Skip to main content
SpringerLink
Log in

Lipoprotein(a) is associated with recurrent cardiovascular events in patients with coronary artery disease and prediabetes or diabetes

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Purpose

Elevated lipoprotein(a) [Lp(a)] and diabetes mellitus (DM) are both associated with adverse events in high-risk patients with established coronary artery disease (CAD). Currently, the association between Lp(a) levels and recurrent cardiovascular (CV) events (CVEs) remained undetermined in patients with different glucose status. Therefore, this study aimed to investigate the prognostic significance of Lp(a) levels for recurrent CVEs in high-risk CAD patients who suffered from first CVEs according to different glycemic metabolism.

Methods

We recruited 5257 consecutive patients with prior CVEs and followed up for recurrent CVEs, including CV death, non-fatal myocardial infarction (MI), and non-fatal stroke. Patients were assigned to low, medium, and high groups according to Lp(a) levels and further stratified by glucose status.

Results

During a median 37-month follow-up, 225 (4.28%) recurrent CVEs occurred. High Lp(a) was independently associated with recurrent CVEs [adjusted Hazard Ratio (HR), 1.57; 95% confidence interval (CI) 1.12–2.19; P = 0.008]. When participants were classified according to Lp(a) levels and glycemic status, high Lp(a) levels were associated with an increased risk of recurrent CVEs in pre-DM (adjusted HR, 2.96; 95% CI 1.24–7.05; P = 0.014). Meanwhile, medium and high Lp(a) levels were both associated with an increased risk for recurrent CVEs in DM (adjusted HR, 3.09; 95% CI 1.30–7.34; P = 0.010 and adjusted HR, 3.13, 95% CI 1.30–7.53; P = 0.011, respectively).

Conclusions

This study demonstrated that elevated Lp(a) levels were associated with an increased recurrent CVE risk in patients with CAD, particularly among those with pre-DM and DM, indicating that Lp(a) may provide incremental value in risk stratification in this population.

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

Similar content being viewed by others

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Timmis A, Vardas P, Townsend N et al (2022) European society of cardiology: cardiovascular disease statistics 2021. Eur Heart J 43(8):716–799

    Article  PubMed  Google Scholar 

  2. Zhao D, Liu J, Wang M et al (2019) Epidemiology of cardiovascular disease in China: current features and implications. Nat Rev Cardiol 16(4):203–212

    Article  PubMed  Google Scholar 

  3. Liu H-H, Cao Y-X, Jin J-L et al (2020) Association of lipoprotein(a) levels with recurrent events in patients with coronary artery disease. Heart 106(16):1228–1235

    Article  PubMed  Google Scholar 

  4. Verma S, Bain SC, Buse JB et al (2019) Occurence of first and recurrent major adverse cardiovascular events with liraglutide treatment among patients with type 2 diabetes and high risk of cardiovascular events: a post hoc analysis of a randomized clinical trial. JAMA Cardiol 4(12):1214–1220

    Article  PubMed  Google Scholar 

  5. Hoogeveen RC, Ballantyne CM (2021) Residual cardiovascular risk at low LDL: remnants, lipoprotein(a), and inflammation. Clin Chem 67(1):143–153

    Article  PubMed  Google Scholar 

  6. Cannon CP, Blazing MA, Giugliano RP et al (2015) Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 372(25):2387–2397

    Article  CAS  PubMed  Google Scholar 

  7. Sabatine MS, Giugliano RP, Keech AC et al (2017) Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 376(18):1713–1722

    Article  CAS  PubMed  Google Scholar 

  8. Nguyen SV, Nakamura T, Kugiyama K (2014) High remnant lipoprotein predicts recurrent cardiovascular events on statin treatment after acute coronary syndrome. Circ J 78(10):2492–2500

    Article  CAS  PubMed  Google Scholar 

  9. Duarte Lau F, Giugliano RP (2022) Lipoprotein(a) and its significance in cardiovascular disease: a review. JAMA Cardiol 7(7):760–769

    Article  PubMed  Google Scholar 

  10. Gudbjartsson DF, Thorgeirsson G, Sulem P et al (2019) Lipoprotein(a) concentration and risks of cardiovascular disease and diabetes. J Am Coll Cardiol 74(24):2982–2994

    Article  CAS  PubMed  Google Scholar 

  11. Liu H-H, Cao Y-X, Jin J-L et al (2020) Predicting cardiovascular outcomes by baseline lipoprotein(a) concentrations: a large cohort and long-term follow-up study on real-world patients receiving percutaneous coronary intervention. J Am Heart Assoc 9(3):e014581

    Article  PubMed  PubMed Central  Google Scholar 

  12. Cui K, Yin D, Zhu C et al (2022) Impact of Lipoprotein(a) concentrations on long-term cardiovascular outcomes in patients undergoing percutaneous coronary intervention: a large cohort study. Nutr Metab Cardiovasc Dis 32(7):1670–1680

