Association of Lipids, Lipoproteins, and Apolipoproteins with Stroke Subtypes in an International Case Control Study (INTERSTROKE)

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  • Martin J O’Donnell
  • Matthew McQueen
  • Allan Sniderman
  • Guillaume Pare
  • Xingyu Wang
  • Graeme J Hankey
  • Sumathy Rangarajan
  • Siu Lim Chin
  • Purnima Rao-Melacini
  • John Ferguson
  • Denis Xavier
  • Liu Lisheng
  • Hongye Zhang
  • Prem Pais
  • Patricio Lopez-Jaramillo
  • Albertino Damasceno
  • Peter Langhorne
  • Annika Rosengren
  • Antonio L Dans
  • Ahmed Elsayed
  • Alvaro Avezum
  • Charles Mondo
  • Conor Judge
  • Hans-Christoph Diener
  • Danuta Ryglewicz
  • Anna Czlonkowska
  • Nana Pogosova
  • Christian Weimar
  • Romana Iqbal
  • Rafael Diaz
  • Khalid Yusoff
  • Afzalhussein Yusufali
  • Aytekin Oguz
  • Ernesto Penaherrera
  • Fernando Lanas
  • Okechukwu S Ogah
  • Adesola Ogunniyi
  • Iversen, Helle Klingenberg
  • German Malaga
  • Zvonko Rumboldt
  • Shahram Oveisgharan
  • Fawaz Al Hussain
  • Yongchai Nilanont
  • Salim Yusuf
  • INTERSTROKE investigators

Background and Purpose The association of dyslipidemia with stroke has been inconsistent, which may be due to differing associations within etiological stroke subtypes. We sought to determine the association of lipoproteins and apolipoproteins within stroke subtypes. Methods Standardized incident case-control STROKE study in 32 countries. Cases were patients with acute hospitalized first stroke, and matched by age, sex and site to controls. Concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (apoA1), and apoB were measured. Non-HDL-C was calculated. We estimated multivariable odds ratio (OR) and population attributable risk percentage (PAR%). Outcome measures were all stroke, ischemic stroke (and subtypes), and intracerebral hemorrhage (ICH). Results Our analysis included 11,898 matched case-control pairs; 77.3% with ischemic stroke and 22.7% with ICH. Increasing apoB (OR, 1.10; 95% confidence interval [CI], 1.06 to 1.14 per standard deviation [SD]) and LDL-C (OR, 1.06; 95% CI, 1.02 to 1.10 per SD) were associated with an increase in risk of ischemic stroke, but a reduced risk of ICH. Increased apoB was significantly associated with large vessel stroke (PAR 13.4%; 95% CI, 5.6 to 28.4) and stroke of undetermined cause. Higher HDL-C (OR, 0.75; 95% CI, 0.72 to 0.78 per SD) and apoA1 (OR, 0.63; 95% CI, 0.61 to 0.66 per SD) were associated with ischemic stroke (and subtypes). While increasing HDL-C was associated with an increased risk of ICH (OR, 1.20; 95% CI, 1.14 to 1.27 per SD), apoA1 was associated with a reduced risk (OR, 0.80; 95% CI, 0.75 to 0.85 per SD). ApoB/A1 (OR, 1.38; 95% CI, 1.32 to 1.44 per SD) had a stronger magnitude of association than the ratio of LDL-C/HDL-C (OR, 1.26; 95% CI, 1.21 to 1.31 per SD) with ischemic stroke (P<0.0001). Conclusions The pattern and magnitude of association of lipoproteins and apolipoproteins with stroke varies by etiological stroke subtype. While the directions of association for LDL, HDL, and apoB were opposing for ischemic stroke and ICH, apoA1 was associated with a reduction in both ischemic stroke and ICH. The ratio of apoB/A1 was the best lipid predictor of ischemic stroke risk.

OriginalsprogEngelsk
TidsskriftJournal of Stroke
Vol/bind24
Udgave nummer2
Sider (fra-til)224-235
Antal sider12
ISSN2287-6391
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
The INTERSTROKE study was funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Vastra Gota-land (Sweden), and through unrestricted grants from several pharmaceutical companies with major contributions from As-traZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Swedish Heart and Lung Foundation, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK-Stroke Research Network. The sponsors had no role in data collection, analyses or the decision to submit for publications.

Publisher Copyright:
© 2022 Korean Stroke Society.

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