Showing papers by "Matthias Nauck published in 2010"

New loci associated with kidney function and chronic kidney disease

Abstract: Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m(2); n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide-significant loci (P < 5 x 10(-8)) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.

The Predictive Value of Different Measures of Obesity for Incident Cardiovascular Events and Mortality

Abstract: 1.74(0.84–3.6),1.71(0.91–3.22),and0.74(0.35–1.57),respectively;all-causemortality,1.86(1.25–2.76), 1.62 (1.22–2.38), 1.36 (0.93–1.69), and 0.77 (0.53–1.13), respectively; and composite endpoint, 2.16 (1.39–3.35), 1.59 (1.04–2.44), 1.49 (1.07–2.07), and 0.57 (0.37–0.89), respectively. Separate analyses of sex and age groups yielded comparable results. Receiver operating characteristics analysis yielded the highest areas under the curve for WHtR for predicting these endpoints. Conclusions:WHtR represents the best predictor of cardiovascular risk and mortality, followed by WC and WHR. Our results discourage the use of the BMI. (J Clin Endocrinol Metab 95: 0000–0000, 2010)

Low serum testosterone levels are associated with increased risk of mortality in a population-based cohort of men aged 20–79

Abstract: Aims Although the association of low serum testosterone levels with mortality has gained strength in recent research, there are few population-based studies on this issue. This study examined whether low serum testosterone levels are a risk factor for all-cause or cause-specific mortality in a population-based sample of men aged 20–79. Methods and results We used data from 1954 men recruited for the prospective population-based Study of Health in Pomerania, with measured serum testosterone levels at baseline and 195 deaths during an average 7.2-year follow-up. A total serum testosterone level of less than 8.7 nmol/L (250 ng/dL) was classified as low. The relationships of low serum testosterone levels with all-cause and cause-specific mortality were analysed by Cox proportional hazards regression models. Men with low serum testosterone levels had a significantly higher mortality from all causes than men with higher serum testosterone levels (HR 2.24; 95% CI 1.41–3.57). After adjusting for waist circumference, smoking habits, high-risk alcohol use, physical activity, renal insufficiency, and levels of dehydroepiandrosterone sulfate, low serum testosterone levels continued to be associated with increased mortality (HR 2.32; 95% CI 1.38–3.89). In cause-specific analyses, low serum testosterone levels predicted increased risk of death from cardiovascular disease (CVD) (HR 2.56; 95% CI 1.15–6.52) and cancer (HR 3.46; 95% CI 1.68–6.68), but not from respiratory diseases or other causes. Conclusion Low serum testosterone levels were associated with an increased risk of all-cause mortality independent of numerous risk factors. As serum testosterone levels are inversely related to mortality due to CVD and cancer, it may be used as a predictive marker.

Periodontal status and A1C change: longitudinal results from the Study of Health in Pomerania (SHIP).

Abstract: OBJECTIVE Infection may be a type 2 diabetes risk factor. Periodontal disease is a chronic infection. We hypothesized that periodontal disease was related to A1C progression in diabetes-free participants. RESEARCH DESIGN AND METHODS The Study of Health in Pomerania (SHIP) is a population-based cohort in Germany including 2,973 diabetes-free participants (53% women; aged 20–81 years). Participants were categorized into four groups according to increasing baseline periodontal disease levels (percentage of sites per mouth with attachment loss ≥5 mm, determined a priori); sample sizes for each respective category were 1,122, 488, 463, and 479 (241 participants were edentulous). Mean absolute changes (year 5 minus baseline) in A1C (ΔA1C) were regressed across periodontal categories while adjusting for confounders (e.g., age, sex, smoking, obesity, physical activity, and family history). RESULTS Across baseline periodontal disease categories, ΔA1C ± SEM values were 0.023 ± 0.02, 0.023 ± 0.02, 0.065 ± 0.03, and 0.106 ± 0.03 ( P trend = 0.02), yielding an approximate fivefold increase in the absolute difference in ΔA1C when dentate participants in the highest versus lowest periodontal disease category were compared; these results were markedly stronger among participants with high-sensitivity C-reactive protein ≥1.0 mg/l ( P interaction = 0.01). When individuals who had neither baseline periodontal disease nor deterioration in periodontal status at 5 years were compared with individuals with both poor baseline periodontal health and longitudinal periodontal deterioration, mean ΔA1C values were 0.005 vs. 0.143% ( P = 0.003). CONCLUSIONS Periodontal disease was associated with 5-year A1C progression, which was similar to that observed for a 2-SD increase in either waist-to-hip ratio or age in this population.

