Annals of Neurology: The Mendel randomization study reveals that apoB is the ecaused by ischemic stroke

Blood lipids are the established cause of stroke.
studies have shown that high levels of low-density lipoprotein (LDL) cholesterol increase the risk of ischemic stroke, while high levels of high-density lipoprotein (HDL) cholesterol may reduce the risk of ischemic stroke, especially small blood vessel stroke.
addition, large-scale randomized clinical trials have shown that lowering cholesterol levels with statins reduces the risk of ischemic stroke and overall stroke, although hemorrhagic stroke increases.
, however, given the high esoploid and genetic correlation between different lipids and lipoproteins, it remains unclear whether one or more lipid-related entities explain the observed association between blood lipids and stroke.
it is of great public health and clinical significance to reveal the association between atherosclerin lipids and stroke risk.
, a better understanding of lipoprotein lipids in stroke is not only conducive to a clearer understanding of the underlying pathophysiology of stroke, but also helps to identify the most effective biomarkers and corresponding drugs.
In addition, such studies could provide a better basis for prevention and treatment for the general population (about a quarter of the population) with uncoordered lipoprotein B (apoB) and LDL cholesterol levels, especially stroke prevention and treatment in people with obesity or diabetes, said Shuai Yuan of sweden's prestigious Karolinska School of Medicine, based on a MEGA consortium study of Mendel randomization (MR) to explore the relative effects of lipids and lipoproteins on hypothyroidism.
they used single nucleotide polymorphisms associated with low-density and high-density lipoprotein (LDL and HDL) cholesterol, triglycerides, and lipoproteins A-I and B (apoA-I and apoB) in UK biobank to be used as tool variables.
summary-level data on ischemic stroke and its subtypes came from the MEGASTROKE Alliance, with a total of 514,791 people (60,341 ischemic strokes and 454,450 non-cases).
results showed that increased levels of apoB, LDL cholesterol, and triglycerides were associated with a higher risk of any ischemic stroke, arterial stroke, and small vascular stroke in major and sensitive single-variable MR analysis.
In a multivariate MR analysis that included apoB, LDL cholesterol, and triglycerides in the same model, apoB retained a robust effect (P -lt;0.05), whereas the LDL cholesterol estimate was the opposite, and triglycerides were largely reduced.
In all single-variable MR analyses, lower apoA-I and HDL cholesterol levels were robustly associated with an increased risk of any ischemic stroke, aortic stroke, and small vascular stroke, but the association between apoA-I decreased to zero after mutual adjustment.
The significance of this Mendel randomization study is the discovery that apoB is the eganological basis for ischemic stroke caused by apoB, LDL cholesterol, and triglycerides, especially in aorta and small blood vessel stroke.
whether HDL cholesterol plays a protective role in ischemic stroke and is independent of apoA-I requires further study.
