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Abnormal Lipoprotein(a) Levels Predict Coronary Artery Calcification in Southeast Asians but Not in Caucasians: Use of Noninvasive Imaging for Evaluation of an Emerging Risk Factor

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Abstract

Subclinical atherosclerosis can be quantified by coronary artery calcium (CAC) scoring. Due to its high specificity for atherosclerosis, CAC is an excellent phenotypic tool for the evaluation of emerging risk markers. Lipoprotein(a) [Lp(a)] is atherogenic due to the presence of apoB and may be thrombogenic through its apo(a) component. Lp(a) has been linked to cardiovascular events in Caucasians; however, its link to atherosclerosis in various ethnicities remains unclear. We evaluated the ability of Lp(a) mass to predict subclinical atherosclerosis in Southeast Asians and Caucasians, as measured by CAC. Traditional lipid measurements, Lp(a) measurements, and CAC by 64-slice multidetector computed tomography was performed in 103 consecutive patients in the USA and in 104 consecutive patients in Jakarta, Indonesia. Proportion of positive CAC and median CAC in Southeast Asians and in Caucasians was 61.5% and 63.1%, and 23.5 (interquartile range, 0–270) and 13 (interquartile range, 0–388), respectively. Significantly higher proportion of Southeast Asians had elevated Lp(a) levels, compared to Caucasians (51.0% vs. 29.2%; p = 0.005). In Southeast Asians, Lp(a) remained an independent predictor of CAC with an odds ratio of 4.97 (95% confidence interval, 1.56–15.88; p < 0.0001), but not in Caucasians. Receiver operating characteristic analysis showed an improvement in area under the curve from 0.81 to 0.86 (p = 0.05) when including Lp(a) in the predictive model in Southeast Asians. This translated to 7% of Southeast Asians reclassified to correct CAC status. Lp(a) measurements may have a role in risk stratification of Southeast Asians. Ethnic variation should be taken into account when considering the use of Lp(a) measurements in risk assessment.

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References

  1. Greenland, P., Bonow, R. O., Brundage, B. H., Budoff, M. J., Eisenberg, M. J., Grundy, S. M., et al. (2007). ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography). Circulation, 115(3), 402–426.

    Article  PubMed  Google Scholar 

  2. Rumberger, J. A., Simons, D. B., Fitzpatrick, L. A., Sheedy, P. F., & Schwartz, R. S. (1995). Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area. A histopathologic correlative study. Circulation, 92(8), 2157–2162.

    PubMed  CAS  Google Scholar 

  3. Detrano, R., Guerci, A. D., Carr, J. J., Bild, D. E., Burke, G., Folsom, A. R., et al. (2008). Coronary calcium as a predictor of coronary events in four racial or ethnic groups. The New England Journal of Medicine, 358(13), 1336–1345.

    Article  PubMed  CAS  Google Scholar 

  4. Joshi, P. H., Krivitsky, E., Qian, Z., Vazquez, G., Voros, S., & Miller, J. (2010). Do we know when and how to lower lipoprotein(a)? Current Treatment Options in Cardiovascular Medicine, 12(4), 396–407.

    Article  PubMed  Google Scholar 

  5. Davidson, M. H. (2005). Reducing residual risk for patients on statin therapy: the potential role of combination therapy. The American Journal of Cardiology, 96(9A), 3K–13K.

    Article  PubMed  CAS  Google Scholar 

  6. Hancock, M. A., Boffa, M. B., Marcovina, S. M., Nesheim, M. E., & Koschinsky, M. L. (2003). Inhibition of plasminogen activation by lipoprotein(a). The Journal of Biological Chemistry, 278(26), 23260–23269.

    Article  PubMed  CAS  Google Scholar 

  7. Loscalzo, J., Weinfeld, M., Fless, G. M., & Scanu, A. M. (1990). Lipoprotein(a), fibrin binding, and plasminogen activation. Arteriosclerosis, Thrombosis, and Vascular Biology, 10(2), 240–245.

    Article  CAS  Google Scholar 

  8. Danesh, J., Collins, R., & Peto, R. (2000). Lipoprotein(a) and coronary heart disease: meta-analysis of prospective studies. Circulation, 102(10), 1082–1085.

    PubMed  CAS  Google Scholar 

  9. Nordestgaard, B. G., Chapman, M. J., Ray, K., Boren, J., Andreotti, F., Watts, G. F., et al. (2010). Lipoprotein(a) as a cardiovascular risk factor: current status. European Heart Journal, 31(23), 2844–2853.

