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; Niloofar Shekoohi; Dimitri P Mikhailidis; Gregory Y H Lip; Adrian V Hernandez; Mohsen Mazidi

doi:10.5114/aoms/145970

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)

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

Authors

Maciej Banach^{1

2

3}, Niloofar Shekoohi⁴, Dimitri P Mikhailidis⁵, Gregory Y H Lip⁶, Adrian V Hernandez^{7

8}, Mohsen Mazidi^{9

10

11}

Affiliations

¹ Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Lodz, Poland.
² Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland.
³ Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland.
⁴ Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
⁵ Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, UK.
⁶ Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, UK.
⁷ Health Outcomes, Policy, and Evidence Synthesis (HOPES) Group, University of Connecticut/Hartford Hospital Evidence-Based Practice Center, Hartford, CT, USA.
⁸ Vicerrectorado de Investigacion, Universidad San Ignacio de Loyola (USIL), Lima, Peru.
⁹ Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
¹⁰ Medical Research Council Population Health Research Unit, University of Oxford, Oxford, UK.
¹¹ Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.

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 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.

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.

Publication types

Review