Association of serum soluble Receptor for Advanced Glycation End-products with subclinical cerebrovascular disease: the Northern Manhattan Study (NOMAS)

Objective: Serum levels of the soluble Receptor for Advanced Glycation End-products (sRAGE) have been associated with risk of cardiovascular disease. We hypothesized that sRAGE levels are associated with subclinical cerebrovascular disease in an ethnically diverse population. Methods: Clinically stroke-free participants in the multi-ethnic Northern Manhattan Study (NOMAS) underwent brain MRI to quantify subclinical brain infarcts (SBI) and white matter hyperintensity volume (WMHV) (n = 1102). Serum levels of sRAGE were measured by ELISA. Logistic and multiple linear regression were employed to estimate associations of sRAGE with SBI and WMHV, after adjusting for demographics and vascular risk factors. Results: Median sRAGE levels were significantly lower in Hispanics (891.9 pg/ml; n = 708) and nonHispanic blacks (757.4 pg/ml; n = 197) than in non-Hispanic whites (1120.5 pg/ml; n = 170), and these differences remained after adjusting for other risk factors. Interactions were observed by race-ethnicity between sRAGE levels and MRI measurements, including for SBI in Hispanics (p = 0.04) and WMHV among blacks (p = 0.03). In Hispanics, increasing sRAGE levels were associated with a lower odds of SBI, with those in the upper sRAGE quartile displaying a 50% lower odds of SBI after adjusting for sociodemographic and vascular risk factors (p = 0.05). Among blacks, those in the upper quartile of sRAGE had a similarly reduced increased risk of SBI (p = 0.06) and greater WMHV (p = 0.04). Conclusion: Compared to whites, Hispanics and blacks have significantly lower sRAGE levels, and these levels were associated with more subclinical brain disease. Taken together, these findings suggest sRAGE levels may be significantly influence by ethnicity. Further studies of sRAGE and stroke risk, particularly in minorities, are warranted.