[Implementation of the principle of supported employment in Germany : Position paper of a task force of the DGPPN]. / Umsetzung der Prinzipien des Supported Employment in Deutschland : Positionspapier einer Task-Force der DGPPN.

The effects of mental diseases on the employment and working situation can be substantial. They are one of the main reasons for inability to work and reduced earning capacity. Against this background the question arises about suitable occupational reintegration measures for people with severe mental illnesses. In recent years, the principle of supported employment has been internationally shown to be increasingly more successful. In this context mentally ill people are primarily placed at a position of the first employment market and supported on-site by a job coach. This concept is inclusive, individual and evidence based. Despite proven effectiveness, it has so far been insufficiently implemented in German-speaking regions. In the future it will be a matter of considering the individual needs for assistance of mentally ill people more intensively than previously and to respond with functional and in a best-case scenario, multiprofessional and flexible offers.

How much does it hurt to be lonely? Mental and physical differences between older men and women in the KORA-Age Study.

OBJECTIVE: Loneliness has a deep impact on quality of life in older people. Findings on sex-specific differences on the experience of loneliness remain sparse. This study compared the intensity of and factors associated with loneliness between men and women. METHODS: Analyses are based on the 2008/2009 data of the KORA-Age Study, comprising 4127 participants in the age range of 64-94 years. An age-stratified random subsample of 1079 subjects participated in a face-to-face interview. Loneliness was measured by using a short German version of the UCLA-Loneliness-Scale (12 items, Likert scaled, ranging from 0 to 36 points). Multiple logistic regression analysis was conducted to analyze the associations of socio-demographic, physical, and psychological factors with loneliness. RESULTS: The mean level of loneliness did not significantly differ between men (17.0 ± 4.5) and women (17.5 ± 5.1). However, among the oldest old (≥85 years), loneliness was higher in women (p value = 0.047). Depression, low satisfaction with life, and low resilience were associated significantly with loneliness, which was more pronounced in men. Living alone was not associated with loneliness, whereas lower social network was associated with a three time higher risk for feeling lonely in both men and women. CONCLUSIONS: The extent of loneliness was equally distributed between men and women, although women were more disadvantaged regarding living arrangements as well as physical and mental health. However, loneliness was stronger associated with adverse mental health conditions in men. These findings should be considered when developing intervention strategies to reduce loneliness.

Serum potassium is associated with prediabetes and newly diagnosed diabetes in hypertensive adults from the general population: the KORA F4-study.

AIMS/HYPOTHESIS: Evidence suggests that low serum potassium concentrations or hypokalaemia induced by the intake of diuretics are associated with incident diabetes and increased risk for diabetes in persons with hypertension. We examined a possible association between serum potassium and prediabetes (defined as isolated impaired fasting glucose [i-IFG], isolated impaired glucose tolerance [i-IGT] or combined IFG/IGT), as well as known and newly diagnosed diabetes (NDD), in 32- to 81-year-old men and women with and without hypertension. METHODS: This cross-sectional analysis was based on 2,948 participants in the Cooperative Health Research in the Region of Augsburg (KORA) F4 study conducted in 2006-2008 in southern Germany. Serum concentrations of potassium were measured by indirect potentiometry. RESULTS: In the total sample there was no association between serum potassium concentrations and prediabetes. In hypertensive persons however serum potassium levels in the first and second quartile compared with the highest quartile were independently significantly associated with prediabetes after multivariable adjustment (OR for prediabetes, 2.02 [95% CI 1.27, 3.21] for quartile 2 and 2.00 [95% CI 1.27, 3.15] for quartile 1), while in persons without hypertension no association was found. In multinomial logistic regression analysis these findings could be confirmed. In hypertensive participants after multivariable adjustment the associations were statistically significant for i-IGT and NDD (i-IGT OR 1.23; NDD OR 1.41). However, in non-hypertensive persons, all associations between serum potassium levels and each of the categories of impaired glucose regulation were non-significant. CONCLUSIONS/INTERPRETATION: Serum potassium levels were independently associated with prediabetes and NDD in hypertensive adults from the general population.

[Association between the social status of city districts and health risks: multilevel analyses concerning the regional distribution of overweight, hypertension and self-rated health in Augsburg, Germany]. / Zusammenhang zwischen dem sozialen status eines stadtgebietes und den gesundheitlichen risiken seiner bewohner: ergebnisse einer mehrebenenanalyse zu übergewicht, hypertonie und gesundheitszustand am beispiel Augsburg.

