Association between elevated lipoprotein (a) and venous thromboembolism: A systematic review and meta-analysis.

Background

Elevated lipoprotein(a) [Lp(a)] is an established cardiovascular risk factor linked to atherogenesis, inflammation, and thrombosis; however, its association with venous thromboembolism (VTE) remains uncertain, with inconsistent findings across observational studies.

Aims

To systematically evaluate the association between elevated Lp(a) levels and VTE risk and to examine differences by study design.

Methods

PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library were searched from inception through January 2026 for observational studies assessing Lp(a) and VTE. Effect estimates (odds ratios [ORs] or hazard ratios [HRs]) were pooled using DerSimonian-Laird random-effects models with Hartung-Knapp adjustment. Heterogeneity was assessed using I2 and τ2. Risk of bias was evaluated with ROBINS-E, publication bias with funnel plots, Egger's and Begg's tests, and certainty of evidence using GRADE. The primary outcome was VTE; secondary outcomes included deep vein thrombosis (DVT), pulmonary embolism (PE), and recurrent VTE.

Results

Eleven studies (6 case-control, 5 cohort; 63,325 participants; 3581 VTE events) were included. Elevated Lp(a) was associated with a borderline increased VTE risk (pooled OR/HR 1.34 [95% CI 1.00-1.80]; P = 0.049), with high heterogeneity (I2 = 77.8%) and a wide prediction interval (0.56-3.21). In stratified analyses, case-control studies showed a significant association (OR 1.88 [1.25-2.81]; I2 = 57.2%), whereas cohort studies showed no association (HR 0.99 [0.85-1.15]; I2 = 0%), with significant between-group differences (p < 0.0001).

Conclusions

The association between elevated Lp(a) and VTE appears limited to case-control studies and is not supported by prospective cohort data, suggesting potential bias or residual confounding. Further large-scale and genetic studies are warranted to clarify this relationship.