Association of adiposity, telomere length and mortality: data from the NHANES 1999-2002.

BACKGROUND/OBJECTIVES: Telomere shortening is associated with age and risk of medical comorbidity. We assessed the relationship between measures of adiposity, leukocyte telomere length, and mortality and whether it is modified by age. SUBJECTS/METHODS: Subjects with dual-energy X-ray absorptiometry measures were identified using the National Health and Nutrition Examination Survey 1999-2002. Obesity was categorized using two body fat definitions (BF1%: men ⩾25%; females ⩾35%; BF2% ⩾28% and ⩾38%, respectively), body mass index (BMI) and waist circumference (WC; men ⩾102 cm; females ⩾88 cm). Telomere length relative to standard reference DNA (T/S ratio) was assessed using quantitative PCR. Weighted multivariable regression models evaluated the association of telomere length with adiposity, both continuously and categorically (low/normal BF%, low/high WC and standard BMI categories). Differences in telomere length by age and adiposity were ascertained and subsequent models were stratified by age. Proportional hazard models assessed the risk of mortality by adiposity status. A telomere by adiposity interaction was tested in the entire cohort and by age category (<60 vs ⩾60 years; <70 vs ⩾70 years). RESULTS: We identified 7827 subjects. Mean age was 46.1 years. Overall telomere length was 1.05±0.01 (s.e.) that differed by BF1% (low/high: 1.12±0.02 vs 1.03±0.02; P<0.001), BF2% (1.02±0.02 vs 1.11±0.02; P<0.001), BMI (underweight 1.08±0.03; normal 1.09±0.02; overweight 1.04±0.02; and obese 1.03±0.02;P<0.001) and WC (low/high 1.09±0.02 vs 1.02±0.02; P<0.001). Adjusted ß-coefficients evaluating the relationship between telomere length and adiposity (measured continuously) were as follows: BF1% (ß=-0.0033±0.0008; P<0.001), BF2% (-0.041±0.008; P<0.001), BMI (ß=-0.025±0.0008; P=0.005) and WC (ß=-0.0011±0.0004; P=0.007). High BF% (BF1%: ß=-0.035±0.011; P=0.002; BF2%: ß=-0.041±0.008; P<0.001) and WC (ß=-0.035±0.011; P=0.008) were inversely related to telomere length (TL). Stratifying by age, high BF1% (-0.061±0.013), BF2% (-0.065±0.01), BMI-obesity (-0.07±0.015) and high WC (-0.048±0.013) were significant (all P<0.001). This association diminished with increasing age. In older participants, TL was inversely related to mortality (hazard ratio 0.36 (0.27, 0.49)), as were those classified by BF1% (0.68 (0.56, 0.81)), BF2% (0.75 (0.65, 0.80)), BMI (0.50 (0.42, 0.60)) and WC (0.72 (0.63, 0.83)). No interaction was observed between adiposity status, telomere length and mortality. CONCLUSIONS: Obesity is associated with shorter telomere length in young participants, a relationship that diminishes with increasing age. It does not moderate the relationship with mortality.

Resilience moderates the association between chronic pain and depressive symptoms in the elderly.

BACKGROUND: Chronic pain is frequent in elderly people and, especially if widespread, associated with poor mental health. We investigated whether a resilient personality protects older adults against the adverse effects of chronic pain. METHODS: Pain status [no pain, chronic local pain (CLP) and chronic widespread pain (CWP)] was determined using the American College of Rheumatologists' criteria for widespread pain in a cross-sectional sample of 724 participants aged 68-92 years drawn from the population-based KORA-Age study in Southern Germany. Depressive symptoms and resilience were assessed via the scales GDS-15 and RS-5. The relation between pain, resilience and depressive symptoms was modelled using logistic and quantile regression. RESULTS: CLP prevalence and CWP prevalence were 57.5% and 12.3%, respectively. Confounder-adjusted logistic regression indicated a fourfold risk of depressed mood (GDS-15 ≥ 5) in CWP, vs. no pain (OR = 4.08, 95% CI 1.90-8.74). However, in quantile regression, the adverse effect of CWP was significantly attenuated by resilience when looking at the GDS-15 score lower quartile (p = 0.011) and median (p = 0.011). This effect appeared to be mainly driven by participants aged 75-84 years. Confounder adjustment reduced the effect of CLP on depressive symptoms to non-significance, and effect modification by resilience was undetectable in regression models of CLP. CONCLUSIONS: Resilience was protective in the association of CWP with depressive symptoms in this analysis. Older adults with CWP may potentially benefit from interventions supporting resilience. Prospective research should investigate the protective role of resilience in the potentially self-perpetuating relation between chronic pain and depressed affect. WHAT DOES THIS STUDY ADD?: The association of chronic widespread pain with depressive symptoms in the elderly population is attenuated by resilience.

