The Spanish Familial Hypercholesterolaemia Cohort Study

NCT02693548 | Recruiting DMC

• 1 other identifier: SAFEHEART
• Study Type: observational
• Target: 4,141
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Familial Hypercholesterolaemia

Keywords

Familial Hypercholesterolaemia; Prognosis; Cardiovascular disease

Outcome Measures

Primary Outcomes (1)

• Prognostic assessment: time to fatal or non-fatal cardiovascular event.

  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 Outcomes (1)

• LDL-cholesterol level (mg/dl) at entry and at follow-up

  up to12 years

Study Arms (2)

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)

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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

You may not qualify if:

• Patient unwillingness

Sponsors & Collaborators

• Fundación Hipercolesterolemia Familiar: lead
• Instituto de Salud Carlos III: collaborator
• Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III: collaborator

Study Sites (1)

Fundacion Hipercolesterolemia Familiar

Madrid, 28010, Spain

RECRUITING

Related Publications (29)

• Vallejo-Vaz AJ, Kondapally Seshasai SR, Cole D, Hovingh GK, Kastelein JJ, Mata P, Raal FJ, Santos RD, Soran H, Watts GF, Abifadel M, Aguilar-Salinas CA, Akram A, Alnouri F, Alonso R, Al-Rasadi K, Banach M, Bogsrud MP, Bourbon M, Bruckert E, Car J, Corral P, Descamps O, Dieplinger H, Durst R, Freiberger T, Gaspar IM, Genest J, Harada-Shiba M, Jiang L, Kayikcioglu M, Lam CS, Latkovskis G, Laufs U, Liberopoulos E, Nilsson L, Nordestgaard BG, O'Donoghue JM, Sahebkar A, Schunkert H, Shehab A, Stoll M, Su TC, Susekov A, Widen E, Catapano AL, Ray KK. Familial hypercholesterolaemia: A global call to arms. Atherosclerosis. 2015 Nov;243(1):257-9. doi: 10.1016/j.atherosclerosis.2015.09.021. Epub 2015 Sep 18. No abstract available.

  PMID: 26408930 BACKGROUND

• Fuentes F, Alcala-Diaz JF, Watts GF, Alonso R, Muniz O, Diaz-Diaz JL, Mata N, Sanchez Munoz-Torrero JF, Brea A, Galiana J, Figueras R, Aguado R, Piedecausa M, Cepeda JM, Vidal JI, Rodriguez-Cantalejo F, Lopez-Miranda J, Mata P; SAFEHEART Investigators. Statins do not increase the risk of developing type 2 diabetes in familial hypercholesterolemia: The SAFEHEART study. Int J Cardiol. 2015 Dec 15;201:79-84. doi: 10.1016/j.ijcard.2015.07.107. Epub 2015 Aug 5.

  PMID: 26296047 BACKGROUND

• Alonso R, Andres E, Mata N, Fuentes-Jimenez F, Badimon L, Lopez-Miranda J, Padro T, Muniz O, Diaz-Diaz JL, Mauri M, Ordovas JM, Mata P; SAFEHEART Investigators. Lipoprotein(a) levels in familial hypercholesterolemia: an important predictor of cardiovascular disease independent of the type of LDL receptor mutation. J Am Coll Cardiol. 2014 May 20;63(19):1982-9. doi: 10.1016/j.jacc.2014.01.063. Epub 2014 Mar 13.

  PMID: 24632281 BACKGROUND

• Alonso R, Mata P, Zambon D, Mata N, Fuentes-Jimenez F. Early diagnosis and treatment of familial hypercholesterolemia: improving patient outcomes. Expert Rev Cardiovasc Ther. 2013 Mar;11(3):327-42. doi: 10.1586/erc.13.7.

  PMID: 23469913 BACKGROUND

• Aledo R, Alonso R, Mata P, Llorente-Cortes V, Padro T, Badimon L. LRP1 gene polymorphisms are associated with premature risk of cardiovascular disease in patients with familial hypercholesterolemia. Rev Esp Cardiol (Engl Ed). 2012 Sep;65(9):807-12. doi: 10.1016/j.recesp.2012.03.013. Epub 2012 Jul 20. English, Spanish.