Childhood maltreatment, the corticotropin-releasing hormone receptor gene and adult depression in the general population

Abstract: Dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis have been implicated in the pathogenesis of depressive disorders and the corticotropin-releasing hormone (CRH) was found to modulate emotional memory consolidation. Recently, two studies have reported an interaction between childhood abuse and the TAT-haplotype of the CRH-Receptor Gene (CRHR1) connecting childhood adversities and genetic susceptibility to adult depression. We tested the hypothesis of an interaction of childhood maltreatment with single nucleotide polymorphisms (SNPs) and haplotypes of the CRHR1 gene not previously investigated. Caucasian subjects (n = 1,638) from the German general population (Study of Health in Pomerania, SHIP) were analyzed. As in the previous studies, childhood abuse and neglect were assessed with the Childhood Trauma Questionnaire (CTQ) and depression with the Beck Depression Inventory (BDI-2). The CRHR1-SNPs were genotyped on the Affymetrix Genome-Wide Human SNP Array 6.0 platform. We identified an interaction between the TAT-haplotype and childhood physical neglect. The interaction with physical neglect showed significant (P < 0.05) results in 23 of the 28 SNPs, with rs17689882 (P = 0.0013) reaching "gene-wide" significance. Although we did not replicate the specific interaction of abuse and the TAT-haplotype of the CRHR1 gene we confirmed the relevance of an interplay between variants within the CRHR1 gene and childhood adversities in the modulation of depression in adults. The largest effect was found for rs17689882, a SNP previously not analyzed. Relevant sample differences between this and prior studies like lower BDI-2 scores, less childhood maltreatment and higher psychosocial functioning may account for the differences in gene-environment interaction findings. © 2010 Wiley-Liss, Inc.

Hepatic steatosis is associated with low serum testosterone and high serum DHEAS levels in men.

Abstract: Obesity and metabolic syndrome are associated with low serum testosterone levels. Hepatic steatosis contributes to the metabolic syndrome and might be regarded as its hepatic manifestation. In this study, we sought to investigate the relationship between hepatic steatosis, serum testosterone and dehydroepiandrosterone sulphate (DHEAS) levels in men. This is a cross-sectional population-based study. We used data of 1912 men recruited for the population-based Study of Health in Pomerania, which was conducted in a region with high prevalence of metabolic syndrome and related diseases. Hepatic steatosis was defined according to sonographic criteria. The relationship of hepatic steatosis with serum testosterone and DHEAS levels was analysed by multivariable logistic regression. Men with low serum testosterone levels had a higher risk of hepatic steatosis than men with high serum testosterone levels. Adjustment for age and further confounders attenuated this association, but did not affect statistical significance (odds ratio 2.36; 95% confidence interval 1.66-3.37; p < 0.05). In the full model, the highest risk of hepatic steatosis was found in subjects with the highest serum DHEAS levels (odds ratio 1.59; 95% confidence interval 1.04-2.43; p < 0.05). Exclusion of men with high alcohol consumption did not affect these results substantially. Hepatic steatosis is associated with low serum testosterone and high serum DHEAS levels. These associations are independent of alcohol consumption.

Prevalence, incidence and risk factors of testosterone deficiency in a population-based cohort of men: results from the study of health in Pomerania.

Abstract: Objective. Low total testosterone levels (TT) have been associated with increased morbidity and mortality. However, the prevalence and incidence of testosterone deficiency (TD) in association with its risk has not been assessed systematically to date.Methods. Data from the prospective population-based Study of Health in Pomerania were used. From the 2117 men aged 20–79 years at baseline, 1490 men with complete TT data were analysed. Crude and age-specific prevalence and incidence rates of TD were estimated by TT levels below the age-specific 10th percentile. Analysis of covariance and Poisson regression models were used to assess the association of socio-demographic characteristics, health-related lifestyle, as well as somatometric, medical and laboratory measures with risk of incident TD.Results. TD baseline prevalence was 10.4% (N = 155) and incidence 11.7 per 1000 person-years. TT levels showed a significant age-related decline with an unadjusted rate of 0.05 nmol/l per year. Obesity, metabolic syndrom...

The association of serum testosterone levels and ventricular repolarization.

