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This systematic review will investigate the risk factors that predict cardiovascular events in patients with a genetic diagnosis of heFH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and analysis<\/jats:title><jats:p>Our literature search will cover publications from database inception until June 2023. We will undertake a search of CINAHL (trial), clinicalKey, Cochrane Library, DynaMed, Embase, Espacenet, Experiments (trial), Fisterra, \u00cdnDICEs CSIC, LILACS, LISTA, Medline, Micromedex, NEJM Resident 360, OpenDissertations, PEDro, Trip Database, PubPsych, Scopus, TESEO, UpToDate, Web of Science and the grey literature for eligible studies. We will screen the title, abstract and full-text papers for potential inclusion and assess the risk of bias. We will employ the Cochrane tool for randomised controlled trials and non-randomised clinical studies and the Newcastle\u2013Ottawa Scale for assessing the risk of bias in observational studies. We will include full-text peer-reviewed publications, reports of a cohort\/registry, case\u2013control and cross-sectional studies, case report\/series and surveys related to adults (\u226518 years of age) with a genetic diagnostic heFH. The language of the searched studies will be restricted to English or Spanish. The Grading of Recommendations, Assessment, Development and Evaluation approach will be used to assess the quality of the evidence. Based on the data available, the authors will determine whether the data can be pooled in meta-analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Ethics and dissemination<\/jats:title><jats:p>All data will be extracted from published literature. Hence, ethical approval and patient informed consent are not required. The findings of the systematic review will be submitted for publication in a peer-reviewed journal and presentation at international conferences.<\/jats:p><\/jats:sec><jats:sec><jats:title>PROSPERO registration number<\/jats:title><jats:p>CRD42022304273.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bmjopen-2022-065551","type":"journal-article","created":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T17:22:28Z","timestamp":1680110548000},"page":"e065551","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Risk factors for cardiovascular events in patients with heterozygous familial hypercholesterolaemia: protocol for a systematic review"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9283-9572","authenticated-orcid":false,"given":"Mar\u00eda Elena","family":"Mansilla-Rodr\u00edguez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel J","family":"Romero-Jimenez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina","family":"Rigabert S\u00e1nchez-Junco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva Nadiedja","family":"Gutierrez-Cortizo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Luis","family":"S\u00e1nchez-Ramos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Mata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9700-6948","authenticated-orcid":false,"given":"Jing","family":"Pang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerald F","family":"Watts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2023,3,29]]},"reference":[{"key":"2023032910151329000_13.3.e065551.1","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/s41569-019-0325-8","article-title":"Familial hypercholesterolaemia: evolving knowledge for designing adaptive models of care","volume":"17","author":"Watts","year":"2020","journal-title":"Nat Rev Cardiol"},{"key":"2023032910151329000_13.3.e065551.2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.044795"},{"key":"2023032910151329000_13.3.e065551.3","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":"2023032910151329000_13.3.e065551.4","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.1161\/01.ATV.17.11.3127","article-title":"Familial hypercholesterolemia in the Finnish North Karelia","volume":"17","author":"Vuorio","year":"1997","journal-title":"ATVB"},{"key":"2023032910151329000_13.3.e065551.5","first-page":"129","article-title":"Familial hypercholesterolemia in childhood and adolescents: a hidden reality","volume":"29","author":"Plana","year":"2017","journal-title":"Cl\u00ednica e Investig En Arterioscler (English Edition)"},{"key":"2023032910151329000_13.3.e065551.6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41569-018-0052-6","article-title":"The complex molecular genetics of familial hypercholesterolaemia","volume":"16","author":"Berberich","year":"2019","journal-title":"Nat Rev Cardiol"},{"key":"2023032910151329000_13.3.e065551.7","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.atherosclerosis.2019.11.028","article-title":"Reaching detection targets in familial hypercholesterolaemia: comparison of identification strategies","volume":"293","author":"Wald","year":"2020","journal-title":"Atherosclerosis"},{"key":"2023032910151329000_13.3.e065551.8","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.atherosclerosissup.2017.07.002","article-title":"Spectrum of mutations in italian patients with familial hypercholesterolemia: new results from the LIPIGEN study","volume":"29","author":"Pirillo","year":"2017","journal-title":"Atheroscler Suppl"},{"key":"2023032910151329000_13.3.e065551.9","doi-asserted-by":"publisher","DOI":"10.1126\/science.1060458"},{"key":"2023032910151329000_13.3.e065551.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.05.044"},{"key":"2023032910151329000_13.3.e065551.11","unstructured":"National Institute for Health and Care Excellence . 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