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.
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.
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.
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