Poor structural social support is associated with an increased risk of Type 2 diabetes mellitus: findings from the MONICA/KORA Augsburg cohort study.

AIMS: Several psychosocial factors have been shown to increase the risk of Type 2 diabetes mellitus. This study investigated the association between structural social support and incidence of Type 2 diabetes mellitus in men and women. METHODS: Data were derived from three population-based MONICA/KORA surveys conducted in 1984-1995 in the Augsburg region (southern Germany) and followed up by 2009. The study population comprised 8952 participants (4669 men/4283 women) aged 30-74 years without diabetes at baseline. Structural social support was assessed using the Social Network Index. Sex-specific hazard ratios were estimated from Cox proportional hazard models. RESULTS: Within follow-up, 904 incident Type 2 diabetes mellitus cases (558 men, 346 women) were observed. Crude incidence rates for Type 2 diabetes mellitus per 10 000 person-years were substantially higher in poor compared with good structural social support (men: 94 vs. 69, women: 58 vs. 43). After adjustment for age, survey, parental history of diabetes, smoking status, alcohol intake, physical activity, hypertension, dyslipidaemia, BMI, education, sleep complaints and depressed mood, risk of Type 2 diabetes mellitus for participants with poor compared with good structural social support was 1.31 [95% confidence interval (CI) = 1.11-1.55] in men and 1.10 (95% CI = 0.88-1.37) in women. Stratified analyses revealed a hazard ratio of 1.50 (95% CI = 1.23-1.83) in men with a low level of education and 0.87 (95% CI = 0.62-1.22) in men with a high level of education (P for interaction: 0.0082). CONCLUSIONS: Poor structural social support is associated with Type 2 diabetes mellitus in men. This association is independent of risk factors at baseline and is particularly pronounced in men with a low level of education.

What prevents old people living alone from feeling lonely? Findings from the KORA-Age-study.

OBJECTIVES: Living alone in later life is an important risk factor of loneliness for elderly people unless they have resources to compensate for that. The aim of this investigation was to identify these resources. METHOD: Data were drawn from the population-based KORA-Age-study (KOoperativen Gesundheitsforschung in der Region Augsburg) conducted in the Region of Augsburg, Germany in 2008/2009 with 1079 elderly men and women (64-94 years). Loneliness was measured by the short version of the UCLA-Loneliness-Scale in a face-to-face interview. Multiple logistic regression analyses were conducted to identify associations between loneliness and potential protecting resources. RESULTS: A total of 346 (32%) subjects reported to be living alone, among them 70% (n = 241) expressed no feelings of loneliness. Participants with a stable social network had a fourfold higher chance (OR 4.08, 95% CI 1.20-13.88, p = 0.025) and with the absence of depression a threefold higher chance (OR 3.04, 95% CI 1.59-5.78, p-value < 0.001) of not feeling lonely. Physical or mental resources were not correlated with lower levels of loneliness. CONCLUSION: Absence of depression and a functioning social network are the most important protecting resources against loneliness for elderly people living alone, while income, level of education and age-related limitations have no impact. These findings should be considered when supporting the elderly in successful aging.

Mind over hormones: sex differences in associations of well-being with IGF-I, IGFBP-3 and physical activity in the KORA-Age study.

OBJECTIVES: A ssociations between well-being, serum levels of insulin-like growth factor 1 (IGF-I), and its primary binding protein IGFBP-3, were examined in an epidemiologic study. The influence of physical activity on the effect of hormones on well-being was considered. METHODS: Cross-sectional data from participants of the KORA-Age study (n=985, age 64-93) was analyzed in sex-specific multivariable regressions of well-being (World Health Organization (WHO) -5) or ill-being (geriatric depression scale (GDS) -15). Models were adjusted for age, physical activity, sleep, BMI, smoking, and cognition. Adjusted WHO-5 means demonstrated the interaction between hormone quintiles with physical activity. RESULTS: Full models indicated that increased IGFBP-3 positively associated with well-being in women (ß estimate=0.14, standard error (SE)=0.06) and less so in men (ß=0.11, SE=0.07). IGF-I associated positively with depression (ß=0.11, SE=0.06) and negatively with well-being (ß=-0.11, SE=0.06) in women. Similar but not statistically discernable effects were observed in men. Adjusted mean WHO-5 scores illustrated the positive effect of physical activity and IGFBP-3 on well-being in women only. CONCLUSIONS: Opposite and independent associations of IGF-I and IGFBP-3 on well-being observed in women suggests neuroprotective effects of IGFBP-3 in age.

