Research Highlights: Highlights from the Latest Articles in Biomarkers in Medicine

Abstract

Predicting the risk of future stroke is important to identify those in need of stroke prevention therapy. In a cohort of 9771 healthy males aged 50-59 years, several plasma proteins were found to be predictive of stroke risk [1]. Study participants were followed for 10 years, during which time 95 ischemic strokes occurred. When these 95 strokes were compared with 190 matched controls, subjects who had a stroke were found to have higher baseline fibrinogen (odds ratio [OR]: 1.5; 95% CI: 1.0-2.3), E-selectin (OR :1.8, 95% CI: 1.1-2.9), IFN-γ-inducible protein-10 (OR: 1.7; 95% CI: 1.1-2.8), resistin (OR: 2.9; 95% CI: 1.3-6.3) and total adiponectin (OR: 1.8; 95% CI: 1.0-3.2). When E-selectin and resistin were added to a traditional risk factor model to predict ischemic stroke, the c-statistic improved from 0.68 (95% CI: 0.61-0.75) to 0.79 (95% CI: 0.79-0.89; p < 0.001) and resulted in a net reclassification improvement of 41.4% (p < 0.001).Resistin is released from adipose tissue and can increase macrophage uptake of oxidized low-density lipoprotein, promote thrombus formation, bind TLR4 and upregulate several proinflammatory molecules (ICAM-1, VCAM-1, IL-6, TNF-α, IL1B and NF-κB). E-selectin is an adhesion involved in leukocyte adhesion to endothelial cells and has previously been associated with carotid atherosclerosis and coronary heart disease. The study focused on males in a narrow age range. Further evaluation is required to determine whether these markers can predict stroke risk in females and in persons outside the 50-59-year range. Although resistin and E-selectin incrementally improved stroke risk stratification beyond that achieved by traditional vascular stroke risk factors, combining them with other factors such as MRI patterns may further improve the prediction of stroke risk. Resistin or E-selectin may also represent novel targets to reduce stroke risk. Of interest, statins and folate can reduce resistin levels. Stroke risk predicted by patterns on MRI brainEvaluation of: Weinstein G, Beiser AS, Decarli C, Au R, Wolf PA, Seshadri S. Brain imaging and cognitive predictors of stroke and Alzheimer disease in the Framingham Heart Study. Stroke 44(10), 2787-2794 (2013).Over time, vascular risk factors can have harmful effects on the brain. These include loss of brain volume and development of white matter hyperintensities. A recent study sought to determine whether features on baseline brain MRI are predictive of future stroke [2]. These MRI features were measured in 1679 patients from the Framingham Heart Study and patients were followed for 10 years for the development of stroke (n = 45) or Alzheimer's disease (n = 28). Participants with low total brain volume and marked cerebral white matter hyperintensities were found to have an increased risk of stroke (hazard ratio: 1.97; 95% CI: 1.03-3.77 and hazard ratio: 2.74; 95% CI: 1.51-5.00, respectively). The risk of stroke increased stepwise with increasing severity of brain volume loss and white matter hyperintensities.