Danish General Suburban Population Study Research Articles

Genome-Wide Association Study of Accessory Atrioventricular Pathways.

Understanding of the genetics of accessory atrioventricular pathways (APs) and affiliated arrhythmias is limited. To investigate the genetics of APs and affiliated arrhythmias. This was a genome-wide association study (GWAS) of APs, defined by International Classification of Diseases (ICD) codes and/or confirmed by electrophysiology (EP) study. Genome-wide significant AP variants were tested for association with AP-affiliated arrhythmias: paroxysmal supraventricular tachycardia (PSVT), atrial fibrillation (AF), ventricular tachycardia, and cardiac arrest. AP variants were also tested in data on other heart diseases and measures of cardiac physiology. Individuals with APs and control individuals from Iceland (deCODE Genetics), Denmark (Copenhagen Hospital Biobank, Danish Blood Donor Study, and SupraGen/the Danish General Suburban Population Study [GESUS]), the US (Intermountain Healthcare), and the United Kingdom (UK Biobank) were included. Time of phenotype data collection ranged from January 1983 to December 2022. Data were analyzed from August 2022 to January 2024. Sequence variants. Genome-wide significant association of sequence variants with APs. The GWAS included 2310 individuals with APs (median [IQR] age, 43 [28-57] years; 1252 [54.2%] male and 1058 [45.8%] female) and 1 206 977 control individuals (median [IQR] year of birth, 1955 [1945-1970]; 632 888 [52.4%] female and 574 089 [47.6%] male). Of the individuals with APs, 909 had been confirmed in EP study. Three common missense variants were associated with APs, in the genes CCDC141 (p.Arg935Trp: adjusted odds ratio [aOR], 1.37; 95% CI, 1.24-1.52, and p.Ala141Val: aOR, 1.55; 95% CI 1.34-1.80) and SCN10A (p.Ala1073Val: OR, 1.22; 95% CI, 1.15-1.30). The 3 variants associated with PSVT and the SCN10A variant associated with AF, supporting an effect on AP-affiliated arrhythmias. All 3 AP risk alleles were associated with higher heart rate and shorter PR interval, and have reported associations with chronotropic response. Associations were found between sequence variants and APs that were also associated with risk of PSVT, and thus likely atrioventricular reentrant tachycardia, but had allele-specific associations with AF and conduction disorders. Genetic variation in the modulation of heart rate, chronotropic response, and atrial or atrioventricular node conduction velocity may play a role in the risk of AP-affiliated arrhythmias. Further research into CCDC141 could provide insights for antiarrhythmic therapeutic targeting in the presence of an AP.

Impact of non-participation bias due to psychiatric illness on mortality and cardiovascular event estimates: a Danish longitudinal population study

ObjectivesThe impact of non-participation due to psychiatric illness on study outcomes in general population studies is insufficiently investigated. Here, we investigate the mental health bias in a population study and...

Neutrophil-to-lymphocyte ratio and all-cause mortality with and without myeloproliferative neoplasms—a Danish longitudinal study

The neutrophil-to-lymphocyte ratio(NLR) is increased in chronic inflammation and myeloproliferative neoplasms (MPN). We hypothesize that NLR is associated with all-cause mortality and mortality by comorbidity burden in the general population and individuals with MPN. We included 835,430 individuals from The Danish General Suburban Population Study, general practitioners, and outpatient clinics. We investigated NLR on mortality stratified by prevalent and incident MPN, essential thrombocythemia (ET), polycythemia vera (PV), myelofibrosis (MF), comorbidity burden (CCI-score), and the Triple-A risk score using hazard ratio (HR) and 95% confidence interval (95%CI). NLR 1–1.9 was the reference level. During a median follow-up of 11.2 years, 197,802 deaths were recorded. All-cause mortality increased for a stepwise increasing NLR with a HR (95%CI) for NLR ≥ 6 of 2.06(2.03–2.09) for the whole population and 2.93(2.44–3.50) in prevalent MPN. ET, PV, and MF had a HR (95%CI) for NLR ≥ 2 of 2.14(1.71–2.69), 2.19(1.89–2.54), and 2.31(1.91–2.80). Results were similar for incident MPN. Mortality was higher for stepwise increasing NLR and CCI-score(pinteraction < 2×10–16), with a HR for NLR ≥ 6 of 2.23(2.17–2.29), 4.10(4.01–4.20), and 7.69(7.50–7.89), for CCI-score 0, 1–2, or ≥3. The Triple-A risk score demonstrated alignment with NLR. Increasing NLR and comorbidity burden were associated with lower survival in individuals without MPN but were even worse in prevalent and incident MPN, ET, PV, and MF.

