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Liver fibrosis screening is recommended in high-risk populations, but the optimal definition of "high risk" remains to be established. We compared the performance of several risk-stratification strategies in a population-based setting.Data were obtained from the Finnish population-based health examination surveys Health 2000 and FINRISK 2002-2012. The Chronic Liver Disease Risk Score (CLivD) was compared to previously published risk-stratification strategies based on elevated liver enzymes, alcohol use, diabetes, fatty liver index, body mass index, and/or metabolic risk factors for their ability to detect either advanced liver fibrosis or incident severe liver events. Advanced fibrosis was defined as an Enhanced Liver Fibrosis (ELFDepending on the cohort, 53%-60% of the population was considered at risk using the CLivD strategy (low-intermediate-high risk, excluding the minimal-risk category), compared to 30%-32% according to the other risk-stratification strategies. The CLivD captured 85%-91% of cases in the population with advanced liver fibrosis and 90% of incident severe liver events within 10 years from baseline. This compares to 33%-44% and 56%-67% captured by the other risk-stratification strategies, respectively. The 10-year cumulative incidence of liver events varied by risk-stratification strategy (1.0%-1.4%).Compared to previously reported traditional risk factor-based strategies, use of the CLivD captured substantially more cases with advanced liver disease in the population and may be superior for targeting further fibrosis screening.

High sodium concentration alters leukocyte activation, and in particular T-helper (Th) lymphocyte polarization, and drives the development of autoimmune diseases in mouse studies. Similar results have been obtained with human leukocytes under in vitro settings and in few observational studies. Therefore, salt has been implicated as a risk factor for autoimmune diseases. Here, we examined whether physiologically relevant changes in salt intake or diet alter cytokine concentrations. In a 20-wk double-blinded, placebo-controlled study 106 participants were randomized to Habitual and Healthy Nordic diets, and further to Usual Sodium and Reduced Sodium intake groups using a cross-over setup. Plasma concentrations of 45 cytokines were measured at three different time-points using a multiplex assay. Repeated analyses of covariance revealed that high salt ingestion (or changes in the diet) did not induce significant changes in any of the signature cytokines controlling Th1, Th2 or Th17 polarization. Several other pro-inflammatory interleukins, chemokines and growth factors were also unaffected by the level of salt intake or changes in the diet. We conclude that in humans clinically relevant changes in salt intake or diet do not have reflections on the systemic concentrations of pro-inflammatory cytokines in vivo.

Publisher Copyright: © 2022 The Author(s) Background: Use of hormonal intrauterine devices has grown during the last decades. Although hormonal intrauterine devices act mostly via local effects on the uterus, measurable concentrations of levonorgestrel are absorbed into the systemic circulation. The possible metabolic changes and large-scale biomarker profiles associated with hormonal intrauterine devices have not yet been studied in detail. Objective: To examine through the metabolomics approach the metabolic profile of patients using hormonal intrauterine devices and how this metabolic profile is affected by duration and discontinuation of use. Study Design: The study consisted of cross-sectional analyses of 5 population-based surveys (FINRISK and FinHealth studies), spanning from 1997 to 2017. All fertile-aged participants (18–49 years) in the surveys with available information on hormonal contraceptive use and metabolomics data (n=5649) were included in the study. Altogether, 211 metabolic measures of users of hormonal intrauterine devices (n=1006) were compared with those of nonusers of hormonal contraception (n=4643) via multivariable linear regression models. To allow comparison across multiple measures, association magnitudes were reported in standard deviation units of difference in biomarker concentration compared with the reference group. Results: After adjustment for covariates, levels of 141 metabolites differed in current users of hormonal intrauterine devices compared with nonusers of hormonal contraception (median difference in biomarker concentration, 0.09 standard deviation): lower levels of particle concentration of larger lipoprotein subclasses, triglycerides, cholesterol and derivatives, apolipoproteins A and B, fatty acids, glycoprotein acetyls, and aromatic amino acids. The metabolic pattern of hormonal intrauterine device use did not change according to duration of use. When comparing previous users and never-users of hormonal intrauterine devices, no significant metabolic differences were observed. Conclusion: The use of hormonal intrauterine devices was associated with several moderate metabolic changes previously associated with reduced arterial cardiometabolic risk. The metabolic effects were independent of duration of use of the hormonal intrauterine devices. Moreover, the metabolic profiles were similar after discontinuation of hormonal intrauterine device use and in never-users.

