Importance: This study adds to the evidence that elevated levels of high-sensitivity C-reactive protein (hsCRP) predict future risk of age-related macular degeneration (AMD). This information might shed light on underlying pathological mechanisms involving inflammation and could be of clinical utility in the identification of persons at high risk of AMD who may benefit from increased adherence to lifestyle recommendations, eye examination schedules, and therapeutic protocols. Objective: To investigate the relationship between hsCRP and future risk of AMD in US men and women. Design: Pooled analysis of prospective nested casecontrol data from the Women's Health Study and 4 other cohorts, the Physicians' Health Study, Women's Antioxidant and Folic Acid Cardiovascular Study, Nurses' Health Study, and Health Professionals Follow-up Study. Setting: A prospective nested case-control study within 5 large cohorts. Participants: Patients were initially free of AMD. We prospectively identified 647 incident cases of AMD and selected age- and sex-matched controls for eachAMDcase (2 controls for each case with dry AMD or 3 controls for each case of neovascular AMD). Main Outcome Measures: We measured hsCRP in baseline blood samples. We used conditional logistic regression models to examine the relationship between hsCRP and AMD and pooled findings using metaanalytic techniques. Results: After adjusting for cigarette smoking status, participants with high (>3 mg/L) compared with low (<1 mg/L) hsCRP levels had cohort-specific odds ratios (ORs) for incident AMD ranging from 0.94 (95% CI, 0.58-1.51) in the Physicians' Health Study to 2.59 (95% CI, 0.58-11.67) in the Women's Antioxidant and Folic Acid Cardiovascular Study. After testing for heterogeneity between studies (Q=5.61; P=.23), we pooled findings across cohorts and observed a significantly increased risk of incidentAMDfor high vs low hsCRP levels (OR, 1.49; 95% CI, 1.06-2.08). Risk of neovascular AMD was also increased among those with high hsCRP levels (OR, 1.84; 95% CI, 1.14-2.98). Conclusions and Relevance: Overall, these pooled findings from 5 prospective cohorts add further evidence that elevated levels of hsCRP predict greater future risk of AMD. This information might shed light on underlying mechanisms and could be of clinical utility in the identification of persons at high risk of AMD who may benefit from increased adherence to lifestyle recommendations, eye examination schedules, and therapeutic protocols.
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