Correlation between allostatic load index and cumulative mortality: a register-based study of Danish municipalities

ObjectivesThe aim of this study was to examine population-based allostatic load (AL) indices as an indicator of community health across 14 municipalities in Denmark.DesignRegister-based study.SettingData derived from: the Lolland-Falster Health...

JAK2V617F mutation is highly prevalent in patients with ischemic stroke: a case-control study

AbstractIschemic stroke has a high recurrence rate despite treatment. This underlines the significance of investigating new possible cerebrovascular risk factors, such as the acquired gene mutation JAK2V617F found in 3.1% of the general population. We aimed to investigate the prevalence of the JAK2V617F mutation in a population with ischemic stroke compared with that in matched controls. We enrolled 538 consecutive Danish patients with ischemic stroke (mean age, 69.5 ± 10.9 years; 39.2% female) within 7 days of symptom onset. Using multiple-adjusted conditional logistic regression analysis, we compared the prevalence of JAK2V617F with that in age- and sex-matched controls free of ischemic cerebrovascular disease (ICVD) from the Danish General Suburban Population Study. DNA was analyzed for JAK2V617F mutation using sensitive droplet digital polymerase chain reaction in patients and controls. Of the 538 patients with ischemic stroke, 61 (11.3%) had JAK2V617F mutation. There were no differences in patient demographics or cerebrovascular comorbidities between the patients with and without mutations. Patients with ischemic stroke were more likely to have the JAK2V617F mutation than matched controls, in whom the JAK2V617F prevalence was 4.4% (odds ratio, 2.37; 95% confidence interval, 1.57-3.58; P < .001). A subanalysis stratified by smoking history revealed that the association was strongest in current smokers (odds ratio, 4.78; 95% confidence interval, 2.22-10.28; P < .001). Patients with ischemic stroke were 2.4 times more likely to have the JAK2V617F mutation than matched controls without ICVD when adjusting for other cerebrovascular risk factors. This finding supports JAK2V617F mutation as a novel cerebrovascular risk factor.

Long-term stability of thyroid peroxidase antibody (anti-TPO) in serum in the Danish General Suburban Population Study.

We evaluated the long-term stability of thyroid peroxidase antibody (anti-TPO). In the Danish General Suburban Population Study (GESUS), serum samples were biobanked at-80°C during 2010-2013. In a paired design with 70 subjects, we compared anti-TPO (30-198U/mL) measured on fresh serum on Kryptor Classic in 2010-2011 (anti-TPOfresh) with anti-TPO remeasured on frozen serum (anti-TPOfrozen) on Kryptor Compact Plus in 2022. Both instruments used the same reagents and the anti-TPOn automated immunofluorescent assay, which was calibrated against the international standard NIBSC 66/387, based on the Time Resolved Amplified Cryptate Emission (TRACE) technology from BRAHMS. Values greater than 60U/mL are regarded as positive in Denmark with this assay. Statistical comparisons included Bland-Altman, Passing-Bablok regression, and Kappa statistic. The mean follow-up time was 11.9 years (SD: 0.43). For anti-TPOfrozen vs. anti-TPOfresh, the line of equality waswithin the confidence interval of the absolute mean difference [5.71 (-0.32; 11.7)U/mL] and the average percentage deviation [+2.22% (-3.89%; +8.34%)]. The average percentage deviation of 2.22% did not exceed analytical variability. Passing-Bablok regression revealed both a statistically significant systematic and proportional difference: Anti-TPOfrozen=-22.6+1.22*(anti-TPOfresh). Frozen samples were correctly classified as positive in 64/70 (91.4%; Kappa=71.8%). Anti-TPO serum samples in the range 30-198U/mL were stable after 12-years of storage at-80°C with an estimated nonsignificant average percentage deviation of +2.22%. This comparison is based on Kryptor Classic and Kryptor Compact Plus, which used identical assays, reagents, and calibrator, but for which the agreement in the range 30-198U/mL is unclarified.

