Cardiovascular risk factors, living and ageing in Halle: the CARLA study.

The CARLA study (Cardiovascular Disease, Living and Ageing in Halle) is a longitudinal population-based cohort study of the general population of the city of Halle (Saale), Germany. The primary aim of the cohort was to investigate risk factors for cardiovascular diseases based on comprehensive cardiological phenotyping of study participants and was extended to study factors associated with healthy ageing. In total, 1779 probands (812 women and 967 men, aged 45-83 years) were examined at baseline (2002-2005), with a first and second follow-up performed 4 and 8 years later. The response proportion at baseline was 64.1% and the reparticipation proportion for the first and second follow-up was 86% and 77% respectively. Sixty-four percent of the study participants were in retirement while 25% were full- or partially-employed and 11% were unemployed at the time of the baseline examination. The currently running third follow-up focuses on the assessment of physical and mental health, with an intensive 4 h examination program, including measurement of cardiovascular, neurocognitive, balance and gait parameters. The data collected in the CARLA Study resulted in answering various research questions in over 80 publications, of which two thirds were pooled analyses with other similar population-based studies. Due to the extensiveness of information on risk factors, subclinical conditions and evident diseases, the biobanking concept for the biosamples, the cohort representativeness of an elderly population, and the high level of quality assurance, the CARLA cohort offers a unique platform for further research on important indicators for healthy ageing.

Association of late-life changes in blood pressure and cognitive status.

BACKGROUND: Disagreement exists on the association between changes in blood pressure and cognitive impairment. We aimed to examine whether 4-year changes in systolic and diastolic blood pressure (SBP and DBP) are associated with cognitive status in a representative sample of older men and women. METHODS: Analysis of longitudinal data from 854 participants of a population-based German sample (aged 60-87 years) was performed with standard cognitive screening and blood pressure measurements. Effects of changes in SBP and DBP (10 mmHg and 5 mmHg respectively as unit of regression effect measure) on cognitive status were evaluated using non-parametric and linear regression modeling. RESULTS: No clear associations were seen between changes in SBP or in DBP and cognitive scores. Small effects were found after stratification for sex and hypertension awareness. Specifically, larger decreases in SBP were associated with higher cognitive scores in those men aware of their hypertension (10 mmHg decrease in SBP, ß = -0.26, 95% CI: -0.51 to -0.02) and men with controlled hypertension (10 mmHg decrease in SBP, ß = -0.44, 95% CI: -0.92 to -0.03). Additionally larger increases in DBP were associated with higher cognitive scores in men with controlled hypertension (5 mmHg increase in DBP, ß = 0.67, 95% CI: 0.19-1.15). For women aware of their hypertension, larger decreases in DBP were associated with higher cognitive scores (5 mmHg decrease in DBP, ß = -0.26; 95%CI: -0.51 to -0.01). CONCLUSIONS: Changes in blood pressure were only weakly associated with cognitive status. Specifically, decreases in SBP were associated with higher cognitive scores in men aware of their hypertension and especially those that were medically controlled.

Socioeconomic status and anthropometric changes-A meta-analytic approach from seven German cohorts.

OBJECTIVE: To study the association between socioeconomic status (SES) and annual relative change in anthropometric markers in the general German adult population. METHODS: Longitudinal data of 56,556 participants aged 18-83 years from seven population-based German cohort studies (CARLA, SHIP, KORA, DEGS, EPIC-Heidelberg, EPIC-Potsdam, PopGen) were analyzed by meta-analysis using a random-effects model. The indicators of SES were education and household income. RESULTS: On average, all participants gained weight and increased their waist circumference over the study's follow-up period. Men and women in the low education group had a 0.1 percentage points greater annual increase in weight (95% CI men: 0.06-0.20; and women: 0.06-0.12) and waist circumference (95% CI men: 0.01-0.45; and women: 0.05-0.22) than participants in the high education group. Women with low income had a 0.1 percentage points higher annual increase in weight (95% CI 0.00-0.15) and waist circumference (95% CI 0.00-0.14) than women with high income. No association was found for men between income and obesity markers. CONCLUSIONS: Participants with lower SES (education and for women also income) gained more weight and waist circumference than those with higher SES. These results underline the necessity to evaluate the risk of weight gain based on SES to develop more effective preventive measures.

