Stig Hansen

Clarithromycin for 2 Weeks for Stable Coronary Heart Disease: 6-Year Follow-Up of the CLARICOR Randomized Trial and Updated Meta-Analysis of Antibiotics for Coronary Heart Disease

Objectives: We have reported increased 2.6-year mortality in clarithromycin- versus placebo-exposed stable coronary heart disease patients, but meta-analysis of randomized trials in coronary heart disease patients showed no significant effect of antibiotics on mortality. Here we report the 6-year mortality of clarithromycin- versus placebo-exposed patients and updated meta-analyses. Methods: Centrally randomized, placebo controlled multicenter trial. All parties were blinded. Analyses were by intention to treat. Meta-analyses followed the Cochrane Collaboration methodology. Results: We randomized 4,372 patients with stable coronary heart disease to clarithromycin 500 mg (n = 2,172) or placebo (n = 2,200) once daily for 2 weeks. Mortality was followed through public register. Nine hundred and twenty-three patients (21.1%) died. Six-year mortality was significantly higher in the clarithromycin group (hazard ratio 1.21, 95% confidence interval 1.06–1.38). Adjustment for entry characteristics (sex, age, prior myocardial infarction, center, and smoking) did not change the results (1.18, 1.04–1.35). Addition of our data to that of other randomized trials on antibiotics for patients with coronary heart disease versus placebo/no intervention (17 trials, 25,271 patients, 1,877 deaths) showed a significantly increased relative risk of death from antibiotics of 1.10 (1.01–1.20) without heterogeneity. Conclusions: Our results stress the necessity to consider carefully the strength of the indication before administering antibiotics to patients with coronary heart disease.

Peripheral Bone Mineral Density and Different Intensities of Physical Activity in Children 6–8 Years Old: The Copenhagen School Child Intervention Study

This study aimed to evaluate the association between objectively measured habitual physical activity and calcaneal and forearm bone mineral density (BMD, g/cm2), one mechanically more loaded and one less loaded skeletal region, in children aged 6–8 years. BMD was measured in 297 boys and 265 girls by peripheral dual-energy X-ray absorptiometry in the forearm and calcaneus. An accelerometer registered the level of physical activity during 4 days (2 weekdays and the weekend). Weight, height, and skinfold thickness were measured. In order to establish thresholds (count · min−1) for bone-stimulating physical activity, we evaluated different definitions of vigorous physical activity. The boys had 3.2% higher distal forearm bone mineral content (BMC, P < 0.001) and 4.5% higher distal forearm BMD (P < 0.001) than the girls. They also carried out 9.7% more daily physical activity and spent 14.6–19.0% more time in vigorous physical activity (all P < 0.05) compared to the girls. In contrast, the girls had 3.8% higher calcaneal BMC (P < 0.01) and 2.5% higher calcaneal BMD (P < 0.05) than the boys. Both calcaneal and forearm BMD were significantly related to total time of daily physical activity as well as with intense physical activity above all the chosen cut-off points (all P < 0.05). The β value for mean count · min−1 physical activity was significantly lower than that for all the chosen cut-off points of vigorous activity both for calcaneal and distal forearm BMD. This study suggests that both habitual daily physical activity and amount of vigorous physical activity in children aged 6–8 years are associated with appendicular BMD.

Sex Differences in Bone Size and Bone Mineral Density Exist before Puberty. The Copenhagen School Child Intervention Study (CoSCIS)

BackgroundThe aim of this study was to provide normative data of bone mineral density (BMD; g/cm2) of the forearm and the calcaneus, evaluated by peripheral dual X ray absorbtiometry (DXA), in children aged 6 to 7 years of age and to evaluate the association with anthropometrics and sex.Material and methods368 boys and 326 girls with a mean age of 6.7 ± 0.4 years participated. BMD was measured by DXA in the forearms and the os calcanei, with average values presented in this report. Measurements of weight, height, skinfolds, the width of distal radius and ulna, and the femur condyles were collected and body composition estimated from skinfolds measurements.ResultsThere was no difference in calcaneus BMD when comparing boys and girls, whereas the boys had 4.5% (0.013 g/cm2) higher forearm BMD than the girls (P < 0.001). Calcaneal BMD (mean 0.318 g/cm2) was 11% higher than forearm BMD (mean 0.283 g/cm2). Linear relationship was found between calcaneus BMD and weight (partial r = 0.50), Fat free mass (FFM) (partial r = 0.50), Fat mass (FM) (partial r = 0.45), % body fat (partial r = 0.29) and knee width (partial r = 0.46), all P < 0.000 respectively. Adjusted for weight the relationship between calcaneus BMD and FFM, FM, %body fat and knee width disappeared. There were significant relationships between the forearm BMD and weight (partial r = 0.37), FFM (partial r = 0.39), FM (partial r = 0.28), %body fat (partial r = 0.14) and wrist width (partial r = 0.24), all P < 0.000 respectively. Adjusted for body weight, the relationship remained between forearm BMD and FFM (r = 0.10), FM (R = −0.10) and % body fat (r = −0.12), all P < 0.000 respectively. Children measured in the spring had 3.5% (P < 0.01) higher calcaneus BMD than children measured in the winter.ConclusionSeven year old boys have higher BMD in the forearm but not in the calcaneus in comparison with girls of a similar age. Body weight is the best predictor of calcaneus BMD, accounting for 25% of the variance whereas body weight and FFM are the best predictors of forearm BMD, each accounting for 17% of the variance, respectively.

