Evaluation of a Population-Based Targeted Screening Approach for Skin Cancer with Long-Time Follow-Up in Austria including Potential Effects on Melanoma Mortality.

BACKGROUND: whether screening for skin cancer affects melanoma-specific mortality in a population-based setting remains unclear. METHODS: in this population-based cohort study, we characterized and evaluated a skin cancer prevention program following a targeted screening approach conducted in 1989-1994 in the Austrian province Vorarlberg, with follow-up until 2019. The general population and attendees of a health examination program served for comparison. RESULTS: in the screening program including full follow-up until 2019, 207 invasive and 187 in situ melanomas were identified in 8997 individuals. Incidences of invasive and in situ melanomas were elevated compared to the general population (IRR 2.92, 95%-CI 2.49-3.41, and IRR 4.13, 95%-CI 3.53-4.83, respectively) and the health examination program (HR 3.02, 95%-CI 2.59-3.52, and HR 3.90, 95%-CI 3.30-4.61, respectively). Breslow thickness and Clark's level at time of invasive diagnosis were significantly lower in 1989-2019, but the tumor characteristics of the melanomas diagnosed during 1989-1994 did not differ from the comparison groups. Moreover, melanoma mortality was significantly elevated in the screening program (IRR 1.66, 95%-CI 1.00-2.75 vs. the general population, HR 2.12, 95%-CI 1.25-3.61 vs. the health examination cohort). Melanoma mortality in Vorarlberg declined until 2004, though statistically non-significantly. CONCLUSIONS: given the uncertain effectiveness and high public expenditures of population-wide mass screening programs, primary prevention and targeted risk-based skin cancer screening might be promising alternatives.

The value of earlier-in-life systolic and diastolic blood pressure for cardiovascular risk prediction.

Blood pressure (BP) varies over a lifetime. This cardiovascular observation study (OS) compared the predictive value of earlier- and later-in-life blood pressure (BP) in 1,497 cardiovascular disease patients utilizing readings taken during a health survey (HS) and 15 years later from the same subjects at the baseline of this OS. Prediction of the cardiovascular risk during the OS follow-up (21 years) was significantly more effective if the earlier BP readings at HS were used instead of recent OS readings (NRI = 0.30, p < 0.001). For HS readings, each 10 mm Hg increase of systolic and diastolic BP was associated with a 17% and 20% higher risk, respectively. At OS, systolic BP lost significance and diastolic BP reversed its association. Noteworthy, different BP categorizations (European vs. US guidelines) yielded similar results. This study highlights the poor predictive power of BP readings in elderly cardiovascular disease patients but emphasizes the significant prognostic value of earlier-in-life BP.

Exposure to ambient air pollution and elevated blood levels of gamma-glutamyl transferase in a large Austrian cohort.

Gamma glutamyl transferase (GGT) is related to oxidative stress and an indicator for liver damage. We investigated the association between air pollution and GGT in a large Austrian cohort (N = 116,109) to better understand how air pollution affects human health. Data come from voluntary prevention visits that were routinely collected within the Vorarlberg Health Monitoring and Prevention Program (VHM&PP). Recruitment was ongoing from 1985 to 2005. Blood was drawn and GGT measured centralized in two laboratories. Land use regression models were applied to estimate individuals' exposure at their home address for particulate matter (PM) with a diameter of <2.5 µm (PM2.5), <10 µm (PM10), fraction between 10 µm and 2.5 µm (PMcoarse), as well as PM2.5 absorbance (PM2.5abs), NO2, NOx and eight components of PM. Linear regression models, adjusting for relevant individual and community-level confounders were calculated. The study population was 56 % female with a mean age of 42 years and mean GGT was 19.0 units. Individual PM2.5 and NO2 exposures were essentially below European limit values of 25 and 40 µg/m3, respectively, with means of 13.58 µg/m3 for PM2.5 and 19.93 µg/m3 for NO2. Positive associations were observed for PM2.5, PM10, PM2.5abs, NO2, NOx, and Cu, K, S in PM2.5 and PM10 fractions and Zn mainly in PM2.5 fraction. The strongest association per interquartile range observed was an increase of serum GGT concentration by 1.40 % (95 %-CI: 0.85 %; 1.95 %) per 45.7 ng/m3 S in PM2.5. Associations were robust to adjustments for other biomarkers, in two-pollutant models and the subset with a stable residential history. We found that long-term exposure to air pollution (PM2.5, PM10, PM2.5abs, NO2, NOx) as well as certain elements, were positively associated with baseline GGT levels. The elements associated suggest a role of traffic emissions, long range transport and wood burning.