  PMID: 22819221 BACKGROUND

• Vazquez C, Alonso R, Garriga M, de Cos A, de la Cruz JJ, Fuentes-Jimenez F, Salas-Salvado J, Mata P. Validation of a food frequency questionnaire in Spanish patients with familial hypercholesterolaemia. Nutr Metab Cardiovasc Dis. 2012 Oct;22(10):836-42. doi: 10.1016/j.numecd.2011.01.007. Epub 2011 Jun 23.

  PMID: 21703832 BACKGROUND

• Mata N, Alonso R, Badimon L, Padro T, Fuentes F, Muniz O, Perez-Jimenez F, Lopez-Miranda J, Diaz JL, Vidal JI, Barba A, Piedecausa M, Sanchez JF, Irigoyen L, Guallar E, Ordovas JM, Mata P. Clinical characteristics and evaluation of LDL-cholesterol treatment of the Spanish Familial Hypercholesterolemia Longitudinal Cohort Study (SAFEHEART). Lipids Health Dis. 2011 Jun 10;10:94. doi: 10.1186/1476-511X-10-94.

  PMID: 21663647 BACKGROUND

• Criado-Garcia J, Fuentes F, Cruz-Teno C, Garcia-Rios A, Jimenez-Morales A, Delgado-Lista J, Mata P, Alonso R, Lopez-Miranda J, Perez-Jimenez F; Spanish Group for the Study of Familiar Hypercholesterolemia. R353Q polymorphism in the factor VII gene and cardiovascular risk in Heterozygous Familial Hypercholesterolemia: a case-control study. Lipids Health Dis. 2011 Apr 9;10:50. doi: 10.1186/1476-511X-10-50.

  PMID: 21477332 BACKGROUND

• Garcia-Rios A, Perez-Martinez P, Mata P, Fuentes F, Lopez-Miranda J, Alonso R, Caballero J, Mata N, Perez-Jimenez F, Ordovas JM. Polymorphism at the TRIB1 gene modulates plasma lipid levels: insight from the Spanish familial hypercholesterolemia cohort study. Nutr Metab Cardiovasc Dis. 2011 Dec;21(12):957-63. doi: 10.1016/j.numecd.2010.04.002. Epub 2010 Aug 6.

  PMID: 20692138 BACKGROUND

• Zambon D, Quintana M, Mata P, Alonso R, Benavent J, Cruz-Sanchez F, Gich J, Pocovi M, Civeira F, Capurro S, Bachman D, Sambamurti K, Nicholas J, Pappolla MA. Higher incidence of mild cognitive impairment in familial hypercholesterolemia. Am J Med. 2010 Mar;123(3):267-74. doi: 10.1016/j.amjmed.2009.08.015.

  PMID: 20193836 BACKGROUND

• Garcia-Rios A, Perez-Martinez P, Fuentes F, Mata P, Lopez-Miranda J, Alonso R, Rodriguez F, Garcia-Olid A, Ruano J, Ordovas JM, Perez-Jimenez F. Genetic variations at ABCG5/G8 genes modulate plasma lipids concentrations in patients with familial hypercholesterolemia. Atherosclerosis. 2010 Jun;210(2):486-92. doi: 10.1016/j.atherosclerosis.2010.01.010. Epub 2010 Jan 22.

  PMID: 20172523 BACKGROUND

• Alonso R, Defesche JC, Tejedor D, Castillo S, Stef M, Mata N, Gomez-Enterria P, Martinez-Faedo C, Forga L, Mata P. Genetic diagnosis of familial hypercholesterolemia using a DNA-array based platform. Clin Biochem. 2009 Jun;42(9):899-903. doi: 10.1016/j.clinbiochem.2009.01.017. Epub 2009 Feb 6.