INTRODUCTION: In empirical studies it has repeatedly been shown that the socioeconomic status (SES) of a region could infl uence the health status of its inhabitants, even if measures of individual SES are controlled for. This research has just started in Germany, but most studies focus on large geographical areas such as rural districts. Taking the example of districts in the city of Augsburg, the analyses focus on the question if these associations can also be found in a small-scale regional comparison. METHODS: We included 1 888 participants of the KORA S4 Survey aged 25-74 years. The city districts were grouped according to the unemployment rate (low, medium, high). The dependent variables were self-rated health and 3 risk factors (obesity, high waist-hip ratio, hypertension). Additional individual variables included are age, sex, educational level and unemployment. The analyses were based on multilevel logistic regressions. RESULTS: After adjustment for individual level variables (age, sex, education, unemployment), the analyses show a signifi cantly increased risk of 'high waist-hip ratio' in the regions with the highest unemployment rate (OR 1.53; 95 % conf. interval 1.03-2.26). A similar association was found for obesity. No signifi cant association was observed between unemployment rate on the one hand and hypertension and self-rated health on the other. CONCLUSION: Some health risks seem to be especially high in city districts characterised by a high unemployment rate. It can be concluded that interventions aimed at reducing these risks should focus on districts with high unemployment rates. Further studies are needed for an understanding of the causes behind the social and regional inequalities shown here.

[Vitamin D and multiple sclerosis : the role for risk of disease and treatment]. / Vitamin D und Multiple Sklerose : Der Stellenwert für das Erkrankungsrisiko und die Behandlung.

In addition to its important role in bone metabolism and calcium homeostasis an increasing number of beneficial effects are being attributed to vitamin D. Because of its suggested immunomodulatory capacity vitamin D deficiency or disturbance in the vitamin D metabolism might be a risk factor for the development of autoimmune diseases, such as multiple sclerosis; but supplementation with vitamin D might also be a therapeutic option. Substantial epidemiologic evidence indicates an association between vitamin D levels and risk of multiple sclerosis, suggesting vitamin D to be one of the long searched environmental factors for the development of this most common chronic inflammatory disease of the central nervous system. Less consistent are the available data for modification of the disease course in already established multiple sclerosis.This review highlights possible interactions between vitamin D and multiple sclerosis and focuses on its putative involvement in the pathogenesis and its possible role for treatment of multiple sclerosis. In particular the as yet insufficiently investigated therapeutic aspect is currently being addressed in several high quality clinical trials.

Age at menarche is associated with prediabetes and diabetes in women (aged 32-81 years) from the general population: the KORA F4 Study.

AIMS/HYPOTHESIS: The aim of this study was to examine the association between age at menarche and prediabetes as well as diabetes, considering confounding factors and the possible mediating role of adult obesity. METHODS: This cross-sectional study analysed data on 1,503 women aged 32-81 years from the German population-based KORA (Cooperative Health Research in the Region of Augsburg, South Germany) F4 Study (2006-2008). Data were collected by standardised interviews, physical examinations, and whole blood and serum measurements, including administration of an OGTT in non-diabetic participants. RESULTS: Of the 1,503 women, 226 showed a prediabetic state (impaired fasting glucose and/or impaired glucose tolerance) and 140 persons had diabetes (45 participants with previously undiagnosed diabetes and 95 with known diabetes). In Poisson regression analysis, age at menarche was significantly inversely associated with prediabetes or diabetes after adjustment for year of birth (RR 0.88; 95% CI 0.82, 0.94, p < 0.0001 per additional year of menarche) and after additional adjustment for a number of confounding factors (RR 0.88; 95% CI 0.83, 0.94, p = 0.0001). Further adjustment for current BMI slightly attenuated the association with prediabetes or diabetes (RR 0.89; 95% CI 0.83, 0.95, p = 0.0009), but the association remained clearly significant. CONCLUSIONS/INTERPRETATION: Age at menarche seems to be inversely associated with prediabetes and diabetes independent of confounding factors including current BMI. Women at risk for diabetes might be identified by a history of young age at menarche.

[Relevance of 'subjective social status' for health risks and health status - results from the KORA-F4-study]. / Einfluss des subjektiven Sozialstatus auf gesundheitliche Risiken und Gesundheitszustand - Ergebnisse der KORA-F4-Studie.