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.

Hypertension and depressed symptomatology: a cluster related to the activation of the renin-angiotensin-aldosterone system (RAAS). Findings from population based KORA F4 study.

CONTEXT: Preliminary evidence points to aldosterone being not only prominently involved in the systemic regulation of the blood pressure but also to play a role in the pathophysiology of depression. OBJECTIVE: We evaluated whether the combination of hypertension and depressed symptomatology is useful to screen for individuals suffering an activation of the renin-angiotensin-aldosterone system (RAAS). DESIGN: We conducted a cross-sectional analysis in participants from the Cooperative Health Research in the Region of Augsburg (KORA) F4 Study conducted between 2006 and 2008 in Southern Germany. A total of 1805 participants of the F4 study were included in the study. METHODS: The association between aldosterone and renin levels and the different combinations of hypertension and depressed symptomatology was examined in four different models of multiple linear regression adjusted for age, sex, creatinine levels, potassium levels, body mass index (BMI) and behavioural risk factors. RESULTS: Individuals suffering both, depressed symptomatology and hypertension exhibited highly significantly increased aldosterone levels (p<0.001) and slightly, not significantly increased renin levels (p=0.08) compared to individuals with no depressed symptomatology and no hypertension. No significant activation of the RAAS was seen in only depressed or only hypertensive individuals. CONCLUSIONS: The finding of highly significantly increased aldosterone levels and increased renin levels in individuals suffering both, depressed symptomatology and hypertension provides further evidence for the involvement of the RAAS in the pathogenesis of depressed symptomatology. These findings have important implications for future research concerning the pathophysiological pathways that link depression and cardiovascular disease.

To live alone and to be depressed, an alarming combination for the renin-angiotensin-aldosterone-system (RAAS).

INTRODUCTION: The renin-angiotensin-aldosterone-system (RAAS) is one of the most important systems involved in the pathogenesis of cardiovascular diseases. Its role in stress response has been generally neglected, although the progression of cardiovascular disease is considerably increased in the presence of stress and especially in the presence of depression risk. With the present analysis we aimed to evaluate whether the activity of the RAAS correlates with depressive symptomatology and with chronic stress. Moreover, we aimed to analyse whether stress response is altered in the presence of depressed symptomatology. We chose "living alone" to be our paradigm of chronic stress. METHODS AND RESULTS: Aldosterone and renin levels were assessed in 1743 (829 men, 914 women) from the population-based KORA study (Cooperative Health Research in the Region of Augsburg). The relationship between aldosterone, renin levels and the different combinations of living alone and depressive symptomatology was examined in three different multiple linear regression models adjusted for age, sex, creatinine levels, potassium levels, body mass index (BMI) and bio-behavioural factors. Neither "living alone" nor depressive symptomatology alone were associated with an activation of the RAAS, but the combination of living alone and depressive symptomatology yielded a highly significant increase in the aldosterone (p<0.01) and renin level (p=0.03). CONCLUSION: Our findings show that depressive symptomatology is associated with a hyper-responsiveness to chronic stress. Under the condition of chronic stress depressed individuals have an activated RAAS. Activation of the RAAS might explain the known increased risk of negative cardiovascular disease outcomes in this group.

Sleep disturbances and depressed mood: a harmful combination associated with increased leptin levels in women with normal weight.

Leptin, involved in energy regulation and contributor to cardiovascular disease, has been implicated to play a role in depression and sleep disturbances, two closely intertwined conditions. Previous results investigating leptin level alterations either in sleep disorders or in depression have been inconsistent. We investigate the association between leptin levels and the different combinations of depressed mood and sleep disturbances in 1369 subjects (706 men, 663 women), derived from the population-based MONIKA/KORA study. As leptin regulation is known to differ by sex and weight, analyses were performed in normal weight and overweight men and women separately. We found a highly significant association between leptin levels and the combination of depressed mood and sleep disturbances in normal-weight women (BMI ≤ 25) (p<0.01). No associations were found in men and in overweight women. Our results suggest that leptin regulation in depressed mood and sleep disturbances very much depend on sex and weight.

