Relationships Between Plasma PCSK9 Levels, LDL-cholesterol Concentrations and Lipoprotein (a) Levels in Familial Hypercholesterolemia

NCT ID: NCT02225340

Last Updated: 2014-08-26

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 348 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2014-04-30

Brief Summary

Familial hypercholesterolemia (FH) is an autosomal codominant single gene disorder caused by mutations in the LDL receptor gene (LDLR) that disrupt the normal clearance of LDL particles from the plasma. Heterozygous patients (HeFH) present a two- to three-fold raise in plasma LDL-cholesterol (LDL-C) concentrations and coronary artery disease occurs earlier among HeFH carrying negative-receptor (NR) mutations as compared with HeFH subjects carrying defective-receptor (DR) variants. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates LDL-C levels by binding to LDLR and by enhancing its intracellular degradation.

The objective of this study is to examine to what extent variations in LDL-C and Lipoprotein (Lp) (a) concentrations are related to PCSK9 levels in a large French-Canadian cohort of HeFH subjects.

The primary hypothesis is that that PCSK9 levels have a significant impact on LDL-C concentration variability and are associated with Lp(a) levels.

Conditions

Familial Hypercholesterolemia

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Controls

No interventions assigned to this group

Familial hypercholesterolemia

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

Subjects with familial hypercholesterolemia:

• Aged between 18-65 years
• Carrier of a mutation in the LDL receptor gene

Controls:

• Aged between 18-60 years
• HDL-cholesterol > 1.1 mmol/L
• Triglycerides < 1.7 mmol/L
• Fasting blood glucose <6.1 mmol/L
• Normal blood pressure (<130/85)

Exclusion Criteria

• Subjects with a previous history of cardiovascular disease
• Subjects with Type 2 diabetes
• Were pregnant or nursing;
• Subjects with a history of cancer
• Subjects with acute liver disease, hepatic dysfunction, or persistent elevations of serum transaminases
• Subjects with a secondary hyperlipidemia due to any cause
• History of alcohol or drug abuse within the past 2 years
• hormonal treatment
• Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Laval University

OTHER

Sponsor Role: lead

Responsible Party

Patrick Couture

MD, FRCP, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Patrick Couture, MD, FRCP, PhD

Role: PRINCIPAL_INVESTIGATOR

Laval University

Locations

Institute of Nutrition and Functional Foods (INAF)

Québec, Quebec, Canada

Countries

Canada

References

Drouin-Chartier JP, Hogue JC, Tremblay AJ, Bergeron J, Lamarche B, Couture P. The elevation of plasma concentrations of apoB-48-containing lipoproteins in familial hypercholesterolemia is independent of PCSK9 levels. Lipids Health Dis. 2017 Jun 15;16(1):119. doi: 10.1186/s12944-017-0502-x.

Reference Type: DERIVED

PMID: 28619117 (View on PubMed)

Other Identifiers

FH-PCSK9

Identifier Type: -

Identifier Source: org_study_id