Cardiovascular disease and stroke following cancer and cancer treatment in older adults.

Background: Cancer survivors can be at risk of cardiovascular disease (CVD) because of either their malignancy or its treatment. Although studies linking cancer and CVD exist, few examine risk in older adults, the impact of cancer treatment, or the effect of aspirin on reducing risk in this cohort.

Methods: The authors conducted a secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial to investigate the impact of cancer and cancer treatment on a composite CVD end point comprising hospitalization for heart failure (HHF), myocardial infarction (MI), and stroke.

Author Correction: The immune response to RNA suppresses nucleic acid synthesis by limiting ribose 5-phosphate.

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The immune response to RNA suppresses nucleic acid synthesis by limiting ribose 5-phosphate.

During infection viruses hijack host cell metabolism to promote their replication. Here, analysis of metabolite alterations in macrophages exposed to poly I:C recognises that the antiviral effector Protein Kinase RNA-activated (PKR) suppresses glucose breakdown within the pentose phosphate pathway (PPP). This pathway runs parallel to central glycolysis and is critical to producing NADPH and pentose precursors for nucleotides.

Expanded statistical analysis plan for legacy and long-term effects of aspirin in the ASPREE-XT observational follow-up study of participants in the ASPREE randomized trial.

The ASPREE randomized controlled trial (2010-2017) of 19,114 community-dwelling older adults without cardiovascular disease and significant disability compared daily 100mg aspirin to placebo. A total of 16,317 (93%) of 17,546 surviving and non-withdrawn participants agreed to continue regular study follow-up visits in the post-trial phase, named ASPREE-XT (2017-2024). We present a statistical analysis plan to underpin three main papers to report aspirin effects through to the fourth post-trial ASPREE-XT study visit with focus areas of: (1) death, dementia, and disability, (2) CVD events and bleeding, and (3) cancer.

Association Between CKD and Major Hemorrhage in Older Persons: Data From the Aspirin in Reducing Events in the Elderly Randomized Trial.

Introduction: Data on the association between chronic kidney disease (CKD) and major hemorrhage in older adults are lacking.

Methods: We used data from a double-blind randomized controlled trial of aspirin in persons aged ≥ 70 years with prospective capture of bleeding events, including hemorrhagic stroke and clinically significant bleeding. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.

Molecular associations of response to the new-generation BTK inhibitor zanubrutinib in marginal zone lymphoma.

Using tissue whole exome sequencing (WES) and circulating tumor cell-free DNA (ctDNA), this Australasian Leukaemia & Lymphoma Group translational study sought to characterize primary and acquired molecular determinants of response and resistance of marginal zone lymphoma (MZL) to zanubrutinib for patients treated in the MAGNOLIA clinical trial. WES was performed on baseline tumor samples obtained from 18 patients. For 7 patients, ctDNA sequence was interrogated using a bespoke hybrid-capture next-generation sequencing assay for 48 targeted genes.

Association of metformin, aspirin, and cancer incidence with mortality risk in adults with diabetes.

Background: Metformin and aspirin are commonly co-prescribed to people with diabetes. Metformin may prevent cancer, but in older people (over 70 years), aspirin has been found to increase cancer mortality. This study examined whether metformin reduces cancer mortality and incidence in older people with diabetes; it used randomization to 100 mg aspirin or placebo in the ASPirin in Reducing Events in the Elderly (ASPREE) trial to quantify aspirin's impact on metformin users.

Cognitive trajectories and incident dementia after a cardiovascular event in older adults.

Introduction: Cardiovascular disease (CVD) is a recognized risk factor for dementia. Here we determined the extent to which an incident CVD event modifies the trajectory of cognitive function and risk of dementia.

Methods: 19,114 adults (65+) without CVD or dementia were followed prospectively over 9 years.

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

Introduction: 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.

Combination of gait speed and grip strength to predict cognitive decline and dementia.

Introduction: To determine whether slowed gait and weakened grip strength independently, or together, better identify risk of cognitive decline or dementia.

Methods: Time to walk 3 meters and grip strength were measured in a randomized placebo-controlled clinical trial involving community-dwelling, initially cognitively healthy older adults (N = 19,114).

Results: Over a median 4.

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

Background: The role of aspirin in reducing lipoprotein(a)-mediated atherothrombotic events in primary prevention is not established.

Objectives: This study sought to assess whether low-dose aspirin benefits individuals with elevated plasma lipoprotein(a)-associated genotypes in the setting of primary prevention.

Methods: The 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.

Integrated clinical and genomic evaluation of guadecitabine (SGI-110) in peripheral T-cell lymphoma.

Peripheral T-cell lymphoma (PTCL) is a rare, heterogenous malignancy with dismal outcomes at relapse. Hypomethylating agents (HMA) have an emerging role in PTCL, supported by shared mutations with myelodysplasia (MDS). Response rates to azacitidine in PTCL of follicular helper cell origin are promising.

A multistate model of health transitions in older people: a secondary analysis of ASPREE clinical trial data.

