Lipoprotein (a), Birth Weight and Neonatal Stroke

Renaud, Cyrille; Bonneau, Christine; Presles, Émilie; Laporte, Silvy; Depeyre, Arnaud; Varlet, Marie-Noëlle; Chabrier, Stéphane

doi:10.1159/000281015

Cited by 6 publications

(3 citation statements)

References 23 publications

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“…Interestingly, in a French study of mother-infant diads of neonatal AIS, elevated maternal Lp(a) was not only implicated in perinatal AIS but also correlated with low birth weight in these infants, leading to a hypothesis that elevated Lp(a) may mediate placental insufficiency. 18 With regard to recurrent AIS in childhood, a prospective multicenter cohort study in Germany 13 demonstrated that Lp(a) >30 mg/dL was an independent risk factor for recurrent AIS (OR: 2.8; 95% CI: 1.1-7.5).…”

Section: Introductionmentioning

confidence: 99%

Elevated lipoprotein (a), small apolipoprotein (a), and the risk of arterial ischemic stroke in North American children

et al. 2013

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Lipoprotein (a) is a risk factor for adult cardiovascular events, in which the apolipoprotein (a) component is thought to promote atherogenesis and impair fibrinolysis. We investigated whether elevated plasma lipoprotein (a) concentration and small predominant apolipoprotein (a) isoform size (number of kringle-4 domains) are risk factors for childhood arterial ischemic stroke and correlate with plasma fibrinolytic function. Patients who had had an arterial ischemic stroke in childhood (29 days -<21 years at onset; n=43) and healthy controls (n=127) were recruited for plasma sampling and laboratory determinations. Cases were followed for recurrence in a prospective cohort study. The median lipoprotein (a) concentration did not differ between groups [cases: median 18.0 nmol/L (7.5 mg/dL) and observed range 0.9-259 nmol/L (0.38-108.0 mg/dL), controls: 20.4 nmol/L (8.5 mg/dL) and 0.2-282 nmol/L (0.08-117.5 mg/dL); P=0.62]. While odds of incident stroke were not significantly increased, risks of recurrent arterial ischemic stroke were each more than ten-times increased for lipoprotein(a) >90 th percentile of racespecific reference values and apolipoprotein (a) <10 th percentiles [odds ratio=14.0 (95% confidence interval: 1.0-184), P=0.05 and odds ratio=12.8 (1.61-101), P=0.02]. Statistically significant but weak correlations were observed between euglobulin lysis time and both lipoprotein (a) level (r=0.18, P=0.03) and apolipoprotein (a) size (r= -0.26, P=0.002). In conclusion, elevated lipoprotein (a) and small apolipoprotein (a) potently increase the risk of recurrent arterial ischemic stroke in children, with a mechanism only partially attributable to impaired fibrinolysis. Collaborative studies are warranted to investigate these findings further and, more broadly, to establish key risk factors for incident and recurrent arterial ischemic stroke in children. More recently, in a study in the USA, 17 the prevalence of elevated Lp(a) among 59 children with porencephaly or a history of perinatal or childhood onset-AIS was significantly increased compared to that of historical controls who had consisted of healthy German children (20% versus 5.4%); however, concomitant USAbased controls were lacking. Interestingly, in a French study of mother-infant diads of neonatal AIS, elevated maternal Lp(a) was not only implicated in perinatal AIS but also correlated with low birth weight in these infants, leading to a hypothesis that elevated Lp(a) may mediate placental insufficiency. Elevated lipoprotein (a), small apolipoprotein (a), and the risk of arterial ischemic stroke in North American children18 With regard to recurrent AIS in childhood, a prospective multicenter cohort study in Germany 13 demonstrated that Lp(a) >30 mg/dL was an independent risk factor for recurrent AIS (OR: 2.8; 95% CI: 1.1-7.5).In consideration of the lack of well-controlled studies of Lp(a) in childhood-onset AIS outside of Germany, and given also that apo(a) size has received little attention in pediatric AIS, we sought to determine the odds of inci...