Long-term air pollution exposure and Parkinson's disease mortality in a large pooled European cohort: An ELAPSE study.

BACKGROUND: The link between exposure to ambient air pollution and mortality from cardiorespiratory diseases is well established, while evidence on neurodegenerative disorders including Parkinson's Disease (PD) remains limited. OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and PD mortality in seven European cohorts. METHODS: Within the project 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE), we pooled data from seven cohorts among six European countries. Annual mean residential concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (O3), as well as 8 PM2.5 components (copper, iron, potassium, nickel, sulphur, silicon, vanadium, zinc), for 2010 were estimated using Europe-wide hybrid land use regression models. PD mortality was defined as underlying cause of death being either PD, secondary Parkinsonism, or dementia in PD. We applied Cox proportional hazard models to investigate the associations between air pollution and PD mortality, adjusting for potential confounders. RESULTS: Of 271,720 cohort participants, 381 died from PD during 19.7 years of follow-up. In single-pollutant analyses, we observed positive associations between PD mortality and PM2.5 (hazard ratio per 5 µg/m3: 1.25; 95% confidence interval: 1.01-1.55), NO2 (1.13; 0.95-1.34 per 10 µg/m3), and BC (1.12; 0.94-1.34 per 0.5 × 10-5m-1), and a negative association with O3 (0.74; 0.58-0.94 per 10 µg/m3). Associations of PM2.5, NO2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM2.5 remained robust when adjusted for NO2 (1.24; 0.95-1.62) or BC (1.28; 0.96-1.71), whereas associations with NO2 or BC attenuated to null. O3 associations remained negative, but no longer statistically significant in models with PM2.5. We detected suggestive positive associations with the potassium component of PM2.5. CONCLUSION: Long-term exposure to PM2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality.

Long-term exposure to air pollution and mortality from dementia, psychiatric disorders, and suicide in a large pooled European cohort: ELAPSE study.

Ambient air pollution is an established risk factor for premature mortality from chronic cardiovascular, respiratory and metabolic diseases, while evidence on neurodegenerative diseases and psychiatric disorders remains limited. We examined the association between long-term exposure to air pollution and mortality from dementia, psychiatric disorders, and suicide in seven European cohorts. Within the multicenter project 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE), we pooled data from seven European cohorts from six countries. Based on the residential addresses, annual mean levels of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), ozone (O3), and 8 PM2.5 components were estimated using Europe-wide hybrid land-use regression models. We applied stratified Cox proportional hazard models to investigate the associations between air pollution and mortality from dementia, psychiatric disorders, and suicide. Of 271,720 participants, 900 died from dementia, 241 from psychiatric disorders, and 164 from suicide, during a mean follow-up of 19.7 years. In fully adjusted models, we observed positive associations of NO2 (hazard ratio [HR] = 1.38; 95 % confidence interval [CI]: 1.13, 1.70 per 10 µg/m3), PM2.5 (HR = 1.29; 95 % CI: 0.98, 1.71 per 5 µg/m3), and BC (HR = 1.37; 95 % CI: 1.11, 1.69 per 0.5 × 10-5/m) with psychiatric disorders mortality, as well as with suicide (NO2: HR = 1.13 [95 % CI: 0.92, 1.38]; PM2.5: HR = 1.19 [95 % CI: 0.76, 1.87]; BC: HR = 1.08 [95 % CI: 0.87, 1.35]), and no association with dementia mortality. We did not detect any positive associations of O3 and 8 PM2.5 components with any of the three mortality outcomes. Long-term exposure to NO2, PM2.5, and BC may lead to premature mortality from psychiatric disorders and suicide.