Background: Understanding the nature of transitions from a healthy state to chronic diseases and death is important for planning health-care system requirements and interventions. We aimed to quantify the trajectories of disease and disability in a population of healthy older people.

Methods: We conducted a secondary analysis of data from the ASPREE trial, which was done in 50 sites in Australia and the USA and recruited community-dwelling, healthy individuals who were aged 70 years or older (≥65 years for Black and Hispanic people in the USA) between March 10, 2010, and Dec 24, 2014.

Prognostic Value of a Polygenic Risk Score for Coronary Heart Disease in Individuals Aged 70 Years and Older.

Background: The use of a polygenic risk score (PRS) to improve risk prediction of coronary heart disease (CHD) events has been demonstrated to have clinical utility in the general adult population. However, the prognostic value of a PRS for CHD has not been examined specifically in older populations of individuals aged ≥70 years, who comprise a distinct high-risk subgroup. The objective of this study was to evaluate the predictive value of a PRS for incident CHD events in a prospective cohort of older individuals without a history of cardiovascular events.

A polygenic risk score predicts mosaic loss of chromosome Y in circulating blood cells.

Background: Mosaic loss of Y chromosome (LOY) is the most common somatic change that occurs in circulating white blood cells of older men. LOY in leukocytes is associated with increased risk for all-cause mortality and a range of common disease such as hematological and non-hematological cancer, Alzheimer's disease, and cardiovascular events. Recent genome-wide association studies identified up to 156 germline variants associated with risk of LOY.

The Effect of Low-Dose Aspirin on Frailty Phenotype and Frailty Index in Community-Dwelling Older Adults in the ASPirin in Reducing Events in the Elderly Study.

Background: Frailty is associated with chronic inflammation, which may be modified by aspirin. The purpose of this study was to determine whether low-dose aspirin reduces incident frailty in healthy older adult participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial.

Methods: In the United States and Australia, 19 114 community-dwelling individuals aged ≥70 and older (U.

Protective lipid-lowering variants in healthy older individuals without coronary heart disease.

Objective: Genetic variants that disrupt the function of the (proprotein convertase subtilisin kexin type 9) and (apolipoprotein B)genes result in lower serum low-density lipoprotein cholesterol (LDL-C) levels and subsequently confer protection against coronary heart disease (CHD). The objective of this study was to measure the prevalence and selective advantage of such variants among healthy older individuals without a history of CHD.

Methods: We performed targeted sequencing of the and genes in 13 131 healthy individuals without CHD aged 70 years or older enrolled into the ASPirin in Reducing Events in the Elderly trial.

Predictive Performance of a Polygenic Risk Score for Incident Ischemic Stroke in a Healthy Older Population.

Background And Purpose: Polygenic risk scores (PRSs) can be used to predict ischemic stroke (IS). However, further validation of PRS performance is required in independent populations, particularly older adults in whom the majority of strokes occur.

Methods: We predicted risk of incident IS events in a population of 12 792 healthy older individuals enrolled in the ASPREE trial (Aspirin in Reducing Events in the Elderly).

Effect of Aspirin on Cancer Incidence and Mortality in Older Adults.

Background: ASPirin in Reducing Events in the Elderly, a randomized, double-blind, placebo-controlled trial of daily low-dose aspirin (100 mg) in older adults, showed an increase in all-cause mortality, primarily due to cancer. In contrast, prior randomized controlled trials, mainly involving younger individuals, demonstrated a delayed cancer benefit with aspirin. We now report a detailed analysis of cancer incidence and mortality.

Major GI bleeding in older persons using aspirin: incidence and risk factors in the ASPREE randomised controlled trial.

Objective: There is a lack of robust data on significant gastrointestinal bleeding in older people using aspirin. We calculated the incidence, risk factors and absolute risk using data from a large randomised, controlled trial.

Design: Data were extracted from an aspirin versus placebo primary prevention trial conducted throughout 2010-2017 ('ASPirin in Reducing Events in the Elderly (ASPREE)', n=19 114) in community-dwelling persons aged ≥70 years.

Cancer history and risk factors in healthy older people enrolling in the ASPREE clinical trial.

Background: Cancer is a leading cause of death globally. Given the elevated risk of cancer with age and an ageing population, it is important to understand the changing burden of cancer in older populations. The ASPirin in Reducing Events in the Elderly (ASPREE) study randomised healthy older individuals to 100 mg aspirin or placebo, with clinical outcomes and disability-free survival endpoints.

Genetic Variation in PEAR1, Cardiovascular Outcomes and Effects of Aspirin in a Healthy Elderly Population.

The platelet endothelial aggregation receptor-1 (PEAR1) rs12041331 variant has been identified as a genetic determinant of platelet aggregation in response to antiplatelet therapies, including aspirin. However, association with atherothrombotic cardiovascular events is less clear, with limited evidence from large trials. Here, we tested association of rs12041331 with cardiovascular events and aspirin use in a randomized trial population of healthy older individuals.