J Stroke.  2022 May;24(2):224-235. 10.5853/jos.2021.02152.

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

• O’Donnell MJ
• McQueen M
• Sniderman A
• Pare G
• Wang X
• Hankey GJ
• Rangarajan S
• Chin SL
• Rao-Melacini P
• Ferguson J
• Xavier D
• Lisheng L
• Zhang H
• Pais P
• Lopez-Jaramillo P
• Damasceno A
• Langhorne P
• Rosengren A
• Dans AL
• Elsayed A
• Avezum A
• Mondo C
• Judge C
• Diener HC
• Ryglewicz D
• Czlonkowska A
• Pogosova N
• Weimar C
• Iqbal R
• Diaz R
• Yusoff K
• Yusufali A
• Oguz A
• Penaherrera E
• Lanas F
• Ogah OS
• Ogunniyi A
• Iversen HK
• Malaga G
• Rumboldt Z
• Oveisgharan S
• Al Hussain F
• Nilanont Y
• Yusuf S
• on Behalf of the INTERSTROKE Investigators

• KMID: 2530525
• DOI: http://doi.org/10.5853/jos.2021.02152

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.

Keyword

Stroke; Risk factor; Dyslipidemia; Lipoproteins; Apolipoproteins; Case-control

Figure

• 

  Figure 1. Association of total cholesterol, lipoproteins and apolipoprotein (Apo), and stroke. Forest plot for association of total cholesterol, non-high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), HDL-C, non-HDL/HDL ratio, LDL/HDL ratio, apoB, apoA1, and apoB/A1 ratio, and ischemic stroke, ischemic stroke subtypes, and intracerebral hemorrhage. Odd ratio and 95% confidence interval (CI) per standard deviation (SD) change.

• 

  Figure 2. (A) Association of lipoproteins with ischemic stroke and intracerebral hemorrhage (ICH). (B) Association of apolipoproteins with ischemic stroke and ICH. Restricted cubic spline plot of association of (A) lipoproteins (low-density lipoprotein cholesterol [LDL-C] and high-density lipoprotein cholesterol [HDL-C]) (X-axis) and (B) apolipoproteins (apoB and apoA1) (X-axis) with ischemic stroke and ICH. Spline curve truncated at highest and lowest 2% of values. All splines adjusted for age, sex, geographic region, and potential confounders (smoking, diabetes mellitus, physical activity, diet risk score, psychosocial factors, waist-to-hip ratio, pre-admission statin, and alcohol intake).

• 

  Figure 3. Association of (A) low-density lipoprotein cholesterol (LDL-C), (B) high-density lipoprotein cholesterol (HDL-C), (C) apolipoprotein B (apoB), (D) apoA1 by ischemic stroke subtype. Restricted cubic spline plot of association of (A) LDL-C (X-axis), (B) HDL-C (X-axis), (C) apoB (X-axis), (D) apoA1 (X-axis) with ischemic stroke subtypes. Spline curve truncated at highest and lowest 2% of values. All splines adjusted for age, sex, geographic region, and potential confounders (smoking, diabetes mellitus, physical activity, diet, psychosocial factors, waist-to-hip ratio, pre-admission statin, and alcohol intake).

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