Abstract: It is assumed that testosterone is an important regulator of gender-related differences in ventricular repolarization. Therefore, our aim was to study whether serum levels of testosterone are associated with QTc, QT and RR interval variation. Setting: two independent population-based cohort studies. Participants: 445 male participants (≥55 years) from the Rotterdam study cohort and 1,428 male participants from the study of health in Pomerania (SHIP) with an electrocardiogram who were randomly sampled for assessment of serum testosterone at baseline, after exclusion of participants with testosterone altering drugs, QTc prolonging drugs or dig(it)oxin, left ventricular hypertrophy and left and right bundle branch block. Endpoints: length of the QTc, QT and RR intervals. Analysis: linear regression model, adjusted for the two individual studies and a pooled analysis of both studies. The pooled analysis of the Rotterdam study and SHIP showed that the QTc interval gradually decreased among the tertiles (P value for trend 0.024). The third tertile of serum testosterone was associated with a lower QTc interval compared to the first tertile [−3.4 ms (−6.5; −0.3)]. However, the third tertile of serum testosterone was not associated with a lower QT interval compared to the first tertile [−0.7 ms (−3.1; 1.8)]. The RR interval gradually increased among the tertiles (P value for trend 0.002) and the third tertile of serum testosterone showed an increased RR interval compared to the first tertile [33.5 ms (12.2; 54.8)]. In the pooled analysis of two population-based studies, serum testosterone levels were not associated with the QT interval, which could be due to a lack of power. Lower QTc intervals in men with higher serum testosterone levels could be due to the association of serum testosterone with prolongation of the RR interval.

Decreased serum TSH levels are not associated with mortality in the adult northeast German population.

Abstract: Objective: Results of cohort studies on the association between decreased serum TSH levels and mortality are conflicting. Some studies demonstrated an increased mortality risk in subjects with decreased serum TSH levels, others did not. Even meta-analyses revealed contradictory results. We undertook the present study to investigate the association between decreased serum TSH levels and mortality in the large population-based Study of Health in Pomerania (SHIP). Design and methods: Data from 3651 individuals from SHIP without known thyroid disorders or thyroid treatment were analyzed. Serum TSH, free triiodothyronine, and free thyroxine levels were determined by immunochemiluminescent procedures. Decreased TSH was defined as serum TSH levels below 0.25 mIU/l. Cox regression was used to associate decreased TSH levels with mortality. Results: The median duration of follow-up was 8.5 years (30 126 person years). During follow-up, 299 individuals (6.9%) died corresponding to a death rate of 9.92 deaths per 1000 person years. Survival time was shorter in subjects with decreased serum TSH levels compared to euthyroid individuals. After adjustment for age and sex, however, there was no association between decreased serum TSH levels and all-cause mortality (hazard ratio: 0.95; 95% confidence interval: 0.67; 1.36). Likewise, decreased serum TSH levels were neither associated with cardiovascular nor with cancer mortality. Conclusions: There is no independent association of decreased serum TSH levels with all-cause, cardiovascular, and cancer mortality in the adult northeast German population. Although our study has some strengths, we cannot finally conclude on therapeutical implications in individuals with subclinical thyroid diseases.

The association between fatty liver disease and blood pressure in a population-based prospective longitudinal study.

Abstract: Objective The aim of the present study was to investigate the association of fatty liver disease (FLD) with blood pressure (BP) and hypertension in a general population sample with prospective 5-year follow-up examinations. Design and methods We used data from the Study of Health in Pomerania, conducted in the northeastern part of Germany. The study population comprised 3191 individuals aged 20-79 years. FLD was defined as the presence of a hyperechogenic pattern of the liver and increased serum alanine transferase (ALT) levels. Results Multivariable analyses revealed that FLD was associated with increased DBP and hypertension at baseline and with increased SBP and hypertension at follow-up. In individuals with FLD, the chance of hypertension at baseline and follow-up was three-fold higher [odds ratio (OR) 2.8; 95% confidence interval (CI) 1.3-6.2 and OR 3.1; 95% CI 1.7―5.8, respectively] compared to individuals without FLD. In the subgroup of individuals not receiving antihypertensive medication, FLD was associated with all BP-related variables at baseline and follow-up. Analyses further suggest that these associations were independent of alcohol consumption and further confounders. Conclusion FLD defined by liver hyperechogenity and increased ALT levels is associated with progression of BP over time and incident hypertension. In individuals with FLD, BP should be checked regularly and interventions addressing behavioural risk factors for FLD and hypertension should be initiated if necessary. Ultrasound should be implemented as a method to detect FLD in individuals with increased ALT levels in routine medical care.