Risk of asthma in offspring of asthmatic fathers versus mothers: A population-based study of 21,000 individuals in Denmark

Parental asthma or allergy have been linked to higher risk of asthma in a child; this occurs to a variable extent in different study populations. Moreover, it is debated whether maternal more so than paternal asthma history is a stronger predisposing factor: while in some countries/populations the maternal effect was clearly seen over paternal, in others the parental effects were equivalent, and in a few studies paternal effect dominated. Here we aimed to determine parental asthma and allergy effect in the Danish GEneral SUburban population Study (GESUS).This cross-sectional study has involved 21,362 adults aged 20+ years in the suburbs of Copenhagen. We used a combination of questionnaire approach, history of prescribed asthma medications and pulmonary function testing to determine odds ratios for maternal and paternal (and combined) asthma and allergy linked to asthma in the test subjects. We found that the input of maternal vs. paternal asthma effect was approximately equal (age and sex-adjusted OR 2.46, 95% CI: 2.15–2.81 for asthmatic mothers vs. 2.97, 2.58–3.42 for asthmatic fathers), except for the “ever asthma” age and sex-adjusted odds ratios where paternal allergy seems to have conferred a marginally greater effect (age and sex-adj. OR 1.96 for maternal allergy vs. 2.44 for paternal allergy, p = 0.03). Stratifying for gestational tobacco smoking did not affect the maternal results.We conclude that in the GESUS study parental asthma or allergy were strongly linked to higher asthma risk in offspring, without a prominent maternal or paternal effect.

Association of Levothyroxine Treatment and Thyroid Peroxidase Antibodies with Antidepressant Use: A Danish Population-Based Longitudinal Study.

Background: Subjects receiving levothyroxine (LT4) treatment have increased prevalence of depression, anxiety, and antidepressant use, but whether the underlying mechanism relates to thyroid autoimmunity is still unclarified. Methods: This is a population-based longitudinal study. Baseline biochemical and questionnaire data from the Danish General Suburban Population Study (GESUS) in 2010-2013 were linked with individual-level longitudinal data in national health registries. The aim was to investigate the associations between thyroid peroxidase antibodies (TPOAbs) and LT4 treatment, separately and through interaction, and at least one redeemed prescription for antidepressants. Logistic and Cox regression were used to evaluate initiation of antidepressant use before and after the baseline examination in GESUS, respectively. All exposures and covariates were fixed at the date of baseline examination. Thyroid autoimmunity was defined as serum TPOAbs >60 U/mL. Adjustments included sex, age, education, income, Charlson comorbidity index, smoking, and alcohol. Sensitivity analyses were performed for missing variables, exclusion of lithium use, exclusion of thyroid surgery, and conservative definitions for LT4 treatment and antidepressant use requiring at least two prescriptions. Results: We included 12,894 individuals, of whom 2353 (18%) had "past or current" antidepressant use at baseline, leaving 10,541 individuals at risk for incident antidepressant use after baseline. The median follow-up was 7.8 years during which 783 individuals (7.4% of 10,541 individuals) had incident antidepressant use. TPOAb positivity was not associated with "past or current" (odds ratio [OR] 0.90 [confidence interval, CI 0.78-1.03], p = 0.13) nor incident antidepressant use (hazard ratio [HR] 1.02 [CI 0.83-1.25], p = 0.88). LT4 treatment was associated with increased "past or current" antidepressant use (OR 1.33 [CI 1.10-1.62], p = 0.004) and increased incident antidepressant use (HR 1.38 [CI 1.03-1.85], p = 0.03). There were no interactions between the effects of TPOAb positivity and LT4 treatment on the use of antidepressants in logistic (p = 0.87) or Cox regression models (p = 0.82). Sensitivity analyses were robust, except that incident use of at least two redeemed antidepressant prescriptions was not statistically significant. Conclusions: LT4 treatment, but not TPOAb positivity, was associated with increased prevalent or incident antidepressant use with at least one prescription. Our findings do not support that thyroid autoimmunity is an important factor for antidepressant use in patients receiving LT4 treatment.

