[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-441092-105":59,"doc-detail-441092-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","missed-and-misdiagnosed-precision-medicine-approaches-to-screening-for-familial-hypercholesterolemia-and-lipoproteina","Missed and Misdiagnosed Precision Medicine Approaches to Screening for Familial Hypercholesterolemia and Lipoprotein(a)","","Precision medicine screening for familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] is challenged by overlapping clinical presentations and shared standard risk factors, including elevated LDL-C, premature ASCVD, and family history. This brief report evaluates how Dutch Lipid Clinic Network (DLCN) criteria and LDL-C-based clinical signals perform against genetically confirmed diagnoses. It demonstrates that LDL-C and personal/family premature ASCVD fail to distinguish genetically confirmed FH, elevated Lp(a), and combined FH + elevated Lp(a).",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/missed-and-misdiagnosed-precision-medicine-approaches-to-screening-for-familial-hypercholesterolemia-and-lipoproteina/441092/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/missed-and-misdiagnosed-precision-medicine-approaches-to-screening-for-familial-hypercholesterolemia-and-lipoproteina/441092.png","ImageObject",300,407,{"name":92,"@type":93},"Asher","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",14,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why are FH and elevated Lp(a) difficult to screen using standard clinical risk factors?","Question",{"text":113,"@type":114},"FH and elevated Lp(a) can present similarly, and elevated LDL-C, premature ASCVD, and family history may not reliably separate genetically confirmed conditions.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What does the study find as the main result?",{"text":118,"@type":114},"LDL-C and personal or family history of premature ASCVD do not distinguish between genetically confirmed FH, elevated Lp(a), and combined FH + elevated Lp(a).",{"name":120,"@type":111,"acceptedAnswer":121},"How were genetic outcomes and Lp(a) used in the diagnostic classification?",{"text":122,"@type":114},"The study assigned mutually exclusive genetic outcomes as FH, elevated Lp(a), FH + elevated Lp(a), or nondiagnostic, and defined elevated Lp(a) using thresholds stratified for analysis to reflect how Lp(a) affects measured LDL-C and DLCN classification.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},441092,1790762309,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":81,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":39,"preview_page_count":4},687197207639,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","JA CC: ADVANCES VOL . 5, NO . 1, 2026  \n© 2026 THE AUTHORS . PUBLISHED BY ELSE VIE R ON BEHALF OF THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION . THIS IS AN OPEN ACCESS ARTICLE UNDER THE CC BY-NC-ND LICENSE ( [http://creative commons . org/licenses/by-nc-nd/4 . 0/](http://creative commons . org/licenses/by-nc-nd/4 . 0/) ) .  \nBRIEF REPORT  \nMissed and Misdiagnosed Precision Medicine Approaches to Screening for Familial Hypercholesterolemia and Lipoprotein(a)  \nBenjamin M. Helm, PHD, MS, CGC,a,b Victor Huerta, MS, CGC,b Julie M. Clary, MD, MBAa,b  \nF  \namilial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] are the most common monogenic dyslipidemias and can  \npresent similarly. Standard risk factors—elevated low-density lipoprotein cholesterol (LDL-C), premature atherosclerotic cardiovascular disease (ASCVD), and family history—may fail to distinguish them. Accurate diagnosis is vital for risk stratification and treatment in individuals, as genetically confirmed FH and elevated Lp(a) independently predict increased ASCVD risk, regardless of LDL-C and other biomarkers.1 ,2 Few studies have assessed commonly used FH clinical diagnostic criteria, like the Dutch Lipid Clinic Network (DLCN) framework, against gold standard genetic diagnosis. The DLCN criteria use a summed score based on clinical presentation, family history, and genetic findings. Scores >8 establish a clinical diagnosis of definite FH, while scores of 0 − 2, 3 − 5, and 6 − 8 represent unlikely, possible, and probable FH, respectively. Although often used for screening, these criteria underperform for definite  \nFH established by genetic testing, and elevated Lp(a) further confounds accurate FH diagnosis.3  \nCLINIC APPROACH AND STUDY AIMS  \nIn our Advanced Lipid Clinic, we target patients with DLCN scores $3 (possible FH) without obvious nongenetic causes of high LDL-C for standardized Lp(a) and genetic testing. This strategy has yielded numerous FH and/or elevated Lp(a) diagnoses. Notably, we are also confirming FH genetic diagnosesin people with LDL-C \u003C190 mg/dL and DLCN scores \u003C3, suggesting a critical need to refine diagnostic approaches and avoid overreliance on clinical criteria. In this brief report, we describe a sample of our clinical population undergoing standardized Lp(a) screening and FH genetic testing. We aim to demonstrate the limitations of LDL-C levels and DLCN criteria for distinguishing FH/elevated Lp(a) phenotypically, especially without Lp(a) levels, and to encourage refined Lp(a) and FH genetic testing practices.  \nWhat is the clinical question being addressed?  \nCan standard clinical risk factors and diagnostic criteria accurately predict genetic diagnoses of FH and elevated Lp(a)?  \nWhat is the main finding?  \nLDL and personal/family history of premature ASCVD fail to distinguish between genetically confirmed FH, elevated Lp(a), and those with combined  \nFH + elevated Lp(a) .  \nMETHODS  \nThis registry-based observational study used a subset of our lipid clinic population at Indiana University Health as of 2025-04-30. The Indiana University Institutional Review Board approved the registry use (IRB\\#: 23922) . Inclusion criteria required probands (excluding cascade-identified cases) with: 1) completed FH genetic testing; 2) $1 LDL-C measurement; and 3) $1 Lp(a) measurement—resulting inn = 348 participants (∼34% of our clinic) . Genetic  \nFrom the aIndiana University School of Medicine, Division of Cardiology, Department of Molecular Genetics and Department of Medicine, Indianapolis, Indiana, USA; and the bIndiana University Health, Indianapolis, Indiana, USA.  \nThe authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.  \nISSN 2772-963X [https://doi.org/10.1016/j.jacadv.2025.102461](https://doi.org/10.1016/j.jacadv.2025.10246","cbCainfPgvxi3HRg","https://ap.wps.com/l/cbCainfPgvxi3HRg","pdf",643676,"English","# Clinic Approach and Study Aims\n## Clinical question being addressed\n## Main finding\n# Methods\n## Study design and inclusion criteria\n## Genetic and Lp(a) definitions","[{\"question\":\"Why are FH and elevated Lp(a) difficult to screen using standard clinical risk factors?\",\"answer\":\"FH and elevated Lp(a) can present similarly, and elevated LDL-C, premature ASCVD, and family history may not reliably separate genetically confirmed conditions.\"},{\"question\":\"What does the study find as the main result?\",\"answer\":\"LDL-C and personal or family history of premature ASCVD do not distinguish between genetically confirmed FH, elevated Lp(a), and combined FH + elevated Lp(a).\"},{\"question\":\"How were genetic outcomes and Lp(a) used in the diagnostic classification?\",\"answer\":\"The study assigned mutually exclusive genetic outcomes as FH, elevated Lp(a), FH + elevated Lp(a), or nondiagnostic, and defined elevated Lp(a) using thresholds stratified for analysis to reflect how Lp(a) affects measured LDL-C and DLCN classification.\"}]","Missed and Misdiagnosed Precision Medicine Approaches to Screening for Familial Hypercholesterolemia and Lipoprotein(a) | PDF",1790694609]