You are here
A proteomic analysis of atrial fibrillation in a prospective longitudinal cohort (AGES-Reykjavik study).
Tuesday,2023-12-05 14:45 America/Los_Angeles — ecterry
| Title | A proteomic analysis of atrial fibrillation in a prospective longitudinal cohort (AGES-Reykjavik study). |
| Publication Type | Journal Article |
| Year of Publication | 2023 |
| Authors | Jonmundsson, T, Steindorsdottir, AE, Austin, TR, Frick, EA, Axelsson, GT, Launer, L, Psaty, BM, Loureiro, J, Orth, AP, Aspelund, T, Emilsson, V, Floyd, JS, Jennings, L, Gudnason, V, Gudmundsdottir, V |
| Journal | Europace |
| Volume | 25 |
| Issue | 11 |
| Date Published | 2023 Nov 02 |
| ISSN | 1532-2092 |
| Keywords | Atrial Fibrillation, Biomarkers, Endosomal Sorting Complexes Required for Transport, Humans, Natriuretic Peptide, Brain, Oxidoreductases Acting on Sulfur Group Donors, Peptide Fragments, Prognosis, Prospective Studies, Proteomics, Risk Factors |
| Abstract | <p><b>AIMS: </b>Atrial fibrillation (AF) is associated with high risk of comorbidities and mortality. Our aim was to examine causal and predictive relationships between 4137 serum proteins and incident AF in the prospective population-based Age, Gene/Environment Susceptibility-Reykjavik (AGES-Reykjavik) study.</p><p><b>METHODS AND RESULTS: </b>The study included 4765 participants, of whom 1172 developed AF. Cox proportional hazards regression models were fitted for 4137 baseline protein measurements adjusting for known risk factors. Protein associations were tested for replication in the Cardiovascular Health Study (CHS). Causal relationships were examined in a bidirectional, two-sample Mendelian randomization analysis. The time-dependent area under the receiver operating characteristic curve (AUC)-statistic was examined as protein levels and an AF-polygenic risk score (PRS) were added to clinical risk models. The proteomic signature of incident AF consisted of 76 proteins, of which 63 (83%) were novel and 29 (38%) were replicated in CHS. The signature included both N-terminal prohormone of brain natriuretic peptide (NT-proBNP)-dependent (e.g. CHST15, ATP1B1, and SVEP1) and independent components (e.g. ASPN, AKR1B, and LAMA1/LAMB1/LAMC1). Nine causal candidates were identified (TAGLN, WARS, CHST15, CHMP3, COL15A1, DUSP13, MANBA, QSOX2, and SRL). The reverse causal analysis suggested that most AF-associated proteins were affected by the genetic liability to AF. N-terminal prohormone of brain natriuretic peptide improved the prediction of incident AF events close to baseline with further improvements gained by the AF-PRS at all time points.</p><p><b>CONCLUSION: </b>The AF proteomic signature includes biologically relevant proteins, some of which may be causal. It mainly reflects an NT-proBNP-dependent consequence of the genetic liability to AF. N-terminal prohormone of brain natriuretic peptide is a promising marker for incident AF in the short term, but risk assessment incorporating a PRS may improve long-term risk assessment.</p> |
| DOI | 10.1093/europace/euad320 |
| Alternate Journal | Europace |
| PubMed ID | 37967346 |
| PubMed Central ID | PMC10685397 |
| Grant List | 1R01AG065596-01A1 / AG / NIA NIH HHS / United States R01 HL149706 / HL / NHLBI NIH HHS / United States R01 AG065596 / AG / NIA NIH HHS / United States R01 HL144483 / HL / NHLBI NIH HHS / United States / NS / NINDS NIH HHS / United States |
ePub date:
23/11