Factors associated with medication adherence among adults with asthma

Objective Asthma medication adherence is of crucial importance for successful disease management. The aim of this study was to identify and rank factors associated with medication adherence among adults with asthma in the general population. Methods We used data on physician-diagnosed asthma, medication adherence, and factors associated with asthma medication adherence from the Danish General Suburban Population Study using a cross-sectional study design. We ranked factors associated with asthma medication adherence based on the magnitude of odds ratios, and the population attributable fractions. Results Among 20,032 individuals from the general population, 1,128 (6%) suffered from asthma and 822 (73%) of these were adherent to asthma medications. Based on odds ratios, the three top-ranked factors associated with asthma medication adherence were asthma attacks within the past year (4.0; 95% CI: 2.9–5.5), allergy medication use (3.8; 2.6–5.6), and age above median (3.4; 2.4–4.7), followed by asthma severity markers like airway obstruction, and coughing with mucus. Based on population attributable fractions, the three top-ranked factors associated with adherence to asthma medications were asthma attacks within the past year (70%), age above median (57%), and use of allergy medication (49%). Conclusions The study showed that in the general population recent asthma attacks, higher age, and taking allergy medication were the three most important factors associated with asthma medication adherence. The importance of maintaining adherence to asthma medications even in the absence of severe disease or expressed asthma symptoms should be better communicated to the general population.

Clonal haematopoiesis of indeterminate potential and impaired kidney function-A Danish general population study with 11 years follow-up.

The myeloproliferative neoplasms are associated with chronic kidney disease but whether clonal haematopoiesis of indeterminate potential (CHIP) is associated with impaired kidney function is unknown. In the Danish General Suburban Population Study (N=19 958) from 2010 to 2013, 645 individuals were positive for JAK2V617F (N=613) or CALR (N=32) mutations. Mutation-positive individuals without haematological malignancy were defined as having CHIP (N=629). We used multiple and inverse probability weighted (IPW)-adjusted linear regression analysis to estimate adjusted mean (95% confidence interval) differences in estimated glomerular filtration rate (eGFR; ml/min/1.73 m2 ) by mutation status, variant allele frequency (VAF%), blood cell counts, and neutrophil-to-lymphocyte ratio (NLR). We performed 11-year longitudinal follow-up of eGFR in all individuals. Compared to CHIP-negative individuals, the mean differences in eGFR were -5.6 (-10.3, -0.8, p=.02) for CALR, -11.9 (-21.4, -2.4, p=0.01) for CALR type 2, and -10.1 (-18.1, -2.2, p =.01) for CALR with VAF ≥ 1%. The IPW-adjusted linear regression analyses showed similar results. NLR was negatively associated with eGFR. Individuals with CALR type 2 had a worse 11-year longitudinal follow-up on eGFR compared to CHIP-negative individuals (p=.004). In conclusion, individuals with CALR mutations, especially CALR type 2, had impaired kidney function compared to CHIP-negative individuals as measured by a lower eGFR at baseline and during 11-year follow-up.

Elevated levels of oxidized nucleosides in individuals with the JAK2V617F mutation from a general population study

It is unknown if the somatic mutations in chronic myeloproliferative neoplasms (MPNs), JAK2V617F and Calreticulin, are associated with oxidative stress, or impaired mitochondrial defense against reactive oxygen species. In the Danish General Suburban Population Study (GESUS), including 116 JAK2V617F-mutated, 8 CALR-mutated, and 3310 mutation-negative participants without overt MPN, and in a study of 39 patients with myelofibrosis, the most advances type of MPNs, and 179 matched controls, we compared the urinary concentration of oxidized nucleosides – 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) – as markers of oxidative stress. In GESUS, we performed Mendelian randomization analyses, using the Ala16Val single nucleotide polymorphism in the superoxide dismutase2 (SOD2) gene. In the multivariate analyses in GESUS, the 8-oxodG and 8-oxoGuo concentration were 13% (95%CI: 6–21%, p < 0.001) and 6% (95%CI: 0.4–11%, p = 0.035) higher in mutation-positive than in mutation-negative participants, respectively. Each SOD2 T allele was associated with an odds ratio of being mutation-positive of 1.69 (95%CI: 1.12–2.55, p = 0.013) through 8-oxodG. The 8-oxodG and 8-oxoGuo concentrations were 77% (95%CI: 49–110%, p < 0.001) and 105% (95%CI: 80–133%, p < 0.001) higher in myelofibrosis patients than in controls, respectively. In conclusion, an impaired mitochondrial antioxidative defense, that is causatively associated with markers of oxidative stress, may contribute to the development of mutations associated with MPNs.

