{"id":"04b3720249bf","type":"article","url":"https://hartvaat.nl/2026/02/27/lp-a-en-atherosclerotisch-vaatlijden-een-niet-lineair-verband/","title":"Lp(a) en atherosclerotisch vaatlijden: een niet-lineair verband","title_en":"Linear and Nonlinear Associations Between Lipoprotein(a) and the Risks of Atherosclerotic Cardiovascular Disease.","category":"cholesterol","category_label":"Cholesterol","professions":["cardioloog","huisarts","internist"],"tags":["atherosclerose","dyslipidemie","ezetimibe","familiaire-hypercholesterolemie-screening","ldl-cholesterol","lipide-aferese","lipoproteïne-a","lipoproteïne-a-therapeutisch-doel","luchtvervuiling","niet-statine-therapie","pelacarsen","plaquekarakterisatie","statines","vrouwen"],"journal":"Circulation journal : official journal of the Japanese Circulation Society","doi":"10.1253/circj.CJ-25-0847","source_url":"https://doi.org/10.1253/circj.CJ-25-0847","authors":["Hsin-Yin Hsu","Hsien-Yu Fan","Ming-Chieh Tsai","Chih-Jun Lai","Lee-Ching Hwang","Kuo-Liong Chien"],"significance":7,"published":"2026-03-09","source_date":"2026-02-27","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/lpa-meten-wanneer-waarom/"],"congress":"","summary_en":"This analysis of over 350,000 UK Biobank participants showed that the association between Lp(a) and atherosclerotic cardiovascular disease is nonlinear, with risk accelerating at higher levels — a finding with implications for treatment thresholds.","created":"2026-07-03T10:32:32Z","updated":"2026-07-03T13:31:29Z","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":"Een analyse van ruim 350.000 UK Biobank-deelnemers laat zien dat het verband tussen lipoproteïne(a) en atherosclerotisch vaatlijden niet-lineair is, met een steilere risicotoename bij hogere concentraties. De combinatie van observationele data en Mendeliaanse randomisatie versterkt de causale onderbouwing.","abstract_original":"BACKGROUND: Lipoprotein(a) [Lp(a)] is a recognized risk factor for atherosclerotic cardiovascular disease (ASCVD), but the shape and potential nonlinearity of its association remain uncertain. We assessed the linear and nonlinear associations between Lp(a) levels and ASCVD risk using observational and Mendelian randomization (MR) approaches. METHODS AND RESULTS: We analyzed 351,858 UK Biobank participants (2006-2023), stratified into Lp(a) percentiles: <70th, 70th-<80th, 80th-<90th, and ≥90th. Outcomes included ASCVD events from hospital, primary care, self-report, and death registry data. Cox models estimated the hazard ratios (HRs). MR analyses used a polygenic risk score from 10 Lp(a)-associated single-nucleotide polymorphisms, with nonlinearity tested by doubly ranked MR. Higher Lp(a) levels were associated with increased ASCVD risk. Compared with the <70th percentile, adjusted HRs (95% confidence interval) were 1.11 (1.07-1.16), 1.18 (1.14-1.22), and 1.25 (1.21-1.30) for the 70th-<80th, 80th-<90th, and ≥90th groups. Kaplan-Meier curves diverged early by group. Spline models suggested nonlinearity with an inflection near 130 nmol/L (P=0.007). MR showed a 2% higher ASCVD risk per 10 nmol/L genetically predicted Lp(a) (P<2×10-16). Nonlinear MR suggested steeper gradients at higher levels, though not statistically significant (P=0.087). CONCLUSIONS: Elevated Lp(a) concentrations were causally associated with ASCVD risk, showing a predominantly graded relationship with possible nonlinearity at very high levels, supporting routine Lp(a) measurement and the development of Lp(a)-lowering therapies."}