Journal
NATURE MEDICINE
Volume 25, Issue 4, Pages 569-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41591-019-0366-x
Keywords
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Funding
- Wellcome Trust [202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z]
- National Natural Science Foundation of China [81390540, 81390541, 81390544]
- National Key Research and Development Program of China [2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904]
- British Heart Foundation
- UK Medical Research Council
- Cancer Research UK
- University of Oxford
- Kadoorie Charitable Foundation, Hong Kong, China
- MRC [MC_U137686851, MC_U137686855, MC_PC_14135, MC_PC_13049, MC_UU_12026/2] Funding Source: UKRI
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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.
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