Blood biomarkers for occupational hand-arm vibration exposure.

Hand-arm vibration is a common occupational exposure that causes neurological impairment, myalgia, and vibration-induced Raynaud's phenomena or vibration white fingers (VWF). The pathological mechanism is largely unknown, though several mechanisms have been proposed, involving both immunological vascular damage and defective neural responses. The aim of this study was to test whether the substances interleukin-33 (IL-33), macrophage-derived chemokine (MDC), interleukin-10 (IL-10), endothelin-1 (ET-1), C-C motif chemokine ligand 20 (CCL20), calcitonin, and thromboxane (TXA2) changed before and after occupational hand-arm vibration exposure. 38 full-time shift workers exposed to hand-arm vibration were recruited. All the participants underwent medical examinations regarding symptoms of Raynaud's phenomena. In 29 of the participants, the concentration of IL-33, MDC, IL-10, ET-1, CCL20, calcitonin, and TXA2 was measured before and after a workday. There was a significant increase in ET-1 and calcitonin concentration and a decrease in the CCL20 concentration after the work shift in all participants. In the group suffering from VWF, but not in the non-VWF group, MDC was statistically significantly lower before the work shift (p = .023). The VWF group also showed a significant increase in MDC after the work shift. Exposure to occupational hand-arm vibration is associated with changes in ET-1, calcitonin, and MDC concentration in subjects suffering from vibration white fingers, suggesting a role of these biomarkers in the pathophysiology of this condition.

LC-MS/MS analysis of 11-nor-9-carboxy-hexahydrocannabinol (HHC-COOH) and 11-hydroxy-hexahydrocannabinol (HHC-OH) for verification of hexahydrocannabinol (HHC) intake.

Natural and semi-synthetic cannabinoid analogs are getting increasing media attention for their recreative use as an alternative to traditional cannabis, in Sweden as well as internationally. To investigate an increasing number of urine samples incoming to our clinical laboratory that were screening positive, using a CEDIA THC-COOH immunoassay from ThermoFisher Scientific, but then testing negative using GC-MS based verification analysis, we developed an LC-MS/MS-method for verification of hexahydrocannabinol (HHC) and Δ8-tetrahydrocannabinol. Assessment of HHC intake was based on identification of the following four metabolites: 11-nor-9(R)-carboxy-hexahydrocannabinol (R-HHC-COOH), 11-nor-9(S)-carboxy-hexahydrocannabinol (S-HHC-COOH), 11-hydroxy-9(R)-hexahydrocannabinol (R-HHC-OH) and 11-hydroxy-9(S)-hexahydrocannabinol (S-HHC-OH). Out of 46 urine samples analysed in this study, 44 showed presence of HHC-metabolites, which indicate HHC as the main explanation for an increased number of negative verifications for THC-COOH. In these samples, the HHC-OH metabolites occurred at a higher concentration than R-HHC-COOH while S-HHC-COOH was only detected in few samples at low concentrations. R-HHC-COOH and S-HHC-COOH can easily be added to a pre-existing verification method for THC-COOH, and still show acceptable results, while HHC-OH requires an enzyme capable of hydrolysing the ether glucuronide bond.

Relative handgrip strength correlates inversely with increased body fat, inflammatory markers and increased serum lipids in young, healthy adults - The LBA study.

BACKGROUND: Handgrip strength (HGS) is a surrogate marker of whole body strength that has been observed to correlate inversely with the metabolic syndrome (MetS). In this study, we examined whether HGS in young, healthy individuals, was associated with surrogate endpoints of the MetS. A secondary goal was to examine whether absolute HGS (absHGS) or relative HGS (relHGS) was a stronger predictor of MetS. METHOD: 834 subjects (577 women), aged 18-26, were recruited. Surrogate endpoints for MetS were waist circumference, HDL, fasting glucose, fasting insulin, triglycerides, and systolic and diastolic blood pressure (BP). We also examined the association between HGS and body fat percentage, HOMA-IR, CRP, orosomucoid and apolipoprotein A-1 and apolipoprotein B. The associations were examined using multivariable linear regression. RESULTS: AbsHGS and relHGS were each associated with several surrogate endpoints of the metabolic syndrome, with RelHGS being statistically significantly associated with a greater number of the variables - all except fasting glucose and diastolic BP. CONCLUSION: RelHGS correlates with components of the MetS even in young, healthy populations. It is a better predictor of MetS components than absHGS. As a cheap and easy to use biomarker, relHGS holds merit as a screening tool for metabolic dysfunction even in preclinical contexts.

