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  • 1
    Keywords: POPULATION ; HEALTH ; RISK FACTOR ; BLOOD-PRESSURE ; DISORDERS ; hyperthyroidism ; HYPOTHYROIDISM ; ARTERIAL STIFFNESS ; SUBCLINICAL THYROID-DYSFUNCTION ; ENDOTHELIUM-DEPENDENT VASODILATATION
    Abstract: Background: Recent data from a population-based study in children and adolescents suggest that serum thyrotropin (TSH) levels are associated with arterial blood pressure and hypertension. These results are in agreement with some but not all population-based studies in adults. Discrepancies in results might be explained by drug intake, different iodine supplies, and sizes of populations investigated. In addition, it is not clear whether an association between TSH and hypertension exists longitudinally or only cross-sectionally. Thus, our aim was to investigate cross-sectional and longitudinal associations between thyroid function and arterial blood pressure in a large consortium of cohort studies in adults. Methods: Data from five population-based studies were pooled resulting in 17,023 individuals being available for cross-sectional and 10,048 individuals for longitudinal analyses. Associations of baseline TSH with baseline blood pressure or hypertension were analyzed by multivariable median or logistic regression models. Multivariable median or Poisson regression models were used to investigate associations of baseline TSH with five-year change in arterial blood pressure or incident hypertension. Results: There was a cross-sectional positive association of TSH with arterial blood pressure (p〈0.001) and hypertension (odds ratio [OR]=1.76 [confidence interval (CI) 1.24-2.50], p=0.002). Likewise, hypothyroidism was associated with systolic (beta=1.1 [CI 0.1-2.1], p=0.040) and diastolic blood pressure (beta=1.4 [CI 0.7-2.0], p〈0.001). TSH, however, was not consistently associated with a five-year change in blood pressure or incident hypertension. Conclusions: High serum TSH levels were associated with current hypertension and blood pressure but not with a five-year change in blood pressure and incident hypertension. This argues for only a short-term effect of thyroid hormone levels on arterial blood pressure or a spurious association that needs further evaluation in population-based studies.
    Type of Publication: Journal article published
    PubMed ID: 23427935
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  • 2
    Keywords: RISK-FACTORS ; CARDIOVASCULAR-DISEASE ; INSULIN SENSITIVITY ; GENERAL-POPULATION ; OBESE WOMEN ; THYROID-STIMULATING HORMONE ; REFERENCE RANGE ; SUBCLINICAL HYPOTHYROIDISM ; EUTHYROID SUBJECTS ; TSH LEVEL
    Abstract: Background: Population-based studies investigating the sex-specific association between thyrotropin (TSH) levels and serum lipid concentrations are scarce. We examined the association between TSH and total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides in men and women from the general population. Furthermore, the association with TSH outside and within the reference range and lipid levels was studied. Methods: Individual data of 13,571 men and women without lipid medication of four population-based studies conducted in Western European adults were pooled for cross-sectional analyses. The association between TSH levels and lipid concentrations were analyzed by calculating sex-specific multivariable median regression models. Results: In the pooled population, serum TSH levels were significantly positively associated with triglyceride values in men and with total cholesterol, LDL cholesterol, and triglyceride values in women. In the pooled male population, low serum TSH levels (〈3.0 mIU/L) were significantly associated with lower total cholesterol, while high serum TSH levels (〉= 3.0 mIU/L) were associated with higher triglyceride values. In the pooled female population, low serum TSH levels were significantly associated with lower total cholesterol, LDL cholesterol, and HDL cholesterol. High TSH levels were associated with higher total cholesterol and LDL cholesterol in the pooled female population. In both sexes, serum TSH levels within the reference range (0.3-3.0 mIU/L) were significantly positively associated with triglyceride concentrations. Conclusions: Increasing levels of TSH were associated with a less favorable lipid profile in both men and women from the general population. In both sexes, TSH levels within the reference range were significantly positively associated with triglyceride concentrations.
    Type of Publication: Journal article published
    PubMed ID: 24102572
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  • 3
    Abstract: Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
    Type of Publication: Journal article published
    PubMed ID: 27252175
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  • 4
  • 5
    Abstract: CONTEXT: Except from associations study with body weight, there are few longitudinal data regarding the association between thyroid function and anthropometric such as waist circumference, waist-to-hip-ratio or waist-to height-ratio. OBJECTIVE: We aimed at investigating the association of thyroid stimulating hormone (TSH) at baseline with changes in different anthropometric markers between baseline and follow-up in the general population. DESIGN AND SETTING: We used data from four population-based longitudinal cohort studies and one population-based cross-sectional study. SUBJECTS: We studied 16,902 (8,204 males and 8,698 females) subjects aged 20 to 95 years from the general population. MAIN OUTCOME MEASURES: We measured body mass index, waist-circumference, waist-to-hip- ratio and waist-to-height-ratio. Multivariable median regression models were calculated adjusting for the following covariates: age, sex, baseline value of the respective anthropometric marker, smoking status, follow-up-time period and study site. RESULTS: In cross-sectional analyses, serum TSH within the reference range was positively associated with waist circumference (beta 0.94 cm (95%CL 0.56; 1.32)) and waist-to-height-ratio (beta 0.029 (95%CL 0.017; 0.042)). These associations were also present for the full range of TSH. In the longitudinal analyses, serum TSH at baseline was inversely associated with 5-year change of all considered anthropometric measures within the prior defined study-specific reference range, as well as in the full range of serum TSH. CONCLUSION: High TSH serum levels were positively associated with current anthropometric markers even in the study-specific reference ranges. In contrast, high TSH serum levels were associated with decreased anthropometric markers over a time span of approximately 5 years. Further research is needed to determine possible clinical implications as well as public health consequences of these findings.
