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Background: The estimated glomerular filtration rate (eGFR), derived from serum creatinine (eGFRcr) or cystatin C (eGFRcys), is crucial for assessing kidney function and predicting health outcomes. While eGFRcr is known to be influenced by muscle mass and diet, eGFRcys is considered unaffected. This study aimed to identify lifestyle and anthropometric determinants of eGFRcys and eGFRcr in young, healthy men, and to explore the differential impact of these factors on the eGFR estimations.

Method: Cross-sectional study on 18 to 25.9-year-old healthy males. Participants completed questionnaires on diet and exercise, and underwent measurements of body composition and creatinine, cystatin C, and other serum analyses. eGFRcys was calculated using the CAPA equation, and eGFRcr using the LM-revised (LMR18) equation. Univariate and multivariate linear regressions were used to analyze associations between lifestyle or anthropometric variables and the eGFR's.

Results: No participants had an eGFR <60 ml/min/1.73 m2. We found novel positive correlations between eGFRcys and adherence to healthy eating guidelines according to a Healthy food habits score, and with serum B12, but a negative correlation with plasma homocysteine, in both univariate and multivariate analyses. In contrast, eGFRcr correlated negatively with fat-free mass, B12, and homocysteine in multivariate analysis, and with handgrip strength and hours of exercise in univariate analysis: it did not correlate with the Healthy food habits score.

Conclusions: Our findings highlight the differential impact of lifestyle and anthropometric factors on eGFRcys versus eGFRcr in young, healthy men. eGFRcys showed a significant association only with long-term dietary habits (Healthy food habits score and inversely with homocysteine), suggesting that eGFRcys may be more sensitive to lifestyle-related determinants of kidney function, whereas eGFRcr is more strongly influenced by non-renal factors such as muscle mass. Healthy food intake may positively affect kidney function in young healthy male subjects.

Chromosomal instability (CIN), impaired telomere biology, and aberrant DNA methylation are implicated in colorectal cancer (CRC) development. Tracking these alterations from precancerous lesions through tumors to metastases may reveal biomarkers of CRC initiation and progression. Tissue samples from 44 patients with either high-grade colorectal dysplasia (HGA; n = 13) or advanced metastatic CRC (n = 31) were analyzed. CIN was assessed in all patients using either low-coverage whole-exome sequencing or microarray-based comparative genomic hybridization. In a subset of patients, genome-wide CpG methylation profiling (n = 19) and telomere length measurements (n = 15) were performed. CIN was detected in 85% of HGA patients, spanning focal CNVs in MALAT1 (46%) to recurrent alterations on chromosomes 11, 13, and 20, with PTK6 being the most frequently amplified (61%). CIN was comparable between primary tumors and synchronous metastases but was significantly elevated in metachronous cases. DEK was amplified in all metastases but the aberration was absent in primaries, irrespective of tissue chronicity. Methylation profiling distinguished HGA from adjacent non-dysplastic mucosa (9859 differentially methylated CpGs) and unrelated tumor tissues (17 638 CpGs), whereas primary tumors and metastases differed at only five CpG sites. Both primary tumors and metastases appeared epigenetically younger than colonic mucosa. Metastases exhibited significantly shorter telomeres than both primary tumors (P = .019) and colonic mucosa (P = .001). The amplification of PTK6 may serve as an early biomarker detectable at the HGA stage, while DEK amplification appears crucial for metastatic progression and may represent a therapeutic target. Further validation is needed.

Purpose: Previous studies on the impact on arterial health of contraceptive use, or across the menstrual phases, have yielded differing results. Furthermore, there is little research on the differences based on the delivery method of the contraceptive, oral vs parenteral contraceptives. In this study, we examined arterial health using three different physiological measures of arterial function and structure in contraceptive users and non-users.

Methods: Young, healthy women, between 18.0–25.9 years of age were enrolled in the study (n = 577). Menstrual phase and contraceptive use and type were assessed by questionnaire. Arterial stiffness was measured using pulse-wave velocity (PWV) and augmentation index (AIx). Arterial thickness was measured using carotid-intima media thickness (cIMT). Blood samples were analysed for various biomarkers, which were used in multivariate regressions to adjust for the effects of contraceptive use on vascular status.