High levels of hemolysis do not affect measurement of PAPP-A, ß-HCG and TRAb on BRAHMS KRYPTOR compact plus.

To assess the impact of high levels of hemolysis on the laboratory results for free ß-hCG, PAPP-A, and TRAb performed on the B·R·A·H·M·S KRYPTOR Compact PLUS. Adapted from the CLSI guidelines EP07-A2, paired difference testing was performed on serum samples from the routine laboratory workflow. Three sample pools for each assessed analyte was prepared and subjected to increased levels of added hemolysate. For ß-hCG and PAPP-A, the relative difference in the measured analyte concentration between the sample with 0 g/L added Hb and the samples with increasing free Hb concentrations (up to 6 g/L), was well below the pre-set acceptance criterion of 10% at all levels. The TRAb results showed greater variation than the other analytes, likely a consequence of imprecision rather than hemolysis. Hemolysis has a negligible effect on the analysis results of free beta-hCG, PAPP-A and TRAb measured on the B·R·A·H·M·S KRYPTOR Compact PLUS.

Handgrip strength reference intervals in Swedish, young, healthy adults: The LBA study.

OBJECTIVES: Handgrip strength (HGS) is a surrogate marker of general risk and nutritional status, frequently used in clinical practice. This study aimed to determine clinically useful reference intervals for healthy, young adults from Northern Europe. METHODS: This cross-sectional study was conducted in central Sweden, recruiting 834 young, nonsmoking adults ages 18 to 26 y. Subjects responded to a questionnaire on general health status, medication (including contraceptives), exercise habits, and parental and their own country of birth. Anthropometry, bioimpedance analysis for determination of fat-free mass (FFM), and HGS was measured. Reference intervals were calculated as mean and standard deviation. Differences between men, women, and women using estrogen contraceptives were analyzed using an analysis of variance with Tukey's post hoc test. Associations between HGS and determinant variables were analyzed using Spearman and linear regressions. RESULTS: Men and women differed in HGS, but no significant difference was found in average HGS based on contraceptive use in women. Mean HGS was 53 kg in men and 34 kg in women, with a range of 22 kg to 90 kg in men and 16 kg to 73 kg in women. Height correlated with HGS. Subjects with a body mass index (BMI) <20 had statistically significantly lower HGS than those in higher BMI groups. There was no statistically significant mean difference between the group of subjects with a BMI of 20 to 25 and those with BMI >25 in neither men nor women. HGS in both sexes showed a gradual increase through tertiles of FFM. In linear regression models, sex, height, and FFM were the main determinants of HGS. CONCLUSIONS: In this study, we established reference intervals for HGS in healthy Swedish adults ages 18 to 26 y. As a surrogate marker of whole-body muscle mass, these reference intervals can be used in health assessments and the planning of health-promoting measures in the individual young adults. Differences in HGS based on height warrant height-specific reference intervals that should be established locally.

Reference interval for type III procollagen (PIIINP) using the Advia centaur PIIINP assay in adults and elderly.

