Relationship of AMD and CVD

Various studies have found that cardiovascular disease (CVD) (hypertension, coronary artery disease), CVD risk factors (total serum cholesterol, body mass index), and CVD treatment with statins or anti-hypertensive medications can influence the risk of age-related macular degeneration (AMD). However, the link between CVD, its risk factors or treatment and AMD has not been consistent across different studies.

The association of these factors with AMD was examined in the Women's Health Initiative Sight Examination (WHISE). The recently published findings from WHISE suggest that smoking, use of calcium channel blockers, diabetes and obesity are risk factors for late AMD in women (1). However, the association of late AMD with systolic blood pressure and the effects of other CVD risk factors on early AMD need to be further explored, according to the study authors.

Design and Methods

The WHISE is an ancillary study to the Women's Health Initiative's (WHI) large scale clinical trial of hormone replacement therapy. Twenty-one of the 39 WHI clinical centers participated in WHISE, enrolling a total of 4,288 women age 63 years and older for whom AMD status could be established for at least one eye by standardized grading of fundus photographs.

Information on CVD and its risk factors were obtained from a standardized questionnaire and examination. The form included questions about diabetes status, lipid-lowering medications, anti-hypertensive medications and medications taken for diabetes. Information on history of myocardial infarction, stroke and anti-hypertensive medication use were collected at the first screening visit of WHI as were measurements of blood pressure and those needed to calculate BMI.

Results

Prevalence of any AMD was 21.4% (919 women). Of those with AMD, only 5.8% had signs of exudative AMD or pure geographic atrophy, which limited the power to examine associations. However, significant and independent associations between late AMD and CVD risk factors were found to be older age, more pack years smoked, increased systolic blood pressure, taking calcium channel blockers, history of diabetes and greater body mass index.

History of myocardial infarction, stroke, use of statins and white blood cell count were not associated with AMD.

Comments

The primary purpose of the WHISE was to examine the effects of hormone replacement therapy on AMD. The results, published in 2006, showed that treatment with conjugated estrogens alone or combined with progestin do not affect early or late-stage AMD, although the combined hormones may reduce the risk of soft drusen or neovascular AMD (2).

In this analysis, there appear to be limited consistent associations of the factors studied and the observed endpoints in women. This is possibly due to differences in the pathogenesis of early AMD and its characteristic lesions (soft drusen and pigmentary abnormalities), and late AMD with its characteristic lesions (exudative AMD and geographic atrophy).

The authors report that higher systolic blood pressure was also found to be associated with soft drusen and inversely associated with RPE de-pigmentation, lesions defining the presence of early AMD. It has been hypothesized that increased blood pressure damages the choroidal circulation affecting the RPE.

Though epidemiologic data regarding this relationship have been inconsistent, people with hypertension in the AREDS trial and in the Beaver Dam Eye Study were more likely to develop neovascular AMD than those with normal blood pressure. It may be time for a randomized clinical trial to test whether lowering blood pressure can slow AMD progression.

References

1. Klein R, et al. Cardiovascular Disease, its Risk Factors and Treatment, and Age-related Macular Degeneration: Women's Health Initiative Sight Exam Ancillary Study. Am J Ophthalmol 143:473-483, 2007.
2. Haan MN, et al. Hormone therapy and age-related macular degeneration: the Women's Health Initiative Sight Exam Study. Arch Ophthalmol 124:988-92, 2006.