{"id":"4b2681c4afc1","type":"article","url":"https://hartvaat.nl/2026/06/29/familiaire-hypercholesterolemie-en-hypertriglyceridemie-nieuw-diagnostisch-algor/","title":"Familiaire hypercholesterolemie en hypertriglyceridemie: nieuw diagnostisch algoritme combineert genetica, ApoB en Lp(a)","title_en":"From Phenotype to Genotype and Beyond: Insights into Familial Hypercholesterolemia and Familial Hypertriglyceridemia.","category":"cholesterol","category_label":"Cholesterol","professions":["cardioloog","huisarts","internist"],"tags":[],"journal":"Medicina (Kaunas, Lithuania)","doi":"10.3390/medicina62071257","source_url":"https://doi.org/10.3390/medicina62071257","authors":["Dragos Cozma","Daniel Florin Lighezan","Cristina Tudoran","Oana Raluca Voinescu","Cristian Mornos"],"significance":5,"published":"2026-08-04","source_date":"2026-06-29","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/familiaire-hypercholesterolemie/","https://hartvaat.nl/kennis/lipiden/dutch-lipid-clinic-network-score/"],"congress":"","summary_en":"This narrative review highlights the limitations of current phenotypic diagnostic criteria for familial hypercholesterolemia (FH) and familial hypertriglyceridemia (FHTG), such as the DLCN score, and proposes a new four-step algorithm integrating genetic testing, ApoB quantification, and lifetime Lp(a) screening. Evidence from Mendelian randomization studies confirms that cardiovascular risk in these conditions is driven by ApoB-containing particles and remnant cholesterol rather than LDL-C or triglycerides alone. For clinical practice, this underscores the need to shift from LDL-C-centric to particle- and genotype-driven diagnostic pathways, improving early detection and cascade screening in primary care and lipid clinics.","created":"2026-07-29T01:03:02Z","updated":"2026-08-10T10:37:09Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Deze narratieve review beschrijft de beperkingen van de huidige fenotypische diagnostiek voor familiaire hypercholesterolemie (FH) en hypertriglyceridemie (FHTG), zoals de DLCN-score, en stelt een nieuw vierstappen-algoritme voor dat genetica, ApoB-metingen en Lp(a)-screening integreert. Mendeliaans randomization-onderzoek bevestigt dat atheroscleroserisico vooral wordt gedreven door ApoB-deeltjes en remnant-cholesterol, niet door triglyceriden of LDL-C op zich. Voor de klinische praktijk betekent dit dat diagnostiek en risicobeoordeling verder moeten evolueren naar een deeltjes- en genetica-gebaseerde aanpak, wat vooral relevant is voor de vroege opsporing en cascade-screening in de huisartsenpraktijk en lipidologie.","abstract_original":"Familial hypercholesterolemia (FH) and familial hypertriglyceridemia (FHTG) represent a spectrum of inherited conditions with profoundly different etiologies, risk profiles, and therapeutic implications. Despite decades of clinical experience, their formal diagnostic definitions remain rooted in frameworks developed before the genomic era (the Dutch Lipid Clinic Network (DLCN) score), leading to substantial gaps in diagnostic accuracy. This review traces the historical evolution of diagnostic criteria for FH and FHTG from early phenotypic observation to contemporary genomic and biomarker-driven models. It systematically evaluates the major limitations of current criteria, including the (DLCN) score, and integrates evidence from landmark Mendelian randomization (MR) studies to identify persistent gaps. A narrative synthesis of landmark clinical, epidemiological, and genetic studies was performed, encompassing the original discovery of the low-density lipoprotein cholesterol (LDL-C) receptor pathway, the development of international diagnostic criteria, and contemporary mendelian randomization (MR) evidence on the causal roles of LDL-C, lipoprotein (a) [Lp(a)], triglyceride-rich lipoprotein remnants, and apolipoprotein B (ApoB). Current diagnostic frameworks suffer from age-dependent confounding of LDL-C measurements, failure to account for Lp(a)-mediated phenocopies, inadequate discrimination between monogenic and polygenic etiologies, sex differences, ethnicity, and inapplicability to pediatric populations. MR data reveal that the causal architecture of cardiovascular risk in these disorders is particle-centric (ApoB) rather than LDL-C-centric, and that remnant cholesterol, not triglyceride per se, drives atherosclerotic cardiovascular disease risk in FHTG. We evidenced the evolution of treatment options and the morbidity and mortality rates for FH and FHTG from the 1970s until the 2020s. Future diagnostic paradigms should integrate lifetime Lp(a) measurement, polygenic risk scoring, ApoB quantification, and cascade genomic testing to replace phenotype-only approaches. This review concludes by proposing a four-step integrated diagnostic algorithm for FH and FHTG."}