scholarly journals Atrial fibrillation and the prognostic performance of biomarkers in heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Tan ◽  
S.P Chan ◽  
W.L Oi ◽  
J.P.C Chong ◽  
T Prickett ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Natriuretic Peptide ◽  
Primary Outcome ◽  
High Sensitivity ◽  
Funding Source ◽  
Prognostic Performance ◽  
High Sensitivity Troponin ◽  
All Cause Mortality ◽  
Galectin 3

Abstract Background Consideration of circulating biomarkers for risk stratification in heart failure (HF) is recommended in authoritative international guidelines but the influence of atrial fibrillation (AF) on the prognostic performance of many markers is unclear. Therefore we investigated the interactions between AF and biomarkers in prediction of important clinical outcomes in HF. Methods NT-proBNP, pro-atrial natriuretic peptide (MR-proANP), C-type natriuretic peptide (CNP), NT-proCNP, high-sensitivity troponin-T, high-sensitivity troponin-I, mid-regional-propeptide adrenomedullin (MR-proADM), co-peptin (PAVP), growth differentiation factor-15 (GDF-15), sST2, Galectin-3 and procalcitonin levels were measured in a prospectively designed, multicenter, longitudinal study of adults with HF. AF was defined as a documented history of AF based on medical records, and/or presence of AF/atrial flutter on baseline 12-lead ECG. The primary outcome considered was the composite of HF-hospitalization or all-cause mortality on prospective follow-up at 2-years. Cox proportional-hazards models were used in the prognostic evaluation of biomarkers, and each was tested for interaction with AF. Results Among 1,099 patients with HF (mean age 62±12 years, 28% female, mean left ventricular ejection fraction 35±16%), 261 (24%) patients had AF. Median levels of NT-proBNP, GDF-15, ST2, MR-proADM, proANP and CNP were higher in AF (p<0.05). Above-median levels of all 12 biomarkers were independently associated with increased risk of the primary outcome. Significant interactions with AF were detected for Galectin-3 and sST2. Galectin-3 (>7.7ng/mL) was associated with increased HF-hospitalizations (adjusted hazard ratio [AHR] 1.75, 95% C.I. 1.10–2.77) and all-cause mortality (AHR 1.95, 95% C.I. 1.04–3.63) only among patients with AF. The prognostic performance of sST2 (>35.6ng/mL) was also stronger in AF especially for the primary outcome (AF: AHR 2.06 95% C.I. 1.32–3.21; non-AF: AHR 1.49 95% C.I. 1.18–1.88) and HF-hospitalization (AF: AHR 1.65, 95% C.I. 1.01–2.69; non-AF: AHR 1.32, 95% C.I. 1.02–1.71). The association of Galectin-3 with the composite outcome was not modified by HF type (HFpEF vs HFrEF) (p for 3-way interaction=0.61) except for sST2 (p for 3-way interaction=0.018) where the association appeared stronger in patients with HFpEF and AF (HR 3.12, 95% C.I. 1.26–7.78) compared to those with HFrEF and AF (HR 1.83, 95% C.I. 1.01–3.33) although numbers of events in each subgroup were small. Notably, no such interactions were observed for the most frequently measured prognostic markers in HF including NT-proBNP and the high-sensitivity cardiac troponins. Conclusion AF modified the prognostic utility of guideline-endorsed HF-biomarkers, wherein prognostic associations of Galectin-3 and ST2 were limited to, or stronger in, patients with AF. Application of markers for prognostic purposes in HF requires consideration of the presence or absence of AF. Figure 1 Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): National Medical Research Council of Singapore

scholarly journals Atrial Fibrillation and the Prognostic Performance of Biomarkers in Heart Failure

