Atrial ectopy and N-terminal pro-B-type natriuretic peptide as predictors of atrial fibrillation: a population-based cohort study.

AIMS: The risk of incident atrial fibrillation (AF) can be estimated by clinical parameters in the Framingham AF risk model. Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) and increased rate of premature atrial contractions (PACs) have been shown to be associated with AF, but the additive value of both of these biomarkers in the Framingham AF risk model has not been fully examined. METHODS AND RESULTS: A total of 646 subjects from the Copenhagen Holter Study (mean age 64.4 ± 6.8 years, 41.6% women) with no history of prior AF, stroke or cardiovascular disease were followed for the diagnosis of incident AF or death (median follow-up time 14.4 years). Median NT-proBNP was 6.7 pmol/L (IQR: 3.6-13.5), median PAC count was 1.4 beats/h (IQR: 0.6-4.5), 71 (11.0%) subjects developed AF, and 244 (37.8%) died. Multiple Cox regression including Framingham AF risk score, log-transformed NT-proBNP, and log-transformed PAC showed a significant increase in AF hazard risk [hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.14-1.85, P = 0.002; HR 1.23, 95% CI 1.09-1.39, P = 0.001]. The addition of PAC to the Framingham AF risk model significantly improved the time-dependent area under the receiver operating characteristic curve (AUC 65.6 vs. 72.6; P = 0.008), while the addition of NT-proBNP did not. CONCLUSION: Atrial fibrillation risk discrimination was significantly improved by the addition of PAC to the Framingham AF risk model, but not by the addition of NT-proBNP.

Troponin T and N-terminal pro B-Type natriuretic peptide and presence of coronary artery disease.

BACKGROUND: We tested the effects of exercise intensity, sampling intervals, degree of coronary artery stenosis, and demographic factors on circulating N-terminal pro B-Type natriuretic peptide (NT-pro-BNP) and cardiac Troponin T (cTnT) in subjects suspected of coronary artery disease (CAD). MATERIALS AND METHODS: A total of 242 subjects referred for diagnostic evaluation of possible CAD had blood samples obtained before, 5 min after, and again 20 h after a symptom-limited exercise test. RESULTS: Totally 40 subjects had CAD with ≥ 50% stenosis, 115 subjects had no stenosis and 87 subjects served as controls. In univariate analysis CAD-subjects had higher median baseline NT-pro-BNP-levels (85.3 ng/L) compared with non-CAD-subjects (41.3 ng/L) and controls (40.1 ng/L), both p < 0.001, but the association disappeared in multivariate analysis adjusted for age and gender. NT-pro-BNP increased similarly after exercise in CAD-subjects, non-CAD-subjects, and controls (median increase 8.14 ng/L) and the increase was positively associated with baseline NT-pro-BNP but not presence of CAD. Median baseline cTnT was 6.25 ng/L in CAD-subjects and 3.00 ng/L in non-CAD-subjects as well as controls, both p < 0.0001. Median ΔcTnT (baseline to 20 h after exercise) was higher in CAD-subjects than non-CAD-subjects and controls (0.62 ng/L vs. 0.0 ng/L, p < 0.001). A linear relationship between ΔcTnT and 'percent of predicted maximal heart rate achieved' was found in subjects with ≥ 70% stenosis (n = 24, r = 0.4067 p = 0.046). CONCLUSIONS: Baseline cTnT and ΔcTnT were found to be independently associated with CAD and also with exercise intensity in stable chest pain subjects. These properties were not identified for NT-pro-BNP.

Soluble urokinase plasminogen activator receptor, C-reactive protein and triglyceride are associated with heart rate variability in non-diabetic Danes.