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

Abstract: 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.

Subclinical hyperthyroidism is not associated with progression of cardiac mass and development of left ventricular hypertrophy in middle-aged and older subjects: results from a 5-year follow-up

Abstract: Background Decreased serum TSH levels are associated with increased cardiovascular mortality in elderly, and subclinical hyperthyroidism (SCH) was associated with left ventricular hypertrophy (LVH) as a predictor of cardiovascular mortality in some cross-sectional and case-control studies. The aim was to assess whether SCH independently impacts development of LVH over time. Methods Of 3300 participants of the population-based Study of Health in Pomerania those with overt hyperthyroidism, hypothyroidism, possible thyroid disease or missing echocardiographic baseline data or follow-up were excluded, resulting in a study population of 1112 individuals (556 women) aged 45-81 years. Echocardiographic left ventricular mass divided by height(2·7) (LVMI(ht)), and LVH(ht) (LVMI(ht) > 44 g/m(2·7) in women and > 48 g/m(2·7) in men) was measured at baseline and after 5-year follow-up (median 5·00; range 4·92; 5·08). Comparison of subjects with (n = 107) and without (n = 1005) SCH were made by linear and logistic regression models adjusted for age, gender, smoking status, hypertension, and waist circumference. Results At follow-up, LVMI(ht) did not differ between subjects with and without SCH (50·2 g/m(2·7), interquartile range (IQR) 41·2; 59·5 vs 47·8 g/m(2·7), IQR 39·3; 56·9; P = 0·29). LVH(ht) was present in 66 (61·7%) subjects with and 543 (54·0%) persons without SCH (P = 0·13). Analyses revealed no association between SCH and progression of LVMI(ht) (β = -0·18; 95%-confidence interval (CI) -2·34; -1·99; P = 0·873), and development of LVH(ht) (relative risk 0·86, 95%-CI 0·60; 1·26; P = 0·462), respectively. Conclusions In this population-based sample, SCH had no impact on progression of LVMI and development of LVH during 5-year follow-up in subjects aged 45 years or older.

Reference Levels for Serum Thyroid Function Tests of Diagnostic and Prognostic Significance

Abstract: A controversy exists on the value of upper thyrotropin (TSH) reference level. Currently available studies are based on cross-sectional data leaving uncertainty about the prognostic significance of the upper TSH reference level. With the present study we sought to establish reference values for serum thyroid function tests that are of both diagnostic and prognostic significance. We used data from the prospective population-based Study of Health in Pomerania (SHIP) with a 5 year follow-up (6080 person-years). We included data from 1203 subjects (525 women) without prevalent subclinical or manifest thyroid disorders. An event-free reference population was separated comprising 1053 subjects (473 women). When comparing reference values as analyzed from either the whole reference population or the event-free reference population, we observed notable differences in TSH reference intervals. While the lower TSH reference values were similar in both populations, the upper value was 1.95 mIU/l and thus by 7.6% lower in subjects without incident events compared to the whole reference population. Both populations did not substantially differ with respect to serum FT3 and FT4 reference intervals. The upper TSH reference value is lower than recommended when both diagnostic and prognostic significance are considered in the definition of the TSH reference range.

Total and cardiovascular disease mortality predicted by metabolic syndrome is inferior relative to its components.

Abstract: OBJECTIVES: This study examined the predictive role of metabolic syndrome (MetS) and its single components for total and cardiovascular disease (CVD) mortality. METHODS: We analyzed data from 3 927 participants aged 20-79 years without history of CVD, recruited for the prospective population-based Study of Health in Pomerania (SHIP). During the mean 7.2 years (25 th , 6.6; 75 th : 8.0) of follow-up, 240 deaths (79 CVD deaths) occurred. MetS was defined by National Cholesterol Education Program Adult Treatment Panel III guidelines. The association of MetS with total and CVD mortality was analyzed by Cox proportional hazards regression models. The impact of single MetS components on survival time was compared using standardized beta coefficients from multivariable linear regression models. RESULTS: Baseline MetS prevalence was 28.8%. Age- and gender-adjusted Cox models revealed that participants with MetS had an increased risk of total mortality (hazard ratio (HR) 1.41; 95% confidence interval (95% CI) 1.09-1.82) and CVD mortality (HR 1.82; 95% CI 1.22-3.13) compared to participants without MetS. Of the single MetS components, participants with increased waist circumference (WC) and glucose levels exposed highest risk of total (HR 1.49; 95% CI 1.10-2.01; HR 2.13; 95% CI 1.58-2.90, respectively) and CVD mortality (HR 2.02; 95% CI 1.13-3.61; HR 3.15; 95% CI 1.94-5.11, respectively). Increasing WC or glucose by 1 standard deviation (SD) significantly decreased age- and gender-adjusted beta coefficients for survival time by 0.09, and 0.08 SD, respectively. CONCLUSION: There was no added predictive value of MetS beyond its individual components with respect to mortality risk. Attention should be redirected to the individual components, particularly visceral obesity and high glucose, to treat each abnormality appropriately.