OBJECTIVES: In public health research, social status is usually assessed by objective indicators such as educational level and income. Recent studies have shown the importance of including 'subjective social status (SSS)'. The aim of this study is to analyse the influence of SSS on health for the first time in Germany, and to find out if there is an effect over and above the objective indicators of social status. METHODS: The KORA F4 study took place in 2006-2008 in the region of Augsburg, Southern Germany, with a study population of 3 080 men and women aged 32-81 years. SSS was assessed by a single question with 6 possible responses. For the analyses, 3 SSS categories were differentiated: low, middle and high. The following dependent variables were included: self-rated health (SRH), hypertension (uncontrolled), diabetes, metabolic syndrome, hay fever, no participation in medical cancer prevention, obesity (assessed by body mass index and waist-hip-ratio), smoking, physical inactivity. Logistic regression models were used to estimate the influence of SSS (e. g. adjusted for educational level and income). RESULTS: About 25% of the participants group themselves into the lowest SSS-category. Without adjustment for educational level and income, SSS is negatively associated with SRH, hypertension, diabetes, metabolic syndrome, obesity, no participation in medical cancer prevention, smoking and physical inactivity; as expected the association with hay fever is positive. After adjustment for educational level and income, not all of these associations remain significant. Some of the adjusted odds ratios (OR) for SSS differ considerably when stratified by gender, for example concerning the variable 'physical inactivity': The comparison of 'SSS low' vs. 'SSS high' shows for men OR 2.35 (95% confidence interval (CI) 1.57-3.50) and for women OR 3.58 (95% CI 2.34-5.47). CONCLUSION: The results from this study strongly suggest that SSS is an important indicator of social status (to date largely disregarded in public health research). Thus, SSS should be applied in addition to other indicators of social status such as educational level and income. The associations with SSS depend on the health indicator studied. Also, sometimes there are large differences when stratified by gender. Further research is needed to fully understand the determinants of SSS and its impact on health.

Implications of prevalent and incident diabetes mellitus on left ventricular geometry and function in the ageing heart: the MONICA/KORA Augsburg cohort study.

BACKGROUND AND AIM: It is unclear to what extent diabetes modulates the ageing-related adaptations of cardiac geometry and function. METHODS AND RESULTS: We examined 1005 adults, aged 25-74 years, from a population-based survey at baseline in 1994/5 and at follow-up in 2004/5. We compared persistently non-diabetic individuals (ND; no diabetes at baseline and at follow-up, n=833) with incident (ID; non-diabetic at baseline and diabetic at follow-up, n=36) and with prevalent diabetics (PD; diabetes at baseline and follow-up examination, n=21). Left ventricular (LV) geometry and function were evaluated by echocardiography. Statistical analyses were performed with multivariate linear regression models. Over ten years the PD group displayed a significantly stronger relative increase of LV mass (+9.34% vs. +23.7%) that was mediated by a more pronounced increase of LV end-diastolic diameter (+0% vs. +6.95%) compared to the ND group. In parallel, LA diameter increased (+4.50% vs. +12.7%), whereas ejection fraction decreased (+3.02% vs. -4.92%) more significantly in the PD group. Moreover, at the follow-up examination the PD and ID groups showed a significantly worse diastolic function, indicated by a higher E/EM ratio compared with the ND group (11.6 and 11.8 vs. 9.79, respectively). CONCLUSIONS: Long-standing diabetes was associated with an acceleration of age-related changes of left ventricular geometry accumulating in an eccentric remodelling of the left ventricle. Likewise, echocardiographic measures of systolic and diastolic ventricular function deteriorated more rapidly in individuals with diabetes.

[Multimorbidity and successful aging: the population-based KORA-Age study]. / Multimorbidität und erfolgreiches Altern: Ein Blick auf die Bevölkerung im Rahmen der KORA-Age-Studie.

BACKGROUND: The objective of the KORA-Age research consortium is to assess the determinants and consequences of multimorbidity in the elderly and to look into reasons for successful aging in the general public. PATIENTS AND METHODS: In the KORA-Age cohort study 9,197 persons were included who where born in the year 1943 or before and participants of previous KORA cohort studies conducted between 1984 and 2001 (KORA: Cooperative Health Research in the Region of Augsburg). The randomized intervention study KORINNA (Coronary infarct follow-up treatment in the elderly) tested a nurse-based case management program with 338 patients with myocardial infarct and included an evaluation in health economics. RESULTS: A total of 2,734 deaths were registered, 4,565 participants submitted a postal health status questionnaire and 4,127 participants were interviewed by telephone (response 76.2% and 68.9% respectively). A gender and age-stratified random sample of the cohort consisting of 1,079 persons took part in a physical examination (response 53.8%). CONCLUSION: The KORA-Age consortium was able to collect data in a large population-based sample and is contributing to the understanding of multimorbidity and successful aging.

