TY - JOUR
T1 - Blood-based cardiometabolic phenotypes in atrial fibrillation and their associated risk
T2 - EAST-AFNET 4 biomolecule study
AU - Fabritz, Larissa
AU - Chua, Winnie
AU - Cardoso, Victor R
AU - Al-Taie, Christoph
AU - Borof, Katrin
AU - Suling, Anna
AU - Krause, Linda
AU - Kany, Shino
AU - Magnussen, Christina
AU - Wegscheider, Karl
AU - Breithardt, Guenter
AU - Crijns, Harry J G M
AU - Camm, A John
AU - Gkoutos, George
AU - Ellinor, Patrick T
AU - Goette, Andreas
AU - Schotten, Ulrich
AU - Wienhues-Thelen, Ursula-Henrike
AU - Zeller, Tanja
AU - Schnabel, Renate B
AU - Zapf, Antonia
AU - Kirchhof, Paulus
PY - 2024/5/1
Y1 - 2024/5/1
N2 - Aims: Atrial fibrillation (AF) and concomitant cardiometabolic disease processes interact and combine to lead to adverse events, such as stroke, heart failure, myocardial infarction, and cardiovascular death. Circulating biomolecules provide quantifiable proxies for cardiometabolic disease processes. The aim of this study was to test whether biomolecule combinations can define phenotypes in patients with AF. Methods and results: This pre-specified analysis of the EAST-AFNET 4 biomolecule study assigned patients to clusters using polytomous variable latent-class analysis based on baseline concentrations of 13 precisely quantified biomolecules potentially reflecting ageing, cardiac fibrosis, metabolic dysfunction, oxidative stress, cardiac load, endothelial dysfunction, and inflammation. In each cluster, rates of cardiovascular death, stroke, or hospitalization for heart failure or acute coronary syndrome, the primary outcome of EAST-AFNET 4, were calculated and compared between clusters over median 5.1 years follow-up. Findings were independently validated in a prospective cohort of 748 patients with AF (BBC-AF; median follow-up 2.9 years). Unsupervised biomolecule analysis assigned 1586 patients (71 years old, 46% women) into four clusters. The highest risk cluster was dominated by elevated bone morphogenetic protein 10, insulin-like growth factor-binding protein 7, N-terminal pro-B-type natriuretic peptide, angiopoietin 2, and growth differentiation factor 15. Patients in the lowest risk cluster showed low concentrations of these biomolecules. Two intermediate-risk clusters differed by high or low concentrations of C-reactive protein, interleukin-6, and D-dimer. Patients in the highest risk cluster had a five-fold higher cardiovascular event rate than patients in the low-risk cluster. Early rhythm control was effective across clusters (P
interaction = 0.63). Sensitivity analyses and external validation in BBC-AF replicated clusters and risk gradients. Conclusion: Biomolecule concentrations identify cardiometabolic subphenotypes in patients with AF at high and low cardiovascular risk.
AB - Aims: Atrial fibrillation (AF) and concomitant cardiometabolic disease processes interact and combine to lead to adverse events, such as stroke, heart failure, myocardial infarction, and cardiovascular death. Circulating biomolecules provide quantifiable proxies for cardiometabolic disease processes. The aim of this study was to test whether biomolecule combinations can define phenotypes in patients with AF. Methods and results: This pre-specified analysis of the EAST-AFNET 4 biomolecule study assigned patients to clusters using polytomous variable latent-class analysis based on baseline concentrations of 13 precisely quantified biomolecules potentially reflecting ageing, cardiac fibrosis, metabolic dysfunction, oxidative stress, cardiac load, endothelial dysfunction, and inflammation. In each cluster, rates of cardiovascular death, stroke, or hospitalization for heart failure or acute coronary syndrome, the primary outcome of EAST-AFNET 4, were calculated and compared between clusters over median 5.1 years follow-up. Findings were independently validated in a prospective cohort of 748 patients with AF (BBC-AF; median follow-up 2.9 years). Unsupervised biomolecule analysis assigned 1586 patients (71 years old, 46% women) into four clusters. The highest risk cluster was dominated by elevated bone morphogenetic protein 10, insulin-like growth factor-binding protein 7, N-terminal pro-B-type natriuretic peptide, angiopoietin 2, and growth differentiation factor 15. Patients in the lowest risk cluster showed low concentrations of these biomolecules. Two intermediate-risk clusters differed by high or low concentrations of C-reactive protein, interleukin-6, and D-dimer. Patients in the highest risk cluster had a five-fold higher cardiovascular event rate than patients in the low-risk cluster. Early rhythm control was effective across clusters (P
interaction = 0.63). Sensitivity analyses and external validation in BBC-AF replicated clusters and risk gradients. Conclusion: Biomolecule concentrations identify cardiometabolic subphenotypes in patients with AF at high and low cardiovascular risk.
U2 - 10.1093/cvr/cvae067
DO - 10.1093/cvr/cvae067
M3 - Article
SN - 0008-6363
VL - 120
SP - 855
EP - 868
JO - Cardiovascular Research
JF - Cardiovascular Research
IS - 8
ER -