CI] 1.53 [1.23-1.90] P<0.001). This increased risk appeared to be driven by increased cancer-related mortality (baseline aHR 1.62, [1.19-2.22] p=0.002) more than cardiovascular-related mortality (baseline aHR 1.34 [0.84-2.12] p=0.21). CHIP at >10% at baseline and Y3 was also associated with increased risk of blood cancer (HR 2.48 [1.59-3.88] and 3.24 [1.98-5.30], both P<0.001) and other cancers at Y3 (HR 1.31 [1.02-1.68] P=0.033). After adjustment for potential confounders, this association remained significant for blood cancers (aHR 2.29 [1.44-3.62] p<0.001) but not non-blood cancers (aHR 1.21 [0.98 -1.48] P=0.07). There was no evidence of an association between CHIP at 2-10% and >10% with MACE (aHR 0.91 [0.74-1.11] P=0.34 and aHR 0.73 [0.50-1.07] P=0.11, respectively). There was no evidence of a differential effect of aspirin on DFS according to presence of CHIP at study entry (CHIP HR 0.91 [0.77-1.07], no-CHIP HR 0.88 [0.70-1.10], test for heterogeneity P=0.83) or on MACE (CHIP HR 1.23 [0.85-1.80], no-CHIP HR 0.80 [0.62-1.03] heterogeneity P=0.06) - Figure 1. There was no subgroup difference for the effect of aspirin on incident cancer or cancer-related mortality. Participants with detectable JAK2V617F (VAF > 0.5%, n=123) had worse outcomes if randomized to aspirin, including the primary outcome of DFS (Fig 1). There was no differential effect of aspirin in the JAK2V617F subgroup for MACE (Fig 1). Conclusions This is the largest primary CVD prevention trial to evaluate the intervention effect according to presence of CHIP in healthy elderly. We found CHIP at >10% VAF was associated with increased all-cause mortality, which appeared to be driven largely by increased cancer-related mortality. There was no evidence that participants with CHIP were more likely to benefit from aspirin, including for MACE. Furthermore, aspirin appeared to reduce DFS for individuals with JAK2V617F mutation, although sub-group numbers were small. Our results suggest aspirin should not be used for primary prevention in older individuals with CHIP, including JAK2V617F. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The association of frailty with chronic kidney disease in older adults using the ASPirin in reducing events in the elderly cohort.

Frailty and chronic kidney disease (CKD) both increase with age and are prevalent in older adults. However, studies in older adults examining the relationship between frailty and milder impairments of kidney function are relatively sparse. We examined the cross-sectional association of baseline estimated glomerular filtration rate (eGFR), albuminuria and CKD ([eGFR <60 ml/min/1.73 m2 ] and/or albuminuria [>3.0mg/mmol]) with prefrailty and frailty in the ASPirin in Reducing Events in the Elderly (ASPREE) trial cohort of healthy older participants. Univariate logistic regression models measured the unadjusted odds ratios (OR) and 95% confidence intervals (CI) for prevalent combined prefrailty and frailty (respectively defined as presence of 1-2 or 3+ of 5 modified fried criteria) for the association between CKD, eGFR, albuminuria and other potential risk factors. Multivariable models calculated OR for prefrailty-frailty adjusted for potential confounders and either CKD, (i) eGFR and albuminuria measured as either continuous variables; (ii) or categorical variables; (iii). Of 17 759 eligible participants, 6934 were classified as prefrail, 389 were frail. CKD, eGFR and albuminuria were all associated with combined prefrailty-frailty on univariate analysis. In the multivariable modelling, neither CKD (reduced eGFR and/or albuminuria), nor eGFR (either continuous or categorical variables) were associated with prefrailty-frailty. However, albuminuria, either as a continuous variable (OR [95% CI] 1.07 [1.04-1.10]; p < .001), or categorical variable (OR 1.21 [1.08-1.36]; p=.001) was consistently associated with prefrailty-frailty. The complex relationship between albuminuria (which may be a biomarker for vascular inflammation), ageing, progressive CKD and frailty requires further investigation.

Aspirin, Risk of Colorectal Cancer, & Genetic Risk-Letter.

