Clinical correlates of sex hormones in women: The study of health in Pomerania.

BACKGROUND: Despite associations of sex hormones in women with increased cardiometabolic risk and mortality, the clinical correlates of altered sex hormone concentrations in women are less clearly understood. We investigated a broad range of clinical correlates of sex hormones in women from a large population-based sample. METHODS: Data from 2560 women from two cohorts of the Study of Health in Pomerania were used. Stepwise multivariable regression models were implemented to investigate a broad range of behavioral, socio-demographic, and cardiometabolic clinical correlates related to total testosterone (TT), free testosterone (fT), androstenedione (ASD), dehydroepiandrosterone-sulfate (DHEAS), estrone (E1), estradiol (E2), and sex hormone-binding globulin (SHBG). RESULTS: Waist circumference and BMI (ß-coefficient: -0.03; 95% CI: -0.04; 0.03) were inversely related to SHBG, and BMI was positively related to TT (ß-coefficient: 0.005; 95% CI: 0.001; 0.009), fT, E1, and E2. Smoking was positively related to TT (ß-coefficient: 0.04; 95% CI: 0.01; 0.06), ASD, and fT. Systolic blood pressure (TT: ß-coefficient: 0.002; 95% CI: 0.001; 0.003), hypertension (TT: ß-coefficient: 0.05; 95% CI: 0.003; 0.11), low-density lipoprotein (LDL) cholesterol (TT: ß-coefficient: 0.02; 95% CI: 0.01; 0.05), and total cholesterol (TT: ß-coefficient: -0.03; 95% CI: 0.01; 0.05) were positively related to TT and ASD. Finally, type 2 diabetes mellitus (T2DM), and metabolic syndrome (MetS) were positively related to fT, but inversely related to SHBG. CONCLUSIONS: Our population-based study, with sex hormone concentrations measured by liquid chromatography tandem mass spectrometry, revealed associations between clinical correlates including waist circumference, smoking, cohabitation, systolic blood pressure, cholesterol, and MetS with sex hormones. Thus, sex hormones and SHBG may play a role in the cardiovascular risk profile of women.

Associations of androgens with health care utilization and costs in women-Perspectives of a population-based cohort study.

OBJECTIVE: Despite associations between total testosterone (TT) concentrations and increased cardiometabolic risk, the impact of serum androgens on health care utilization and costs among women is unknown. METHODS: We used data from 1521 women in the population-based cohort Study of Health in Pomerania (SHIP) to investigate the associations of serum TT (measured by liquid chromatography-tandem mass spectrometry), sex hormone-binding globulin (SHBG), and free testosterone (free T) with health care utilization and costs at baseline and five-year follow-up (N=1210), implementing multivariable-adjusted econometric models. RESULTS: Cross-sectional analyses showed no association of TT, SHBG, or free T with hospitalization or total health costs (outpatient as well as inpatient costs). Prospective analyses revealed an inverse association of baseline SHBG with follow-up total health care costs (% change per standard deviation (SD): -26.2%, 95% confidence interval (CI): -42.2%; -8.9%) and inpatient costs (% change per SD: -26.5%%, 95% CI: -45.5%; -2.5%). Baseline free T was positively associated with total health care costs at the five-year follow-up (% change per SD: +37.7%, 95% CI: +4.6%; +81.4%). CONCLUSIONS: In this first cost analysis among women from the general population, we observed no association of androgen serum concentration with health care utilization and costs. However, baseline SHBG appeared to be inversely correlated and free T positively correlated with long-term health care costs.

Association of PNPLA3 rs738409 and TM6SF2 rs58542926 with health services utilization in a population-based study.

