Gamma-glutamyl-transferase is associated with incident hip fractures in women and men ≥ 50 years: a large population-based cohort study.

The association of serum gamma-glutamyl-transferase (GGT) with hip fracture risk has not been examined in women and men ≥ 50 years. We show that elevated GGT was associated with increased hip fracture risk, particularly in men. GGT could be a candidate serum marker of long-term hip fracture risk in the elderly. INTRODUCTION: We herein examined a possible relation between serum levels of GGT and hip fracture risk in women and men aged ≥ 50 years, which has not been investigated before. METHODS: In this population-based prospective cohort study, approximately 41,000 women and nearly 33,000 men ≥ 50 years participating in a medical prevention program 1985-2005 in western Austria were followed up for the occurrence of osteoporotic hip fractures during 2003-2013. ICD-10 based discharge diagnoses for hip fracture included S72.0, S72.1, and S72.2 available from all regional hospitals. GGT-related hip fracture risk was ascertained at each participant´s first and last examination during the prevention program. In a subset of 5445 participants, alcohol consumption could be included as a covariate. RESULTS: In men, hip fracture risk rose significantly by 75% and 86% for every tenfold increase of GGT measured at the first and last examination, respectively, and in women, hip fracture risk rose by 22% from the last examination. Elevated GGT (≥ 36 U/l in women, ≥ 56 U/l in men) at the first examination was associated with increased hip fracture risk only in men (HR 1.51, 95% CI 1.25-1.82), and at the last examination in both women (HR 1.14, 95% CI 1.02-1.28) and men (HR 1.61, 95% CI 1.33-1.95). Alcohol consumption had no significant influence on GGT-mediated hip fracture risk in women and men. CONCLUSIONS: Our findings identified an association of elevated GGT and hip fracture in women and men ≥ 50 years and suggest GGT as a candidate serum marker of long-term hip fracture risk in an elderly population.

The effect of age on the shape of the BMI-mortality relation and BMI associated with minimum all-cause mortality in a large Austrian cohort.

BACKGROUND: It is unclear if the body mass index (BMI) associated with minimum all-cause mortality is constant throughout adult life or increasing with age. METHODS: We applied multivariable fractional polynomials to the data of the Vorarlberg Health Monitoring and Prevention Program to quantify the BMI associated with minimum mortality over age. The analysis included data of 129,904 never-smoking women and men (mean age: 45.4 years) who were followed for a median of 18.6 years. RESULTS: Optimum BMI in women increased with age, lying within the normal BMI category (according to the World Health Organization definition) from the age of 20 years (23.3 kg m(-2), 95% confidence interval (CI): 22.2-24.3) to the age of 54 years and in the lower half of the overweight category from the age of 55 years onwards, reaching 26.2 kg m(-2) (95% CI: 25.1-27.3) at the age of 69 years. In men, optimum BMI increased slightly from 23.7 kg m(-2) (95% CI: 22.1-25.2) at the age of 20 years until the age of 59 years, reaching a BMI of 25.4 kg m(-2) (95% CI: 24.8-26.0) and decreased afterwards to 22.7 kg m(-2) (95% CI: 20.9-24.6) at the age of 80 years. CONCLUSIONS: Our results indicate that BMI associated with minimum all-cause mortality changes with age and that patterns differ by sex. Sex- and age-independent BMI recommendations might therefore be inappropriate. Further studies using flexible methods instead of predefined categories are necessary to revise BMI recommendations.

Metabolic risk factors and skin cancer in the Metabolic Syndrome and Cancer Project (Me-Can).