The Association of Excess Body Weight with Risk of ESKD Is Mediated Through Insulin Resistance, Hypertension, and Hyperuricemia.

BACKGROUND: Insulin resistance, hypertension, hyperuricemia, and hypercholesterolemia are hypothesized to be important intermediates in the relationship between excess body weight and CKD risk. However, the magnitude of the total effect of excess body weight on ESKD mediated through these four pathways remains to be quantified. METHODS: We applied a model for analysis of correlated mediators to population-based data from 100,269 Austrian individuals (mean age 46.4 years). Association of body mass index (BMI) was coalesced with ESKD risk into direct association. Indirect associations were mediated through the triglyceride-glucose (TyG) index (as an indicator of insulin resistance), mean arterial pressure (MAP), uric acid (UA), and total cholesterol (TC). RESULTS: Mean follow-up was 23.1 years with 463 (0.5%) incident ESKD cases. An unhealthy metabolic profile (prevalence 32.4%) was associated with a markedly increased ESKD risk (multivariably adjusted hazard ratio (aHR), 3.57; 95% CI, 2.89 to 4.40), independent of BMI. A 5-kg/m2 higher BMI was associated with a 57% increased ESKD risk (aHRtotal association, 1.57; 1.38 to 1.77). Of this association, 99% (76% to 140%) arose from all mediators jointly; 33% (22% to 49%) through TyG index; 34% (24% to 50%) through MAP; 30% (21% to 45%) through UA; and 2% (-1% to 4%) through TC. The remaining direct association was nonsignificant (aHRdirect association, 1.01; 0.88 to 1.14). CONCLUSIONS: TyG index, MAP, and UA, but not TC, mediate the association of BMI with ESKD in middle-aged adults. Our findings highlight that in addition to weight reduction, the control of metabolic risk factors might be essential in mitigating the adverse effects of BMI on kidney function.

Long-term Air Pollution Exposure and Pneumonia-related Mortality in a Large Pooled European Cohort.

Rationale: Ambient air pollution exposure has been linked to mortality from chronic cardiorespiratory diseases, while evidence on respiratory infections remains more limited. Objectives: We examined the association between long-term exposure to air pollution and pneumonia-related mortality in adults in a pool of eight European cohorts. Methods: Within the multicenter project ELAPSE (Effects of Low-Level Air Pollution: A Study in Europe), we pooled data from eight cohorts among six European countries. Annual mean residential concentrations in 2010 for fine particulate matter, nitrogen dioxide (NO2), black carbon (BC), and ozone were estimated using Europe-wide hybrid land-use regression models. We applied stratified Cox proportional hazard models to investigate the associations between air pollution and pneumonia, influenza, and acute lower respiratory infections (ALRI) mortality. Measurements and Main Results: Of 325,367 participants, 712 died from pneumonia and influenza combined, 682 from pneumonia, and 695 from ALRI during a mean follow-up of 19.5 years. NO2 and BC were associated with 10-12% increases in pneumonia and influenza combined mortality, but 95% confidence intervals included unity (hazard ratios, 1.12 [0.99-1.26] per 10 µg/m3 for NO2; 1.10 [0.97-1.24] per 0.5 10-5m-1 for BC). Associations with pneumonia and ALRI mortality were almost identical. We detected effect modification suggesting stronger associations with NO2 or BC in overweight, employed, or currently smoking participants compared with normal weight, unemployed, or nonsmoking participants. Conclusions: Long-term exposure to combustion-related air pollutants NO2 and BC may be associated with mortality from lower respiratory infections, but larger studies are needed to estimate these associations more precisely.

