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Eur J Prev Cardiol. 2019 Feb 20:2047487319830503. doi: 10.1177/2047487319830503. [Epub ahead of print]

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

Author information

1
1 Department of Neurology, Sungkyunkwan University School of Medicine, Republic of Korea.
2
2 Department of Biostatistics, Korea University College of Medicine, Republic of Korea.
3
3 Department of Neurology, Ilsan Paik Hospital, Inje University, Republic of Korea.
4
4 Department of Digital Health, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.

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, I2 = 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.

KEYWORDS:

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

PMID:
30782002
DOI:
10.1177/2047487319830503

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