    Article  PubMed  CAS  Google Scholar 

  10. Guerra, R., Yu, Z., Marcovina, S., Peshock, R., Cohen, J. C., & Hobbs, H. H. (2005). Lipoprotein(a) and apolipoprotein(a) isoforms: no association with coronary artery calcification in the Dallas Heart Study. Circulation, 111(12), 1471–1479.

    Article  PubMed  CAS  Google Scholar 

  11. Kullo, I. J., Bailey, K. R., Bielak, L. F., Sheedy, P. F., Klee, G. G., Kardia, S. L., et al. (2004). Lack of association between lipoprotein(a) and coronary artery calcification in the Genetic Epidemiology Network of Arteriopathy (GENOA) study. Mayo Clinic Proceedings, 79(10), 1258–1263.

    Article  PubMed  CAS  Google Scholar 

  12. Shen, C., Bao, J., Chen, X., & Ma, G. (2010). Serum lipoprotein (a) is positively correlated with coronary artery calcification in low risk Chinese patients. Heart, 96(Suppl 3), A107–A108.

    Google Scholar 

  13. Kraft, H. G., Lingenhel, A., Pang, R. W., Delport, R., Trommsdorff, M., Vermaak, H., et al. (1996). Frequency distributions of apolipoprotein(a) kringle IV repeat alleles and their effects on lipoprotein(a) levels in Caucasian, Asian, and African populations: the distribution of null alleles is non-random. European Journal of Human Genetics, 4(2), 74–87.

    PubMed  CAS  Google Scholar 

  14. Mooser, V., Scheer, D., Marcovina, S. M., Wang, J., Guerra, R., Cohen, J., et al. (1997). The Apo(a) gene is the major determinant of variation in plasma Lp(a) levels in African Americans. American Journal of Human Genetics, 61(2), 402–417.

    Article  PubMed  CAS  Google Scholar 

  15. Agatston, A. S., Janowitz, W. R., Hildner, F. J., Zusmer, N. R., Viamonte, M., Jr., & Detrano, R. (1990). Quantification of coronary artery calcium using ultrafast computed tomography. Journal of the American College of Cardiology, 15(4), 827–832.

    Article  PubMed  CAS  Google Scholar 

  16. Erqou, S., Kaptoge, S., Perry, P. L., Di, A. E., Thompson, A., White, I. R., et al. (2009). Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA, 302(4), 412–423.

    Article  PubMed  CAS  Google Scholar 

  17. Geethanjali, F. S., Luthra, K., Lingenhel, A., Kanagasaba-Pathy, A. S., Jacob, J., Srivastava, L. M., et al. (2003). Analysis of the apo(a) size polymorphism in Asian Indian populations: association with Lp(a) concentration and coronary heart disease. Atherosclerosis, 169(1), 121–130.

    Article  PubMed  CAS  Google Scholar 

  18. Marcovina, S. M., & Koschinsky, M. L. (2011). Lipoprotein(a):structure, measurement and clinical significance. In N. Rifai, G. R. Warnick, & M. H. Dominiczak (Eds.), Handbook of lipoprotein testing (2nd ed., pp. 345–368). Washington: AACC.

    Google Scholar 

  19. Marcovina, S. M., Albers, J. J., Wijsman, E., Zhang, Z., Chapman, N. H., & Kennedy, H. (1996). Differences in Lp[a] concentrations and apo[a] polymorphs between black and white Americans. Journal of Lipid Research, 37(12), 2569–2585.

    PubMed  CAS  Google Scholar 

  20. Clarke, R., Peden, J. F., Hopewell, J. C., Kyriakou, T., Goel, A., Heath, S. C., et al. (2009). Genetic variants associated with Lp(a) lipoprotein level and coronary disease. The New England Journal of Medicine, 361(26), 2518–2528.

    Article  PubMed  CAS  Google Scholar 

  21. Niendorf, A., Rath, M., Wolf, K., Peters, S., Arps, H., Beisiegel, U., et al. (1990). Morphological detection and quantification of lipoprotein(a) deposition in atheromatous lesions of human aorta and coronary arteries. Virchows Archiv, 417(2), 105–111.

    Article  PubMed  CAS  Google Scholar 

  22. Dangas, G., Mehran, R., Harpel, P. C., Sharma, S. K., Marcovina, S. M., Dube, G., et al. (1998). Lipoprotein(a) and inflammation in human coronary atheroma: association with the severity of clinical presentation. Journal of the American College of Cardiology, 32(7), 2035–2042.

