The Spanish Familial Hypercholesterolaemia Cohort Study
The Spanish Familial Hypercholesterolaemia Cohort Study
SAFEHEART is a large, on-going registry study in molecularly defined patients with
 heterozygous FH treated in Spain.
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.
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