Genetic determinants of LDL cholesterol and risk of intracerebral haemorrhage

Curr Opin Lipidol. 2021 Aug 1;32(4):244-248. doi: 10.1097/MOL.0000000000000761.


Purpose of review: The role of lipids in spontaneous, nontraumatic intracerebral haemorrhage (ICH) remains controversial, as some studies suggest that lower levels of total and LDL cholesterol could increase the risk of this disease. Because of their random assortment during meiosis, genetic variants known to associate with lipid levels can be used as instruments to evaluate this relationship from a causal perspective. The purpose of this review is to summarize the existing literature related to genetically determined LDL cholesterol levels and risk of ICH.

Recent findings: A number of studies have demonstrated that lower LDL levels are associated with a higher risk of ICH and a higher burden of neuroimaging markers of cerebral small vessel disease, such as microbleeds and white matter hyperintensity volume. As for genetically elevated lipid levels, several studies confirmed an inverse association between LDL levels and ICH. However, a number of observational studies and large meta-analyses of clinical trials of statins have failed to show such association.

Summary: Observational studies and clinical trials of statins have yielded inconsistent results regarding a possible link between LDL levels and the risk of ICH. Genetic studies focused on genetically elevated LDL levels and risk of ICH have, for the most, found an inverse association.

Trial registration: NCT03936361.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cerebral Hemorrhage* / genetics
  • Cholesterol, LDL*
  • Clinical Trials as Topic
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • Observational Studies as Topic


  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors

Associated data