Genes and lifestyle factors in obesity: results from 12,462 subjects from MONICA/KORA.

BACKGROUND: Data from meta-analyses of genome-wide association studies provided evidence for an association of polymorphisms with body mass index (BMI), and gene expression results indicated a role of these variants in the hypothalamus. It was consecutively hypothesized that these associations might be evoked by a modulation of nutritional intake or energy expenditure. OBJECTIVE: It was our aim to investigate the association of these genetic factors with BMI in a large homogenous population-based sample to explore the association of these polymorphisms with lifestyle factors related to nutritional intake or energy expenditure, and whether such lifestyle factors could be mediators of the detected single-nucleotide polymorphism (SNP)-association with BMI. It was a further aim to compare the proportion of BMI explained by genetic factors with the one explained by lifestyle factors. DESIGN: The association of seven polymorphisms in or near the genes NEGR1, TMEM18, MTCH2, FTO, MC4R, SH2B1 and KCTD15 was analyzed in 12,462 subjects from the population-based MONICA/KORA Augsburg study. Information on lifestyle factors was based on standardized questionnaires. For statistical analysis, regression-based models were used. RESULTS: The minor allele of polymorphism rs6548238 C>T (TMEM18) was associated with lower BMI (-0.418 kg m(-2), P=1.22 × 10(-8)), and of polymorphisms rs9935401 G>A (FTO) and rs7498665 A>G (SH2B1) with increased BMI (0.290 kg m(-2), P=2.85 × 10(-7) and 0.145 kg m(-2), P=9.83 × 10(-3)). The other polymorphisms were not significantly associated. Lifestyle factors were correlated with BMI and explained 0.037% of the BMI variance as compared with 0.006% of explained variance by the associated genetic factors. The genetic variants associated with BMI were not significantly associated with lifestyle factors and there was no evidence of lifestyle factors mediating the SNP-BMI association. CONCLUSIONS: Our data first confirm the findings for TMEM18 with BMI in a single study on adults and also confirm the findings for FTO and SH2B1. There was no evidence for a direct SNP-lifestyle association.

Reference intervals for aldosterone, renin, and the aldosterone-to-renin ratio in the population-based Study of Health in Pomerania (SHIP-1).

The renin-angiotensin-aldosterone system plays a key role in the regulation of human blood pressure. The aldosterone-to-renin ratio (ARR) is widely accepted for screening the primary hyperaldosteronism (PAL). Various cutoffs for positive PAL screening have been defined in patient cohorts from endocrinological referral centers and primary care. However, the distribution of the ARR in the general population is largely unknown. We aim to provide reference ranges for plasma aldosterone concentration (PAC), plasma renin concentration (PRC), and the ARR for the general population of north-east Germany. A cohort of 3 300 subjects participated in the first follow-up of the longitudinal, population-based Study of Health in Pomerania (SHIP). PAC and PRC were measured by radioimmunometric procedures. The reference interval was defined as the central 95% range between the 2.5(th) and 97.5(th) percentiles. A reference population comprising 1,347 healthy subjects was selected. Sex and age-specific (25-54 and 55-74 years) reference ranges are presented. The upper reference limit for the ARR was 14.2 and 20.3 in younger, and 22.4 and 25.5 in older men and women, respectively. Time of blood sampling had no influence on the ARR, while beta blockers, and agents acting on the renin-angiotensin system were associated with higher and lower ARR, respectively. Our upper reference limit for the ARR is clearly lower than previously reported values from studies of hypertensive patients in primary care or hypertension referral centers. We confirm that PAC and PRC are associated with various factors, including sex, age, intake of estrogen, and various antihypertensive medications.

[The BSD Health Study: a pilot study to examine the comparability of Bavarian blood donors with the Bavarian general population by a comparison with KORA S4]. / Die BSD Gesundheitsstudie: eine Pilotstudie zur Untersuchung der Vergleichbarkeit bayerischer Blutspender mit der Allgemein-bevölkerung Bayerns durch einen Vergleich mit KORA S4.

