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July 30, 2019; 93 (5) Article

Low-density lipoprotein cholesterol and risk of intracerebral hemorrhage

A prospective study

Chaoran Ma, M. Edip Gurol, Zhe Huang, Alice H. Lichtenstein, Xiuyan Wang, Yuzhen Wang, Samantha Neumann, Shouling Wu, Xiang Gao
First published July 2, 2019, DOI: https://doi.org/10.1212/WNL.0000000000007853
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Abstract

Objective To prospectively examine the association between low-density lipoprotein (LDL) cholesterol (LDL-C) concentrations and intracerebral hemorrhage (ICH) risk.

Methods The current cohort study included 96,043 participants (mean age 51.3 years) who were free of stroke, myocardial infarction, and cancer at baseline (2006). Serum LDL-C concentrations were assessed in 2006, 2008, 2010, and 2012. Cumulative average LDL-C concentrations were calculated from all available LDL-C data during that period. Incident ICH was confirmed by review of medical records.

Results We identified 753 incident ICH cases during 9 years of follow-up. The ICH risk was similar among participants with LDL concentrations of 70 to 99 mg/dL and those with LDL-C concentrations ≥100 mg/dL. In contrast, participants with LDL-C concentrations <70 mg/dL had a significantly higher risk of developing ICH than those with LDL-C concentrations of 70 to 99 mg/dL; adjusted hazard ratios were 1.65 (95% confidence interval [CI] 1.32–2.05) for LDL-C concentrations of 50 to 69 mg/dL and 2.69 (95% CI 2.03–3.57) for LDL-C concentrations <50 mg/dL.

Conclusions We observed a significant association between lower LDL-C and higher risk of ICH when LDL-C was <70 mg/dL, and the association became nonsignificant when LDL-C ≥70 mg/dL. These data can help determination of the ideal LDL range in patients who are at increased risk of both atherosclerotic disease and hemorrhagic stroke and guide planning of future lipid-lowering studies.

Glossary

ASTEROID=
A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden;
BMI=
body mass index;
CI=
confidence interval;
CVD=
cardiovascular disease;
eGFR=
estimated glomerular filtration rate;
FOURIER=
Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk;
HDL-C=
high-density lipoprotein cholesterol;
HR=
hazard ratio;
hs-CRP=
high-sensitivity C-reactive protein;
ICD-9=
International Classification of Diseases, 9th revision;
ICD-10=
International Classification of Diseases, 10th revision;
ICH=
intracerebral hemorrhage;
IMPROVE-IT=
Improved Reduction of Outcomes: Vytorin Efficacy International Trial;
JUPITER=
Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin;
LDL-C=
low-density lipoprotein cholesterol;
NHANES=
National Health and Nutrition Examination Survey;
PCSK9=
proprotein convertase subtilisin/kexin type 9;
PROVE-IT=
Pravastatin or Atorvastatin Evaluation and Infection Therapy;
REVERSAL=
Reversal of Atherosclerosis With Aggressive Lipid Lowering;
SPARCL=
Stroke Prevention by Aggressive Reduction in Cholesterol Levels;
TC=
total cholesterol

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received October 12, 2018.
  • Accepted in final form March 13, 2019.
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