Association of HbA1c values with mortality and cardiovascular events in O

Abstract Background: Improved glycemic control reduces complications in patients with diabetes mellitus (DM). However, it is discussed controversially whether patients with diabetes mellitus and end-stage renal disease benefit from strict glycemic control

The Association of Mid-Regional Pro-Adrenomedullin and Mid-Regional Pro-Atrial Natriuretic Peptide with Mortality in an Incident Dialysis Cohort

High levels of the plasma peptides mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-atrial natriuretic peptide (MR-proANP) are associated with clinical outcomes in the general population. Data in patients with chronic kidney disease are sparse. We therefore investigated the association of MR-proANP and MR-proADM levels with all-cause and cardiovascular (CV) mortality, CV events and peripheral arterial disease in 201 incident dialysis patients of the INVOR-Study prospectively followed for a period of up to more than 7 years. The overall mortality rate was 43%, thereof 43% due to CV events. Both baseline MR-proANP and MR-proADM were associated with higher risk of all-cause (HR = 1.44, p = 0.001 and HR = 1.32, p = 0.002, respectively) and CV mortality (HR = 1.75, p<0.001 and HR = 1.41, p = 0.007, respectively) after adjustment for age, sex, previous CV events, diabetes mellitus and time-dependent type of renal replacement therapy. We then stratified patients in high risk (both peptides in the upper tertile), intermediate risk (only one of the two peptides in the upper tertile) and low risk (none in the upper tertile). Although demographic, clinical and laboratory variables were similar among the intermediate and high risk group, to be with both parameters in the upper tertile was associated with a 3-fold higher risk for all-cause (HR = 2.87, p<0.001) and CV mortality (HR = 3.58, p = 0.001). In summary, among incident dialysis patients MR-proANP and MR-proADM were shown to be associated with all-cause and CV mortality, with the highest risk when both parameters were in the upper tertiles

Metabolically (un)healthy obesity and risk of obesity-related cancers: a pooled study

Background Studies of obesity with or without metabolic aberrations, commonly termed metabolically unhealthy or healthy obesity, in relation to cancer risk are scarce. Methods We investigated body mass index (normal weight, overweight, obesity) jointly and in interaction with metabolic health status in relation to obesity-related cancer risk (n = 23 630) among 797 193 European individuals. A metabolic score comprising mid-blood pressure, plasma glucose, and triglycerides was used to define metabolically healthy and unhealthy status. Hazard ratios (HRs) and multiplicative interactions were assessed using Cox regression, and additive interactions were assessed using the relative excess risk for interaction. All statistical tests were 2-sided. Results Metabolically unhealthy obesity, with a baseline prevalence of 7%, was, compared with metabolically healthy normal weight, associated with an increased relative risk of any obesity-related cancer and of colon, rectal, pancreas, endometrial, liver, gallbladder, and renal cell cancer (P < .05), with the highest risk estimates for endometrial, liver, and renal cell cancer (HR = 2.55-3.00). Metabolically healthy obesity showed a higher relative risk for any obesity-related cancer and colon (in men), endometrial, renal cell, liver, and gallbladder cancer, though the risk relationships were weaker. There were no multiplicative interactions, but there were additive, positive interactions between body mass index and metabolic health status on obesity-related and rectal cancer among men and on endometrial cancer (P < .05). Conclusions This study highlights that the type of metabolic obesity phenotype is important when assessing obesity-related cancer risk. In general, metabolic aberrations further increased the obesity-induced cancer risk, suggesting that obesity and metabolic aberrations are useful targets for prevention.publishedVersio

Association of HbA1c Values with Mortality and Cardiovascular Events in Diabetic Dialysis Patients. The INVOR Study and Review of the Literature

BACKGROUND: Improved glycemic control reduces complications in patients with diabetes mellitus (DM). However, it is discussed controversially whether patients with diabetes mellitus and end-stage renal disease benefit from strict glycemic control. METHODS: We followed 78 patients with DM initiating dialysis treatment of the region of Vorarlberg in a prospective cohort study applying a time-dependent Cox regression analysis using all measured laboratory values for up to more than seven years. This resulted in 880 HbA(1c) measurements (with one measurement every 3.16 patient months on average) during the entire observation period. Non-linear P-splines were used to allow flexible modeling of the association with mortality and cardiovascular disease (CVD) events. RESULTS: We observed a decreased mortality risk with increasing HbA(1c) values (HR = 0.72 per 1% increase, p = 0.024). Adjustment for age and sex and additional adjustment for other CVD risk factors only slightly attenuated the association (HR = 0.71, p = 0.044). A non-linear P-spline showed that the association did not follow a fully linear pattern with a highly significant non-linear component (p = 0.001) with an increased risk of all-cause mortality for HbA(1c) values up to 6-7%. Causes of death were associated with HbA(1c) values. The risk for CVD events, however, increased with increasing HbA(1c) values (HR = 1.24 per 1% increase, p = 0.048) but vanished after extended adjustments. CONCLUSIONS: This study considered the entire information collected on HbA(1c) over a period of more than seven years. Besides the methodological advantages our data indicate a significant inverse association between HbA(1c) levels and all-cause mortality. However, for CVD events no significant association could be found