BACKGROUND: Little is known about the associations of metabolic aberrations with malignant melanoma (MM) and nonmelanoma skin cancer (NMSC). OBJECTIVES: To assess the associations between metabolic factors (both individually and combined) and the risk of skin cancer in the large prospective Metabolic Syndrome and Cancer Project (Me-Can). METHODS: During a mean follow-up of 12 years of the Me-Can cohort, 1728 (41% women) incident MM, 230 (23% women) fatal MM and 1145 (33% women) NMSC were identified. Most NMSC cases (76%) were squamous cell carcinoma (SCC) (873, 33% women). Hazard ratios (HRs) were estimated by Cox proportional hazards regression for quintiles and standardized z-scores (with a mean of 0 and SD of 1) of body mass index (BMI), blood pressure, glucose, cholesterol, triglycerides and for a combined metabolic syndrome score. Risk estimates were corrected for random error in the measurements. RESULTS: Blood pressure per unit increase of z-score was associated with an increased risk of incident MM cases in men and women [HR 1·17, 95% confidence interval (CI) 1·04-1·31 and HR 1·18, 95% CI 1·03-1·36, respectively] and fatal MM cases among women (HR 2·39, 95% CI 1·58-3·64). In men, all quintiles for BMI above the reference were associated with a higher risk of incident MM. In women, SCC NMSC risk increased across quintiles for glucose levels (P-trend 0·02) and there was a trend with triglyceride concentration (P-trend 0·09). CONCLUSION: These findings suggest that mechanisms linked to blood pressure may be involved in the pathogenesis of MM. SCC NMSC in women could be related to glucose and lipid metabolism.

Metabolic syndrome and rare gynecological cancers in the metabolic syndrome and cancer project (Me-Can).

BACKGROUND: Risk factors for rare gynecological cancers are largely unknown. Initial research has indicated that the metabolic syndrome (MetS) or individual components could play a role. MATERIALS AND METHODS: The Metabolic syndrome and Cancer project cohort includes 288,834 women. During an average follow-up of 11 years, 82 vulvar, 26 vaginal and 43 other rare gynecological cancers were identified. Hazard ratios (HRs) were estimated fitting Cox proportional hazards regression models for tertiles and standardized z-scores [with a mean of 0 and a standard deviation (SD) of 1] of body mass index (BMI), blood pressure, glucose, cholesterol, triglycerides and MetS. Risk estimates were corrected for random error in the measurement of metabolic factors. RESULTS: The MetS was associated with increased risk of vulvar [HR 1.78, 95% confidence interval (CI) 1.30-2.41) and vaginal cancer (HR 1.87, 95% CI 1.07-3.25). Among separate MetS components, 1 SD increase in BMI was associated with overall risk (HR 1.43, 95% CI 1.23-1.66), vulvar (HR 1.36, 95% CI 1.11-1.69) and vaginal cancer (HR 1.79, 95% CI 1.30-2.46). Blood glucose and triglyceride concentrations were associated with increased risk of vulvar cancer (HR 1.98, 95% CI 1.10-3.58 and HR 2.09, 95% CI 1.39-3.15, respectively). CONCLUSION: The results from this first prospective study on rare gynecological cancers suggest that the MetS and its individual components may play a role in the development of these tumors.

Serum triglyceride concentrations and cancer risk in a large cohort study in Austria.

BACKGROUND: Blood lipid levels as part of the metabolic syndrome are thought to be linked to cancer risk. Few epidemiological studies have addressed the association between serum triglyceride (STG) concentrations and cancer risk. METHODS: Serum triglyceride concentrations were collected in a health investigation (1988-2003). The analyses included 156 153 subjects (71 693 men and 84 460 women), with 5079 incident cancers in men and 4738 cancers in women, and an average of 10.6 years of follow-up. All malignancies were ascertained from the population cancer registry. Multivariate Cox proportional hazard models stratified by age and sex were used to determine adjusted cancer risk estimates and 95% confidence interval (95% CI). RESULTS: In men and women combined, higher STG concentrations were associated with increased risk of lung (4th vs 1st quartile: HR, 1.94; 95% CI, 1.47-2.54), rectal (HR, 1.56; 95% CI, 1.00-2.44), and thyroid cancer (HR, 1.96; 95% CI, 1.00-3.84). Serum triglyceride concentrations were inversely associated with non-Hodgkin's lymphoma. In men, STG concentrations were inversely associated with prostate cancer and positively with renal cancer. In women, STG concentrations were positively associated with gynaecological cancers. Stratification by BMI revealed a higher risk of gynaecological cancers in overweight than in normal weight women. No other associations were found. CONCLUSIONS: Our findings support the hypothesis that STG concentrations are involved in the pathogenesis of lung, rectal, thyroid, prostate, and gynaecological cancers.

