{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T14:07:55Z","timestamp":1777039675460,"version":"3.51.4"},"reference-count":57,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,29]],"date-time":"2023-01-29T00:00:00Z","timestamp":1674950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III (ISCIII)","award":["PI22\/00705"],"award-info":[{"award-number":["PI22\/00705"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Familial hypercholesterolemia (FH) is the most common genetic disorder associated with premature atherosclerotic cardiovascular (CV) disease (ASCVD). However, it still is severely underdiagnosed. Initiating lipid-lowering therapy (LLT) in FH patients early in life can substantially reduce their ASCVD risk. As a result, identifying FH is of the utmost importance. The increasing availability of genetic testing may be useful in this regard. We aimed to evaluate the genetic profiles, clinical characteristics, and gender differences between the first consecutive patients referred for genetic testing with FH clinical suspicion in our institution (a Spanish cohort). Clinical information was reviewed, and all participants were sequenced for the main known genes related to FH: LDLR, APOB, PCSK9 (heterozygous FH), LDLRAP1 (autosomal recessive FH), and two other genes related to hyperlipidaemia (APOE and LIPA). The genetic yield was 32%. Their highest recorded LDLc levels were 294 \u00b1 65 SD mg. However, most patients (79%) were under &gt; 1 LLT medication, and their last mean LDLc levels were 135 \u00b1 51 SD. LDLR c.2389+4A&gt;G was one of the most frequent pathogenic\/likely pathogenic variants and its carriers had significantly worse LDLc highest recorded levels (348 \u00b1 61 SD vs. 282 \u00b1 60 SD mg\/dL, p = 0.002). Moreover, we identified an homozygous carrier of the pathogenic variant LDLRAP1 c.207delC (autosomal recessive FH). Both clinical and genetic hypercholesterolemia diagnosis was significantly established earlier in men than in women (25 years old \u00b1 15 SD vs. 35 years old \u00b1 19 SD, p = 0.02; and 43 \u00b1 17 SD vs. 54 \u00b1 19 SD, p = 0.02, respectively). Other important CV risk factors were found in 44% of the cohort. The prevalence of family history of premature ASCVD was high, whereas personal history was exceptional. Our finding reaffirms the importance of early detection of FH to initiate primary prevention strategies from a young age. Genetic testing can be very useful. As it enables familial cascade genetic testing, early prevention strategies can be extended to all available relatives at concealed high CV risk.<\/jats:p>","DOI":"10.3390\/jcm12031030","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T01:33:37Z","timestamp":1675042417000},"page":"1030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinical Evaluation of Patients with Genetically Confirmed Familial Hypercholesterolemia"],"prefix":"10.3390","volume":"12","author":[{"given":"Andrea","family":"Aparicio","sequence":"first","affiliation":[{"name":"\u00c1rea del Coraz\u00f3n, Hospital Universitario Central Asturias (HUCA), 33011 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Villaz\u00f3n","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda y Nutrici\u00f3n, Hospital Universitario Central Asturias (HUCA), 33011 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorena","family":"Su\u00e1rez-Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda y Nutrici\u00f3n, Hospital Universitario Central Asturias (HUCA), 33011 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3318-4649","authenticated-orcid":false,"given":"Juan","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain"},{"name":"Departamento de Gen\u00e9tica Molecular, Hospital Universitario Central Asturias (HUCA), 33011 Oviedo, Spain"},{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORs), 28029 Madrid, Spain"},{"name":"Unidad de Cardiopat\u00edas Familiares, Hospital Universitario Central Asturias (HUCA), 33011 Oviedo, Spain"},{"name":"CIBER-Enfermedades Respiratorias, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ceferino","family":"Mart\u00ednez-Faedo","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda y Nutrici\u00f3n, Hospital Universitario Central Asturias (HUCA), 33011 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edelmiro","family":"M\u00e9ndez-Torre","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda y Nutrici\u00f3n, Hospital Universitario Central Asturias (HUCA), 33011 