Glutathione S-transferase polymorphisms, passive smoking, obesity, and heart rate variability in nonsmokers

BACKGROUND: Disturbances of heart rate variability (HRV) may represent one pathway by which second-hand smoke (SHS) and air pollutants affect cardiovascular morbidity and mortality. The mechanisms are poorly understood. OBJECTIVES: We investigated the hypothesis that oxidative stress alters cardiac autonomic control. We studied the association of polymorphisms in oxidant-scavenging glutathione S-transferase (GST) genes and their interactions with SHS and obesity with HRV. METHODS: A total of 1,133 nonsmokers > 50 years of age from a population-based Swiss cohort underwent ambulatory 24-hr electrocardiogram monitoring and reported on lifestyle and medical history. We genotyped GSTM1 and GSTT1 gene deletions and a GSTP1 (Ile105Val) single nucleotide polymorphism and analyzed genotype-HRV associations by multiple linear regressions. RESULTS: Homozygous GSTT1 null genotypes exhibited an average 10% decrease in total power (TP) and low-frequency-domain HRV parameters. All three polymorphisms modified the cross-sectional associations of HRV with SHS and obesity. Homozygous GSTM1 null genotypes with > 2 hr/day of SHS exposure exhibited a 26% lower TP [95% confidence interval (CI), 11 to 39%], versus a reduction of -5% (95% CI, -22 to 17%) in subjects with the gene and the same SHS exposure compared with GSTM1 carriers without SHS exposure. Similarly, obese GSTM1 null genotypes had, on average, a 22% (95% CI, 12 to 31%) lower TP, whereas with the gene present obesity was associated with only a 3% decline (95% CI, -15% to 10%) compared with nonobese GSTM1 carriers. CONCLUSIONS: GST deficiency is associated with significant HRV alterations in the general population. Its interaction with SHS and obesity in reducing HRV is consistent with an impact of oxidative stress on the autonomous nervous system

Follow-up of the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA 2) 1991-2003: methods and characterization of participants

OBJECTIVES: The Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) was designed to investigate the health effects from long-term exposure to air pollution. METHODS: The health assessment at recruitment (1991) and at the first reassessment (2001-3) consisted of an interview about respiratory health, occupational and other exposures, spirometry, a methacholine bronchial challenge test, end-expiratory carbon monoxide (CO) measurement and measurement for atopy. A bio bank for DNA and blood markers was established. Heart rate variability was measured using a 24-hour ECG (Holter) in a random sample of participants aged 50 years and older. Concentrations of nitrogen dioxide (NO2), sulphur dioxide (SO2), ozone (O3) and particulates in ambient air have been monitored in all study areas since 1991. Residential histories collected over the 11 year follow-up period coupled with GIS modelling will provide individual long-term air pollutant exposure estimates. RESULTS: Of 9651 participants examined in 1991, 8715 could be traced for the cohort study and 283 died. Basic information about health status was obtained for 8047 individuals (86% of alive persons), 6 528 individuals (70%) agreed to the health examination and 5 973 subjects (62%) completed the entire protocol. Non-participants in the reassessment were on average younger than participants and more likely to have been smokers and to have reported respiratory symptoms in the first assessment. Average weight had increased by 5.5 kg in 11 years and 28% of smokers in 1991 had quit by the time of the reassessment

Effect of physical activity on heart rate variability in normal weight, overweight and obese subjects: results from the SAPALDIA study

Many studies have demonstrated an association of both a sedentary lifestyle and a high body mass index (BMI) with greater risk for cardiovascular disease. Within the prospective SAPALDIA cohort (Swiss cohort Study on Air Pollution and Lung Diseases in Adults), we investigated whether regular exercise was protective against reduced heart rate variability (HRV), a clinically relevant predictor of cardiovascular morbidity and mortality, and whether adverse effects of obesity and weight gain on HRV were modified by regular exercise. Twenty-four-hour electrocardiograms were recorded in 1,712 randomly selected SAPALDIA participants aged >or=50, for whom BMI was assessed in the years 1991 and 2001-2003. Other examinations included an interview investigating health status (especially respiratory and cardiovascular health and health relevant behaviours including physical activity) and measurements of blood pressure, body height and weight. The association between regular physical activity and HRV and interactions with BMI and BMI change was assessed in multivariable linear regression analyses. Compared to sedentary obese subjects, SDNN (standard deviation of all RR intervals) was 14% (95% CI: 8-20%) higher in sedentary normal weight subjects; 19% (CI: 12-27%) higher in normal weight subjects exercising regularly >or=2 h/week; and 19% (CI: 11-28%) higher in obese subjects exercising regularly >or=2 h/week. Compared with sedentary subjects who gained weight, those who gained weight but did exercise regularly had a 13% higher SDNN (CI: 7-20%). Regular physical exercise has strong beneficial effects on cardiac autonomic nervous function and thus appears to offset the negative effect of obesity on HRV

