Marked association between obesity and glomerular hyperfiltration: a cross-sectional study in an African population.

BACKGROUND: Obesity and African American ethnicity are established independent risk factors for the development of chronic kidney disease. No data exist about the association between obesity and renal hemodynamics in the African region. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 301 nondiabetic participants (97 lean, 108 overweight, and 96 obese) of African descent with a positive family history of hypertension from the Seychelles islands. PREDICTOR: Body mass index (BMI). OUTCOMES: Glomerular hyperfiltration, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and filtration fraction. MEASUREMENTS: GFR and ERPF were measured using inulin and para-aminohippurate clearances, respectively. Participants' baseline demographics, laboratory data, and blood pressure were measured using standard techniques. RESULTS: The prevalence of glomerular hyperfiltration (defined as GFR >or=140 mL/min) increased across BMI categories (7.2%, 14.8%, and 27.1% for lean, overweight, and obese participants, respectively; P < 0.001). Higher BMI was associated with higher median GFR (99, 110, and 117 mL/min for lean, overweight, and obese participants, respectively; P < 0.001), ERPF (424, 462, and 477 mL/min, respectively; P = 0.01), and filtration fraction (0.23, 0.24, and 0.25; P < 0.001). Multivariate analyses adjusting for age, sex, blood pressure, fasting glucose level, and urinary sodium excretion and accounting for familial correlations confirmed the associations between high BMI (>25 kg/m(2)) and increased GFR, ERPF, and filtration fraction. No association between BMI categories and GFR was found with adjustment for body surface area. LIMITATIONS: Participants had a positive family history of hypertension. CONCLUSION: Overweight and obesity are associated with increased GFR, ERPF, and filtration fraction and a high prevalence of glomerular hyperfiltration in nondiabetic individuals of African descent. The absence of associations between BMI categories and GFR indexed for body surface area raises questions regarding the appropriateness of indexing GFR for body surface area in overweight populations.

Association between smoking and total energy expenditure in a multi-country study.

BACKGROUND: The association between smoking and total energy expenditure (TEE) is still controversial. We examined this association in a multi-country study where TEE was measured in a subset of participants by the doubly labeled water (DLW) method, the gold standard for this measurement. METHODS: This study includes 236 participants from five different African origin populations who underwent DLW measurements and had complete data on the main covariates of interest. Self-reported smoking status was categorized as either light (<7 cig/day) or high (≥7 cig/day). Lean body mass was assessed by deuterium dilution and physical activity (PA) by accelerometry. RESULTS: The prevalence of smoking was 55% in men and 16% in women with a median of 6.5 cigarettes/day. There was a trend toward lower BMI in smokers than non-smokers (not statistically significant). TEE was strongly correlated with fat-free mass (men: 0.70; women: 0.79) and with body weight (0.59 in both sexes). Using linear regression and adjusting for body weight, study site, age, PA, alcohol intake and occupation, TEE was larger in high smokers than in never smokers among men (difference of 298 kcal/day, p = 0.045) but not among women (162 kcal/day, p = 0.170). The association became slightly weaker in men (254 kcal/day, p = 0.058) and disappeared in women (-76 kcal/day, p = 0.380) when adjusting for fat-free mass instead of body weight. CONCLUSION: There was an association between smoking and TEE among men. However, the lack of an association among women, which may be partly related to the small number of smoking women, also suggests a role of unaccounted confounding factors.

Cytochrome P450 and ABCB1 genetics: association with quetiapine and norquetiapine plasma and cerebrospinal fluid concentrations and with clinical response in patients suffering from schizophrenia. A pilot study.

Variability in response to atypical antipsychotic drugs is due to genetic and environmental factors. Cytochrome P450 (CYP) isoforms are implicated in the metabolism of drugs, while the P-glycoprotein transporter (P-gp), encoded by the ABCB1 gene, may influence both the blood and brain drug concentrations. This study aimed to identify the possible associations of CYP and ABCB1 genetic polymorphisms with quetiapine and norquetiapine plasma and cerebrospinal fluid (CSF) concentrations and with response to treatment. Twenty-two patients with schizophrenia receiving 600 mg of quetiapine daily were genotyped for four CYP isoforms and ABCB1 polymorphisms. Quetiapine and norquetiapine peak plasma and CSF concentrations were measured after 4 weeks of treatment. Stepwise multiple regression analysis revealed that ABCB1 3435C > T (rs1045642), 2677G > T (rs2032582) and 1236C > T (rs1128503) polymorphisms predicted plasma quetiapine concentrations, explaining 41% of the variability (p = 0.001). Furthermore, the ABCB1 polymorphisms predicted 48% (p = 0.024) of the variability of the Δ PANSS total score, with the non-carriers of the 3435TT showing higher changes in the score. These results suggest that ABCB1 genetic polymorphisms may be a predictive marker of quetiapine treatment in schizophrenia.

