| Title: |
Risk-weighted apoB: a novel summary metric outperforming traditional lipid biomarkers in predicting coronary heart disease |
| Authors: |
Rehman, Michaela B.; Bjornson, Elias; Adiels, Martin; Morze, Jakub; Bergstrom, Goran; Gummesson, Anders; Erlinge, David; Fall, Tove; Matic, Ljubica; Soderberg, Stefan; Östgren, Carl Johan; Packard, Chris J.; Boren, Jan |
| Publisher Information: |
Linköpings universitet, Avdelningen för prevention, rehabilitering och nära vård; Linköpings universitet, Medicinska fakulteten; Region Östergötland, Vårdcentralen Ekholmen; Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV; Medipole Lyon Villeurbanne, France; Univ Gothenburg, Sweden; Univ Gothenburg, Sweden; Chalmers Univ Technol, Sweden; Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; Lund Univ, Sweden; Uppsala Univ, Sweden; Karolinska Inst, Sweden; Umeå Univ, Sweden; Univ Glasgow, Scotland; OXFORD UNIV PRESS |
| Publication Year: |
2026 |
| Collection: |
Linköping University Electronic Press (LiU E-Press) |
| Subject Terms: |
Mendelian randomization; Cardiovascular disease; apoB; Lp(a); LDL; LDL cholesterol; UK Biobank; Cardiology and Cardiovascular Disease; Kardiologi och kardiovaskulära sjukdomar |
| Description: |
Background and Aims LDL-C and non-HDL-C do not fully capture coronary heart disease (CHD) risk attributed to all apoB-containing lipoproteins. Use of apolipoprotein B (apoB) as a marker of total atherogenic particle number improves risk prediction, but risk may still be underestimated when triglyceride-rich lipoproteins (TRL/remnants) and lipoprotein(a) [Lp(a)] are elevated. The aim was to formulate a new metric-risk-weighted apoB (RW-apoB)-designed to capture risk from LDL, TRL/remnants, and Lp(a) in a single number. Methods Based on previously published estimates of the relative atherogenicity of LDL, TRL/remnant, and Lp(a) particles, RW-apoB was developed (using UK Biobank data) as an atherogenicity-weighted apoB-sum calculated as: RW-apoB = 11.65xTG(mmol/L) + 0.215xlipoprotein(a)(nmol/L) + 0.736xapoB(mg/dL). Results Assigning RW-apoB to individuals substantially reclassified their risk status. Compared with ranking by measured apoB, 52% of individuals were up- or down-ranked by >= 10 percentiles. About one-third of those in the top RW-apoB quintile-with elevated TRL and Lp(a) and a CHD event rate of 5.4%-were misclassified as lower risk by apoB. Conversely, individuals in the top measured apoB quintile but with low TRL and Lp(a) had a lower event rate (3.9%) and were correctly down-ranked. RW-apoB improved risk prediction, significantly increasing Harrell's C-index relative to apoB (P < .0001). In statin-treated subjects, RW-apoB was potentially a better index of residual risk. RW-apoB consistently outperformed apoB as a risk predictor in Cox models across the UK Biobank and three other large population cohorts. Conclusions RW-apoB represents not only particle number but also accounts for the higher atherogenicity of TRL and Lp(a). It offers clinically meaningful improvements in CHD risk stratification. ; Funding Agencies|ALFagreement [ALFGBG-965404]; Swedish Heart Lung Foundation; Swedish government; Swedish Research Council |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
European Heart Journal, 0195-668X, 2026; PMID 41568673; ISI:001667375400001 |
| DOI: |
10.1093/eurheartj/ehaf1124 |
| Availability: |
http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-220939; https://doi.org/10.1093/eurheartj/ehaf1124 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.2F6F35BB |
| Database: |
BASE |