UM Neurologist Awarded $1.3 Million NIH Grant to Study Stroke Risk Factor
Clinton B. Wright, M.D., M.S., associate professor of neurology and scientific director of the Evelyn F. McKnight Brain Institute, has been awarded a four-year $1.3 million grant from the National Heart Lung and Blood Institute at the National Institutes of Health to examine mineral metabolism as a risk factor for stroke, subclinical small and large vessel injury, and cognitive decline.
Wright, who is principal investigator, will collaborate with Ralph L. Sacco, M.D., M.S., Olemberg Family Chair in Neurological Disorders and Leonard M. Miller Professor of Neurology, Epidemiology and Human Genetics; Myles Wolf, M.D., M.M.Sc., associate professor of medicine; Tatjana Rundek, M.D., Ph.D., professor of neurology; and Chuanhui Dong, Ph.D., research assistant professor of neurology, who will serve as biostatistician for the study. The Miller School researchers also will collaborate with investigators at Columbia University Medical Center.
Subclinical cerebrovascular damage has been associated with a greater risk of clinical stroke, disability, and cognitive decline. Unfortunately, known modifiable risk factors for vascular disease do not completely explain the risk for stroke, and other vascular outcomes, including vascular cognitive impairment, mandating the identification of novel mechanisms and biomarkers of disease. Increased levels of serum fibroblast growth factor 23 (FGF23) and phosphate have emerged as novel risk factors for cardiovascular disease and mortality.
Dr. Wolf and a UM team of researchers were the first to demonstrate that increased FGF23 levels at the initiation of dialysis are independently associated with an increased risk of mortality, and these results have now been validated in the general population. However, few studies have examined the markers in relation to stroke risk, especially among Hispanic and black populations that may be at increased risk of stroke and dementia compared to non-Hispanic whites. In the population-based multi-ethnic Northern Manhattan Study, subclinical brain infarction and cerebral small vessel disease were found to be prevalent and associated with poor cognitive function.
Increased FGF23 and phosphate can be lowered, so demonstrating that these factors are independently associated with adverse neurological outcomes could have important therapeutic potential.
Wright and his group plan to test the hypothesis that elevated FGF23 and serum phosphate are independent risk factors for stroke, subclinical vascular damage and cognitive decline. They believe that higher FGF23 levels are the key marker of phosphorus-related cardiovascular disease risk and will measure FGF23 and phosphate in the existing Northern Manhattan Study participants in addition to a subsample that underwent quantitative brain MRI and carotid ultrasound to measure subclinical vascular damage, and detailed global neuropsychological assessments.
“We anticipate that the results of this study, in concert with ongoing projects on FGF23 in more advanced CKD, will rapidly set the stage for randomized controlled trials”, said Wright.