BACKGROUND: Hepatic steatosis confers an increased risk of metabolic and cardiovascular disease and higher health services use. Associations of the single nucleotide polymorphisms (SNP) PNPLA3 rs738409 and TM6SF2 rs58542926 with hepatic steatosis have recently been established. This study investigates the association between rs738409 and rs58542926 with health services utilization in a general population. METHODS: Data of 3759 participants from Study of Health in Pomerania (SHIP), a population-based study in Germany, were obtained. The annual number of outpatient visits, hospitalization and length of hospital stay was regressed on rs738409 and rs58542926 and adjusted for socio-economic factors, lifestyle habits, clinical factors, and health status. RESULTS: Minor allele homozygous subjects of rs738409 had an increased odds of hospitalization as compared to major allele homozygous subjects (odds ratio [OR] 1.51; 95% confidence interval [CI], 1.02 to 2.15). Heterozygous subjects did not differ from major allele homozygous subjects with respect to their odds of hospitalization. The three genotype groups of rs738409 were similar with respect to the number of outpatient visits and inpatient days. Minor allele homozygous and heterozygous subjects of rs58542926 had higher outpatient utilization (+53.04% and +67.56%, p < 0.05, respectively) and inpatient days than major allele homozygous subjects. CONCLUSIONS: After adjustment for several confounding factors, PNPLA3 rs738409 and TM6SF2 rs58542926 were associated with the number of outpatient visits, hospitalization, and inpatient days. Further studies are warranted to replicate our findings and to evaluate whether genetic data can be used to identify subjects with excess health services utilization.

Genetic, physiological, and lifestyle predictors of mortality in the general population.

OBJECTIVES: We investigated the quality of 162 variables, focusing on the contribution of genetic markers, used solely or in combination with other characteristics, when predicting mortality. METHODS: In 5974 participants from the Rotterdam Study, followed for a median of 15.1 years, 7 groups of factors including age and gender, genetics, socioeconomics, lifestyle, physiological characteristics, prevalent diseases, and indicators of general health were related to all-cause mortality. Genetic variables were identified from 8 genome-wide association scans (n = 19,033) and literature review. RESULTS: We observed 3174 deaths during follow-up. The fully adjusted model (C-statistic for 15-year follow-up [C15y] = 0.80; 95% confidence interval [CI] = 0.79, 0.81) predicted mortality well [corrected]. Most of the additional information apart from age and sex stemmed from physiological markers, prevalent diseases, and general health. Socioeconomic factors and lifestyle contributed meaningfully to mortality risk prediction with longer prediction horizon. Although specific genetic factors were independently associated with mortality, jointly they contributed little to mortality prediction (C(15y) = 0.56; 95% CI = 0.55, 0.57). CONCLUSIONS: Mortality can be predicted reasonably well over a long period. Genetic factors independently predict mortality, but only modestly more than other risk indicators.

Structured assessment of hypopituitarism after traumatic brain injury and aneurysmal subarachnoid hemorrhage in 1242 patients: the German interdisciplinary database.

Clinical studies have demonstrated that traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH) are frequent causes of long-term disturbances of hypothalamo-pituitary function. This study aimed to assess the prevalence and associated factors of post-traumatic hypopituitarism in a large national registry of patients with TBI and SAH. Data were collected from 14 centers in Germany and Austria treating patients for TBI or SAH and performing endocrine assessments. Data were collected using a structured, internet-based study sheet, obtaining information on clinical, radiological, and hormonal parameters. A total of 1242 patients (825 TBI, age 43.5±19.7 years; 417 SAH, age 49.7±11.8 years) were included. We studied the prevalence of hypopituitarism reported based on different definitions of laboratory values and stimulation tests. Stimulation tests for the corticotropic and somatotropic axes were performed in 26% and 22% of the patients, respectively. The prevalence of hypopituitarism in the chronic phase (at least 5 months after the event) by laboratory values, physician diagnoses, and stimulation tests, was 35%, 36%, and 70%, respectively. Hypopituitarism was less common in the acute phase. According to the frequency of endocrine dysfunction, pituitary hormone secretion was impaired in the following sequence: ACTH, LH/FSH, GH, and TSH. TBI patients with abnormal stimulation tests had suffered from more severe TBI than patients with normal stimulation tests. In conclusion, our data confirm that hypopituitarism is a common complication of TBI and SAH. It is possible that patients with a higher likelihood of hypopituitarism were selected for endocrine stimulation tests.

Association of IGF-I and IGFBP-3 with health care costs and hospitalization: results from a prospective observational study.