    Article  CAS  PubMed  Google Scholar 

  13. Reyes-Soffer G, Ginsberg HN, Berglund L et al (2022) Lipoprotein(a): a Genetically determined, causal, and prevalent risk factor for atherosclerotic cardiovascular disease: a scientific statement from the American heart association. Arterioscler Thromb Vasc Biol 42(1):e48–e60

    Article  CAS  PubMed  Google Scholar 

  14. Kronenberg F, Mora S, Stroes ESG et al (2022) Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European atherosclerosis society consensus statement. Eur Heart J. https://doi.org/10.1093/eurheartj/ehac361

    Article  PubMed  PubMed Central  Google Scholar 

  15. Catapano AL, Tokgözoğlu L, Banach M et al (2023) Evaluation of lipoprotein(a) in the prevention and management of atherosclerotic cardiovascular disease: a survey among the lipid clinics network. Atherosclerosis 370:5–11

    Article  CAS  PubMed  Google Scholar 

  16. Li J-J, Ma C-S, Zhao D et al (2022) Lipoprotein(a) and cardiovascular disease in Chinese population: a Beijing heart society expert scientific statement. JACC Asia 2(6):653–665

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kavousi M, Leening MJG, Nanchen D et al (2014) Comparison of application of the ACC/AHA guidelines, adult treatment panel iii guidelines, and European society of cardiology guidelines for cardiovascular disease prevention in a European cohort. JAMA 311(14):1416–1423

    Article  PubMed  Google Scholar 

  18. Saeed A, Sun W, Agarwala A et al (2019) Lipoprotein(a) levels and risk of cardiovascular disease events in individuals with diabetes mellitus or prediabetes: the atherosclerosis risk in communities study. Atherosclerosis 282:52–56

    Article  CAS  PubMed  Google Scholar 

  19. Waldeyer C, Makarova N, Zeller T et al (2017) Lipoprotein(a) and the risk of cardiovascular disease in the European population: results from the BiomarCaRE consortium. Eur Heart J 38(32):2490–2498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhang Y, Jin J-L, Cao Y-X et al (2020) Lipoprotein (a) predicts recurrent worse outcomes in type 2 diabetes mellitus patients with prior cardiovascular events: a prospective, observational cohort study. Cardiovasc Diabetol 19(1):111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wang L, Gao P, Zhang M et al (2017) Prevalence and ethnic pattern of diabetes and prediabetes in China in 2013. JAMA 317(24):2515–2523

    Article  PubMed  PubMed Central  Google Scholar 

  22. Jin J-L, Cao Y-X, Zhang H-W et al (2019) Lipoprotein(a) and cardiovascular outcomes in patients with coronary artery disease and prediabetes or diabetes. Diabetes Care 42(7):1312–1318

    Article  CAS  PubMed  Google Scholar 

  23. Zhang Y, Jin J-L, Cao Y-X et al (2020) Prognostic utility of lipoprotein(a) combined with fibrinogen in patients with stable coronary artery disease: a prospective, large cohort study. J Transl Med 18(1):373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. AD Association (2022) 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2022. Diabetes Care 45(Suppl 1):S17–S38

    Google Scholar 

  25. He J, Bian X, Song C et al (2022) High neutrophil to lymphocyte ratio with type 2 diabetes mellitus predicts poor prognosis in patients undergoing percutaneous coronary intervention: a large-scale cohort study. Cardiovasc Diabetol 21(1):156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hess CN, Clare RM, Neely ML et al (2017) Differential occurrence, profile, and impact of first recurrent cardiovascular events after an acute coronary syndrome. Am Heart J 187:194–203

    Article  PubMed  Google Scholar 

  27. Smolina K, Wright FL, Rayner M et al (2012) Long-term survival and recurrence after acute myocardial infarction in England, 2004 to 2010. Circ Cardiovasc Qual Outcomes 5(4):532–540

    Article  PubMed  Google Scholar 

  28. Feng W, Hendry RM, Adams RJ (2010) Risk of recurrent stroke, myocardial infarction, or death in hospitalized stroke patients. Neurology 74(7):588–593

    Article  PubMed  Google Scholar 

  29. Kaasenbrood L, Boekholdt SM, van der Graaf Y et al (2016) Distribution of estimated 10-year risk of recurrent vascular events and residual risk in a secondary prevention population. Circulation 134(19):1419–1429

    Article  PubMed  Google Scholar 

  30. Gencer B, Kronenberg F, Stroes ES et al (2017) Lipoprotein(a): the revenant. Eur Heart J 38(20):1553–1560

    Article  CAS  PubMed  Google Scholar 

  31. Schwartz GG, Ballantyne CM, Barter PJ et al (2018) Association of lipoprotein(a) with risk of recurrent ischemic events following acute coronary syndrome: analysis of the dal-outcomes randomized clinical trial. JAMA Cardiol 3(2):164–168

