, Volume 37, Issue 3, pp 686–693 | Cite as

The Relationship Between Serum Lipoprotein (a) Levels and Ischemic Stroke Risk: A Cohort Study in the Chinese Population

  • Shao-yi Li
  • Yun Gao
  • Wei-ning Ma
  • Hua-chao Wang
  • Gang Zhou
  • Wen-chang Guo
  • Yun-hui Liu


The role of atherosclerosis in ischemic stroke has been intensively investigated in recent years, and lipoprotein (a) [Lp(a)] is found to have roles during the process. The aim of this study was to investigate the relationship between acute ischemic stroke (AIS) and serum Lp(a) levels in the Chinese population. All consecutive patients with first-ever acute ischemic stroke during 2011–2012 were recruited to participate in the study. Serum Lp(a) levels and routine tests were examined in both groups. The National Institutes of Health Stroke Scale (NIHSS) score was assessed on admission blinded to Lp(a) levels. In this study, 181 patients with acute ischemic stroke were included. There was a significant difference in median serum Lp(a) levels between acute ischemic stroke patients and control cases (328 [IQR, 173–554] vs. 145 [IQR, 66–254] mg/L, respectively; P = 0.000). Lp(a) levels increased with increasing severity of stroke as defined by the NIHSS score (P = 0.000). For the entire group, when adjusting for other possible risk factors, an elevated Lp(a) level was an independent risk factor for stroke, and a serum Lp(a) level ≥300 mg/L was associated with a 2.23-fold increase in AIS (P = 0.015). In addition, this association was stronger in male than in female patients. High Lp(a) levels are significantly related to stroke, independent from other traditional and emerging risk factors, suggesting that they may play a role in its pathogenesis. It should be considered as a routine risk factor for stroke in the Chinese population.


acute ischemic stroke lipoprotein (a) Chinese risk serum biomarker 



We express our gratitude to all the patients who participated in this study, thereby making this work possible. The content has not been published or submitted for publication elsewhere.


