A recent Mayo Clinic cohort study published in JAMA Cardiology reveals that elevated lipoprotein(a), or Lp(a), is consistently linked to an increased risk of incident venous thromboembolism, including deep vein thrombosis and pulmonary embolism, independent of major thrombophilia and active cancer.
High lipoprotein(a) levels increase risk of blood clots
- What was found: People with higher levels of lipoprotein(a)—a specific type of cholesterol particle—face a significantly higher statistical probability of developing blood clots in their legs (deep vein thrombosis) or lungs (pulmonary embolism).
- Why it changes things: Traditionally, medicine has focused on Lp(a) as a driver of blocked arteries (arterial disease). This large study shows it also plays a measurable role in venous circulation problems.
- What comes next: As new therapies designed to lower Lp(a) move through clinical trials, researchers suggest these treatments should track venous blood clot outcomes alongside traditional heart and stroke outcomes.
Evaluating the Mayo Clinic Cohort Data
Led by Luke Dreher, MD, an internal medicine resident in the department of cardiovascular medicine at Mayo Clinic Arizona, investigators sought to clarify a long-standing grey area in vascular medicine. While in vitro laboratory studies have long pointed to the antifibrinolytic and prothrombotic properties of Lp(a), clinical and genetic investigations yielded mixed results. Previous research frequently tied venous thromboembolism only to extreme, outlier levels of the protein.
To establish clearer epidemiological parameters, the team conducted a retrospective cohort study using data from the Mayo Clinic Enterprise spanning from 1997 to 2026. The analysis included 69,214 adult patients who had at least one routine-care Lp(a) measurement recorded in milligrams per deciliter (mg/dL). Investigators designated the first recorded value as the index measurement to track subsequent health events.
Among the broad cohort, 19,553 individuals—representing 28.3% of the total population—exhibited baseline Lp(a) concentrations of 50 mg/dL or higher. Over the follow-up period, 1,492 patients (2.2%) experienced an incident venous thromboembolism event. Breaking down those primary outcomes, 1,010 patients (1.5%) developed a deep vein thrombosis, and 839 patients (1.2%) experienced a pulmonary embolism.
Statistical Breakdown and Threshold Analysis
| Lp(a) Threshold / Metric | Adjusted Odds Ratio (AOR) | 95% Confidence Interval (CI) |
|---|---|---|
| Baseline Threshold (≥50 mg/dL) | 1.36 (Primary VTE Model) | 1.22 – 1.52 |
| Incremental Rise (Per 10 mg/dL increase) | 1.05 | 1.04 – 1.06 |
| Elevated Threshold (≥100 mg/dL) | 1.74 | 1.50 – 2.01 |
| High-Risk Threshold (≥150 mg/dL) | 2.66 | 2.16 – 3.28 |
Crude venous thromboembolism rates were noticeably elevated among patients with an Lp(a) level of 50 mg/dL or greater, registering at 2.8% compared to 1.9% in those below the threshold. Utilizing a multivariable model, researchers calculated an adjusted odds ratio of 1.36 for overall venous thromboembolism, alongside matching 1.33 odds ratios for both deep vein thrombosis and pulmonary embolism independently.
Dose-response analyses demonstrated that each incremental 10 mg/dL rise in Lp(a) correlated with a statistically significant increase in risk. To ensure the findings were not skewed by high-risk confounders, investigators ran sensitivity analyses excluding patients with active cancer or major thrombophilia. The risk signal remained entirely stable, proving that the association is not driven solely by patient populations already prone to hypercoagulability.
Study references
- Dreher 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.2026.3964
- Pfeferman 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.