Time-dependent association of total serum cholesterol and cancer incidence in a cohort of 172,210 men and women: a prospective 19-year follow-up study.

BACKGROUND: The relationship between serum cholesterol and cancer incidence remains controversial. PATIENTS AND METHODS: We investigated the association of total serum cholesterol (TSC) with subsequent cancer incidence in a population-based cohort of 172 210 Austrian adults prospectively followed up for a median of 13.0 years. Cox regression, allowing for time-dependent effects, was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) for the association of TSC with cancer. RESULTS: We observed pronounced short-term associations of TSC and overall cancer incidence in both men and women. For malignancies diagnosed shortly (<5 months) after baseline TSC measurement, the highest TSC tertile (>235.0 mg/dl in men and >229.0 in women) compared with the lowest tertile (<194.0 mg/dl in men and <190.0 in women) was associated with a significantly lower overall cancer risk [HR = 0.58 (95% CI 0.43-0.78, P(trend) = 0.0001) in men, HR = 0.69 (95% CI 0.49-0.99, P(trend) = 0.03) in women]. However, after roughly 5 months from baseline measurement, overall cancer risk was not significantly associated with TSC. The short-term inverse association of TSC with cancer was mainly driven by malignancies of the digestive organs and lymphoid and hematopoietic tissue. CONCLUSION: The short-term decrease of cancer risk seen for high levels of TSC may largely capture preclinical effects of cancer on TSC.

Weight change and cancer risk in a cohort of more than 65,000 adults in Austria.

BACKGROUND: To investigate relations between weight loss or weight gain and the incidence of cancer. PATIENTS AND METHODS: Weight change was assessed in a population-based cohort of >65 000 Austrian adults (28 711 men and 36 938 women) for a period of 7 years, after which participants were followed for incident cancers over 8 years on average. Incident cancers (other than nonmelanoma skin cancers) were ascertained by a population-based cancer registry (n = 3128). Cox proportional hazards models were used to estimate hazard rate ratios (HRs) stratified by age and adjusted for smoking, occupational group, blood glucose and body mass index at baseline. RESULTS: In both men and women, neither weight loss nor weight gain was clearly associated with the incidence of all cancers combined. Weight loss (>0.10 kg/m(2)/year) was inversely associated with colon cancer in men [HR 0.50; 95% confidence interval (CI) 0.29-0.87], while high weight gain (> or =0.50 kg/m(2)/year) was inversely associated with prostate cancer (HR 0.43; 95% CI 0.24-0.76). Among women, high weight gain was positively associated with ovarian cancer (HR 2.48; 95% CI 1.05-5.85). CONCLUSION: These findings indicate that recent weight change may influence the incidence of several types of cancer.

Prevalence of pre-malignant and malignant lesions in prophylactic mastectomy specimens of BRCA1 mutation carriers: comparison with a control group.

PURPOSE: BRCA1 mutation carriers are at high risk for breast cancer (BC). The risk management strategy may include radiological investigations for early detection or prophylactic mastectomy (PM). For a mutation carrier, PM may be more significant than surveillance alone when pre-malignant and malignant changes occur increasingly in mastectomy specimens, given normal findings on radiological investigations. In the present study we retrospectively investigated the differences between histological findings in PM specimens of BRCA1 carriers and those of a control group. METHODS: Twenty-four healthy and 28 affected carriers in the presence of normal preoperative radiological findings were included in the study. To compare the frequency of pre-malignant and malignant lesions in PM specimens, a control group matched for age and disease status was included. T-tests for independent samples and Wilcoxon's signed-rank test were used for comparison of groups. RESULTS: The entire study group differed significantly from the control group (42.3 vs. 5.8%; P < 0.001) in terms of the occurrence of pre-malignant and malignant lesions. Both, the sub-group comparison of healthy mutation carriers as well as diseased carriers with their controls, showed a significant difference in terms of the occurrence of pre-malignant and malignant changes (45.8 vs. 0%; P = 0.002; 39.3 vs. 10.7%; P = 0.03). In PM specimens of mutation carriers, carcinomas were identified in 5.8% (3/52) and pre-malignant changes in 36.5% (19/52). CONCLUSIONS: BRCA1 mutation carriers should be informed of the fact that pre-malignant and even malignant changes are frequently found in PM specimens despite normal radiological findings.