  PMID: 19318025 BACKGROUND

• Alonso R, Mata N, Castillo S, Fuentes F, Saenz P, Muniz O, Galiana J, Figueras R, Diaz JL, Gomez-Enterria P, Mauri M, Piedecausa M, Irigoyen L, Aguado R, Mata P; Spanish Familial Hypercholesterolaemia Group. Cardiovascular disease in familial hypercholesterolaemia: influence of low-density lipoprotein receptor mutation type and classic risk factors. Atherosclerosis. 2008 Oct;200(2):315-21. doi: 10.1016/j.atherosclerosis.2007.12.024. Epub 2008 Feb 20.

  PMID: 18243212 BACKGROUND

• Merino-Ibarra E, Castillo S, Mozas P, Cenarro A, Martorell E, Diaz JL, Suarez-Tembra M, Alonso R, Civeira F, Mata P, Pocovi M; Spanish Group of Familial Hypercholesterolemia. Screening of APOB gene mutations in subjects with clinical diagnosis of familial hypercholesterolemia. Hum Biol. 2005 Oct;77(5):663-73.

  PMID: 16596945 BACKGROUND

• Civeira F, Castillo S, Alonso R, Merino-Ibarra E, Cenarro A, Artied M, Martin-Fuentes P, Ros E, Pocovi M, Mata P; Spanish Familial Hypercholesterolemia Group. Tendon xanthomas in familial hypercholesterolemia are associated with cardiovascular risk independently of the low-density lipoprotein receptor gene mutation. Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1960-5. doi: 10.1161/01.ATV.0000177811.14176.2b. Epub 2005 Jul 14.

  PMID: 16020744 BACKGROUND

• Alonso R, Castillo S, Civeira F, Puzo J, de la Cruz JJ, Pocovi M, Mata P. [Heterozygous familial hypercholesterolemia in Spain. Description of 819 non related cases]. Med Clin (Barc). 2002 Apr 13;118(13):487-92. doi: 10.1016/s0025-7753(02)72428-7. Spanish.

  PMID: 11975885 BACKGROUND

• Castillo S, Tejedor D, Mozas P, Reyes G, Civeira F, Alonso R, Ros E, Pocovi M, Mata P. The apolipoprotein B R3500Q gene mutation in Spanish subjects with a clinical diagnosis of familial hypercholesterolemia. Atherosclerosis. 2002 Nov;165(1):127-35. doi: 10.1016/s0021-9150(02)00190-9.

  PMID: 12208478 BACKGROUND

• Alonso R, Mata P, De Andres R, Villacastin BP, Martinez-Gonzalez J, Badimon L. Sustained long-term improvement of arterial endothelial function in heterozygous familial hypercholesterolemia patients treated with simvastatin. Atherosclerosis. 2001 Aug;157(2):423-9. doi: 10.1016/s0021-9150(00)00733-4.

  PMID: 11472743 BACKGROUND

• de Isla LP, Vallejo-Vaz AJ, Watts GF, Muniz-Grijalvo O, Alonso R, Diaz-Diaz JL, Arroyo-Olivares R, Aguado R, Argueso R, Mauri M, Romero MJ, Alvarez-Banos P, Manas D, Cepeda JM, Gonzalez-Bustos P, Casanas M, Michan A, Munoz-Torrero JFS, Faedo C, Barba MA, Dieguez M, de Andres R, Hernandez AM, Gonzalez-Estrada A, Padro T, Fuentes F, Badimon L, Mata P; SAFEHEART Investigators. Long-term sex differences in atherosclerotic cardiovascular disease in individuals with heterozygous familial hypercholesterolaemia in Spain: a study using data from SAFEHEART, a nationwide, multicentre, prospective cohort study. Lancet Diabetes Endocrinol. 2024 Sep;12(9):643-652. doi: 10.1016/S2213-8587(24)00192-X. Epub 2024 Aug 1.