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Section: Introductionmentioning

confidence: 99%

Elevated lipoprotein (a), small apolipoprotein (a), and the risk of arterial ischemic stroke in North American children

et al. 2013

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“…These data suggest that the demonstrated increased risk of AIS in children with elevated maternal Lp(a) may be mediated through impaired vascular placental function. 55 In another study involving 60 mother-child pairs, a statistically significant difference (p < 0.0001) was observed between the general population and mothers of children with perinatal arterial stroke with regard to elevated serum Lp(a) levels, among other prothrombotic factors. In addition, in this study, 33% of mothers and 21% of children with perinatal AIS presented elevated Lp(a) levels.…”

Section: Lp(a) and Cerebrovascular Accidentsmentioning

confidence: 93%

Lipoprotein (a) and cerebrovascular disease

Kosmas,

Bousvarou,

Papakonstantinou

et al. 2024

J Int Med Res

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The role of lipoprotein (a) [Lp(a)] in cerebrovascular disease is a topic of importance. In this narrative review, pertinent studies have been leveraged to comprehensively examine this relationship from diverse perspectives. Lp(a) shares structural traits with low-density lipoprotein cholesterol. Lp(a) is synthesized by hepatocytes, and its plasma levels are genetically determined by the LPA gene, which produces apolipoprotein (a). Numerous epidemiological studies have confirmed the positive correlation between elevated serum Lp(a) levels and the occurrence or recurrence of cerebrovascular events, especially ischemic strokes, in adults. It should be noted that the correlation strength varies among studies and is marginal in Mendelian randomization studies. Regarding pediatric patients, screening is currently limited to those with a relevant medical history. Lp(a) seems to play a significant role in the pathogenesis of arterial ischemic stroke in children because environmental thrombotic and atherogenic factors are generally not present. Phase 3 trials of novel Lp(a) targeting agents, such as pelacarsen and olpasiran, are anticipated to demonstrate their efficacy in reducing the incidence of stroke. Given the richness of the literature, new guidelines regarding Lp(a) screening and management in targeted populations are warranted to provide more effective primary and secondary prevention.

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“… 137 Of note, the risk of hemorrhagic stroke is reduced in patients with high Lp(a) levels. 138 Lp(a) is a particularly strong predictor of ischemic stroke in neonates, 139 children, 140 , 141 and young adults. 142 Children with high Lp(a) levels have a 4-fold risk of ischemic stroke with an even higher risk for recurrent stroke.…”

Section: Lp(a) and Non-coronary Diseasesmentioning

confidence: 99%

Lipoprotein(a): An independent, genetic, and causal factor for cardiovascular disease and acute myocardial infarction

Enas¹,

Varkey

Dharmarajan

et al. 2019

Indian Heart Journal

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Lipoprotein(a) [Lp(a)] is a circulating lipoprotein, and its level is largely determined by variation in the Lp(a) gene (LPA) locus encoding apo(a). Genetic variation in the LPA gene that increases Lp(a) level also increases coronary artery disease (CAD) risk, suggesting that Lp(a) is a causal factor for CAD risk. Lp(a) is the preferential lipoprotein carrier for oxidized phospholipids (OxPL), a proatherogenic and proinflammatory biomarker. Lp(a) adversely affects endothelial function, inflammation, oxidative stress, fibrinolysis, and plaque stability, leading to accelerated atherothrombosis and premature CAD. The INTER-HEART Study has established the usefulness of Lp(a) in assessing the risk of acute myocardial infarction in ethnically diverse populations with South Asians having the highest risk and population attributable risk. The 2018 Cholesterol Clinical Practice Guideline have recognized elevated Lp(a) as an atherosclerotic cardiovascular disease risk enhancer for initiating or intensifying statin therapy.

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Lipoprotein (a), Birth Weight and Neonatal Stroke

Cited by 6 publications

References 23 publications

Elevated lipoprotein (a), small apolipoprotein (a), and the risk of arterial ischemic stroke in North American children

Elevated lipoprotein (a), small apolipoprotein (a), and the risk of arterial ischemic stroke in North American children

Lipoprotein (a) and cerebrovascular disease

Lipoprotein(a): An independent, genetic, and causal factor for cardiovascular disease and acute myocardial infarction

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