Outcomes of Primary vs. Delayed Strategy of Implanting a Cardiac Monitor for Unexplained Syncope.

Objective: Implantable cardiac monitors (ILR) have an important role in diagnosing unexplained syncope. However, outcomes of primary vs. delayed ILR implantation after initial syncope evaluation have not been explored. Methods: A total of 1705 patients with unexplained syncope were prospectively enrolled in the SYSTEMA (Syncope Study of Unselected Population in Malmö) cohort. Patients who underwent cardiovascular autonomic testing (CAT) and ILR were grouped into those referred to CAT after ILR implantation (primary ILR) and those in whom ILR was indicated after CAT (post-CAT ILR). Results: One-hundred-and-fifteen patients (6.7%) received ILRs. ILR recipients were older (58 vs. 52 years; p = 0.002), had more syncope recurrences (6 vs. 4; p < 0.001), more traumatic falls (72% vs. 53%; p < 0.001), and less prodrome (40% vs. 55%; p = 0.005) than patients without ILRs. During follow-up ≥16 months after ILR, 67 (58%) had normal sinus rhythm, 10 (8.7%) had sinus arrest, 10 (8.7%) AV-block, 13 (11.3%) atrial fibrillation, 9 (7.8%) supraventricular tachycardia, 4 (3.5%) sinus tachycardia and 2 (1.7%) ventricular tachycardia with clinical symptom reproduction. There were 52 patients (45%) in the primary-ILR group and 63 (55%) in the post-CAT ILR group. Proportions of negative ILR monitoring (17/52 vs. 25/63; p = 0.56) and pacemaker implantations (7/52 vs. 15/63; p = 0.23) did not differ between groups. Baseline ECG conduction disorders predicted pacemaker implantation (n = 11/17; odds ratio:10.6; 95%CI: 3.15−35.3; p < 0.001). CAT was more often positive (73% vs. 40%; p < 0.001) in primary-ILR group. Conclusions: Primary ILR implantation was associated with more positive CAT compared with delayed ILR implantation, but negative monitoring and pacemaker implantations were not different between groups. ECG conduction disorders predicted subsequent pacemaker implantation.

Diagnostic value of exercise-induced changes in circulating high sensitive troponin T in stable chest pain patients.

OBJECTIVE: We investigated the diagnostic value of exercise-induced increase in cardiac Troponin T (cTnT) in stable chest pain subjects. METHODS: CTnT was measured before and 20 h after an exercise test in 157 subjects suspected of coronary artery disease (CAD). RESULTS: CAD subjects (n = 41) had higher baseline cTnT levels compared to non-CAD subjects (n = 116), 6.39 ng/l and 3.00 ng/l, respectively, p < 0.0001, and were more likely to increase in cTnT (70.7% versus 27.6%, p < 0.0001). Net Reclassification Index for the combined variable was 19%, p = 0.02. CONCLUSIONS: Exercise-induced increase in cTnT was found to be associated with CAD and cTnT measurements improved the diagnostic evaluation.

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.

Prognostic value of high sensitive C-reactive protein in subjects with silent myocardial ischemia.

OBJECTIVES: The aim of this study was to evaluate the prognostic value of high sensitive C-reactive protein (CRP) in subjects with silent myocardial ischemia (SMI). DESIGN: In total, 678 healthy men and women aged 55 to 75 years with no history of cardiovascular disease or stroke were included. High-sensitive CRP and 48-hour ambulatory ECG monitoring were performed. The primary endpoint was the combined endpoint of death and myocardial infarction. RESULTS: The median follow-up time was 76 months. Seventy-seven subjects (11.4%) had SMI. The combined endpoint occurred in 26% of the subjects with SMI and 14% of the subjects without SMI (P = .005). SMI had a poor prognosis in the group with an elevated CRP ≥ 3.0 µg/mL (hazard ratio, 3.46; 95% confidence interval, 1.67-7.16; P = .001) compared with the group of subjects with SMI and a low CRP <3.0 µg/mL (hazard ratio, 1.37; 95% confidence interval, 0.63-2.98; P = .54). CONCLUSIONS: In apparently healthy subjects, a low level of CRP <3.0 µg/mL selects a low-risk subgroup, despite the presence of SMI.

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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Excessive supraventricular ectopic activity and increased risk of atrial fibrillation and stroke.

BACKGROUND: Prediction of stroke and atrial fibrillation in healthy individuals is challenging. We examined whether excessive supraventricular ectopic activity (ESVEA) correlates with risk of stroke, death, and atrial fibrillation in subjects without previous stroke or heart disease. METHODS AND RESULTS: The population-based cohort of the Copenhagen Holter Study, consisting of 678 healthy men and women aged between 55 and 75 years with no history of cardiovascular disease, atrial fibrillation, or stroke, was evaluated. All had fasting laboratory tests and 48-hour ambulatory ECG monitoring. ESVEA was defined as >or=30 supraventricular ectopic complexes (SVEC) per hour or as any episodes with runs of >or=20 SVEC. The primary end point was stroke or death, and the secondary end points were total mortality, stroke, and admissions for atrial fibrillation. Median follow-up was 6.3 years. Seventy subjects had SVEC>or=30/h, and 42 had runs of SVEC with a length of >or=20 SVEC. Together, 99 subjects (14.6%) had ESVEA. The risk of primary end point (death or stroke) was significantly higher in subjects with ESVEA compared with those without ESVEA after adjustment for conventional risk factors (hazard ratio=1.64; 95% confidence interval, 1.03 to 2.60; P=0.036). ESVEA was also associated with admissions for atrial fibrillation (hazard ratio=2.78; 95% confidence interval, 1.08 to 6.99; P=0.033) and stroke (hazard ratio=2.79; 95% confidence interval, 1.23 to 6.30; P=0.014). SVEC, as a continuous variable, was also associated with both the primary end point of stroke or death and admissions for atrial fibrillation. CONCLUSIONS: ESVEA in apparently healthy subjects is associated with development of atrial fibrillation and is associated with a poor prognosis in term of death or stroke.