  PMID: 39098315 DERIVED

• Alonso R, Arroyo-Olivares R, Diaz-Diaz JL, Fuentes-Jimenez F, Arrieta F, de Andres R, Gonzalez-Bustos P, Argueso R, Martin-Ordiales M, Martinez-Faedo C, Illan F, Saenz P, Donate JM, Sanchez Munoz-Torrero JF, Martinez-Hervas S, Mata P. Improved lipid-lowering treatment and reduction in cardiovascular disease burden in homozygous familial hypercholesterolemia: The SAFEHEART follow-up study. Atherosclerosis. 2024 Jun;393:117516. doi: 10.1016/j.atherosclerosis.2024.117516. Epub 2024 Mar 16.

  PMID: 38523000 DERIVED

• Alonso R, Arroyo-Olivares R, Muniz-Grijalvo O, Diaz-Diaz JL, Munoz-Torrero JS, Romero MJ, de Andres R, Zambon D, Manas MD, Fuentes-Jimenez F, Aguado R, Alvarez-Banos P, Arrieta F, Gonzalez-Bustos P, Cepeda J, Martin-Ordiales M, Mosquera D, Michan A, de Isla LP, Argueso R, Mata P. Persistence with long-term PCSK9 inhibitor treatment and its effectiveness in familial hypercholesterolaemia: data from the SAFEHEART study. Eur J Prev Cardiol. 2023 Mar 1;30(4):320-328. doi: 10.1093/eurjpc/zwac277.

  PMID: 36416136 DERIVED

• Perez de Isla L, Watts GF, Muniz-Grijalvo O, Diaz-Diaz JL, Alonso R, Zambon D, Fuentes-Jimenez F, Mauri M, Padro T, Vidal-Pardo JI, Barba MA, Ruiz-Perez E, Michan A, Mediavilla JD, Hernandez AM, Romero-Jimenez MJ, Badimon L, Mata P; SAFEHEART Investigators. A resilient type of familial hypercholesterolaemia: case-control follow-up of genetically characterized older patients in the SAFEHEART cohort. Eur J Prev Cardiol. 2022 May 5;29(5):795-801. doi: 10.1093/eurjpc/zwab185.

  PMID: 34864959 DERIVED

• Perez de Isla L, Watts GF, Alonso R, Diaz-Diaz JL, Muniz-Grijalvo O, Zambon D, Fuentes F, de Andres R, Padro T, Lopez-Miranda J, Mata P. Lipoprotein(a), LDL-cholesterol, and hypertension: predictors of the need for aortic valve replacement in familial hypercholesterolaemia. Eur Heart J. 2021 Jun 7;42(22):2201-2211. doi: 10.1093/eurheartj/ehaa1066.

  PMID: 33437997 DERIVED

• Perez de Isla L, Alonso R, Gomez de Diego JJ, Muniz-Grijalvo O, Diaz-Diaz JL, Zambon D, Miramontes JP, Fuentes F, de Andres R, Werenitzky J, Padro T, Saltijeral A, Mata P; SAFEHEART investigators. Coronary plaque burden, plaque characterization and their prognostic implications in familial hypercholesterolemia: A computed tomographic angiography study. Atherosclerosis. 2021 Jan;317:52-58. doi: 10.1016/j.atherosclerosis.2020.11.012. Epub 2020 Nov 18.

  PMID: 33261814 DERIVED

• Perez de Isla L, Arroyo-Olivares R, Alonso R, Muniz-Grijalvo O, Diaz-Diaz JL, Zambon D, Fuentes F, Mata N, Piedecausa M, Manas MD, Sanchez Munoz-Torrero JF, Miramontes-Gonzalez JP, de Andres R, Mauri M, Aguado R, Brea A, Cepeda JM, Vidal-Pardo JI, Martinez-Faedo C, Barba MA, Argueso R, Ruiz-Perez E, Michan A, Arrieta F, Riestra Fernandez M, Perez L, Pinilla JM, Diaz-Soto G, Pinto X, Padro T, Badimon L, Mata P; SAFEHEART researchers. Incidence of cardiovascular events and changes in the estimated risk and treatment of familial hypercholesterolemia: the SAFEHEART registry. Rev Esp Cardiol (Engl Ed). 2020 Oct;73(10):828-834. doi: 10.1016/j.rec.2019.10.028. Epub 2020 Mar 20. English, Spanish.