    Type of Publication: Journal article published
    PubMed ID: 27393002
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  • 6
    Abstract: Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
    Type of Publication: Journal article published
    PubMed ID: 27252175
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  • 7
    Abstract: BACKGROUND: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease. METHODS: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose-response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12.5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5.6 years [5th-95th percentile 1.04-13.5]) from 71 011 participants from 37 studies. FINDINGS: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5.4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1.14, 95% CI, 1.10-1.17), coronary disease excluding myocardial infarction (1.06, 1.00-1.11), heart failure (1.09, 1.03-1.15), fatal hypertensive disease (1.24, 1.15-1.33); and fatal aortic aneurysm (1.15, 1.03-1.28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0.94, 0.91-0.97). In comparison to those who reported drinking 〉0-〈/=100 g per week, those who reported drinking 〉100-〈/=200 g per week, 〉200-〈/=350 g per week, or 〉350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1-2 years, or 4-5 years, respectively. INTERPRETATION: In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines. FUNDING: UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council.
    Type of Publication: Journal article published
    PubMed ID: 29676281
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  • 8
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In 1990, a random sample of 567 persons of the 15–69-year-old population living in the Western part of Copenhagen County, Denmark, was patch tested in a cross-sectional study. In 1998, a follow-up study was performed. Out of 540 invited, 365 (68%) were re-patch tested. In the follow-up study, the persistence of allergic contact sensitivity, defined as 1 or more positive patch tests in both surveys, was 71% (37 out of 52 subjects). Nickel allergy persisted in 79% (19 out of 24 subjects), while 60% (21 out of 35 subjects) had a positive patch test reaction to 1 or more allergens, other than nickel, in both surveys. The lowest persistence was 50% (5 out of 10 subjects) and this was found for patch test reactivity to 1 or more of the cosmetic ingredients included in the patch test series. 8 years after the baseline study had demonstrated allergic contact sensitivity, 71% of the subjects still had at least 1 positive patch test. Nickel allergy persisted in 79%. Allergen avoidance should probably be lifelong to prevent elicitation of contact dermatitis.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Objectives:  To investigate symptoms from the eyes and airways, elicited by perfume and fragrance products and associations between such symptoms and skin prick test reactivity, metacholine bronchial hyperreactivity (BHR), contact allergy, and eczema in a population based sample.Methods:  A questionnaire on mucosal symptoms elicited by fragrance products was mailed to 1189 persons who had participated in a Danish population-based study of allergic diseases in 1997/98. The study included measurement of BHR, skin prick testing, patch testing and history of hand eczema.Results:  The response rate to the questionnaire was 80%. Symptoms from the eyes or airways elicited by fragrance products were reported by 42%. There were no significant associations between these symptoms and skin prick test reactivity. Positive and independent statistical significant associations were found between BHR, perfume contact allergy and hand eczema, and symptoms from the eyes and airways elicited by fragrance products, also when adjusting for nickel contact allergy, age, gender psychological vulnerability, educational level and social class.Conclusions:  Individuals with BHR, hand eczema and/or perfume contact allergy, as opposed to those without, are more frequently and more severely bothered from the eyes or airways after volatile exposure to fragrance products. The lack of association with skin prick test reactivity indicates that IgE mediated allergic mechanisms do not play a major role in the development of these symptoms. Having hand eczema has the greatest impact on reporting mucosal symptoms elicited by fragrance products.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: It has been hypothesized that allergic rhinitis and allergic asthma are manifestations of the same disease entity. We aimed to investigate the relationship between allergic rhinitis and allergic asthma.Methods: Participants in a population-based study of 15–69-year-olds in 1990 were invited to a follow-up in 1998. A total of 734 subjects were examined on two occasions eight years apart. Allergic rhinitis to pollen was defined as a history of nasal symptoms on exposure to pollens and IgE specific to pollen. Allergic asthma to pollen was defined as a history of lower airway symptoms on exposure to pollens and IgE specific to pollen. Similarly, diagnoses of allergic rhinitis and allergic asthma to animals or mite were defined.Results: At follow-up, all subjects with allergic asthma to pollen (n = 52) had in addition allergic rhinitis to pollen. In the longitudinal analysis, there were a total of 28 new (incident) cases of allergic asthma to pollen. They all had allergic rhinitis to pollen at baseline, or had developed allergic rhinitis to pollen at follow-up. Accordingly, allergic rhinitis to animals and mite were ubiquitous in subjects with allergic asthma to animals and mite, respectively.Conclusions: The results support the hypothesis that allergic rhinitis and allergic asthma are manifestations of the same disease entity.
    Type of Medium: Electronic Resource
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