Cardiovascular disease, risk factors and heart rate variability in the elderly general population: Design and objectives of the CARdiovascular disease, Living and Ageing in Halle (CARLA) Study

BACKGROUND: The increasing burden of cardiovascular diseases (CVD) in the ageing population of industrialized nations requires an intensive search for means of reducing this epidemic. In order to improve prevention, detection, therapy and prognosis of cardiovascular diseases on the population level in Eastern Germany, it is necessary to examine reasons for the East-West gradient of CVD morbidity and mortality, potential causal mechanisms and prognostic factors in the elderly. Psychosocial and nutritional factors have previously been discussed as possible causes for the unexplained part of the East-West gradient. A reduced heart rate variability appears to be associated with cardiovascular disease as well as with psychosocial and other cardiovascular risk factors and decreases with age. Nevertheless, there is a lack of population-based data to examine the role of heart rate variability and its interaction with psychosocial and nutritional factors regarding the effect on cardiovascular disease in the ageing population. There also is a paucity of epidemiological data describing the health situation in Eastern Germany. Therefore, we conduct a population-based study to examine the distribution of CVD, heart rate variability and CVD risk factors and their associations in an elderly East German population. This paper describes the design and objectives of the CARLA Study. METHODS/DESIGN: For this study, a random sample of 45–80 year-old inhabitants of the city of Halle (Saale) in Eastern Germany was drawn from the population registry. By the end of the baseline examination (2002–2005), 1750 study participants will have been examined. A multi-step recruitment strategy aims at achieving a 70 % response rate. Detailed information is collected on own and family medical history, socioeconomic, psychosocial, behavioural and biomedical factors. Medical examinations include anthropometric measures, blood pressure of arm and ankle, a 10-second and a 20-minute electrocardiogram, a general physical examination, an echocardiogram, and laboratory analyses of venous blood samples. On 200 participants, a 24-hour electrocardiogram is recorded. A detailed system of quality control ensures high data quality. A follow-up examination is planned. DISCUSSION: This study will help to elucidate pathways to CVD involving autonomic dysfunction and lifestyle factors which might be responsible for the CVD epidemic in some populations

DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders?

There is now compelling evidence that gene by environment interactions are important in the etiology of autism spectrum disorders (ASDs). However, the mechanisms by which environmental factors interact with genetic susceptibilities to confer individual risk for ASD remain a significant knowledge gap in the field. The epigenome, and in particular DNA methylation, is a critical gene expression regulatory mechanism in normal and pathogenic brain development. DNA methylation can be influenced by environmental factors such as diet, hormones, stress, drugs, or exposure to environmental chemicals, suggesting that environmental factors may contribute to adverse neurodevelopmental outcomes of relevance to ASD via effects on DNA methylation in the developing brain. In this review, we describe epidemiological and experimental evidence implicating altered DNA methylation as a potential mechanism by which environmental chemicals confer risk for ASD, using polychlorinated biphenyls (PCBs), lead, and bisphenol A (BPA) as examples. Understanding how environmental chemical exposures influence DNA methylation and how these epigenetic changes modulate the risk and/or severity of ASD will not only provide mechanistic insight regarding gene-environment interactions of relevance to ASD but may also suggest potential intervention strategies for these and potentially other neurodevelopmental disorders