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.

Low-dose aspirin use linked to increased risk of serious falls in elderly

18th November 2022

An RCT has found that low-dose aspirin use failed to reduce fracture risk but was associated with higher risk of serious falls in the elderly

Daily low-dose aspirin (100 mg) given to healthy elderly patients failed to reduce the risk of fractures but did increase the risk of a serious fall according to the findings of a randomised, placebo-controlled trial by Australian researchers.

In a 2017 study it was found that, globally, falls resulted in 695,771 deaths and more than 95% of hip fractures are caused by falling. Low-dose aspirin is often taken by elderly patients with cardiovascular disease although interestingly, there is some evidence to suggest that aspirin inhibits osteoclastogenesis by suppressing the activation of NF‑κB and therefore may possess therapeutic potential for use in the prevention and treatment of osteoporosis.

By inhibiting osteoclasts, aspirin may increase bone mineral density and therefore reduce the risk of fractures. In fact, a systematic review of 12 observational studies found that aspirin use was associated with 17% lower odds for any fracture. Nevertheless, to date, no randomised, placebo-controlled trials have examined the potential role of low-dose aspirin as an approach to reduce fracture risk among older adults.

In the present study, the Australian researchers created the ASPREE-FRACTURE study which was actually a sub-study of the Aspirin in Reducing Events in the Elderly trial designed to examine if daily low-dose aspirin use outweigh the risks in older healthy individuals. Participants in the trial received low-dose aspirin (100 mg daily) or matching placebo and the primary outcome was the occurrence of any fracture whereas the secondary outcome was set as a serious fall that resulted in hospital presentation. All participants were free of cardiovascular disease, dementia or physical disability at the start of the study.

Low-dose aspirin and fracture outcomes

A total of 16,703 individuals with a median age of 74 years (55% female) were recruited and randomised to either aspirin (8,322) or placebo and followed-up for a median of 4.6 years.

During follow-up there was no difference in the risk of first (hazard ratio, HR = 0.96, 95% CI -087 – 1.06, p = 0.50) or recurrent (HR = 0.96, 95% CI 0.87 – 1.06, p = 0.40) fracture events. In subgroup analysis based on several factors such as gender, body mass index or frailty, there were no significant differences in the risk of a first fracture event.

However, when researchers looked at the secondary out, 9% of those receiving aspirin compared to 8.2% in the placebo arm, experienced a serious fall, indicating that use of low-dose aspirin used was associated with a significant increase in the risk of such falls (HR = 1.17, 95% CI 1.03 – 1.33, p = 0.01).

The authors concluded that the use of low-dose aspirin provides little favourable benefit in a healthy, older adult population.

Citation
Barker AL et al. Daily Low-Dose Aspirin and Risk of Serious Falls and Fractures in Healthy Older People: A Substudy of the ASPREE Randomized Clinical Trial. JAMA Intern Med 2022.

Intrathoracic bleeding after rib fracture similar for DOACs and vitamin K antagonists

7th January 2022

Intrathoracic bleeding in elderly patients seen in an ED after a rib fracture is not influenced by the type of anticoagulant taken

The incidence of intrathoracic bleeding seen in an emergency department (ED) after elderly patients sustain a rib fracture due to a fall, is similar whether patients have been prescribed a direct oral anticoagulant (DOAC) or a vitamin K antagonist (VKA) such as warfarin. This was the conclusion of a study undertaken by researchers from the Department of Emergency Medicine, Hospital of Merano, Verona, Italy.

Falls are the leading cause of ED presentations in people aged 60 years and older, accounting for almost 50% of all incident injury presentations. Thoracic trauma which is associated with blunt or penetrating injury is a major cause of hospitalisation throughout the world and accounts for 10–15% of all traumas with 23.9% of these patients experiencing one or two rib fractures.

The incidence of intrathoracic bleeding after rib fractures remains uncertain and the extent to which any bleeding is associated with the type of anticoagulation taken is also unclear. For the present study, the researchers wanted to examine whether preinjury treatment with either VKAs or DOACs had an effect on the incidence of complications, such as bleeding, among elderly patients who experienced blunt thoracic trauma after a fall.

They undertook a retrospective, observational study and included patients aged 75 years and older receiving oral anti-coagulants and who were found to have sustained at least one rib fracture due to a blunt chest trauma during their ED evaluation. Patients who trauma was caused by a car accident, who had a penetrating chest trauma, experienced severe changes in consciousness or who were haemodynamically unstable were excluded.