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4958-6108","authenticated-orcid":false,"given":"Pablo","family":"Avanzas","sequence":"additional","affiliation":[{"name":"\u00c1rea del Coraz\u00f3n, Hospital Universitario Central Asturias (HUCA), 33011 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain"},{"name":"Medicine Department, Universidad de Oviedo, 33003 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2837-7374","authenticated-orcid":false,"given":"Rut","family":"\u00c1lvarez-Velasco","sequence":"additional","affiliation":[{"name":"\u00c1rea del Coraz\u00f3n, Hospital Universitario Central Asturias (HUCA), 33011 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0924-0962","authenticated-orcid":false,"given":"El\u00edas","family":"Cuesta-Llavona","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain"},{"name":"Departamento de Gen\u00e9tica Molecular, Hospital Universitario Central Asturias (HUCA), 33011 Oviedo, Spain"},{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORs), 28029 Madrid, Spain"},{"name":"Unidad de Cardiopat\u00edas Familiares, Hospital Universitario Central Asturias (HUCA), 33011 Oviedo, Spain"},{"name":"CIBER-Enfermedades Respiratorias, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Garc\u00eda-Lago","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain"},{"name":"Departamento de Gen\u00e9tica Molecular, Hospital Universitario Central Asturias (HUCA), 33011 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Neuhalfen","sequence":"additional","affiliation":[{"name":"Medicine Department, Universidad de Oviedo, 33003 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8649-9150","authenticated-orcid":false,"given":"Eliecer","family":"Coto","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain"},{"name":"Departamento de Gen\u00e9tica Molecular, Hospital Universitario Central Asturias (HUCA), 33011 Oviedo, Spain"},{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORs), 28029 Madrid, Spain"},{"name":"Unidad de Cardiopat\u00edas Familiares, Hospital Universitario Central Asturias (HUCA), 33011 Oviedo, Spain"},{"name":"CIBER-Enfermedades Respiratorias, 28029 Madrid, Spain"},{"name":"Medicine Department, Universidad de Oviedo, 33003 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7803-4011","authenticated-orcid":false,"given":"Rebeca","family":"Lorca","sequence":"additional","affiliation":[{"name":"\u00c1rea del Coraz\u00f3n, Hospital Universitario Central Asturias (HUCA), 33011 Oviedo, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain"},{"name":"Unidad de Cardiopat\u00edas Familiares, Hospital Universitario Central Asturias (HUCA), 33011 Oviedo, Spain"},{"name":"CIBER-Enfermedades Respiratorias, 28029 Madrid, Spain"},{"name":"Medicine Department, Universidad de Oviedo, 33003 Oviedo, Spain"},{"name":"Departamento de Morfolog\u00eda y Biolog\u00eda Celular, Universidad de Oviedo, 33003 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.1093\/eurheartj\/ehab484","article-title":"2021 ESC Guidelines on cardiovascular disease prevention in clinical practice","volume":"42","author":"Visseren","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1093\/eurheartj\/ehx144","article-title":"Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel","volume":"38","author":"Ference","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Cholesterol Treatment Trialists\u2019 (CTT) Collaborators, Mihaylova, B., Emberson, J., Blackwell, L., Keech, A., Simes, J., Barnes, E.H., Voysey, M., Gray, A., and Collins, R. (2012). The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: Meta-analysis of individual data from 27 randomised trials. Lancet, 380, 581\u2013590.","DOI":"10.1016\/S0140-6736(12)60367-5"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"a2423","DOI":"10.1136\/bmj.a2423","article-title":"Efficacy of statins in familial hypercholesterolaemia: A long term cohort study","volume":"337","author":"Versmissen","year":"2008","journal-title":"BMJ"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1093\/eurheartj\/ehn422","article-title":"Reductions in all-cause, cancer, and coronary mortality in statin-treated patients with heterozygous familial hypercholesterolaemia: A prospective registry study","volume":"29","author":"Neil","year":"2008","journal-title":"Eur. Heart J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1161\/CIRCULATIONAHA.115.018791","article-title":"Prevalence of Familial Hypercholesterolemia in the 1999 to 2012 United States National Health and Nutrition Examination Surveys (NHANES)","volume":"133","author":"Rodday","year":"2016","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1055\/s-2004-822987","article-title":"Advanced method for the identification of patients with inherited hypercholesterolemia","volume":"4","author":"Defesche","year":"2004","journal-title":"Semin. Vasc. