BUSM’s Seshardri Investigates Biomarkers and Stroke Risk

A recent study led by Boston University School of Medicine (BUSM) researchers has found that many circulating biomarkers from different biological pathways have been independently implicated in causing stroke and cerebrovascular disease. However, their relative contribution to the prediction of stroke risk was unclear. The study also investigated whether the biomarkers contribute over and above the traditional stroke risk factors (such as hypertension, age, diabetes) that are summarized in the Framingham Stroke Risk Profile.

Sudha Seshadri, MD, professor of neurology at BUSM, served as the study’s senior author, which was published online in the journal Circulation on March 28.

The researchers examined a middle-aged community sample from the Framingham Offspring Study. They related eight of the most promising biomarkers to the risk of subsequent stroke. They also related this same panel to brain volume (a measure of subclinical injury) in persons without a clinical stroke. In analyses adjusted for the traditional stroke risk factors, the researchers found that this aggregate panel of biomarkers, which included markers of inflammation (C-reactive protein[CRP]), hemostasis (D-dimer and plasminogen activator inhibitor-1), neurohormonal activity (aldosterone-to renin ratio, B-type natriuretic peptide [BNP] and N-terminal pro-atrial natriuretic peptides) and endothelial function (plasma homocysteine] and albuminuria measured as a urinary albumin/creatinine ratio) helped refine the prediction of stroke risk, especially in persons who were at intermediate risk based on traditional risk factors alone. The results also showed that higher levels of albuminuria and CRP, D-dimer and homocysteine were associated with smaller brain volumes with one standard deviation risk in level of each marker, having the same effect on brain volume as approximately one year of aging.

“The most helpful biomarkers in predicting stroke risk were higher BNP levels and albuminuria, each of which was associated with an approximately 30 percent increase in risk,” explained Seshadri. “These biomarkers may be useful to identify individuals at risk of stroke for more targeted monitoring and perhaps intensified primary prevention efforts.”