Advanced Lipoproptein Profiling and Cardiovascular Risk Stratification in Familial Hypercholesterolemia

NCT05066932 | Unknown

• 2 other identifiers: APHP2104552021-A00747-34
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Familial hypercholesterolaemia (FH) is a genetic disorder characterised by elevated plasma LDLC levels. The causal role of low-density lipoprotein cholesterol (LDLC) in the progression of cardiovascular disease (CVD) is indisputable: genetic, epidemiological and interventional trials have unanimously shown that a reduction in LDL-C is associated with a reduced risk of CVD. Some drawbacks related to the limitations of the analytical methods are slowly surfacing due to the lower LDLC target achieved with the combination of several new treatments. This is mainly due to the fact that LDLC is not a comprehensive marker to stratify cardiovascular risk in subjects with increased levels of other atherogenic lipoproteins. Direct measurement of the concentration of apolipoproteins involved in cholesterol and triglycerides transportation, may provide more information than the simple measure of the cholesterol contained in these particles. There is an interest in measuring the various players involved in the lipoprotein processing chain. These apolipoproteins are increasingly being considered as possible biomarkers of cardiovascular disease risk. Indeed, there is increasing evidence that advanced lipoprotein testing methods, such as multiplexed measurements of apolipoprotein panels (ApoA-I, A-II, A-IV, B-100, C-I, C-II, C-III, E), provide more detailed information on the dyslipidaemic profiles of patients compared to conventional lipid testing, finally allowing a better understanding and stratification of subclinical atherosclerosis in these patients. The main objective of this study is to compare the apolipoprotein profile of patients with FH by comparing those with associated hypertriglyceridemia (hyperTG) to those with isolated hypercholesterolaemia. Adult subjects with a molecular diagnosis of Familial Hypercholesterolemia, treated by a statin, on primary prevention, asymptomatic for cardiovascular symptoms, will be recruited and stratified according to the presence/absence of hyperTG in a case-control prospective observational study design.

Conditions

Familial Hypercholesterolemia; Atherosclerosis

Keywords

Familial hypercholesterolemia; Primary prevention; Apolipoproteins; Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• Apolipoprotein score

  Apolipoprotein score (ApoA-I, A-II, A-IV, B-100, C-I, C-II, C-III, E) will be measured in gram per liter (g/l) and assessed by liquid chromatography-mass spectrometry (LC-MS).

  At day 1

Secondary Outcomes (5)

• Calcium score

  At day 1

• Intima-media thickening of the distal common carotid artery

  At day 1

• Presence of carotid plaque

  At day 1

• Intima-media thickening of the distal common femoral artery

  At day 1

• Presence of femoral plaque

  At day 1

Study Arms (2)

Familial Hypercholesterolemia and hyperTriglyceridemia

Patients with Familial Hypercholesterolemia and hyperTriglyceridemia

Other: Additionnal blood samples

Familial Hypercholesterolemia without hyperTriglyceridemia

Patients with Familial Hypercholesterolemia and without hyperTriglyceridemia

Other: Additionnal blood samples

Interventions

Additionnal blood samples OTHER

Additionnal blood samples

Familial Hypercholesterolemia and hyperTriglyceridemia; Familial Hypercholesterolemia without hyperTriglyceridemia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients with familial hypercholesterolemia (FH), with or without hyperTG

You may qualify if:

• A. Patients with familial hypercholesterolemia (FH) and with hyperTG :
• Age \> 18 years
• Molecular or clinical diagnosis of FH
• Primary prevention (no coronary artery disease, cerebrovascular disease or lower limb arterial disease)
• HyperTG or TG levels between 135-500 mg/dl on statin therapy
• Patient informed of the research, not having objected to participation and having provided written consent for genetic analysis
• B. Patients with familial hypercholesterolemia (FH) and without hyperTG :
• Age \> 18 years
• Mild diagnosis
• Primary prevention (no coronary artery disease, cerebrovascular disease or lower limb arterial disease)
• TG \<135mg/dl on statin therapy
• Patient informed of the research, did not object to participation and provided written consent for genetic testing

You may not qualify if:

• Secondary prevention or planned coronary intervention or cardiac surgery
• History of acute or chronic pancreatitis
• Statin-intolerant patient
• Glycated haemoglobin level greater than 10.0%.
• Human Immunodeficiency Virus infection on treatment,
• Use of corticosteroids
• Severe renal impairment (Glomerular filtration rate \< 30 ml/min)
• Pregnant women

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital de la Pitié Salpêtrière

Paris, 75013, France

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Plasma, serum

MeSH Terms

Conditions

Hyperlipoproteinemia Type II; Atherosclerosis

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Eric BRUCKERT

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eric BRUCKERT

CONTACT

01 42 17 57 84; eric.bruckert@aphp.fr

Antonio GALLO

CONTACT

01 84 82 76 44; antonio.gallo@aphp.fr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2021
• First Posted: October 4, 2021
• Study Start: October 20, 2021
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2022
• Last Updated: August 3, 2022

Record last verified: 2022-01

Locations

FR (1)