Association of statins with inflammatory cytokines: a population-based Colaus study.

PURPOSE: A pleiotropic effect of statins has been reported in numerous studies. However, the association between statin use and inflammatory cytokines is controversial. We examined the associations between statin use and C-reactive protein (CRP), tumour necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in a healthy Caucasian population. METHODS: Cross-sectional study of 6184 participants aged 35-75years from Lausanne, Switzerland. Cytokines were assessed by multiplexed particle-based flow cytometric assay. Self-reported history of medication was collected for statins and other medication. 99 participants without cytokine data were excluded. RESULTS: Among the 6085 participants, 2289 (37.6%), 451 (7.4%) and 43 (0.7%) had IL-1β, IL-6 and TNF-α levels below detection limits, respectively. On multivariate analysis adjusting for age, gender, smoking status, body mass index, hypertension, diabetes, baseline cardiovascular disease, total cholesterol, anti-inflammatory use, other cytokine modifying drugs and other drugs, participants on statins had significantly lower CRP levels (adjusted mean±standard error: 1.22±1.05 vs. 1.38±1.04mg/L for use and non-use, respectively, p<0.01 on log-transformed data). Conversely, no association was found between statin use and IL-1β (p=0.91), IL-6 (p=0.25) or TNF-α (p=0.28) levels. On multivariate analysis, individuals in the statin group (β coefficient=-0.12; 95% CI=-0.21, -0.03) had lower levels of CRP as compared to those in the reference group (i.e. those not using statin). However, no significant associations were observed between IL-1β, IL-6 and TNF-α and statins. CONCLUSION: Individuals on statins have lower CRP levels; conversely, no effect was found for IL-1β, IL-6 and TNF-α levels.

Association between bipolar disorder and monoamine oxidase A gene polymorphisms: results of a multicenter study

OBJECTIVE: Although genetic factors have been implicated in the etiology of bipolar disorder, no specific gene has been conclusively identified. Given the link between abnormalities in serotonergic neurotransmission and bipolar disorder, a candidate gene association approach was applied to study the involvement of the monoamine oxidase A (MAOA) gene, which codes for a catabolic enzyme of serotonin, in the susceptibility to bipolar disorder. METHOD: In France and Switzerland, 272 patients with bipolar disorder and 122 healthy subjects were typed for three polymorphic markers of the MAOA gene: the MAOA-CA repeat, the MAOA restriction fragment length polymorphism (RFLP), and a repeat directly adjacent to the variable number of tandem repeats (VNTR) locus. RESULTS: A significant difference in the distribution of the alleles for the MAOA-CA repeat was observed between the female bipolar patients and comparison group. CONCLUSIONS: The results obtained in the French and Swiss population confirm findings from two studies conducted in the United Kingdom.

Association of work related chronic stressors and psychiatric symptoms in a Swiss sample of police officers : a cross sectional questionnaire study

Purpose (1) To identify work related stressors that are associated with psychiatric symptoms in a Swiss sample of policemen and (2) to develop a model for identifying officers at risk for developing mental health problems. Method The study design is cross sectional. A total of 354 male police officers answered a questionnaire assessing a wide spectrum of work related stressors. Psychiatric symptoms were assessed using the "TST questionnaire" (Langner in J Health Hum Behav 4, 269-276, 1962). Logistic regression with backward procedure was used to identify a set of variables collectively associated with high scores for psychiatric symptoms. Results A total of 42 (11.9%) officers had a high score for psychiatric symptoms. Nearly all potential stressors considered were significantly associated (at P < 0.05) with a high score for psychiatric symptoms. A significant model including 6 independent variables was identified: lack of support from superior and organization OR = 3.58 (1.58-8.13), self perception of bad quality work OR = 2.99 (1.35-6.59), inadequate work schedule OR = 2.84 (1.22-6.62), high mental/intellectual demand OR = 2.56 (1.12-5.86), age (in decades) OR = 1.82 (1.21-2.73), and score for physical environment complaints OR = 1.30 (1.03-1.64). Conclusions Most of work stressors considered are associated with psychiatric symptoms. Prevention should target the most frequent stressors with high association to symptoms. Complaints of police officers about stressors should receive proper consideration by the management of public administration. Such complaints might be the expression of psychiatric caseness requiring medical assistance. Particular attention should be given to police officers complaining about many stressors identified in this study's multiple model. [Authors]

Association between Inflammatory and Obesity Markers in a Swiss Population-Based Sample (CoLaus Study).

