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The Spanish Familial Hypercholesterolaemia Cohort Study (SAFEHEART)

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ClinicalTrials.gov Identifier: NCT02693548
Recruitment Status : Recruiting
First Posted : February 26, 2016
Last Update Posted : February 15, 2023
Instituto de Salud Carlos III
Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Information provided by (Responsible Party):
Fundación Hipercolesterolemia Familiar

Brief Summary:
SAFEHEART is a large, on-going registry study in molecularly defined patients with heterozygous FH treated in Spain.

Condition or disease
Familial Hypercholesterolaemia

Detailed Description:

Familiar hypercholesterolemia (FH) is the most common genetic disorder associated with the development of severe and premature coronary artery disease (CAD). The disorder is caused by mutations in the gene that encodes the low-density lipoprotein receptor (LDL-r), resulting in a lower expression of functional LDL-r in the liver. FH has autosomal dominant transmission with high penetrance and the prevalence of heterozygous individuals is one in 400 to 500 in the general population. To date, more than 800 different functional mutations of the LDL-r gene have been described worldwide, and more than 200 have been documented in Spain. In addition, a much less common disorder that resemble FH is familial defective apoB 100 disorder (FDB) produced by a mutation in the Apo B 100 gene. FDB accounts for a significant proportion of FH in some localized regions of Spain.

Life expectancy is shortened by 20 to 30 years in FH patients, and sudden death and myocardial infarction are the principal causes of death. The Simon Broome Register of FH in Great Britain, has shown that FH has a 100-fold increase in coronary mortality and a nearly 10-fold increase in total mortality, especially in young adults.

Since the 1990's, coronary mortality and total mortality in FH patients have decreased remarkably in part due to the use of more effective lipid-lowering therapy such as statins. The analysis of the Dutch FH cohort showed that an early treatment with statins after the diagnosis of the disorder leads to near normalisation of coronary heart disease risk comparable to the general population. Therefore, most of patients require an early, continuous and more intensive lipid-lowering therapy.

Despite the use of statins, this population still have a high risk for the development of premature CAD. Therefore, the need to study the relatives of a known FH case, know as cascade screening, is essential to detect those cases that are younger, probably with a less severe form of FH and are not receiving treatment to prevent cardiovascular disease development.

Although the genetic defect is probably the most important factor in the clinical expression of FH, other genetic (gene-gene interactions), environmental (particularly those relating to diet, tobacco consumption and physical activity) and metabolic factors could play an important role in modulating the atherosclerotic burden in this population.

To gain insight into the prognostic factors and mechanisms that influence the development of CAD and mortality in FH, a long-term prospective follow-up of a molecularly well-defined FH cohort using a multidisciplinary approach is necessary. This cohort is an excellent tool of translational research to evaluate and determine the principal prognostic factors related to CAD morbidity and mortality.

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Study Type : Observational
Estimated Enrollment : 4141 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Spanish Familial Hypercholesterolaemia Cohort Study
Study Start Date : January 2004
Estimated Primary Completion Date : October 2030
Estimated Study Completion Date : October 2030

Familial hypercholesterolaemia patients
Index cases with genetic diagnosis of FH and their relatives over 15 years old with a genetic diagnosis of FH.
Unaffected relatives
Relatives of FH patients without FH (genetically defined)

Primary Outcome Measures :
  1. Prognostic assessment: time to fatal or non-fatal cardiovascular event. [ Time Frame: up to 12 years ]
    Time to first cardiovascular event: fatal or non-fatal myocardial infarction, fatal or non-fatal ischemic stroke, coronary revascularization, peripheral artery revascularization, aortic valve replacement or cardiovascular death.

Secondary Outcome Measures :
  1. LDL-cholesterol level (mg/dl) at entry and at follow-up [ Time Frame: up to12 years ]
    LDL-cholesterol measurement at enrolment and after follow-up. At enrolment, a central core lab is in charge of the analysis. During follow-up, a yearly-based phone call is used to contact every subject and a complete lipid profile is obtained from the patient (obtained in his/her usual medical care).

Biospecimen Retention:   Samples With DNA
Venous blood samples were taken after 12 hours of fasting. Serum, plasma and DNA samples were aliquoted and preserved at -80°C. Serum total cholesterol, triglycerides and HDL-cholesterol levels were measured in a centralized laboratory using enzymatic methods

Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Index cases with genetic diagnosis of FH and their relatives over 15 years old with a genetic diagnosis of FH and their unaffected relatives

Inclusion Criteria:

  • Index cases with genetic diagnosis of FH and their relatives over 15 years old with a genetic diagnosis of FH and their first-degree relatives

Exclusion Criteria:

  • Patient unwillingness

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02693548

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Contact: Pedro Mata, MD 0034915570071 pmata@colesterolfamiliar.org
Contact: Leopoldo Perez de Isla, MD 0034609084225 leopisla@hotmail.com

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Fundacion Hipercolesterolemia Familiar Recruiting
Madrid, Spain, 28010
Contact: Pedro Mata, MD    0034915 570 071    fhfsecretaria@colesterolfamiliar.org   
Contact: Leopoldo Perez de Isla, MD    0034609084225    leopisla@hotmail.com   
Sponsors and Collaborators
Fundación Hipercolesterolemia Familiar
Instituto de Salud Carlos III
Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
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Study Chair: Pedro Mata, MD Fundacion Hipercolesterolemia Familiar

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Fundación Hipercolesterolemia Familiar
ClinicalTrials.gov Identifier: NCT02693548    
Other Study ID Numbers: SAFEHEART
First Posted: February 26, 2016    Key Record Dates
Last Update Posted: February 15, 2023
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Available access for publication
Keywords provided by Fundación Hipercolesterolemia Familiar:
Familial Hypercholesterolaemia
Cardiovascular disease
Additional relevant MeSH terms:
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Hyperlipoproteinemia Type II
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn