Physicians' Academy for Cardiovascular Education

Differential effect of LDL- and HDL-levels on small and large vessel disease and stroke type

Role of Blood Lipids in the Development of Ischemic Stroke and its Subtypes: A Mendelian Randomization Study

Literature - Hindy G, Engström G, Larsson SC, et al. - Stroke. 2018;49:820-827

Introduction and methods

LDL-c lowering trials show that statin therapy leads to a risk reduction of first and recurrent ischemic stroke (IS) [1-3]. However, it is unclear whether the same holds true for different IS subtypes, and whether HDL-c and triglycerides (TGs) may be causally involved in the development of IS as well.

This Mendelian Randomization (MR) study investigated the causal relationship of LDL-c, HDL-c, and TGs in the development of IS and its subtypes. The subtypes studied were cardio-embolic, large artery atherosclerosis stroke, and small artery occlusion.

Summary-level data for 185 genome-wide single nucleotide polymorphisms associated with LDL-c, HDL-c, and TGs were obtained from the publicly available genome-wide association study data through the Global Lipids Genetics Consortium, including 188,577 individuals of primarily European ancestry [4]. The summary-level data for IS and its subtypes were obtained from the National Institute of Neurological Disorders and Stroke−Stroke Genetics Network, which includes 16,851 IS cases and 32,473 controls of predominantly European ancestry [5]. Based on the Org 10172 in Acute Stroke Treatment criteria [6], 2,410 cases were large artery atherosclerosis IS, 3,186 were small artery occlusion IS, and 3,427 were cardio-embolic IS cases.

Main results


This MR study showed that genetically elevated LDL-c levels increase the risk for IS, and in particular the risk of large artery atherosclerosis IS. Genetically predicted elevated HDL-c levels associated with a reduced risk of small artery occlusion IS. Genetically elevated TGs were not associated with a risk reduction of IS or any of its subtypes.


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