We read with interest the study by Bakshi and colleagues in which they explored the association between genetic susceptibility to colorectal cancer and aspirin, using a 95-variant colorectal cancer polygenic risk score (PRS) in the participants of ASPREE (ASPirin in Reducing Events in the Elderly) trial (1). The ASPREE trial was a prospective double-blinded, placebo-controlled randomized trial in which 12,609 individuals of European descent ages ≥70 years were enrolled. They concluded that the 95-SNP PRS continues to identify individuals at higher risk of colorectal cancer, including individuals with no family history of colorectal cancer. Recently, Chen and colleagues, using data collected from a large population-based case–control study on colorectal cancer in Germany, analyzed PRS based on 140 colorectal cancer–related risk loci to quantify the genetic risk, reported that regular use of NSAIDs, including aspirin, was associated with significantly reduced colorectal cancer risk regardless of individual genetic profile (2). However, randomization of aspirin treatment in the ASPREE trial was not associated with a reduced incidence of colorectal cancer (P = 0.7).Also, a pooled analysis of two large U.S. cohort studies was published, the Nurses’ Health Study and Health Professionals Follow-up Study, with a total of 94,540 participants ages ≥70 years old (3). The analysis showed that initiating aspirin at an older age was not associated with a lower risk of colorectal cancer. In contrast, those who used aspirin before age 70 years and continued into their 70s or later had a reduced risk of colorectal cancer. A possible explanation is that a beneficial effect of aspirin for colorectal cancer requires at least 5 to 10 years of use (3).Over the last decades, aspirin has been an extensively prescribed drug with antiplatelet and anti-inflammatory effects (4). The mechanism of aspirin's possible anticancer effect is under investigation, but it is believed that it is through inhibiting catalytic enzymes COX-1 and COX-2 involved in prostaglandin synthesis. Therefore, in subjects taking aspirin, gut microbiome composition will shift toward a lower proportion of proinflammatory, colorectal cancer–predisposing bacteria (e.g., Fusobacteria) and a higher proportion of anti-inflammatory, colorectal cancer–protective bacteria (e.g., butyrate-producing bacteria; ref. 5).The recent study by Bakshi and colleagues and other recent high impacted trials on the effect of aspirin on cardiovascular disease and colorectal cancer risks have high translational values into the daily practice. However, there is a need for future preclinical and clinical trials on the impact of aspirin on gut microbiota and their metabolic and immunoregulatory potential.See the Response, p. 703No disclosures were reported.

Aspirin for Primary Prevention of Cardiovascular Events in Relation to Lipoprotein(a) Genotypes

BackgroundThe role of aspirin in reducing lipoprotein(a)-mediated atherothrombotic events in primary prevention is not established. ObjectivesThis study sought to assess whether low-dose aspirin benefits individuals with elevated plasma lipoprotein(a)-associated genotypes in the setting of primary prevention. MethodsThe study analyzed 12,815 genotyped individuals ≥70 years of age of European ancestry and without prior cardiovascular disease events enrolled in the ASPREE (ASPirin in Reducing Events in the Elderly) randomized controlled trial of 100 mg/d aspirin. We defined lipoprotein(a)-associated genotypes using rs3798220-C carrier status and quintiles of a lipoprotein(a) genomic risk score (LPA-GRS). We tested for interaction between genotypes and aspirin allocation in Cox proportional hazards models for incidence of major adverse cardiovascular events (MACE) and clinically significant bleeding. We also examined associations in the aspirin and placebo arms of the trial separately. ResultsDuring a median 4.7 years (IQR: 3.6-5.7 years) of follow-up, 435 MACE occurred, with an interaction observed between rs3798220-C and aspirin allocation (P = 0.049). rs3798220-C carrier status was associated with increased MACE risk in the placebo group (HR: 1.90; 95% CI: 1.11-3.24) but not in the aspirin group (HR: 0.54; 95% CI: 0.17-1.70). High LPA-GRS (vs low) was associated with increased MACE risk in the placebo group (HR: 1.70; 95% CI: 1.14-2.55), with risk attenuated in the aspirin group (HR: 1.41; 95% CI: 0.90-2.23), but the interaction was not statistically significant. In all participants, aspirin reduced MACE by 1.7 events per 1,000 person-years and increased clinically significant bleeding by 1.7 events per 1,000 person-years. However, in the rs3798220-C and high LPA-GRS subgroups, aspirin reduced MACE by 11.4 and 3.3 events per 1,000 person-years respectively, without significantly increased bleeding risk. ConclusionsAspirin may benefit older individuals with elevated lipoprotein(a) genotypes in primary prevention.

Aspirin for Colorectal Cancer Prevention: Age Matters

Further data from the Aspirin in Reducing Events in the Elderly (ASPREE) trial heightens the concern regarding aspirin use for colorectal cancer prevention in elderly subjects. A 95-variant colorectal cancer polygenic risk score (PRS) failed to identify a subset of elderly individuals who could have benefited from aspirin preventive activity. Further research to define predictive biomarkers of aspirin preventive activity is needed. Meanwhile, the use of aspirin for colorectal cancer prevention in the elderly becomes more questionable. See Cancer Prev Res 15(7):447-53.

