TY - JOUR

T1 - Association of Lipids, Lipoproteins, and Apolipoproteins with Stroke Subtypes in an International Case Control Study (INTERSTROKE)

AU - O’Donnell, Martin J

AU - McQueen, Matthew

AU - Sniderman, Allan

AU - Pare, Guillaume

AU - Wang, Xingyu

AU - Hankey, Graeme J

AU - Rangarajan, Sumathy

AU - Chin, Siu Lim

AU - Rao-Melacini, Purnima

AU - Ferguson, John

AU - Xavier, Denis

AU - Lisheng, Liu

AU - Zhang, Hongye

AU - Pais, Prem

AU - Lopez-Jaramillo, Patricio

AU - Damasceno, Albertino

AU - Langhorne, Peter

AU - Rosengren, Annika

AU - Dans, Antonio L

AU - Elsayed, Ahmed

AU - Avezum, Alvaro

AU - Mondo, Charles

AU - Judge, Conor

AU - Diener, Hans-Christoph

AU - Ryglewicz, Danuta

AU - Czlonkowska, Anna

AU - Pogosova, Nana

AU - Weimar, Christian

AU - Iqbal, Romana

AU - Diaz, Rafael

AU - Yusoff, Khalid

AU - Yusufali, Afzalhussein

AU - Oguz, Aytekin

AU - Penaherrera, Ernesto

AU - Lanas, Fernando

AU - Ogah, Okechukwu S

AU - Ogunniyi, Adesola

AU - Iversen, Helle K.

AU - Malaga, German

AU - Rumboldt, Zvonko

AU - Oveisgharan, Shahram

AU - Hussain, Fawaz Al

AU - Nilanont, Yongchai

AU - Yusuf, Salim

AU - INTERSTROKE investigators

N1 - Publisher Copyright: © 2022 Korean Stroke Society.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Apolipoproteins

KW - Case-control

KW - Dyslipidemia

KW - Lipoproteins

KW - Risk factor

KW - Stroke

U2 - 10.5853/jos.2021.02152

DO - 10.5853/jos.2021.02152

M3 - Journal article

C2 - 35677977

AN - SCOPUS:85131863063

VL - 24

SP - 224

EP - 235

JO - Journal of Stroke

JF - Journal of Stroke

SN - 2287-6391

IS - 2

ER -