Severe hypokalaemia can aggravate arrhythmia tendency and prognosis, but less is known about risk of mild hypokalaemia, which is a frequent finding. We examined the associations between mild hypokalaemia and ambulatory cardiac arrhythmias and their prognosis.
Subjects from the cohort of the 'Copenhagen Holter Study' (n = 671), with no history of manifest cardiovascular (CV) disease or stroke, were studied. All had laboratory tests and 48-h ambulatory electrocardiogram (ECG) recording. The median follow-up was 6.3 years. p-Potassium was inversely associated with frequency of premature ventricular complexes (PVCs) especially in combination with diuretic treatment (r = -0.22, P = 0.015). Hypokalaemia was not associated with supraventricular arrhythmias. Subjects at lowest quintile of p-potassium (mean 3.42, range 2.7-3.6 mmol/L) were defined as hypokalaemic. Cardiovascular mortality was higher in the hypokalaemic group (hazard ratio and 95% confidence intervals: 2.62 (1.11-6.18) after relevant adjustments). Hypokalaemia in combination with excessive PVC worsened the prognosis synergistically; event rates: 83 per 1000 patient-year in subjects with both abnormalities, 10 and 15 per 1000 patient-year in those with one abnormality, and 3 per 1000 patient-year in subjects with no abnormality. One variable combining hypokalaemia with excessive supraventricular arrhythmias gave similar results in univariate analysis, but not after multivariate adjustments.
In middle-aged and elderly subjects with no manifest heart disease, mild hypokalaemia is associated with increased rate of ventricular but not supraventricular arrhythmias. Hypokalaemia interacts synergistically with increased ventricular ectopy to increase the risk of adverse events.
Coronary artery disease (CAD) is accountable for more than 7 million deaths each year according to the World Health Organization (WHO). In a European population 80% of patients diagnosed with CAD are overweight and 31% are obese. Physical inactivity and overweight are major risk factors in CAD, thus central strategies in secondary prevention are increased physical activity and weight loss.
In a randomized controlled trial 70 participants with stable CAD, age 45-75, body mass index 28-40 kg/m2 and no diabetes are randomized (1:1) to 12 weeks of intensive exercise or weight loss both succeeded by a 40-week follow-up. The exercise protocol consist of supervised aerobic interval training (AIT) at 85-90% of VO2peak 3 times weekly for 12 weeks followed by supervised AIT twice weekly for 40 weeks. In the weight loss arm dieticians instruct the participants in a low energy diet (800-1000 kcal/day) for 12 weeks, followed by 40 weeks of weight maintenance combined with supervised AIT twice weekly. The primary endpoint of the study is change in coronary flow reserve after the first 12 weeks' intervention. Secondary endpoints include cardiovascular, metabolic, inflammatory and anthropometric measures.
The study will compare the short and long-term effects of a protocol consisting of AIT alone or a rapid weight loss followed by AIT. Additionally, it will provide new insight in mechanisms behind the benefits of exercise and weight loss. We wish to contribute to the creation of effective secondary prevention and sustainable rehabilitation strategies in the large population of overweight and obese patients diagnosed with CAD.
Approximately 30% of ischemic strokes have an unknown cause. Increased atrial ectopy (AE) increases the risk of atrial fibrillation (AF), but the risk of stroke in patients with increased AE is unknown.
This study aimed to examine whether increased AE and short atrial runs increase the risk of stroke beyond incident AF.
Data were collected during a 15-year follow-up of the Copenhagen Holter Study cohort with 678 men and women between 55 and 75 years of age, with no earlier history of cardiovascular disease, stroke, or AF. Study subjects underwent 48-h ambulatory electrocardiography, fasting blood tests, and clinical examination. Excessive supraventricular ectopic activity (ESVEA) was defined as the presence of either =30 premature atrial contractions (PACs)/hour daily or any runs of =20 PACs.
Ninety-nine subjects (15%) demonstrated ESVEA. After adjusting for baseline risk factors, ESVEA was associated with ischemic stroke when censoring subjects at time of AF (hazard ratio [HR]: 1.96; 95% confidence interval [CI]: 1.10 to 3.49) or when modeling AF as a time-varying exposure (HR: 2.00; 95% CI: 1.16 to 3.45). Among subjects with ESVEA who developed a stroke, 14.3% had diagnosed AF before their stroke. The incidence of stroke in subjects with ESVEA and a CHA2DS2-VASc (congestive heart failure, hypertension, age 75 years or older, diabetes mellitus, previous stroke or transient ischemic attack, vascular disease, age 65 to 74 years, female) score of =2 was 2.4% per year, comparable to the risk observed in AF. In day-to-day analysis, ESVEA was a consistent finding.