Age- and gender-specific reference ranges for serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 concentrations on the Immulite 2500: results of the Study of Health in Pomerania (SHIP).

Abstract: Background The objective of the present study was to calculate age- and gender-specific reference ranges for serum insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) concentrations using quantile regression. Methods From the Study of Health in Pomerania (SHIP), 1798 men and women aged 25-85 years were recruited. Serum IGF-I and IGFBP-3 concentrations were determined using a chemiluminescent immunometric assay on an Immulite 2500 analyzer. Quantile regressions were performed to calculate the 2.5th and 97.5th percentiles. Results The reference ranges identified 43 (4.6%) women and 41 (4.8%) men with serum IGF-I concentrations, and 47 (5.0%) women and 42 (5.0%) men with serum IGFBP-3 concentrations outside the reference range. Conclusions The use of quantile regression results in accurate calculation of age- and gender-specific reference ranges for serum IGF-I and IGFBP-3.

Association between glycemia, serum lipoproteins, and the risk of oral leukoplakia: the population-based Study of Health in Pomerania (SHIP).

Abstract: OBJECTIVE Oral leukoplakia is an oral lesion with a premalignant character. Besides smoking and alcohol, diabetes could be a risk factor. The aim is to search for such an association. RESEARCH DESIGN AND METHODS Subjects with leukoplakia ( N = 123) from the population-based Study of Health in Pomerania (SHIP) were matched 1:2 for age and sex with unaffected control subjects. Behavioral and lifestyle factors were assessed by a questionnaire. Lipoprotein concentrations, glycemia, and inflammation parameters were determined. RESULTS Subjects with oral leukoplakia showed higher levels of diabetes-related metabolites, a higher LDL/HDL cholesterol ratio ( P = 0.004), and higher A1C ( P = 0.002), and they were more frequently smokers ( P < 0.001). Assessed by conditional logistic regression, the probability of leukoplakia increases with current smoking (odds ratio 2.20 [95% CI 1.16–4.17]) and higher levels of A1C (1.51 [95% CI 1.08–2.12]), revealing interaction between both factors ( P = 0.012). CONCLUSIONS Diabetes is associated with the risk of oral leukoplakia, which is exaggerated by smoking. The risk is positively correlated with A1C concentrations.

Low total testosterone is associated with increased risk of incident type 2 Diabetes mellitus in men: Results from the Study of Health in Pomerania (SHIP)

Abstract: Objective. There is increasing evidence suggesting that low total testosterone concentration is associated with incident type 2 diabetes mellitus (T2DM) in men. The aim of this study was to evaluate the association between total testosterone and incident T2DM in a large population-based cohort.Methods. Of 2117 men at baseline, 1589 were followed up 5 years later. Low total testosterone concentration at baseline determined by <10th percentile (10-year age-strata) were used as a risk factor for incident T2DM at follow-up. To evaluate for potential non-response bias, drop out weights were used in sensitivity analysis.Results. From 1339 men eligible for analyses, 68 (5.1%) developed T2DM. Men with low total testosterone concentration had an increased risk of developing T2DM (odds ratio [OR] 3.4, 95% CI 1.9–6.1), even after adjustment for age, waist circumference and smoking, OR 3.0; (95% CI 1.6–5.7). Recalculated weighted models revealed almost identical estimates indicating no relevant non-response bias.Disc...

Thyroid function tests in patients taking thyroid medication in Germany: Results from the population-based Study of Health in Pomerania (SHIP).