Background The optimal screening strategy for dysglycaemia, including type 2 diabetes (T2DM) and impaired glucose tolerance (IGT), in patients with coronary artery disease (CAD) is debated. Purpose We tested the hypothesis that measures of insulin resistance by homeostasis model assessment (HOMA) indexes may constitute accurate screening methods in a CAD population. Methods Insulin, C-peptide, glycated haemoglobin A1c (HbA1c) and an oral glucose tolerance test (OGTT) were centrally assessed in 3534 CAD patients without known dysglycaemia from the EUROASPIRE V survey. Three different HOMA indexes were calculated: HOMA-IR, HOMA2 based on insulin (HOMA2-ins), and HOMA2 based on C-peptide (HOMA2-Cpep). Dysglycaemia was diagnosed based on the two-hour postload glucose (2hPG) value obtained from the OGTT. Information on study participants was obtained by standardised visits. The optimal thresholds of the three HOMA indexes for dysglycaemia diagnosis were obtained by the maximum value of Youden's J statistic on receiver operator characteristics curves. The diagnostic performance of such thresholds was tested for both T2DM (i.e. in reference to a 2hPG value ≥11 mmol/L) and dysglycaemia (i.e. in reference to 2hPG value ≥7.8 mmol/L) and their correlation with several clinical parameters was assessed by Spearman's coefficients. Results The mean age of the patients was 63 years and 25% were women. Fifty-four percent of the patients had central obesity, 18% were current smokers, mean blood pressure was 133/80 mmHg and mean LDL-cholesterol 2.4 mmol/L. The OGTT revealed that 41% were dysglycaemic (IGT = 24% and T2DM = 16%). Mean insulin, C-peptide and HOMA indexes were significantly higher in patients with vs. without newly detected dysglycaemia (all p Conclusion Screening for dysglycaemia in CAD patients by insulin, C-peptide, HOMA-IR, HOMA2-ins and HOMA2-Cpep had insufficient diagnostic performance to detect dysglycaemia with reference to the yield of an OGTT, which should still be prioritized. Further studies are warranted to assess whether measures of insulin resistance might be better markers of unfavourable metabolic derangement beyond dysglycaemia. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): European Society of CardiologyErling-Perssons Stiftelse

Objective Iodine is an essential part of the thyroid hormones thyroxine and triiodothyronine. Therefore, it is essential to monitor iodine supply in a population. The biochemical marker for assessing and controlling iodine is urinary iodine concentration (UIC). Materials and Methods This cross-sectional study included 180 pregnant women and 308 women of reproductive age. Urine specimens from 185 of the 488 volunteers were used. The urine specimens were measured using 2 methods: (1) ammonium persulfate digestion (APD), followed by the Sandell-Kolthoff (S-K) reaction modified on microplate for spectrophotometric detection; and (2) the reference method, inductively coupled plasma mass spectrometry (ICP-MS). Results The regression equation between the methods was ICP-MS method = 1.137*(APD S-K)-5.57. A Passing-Bablok regression showed no deviation from linearity (P = .17). A Bland-Altman plot showed a negative mean bias of –2.7%. Conclusion The APD S-K reaction modified on microplate for spectrophotometric detection of UIC can be implemented into routine work. Its results are comparable to those of laboratories worldwide and to ICP-MS.

Background Maternal diabetes is a well-known risk factor for pregnancy complications. Possible links between long-term maternal blood sugar in the normal range and pregnancy complications are less well described. Methods We assayed glycated haemoglobin (HbA1c) in blood samples collected around the 18th week of pregnancy for 2937 singleton pregnancies in the Norwegian Mother, Father and Child Cohort Study (2000–09). Perinatal outcomes (gestational length, birthweight, birth length and head circumference, large-for-gestational age, small-for-gestational age, congenital malformations, preterm delivery and preeclampsia) were obtained from medical records. We tested associations using linear and log-binomial regression, adjusting for maternal age, body mass index (BMI) and smoking. Results Size at birth increased modestly but linearly with HbA1c. Birthweight rose 0.10 standard deviations [95% confidence interval (CI): 0.03, 0.16], for each 5-mmol/mol unit increase in HbA1c, corresponding to about 40 g at 40 weeks of gestation. Large-for-gestational age rose 23% (95% CI: 1%, 50%) per five-unit increase. Other pregnancy complications increased in non-linear fashion, with strongest associations within the top quartile of HbA1c (>35 mmol/mol or >5.4%). Per unit HbA1c within the top quartile, preterm delivery increased by 14% (95% CI: 1%, 31%), preeclampsia increased by 20% (95% CI: 5%, 37%) and gestational duration decreased by 0.7 days (95% CI: −1.0, −0.3). Conclusions Among women with no recorded diabetes, higher HbA1c levels at 18 gestational weeks were associated with important perinatal outcomes independent of mother’s age, smoking or BMI.

Background & Aims Non-alcoholic fatty liver disease (NAFLD) increases morbidity and mortality. However, patients in biopsy-based cohorts are highly selected and the absolute risks of liver- and non-liver outcomes in NAFLD in population remains undefined. We analysed both liver-related and non-liver-related outcomes in Finnish population cohorts of NAFLD. Methods We included 10 993 individuals (6707 men, mean age 53.3 +/- 12.6 years) with NAFLD (fatty liver index >= 60) from the Finnish population-based FINRISK and Health 2000 studies. Liver fibrosis was assessed by the dAAR score, and genetic risk by a recent polygenic risk score (PRS-5). Incident liver-related outcomes, cardiovascular disease (CVD), cancer and chronic kidney disease (CKD) were identified through linkage with national registries. Results Mean follow-up was 12.1 years (1128 069 person-years). The crude incidence rate of liver-related outcomes in NAFLD was 0.97/1000 person-years. The cumulative incidence increased with age, being respectively 2.4% and 1.5% at 20 years in men and women aged 60 years at baseline, while the relative risks for CVD and cancer were 9-16 times higher. The risk of CKD exceeded that of liver outcomes at a baseline age around 50 years. 20-year cumulative incidence of liver-related outcomes was 4.3% in the high, and 1.5% in the low PRS-5 group. The dAAR score associated with liver outcomes, but not with extra-hepatic outcomes. Conclusion The absolute risk of liver-related outcomes in NAFLD is low, with much higher risk of CVD and cancer, emphasizing the need for more individualized and holistic risk-stratification in NAFLD.