Prevalence and Incidence of Hypertension in the General Adult Population: Results of the CARLA-Cohort Study.

Hypertension is a leading cause of cardiovascular disease. There are very few studies dealing with the incidence of hypertension and changes in blood pressure (BP) over time. We aimed to evaluate the prevalence and incidence of hypertension within an adult population-based cohort.The sample included 967 men and 812 women aged 45 to 83 years at baseline, 1436 subjects completed follow-up1 after 4 years and 1079 completed follow-up2 after 9 years. BP was measured according to a standardized protocol with oscillometric devices and hypertension was defined as mean systolic BP (SBP) ≥140  mmHg and/or diastolic BP (DBP) ≥90  mmHg and/or use of antihypertensive medication if hypertension was known. We examined prevalence and incidence of hypertension, by age and sex.The age-standardized prevalence of hypertension at baseline was 74.3% for men and 70.2% for women. The age-standardized annual incidence rate of hypertension for men was 8.6 (95% confidence interval [95% CI] 4.3-12.9) for follow-up period1 and 5.4 (95% CI 2.8-10.6) for follow-up period2 and for women 8.2 (95% CI 3.6-12.8) for follow-up1 and 5.6 (95%CI 2.7-11.4) for follow-up2. A clear decrease in SBP and DBP between baseline and follow-up1 and follow-up2 was seen, accompanied by an increase in anti-hypertensive medication consumption and a higher awareness of the condition.Hypertension prevalence and incidence in the CARLA Study appear to be elevated compared with other studies. The decrease of BP over time seems to be caused by improved hypertension control due to interventional effects of our observational study and improved health care.

The association between resilience and diabetic neuropathy by socioeconomic position: cross-sectional findings from the KORA-Age study.

We investigated whether older adults with diabetes mellitus and lower resilience have an increased risk of diabetic neuropathy as compared to older adults with higher resilience, and whether this association varies by socioeconomic position. In total, 3942 individuals took part in a health survey in Augsburg, Germany, in 2008-2010 (KORA-Age study). We found that among participants with low socioeconomic position, those with higher resilience had a lower probability of suffering from neuropathy as compared to participants with lower resilience (absolute risk reduction = 10%). Adjusted odds ratio with 95% confidence intervals for the outcome diabetic neuropathy also showed that lower resilience scores had an independent effect in increasing the risk of diabetic neuropathy among elderly individuals with a low socioeconomic position (odds ratio: 1.83; confidence interval: 1.09-3.08). Health-promoting strategies focussing on resilience should be further explored.

Diagnostic utility of a one-item question to screen for depressive disorders: results from the KORA F3 study.

BACKGROUND: Screening for depressive disorders in the general adult population is recommended, however, it is unclear which instruments combine user friendliness and diagnostic utility. We evaluated the test performance of a yes/no single item screener for depressive disorders ("Have you felt depressed or sad much of the time in the past year?") in comparison to the depressive disorder module of the Patient Health Questionnaire (PHQ-9). METHODS: Data from 3184 participants of the population-based KORA F3 survey in Augsburg/ Germany were used to analyse sensitivity, specificity, ROC area, positive likelihood ratio (LR+), negative likelihood ratio (LR-), positive predictive value (PPV), and negative predictive value (NPV) of the single item screener in comparison with "depressive mood" and "major depressive disorder" defined according to PHQ-9 (both interviewer-administered versions). RESULTS: In comparison to PHQ-9 "depressive mood", sensitivity was low (46%) with an excellent specificity (94%), (PPV 76%; NPV 82%; LR + 8.04; LR- .572, ROC area .702). When using the more conservative definition for "major depressive disorder", sensitivity increased to 83% with a specificity of 88%. The PPV under the conservative definition was low (32%), but NPV was 99% (LR + 6.65; LR- .196; ROC area .852). Results varied across age groups and between males and females. CONCLUSIONS: The single item screener is able to moderately decrease post-test probability of major depressive disorders and to identify populations that should undergo additional, more detailed evaluation for depression. It may have limited utility in combination with additional screening tests or for selection of at-risk populations, but cannot be recommended for routine use as a screening tool in clinical practice.

Metabolomic profiles in individuals with negative affectivity and social inhibition: a population-based study of Type D personality.

