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Increased lipoprotein (a) levels as an independent risk factor for venous thromboembolism
M von Depka1, U Nowak-Göttl, R Eisert
1Department of Hematology/Oncology, Hannover Medical School, Hannover, Germany. depka.mario@mhhannover.de
Insights
Elevated lipoprotein (a) [Lp(a)] is a significant, independent risk factor for venous thromboembolism (VTE). High Lp(a) levels may also increase VTE risk in individuals with other prothrombotic defects, like the Factor V G1691A mutation.
Area of Science:
- Cardiovascular and Thrombotic Disorders
- Genetics and Molecular Biology
- Clinical Risk Factor Analysis
Background:
- Elevated serum lipoprotein (a) [Lp(a)] is a recognized risk factor for arterial cardiovascular and cerebrovascular diseases.
- The specific role of increased Lp(a) in the pathogenesis of venous thromboembolism (VTE) remains less understood.
- Investigating Lp(a) in conjunction with established hereditary thrombogenic defects is crucial for a comprehensive understanding of VTE risk.
Purpose of the Study:
- To evaluate the association between elevated serum lipoprotein (a) [Lp(a)] levels and venous thromboembolism (VTE).
- To assess the role of Lp(a) in patients with known hereditary thrombogenic defects.
- To determine if Lp(a) acts as an independent risk factor or modifies the risk associated with other thrombophilic mutations.
Main Methods:
- A cohort of 685 consecutive VTE patients and 266 matched healthy controls were analyzed.
- Screening included assays for activated protein C resistance, protein C, protein S, antithrombin deficiency, and serum Lp(a) levels.
- Genetic analysis for factor V G1691A, MTHFR C677T, and prothrombin G20210A mutations was performed.
Main Results:
- Elevated Lp(a) levels (>30 mg/dL) were observed in 20% of VTE patients versus 7% of controls (OR 3.2, P <.001).
- The combination of Factor V G1691A mutation and elevated Lp(a) was significantly more frequent in VTE patients (7% vs. 0.8%, OR 9.8, P <.001).
- No other tested prothrombotic risk factors showed a significant combined association with increased Lp(a).
Conclusions:
- Serum lipoprotein (a) concentrations greater than 30 mg/dL represent a frequent and independent risk factor for VTE.
- Elevated Lp(a) may enhance the penetrance of thromboembolic disease in individuals with coexisting prothrombotic defects, such as the Factor V G1691A mutation.
Abstract:
Elevation of serum lipoprotein (a) (Lp[a]) is a known risk factor predisposing to cardiovascular and cerebrovascular disease. However, little is known about the role of increased Lp(a) in venous thromboembolism (VTE). This study evaluated the role of Lp(a) among a panel of established hereditary thrombogenic defects in patients with VTE. A total of 685 consecutive patients with at least one episode of VTE and 266 sex- and age-matched healthy controls were screened with regard to activated protein C resistance, protein C, protein S, and antithrombin deficiency, elevated serum levels of Lp(a), and the factor V G1691A, MTHFR C677T, and prothrombin G20210A mutations. Elevated Lp(a) levels above 30 mg/dL were found in 20% of all patients, as compared to 7% among healthy controls (P <.001, odds ratio [OR] 3.2, 95% confidence interval [CI], 1.9-5.3). The coexistence of FV G1691A and elevated Lp(a) was significantly more prevalent among patients with VTE than in the control group (7% versus 0.8%; P <.001, OR 9.8, 95% CI, 2.4-40.7). No other established prothrombotic risk factor was found to be significantly combined with increased Lp(a). These data suggest that Lp(a) concentrations greater than 30 mg/dL are a frequent and independent risk factor for VTE. Furthermore, elevated Lp(a) levels might contribute to the penetrance of thromboembolic disease in subjects being affected by other prothrombotic defects, such as FV G1691A mutation.