Lipoprotein (a): Its Role in Childhood Thromboembolism

Abstract

ABSTRACT. Purpose. Elevated lipoprotein (a) [LP (a)] concentrations are independent risk factors of coronary heart disease or stroke in young adults. To clarify its role in childhood thromboembolism, Lp (a) was measured in 72 children with thromboembolism.Methods. In addition to Lp (a), defects of the protein C anticoagulant system, antithrombin, and antiphospholipid antibodies were investigated in children with arterial (n ‫؍‬ 36) or venous (n ‫؍‬ 36) thrombosis.Results. Enhanced Lp (a) >50 mg/dL was diagnosed in 8 out of 36 children with arterial and 5 out of 36 patients with venous thrombosis. Of the 72 children, 25 showed the factor V Leiden mutation, 10 showed protein C deficiency, 2 showed antithrombin deficiency, and 4 showed primary antiphospholipid syndrome. Three children with increased Lp (a) were heterozygous for the factor V Leiden mutation, and 1 girl showed additional protein C deficiency.Conclusions. Lipoprotein (a) [Lp (a)] is a cholesterol-rich plasma lipoprotein with a lipid composition similar to that of low-density lipoproteins (LDL). The protein composition is different from that of LDL, consisting of two major proteins, apolipoprotein (apo) B and apo (a). 1,2Lp (a) levels vary from person to person but are genetically determined as a dominant trait, minimally affected by race, age, and sex.3,4 Numerous groups agree in their findings that individuals with increased concentrations of Lp (a) have a higher risk of premature coronary heart disease, 5-7 unrelated to the remaining lipoproteins. In addition, the risk of stroke 3,8 -12 as well as for restenosis after coronary artery bypass surgery 13,14 correlates highly with increased Lp (a) concentrations. Little is known, however, about the relation between increased Lp (a) concentrations and childhood thrombosis at various sites. We used a commercially available enzyme-linked immunosorbent assay to measure Lp (a) in a population of children with arterial or venous thrombosis. METHODSSeventy-two infants and children aged from birth to 18 years consecutively recruited between 1992 and 1996 and primarily treated for arterial (n ϭ 36) or venous (n ϭ 36) thrombosis were enrolled in this study. In the majority of cases arterial thrombosis occurred in the central nervous system. Sixteen of 36 infants developed embolic stroke or multiple thrombosis in the neonatal period (attributable to the uncertainty in differentiating between embolic and local stroke in the majority of cases investigated, all children with initial symptoms of stroke were categorized in the arterial group). In addition, 11 children Ͼ1 year of age suffered an ischemic embolic, local, or lacunar stroke. Left intracardial thrombus formation was diagnosed in 4 of 36 patients, the femoral artery was occluded in two children and aortic thrombosis was found in two infants. Venous thromboses were found in the femoral vein (n ϭ 10), renal veins (n ϭ 8), superior caval vein (n ϭ 6), central nervous system (n ϭ 7), and portal vein (n ϭ 5), respectively. In the majority of cases, underlying di...

Increased Stroke Risk and Lipoprotein(a) in a Multiethnic Community: The Northern Manhattan Stroke Study

“…For the entire group, when adjusting for other established risk factors, an elevated Lp(a) level was an independent stroke risk factor, and Lp(a) levels ≥30 mg/dl were associated with an almost 2-fold increase in IS. Conflicting results have been reported on the relationship between Lp(a) and stroke risk [7,12,15,16,17,18,19,20,28,29,30,31]. While Lp(a) levels have been reported to be generally higher in IS cases than controls, these levels have not been consistently predictive of cerebral infarction [12].…”

“…To date, conflicting results have been reported on the relationship between Lp(a) and IS risk [15,16,17,18,19,20]. Although Lp(a) levels have generally been shown to be higher in IS cases than in controls, serum Lp(a) levels have not been consistently predictive of cerebral infarction [20].…”

Lipoprotein (a) and Venous Thromboembolism in Adults: A Meta-Analysis

“…The contrasting results of the available studies on Lp(a) and venous thromboembolism can be explained by several issues. Half of the studies available in the literature have been conducted among children, [15][16][17][18][19][20][21][22][23][24][25][26] and most of the studies involving adults have investigated less than a hundred cases. [28][29][30] In addition, some studies are old and contain scarce and limited information regarding the diagnosis of venous thromboembolism.…”

“…Our search strategy yielded 24 reports [8][9][10][11][12][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] ; of them, 12 were excluded on the basis of title/abstract because they studied venous thrombosis in children. [15][16][17][18][19][20][21][22][23][24][25][26] Of the remaining 12 articles, one was excluded because it did not report Lp(a) levels but only apoLipoprotein (a) concentrations, 27 and another study was eliminated because it was, as a matter of fact, a family study that studied the co-segregation of thrombophilic disorders in factor V Leiden carriers. 31 Among the 10 case-control studies selected to be included in the meta-analysis, however, 3 potentially eligible studies 9,32,33 were finally excluded because the authors were not able, upon specific request, to collect the exact number of subjects with Lp(a) levels above the con-…”

Lipoprotein (a) as a cause of cardiovascular disease: insights from epidemiology, genetics, and biology

“…However, in a study including 109,169 individuals from the Copenhagen City Heart Study and the Copenhagen General Population study combined, we found that high Lp(a) concentrations of venous thromboembolism, with conflicting results (232)(233)(234)(235)(236)(237)(238)(239)(240)(241)(242).…”