    Article  PubMed  CAS  Google Scholar 

  23. Ragab, M. S., Selvaraj, P., & Sgoutas, D. S. (1996). Oxidized lipoprotein (a) induces cell adhesion molecule Mac-1 (CD 11b) and enhances adhesion of the monocytic cell line U937 to cultured endothelial cells. Atherosclerosis, 123(1–2), 103–113.

    Article  PubMed  CAS  Google Scholar 

  24. Poon, M., Zhang, X., Dunsky, K. G., Taubman, M. B., & Harpel, P. C. (1997). Apolipoprotein(a) induces monocyte chemotactic activity in human vascular endothelial cells. Circulation, 96(8), 2514–2519.

    PubMed  CAS  Google Scholar 

  25. Argraves, K. M., Kozarsky, K. F., Fallon, J. T., Harpel, P. C., & Strickland, D. K. (1997). The atherogenic lipoprotein Lp(a) is internalized and degraded in a process mediated by the VLDL receptor. Journal of Clinical Investigation, 100(9), 2170–2181.

    Article  PubMed  CAS  Google Scholar 

  26. Grainger, D. J., Kirschenlohr, H. L., Metcalfe, J. C., Weissberg, P. L., Wade, D. P., & Lawn, R. M. (1993). Proliferation of human smooth muscle cells promoted by lipoprotein(a). Science, 260(5114), 1655–1658.

    Article  PubMed  CAS  Google Scholar 

  27. Kojima, S., Harpel, P. C., & Rifkin, D. B. (1991). Lipoprotein (a) inhibits the generation of transforming growth factor beta: an endogenous inhibitor of smooth muscle cell migration. The Journal of Cell Biology, 113(6), 1439–1445.

    Article  PubMed  CAS  Google Scholar 

  28. Sugiyama, N., Marcovina, S., Gown, A. M., Seftel, H., Joffe, B., & Chait, A. (1992). Immunohistochemical distribution of lipoprotein epitopes in xanthomata from patients with familial hypercholesterolemia. The American Journal of Pathology, 141(1), 99–106.

    PubMed  CAS  Google Scholar 

  29. Shai, I., Rimm, E. B., Hankinson, S. E., Cannuscio, C., Curhan, G., Manson, J. E., et al. (2005). Lipoprotein (a) and coronary heart disease among women: beyond a cholesterol carrier? European Heart Journal, 26(16), 1633–1639.

    Article  PubMed  CAS  Google Scholar 

  30. Rajasekhar, D., Srinivasa Rao, P. V., Latheef, S. A., Saibaba, K. S., & Subramanyam, G. (2004). Association of serum antioxidants and risk of coronary heart disease in South Indian population. Indian Journal of Medical Sciences, 58(11), 465–471.

    PubMed  CAS  Google Scholar 

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Acknowledgments

Dr. Szilard Voros has received grant support from Siemens Medical Solutions in the past but not specifically for this study.

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Authors and Affiliations

  1. Piedmont Heart Institute, 95 Collier Road, 2nd Floor Suite 2085, Atlanta, GA, 30309, USA

    Abhinav Sharma, Parag H. Joshi, Zhen Qian, Eric Krivitsky, Kamran Akram, Sarah Rinehart, Gustavo Vazquez, Joseph Miller & Szilard Voros

  2. National Cardiovascular Center, University of Indonesia, Jakarta, Indonesia

    Manoefris Kasim & Mohammad Saifur Rohman

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  1. Abhinav Sharma
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  2. Manoefris Kasim
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  3. Parag H. Joshi
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Correspondence to Abhinav Sharma.

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Statement of Ethical Standards and Compliance

The procedures followed were in accordance with the ethical standards of the responsible institutional committees and national laws on human experimentation of the United States of America and Indonesia (National Cardiovascular Center, Jakarta, Indonesia) and with the Helsinki Declaration of 1975, as revised in 2000.

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Sharma, A., Kasim, M., Joshi, P.H. et al. Abnormal Lipoprotein(a) Levels Predict Coronary Artery Calcification in Southeast Asians but Not in Caucasians: Use of Noninvasive Imaging for Evaluation of an Emerging Risk Factor. J. of Cardiovasc. Trans. Res. 4, 470–476 (2011). https://doi.org/10.1007/s12265-011-9273-3

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