OBJECTIVE: Previous cohort studies found robust associations of serum insulin-like growth factor I (IGF-I) and its main binding protein IGFBP-3 with increased morbidity or mortality. This study investigates the relationships between IGF-I and IGFBP-3 with health care costs and hospitalization in a general population and whether adding IGF-I or IGFBP-3 to a model of established health care predictors improves prediction. METHODS: Data from a population-based cohort study of 3139 men and women in Germany, aged 20 to 80 years at baseline were used (median follow-up time: 5.0 years). Self-reported physician visits, length of hospital stay were used to estimate annual costs. IGF-I and IGFBP-3 were categorized at the 10th and 90th percentile, to indicate 'low', 'intermediate', and 'high' concentrations, respectively. RESULTS: Total annual health care costs, with the major component of inpatient costs, and risk of hospitalization at baseline and follow-up were higher in subjects with low compared to intermediate IGF-I or IGFBP-3, after multivariable-adjustment. Subjects with low in contrast to intermediate IGF-I exhibited 30.6% higher annual total costs 5 years after baseline examination, corresponding to a difference in adjusted costs of EUR436.61. CONCLUSIONS: Low IGF-I and IGFBP-3 independently predict future health care costs and hospitalization. IGF-I or IGFBP-3 might be useful to identify subjects with excess health care use. The predictive performance of cross-sectional and longitudinal models of total and inpatient costs were slightly improved by adding IGF-I or IGFBP-3 but the cost-effectiveness of inclusion into prediction models needs to be examined.

Mortality and serum insulin-like growth factor (IGF)-I and IGF binding protein 3 concentrations.

BACKGROUND: Previous studies provided conflicting results regarding the association of serum IGF-I or IGF-binding protein-3 (IGFBP-3) and mortality. The aim of this study was to assess the relation of IGF-I and IGFBP-3 levels with mortality from all causes, cardiovascular disease (CVD), and cancer in a prospective population-based study. METHODS: From the Study of Health in Pomerania (SHIP) 1988 men and 2069 women aged 20-79 yr were followed up on average 8.5 yr. Causes of deaths were coded according to the International Classification of Diseases, 10th revision. Serum IGF-I and IGFBP-3 levels were determined by chemiluminescence immunoassays and categorized into three groups (low, normal, high) according to the sex- and age-specific 10th and 90th percentiles. RESULTS: Adjusted analyses revealed that men with low but not high IGF-I levels had an almost 2-fold higher risk of all-cause mortality [hazard ratio (HR) 1.92 (95% confidence interval [CI] 1.35; 2.73)], CVD mortality [HR 1.92 (95% CI 1.00; 3.71)], and cancer mortality [HR 1.85 (95% CI 1.00; 3.45)] compared with men with normal IGF-I levels. In women, no association between IGF-I and mortality was found. Moreover, low IGFBP-3 levels were associated with higher all-cause mortality in men [HR 1.87 (95% CI 1.31; 2.64)] and women [HR 1.63 (95% CI 0.96; 2.76)]. CONCLUSIONS: The present study found inverse associations between IGF-I or IGFBP-3 levels and mortality from all causes, CVD, or cancer in men and between IGFBP-3 and all-cause mortality in women.

Extended recruitment efforts minimize attrition but not necessarily bias.

OBJECTIVES: There has been a debate about the effect of extended recruitment efforts on attrition and bias. The aims of the present study are (1) to investigate the effectiveness of extensive multimode recruitment procedures; (2) to study their effect on attrition and bias; and (3) to determine the potential predictors of attrition. STUDY DESIGN AND SETTING: We used data from the longitudinal population-based study of health in Pomerania. RESULTS: Using multimode recruitment methods, we reached a follow-up response proportion of 83.6%. In-person contacts at home turned out to be an effective recruitment tool. Sociodemographic and health characteristics of late respondents and converted nonrespondents were most distinct from early respondents but not necessarily indicative of nonrespondents. Analyzing attrition bias, extended recruitment efforts produced an effect only for sociodemographic characteristics but not for health-related indicators. The strongest predictors for attrition from the regression model were late recruitment at baseline, unemployment, low educational level, female sex, and smoking habit. CONCLUSION: Extended recruitment efforts appeared justified in terms of response maximization. However, enhanced response proportions may not necessarily minimize bias. In our analysis, aiming for a high-response proportion in terms of health-related indicators had no effect, because late respondents did not differ from early respondents.