Results: Contraceptive users had a higher PWV than non-users. The menstrual phase did not impact PWV. In a smaller subgroup analysis, comparing the types of contraceptives, oral or parenteral, did not impact PWV. AIx and cIMT did not differ significantly between any studied groups. Systolic blood pressure, BMI, serum lipids, C-reactive protein, and sex hormone binding globulin concentrations were higher in the contraceptive using group, but in multivariable models, these biomarkers had only limited impact on the association between contraceptive use and PWV.

Conclusion: In a population of young, healthy women, contraceptive users displayed higher PWV values. The effect could not be explained by the effect of contraceptives on androgenicity, blood pressure or lipids.

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.

Objectives: Cystathionine-gamma-lyase (CSE) in the transsulfuration pathway generates hydrogen sulfide (H2S), suggested regulating cardiovascular function. The G1208T polymorphism in the CTH gene, rs1021737, has, in addition to MTHFR, been found to increase homocysteine, related to myocardial infarction (MI) risk. This study aimed, for the first time, to investigate the associations of the polymorphisms CTH G1208T, MTHFR C677T, and A1298C with the prospective risk of developing a fatal or non-fatal first MI.

Methods: This case-referent study included 545 cases later developing a first-ever MI and 1,054 referents from the Northern Sweden Health and Disease Study. Fatal MI was defined as death within 28 days after MI symptoms.

Results: Women, but not men, had a positive association between fatal MI and the CTH G1208T, odds ratio [95% confidence interval] 3.14 [1.16-8.54] for heterozygotes, and the dominant model 3.22 [1.22-8.51], and for the MTHFR A1298C heterozygotes 3.24 [1.26-8.34] and the dominant model 2.63 [1.06-6.50]. The MTHFR C677T polymorphism was not related to MI.

Conclusions: This study indicates that the minor alleles of CTH G1208T and MTHFR A1298C polymorphisms are associated with a higher risk for a fatal MI among women but not for non-fatal MI. No association was found in men.

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.

Higher milk intake has been associated with a lower stroke risk, but not with risk of coronary heart disease (CHD). Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29,328 participants (4,611 stroke; 9,828 CHD) of the EPIC-CVD (8 European countries) and EPIC-NL case-cohort studies. rs4988235, a lactase persistence (LP) single nucleotide polymorphism which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777,024 participants (50,804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483,966 participants (61,612 cases) from CARDIoGRAM, UK Biobank and EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (β=13.7 g/day; 95%CI: 8.4-19.1) and EPIC-NL (36.8 g/day; 20.0-53.5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/day 1.05; 95%CI: 0.94-1.16) or CHD (1.02; 0.96-1.08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (odds ratios 1.02; 0.99-1.05) or CHD (0.99; 0.95-1.03). Current Mendelian Randomization analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.

Objectives: In a previous pilot study, we found an association between high factorXII levels and risk of haemorrhagic stroke suggesting that factor XII is a risk markerfor intracerebral haemorrhage (ICH). The aim of this study was to further investigate the association between factor XII and risk of ICH in a larger population.

Materials and Methods:This study was conducted as a prospective nested case-referent study. All participants underwent a health examination and blood sampling for factor XII analysis at baseline. Cases were defined as participants who were diagnosed with a first-ever ICH between 1985 and 2000. Two referents were matched to eachcase.

Results:We identified 70 individuals withfirst-ever ICH and 137 matchedreferents who had undergone a health examination and donated blood samples Factor XII Concentrations and Risk of Intracerebral Haemorrhage. A Prospective Case-Referent Studybefore the ICH event. The mean age was 54 years, and 33% were women. The median time-to-event was 3.5 years (range 0.04 to 10.2 years). Conditional logistic regression showed no association between factor XII and risk of ICH, (odds ratio1.06 per SD; [95% confidence interval: 0.57–1.97] in a multivariable model).

Conclusions: A previous finding of an association between high concentration of factor XII and risk of ICH could not be replicated in this larger study

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.