Baseline characteristics and age-related macular degeneration in participants of the “ASPirin in Reducing Events in the Elderly” (ASPREE)-AMD trial

Robman, Liubov; Thảo, Lê Thị Phương; Guymer, Robyn H.; Wolfe, Rory; Woods, Robyn L.; Hodgson, Lauren; Phung, James; Makeyeva, Galina; Le-Pham, Y-Anh; Orchard, Suzanne G; Suleiman, Jewhara; Maguire, Emily; Trevaks, Ruth E; Ward, Stéphanie; Riaz, Moeen; Lacaze, Paul; Storey, Elsdon; Abhayaratna, W.; Nelson, Mark; Ernst, Michael E.; Reid, C.; McNeil, John J

doi:10.1016/j.conctc.2020.100667

Cited by 12 publications

(7 citation statements)

References 78 publications

(63 reference statements)

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“…A randomized double-blind clinical trial is currently being conducted to evaluate the potential efficacy of low-dose aspirin in the treatment of presbycusis, 652 . 653 However, aspirin has been reported to increase the risk of gastrointestinal bleeding in healthy elderly individuals. 654 Stem cell therapy is also used in the treatment of presbycusis.…”

Section: Chronic Obstructive Pulmonary Disease (Copd)mentioning

confidence: 99%

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Guo

Huang

Dou

et al. 2022

Sig Transduct Target Ther

244

160

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Aging is a gradual and irreversible pathophysiological process. It presents with declines in tissue and cell functions and significant increases in the risks of various aging-related diseases, including neurodegenerative diseases, cardiovascular diseases, metabolic diseases, musculoskeletal diseases, and immune system diseases. Although the development of modern medicine has promoted human health and greatly extended life expectancy, with the aging of society, a variety of chronic diseases have gradually become the most important causes of disability and death in elderly individuals. Current research on aging focuses on elucidating how various endogenous and exogenous stresses (such as genomic instability, telomere dysfunction, epigenetic alterations, loss of proteostasis, compromise of autophagy, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, deregulated nutrient sensing) participate in the regulation of aging. Furthermore, thorough research on the pathogenesis of aging to identify interventions that promote health and longevity (such as caloric restriction, microbiota transplantation, and nutritional intervention) and clinical treatment methods for aging-related diseases (depletion of senescent cells, stem cell therapy, antioxidative and anti-inflammatory treatments, and hormone replacement therapy) could decrease the incidence and development of aging-related diseases and in turn promote healthy aging and longevity.

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Section: Chronic Obstructive Pulmonary Disease (Copd)mentioning

confidence: 99%

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Guo

Huang

Dou

et al. 2022

Sig Transduct Target Ther

244

160

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“… 21 , 22 Therefore, we investigated associations between the 2 lead SNPs with risk of prevalent AMD in the ASPREE trial, as detected by nonmydriatic color digital images in a subset of 3917 participants in whom both retinal imaging and genetic data were available. 23 In this subcohort, there were 795 cases of early AMD, 623 cases of intermediate AMD, 46 cases of late AMD, and 2453 participants with no signs of AMD at baseline. We found no associations between CETP allele carrier status and any stage of AMD (all P >0.05) (Tables S8 and S9 ).…”

Section: Resultsmentioning

confidence: 99%

“… 21 , 22 We investigated associations between the lead SNPs identified by GWAS with the risk of prevalent AMD in the ASPREE trial population. In a subset of 3917 participants in whom both retinal imaging and genetic data were available, 23 we used logistic regression models, adjusted for age, sex, first 20 PCs, and smoking status, to test associations between carrier status for SNPs of interest and risk of AMD at baseline, detected on nonmydriatic 45° macular images, following methods described previously 23 (Data S1 ). A flowchart showing an overview of the study is shown in Figure 2 .…”

Section: Methodsmentioning

confidence: 99%

Genome‐Wide Association Study of Cardiovascular Resilience Identifies Protective Variation in the CETP Gene

