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Johanna M. Seddon, MD, ScM; Gary Gensler, MS; Roy C. Milton, PhD; Michael L. Klein, MD; Nader Rifai, PhD

JAMA. 2004;291:704-710.

Context  C-reactive protein (CRP) is a systemic inflammatory marker associated with risk for cardiovascular disease (CVD). Some risk factors for CVD are associated with age-related macular degeneration (AMD), but the association between CRP and AMD is unknown.

Objective  To test the hypothesis that elevated CRP levels are associated with an increased risk for AMD.

Design, Setting, and Participants  A total of 930 (91%) of 1026 participants at 2 centers in the Age-Related Eye Disease Study (AREDS), a multicenter randomized trial of antioxidant vitamins and minerals, were enrolled in this case-control study. There were 183 individuals without any maculopathy, 200 with mild maculopathy, 325 with intermediate disease, and 222 with advanced AMD (geographic atrophy or neovascular AMD). The AMD status was assessed by standardized grading of fundus photographs, and stored fasting blood specimens drawn between January 1996 and April 1997 were analyzed for high-sensitivity CRP levels.

Main Outcome Measure  Association between CRP and AMD.

Results  The CRP levels were significantly higher among participants with advanced AMD (case patients) than among those with no AMD (controls; median values, 3.4 vs 2.7 mg/L; P = .02). After adjustment for age, sex, and other variables, including smoking and body mass index, CRP levels were significantly associated with the presence of intermediate and advanced stages of AMD. The odds ratio (OR) for the highest vs the lowest quartile of CRP was 1.65 (95% confidence interval [CI], 1.07-2.55; P for trend = .02). The OR for CRP values at or above the 90th percentile (10.6 mg/L) was 1.92 (95% CI, 1.20-3.06), and the OR for CRP values at or above the mean plus 2 SDs (16.8 mg/L) was 2.03 (95% CI, 1.03-4.00). A trend for an increased risk for intermediate and advanced AMD with higher levels of CRP was seen for smokers (OR, 2.16; 95% CI, 1.33-3.49) and those who never smoked (OR, 2.03; 95% CI, 1.19-3.46) with the highest level of CRP.

Conclusion  Our results suggest that elevated CRP level is an independent risk factor for AMD and may implicate the role of inflammation in the pathogenesis of AMD.

Author Affiliations: Epidemiology Unit, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, and Department of Epidemiology, Harvard School of Public Health, Boston, Mass (Dr Seddon); The EMMES Corporation, Rockville, Md (Mr Gensler and Dr Milton); Casey Eye Institute, Oregon Health and Science University, Portland (Dr Klein); and Department of Laboratory Medicine, Children's Hospital, Harvard Medical School, Boston, Mass (Dr Rifai).

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