Smoking, blood cells and myeloproliferative neoplasms: meta-analysis and Mendelian randomization of 2·3 million people.

Meta-analyses and Mendelian randomization (MR) may clarify the associations of smoking, blood cells and myeloproliferative neoplasms (MPN). We investigated the association of smoking with blood cells in the Danish General Suburban Population Study (GESUS, n=11083), by meta-analyses (including GESUS) of 92 studies (n=531741) and MR of smoking variant CHRNA3 (rs1051730[A]) in UK Biobank, and with MPN in a meta-analysis of six studies (n (total/cases):1425529/2187), totalling 2307745 participants. In the meta-analysis the random-effects standardized mean difference (SMD) in current smokers versus non-smokers was 0·82 (0·75-0·89, P=2·0*10-108 ) for leukocytes, 0·09 (-0·02 to 0·21, P=0·12) for erythrocytes, 0·53 (0·42-0·64, P=8·0*10-22 ) for haematocrit, 0·42 (0·34-0·51, P=7·1*10-21 ) for haemoglobin, 0·19 (0·08-0·31, P=1·2*10-3 ) for mean corpuscular haemoglobin (MCH), 0·29 (0·19-0·39, P=1·6*10-8 ) for mean corpuscular volume (MCV), and 0·04 (-0·04 to 0·13, P=0·34) for platelets with trends for ever/ex-/current smokers, light/heavy smokers and female/male smokers. Analyses presented high heterogeneity but low publication bias. Per allele in CHRNA3, cigarettes per day in current smokers was associated with increased blood cell counts (leukocytes, neutrophils), MCH, red cell distribution width (RDW) and MCV. The pooled fixed-effects odds ratio for MPN was 1·44 [95% confidence interval(CI): 1·33-1·56; P=1·8*10-19 ; I2 =0%] in current smokers, 1·29 (1·15-1·44; P=8·0*10-6 ; I2 =0%) in ex-smokers, 1·49 (1·26-1·77; P=4·4*10-6 ; I2 =0%) in light smokers and 2·04 (1·74-2·39, P=2·3*10-18 ; I2 =51%) in heavy smokers compared with non-smokers. Smoking is observationally and genetically associated with increased leukocyte countsand red blood cell indices (MCH, MCV, RDW)and observationally with risk of MPN in current and ex-smokers versus non/never-smokers.

Prevalence and phenotypes of JAK2 V617F and calreticulin mutations in a Danish general population

AbstractThe JAK2 V617F and calreticulin mutations (CALR) are frequent within myeloproliferative neoplasms (MPNs). JAK2 V617F has been detected in the general population, but no studies have previously investigated the CALR prevalence. Thus, we aimed to determine the CALR and JAK2 V617F population prevalence and assess the biochemical profile and lifestyle factors in mutation-positive individuals with and without MPN. 19 958 eligible participants, enrolled from 2010-2013, from the Danish General Suburban Population Study were screened for JAK2 V617F and CALR by droplet digital polymerase chain reaction with (3.2%) mutation positives of which 16 (2.5%) had MPN at baseline. Of 645 participants, 613 were JAK2 V617F positive, and 32 were CALR positive, corresponding to a population prevalence of 3.1% (confidence interval [CI], 2.8-3.3) and 0.16% (CI, 0.11-0.23), respectively. Increasing age, smoking, and alcohol were risk factors for the mutations. JAK2 V617F positives with and without MPN presented elevated odds for prevalent venous thromboembolism. The odds ratio for a diagnosis of MPN per percentage allele burden was 1.14 (95% CI, 1.09-1.18; P = 1.6 × 10−10). Mutation positives displayed higher blood cell counts than nonmutated participants, and 42% of mutation positives without MPN presented elevation of ≥1 blood cell counts; 80 (13%) even presented blood cell counts in accordance with current MPN diagnostic criteria. In conclusion, we present a novel population prevalence of CALR and a JAK2 V617F prevalence that is 3 to 30 times higher compared with less sensitive methods. Mutation-positive non-MPNs with elevated blood cell counts raise concerns of MPN underdiagnosis in the population.

