Lipoprotein(a) as a Risk Factor for Venous Thromboembolism: A Systematic Review and Meta-analysis of the Literature

Dentali, Francesco; Gessi, V.; Marcucci, Rossella; Gianni, Monica; Grandi, Anna Maria; Franchini, Massimo

doi:10.1055/s-0036-1598002

Cited by 57 publications

(19 citation statements)

References 27 publications

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“…The majority of studies which investigated the association of Lp(a) with VTE were cross-sectional rather than prospective. The most recent meta-analysis analyzed the data of ten studies encompassing 13,541 subjects of whom 5660 had a history of deep vein thrombosis and/or pulmonary embolism [23]. As the cut-off defining elevated Lp(a), the authors used the upper limit of the manufacturer's product reference range (usually 30 mg/dL) in nine studies and the 75th percentile of Lp(a) value in the control group in one study.…”

Section: Venous Thromboembolism In Adultsmentioning

confidence: 99%

Is lipoprotein(a) a risk factor for ischemic stroke and venous thromboembolism?

Nave

Eckardstein

2019

Clin Res Cardiol Suppl

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The structural similarity with plasminogen as well as thrombogenic and atherogenic in vitro functions raise the question if lipoprotein(a) (Lp(a)) is a risk factor for venous thromboembolism (VTE) and ischemic stroke. Numerous case-control and prospective studies using different cut-off values to define high Lp(a) generated conflicting evidence for both VTE and ischemic stroke. Several meta-analyses demonstrated independent associations of elevated Lp(a) with a history of VTE or ischemic stroke. However, the evidence of prospective studies for associations of Lp(a) with incident stroke or recurrent VTE remains inconclusive. For ischemic stroke, data suggest that Lp(a) increases the risk of large-artery atherosclerosis stroke, but not cardioembolic or lacunar stroke. Lp(a) may increase the risk of VTE in the presence of additional thrombophilic risk factors. Larger cohort studies are needed to elaborate the importance of higher Lp(a) cut-offs and interactions with other risk factors and subgroups of stroke or VTE. The value of Lp(a) to estimate residual vascular risk after the first thromboembolic event remains to be adequately explored. Keywords Lipoprotein a · Atherosclerosis · Low-density lipoproteins · Ischemic stroke · Venous thrombosisLipoprotein(a) [Lp(a)] resembles to low-density lipoprotein (LDL) by the presence of one molecule apolipoprotein B (apoB) and its relatively high content of cholesteryl esters in the core. These features lend several in vitro atherogenic properties to Lp(a) which are also exerted by LDL, for example proteoglycan binding and induction of foam cell formation [1]. Lp(a) differs from LDL by the presence of an additional apolipoprotein, termed apolipoprotein(a) (apo(a)), which is covalently bound to apoB by one disulfide bond. Apo(a) is homologous to plasminogen by

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Section: Venous Thromboembolism In Adultsmentioning

confidence: 99%

Is lipoprotein(a) a risk factor for ischemic stroke and venous thromboembolism?

Nave

Eckardstein

2019

Clin Res Cardiol Suppl

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“…Evidence linking increased Lp(a) with venous thrombosis is inconsistent [ 19 – 21 ]. Associations of elevated Lp(a) with CVST are unclear.…”

Section: Introductionmentioning

confidence: 99%

Elevated lipoprotein(a) as a new risk factor of cerebral venous sinus thrombosis: association with fibrin clot properties