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/0002-9149(93)90155-6","article-title":"Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics","volume":"72","author":"Williams","year":"1993","journal-title":"Am. J. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Scientific Steering Committee on behalf of the Simon Broome Register Group (1991). Risk of fatal coronary heart disease in familial hypercholesterolaemia. BMJ, 303, 893\u2013896.","DOI":"10.1136\/bmj.303.6807.893"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.jacc.2018.05.044","article-title":"Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel","volume":"72","author":"Sturm","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1097\/MOL.0b013e32830636e5","article-title":"What is the clinical utility of DNA testing in patients with familial hypercholesterolaemia?","volume":"19","author":"Humphries","year":"2008","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ijcard.2013.11.025","article-title":"Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation","volume":"171","author":"Watts","year":"2014","journal-title":"Int. J. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/j.jacc.2016.01.008","article-title":"Attainment of LDL-Cholesterol Treatment Goals in Patients With Familial Hypercholesterolemia: 5-Year SAFEHEART Registry Follow-Up","volume":"67","author":"Alonso","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1093\/eurheartj\/ehu058","article-title":"Homozygous autosomal dominant hypercholesterolaemia in the Netherlands: Prevalence, genotype-phenotype relationship, and clinical outcome","volume":"36","author":"Sjouke","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1172\/JCI107332","article-title":"Hyperlipidemia in coronary heart disease. II. Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia","volume":"52","author":"Goldstein","year":"1973","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s12687-018-0383-3","article-title":"Barriers to the identification of familial hypercholesterolemia among primary care providers","volume":"10","author":"Zimmerman","year":"2019","journal-title":"J. Community Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1093\/nar\/16.3.1215","article-title":"A simple salting out procedure for extracting DNA from human nucleated cells","volume":"16","author":"Miller","year":"1988","journal-title":"Nucl. Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2963","DOI":"10.1253\/circj.CJ-14-0628","article-title":"Mutation Analysis of the Main Hypertrophic Cardiomyopathy Genes Using Multiplex Amplification and Semiconductor Next-Generation Sequencing","volume":"78","author":"Reguero","year":"2014","journal-title":"Circ. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e001584","DOI":"10.1161\/CIRCGENETICS.116.001584","article-title":"Screening of the Filamin C Gene in a Large Cohort of Hypertrophic Cardiomyopathy Patients","volume":"10","author":"Lorca","year":"2017","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lorca, R., Aparicio, A., Cuesta-Llavona, E., Pascual, I., Junco, A., Hevia, S., Villaz\u00f3n, F., Hernandez-Vaquero, D., Rodr\u00edguez Reguero, J.J., and Moris, C. (2020). Familial Hypercholesterolemia in Premature Acute Coronary Syndrome. Insights from CholeSTEMI Registry. J. Clin. Med., 9.","DOI":"10.3390\/jcm9113489"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lorca, R., Junco-Vicente, A., P\u00e9rez-P\u00e9rez, A., Pascual, I., Persia-Paulino, Y.R., Gonz\u00e1lez-Urbistondo, F., Cuesta-Llavona, E., Fern\u00e1ndez-Barrio, B.C., Mor\u00eds, C., and Rub\u00edn, J.M. (2022). KCNH2 p.Gly262AlafsTer98: A New Threatening Variant Associated with Long QT Syndrome in a Spanish Cohort. Life, 12.","DOI":"10.3390\/life12040556"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1002\/humu.20105","article-title":"LDL-receptor mutations in Europe","volume":"24","author":"Dedoussis","year":"2004","journal-title":"Hum. Mutat."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1136\/jmedgenet-2016-104054","article-title":"The UCL low-density lipoprotein receptor gene variant database: Pathogenicity update","volume":"54","author":"Leigh","year":"2017","journal-title":"J. Med. