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Luo, H. ; Huemer, M.-T. ; Petrera, A. ; Hauck, S.M. ; Rathmann, W.* ; Herder, C.* ; Koenig, W.* ; Hoyer, A.* ; Peters, A. ; Thorand, B.

Association of plasma proteomics with incident coronary heart disease in individuals with and without type 2 diabetes: Results from the population-based KORA study.

Cardiovasc. Diabetol. 23:53 (2024)
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BACKGROUND: Coronary heart disease (CHD) is a major global health concern, especially among individuals with type 2 diabetes (T2D). Given the crucial role of proteins in various biological processes, this study aimed to elucidate the aetiological role and predictive performance of protein biomarkers on incident CHD in individuals with and without T2D. METHODS: The discovery cohort included 1492 participants from the Cooperative Health Research in the Region of Augsburg (KORA) S4 study with 147 incident CHD cases (45 vs. 102 cases in the group with T2D and without T2D, respectively) during 15.6 years of follow-up. The validation cohort included 888 participants from the KORA-Age1 study with 70 incident CHD cases (19 vs. 51 cases in the group with T2D and without T2D, respectively) during 6.9 years of follow-up. We measured 233 plasma proteins related to cardiovascular disease and inflammation using proximity extension assay technology. Associations of proteins with incident CHD were assessed using Cox regression and Mendelian randomization (MR) analysis. Predictive models were developed using priority-Lasso and were evaluated on top of Framingham risk score variables using the C-index, category-free net reclassification index (cfNRI), and relative integrated discrimination improvement (IDI). RESULTS: We identified two proteins associated with incident CHD in individuals with and 29 in those without baseline T2D, respectively. Six of these proteins are novel candidates for incident CHD. MR suggested a potential causal role for hepatocyte growth factor in CHD development. The developed four-protein-enriched model for individuals with baseline T2D (ΔC-index: 0.017; cfNRI: 0.253; IDI: 0.051) and the 12-protein-enriched model for individuals without baseline T2D (ΔC-index: 0.054; cfNRI: 0.462; IDI: 0.024) consistently improved CHD prediction in the discovery cohort, while in the validation cohort, significant improvements were only observed for selected performance measures (with T2D: cfNRI: 0.633; without T2D: ΔC-index: 0.038; cfNRI: 0.465). CONCLUSIONS: This study identified novel protein biomarkers associated with incident CHD in individuals with and without T2D and reaffirmed previously reported protein candidates. These findings enhance our understanding of CHD pathophysiology and provide potential targets for prevention and treatment.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Cohort Study ; Coronary Heart Disease ; Mendelian Randomization ; Proteomics ; Type 2 Diabetes; Myocardial-infarction; Growth-factor; Risk-factors; Mellitus; Mortality; Profile; Events; Health; Artery; Men
ISSN (print) / ISBN 1475-2840
e-ISSN 1475-2840
Journal Cardiovascular Diabetology
Quellenangaben Volume: 23, Issue: 1, Pages: , Article Number: 53 Supplement: ,
Publisher BioMed Central
Publishing Place Campus, 4 Crinan St, London N1 9xw, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
CF Metabolomics & Proteomics (CF-MPC)
Grants Helmholtz Zentrum Mnchen - Deutsches Forschungszentrum fr Gesundheit und Umwelt (GmbH) (4209)