The Risk of Severe Infections Following Rituximab Administration in Patients With Autoimmune Kidney Diseases: Austrian ABCDE Registry Analysis.

OBJECTIVE: To characterize the incidence, type, and risk factors of severe infections (SI) in patients with autoimmune kidney diseases treated with rituximab (RTX). METHODS: We conducted a multicenter retrospective cohort study of adult patients with immune-related kidney diseases treated with at least one course of RTX between 2015 and 2019. As a part of the ABCDE Registry, detailed data on RTX application and SI were collected. SI were defined by Common Terminology Criteria for Adverse Events v5.0 as infectious complications grade 3 and above. Patients were dichotomized between "nephrotic" and "nephritic" indications. The primary outcome was the incidence of SI within 12 months after the first RTX application. RESULTS: A total of 144 patients were included. Twenty-five patients (17.4%) presented with SI, mostly within the first 3 months after RTX administration. Most patients in the nephritic group had ANCA-associated vasculitis, while membranous nephropathy was the leading entity in the nephrotic group. Respiratory infections were the leading SI (n= 10, 40%), followed by urinary tract (n=3, 12%) and gastrointestinal infections (n=2, 8%). On multivariable analysis, body mass index (BMI, 24.6 kg/m2versus 26.9 kg/m2, HR: 0.88; 95%CI: 0.79-0.99; p=0.039) and baseline creatinine (HR: 1.25; 95%CI: 1.04-1.49; p=0.017) were significantly associated with SI. All patients in the nephritic group (n=19; 100%) who experienced a SI received oral glucocorticoid (GC) treatment at the time of infection. Hypogammaglobulinemia was frequent (58.5%) but not associated with SI. CONCLUSIONS: After RTX administration, impaired kidney function and lower BMI are independent risk factors for SI. Patients with nephritic glomerular diseases having concomitant GC treatment might be at higher risk of developing SI

Long-term exposure to several constituents and sources of PM 2.5 is associated with incidence of upper aerodigestive tract cancers but not gastric cancer: Results from the large pooled European cohort of the ELAPSE project.

It is unclear whether cancers of the upper aerodigestive tract (UADT) and gastric cancer are related to air pollution, due to few studies with inconsistent results. The effects of particulate matter (PM) may vary across locations due to different source contributions and related PM compositions, and it is not clear which PM constituents/sources are most relevant from a consideration of overall mass concentration alone. We therefore investigated the association of UADT and gastric cancers with PM 2.5 elemental constituents and sources components indicative of different sources within a large multicentre population based epidemiological study. Cohorts with at least 10 cases per cohort led to ten and eight cohorts from five countries contributing to UADT- and gastric cancer analysis, respectively. Outcome ascertainment was based on cancer registry data or data of comparable quality. We assigned home address exposure to eight elemental constituents (Cu, Fe, K, Ni, S, Si, V and Zn) estimated from Europe-wide exposure models, and five source components identified by absolute principal component analysis (APCA). Cox regression models were run with age as time scale, stratified for sex and cohort and adjusted for relevant individual and neighbourhood level confounders. We observed 1139 UADT and 872 gastric cancer cases during a mean follow-up of 18.3 and 18.5 years, respectively. UADT cancer incidence was associated with all constituents except K in single element analyses. After adjustment for NO 2, only Ni and V remained associated with UADT. Residual oil combustion and traffic source components were associated with UADT cancer persisting in the multiple source model. No associations were found for any of the elements or source components and gastric cancer incidence. Our results indicate an association of several PM constituents indicative of different sources with UADT but not gastric cancer incidence with the most robust evidence for traffic and residual oil combustion

Long-term exposure to air pollution and incidence of gastric and the upper aerodigestive tract cancers in a pooled European cohort: The ELAPSE project

