Proteomic exploration of common pathophysiological pathways in diabetes and cardiovascular disease

• Published in: ESC Heart Failure Vol. 7; no. 6; pp. 4151 - 4158
• Main Authors: Molvin, John, Jujić, Amra, Melander, Olle, Pareek, Manan, Råstam, Lennart, Lindblad, Ulf, Daka, Bledar, Leósdóttir, Margrét, Nilsson, Peter M., Olsen, Michael H., Magnusson, Martin
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-12-2020; John Wiley and Sons Inc; Wiley
• Subjects: Age; Allmän medicin; Antihypertensives; Blood pressure; Body mass index; Cardiac and Cardiovascular Systems; Cardiac arrhythmia; Cardiometabolic disease; Cardiovascular disease; Cathepsin D; Cholesterol; Clinical Medicine; Diabetes; Endocrinology and Diabetes; Endokrinologi och diabetes; Family Medicine; Galectin‐4; Glucose; Health Sciences; Heart attacks; Heart failure; Heart rate; High density lipoprotein; Hypertension; Hälsovetenskaper; Kardiologi; Klinisk medicin; Laboratories; Medical and Health Sciences; Medicin och hälsovetenskap; Mortality; Original; Original s; Peptides; Population; Proteins; Proteomics; Sweden; Cardiometabolic disease; Cardiovascular disease; Cathepsin D; Diabetes; Galectin-4; Proteomics
• ISSN: 2055-5822; 2055-5822
• DOI: 10.1002/ehf2.13036

Aims
The epidemiological association between diabetes and cardiovascular disease is well established, but the pathophysiological link is complex and multifactorial. We investigated seven proteins, previously linked to incident diabetes mellitus, and their association with cardiovascular disease and mortality.
Methods and results
Plasma samples from 1713 individuals from the Swedish population‐based Malmö Preventive Project (mean age 67.4 ± 6.0 years; 29.1% women) were analysed with a proximity extension assay panel. Seven proteins [scavenger receptor cysteine rich type 1 protein M130 (CD163), fatty acid‐binding protein 4 (FABP4), plasminogen activator inhibitor 1 (PAI), insulin‐like growth factor‐binding protein 2 (IGFB2), cathepsin D (CTSD), galectin‐4 (GAL4), and paraoxonase‐3 (PON3)] previously shown to be associated with incident diabetes were analysed for associations with all‐cause mortality (ACM), cardiovascular mortality (CVM), incident coronary events (CEs), and incident heart failure (HF). After exclusion of prevalent cases of respective outcome, proteins that met Bonferroni‐corrected significance were analysed in multivariable Cox regression models. Significant associations were identified between five proteins [GAL4 (hazard ratio; 95% confidence interval: 1.17–1.41), CTSD (1.15–1.37), CD163 (1.09–1.30), IGFBP2 (1.05–1.30), and FABP4 (1.04–1.29)] and ACM and four proteins [GAL4 (1.38–1.56), CTSD (1.14–1.43), CD163 (1.09–1.36), and IGFBP2 (1.03–1.35)] with CVM. Three proteins [GAL4 (1.14–1.57), CTSD (1.12–1.50), and FABP4 (1.05–1.55)] were significantly associated with incident CE and two [GAL4 (1.03–1.54) and CTSD (1.01–1.46)] were associated with incident HF after adjusting for traditional risk factors including N‐terminal pro‐brain natriuretic peptide.
Conclusions
In a general Swedish population, four proteins previously shown to be associated with diabetes were associated with ACM and CVM. Three proteins were associated with incident CE. Finally, GAL4 and CTSD displayed novel associations with incident HF and were the only proteins associated with all outcomes.