2020 ◽  
Author(s):  
Eugene S J Tan ◽  
Siew-Pang Chan ◽  
Oi-Wah Liew ◽  
Jenny P C Chong ◽  
Gerard K T Leong ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Risk Stratification ◽  
Natriuretic Peptide ◽  
Primary Outcome ◽  
High Sensitivity ◽  
Circulating Biomarkers ◽  
Prognostic Performance ◽  
All Cause Mortality ◽  
Galectin 3

Abstract Background Consideration of circulating biomarkers for risk stratification in heart failure (HF) is recommended, but the influence of atrial fibrillation (AF) on prognostic performance of many markers is unclear. We investigated the influence of AF on the prognostic performance of circulating biomarkers in HF. Methods N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional-pro-atrial natriuretic peptide, C-type natriuretic peptide (CNP), NT-proCNP, high-sensitivity troponin-T, high-sensitivity troponin-I, mid-regional-propeptide adrenomedullin, co-peptin, growth differentiation factor-15, soluble Suppressor of Tumorigenicitiy (sST2), galectin-3, and procalcitonin plasma concentrations were measured in a prospective, multicenter study of adults with HF. AF was defined as a previous history of AF, and/or presence of AF/flutter on baseline 12-lead electrocardiogram. The primary outcome was the composite of HF-hospitalization or all-cause mortality at 2 years. Results Among 1099 patients (age 62 ± 12years, 28% female), 261(24%) patients had AF. Above-median concentrations of all biomarkers were independently associated with increased risk of the primary outcome. Significant interactions with AF were detected for galectin-3 and sST2. In considering NT-proBNP for additive risk stratification, sST2 (adjusted hazard ratio [AHR]1.85, 95%confidence interval [C.I.] 1.17-2.91) and galectin-3 (AHR1.85, 95%C.I. 1.09-2.45) were independently associated with increased primary outcome only in the presence of AF. The prognostic performance of sST2 was also stronger in AF for all-cause mortality (AF: AHR2.82, 95%C.I. 1.26-6.21; non-AF: AHR1.78, 95% C.I. 1.14-2.76 without AF), while galectin-3 predicted HF-hospitalization only in AF (AHR1.64, 95%C.I. 1.03-2.62). Conclusions AF modified the prognostic utility of selected guideline-endorsed HF-biomarkers. Application of markers for prognostic purposes in HF requires consideration of the presence or absence of AF. Clinical trial registration ACTRN12610000374066

Galectin-3 predicts cardiovascular events in patients with type-2 diabetes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Lorenzo-Almoros ◽  
A Pello ◽  
A Acena ◽  
J Martinez-Milla ◽  
N Tarin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Plasma Levels ◽  
Cardiovascular Events ◽  
Primary Outcome ◽  
Funding Source ◽  
Increased Risk ◽  
Galectin 3 ◽  
Secondary Outcomes

Abstract Introduction Type-2 diabetes mellitus (T2DM) is associated with early and severe atherosclerosis. However, few biomarkers can predict cardiovascular events in this population. Methods We followed 964 patients with coronary artery disease (CAD), assessing at baseline galectin-3, monocyte chemoattractant protein-1 (MCP-1) and N-terminal fragment of brain natriuretic peptide (NT-proBNP) plasma levels. Secondary outcomes were acute ischemia and heart failure or death. Primary outcome was the combination of the secondary outcomes. Results Male patients were 75.0% in T2DM and 76.6% in the non-T2DM subgroup (p=0.609). Age was 61.0 (54–72) and 60.0 (51–71) years, respectively (p=0.092). 232 patients had T2DM. Patients with T2DM showed higher MCP-1 [144 (113–195) vs. 133 (105–173) pg/ml, p=0.006] and galectin-3 [8.3 (6.5–10.5) vs. 7.8 (5.9–9.8) ng/ml, p=0.049] levels. Median follow-up was 5.39 years (2.81- 6.92). Galectin-3 levels were associated with increased risk of the primary outcome in T2DM patients [HR 1.57 (1.07–2.30); p=0.022], along with a history of cerebrovascular events. Treatment with clopidogrel was associated with lower risk. In contrast, NT-proBNP and MCP-1, but not galectin-3, were related to increased risk of the event in non-diabetic patients [HR 1.21 (1.04–1.42); p=0.017 and HR 1.23 (1.05–1.44); p=0.012, respectively], along with male sex and age. Galectin-3 was also the only biomarker that predicted the development of acute ischemic events and heart failure or death in T2DM patients, while in non-diabetics MCP-1 and NT-proBNP, respectively, predicted these events. Conclusion In CAD patients, cardiovascular events are predicted by galectin-3 plasma levels in patients with T2DM, and by MCP-1 and NT-proBNP in those without T2DM. Effect of Gal-3 on the primary endpoint Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Insituto de Salud Carlos III

