Serum Phosphate and Retinal Microvascular Changes: The Multi-Ethnic Study of Atherosclerosis and the Beaver Dam Eye Study

Purpose: Higher levels of serum phosphate are strongly linked to increased risk of cardiovascular disease and therapies aimed to lower serum phosphate are employed in the management of patients with chronic kidney disease (CKD). Data are limited, however, on serum phosphate as a risk factor for microvascular disease in community-based populations. It is important to determine the impact of novel risk factors, such as phosphate, on the microvasculature. Methods: We conducted a prospective study of 3919 individuals in the Multi-Ethnic Study of Atherosclerosis (MESA) and 3544 individuals in the Beaver Dam Eye Study (BDES) to test the associations of serum phosphate with retinopathy and retinal vessel caliber, and change in retinopathy severity and change in retinal vessel caliber. Results: Mean (standard deviation) serum phosphate was 3.66 (0.52) mg/dl in the MESA and 3.77 (0.55) mg/dl in the BDES. In multivariable adjusted models, phosphate was significantly associated with prevalent retinopathy in the MESA (Odds Ratio [OR] per 1 mg/dl increase in phosphate, 1.22; Confidence Interval [CI] 1.02–1.47) and the BDES (OR 1.06; CI 1.01–1.11). In stratified analyses, these relationships were even stronger and only seen in individuals with diabetes in both the MESA (OR 1.81; CI 1.30–2.53) and the BDES (OR 1.16; CI 1.05–1.29). Phosphate was not associated with incident or change in retinopathy severity, nor any retinal caliber outcome. Conclusions: Among community-living individuals with low prevalence of CKD, higher serum phosphate was associated with prevalent retinopathy in individuals with diabetes. Further longitudinal assessments in patients with diabetes necessitate further investigation.