Increased Ferritin Concentration and Risk of Atrial Fibrillation and Heart Failure in Men and Women: Three Studies of the Danish General Population Including 35799 Individuals.

Moderately increased plasma ferritin, as a biomarker of iron overload, has been associated with higher rates of cardiovascular death and heart failure. However, the association of moderately increased plasma ferritin with risk of atrial fibrillation in the general population is unknown. We examined the association of plasma ferritin concentrations with risk of atrial fibrillation and heart failure in metaanalyses of 35799 men and women from 3 studies of the Danish general population: the Copenhagen City Heart Study, the Danish General Suburban Population Study, and the Copenhagen General Population Study. Multivariable adjusted fixed effects odds ratios for atrial fibrillation were 1.23 (95% CI, 1.05-1.44; P = 0.005) in men for ferritin concentration ≥300 μg/L vs <300 μg/L, 1.13 (95% CI, 0.93-1.38; P = 0.22) in women for ≥200 μg/L vs <200 μg/L, and 1.19 (95% CI, 1.06-1.35; P = 0.005) in both sexes combined (P sex interaction = 0.52). Corresponding fixed effects odds ratios for heart failure were 1.16 (95% CI, 0.98-1.37; P = 0.08) in men, 0.86 (95% CI, 0.67-1.10; P = 0.23) in women, and 1.05 (95% CI, 0.91-1.21; P = 0.45) in both sexes combined (P sex interaction = 0.05). Multivariable adjusted fixed effects odds ratio for atrial fibrillation per step increase in ferritin concentrations was 1.13 (95% CI, 1.06-1.21; P trend = 0.0005) in both sexes combined (P sex interaction = 0.59); the corresponding value for heart failure was 1.03 (95% CI, 0.95-1.11; P trend = 0.47) (P sex interaction = 0.08). In sensitivity analyses, there was no evidence of U-shaped relationships between plasma ferritin concentrations and risk of atrial fibrillation or heart failure in men or women. Increased ferritin concentration is associated with increased risk of atrial fibrillation in the general population.

Statin treatment, oxidative stress and inflammation in a Danish population

BackgroundWhile statins may have anti-inflammatory effects, anti-oxidative effects are controversial. We investigated if statin treatment is associated with differences in oxidatively generated nucleotide damage and chronic inflammation, and the relationship between nucleotide damage and chronic inflammation. MethodsWe included 19,795 participants from the Danish General Suburban Population Study. In 3420 participants, we measured urinary 8-oxodG and 8-oxoGuo by liquid chromatography-tandem mass spectrometry as markers of oxidatively generated damage to DNA and RNA, respectively. We used a composite score for chronic inflammation (INFLA score) of hsCRP, WBC, platelet count, and neutrophil granulocyte to lymphocyte ratio. Associations were assessed using multivariate linear regression models. ResultsCompared with non-users, statin users had 4.3–6.0% lower 8-oxodG in three separate models (p < 0.05); there were no differences in 8-oxoGuo. Among participants aged > 60 y, statin users had 11.4% lower 8-oxodG (95%CI: 6.7–15.9%, pinteraction<0.001) and 3.9% lower 8-oxoGuo (95%CI: 0.1–7.5%, pinteraction = 0.002), compared with non-users. Compared with non-users, statin users had 11.1% (95%CI: 5.4–16.5%, pinteraction<0.001) lower 8-oxodG in participants treated for hypertension, and 18.6% (95%CI: 6.8–28.9%, pinteraction<0.001) lower 8-oxodG in participants with decreased renal function. Compared with non-users, statin users had significantly lower INFLA score (p < 0.001). 8-oxodG and 8-oxoGuo associated positively with markers of chronic inflammation. ConclusionsOxidatively generated DNA damage and inflammatory burden are lower in statin users compared with non-users. Together, anti-oxidative and anti-inflammatory effects may contribute to the beneficial effects of statins.