B-Type natriuretic peptide predicts major adverse cardiac and cerebrovascular events after catheter ablation of atrial fibrillation: insights from AF frontier ablation registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Kato ◽  
K Usuda ◽  
H Tada ◽  
T Tsuda ◽  
K Takeuchi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Natriuretic Peptide ◽  
Cardiovascular Events ◽  
Curve Analysis ◽  
Funding Source ◽  
Coronary Syndrome ◽  
Cerebrovascular Events

Abstract Background High plasma B-Type natriuretic peptide (BNP) level is associated with cardiac events or stroke in patients with atrial fibrillation (AF). However, it is still unknown whether BNP predicts worse clinical outcomes after catheter ablation ofAF. Purpose We aimed to see if plasma BNP level is associated with major adverse cardiac and cerebrovascular events (MACCE) after catheter ablation of AF. Methods We retrospectively analyzed 1,853 participants (73.1% men, mean age 63.3±10.3 years, 60.7% paroxysmal AF) who received first catheter ablation of AF with pre-ablation plasma BNP level measurement and completed follow-up more than 3 months after the procedure from AF Frontier Ablation Registry, a multicenter cohort study in Japan. We evaluated an association between plasma BNP level before catheter ablation and first MACCE in cox-regression hazard models adjusted for known risk factors. MACCE were defined as stroke/transient ischemic attack (TIA), cardiovascular events or all-cause death. Results The mean plasma BNP level was 120.2±3.7 pg/mL. During a mean follow-up period of 21.9 months, 57 patients (3.1%) suffered MACCE (ischemic stroke 8 [14.0%], hemorrhagic stroke 5 [8.8%], TIA 5 [8.8%], hospitalization for heart failure 11 [19.2%], acute coronary syndrome 9 [15.8%], hospitalization for other cardiovascular events 8 [14.0%] and all-cause death 11 [19.2%]). Plasma BNP level of patients with MACCE were significantly higher than those without MACCE (291.7±47.0 vs 114.7±3.42 pg/mL, P<0.001). Multivariate analysis revealed that plasma BNP level (hazard ratio [HR] per 10 pg/mL increase 1.014; 95% confidence interval [CI] 1.005–1.023; P=0.001), baseline age (HR 1.052; 95% CI 1.022–1.084; P=0.001), heart failure (HR 2.698; 95% CI 1.512–4.815; P=0.001), old myocardial infarction (HR 3.593; 95% CI 1.675–7.708; P=0.001) and non-ischemic cardiomyopathy (HR 2.676; 95% CI 1.337 - 5.355; P=0.005) were independently associated with MACCE. At receiver-operating characteristic curve analysis, plasma BNP level before catheter ablation ≥162.7 pg/mL was the best threshold to predict MACCE (area under the curve: 0.71). Kaplan-Meier curve analysis (Figure) showed that the cumulative incidence of MACCE was significantly higher in patients with a BNP ≥162.7 pg/mL than in those with a BNP below 162.7 pg/mL (HR 4.85; 95% CI 2.86–8.21; P<0.001). Conclusions Elevation of plasma BNP level was independently related to the increased risk of MACCE after catheter ablation ofAF. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Bristol-Meiers Squibb

scholarly journals Quantification of fibroblast growth factor 23 and N-terminal pro-B-type natriuretic peptide to identify patients with atrial fibrillation using a high-throughput platform: A validation study

