Atrial fibrillation progression risk factors and associated cardiovascular outcome in well-phenotyped patients: data from the AF-RISK study.

AIMS: Atrial fibrillation (AF) is a progressive disease, but identifying patients at risk for AF progression is challenging. We aimed to identify factors associated with AF progression. METHODS AND RESULTS: Atrial fibrillation progression was assessed in 392 patients with recent-onset paroxysmal or persistent AF included in the prospective, observational, multicentre identification of a risk profile to guide atrial fibrillation (AF-RISK) study. Progression of AF was assessed by Holter monitoring and 2-week event recorder at baseline and 1-year follow-up. AF progression was defined as: (i) doubling in AF burden at 1 year compared to baseline with a minimum AF burden of 10% in paroxysmal AF; or (ii) transition from paroxysmal to persistent or permanent AF; or (iii) persistent to permanent AF. Age was 60 ± 11 years, 62% were men, and 83% had paroxysmal AF. At 1 year, 52 (13%) had AF progression (11% in paroxysmal; 26% in persistent AF). Multivariable logistic regression showed that left atrial volume [odds ratio (OR) per 10 mL 1.251, 95% confidence interval (CI) 1.078-1.450; P < 0.001], N-terminal pro-B-type natriuretic peptide (NT-proBNP; OR per standard deviation increase 1.583, 95% CI 1.099-2.281; P = 0.014), and plasminogen activator inhibitor-1 (PAI-1; OR per standard deviation increase 0.660, 95% CI 0.472-0.921; P = 0.015) were associated with AF progression. In an additional follow-up of 1.9 (0.9-3.3) years patients with AF progression developed more cardiovascular events and all-cause mortality (12.4%/year vs. 2.3%/year, P < 0.001). CONCLUSION: Atrial fibrillation progression occurred in 13% of patients with recent-onset AF during 1-year follow-up. Left atrial volume, NT-proBNP, and PAI-1 were associated with AF progression. Patients with AF progression had a higher event rate. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT01510210.

Young-onset atrial fibrillation: Sex differences in clinical profile, progression rate and cardiovascular outcome.

BACKGROUND: Women are underrepresented in major atrial fibrillation (AF) trials. In addition, data regarding clinical profile and outcome in young AF patients is limited. Therefore we aimed to investigate the clinical profile, AF progression rate and cardiovascular outcome between sexes in patients with young-onset AF. METHODS: A total of 497 patients with AF-onset <60 years of age were included. Data on clinical profile and cardiovascular outcome were prospectively collected. RESULTS: Of 497 patients, 125 (25%) patients were women. Women had more often familial AF (34% versus 22%, P = 0.012) and obesity (26% versus 18%, P = 0.03). Men had more often coronary artery disease (11% versus 5%, P = 0.04), a longer PR interval [163 (148-180) versus 150 (138-167) ms, P < 0.001] and higher left ventricular mass index [82 (71-96) versus 72 (61-83) g/m2, P < 0.001]. During a median follow-up of 7.0 (2.7-10.0) years AF progression rate was comparable (HR 2.03 for men versus women, 95%CI 0.92-4.48; P = 0.08), and no difference in cardiovascular events was observed between women and men (Log rank P-value = 0.07). CONCLUSIONS: In young patients with AF, clinical patient profile is different between the sexes but did not result in differences in cardiovascular outcome.

Atrial fibrillation progression and outcome in patients with young-onset atrial fibrillation.