The role of serum uric acid as an antioxidant protecting against cancer: prospective study in more than 28 000 older Austrian women.

BACKGROUND: It has been hypothesized that serum uric acid (SUA), via its antioxidant properties may protect against carcinogenesis. However, few epidemiological investigations have addressed this association and previous findings are inconsistent. PATIENTS AND METHODS: We prospectively investigated the relation of SUA levels to subsequent cancer mortality in a large cohort of 28613 elderly Austrian women with a median follow-up of 15.2 years. Adjusted Cox proportional hazards models were calculated to evaluate SUA as an independently related factor to fatal cancer events. RESULTS: High SUA (>5.41 mg/dL) was independently associated with increased risk of total cancer mortality (p<0.0001); the adjusted hazard ratio for the highest versus lowest quartile of SUA was 1.27 (1.08-1.48). SUA levels were further positively related to deaths from malignant neoplasms of breast and female genital organs (P = 0.02) and nervous system and unspecified sites (P = 0.02). We found no evidence for an inverse relationship between SUA levels and risk of total or site-specific cancer mortality. CONCLUSION: Our results are contrary to the proposed antioxidant and protective effect of SUA against cancer and rather suggest high SUA concentrations to be associated with outcome possibly reflecting more serious prognostic indication.

Bone mineral density and breast cancer risk: Results from the Vorarlberg Health Monitoring & Prevention Program and meta-analysis.

We investigated the association between bone mineral density (BMD) and breast cancer risk in a large prospective cohort and quantified the evidence in a meta-analysis of prospective studies. Baseline BMD has been measured by dual energy X-ray absorptiometry (DXA, N = 1418). Data on medication and lifestyle has been collected by questionnaire. Cox proportional Hazards models were applied to calculate Hazard Ratios for breast cancer. In addition, a meta-analysis on categorical and dose-response values including the current results has been performed applying random-effects models. During mean follow-up of 16.3 (SD 3.3) years of 1380 women (mean age 55.5 ± 6.3 years), 52 cases of invasive breast cancer were identified. We found no statistically significant association of BMD with breast cancer risk (per one z-score increase, HR 0.91, 95% CI 0.67-1.23). In the meta-analysis, however, breast cancer risk increased by 15% and 16% per 0.1 g/m2 increase in BMD at the lumbar spine (95% CI 0.99-1.33) and at the femoral neck (95% CI 1.02-1.32), respectively. Compared to the lowest, the HRs for breast cancer were statistically significant for the highest BMD category, i.e. 1.49 (95% CI 1.04-2.13) at the lumbar spine and 1.66 (95% CI 1.26-2.18) at the femur. We found no association between BMD (DXA) and breast cancer risk in our cohort. However, overall the present meta-analysis extends and confirms the statistically significant association between increasing BMD and increased breast cancer risk.

Particulate matter air pollution components and risk for lung cancer.

