Journal of Stroke (May 2022)
Association of Lipids, Lipoproteins, and Apolipoproteins with Stroke Subtypes in an International Case Control Study (INTERSTROKE)
- 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,
- Helle K. Iversen,
- German Malaga,
- Zvonko Rumboldt,
- Shahram Oveisgharan,
- Fawaz Al Hussain,
- Yongchai Nilanont,
- Salim Yusuf,
Affiliations
- Martin J. O’Donnell
- Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada
- Matthew McQueen
- Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada
- Allan Sniderman
- Division of Cardiology, McGill University Health Center, Montreal, QC, Canada
- Guillaume Pare
- Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada
- Xingyu Wang
- National Center of Cardiovascular Disease, Beijing, China
- Graeme J. Hankey
- School of Medicine and Pharmacology, The University of Western Australia, Perth, Australia
- Sumathy Rangarajan
- Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada
- Siu Lim Chin
- Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada
- Purnima Rao-Melacini
- Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada
- John Ferguson
- Department of Medicine, HRB-Clinical Research Facility, NUI Galway, Galway, Ireland
- Denis Xavier
- St John’s Medical College and Research Institute, Bangalore, India
- Liu Lisheng
- National Center of Cardiovascular Disease, Beijing, China
- Hongye Zhang
- Beijing Hypertension League Institute, Beijing, China
- Prem Pais
- St John’s Medical College and Research Institute, Bangalore, India
- Patricio Lopez-Jaramillo
- Fundacion Oftalmologica de Santander-Clinica Carlos Ardila Lulle (FOSCAL), Bucaramanga, Colombia
- Albertino Damasceno
- Faculty of Medicine, Eduardo Mondlane University, Maputo, Mozambique
- Peter Langhorne
- Department of Geriatric Medicine, Glasgow Royal Infirmary, University of Glasgow, Glasgow, UK
- Annika Rosengren
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy and University Hospital, University of Gothenburg, Gothenburg, Sweden
- Antonio L. Dans
- College of Medicine, University of Philippines, Manila, Philippines
- Ahmed Elsayed
- Department of Surgery, Al Shaab Teaching Hospital, Khartoum, Sudan
- Alvaro Avezum
- International Research Center, Hospital Alemão Oswaldo Cruz, Sao Paulo, Brazil
- Charles Mondo
- Department of Cardiology, Kiruddu National Referral Hospital, Kampala, Uganda
- Conor Judge
- Department of Medicine, HRB-Clinical Research Facility, NUI Galway, Galway, Ireland
- Hans-Christoph Diener
- Institute for Medical Informatics, Department of Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany
- Danuta Ryglewicz
- Institute of Psychiatry and Neurology, Warsaw, Poland
- Anna Czlonkowska
- Department of Neurology, Military Institute of Aviation Medicine, Warsaw, Poland
- Nana Pogosova
- National Research Center for Preventive Medicine, Ministry of Healthcare of the Russian Federation, Moscow, Russia
- Christian Weimar
- Institute for Medical Informatics, Department of Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany
- Romana Iqbal
- Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
- Rafael Diaz
- Estudios Clínicos Latino America (ECLA), Instituto Cardiovascular de Rosario (ICR), Rosario, Argentina
- Khalid Yusoff
- University College Sedaya International (UCSI) University, Kuala Lumpur, Malaysia
- Afzalhussein Yusufali
- Department of Medicine, Hatta Hospital, Dubai Health Authority, Dubai Medical College, Dubai, United Arab Emirates
- Aytekin Oguz
- Department of Medicine, Istanbul Medeniyet University, Istanbul, Turkey
- Ernesto Penaherrera
- Department of Cardiology, Hospital Luis Vernaza, Guayaquil, Ecuador
- Fernando Lanas
- Faculty of Medicine, University of La Frontera, Temuco, Chile
- Okechukwu S. Ogah
- Division of Cardiovascular Medicine, Department of Medicine, University College Hospital, Ibadan, Nigeria
- Adesola Ogunniyi
- Department of Medicine, University College Hospital, Ibadan, Nigeria
- Helle K. Iversen
- Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- German Malaga
- Cayetano Heredia University, Lima, Peru
- Zvonko Rumboldt
- Department of Medicine, University of Split, Split, Croatia
- Shahram Oveisgharan
- Department of Neurology, Rush Alzheimer’s Disease Center, Chicago, IL, USA
- Fawaz Al Hussain
- King Saud University, Riyadh, Saudi Arabia
- Yongchai Nilanont
- Neurology Division, Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Salim Yusuf
- Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada
- DOI
- https://doi.org/10.5853/jos.2021.02152
- Journal volume & issue
-
Vol. 24,
no. 2
pp. 224 – 235
Abstract
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.
Keywords