Abstract: Background: Studies from iodine-sufficient areas have shown that a high proportion of patients taking medication for thyroid diseases have thyroid stimulating hormone (TSH) levels outside the reference range. Next to patient compliance, inadequate dosing adjustment resulting in under- and over-treatment of thyroid disease is a major cause of poor therapy outcomes. Using thyroid function tests, we aim to measure the proportions of subjects, who are under- or over-treated with thyroid medication in a previously iodine-deficient area. Findings: Data from 266 subjects participating in the population-based Study of Health in Pomerania (SHIP) were analysed. All subjects were taking thyroid medication. Serum TSH levels were measured using immunochemiluminescent procedures. TSH levels of 2.15 mIU/L in subjects younger than 50 years and 2.09 mIU/L in subjects 50 years and older, were defined as decreased or elevated, according to the established reference range for the specific study area. Our analysis revealed that 56 of 190 (29.5%) subjects treated with thyroxine had TSH levels outside the reference range (10.0% elevated, 19.5% decreased). Of the 31 subjects taking antithyroid drugs, 12 (38.7%) had TSH levels outside the reference range (9.7% elevated, 29.0% decreased). These proportions were lower in the 45 subjects receiving iodine supplementation (2.2% elevated, 8.9% decreased). Among the 3,974 SHIP participants not taking thyroid medication, TSH levels outside the reference range (2.8% elevated, 5.9% decreased) were less frequent. Conclusion: In concordance with previous studies in iodine-sufficient areas, our results indicate that a considerable number of patients taking thyroid medication are either under- or over-treated. Improved monitoring of these patients’ TSH levels, compared to the local reference range, is recommended.

Association of serum IGF1 with endothelial function: results from the population-based study of health in Pomerania.

Abstract: Objective: IGF1 mediates multiple physiological and pathophysiological responses in the cardiovascular system. The aim of this study was to analyze the association between serum IGF1 as well as IGF-binding protein 3 (IGFBP3) levels and endothelial function measured by flow-mediated dilation (FMD). Design: Cross-sectional population-based observational study. Methods: The study population comprised 1482 subjects (736 women) aged 25–85 years from the Study of Health in Pomerania. Serum IGF1 and IGFBP3 levels were determined by chemiluminescence immunoassays. FMD measurements were performed using standardized ultrasound techniques. FMD values below the sex-specific median were considered low. Results: In males, logistic regression analyses revealed an odds ratio (OR) of 1.27 (95% confidence interval (CI) 1.07–1.51; PZ0.008) for decreased FMD for each decrement of IGF1 S.D. after adjustment for major cardiovascular confounders. In females, no significant relationship between serum IGF1 and FMD was found (OR 0.88, CI 0.74–1.05; PZ0.147). After exclusion of subjects with the current use of antihypertensive medication, these findings were similar (males: OR 1.40, CI 1.12–1.75; PZ0.003; females: OR 0.95, CI 0.77–1.16;PZ0.595). There was no association between serum IGFBP3 levels and FMD in both sexes. Conclusions: Low serum IGF1 levels are associated with impaired endothelial function in males. In women, serum IGF1 is not associated with endothelial function.

Association of circulating IGF-I and IGFBP-3 concentrations and exercise capacity in healthy volunteers: Results of the Study of Health in Pomerania

Abstract: Background Insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) are central mediators of endocrine effects of growth hormone and there is increasing evidence for an association with muscle strength and exercise capacity. The aim of the present study was to clarify the possible association of circulating IGF-I and IGFBP-3 concentrations and exercise capacity in a general adult population. Materials and methods From the Study of Health in Pomerania (SHIP) 1332 subjects aged 25 to 85 years participated in a standardised symptom limited cardiopulmonary exercise test on a bicycle. Exercise capacity was characterized by oxygen uptake at anaerobic threshold (VO 2 @AT), peak exercise (peakVO 2 ), oxygen pulse and maximum power output at peak exertion. Multivariable linear regression analyses adjusted for age, sex, body mass index, physical activity and smoking were performed. Results At peak exercise performance, in women IGF-I showed significant associations to peakVO 2 and maximum power output, IGF-I/IGFBP-3 ratio was associated with maximum power output. In men, this association was not consistently reproducible. Neither IGF-I nor IGFBP-3 did reveal any association to VO 2 @AT in both genders. Conclusion Serum IGF-I concentrations are associated with peak exercise capacity in healthy women, but not in men over a wide range in ages, body sizes and activity scores.

Reference intervals for eight measurands of the blood count in a large population based study.