AIM: The aim of this pilot study was to compare the health status of Bavarian blood donors to the general population in Bavaria (Southern Germany). METHODS: Blood donors in Bavaria were evaluated with respect to socio-demographic characteristics, smoking status and selected diseases. The subset of blood donors from rural areas and aged 35-74 years (n=1 187), was compared to participants in the population-based survey KORA S4 living in rural areas near Augsburg (n=1 870). The comparison was based on logistic regression models adjusted for age and sex. RESULTS: Bavarian blood donors lived significantly more often in communities with less than 20 000 inhabitants (OR=4.73, KI: 3.69-6.13). They were more often born in Germany (OR=2.71, KI: 2.12-3.50) and had less university degrees (OR=0.60, KI: 0.44-0.81). Never smoking is more common in blood donors (OR=1.53, 95% KI: (1.30; 1.80)). The prevalence of asthma, myocardial infarction (HI) and cancer (men only) is significantly lower in blood donors compared to the general population both living in rural areas (OR (Asthma)=0.32, 95% KI: (0.20; 0.52); OR (HI)=0.17, 95% KI: (0.08; 0.34)). The initially significantly lower number of cancer cases in male blood donors disappeared after adjustment for smoking status and community size. No difference was detected for type 2 diabetes. CONCLUSION: With the exception of type 2 dia-betes, the prevalence of the investigated diseases was lower in blood donors than in the general population. Differences can probably be explained by lifestyle factors as there might be a selection of healthier and more health-conscious blood donors. In the literature, a reduced risk of MI is discussed to be related to the frequency of blood donation. However, these questions need further research.

Serum gamma-glutamyltransferase is a predictor of incident coronary events in apparently healthy men from the general population.

OBJECTIVE: To investigate whether serum gamma-glutamyltransferase (GGT) is an independent predictor for incident coronary events in initially healthy men from the general population. METHODS AND RESULTS: The study was based on 1878 men (aged 25-64 years) who participated in the first MONICA Augsburg survey 1984/1985, and who were free of coronary heart disease at baseline. Up to 2002 a total of 150 incident acute coronary events occurred. Baseline levels of GGT were higher in men who experienced an event than in event-free men (28.4+/-2.0 units/l versus 22.4+/-2.1 units/l, p 0.0002). GGT was highly correlated with other cardiovascular risk factors. In a Cox proportional hazards model after age adjustment hazard ratios (HR) for incident myocardial infarction across GGT quartiles (<13, 13 to <20, 20 to <35, and >/=35 units/l) were 1.0, 1.84, 2.02, and 3.08 (p for trend 0.0001). Further adjustment for hypertension, TC/HDL ratio, diabetes, smoking, physical activity, alcohol intake, education years and BMI attenuated the association; comparing the highest versus lowest quartile of GGT the HR for a first-ever coronary event was then 2.34 (95% CI, 1.23-4.44). CONCLUSIONS: Serum GGT is a strong predictor of acute coronary events in apparently healthy men from the general population, independent of other risk factors for cardiovascular disease.

Association of the 103I MC4R allele with decreased body mass in 7937 participants of two population based surveys.

BACKGROUND: The melanocortin-4-receptor gene (MC4R) is part of the melanocortinergic pathway that controls energy homeostasis. In a recent meta-analysis, the MC4R V103I (rs2229616) polymorphism was shown to be associated with body weight regulation. Although no functional differences between the isoleucine comprising receptor and the wild type receptor have been detected as yet, this meta-analysis of 14 case-control studies reported a mild negative association with obesity (odds ratio (OR) 0.69, p = 0.03). However, evidence in a large population based study in a homogeneous population and a significant estimate of the change in quantitative measures of obesity is still lacking. METHODS: We analysed the data of two surveys of a white population with the same high quality study protocol, giving a total of 7937 participants. RESULTS: By linear regression, we found a significant decrease of 0.52 body mass index (BMI) units (95% confidence interval (CI) -0.02 to -1.03, p = 0.043) for carriers of the heterozygote rs2229616G/A genotype, which was observed in 3.7% of the participants. Logistic regression yielded a significantly negative association of the MC4R variant with "above average weight" (BMI > or = median BMI) yielding an OR of 0.75 (95% CI 0.59 to 0.95 p = 0.017). We obtained similar results comparing obese (BMI > or =30 kg/m2, World Health Organization results for 1997) with non-obese (BMI < 30 kg/m2) participants. The results were found for both sexes and each survey separately, and did not depend on the modelling of age, sex, or survey effects. CONCLUSIONS: Our study confirms previous findings of a meta-analysis that the relatively infrequent G/A genotype of the V103I MC4R polymorphism is negatively associated with above average weight and obesity in population based original data of 7937 participants, and extends previous findings by showing for the first time a significantly lower BMI in individuals carrying the infrequent allele of this MC4R variant.

