| 1. |
- Karefylakis, Christos, 1982-, et al.
(author)
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Vitamin D C3 epimer in a mid-Swedish region : Analytical measurement and epidemiology
- 2018
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In: Clinica Chimica Acta. - Amsterdam, Netherlands : Elsevier. - 0009-8981 .- 1873-3492. ; 478, s. 182-187
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Journal article (peer-reviewed)abstract
- Background: The discovery of an epimeric form of 25(OH)D3 may complicate the interpretation of vitamin Dstatus. The aim of this study was to examine the prevalence and determinants of 25-hydroxy-3-epi-vitamin D3 (3- epi-25(OH)D3) in a mid-Swedish region and to investigate how the measurement of 3-epi-25(OH)D3 would affect the assessment of vitamin D status using current thresholds.Methods: We conducted a cross-sectional study of 8286 in- and outpatients in primary as well as secondary care settings. Plasma 25(OH)D, 25(OH)D2, 25(OH)D3 and 3-epi-25(OH)D3 were measured using High Pressure Liquid Chromatography – Tandem Mass Spectrometry (HPLC – MS/MS). The relative 3-epi-25(OH)D3 contribution was calculated as a percentage of the total 25(OH)D3. Blood samples were collected between March 2014 and July 2015 providing a seasonal aspect to the results.Results: 3-epi-25(OH)D3was detected in 635 cases (7.7% of all subjects), and the mean concentration was8.4 ± 3.5 nmol/L. 3-epi-25(OH)D3correlated significantly with 25(OH)D3(r =0.38, p < 0.001).A multivariateanalysis among the detected showed that male gender and winter season were independently associatedwith higher 3-epi-25(OH)D3/25(OH)D3percentage ratio (R2=0.044). Infants and children had a significantlyhigher detection rate compared to the reference age category (18–45 years) as well as those who were testedduring the summer season.Conclusions: We report findings from the first epidemiologic study of 3-epi-25(OH)D3 conducted in Sweden, based on a large population sample. 3-epi-25(OH)D3 was detected in 7.7% of the study population and the mean concentration was 8.4 nmol/L. The quantification of 3-epi-25(OH)D3 would not significantly influence the clinical interpretation of vitamin D levels. Additional studies are needed to understand the metabolic pathway and the possible physiological functions of this metabolite.
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| 2. |
- Pettersson-Pablo, Paul, 1986-
(author)
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Biomarkers of vascular function and structure in young healthy adults
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Atherosclerosis is a disease affecting the blood vessels in the body. Its pathophysiologic mechanisms involve infiltration of the vessel walls by fatty matter and immune cells. This process is slow, starting in childhood but typically not manifesting as symptomatic disease until late adulthood (after 60 years of age). The identification of younger individuals with a high risk for early intervention has a higher potential of preventing morbidity and mortality.In this thesis, part of the Lifestyle, Biomarkers and Atherosclerosis study (LBA), the earliest stages of vascular dysfunction have been examined in a population of young, healthy, non-smoking subjects. Vascularfunction and structure measurements predict a future risk of cardiovascular disease (CVD). The measurements were analyzed in relation to clinical chemistry analyses of various biomarkers in serum and plasma that have been associated with inflammation or cardiovascular risk. A secondary aim was to examine estrogen containing contraceptive use and its relation to the CVD biomarkers.In Paper I and Paper II of the thesis, the association between inflammatory biomarkers, body fat percentage and vascular function and structure measurements was examined in multivariable linear regression models. A higher body fat percentage predicted an increased serum concentration of C-reactive protein (CRP) and orosomucoid. In Paper II, a higher body fat percentage and a higher CRP were associated with a more unfavorable vascular function and structure.In Paper III and Paper IV, we employed two multiplex proteomics panels to analyze inflammatory proteins and proteins previously implicated in CVD. In multivariable linear regression models, proteins implicated in hemostasis, inflammatory signaling and chemoattraction correlated with different vascular function and structure measurements. InPaper IV, insulin-like growth factor-binding protein 1 (IGFBP1) and IGFBP2 were independently predictive of an increased vascular stiffness.In conclusion, even in young, healthy individuals, altered concentrations of serum biomarkers can be detected in subjects with increased body fat and unfavorable vascular function and structure.
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| 3. |
- Pettersson-Pablo, Paul, 1986-, et al.
(author)
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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
- 2020
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In: BMC Cardiovascular Disorders. - : BioMed Central. - 1471-2261 .- 1471-2261. ; 20:1
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Journal article (peer-reviewed)abstract
- 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.
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| 4. |
- Pettersson-Pablo, Paul, 1986-, et al.
(author)
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Body fat percentage is more strongly associated with biomarkers of low-grade inflammation than traditional cardiometabolic risk factors in healthy young adults : he Lifestyle, Biomarkers, and Atherosclerosis study
- 2019
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In: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 79:3, s. 182-187
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Journal article (peer-reviewed)abstract
- 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 β 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.
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| 5. |
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| 6. |
- Pettersson-Pablo, Paul, 1986-, et al.
(author)
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Handgrip strength reference intervals in Swedish, young, healthy adults : The LBA study
- 2023
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In: Nutrition. - : Elsevier. - 0899-9007 .- 1873-1244. ; 105
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Journal article (peer-reviewed)abstract
- 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.
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| 7. |
- Pettersson-Pablo, Paul, 1986-, et al.
(author)
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High levels of hemolysis do not affect measurement of PAPP-A, β-HCG and TRAb on BRAHMS KRYPTOR compact plus
- 2023
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In: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 83:6, s. 367-370
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Journal article (peer-reviewed)abstract
- To assess the impact of high levels of hemolysis on the laboratory results for free β-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 β-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.
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| 8. |
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| 9. |
- Pettersson-Pablo, Paul, 1986-, et al.
(author)
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LC-MS/MS analysis of 11-nor-9-carboxy-hexahydrocannabinol (HHC-COOH) and 11-hydroxy-hexahydrocannabinol (HHC-OH) for verification of hexahydrocannabinol (HHC) intake
- 2024
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In: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 84:2, s. 109-114
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Journal article (peer-reviewed)abstract
- 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.
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| 10. |
- Pettersson-Pablo, Paul, 1986-, et al.
(author)
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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
- 2020
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In: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 313, s. 150-155
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Journal article (peer-reviewed)abstract
- 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.
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