Abstract: BACKGROUND The blood count is widely used in clinical practice. Well defined reference intervals for each measurand are essential for correct clinical interpretation of results. Most previous studies have not been population-based. We therefore calculated reference intervals for several hematological measurands from a sample of the general adult population of Northeastern Germany. METHODS AND RESULTS We used data from 2967 healthy individuals recruited for the population-based Study of Health in Pomerania (SHIP). Reference intervals were calculated according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI) using the bootstrap method for the age range from 20 to 79 years and, in addition, stratified according to age and gender with both bootstrap and quantile regression procedures. Reference ranges for erythrocytes, hemoglobin and hematocrit increased with age in women but decreased in men. CONCLUSIONS Our reference intervals were lower than those previously published for erythrocytes, hemoglobin, hematocrit and leukocytes but higher for Mean Corpuscular Volume (MCV) and Mean Corpuscular Hemoglobin (MCH). Different laboratory methods and study populations may lead to disparity in results.

Lack of association between insulin-like growth factor-1 or insulin-like growth factor-binding protein-3 and left ventricular hypertrophy: results of the Study of Health in Pomerania.

Abstract: Objective Left ventricular hypertrophy (LVH) is a major cardiac sequel of hypertension and a powerful predictor of cardiovascular morbidity and mortality. Several nonpopulation-based studies explored the association between insulin-like growth factor-1 (IGF-I) and LVH with conflicting results. The aim of the present study was to investigate the association of serum IGF-I or IGF-binding protein-3 (IGFBP-3) levels with LVH in a population-based study. Methods From the cross-sectional Study of Health in Pomerania, 1865 participants aged 45-79 years were included. Echocardiography was performed and left ventricular mass index calculated. LVH was defined as left ventricular mass index more than 48g/m 2.7 for men and more than 44g/m 2.7 for women. Serum IGF-I and IGFBP-3 levels were determined by chemiluminescence immunoassays. Analysis of variance and logistic regression were performed. Results LVH was present in 52.0% of the women and 50.8% of the men. Our data did not obtain any significant association between serum IGF-I levels and left ventricular mass index or LVH in both men and women. Regarding IGFBP-3, women with low IGFBP-3 levels had an almost two-fold higher odds of LVH [odds ratio 1.76 (95% confidence limit 1.04-2.95)] compared with women with moderate IGFBP-3 levels. No such relation became apparent in men. Conclusion No association between IGF-I levels and LVH was found. Potential hypertrophic effects of free serum IGF-I levels might be mediated by lower IGFBP-3 levels.

Potassium – reference intervals for lithium-heparin plasma and serum from a population-based cohort / Kalium – Referenzbereiche für Lithium-Heparin-Plasma und Serum aus einer bevölkerungsbezogenen Studie

