Relationship between low-density lipoprotein cholesterol, lipid-lowering agents and risk of stroke: a meta-analysis of observational studies (<i>n</i> = 355,591) and randomized controlled trials (<i>n</i> = 165,988).

Banach, Maciej, Shekoohi, Niloofar, Mikhailidis, Dimitri P, Lip, Gregory YH ORCID: 0000-0002-7566-1626, Hernandez, Adrian V and Mazidi, Mohsen (2022) Relationship between low-density lipoprotein cholesterol, lipid-lowering agents and risk of stroke: a meta-analysis of observational studies (<i>n</i> = 355,591) and randomized controlled trials (<i>n</i> = 165,988). Archives of medical science : AMS, 18 (4). pp. 912-929.

PDF Relationship between low-density lipoprotein cholesterol, lipid-lowering agents and risk of stroke a meta-analysis of observ.pdf - Published version Download (154kB) | Preview

Abstract

<h4>Introduction</h4>The impact of low-density lipoprotein cholesterol (LDL-C) on the risk of different types of strokes is unclear. Therefore, we systematically evaluated the impact of LDL-C levels (cohort studies) and lipid-lowering agents (LLAs) (randomized controlled trials) on the different types of stroke.<h4>Material and methods</h4>PubMed, SCOPUS, Web of Science and Google Scholar were searched up to 1^st September 2019. The DerSimonian-Laird method and generic inverse variance methods were used for quantitative data synthesis. The leave-one-out method was performed as sensitivity analysis. Trial sequential analysis (TSA) was used to evaluate the optimal sample size to detect a 35% reduction in outcomes after administration of LLAs.<h4>Results</h4>Participants in the highest category of LDL-C had a lower risk of hemorrhagic stroke (RR = 0.91, 95% CI: 0.85-0.98, <i>I</i> ² = 0%) compared with the lowest category of LDL-C. Subjects with the highest category of LDL-C had a higher risk of ischemic stroke (RR = 1.11, 95% CI: 1.07-1.14, <i>I</i> ² = 0%) compared to the lowest LDL-C category. LLAs decreased the risk of all types of strokes for those who achieved LDL-C < 1.8 mmol/l (< 70 mg/dl; RR = 0.88, 95% CI: 0.80-0.96, absolute risk reduction (ARR): 0.7%, number needed to treat (NNT): 143, <i>I</i> ² = 53%, <i>n</i> = 13). Statin therapy decreased the risk of all strokes (RR = 0.88, 95% CI: 0.80-0.97, ARR = 0.6%, NNT = 167, <i>I</i> ² = 56%). With regard to ischemic stroke only, LLAs decreased the risk of ischemic stroke for those who achieved LDL-C < 1.8 mmol/l (< 70 mg/dl; RR = 0.75, 95% CI: 0.67-0.83, ARR = 1.3%, NNT = 77, <i>I</i> ² = 0%); the same was observed for statins (RR = 0.76, 95% CI: 0.69-0.84, ARR = 1.3%, NNT = 77, <i>I</i> ² = 32%). TSA indicated that both benefit boundaries and optimal sample size were reached. There was no significant effect of LLAs regardless of the achieved level of LDL-C on the risk of hemorrhagic stroke; however, TSA indicated that further studies are needed to settle the question and most of the effects were subject to high levels of heterogeneity.<h4>Conclusions</h4>Our study sheds light on the debatable association between low LDL-C and different type of strokes. This information can help determine the optimal LDL-C range for stroke prevention, and help plan future LLA studies.

Item Type:	Article
Uncontrolled Keywords:	low-density lipoprotein cholesterol, meta-analysis, stroke, systematic review
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	26 Oct 2022 14:31
Last Modified:	18 Jan 2023 19:49
DOI:	10.5114/aoms/145970
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3165797