{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T12:53:23Z","timestamp":1783688003054,"version":"3.55.0"},"reference-count":32,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T00:00:00Z","timestamp":1633824000000},"content-version":"unspecified","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013374","name":"NIHR School for Primary Care Research","doi-asserted-by":"crossref","award":["FR12-332"],"award-info":[{"award-number":["FR12-332"]}],"id":[{"id":"10.13039\/501100013374","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Open Heart"],"accepted":{"date-parts":[[2021,9,7]]},"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Familial hypercholesterolaemia (FH) is a common inherited disorder causing premature coronary heart disease (CHD) and death. We have developed the novel Familial Hypercholesterolaemia Case Ascertainment Tool (FAMCAT 1) case-finding algorithm for application in primary care, to improve detection of FH. The performance of this algorithm was further improved by including personal history of premature CHD (FAMCAT 2 algorithm). This study has evaluated their performance, at 95% specificity, to detect genetically confirmed FH in the general population. We also compared these algorithms to established clinical case-finding criteria.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Prospective validation study, in 14 general practices, recruiting participants from the general adult population with cholesterol documented. For 260 participants with available health records, we determined possible FH cases based on FAMCAT thresholds, Dutch Lipid Clinic Network (DLCN) score, Simon-Broome criteria and recommended cholesterol thresholds (total cholesterol &gt;9.0 mmol\/L if \u226530 years or &gt;7.5 mmol\/L if &lt;30 years), using clinical data from electronic and manual extraction of patient records and family history questionnaires. The reference standard was genetic testing. We examined detection rate (DR), sensitivity and specificity for each case-finding criteria.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>At 95% specificity, FAMCAT 1 had a DR of 27.8% (95% CI 12.5% to 50.9%) with sensitivity of 31.2% (95% CI 11.0% to 58.7%); while FAMCAT 2 had a DR of 45.8% (95% CI 27.9% to 64.9%) with sensitivity of 68.8% (95% CI 41.3% to 89.0%). DLCN score \u22656 points yielded a DR of 35.3% (95% CI 17.3% to 58.7%) and sensitivity of 37.5% (95% CI 15.2% to 64.6%). Using recommended cholesterol thresholds resulted in DR of 28.0% (95% CI 14.3% to 47.6%) with sensitivity of 43.8% (95% CI 19.8% to 70.1%). Simon-Broome criteria had lower DR 11.3% (95% CI 6.0% to 20.0%) and specificity 70.9% (95% CI 64.8% to 76.5%) but higher sensitivity of 56.3% (95% CI 29.9% to 80.2%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In primary care, in patients with cholesterol documented, FAMCAT 2 performs better than other case-finding criteria for detecting genetically confirmed FH, with no prior clinical review required for case finding.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03934320\">NCT03934320<\/jats:ext-link>.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/openhrt-2021-001752","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T15:25:13Z","timestamp":1633965913000},"page":"e001752","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Comparing the performance of the novel FAMCAT algorithms and established case-finding criteria for familial hypercholesterolaemia in primary care"],"prefix":"10.1136","volume":"8","clinical-trial-number":[{"clinical-trial-number":"nct03934320","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03934320","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4909-0644","authenticated-orcid":false,"given":"Nadeem","family":"Qureshi","sequence":"first","affiliation":[{"name":"Primary Care Stratified Medicine (PRISM) Research Group, School of Medicine, University of Nottingham, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4529-8237","authenticated-orcid":false,"given":"Ralph K","family":"Akyea","sequence":"additional","affiliation":[{"name":"Primary Care Stratified Medicine (PRISM) Research Group, School of Medicine, University of Nottingham, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5146-4911","authenticated-orcid":false,"given":"Brittany","family":"Dutton","sequence":"additional","affiliation":[{"name":"Primary Care Stratified Medicine (PRISM) Research Group, School of Medicine, University of Nottingham, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo","family":"Leonardi-Bee","sequence":"additional","affiliation":[{"name":"Primary Care Stratified Medicine (PRISM) Research Group, School of Medicine, University of Nottingham, Nottingham, UK"},{"name":"Centre for Evidence Based Healthcare, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve E","family":"Humphries","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5281-9590","authenticated-orcid":false,"given":"Stephen","family":"Weng","sequence":"additional","affiliation":[{"name":"Cardiovascular and Metabolism, Janssen Research & Development, High Wycombe, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9040-9384","authenticated-orcid":false,"given":"Joe","family":"Kai","sequence":"additional","affiliation":[{"name":"Primary Care Stratified Medicine (PRISM) Research Group, School of Medicine, University of Nottingham, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"2025081709374035000_8.2.e001752.1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.303.6807.893"},{"key":"2025081709374035000_8.2.e001752.2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.atherosclerosis.2018.04.040","article-title":"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":"2025081709374035000_8.2.e001752.3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.atherosclerosis.2019.05.017","article-title":"Risk of cardiovascular disease outcomes in primary care subjects with familial hypercholesterolaemia: a cohort 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Familial hypercholesterolaemia: identification and management Clinical guideline [CG71]., 2017. Available: https:\/\/www.nice.org.uk\/guidance\/cg71 [Accessed 08 Aug 2021]."