Increased lipoprotein (a) levels as an independent risk factor for venous thromboembolism

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.

Lipoprotein(a), polymorphisms in the LPA gene, and incident venous thromboembolism among 21 483 women

“…The data expand on varying evidence regarding plasma Lp(a) levels and VTE, as some [4][5][6]15] but not all [7,9,16] studies have shown an association of Lp(a) with VTE. Our findings are concordant with those of the Longitudinal Investigation of Thromboembolism Etiology study (LITE) study that pooled the Atherosclerosis Risk in Communities Study (ARIC) and Cardiovascular Health Study (CHS) studies and found no relationship between Lp(a) levels (> 30 mg dL )1 ) and VTE [8].…”

“…increased incidence of VTE, as some [4][5][6] but not all [7][8][9] studies have reported positive associations. To address whether circulating Lp(a) levels have an impact on the development of VTE, we assessed its relationship to incident VTE.…”

Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac‐1 integrin

“…Thus, the proinflammatory action of Lp(a)/apo(a) can be extended to events downstream of integrin activation. Emerging evidence has suggested that Lp(a) is also a risk factor for venous thrombotic disease (2,60). As tissue factor is the major initiator of hemostasis and thrombosis after vascular injury, its up-regulation by Lp(a)/apo(a) identifies an additional prothrombotic action of Lp(a).…”

Prothrombotic conditions in an unselected cohort of children with venous thromboembolic disease

“…Thus, the prevalence of protein S deficiency in our cohort seems to be not different from the reported incidence. The prevalence of increased lipoprotein (a) in the normal population is derived from the control groups of large German studies in adults (7%) [7] and in children (10.3%) [8].…”

“…The established causes of thrombosis with known inheritance are deficiencies of antithrombin, protein C and protein S, activated protein C resistance/FV Leiden mutation and the prothrombin G20210A (IIG20210A) polymorphism [6]. Recently, increased levels of plasma lipoprotein (a) and homocysteine were found to be possible inherited prothrombotic conditions both in children and adults [7][8][9]. Increased plasma concentrations of FVIII coagulant (FVIII:C), IX coagulant (FIX:C) and XI coagulant (FXI:C) have been linked with TEs in adults [10][11][12].…”