Causal associations of blood lipids with risk of ischemic stroke and intracerebral hemorrhage in Chinese adults

Nat Med. 2019 Apr;25(4):569-574. doi: 10.1038/s41591-019-0366-x. Epub 2019 Mar 11.


Stroke is the second leading cause of death worldwide and accounts for >2 million deaths annually in China1,2. Ischemic stroke (IS) and intracerebral hemorrhage (ICH) account for an equal number of deaths in China, despite a fourfold greater incidence of IS1,2. Stroke incidence and ICH proportion are higher in China than in Western populations3-5, despite having a lower mean low-density lipoprotein cholesterol (LDL-C) concentration. Observational studies reported weaker positive associations of LDL-C with IS than with coronary heart disease (CHD)6,7, but LDL-C-lowering trials demonstrated similar risk reductions for IS and CHD8-10. Mendelian randomization studies of LDL-C and IS have reported conflicting results11-13, and concerns about the excess risks of ICH associated with lowering LDL-C14,15 may have prevented the more widespread use of statins in China. We examined the associations of biochemically measured lipids with stroke in a nested case-control study in the China Kadoorie Biobank (CKB) and compared the risks for both stroke types associated with equivalent differences in LDL-C in Mendelian randomization analyses. The results demonstrated positive associations of LDL-C with IS and equally strong inverse associations with ICH, which were confirmed by genetic analyses and LDL-C-lowering trials. Lowering LDL-C is still likely to have net benefit for the prevention of overall stroke and cardiovascular disease in China.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asians*
  • Brain Ischemia / blood*
  • Brain Ischemia / epidemiology*
  • Case-Control Studies
  • Cerebral Hemorrhage / blood*
  • Cerebral Hemorrhage / epidemiology*
  • China / epidemiology
  • Female
  • Humans
  • Lipids / blood*
  • Male
  • Middle Aged
  • Odds Ratio
  • Proportional Hazards Models
  • Risk Factors
  • Stroke / blood*
  • Stroke / epidemiology*
  • Triglycerides / blood


  • Lipids
  • Triglycerides