Objective: To assess the associations between obesity markers (BMI, waist circumference and %body fat) and inflammatory markers (interleukin-1β (IL-1β); interleukin-6 (IL-6); tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hs-CRP)). Methods: Population sample of 2,884 men and 3,201 women aged 35-75 years. Associations were assessed using ridge regression adjusting for age, leisure-time physical activity, and smoking. Results: No differences were found in IL-1β levels between participants with increased obesity markers and healthy counterparts; multivariate regression showed %body fat to be negatively associated with IL-1β. Participants with high %body fat or abdominal obesity had higher IL-6 levels, but no independent association between IL-6 levels and obesity markers was found on multivariate regression. Participants with abdominal obesity had higher TNF-α levels, and positive associations were found between TNF-α levels and waist circumference in men and between TNF-α levels and BMI in women. Obese participants had higher hs-CRP levels, and these differences persisted after multivariate adjustment; similarly, positive associations were found between hs-CRP levels and all obesity markers studied. Conclusion: Obesity markers are differentially associated with cytokine levels. %Body fat is negatively associated with IL-1β; BMI (in women) and waist circumference (in men) are associated with TNF-α; all obesity markers are positively associated with hs-CRP. Copyright © 2012 S. Karger GmbH, Freiburg.

Traitement de la dépression résistante par l'association citalopram-lithium. Méthodologie d'une étude multicentrique en double aveugle et résultats préliminaires [Treatment of resistant depression with the citalopram-lithium combination. Methodology of a double-blind multicenter study and preliminary results].

Citalopram, a new bicyclic antidepressant, is the most selective serotonin reuptake inhibitor. In a number of double-blind controlled studies, citalopram was compared to placebo and to known tricyclic antidepressants. These studies have shown their efficacy and good safety. The inefficacy of a psychotropic treatment in at least 20% of depressives has led a number of authors to propose original drug combinations and associations, like antidepressant/lithium (Li), antidepressant/sleep deprivation (agrypnia), antidepressant/ECT, or antidepressant/LT3. The aim of this investigation is to evaluate the clinical effectiveness and safety of a combined citalopram/lithium treatment in therapy-resistant patients, taking account of serotonergic functions, as tested by the fenfluramine/prolactin test, and of drug pharmacokinetics and pharmacogenetics of metabolism. DESIGN OF THE STUDY: A washout period of 3 days before initiating the treatment is included. After an open treatment phase of 28 days (D) with citalopram (20 mg D1-D3; 40 mg D4-D14; 40 or 60 mg D15-D28; concomitant medication allowed: chloral, chlorazepate), the nonresponding patients [less than 50% improvement in the total score on the 21 item-Hamilton Depression Rating Scale (HDRS)] are selected and treated with or without Li (randomized in double-blind conditions: citalopram/Li or citalopram/placebo) during the treatment (D29-D35). Thereafter, all patients included in the double-blind phase subsequently receive an open treatment with citalopram/Li for 7 days (D36-D42). The hypothesis of a relationship between serotoninergic functions in patients using the fenfluramine/prolactin test (D1) and the clinical response to citalopram (and Li) is assessed. Moreover, it is evaluated whether the pharmacogenetic status of the patients, as determined by the mephenytoin/dextromethorphan test (D0-D28), is related to the metabolism of fenfluramine and citalopram, and also to the clinical response. CLINICAL ASSESSMENT: Patients with a diagnosis of major depressive disorders according to DSM III are submitted to a clinical assessment of D1, D7, D14, D28, D35, D42: HDRS, CGI (clinical global impression), VAS (visual analog scales for self-rating of depression), HDRS (Hamilton depression rating scale, 21 items), UKU (side effects scale), and to clinical laboratory examens, as well as ECG, control of weight, pulse, blood pressure at D1, D28, D35. Fenfluramine/prolactin test: A butterfly needle is inserted in a forearm vein at 7 h 45 and is kept patent with liquemine. Samples for plasma prolactin, and d- and l-fenfluramine determinations are drawn at 8 h 15 (base line). Patients are given 60 mg fenfluramine (as a racemate) at 8 h 30. Kinetic points are determined at 9 h 30, 10 h 30, 11 h 30, 12 h 30, 13 h 30. Plasma levels of d- and l-fenfluramine are determined by gas chromatography and prolactin by IRNA. Mephenytoin/dextromethorphan test: Patients empty their bladders before the test; they are then given 25 mg dextropethorphan and 100 mg mephenytoin (as a racemate) at 8 h 00. They collect all urines during the following 8 hours. The metabolic ratio is determined by gas chromatography (metabolic ratio dextromethorphan/dextrorphan greater than 0.3 = PM (poor metabolizer); mephenytoin/4-OH-mephenytoin greater than 5.6, or mephenytoin S/R greater than 0.8 = PM). Citalopram plasma levels: Plasma levels of citalopram, desmethylcitalopram and didesmethylcitalopram are determined by gas chromatography--mass spectrometry. RESULTS OF THE PILOT STUDY. The investigation has been preceded by a pilot study including 14 patients, using the abovementioned protocol, except that all nonresponders were medicated with citalopram/Li on D28 to D42. The mean total score (n = 14) on the 21 item Hamilton scale was significantly reduced after the treatment, ie from 26.93 +/- 5.80 on D1 to 8.57 +/- 6.90 on D35 (p less than 0.001). A similar patCitalopram, a new bicyclic antidepressant, is the most selective serotonin reu