OBJECTIVE: The amino-terminal peptide of type III procollagen (PIIINP) is a byproduct of type III collagen synthesis that exhibits promise as a biomarker of fibrosis, specifically in monitoring hepatic fibrosis in methotrexate treated patients. The Advia Centaur® PIIINP assay is developed for track-based automated laboratory systems and is suitable for large volume analysis. Reference intervals in children and younger adults have been published previously. Here we measured PIIINP to determine reference ranges, specifically including elderly patients, for whom such are currently lacking. METHODS: Samples were collected from subjects ranging from 20 to 98 years of age. Blood donors and clinical samples from primary care patients were used for reference interval calculation. Samples were analysed using the Advia Centaur® PIIINP assay. After exclusion of samples high in alanine transaminase (AST), aspartate transaminase (ALT), and C-reactive protein (CRP) 386 samples were used in the reference interval calculation. RESULTS AND CONCLUSION: We determined the following reference interval for the Advia Centaur® PIIINP assay: the lower limit of the reference interval (2.5% percentile with 95% CI) was 4.42 (4.20-4.65) µg/L and the upper limit of the reference interval (97.5% percentile 95% CI) 16.0 (15.04-17.02) µg/L.No significant differences in mean PIIINP concentrations were found between men and women. While differing mean PIIINP concentrations were seen among subjects in different age groups, the differences were small and partitioning of reference range was determined not to be necessary.

IGFBP-1 and IGFBP-2 are associated with a decreased pulse-wave velocity in young, healthy adults.

BACKGROUND AND AIMS: In healthy, young adults we analyzed a panel of cardiovascular disease related proteins in plasma and compared them with the vascular health of the subjects. The aim was to identify proteins with a relationship to the early atherosclerotic process in healthy individuals. METHODS: We employed the proximity extension assay from OLINK proteomics to analyze 92 cardiovascular disease (CVD) related proteins on 833 subjects (men and women, ages 18-26). The women were further divided into an estrogen-using group and non-users. Protein expression was analyzed using principal component analysis (PCA). The following vascular examinations were performed: Pulse-wave velocity (PWV), augmentation index (AIX), carotid-intima media thickness (cIMT). RESULTS: Three principal components were obtained using PCA to analyze the protein expression. None of the obtained principal components correlated significantly with AIX or cIMT. One of the components, explaining 6% of the total variance of the data, was significantly correlated with PWV. Upon examination of the proteins with the highest factor loadings on this component independently in a multivariable model, adjusting for established CVD risk biomarkers, insulin-like growth factor-binding protein 1 (IGFBP-1) and insulin-like growth factor-binding protein 2 (IGFBP-2) were found to independently, negatively correlate with PWV. Among the established risk factors included in the multivariable model, age was significantly and adversely correlated with all vascular measurements. CONCLUSIONS: In this population of healthy, young adults, groups of CVD related proteins correlate with PWV, but not AIX or cIMT. This group of proteins, of which IGFBP-1 and IGFBP-2 were independently, negatively correlated in a multivariable model with PWV, could have benificial effects on vascular stiffness. The robust association between age and PWV, AIX and cIMT provide insight into the impact of aging on the vasculature, which is detectable even in a population of young, healthy, non-smoking individuals of ages spanning only 8 years.

Pulse wave velocity, augmentation index, and carotid intima-media thickness are each associated with different inflammatory protein signatures in young healthy adults: The lifestyle, biomarkers and atherosclerosis study.

BACKGROUND AND AIMS: We aimed to identify plasma protein biomarkers related to inflammation that correlated with physiological measurements of vascular function and structure in healthy individuals. METHODS: We used the OLINK proteomics panel, which measures 92 inflammatory proteins, in 834 young, healthy non-smokers (ages 18-26). Principal component analysis (PCA) was employed to identify patterns of proteins. The following measurements were used: pulse-wave velocity (PWV), carotid intima-media thickness (cIMT) and augmentation index (AIX). Established cardiovascular risk factors were included in multivariable models. RESULTS: PCA showed four principal components (PC 1, PC 2, PC 3, PC 4). PC 3, comprising proteins related to hemostasis, was significantly and inversely correlated with PWV. Among the proteins with the highest factor loadings on PC 3, uPA was negatively correlated with PWV in multivariable regression models. AIX was significantly correlated with PC 2, comprising inflammatory cytokines. Among the proteins with the highest factor loadings on PC 2, interleukin-6 was significantly correlated with AIX in the multivariable model. cIMT was significantly correlated with PC 4, comprising proteins related to chemotaxis. Among the proteins with the highest factor loadings on PC 4, fractalkine was significantly correlated with cIMT in the multivariable model. CONCLUSIONS: In young, healthy individuals, OLINK inflammatory proteins correlated with measures of vascular status. Each of the three measures PWV, AIX, and cIMT, which target different parts of the vasculature, correlated with its own specific protein signature, indicating that different subsets of inflammatory mediators affect different parts of the vasculature and are detectable already in young healthy adults.

