Skip to main content
SpringerLink
Log in

Lipoprotein(a) concentration is associated with risk of type 2 diabetes and cardiovascular events in a Chinese population with very high cardiovascular risk

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

Evidences have shown that elevated lipoprotein(a) [Lp(a)] levels were associated with a lower risk of type 2 diabetes, but a higher risk of cardiovascular events in general populations. We aim to demonstrate the effect of Lp(a) concentrations on type 2 diabetes and cardiovascular events in a Chinese population with very high cardiovascular risk.

Methods

Seven hundred ninety-eight participants who underwent coronary angiography between March and November 2013 with normal glucose metabolism were followed up from July to December 2018.

Results

Five hundred thirty-five participants completed follow-up, and 395 of them had blood glucose data. Among 395 participants with blood glucose data, a total of 28 incident type 2 diabetes were identified during a median follow-up period of 4.42 years. Compared with the patients in the lowest tertile of Lp(a), the multifactorial adjusted HR for type 2 diabetes was 0.29 in the highest tertile (95% confidence intervals (CI) 0.10–0.89; P for trend = 0.03). Among 535 patients who completed follow-up, a total of 80 cases of major adverse cardiovascular events (MACE) were identified during a median follow-up period of 5.08 years. Compared with the patients in the lowest tertile of Lp(a), the multifactorial adjusted HR for MACE was 1.95 in the highest tertile (95% CI 1.05–3.65; P for trend = 0.03).

Conclusions

Elevated Lp(a) levels were associated with a lower risk of type 2 diabetes, but a higher risk of cardiovascular events in a Chinese population with very high cardiovascular risk.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. M.P. Stern, Diabetes and cardiovascular disease. The “common soil” hypothesis. Diabetes 44(4), 369–374 (1995). https://doi.org/10.2337/diab.44.4.369

    Article  CAS  PubMed  Google Scholar 

  2. D.L. Eaton, G.M. Fless, W.J. Kohr, J.W. McLean, Q.T. Xu, C.G. Miller, R.M. Lawn, A.M. Scanu, Partial amino acid sequence of apolipoprotein(a) shows that it is homologous to plasminogen. Proc. Natl Acad. Sci. USA 84(10), 3224–3228 (1987)

    Article  CAS  Google Scholar 

  3. K. Schmidt, A. Noureen, F. Kronenberg, G. Utermann, Structure, function, and genetics of lipoprotein (a). J. Lipid Res. 57(8), 1339–1359 (2016). https://doi.org/10.1194/jlr.R067314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. P.R. Kamstrup, A. Tybjærg-Hansen, R. Steffensen, B.G. Nordestgaard, Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA 301(22), 2331–2339 (2009). https://doi.org/10.1001/jama.2009.801

    Article  CAS  PubMed  Google Scholar 

  5. D. Saleheen, P.C. Haycock, W. Zhao, A. Rasheed, A. Taleb, A. Imran, S. Abbas, F. Majeed, S. Akhtar, N. Qamar, K.S. Zaman, Z. Yaqoob, T. Saghir, S. Rizvi, A. Memon, N.H. Mallick, M. Ishaq, S.Z. Rasheed, F.U. Memon, K. Mahmood, N. Ahmed, P. Frossard, S. Tsimikas, J.L. Witztum, S. Marcovina, M. Sandhu, D.J. Rader, J. Danesh, Apolipoprotein(a) isoform size, lipoprotein(a) concentration, and coronary artery disease: a mendelian randomisation analysis. Lancet Diabetes Endocrinol. 5(7), 524–533 (2017). https://doi.org/10.1016/S2213-8587(17)30088-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. P.R. Kamstrup, M. Benn, A. Tybjærg-Hansen, B.G. Nordestgaard, Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population. Circulation 117(2), 176–184 (2008). https://doi.org/10.1161/CIRCULATIONAHA.107.715698

    Article  CAS  PubMed  Google Scholar 

  7. S.S. Virani, A. Brautbar, B.C. Davis, V. Nambi, R.C. Hoogeveen, A.R. Sharrett, J. Coresh, T.H. Mosley, J.D. Morrisett, D.J. Catellier, A.R. Folsom, E. Boerwinkle, C.M. Ballantyne, Associations between lipoprotein(a) levels and cardiovascular outcomes in black and white subjects. Circulation 125(2), 241–249 (2012). https://doi.org/10.1161/CIRCULATIONAHA.111.045120