Prescribed opioid use is associated with adverse cardiovascular outcomes in community-dwelling older persons.

Prescribed opioids are commonly used in the older community-dwelling population for the treatment of chronic pain. Although the harmful effects of opioid abuse and overdose are well understood, little is known about the long-term cardiovascular (CV) effects of prescribed opioids. The aim of this study was to investigate the CV effects associated with prescribed opioid use. A post hoc analysis of participants in the Aspirin in Reducing Events in the Elderly (ASPREE) trial was conducted. Participants in the ASPREE trial included community-dwelling older adults without a prior history of CV disease (CVD). Prescribed opioid use was defined as opioid use at baseline and/or at the first annual visit (AV1). Cox proportional hazards regression was used to calculate hazard ratios and 95% confidence intervals (95% CI) for associations between opioid use and CVD events following AV1. Of the 17 701 participants included (mean age 75.2years, 58.2% female), 813 took opioids either at baseline or at AV1. Over a median follow-up period of 3.58years (IQR 2.50-4.62), CVD events, most notably heart failure hospitalization, occurred in 7% (n=57) amongst opioid users and 4% (n=680) amongst non-opioid users. After adjustment for multiple covariates, opiate use was associated with a 1.67-fold (CI 1.26-2.23, P<0.001) increase in the hazard ratio for CVD events. These findings identify opioid use as a non-traditional risk factor for CVD events in community-dwelling older adults.

USPSTF concludes daily aspirin may hurt more than help, especially for older adults

USPSTF concludes daily aspirin may hurt more than help, especially for older adults

1005 HEALTH-RELATED QUALITY OF LIFE AND FUTURE RISK OF HEALTH OUTCOMES AMONG OLDER ADULTS LIVING IN AUSTRALIA AND THE UNITED STATES

Abstract Introduction Poor health-related quality of life (HRQoL) is associated with higher morbidity and mortality in patient populations. However, whether HRQoL is associated with health outcomes among community-dwelling older people requires further investigation. This study aimed to examine whether HRQoL predicts cognitive decline, dementia, cardiovascular disease (CVD), and mortality in community-dwelling older people living in Australia and the United States. Method A cohort of 19,106 individuals from the ASPirin in Reducing Events in the Elderly (ASPREE) study, aged 65–98 years, initially free of dementia or CVD, and who completed the HRQoL 12-item short form (SF-12, version-2) at baseline (2010–2014), were followed until June 2017. The physical (PCS) and mental component scores (MCS) of SF-12 were generated using standardized norm-based method. Results Over a median of 4.7 years, there were 2,412 cognitive declines, 574 dementia, 922 incident CVD events, and 1,052 deaths. Using Cox proportional-hazard regression adjusted for a range of covariates, every 10-unit increase in PCS was associated with a 6% lower risk of cognitive decline, a 14% lower risk of incident CVD, and 17% lower risk of all-cause mortality, but was not associated with incident dementia. In contrast, higher MCS was only associated with a 12% and 15% lower risk of cognitive decline and dementia, respectively. Findings did not differ by sex. Conclusion Our study provides some of the first evidence that HRQoL can be used in combination with clinical data to identify the future risks of health outcomes among older individuals living in the community. Our findings support the decision of the Australian Commission on Safety and Quality in Health Care to incorporate the SF-12 into the annual Patient-Reported Outcome Measures (PROMs assessment.

Cancer diagnosis, cancer treatment, and association with cardiovascular disease in older adults: Results from ASPREE.

