We offer our thanks to Willey and colleagues1 for their rigorous and thorough investigation in the Northern Manhattan Study of the relationship between lipid profile components and risk of ischemic stroke. This important work has given us reason to think about the unexpected finding that elevated low-density lipoprotein cholesterol (LDL-C) was associated with reduced hazard of subsequent ischemic stroke when modeled in the primary analysis as a continuous or dichotomous variable. We first wondered if this relationship might reflect the influence of a confounding factor, namely that statin therapy is recognized to have potentially beneficial effects beyond the canonical mechanisms involving cholesterol metabolism.2 This possibility might be supported if the authors felt that the absence of a similar paradoxical effect in those not exposed to cholesterol-lowering medication was not owing to lack of power.
Connick P, Stacpoole SRL. Lipid Profile Components and Risk of Ischemic Stroke: A Role for the Pleiotropic Effects of Statins. Arch Neurol. 2010;67(10):1284-1285. doi:10.1001/archneurol.2010.240