Schmidt, H.

Tiotropium versus salmeterol for the prevention of exacerbations of COPD (Article)

2011-03-24T00:00:00Z

BACKGROUND: Treatment guidelines recommend the use of inhaled long-acting bronchodilators to alleviate symptoms and reduce the risk of exacerbations in patients with moderate-tovery-severe chronic obstructive pulmonary disease (COPD) but do not specify whether a long-acting anticholinergic drug or a β2-agonist is the preferred agent. We investigated whether the anticholinergic drug tiotropium is superior to the β2-agonist salmeterol in preventing exacerbations of COPD. METHODS: In a 1-year, randomized, double-blind, double-dummy, parallel-group trial, we compared the effect of treatment with 18 μg of tiotropium once daily with that of 50 μg of salmeterol twice daily on the incidence of moderate or severe exacerbations in patients with moderate-to-very-severe COPD and a history of exacerbations in the preceding year. RESULTS: A total of 7376 patients were randomly assigned to and treated with tiotropium (3707 patients) or salmeterol (3669 patients). Tiotropium, as compared with salmeterol, increased the time to the first exacerbation (187 days vs. 145 days), with a 17% reduction in risk (hazard ratio, 0.83; 95% confidence interval [CI], 0.77 to 0.90; P<0.001). Tiotropium also increased the time to the first severe exacerbation (hazard ratio, 0.72; 95% CI, 0.61 to 0.85; P<0.001), reduced the annual number of moderate or severe exacerbations (0.64 vs. 0.72; rate ratio, 0.89; 95% CI, 0.83 to 0.96; P = 0.002), and reduced the annual number of severe exacerbations (0.09 vs. 0.13; rate ratio, 0.73; 95% CI, 0.66 to 0.82; P<0.001). Overall, the incidence of serious adverse events and of adverse events leading to the discontinuation of treatment was similar in the two study groups. There were 64 deaths (1.7%) in the tiotropium group and 78 (2.1%) in the salmeterol group. CONCLUSIONS: These results show that, in patients with moderate-to-very-severe COPD, tiotropium is more effective than salmeterol in preventing exacerbations. Copyright

Association of health behaviour with heart rate variability: A population-based study (Article)

2010-11-25T00:00:00Z

Background: Reduced heart rate variability (HRV), a non-invasive marker of autonomic dysfunction, and an unhealthy lifestyle are associated with an increased morbidity and mortality of cardiovascular diseases (CVD). The autonomic dysfunction is a potential mediator of the association of behavioural risk factors with adverse health outcomes. We studied the association of HRV with behavioural risk factors in an elderly population.Methods: This analysis was based on the cross-sectional data of 1671 participants (age range, 45-83 years) of the prospective, population-based Cardiovascular Disease, Living and Ageing in Halle (CARLA) Study. Physical activity, smoking habits, alcohol consumption and dietary patterns were assessed in standardized interviews. Time and frequency domain measures of HRV were computed from 5-min segments of highly standardized 20-min electrocardiograms. Their association with behavioural risk factors was determined by linear and non-parametric regression modelling.Results: There were only weak and inconsistent associations of higher physical activity, moderate consumption of alcohol, and non-smoking with higher time and frequency domain HRV in both sexes, and no association with dietary pattern. Results changed only marginally by excluding subjects with CVD, diabetes mellitus and use of cardioactive medication.Conclusion: We hypothesized that HRV is associated with behavioural factors and therefore might be a mediator of the effect of behavioural risk factors on CVD, but this hypothesis was not confirmed by our results. These findings support the interpretation that there may be no true causal association of behavioural factors with HRV.

Cardiovascular diseases, risk factors and short-term heart rate variability in an elderly general population: The CARLA study 2002-2006 (Article)

2009-03-01T00:00:00Z

Background: A reduced heart rate variability (HRV) is associated with worse prognosis, increased incidence of cardiovascular disease (CVD) and mortality. There are conflicting results and a lack of population-based data regarding the association of HRV with CVD risk factors and its potential role as independent cause or mediator of CVD risk. Methods: Cross-sectional data of a population-based cohort including 1,779 women and men aged 45-83 years were used to analyse associations of time and frequency domain measures of HRV (derived from 5-min ECG segments) with age, behavioural and biomedical risk factors and disease in the whole sample and in a "healthy" subgroup. Results: Age was inversely associated with all measures of HRV (mean standard deviation of normal intervals across 10-year age-groups 32.1, 26.9, 27.1 and 24.8 ms in women, 29.3, 25.9, 23.8 and 25.7 ms in men). There was no association of physical activity, current smoking or alcohol with HRV. In age-adjusted models, triglycerides, glucose, waist-to-hip ratio and diabetes were inversely associated with HRV in men and women, and low/high density cholesterol and hypertension in men only (up to 43% difference across risk factor quartiles). Multivariable adjustment and restriction to the "healthy" subgroup attenuated the associations. Conclusions: We found only weak and inconsistent associations of HRV with cardiovascular risk factors. However, these results as well as those from previous studies are still compatible with the hypothesis that short-term HRV may be a marker of ill health or a mediator of the effect of selected biomedical risk factors on CVD.

Genetic Determinants of Cerebral Small Vessel Disease (Doctoral Thesis)

2005-09-14T00:00:00Z

The study demonstrates the firstevidence of a significant association between the T/T148 genotype at the .-fibrinogen gene and carotid atherosclerosis. The results should be interpreted with caution, given the small number of T/T homozygotes. A larger cohort will ultimately be required to confirm whether or not this association is real.

Angiotensinogen gene promoter haplotype and microangiopathy-related cerebral damage: results of the Austrian Stroke Prevention Study (Article)

2001-01-01T00:00:00Z

BACKGROUND AND PURPOSE: Microangiopathy-related cerebral damage (MARCD) is a common finding in the elderly. It may lead to cognitive impairment and gait disturbances. Arterial hypertension and age are the most important risk factors. We assessed the association between MARCD and sequence alterations in the promoter region of the angiotensinogen (AGT) gene. METHODS: We studied 410 randomly selected community-dwelling individuals aged 50 to 75 years. MARCD was defined as early confluent or confluent white matter hyperintensities or lacunes on a 1.5-T MRI. The AGT promoter was analyzed by temporal temperature gradient gel electrophoresis and automated sequencing. RESULTS: We detected 4 polymorphic sites, at positions -6, -20, -153, and -218. They created 5 haplotypes, which we coded as A (-6:g, -20:a, -153:g, -218g), B (-6:a, -20:c, -153:g, -218:g), C (-6:a, -20:c, -153:a, -218:g), D (-6:a, -20:a, -153:g, -218:g), and E (-6:a, -20:a, -153:g, -218:a). MARCD was seen in 7 subjects (63.6%) carrying 2 copies of the B haplotype (B/B), in 12 subjects (38.7%) carrying 1 copy of the B haplotype in the absence of the A haplotype (B+/A-), but in only 70 subjects (19.0%) in the remaining cohort (P:<0.001). The odds ratios for the B/B and the B+/A- genotypes were 8.0 (95% CI, 2.1 to 31.1; P:=0.003) and 1.8 (95% CI, 0.8 to 4.2; P:=0.14) after adjustment for possible confounders. CONCLUSIONS: The B haplotype of the AGT promoter in the absence of the wild-type A haplotype might represent a genetic susceptibility factor for MARCD.