Thirty years of hip fracture incidence in Austria: is the worst over?

Nationwide hip fracture incidence in the Austrian population was assessed over a period of 30 years (1989-2018), including 20 years data from a previous study and a recent 10 years follow-up. While absolute numbers in men continued to increase, absolute numbers in women and age-standardized incidences in both men and women decreased. PURPOSE: In the Austrian population ≥ 50 years, nationwide hip fracture incidences over a period of 20 years (1989-2008) have shown an initial steep increase, followed by a leveling-off during the last few years of observation. The purpose of the present study was to follow up on hip fracture incidences for another 10 years (2009-2018) and to analyze trends over the entire period of 30 years. METHODS: ICD-10 code classes S72.0, S72.1, and S72.2 were applied. All data were retrieved from the Statistics Austria database and its hospital discharge register. Annual absolute numbers, crude and age-standardized incidences, and incidence rate ratios (IRR) were stratified by sex and 5-year age intervals, and calculated by using a correction factor for multiple registrations. RESULTS: Total number of hip fracture cases increased from 13,984 (2009) to 14,640 (2015), and decreased thereafter to 14,457 (2018), despite a persistent increase in men. Age-standardized incidences peaked at 476/100,000 (2010), followed by a decrease to 408/100,000 (2018). The observed overall decrease was mainly driven by the female population. Incidence rate ratios (IRRs) yielded a statistically significant average annual decrease of age-standardized incidences in both women and men (∆IRR 0.984; 0.981-0.987). CONCLUSION: While absolute numbers of hip fracture in women showed a slight decrease during the last 10 years of observation, numbers in men continued to increase. Age-standardized incidences nevertheless decreased in both men and women, which may be interpreted as a trend in the right direction. However, due to the rapid aging of the population, it cannot be precluded that this trend will be compromised during the next few decades.

Long term exposure to low level air pollution and mortality in eight European cohorts within the ELAPSE project: pooled analysis.

OBJECTIVE: To investigate the associations between air pollution and mortality, focusing on associations below current European Union, United States, and World Health Organization standards and guidelines. DESIGN: Pooled analysis of eight cohorts. SETTING: Multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) in six European countries. PARTICIPANTS: 325 367 adults from the general population recruited mostly in the 1990s or 2000s with detailed lifestyle data. Stratified Cox proportional hazard models were used to analyse the associations between air pollution and mortality. Western Europe-wide land use regression models were used to characterise residential air pollution concentrations of ambient fine particulate matter (PM2.5), nitrogen dioxide, ozone, and black carbon. MAIN OUTCOME MEASURES: Deaths due to natural causes and cause specific mortality. RESULTS: Of 325 367 adults followed-up for an average of 19.5 years, 47 131 deaths were observed. Higher exposure to PM2.5, nitrogen dioxide, and black carbon was associated with significantly increased risk of almost all outcomes. An increase of 5 µg/m3 in PM2.5 was associated with 13% (95% confidence interval 10.6% to 15.5%) increase in natural deaths; the corresponding figure for a 10 µg/m3 increase in nitrogen dioxide was 8.6% (7% to 10.2%). Associations with PM2.5, nitrogen dioxide, and black carbon remained significant at low concentrations. For participants with exposures below the US standard of 12 µg/m3 an increase of 5 µg/m3 in PM2.5 was associated with 29.6% (14% to 47.4%) increase in natural deaths. CONCLUSIONS: Our study contributes to the evidence that outdoor air pollution is associated with mortality even at low pollution levels below the current European and North American standards and WHO guideline values. These findings are therefore an important contribution to the debate about revision of air quality limits, guidelines, and standards, and future assessments by the Global Burden of Disease.

Long-term exposure to air pollution and liver cancer incidence in six European cohorts.

