The Spanish Familial Hypercholesterolaemia Cohort Study (SAFEHEART)

February 22, 2024 updated by: Fundación Hipercolesterolemia Familiar
SAFEHEART is a large, on-going registry study in molecularly defined patients with heterozygous FH treated in Spain.

Study Overview

Status

Recruiting

Conditions

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.

Study Type

Observational

Enrollment (Estimated)

4141

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years and older (Child, Adult, Older Adult)

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
up to 12 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
up to12 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundación Hipercolesterolemia Familiar

Collaborators

Instituto de Salud Carlos III
Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III

Investigators

  • Study Chair: Pedro Mata, MD, Fundacion Hipercolesterolemia Familiar

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2004

Primary Completion (Estimated)

October 1, 2030

Study Completion (Estimated)

October 1, 2030

Study Registration Dates

First Submitted

February 9, 2016

First Submitted That Met QC Criteria

February 23, 2016

First Posted (Estimated)

February 26, 2016

Study Record Updates

Last Update Posted (Estimated)

February 23, 2024

Last Update Submitted That Met QC Criteria

February 22, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SAFEHEART

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Available access for publication

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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