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Arnold, N.* ; Goßling, A.* ; Weimann, J.* ; Bay, B.* ; Zeller, T.* ; Ferrario, M.M.* ; Palmieri, L.* ; Amouyel, P.* ; Moitry, M.* ; Ferrieres, J.* ; Brenner, H.* ; Tamosiunas, A.* ; Malyutina, S.* ; Männistö, S.* ; Drygas, W.* ; Grassi, G.* ; Grimsgaard, S.* ; Linneberg, A.* ; Söderberg, S.* ; Iacoviello, L.* ; Sans, S.* ; Schnabel, R.* ; Veronesi, G.* ; Thorand, B. ; Tunstall-Pedoe, H.* ; Kee, F.* ; Salomaa, V.* ; Kuulasmaa, K.* ; Blankenberg, S.* ; Waldeyer, C.* ; Ojeda, F.* ; Magnussen, C.* ; Koenig, W.*

Occurrence of coronary events in the absence of traditional risk factors: Understanding residual risk.

Atherosclerosis 409:120475 (2025)

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BACKGROUND AND AIMS: The major predictors of future coronary heart disease (CHD) events in individuals without traditional modifiable cardiovascular risk factors (CVRFs) remain unknown. We investigated the association between circulating biomarkers, reflecting residual risk, with incident CHD in a general population, according to the presence of five CVRFs (hypertension, diabetes mellitus, hypercholesterolemia, smoking and obesity) at baseline. METHODS: Overall 212,598 CHD-free individuals from 21 European population-based cohorts were stratified by CVRF burden into three groups, having zero (n = 35,707), one (n = 68,548) or ≥2 (n = 108,343) risk factors at baseline. Five biomarkers (triglycerides (TGs), high-sensitivity C-reactive protein (hsCRP), cystatin C, N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I) were assessed in a subset with available measurements. RESULTS: During a median follow-up of 13.97 years, 17,499 participants developed incident CHD with 453 events occurring among individuals without CVRFs. Although increased concentrations of all biomarkers were related to incident CHD, significant risk modulation by CVRFs was seen only for TGs and, to a lesser extent, for hsCRP. The fully-adjusted sub-distribution Hazard Ratios (95 % CI) were for TGs (≥vs < 1.70 mmol/L) 1.66 (1.29-2.15) in those without CVRFs versus 1.35 (1.21-1.49)/1.14 (1.07-1.20) in those with 1 or ≥2 risk factors (p_interaction<0.01) and for hsCRP (≥vs < 2 mg/L) 1.39 (1.02-1.90) versus 1.42 (1.26-1.61) or 1.22 (1.13-1.32), respectively (p_interaction = 0.092). CONCLUSION: Even in the absence of CVRFs, elevated triglycerides and hsCRP were significantly associated with an increased risk of CHD. These results highlight the importance of residual risk assessment using those biomarkers in individuals deemed metabolically healthy by conventional standards.

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Publication type Article: Journal article

Document type Scientific Article

Keywords Cardiovascular Risk Factors (cvrfs) ; Circulating Biomarkers ; Coronary Heart Disease ; General Population ; High-sensitivity C-reactive Protein (hscrp) ; Triglycerides; Atherosclerotic Cardiovascular-disease; Triglyceride-rich Lipoproteins; Cystatin C; Population; Mortality; Genetics; Insights; Remnants; Morgam

ISSN (print) / ISBN 0021-9150

e-ISSN 1879-1484

Journal Atherosclerosis

Quellenangaben Volume: 409, Article Number: 120475

Publisher Elsevier

Publishing Place Amsterdam

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology (EPI)

Grants Umea University
Swedish Heart-Lung Foundation
German Center of Cardiovascular Research (DZHK e.V.)
German Heart Foundation
Medical Research Council, London
Digital, Risk-based Screening for Atrial Fibrillation in the European Community project-European Union (AFFECT-EU) (Horizon 2020)
Eu-CanSHare (Horizon 2020)
National Institute of Health Research United Kingdom
County Council of Vasterbotten (ALF)
Loewenstein Medical
NDD
Dr. Rolf M. Schwiete Stiftung
German Heart Research Foundation (Deutsche Stiftung fuer Herzforschung)
German Center of Cardiovascular Research (DZHK e.V.) (Promotion of women scientists programme)
Abbott Diagnostics
German Center for Cardiovascular Research (DZHK e.V.)
German Ministry of Research and Education
European Research Council (ERC) under the European Union
Juho Vainio Foundation
Finnish Foundation for Cardiovascular Research
European Union