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

Stroke is the second leading cause of death worldwide and accounts for >2 million deaths annually in China(1,2). 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 populations(3-5), 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 results(11-13), and concerns about the excess risks of ICH associated with lowering LDL-C-14,C-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.