Body fat percentage and CRP correlates with a composite score of vascular risk markers in healthy, young adults - The Lifestyle, Biomarkers, and Atherosclerosis (LBA) study.

BACKGROUND: Identification of early signs of atherosclerosis in young adults have the potential to guide early interventions to prevent later cardiovascular disease. We therefore analyzed measures of vascular structure and function and biomarkers of cardiovascular risk in a sample of young healthy adults. METHODS: Pulse-wave velocity (PWV), carotid-intima media thickness (cIMT) and augmentation index (AIX) were measured in 834 healthy non-smokers (ages 18.0-25.9). Emphasis was put on discriminating between individuals having a vascular structure and function associated with a higher or lower risk, and cluster analysis algorithms were employed to assign the subjects into groups based on these vascular measurements. In addition, a vascular status score (VSS) was calculated by summarizing the results according to quintiles of the vascular measurements. The associations between VSS and cardiovascular biomarkers were examined by regression analyses. RESULTS: The cluster analyses did not yield sufficiently distinct clustering (groups of individuals that could be categorized unequivocally as having either a vascular structure and function associated with a higher or lower CVD risk). VSS proved a better classificatory variable. The associations between VSS and biomarkers of cardiovascular risk were analyzed by univariable and multivariable regressions. Only body fat percentage and C-reactive protein (CRP) were independently associated with VSS. CONCLUSIONS: A VSS calculation, which integrates PWV, cIMT, and AIX measurements is better suited for cardiovascular risk evaluation in young adults than cluster analyses. The independent associations of VSS with body fat percentage and CRP highlight the decisive role of adiposity and systemic inflammation in early atherosclerotic progression and suggests a subordinate role of insulin and lipid metabolism in this age span.

Body fat percentage is more strongly associated with biomarkers of low-grade inflammation than traditional cardiometabolic risk factors in healthy young adults - the Lifestyle, Biomarkers, and Atherosclerosis study.

The primary aim was to appraise the relationship between body fat percentage and the inflammatory markers C-reactive protein (CRP) and orosomucoid in a population of young, non-smoking, healthy, Swedish adults, without any chronic diseases. A secondary aim was to compare whether these associations differed between the women using estrogen contraceptives and those who did not. We assessed the association in linear regression models between body fat percentage based on a bio-impedance measurement and plasma concentrations of CRP and orosomucoid in men and women aged 18-26 years, n = 834. Statistically significant associations were found between body fat percentage and both biomarkers of inflammation, with ß coefficients of 0.30 (95% CI 0.24-0.37) and 0.28 (0.22-0.35) for CRP and orosomucoid, respectively (p < .001). Adjustment for established risk factors marginally lowered the effects sizes (partial betas, 0.28 and 0.20, respectively), while the strong statistically significant associations remained. In the female cohort, estrogen and non-estrogen using subpopulations did not significantly differ in the correlations between body fat percentage and the inflammatory biomarkers, even adjusted for established cardiometabolic risk factors. In conclusion, in healthy young adults, higher levels of body fat percentage are associated with elevations in plasma biomarkers of inflammation, suggesting that a systemic inflammatory process, promoting atherosclerosis, may commence already at this early stage in life. CRP and orosomucoid plasma concentrations differed between users and non-users of estrogen contraceptives, but both subgroups showed similar correlations between increasing body fat percentage and increasing plasma concentrations of the biomarkers of inflammation.