Assessment of Lipoprotein(a) and Endogenous Fibrinolysis in Atherosclerotic Cardiovascular Disease/Aortic Valve Disease

Summary

Prior studies have shown that impaired endogenous fibrinolysis is a novel, independent cardiovascular risk factor in patients with myocardial infarction and there is currently no known chronic treatment to enhance endogenous fibrinolysis.

To date, no therapies have been able to sufficiently reduce Lp(a) and therefore it was considered to be a non-modifiable cardiovascular risk factor. New data, however, has shown that PCSK9 inhibitors and inclisiran (medication that you have been deemed eligible for in order to help further reduce your cholesterol levels) to reduce Lp(a) levels by approximately 20-25%.

The aim of this study to is to assess:

1. if there is an association between raised Lp(a) level in blood and the effectiveness of endogenous fibrinolysis (lysis time).
2. whether lowering Lp(a) with PCSK9i or inclisiran can enhance endogenous fibrinolysis

Conditions

• Atherosclerosis
• Aortic Valve Disease

Interventions

DIAGNOSTIC_TEST

Thrombotic assessment

The Global Thrombosis Test (Thromboquest Limited, UK) is an in vitro method imitating high shear stress conditions akin to that which exist in a severely stenosed artery. The test measures platelet reactivity (occlusion time) and endogenous fibrinolysis time (lysis time). Thromboelastography is a technique that assesses the whole process of clotting and its viscoelastic properties, from the initial activation and aggregation of platelets, to the role of thrombin and finally the stability of the formed clot, as a measure of fibrinolytic resistance. Plasma will be stored for subsequent analysis of other thrombotic, fibrinolytic, inflammatory and coagulation markers as deemed appropriate. For patients deemed eligible for treatment with either a PCSK9i or inclisiran, this will be assessed prior to commencing treatment and also 3-6 months after starting treatment. This will only be assessed once for patients with moderate or severe aortic valve calcification.

DIAGNOSTIC_TEST

Measurement of Lp(a)

Lp(a) will be measured by particle enhanced immunotubidimetricassay. Human lipoprotein (a) agglutinates with latex particles coated with anti-Lp(a) antibodies. The precipitate is determined turbidimetrically at 800 / 660 nm. The platform employed will be the Roche® Immunoassay Analyser (Roche Diagnostics GmbH, Sandhofer Strasse 116, D-68305 Mannheim). Traceability: This method has been standardized against the IFCC (International Federation of Clinical Chemistry) reference material SRM2B for nmol/L. For patients deemed eligible for treatment with either a PCSK9i or inclisiran, this will be assessed prior to commencing treatment and also 3-6 months after starting treatment. This will only be assessed once for patients with moderate or severe aortic valve calcification.

Sponsors & Collaborators

• East and North Hertfordshire NHS Trust

  lead OTHER_GOV

Principal Investigators

• Diana A Gorog, MD, PhD · East and North Hertfordshire NHS Trust

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-10-20

Primary Completion

2027-10-01

Completion

2027-10-01

Countries

• United Kingdom

Study Locations