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Prospective Assessment of C-Reactive Protein, Interleukin 6, and Other Cardiovascular Biomarkers

Johanna M. Seddon, MD; Sarah George, MPH; Bernard Rosner, PhD; Nader Rifai, PhD

Arch Ophthalmol. 2005;123:774-782.

Background  Age-related macular degeneration (AMD) and cardiovascular disease share common risk factors. Inflammatory biomarkers, including C-reactive protein (CRP), interleukin 6 (IL-6), soluble tumor necrosis factor alpha receptor 2, soluble intercellular and vascular adhesion molecules (intercellular adhesion molecule 1 and vascular cell adhesion molecule 1), and lipid biomarkers, including lipoprotein(a) and apolipoprotein B, have all been associated with cardiovascular disease. We previously found an association between AMD and CRP in a cross-sectional analysis, but the prospective relationships between AMD, CRP, and the other cardiovascular disease markers are unknown.

Objective  To test the hypothesis that baseline cardiovascular disease biomarkers are associated with subsequent increased risk for progression of AMD.

Design, Setting, and Participants  This prospective cohort study involved 251 participants aged 60 years and older who had some sign of nonexudative AMD and visual acuity of 20/200 or better in at least one eye at baseline. The AMD status was assessed by standardized grading of fundus photographs, and stored fasting blood specimens obtained at baseline were analyzed for levels of the various biomarkers. The average follow-up time was 4.6 years.

Main Outcome Measures  Relationship between biomarkers and incidence rates of progression of AMD.

Results  Comparing the highest quartile with the lowest quartile, CRP was associated with progression of AMD, with a multivariate adjusted relative risk (RR) of 2.10 (95% confidence interval [CI], 1.06-4.18; P for trend, .046) controlling for body mass index, smoking, and other cardiovascular variables and a multivariate adjusted RR of 2.02 (95% CI, 1.00-4.04; P for trend, .06) controlling additionally for antioxidant nutrients. Interleukin 6 was also related to progression of AMD, with a multivariate adjusted RR of 1.81 (95% CI, 0.97-3.36; P for trend, .03). Comparing the highest quartile with the lowest quartile, the effect estimates for vascular cell adhesion molecule 1 (multivariate adjusted RR, 1.94) and apolipoprotein B (adjusted RR, 1.39) were in the positive direction but were not statistically significant (P for trend, .08 and .24, respectively). The CRP and IL-6 levels were both significantly related to higher body mass index and current smoking.

Conclusions  Higher levels of the systemic inflammatory markers CRP and IL-6 are independently associated with progression of AMD.

Author Affiliations: From the Epidemiology Unit, Massachusetts Eye and Ear Infirmary (Dr Seddon and Ms George); Departments of Ophthalmology (Dr Seddon), Medicine (Dr Rosner), and Laboratory Medicine (Dr Rifai), Children’s Hospital, Harvard Medical School; and Departments of Epidemiology (Dr Seddon) and Biostatistics (Dr Rosner), Harvard School of Public Health; Boston, Mass.

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