{"id":"45972","type":"article","url":"https://hartvaat.nl/2026/05/20/klinisch-en-genetisch-risico-op-atriumfibrilleren-versterken-elkaar-additief-13-/","title":"Klinisch en genetisch risico op atriumfibrilleren versterken elkaar additief — 13× risico bij beide hoog","title_en":"","category":"algemeen","category_label":"Algemeen","professions":["cardioloog","huisarts","internist"],"tags":[],"journal":"Open Heart","doi":"http://openheart.bmj.com/cgi/content/short/13/1/e004078?rss=1","source_url":"https://doi.org/http://openheart.bmj.com/cgi/content/short/13/1/e004078?rss=1","authors":["Frederiksen","T. C.","Nadarajah","R.","Christiansen","M. K.","Wu","J.","Gale","C. P.","Benjamin","E. J.","Olsen","A.","Andersen","M. K.","Hansen","T.","Grarup","N.","Dahm","C. C.","Jensen","H. K."],"significance":7,"published":"2026-07-06","source_date":"2026-05-20","image":"","kennis":["https://hartvaat.nl/kennis/kleplijden/tavi-transcatheter-aortaklepimplantatie/","https://hartvaat.nl/kennis/kleplijden/esc-richtlijn-kleplijden-2021/"],"congress":"","summary_en":"Case-cohort study within the Danish Diet, Cancer and Health cohort (subcohort n=4,040 plus AF cases) combining the FIND-AF clinical risk score (low 0-3, high 4-6, very high 7-14 points) with a genetic risk score (GRS) based on 142 variants, categorised as low (Q1), intermediate (Q2-4), or high (Q5) genetic risk. Over a median follow-up of 12.9 years, 3,094 participants developed AF. Compared with those at low clinical and genetic risk, the adjusted hazard ratio for AF was 3.47 with high clinical + high genetic risk, and 12.76 with very high clinical + high genetic risk. The relative excess risk due to interaction (RERI) was 0.56 — a positive additive interaction between GRS and FIND-AF. Combining clinical and genetic risk stratification can therefore better target future AF prevention and screening.","created":"2026-07-03T20:27:00Z","updated":"2026-07-04T19:09:36Z","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":"Case-cohort studie binnen het Deense Diet, Cancer and Health-cohort (subcohort n=4.040 plus AF-cases) waarin de FIND-AF klinische risicoscore (laag 0-3, hoog 4-6, zeer hoog 7-14 punten) werd gecombineerd met een genetische risicoscore (GRS) op basis van 142 varianten, ingedeeld in lage (Q1), intermediaire (Q2-4) of hoge (Q5) genetische risicogroep. Over mediaan 12,9 jaar follow-up ontwikkelden 3.094 deelnemers AF. Vergeleken met lage klinische én genetische risico-personen was de gecorrigeerde hazard ratio voor AF 3,47 bij hoog klinisch én hoog genetisch risico, en 12,76 bij zeer hoog klinisch + hoog genetisch risico. Relative excess risk due to interaction (RERI) was 0,56 — een positieve additieve interactie tussen GRS en FIND-AF. Combinatie van klinische en genetische risicostratificatie kan dus toekomstige preventie en screening op AF gericht maken.","abstract_original":"<sec><st>Background</st>\n<p>The interplay between genetic susceptibility and clinical risk for incident atrial fibrillation (AF) is unclear.</p>\n</sec>\n<sec><st>Methods</st>\n<p>We used a case-cohort study design and included AF cases and a randomly drawn subcohort of 4040 participants from the Danish Diet, Cancer and Health cohort. The simplified version of the Future Innovations in Novel Detection of Atrial Fibrillation (FIND-AF) risk score was used to quantify individual participant clinical risk of incident AF as low (0&ndash;3 points), high (4&ndash;6 points) and very high risk (7&ndash;14 points). We calculated individual participant Genetic Risk Scores (GRS) from 142 variants to categorise participants as low (quintile 1), intermediate (quintile 2&ndash;4) or high (quintile 5) genetic risk of AF. We used weighted Cox proportional hazards regression to quantify risk of incident AF according to FIND-AF risk and GRS and assessed the relative excess risk due to interaction (RERI) for interaction on an additive scale.</p>\n</sec>\n<sec><st>Results</st>\n<p>During a median follow-up of 12.9 years, 3094 participants developed AF. Compared with individuals with low FIND-AF risk score and low GRS, the multivariable-adjusted HR for AF was 3.47 (95% CI 2.64 to 4.55) for those with high FIND-AF risk score and high GRS and 12.76 (95% CI 5.07 to 32.11) for those with very high FIND-AF risk score and high GRS. The RERI was 0.56 (95% CI 0.43 to 0.70), indicating a positive additive interaction between GRS and FIND-AF risk score.</p>\n</sec>\n<sec><st>Conclusions</st>\n<p>Genetic susceptibility and clinical risk interacted on an additive scale to elevate AF risk. These results highlight the need for future research on prevention and screening among individuals with both high genetic and clinical risk for AF.</p>\n</sec>"}