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1080\/14737159.2017.1332997","article-title":"Recent advances in genetic testing for familial hypercholesterolemia","volume":"17","author":"Iacocca","year":"2017","journal-title":"Expert. Rev. Mol. Diagn."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1111\/j.1399-0004.2009.01356.x","article-title":"Mutation detection rate and spectrum in familial hypercholesterolaemia patients in the UK pilot cascade project","volume":"77","author":"Taylor","year":"2010","journal-title":"Clin. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1136\/jmg.2006.038356","article-title":"Genetic causes of familial hypercholesterolaemia in patients in the UK: Relation to plasma lipid levels and coronary heart disease risk","volume":"43","author":"Humphries","year":"2006","journal-title":"J. Med. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1038\/ejhg.2013.271","article-title":"Clinical utility gene card for: Hyperlipoproteinemia, TYPE II","volume":"22","author":"Kassner","year":"2014","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1161\/CIRCGENETICS.115.001129","article-title":"Characterization of Autosomal Dominant Hypercholesterolemia Caused by PCSK9 Gain of Function Mutations and Its Specific Treatment With Alirocumab, a PCSK9 Monoclonal Antibody","volume":"8","author":"Hopkins","year":"2015","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1161\/01.ATV.0000190668.94752.ab","article-title":"Severe hypercholesterolemia in four British families with the D374Y mutation in the PCSK9 gene: Long-term follow-up and treatment response","volume":"25","author":"Naoumova","year":"2005","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1006\/geno.1997.4898","article-title":"Estimation of the age of the ancestral arginine3500-->glutamine mutation in human apoB-100","volume":"45","author":"Myant","year":"1997","journal-title":"Genomics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1016\/j.jacl.2016.09.009","article-title":"Familial defective apolipoprotein B-100: A review","volume":"10","author":"Andersen","year":"2016","journal-title":"J. Clin. Lipidol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1093\/eurheartj\/ehs010","article-title":"Advances in genetics show the need for extending screening strategies for autosomal dominant hypercholesterolaemia","volume":"33","author":"Motazacker","year":"2012","journal-title":"Eur. Heart J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/mgg3.17","article-title":"Identification and biochemical analysis of a novel APOB mutation that causes autosomal dominant hypercholesterolemia","volume":"1","author":"Thomas","year":"2013","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1172\/JCI117772","article-title":"Familial ligand-defective apolipoprotein B. Identification of a new mutation that decreases LDL receptor binding affinity","volume":"95","author":"Pullinger","year":"1995","journal-title":"J. Clin. Investig."},{"key":"ref_36","first-page":"E76","article-title":"R3531C mutation in the apolipoprotein B gene is not sufficient to cause hypercholesterolemia","volume":"20","author":"Varret","year":"2000","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1056\/NEJM199805283382203","article-title":"Association of mutations in the apolipoprotein B gene with hypercholesterolemia and the risk of ischemic heart disease","volume":"338","author":"Steffensen","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1161\/CIRCGENETICS.116.001381","article-title":"Treatment Gaps in Adults With Heterozygous Familial Hypercholesterolemia in the United States: Data from the CASCADE-FH Registry","volume":"9","author":"deGoma","year":"2016","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.atherosclerosis.2020.10.895","article-title":"Sex differences in cardiovascular morbidity associated with familial hypercholesterolaemia: A retrospective cohort study of the UK Simon Broome register linked to national hospital records","volume":"315","author":"Iyen","year":"2020","journal-title":"Atherosclerosis"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1016\/j.jacc.2017.08.009","article-title":"Genetically Confirmed Familial Hypercholesterolemia in Patients with Acute Coronary Syndrome","volume":"70","author":"Castillo","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.atherosclerosis.2017.06.917","article-title":"Evaluation of clinical and laboratory parameters used in the identification of index