Study links AMD to higher cardiovascular disease mortality in high-risk patients

Australian researchers identified in a recent study an association between age-related macular degeneration (AMD) and cardiovascular disease (CVD): they showed that the presence of AMD predicted an increased risk of all-cause and CVD mortality in patients with a high risk of CVD, even in the early stages of AMD,¹ according to Richard Kha, first author and medical student from the Centre for Vision Research, Westmead Institute for Medical Research, Westmead, New South Wales, Australia.

Kha was joined in this study by researchers from the Department of Cardiology, Westmead Hospital, Westmead, and the Department of Cardiology, Bankstown Hospital, Sydney, both in New South Wales, Australia.

The research team explained that while numerous studies have evaluated the relationship between AMD and CVD, no consensus was reached and the results were inconsistent.^2-10 Because there are no data that evaluated the impact of AMD on mortality in a high CVD risk cohort, they undertook a prospective cohort study that included 1,545 patients who presented with acute coronary syndrome.

Importantly, they emphasized the high impact the two diseases have. AMD affects the central retina¹¹ resulting in an increased risk of falls,¹² fractures,¹³ depression,¹⁴ and loss of independence.¹⁵

CVD is the leading cause of mortality despite advances in cardiac diagnosis and management and accounts for in excess of 30% of all deaths globally.¹⁶

“It has been hypothesized,” they noted, “that AMD shares a similar risk profile to CVD.^17,18 Many CVD risk factors that lead to shorter survival, such as advanced age, smoking, obesity, ethnicity, hypertension, and elevated serum cholesterol levels are also associated with AMD.^17,18

All study patients underwent coronary angiography and fundus photography; the photographs were graded as any, early, and late AMD. The investigators’ stated goal was “to improve the current understanding of 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. They hypothesized that patients with AMD in a high-risk cohort will have an increased risk of CVD-specific mortality.”

What was the relationship between AMD and CVD?

Kha and colleagues reported the presence of any AMD in 107 (6.9%) participants, including those with early (n = 86) and late AMD (n = 21).

“Over 9 years of follow-up, 234 (15.1%) participants had died, including 174 (11.3%) participants from fatal CVD events. After controlling for age, sex, body mass index, total cholesterol, smoking status, history of diabetes, hypertension, myocardial infarction, stroke, and macrovascular coronary artery disease severity using the Gensini score, there was an increased rate of all-cause mortality for those with any AMD (HR, 2.37; 95% confidence interval [CI], 1.54–3.64), early AMD (HR, 2.42; 95% CI, 1.48–3.94), and late AMD (HR, 2.25; 95% CI, 1.08–4.71),” they said.

They also found that any AMD (HR, 2.62; 95% CI, 1.61–4.26) and early AMD (HR, 2.61; 95% CI, 1.50–4.64) also were associated with a greater likelihood of CVD mortality. However, late AMD was not associated with CVD mortality.

Discussing possibilities

Currently, the mechanisms underlying the association between AMD and CVD mortality are not clear.

“It is possible that AMD shares common antecedents with macrovascular diseases such as CVD. Chronic inflammation, oxidative stress, atherosclerosis, and abnormal lipid homeostasis are common biological mechanisms implicated in the development of AMD and CVD.^19,20 In AMD, oxidative stress, inflammation, and complement pathway activation lead to retinal pigment epithelial cell death and drusen formation.²¹ Drusen consist of lipids and apolipoproteins, and the mechanism behind drusen formation is thought to be similar to that of atherosclerotic plaques.²² Oxidized lipids interact with macrophages, initiating an inflammatory cascade resulting in atherosclerosis.²³ The excessive formation of arterial plaques increases the risk of adverse CVD events, such as stroke or fatal myocardial infarction,” the authors theorized.

Other factors are the strong association between genetic variants of complement factors and development of AMD,²⁴ and the activation of the complement pathway that predicts CVD and stroke risk.^25,26 In the systemic vasculature, interactions between oxidative stress, inflammation, and atherosclerosis lead to CVD and its adverse events.²⁷ In addition, the presence of reticular pseudodrusen, which is linked with the Y402H and ARMS2 69S alleles, has also been found to be associated with CVD and higher mortality rates.^28,29

The authors concluded, “AMD is a complex multifactorial disease that shares similar processes with CVD, and the association between AMD and CVD mortality is likely to be a combination of multiple factors rather than a single shared risk factor or biological pathway. Future research should seek to clarify the impact of reticular pseudodrusen and genetic variations in the complement pathway on AMD and CVD events.”

References

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