original origin: Yuan, S., Tang, B., Zheng, J., and Larsson, S.C. (2020). Circulating lipoprotein lipids, apolipoproteins and ischemic stroke. Annals of neurology, 88(6), 1229-1236.<!--5f39ae17-8c62-4a45-bc43-b32064c9388a: W3siYmxvY2tJZCI6IjM4NjgtMTYxMDgzNTcxNzUzMyIsImJsb2NrVHlwZSI6InBhcmFncmFwaCIsInN0eWxlcyI6eyJhbGlnbiI6ImxlZnQiLCJpbmRlbnQiOjAsInRleHQtaW5kZW50IjowLCJsaW5lLWhlaWdodCI6MS43NSwiYmFjay1jb2xvciI6IiIsInBhZGRpbmciOiIifSwidHlwZSI6InBhcmFncmFwaCIsInJpY2hUZXh0Ijp7ImRhdGEiOlt7ImNoYXIiOiJBIn0seyJjaGFyIjoibiJ9LHsiY2hhciI6Im4ifSx7ImNoYXIiOiJhIn0seyJjaGFyIjoibCJ9LHsiY2hhciI6InMifSx7ImNoYXIiOiIgIn0seyJjaGFyIjoibyJ9LHsiY2hhciI6ImYif Sx7ImNoYXIiOiIgIn0seyJjaGFyIjoiTiJ9LHsiY2hhciI6ImUifSx7ImNoYXIiOiJ1In0seyJjaGFyIjoiciJ9LHsiY2hhciI6Im8ifSx7ImNoYXIiOiJsIn0seyJjaGFyIjoibyJ9LHsiY2hhciI6ImcifSx7ImNoYXIiOiJ5In0seyJjaGFyIjoiICJ9LHsiY2hhciI6Ii0ifSx7ImNoYXIiOiLlrZ8ifSx7ImNoYXIiOiLlvrcifSx7ImNoYXIiOiLlsJQifSx7ImNoYXIiOiLpmo8ifSx7ImNoYXIiOiLmnLoifSx7ImNoYXIiOiLljJYifSx7ImNoYXIiOiLnoJQifSx7ImNoYXIiOiLnqbYifSx7ImNoYXIiOiLmj60ifSx7ImNoYXIiOiLnpLoifSx7ImNoYX IiOiJhIn0seyJjaGFyIjoicCJ9LHsiY2hhciI6Im8ifSx7ImNoYXIiOiJCIn0seyJjaGFyIjoi5pivIn0seyJjaGFyIjoi57y6In0seyJjaGFyIjoi6KGAIn0seyJjaGFyIjoiZCJ9LHsiY2hhciI6IuaApyJ9LHsiY2hhciI6IuS4rSJ9LHsiY2hhciI6IumjjiJ9LHsiY2hhciI6IueahCJ9LHsiY2hhciI6IueXhSJ9LHsiY2hhciI6IuWboCJ9LHsiY2hhciI6IuWtpiJ9LHsiY2hhciI6IuWfuiJ9LHsiY2hhciI6IuehgCJ9XSwiaXNSaWNoVGV4dCI6dHJ1ZSwia2VlcExpbmVCcmVhayI6dHJ1ZX19LHsiYmxvY2tJZCI6IjQ4NTEtMTYxMDg4MTMxNTk5NSI sImJsb2NrVHlwZSI6InBhcmFncmFwaCIsInN0eWxlcyI6eyJhbGlnbiI6ImxlZnQiLCJpbmRlbnQiOjAsInRleHQtaW5kZW50IjowLCJsaW5lLWhlaWdodCI6MS43NSwiYmFjay1jb2xvciI6IiIsInBhZGRpbmciOiIifSwidHlwZSI6InBhcmFncmFwaCIsInJpY2hUZXh0Ijp7ImRhdGEiOltdLCJpc1JpY2hUZXh0Ijp0cnVlLCJrZWVwTGluZUJyZWFrIjp0cnVlfX0seyJibG9ja0lkIjoiODA3My0xNjEwODgxMzE2MTMxIiwiYmxvY2tUeXBlIjoicGFyYWdyYXBoIiwic3R5bGVzIjp7ImFsaWduIjoibGVmdCIsImluZGVudCI6MCwidGV4dC1pbmRlbnQi