Determinants of inadequate use of pediatric health care services in Switzerland

Background and current state of (inter)national research: Exposure to unfavorable circumstances in childhood has been shown to have negative implications on physical, cognitive and psychological health in adulthood. Health problems in childhood should, therefore, be detected and treated at an early stage. Adequate pediatric health care, particularly preventive pediatric health screenings, play a key role in this context. In Switzerland, children and adolescents from 0-14 years are recommended to go through ten preventive health screenings. These screenings are performed at the parents’ initiative by the pediatrician or family doctor, except for two to three compulsory screenings at around the age of 6, 10 and 14 years, which are typically performed by the school medical services. However, little is known about the extent to which these screenings are performed and about potential barriers limiting the utilization of health care services. Research questions and objectives: The aim of our study is to evaluate children’s access to adequate health care in Switzerland. Specifically, we aim to identify potential inequalities in the use of pediatric health care between socioeconomic groups. Methods or hypothesis: We employ the following two strategies using a quantitative descriptive research design: - Using panel data from the school medical services in the city of Bern, we assess the extent of foregone pediatric health care in different socioeconomic groups by evaluating the incidence of untreated or inadequately treated health problems. - Using claims data from a large Swiss health insurance company, we assess the health care utilization patterns throughout childhood and the extent to which preventive health screenings are performed. Results/Discussion/Practical implications: The identification of groups at risk of inadequate health care and a better understanding of the underlying mechanisms can contribute to improving access to preventive health care services and, hence, to reducing health inequalities in childhood

Joint effect of obesity and TNFA variability on asthma: two international cohort studies

Obesity is a risk factor for asthma. Adipose tissue expresses pro-inflammatory molecules including tumour necrosis factor (TNF), and levels of TNF are also related to polymorphisms in the TNF-a (TNFA) gene. The current authors examined the joint effect of obesity and TNFA variability on asthma in adults by combining two population-based studies. The European Community Respiratory Health Survey and the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults used comparable protocols, questionnaires and measures of lung function and atopy. DNA samples from 9,167 participants were genotyped for TNFA -308 and lymphotoxin-a (LTA) +252 gene variants. Obesity and TNFA were associated with asthma when mutually adjusting for their independent effects (odds ratio (OR) for obesity 2.4, 95% confidence interval (CI) 1.7–3.2; OR for TNFA -308 polymorphism 1.3, 95% CI 1.1–1.6). The association of obesity with asthma was stronger for subjects carrying the G/A and A/A TNFA -308 genotypes compared with the more common G/G genotype, particularly among nonatopics (OR for G/A and A/A genotypes 6.1, 95% CI 2.5–14.4; OR for G/G genotype 1.7, 95% CI 0.8–3.3). The present findings provide, for the first time, evidence for a complex pattern of interaction between obesity, a pro-inflammatory genetic factor and asthma

Sex-specific effect of body weight gain on systemic inflammation in subjects with COPD: results from the SAPALDIA cohort study 2

Systemic inflammation may mediate the association between chronic obstructive pulmonary disease (COPD) and extrapulmonary comorbidities. We measured high-sensitivity C-reactive protein (hs-CRP) in COPD and quantified the effect modification by body weight change and sex. Using data from the Swiss study on Air Pollution and Lung Diseases in Adults (SAPALDIA; n = 5,479) with measurements of forced expiratory volume in 1 s (FEV(1)), body weight and hs-CRP, we examined the association of hs-CRP and categories of body weight change (lost weight and weight gained 0-5%, 5-9%, 9-14% and >14%) with fast FEV(1) decline. hs-CRP was elevated both in association with fast FEV(1) decline and body weight gain. Subjects with fast FEV(1) decline and weight gain (>14%) had higher hs-CRP (2.0 mg L(-1) for females versus 1.6 mg L(-1) for males). After adjustment for age, smoking, physical activity, hormonal therapy and diabetes, elevated hs-CRP (>3 mg) was found to be more likely in subjects with fast FEV(1) decline (OR(males) 1.38, OR(females) 1.42) and in those with weight gain >14% (OR(males) 2.04, OR(females) 4.51). The association of weight gain and fast FEV(1) decline predicts a higher level of systemic inflammation. Since the effect of weight gain on systemic inflammation is larger in females than in males, weight gain may be a risk factor for extrapulmonary comorbidities in females with COPD