    Article  CAS  PubMed  Google Scholar 

  8. M.L. O’Donoghue, D.A. Morrow, S. Tsimikas, S. Sloan, A.F. Ren, E.B. Hoffman, N.R. Desai, S.D. Solomon, M. Domanski, K. Arai, S.E. Chiuve, C.P. Cannon, F.M. Sacks, M.S. Sabatine, Lipoprotein(a) for risk assessment in patients with established coronary artery disease. J. Am. Coll. Cardiol. 63(6), 520–527 (2014). https://doi.org/10.1016/j.jacc.2013.09.042

    Article  CAS  PubMed  Google Scholar 

  9. W. Dai, J. Long, Y. Cheng, Y. Chen, S. Zhao, Elevated plasma lipoprotein(a) levels were associated with increased risk of cardiovascular events in Chinese patients with stable coronary artery disease. Sci. Rep. 8(1) (2018). https://doi.org/10.1038/s41598-018-25835-5

  10. K.L. Chien, H.C. Hsu, T.C. Su, F.C. Sung, M.F. Chen, Y.T. Lee, Lipoprotein(a) and cardiovascular disease in ethnic Chinese: The Chin-Shan Community Cardiovascular Cohort Study. Clin. Chem. 54(2), 285–291 (2008). https://doi.org/10.1373/clinchem.2007.090969

    Article  CAS  PubMed  Google Scholar 

  11. S. Mora, P.R. Kamstrup, N. Rifai, B.G. Nordestgaard, J.E. Buring, P.M. Ridker, Lipoprotein(a) and risk of type 2 diabetes. Clin. Chem. 56(8), 1252–1260 (2010). https://doi.org/10.1373/clinchem.2010.146779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Z. Ye, P.C. Haycock, D. Gurdasani, C. Pomilla, S.M. Boekholdt, S. Tsimikas, K.T. Khaw, N.J. Wareham, M.S. Sandhu, N.G. Forouhi, The association between circulating lipoprotein(a) and type 2 diabetes: is it causal? Diabetes 63(1), 332–342 (2013). https://doi.org/10.2337/db13-1144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. E. Rhee, J.H. Cho, D.Y. Lee, H. Kwon, S.E. Park, C. Park, K. Oh, S. Park, W. Lee, Insulin resistance contributes more to the increased risk for diabetes development in subjects with low lipoprotein(a) level than insulin secretion. PLoS ONE 12(5), e177500 (2017). https://doi.org/10.1371/journal.pone.0177500

    Article  CAS  Google Scholar 

  14. E. Paige, K.L. Masconi, S. Tsimikas, F. Kronenberg, P. Santer, S. Weger, J. Willeit, S. Kiechl, P. Willeit, Lipoprotein(a) and incident type-2 diabetes: results from the prospective Bruneck study and a meta-analysis of published literature. Cardiovasc. Diabetol. 16(1) (2017). https://doi.org/10.1186/s12933-017-0520-z

  15. L. Ding, A. Song, M. Dai, M. Xu, W. Sun, B. Xu, J. Sun, T. Wang, Y. Xu, J. Lu, W. Wang, Y. Bi, G. Ning, Serum lipoprotein (a) concentrations are inversely associated with T2D, prediabetes, and insulin resistance in a middle-aged and elderly Chinese population. J. Lipid Res. 56(4), 920–926 (2015). https://doi.org/10.1194/jlr.P049015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. D. Mu-Han-Ha-Li, T. Zhai, Y. Ling, X. Gao, LPA kringle IV type 2 is associated with type 2 diabetes in a Chinese population with very high cardiovascular risk. J. Lipid Res. 59(5), 884–891 (2018). https://doi.org/10.1194/jlr.P082792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. American Diabetes Association, 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2018. Diabetes Care 41(Suppl. 1), S13–S27 (2018). https://doi.org/10.2337/dc18-S002