Association of calcemia and serum vitamin D with 24H-urinary calcium excretion in a swiss population-based study

Background: Elevated urinary calcium excretion is associated with reduced bone mineral density. Population-based data on urinary calcium excretion are scarce. We explored the association of serum calcium and circulating levels of vitamin D (including 25(OH)D2 and 25(OH)D3) with urinary calcium excretion in men and women in a population-based study. Methods: We used data from the "Swiss Survey on Salt" conducted between 2010 and 2012 and including people aged 15 years and over. Twenty-four hour urine collection, blood analysis, clinical examination and anthropometric measures were collected in 11 centres from the 3 linguistic regions of Switzerland. Vitamin D was measured centrally using liquid chromatography - tandem mass spectrometry. Hypercalciuria was defined as urinary calcium excretion >0.1 mmol/kg/24h. Multivariable linear regression was used to explore factors associated with 24-hour urinary calcium excretion (mmol/24h) squared root transformed, taken as the dependant variable. Vitamin D was divided into monthspecific tertiles with the first tertile having the lowest value and the third tertile having the highest value. Results: The 669 men and 624 women had mean (SD) age of 49.2 (18.1) and 47 (17.9) years and a prevalence of hypercalciuria of 8.9% and 8.0%, respectively. In adjusted models, the association of urinary calcium excretion with protein-corrected serum calcium was (β coefficient } standard error, according to urinary calcium squared root transformed) 1.125 } 0.184 mmol/L per square-root (mmol/24h) (P<0.001) in women and 0.374 } 0.224 (P=0.096) in men. Men in the third month-specific vitamin D tertile had higher urinary calcium excretion than men in the first tertile (0.170 } 0.05 nmol/L per mmol/24h, P=0.001) and the corresponding association was 0.048 } 0.043, P= 0.272 in women. Conclusion: About one in eleven person has hypercalciuria in the Swiss population. The positive association of serum calcium with urinary calcium excretion was steeper in women than in men, independently of menopausal status. Circulating vitamin D was associated positively with urinary calcium excretion only in men. The reasons underlying the observed sex differences in the hormonal control of urinary calcium excretion need to be explored in further studies.

The PsyCoLaus study: methodology and characteristics of the sample of a population-based survey on psychiatric disorders and their association with genetic and cardiovascular risk factors.