OjAsImxpbmUtaGVpZ2h0IjoxLjc1LCJiYWNrLWNvbG9yIjoiIiwicGFkZGluZyI6IiJ9LCJ0eXBlIjoicGFyYWdyYXBoIiwicmljaFRleHQiOnsiZGF0YSI6W3siY2hhciI6IuihgCJ9LHsiY2hhciI6IuiEgiJ9LHsiY2hhciI6IuaYryJ9LHsiY2hhciI6IuS4rSJ9LHsiY2hhciI6IumjjiJ9LHsiY2hhciI6IuWPkSJ9LHsiY2hhciI6IueXhSJ9LHsiY2hhciI6IueahCJ9LHsiY2hhciI6IuaXoiJ9LHsiY2hhciI6IuWumiJ9LHsiY2hhciI6IuiHtCJ9LHsiY2hhciI6IueXhSJ9LHsiY2hhciI6IuWboCJ9LHsiY2hhciI6Iue0oCJ9LHsiY2hhciI6IuOAg iJ9LHsiY2hhciI6IuW3siJ9LHsiY2hhciI6IuaciSJ9LHsiY2hhciI6IueglCJ9LHsiY2hhciI6IueptiJ9LHsiY2hhciI6IuihqCJ9LHsiY2hhciI6IuaYjiJ9LHsiY2hhciI6Iu+ 8jCJ9LHsiY2hhciI6IuS9jiJ9LHsiY2hhciI6IuWvhiJ9LHsiY2hhciI6IuW6piJ9LHsiY2hhciI6IuiEgiJ9LHsiY2hhciI6IuibiyJ9LHsiY2hhciI6IueZvSJ9LHsiY2hhciI6IigifSx7ImNoYXIiOiJMIn0seyJjaGFyIjoiRCJ9LHsiY2hhciI6IkwifSx7ImNoYXIiOiIpIn0seyJjaGFyIjoi6IOGIn0seyJjaGFyIjoi5Zu6In0seyJjaGFyIjoi6YaHIn0seyJjaGFyIjoi55qEIn0seyJjaGFyIjoi6auYIn0seyJjaGFyIjoi5rWTIn0seyJjaGFyIjoi5bqmIn0seyJjaGFyIjoi5LyaIn0seyJjaGFyIjoi5aKeIn0seyJjaGFyIjoi5YqgIn0seyJj aGFyIjoi57y6In0seyJjaGFyIjoi6KGAIn0seyJjaGFyIjoi5oCnIn0seyJjaGFyIjoi5LitIn0seyJjaGFyIjoi6aOOIn0seyJjaGFyIjoi55qEIn0seyJjaGFyIjoi6aOOIn0seyJjaGFyIjoi6ZmpIn0seyJjaGFyIjoi77yMIn0seyJjaGFyIjoi6ICMIn0seyJjaGFyIjoi6auYIn0seyJjaGFyIjoi5a+ GIn0seyJjaGFyIjoi5bqmIn0seyJjaGFyIjoi6ISCIn0seyJjaGFyIjoi6JuLIn0seyJjaGFyIjoi55m9In0seyJjaGFyIjoiKCJ9LHsiY2hhciI6IkgifSx7ImNoYXIiOiJEIn0seyJjaGFyIjoiTCJ9LHsiY2hhciI6IikifSx7ImNoYXIiOiLog4YifSx7ImNoYXIiOiLlm7oifSx7ImNoYXIiOiLphocifSx7ImNoYXIiOiLnmoQifSx7ImNoYXIiOiLpq5gifSx7ImNoYXIiOiLmtZMifSx7ImNoYXIiOiLluqYifSx7ImNoYXIiOiLlj68ifSx7ImNoYXIiOiLog70ifSx7ImNoYXIiOiLkvJoifSx7ImNoYXIiOiLpmY0ifSx7ImNoYXIiOiLkvY4ifSx7ImNo YXIiOiLnvLoifSx7ImNoYXIiOiLooYAifSx7ImNoYXIiOiLmgKcifSx7ImNoYXIiOiLkuK0ifSx7ImNoYXIiOiLpo44ifSx7ImNoYXIiOiLvvIwifSx7ImNoYXIiOiLnibkifSx7ImNoYXIiOiLliKsifSx7ImNoYXIiOiLmmK8ifSx7ImNoYXIiOiLlsI8ifSx7ImNoYXIiOiLooYAifSx7ImNoYXIiOiLnrqEifSx7ImNoYXIiOiLkuK0ifSx7ImNoYXIiOiLpo44ifSx7ImNoYXIiOiLnmoQifSx