PLoS Medicine ◽  
2021 ◽  
Vol 18 (2) ◽  
pp. e1003405
Author(s):  
Winnie Chua ◽  
Jonathan P. Law ◽  
Victor R. Cardoso ◽  
Yanish Purmah ◽  
Georgiana Neculau ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Natriuretic Peptide ◽  
High Throughput ◽  
Fibroblast Growth Factor 23 ◽  
High Sensitivity ◽  
Fibroblast Growth ◽  
C Statistic

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

Association of biomarkers of inflammation with hospitalization for heart failure and death in patients with atrial fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A.P Benz ◽  
S Aeschbacher ◽  
P Krisai ◽  
S Blum ◽  
P Meyre ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Plasma Levels ◽  
Incidence Rates ◽  
Adverse Outcomes ◽  
Funding Source ◽  
All Cause Mortality ◽  
Hs Crp ◽  
Multivariable Adjustment ◽  
Inflammation Score

Abstract Background Hospitalization for heart failure and death are among the most common adverse clinical outcomes in patients with atrial fibrillation (AF). The underlying mechanisms are poorly understood. Purpose We hypothesised that inflammation, quantified by plasma levels of C-reactive protein (CRP) and interleukin 6 (IL-6), is independently associated with hospitalization for heart failure and death in a large, contemporary cohort of AF patients. Methods Patients with established AF and 65 years of age or older were enrolled in two large, prospective, multicentre cohort studies in Switzerland. Plasma levels of high-sensitivity (hs) CRP and IL-6 were measured from frozen EDTA plasma samples obtained at baseline. Using these two biomarkers, we calculated an inflammation score ranging from 0 to 4 (1 point for each biomarker between the 50th and 75th percentile, 2 points for each biomarker above the 75th percentile). We constructed multivariable Cox proportional hazards models to quantify the associations of hs-CRP, IL-6 and the inflammation score with time to first hospitalization for heart failure and time to all-cause mortality, respectively. Results A total of 3,784 patients with AF (median age 72 years, 28% women, 24% with a prior history of heart failure and 84% anticoagulation use at baseline) were followed for a median (interquartile range [IQR]) of 4.0 (2.9–5.1) years. The median (IQR) plasma levels of hs-CRP and IL-6 at baseline were 1.64 (0.81–3.69) mg/L and 3.42 (2.14–5.60) pg/mL, respectively. The incidence rates of hospitalization for heart failure and death were 3.04 and 2.80 per 100 person-years, respectively. After multivariable adjustment, both biomarkers were significantly associated with the risk of hospitalization for heart failure (per increase in 1 standard deviation [SD], adjusted hazard ratio [aHR] 1.22, 95% confidence interval [CI] 1.11–1.34 for log-transformed hs-CRP, and aHR 1.48, 95% CI 1.35–1.62 for log-transformed IL-6) and death (per increase in 1 SD, aHR 1.40, 95% CI 1.27–1.54 for log-transformed hs-CRP, and aHR 1.67, 95% CI 1.53–1.81 for log-transformed IL-6). Incidence rates of hospitalization for heart failure increased from 1.34 to 7.31 per 100 person-years across categories of the inflammation score (Figure 1). A strong relationship persisted after multivariable adjustment. Similar findings were observed for all-cause mortality. Conclusions Inflammation is a strong predictor of hospitalization for heart failure and death in patients with AF. Targeting inflammation may be a promising treatment strategy to improve outcomes in these patients at high risk for adverse outcomes. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Swiss National Science Foundation

scholarly journals Identification of the optimal hsTnI cut-off value for risk stratification of normotensive patients with pulmonary embolism