BACKGROUND: Particulate matter (PM) air pollution is a human lung carcinogen; however, the components responsible have not been identified. We assessed the associations between PM components and lung cancer incidence. METHODS: We used data from 14 cohort studies in eight European countries. We geocoded baseline addresses and assessed air pollution with land-use regression models for eight elements (Cu, Fe, K, Ni, S, Si, V and Zn) in size fractions of PM2.5 and PM10. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effect models for meta-analysis. RESULTS: The 245,782 cohort members contributed 3,229,220 person-years at risk. During follow-up (mean, 13.1 years), 1878 incident cases of lung cancer were diagnosed. In the meta-analyses, elevated hazard ratios (HRs) for lung cancer were associated with all elements except V; none was statistically significant. In analyses restricted to participants who did not change residence during follow-up, statistically significant associations were found for PM2.5 Cu (HR, 1.25; 95% CI, 1.01-1.53 per 5 ng/m(3)), PM10 Zn (1.28; 1.02-1.59 per 20 ng/m(3)), PM10 S (1.58; 1.03-2.44 per 200 ng/m(3)), PM10 Ni (1.59; 1.12-2.26 per 2 ng/m(3)) and PM10 K (1.17; 1.02-1.33 per 100 ng/m(3)). In two-pollutant models, associations between PM10 and PM2.5 and lung cancer were largely explained by PM2.5 S. CONCLUSIONS: This study indicates that the association between PM in air pollution and lung cancer can be attributed to various PM components and sources. PM containing S and Ni might be particularly important.

[Follow-up studies of routine health screening in Vorarlberg 1986-1994]. / Verlaufsbeobachtungen bei Gesundenuntersuchungen in Vorarlberg 1986 bis 1994.

In this longitudinal study we observed a sample of people who participated in the general health screening program in Vorarlberg between 1986 and 1994. The aim was to analyse the changes in the parameters, body-mass index, diastolic and systolic blood pressure, blood glucose, cholesterol, gamma-GT and triglycerides of 1205 women and 718 men over this period. Using the baseline values recorded in 1986 as reference the sample was divided into groups with normal, slightly increased and highly increased values for the parameters. On average, the risk factors of people with highly increased baseline values decreased on both a short-term (1986-1988), and a long-term basis (1986-1994). The only exception was the body-mass index, which showed a slight reduction in the first two years and a slight increase in the long run. The normal baseline values rose in all the variables within the period of observation. Sex differences must be considered with regard to body-mass index, cholesterol and triglycerides, age differences are significant with regard to body-mass index, systolic blood pressure and cholesterol. The results of the study point to the usefulness of regular participation in general health screening programs. They show, in particular, that the risk factors for civilization-induced diseases diminish visibly in the group of highly endangered people.

Recent trends and sociodemographic distribution of cardiovascular risk factors: results from two population surveys in the Austrian WHO CINDI demonstration area.

OBJECTIVE: The major risk factors for cardiovascular diseases are well established; however, only a few studies report on recent trends in risk factor profiles. This study analyses the sociodemographic distribution of risk factors and gives an account of their changes from 1991 to 1999. METHODS: Two cross-sectional population surveys as part of the CINDI (Countrywide Integrated Noncommunicable Diseases Intervention) program of the World Health Organization were performed in 1991 and 1999 in the province of Vorarlberg (Austria). The surveys included a standardized interview and a medical examination. 1863 persons aged 25 to 64 years in 1991 and 1550 persons in 1999 participated in the interview section of the surveys. From these, 1446 in 1991 and 841 persons in 1999 underwent medical examination. Prevalence of overweight and obesity, mild and severe hypertension, hypercholesterolemia, hypertriglyceridemia, hyperglycemia, regular smoking and lack of physical activity were estimated. Framingham risk functions were calculated to compare overall risk for coronary heart disease. RESULTS: In women, prevalence of overweight including obesity increased from 34% in 1991 to 41% in 1999. Almost 50% of the male population were estimated to be overweight or obese in 1991 and 1999. Hypertension showed a favorable trend and decreased substantially in both genders. Hypercholesterolemia decreased only in men, from 27% to 21%. In 1999, women aged 55-64 showed a prevalence of over 50% in highly elevated cholesterol. Hypertriglyceridemia decreased in men from 21% to 18%, in women it remained almost unchanged. Total prevalence of smoking did not change from 1991 to 1999. 34% of the men and 24% of the women reported to smoke more than one cigarette daily. In women under 45 years of age, regular smoking increased slightly and reached a prevalence of over 30%. Less educated people and people of non-national origin had significantly higher risk factor levels. The risk functions did not reveal a significant difference in 10 year risk for coronary heart disease between the two surveys. CONCLUSIONS: Decreasing levels in hypertension and in male hypercholesterolemia showed favorable developments in risk factor prevalence. Preventive measures should concentrate on reducing overweight in older people and smoking in young women as well as on intensifying the care for less educated people and people of non-national origin.

