Tags

Type your tag names separated by a space and hit enter

Circulating Lipoprotein Lipids, Apolipoproteins and Ischemic Stroke.
Ann Neurol. 2020 12; 88(6):1229-1236.AN

Abstract

OBJECTIVE

We conducted a Mendelian randomization (MR) study to disentangle the comparative effects of lipids and apolipoproteins on ischemic stroke.

METHODS

Single-nucleotide polymorphisms associated with low- and high-density lipoprotein (LDL and HDL) cholesterol, triglycerides, and apolipoprotein A-I and B (apoA-I and apoB) at the level of genomewide significance (p < 5 × 10-8) in the UK Biobank were used as instrumental variables. Summary-level data for ischemic stroke and its subtypes were obtained from the MEGASTROKE consortium with 514,791 individuals (60,341 ischemic stroke cases, and 454,450 non-cases).

RESULTS

Increased levels of apoB, LDL cholesterol, and triglycerides were associated with higher risk of any ischemic stroke, large artery stroke, and small vessel stroke in the main and sensitivity univariable MR analyses. In multivariable MR analysis including apoB, LDL cholesterol, and triglycerides in the same model, apoB retained a robust effect (p < 0.05), whereas the estimate for LDL cholesterol was reversed, and that for triglycerides largely attenuated. Decreased levels of apoA-I and HDL cholesterol were robustly associated with increased risk of any ischemic stroke, large artery stroke, and small vessel stroke in all univariable MR analyses, but the association for apoA-I was attenuated to the null after mutual adjustment.

INTERPRETATION

The present MR study reveals that apoB is the predominant trait that accounts for the etiological basis of apoB, LDL cholesterol, and triglycerides in relation to ischemic stroke, in particular large artery and small vessel stroke. Whether HDL cholesterol exerts a protective effect on ischemic stroke independent of apoA-I needs further investigation. ANN NEUROL 2020;88:1229-1236.

Authors+Show Affiliations

Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK. Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32981134

Citation

Yuan, Shuai, et al. "Circulating Lipoprotein Lipids, Apolipoproteins and Ischemic Stroke." Annals of Neurology, vol. 88, no. 6, 2020, pp. 1229-1236.
Yuan S, Tang B, Zheng J, et al. Circulating Lipoprotein Lipids, Apolipoproteins and Ischemic Stroke. Ann Neurol. 2020;88(6):1229-1236.
Yuan, S., Tang, B., Zheng, J., & Larsson, S. C. (2020). Circulating Lipoprotein Lipids, Apolipoproteins and Ischemic Stroke. Annals of Neurology, 88(6), 1229-1236. https://doi.org/10.1002/ana.25916
Yuan S, et al. Circulating Lipoprotein Lipids, Apolipoproteins and Ischemic Stroke. Ann Neurol. 2020;88(6):1229-1236. PubMed PMID: 32981134.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Circulating Lipoprotein Lipids, Apolipoproteins and Ischemic Stroke. AU - Yuan,Shuai, AU - Tang,Bowen, AU - Zheng,Jie, AU - Larsson,Susanna C, Y1 - 2020/10/10/ PY - 2020/07/07/received PY - 2020/09/20/revised PY - 2020/09/21/accepted PY - 2020/9/28/pubmed PY - 2020/12/22/medline PY - 2020/9/27/entrez SP - 1229 EP - 1236 JF - Annals of neurology JO - Ann Neurol VL - 88 IS - 6 N2 - OBJECTIVE: We conducted a Mendelian randomization (MR) study to disentangle the comparative effects of lipids and apolipoproteins on ischemic stroke. METHODS: Single-nucleotide polymorphisms associated with low- and high-density lipoprotein (LDL and HDL) cholesterol, triglycerides, and apolipoprotein A-I and B (apoA-I and apoB) at the level of genomewide significance (p < 5 × 10-8) in the UK Biobank were used as instrumental variables. Summary-level data for ischemic stroke and its subtypes were obtained from the MEGASTROKE consortium with 514,791 individuals (60,341 ischemic stroke cases, and 454,450 non-cases). RESULTS: Increased levels of apoB, LDL cholesterol, and triglycerides were associated with higher risk of any ischemic stroke, large artery stroke, and small vessel stroke in the main and sensitivity univariable MR analyses. In multivariable MR analysis including apoB, LDL cholesterol, and triglycerides in the same model, apoB retained a robust effect (p < 0.05), whereas the estimate for LDL cholesterol was reversed, and that for triglycerides largely attenuated. Decreased levels of apoA-I and HDL cholesterol were robustly associated with increased risk of any ischemic stroke, large artery stroke, and small vessel stroke in all univariable MR analyses, but the association for apoA-I was attenuated to the null after mutual adjustment. INTERPRETATION: The present MR study reveals that apoB is the predominant trait that accounts for the etiological basis of apoB, LDL cholesterol, and triglycerides in relation to ischemic stroke, in particular large artery and small vessel stroke. Whether HDL cholesterol exerts a protective effect on ischemic stroke independent of apoA-I needs further investigation. ANN NEUROL 2020;88:1229-1236. SN - 1531-8249 UR - https://www.unboundmedicine.com/medline/citation/32981134/Circulating_Lipoprotein_Lipids_Apolipoproteins_and_Ischemic_Stroke_ L2 - https://doi.org/10.1002/ana.25916 DB - PRIME DP - Unbound Medicine ER -