BACKGROUND: Individuals with negative affectivity who are inhibited in social situations are characterized as distressed, or Type D, and have an increased risk of cardiovascular disease (CVD). The underlying biomechanisms that link this psychological affect to a pathological state are not well understood. This study applied a metabolomic approach to explore biochemical pathways that may contribute to the Type D personality. METHODS: Type D personality was determined by the Type D Scale-14. Small molecule biochemicals were measured using two complementary mass-spectrometry based metabolomics platforms. Metabolic profiles of Type D and non-Type D participants within a population-based study in Southern Germany were compared in cross-sectional regression analyses. The PHQ-9 and GAD-7 instruments were also used to assess symptoms of depression and anxiety, respectively, within this metabolomic study. RESULTS: 668 metabolites were identified in the serum of 1502 participants (age 32-77); 386 of these individuals were classified as Type D. While demographic and biomedical characteristics were equally distributed between the groups, a higher level of depression and anxiety was observed in Type D individuals. Significantly lower levels of the tryptophan metabolite kynurenine were associated with Type D (p-value corrected for multiple testing=0.042), while no significant associations could be found for depression and anxiety. A Gaussian graphical model analysis enabled the identification of four potentially interesting metabolite networks that are enriched in metabolites (androsterone sulfate, tyrosine, indoxyl sulfate or caffeine) that associate nominally with Type D personality. CONCLUSIONS: This study identified novel biochemical pathways associated with Type D personality and demonstrates that the application of metabolomic approaches in population studies can reveal mechanisms that may contribute to psychological health and disease.

In vivo neuronal firing patterns during human epileptiform discharges replicated by electrical stimulation.

OBJECTIVE: To describe neuronal firing patterns observed during human spontaneous interictal epileptiform discharges (IEDs) and responses to single pulse electrical stimulation (SPES). METHODS: Activity of single neurons was recorded during IEDs and after SPES in 11 consecutive patients assessed with depth EEG electrodes and attached microelectrodes. RESULTS: A total of 66 neurons were recorded during IEDs and 151 during SPES. We have found essentially similar patterns of neuronal firing during IEDs and after SPES, namely: (a) a burst of high frequency firing lasting less than 100 ms (in 39% and 25% of local neurons, respectively for IED and SPES); (b) a period of suppression in firing lasting around 100-1300 ms (in 19% and 14%, respectively); (c) a burst followed by suppression (in 10% and 12%, respectively); (d) no-change (in 32% and 50%, respectively). CONCLUSIONS: The similarities in neuronal firing patterns associated with IEDs and SPES suggest that, although both phenomena are initiated differently, they result in the activation of a common cortical mechanism, probably initiated by brief synchronised burst firing in some cells followed by long inhibition. SIGNIFICANCE: The findings provide direct in vivo human evidence to further comprehend the pathophysiology of human focal epilepsy.

Socioeconomic position, resilience, and health behaviour among elderly people.

OBJECTIVES: Healthy psychological functioning, the ability to respond rapidly to environmental changes, has been associated with better health outcomes. Less work has examined the association with health behaviour. This study explores whether resilience (a specific expression of healthy psychological functioning) is positively associated with health behaviour in an elderly population aged ≥65 years and whether this association differs in different socioeconomic groups. METHODS: Resilience was measured in 3,942 elderly participating in a population-based cohort study (KORA-Age study) in Germany through a short version of the Resilience Scale developed by Wagnild and Young. Regression analyses were performed by socioeconomic position (low/high educational level or income) for two outcome variables, i.e. high consumption of fruit and vegetables and high/moderate physical activity. RESULTS: Resilient people were more likely to consume ≥5 servings of fruit and vegetables a day and to perform high/moderate physical activity as compared to non-resilient people (ORs ranging from 1.5 to 2.2), irrespective of socioeconomic position. CONCLUSIONS: Resilience could provide an important starting point for health promotion strategies, addressing resources rather than deficits and risk factors.

Do diabetes and depressed mood affect associations between obesity and quality of life in postmenopause? Results of the KORA-F3 Augsburg population study.

