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Association between C-reactive protein and age-related macular degeneration
Johanna M Seddon1, Gary Gensler, Roy C Milton
1Epidemiology Unit, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Mass 02114, USA. Johanna_Seddon@meei.harvard.edu
Insights
Elevated C-reactive protein (CRP) levels are linked to an increased risk of developing age-related macular degeneration (AMD). This finding suggests inflammation plays a role in AMD development.
Area of Science:
- Ophthalmology
- Inflammation Research
- Cardiovascular Disease Risk Factors
Background:
- C-reactive protein (CRP) is a key marker of systemic inflammation.
- Certain cardiovascular disease (CVD) risk factors overlap with those for age-related macular degeneration (AMD).
- The relationship between CRP and AMD risk was previously unestablished.
Purpose of the Study:
- To investigate the association between elevated C-reactive protein (CRP) levels and the risk of developing age-related macular degeneration (AMD).
Main Methods:
- A case-control study involving 930 participants from the Age-Related Eye Disease Study (AREDS).
- Participants were categorized into groups with no AMD, mild, intermediate, and advanced AMD based on fundus photograph grading.
- Fasting blood specimens were analyzed for high-sensitivity CRP levels.
Main Results:
- CRP levels were significantly higher in individuals with advanced AMD compared to those without AMD (median 3.4 vs 2.7 mg/L).
- Elevated CRP levels were independently associated with intermediate and advanced AMD stages after adjusting for confounding factors.
- The odds ratio for advanced AMD increased with higher CRP levels, particularly in the highest quartile and at the 90th percentile.
Conclusions:
- Elevated CRP levels represent an independent risk factor for age-related macular degeneration (AMD).
- These findings implicate inflammation in the underlying pathogenesis of AMD.
- CRP may serve as a potential biomarker for AMD risk assessment.
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.
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