Abstract: Abstract Background: Serum, as a standard material for the determination of numerous analytes, has disadvantages. The coagulation process leads to an artificial increase of the potassium concentration of approximately 0.3 mmol/L in serum samples compared to plasma. Consequently, plasma reflects the in vivo situation more accurately. The aim of the present analyses was to establish reference intervals (RIs) for potassium using data from a population-based study for serum (PS) and plasma (PP). Methods: Serum was used from 2897 subjects aged 20–79 years, participating in the 5-year follow-up of the Study of Health in Pomerania (SHIP 1), a population-based study in northeast Germany. In addition, 2483 samples (serum and plasma) from a population of blood donors (DONOR-SHIP) were used. Finally, calculated RIs were reevaluated in 202,350 potassium values from hospitalized patients. All measurements were performed on a Siemens Dimension RxL Max HM with ion-selective electrodes. Using the sample pairs from DONOR-SHIP, a regression formula for the transformation of PS to PP was calculated. This formula was applied to the serum data from SHIP 1 to calculate corresponding plasma values. RIs (2.5th and 97.5th percentile) were defined with quantile regression and bootstrap method in SHIP 1. Results: RIs for PS and PP were 3.7–5.1 mmol/L and 3.5–4.6 mmol/L, respectively. Clinically relevant age- or sex-specific tendencies were not detected. The difference between PS and PP is dependent on platelet count and potassium concentration. Conclusions: The study permitted the establishment of RIs for PS and PP on a population-based study. For serum, the influence of platelet count and absolute potassium concentration on the results should be taken into account. Zusammenfassung Hintergrund: Serum als ein weit verbreitetes Prüfmaterial für die Bestimmung einer Vielzahl von Analyten hat Nach-teile. Der Prozess der Gerinnung führt zu einem artifiziellen Anstieg der Kaliumkonzentration um etwa 0.3 mmol/L verglichen mit Plasma, weshalb Plasma die Situation in vivo besser abbildet. Das Ziel der vorliegenden Analysen war die Ermittlung von Referenzbereichen aus einer populations-basierten Studie für Kalium im Serum (PS) und im Plasma (PP). Methoden: Verwendet wurde Serum von 2897 Teilnehmern des 5-Jahres-Follow-up der Study of Health in Pomerania (SHIP 1), einer bevölkerungsbezogenen Studie im Nordosten Deutschlands. Weiterhin wurden 2482 Serum- und Plasmaproben aus einem Querschnitt von Blutspendern (DONOR-SHIP) benutzt. Die ermittelten Referenzbereiche wurden außerdem in 202.350 Kaliumergebnissen aus unserer klinischen Routine evaluiert. Alle Messungen erfolgten auf Geräten von Siemens der Reihe Dimension RxL Max HM mit ionenselektiven Elektroden. Mittels der Probenpaare aus DONOR-SHIP wurden die Konversionsfaktoren für die Umrechnung von PS zu PP erstellt. In SHIP wurde diese Formel auf die PS Messergebnisse angewandt und PP errechnet. Referenzbereiche (2,5 und 97,5 Perzentile) wurden mit der Quantilregression und der Bootstrap-Methode in SHIP berechnet. Ergebnisse: Für PS reicht der Referenzbereich von 3,7 mmol/L bis 5,1 mmol/L, für PP von 3,5 mmol/L bis 4,6 mmol/L. Die Differenz zwischen Serum und Plasma ist abhängig von der absoluten Kaliumkonzentration und der Thrombozytenzahl. Schlussfolgerung: Es können Referenzbereiche für Kalium auf Basis einer populationsbasierten Studie berichtet werden. Bei der Bestimmung von Kalium im Serum sollte die Abhängigkeit von der Thrombozytenzahl und der absoluten Kaliumkonzentration beachtet werden.

A descriptive analysis of relations between parents' self-reported smoking behavior and infants' daily exposure to environmental tobacco smoke.

Abstract: The aims of the present study were to examine relations between parents' self-reported smoking behavior and infants' daily exposure to environmental tobacco smoke, as assessed by urinary cotinine-to-creatinine ratio (CCR), and to describe the CCR over seven days among infants at home. A convenience sample of 27 households was drawn. Each household had to have at least one daily tobacco smoker and one child up to three years of age. Over a seven-day period, urine samples were obtained from the child daily. To examine relations between parents' self-reported smoking and infants' daily CCR, generalized estimating equation (GEE) analysis was used. The data revealed that infants from households with indoor smoking had higher CCRs than infants in households with outdoor smoking. CCRs were higher in girls than in boys. Older infants had lower CCRs than younger infants. Smoking outside the home versus inside the home, infant's gender, and infants' age accounted for 68% of the variance in CCR in a GEE data analysis model. No increase or decrease of CCR over time was found. The findings suggest that parents' self-reported smoking indoors at home versus outdoors is predictive of CCR among infants three and younger. Higher CCR concentrations in girls' urine need further examination. Furthermore, significant fluctuations in daily CCR were not apparent in infants over a seven-day time period.

Predictive modeling of health care costs: do cardiovascular risk markers improve prediction?

Abstract: BackgroundTo investigate the ability of multiple cardiovascular disease (CVD) markers to predict future health care costs. CVD markers included traditional risk factors (smoking status, body mass index, waist circumference, alcohol intake, diabetes, total: high-density lipoprotein cholesterol ratio, actual hypertension, physical activity) and newer markers (carotid intima-media thickness, hemoglobin A1c, apolipoprotein B: apolipoprotein A-1 ratio, lipoprotein (a), leukocyte count, highsensitive C-reactive protein, plasma fibrinogen, estimated glomerular filtration rate, urinary albumin: creatinine ratio).Design and methodsThe study sample consisted of 2233 participants without history of myocardial infarction, stroke, heart failure, and angina pectoris at baseline (50.6% women; mean age 60.9 years; age range 45–81 years) from the cohort Study of Health in Pomerania, Germany (median follow-up 5 years).ResultsPredictive modeling revealed that a basic model with sex, age, years of school education, insurance...