Tuesday October 4 2011
The study cannot show that aspirin use causes sight problems
“People who take a daily dose of aspirin are twice as likely to suffer blindness in later life,” The Daily Telegraph reported. The newspaper said that an international study of over 4,000 elderly people found that daily aspirin users are twice as likely to be diagnosed with a late-stage form of age-related macular degeneration (AMD), a common cause of vision problems in older people.
The study examined the association between aspirin use among older people and AMD. To examine the relationship, researchers tested the eyes of 4,691 adults aged over 65. They also assessed their aspirin use and other medical and lifestyle factors. The researchers found that people who took aspirin daily were more than twice as likely to have a more severe, later stage of AMD. This is known as “wet” AMD, and about 15% of people with AMD develop it. However, the relationship between aspirin use and other stages of AMD was not consistent, with aspirin users being no more likely to have mid-stage AMD.
As this study assessed AMD and aspirin use at the same time, it cannot show that regular aspirin use causes or increases the risk of vision problems. As such, we cannot tell whether aspirin use or vision problems came first. On the evidence provided by this particular study, it is not possible to tell how or whether the two are related, or if some unaccounted for factor is linked to both aspirin use and AMD. For example, aspirin is often prescribed to people with cardiovascular problems, which are themselves associated with smoking and obesity. Both of these are risk factors for AMD.
However, the study does raise questions about whether there could be an association between AMD and regular aspirin use, and the subject warrants further investigation.
Where did the story come from?
The study was carried out by researchers from a number of European centres, including Queen’s University, Belfast, and the London School of Hygiene and Tropical Medicine. It was funded by several organisations including the EU and the Macular Disease Society UK. The study was published in Ophthalmology, the peer-reviewed journal of the American Academy of Ophthalmology.
While headlines tended to overstate the certainty of the study’s findings, both the Daily Mail and the Telegraph pointed out that the study provided no evidence that aspirin use itself caused the participants’ AMD. The newspapers also explained that the relationship may be due to confounding factors. For example, it is possible that AMD was caused by cardiovascular disease, which might typically be treated using aspirin.
Some reports suggested that aspirin use was associated with “blindness”, but this may not reflect the nature of AMD. For example, the degree of visual impairment experienced by people with AMD can vary, and people may have distorted vision rather than no vision at all. Although it can cause severe visual impairment as central vision is lost (affecting everyday activities such as reading and writing), it does not usually affect peripheral vision and generally does not cause profound blindness.
What kind of research was this?
This cross-sectional study of nearly 4,700 older people explored the possible association between use of aspirin and the development of age-related macular degeneration (AMD). This type of study can provide a “snapshot” of health-related issues in a particular population at a certain point in time, but it cannot show cause and effect.
AMD (referred to in the research paper as aging macular disorder) is the most common cause of vision loss in people over 50. It occurs when problems affect the workings of the macula, the spot on the back of the eye that is responsible for central vision. This leads to a gradual loss of central vision, which is needed for detailed work and for tasks like driving or reading. However, it does not normally lead to complete blindness.
There are two main types of AMD, called wet and dry AMD. Dry AMD is the most common form. It usually progresses in stages causing gradual loss of vision over time. About 15% of people with AMD develop wet AMD. It is called wet because it is associated with the growth of abnormal new blood vessels in the retina, which are fragile and prone to bleeding.
The researchers say that while previous research has explored an association between aspirin use and AMD, findings have so far been inconsistent.
What did the research involve?
Between 2000 and 2003, researchers recruited participants aged 65 or over by randomly sampling people from national population registers of seven European countries. Participants were interviewed and given a structured questionnaire. This asked about their aspirin intake and other factors such as socioeconomic background, medical history, smoking and alcohol consumption. Aspirin intake was split into four categories ranging from “never” to “daily use”. Researchers also took into account other health measures, such a body mass index, blood pressure and cholesterol levels.
Participants underwent standard ophthalmic tests for AMD, with their AMD progression graded using a five-stage scale. A score of 0 indicated no AMD and the last stage – stage 4 – was also classified as being either dry or wet (not everyone with late-stage AMD will progress to the wet form). The classification system they used is a recognised international grading system.
The researchers then used standard statistical methods to analyse any association between aspirin use and AMD.
What were the basic results?
Of the initial 4,753 participants, the researchers excluded 62 for whom information on aspirin use was missing. This left 4,691 participants. They found that 36.4% (1,706) had early AMD (stages 0–3) and 3.3% (157) had late AMD (stage 4). Of those with stage 4 AMD, 108 had the wet form and 49 the dry form.
Within the whole study population, 41.2% took aspirin once a month, 7% at least once a week and 17.3% took aspirin daily.
After the researchers had adjusted for potential confounders, they calculated the associations between daily aspirin use and each grade of AMD. They found that there was:
- a 26% increased risk of grade 1 AMD (odds ratio [OR] 1.26, 95% confidence interval [CI] 1.08–1.46)
- a 42% increased risk of grade 2 AMD (OR 1.42, 95% CI 1.18–1.70)
- no increased risk of grade 3 AMD
- a more than double risk of grade 4 wet AMD (OR 2.22, 95% CI 1.61–3.05)
- no increased risk of grade 4 dry AMD
How did the researchers interpret the results?
The researchers say that frequent aspirin use was associated with early AMD and wet late AMD. The risk rose with increasing frequency of aspirin use. They consider that, as aspirin acts on the body in several ways, it is possible that it affects blood vessels in the eye. However, further study of this is needed.
This large study had strengths, including the fact that it took a random sample of the population and established the presence of AMD using validated methods and accepted grading procedures for AMD. The researchers also tried to take account of other factors that could have affected the risk of AMD, in particular cardiovascular disease, smoking and excess weight, which are known risk factors for AMD.
The study’s major limitation is its cross-sectional design, which means it cannot establish cause and effect. As such, while the study has shown associations between aspirin use and vision problems, it cannot tell how or whether the two are directly related, nor which came first. While we could speculate that aspirin somehow causes AMD, it could also be suggested that AMD might be the result of cardiovascular conditions that require treatment with aspirin. Also, although the researchers attempted to adjust their analyses for confounders – including those known to be associated with AMD – other factors may be independently related to both aspirin use and AMD and could account for the observed relationship.
The relationship was also not completely consistent. Aspirin use was not associated with grade 3 AMD or grade 4 dry AMD. This suggests that the findings could possibly have happened by chance.
The limitations of the study’s design, together with the inconsistent results of other studies on the matter, mean it is hard to tell if there truly is an association between regular aspirin use and AMD. However, the possibility of an association seems worthy of further exploration. Ideally, this would involve examining people’s eyes to check they do not have AMD and following them over time to see whether people taking aspirin daily are more likely to develop the condition in the future.