Lipoprotein(a): A missing culprit in the management of athero‐thrombosis?

Ferretti, Gianna; Bacchetti, Tiziana; Johnston, Thomas P.; Banach, Maciej; Pirro, Matteo; Sahebkar, Amirhossein

doi:10.1002/jcp.26050

Cited by 74 publications

(66 citation statements)

References 104 publications

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“…Elevated Lp(a) could be also involved in atherothrombotic disorders. Lp(a) influences different coagulation factors resulting in thrombus formation [38]. Patients suffering from thrombophilia Lp(a) may aggravate the coagulation situation, leading e. g. to placenta-mediated pregnancy complications resulting in early miscarriages [39,40].…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein apheresis is an optimal therapeutic option to reduce increased Lp(a) levels

Schettler¹,

Neumann²,

Pristipino³

et al. 2019

Clin Res Cardiol Suppl

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Background Lipoprotein(a) (Lp(a)) is a genetic risk factor for cardiovascular disease (CVD) and is associated with the induction and sustaining of atherosclerotic cardiovascular diseases (ASCVD). Since 2008 Lp(a) along with progressive CVD has been approved as an indication for regular lipoprotein apheresis (LA) in Germany. The German Lipoprotein Apheresis Registry (GLAR) has been initiated to provide statistical evidence for the assessment of extracorporeal procedures to treat dyslipidemia for both LDL-cholesterol (LDL-C) and Lp(a). The GLAR now allows prospective investigations over a 5-year period about annual incidence rates of cardiovascular events. Here Lp(a) patients (LDL-C < 100 mg/dl; Lp(a) > 60 mg/dl or >120 nmol/l) showed the same reduction of major coronary (83%) and non-coronary events (63%) as had been formerly shown in the Pro(a)LiFe study. However, Lp(a) is not only an apolipoprotein(a) (apo(a)) and LDL-C containing particle, which is covalently bound to a LDL-C core by a disulphide bridge. The composition of this particle, inter alia containing oxidized phospholipids, gives pro-atherosclerotic, pro-inflammatory, and pro-thrombotic properties, inducing atherosclerotic processes mainly in the arterial wall. However, recent investigations have shown that a reduction of inflammatory settings without LDL-C or Lp(a) reduction may reduce ASCVD events. Lipoprotein apheresis (LA) could not only reduce LDL-C and Lp(a) in parallel, but also different inflammatory and coagulation parameters. In summary lipoprotein apheresis is not only anti-atherosclerotic, but also anti-inflammatory and anti-thrombotic and therefore an ideal treatment option with respect to the shown reduction of major adverse coronary events (MACE) and major adverse non-coronary events (MANCE) by reducing Lp(a) levels.Keywords Lipoprotein apheresis · Lipoprotein (a) · Cardiovascular disease · Coronary artery disease · Major coronary events · Major non-coronary events · Inflammation · Prevention This article is part of the special issue "Lp(a) -Update 2018"

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Section: Discussionmentioning

confidence: 99%

Lipoprotein apheresis is an optimal therapeutic option to reduce increased Lp(a) levels

Schettler¹,

Neumann²,

Pristipino³

et al. 2019

Clin Res Cardiol Suppl

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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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“…[ 2 , 3 ] As conventional risk factors such as hyperglycemia, hyperlipidemia, and blood pressure are inadequate in predicting stroke, [ 4 , 5 ] novel predictive biomarkers were investigated to predict high-risk subjects. [ 6 , 7 ]…”

Section: Introductionmentioning

confidence: 99%

The associations of stroke, transient ischemic attack, and/or stroke-related recurrent vascular events with Lipoprotein-associated phospholipase A2

Tian

Jia

et al. 2017

Medicine

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Background:Studies on stroke and lipoprotein-associated phospholipase A2 (Lp-PLA2) have produced conflicting results.Objective:The aim of the study was to assess the associations of Lp-PLA2 levels (mass and activity) with recurrent vascular events in patients with transient ischemic attack (TIA) and/or first ischemic stroke and with stroke in the general population.Methods:The MEDLINE, Embase, the Cochrane Library, Web of Science, Science Direct, China National Knowledge Infrastructure, China Biology Medical Disc (CBMdisc), and WanFang were searched for prospective observational studies reported until January 2017. Eligible studies reported Lp-PLA2 levels and adjusted risk estimates of recurrent vascular events and/or stroke. Risk ratio (RR) with corresponding 95% confidence intervals (CIs) were used to express the pooled data in a random-effects model.Results:A total of 11 studies that comprised 20,284 participants (4,045 were TIA and/or first ischemic stroke patients and 16,239 were residents in general population) were identified, which reported either Lp-PLA2 mass levels (4 studies) or Lp-PLA2 activity levels (10 studies). The pooled RR of recurrent vascular events (467 cases) in TIA and/or first ischemic group was 2.24 (95% CI, 1.33–3.78), whereas the pooled RR of stroke (1604 cases) in the general population was 1.47 (95% CI, 1.10–1.97). The pooled RRs of Lp-PLA2 mass and activity levels with the risk of stroke in the general population were 1.69 (95% CI, 1.03–2.79) and 1.28 (95% CI, 0.88–1.85), respectively.Conclusions:In patients with TIA and first ischemic stroke, elevated Lp-PLA2 activity levels were associated with recurrent vascular events. And in the general population elevated Lp-PLA2 levels were associated with the risk of stroke, although the association between Lp-PLA2 activity levels and the risk of stroke was less profound compared with the corresponding association of stroke risk with the Lp-PLA2 mass levels.

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Lipoprotein(a): A missing culprit in the management of athero‐thrombosis?

Cited by 74 publications

References 104 publications

Lipoprotein apheresis is an optimal therapeutic option to reduce increased Lp(a) levels

Lipoprotein apheresis is an optimal therapeutic option to reduce increased Lp(a) levels

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

The associations of stroke, transient ischemic attack, and/or stroke-related recurrent vascular events with Lipoprotein-associated phospholipase A2

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