Achieved low-density lipoprotein cholesterol level and stroke risk: A meta-analysis of 23 randomised trials

Jaewon Shin, Jong Won Chung, Hyun Soon Jang, Juneyoung Lee, Keun Sik Hong, Oh Young Bang, Gyeong Moon Kim, Woo Keun Seo

Research output: Contribution to journalArticle

Abstract

Aims: Lowering the low-density lipoprotein cholesterol level reduces the risk of stroke, but it has not been clear whether the stroke risk would continuously decrease by lowering low-density lipoprotein cholesterol to a very low level. The purpose of this study was to evaluate the association between achieved low-density lipoprotein cholesterol levels and stroke risk. Methods and results: A systematic search of MEDLINE, EMBASE and Cochrane Library databases was conducted to identify randomised controlled trials that tested cholesterol-lowering pharmacological therapies and reported both achieved low-density lipoprotein cholesterol levels and stroke outcomes. A meta-regression analysis was conducted to assess the linear association between the achieved low-density lipoprotein cholesterol levels and stroke risk. In addition, we evaluated pooled estimates of low-density lipoprotein cholesterol-lowering effect stratified by achieved low-density lipoprotein cholesterol levels of active arms. A total of 222,149 participants in 23 trials (52 arms of 26 studies) were included. The meta-regression analysis showed that each 1 mmol/L decrease in the achieved low-density lipoprotein cholesterol level (down to 0.78 mmol/L) was associated with a significant reduction of 23.5% (slope 0.235, 95% confidence interval 0.007–0.464, P = 0.044) in stroke risk. Irrespective of achieved low-density lipoprotein cholesterol levels in the active arms, the effects of lowering the low-density lipoprotein cholesterol level on stroke risk were significant and consistent (test for subgroup difference, P = 0.23, I 2 = 31%). However, there was no significant increase in haemorrhagic stroke risk with lower achieved low-density lipoprotein cholesterol levels. Conclusion: In this meta-analysis of randomised controlled trials, the stroke risk monotonically reduced with lowering of low-density lipoprotein cholesterol to very low levels.

Original languageEnglish
JournalEuropean Journal of Preventive Cardiology
DOIs
Publication statusPublished - 2019 Jan 1

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LDL Cholesterol
Meta-Analysis
Stroke
Randomized Controlled Trials
Regression Analysis
VLDL Cholesterol
MEDLINE
Libraries
Cholesterol
Databases
Pharmacology
Confidence Intervals

Keywords

  • LDL-cholesterol
  • meta-analysis
  • PCSK9 inhibitor
  • statin
  • Stroke

ASJC Scopus subject areas

  • Epidemiology
  • Cardiology and Cardiovascular Medicine

Cite this

Achieved low-density lipoprotein cholesterol level and stroke risk : A meta-analysis of 23 randomised trials. / Shin, Jaewon; Chung, Jong Won; Jang, Hyun Soon; Lee, Juneyoung; Hong, Keun Sik; Bang, Oh Young; Kim, Gyeong Moon; Seo, Woo Keun.

In: European Journal of Preventive Cardiology, 01.01.2019.

Research output: Contribution to journalArticle

Shin, Jaewon ; Chung, Jong Won ; Jang, Hyun Soon ; Lee, Juneyoung ; Hong, Keun Sik ; Bang, Oh Young ; Kim, Gyeong Moon ; Seo, Woo Keun. / Achieved low-density lipoprotein cholesterol level and stroke risk : A meta-analysis of 23 randomised trials. In: European Journal of Preventive Cardiology. 2019.
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abstract = "Aims: Lowering the low-density lipoprotein cholesterol level reduces the risk of stroke, but it has not been clear whether the stroke risk would continuously decrease by lowering low-density lipoprotein cholesterol to a very low level. The purpose of this study was to evaluate the association between achieved low-density lipoprotein cholesterol levels and stroke risk. Methods and results: A systematic search of MEDLINE, EMBASE and Cochrane Library databases was conducted to identify randomised controlled trials that tested cholesterol-lowering pharmacological therapies and reported both achieved low-density lipoprotein cholesterol levels and stroke outcomes. A meta-regression analysis was conducted to assess the linear association between the achieved low-density lipoprotein cholesterol levels and stroke risk. In addition, we evaluated pooled estimates of low-density lipoprotein cholesterol-lowering effect stratified by achieved low-density lipoprotein cholesterol levels of active arms. A total of 222,149 participants in 23 trials (52 arms of 26 studies) were included. The meta-regression analysis showed that each 1 mmol/L decrease in the achieved low-density lipoprotein cholesterol level (down to 0.78 mmol/L) was associated with a significant reduction of 23.5{\%} (slope 0.235, 95{\%} confidence interval 0.007–0.464, P = 0.044) in stroke risk. Irrespective of achieved low-density lipoprotein cholesterol levels in the active arms, the effects of lowering the low-density lipoprotein cholesterol level on stroke risk were significant and consistent (test for subgroup difference, P = 0.23, I 2 = 31{\%}). However, there was no significant increase in haemorrhagic stroke risk with lower achieved low-density lipoprotein cholesterol levels. Conclusion: In this meta-analysis of randomised controlled trials, the stroke risk monotonically reduced with lowering of low-density lipoprotein cholesterol to very low levels.",
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AU - Bang, Oh Young

AU - Kim, Gyeong Moon

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