[Hormone replacement therapy with a transdermal estradiol gel and oral micronized progesterone. Effect on menopausal symptoms and lipid metabolism]. / Die Hormonersatztherapie mit einem perkutan wirksamen Oestradiol-Gel und oral verabreichtem mikronisierten Progesteron. Auswirkung auf klimakterische Symptome und den Lipidstoffwechsel.

In a multicenter observational study, the efficacy and acceptance of two different regimens of postmenopausal hormone replacement therapy in the form of a combination of 17 beta-estradiol in percutaneous gel application and micronized oral progesterone were evaluated. Forty-eight patients (aged 40-66 years) received 2.5 g estradiol gel plus either continuously micronized progesterone 100 per day (group A) or, sequentially, 200 mg per day between day 16 and 25 of a monthly cycle (group B) for two months. A significant reduction in typical menopausal symptoms, especially vasomotor complaints like hot flushes or sweating, was observed in both groups (score average at the beginning for hot flushes: 2.0 in group A and 1.8 in group B; after two months of treatment, 0.7 in group A and 0.4 in group B). Cholesterol levels were slightly reduced but statistically significant (235.9 +/- 49.55 mg/dl vs. 226.3 +/- 52.24 mg/dl; p < 0.05) only in group A; a trend towards lower cholesterol was observed in group B (236.5 +/- 47.82 mg/dl vs. 227.4 +/- 44.72 mg/dl). Lipoprotein (a) was also significantly reduced in group A (32.57 +/- 36.52 mg/dl vs. 28.28 +/- 31.03 mg/dl in group A; 31.7 +/- 28.42 mg/dl vs. 28.34 +/- 23.71 in group B; p < 0.05). The overall acceptance of this therapy was excellent or good in 91.3% of group A and 92.8% of group B patients.

[Hormone replacement therapy and endometrial cancer]. / Hormonsubstitution nach Endometriumkarzinom.

It is well known that the endometrial cancer risk can be diminished by adding progestin to the estrogen regimen. By the time, there seems to be no evidence that estrogen increases the risk of recurrence after treatment for endometrial cancer in early-stage disease. In the treatment of osteoporosis, vasomotor symptoms, and cardiovascular diseases hormone replacement therapy has to be given. Informed consent, patient desire and risk-benefit considerations must be included into the decision on estrogen replacement therapy, as long as there is no prospective trial to resolve the controversy.

Secular trends in cardiovascular risk factors: an age-period cohort analysis of 698,954 health examinations in 181,350 Austrian men and women.

OBJECTIVES: It is well established that morbidity and mortality patterns in cardiovascular diseases vary strongly over time, yet the determinants of such trends remain poorly understood. To assess the potential contribution of secular or cross-generation patterns, we evaluated birth cohort-related trends across the 20th century of risk factors in a large database of Austrian men and women. SUBJECTS AND SETTING: Trends in risk factors were investigated for 181,350 adults aged 20-79 years born between 1905 and 1975 undergoing 698,954 health examinations between 1985 and 2005 as participants of the Vorarlberg Health Monitoring and Promotion Programme. RESULTS: There was clear evidence of cohort-related shifts in all risk factors. Total serum cholesterol and triglyceride declined markedly, particularly in the youngest cohorts, as did systolic and diastolic blood pressure in both men and women. By contrast, fasting glucose showed a strong rising tendency in both sexes and at all ages, most markedly in young males. Average glucose levels were between 4 and 15 mg dL(-1) higher in individuals at the same age born 20 years later. In males, body weight expressed in kg m(-2) (body mass index) was increasing as well; however, in women, patterns were most marked at the 90th percentile. CONCLUSION: These findings provide strong evidence of population wide secular shifts and suggest that in addition to period influences, most probably through treatment intervention and lifestyle change, determinants across the life-course are programming shifts from childhood onwards.