The Effects of Renal Function and Atrial Fibrillation on Lipoproteins and Clot Structure/Function

Study Overview
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Brief Summary
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This study is designed to investigate the role of lipids/lipoproteins as a potential cause for the harmful changes seen in fibrin clot properties with renal dysfunction and atrial fibrillation

Detailed Description
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This is a prospective, observational, blinded study that will be conducted in two parts. The first study will assess the relationship between lipids/lipoproteins and fibrin clot properties among anticoagulated atrial fibrillation patients with and without renal dysfunction. The second study will assess the effects of statin therapy on lipids/lipoproteins and fibrin clot properties in anticoagulated atrial fibrillation patients with renal dysfunction. Renal dysfunction is defined as an estimated glomerular filtration rate below 50 ml/min/1.73m2 for the purposes for this trial.

Official Title
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Stratifying Clinical Risk in Patients With Atrial Fibrillation and Chronic Kidney Disease by Studying How Abnormalities in Clot Structure/Function and Lipoproteins Contribute to Thrombosis and Bleeding

Conditions
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Atrial Fibrillation, Chronic Kidney Disease

Intervention / Treatment
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* Drug: Statin


Participation Criteria
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Eligibility Criteria
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6.1 Inclusion criteria WP1: On anticoagulation therapy Informed consent obtained WP2: Not receiving statins prior to recruitment Diagnosed atrial fibrillation On anticoagulation therapy Estimated glomerular filtration rate of <50 ml/min/1.73m2 Informed consent obtained 6.2 Exclusion criteria Age <18 years Severe mitral stenosis or presence of metallic prosthetic valve Active or recent malignancy (<6 months) Active immunological disease Connective tissue disease Chronic liver disease Recent or chronic serious infection Chronic inflammatory disease Known haemophilia or thrombophilia Active bleeding Untreated hypothyroidism or hyperthyroidism Recent surgery (<3 months) Familial lipid disorders Concurrent use of steroids Dietary supplements known to influence lipids Contraindications/inability/unwillingness to commence statin (WP2)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| WP1: AF + CKD<br>Anticoagulated participants with atrial fibrillation and chronic kidney disease | |
| WP1: AF + no CKD<br>Anticoagulated participants with atrial fibrillation and no chronic kidney disease | |
| WP1: no AF + CKD<br>Anticoagulated participants with chronic kidney disease and no atrial fibrillation | |
| WP1: no AF + no CKD<br>Anticoagulated participants without atrial fibrillation or chronic kidney disease | |
| WP2: AF + CKD<br>Anticoagulated participants with atrial fibrillation and chronic kidney disease, and are commencing statin therapy | Drug: Statin<br>* Any statin therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WP1: Fibrin clot structure and function assessment using validated turbidity and fibrinolysis test | Lag time, maximum absorbance, time to maximum absorbance and clot lysis time | At baseline | 
| WP1: Fibrin permeation analysis using validated test | Permeation constant (Ks) | At baseline | 
| WP1: Low density lipoprotein fractions | Measure of low density lipoprotein subclass fractions | At baseline | 
| WP1: Oxidised low density lipoprotein | Measure of oxidised low density lipoprotein | At baseline | 
| WP2: Fibrin clot structure and function assessment using validated turbidity and fibrinolysis test | Lag time, maximum absorbance, time to maximum absorbance and clot lysis time | At baseline and after 6 weeks of statin therapy | 
| WP2: Fibrin permeation analysis using validated test | Permeation constant (Ks) | At baseline and after 6 weeks of statin | 
| WP2: Low density lipoprotein fractions | Measure of low density lipoprotein subclass fractions | At baseline and after 6 weeks of statin | 
| WP2: Oxidised low density lipoprotein | Measure of oxidised low density lipoprotein | At baseline and after 6 weeks of statin | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WP1: Scanning electron microscopy | Qualitative assessment of fibril indices | At baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anticoagulation, Fibrin clot structure and function, Lipids, Lipoproteins, Statin