Air pollution has been shown to significantly impact human health including cancer. Gastric and upper aerodigestive tract (UADT) cancers are common and increased risk has been associated with smoking and occupational exposures. However, the association with air pollution remains unclear. We pooled European subcohorts (N = 287,576 participants for gastric and N = 297,406 for UADT analyses) and investigated the association between residential exposure to fine particles (PM 2.5 ), nitrogen dioxide (NO 2 ), black carbon (BC) and ozone in the warm season (O 3w ) with gastric and UADT cancer. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. During 5,305,133 and 5,434,843 person-years, 872 gastric and 1139 UADT incident cancer cases were observed, respectively. For gastric cancer, we found no association with PM 2.5 , NO 2 and BC while for UADT the hazard ratios (95% confidence interval) were 1.15 (95% CI: 1.00-1.33) per 5 μg/m 3 increase in PM 2.5 , 1.19 (1.08-1.30) per 10 μg/m 3 increase in NO 2 , 1.14 (1.04-1.26) per 0.5 × 10 -5  m -1 increase in BC and 0.81 (0.72-0.92) per 10 μg/m 3 increase in O 3w . We found no association between long-term ambient air pollution exposure and incidence of gastric cancer, while for long-term exposure to PM 2.5 , NO 2 and BC increased incidence of UADT cancer was observed

Long-term exposure to ambient air pollution and risk of leukemia and lymphoma in a pooled European cohort

Leukemia and lymphoma are the two most common forms of hematologic malignancy, and their etiology is largely unknown. Pathophysiological mechanisms suggest a possible association with air pollution, but little empirical evidence is available. We aimed to investigate the association between long-term residential exposure to outdoor air pollution and risk of leukemia and lymphoma. We pooled data from four cohorts from three European countries as part of the “Effects of Low-level Air Pollution: a Study in Europe” (ELAPSE) collaboration. We used Europe-wide land use regression models to assess annual mean concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone (O3) at residences. We also estimated concentrations of PM2.5 elemental components: copper (Cu), iron (Fe), zinc (Zn); sulfur (S); nickel (Ni), vanadium (V), silicon (Si) and potassium (K). We applied Cox proportional hazards models to investigate the associations. Among the study population of 247,436 individuals, 760 leukemia and 1122 lymphoma cases were diagnosed during 4,656,140 person-years of follow-up. The results showed a leukemia hazard ratio (HR) of 1.13 (95% confidence intervals [CI]: 1.01–1.26) per 10 μg/m3 NO2, which was robust in two-pollutant models and consistent across the four cohorts and according to smoking status. Sex-specific analyses suggested that this association was confined to the male population. Further, the results showed increased lymphoma HRs for PM2.5 (HR = 1.16; 95% CI: 1.02–1.34) and potassium content of PM2.5, which were consistent in two-pollutant models and according to sex. Our results suggest that air pollution at the residence may be associated with adult leukemia and lymphoma

Long-term exposure to air pollution and chronic kidney disease-associated mortality - results from the pooled cohort of the European multicentre ELAPSE-study

Despite the known link between air pollution and cause-specific mortality, its relation to chronic kidney disease (CKD)-associated mortality is understudied. Therefore, we investigated the association between long-term exposure to air pollution and CKD-related mortality in a large multicentre population-based European cohort. Cohort data were linked to local mortality registry data. CKD-death was defined as ICD10 codes N18-N19 or corresponding ICD9 codes. Mean annual exposure at participant's home address was determined with fine spatial resolution exposure models for nitrogen dioxide (NO 2), black carbon (BC), ozone (O 3), particulate matter ≤2.5μm (PM 2.5) and several elemental constituents of PM 2.5. Cox regression models were adjusted for age, sex, cohort, calendar year of recruitment, smoking status, marital status, employment status and neighbourhood mean income. Over a mean follow-up time of 20.4 years, 313 of 289 564 persons died from CKD. Associations were positive for PM 2.5 (hazard ratio (HR) with 95% confidence interval (CI) of 1.31 (1.03-1.66) per 5μg/m 3, BC (1.26 (1.03-1.53) per 0.5×10 - 5/m), NO 2 (1.13 (0.93-1.38) per 10μg/m 3) and inverse for O 3 (0.71 (0.54-0.93) per 10μg/m 3). Results were robust to further covariate adjustment. Exclusion of the largest sub-cohort contributing 226 cases, led to null associations. Among the elemental constituents, Cu, Fe, K, Ni, S and Zn, representing different sources including traffic, biomass and oil burning and secondary pollutants, were associated with CKD-related mortality. In conclusion, our results suggest an association between air pollution from different sources and CKD-related mortality