ABSTRACT: BACKGROUND: The Psychiatric arm of the population-based CoLaus study (PsyCoLaus) is designed to: 1) establish the prevalence of threshold and subthreshold psychiatric syndromes in the 35 to 66 year-old population of the city of Lausanne (Switzerland); 2) test the validity of postulated definitions for subthreshold mood and anxiety syndromes; 3) determine the associations between psychiatric disorders, personality traits and cardiovascular diseases (CVD), 4) identify genetic variants that can modify the risk for psychiatric disorders and determine whether genetic risk factors are shared between psychiatric disorders and CVD. This paper presents the method as well as somatic and sociodemographic characteristics of the sample. METHODS: All 35 to 66 year-old persons previously selected for the population-based CoLaus survey on risk factors for CVD were asked to participate in a substudy assessing psychiatric conditions. This investigation included the Diagnostic Interview for Genetic Studies to elicit diagnostic criteria for threshold disorders according to DSM-IV and algorithmically defined subthreshold syndromes. Complementary information was gathered on potential risk and protective factors for psychiatric disorders, migraine and on the morbidity of first-degree family members, whereas the collection of DNA and plasma samples was part of the original somatic study (CoLaus). RESULTS: A total of 3,691 individuals completed the psychiatric evaluation (67% participation). The gender distribution of the sample did not differ significantly from that of the general population in the same age range. Although the youngest 5-year band of the cohort was underrepresented and the oldest 5-year band overrepresented, participants of PsyCoLaus and individuals who refused to participate revealed comparable scores on the General Health Questionnaire, a self-rating instrument completed at the somatic exam. CONCLUSIONS: Despite limitations resulting from the relatively low participation in the context of a comprehensive and time-consuming investigation, the PsyCoLaus study should significantly contribute to the current understanding of psychiatric disorders and comorbid somatic conditions by: 1) establishing the clinical relevance of specific psychiatric syndromes below the DSM-IV threshold; 2) determining comorbidity between risk factors for CVD and psychiatric disorders; 3) assessing genetic variants associated with common psychiatric disorders and 4) identifying DNA markers shared between CVD and psychiatric disorders.

Association of socioeconomic status with sleep disturbances in the Swiss population-based CoLaus study.

OBJECTIVE: To examine the association of socioeconomic status (SES) with subjective and objective sleep disturbances and the role of socio-demographic, behavioural and psychological factors in explaining this association. METHODS: Analyses are based on 3391 participants (53% female, aged 40-81 years) of the follow-up of the CoLaus study (2009-2012), a population-based sample of the city of Lausanne, Switzerland. All participants completed a sleep questionnaire and a sub-sample (N = 1569) underwent polysomnography. RESULTS: Compared with men with a high SES, men with a low SES were more likely to suffer from poor sleep quality [prevalence ratio (PR) for occupational position = 1.68, 95% Confidence Interval (CI): 1.30-2.17], and to have long sleep latency (PR = 4.90, 95%CI: 2.14-11.17), insomnia (PR = 1.47, 95% CI: 1.12-1.93) and short sleep duration (PR = 3.03, 95% CI: 1.78-5.18). The same pattern was observed among women (PR = 1.29 for sleep quality, 2.34 for sleep latency, 2.01 for daytime sleepiness, 3.16 for sleep duration, 95%CIs ranging from 1.00 to 7.51). Use of sleep medications was not patterned by SES. SES differences in sleep disturbances were only marginally attenuated by adjustment for other socio-demographic, behavioural and psychological factors. Results from polysomnography confirmed poorer sleep patterns among participants with low SES (p <0.05 for sleep efficiency/stage shifts), but no SES differences were found for sleep duration. CONCLUSIONS: In this population-based sample, low SES was strongly associated with sleep disturbances, independently of socio-demographic, behavioural, and psychological factors. Further research should establish the extent to which social differences in sleep contribute to socioeconomic differences in health outcomes.

Association of car ownership and physical activity across the spectrum of human development : Modeling the Epidemiologic Transition Study (METS).

BACKGROUND: Variations in physical activity (PA) across nations may be driven by socioeconomic position. As national incomes increase, car ownership becomes within reach of more individuals. This report characterizes associations between car ownership and PA in African-origin populations across 5 sites at different levels of economic development and with different transportation infrastructures: US, Seychelles, Jamaica, South Africa, and Ghana. METHODS: Twenty-five hundred adults, ages 25-45, were enrolled in the study. A total of 2,101 subjects had valid accelerometer-based PA measures (reported as average daily duration of moderate to vigorous PA, MVPA) and complete socioeconomic information. Our primary exposure of interest was whether the household owned a car. We adjusted for socioeconomic position using household income and ownership of common goods. RESULTS: Overall, PA levels did not vary largely between sites, with highest levels in South Africa, lowest in the US. Across all sites, greater PA was consistently associated with male gender, fewer years of education, manual occupations, lower income, and owning fewer material goods. We found heterogeneity across sites in car ownership: after adjustment for confounders, car owners in the US had 24.3 fewer minutes of MVPA compared to non-car owners in the US (20.7 vs. 45.1 minutes/day of MVPA); in the non-US sites, car-owners had an average of 9.7 fewer minutes of MVPA than non-car owners (24.9 vs. 34.6 minutes/day of MVPA). CONCLUSIONS: PA levels are similar across all study sites except Jamaica, despite very different levels of socioeconomic development. Not owning a car in the US is associated with especially high levels of MVPA. As car ownership becomes prevalent in the developing world, strategies to promote alternative forms of active transit may become important.