Body composition and prevalence of left ventricular hypertrophy.

BACKGROUND: Fat-free mass (FFM) has been proposed as an optimal normalization of left ventricular (LV) mass to body size. We sought to evaluate the novel FFM-based criteria of LV hypertrophy (LVH). METHODS AND RESULTS: A population sample of 1371 men and women aged 25 to 74 years was examined by echocardiography and bioelectrical impedance analysis. Internal partition values for LVH were generated in a healthy population subgroup on the basis of LV mass divided by FFM and by the traditional indexations to body height, height(2.7), and body surface area. In contrast to the sex-specific criteria required by traditional indexations, the value of LV mass/FFM that divided individuals with and without LVH was identical for men and women (4.1 g/kg). Estimates of LVH prevalence varied significantly by type of indexation used, internally or externally derived cut points, and by population subgroups. Differences were pronounced among hypertensives and the obese. Thus, the application of LV mass/FFM more than halved the risk of LVH in obese versus nonobese women (odds ratio, 2.5; 95% confidence interval, 1.6 to 4.0) compared with criteria based on LV mass/height(2.7) (odds ratio, 5.5; 95% confidence interval, 3.6 to 8.3). Implications among hypertensives were less marked. CONCLUSIONS: Indexation of LV mass to FFM eliminates sex-specific LVH criteria. The proportion of individuals defined as having LVH using the new criteria deviate markedly from traditional indexations. Prospective investigations will be needed to identify the prognostic implications of different indexations, especially in subgroups such as the obese.

C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992.

BACKGROUND: Inflammatory reactions in coronary plaques play an important role in the pathogenesis of acute atherothrombotic events; inflammation elsewhere is also associated with both atherogenesis generally and its thrombotic complications. Recent studies indicate that systemic markers of inflammation can identify subjects at high risk of coronary events. METHODS AND RESULTS: We used a sensitive immunoradiometric assay to examine the association of serum C-reactive protein (CRP) with the incidence of first major coronary heart disease (CHD) event in 936 men 45 to 64 years of age. The subjects, who were sampled at random from the general population, participated in the first MONICA Augsburg survey (1984 to 1985) and were followed for 8 years. There was a positive and statistically significant unadjusted relationship, which was linear on the log-hazards scale, between CRP values and the incidence of CHD events (n=53). The hazard rate ratio (HRR) of CHD events associated with a 1-SD increase in log-CRP level was 1.67 (95% CI, 1.29 to 2. 17). After adjustment for age, the HRR was 1.60 (95% CI, 1.23 to 2. 08). Adjusting further for smoking behavior, the only variable selected from a variety of potential confounders by a forward stepping process with a 5% change in the relative risk of CRP as the selection criterion, yielded an HRR of 1.50 (95% CI, 1.14 to 1.97). CONCLUSIONS: These results confirm the prognostic relevance of CRP, a sensitive systemic marker of inflammation, to the risk of CHD in a large, randomly selected cohort of initially healthy middle-aged men. They suggest that low-grade inflammation is involved in pathogenesis of atherosclerosis, especially its thrombo-occlusive complications.

Lack of association between a polymorphism of the aldosterone synthase gene and left ventricular structure.

