Atherosclerotic cardiovascular disease (CVD), a leading cause of death globally, has origins in childhood. Major risk factors include family history of premature CVD, dyslipidemia, diabetes mellitus, and hypertension. Lipoprotein (a) [Lp(a)], an inherited lipoprotein, is associated with premature CVD, but its impact on cardiovascular health during childhood is less understood. The objective of the study was to examine the relationship between Lp(a), family history of premature CVD, dyslipidemia, and vascular function and structure in a high-risk pediatric population. This is a single-center, cross-sectional study of 257 children referred to a preventive cardiology clinic. The independent variable, Lp(a), separated children into high-Lp(a) [Lp(a) ≥ 30 mg/dL] and normal-Lp(a) groups [Lp(a) < 30 mg/dL]. Dependent variables included family history of premature CVD; dyslipidemia, defined as low-density lipoprotein cholesterol > 130 mg/dL, high-density lipoprotein cholesterol (HDL-C) < 45 mg/dL, triglycerides (TG) > 100 mg/dL; and vascular changes suggesting early atherosclerosis, as measured by carotid–femoral pulse wave velocity (PWV) and carotid artery intima-media thickness (CIMT). Of the 257 children, 110 (42.8%) had high Lp(a) and 147 (57.2%) had normal Lp(a). There was a higher prevalence of African-American children in the high-Lp(a) group (19.3%) compared to the normal-Lp(a) group (2.1%) (p < 0.001). High Lp(a) was associated with positive family history of premature CVD (p = 0.03), higher-than-optimal HDL-C (p = 0.02), and lower TG (p < 0.001). There was no difference in PWV or CIMT between groups. High Lp(a) in children is associated with family history of premature CVD and is prevalent in African-American children. In children with high Lp(a), promotion of intensive lifestyle modifications is prudent to decrease premature CVD-related morbidity.
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National Heart, Lung, and Blood Institute (2009) Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics 128(Suppl 5):S213–S256. https://doi.org/10.1542/peds.2009-2107C
Mozaffarian D, Benjamin EJ, Go AS et al (2016) Executive summary: heart disease and stroke statistics–2016 update: a report from the American Heart Association. Circulation 133:447–454. https://doi.org/10.1161/CIR.0000000000000366
Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, Nordestgaard BG (2009) Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA 301:2331–2339. https://doi.org/10.1001/jama.2009.801
Willeit J, Kiechl S, Santer P et al (1995) Lipoprotein(a) and asymptomatic carotid artery disease. Evidence of a prominent role in the evolution of advanced carotid plaques: the Bruneck Study. Stroke 26:1582–1587. https://doi.org/10.1161/01.STR.26.9.1582
Nordestgaard BG, Langsted A (2015) How does elevated lipoprotein(a) cause aortic valve stenosis? J Am Coll Cardiol 66:1247–1249. https://doi.org/10.1016/j.jacc.2015.07.045
Kronenberg F, Kronenberg MF, Kiechl S et al (1999) Role of lipoprotein(a) and apolipoprotein(a) phenotype in atherogenesis: prospective results from the Bruneck study. Circulation 100:1154–1160. https://doi.org/10.1161/01.CIR.100.11.1154
Maranhão RC, Carvalho PO, Strunz CC, Pileggi F (2014) Lipoprotein (a): structure, pathophysiology and clinical implications. Arq Bras Cardiol 103:76–84. https://doi.org/10.5935/abc.20140101
van der Valk FM, Bekkering S, Kroon J et al (2016) Oxidized phospholipids on lipoprotein(a) elicit arterial wall inflammation and an inflammatory monocyte response in humans. Circulation 134:611–624. https://doi.org/10.1161/CIRCULATIONAHA.116.020838
Koschinsky ML, Boffa MB (2014) Lipoprotein(a): an important cardiovascular risk factor and a clinical conundrum. Endocrinol Metab Clin N Am 43:949 – 62. https://doi.org/10.1016/j.ecl.2014.08.002
Tsimikas S, Hall JL (2012) Lipoprotein(a) as a potential causal genetic risk factor of cardiovascular disease: a rationale for increased efforts to understand its pathophysiology and develop targeted therapies. J Am Coll Cardiol 60:716–721. https://doi.org/10.1016/j.jacc.2012.04.038
Terrados N, Valcárcel G, Venta R (2010) New cardiovascular risk factors and physical activity. Apunts Med Esport 45(167):201–208
De Simone M, Verrotti A, Cappa M et al (2003) Lipoprotein (a) in childhood: correlations with family history of cardiovascular disease. J Endocrinol Invest 26:414–419. https://doi.org/10.1007/BF03345196
Glowinska B, Urban M, Koput A (2002) Cardiovascular risk factors in children with obesity, hypertension and diabetes: lipoprotein(a) levels and body mass index correlate with family history of cardiovascular disease. Eur J Pediatr 161:511–518. https://doi.org/10.1007/s00431-002-1040-7