The Association between Circulating Inflammatory Markers and Metabolic Syndrome: A General Population Study

INTRODUCTIONChronic inflammation has recently been proposed as the driving force for the development of the Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). Chronic inflammation is associated with various metabolic disturbances and may also contribute to the massive comorbidity burden in MPNs, which include e.g. inflammatory bowel diseases (Crohn's disease and ulcerative colitis) and polymyalgia rheumatica. Accordingly, MPNs have also been described as “inflammatory diseases”. The metabolic syndrome has so far not been shown to be prevalent in patients with MPNs although the chronic inflammatory state might induce insulin resistance as in other chronic inflammatory diseases. If MPNs indeed are preceded by a chronic inflammatory drive eliciting persistent leukocytosis, monocytosis and thrombocytosis, and ultimately clonal myeloproliferation it is intriguing to consider if MPNs and metabolic syndrome share common pathways. If so, an MPN-phenotype might be expected to be associated with metabolic syndrome in the background population. Therefore, in this study, we tested the association between circulating inflammatory markers (CIMs), a phenotypical presentation of MPNs (e.g. erythrocytosis, leukocytosis, and thrombocytosis), and the metabolic syndrome in a general population study.METHODSData sourcesIn this cross-sectional study, we used data from 20,872 individuals from the Danish General Suburban Population Study (GESUS). Individuals were invited between January 2010 and October 2013 and data were collected through questionnaires, health examinations, and biochemical measurements.AnalysesWe analyzed eight CIMs (leukocytes, neutrophils, monocytes, thrombocytes, erythrocytes, hematocrit, hemoglobin, and high-sensitive CRP) and their linear association with indicators of the metabolic syndrome (according to a modified version of the US National Cholesterol Education Program Adult Treatment Panel III): HbA1c, non-fasting plasma glucose, body mass index, blood pressure, cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides. With logistic regression, we calculated odds ratios (ORs) of metabolic syndrome in individuals with increased levels of CIMs compared to individuals with normal levels based on current Danish reference ranges.RESULTSIn general, there was a positive correlation between most CIMs and indicators of the metabolic syndrome both in the age-sex-adjusted and multivariable linear regression analyses. In the age-sex-adjusted logistic regression analyses, increased levels of all CIMs were associated with increased prevalence of dyslipidemia (OR: 1.4-2.2), hypertension (OR: 1.3-3.1), diabetes mellitus (OR: 1.5-3.4), obesity (1.4-4.6), and the metabolic syndrome (OR: 1.4-2.8). However, neutrophils and thrombocytes were not significant when it came to hypertension and diabetes mellitus, respectively (Table 1).DISCUSSION & CONCLUSIONIn this study we examined the association between different CIMs and a wide variety of metabolic changes. To our knowledge it is the first comprehensive epidemiological study linking the phenotypical presentation of MPNs in a general population of more than 20.000 individuals with a broad spectrum of metabolic disturbances.With chronic inflammation being proposed as a trigger and consequence of both MPNs and metabolic syndrome and considering the results in the present study it is intriguing to postulate chronic inflammation as the common denominator in both metabolic syndrome leading to MPNs and MPNs leading to metabolic syndrome(Figure 1). It is of great clinical interest to investigate if an increased risk of metabolic syndrome exists in e.g. a cohort of MPN patients and whether people with incident metabolic syndrome have increased risk of MPNs and second cancer.An increased prevalence of a wide variety of metabolic disturbances following increased CIMs could potentially, if similar results are found in the MPN population, support a future change in the MPN-risk stratification. Amongst the tested CIMs only thrombocytes (> 1500 Mia/L) are currently used as a risk factor.In conclusion, elevated levels of CIMs were associated with an increased prevalence of metabolic disturbances. Our results substantiate the need for similar studies in MPN patients, being characterized by chronic inflammation and elevated cell counts. [Display omitted] DisclosuresHasselbalch:Novartis: Research Funding.

Socioeconomic position, symptoms of depression and subsequent mental healthcare treatment: a Danish register-based 6-month follow-up study on a population survey

ObjectiveExamine whether the severity of symptoms of depression was associated with the type of mental healthcare treatment (MHCT) received, independent of socioeconomic position (SEP).DesignRegister-based 6-month follow-up study on participants from...

Prenatal smoking exposure and cardio-metabolic risk factors in adulthood: a general population study and a meta-analysis.