cases for genetic screening of familial hypercholesterolemia in Brazil","volume":"263","author":"Silva","year":"2017","journal-title":"Atherosclerosis"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.atherosclerosis.2015.03.003","article-title":"Clinical experience of scoring criteria for Familial Hypercholesterolaemia (FH) genetic testing in Wales","volume":"240","author":"Haralambos","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1016\/j.jacc.2016.03.520","article-title":"Diagnostic Yield and Clinical Utility of Sequencing Familial Hypercholesterolemia Genes in Patients With Severe Hypercholesterolemia","volume":"67","author":"Khera","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1161\/CIRCULATIONAHA.111.042523","article-title":"Reduction in mortality in subjects with homozygous familial hypercholesterolemia associated with advances in lipid-lowering therapy","volume":"124","author":"Raal","year":"2011","journal-title":"Circulation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1016\/S0140-6736(69)90930-1","article-title":"Risks of ischaemic heart-disease in familial hyperlipoproteinaemic states","volume":"2","author":"Slack","year":"1969","journal-title":"Lancet"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0021-9150(02)00330-1","article-title":"A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia","volume":"168","author":"Marks","year":"2003","journal-title":"Atherosclerosis"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.atherosclerosis.2018.04.040","article-title":"Simon Broome Familial Hyperlipidaemia Register Group Coronary heart disease mortality in treated familial hypercholesterolaemia: Update of the UK Simon Broome FH register","volume":"274","author":"Humphries","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.jacl.2017.05.012","article-title":"Familial hypercholesterolemia in a European Mediterranean population-Prevalence and clinical data from 2.5 million primary care patients","volume":"11","author":"Zamora","year":"2017","journal-title":"J. Clin. Lipidol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.atherosclerosis.2017.10.006","article-title":"Health disparities among adult patients with a phenotypic diagnosis of familial hypercholesterolemia in the CASCADE-FHTM patient registry","volume":"267","author":"Amrock","year":"2017","journal-title":"Atherosclerosis"},{"key":"ref_50","first-page":"123","article-title":"Time trends in the prescription of statins for the primary prevention of cardiovascular disease in the United Kingdom: A cohort study using The Health Improvement Network primary care data","volume":"8","author":"Nazareth","year":"2016","journal-title":"Clin. Epidemiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1007\/s12471-010-0841-y","article-title":"Gender differences in coronary heart disease","volume":"18","author":"Maas","year":"2010","journal-title":"Neth. Heart J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1002\/clc.22767","article-title":"Comprehensive primary prevention of cardiovascular disease in women","volume":"40","author":"Lee","year":"2017","journal-title":"Clin. Cardiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1161\/CIR.0000000000000297","article-title":"The Agenda for Familial Hypercholesterolemia: A Scientific Statement From the American Heart Association","volume":"132","author":"Gidding","year":"2015","journal-title":"Circulation"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"S46","DOI":"10.1016\/j.jacl.2011.04.002","article-title":"Future issues, public policy, and public awareness of familial hypercholesterolemias: Recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia","volume":"5","author":"Goldberg","year":"2011","journal-title":"J. Clin. Lipidol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.atherosclerosis.2018.08.019","article-title":"Screening for familial hypercholesterolaemia in primary care: Time for general practice to play its part","volume":"277","author":"Brett","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1056\/NEJMoa1602777","article-title":"Child-Parent Familial Hypercholesterolemia Screening in Primary Care","volume":"375","author":"Wald","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1016\/j.jacc.2020.03.057","article-title":"Worldwide Prevalence of Familial Hypercholesterolemia: Meta-Analyses of 11 Million Subjects","volume":"75","author":"Beheshti","year":"2020","journal-title":"J. Am. Coll. 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