Background Natriuretic peptides are routinely quantified to diagnose heart failure (HF). Their concentrations are also elevated in atrial fibrillation (AF). To clarify their value in predicting future cardiovascular events, we measured natriuretic peptides in unselected patients with cardiovascular conditions and related their concentrations to AF and HF status and outcomes. Methods and Results Consecutive patients with cardiovascular conditions presenting to a large teaching hospital underwent clinical assessment, 7‐day ECG monitoring, and echocardiography to diagnose AF and HF. NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) was centrally quantified. Based on a literature review, four NT‐proBNP groups were defined (<300, 300–999, 1000–1999, and ≥2000 pg/mL). Clinical characteristics and NT‐proBNP concentrations were related to HF hospitalization or cardiovascular death. Follow‐up data were available in 1616 of 1621 patients (99.7%) and analysis performed at 2.5 years (median age, 70 [interquartile range, 60–78] years; 40% women). HF hospitalization or cardiovascular death increased from 36 of 488 (3.2/100 person‐years) in patients with neither AF nor HF, to 55 of 354 (7.1/100 person‐years) in patients with AF only, 92 of 369 (12.1/100 person‐years) in patients with HF only, and 128 of 405 (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, 0.77–0.86; P <0.001) and in other phenotype groups (C‐statistic in AF plus HF, 0.66; [95% CI, 0.61–0.70]; P <0.001). Conclusions Elevated NT‐proBNP concentrations predict future HF events in patients with AF irrespective of the presence of HF, encouraging routine quantification of NT‐proBNP in the assessment of patients with AF.
Background Large-scale screening for atrial fibrillation (AF) requires reliable methods to identify at-risk populations. Using an experimental semi-quantitative biomarker assay, B-type natriuretic peptide (BNP) and fibroblast growth factor 23 (FGF23) were recently identified as the most suitable biomarkers for detecting AF in combination with simple morphometric parameters (age, sex, and body mass index [BMI]). In this study, we validated the AF model using standardised, high-throughput, high-sensitivity biomarker assays. Methods and findings For this study, 1,625 consecutive patients with either (1) diagnosed AF or (2) sinus rhythm with CHA2DS2-VASc score of 2 or more were recruited from a large teaching hospital in Birmingham, West Midlands, UK, between September 2014 and February 2018. Seven-day ambulatory ECG monitoring excluded silent AF. Patients with tachyarrhythmias apart from AF and incomplete cases were excluded. AF was diagnosed according to current clinical guidelines and confirmed by ECG. We developed a high-throughput, high-sensitivity assay for FGF23, quantified plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and FGF23, and compared results to the previously used multibiomarker research assay. Data were fitted to the previously derived model, adjusting for differences in measurement platforms and known confounders (heart failure and chronic kidney disease). In 1,084 patients (46% with AF; median [Q1, Q3] age 70 [60, 78] years, median [Q1, Q3] BMI 28.8 [25.1, 32.8] kg/m2, 59% males), patients with AF had higher concentrations of NT-proBNP (median [Q1, Q3] per 100 pg/ml: with AF 12.00 [4.19, 30.15], without AF 4.25 [1.17, 15.70]; p < 0.001) and FGF23 (median [Q1, Q3] per 100 pg/ml: with AF 1.93 [1.30, 4.16], without AF 1.55 [1.04, 2.62]; p < 0.001). Univariate associations remained after adjusting for heart failure and estimated glomerular filtration rate, known confounders of NT-proBNP and FGF23. The fitted model yielded a C-statistic of 0.688 (95% CI 0.656, 0.719), almost identical to that of the derived model (C-statistic 0.691; 95% CI 0.638, 0.744). The key limitation is that this validation was performed in a cohort that is very similar demographically to the one used in model development, calling for further external validation. Conclusions Age, sex, and BMI combined with elevated NT-proBNP and elevated FGF23, quantified on a high-throughput platform, reliably identify patients with AF. Trial registration Registry IRAS ID 97753 Health Research Authority (HRA), United Kingdom
ObjectiveThe pharmacological management of atrial fibrillation (AF) comprises anticoagulation, for stroke prophylaxis, and rate or rhythm control drugs to alleviate symptoms and prevent heart failure. The aim of this study was to investigate trends in the proportion of patients with AF prescribed pharmacological therapies in the UK between 2008 and 2018.MethodsEleven sequential cross-sectional analyses were performed yearly from 2008 to 2018. Data were derived from an anonymised UK primary care database. Outcomes were the proportion of patients with AF prescribed anticoagulants, rhythm and rate control drugs in the whole cohort, those at high risk of stroke and those with coexisting heart failure.ResultsBetween 2008 and 2018, the proportion of patients prescribed anticoagulants increased from 45.3% (95% CI 45.0% to 45.7%) to 71.1% (95% CI 70.7% to 71.5%) driven by increased prescription of non-vitamin K antagonist anticoagulants. The proportion of patients prescribed rate control drugs remained constant between 2008 and 2018 (69.3% (95% CI 68.9% to 69.6%) to 71.6% (95% CI 71.2% to 71.9%)). The proportion of patients prescribed rhythm control therapy by general practitioners (GPs) decreased from 9.5% (95% CI 9.3% to 9.7%) to 5.4% (95% CI 5.2% to 5.6%).ConclusionsThere has been an increase in the proportion of patients with AF appropriately prescribed anticoagulants following National Institute for Health and Care Excellence and European Society of Cardiology guidelines, which correlates with improvements in mortality and stroke outcomes. Beta-blockers appear increasingly favoured over digoxin for rate control. There has been a steady decline in GP prescribing rates for rhythm control drugs, possibly related to concerns over efficacy and safety and increased availability of AF ablation.
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