Clinical Significance of Lipoprotein(a) in Cardiovascular Risk Stratification Among Patients with Type 2 Diabetes Mellitus: A Systematic Review
DOI:
https://doi.org/10.65761/pjcr.2026.312Keywords:
Lipoprotein(a); Type 2 diabetes mellitus; cardiovascular disease; Cardiovascular risk; Cardiovascular mortality; Myocardial infarction; Stroke; Systematic reviewAbstract
Background: Lipoprotein(a) [Lp(a)] is an established atherogenic lipoprotein, but its clinical significance for cardiovascular risk stratification in patients with type 2 diabetes mellitus (T2DM) remains incompletely characterized. This systematic review evaluated the association between Lp(a) concentrations and cardiovascular outcomes in adults with T2DM.
Methods: A literature search was conducted in PubMed, Embase, Scopus, Cochrane Library, and ClinicalTrials.gov from database inception through August 2026. Eligible observational cohort studies involving adults with T2DM assessed circulating Lp(a) concentrations and reported cardiovascular outcomes. Data on study characteristics, Lp(a) measurement, outcomes, follow-up, and adjusted effect estimates were extracted. Methodological quality was assessed using the Newcastle–Ottawa Scale. Findings were synthesized narratively because of substantial heterogeneity.
Results: Four cohort studies involving 7,220 patients from South Korea, Japan, China, and Slovenia were included. Higher Lp(a) concentrations were consistently associated with increased cardiovascular risk. Elevated Lp(a) was associated with incident cardiovascular disease, cardiac death or acute coronary syndrome, recurrent cardiovascular events, myocardial infarction, and cardiovascular mortality. Adjusted hazard ratios ranged from 1.20 to 3.02 across different comparisons and outcomes. Associations were particularly evident among patients with markedly elevated Lp(a) concentrations and, in one study, among women for myocardial infarction.
Conclusion: Elevated Lp(a) concentrations were consistently associated with adverse cardiovascular outcomes in patients with T2DM. Lp(a) measurement may provide additional information for cardiovascular risk stratification beyond conventional risk factors. Prospective multicenter studies using standardized assays and consistent thresholds are warranted.
References
1. American Diabetes Association Professional Practice Committee for Diabetes. 10. Cardiovascular disease and risk management: Standards of Care in Diabetes—2026. Diabetes Care. 2026;49(Suppl 1). doi:10.2337/dc26-S010.
2. American Diabetes Association Professional Practice Committee for Diabetes. 2. Diagnosis and classification of diabetes: Standards of Care in Diabetes—2026. Diabetes Care. 2026;49(Suppl 1). doi:10.2337/dc26-S002.
3. Kronenberg F, Mora S, Stroes ESG, Ference BA, Arsenault BJ, Berglund L, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43(39):3925-3946. doi:10.1093/eurheartj/ehac361.
4. Nordestgaard BG, Chapman MJ, Ray K, Borén J, Andreotti F, Watts GF, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31(23):2844-2853. doi:10.1093/eurheartj/ehq386.
5. Tsimikas S. A test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol. 2017;69(6):692-711. doi:10.1016/j.jacc.2016.11.042.
6. Lamina C, Ward NC. Lipoprotein(a) and diabetes mellitus. Atherosclerosis. 2022;349:63-71. doi:10.1016/j.atherosclerosis.2022.04.016.
7. Lim TS, Yun JS, Cha SA, Song KH, Yoo KD, Ahn YB, et al. Elevated lipoprotein(a) levels predict cardiovascular disease in type 2 diabetes mellitus: a 10-year prospective cohort study. Korean J Intern Med. 2016;31(6):1110-1119. doi:10.3904/kjim.2016.030.
8. Zhang HW, Zhao X, Guo YL, Gao Y, Zhu CG, Wu NQ, et al. Elevated lipoprotein(a) levels are associated with the presence and severity of coronary artery disease in patients with type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis. 2018;28(10):980-986. doi:10.1016/j.numecd.2018.05.010.
9. Senapati SG, Borra V, Kattamuri LPV, Machineni NVK, Borra N, Kukkala S, et al. Elevated lipoprotein(a) and cardiovascular outcomes in prediabetes and diabetes: a systematic review and meta-analysis. Cardiovasc Diagn Ther. 2025;15(1):163-172. doi:10.21037/cdt-24-162.
10. Blumenthal RS, Morris PB, Gaudino M, Johnson HM, Anderson TS, Bittner VA, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of dyslipidemia: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2026;87(19):2624-2757. doi:10.1016/j.jacc.2025.11.016.
11. Konishi H, Miyauchi K, Shitara J, Endo H, Wada H, Doi S, et al. Impact of lipoprotein(a) on long-term outcomes in patients with diabetes mellitus who underwent percutaneous coronary intervention. Am J Cardiol. 2016;118(12):1781-1785. doi:10.1016/j.amjcard.2016.08.067.
12. Zhang Y, Jin JL, Cao YX, Zhang HW, Guo YL, Wu NQ, et al. Lipoprotein(a) predicts recurrent worse outcomes in type 2 diabetes mellitus patients with prior cardiovascular events: a prospective, observational cohort study. Cardiovasc Diabetol. 2020;19:111. doi:10.1186/s12933-020-01083-8.
13. Čuješ J, Kanič V, Povalej Bržan P, Šuran D. Lipoprotein(a) as a risk factor for myocardial infarction, cardiovascular, and all-cause mortality in patients with type 2 diabetes mellitus. Diagnostics (Basel). 2026;16(10):1520. doi:10.3390/diagnostics16101520.
14. Reyes-Soffer G, Ginsberg HN, Berglund L, Duell PB, Heffron SP, Kamstrup PR, et al. 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. 2022;42(1). doi:10.1161/ATV.0000000000000147.
15. Lau FD, Giugliano RP. Lipoprotein(a) and its significance in cardiovascular disease: a review. JAMA Cardiol. 2022;7(7):760-769. doi:10.1001/jamacardio.2022.0987.
16. Amiri M, Raeisi-Dehkordi H, Verkaar AJCF, Wu Y, van Westing AC, Berk KA, et al. Circulating lipoprotein(a) and all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis. Eur J Epidemiol. 2023;38(5):485-499. doi:10.1007/s10654-022-00956-4.
17. Einarson TR, Acs A, Ludwig C, Panton UH. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017. Cardiovascular diabetology. 2018 Jun 8;17(1):83.
18. Granata LG, Giubilato S, Campanella F, Amico F, Di Fusco SA, Colivicchi F. Lipoprotein (a) in cardiovascular disease: pathophysiology, residual risk, and emerging therapeutic strategies. Frontiers in Medicine. 2026 Aug 11;13:1886347.
19. McGinnis T, Saxon DR. Approach to the patient with elevated lipoprotein (a). The Journal of Clinical Endocrinology & Metabolism. 2026 Jul 16:dgag286
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Areeb Jehangir Chaudhary, Katakyie Kofi Koduah, Rana Ali Murtaza, Muhammad Jawwad, Saba Bibi, Ammar Javed, Zakaullah, Tosin Ayantoyinbo, Habiba Khalil
This work is licensed under a Creative Commons Attribution 4.0 International License.
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