Association between social isolation and inflammatory markers in depressed and non-depressed individuals: results from the MONICA/KORA study.

INTRODUCTION: Depressed individuals not only suffer from chronic low grade inflammation, but also exhibit an inflammatory hyper-responsiveness to acute stress. We investigate whether chronic stress also induces an exaggerated inflammatory response in individuals with increased depression features. As model for chronic stress, social isolation was chosen. METHODS: Interleukin (IL)-6 and hs-CRP levels were assessed in 1547 subjects (847 men and 700 women), derived from the population-based MONICA/KORA study. Standardized questionnaires were used to assess depressed mood (depression and exhaustion subscale) and social isolation (social network index). The relationship between the two inflammatory markers, social isolation and depressed mood was examined taking into account interactions social isolation × depressed mood using multivariable linear regression models, adjusted for age, BMI, smoking, alcohol, and physical activity. Analyses were performed in men and women separately. RESULTS: We observed a significant interaction between depressed mood and social isolation regarding IL-6 and hs-CRP, respectively in men (p-value=0.02 for IL-6 and <0.01 for hs-CRP), evidencing a substantial synergistic effect of social isolation, and depressed mood on inflammatory responses. Furthermore, depressed and socially isolated men had highly significantly elevated IL-6 levels (geometric mean: 3.76 vs. 1.92 pg/ml, p-value <0.01) and heightened hs-CRP levels (geometric mean: 2.01 vs. 1.39 mg/l, p=0.08) in comparison with non-depressed and socially integrated men. In women, no significant associations were seen. CONCLUSION: The interaction of depressed mood and social isolation elicits a substantial synergistic impact on inflammatory markers in men, but not in depressed women.

[Depression. An underestimated risk for the development and progression of coronary heart disease]. / Depression. Ein nach wie vor unterschätztes Risiko für die Entwicklung und Progression der koronaren Herzerkrankung.

The aim of this article is to provide an overview on depression as a risk factor for the onset and follow-up of cardiovascular disease (CVD). In brief, the current state of psychobiological mechanisms bridging the gap between affective states and somatic consequences are presented. Four meta-analyses dealing with depression as a CVD risk factor in apparently healthy populations with >100,000 participants included, extracted an adjusted effect estimator of 1.60-1.90. Depressed subjects present with an unhealthier lifestyle (nutrition, smoking, physical activity). Three major psychobiological pathways directly acting on the circulatory system are under discussion: (1) hyperregulation of the autonomic nervous system (e.g., increased mean heart rate, increased heart rate responses, impaired heart rate variability), (2) overshooting stress responses of the endocrine system with impaired feedback mechanisms (e.g., for cortisol release), and (3) the immune system with dysregulated release of acute phase proteins and proinflammatory cytokines, all involved in a bidirectional crosstalk with the patient's affective state and leading to platelet activation and flow mediated endothelial (dys-)function. Nonadherence and adverse side effects of medications also contribute to the lethal properties of depression in CVD.

Social isolation and depressed mood are associated with elevated serum leptin levels in men but not in women.

BACKGROUND: Leptin, involved in energy homeostasis and a predictor of cardiovascular disease, has recently been recognized as mediator in stress reactions. We aimed to explore the association between leptin levels and two stress-related conditions, social isolation and depressed mood, both associated with increased cardiovascular mortality. METHODS: We analysed leptin levels in 1229 subjects (643 men, 586 women), derived from the population-based MONIKA/KORA study. Standardized questionnaires were used to assess depressive mood and social isolation. In a multiple linear regression adjusted for body weight, age and survey, the association between leptin, social isolation and depressed mood and its interaction was explored in men and women separately. Leptin was then dichotomized and four analyses, adjusted for age, BMI, lifestyle factors, psychosomatic complaints and metabolic variables were performed to compare the risk of elevated leptin levels in the risk groups. RESULTS: Increased leptin levels were associated with social isolation (p=0.04) and the interaction between social isolation and depressed mood (p=0.02) in men but not in women. In socially isolated and depressed men, leptin levels (mean: 6.07 ng/ml) were significantly increased compared to neither depressed nor isolated men (mean: 4.51 ng/ml, p=0.04). In the multivariate adjusted logistic regression model, the combination of depressed state and social isolation was associated with a 4-fold increased risk (p<0.001) for elevated leptin levels. CONCLUSION: The finding of elevated leptin levels in socially isolated and depressed men raises the possibility that increased cardiovascular mortality in socially isolated men is partially mediated by hyperleptinemia.

