In post-mortem material, structural changes in the atria were not associated with age, but were significantly correlated with presence of AF and its severity. Our findings suggest that age-related changes per se are unlikely to be the sole cause of advanced fibrosis underlying AF.

No abstract

Objectives To assess the predictive accuracy of conventional cardiovascular risk factors for incident heart failure(HF) and atrial fibrillation(AF) and the added benefit of multiple biomarkers reflecting diverse pathophysiological pathways. Background HF and AF are interrelated cardiac diseases associated with substantial morbidity and mortality and increasing incidence. Data on prediction and prevention of these diseases in healthy individuals is limited. Methods In 5,187 individuals from the community-based Malmö Diet and Cancer study, we studied the performance of conventional risk factors and six biomarkers including midregional pro-atrial natriuretic peptide(MR-proANP), N-terminal pro-B-type natriuretic peptide(Nt-proBNP), midregional pro-adrenomedullin, cystatin C, C-reactive protein(CRP) and copeptin. Results During a mean follow-up of 14 years,112 individuals were diagnosed with HF and 284 individuals with AF. Nt-proBNP(HR=1.63 per SD,95%CI=1.29–2.06,p<0.001), CRP(HR=1.57 per SD,95%CI=1.28–1.94,p<0.001) and MR-proANP(HR=1.26 per SD,95%CI=1.02-1-56,p=0.03) predicted incident HF independently of conventional risk factors and other biomarkers. MR-proANP(HR=1.62,95%CI=1.42-1.84,p<0.001) and CRP(HR=1.18,95%CI=1.03–1.34,p=0.01) independently predicted AF. Addition of biomarkers to conventional risk factors improved C-statistics from 0.815 to 0.842 for HF and from 0.732 to 0.753 for AF and the Integrated discriminatory index for both diseases(p<0.001). Net reclassification improvement with biomarkers was observed in 22% of individuals for HF(NRI,p<0.001) and in 7% for AF(NRI,p=0.06), mainly due to up-classification of individuals who developed disease(HF:29%,AF:19%). Addition of CRP to natriuretic peptides did not improve discrimination or reclassification. Conclusions Conventional cardiovascular risk factors predict incident HF and AF with reasonable accuracy in middle-aged individuals free from disease. Natriuretic peptides, but not other biomarkers, improve discrimination modestly for both diseases above and beyond conventional risk factors and substantially improve classification for HF.

The validity of atrial fibrillation (AF) diagnoses in national registers for use as endpoints in prospective studies has not been evaluated. We studied the validity of AF diagnoses in Swedish national hospital discharge and cause of death registers and the occurrence of and risk factors for AF in a middle-aged Swedish population using these registers. Our study included the 30,447 individuals(age 44-73) who attended baseline visits in 1991-1996 of the Malmö Diet and Cancer study. Individuals with a first AF diagnosis were identified by record linkage with national registers. A subset of cases was randomly selected for validation by examination of electrocardiograms and patient records. Electrocardiograms were available in 98%of the validation sample (95% definitive AF, 3% no AF).The 2% with ECGs unavailable had probable AF. Baseline AF prevalence was 1.3%, higher in men and increased with age. During 11.2 years of follow-up 1430 first AF diagnoses occurred. Risk factors were age, hypertension, BMI,diabetes, history of heart failure, history of myocardial infarction and, in men but not women, current smoking.The strongest risk factors were history of heart failure(hazard ratio men 4.5, women 8.7) and myocardial infarction(hazard ratio men 2.0, women 1.8). The largest population-attributable risks were observed for hypertension (men 38%, women 34%) and obesity (men 11%, women 10%).In conclusion, case misclassification of AF in national registers is small, indicating feasibility of use in prospective studies. Hypertension and obesity account for large portions of population risk in middle-aged individuals with low prevalence of manifest cardiac disease.

Objectives This study was designed to assess the clinical course and to identify risk factors for life-threatening events in patients with long-QT syndrome (LQTS) with normal corrected QT (QTc) intervals. Background Current data regarding the outcome of patients with concealed LQTS are limited. Methods Clinical and genetic risk factors for aborted cardiac arrest (ACA) or sudden cardiac death (SCD) from birth through age 40 years were examined in 3,386 genotyped subjects from 7 multinational LQTS registries, categorized as LQTS with normal-range QTc (≤440 ms [n = 469]), LQTS with prolonged QTc interval (>440 ms [n = 1,392]), and unaffected family members (genotyped negative with ≤440 ms [n = 1,525]). Results The cumulative probability of ACA or SCD in patients with LQTS with normal-range QTc intervals (4%) was significantly lower than in those with prolonged QTc intervals (15%) (p < 0.001) but higher than in unaffected family members (0.4%) (p < 0.001). Risk factors ACA or SCD in patients with normal-range QTc intervals included mutation characteristics (transmembrane-missense vs. nontransmembrane or nonmissense mutations: hazard ratio: 6.32; p = 0.006) and the LQTS genotypes (LQTS type 1:LQTS type 2, hazard ratio: 9.88; p = 0.03; LQTS type 3:LQTS type 2, hazard ratio: 8.04; p = 0.07), whereas clinical factors, including sex and QTc duration, were associated with a significant increase in the risk for ACA or SCD only in patients with prolonged QTc intervals (female age >13 years, hazard ratio: 1.90; p = 0.002; QTc duration, 8% risk increase per 10-ms increment; p = 0.002). Conclusions Genotype-confirmed patients with concealed LQTS make up about 25% of the at-risk LQTS population. Genetic data, including information regarding mutation characteristics and the LQTS genotype, identify increased risk for ACA or SCD in this overall lower risk LQTS subgroup.