  18. D.L. Rainwater, S.M. Haffner, Insulin and 2-hour glucose levels are inversely related to Lp(a) concentrations controlled for LPA genotype. Arterioscler. Thromb. Vasc. Biol. 18(8), 1335–1341 (1998). https://doi.org/10.1161/01.ATV.18.8.1335

    Article  CAS  PubMed  Google Scholar 

  19. A. Kaya, A. Onat, H. Yuksel, G. Can, M. Yuksel, E. Ademoglu, Lipoprotein(a)-activated immunity, insulin resistance and new-onset diabetes. Postgrad. Med. 129(6), 611–618 (2017). https://doi.org/10.1080/00325481.2017.1342508

    Article  PubMed  Google Scholar 

  20. D.M. Neele, E.C. de Wit, H.M. Princen, Insulin suppresses apolipoprotein(a) synthesis by primary cultures of cynomolgus monkey hepatocytes. Diabetologia 42(1), 41–44 (1999)

    Article  CAS  Google Scholar 

  21. M.B. Boffa, M.L. Koschinsky, Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease? J. Lipid Res. 57(5), 745–757 (2016). https://doi.org/10.1194/jlr.R060582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. F.M. van der Valk, S. Bekkering, J. Kroon, C. Yeang, J. Van den Bossche, J.D. van Buul, A. Ravandi, A.J. Nederveen, H.J. Verberne, C. Scipione, M. Nieuwdorp, L.A. Joosten, M.G. Netea, M.L. Koschinsky, J.L. Witztum, S. Tsimikas, N.P. Riksen, E.S. Stroes, Oxidized phospholipids on lipoprotein(a) elicit arterial wall inflammation and an inflammatory monocyte response in humans. Circulation 134(8), 611–624 (2016). https://doi.org/10.1161/CIRCULATIONAHA.116.020838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. H.G. Kraft, H.J. Menzel, F. Hoppichler, W. Vogel, G. Utermann, Changes of genetic apolipoprotein phenotypes caused by liver transplantation. Implications for apolipoprotein synthesis. J. Clin. Investig. 83(1), 137–142 (1989). https://doi.org/10.1172/JCI113849

    Article  CAS  PubMed  Google Scholar 

  24. S. Erqou, A. Thompson, E. Di Angelantonio, D. Saleheen, S. Kaptoge, S. Marcovina, J. Danesh, Apolipoprotein(a) isoforms and the risk of vascular disease. J. Am. Coll. Cardiol. 55(19), 2160–2167 (2010). https://doi.org/10.1016/j.jacc.2009.10.080

    Article  CAS  PubMed  Google Scholar 

  25. A. Tolbus, M.B. Mortensen, S.F. Nielsen, P.R. Kamstrup, S.E. Bojesen, B.G. Nordestgaard, Kringle IV type 2, not low lipoprotein(a), as a cause of diabetes: a novel genetic approach using SNPs associated selectively with lipoprotein(a) concentrations or with kringle IV type 2 repeats. Clin. Chem. 63(12), 1866–1876 (2017). https://doi.org/10.1373/clinchem.2017.277103

    Article  CAS  PubMed  Google Scholar 

  26. P.R. Kamstrup, B.G. Nordestgaard, Lipoprotein(a) concentrations, isoform size, and risk of type 2 diabetes: a Mendelian randomisation study. The lancet. Diabetes Endocrinol. 1(3), 220–227 (2013). https://doi.org/10.1016/S2213-8587(13)70064-0

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai, 200032, China

    Dilidaer Muhanhali, Tianyu Zhai, Zhenqin Cai & Yan Ling

Authors
  1. Dilidaer Muhanhali
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tianyu Zhai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhenqin Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yan Ling
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Y.L. conceived and designed the study. D.M., T.Z., and Z.C. contributed to the data collection. D.M. contributed to the management and analysis of data. D.M. and Y.L. wrote and revised the paper.

Corresponding author

Correspondence to Yan Ling.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Muhanhali, D., Zhai, T., Cai, Z. et al. Lipoprotein(a) concentration is associated with risk of type 2 diabetes and cardiovascular events in a Chinese population with very high cardiovascular risk. Endocrine 69, 63–72 (2020). https://doi.org/10.1007/s12020-020-02286-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-020-02286-5

Keywords

Search

Navigation