A study recently published in Ophthalmology Retina reported on the association between age-related macular degeneration (AMD) and the risk of all-cause and cardiovascular disease (CVD) mortality in a cohort at high risk of CVD.
Give me some background.
CVD remains the leading cause of mortality, accounting for more than 30% of all deaths globally.
In fact: Previous studies have demonstrated that many CVD risk factors leading to shorter survival are also associated with AMD, including:
- Advanced age
- Smoking
- Obesity
- Hypertension
- Elevated serum cholesterol levels
However: No clear consensus has been reached on the association between CVD and AMD, and there have been inconsistent findings on the link between AMD and all-cause and CVD-specific mortality.
- Consequently: An Australian research team sought to elucidate whether AMD is a useful prognostic indicator for identifying adults with a lower chance of survival in a population that already has a higher baseline risk of mortality.
Now, talk about the study.
In this prospective cohort study, investigators included 1,545 individuals who presented to an Australian tertiary referral hospital for evaluation of acute coronary syndrome from June 2009 to January 2012.
The research team evaluated and graded acute coronary syndrome and AMD using:
- Coronary angiography
- Coronary artery disease (CAD) graded using the Gensini score
- Mydriatic fundus photographs
- Images graded using the Wisconsin grading system into categories of:
- Any AMD
- Early AMD
- Late AMD
- Images graded using the Wisconsin grading system into categories of:
Mortality data was obtained 9 years after the baseline examination through data linkage with the Australian National Death Index.
Findings?
Any AMD was identified in 107 (6.9%) participants, including those with early (n=86) and late AMD (n=21).
Over the 9-year follow-up period, 234 (15.1%) individuals died, including 174 (11.3%) from fatal CVD events.
- Note: Nearly 75% of the deaths were related to CVD.
There remained an increased risk of all-cause mortality for those with AMD even after controlling for confounding factors, such as:
- Age
- Sex
- Body mass index (BMI)
- Total cholesterol
- Smoking status
- History of diabetes
- Hypertension
- Myocardial infarction
- Stroke and macrovascular CVD severity using the Gensini score
Tell me more.
The risk of all-cause mortality due to AMD was as follows:
- Any AMD (hazard ratio [HR]: 2.37, 95% confidence interval [CI] 1.54-3.64)
- Early AMD (HR: 2.42, 95% CI: 1.48-3.94)
- Late AMD (HR: 2.25, 95% CI 1.08-4.71)
In addition: Any AMD (HR: 2.62, 95% CI 1.61-4.26) and early AMD (HR: 2.61, 95% CI 1.50-4.64) were also associated with a greater likelihood of CVD mortality.
- Note: Late AMD was not associated with CVD mortality.
Expert opinion?
“Even in its early stage, AMD could serve as a prognostic tool for those at higher risk of CVD mortality; thus, individuals with high CVD risk profiles may benefit from more intensive monitoring and follow-up to reduce risk of adverse cardiac events,” the study authors noted.
In addition: Because AMD is a complex multifactorial disease that shares similar processes with CVD, the association between AMD and CVD mortality is likely a combination of multiple factors rather than a single shared risk factor or biological pathway.
Limitations?
These included:
- The study cohort was fairly representative of high cardiovascular risk patients, though it may not have been representative of the general AMD population
- There was a low number of participants with late AMD, which likely had insufficient power to detect the relationship between late AMD and mortality—particularly for CVD-related mortality
- Although the research team adjusted for a range of confounding factors, they could not rule out the residual effects of other confounders such as history of falls or severe vision impairment
Take home.
In individuals with a high risk of CVD, the presence of AMD at any stage independently predicted increased all-cause mortality.
- Moreover, any and early AMD increased the risk of CVD mortality.
What this means: While the exact mechanisms underlying this association remain unclear, this potentially reflects shared pathways between AMD and CVD.
Next steps?
Future analysis could elucidate the impact of reticular pseudodrusen and genetic variations in the complement pathway on AMD and CVD events.