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

Abstract

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.

Serum Phosphate and Microvascular Function in a Population-Based Cohort

“…The persons randomized to the high-phosphate diet still had an average phosphate in the normal range (around 4 mg/dl). In larger community-living populations, Mehta et al reported an association between higher serum phosphate and prevalence of retinopathy, even among persons with a serum phosphate in the normal range in the Multi-Ethnic Study of Atherosclerosis, a finding confirmed in our study (30). In that study, serum phosphate was not associated with central retinal arteriolar or venular diameter; however, these measurements were made without flicker-light stimulation, thus this would only reflect the baseline diameter.…”

Serum and Macular Carotenoids in Relation to Retinal Vessel Caliber Fifteen Years Later, in the Second Carotenoids in Age-Related Eye Disease Study

“…This finding is consistent with other recent studies of modifiable exposures (e.g., nutrients in diet or bloodstream) and retinal vessel outcomes. [26][27][28] Although this observational study was not designed to identify a causal relationship between L/Z exposure and retinal vessel caliber, our findings support increasing evidence that carotenoids L/Z may have a role in modulating ocular blood flow, 11,12 in addition to their well-known antioxidant properties in the macula of the retina. 3,29 Although speculative, it is plausible that increased ocular blood flow may contribute to the protective associations observed for L/Z and macular pigment in observational studies, including protective associations observed for AMD.…”

Normal parathyroid hormone and non‐proliferative diabetic retinopathy in patients with type 2 diabetes

“…The evidence shows that the increase of serum calcium might trigger the self‐regeneration cycle of ionized calcium influx and depolarization, resulting in increased retinal photoreceptor ellipsoid zone disruption in DR, leading to the impairment of retinal photoreceptor cell function and apoptosis 16,17 . Rupal et al 14 . and other scholars put forward that elevated phosphate has toxic effects on the vascular endothelium, which leads to retinopathy.…”

“…The evidence shows that the increase of serum calcium might trigger the self-regeneration cycle of ionized calcium influx and depolarization, resulting in increased retinal photoreceptor ellipsoid zone disruption in DR, leading to the impairment of retinal photoreceptor cell function and apoptosis 16,17 . Rupal et al 14 and other scholars put forward that elevated phosphate has toxic effects on the vascular endothelium, which leads to retinopathy. In vivo and in vitro studies have found that endothelial cells exposed to high phosphate concentration reduce the content of endothelial nitric oxide synthase, resulting in decreased vasodilation and vascular dysfunction 18,19 .…”

“…The relationship between parathyroid function and type 2 diabetes mellitus has been a research focus for concern, and this relationship has extended to the field of normal parathyroid function. Recent cohort studies showed that elevated serum phosphate concentration within the normal range was associated with microvascular dysfunction in participants 13,14 . However, there are scarce data on the relationship between normal PTH levels and DR.…”