12086 Background: New treatments and early detection measures have led to declines in cancer mortality rates and a growing population of cancer survivors at risk of short- and long-term effects of cancer and cancer treatment (C&amp;CT), including cardiovascular disease (CVD). Although shared risk factors may contribute, several C&amp;CT-related mechanisms including inflammation, treatment-related cardiotoxicity, and coagulation disorders may play a role. There are several studies exploring the link between C&amp;CT and CVD; however, many do not examine risk stratified by cancer type or disease extent, nor investigate the impact of different treatment modalities. Methods: This analysis utilized data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial, an international, multi-center, double-blinded randomized controlled trial that investigated the benefits and risks of aspirin in healthy older people. Multivariate time-dependent Cox regression models (adjusted for clinically significant factors including age, gender, smoking, and metabolic disease) were used to investigate the impact of C&amp;CT on myocardial infarction, stroke, hospitalization for heart failure, and a composite endpoint combining these. Crude incidence rates were estimated using a competing risks regression model. Subgroup analysis was performed by metastatic status, cancer type, and treatment modality. Results: Of the 19,114 ASPREE participants (56% female; median age 75.1 years; median follow up 4.7 years), 1,933 received a post-randomisation cancer diagnosis. Participants with cancer had a greater rate and risk of CVD than those without cancer (15.3 per 1000 person-years (/1000pyrs] vs 10.5/1000pyrs, respectively; Hazard Ratio [HR] = 1.70, 95% Confidence Interval [CI] 1.32-2.10). The greatest increase in risk was seen for hospitalization for heart failure (HR 2.00, 1.18-3.38, 95% CI 1.18-3.38), although increases in risk were also seen for myocardial infarction, all-stroke, and ischaemic stroke. In subgroup analysis by cancer type, blood cancer (HR 2.33, 95% CI 1.25-4.36), lung cancer (HR 2.76, 95% CI 1.23-6.19), and melanoma (HR 1.97, 95% CI 1.02-3.82) were associated with an increased risk of composite CVD. ‘Any cancer treatment’ conferred increased risk of hospitalisation for heart failure (HR 1.78, 95% CI 1.15-2.75), although individual treatment modalities, including cytotoxic chemotherapy, targeted therapy, and radiotherapy conferred increased risks of various cardiovascular outcomes. Conclusions: Our findings indicate that both cancer and anti-cancer treatment confer risk for CVD in the elderly, the magnitude of which varied depending on cancer type and treatment modality. Given the implications of cardiovascular events for quality of life and mortality, these results support the integration of CVD screening and management into routine care for cancer survivors.

How does the onset of physical disability or dementia in older adults affect economic wellbeing and co-payments for health care? the impact of gender

BackgroundExisting studies have illustrated how the onset of physical disability or dementia negatively impacts economic wellbeing and increases out of pocket costs. However, little is known about this relationship in older individuals. Consequently, this study aimed to identify how the onset of physical disability or dementia in older adults affects economic wellbeing and out of pocket costs, and to explore the impact of gender in the context of Australia.MethodsThe data was collected from a large, randomized clinical study, ASPirin in Reducing Events in the Elderly (ASPREE). Two generalized linear models (with and without interaction effects) of total out of pocket costs for those who did and did not develop physical disability or dementia were generated, with adjustment for sociodemographic characteristics at baseline.ResultsWe included 8,568 older Australian individuals with a mean age of 74.8 years and 53.2% being females. After adjustment for the baseline sociodemographic characteristics, the onset of physical disability did statistically significantly raise out of pocket costs (cost ratio = 1.25) and costs among females were 13.1% higher than males.ConclusionsThis study highlights that classifying different types of health conditions to identify the drivers of out of pocket costs and to explore the gender differences in a long-term follow-up is of importance to examine the financial impact on the older population. These negative financial impacts and gender disparities of physical disability and dementia must be considered by policymakers.

Association between hypertension and cutaneous melanoma, and the effect of aspirin: extended follow-up of a large randomised controlled trial

BackgroundThe association between hypertension and melanoma is unclear, and previous analyses of data from the ASPirin in Reducing Events in the Elderly (ASPREE) study demonstrated a reduced number of invasive melanoma events amongst aspirin-exposed hypertensive individuals. MethodsData from the ASPREE study which included (1) the intervention period with a median follow-up of 4.7 years, and (2) the observational period with an additional 2 years follow-up, were combined for this analysis. Logistic regression analyses examined the association between baseline hypertension and treatment status and past melanoma history. Survival analyses examined the association between hypertension and melanoma risk, and the effect of aspirin across hypertension groups. Cox proportional hazards models were used to compare incidence across groups. Results19,114 participants (median age of 74 years) were randomised to daily 100 mg aspirin or placebo. At baseline, hypertension and past melanoma history were recorded in 14,195 and 685 individuals, respectively. After adjustment for confounders, hypertension was significantly associated with past melanoma history (OR=1.34, 95%CI: 1.11–1.62). In a prospective analysis, baseline hypertension was not associated with melanoma risk. However, aspirin was associated with a reduced risk of incident melanoma amongst individuals with uncontrolled hypertension (blood pressure ≥140/90 mmHg; HR=0.63, 95%CI 0.44–0.89), but not in those with controlled hypertension (HR=1.04, 95%CI 0.74–1.46). ConclusionOur results support a reduced melanoma incidence amongst individuals with uncontrolled hypertension exposed to aspirin. Additional studies are required to confirm these findings.