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Ebner ◽  
N Guddat ◽  
K Keller ◽  
M.C Merten ◽  
M.H Lerchbaumer ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Risk Stratification ◽  
Troponin I ◽  
Adverse Outcome ◽  
High Sensitivity ◽  
Receiver Operating Curve ◽  
Funding Source ◽  
Prognostic Relevance ◽  
High Sensitivity Troponin ◽  
All Cause Mortality

Abstract Background/Introduction While numerous studies confirmed the prognostic role of high-sensitivity troponin T (hsTnT) in pulmonary embolism (PE), the prognostic relevance of high-sensitivity troponin I (hsTnI) is inappropriately studied and disease specific cut-off values remain undefined. Purpose To investigate the prognostic relevance of hsTnI in normotensive PE patients, establish the optimal cut-off value for risk stratification and compare the prognostic performances of hsTnI and hsTnT. Methods Consecutive PE patients enrolled in a prospective single-centre registry between 09/2008 and 04/2018 were studied. Using receiver operating curve analysis, an optimised hsTnI cut-off concentration was identified and the prognostic value for the prediction of in-hospital adverse outcomes (PE-related death, cardiopulmonary resuscitation or vasopressor treatment) and all-cause mortality analysed. Results We analysed data from 459 PE patients (age 69 [interquartile range (IQR) 57–77] years, 52% female). Patients who suffered an in-hospital adverse outcome (4.8%) had higher median hsTnI concentrations compared to those with a favorable clinical course (57 [IQR 22–197] vs. 15 [IQR 10–86] pg/ml, p=0.03). A hsTnI cut-off value of 16 ng/ml provided the best prognostic performance and predicted an in-hospital adverse outcome (Odds ratio [OR] 6.5, 95% confidence interval [CI] 1.9–22.4) and all-cause mortality (OR 3.7, 95% CI 1.0–13.3). Between female and male patients, no relevant differences in hsTnI concentrations (17 [IQR 10–97] vs. 17 [IQR 10–92] pg/ml, p=0.79) or optimized cut-off values (17 pg/ml and 19 pg/ml, respectively) were observed. Stratification of patients to risk classes according to the 2019 European Society of Cardiology (ESC) algorithm revealed no differences if calculated based on either hsTnI or hsTnT (Table). Conclusions Our findings confirm the prognostic relevance of hsTnI in normotensive PE. An optimal hsTnI cut-off value of 16 pg/ml predicted in-hospital adverse outcome and all-cause mortality. The use of sex specific cut-off values does not appear necessary. Importantly, our results suggest that hsTnI and hsTnT can be used interchangeably for risk stratification. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was supported by the German Federal Ministry of Education and Research (BMBF 01EO1503). BRAHMS GmbH, part of Thermo Fisher Scientific, Hennigsdorf/Berlin, Germany provided financial support for biomarker measurements. The sponsor was neither involved in biomarker measurements, statistical analyses, writing of the abstract nor had any influence on the scientific contents.

scholarly journals Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure – a Mendelian randomization study in the FINRISK cohort

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Boerschel ◽  
B Geelhoed ◽  
T Niiranen ◽  
A.S Havulinna ◽  
C.J.K Fouodo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Causal Relationship ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Mendelian Randomization ◽  
Causal Relation ◽  
Risk Scores ◽  
Funding Source ◽  
Nucleotide Polymorphisms

