Natriuretic peptides predict future heart failure and cardiovascular death in an unselected population of patients presenting to hospital: interactions with atrial fibrillation

Abstract

Aims Natriuretic peptides are routinely quantified to diagnose heart failure (HF). Their concentrations are also elevated in atrial fibrillation (AF). To clarify their interpretation, we measured natriuretic peptides in unselected patients with cardiovascular conditions and related their concentrations to AF and HF status and to outcomes.

Methods and results Consecutive patients with cardiovascular conditions presenting to a large teaching hospital (median age 70 [IQR 60–78] years, 40% women) underwent clinical assessment, 7-day ECG-monitoring, and echocardiography to diagnose AF and HF. N-terminal pro B-type natriuretic peptide (NT-proBNP) was centrally quantified. Clinical characteristics and NT-proBNP concentrations were related to HF hospitalization or cardiovascular death. Follow-up data was available in 1611/1616 patients (99.7%) and analysis performed at 2.5 years. Based on a literature review, four NT-proBNP groups were defined (<300pg/ml, 300–999pg/ml, 1000–1999pg/ml and ≥2000pg/ml).

Multivariate Cox proportional hazards analysis of the composite outcome against AF and HF phenotype groups. This was adjusted for confounding factors including age, sex, race, body mass index, hypertension, diabetes, coronary artery disease, severe valvular heart disease, left bundle branch block, hyponatraemia, urea, haemoglobin, estimated glomerular filtration rate, NT-proBNP, medical treatment with ACE inhibitors or angiotensin receptor blockers, beta-blockers, diuretic (thiazide or loop diuretics), and anticoagulants (novel oral anticoagulant or vitamin K antagonist). Cox proportional hazards analysis adjusted for confounding variables for the composite outcome against baseline NT-proBNP concentration ranges was also performed in each patient group based on AF and HF status.

HF hospitalization or cardiovascular death increased from patients with neither AF nor HF (36/488, 3.2/100 person-years), to 55/353 (7.1/100 person-years) in patients with AF only, 91/366 (12.1/100 person-years) in patients with HF only, and, 128/404 (17.7/100 person-years) in patients with AF plus HF (p<0.001). Higher NT-proBNP concentrations predicted the outcome in patients with AF only (C-statistic 0.82 [95% CI 0.77 to 0.86], p-value<0.001) and in other phenotype groups (C statistic in AF plus HF 0.66 [95% CI 0.61 to 0.70], p-value<0.001)). Sensitivity analyses confirmed these findings.

Conclusion Elevated NT-proBNP concentrations predict future HF events in patients with AF irrespective of the presence of HF. In line with previous studies in HF, an NT-proBNP threshold of 1000 pg/ml is useful to identify high-risk patients with AF whether or not they are diagnosed with HF at the time of assessment. Pending external validation, these findings encourage the routine quantification of NT-proBNP in the initial assessment of patients with AF.

Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): 1) This study was partially supported by European Union BigData@Heart and 2) CATCH ME (Characterising Afib by Translating its Causes into Health Modifiers in the Elderly)