Particulate matter air pollution and diesel engine exhaust have been classified as carcinogenic for lung cancer, yet few studies have explored associations with liver cancer. We used six European adult cohorts which were recruited between 1985 and 2005, pooled within the "Effects of low-level air pollution: A study in Europe" (ELAPSE) project, and followed for the incidence of liver cancer until 2011 to 2015. The annual average exposure to nitrogen dioxide (NO2 ), particulate matter with diameter <2.5 µm (PM2.5 ), black carbon (BC), warm-season ozone (O3 ), and eight elemental components of PM2.5 (copper, iron, zinc, sulfur, nickel, vanadium, silicon, and potassium) were estimated by European-wide hybrid land-use regression models at participants' residential addresses. We analyzed the association between air pollution and liver cancer incidence by Cox proportional hazards models adjusting for potential confounders. Of 330 064 cancer-free adults at baseline, 512 developed liver cancer during a mean follow-up of 18.1 years. We observed positive linear associations between NO2 (hazard ratio, 95% confidence interval: 1.17, 1.02-1.35 per 10 µg/m3 ), PM2.5 (1.12, 0.92-1.36 per 5 µg/m3 ), and BC (1.15, 1.00-1.33 per 0.5 10-5 /m) and liver cancer incidence. Associations with NO2 and BC persisted in two-pollutant models with PM2.5 . Most components of PM2.5 were associated with the risk of liver cancer, with the strongest associations for sulfur and vanadium, which were robust to adjustment for PM2.5 or NO2 . Our study suggests that ambient air pollution may increase the risk of liver cancer, even at concentrations below current EU standards.

Value of total cholesterol readings earlier versus later in life to predict cardiovascular risk.

BACKGROUND: Prognostic implications of blood cholesterol may differ at different stages of life. This cohort study compares the value of total cholesterol (TC) readings earlier versus later in life for the prediction of coronary atherosclerosis, cardiovascular events, and cardiovascular death. METHODS: In a cardiovascular observation study (CVOS) we performed coronary angiography and prospectively recorded cardiovascular events in 1090 patients over up to 19 years. These patients had participated in a health survey (HS) 15 years prior to the CVOS baseline. TC was measured twice, first at the earlier HS and then later at CVOS recruiting. FINDINGS: Patients in the highest versus the lowest TC-category of the HS had an OR of 4.30 [2.41-7.65] for significant CAD at angiography, a HR of 1.74 [1.10-2.76] for cardiovascular events, and a HR of 7.55 [1.05-54.49] for cardiovascular death after multivariate adjustment. In contrast, TC as measured at the baseline of the CVOS was neither significantly associated with significant CAD (OR= 0.75 [0.49-1.13]) nor with cardiovascular events or death during follow-up (HR= 0.86 [0.62-1.18] and 0.79 [0.41-1.53], respectively). Moreover, the ESC/EAS-SCORE was found to be more powerful in predicting cardiovascular mortality when using earlier instead of later TC, with a continuous net reclassification improvement of 0.301 (p<0.001). INTERPRETATION: Early measurement not only enables early intervention in keeping with the concept of lifelong exposure to atherogenic lipoproteins. These data also suggest that cardiovascular risk prediction is more accurate if using earlier in life TC readings. FUNDING: The present study did not receive any particular funding.

Serum uric acid is associated with incident hip fractures in women and men - Results from a large Austrian population-based cohort study.

