Risk of anaemia increased among elderly patients taking low-dose aspirin

26th June 2023

The risk of anaemia is higher among patients aged 70 years and older taking a daily dose of 100 mg of enteric-coated aspirin, according to a post hoc analysis of the ASPREE randomised controlled trial.

The Aspirin in Reducing Events in the Elderly (ASPREE) trial was designed to examine whether a daily dose of 100 mg of aspirin would prolong the healthy life span of older adults. While it is recognised that aspirin use in patients without cardiovascular disease lowers the risk of cardiac events but increases the risk of a major bleed, whether aspirin use also associated with anaemia is less certain.

Details of the ASPREE trial have been already published and revealed a higher all-cause mortality, largely due to cancer-related deaths, in those assigned to daily aspirin compared to placebo.

In the post hoc analysis of the ASPREE trial, published in the Annals of Internal Medicine, researchers investigated the effect of low-dose aspirin on incident anaemia, haemoglobin and serum ferritin concentrations.

Researchers assessed haemoglobin levels annually and ferritin levels at both baseline and after three years. The primary outcome was defined as incident anaemia but researchers also considered changes in haemoglobin and ferritin levels over time.

Aspirin use and anaemia

A total of 18,153 participants with a mean age of 74 years (44% male) were included, of whom 9,047 were randomised to a daily dose of 100 mg of enteric coated aspirin. Participants were followed for a median of 4.7 years after randomisation.

The incidence of anaemia was significantly higher in the aspirin group (hazard ratio, HR = 1.20, 95% CI 1.12 – 1.29). In addition, haemoglobin concentrations declined more steeply in those assigned to aspirin.

By year three, serum ferritin levels had reduced by an average of 11.5% in the aspirin group compared to those assigned to placebo. A higher proportion of patients assigned to aspirin experienced a major bleeding event compared to placebo (3% vs 2.1%). However, in sensitivity analysis, this difference did not account for the levels of anaemia seen between the two groups.

Overall the results suggested that the risk of developing anaemia within five years was 23.5% among those taking low dose aspirin.

Higher HDL cholesterol associated with increased fracture risk

27th January 2023

A higher HDL cholesterol level has been found to be linked with a greater risk of all types of fracture in those aged 70 years and older

Greater high-density lipoprotein cholesterol (HDL) levels in older people are associated with an increased risk of fractures according to a post hoc analysis of data collected as part of the Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial and the ASPREE fracture substudy by Australian researchers.

Fractures are a common problem with one study estimating that one in 3 women and one in 5 men would be expected to have a minimal trauma fracture after the age of 50. Interestingly, a recent meta-analysis of 12 studies with over 12,000 patients found that HDL cholesterol levels were higher among those with osteoporosis. While HDL cholesterol as a recognised protective role in cardiovascular disease, more recently, it has been found that the lipid also has a role in the pathogenesis of degenerative and metabolic bone diseases in experimental mouse models. Nevertheless, the evidence from human studies is mixed, with one study in over 2000 women finding no association between fracture risk and higher HDL cholesterol, whereas in another, higher HDL particle size was linked to a higher fracture risk.

With an element of uncertainty surrounding the role of lipids and fracture risk, in the current study, the Australian team sought to clarify this connection. They turned to data from the two ASPREE studies and examined the association between plasma HDL cholesterol levels, which were categorised into quintiles, and incident fractures. The researchers used regression analysis, adjusting for various factors including age, gender, physical activity and measures of fragility.

Higher HDL levels and incident fracture risk

A total of 16,264 individuals with a mean age of 75 years (55% female) were included in the analysis and followed for a median of 4 years. During follow-up, 10.2% of the cohort experienced at least one fracture, 4% defined as minimal trauma (i.e., falls from standing height) and the remainder trauma (i.e., falling on stairs, ladders etc).

In fully adjusted models, among those with the highest quintile HDL cholesterol, there was a 33% higher risk of fracture, compared to the lowest quintile (hazard ratio, HR = 1.33, 95% CI 1.14 – 1.54). When stratified by gender, there was still an elevated risk for both men (HR = 1.45) and women (HR = 1.29) with higher HDL levels. There were no important associations between other plasma lipids and fracture risk.

The authors concluded that a higher HDL cholesterol level was associated with an increased fracture risk in older adults, independently of common fracture risk factors.

Citation
Hussain SM et al. Association of Plasma High-Density Lipoprotein Cholesterol Level With Risk of Fractures in Healthy Older Adults. JAMA Cardiol 2023.