Premature Heart disease
- Lipoprotein(a) (Lp(a)) is capable of promoting both early and advanced stages of atherosclerosis (plaque build-up) leading to heart attack, stroke or cardiac death at a very young age.1-4 This risk, which appears to be limited to premature vascular disease, is strongest before age 45, declines after age 55, and often disappears after age 65.5
- In the Framingham Heart Study, premature CAD (coronary artery disease) attributable to elevated Lp(a) level was double that of high blood pressure or diabetes.3
- Lipoprotein(a) levels stabilize by age 2 and remain constant throughout life.6, 7 Because stable lifelong levels of Lp(a)are attained in infancy, the pathological processes associatedwith elevated Lp(a) also begin in infancy (20 yearsearlier than other risk factors such as high blood pressure, cigarettesmoking, and diet-related dyslipidemia). 5
- The early onset ofhigh-risk status, along with the high atherogenicity (10 timesmore atherogenic than LDL) and the high thrombogenicity of Lp(a),appears to explain its strong association with premature CAD.5
- Individuals with high levels of Lp(a) develop heart attack or stroke in their 30s and 40s, about 10 to 20 years earlier than those who develop these conditions attributable to other risk factors.8-12 The higher the Lp(a), the younger the age at first heart attack, with the strongest correlation in patients <45 years old.8, 11, 13, 14 This is particularly true for those with small Lp(a) isoforms.9, 14
- The risk is markedly increased in people who also have low HDL, high LDL or diabetes.15 (see Multiplicative Effects of Lp(a))
- The impact of elevated Lp(a) levels is heterogeneous, with greater risk imposed on certain populations such as Asian Indians, a population with the highest rate of premature and malignant CAD.16-19
- Since Lp(a) concentrations are largely genetically determined through autosomal-dominant transmission, fully 50% of the first degree relatives of people with elevated Lp(a) would have this abnormality. 20-22 (see Lp(a) and Genetics)
1. Kronenberg F, Kronenberg MF, Kiechl S, et al. Role of lipoprotein(a) and apolipoprotein(a) phenotype in atherogenesis: prospective results from the Bruneck study. Circulation. 1999;100(11):1154-1160.
2. Gazzaruso C, Garzaniti A, Giordanetti S, et al. Assessment of asymptomatic coronary artery disease in apparently uncomplicated type 2 diabetic patients: a role for lipoprotein(a) and apolipoprotein(a) polymorphism. Diabetes Care. 2002;25(8):1418-1424.
3. Bostom AG, Cupples LA, Jenner JL, et al. Elevated plasma lipoprotein(a) and coronary heart disease in men aged 55 years and younger. A prospective study. Jama. 1996;276(7):544-548.
4. Orth-Gomer K, Mittleman MA, Schenck-Gustafsson K, et al. Lipoprotein(a) as a determinant of coronary heart disease in young women. Circulation. 1997;95(2):329-334.
5. 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.
6. Wilcken DE, Wang XL, Dudman NP. The relationship between infant and parent Lp(a) levels. Chem Phys Lipids. 1994;67-68:299-304.
7. Rifai N, Heiss G, Doetsch K. Lipoprotein(a) at birth, in blacks and whites. Atherosclerosis. Feb 1992;92(2-3):123-129.
8. Gambhir JK, Kaur H, Gambhir DS, Prabhu KM. Lipoprotein(a) as an independent risk factor for coronary artery disease in patients below 40 years of age. Indian Heart J. 2000;52(4):411-415.
9. Gazzaruso C, Garzaniti A, Buscaglia P, et al. Association between apolipoprotein(a) phenotypes and coronary heart disease at a young age. J Am Coll Cardiol. 1999;33(1):157-163.
10. Kazumi T, Maeda T, Masuda T, et al. Concurrent development of hemiplegia and angina pectoris in a 46-year- old man with familial hypercholesterolemia and elevated serum Lp(a) concentrations. J Atheroscler Thromb. 1994;1(2):129-131.
11. Isser HS, Puri VK, Narain VS, Saran RK, Dwivedi SK, Singh S. Lipoprotein (a) and lipid levels in young patients with myocardial infarction and their first-degree relatives. Indian Heart J. 2001;53(4):463-466.
12. Sandkamp M, Assman G. Lipoprotein (a) in PROCAM participants and young myocardial infarction survivors. In: Scanu A, ed. Lipoprotein (a). San Diego: Academic Press; 1990:205-209.
13. Parlavecchia M, Pancaldi A, Taramelli R, et al. Evidence that apolipoprotein(a) phenotype is a risk factor for coronary artery disease in men < 55 years of age. Am J Cardiol. 1994;74(4):346-351.
14. Ardissino D, Berzuini C, Merlini PA, et al. Influence of 9p21.3 genetic variants on clinical and angiographic outcomes in early-onset myocardial infarction. J Am Coll Cardiol. Jul 19 2011;58(4):426-434.
15. Kitamura A, Iso H, Naito Y, et al. High-density lipoprotein cholesterol and premature coronary heart disease in urban Japanese men. Circulation. Jun 1994;89(6):2533-2539.
16. Enas EA. Lipoprotein(a) is an important genetic risk factor for coronary artery disease in Asian Indians. Am J Cardiol. 2001;88:201-202.
17. Enas EA, Mehta J. Malignant coronary artery disease in young Asian Indians: thoughts on pathogenesis, prevention, and therapy. Coronary Artery Disease in Asian Indians (CADI) Study. Clin Cardiol. Mar 1995;18(3):131-135.
18. Enas EA, Dhawan J, Petkar S. Coronary artery disease in Asian Indians: lessons learnt and the role of lipoprotein(a). Indian Heart J. Jan-Feb 1997;49(1):25-34.
19. Anand SS, Enas EA, Pogue J, Haffner S, Pearson T, Yusuf S. Elevated lipoprotein(a) levels in South Asians in North America. Metabolism. Feb 1998;47(2):182-184.
20. Lawn RM. Lipoprotein(a) in heart disease. Sci Am. 1992;266(6):54-60.
21. Austin MA, Sandholzer C, Selby JV, Newman B, Krauss RM, Utermann G. Lipoprotein(a) in women twins: heritability and relationship to apolipoprotein(a) phenotypes. Am J Hum Genet. Oct 1992;51(4):829-840.
22. Lindahl G, Gersdorf E, Menzel HJ, et al. The gene for the Lp(a)-specific glycoprotein is closely linked to the gene for plasminogen on chromosome 6. Hum Genet. Jan 1989;81(2):149-152.