Lipoprotein(a ) status as a risk factor for coronary heart disease

1. Lipoprotein(a) status as a risk factor for coronary heart disease Kelly Harnish, BS, CHES

2. Outline • Coronary heart disease (CHD) in the U.S. population • Lipoprotein (A) [Lp (A)] • Lp (A) measurement • Limitations • Public health issues • Further research

3. Coronary Heart Disease (CHD) • Is caused by artherosclerosis • Results may include angina pectoris and/or heart attack • Caused 425,425 deaths in 2006 • Is currently the leading cause of death • An estimated 1.26 million Americans will have a recurrent coronary attack American Heart Association

4. Lipoprotein (A) • Low density lipoprotein (LDL) particle • Consists of apolipoprotein B100 and apolipoprotein (a). The Emerging Risk Factors Collaboration.

5. Lp(A) Measurement • In a review of 36 studies investigating the relationship b/t Lp(a) and CHD, a variety of measurements were used: • “In house” assays • Commercially available assays • Enzyme linked immunosorbent assay methods • Immunoturbimetry or nephelometry • Immunoradiometry • Enzyme immunodiffusion The Emerging Risk Factors Collaboration.

6. Public Health Issues • Lp(a) excess increases the risk of premature CHD 3 to 100 fold depending on the absence or presence of concomitant risk factors. (Rajasekhar, et al) • Individuals with smaller apo(a) isoforms have an approximately 2-fold higher risk of CHD than those with larger proteins. (Erqou, et al) • Genetically elevated Lp(a) is associated with an increased risk of myocardial infarction. (Kamstrup, et al)

7. Public Health Issues • Lp(a) levels are positively correlated with vessel disease severity (P<0.005). In other words, the greater the level of Lp(a), the greater the vessel disease severity. (Rajasekhar, et al) • Lp(a) can cross the endothelial barrier between plasma and the arterial intima. This can lead to the development of artherosclerotic plaques. (Kamstrup, et al)

8. Public Health Issues • An increased level of Lp(a) lipoprotein is highly heritable. • Three chromosomal regions are strongly associated with the risk of coronary disease.

9. Public Health Issues • Because genotypes are fixed, testing for chromosomal markers for elevated Lp (a) may be superior than blood measurements, which are affected by various lifestyle factors. This type of testing can identify individuals with greatest risk for CHD so that appropriate treatment can be initiated.

10. Public Health Issues • Rajasekhar and colleagues found that women had higher risk for elevated Lp(a) levels than men. Though influence of sex on Lp(a) is not confirmed the higher levels of Lp(a) in females than in males may be due to lowering effect of testosterone in males and presence of menopausal status in women with CHD.

11. Limitations • A couple of the studies I reviewed used data from the 1970s to current day. With such a long time span, medical technologies (medications, procedures), diagnostic criteria, and lifestyle norms have changed, which would change the outcome of myocardial infarction rates.

12. Continued Research • The Emerging Risk Factors Collaboration recommend that further research be conducted on: • The promotion of vascular disease through oxidative damage • Lp(a) particles with smaller apo(a) isoforms to confirm suspicions that these result in higher risk for MI. • The joint effects of Lp(a) with other elevated lipid markers.

13. Continued Research • Further studies should be conducted to explore gender differences in risk for elevated Lp(a) due to hormonal influence as a follow up to Rajasekhar and colleague’s findings.

14. Continued Research • Validity studies should be conducted to determine if genetic testing for Lp(a) chromosomal markers is a better test than lipid panels in identifying at risk individuals. Cost, accuracy, and practicality should all be taken into account in this comparison.

15. References American Heart Association, Cardiovascular Disease Statistics http://americanheart.com/presenter.jhtml?identifier=4478, accessed June 21, 2010.Clarke R, Peden JF, Hopewell JC, Kyriakou T, Goel A, Heath SC, Parish S, Barlera S, Franzosi MG, Rust S, Bennett D, Silveira A, Malarstig A, Green FR, Lathrop M, Gigante B, Leander K, de Faire U, Seedorf U, Hamsten A, Collins R, Watkins H, Farrall M. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med. 2009, 361(26):2518-28. The Emerging Risk Factors Collaboration. Lipoprotein (a) Concentration and the Risk of Coronary Heart Disease, stroke, and nonvascular mortality. JAMA. 2009; 302(4): 412-422. Erqou S, Thompson A, Di Angelantonio E, Saleheen D, Kaptoge S, Marcovina S, Danesh J.Apolipoprotein(a) isoforms and the risk of vascular disease: systematic review of 40 studies involving 58,000 participants. J Am Coll Cardiol. 2010, 55(19):2160-7. Kamstrup, PR, Tybjaerg-Hansen, A, Steffensen, R, Nordestgaard, BG. Genetically elevated lipoprotein (a) and increased risk of myocardial infarction. JAMA. 2009, 301(22): 2331-2339. Rajasekhar, D, Saibaba KSS, Srinivasa Rao PVLN, Latheef, SAA, Subramanyam, G. Lipoprotein (A): Better assessor of coronary heart disease risk in South Indian population. Indian Journal of Clinical Biochemistry. 2004, 19(2): 53-59.