Aims: Clinicians increasingly encounter patients with young-onset atrial fibrillation (AF). Aim is to study clinical profile, AF progression, and outcome of patients with young-onset AF. Methods and results: A total of 468 patients with paroxysmal or persistent AF starting <60 years of age were included. Clinical profile, AF progression, defined as development of permanent AF, and cardiovascular events were prospectively collected. Onset of AF was at 46 ± 10 years, 354 (76%) were men, 329 (70%) had paroxysmal AF, 50 (11%) had AF without risk factors or comorbidities, and 118 (25%) had familial AF. Hypertension was present in 207 (44%), heart failure in 44 (9%). During 7.2 (2.7-10.0) years, 56 (11%) had AF progression (2.0%/year). Progression rate in patients receiving antiarrhythmic drugs or pulmonary vein isolation during follow-up was not different from patients who did not. Multivariable determinants of AF progression included diastolic blood pressure [hazard ratio (HR) 1.031, 95% confidence interval (95% CI) 1.007-1.055; P = 0.010] and left atrial size (HR 1.055, 95% CI 1.012-1.099; P = 0.012). Cardiovascular events occurred in 61 patients (13%; 2.4%/year). Multivariable determinants of cardiovascular events were PR interval (HR 1.015, 95% CI 1.005-1.024; P = 0.002) and left ventricular hypertrophy (HR 3.429, 95% CI 1.712-6.868; P = 0.001). Yearly event rate was higher in patients who had developed AF progression, compared to patients without progression [4.9 (2.3-9.0)% vs. 1.9 (1.4-2.6)%; P = 0.006]. Conclusion: Nine of 10 patients with young-onset AF had risk factors and comorbidities, 25% had familial AF. Atrial fibrillation progression to permanent AF and cardiovascular events occurred in 2.0% and 2.4% per year, respectively. Cardiovascular events increased after AF progression had occurred.

Relation of renal dysfunction with incident atrial fibrillation and cardiovascular morbidity and mortality: The PREVEND study.

AIMS: Renal dysfunction is a risk factor for cardiovascular disease, including atrial fibrillation (AF) and mortality. However, the exact pathobiology linking different renal dysfunction measures, such as albumin excretion or glomerular filtration rate (GFR), to cardiovascular- and AF risk are unclear. In this study, we investigated the association of several renal function measures and incident AF, and whether the relation between renal measures and outcomes is modified by AF. METHODS AND RESULTS: We examined 8265 individuals (age 49 ± 13 years, 50% women) included in the PREVEND study. We used albumin excretion (morning void and 24-h urine samples), serum creatinine, cystatin C, and Cystatin C-based, creatinine-based, and creatinine-cystatin C-based GFR as renal function measures; results: During a follow-up of 9.8 ± 2.3 years, 267 participants (3.2%) developed AF. In the multivariate-adjusted model, GFR, estimated by creatinine, cystatin C, or the combination was not associated with incident AF. However, increased albumin excretion was strongly associated with incident AF; urine albumin concentration and excretion (HRmorning void 1.10, P = 0.005 and HR24-hr collection 1.05, P = 0.033) and albumin creatinine ratio (HRmorning void 1.05, P = 0.010 and HR24-hr collection 1.06, P < 0.001). Interaction terms of incident AF and renal measures were not significant for incident cerebrovascular events, peripheral vascular events, ischemic heart disease, heart failure, and mortality. CONCLUSION: In this community-based cohort, increased albumin excretion, and not GFR, was associated with incident AF, independent of established cardiovascular risk factors. Incidence of AF did not largely alter the association of renal dysfunction and cardiovascular outcomes.

Metabolomic Profiling in Relation to New-Onset Atrial Fibrillation (from the Framingham Heart Study).

Previous studies have shown several metabolic biomarkers to be associated with prevalent and incident atrial fibrillation (AF), but the results have not been replicated. We investigated metabolite profiles of 2,458 European ancestry participants from the Framingham Heart Study without AF at the index examination and followed them for 10 years for new-onset AF. Amino acids, organic acids, lipids, and other plasma metabolites were profiled by liquid chromatography-tandem mass spectrometry using fasting plasma samples. We conducted Cox proportional hazard analyses for association between metabolites and new-onset AF. We performed hypothesis-generating analysis to identify novel metabolites and hypothesis-testing analysis to confirm the previously reported associations between metabolites and AF. Mean age was 55.1 ± 9.9 years, and 53% were women. Incident AF developed in 156 participants (6.3%) in 10 years of follow-up. A total of 217 metabolites were examined, consisting of 54 positively charged metabolites, 59 negatively charged metabolites, and 104 lipids. None of the 217 metabolites met our a priori specified Bonferroni corrected level of significance in the multivariate analyses. We were unable to replicate previous results demonstrating associations between metabolites that we had measured and AF. In conclusion, in our metabolomics approach, none of the metabolites we tested were significantly associated with the risk of future AF.