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

• Published in: Nature medicine Vol. 25; no. 4; pp. 569 - 574
• Main Authors: Sun, Luanluan, Clarke, Robert, Bennett, Derrick, Guo, Yu, Walters, Robin G., Hill, Michael, Parish, Sarah, Millwood, Iona Y., Bian, Zheng, Chen, Yiping, Yu, Canqing, Lv, Jun, Collins, Rory, Chen, Junshi, Peto, Richard, Li, Liming, Chen, Zhengming
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.04.2019; Nature Publishing Group
• Subjects: 692/499; 692/53; 692/617/375/534; 692/699/75; 692/700; Adult; Adults; Aged; Asian People; Biomedical and Life Sciences; Biomedicine; Blood; Blood lipids; Brain Ischemia - blood; Brain Ischemia - epidemiology; Cancer Research; Cardiovascular disease; Cardiovascular diseases; Case studies; Case-Control Studies; Cerebral Hemorrhage - blood; Cerebral Hemorrhage - epidemiology; China - epidemiology; Cholesterol; Clinical trials; Coronary artery disease; Coronary heart disease; Death; Fatalities; Female; Genetic analysis; Genetic research; Health aspects; Heart diseases; Hemorrhage; Humans; Incidence; Infectious Diseases; Intracerebral hemorrhage; Ischemia; Letter; Lipids; Lipids - blood; Low density lipoprotein; Low density lipoproteins; Male; Metabolic Diseases; Middle Aged; Molecular Medicine; Neurosciences; Observational studies; Odds Ratio; Patient outcomes; Prevention; Proportional Hazards Models; Randomization; Risk Factors; Statins; Stroke; Stroke - blood; Stroke - epidemiology; Triglycerides - blood; China
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/s41591-019-0366-x

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 IS 1 , 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 CHD 8 – 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 , 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. In a nested case-control study from the China Kadoorie Biobank, lowering blood low-density lipoprotein cholesterol levels confers lower risk for ischemic stroke but elevated risk for intracerebral hemorrhage, which was confirmed by genetic Mendelian randomization analyses.