In this article, Marsh et al. attempt to answer the question of why some patients differentially have hemorrhagic versus ischemic stroke, when hypertension is the predominant risk factor identified in both cases. They reviewed all patients presenting to a single center with stroke, for presence of either lacunar stroke of hemorrhagic stroke. All patients had a history of hypertension, and medical histories were reviewed for presence for laboratory values and imaging was reviewed to rate white matter hyperintensities and degree of microhemorrhages on MRI sequences.

The authors found in their analysis, that patients who presented with hemorrhagic stroke had increased odds of micro bleeds on MRI. In contrast patients with lacunar stroke had increased odds of severe white matter hyperintensities. In addition, elevated AST and ESR increased the odds of hemorrhagic stroke. The authors suggest that these findings demonstrate that the underlying subclinical pathology predicts the clinical presentation. They also suggest that the elevated ESR may suggest a role for inflammation in blood brain barrier permeability, which causes a “leaky” endothelium, which may be causal in microhemorrhage development.

This work is important because it emphasizes that there is a complex interaction, greater than an individual’s risk factors, such as hypertension, that predict the clinical phenotype (i.e. hemorrhage vs. infarction). Future research can focus on biomarkers that are different in patients with hemorrhages and lacunar stroke, both of which affect small vessels. Understanding the pathophysiology may lead to greater understanding of the gene-environment interaction that is likely present to predispose an individual to a particular disease endpoint.