[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.

Comparison of variant-specific hybridization and single-strand conformational polymorphism methods for detection of mixed human papillomavirus type 16 variant infections.

PCR-based variant-specific hybridization (VSH) and single-strand conformational polymorphism (SSCP) analyses were compared for their capacities to detect mixed human papillomavirus type 16 (HPV-16) variant infections within clinical specimens. The SSCP assay used in this comparison targets a 682-bp fragment that spans nucleotides 7445 to 222 within the HPV-16 genome. This fragment includes portions of the HPV-16 long control region and the E6 open reading frame and identifies three categories of SSCP patterns: those identical to the patterns of prototype HPV-16 (P), those identical to the patterns of Caski-derived HPV-16 (C), or those that are different from the P and C HPV-16 patterns and that are therefore classified as belonging to novel (N) HPV-16 variants. VSH targets the entire HPV-16 E6-coding region (nucleotides 56 to 640) and distinguishes previously described variant nucleotides at positions 109, 131, 132, 143, 145, 178, 286, 289, 350, 403, and 532. Clinical samples used in VSH and SSCP analyses were subjected to multiple independent amplification reactions. The resultant amplicons were cloned, and 14 to 78 clones per clinical specimen were evaluated by VSH. VSH detected an HPV-16 variant that represented at least 20% of the amplified HPV-16 variant population. In contrast, SSCP analysis detected HPV-16 variants that represented 36% of the amplified HPV-16 population. Comparison studies were conducted with mixed HPV-16 variant laboratory constructs. Again, VSH had a higher sensitivity than SSCP analysis in detecting mixed HPV-16 variant infections in these constructed amplicon targets. Accurate detection of HPV-16 variants may enhance our understanding of the natural history of HPV-16 infections.

Oxytocin in mares: lack of evidence for oxytocin production by or action on preovulatory follicles.

It is not known whether the equine preovulatory follicle produces oxytocin or is a target tissue for oxytocin, as has been reported for other species, especially ruminants. Bovine granulosa cells secrete oxytocin, and oxytocin modulates the production of progesterone by granulosa cells in vitro. We examined whether oxytocin plays a comparable role in the equine preovulatory follicle. To test the hypothesis that the equine preovulatory follicle produces oxytocin during estrus and that its production increases in late estrus, preovulatory follicles were isolated during early (Days 1 to 2; n = 4) and late (Days 4 to 5; n = 4) estrus. Granulosa cells, pieces of theca interna and pieces of follicle wall (theca with attached granulosa cells) were cultured for 3 d with or without equine gonadotropins. Culture media were collected, replaced at 3, 6, 12, 24, 48, and 72 hr of culture, and assayed for oxytocin. Granulosa cells from preovulatory follicles secreted negligible amounts of oxytocin during 3 d of culture, irrespective of gonadotropin treatment or stage of estrus. Likewise, negligible amounts of oxytocin were measured in theca and follicle wall cultures at both developmental stages, in the presence or absence of gonadotropins. Furthermore, follicular fluid from early or late estrous follicles contained only negligible amounts of oxytocin. To determine if oxytocin affects steroidogenesis by equine granulosa cells, granulosa cells from follicles obtained on Day 2 of estrus were cultured with graded doses of oxytocin (0, 1, 10, 100, and 1,000 ng/ml) in defined medium supplemented with testosterone (0.5 microM) and culture media were assayed for estradiol-17 beta and progesterone. Estradiol was secreted throughout the culture period, and its production was not significantly affected by oxytocin treatment (P > 0.05). Progesterone secretion was relatively low during the first 24 hr of culture, increased dramatically on the second day of culture, and remained high through the third day. No dose of oxytocin had a significant effect on progesterone secretion (P > 0.05). In conclusion, the results indicate that equine preovulatory follicles, isolated during early or late estrus, are neither a source of oxytocin nor a target for oxytocin action on steroidogenesis. Although ovarian oxytocin appears to play a role in regulating follicular function in some other mammalian species, our data provide no support for such a role for oxytocin in mares.