Cadi > Topic > Lipoprotein(a) > Lp(a) and Family History

Lp(a) and Family History

Family History of Early Heart Disease

  • Healthy young subjects with family history of premature heart disease often have elevated lipoprotein(a) (Lp(a)) levels with or without abnormalities of other lipoproteins.1 By definition, the history of heart disease in a male relative before the age of 55 or female relative before age 65 is considered a family history of premature heart disease.
  • Because of its strong heritability, Lp(a) is widely recognized as a biological marker for premature CAD (coronary artery disease).2-4   Blood Lp(a) levels account for much of the genetic component of atherosclerosis not expressed through any of the major traditional risk factors.2, 3, 5-7
  • Since Lp(a) levels are two to three times higher in children with a parental or grandparental history of premature CAD than in those without such a history, measurement of Lp(a) in children may help to identify families with an increased risk of CAD.1, 3, 4, 6, 8, 9
  • Lp(a) levels in children is a strong predictor of early heart attack in young adulthood. Besides, elevated   Lp(a) levels also predict heart attack in their parents and grandparents.3, 10 Out of new atherosclerosis risk factors, Lp(a) and apolipoprotein B may have real value in predicting future CVD (cardiovascular disease) in the child.11
  • Parents of white children with high Lp(a) levels have a two- to three-fold higher rate of premature CAD than parents of children with lower levels.5, 12 This relationship is absent in blacks which may be due to issues related to Lp(a) particle size and method of measurement (see Lipoprotein(a) Testing).12
  • Given that Lp(a) is a predictor of early heart attack, stroke, and/or sudden death in people with a family history of premature CAD, Lp(a) levels must be measured in such individuals and target them for more aggressive lifestyle modification and treatment at an earlier age.13-15
  • Statin therapy may be needed in people with elevated LDL-C and statin-niacin combination therapy for those who have elevations in both LDL-C and Lp(a). (see Lipoprotein(a) Treatment)
  • Elevated Lp(a) levels confer genetic predisposition to CAD in young Asian Indians as well as all South Asians who share a national history of premature heart disease.16 (see Lipoprotein(a) in Asian Indians)

Sources

1. Enas EA, Chacko V, Senthilkumar A, Puthumana N, Mohan V. Elevated lipoprotein(a)–a genetic risk factor for premature vascular disease in people with and without standard risk factors: a review. Dis Mon. Jan 2006;52(1):5-50.

2. Durrington PN, Ishola M, Hunt L, Arrol S, Bhatnagar D. Apolipoproteins (a), AI, and B and parental history in men with early onset ischaemic heart disease. Lancet. 1988;1(8594):1070-1073.

3. Wilcken DE, Wang XL, Greenwood J, Lynch J. Lipoprotein(a) and apolipoproteins B and A-1 in children and coronary vascular events in their grandparents. The Journal of pediatrics. 1993;123(4):519-526.

4. Peros E, Geroldi D, D’Angelo A, et al. Apolipoprotein(a) phenotypes are reliable biomarkers for familial aggregation of coronary heart disease. International journal of molecular medicine. Feb 2004;13(2):243-247.

5. Hoefler G, Harnoncourt F, Paschke E, Mirtl W, Pfeiffer KH, Kostner GM. Lipoprotein Lp(a). A risk factor for myocardial infarction. Arteriosclerosis. 1988;8(4):398-401.

6. Vella JC, Jover E. Relation of lipoprotein(a) in 11- to 19-year-old adolescents to parental cardiovascular heart disease. Clinical chemistry. 1993;39(3):477-480.

7. Hegele RA, Connelly P, Cullen-Dean G, Rose V. Elevated plasma lipoprotein(a) associated with abnormal stress thallium scans in children with familial hypercholesterolemia. Am J Cardiol. 1993;72(5):402-406.

8. Wilcken DE, Wang XL, Dudman NP. The relationship between infant and parent Lp(a) levels. Chem Phys Lipids. 1994;67-68:299-304.

9. De Simone M., Verrotti A, Cappa M, et al. Lipoprotein (a) in childhood: correlations with family history of cardiovascular disease. Journal of endocrinological investigation. May 2003;26(5):414-419.

10. Sanchez Bayle M, Baeza Minguez J, Vila Dupla S, et al. [Lipoprotein (a) and family history in 6-year-old children from Rivas-Vaciamadrid]. An Esp Pediatr. Jul 1999;51(1):45-48.

11. Glowinska B, Urban M, Koput A. 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. Oct 2002;161(10):511-518.

12. Srinivasan SR, Dahlen GH, Jarpa RA, Webber LS, Berenson GS. Racial (black-white) differences in serum lipoprotein (a) distribution and its relation to parental myocardial infarction in children. Bogalusa Heart Study. Circulation. 1991;84(1):160-167.

13. Pay  S, Ozcan N, Tokgozoglu SL. Elevated Lp(a) is the most frequent familial lipoprotein disorder leading to premature myocardial infarction in a country with low cholesterol levels. Int J Cardiol. 1997;60(3):301-305.

14. Torbus-Lisiecka B, Bukowska H, Jastrzebska M, Chelstowski K, Honczarenko K, Naruszewicz M. Lp(a), homocysteine and a family history of early ischemic cerebral stroke. Nutr Metab Cardiovasc Dis. Oct 2001;11 Suppl 5:52-59.

15. Casas J P, Shah T, Cooper J, et al. Insight into the nature of the CRP-coronary event association using Mendelian randomization. Int J Epidemiol. Aug 2006;35(4):922-931.

16. Gambhir JK, Kaur H, Prabhu KM, Morrisett JD, Gambhir DS. Association between lipoprotein(a) levels, apo(a) isoforms and family history of premature CAD in young Asian Indians. Clinical biochemistry. Feb 5 2008.

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