OBJECTIVES: Serum markers that can be used to estimate the risk of bone fractures are rare, and findings for one candidate marker, uric acid, are heterogeneous. Our aim was to investigate the potential of serum uric acid (SUA) to predict hip fractures occurring in people aged 50 years and over. STUDY DESIGN: During a medical prevention program over the period 1985-2005 in Vorarlberg, baseline data were collected on SUA levels and covariates (age, BMI, blood pressure, smoking status, diabetes, triglycerides and cholesterol) from 185,397 individuals, of whom 42,488 women and 35,908 men met the inclusion criteria of this population-based cohort study. Information on incident cancer and end-stage kidney disease was acquired from registries. MAIN OUTCOME MEASURE: Incident hip fracture occurring in participants aged 50 years and over during the observation period 2003-2013. RESULTS: SUA was associated with a rise in female hip fracture risk by 6% per unit increase (HR 1.06, 95 %-CI 1.01-1.10), and risk in the highest vs. lowest SUA quartile was significantly increased (HR 1.17, 95 %-CI 1.01-1.35), but not at hyperuricemic (>5.7 mg/dl) vs. normouricemic (≤5.7 mg/dl) levels. In men, hip fracture risk rose by 15 % per unit increase (HR 1.15, 95 %-CI 1.08-1.22), and risk was significantly higher in the highest vs. lowest SUA quartile (HR 1.50, 95 %-CI 1.17-1.91) as well as at hyperuricemic (>7.0 mg/dl) vs. normouricemic (≤7.0 mg/dl) levels (HR 1.48, 95 %-CI 1.19-1.84). CONCLUSIONS: Our results link SUA with increased risk of hip fractures, particularly in men.

Long-Term Exposure to Fine Particle Elemental Components and Natural and Cause-Specific Mortality-a Pooled Analysis of Eight European Cohorts within the ELAPSE Project.

BACKGROUND: Inconsistent associations between long-term exposure to particles with an aerodynamic diameter ≤2.5 µm [fine particulate matter (PM2.5)] components and mortality have been reported, partly related to challenges in exposure assessment. OBJECTIVES: We investigated the associations between long-term exposure to PM2.5 elemental components and mortality in a large pooled European cohort; to compare health effects of PM2.5 components estimated with two exposure modeling approaches, namely, supervised linear regression (SLR) and random forest (RF) algorithms. METHODS: We pooled data from eight European cohorts with 323,782 participants, average age 49 y at baseline (1985-2005). Residential exposure to 2010 annual average concentration of eight PM2.5 components [copper (Cu), iron (Fe), potassium (K), nickel (Ni), sulfur (S), silicon (Si), vanadium (V), and zinc (Zn)] was estimated with Europe-wide SLR and RF models at a 100×100 m scale. We applied Cox proportional hazards models to investigate the associations between components and natural and cause-specific mortality. In addition, two-pollutant analyses were conducted by adjusting each component for PM2.5 mass and nitrogen dioxide (NO2) separately. RESULTS: We observed 46,640 natural-cause deaths with 6,317,235 person-years and an average follow-up of 19.5 y. All SLR-modeled components were statistically significantly associated with natural-cause mortality in single-pollutant models with hazard ratios (HRs) from 1.05 to 1.27. Similar HRs were observed for RF-modeled Cu, Fe, K, S, V, and Zn with wider confidence intervals (CIs). HRs for SLR-modeled Ni, S, Si, V, and Zn remained above unity and (almost) significant after adjustment for both PM2.5 and NO2. HRs only remained (almost) significant for RF-modeled K and V in two-pollutant models. The HRs for V were 1.03 (95% CI: 1.02, 1.05) and 1.06 (95% CI: 1.02, 1.10) for SLR- and RF-modeled exposures, respectively, per 2 ng/m3, adjusting for PM2.5 mass. Associations with cause-specific mortality were less consistent in two-pollutant models. CONCLUSION: Long-term exposure to V in PM2.5 was most consistently associated with increased mortality. Associations for the other components were weaker for exposure modeled with RF than SLR in two-pollutant models. https://doi.org/10.1289/EHP8368.

The Triglyceride-Glucose Index and Obesity-Related Risk of End-Stage Kidney Disease in Austrian Adults.

