Clinical Significance of Lipoprotein(a) in Cardiovascular Risk Stratification Among Patients with Type 2 Diabetes Mellitus: A Systematic Review
Abstract
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.