  1. 1.
    Vucković, B.A., M.J. Djerić, T.A. Ilić, V.B. Canak, S.L.J. Kojić-Damjanov, M.G. Zarkov, and V.S. Cabarkapa. 2010. Fibrinolytic parameters, lipid status and lipoprotein(a) in ischemic stroke patients. Srpski Arhiv za Celokupno Lekarstvo 138(1): 12–17.PubMedGoogle Scholar
  2. 2.
    Tu, W.J., X. Dong, S.J. Zhao, D.G. Yang, and H. Chen. 2013. Prognostic value of plasma neuroendocrine biomarkers in patients with acute ischaemic stroke. Journal of Neuroendocrinology 25: 771–778.PubMedCrossRefGoogle Scholar
  3. 3.
    Unal, E., S. Mungan, S. Bilen, Y. Karadag, N. Oztekin, F. Bakir, and F. Ak. 2013. The effects of lipoprotein(a) and homocysteine on prognosis and risk factors in acute ischemic stroke. International Journal of Neuroscience 123: 532–536.PubMedCrossRefGoogle Scholar
  4. 4.
    Uno, M., K.T. Kitazato, K. Nishi, H. Itabe, and S. Nagahiro. 2003. Raised plasma oxidized LDL in acute cerebral infarction. Journal of Neurology, Neurosurgery and Psychiatry 74: 312–316.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Nordestgaard, B.G., M.J. Chapman, K. Ray, J. Borén, F. Andreotti, G.F. Watts, H. Ginsberg, P. Amarenco, A. Catapano, O.S. Descamps, E. Fisher, P.T. Kovanen, J.A. Kuivenhoven, P. Lesnik, L. Masana, Z. Reiner, M.R. Taskinen, L. Tokgözoglu, and A. Tybjærg-Hansen. 2010. European Atherosclerosis Society Consensus Panel. Lipoprotein(a) as a cardiovascular risk factor: current status. European Heart Journal 31: 2844–2853.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Morishita, R., J. Ishii, Y. Kusumi, S. Yamada, N. Komai, M. Ohishi, M. Nomura, H. Hishida, M. Niihashi, and M. Mitsumata. 2009. Association of serum oxidized lipoprotein(a) concentration with coronary artery disease: potential role of oxidized lipoprotein(a) in the vascular wall. Journal of Atherosclerosis and Thrombosis 16: 410–418.PubMedCrossRefGoogle Scholar
  7. 7.
    Rosas, S., M. Joffe, M. Wolfe, K. Brayman, and D.J. Rader. 2008. Effects of renal replacement therapy on plasma lipoprotein(a) levels. American Journal of Nephrology 28: 361–365.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Bruckert, E., P. Davidoff, A. Grimaldi, J. Truffert, P. Giral, R. Doumith, F. Thervet, and J.L. De Gennes. 1990. Increased serum levels of lipoprotein(a) in diabetes mellitus and their reduction with glycemic control. JAMA 263: 35–36.PubMedCrossRefGoogle Scholar
  9. 9.
    Wright, L.C., D.R. Sullivan, M. Muller, M. Dyne, M.H. Tattersall, and C.E. Mountford. 1989. Elevated apolipoprotein(a) levels in cancer patients. International Journal of Cancer 43: 241–244.CrossRefGoogle Scholar
  10. 10.
    Engler, H., and W.F. Riesen. 1993. Effect of thyroid function on concentrations of lipoprotein(a). Clinical Chemistry 39: 2466–2469.PubMedGoogle Scholar
  11. 11.
    Milionis, H.J., V. Mittari, G. Exarchakos, R. Kalaitzidis, A.T. Skevas, and M.S. Elisaf. 2003. Lipoprotein (a) and acute-phase response in patients with vestibular neuronitis. European Journal of Clinical Investigation 33: 1045–1050.PubMedCrossRefGoogle Scholar
  12. 12.
    Bernick, C., L. Kuller, C. Dulberg, et al. 2001. Silent MRI infarcts and the risk of future stroke: the cardiovascular health study. Neurology 57: 1222–1229.PubMedCrossRefGoogle Scholar
  13. 13.
    Safarova, M.S., M.V. Ezhov, O.I. Afanasieva, Y.G. Matchin, R.V. Atanesyan, I.Y. Adamova, E.A. Utkina, G.A. Konovalov, and S.N. Pokrovsky. 2013. Effect of specific lipoprotein(a) apheresis on coronary atherosclerosis regression assessed by quantitative coronary angiography. Atherosclerosis Supplements 14: 93–99.PubMedCrossRefGoogle Scholar
  14. 14.
    Berglund, L., and R. Ramakrishnan. 2004. Lipoprotein(a): an elusive cardiovascular risk factor. Arteriosclerosis, Thrombosis, and Vascular Biology 24: 2219–2226.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Smolders, B., R. Lemmens, and V. Thijs. 2007. Lipoprotein (a) and stroke: a meta-analysis of observational studies. Stroke 38: 1959–1966.PubMedCrossRefGoogle Scholar