Importance: It is unknown whether the triglyceride-glucose (TyG) index as a measure of insulin resistance is associated with the risk of developing end-stage kidney disease (ESKD). Because individuals who are overweight or obese often develop insulin resistance, mediation of the association between body mass index (BMI) and ESKD risk through the TyG index seems plausible but has not been investigated. Objective: To evaluate whether the TyG index is associated with ESKD risk and, if so, to what extent the TyG index mediates the association between BMI and ESKD. Design, Setting, and Participants: A total of 176 420 individuals were recruited during routine health examinations to participate in the Austrian Vorarlberg Health Monitoring and Promotion Program (VHM&PP), a prospective, population-based cohort study with participant enrollment between January 1, 1988, and June 30, 2005, and a mean follow-up of 22.7 years. Data analysis was conducted from March 1, 2020, to September 30, 2020. Exposures: Body mass index and the logarithmized product of fasting triglyceride and glucose concentrations (TyG index), as determined during the baseline health examination. Main Outcomes and Measures: End-stage kidney disease, as indicated by initiation of kidney replacement therapy, either dialysis or kidney transplantation. Results: Of the 176 420 participants, 94 885 were women (53.8%); mean (SD) age was 42.5 (15.4) years. During a mean (SD) follow-up of 22.7 (6.9) years, 454 (0.3%) participants developed ESKD and 35 234 (20.0%) died. In multivariable-adjusted Cox proportional hazards models, the TyG index was significantly associated with the risk of ESKD, both with (hazard ratio [HR] per 1-SD increase, 1.68; 95% CI, 1.56-1.82) and without (HR per 1-SD increase, 1.79; 95% CI, 1.66-1.93) the inclusion of BMI as a covariate. Mediation analysis using a newly proposed 2-stage regression method for survival data showed that a 5-point increase in BMI increased the risk of ESKD by 58% (HR [total association], 1.58; 95% CI, 1.43-1.75), and that 41.7% of the total association (95% CI, 31.6%-51.8%) was mediated through the TyG index (HR [indirect association], 1.21; 95% CI, 1.18-1.25). Conclusions and Relevance: This study found that the TyG index appeared to be associated with ESKD risk and mediates nearly half of the total association between BMI and ESKD in the general population. Public health efforts aiming at the reduction of body weight might decrease the kidney sequelae of insulin resistance and the burden of ESKD.

Metabolic factors and the risk of small intestine cancers: Pooled study of 800 000 individuals in the metabolic syndrome and cancer project.

To explore the largely unknown etiology of small intestine cancer, we examined metabolic factors and risk of small intestine cancer overall and by subtypes. Among 404 220 women and 403 265 men in six European cohorts, we applied Cox regression with adjustment for smoking and body mass index (BMI), to calculate sex-specific hazard ratios (HRs) of small intestine cancer by levels of BMI, mean arterial pressure (MAP) and plasma total cholesterol, triglycerides and glucose. We also calculated HRs for these factors combined (metabolic score; MetS) and used Wald test statistics to investigate pairwise interactions between metabolic factors on risk. We also performed analyses separately per subtype (neuroendocrine tumors [NETs] and adenocarcinomas). During a median follow-up of 16.9 years, 144 women and 195 men were diagnosed with small intestine cancer, including 184 NETs and 99 adenocarcinomas. Among men, no main associations or interactions between metabolic factors were observed in relation to the risk of small intestine cancer. Among women, triglycerides were positively and linearly associated with risk (HR per standard deviation [SD]: 1.23, 95% confidence interval [CI]: 1.04-1.46), and a positive association was also observed for the MetS (HR per SD: 1.25, 95% CI: 1.02-1.52). Positive interactions were observed among women between triglycerides and cholesterol (P = .0005), and between MAP and glucose (P = .009), on risk. Glucose was positively associated with adenocarcinomas among women. This large, prospective study suggests that elevated triglycerides, and metabolic factors in interaction, confer an increased risk of small intestine cancer among women, but not among men.

Long-term exposure to fine particle elemental components and lung cancer incidence in the ELAPSE pooled cohort.