Yu,

Bakshi,

Watts

et al. 2023

JAHA

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Background The risk of atherosclerotic cardiovascular disease (ASCVD) increases sharply with age. Some older individuals, however, remain unaffected despite high predicted risk. These individuals may carry cardioprotective genetic variants that contribute to resilience. Our aim was to assess whether asymptomatic older individuals without prevalent ASCVD carry cardioprotective genetic variants that contribute to ASCVD resilience. Methods and Results We performed a genome‐wide association study using a 10‐year predicted ASCVD risk score as a quantitative trait, calculated only in asymptomatic older individuals aged ≥70 years without prevalent ASCVD. Our discovery genome‐wide association study of N=12 031 ASCVD event‐free individuals from the ASPREE (Aspirin in Reducing Events in the Elderly) trial identified 2 independent variants, rs9939224 ( P <5×10 −8 ) and rs56156922 ( P <10 −6 ), in the CETP (cholesteryl ester transfer protein) gene. The CETP gene is a regulator of plasma high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, and lipoprotein(a) levels, and it is a therapeutic drug target. The associations were replicated in the UK Biobank (subpopulation of N=13 888 individuals aged ≥69 years without prevalent ASCVD). Carriers of the identified CETP variants (versus noncarriers) had higher plasma high‐density lipoprotein cholesterol levels, lower plasma low‐density lipoprotein cholesterol levels, and reduced risk of incident ASCVD events during follow‐up. Expression quantitative trait loci analysis predicted the identified CETP variants reduce CETP gene expression across various tissues. Previously reported associations between genetic CETP inhibition and increased risk of age‐related macular degeneration were not observed among the 3917 ASPREE trial participants with retinal imaging and genetic data available. Conclusions Common genetic variants in the CETP gene region are associated with cardiovascular resilience during aging. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01038583.

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“…Of these, 429 (8%) were excluded from further participation due to low quality of baseline macular images or retinal data collection outside the time window for enrollment. A total 4993 participants were included in ASPREE-AMD …”

Section: Methodsmentioning

confidence: 99%

Effect of Low-Dose Aspirin on the Course of Age-Related Macular Degeneration

Robman,

Wolfe,

Woods

et al. 2024

JAMA Ophthalmol

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ImportanceAge-related macular degeneration (AMD) is the leading cause of irreversible vision loss in old age. There is no proven intervention to prevent AMD and, apart from lifestyle, nutritional, and supplement advice, there is no intervention to delay its progression.ObjectiveTo determine the impact of long-term low-dose aspirin on the incidence and progression of AMD.Design, Setting and ParticipantsThe Aspirin in Reducing Events in the Elderly–AMD (ASPREE-AMD) study was an Australian-based substudy of the ASPREE trial, a multicenter, international, randomized, double-masked, placebo-clinical trial investigating the efficacy of low-dose aspirin in prolonging disability-free survival among older individuals. Retinal photography was conducted at baseline from March 2010 to January 2015, then 3 and 5 years after randomization. AMD status was determined using color retinal images and treatment records. Australian participants in ASPREE aged 70 years and older without dementia, independence-limiting physical disability, cardiovascular disease, or chronic illness limiting 5-year survival and with gradable retinal images at baseline were included. Data were analyzed from December 2022 to December 2023.InterventionsAspirin (100 mg daily, enteric coated) or placebo.Main Outcomes and MeasuresIncidence of AMD and progression from early/intermediate to late AMD. Outcomes were analyzed by modified intention-to-treat analysis.ResultsA total of 4993 participants were enrolled in this substudy. Baseline characteristics were similar between groups. At the time of sponsor-determined trial termination, retinal follow-up data were available for 3208 participants, 3171 of whom were analyzed for AMD incidence and progression, with a median (IQR) age of 73.5 (71.5-76.4) years and even sex distribution (1619 [51%] female). Median (IQR) follow-up time was 3.1 (3.0-3.5) years. Cumulative AMD incidence was 195 of 1004 (19.4%) in the aspirin group and 187 of 979 (19.1%) in the placebo group (relative risk [RR], 1.02; 95% CI, 0.85-1.22; P = .86). Cumulative progression from early/intermediate AMD to late AMD was observed in 14 of 615 (2.3%) participants in the aspirin group and 18 of 573 (3.1%) in the placebo group (RR, 0.72; 95% CI, 0.36-1.44; P = .36).Conclusions and RelevanceIn this trial, low-dose aspirin administered for 3 years did not affect the incidence of AMD. The evidence was weaker for progression of AMD due to low number of progressed cases. Overall, these results do not support suggestion that low-dose daily aspirin prevents the development or progression of AMD.Trial Registrationanzctr.org Identifier: ACTRN12613000755730

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Baseline characteristics and age-related macular degeneration in participants of the “ASPirin in Reducing Events in the Elderly” (ASPREE)-AMD trial

Cited by 12 publications

References 78 publications

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Genome‐Wide Association Study of Cardiovascular Resilience Identifies Protective Variation in the CETP Gene

Effect of Low-Dose Aspirin on the Course of Age-Related Macular Degeneration

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