BACKGROUND: To assess associations of obesity with health-related quality of life (HRQL) in postmenopausal women, and whether depressed mood and diabetes moderate these associations. METHODS: Survey of 983 postmenopausal women aged 35-74, general population, Augsburg region/Germany, 2004/2005. Body weight/height and waist/hip circumference were assessed anthropometrically and classified via BMI ≥ 30 as obese, and WHR ≥ 0.85 as abdominally obese (vs. not). Depressed mood was assessed by the Depression and Exhaustion-(DEEX-)scale, diabetes and postmenopausal status by self-report/medication, and HRQL by the SF-12. RESULTS: General linear models revealed negative associations of obesity and abdominal obesity with physical but not mental HRQL. Both forms of excess weight were associated with diabetes but not depressed mood. Moderation depended on the HRQL-domain in question. In non-diabetic women, depressed mood was found to amplify obesity-associated impairment in physical HRQL (mean "obese"-"non-obese" difference given depressed mood: -6.4, p < .001; among those without depressed mood: -2.5, p = .003). Reduced mental HRQL tended to be associated with obesity in diabetic women (mean "obese"-"non-obese" difference: -4.5, p = .073), independent of depressed mood. No interactions pertained to abdominal obesity. CONCLUSIONS: In postmenopausal women, depressed mood may amplify the negative impact of obesity on physical HRQL, while diabetes may be a precondition for some degree of obesity-related impairments in mental HRQL.

Prospective association between self-reported life satisfaction and mortality: results from the MONICA/KORA Augsburg S3 survey cohort study.

BACKGROUND: To identify factors which determine high life satisfaction (LS) and to analyse the prognostic influence of LS on mortality. METHODS: Data collection was conducted on 2,675 participants, age 25-74 years, as part of the MONICA Augsburg Project 1994-95. Multivariate logistic regression analyses were used to determine factors associated with high LS (measured with one item, 6-level Likert scale, where "high" = very satisfied/most of the time very satisfied with ones personal life). After 12 years mean follow-up, a total of 245 deaths occurred. We calculated age- and sex-adjusted incident mortality rates per 10,000. Hazard ratios (HRs) were estimated from Cox proportional hazards models. RESULTS: Independent determinants of LS were income, health-perception, and social support, as well as somatisation, anger or depressive symptoms (all p < 0.05). Participants with higher LS (n = 721, 27%) benefited the most with respect to absolute mortality risk reduction (higher LS = 67; mid = 98; low = 140 per 10,000). The sex-stratified analyses indicated an independent association of higher LS and survival for men (HR 0.55; 95% CI 0.37 - 0.81) but not for women. CONCLUSIONS: Baseline assessment demonstrated that psychological, social and life-style factors, but not somatic co-morbidities, were relevant determinants of LS. Moreover, the analysis showed that men with higher LS have a substantial long-term survival benefit. The observed association between LS and mortality may be attributed to common underlying causes such as social network integration and/or self-rated health.

Mental health in the aged: prevalence, covariates and related neuroendocrine, cardiovascular and inflammatory factors of successful aging.

BACKGROUND: Although aging is accompanied by diminished functioning, many elderly individuals preserve a sense of well-being. While the concept of "successful aging" has been popular for many decades, little is known about its psycho-physiologic and endocrine underpinnings. KORA-Age is a population-based, longitudinal study designed to determine the prevalence of successfully aged men and women between 65 and 94 years old in the MONICA/KORA Augsburg cohort of randomly selected inhabitants. Specifically, we aim to identify predictors of successful aging and to elucidate bio-psychosocial mechanisms that maintain mental health and successful adaptation despite adverse experiences of life and aging. METHODS/DESIGN: Components of successful aging were assessed in a telephone survey of 4,127 participants (2008-2009) enrolled in the MONICA/KORA cohort, on average, 13 years earlier. Psychosocial, somatic and behavioural predictors are used to determine factors that contribute to successful aging. An age-stratified random sub-sample (n = 1,079) participated in a personal interview where further psychological mechanisms that may underlie successful adaptation (resilience, social support, attachment) were examined. The interactions among neuroendocrine systems in the aging process are investigated by studying the cortisol/dehydroepiandrosterone-sulfate ratio, the level of insulin-like growth factor I, and oxytocin. DISCUSSION: Longitudinal determinants of successful aging can be assessed based on a follow-up of an average of 13 years. A comprehensive analysis of biological as well as physio-psychological information provides a unique opportunity to investigate relevant outcomes such as resilience and frailty in the elderly population.