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

Stroke Vasc Neurol. 2023 Apr;8(2):119-126. doi: 10.1136/svn-2022-001668. Epub 2022 Sep 23.

Abstract

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.

Keywords: cerebrovascular circulation; cerebrovascular disorders; mortality; prospective studies; risk factors.

MeSH terms

  • Biological Specimen Banks
  • Brain Ischemia* / diagnosis
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Hemorrhagic Stroke* / complications
  • Humans
  • Ischemic Stroke* / complications
  • Ischemic Stroke* / diagnosis
  • Lipoproteins, HDL
  • Longitudinal Studies
  • Myocardial Infarction* / complications
  • Myocardial Infarction* / diagnosis
  • Risk Factors
  • Stroke* / diagnosis
  • Stroke* / etiology
  • United Kingdom / epidemiology

Substances

  • Cholesterol, LDL
  • Lipoproteins, HDL
  • Cholesterol, HDL