Is CVD a Major Risk Factor for AMD?

That very question was addressed in an editorial (1) appearing in the September issue of the American Journal of Ophthalmology, and the evidence to date suggests that CVD is an important risk factor for AMD. Epidemiologic studies conducted over the past two decades indicate (with the possible exception of diabetes) that all of the traditional cardiovascular risk factors such as smoking, hypertension, elevated cholesterol levels, and higher body mass index (BMI) are associated with AMD risk.

So far, the link between smoking, hypertension and AMD is stronger than that between cholesterol, BMI and AMD, while newer studies suggest that less traditional markers of CVD such as inflammation and endothelial dysfunction are also involved in AMD pathogenesis. Overall, there is good evidence that AMD and CVD share similar risk factors and mechanisms that underlie disease development, according to the editorial.

Are AMD Patients at Greater Risk for CVD?

Conversely, emerging data indicates that the presence of AMD also signals an increased risk of CVD, independent of the effects of age and shared risk factors. “Taken in totality, these newer data suggest that patients with signs of AMD, particularly younger patients, may be at increased risk of CVD”, the editorial concludes.

Newly published findings from The Cardiovascular Health Study (2) provide further support that AMD is associated with underlying systemic vascular disease.

Study Design and Methods

The Cardiovascular Health Study is a population-based prospective cohort study of CVD in adults 65 years of age and older. To examine the associations of AMD with incident coronary heart disease (CHD), AMD was evaluated by fundus photographs in 1,786 white and Afro-American participants free of CHD or 2,228 participants free of stroke, aged 69-97 years.

Early AMD was defined as the presence of soft drusen alone, retinal pigment epithelium (RPE) depigmentation alone, or a combination of soft drusen with increased retinal pigment or RPE depigmentation in the absence of late AMD. Late AMD was defined as the presence of signs of exudative AMD or pure geographic atrophy.

Incident CHD and stroke were ascertained using standardized methods. Participants underwent a
standardized assessment of cardiovascular risk factors, including examiner-administered questionnaires,

electrocardiography, carotid ultrasonography, echocardiography, and blood chemistry profiles.

Results

Of the 1786 persons free of CHD, 303 developed incident CHD over 7 years. The 277 participants with early AMD had a higher cumulative incidence of CHD than participants without early AMD (25.8% vs. 18.9%,
P = 0.001).

The presence of early AMD was associated with a 57% increased risk of CHD, after adjusting for age, gender, race, systolic and diastolic blood pressure, hypertension status, fasting glucose, triglyceride, low-density lipoprotein cholesterol, cigarette smoking, pack years of smoking, and C-reactive protein. Late AMD (n= 25) was not associated with incident CHD. Among 2228 persons at risk, 198 developed incident stroke; neither early nor late AMD was associated with incident stroke.

Comments

The findings suggest that early AMD raises the risk of CHD, though not stroke. According to the authors, the association may be explained by broad underlying pathogenic mechanisms shared with both conditions. For example, atherosclerosis may represent a pathogenic process in AMD development, based on its effects upon the choroid capillaries and extracellular drusen (lipid) deposits. Inflammatory mechanisms seem to be another plausible biological basis that may involve both coronary and retinal circulation.

References

1. Wong TY. Age-related macular degeneration and cardiovascular disease in the era of anti-vascular endothelial growth factor therapies. Am J Ophthalmol 327-329, 2009.
2. Sun C, et al. Age-related macular degeneration and risk of coronary heart disease and stroke: The Cardiovascular Health Study. July 8, 2009 Ophthalmology [Epub ahead of print]