Apolipoproteins B and AI and the risk of ischemic cerebrovascular events in patients with pre-existing atherothrombotic disease
Introduction
The risk of coronary heart disease increases with increasing concentrations of low-density lipoprotein (LDL) cholesterol and decreases with increasing high-density lipoprotein (HDL) cholesterol [1], but these associations are less clear for ischemic stroke [2], [3]. In a recent updated meta-analysis no robust independent positive association of cholesterol with overall stroke mortality was observed [3], but, several studies examining the associations with incident ischemic events and addressing in-particular cerebrovascular atherosclerotic disease and atherothrombotic ischemic stroke found comparable associations to that of coronary heart disease, albeit with somewhat weaker magnitude [4], [5], [6], [7]. We have observed in a cohort of patients with coronary heart disease associations between blood lipids and incident ischemic stroke as previously reported [6], [7].
Apolipoprotein B (Apo B), which reflects the concentration of potentially atherogenic lipoprotein particles, and apolipoprotein AI (Apo A-I), which reflects the corresponding concentration of the anti-atherogenic HDL, represent additional lipoprotein-related variables that may indicate vascular risk. A growing body of evidence suggests that blood levels of Apo B, Apo A-1 and the Apo A-I/Apo B ratio, as do blood lipids, predict cardiovascular disease [8], [9], [10], [11], [12], [13], [14], [15], [16], [17]. Studies on the relationship of apolipoproteins and stroke have been sparse and less conclusive [18], [19], [20], [21], [22], but recent reports have suggested an association also with cerebrovascular events [21], [22]. Moreover, the Apo B/Apo A-I ratio was found to be related to the change in carotid artery intima-media thickness [23] and to carotid atheroma [24]. The aim of the current analysis was, therefore, to examine whether Apo B, Apo A-I and the Apo A-I/Apo B ratio predict incident ischemic cerebrovascular events among patients with pre-existing atherothrombotic disease.
Section snippets
Study population
Patients with documented coronary heart disease, aged 45–74 years, were screened for inclusion in a study of lipid modification (the Bezafibrate Infarction Prevention study; BIP) [25] between February 1990 and October 1992. The screening procedure was undertaken to recruit patients into the study who had evidence of a non-recent myocardial infarction, or other manifestations of coronary insufficiency. Of 15,078 screened patients, free of prior cerebrovascular events, 6,995 had total cholesterol
Results
Among the 3,434 patients included in the current analysis, 266 (7.7%) developed an ischemic cerebrovascular event during follow-up. Apo B levels ranged from 0.39 to 1.77 g/L (mean ± SD, 1.04 ± 0.18) and Apo A-I from 0.56 to 1.82 g/L (mean ± SD, 1.10 ± 0.17). Patients with ischemic cerebrovascular events were older, had higher proportions of hypertension, diabetes mellitus and peripheral vascular disease, higher mean glucose and Apo B and lower HDL as percent of total cholesterol (%HDL), Apo A-I
Discussion
Our main finding is that among patients with preexisting cardiovascular disease, high serum levels of Apo B and low Apo A-I are associated with increased risk of incident ischemic cerebrovascular events. Apolipoproteins remained independent risk factors upon adjustment for traditional stroke risk factors. In addition, our findings strengthen the notion of the ApoA-I/ApoB ratio as a useful indicator of ischemic stroke risk in patients with preexisting atherothrombotic disease. These findings
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Cited by (15)
Association of the ApoB/ApoA-I ratio with stroke risk: Findings from the China Health and Nutrition Survey (CHNS)
2022, Nutrition, Metabolism and Cardiovascular DiseasesCitation Excerpt :Apart from single lipid parameters of TC, HDL-C, LDL-C, ApoA-I and ApoB, another study further examined the ApoB/ApoA-I ratio and reported that none of these were associated with the risk of stroke [18]. However, a clinical trial followed over 4.8–8.1 years in Israel found that all ApoB, ApoA-I and the ApoA-I/ApoB ratio significantly predicted incident stroke [24]. This may be due to different characteristics of the study populations (preexisting diseases and ethnic background) between the studies.
Apolipoprotein A-I and paraoxonase-1 are potential blood biomarkers for ischemic stroke diagnosis
2016, Journal of Stroke and Cerebrovascular DiseasesCitation Excerpt :Apo A-I is the primary lipoprotein associated with HDL in plasma.19 Lower Apo A-I levels were predictive of higher stroke risk in a large cohort study with over 175,000 patients,20 as well as ischemic stroke risk in patients with documented coronary artery disease.21 Apo C-I is associated with very low-density lipoprotein, low-density lipoprotein, and HDL.14,22
Sex differences in risk factors, etiology, and short-term outcome of cerebral infarction in young patients
2011, AtherosclerosisCitation Excerpt :In this Chinese population, they determine that the only independent risk factors for all strokes were a low serum Apo A1 concentration and a high serum Lp(a) concentration [18]. In the west, Koren-Morag et al. had confirmed that Apo B, Apo A1 and the Apo A1/Apo B ratio predict incident ischemic stroke among patients with preexisting atherothrombotic disease in 266 patients with cerebral infarction, and high serum levels of Apo B and low Apo A1 are associated with increased risk of incident ischemic cerebrovascular events [19]. The protective effect of Apo A1 maybe related to its action against the accumulation of platelet thrombi at sites of vascular damage since it has recently been identified as a prostacyclin-stabilizing factor [20].
Apolipoprotein B levels, APOB alleles, and risk of ischemic cardiovascular disease in the general population, a review
2009, AtherosclerosisCitation Excerpt :Several studies have shown that plasma levels of apolipoprotein B predict risk of ischemic cardiovascular disease and ischemic heart disease in the general population, as well as in patients with a previous myocardial infarction or the metabolic syndrome [14–19,21–24]. Apolipoprotein B as a predictor of ischemic cerebrovascular disease is not so well established, but results from the AMORIS study and the Chin-Shan Community Cohort have shown that apolipoprotein B predicts risk of fatal ischemic stroke in the general population, and in patients with a previous myocardial infarction [25–27]. The Copenhagen City Heart Study is the first prospective study to simultaneously examine prediction of ischemic heart disease, myocardial infarction, ischemic cerebrovascular disease, ischemic stroke, and any ischemic cardiovascular disease risk in the same general population study including both women and men, and to compare apolipoprotein B and LDL cholesterol levels as predictors of these events [28].
Predictive value of ApoB/ApoA-I for recurrence within 1 year after first incident stroke
2023, Frontiers in Neurology