  16. 16.
    Boden-Albala, B., D.E. Kargman, I.F. Lin, M.C. Paik, R.L. Sacco, and L. Berglund. 2010. Increased stroke risk and lipoprotein (a) in a multiethnic community: the Northern Manhattan Stroke Study. Cerebrovascular Diseases 30: 237–243.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Ariyo, A.A., C. Thach, and R. Tracy. 2003. Cardiovascular Health Study Investigators. Lp(a) lipoprotein, vascular disease, and mortality in the elderly. New England Journal of Medicine 349: 2108–2115.PubMedCrossRefGoogle Scholar
  18. 18.
    Milionis, H.J., A.F. Winder, and D.P. Mikhailidis. 2000. Lipoprotein (a) and stroke. Journal of Clinical Pathology 53: 487–496.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Ohira, T., P. Schreiner, J. Morrisett, L. Chambless, W. Rosamond, and A. Folsom. 2006. Lipoprotein(a) and incident ischemic stroke: the Atherosclerotic Risk in Communities (ARIC) study. Stroke 37: 1407–1412.PubMedCrossRefGoogle Scholar
  20. 20.
    Danesh, J., R. Collins, and R. Peto. 2000. Lipoprotein (a) and coronary heart disease. Meta analysis of prospective studies. Circulation 102: 1082–1085.PubMedCrossRefGoogle Scholar
  21. 21.
    Alfthan, G., J. Pekkanen, M. Jauhiainen, J. Pitkäniemi, M. Karvonen, J. Tuomilehto, J.T. Salonen, and C. Ehnholm. 1994. Relation of serum homocysteine and lipoprotein(a) concentrations to atherosclerotic disease in a prospective Finnish population based study. Atherosclerosis 106: 9–19.PubMedCrossRefGoogle Scholar
  22. 22.
    Ridker, P.M., M.J. Stampfer, and C.H. Hennekens. 1995. Plasma concentration of lipoprotein(a) and the risk of future stroke. JAMA 273: 1269–1273.PubMedCrossRefGoogle Scholar
  23. 23.
    Hatano, S. 1976. Experience from a multicentre stroke register: a preliminary report. Bulletin of the World Health Organization 54: 541–553.PubMedCentralPubMedGoogle Scholar
  24. 24.
    Katan, M., F. Fluri, and N.G. Morgenthaler. 2009. Copeptin: a novel, independent prognostic marker in patients with ischemic stroke. Annals of Neurology 66: 799–808.PubMedCrossRefGoogle Scholar
  25. 25.
    Brott, T., J.R. Marler, C.P. Olinger, et al. 1989. Measurements of acute cerebral infarction: lesion size by computed tomography. Stroke 20: 871–875.PubMedCrossRefGoogle Scholar
  26. 26.
    Adams Jr., H.P., B.H. Bendixen, L.J. Kappelle, J. Biller, B.B. Love, D.L. Gordon, and E.E. Marsh 3rd. 1993. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial. TOAST: Trial of Org 10172 in Acute Stroke Treatment. Stroke 24: 35–41.PubMedCrossRefGoogle Scholar
  27. 27.
    Kamstrup, P.R., A. Tybjaerg-Hansen, R. Steffensen, and B.G. Nordestgaard. 2009. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA 301: 2331–2339.PubMedCrossRefGoogle Scholar
  28. 28.
    Matthews, K.A., M.F. Sowers, C.A. Derby, E. Stein, H. Miracle-McMahill, S.L. Crawford, and R.C. Pasternak. 2005. Ethnic differences in cardiovascular risk factor burden among middle-aged women: Study of Women's Health Across the Nation (SWAN). American Heart Journal 149: 1066–1073.PubMedCrossRefGoogle Scholar
  29. 29.
    Tu, W.J., S.J. Zhao, T.G. Liu, D.G. Yang, and H. Chen. 2013. Combination of high-sensitivity C-reactive protein and homocysteine predicts the short-term outcomes of Chinese patients with acute ischemic stroke. Neurological Research 35: 912–921.PubMedCrossRefGoogle Scholar
  30. 30.
    Ridker, P.M., J.E. Buring, J. Shih, M. Matias, and C.H. Hennekens. 1998. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 98: 731–733.PubMedCrossRefGoogle Scholar
  31. 31.
    Kistorp, C., I. Raymond, F. Pedersen, F. Gustafsson, J. Faber, and P. Hildebrandt. 2005. N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults. JAMA 293: 1609–1616.PubMedCrossRefGoogle Scholar
  32. 32.