Abstract Background Natriuretic peptides are extensively studied biomarkers for atrial fibrillation (AF) and heart failure (HF). Their role in the pathogenesis of both diseases is not entirely understood and in previous studies several single nucleotide polymorphisms (SNPs) at the NPPA-NPPB locus associated with natriuretic peptides have been identified. Purpose We investigated whether a causal relationship exists between natriuretic peptides and AF as well as HF using a Mendelian randomization approach. Methods N-terminal pro B-type natriuretic peptide (NT-proBNP) (N=6669), B-type natriuretic peptide (BNP) (N=6674) and mid-regional pro atrial natriuretic peptide (MR-proANP) (N=6813) were measured in the FINRISK 1997 cohort. Thirty common SNPs related to NT-proBNP, BNP and MR-proANP were selected from prior studies. We performed six Mendelian randomizations for all three natriuretic peptide biomarkers and for both outcomes, AF and HF separately. Polygenic risk scores (PRS) based on multiple SNPs were used as the genetic instrumental variable in Mendelian randomizations. Results PRS were significantly associated with the three natriuretic peptides. PRS were not significantly associated with incident AF nor HF. Most cardiovascular risk factors showed significant confounding percentages, but no association with PRS. A causal relation, other than a weak one, is unlikely. Conclusion In our Mendelian randomization approach, based on common genetic variation at the NPPA-NPPB locus, associations of the common polymorphisms with natriuretic peptides and the protein biomarkers themselves with incident disease could be confirmed. A strong causal relationship between natriuretic peptides and incidence of AF as well as HF was ruled out. Therapeutic approaches targeting natriuretic peptides will therefore very likely work through indirect mechanisms. Comparison of hazard ratios Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme, German Ministry of Research and Education

The effect of body mass index on clinical outcomes in patients with newly diagnosed atrial fibrillation in the GARFIELD-AF registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C.J.F Camm ◽  
A.J Camm ◽  
S Virdone ◽  
J.-P Bassand ◽  
D.A Fitzmaurice ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Body Mass Index ◽  
Risk Factor ◽  
Body Mass ◽  
Funding Source ◽  
Newly Diagnosed ◽  
Risk Of Mortality ◽  
All Cause Mortality

Abstract Introduction Higher body mass index (BMI) is associated with a higher risk of atrial fibrillation (AF). However, previous evidence has suggested an inverse association between BMI and risk of AF outcomes. Purpose To explore the association between BMI and outcomes in those with newly diagnosed AF in the GARFIELD-AF registry. Methods GARFIELD-AF is an international registry of consecutively recruited patients aged ≥18 years with newly diagnosed AF and ≥1 stroke risk factor. Data were collected prospectively on 52,080 patients. Participants with missing or extreme BMI values and those without two-year follow-up were excluded. Cox proportional hazard models were used to estimate the effect of BMI on the risk of outcomes. Models were adjusted for age, sex, ethnicity, smoking, alcohol, and ≥moderate chronic kidney disease. Where appropriate participants were divided into groups based on BMI. Restricted cubic splines were used to assess non-linear relationships. Results BMI and outcome data were available for 40,495 patients. Those with higher BMI were generally younger, and more likely to have pre-existing hypertension, diabetes, or vascular disease (Table). Underweight patients received anticoagulation less often than those in other groups (60.3% vs 67.9%, respectively). During follow-up, 2,801 participants (6.9%) died and 603 (1.5%) had new/worsening heart failure. Following adjustment for potential confounders, a U-shaped relationship was seen between BMI and all-cause mortality and new/worsening heart failure (Figure). For all-cause mortality, the lowest risk was at 30kg/m2. Below this level, there was an 8% higher risk of mortality (95% confidence interval (CI) 6 to 9%) per 1kg/m2 lower BMI. Above 30kg/m2, there was a 5% higher risk of mortality per 1kg/m2 higher BMI (95% CI 4 to 7%). For new/worsening heart failure, the lowest risk was at 25kg/m2. Above this level, 1kg/m2 higher BMI was associated with an 5% higher risk (95% CI 13 to 6%). Conclusions BMI was an important risk factor for both all-cause mortality and new/worsening heart failure in AF. Those at both extremes of BMI are at higher risk. BMI and selected outcomes Funding Acknowledgement Type of funding source: Private company. Main funding source(s): The GARFIELD-AF registry is funded by an unrestricted research grant from Bayer AG.

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