Eligible patients were then divided into two groups: those taking a DOAC and those prescribed a VKA and both clinical and demographic data was collected for all patients. Regression analysis was used to determine which, if any clinical of demographic factors were associated with the risk of bleeding.

Findings

Over a 2-year period, 342 patients with a median age of 84 years (gender not reported) met the eligibility criteria for inclusion, of whom, 38.9% were treated with DOACs. There were a total of 24 (7%) of patients who presented with intrathoracic bleeding of which 17 (5%) required a surgical intervention or died because of their bleeding.

Overall, 4.5% of patients taking a DOAC developed intra-thoracic bleeding after rib fractures compared to 8.6% of those taking a VKA (p = 0.19). In addition, 4.5% of DOAC and 4.3% of VKA patients required surgery or died due to their bleed (p = 0.98).

Using regression analysis, the authors reported that the most significant factors associated with a bleed were age (p = 0.045), the presence of chronic heart failure (p = 0.046), chronic renal failure (p = 0.012), the number of rib fractures (p < 0.001), a high injury severity score (p < 0.001) and dangerous trauma dynamics (p < 0.001). Furthermore, none of these factors were affected by the type of anticoagulant taken.

Commenting on these results, the authors suggested that DOACs and VKAs presented a comparable risk for intra-thoracic bleeding, concluding that the risk of bleeding in the elderly prescribed anticoagulants and sustaining a non-severe trauma appeared to be low.

Citation

Turcato G et al. Safety and differences between direct oral anticoagulants and vitamin K antagonists in the risk of post-traumatic intrathoracic bleeding after rib fractures in elderly patients Emergency Care Journal 2021.

Low dose aspirin used by nearly half of those over 70 for primary prevention

4th January 2022

Low dose aspirin use was found in nearly half of patients over 70 years of age for primary prevention despite recommendations against its use

The use of low dose aspirin as a primary prevention strategy was found in nearly half of patients aged 70 years of age and older despite current recommendations against its use in this age group. This was an important finding of an analysis by researchers from the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Diseases, Baltimore, US.

Low dose aspirin (LDA) has antithrombotic effects and has been used to reduce the incidence of cardiovascular events such as a myocardial infarction as both a primary and secondary preventative strategy.

However, in recent years, the value of LDA for primary prevention, especially in those aged 70 years and older has been questioned, given the increased incidence of major haemorrhage.

US guidance in 2019 from the American College of Cardiology and American Heart Association, states that ‘Low-dose aspirin (75-100 mg orally daily) should not be administered on a routine basis for the primary prevention of ASCVD (atherosclerotic cardiovascular disease) among adults>70 years of age.’

Similarly, the European Society of Cardiology also do not recommend aspirin use in those 70 years of age and older who are free from cardiovascular disease.

Given this clear recommendation against the use of LDA in the elderly, for the present study, the US researchers examined trends in the use of aspirin over the past two decades (1998 to 2019) in both primary and secondary prevention and to determine the factors associated with use in both scenarios.

Data were obtained from the Behavioural Risk Factor Surveillance (BRFSS), which represents a nationally representative telephone survey of adults across the US. The researchers focused on adults aged 40 years and over to examine trends in aspirin use and individuals were given a score of 0 to 5, based on the presence of cardiovascular risk factors.

Findings

Low dose aspirin use increased between 1998 and 2009 from 29% to 37.5% but then decreased from 35.6% (2011) to 33.5% in 2019.

In 2019, 54,388 participants aged 40 years and older responded to questions on aspirin use in BRFSS and overall, 33.5% of them were using the drug. Among those without cardiovascular disease, LDA use was reported by 27.5% for primary prevention and 69.7% for secondary prevention.

However, 45.6% of adults > 70 years of age reported using aspirin as a primary preventative strategy. In addition, 12.6% of aspirin users had a score of 0 (i.e., no cardiovascular risk factors).

Among those without any cardiovascular risk factors, males had a higher odds of primary prevention LDA use (adjusted odds ratio, aOR = 1.60, 95% CI 1.12 – 2.27) as did adults aged 70 years and older (aOR = 3.22, 95% CI 2.27 – 4.55) compared to those aged 40 to 69 years. A further factor associated with a higher odds of aspirin use for primary prevention was healthcare coverage (aOR = 2.28).

The authors concluded that despite declines in overall aspirin use, a significant proportion of elderly patients were prescribed the drug and that given the potential risks, clinicians should discuss these risks with a view to discontinuing the drug.

Citation

Boakye E et al. Aspirin for cardiovascular disease prevention among adults in the United States: Trends, prevalence, and participant characteristics associated with use. Am J Prev Cardiol 2021.