Relevance of Plasma PCSK9 Concentration as a Biomarker in Acute Coronary Syndrome. (PC-SCA-9)

PCSK9 (Proprotein convertase subtilisin kexin type 9) plays a key role in LDL-cholesterol (LDLC) metabolism by inhibiting LDL receptor (LDLR) at post-transcriptional level. PCSK9 loss of function mutations are associated to decreased LDLC levels and a cardiovascular protection. In this context, the development of pharmacological inhibitors of PCSK9, in association with statins treatment, represents a major therapeutic issue for LDLC modulation. It was previously shown that PCSK9 plasmatic concentration correlated with plasmatic LDLC, TG and glucose concentrations. However, no data are available on predictive value of PCSK9 plasmatic level concerning coronary disease severity.

The main objective of this study is to determine whether plasmatic PCSK9 concentration is linked to coronary damage severity in patients with acute coronary syndrome.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Other: biological parameters dosage

• Study Type: Observational
• Enrollment (Actual): 175

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44093
    • Nantes University Hospital
  • Nantes, France, 44000
    • Nantes University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients of both sexes, 18 years old minimum, with an acute coronary syndrome, treated or not with statins, admitted to cardiological intensive care unit.

Description

Inclusion criteria:

• more than 18 years old
• Acute coronary syndrome (ST+ or ST-)
• 2 groups of patients: with statin, and without statin treatment

Exclusion criteria:

• Patient who had cancer during the last 5 years or with cancer in progress
• Patient with severe infection in progress
• Hepatic failure (TP<50%)
• Severe kidney failure
• Patient unable to give his consent to the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
patient treated by statines	Other: biological parameters dosage; 200 patients will be enrolled in the study (n=100 patients under statin treatment, n=100 patients without statin). After checking inclusion and non-inclusion criteria and obtaining informed consent from the patients. The SYNTAX score will be calculated and will allow to determine coronary analysis will be done at J1 and J4 (glucose, HbA1C, lipids, ApoA1, ApoB, sterols, plasmatic bile acids, insulinemia, creatinin clearance, hepatic function panel, CRPus and PCSK9 level assessment). Then, a sub-group of 30 patients will have supplementary blood analysis at 1 and 6 months after their admission, during their usual follow-up.
patient without normolipidemic treatment	Other: biological parameters dosage; 200 patients will be enrolled in the study (n=100 patients under statin treatment, n=100 patients without statin). After checking inclusion and non-inclusion criteria and obtaining informed consent from the patients. The SYNTAX score will be calculated and will allow to determine coronary analysis will be done at J1 and J4 (glucose, HbA1C, lipids, ApoA1, ApoB, sterols, plasmatic bile acids, insulinemia, creatinin clearance, hepatic function panel, CRPus and PCSK9 level assessment). Then, a sub-group of 30 patients will have supplementary blood analysis at 1 and 6 months after their admission, during their usual follow-up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Syntax score (for evaluate coronary damages) and plasmatic concentration of PCSK9	Assessing the correlation between plasma concentration of PCSK9 and coronary damage severity in patients with acute coronary syndrome. Coronary lesions will be measured using the SYNTAX score (J0: admission day), and PCSK9 concentration will be evaluated using blood analysis (J0 (admission), J1, J2, J3 & J4).	Day 1, Day 2, Day 3, Day 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between PCSK9 and morbidity/mortality	Assessing the correlation between plasma PCSK9 (J1, J2, J3, J4) concentration and one-year morbidity/mortality of patients with acute coronary syndrome	Day 1, Day 2, Day 3, Day 4
association between PCSK9 and metabolic/inflammatory factors	Identification of metabolic and inflammatory factors (glycemia, insulinemia, HbA1C, CRPus…) associated to plasma PCSK9 concentration	Day 1, Day 2, Day 3, Day 4
kinetic of PCSK9 for statin-treated patients	Measurement of PCSK9 kinetic variation during ACS acute phase in patients treated with artovastatin 80 mg/day (J1, J2, J3, and J4)	Day 1, Day 2, Day 3, Day 4
kinetic of PCSK9 after intensive care	Determination of PCSK9 kinetic variation at 1 and 6 months after intensive care, during their normal follow-up	Day 1, Day 2, Day 3, Day 4

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Principal Investigator: Bertrand Cariou, MD, Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2011
• Primary Completion (Actual): September 24, 2013
• Study Completion (Actual): July 16, 2015

Study Registration Dates

• First Submitted: April 20, 2010
• First Submitted That Met QC Criteria: April 22, 2010
• First Posted (Estimate): April 23, 2010

Study Record Updates

• Last Update Posted (Actual): September 20, 2021
• Last Update Submitted That Met QC Criteria: September 13, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Acute coronary syndrome; PCSK9; cardiovascular safety
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Acute Coronary Syndrome
• Other Study ID Numbers: BRD/10/03-ZE