BACKGROUND: An association between long-term exposure to fine particulate matter (PM2.5) and lung cancer has been established in previous studies. PM2.5 is a complex mixture of chemical components from various sources and little is known about whether certain components contribute specifically to the associated lung cancer risk. The present study builds on recent findings from the "Effects of Low-level Air Pollution: A Study in Europe" (ELAPSE) collaboration and addresses the potential association between specific elemental components of PM2.5 and lung cancer incidence. METHODS: We pooled seven cohorts from across Europe and assigned exposure estimates for eight components of PM2.5 representing non-tail pipe emissions (copper (Cu), iron (Fe), and zinc (Zn)), long-range transport (sulfur (S)), oil burning/industry emissions (nickel (Ni), vanadium (V)), crustal material (silicon (Si)), and biomass burning (potassium (K)) to cohort participants' baseline residential address based on 100 m by 100 m grids from newly developed hybrid models combining air pollution monitoring, land use data, satellite observations, and dispersion model estimates. We applied stratified Cox proportional hazards models, adjusting for potential confounders (age, sex, calendar year, marital status, smoking, body mass index, employment status, and neighborhood-level socio-economic status). RESULTS: The pooled study population comprised 306,550 individuals with 3916 incident lung cancer events during 5,541,672 person-years of follow-up. We observed a positive association between exposure to all eight components and lung cancer incidence, with adjusted HRs of 1.10 (95% CI 1.05, 1.16) per 50 ng/m3 PM2.5 K, 1.09 (95% CI 1.02, 1.15) per 1 ng/m3 PM2.5 Ni, 1.22 (95% CI 1.11, 1.35) per 200 ng/m3 PM2.5 S, and 1.07 (95% CI 1.02, 1.12) per 200 ng/m3 PM2.5 V. Effect estimates were largely unaffected by adjustment for nitrogen dioxide (NO2). After adjustment for PM2.5 mass, effect estimates of K, Ni, S, and V were slightly attenuated, whereas effect estimates of Cu, Si, Fe, and Zn became null or negative. CONCLUSIONS: Our results point towards an increased risk of lung cancer in connection with sources of combustion particles from oil and biomass burning and secondary inorganic aerosols rather than non-exhaust traffic emissions. Specific limit values or guidelines targeting these specific PM2.5 components may prove helpful in future lung cancer prevention strategies.

Effect of Secular Trend, Age, and Length of Follow-up on Optimum Body Mass Index From 1985 Through 2015 in a Large Austrian Cohort.

BACKGROUND: Obesity and its health consequences will dominate health care systems in many countries during the next decades. However, the body mass index (BMI) optimum in relation to all-cause mortality is still a matter of debate. MATERIAL AND METHODS: Data of the Vorarlberg Health Monitoring & Prevention Program (VHM&PP, 1985-2005) and data provided by the Main Association of Austrian Social Security Institutions (MAASSI, 2005-2015) were analyzed. Information was available on age, sex, smoking status, measured height and weight, and mortality. Generalized additive models were used to model mortality as a function of BMI, calendar time, age, and follow-up. RESULTS: In MAASSI (N = 282,216, 46.0% men), men and women were on average 2.7 years older than in VHM&PP (N = 185,361, 46.1% men). Average BMI was slightly higher in men (26.1 vs 25.7 kg/m2) but not in women (24.6 vs 24.7 kg/m2). We found an interactive effect of age and follow-up on the BMI optimum. Over age 35 years in men and 55 years in women, the BMI optimum decreased with length of follow-up. While keeping covariates fixed, BMI optimum increased slightly between 1985 and 2015 in men and women, 24.9 (95% CI, 23.9-25.9) to 26.4 (95% CI, 25.3-27.3), and 22.4 (95% CI, 21.7-23.1) to 23.3 (95% CI, 22.6-24.5) kg/m2, respectively. CONCLUSION: Age and length of follow-up have a pronounced effect on the BMI associated with the lowest all-cause mortality. After controlling for age and length of follow-up, the BMI optimum increased slightly over 30 years in this large study sample.