    Article  PubMed  Google Scholar 

  32. Gencer B, Rigamonti F, Nanchen D et al (2019) Prognostic value of elevated lipoprotein(a) in patients with acute coronary syndromes. Eur J Clin Invest 49(7):e13117

    Article  PubMed  Google Scholar 

  33. Sun H, Saeedi P, Karuranga S et al (2022) IDF diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract 183:109119

    Article  PubMed  Google Scholar 

  34. Huth C, Bauer A, Zierer A et al (2020) Biomarker-defined pathways for incident type 2 diabetes and coronary heart disease-a comparison in the MONICA/KORA study. Cardiovasc Diabetol 19(1):32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Tolbus A, Mortensen MB, Nielsen SF et al (2017) 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

    Article  CAS  PubMed  Google Scholar 

  36. Liu H-H, Cao Y-X, Li S et al (2018) Impacts of prediabetes mellitus alone or plus hypertension on the coronary severity and cardiovascular outcomes. Hypertension 71(6):1039–1046

    Article  CAS  PubMed  Google Scholar 

  37. Lawler PR, Bhatt DL, Godoy LC et al (2021) Targeting cardiovascular inflammation: next steps in clinical translation. Eur Heart J 42(1):113–131

    Article  CAS  PubMed  Google Scholar 

  38. Mach F, Baigent C, Catapano AL et al (2020) 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 41(1):111–188

    Article  PubMed  Google Scholar 

  39. Willeit P, Ridker PM, Nestel PJ et al (2018) Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials. Lancet 392(10155):1311–1320

    Article  CAS  PubMed  Google Scholar 

  40. Waldmann E, Parhofer KG (2016) Lipoprotein apheresis to treat elevated lipoprotein (a). J Lipid Res 57(10):1751–1757

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. O’Donoghue ML, Fazio S, Giugliano RP et al (2019) Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk. Circulation 139(12):1483–1492

    Article  CAS  PubMed  Google Scholar 

  42. Szarek M, Bittner VA, Aylward P et al (2020) Lipoprotein(a) lowering by alirocumab reduces the total burden of cardiovascular events independent of low-density lipoprotein cholesterol lowering: ODYSSEY OUTCOMES trial. Eur Heart J 41(44):4245–4255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Tsimikas S, Karwatowska-Prokopczuk E, Gouni-Berthold I et al (2020) Lipoprotein(a) reduction in persons with cardiovascular disease. N Engl J Med 382(3):244–255

    Article  CAS  PubMed  Google Scholar 

  44. Koren MJ, Moriarty PM, Baum SJ et al (2022) Preclinical development and phase 1 trial of a novel siRNA targeting lipoprotein(a). Nat Med 28(1):96–103

    Article  CAS  PubMed  Google Scholar 

  45. He J, Song C, Wang H et al (2023) Diabetes mellitus with mild or moderate kidney dysfunction is associated with poor prognosis in patients with coronary artery disease: a large-scale cohort study. Diabetes Res Clin Pract 200:110693

    Article  PubMed  Google Scholar 

Download references

Funding

This study was supported by CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-008).

Author information

Author notes

  1. Jining He and Min Yang contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Cardiovascular Disease, Beijing, China

    J. He, C. Song, R. Zhang, S. Yuan, J. Li & K. Dou

  2. Cardiometabolic Medicine Center, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 167A Beilishi Road, Xi Cheng District, Beijing, 100037, China

    J. He, C. Song, R. Zhang, S. Yuan, J. Li & K. Dou

  3. Department of Cardiology, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    J. He, M. Yang, C. Song, R. Zhang, S. Yuan & K. Dou

  4. National Clinical Research Center for Cardiovascular Diseases, Beijing, China

    R. Zhang & K. Dou

Authors
  1. J. He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. K. Dou
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JH and MY contributed to the study design and interpretation of the results. CS, RZ, and SY contributed to the collection, analysis, or interpretation of data. JH and MY prepared the manuscript. JL and KD critically revised the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to J. Li or K. Dou.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

This study complied with the Declaration of Helsinki and the study protocol was authorized by the institutional review board of Fuwai Hospital (Beijing, China).

Informed consent

Written informed consent was collected from all study participants.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 318 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

He, J., Yang, M., Song, C. et al. Lipoprotein(a) is associated with recurrent cardiovascular events in patients with coronary artery disease and prediabetes or diabetes. J Endocrinol Invest 47, 883–894 (2024). https://doi.org/10.1007/s40618-023-02203-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-023-02203-3

Keywords

Search

Navigation