ESVEA was associated with an increased risk of ischemic stroke beyond manifest AF in this middle-aged and older population. Stroke was more often the first clinical presentation, rather than AF, in these study subjects.
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.
Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark; Laboratory for Molecular Cardiology, Rigshospitalet, Copenhagen, Denmark; The Ion Channel Group, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Both shortening and prolongation of the QTc interval have been associated with atrial fibrillation (AF). We investigated whether 8 single nucleotide polymorphisms (SNPs) at loci previously shown to affect QTc interval duration were associated with lone AF.
We included 358 patients diagnosed with lone AF (defined as onset of AF at
Stroke is independently associated with the common conditions of hypokalemia and supraventricular ectopy, and we hypothesize that the combination of excessive supraventricular ectopic activity and hypokalemia has a synergistic impact on the prognosis in terms of stroke in the general population.
Subjects (55-75 years old) from the Copenhagen Holter Study cohort (N=671) with no history of atrial fibrillation or stroke were studied-including baseline values of potassium and ambulatory 48-hour Holter monitoring. Excessive supraventricular ectopic activity is defined as =30 premature atrial complexes per hour or any episodes of runs of =20. Hypokalemia was defined as plasma-potassium =3.6 mmol/L. The primary end point was ischemic stroke. Cox models were used.
Hypokalemia was mild (mean, 3.4 mmol/L; range, 2.7-3.6). Hypokalemic subjects were older (67.0±6.94 versus 64.0±6.66 years; P
To evaluate the effects of weight loss on heart rate (HR) and heart rate variability (HRV) parameters in overweight postmenopausal women.
Forty-nine overweight postmenopausal women with an average body mass index of 28.8 ± 1.9 kg/m(2) underwent a 12-week dietary weight-loss programme. Accepted variables for characterization of HRV were analysed before and after the weight loss by 24-h ambulatory ECG monitoring; mean and standard deviation for the time between normal-to-normal complexes (MeanNN and SDNN, respectively), and the mean of standard deviations of normal-to-normal intervals for each 5-min period (SDNNindex). Baseline body fat mass (FM%) and changes in body composition was determined by dual X-ray absorptiometry. Before and after the weight-loss period, total abdominal fat, intra-abdominal fat (IAAT), and subcutaneous abdominal fat (SCAT) were measured by single-slice MRI at L3.
The weight loss of 3.9 ± 2.0 kg was accompanied by an improvement of HRV. SDNN increased by 9.2% (p = 0.003) and SDNNindex increased by 11.4% (p = 0.0003). MeanNN increased by 2.4%, reflecting a decrease in mean heart rate from 74.1 to 72.3 beats/min (p = 0.033). Systolic blood pressure (SBP) decreased by 2.7%, total cholesterol by 5.1% and high-sensitivity C-reactive protein (hsCRP) by 15.8% (p = 0.002). Improvements in SDNN and cholesterol were correlated with weight loss (r = -0.329, p = 0.024 and r = 0.327, p = 0.020, respectively) but changes in HR, SBP, and hsCRP were not. IAAT and the IAAT/SCAT-ratio were found to be negatively associated with HRV parameters but changes in body composition were not associated with changes in HRV.
The observed improvement of HRV seems to be facilitated by weight loss. IAAT and the IAAT/SCAT ratio were found to be associated with low HRV.
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.
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.
Fifty-two subjects developed cancer and 83 subjects died during follow-up. The upper quintile of monocyte number (median 0.44×10?/L, lower 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 0.1×10?/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)).
In healthy middle-aged and elderly community-dwelling Danes circulating monocytes independently predicted incident cancer and mortality.
AIMS: We aimed to determine the prevalence and prognostic significance of daily-life silent myocardial ischaemia (SMI) in healthy middle-aged and elderly subjects with no previous heart disease. METHODS AND RESULTS: Six hundred and seventy-eight healthy men and women between 55 and 75 years of age and with no history of cardiovascular disease or stroke were included. Baseline examinations included physical examination, fasting laboratory testing, and 48 h ambulatory electrocardiogram monitoring. An episode of ischaemia was defined by a down-sloped or horizontal ST depression of at least 1 mm at a duration of at least 1 min. Seventy-seven subjects (11.4%) had SMI. All participants were followed for up to 5 years. In 77 subjects with SMI, 16 (20.7%) had an event (death or myocardial infarction). In 601 subjects without SMI, 50 (8.3%) had an event. The hazard ratios for SMI in relation to cardiac and combined events after correction for conventional risk factors were 3.1 [(1.24-7.97), P=0.016] and 1.97 [(1.06-3.69), P=0.033], respectively. CONCLUSION: SMI as detected by Holter monitoring was detected in 11.4% of these subjects and was associated with more than three-fold increase in the cardiac event rate after correction for risk factors, implying that this test could be used to identify high-risk individuals among these subjects.
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).
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.
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