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Review
. 2022 Jan 19;18(4):912-929.
doi: 10.5114/aoms/145970. eCollection 2022.

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

Maciej Banach  1   2   3 , Niloofar Shekoohi  4 , Dimitri P Mikhailidis  5 , Gregory Y H Lip  6 , Adrian V Hernandez  7   8 , Mohsen Mazidi  9   10   11
Affiliations
Review

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

Maciej Banach et al. Arch Med Sci. .

Abstract

Introduction: 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.

Material and methods: PubMed, SCOPUS, Web of Science and Google Scholar were searched up to 1st 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.

Results: 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 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 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 2 = 53%, n = 13). Statin therapy decreased the risk of all strokes (RR = 0.88, 95% CI: 0.80-0.97, ARR = 0.6%, NNT = 167, 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 2 = 0%); the same was observed for statins (RR = 0.76, 95% CI: 0.69-0.84, ARR = 1.3%, NNT = 77, 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.

Conclusions: 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.

Keywords: low-density lipoprotein cholesterol; meta-analysis; stroke; systematic review.

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Conflict of interest statement

MB has received research grant(s)/support from Amgen, Sanofi Valeant, Viatris, and has served as a consultant for Abbott Medical, Amgen, Daichii Sankyo, Esperion, Herbapol, Kogen, KRKA, Polfarmex, Polpharma, Roche Diagnostics, Sanofi-Aventis, Servier, Teva, Zentiva; he is CMO at Nomi Biotech Corporation; DPM has given talks and attended conferences sponsored by MSD, AstraZeneca and Libytec; GYHL: Consultant for Bayer/Janssen, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Novartis, Verseon and Daiichi-Sankyo. Speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo – no fees are directly received personally. The other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow chart for the selection of cohort studies
Figure 2
Figure 2
Forest plot of impact of LDL-C on stroke events
Figure 3
Figure 3
Forest plot of impact of LDL-C on hemorrhagic stroke events
Figure 4
Figure 4
Forest plot of impact of LDL-C on ischemic stroke events
Figure 5
Figure 5
PRISMA flow chart for the selection of RCTs
Figure 6
Figure 6
Forest plot of impact of lipid-lowering agents on all strokes (those at ≥ 1.8 mmol/l)
Figure 7
Figure 7
Forest plot of impact of statin therapy on all strokes
Figure 8
Figure 8
Forest plot of impact of lipid-lowering agents on all strokes (those at primary prevention)
See this image and copyright information in PMC

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