BACKGROUND: Heart rate variability (HRV) is associated with an increased risk of cardiovascular morbidity and mortality. HRV is in part a function of the activity of the autonomic nervous system and has been associated with low-grade inflammation. In patients with type 2 diabetes, HRV is decreased and is a predictor of poor outcome. As HRV and its determinants in non-diabetic individuals have not been studied properly, the aim of this observational study was to evaluate possible associations between HRV vs. impaired fasting glucose, insulin resistance, lipidaemia and markers of inflammation and immune activation in these individuals. MATERIALS AND METHODS: Healthy individuals (n = 596, 55-75 years) from the community were evaluated with ambulant 48-h continuous electrocardiogram monitoring and fasting markers of lipidaemia, inflammation and immune activation, respectively. Insulin resistance was estimated by HOMA-IR. Time domain components of HRV were calculated. RESULTS: Heart rate and HRV were not associated with glucose metabolic parameters but were inversely associated with soluble urokinase plasminogen activator receptor (suPAR), high-sensitive CRP and leucocyte number (P < 0·001), respectively. Both 24-h and night-time HRV were inversely associated with plasma triglyceride, whereas HDL, LDL and total cholesterol were not. A model including suPAR, CRP, gender, triglyceride, age, systolic blood pressure, physical activity and smoking status explained 12·2% (P < 0·0001) of the 24-h HRV and 7·3% (P < 0·0001) of the night-time HRV. The single strongest factor to explain 24-h and night-time HRV appeared to be suPAR (P = 0·001 and P = 0·0067, respectively). CONCLUSION: A low HRV is not related to prediabetes, that is, insulin resistance and impaired fasting glucose, but is related to the immune and inflammatory markers suPAR and CRP and plasma triglyceride.

Resting, night-time, and 24 h heart rate as markers of cardiovascular risk in middle-aged and elderly men and women with no apparent heart disease.

AIMS: Increased heart rate (HR) is a predictor of all-cause and cardiovascular (CV) mortality. We tested which measure of HR had the strongest prognostic value in a population with no apparent heart disease. METHODS AND RESULTS: Six hundred and fifty-three men and women between the age of 55 and 75 years were included in the Copenhagen Holter Study and underwent 48 h ambulatory electrocardiographic (ECG) monitoring. Resting HR was measured after at least 10 min of rest. Twenty-four-hour HR was derived from the mean time between normal-to-normal RR intervals (MEANNN). Night-time HR was derived from a 15 min sequence between 2:00 and 2:15 a.m. The median follow-up time was 76 months, and an adverse outcome was defined as all-cause mortality and the combined endpoint of CV death, acute myocardial infarction (AMI), and revascularization. All three measures of HR were significantly associated with all-cause mortality, also after adjustment for conventional risk factors. We found an association between all three measures of HR and CV events in analyses adjusted for sex and age. However, when adjusting for CV risk factors, the association with resting HR and 24 h HR disappeared. In a fully adjusted model, only night-time HR remained in the model, hazard ratio = 1.17 (1.05-1.30), P = 0.005. CONCLUSION: In middle-aged subjects with no apparent heart disease, all measures of increased HR were associated with increased mortality and CV risk. However, night-time HR was the only parameter with prognostic importance after multivariable adjustment.

Monocyte number associated with incident cancer and mortality in middle-aged and elderly community-dwelling Danes.

BACKGROUND: Monocytes play an important role in innate immunity and exhibit prognostic value in some cancers. It was hypothesised that activation of the innate immune system through mobilisation of monocytes to tissue macrophages develops an inflammatory state associated with increased risk of cancer and mortality. METHODS: To test this hypothesis monocyte number was measured in a sample of 669 Danish men (59%) and women (41%) aged 55 to 75 years who were free of any known prevalent cancer or cardiovascular disease. The population was followed for 6.3 years, during which period incident cancers and deaths were compiled from validated national registries. RESULTS: Fifty-two subjects developed cancer and 83 subjects died during follow-up. The upper quintile of monocyte number (median 0.44×109/L, lower quintile <0.33, upper quintile >0.60) was associated with an increased risk of cancer (hazard ratio [HR] 2.00 [95% CI 1.12-3.57]) and deaths (HR 1.67 [1.03-2.72]) in univariate analyses, after correction for age and gender (cancer HR 2.15 [1.20-3.86] and death HR 1.63 [1.00-2.67]), and following additional correction for smoking habits, diabetes, systolic blood pressure, and total cholesterol (cancer HR 2.00 [1.10-3.70] and death HR 1.30 [0.78-2.16]). COX regression models, with inclusion of the aforementioned explanatory variables and added heart rate variability, alcohol use, and CRP, revealed monocyte count (per 0.1×109/L increase) to be independently associated with incident cancer (HR 1.12 (1.05-1.19)) and death (HR 1.13 (1.06-1.19)). CONCLUSIONS: In healthy middle-aged and elderly community-dwelling Danes circulating monocytes independently predicted incident cancer and mortality.

WITHDRAWN: Monocytes associate to incident cancer and mortality in man.

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