Prenatal smoking exposure is associated with obesity and other cardio-metabolic risk factors in children, but no previous meta-analysis has been conducted in adults. We investigated the association of prenatal smoking exposure in the Danish General Suburban Population Study (GESUS) with BMI, waist circumference, total cholesterol, type 2 diabetes, gestational type 2 diabetes, and hypertension in adulthood. We subsequently performed a meta-analysis, adding published studies investigating the association between prenatal smoking and the risk of cardio-metabolic outcomes among individuals at least 18 years of age. We included 19 eligible observational studies with various cardio-metabolic outcomes (N = 24,201-308,981 adults). In individuals exposed to prenatal smoking, the pooled random effects adjusted odds ratio were 1.35 (95% CI: 1.16-1.56) for being overweight, 1.46 (1.39-1.54) for being obese, 1.07 (0.89-1.29) for type 2 diabetes, 1.17 (0.92-1.48) for hypertension, and 1.38 (1.19-1.61) for gestational diabetes mellitus (GDM), compared with no exposure. The standardized means in waist circumference, total cholesterol, diastolic, and systolic blood pressure were not different in individuals exposed vs. not exposed to prenatal smoking. Heterogeneity was moderate to high (51% < I2 < 99%). However, removal of the high heterogeneity removed the associated uncertainty in the point estimate and revealed that prenatal smoking is associated with increased BMI in adulthood. There was also no evidence of publication bias in themeta-analyses. The findings from the meta-analyses suggested that prenatal smoking exposure is associated with an increased odds ratio of overweight, obesity, and GDM in adulthood, but not with type 2 diabetes, hypertension, waist circumference, or total cholesterol. These findings highlight the importance of abstaining from smoking by pregnant women.

Estimates of prediabetes and undiagnosed type 2 diabetes in Denmark: The end of an epidemic or a diagnostic artefact?

Background: Up-to-date information on undiagnosed type 2 diabetes and prediabetes based on current diagnostic criteria is lacking. The study aimed to model the total numbers of people with undiagnosed type 2 diabetes and prediabetes in Denmark based on existing population-based surveys. Methods: Two population-based Danish studies with information on HbA1c, date of examination, gender, age and known type 2 diabetes were identified: the Danish General Suburban Population Study, n = 21,205, and the Danish Health Examination Survey, n = 18,065. The prevalence of known, undiagnosed and pre-diabetes were estimated in the Danish General Suburban Population Study, and population-level age-specific prevalence of known type 2 diabetes was estimated from national registers. The Danish Health Examination Survey was included for sensitivity analysis. Combining estimates of the survey participation rate among known type 2 diabetes patients with known overall participation rates from the studies allowed for the correction of survey prevalence to plausible population-level estimates of age- and gender-specific prevalence. Results: The prevalence of known, undiagnosed and pre-diabetes was highest among men, increasing with age with a peak at age 70. Applying the survey-based prevalence to the entire Danish population, the estimated number (May 2011) with undiagnosed type 2 diabetes was 60,681, corresponding to 24% of all type 2 diabetes cases, and 292,715 had prediabetes, about 50% more than the total type 2 diabetes population. Conclusions: Estimates of undiagnosed type 2 diabetes and prediabetes are dramatically lower than reported in previous studies (60,681 vs 200,000 and 292,715 vs 750,000); however, whether this reflects a true decrease in incidence or the change to HbA1c-based diagnostic criteria is not clear.

Lactase Persistence, Milk Intake, and Adult Acne: A Mendelian Randomization Study of 20,416 Danish Adults

Whether there is a causal relationship between milk intake and acne is unknown. We tested the hypothesis that genetically determined milk intake is associated with acne in adults using a Mendelian randomization design. LCT-13910 C/T (rs4988235) is associated with lactase persistence (TT/TC) in Northern Europeans. We investigated the association between milk intake, LCT-13910 C/T (rs4988235), and acne in 20,416 adults (age-range: 20–96) from The Danish General Suburban Population Study (GESUS). The adjusted observational odds ratio for acne in any milk intake vs. no milk intake was 0.93(95% confidence interval: 0.48–1.78) in females and 0.49(0.22–1.08) in males aged 20–39 years, and 1.15(95% confidence interval: 0.66–1.99) in females and 1.02(0.61–1.72) in males above 40 years. The unadjusted odds ratio for acne in TT+TC vs. CC was 0.84(0.43–1.62) in the age group 20–39 years, and 0.99(0.52–1.88) above 40 years. We did not find any observational or genetic association between milk intake and acne in our population of adults.