Guardamagna O, Abello F, Anfossi G, Pirro M (2011) Lipoprotein(a) and family history of cardiovascular disease in children with familial dyslipidemias. J Pediatr 159:314–319. https://doi.org/10.1016/j.jpeds.2011.01.038
Gaeta G, Cuomo S, Capozzi G et al (2008) Lipoprotein(a) levels are increased in healthy young subjects with parental history of premature myocardial infarction. Nutr Metab Cardiovasc Dis 18:492–496. https://doi.org/10.1016/j.numecd.2007.03.006
Sorensen KE, Celermajer DS, Georgakopoulos D, Hatcher G, Betteridge DJ, Deanfield JE (1994) Impairment of endothelium-dependent dilation is an early event in children with familial hypercholesterolemia and is related to the lipoprotein(a) level. J Clin Invest 93:50–55. https://doi.org/10.1172/JCI116983
Lapinleimu J, Raitakari OT, Lapinleimu H et al (2015) High lipoprotein(a) concentrations are associated with impaired endothelial function in children. J Pediatr 166:947–952.e1-2. https://doi.org/10.1016/j.jpeds.2014.12.051
Frolow M, Drozdz A, Kowalewska A, Nizankowski R, Chlopicki S (2015) Comprehensive assessment of vascular health in patients; towards endothelium-guided therapy. Pharmacol Rep 67:786 – 92. https://doi.org/10.1016/j.pharep.2015.05.010
Levine DM, Sloan BJ, Donner JE, Lorenz JD, Heinzerling RH (1992) Automated measurement of lipoprotein(a) by immunoturbidimetric analysis. Int J Clin Lab Res 22:173–178. https://doi.org/10.1007/BF02591419
Langer C, Tambyrayah B, Thedieck S, Nowak-Göttl U (2011) Testing for lipoprotein(a) concentration and apolipoprotein(a) phenotypes: method standardization and pediatric reference values. Semin Thromb Hemost 37:810–813. https://doi.org/10.1055/s-0031-1297172
Omboni S, Posokhov IN, Kotovskaya YV et al (2016) Twenty-four-hour ambulatory pulse wave analysis in hypertension management: current evidence and perspectives. Curr Hypertens Rep. https://doi.org/10.1007/s11906-016-0681-2
Zou G (2004) A modified poisson regression approach to prospective studies with binary data. Am J Epidemiol 159:702–706. https://doi.org/10.1093/aje/kwh090
Dirisamer A, Widhalm K (2002) Lipoprotein(a) as a potent risk indicator for early cardiovascular disease. Acta Paediatr 91:1313–1317. https://doi.org/10.1111/j.1651-2227.2002.tb02826.x
Obisesan TO, Aliyu MH, Adediran AS, Bond V, Maxwell CJ, Rotimi CN (2004) Correlates of serum lipoprotein (A) in children and adolescents in the United States. The third National Health Nutrition and Examination Survey (NHANES-III). Lipids Health Dis 3:29. https://doi.org/10.1186/1476-511X-3-29
Srinivasan SR, Dahlen GH, Jarpa RA, Webber LS, Berenson GS (1991) Racial (black-white) differences in serum lipoprotein (a) distribution and its relation to parental myocardial infarction in children. Bogalusa Heart Study. Circulation 84:160–167. https://doi.org/10.1161/01.CIR.84.1.160
Virani SS, Brautbar A, Davis BC et al (2012) Associations between lipoprotein(a) levels and cardiovascular outcomes in black and white subjects: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation 125:241–249. https://doi.org/10.1161/CIRCULATIONAHA.111.045120
Paultre F, Pearson TA, Weil HF et al (2000) High levels of Lp(a) with a small apo(a) isoform are associated with coronary artery disease in African American and white men. Arterioscler Thromb Vasc Biol 20:2619–2624. https://doi.org/10.1161/01.ATV.20.12.2619
Enkhmaa B, Anuurad E, Berglund L (2016) Lipoprotein (a): impact by ethnicity and environmental and medical conditions. J Lipid Res 57:1111–1125. https://doi.org/10.1194/jlr.R051904
Willeit P, Kiechl S, Kronenberg F et al (2014) Discrimination and net reclassification of cardiovascular risk with lipoprotein(a): prospective 15-year outcomes in the Bruneck Study. J Am Coll Cardiol 64:851–860. https://doi.org/10.1016/j.jacc.2014.03.061
This study was supported by the Sarah Morrison Student Research Award at the University of Missouri-Kansas City School of Medicine (Kansas City, MO).
Conflict of interest
The authors declare that they have no conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
For this type of study formal consent is not required.
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Qayum, O., Alshami, N., Ibezim, C.F. et al. Lipoprotein (a): Examination of Cardiovascular Risk in a Pediatric Referral Population. Pediatr Cardiol 39, 1540–1546 (2018). https://doi.org/10.1007/s00246-018-1927-3
- Lipoprotein (a)
- Pulse wave velocity
- Carotid artery intima-media thickness
- Premature cardiovascular disease