},{"key":"2025081709374035000_8.2.e001752.8","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.atherosclerosis.2019.08.014","article-title":"2019 ESC\/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk","volume":"290","year":"2019","journal-title":"Atherosclerosis"},{"key":"2025081709374035000_8.2.e001752.9","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000297"},{"key":"2025081709374035000_8.2.e001752.10","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2016-011734"},{"key":"2025081709374035000_8.2.e001752.11","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.118.011822","article-title":"Hidden burden of electronic health record-Identified familial hypercholesterolemia: clinical outcomes and cost of medical care","volume":"8","author":"Patel","year":"2019","journal-title":"J Am Heart Assoc"},{"key":"2025081709374035000_8.2.e001752.12","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.2147\/CLEP.S176853","article-title":"How well can familial hypercholesterolemia be identified in an electronic health record database?","volume":"10","author":"Mues","year":"2018","journal-title":"Clin Epidemiol"},{"key":"2025081709374035000_8.2.e001752.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.hlc.2016.09.012"},{"key":"2025081709374035000_8.2.e001752.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2014.12.034"},{"key":"2025081709374035000_8.2.e001752.15","doi-asserted-by":"crossref","first-page":"e256","DOI":"10.1016\/S2468-2667(19)30061-1","article-title":"Detection of familial hypercholesterolaemia: external validation of the FAMCAT clinical case-finding algorithm to identify patients in primary care","volume":"4","author":"Weng","year":"2019","journal-title":"Lancet Public Health"},{"key":"2025081709374035000_8.2.e001752.16","doi-asserted-by":"publisher","DOI":"10.3399\/bjgpopen20X101114"},{"key":"2025081709374035000_8.2.e001752.17","unstructured":"PRIMIS . Familial hypercholesterolaemia quality improvement tool. Available: https:\/\/www.nottingham.ac.uk\/primis\/documents\/quickguides\/fh-quickguide-2019-nb-v1.0.pdf [Accessed 02 Aug 2021]."},{"key":"2025081709374035000_8.2.e001752.18","doi-asserted-by":"publisher","DOI":"10.1093\/fampra\/cmi073"},{"key":"2025081709374035000_8.2.e001752.19","doi-asserted-by":"publisher","DOI":"10.1214\/ss\/1009213286"},{"key":"2025081709374035000_8.2.e001752.20","article-title":"Improving detection and management of familial hypercholesterolaemia in Australian general practice","author":"Brett","year":"2021","journal-title":"Heart"},{"key":"2025081709374035000_8.2.e001752.21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2009.01356.x"},{"key":"2025081709374035000_8.2.e001752.22","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2012-302917"},{"key":"2025081709374035000_8.2.e001752.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2004.12.001"},{"key":"2025081709374035000_8.2.e001752.24","doi-asserted-by":"crossref","DOI":"10.3390\/jpm11040302","article-title":"Systematic identification of familial hypercholesterolaemia in primary care\u2014a systematic review","volume":"11","author":"Silva","year":"2021","journal-title":"J Pers Med"},{"key":"2025081709374035000_8.2.e001752.25","doi-asserted-by":"publisher","DOI":"10.1111\/jep.12481"},{"key":"2025081709374035000_8.2.e001752.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.hlc.2014.09.011"},{"key":"2025081709374035000_8.2.e001752.27","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":"2025081709374035000_8.2.e001752.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosissup.2011.06.001"},{"key":"2025081709374035000_8.2.e001752.29","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2021-319266"},{"key":"2025081709374035000_8.2.e001752.30","article-title":"Application of a risk stratification tool for familial hypercholesterolaemia in primary care: an observational cross-sectional study in an unselected urban population","author":"Carvalho","year":"2021","journal-title":"Heart"},{"key":"2025081709374035000_8.2.e001752.31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0081998"},{"key":"2025081709374035000_8.2.e001752.32","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-156-4-201202210-00002"}],"container-title":["Open Heart"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/openhrt-2021-001752","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,17]],"date-time":"2025-08-17T16:37:48Z","timestamp":1755448668000},"score":1,"resource":{"primary":{"URL":"https:\/\/openheart.bmj.com\/lookup\/doi\/10.1136\/openhrt-2021-001752"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":32,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,10,11]]},"published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1136\/openhrt-2021-001752"],"URL":"https:\/\/doi.org\/10.1136\/openhrt-2021-001752","relation":{},"ISSN":["2053-3624"],"issn-type":[{"value":"2053-3624","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10]]}}}