Intervention with Clarithromycin in Patients with Stable Coronary Heart Disease

Background: There is a growing body of evidence linking Chlamydia pneumoniae to the progression of coronary heart disease. Smaller studies have indicated that intervention with macrolide antibiotics might reduce coronary events in patients with cardiovascular diseases. Objective: To describe the design of a large-scale intervention study on the effects of a macrolide antibiotic on coronary events in patients with stable coronary heart disease (documented myocardial infarction and/or angina pectoris). Methods: This study is a double-blind, randomised, placebo-controlled, multicentre study with parallel groups. Patients are randomised to 14 days of treatment with clarithromycin (500 mg, once daily) or matching placebo. The follow-up period is 2 years, and the primary end point is a composite end point of death, non-fatal myocardial infarction or unstable angina pectoris, whichever occurs first. Recruitment began in October 1999 and will be completed in 2000. In total, 4,600 patients will be randomised. Prospectives: The study is powered to detect a reduction in coronary events of 20%. Also, the study will examine the question of whether the presence of a C. pneumoniae antibody titre is associated with a significantly increased risk of future coronary events. Finally, in the case of a significant outcome, it will be possible to test whether the effect is restricted to patients with C. pneumoniae antibodies only, or to a universal effect without any coherence to C. pneumoniae antibodies.

QT intervals and QT dispersion determined from a 12-lead 24-hour Holter recording in patients with coronary artery disease and patients with heart failure.

Background: QT dispersion is considered an index of spatial inhomogeneity of repolarization duration and increased dispersion of ventricular repolarization is supposed to increase the risk of ventricular arrhythmia. Circadian variation in QT dispersion was investigated.

Statin Treatment Prevents Increased Cardiovascular and All-Cause Mortality Associated With Clarithromycin in Patients With Stable Coronary Heart Disease

In the CLARICOR trial, significantly increased cardiovascular (CV) and all-cause mortality in stable patients with coronary heart disease were observed after a short course of clarithromycin. We report on the impact of statin treatment at entry on the CV and all-cause mortality. The multicenter CLARICOR trial randomized patients to oral clarithromycin (500 mg daily; n = 2172) versus matching placebo (daily; n = 2201) for 2 weeks. Patients were followed through public databases. In the 41% patients on statin treatment at entry, no significant effect of clarithromycin was observed on CV (hazard ratio [HR], 0.68, 95% confidence interval [CI], 0.38-1.22; P = 0.20) or all-cause mortality (HR, 1.08; 95% CI, 0.71-1.65; P = 0.72) at 2.6-year follow up. In the patients not on statin treatment at entry, clarithromycin was associated with a significant increase in CV (HR, 1.90; 95% CI, 1.34-2.67; P = 0.0003; statin-clarithromycin interaction P = 0.0029) and all-cause mortality (HR, 1.33; 95% CI, 1.05-1.67; P = 0.016; statin-clarithromycin interaction P = 0.41). Multivariate analysis and 6-year follow up confirmed these results. Concomitant statin treatment in stable patients with coronary heart disease abrogated the observed increased CV mortality associated with 2 weeks of clarithromycin.

Circadian Variation in QT Dispersion Determined from a 12-Lead Holter Recording: A Methodological Study of an Age- and Sex-Stratified Group of Healthy Subjects

Background: QT dispersion is considered to reflect inhomogeneity of myocardial repolarization.

Validering af “Om mig selv”—et spørgeskema til børn

Grønfeldt, V. et al. (2003). Validating “About my self”—an questionnaire for children. Nordisk Psykologi, 55, 94–106. One of the aims in the “Ballerup-projekt” is to investigate approximately 1000, 7 years old childrens “thoughts about themselves”. For that purpose a questionnaire, for group administration in a schoolsetting, has been developed and validated. The questionnaire contains 30 items monitoring the childrens concept of themselves with regard to social accept, academic competence, physical competence, social competence, thriving in school and social status. 254 7–8 years old children have tried the questionnaire and 90 of these have retried after 10–12 weeks. The response has been investigated with concern for the childrens understanding of the structure and content. The response has also been statistically described, examined for missing values, internal factors, gender differences and reproducibility. The questionnaire has been found valid for the purpose, especially for a short term measure.