Skuza

Polak

Undas

2018

J Thromb Thrombolysis

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Elevated lipoprotein(a) [Lp(a)] has been reported to be associated with prothrombotic clot phenotype. We hypothesized that increased Lp(a) contributes to cerebral venous sinus thrombosis (CVST) and its recurrence in relation to clot features. In 80 consecutive patients (aged 39.36 ± 10.18 years, 61 women) following the first CVST after anticoagulation withdrawal, we assessed Lp(a) levels and plasma clot properties. Recurrence of CVST was recorded during follow-up (median 53, interquartile range 40–59 months). Lp(a) levels were inversely associated with clot permeability (Ks, r = − 0.58, P < 0.001) and the rate of D-dimer release from clots in the presence of tissue plasminogen activator (r = − 0.27, P = 0.017) along with increased maximum absorbance of fibrin gels (r = 0.42, P < 0.001) and maximum D-dimer levels achieved during lysis (D–Dmax, r = 0.29, P = 0.01). Recurrence of CVST was observed in 12 patients (15%) after median follow-up of 26 months. Lp(a) concentrations were higher in patients with recurrence of CVST compared to the remainder (14.15 [8.85–25.25] vs. 28.3 [18.9–35.6] mg/dL; P = 0.001). The risk of recurrent CVST was fourfold higher among 17 (21.25%) patients with Lp(a) > 30 mg/dL compared to the remainder (adjusted hazard ratio, 3.9; 95% confidence interval [CI] 1.23–12.4). Recurrence of CVST was associated with 14% lower Ks (P = 0.001) and 10% higher D–Dmax (P = 0.008), with no differences in other clot features. Multiple logistic regression model showed that CVST recurrence was independently associated with Lp(a) (odds ratio 1.09, 95% CI 1.02–1.16). Increased Lp(a) characterizes subjects at elevated risk of recurrent CVST after anticoagulation withdrawal, which could be partly explained by formation of denser fibrin clots.

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“…Moreover, Lp(a) has also been suggested to have pro-thrombotic properties. Indeed, its similarity to plasminogen, causing thrombosis through antifibrinolytic properties, and a variety of clinical studies support this Lp (a)-thrombus axis [54,55]. However, few factors (pharmaceutical or dietary) influences the plasma level of this lipid parameter; even though treatment with PCSK9 inhibitors seem to have a Lp(a) lowering effect of approximately 30% [56].…”

Section: Discussionmentioning

confidence: 99%

Effect of hormone replacement therapy on atherogenic lipid profile in postmenopausal women

Gregersen

Høibraaten

Holven

et al. 2019

Thrombosis Research

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Background: Women develop cardiovascular disease (CVD) approximately 7-10 years later than men, but progress with similar risk after menopause. Recent studies suggest that hormone replacement therapy (HRT) is cardioprotective when initiated early after menopause, but the mechanisms involved are still unclear. Objective: In the current study, we aimed to examine the effects of HRT treatment on the plasma atherogenicity in postmenopausal women. We studied the total lipid profile in blood samples collected in a randomized, doubleblinded, placebo controlled clinical trial of women with a history of venous thrombosis (VT), the EVTET study. Methods: One-hundred and forty postmenopausal women < 70 years were included in EVTET and randomized either to active treatment (one tablet of 2 mg estradiol and 1 mg norethisterone acetate daily) (n = 71) or placebo (n = 69). Blood samples were taken at baseline and after 3 months and subjected to routine assessment of hemostatic factors and lipids. Results: Our study show that HRT compared to placebo significantly reduced plasma levels of Lp(a), ApoA1, ApoB, total cholesterol (TC), HDL-C, LDL-C, TC/HDL-C and LDL-C/HDL-C ratio at 3 months. No effect was observed on ApoB/ApoA1 ratio or triglycerides. The change in Lp(a) was significantly and inversely correlated with the change in estradiol (r = −0.32; P = 0.001) and positively correlated to the change in lipids, tissue factor pathway inhibitor activity and antigen, protein C and fibrinogen (r between 0.26 and 0.45, p < 0.01). Conclusion: In sum, this study confirms a strong effect of HRT on atherogenic lipids with a large reduction in the pro-thrombotic Lp(a), suggesting an overall favorable effect on thrombogenicity after HRT replacement therapy in post-menopausal women at risk of VT.

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Lipoprotein(a) as a Risk Factor for Venous Thromboembolism: A Systematic Review and Meta-analysis of the Literature

Cited by 57 publications

References 27 publications

Is lipoprotein(a) a risk factor for ischemic stroke and venous thromboembolism?

Is lipoprotein(a) a risk factor for ischemic stroke and venous thromboembolism?

Elevated lipoprotein(a) as a new risk factor of cerebral venous sinus thrombosis: association with fibrin clot properties

Effect of hormone replacement therapy on atherogenic lipid profile in postmenopausal women

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