Biomarkers of Cardiovascular Disease as
Risk Factors for Age-Related Macular
Degeneration
Andrew K. Vine, MD,
1
Jacqueline Stader, COT,
1
Kari Branham, MS,
1
David C. Musch, PhD, MPH,
1,2
Anand Swaroop, PhD
1,3
Purpose: To measure and contrast 2 biomarkers of cardiovascular disease, C-reactive protein (CRP) and
plasma homocysteine, in individuals with age-related macular degeneration (AMD) and control individuals
without AMD.
Design: Case– control study.
Participants: Seventy-nine affected individuals and 77 unaffected individuals from the AMD Genetic Study
Group returned to obtain CRP and homocysteine levels.
Methods: Both affected and unaffected individuals underwent testing for CRP and homocysteine. A detailed
cardiovascular history was taken.
Main Outcome Measures: Mean CRP and homocysteine levels in affected and unaffected individuals.
Results: Mean CRP levels for affected and unaffected individuals were 3.42 and 2.30 mg/l, respectively (P
= 0.03). Mean homocysteine levels for affected and unaffected individuals were 11.72 and 8.88 mol/l,
respectively (P0.0001). In logistic regression models, older age, higher CRP, and higher homocysteine were risk
factors for AMD. There were no significant differences between cases and controls in terms of gender, diabetes,
hypertension, use of statin drugs, and smoking. The control group was significantly younger and had a lower rate
of vitamin usage than the affected group.
Conclusions: Elevated CRP and homocysteine levels are associated with AMD and implicate the role of
chronic inflammation and atherosclerosis. Ophthalmology 2005;112:2076 –2080 © 2005 by the American Acad-
emy of Ophthalmology.
Age-related macular degeneration (AMD) is the leading
cause of irreversible vision loss and blindness
1
in the United
States. It is a complex multifactorial disease whose patho-
genesis is poorly understood. Epidemiological studies have
implicated an interaction of genetic and environmental fac-
tors in the pathogenesis of AMD. Population studies
2–4
have suggested familial aggregation of AMD and genetic
predisposition to disease pathogenesis. Numerous epidemi-
ological studies
5–14
have tried to elucidate modifiable envi-
ronmental risk factors for macular degeneration. Many of
these documented risk factors represent a cardiovascular
risk profile. Smoking,
5,10
obesity,
6,10
and elevated plasma
fibrinogen
10
increase the risk of AMD. The Eye Disease
Case–Control Study
7
demonstrated 4-fold increased odds of
having neovascular AMD in the group with the highest total
serum cholesterol level. The Age-Related Macular Degen-
eration Risk Factors Study Group
9
reported that moderate to
severe hypertension was linked to neovascular AMD.
Plaques in the carotid bifurcation and lower-extremity arte-
rial disease
8
are also associated with AMD.
These epidemiological studies have evaluated risk fac-
tors that are common to both cardiovascular disease and
AMD and suggest that the diseases may have similar etio-
logical mechanisms. Evaluating new biomarkers of cardio-
vascular disease may provide insight into the etiological
mechanisms of AMD. Two novel markers of cardiovascular
disease are particularly interesting: high-sensitivity C-reactive
protein (CRP) and homocysteine. High-sensitivity CRP is an
ultrasensitive assay of CRP, a marker of systemic inflamma-
tion,
15
and has been shown to be an independent risk factor
and predictor of cardiovascular disease.
16,17
Plasma homo-
cysteine, a sulfur-containing amino acid formed during the
metabolism of methionine,
18
is an independent risk factor
19
for cardiovascular disease, similar to smoking or hyperlip-
idemia. Evaluation of these 2 biomarkers of inflammation
Originally received: January 13, 2005.
Accepted: July 4, 2005. Manuscript no. 2005-41.
1
Department of Ophthalmology, University of Michigan, Ann Arbor,
Michigan.
2
Department of Epidemiology, University of Michigan, Ann Arbor,
Michigan.
3
Department of Human Genetics, University of Michigan, Ann Arbor,
Michigan.
Paper presented at: American Academy of Ophthalmology annual meeting,
October 23–26, 2004; New Orleans, Louisiana.
None of the authors has a financial interest in the article’s subject matter.
This study was partially supported by a grant from the Vice President for
Research of the University of Michigan.
Correspondence and reprint request to Andrew K. Vine, MD, University of
Michigan Kellogg Eye Center, 1000 Wall Street, Ann Arbor, MI 48105.
E-mail: akv@umich.edu.
2076 © 2005 by the American Academy of Ophthalmology ISSN 0161-6420/05/$–see front matter
Published by Elsevier Inc. doi:10.1016/j.ophtha.2005.07.004