RT Journal Article SR Electronic T1 Associations of HDL-C/LDL-C with myocardial infarction, all-cause mortality, haemorrhagic stroke and ischaemic stroke: a longitudinal study based on 384 093 participants from the UK Biobank JF Stroke and Vascular Neurology JO Stroke Vasc Neurol FD BMJ Publishing Group Ltd SP svn-2022-001668 DO 10.1136/svn-2022-001668 A1 Yuan, Shiqi A1 Huang, Xiaxuan A1 Ma, Wen A1 Yang, Rui A1 Xu, Fengshuo A1 Han, Didi A1 Huang, Tao A1 Peng, MIn A1 Xu, Anding A1 Lyu, Jun YR 2022 UL http://svn.bmj.com/content/early/2022/09/23/svn-2022-001668.abstract AB Objective To explore the correlations of high-density lipoprotein cholesterol (HDL-C)/low-density lipoprotein cholesterol (LDL-C) with myocardial infarction (MI), all-cause mortality, haemorrhagic stroke and ischaemic stroke, as well as the joint association of genetic susceptibility and HDL-C/LDL-C with the MI risk.Methods and results This study selected 384 093 participants from the UK Biobank (UKB) database. First, restricted cubic splines indicated non-linear associations of HDL-C/LDL-C with MI, ischaemic stroke and all-cause mortality. Second, a Cox proportional-hazards model indicated that compared with HDL-C/LDL-C=0.4–0.6, HDL-C/LDL-C<0.4 and >0.6 were correlated with all-cause mortality (HR=0.97 for HDL-C/LDL-C<0.4, 95% CI=0.939 to 0.999, p<0.05; HR=1.21 for HDL-C/LDL-C>0.6, 95% CI=1.16 to 1.26, p<0.001) after full multivariable adjustment. HDL-C/LDL-C<0.4 was correlated with a higher MI risk (HR=1.36, 95% CI=1.28 to 1.44, p<0.05) and ischaemic stroke (HR=1.12, 95% CI=1.02 to 1.22, p<0.05) after full multivariable adjustment. HDL-C/LDL-C>0.6 was associated with higher risk haemorrhagic stroke risk after full multivariable adjustment (HR=1.25, 95% CI=1.03 to 1.52, p<0.05). Third, after calculating the coronary heart disease Genetic Risk Score (CHD-GRS) of each participant, the Cox proportional-hazards model indicated that compared with low CHD-GRS and HDL-C/LDL-C=0.4–0.6, participants with a combination of high CHD-GRS and HDL-C/LDL-C<0.4 were associated with the highest MI risk (HR=2.45, 95% CI=2.15 to 2.8, p<0.001). Participants with HDL-C/LDL-C<0.4 were correlated with a higher MI risk regardless of whether they had a high, intermediate or low CHD-GRS.Conclusion In UKB participants, HDL-C/LDL-C ratio of 0.4–0.6 was correlated with lower MI risk, all-cause mortality, haemorrhagic stroke and ischaemic stroke. Participants with HDL-C/LDL-C<0.4 were correlated with a higher MI risk regardless of whether they had a high, intermediate or low CHD-GRS. The clinical significance and impact of HDL-C/LDL-C need to be further verified in future studies.Data are available in a public, open access repository. Data are available on reasonable request and with the permission of the UK Biobank.