  PMID: 32201274 DERIVED

• Perez de Isla L, Alonso R, Muniz-Grijalvo O, Diaz-Diaz JL, Zambon D, Miramontes JP, Fuentes F, Gomez de Diego JJ, Gonzalez-Estrada A, Mata N, Saltijeral A, Barreiro M, Tomas M, de Andres R, Argueso R, Serrano Gotarredona MP, Navarro Herrero S, Perea Palazon RJ, de Caralt TM, Suarez de Centi LA, Zhilina S, Espejo Perez S, Padro T, Mata P; SAFEHEART investigators. Coronary computed tomographic angiography findings and their therapeutic implications in asymptomatic patients with familial hypercholesterolemia. Lessons from the SAFEHEART study. J Clin Lipidol. 2018 Jul-Aug;12(4):948-957. doi: 10.1016/j.jacl.2018.04.003. Epub 2018 Apr 17.

  PMID: 29753733 DERIVED

• Lazaro P, Perez de Isla L, Watts GF, Alonso R, Norman R, Muniz O, Fuentes F, Mata N, Lopez-Miranda J, Gonzalez-Juanatey JR, Diaz-Diaz JL, Blasco AJ, Mata P. Cost-effectiveness of a cascade screening program for the early detection of familial hypercholesterolemia. J Clin Lipidol. 2017 Jan-Feb;11(1):260-271. doi: 10.1016/j.jacl.2017.01.002. Epub 2017 Jan 10.

  PMID: 28391894 DERIVED

• Perez de Isla L, Alonso R, Mata N, Fernandez-Perez C, Muniz O, Diaz-Diaz JL, Saltijeral A, Fuentes-Jimenez F, de Andres R, Zambon D, Piedecausa M, Cepeda JM, Mauri M, Galiana J, Brea A, Sanchez Munoz-Torrero JF, Padro T, Argueso R, Miramontes-Gonzalez JP, Badimon L, Santos RD, Watts GF, Mata P. Predicting Cardiovascular Events in Familial Hypercholesterolemia: The SAFEHEART Registry (Spanish Familial Hypercholesterolemia Cohort Study). Circulation. 2017 May 30;135(22):2133-2144. doi: 10.1161/CIRCULATIONAHA.116.024541. Epub 2017 Mar 8.

  PMID: 28275165 DERIVED

• Perez de Isla L, Alonso R, Mata N, Saltijeral A, Muniz O, Rubio-Marin P, Diaz-Diaz JL, Fuentes F, de Andres R, Zambon D, Galiana J, Piedecausa M, Aguado R, Mosquera D, Vidal JI, Ruiz E, Manjon L, Mauri M, Padro T, Miramontes JP, Mata P; SAFEHEART Investigators. Coronary Heart Disease, Peripheral Arterial Disease, and Stroke in Familial Hypercholesterolaemia: Insights From the SAFEHEART Registry (Spanish Familial Hypercholesterolaemia Cohort Study). Arterioscler Thromb Vasc Biol. 2016 Sep;36(9):2004-10. doi: 10.1161/ATVBAHA.116.307514. Epub 2016 Jul 21.

  PMID: 27444203 DERIVED

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

MeSH Terms

Conditions

Hyperlipoproteinemia Type II; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Pedro Mata, MD

  Fundacion Hipercolesterolemia Familiar

  STUDY CHAIR

Central Study Contacts

Pedro Mata, MD

CONTACT

0034915570071; pmata@colesterolfamiliar.org

Leopoldo Perez de Isla, MD

CONTACT

0034609084225; leopisla@hotmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2016
• First Posted: February 26, 2016
• Study Start: January 1, 2004
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2030
• Last Updated: February 28, 2025

Record last verified: 2025-02

Locations

ES (1)