Elevated lipoprotein(a) (Lp(a)) appeared to be consistently associated with incident venous thromboembolism (VTE) in a recent cohort study from Mayo Clinic.1
Although Lp(a) is a well-established risk factor for cardiovascular, and more specifically arterial, disease, its relationship with VTE is relatively uncertain. Existing in vitro studies have suggested antifibrinolytic and prothrombotic properties for Lp(a), while clinical and genetic studies are largely inconsistent. Some studies have only reflected an association between VTE and extremely high Lp(a) levels.2
“As Lp(a)-lowering therapies advance and testing expands, clarifying whether elevated Lp(a) tracks with venous events is increasingly important,” Luke Dreher, MD, an internal medicine resident in the department of cardiovascular medicine at Mayo Clinic Arizona, and colleagues wrote. “We examined the association between measured Lp(a) and incident VTE.”1
Investigators conducted a retrospective cohort study with data from Mayo Clinic Enterprise, encompassing the period from 1997 to 2026. Adults with ≥1 routine-care Lp(a) measurement reported in mg/dL were included, using the first value as an index measurement. The study’s primary outcome was incident VTE, defined as documented deep vein thrombosis (DVT) or pulmonary embolism (PE) that occurred on or after the index Lp(a) measurement. Additional outcomes included DVT and PE independently.1
A total of 69,214 patients were included in the cohort, of whom 19,553 (28.3%) had Lp(a) ≥50 mg/dL. During follow-up, a total of 1492 patients (2.2%) experienced incident VTE, with 1010 (1.5%) logged as DVT events and 839 (1.2%) PE events. Crude VTE rates were notably higher with Lp(a) ≥50 mg/dL (2.8% vs 1.9%). Based on the primary multivariable model, Dreher and colleagues noted an association between the 2 components (adjusted odds ratio [AOR], 1.36; 95% CI, 1.22-1.52), DVT (AOR, 1.33; 95% CI, 1.16-1.52), and PE (AOR, 1.33; 95% CI, 1.15-1.54).1
Additionally, each 10 mg/dL increase in Lp(a) was associated with VTE (AOR, 1.05; 95% CI, 1.04-1.06), with similar estimates noted for DVT and PE. After excluding active cancer and major thrombophilia, findings remained unchanged, and higher threshold analyses showed greater effect sizes at Lp(a) of ≥100 mg/dL (AOR, 1.74; 95% CI, 1.5-2.01) and ≥150 mg/dL (AOR, 2.66; 95% CI, 2.16-3.28).1
Dreher and colleagues ultimately concluded that the association was present and distinct. Additionally, the persistence of this association after the exclusion of major thrombophilia and active cancer indicated that the signal is not solely driven by the groups with the highest risk of hypercoagulability.1
However, the investigators also noted several potential limitations. Among these were the retrospective design, clinically triggered Lp(a) testing in a tertiary care setting, nonstandardized indications for measurement, a predominantly white cohort, outcomes identified through text-based extraction of documentation rather than direct adjudication, and restriction to patients with Lp(a) reported in mg/dL, the last of which may have introduced selection bias.1
“The consistency of the association across primary and sensitivity analyses supports future prospective study of venous outcomes in patients with markedly elevated Lp(a) and suggests that future Lp(a)-lowering trials may benefit from tracking VTE in addition to arterial events,” Dreher and colleagues wrote.1
ReferencesDreher LA, Abdul Nabi H, Abdelnabi M, et al. Lipoprotein(a) and Incident Venous Thromboembolism. JAMA Cardiol. Published online September 23, 2026. doi:10.1001/jamacardio.2026.3964Pfeferman MB, Rashedi S, Lip GYH, et al. Lipoprotein(a) and Venous Thromboembolism: Association, Causality, and Medications. Thromb Haemost. 2025 Nov;125(11):1069-1084. doi: 10.1055/a-2674-5114.