    Wiberg, B., J. Sundstrom, J. Arnlov, A. Terent, B. Vessby, B. Zethelius, and L. Lind. 2006. Metabolic risk factors for stroke and transient ischemic attacks in middle-aged men: a community-based study with long-term follow-up. Stroke 37: 2898–2903.PubMedCrossRefGoogle Scholar
  33. 33.
    Dhamija, R.K., P. Gaba, S. Arora, A. Kaintura, M. Kumar, and J. Bhattacharjee. 2009. Homocysteine and lipoprotein (a) correlation in ischemic stroke patients. Journal of Neurological Sciences 281: 64–68.CrossRefGoogle Scholar
  34. 34.
    Hachinski, V., C. Graffagnino, M. Beaudry, et al. 1996. Lipids and stroke paradox resolved. Archives of Neurology 53: 303–308.PubMedCrossRefGoogle Scholar
  35. 35.
    van Kooten, F., J. van Krimpen, D.W. Dippel, N. Hoogerbrugge, and P.J. Koudstaal. 1996. Lipoprotein(a) in patients with acute cerebral ischemia. Stroke 27: 1231–1235.PubMedCrossRefGoogle Scholar
  36. 36.
    Ariyo, A.A., C. Thach, and R. Tracy. 2003. Lp(a) lipoprotein, vascular disease, and mortality in the elderly. New England Journal of Medicine 349: 2108–2115.PubMedCrossRefGoogle Scholar
  37. 37.
    Hajjar, K.A., and D. Gavish. 1989. Lipoprotein (a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis. Nature 339: 303–305.PubMedCrossRefGoogle Scholar
  38. 38.
    Boerwinkle, E., C.C. Leffert, J. Lin, C. Lackner, G. Chiesa, and H.H. Hobbs. 1992. Apolipoprotein(a) gene accounts for greater than 90 % of the variation in plasma lipoprotein(a) concentrations. Journal of Clinical Investigation 90: 52–60.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Tascilar, N., S. Ekem, and E. Aciman. 2009. Hyperhomocysteinemia as an independent risk factor for cardioembolic stroke in Turkish population. Tohoku Journal of Experimental Medicine 218: 293–300.PubMedCrossRefGoogle Scholar
  40. 40.
    Rath, M., A. Niendorf, T. Reblin, M. Dietel, H.J. Krebber, and U. Beisiegel. 1989. Detection and quantification of lipoprotein(a) in the arterial wall of 107 coronary bypass patients. Arteriosclerosis 9: 579–592.PubMedCrossRefGoogle Scholar
  41. 41.
    Kim, B.S., H.S. Jung, O.Y. Bang, C.S. Chung, K.H. Lee, and G.M. Kim. 2010. Elevated serum lipoprotein(a) as a potential predictor for combined intracranial and extracranial artery stenosis in patients with ischemic stroke. Atherosclerosis 212: 682–688.PubMedCrossRefGoogle Scholar
  42. 42.
    Von Depka, M., U. Nowka-Göttl, R. Eisert, C. Dieterich, M. Barthels, I. Scharrer, A. Ganser, and S. Ehrenforth. 2000. Increased lipoprotein (a) levels as an independent risk factor for venous thromboembolism. Blood 96: 3364–3368.Google Scholar
  43. 43.
    Barre, D.E., O. Griscti, K.A. Mizier-Barre, and K. Hafez. 2005. Flaxseed oil and lipoprotein (a) significantly increase bleeding time in type 2 diabetes patients in Cape Breton, Nova Scotia. Canada. Journal of Oleo Science 54: 347–354.CrossRefGoogle Scholar
  44. 44.
    Dangas, G., R. Mehran, P.C. Harpel, 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: 2035–2042.PubMedCrossRefGoogle Scholar
  45. 45.
    Ohtahara, A., I. Hisatome, Y. Yamamoto, M. Furuse, K. Sonoyama, Y. Furuse, et al. 2001. The release of the substrate for xanthine oxidase in hypertensive patients was suppressed by angiotensin converting enzyme inhibitors and [alpha] 1-blockers. Journal of Hypertension 19: 575–582.PubMedCrossRefGoogle Scholar
  46. 46.
    Harpel PC, Chang VT, Borth W. Homocysteine and other sulfhydryl compounds enhance the binding of lipoprotein(a) to fibrin: a potential biochemical link between thrombosis, atherogenesis, and sulfhydryl compound metabolism. PNAS 1992:10193–10197.Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Shao-yi Li
    • 1
  • Yun Gao
    • 2
  • Wei-ning Ma
    • 1
  • Hua-chao Wang
    • 1
  • Gang Zhou
    • 1
  • Wen-chang Guo
    • 1
  • Yun-hui Liu
    • 1
  1. 1.Department of NeurosurgeryShengjing Hospital of China Medical UniversityShenyangChina
  2. 2.Institute of EndocrinologyFirst Affiliated Hospital of China Medical UniversityShenyangChina

Personalised recommendations