BACKGROUND: Cardiac growth and function may be modulated in part by trophic effects of neurohormones. Specifically, aldosterone has been shown to stimulate the growth of cardiac myocytes and the accumulation of cardiac extracellular matrix proteins. Moreover, a variant of the aldosterone synthase gene (a cytosine/thymidine exchange at position -344 in the transcriptional regulatory region) has been associated with enlargement and disturbed filling of the left ventricle (LV) in a small sample of young white adults. The aim of the present study was to reinvestigate the implications of aldosterone synthase -344C/T allele status for serum aldosterone levels, blood pressure, and LV structure and function in large population-based samples. METHODS AND RESULTS: Individuals who participated in the echocardiographic substudy of the third MONICA (MONitoring trends and determinants in CArdiovascular disease) survey (n=1445) or in the second follow-up of the first MONICA survey (n=562) were studied by standardized anthropometric, echocardiographic, and biochemical measurements as well as genotyping for aldosterone synthase -344C/T allele status. In both surveys, the distribution of sex, age, arterial blood pressure, and body mass index was homogeneous in the aldosterone synthase genotype groups. Echocardiographic LV wall thicknesses, dimensions, and mass indexes were not significantly associated with a specific aldosterone synthase genotype. Likewise, no association was detectable with echocardiographic measures of LV systolic or diastolic function. Data were consistent in both samples and not materially different in subgroups defined by age, sex, or intake of antihypertensive medication. Finally, no significant association was observed for aldosterone synthase allele status and serum aldosterone levels in the group of 562 individuals. CONCLUSIONS: The data are not in favor of a significant contribution of the C/T exchange at position -344 in the aldosterone synthase transcriptional regulatory region to the variability of serum aldosterone levels, blood pressure, or cardiac size or function as found in 2 white population-based samples.

Familial predisposition of left ventricular hypertrophy.

OBJECTIVES: The study evaluated the contribution of familial predisposition to the risk of left ventricular hypertrophy (LVH). BACKGROUND: Left ventricular hypertrophy is a multifactorial condition that serves as an important predictor of cardiovascular mortality. At present it is unclear whether familial predisposition contributes to the manifestation of LVH. Thus, we determined whether siblings of subjects with LVH are at increased risk to present with an elevation of LV mass or an abnormal LV geometry. METHODS: Echocardiographic and anthropometric measurements were performed in 2,293 individuals who participated in the echocardiographic substudies of population-based MONICA Augsburg surveys. In addition, a total of 319 siblings of survey participants with echocardiographic evidence of LVH were evaluated. The risk of these siblings to present with LVH or abnormal LV geometry was estimated by comparison with 636 subjects matched for gender and age that were selected from the entire echocardiography study base. RESULTS: Blood pressure, body mass index, age, and gender (i.e., known determinants of LV mass) were comparable in LVH-siblings and the matched comparison group. However, septal and posterior wall thicknesses, relative wall thickness as well as LV mass index were significantly elevated in LVH-siblings (p < 0.001, each) whereas LV dimensions did not differ. Likewise, the prevalence of LVH was raised in LVH-siblings, as was the relative risk of LVH after adjustment for confounders (p < 0.05). More specifically, LVH-siblings displayed increased prevalences of concentric remodeling and concentric LVH (p < 0.05) but not of eccentric LVH. CONCLUSIONS: Familial predisposition appears to contribute to increased LV wall thickness, to the development of LV hypertrophy and abnormal LV geometry.

BNP as a marker of diastolic dysfunction in the general population: Importance of left ventricular hypertrophy.

BNP is a marker of systolic left ventricular dysfunction (LVSD) and heart failure. To assess BNP for the detection of diastolic dysfunction in the general population, we examined 1678 subjects within an age- and sex-stratified survey (MONICA Augsburg). BNP was measured using a commercially available RIA (Shionogi). BNP increased in subjects with diastolic dysfunction (mean 20.3+/-4.7 pg/ml vs. control 9.6+/-0.5 pg/ml, p<0.001), but to a lesser extent than in subjects with LV hypertrophy (LVH, mean 37.3+/-49.1 pg/ml, p<0.001 vs. control) or LVSD (mean 76.2+/-23.2 pg/ml, p<0.001 vs. control). Individuals with sole diastolic abnormality displayed BNP concentrations at the control level (mean 9.7+/-1.7 pg/ml). In univariate analysis, age, BMI, systolic blood pressure, left atrial size, LV mass index, diastolic dysfunction and EF displayed a significant correlation with BNP (p<0.001). However, LV mass index displaced diastolic dysfunction as a significant predictor of BNP in multivariate analysis. Upon ROC analysis, sensitivity and specificity for the detection of diastolic dysfunction by BNP were only 61% and 55%, respectively. Nevertheless, a normal BNP test virtually excluded the presence of diastolic dysfunction and concomitant LVH (NPV 99.9%). Increased BNP concentrations in subjects with diastolic dysfunction are strongly related to LVH. Population-wide screening for diastolic dysfunction with BNP cannot be recommended although a normal BNP test usually excludes diastolic dysfunction and LV hypertrophy.