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1.
Nat Genet ; 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462485

RESUMO

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10-8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10-20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10-10 < P < 5 × 10-8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.

2.
Eur Heart J ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33438022

RESUMO

AIMS : There is inconsistent evidence on the relation of alcohol intake with incident atrial fibrillation (AF), in particular at lower doses. We assessed the association between alcohol consumption, biomarkers, and incident AF across the spectrum of alcohol intake in European cohorts. METHODS AND RESULTS : In a community-based pooled cohort, we followed 107 845 individuals for the association between alcohol consumption, including types of alcohol and drinking patterns, and incident AF. We collected information on classical cardiovascular risk factors and incident heart failure (HF) and measured the biomarkers N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I. The median age of individuals was 47.8 years, 48.3% were men. The median alcohol consumption was 3 g/day. N = 5854 individuals developed AF (median follow-up time: 13.9 years). In a sex- and cohort-stratified Cox regression analysis alcohol consumption was non-linearly and positively associated with incident AF. The hazard ratio for one drink (12 g) per day was 1.16, 95% CI 1.11-1.22, P < 0.001. Associations were similar across types of alcohol. In contrast, alcohol consumption at lower doses was associated with reduced risk of incident HF. The association between alcohol consumption and incident AF was neither fully explained by cardiac biomarker concentrations nor by the occurrence of HF. CONCLUSIONS : In contrast to other cardiovascular diseases such as HF, even modest habitual alcohol intake of 1.2 drinks/day was associated with an increased risk of AF, which needs to be considered in AF prevention.

3.
BMJ Open ; 10(12): e042880, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33303469

RESUMO

OBJECTIVE: The bodily distress syndrome (BDS) checklist has proven to be useful in the diagnostic categorisation and as screening tool for functional somatic disorders (FSD). This study aims to investigate whether the BDS checklist total sum score (0-100) can be used as a measure of physical symptom burden and FSD illness severity. DESIGN: Cross-sectional. SETTING: Danish general population, primary care and specialised clinical setting. PARTICIPANTS: A general population cohort (n=9656), a primary care cohort (n=2480) and a cohort of patients with multiorgan BDS from specialised clinical setting (n=492). OUTCOME MEASURES: All data were self-reported. Physical symptoms were measured with the 25-item BDS checklist. Overall self-perceived health was measured with one item from the 36-item Short-Form Health Survey (SF-36). Physical functioning was measured with an aggregate score of four items from the SF-36/SF-12 scales 'physical functioning', 'bodily pain' and 'vitality'. Emotional distress was measured with the mental distress subscale (SCL-8) from the Danish version of the Hopkins Symptom Checklist-90. Illness worry was measured with the six-item Whiteley Index. RESULTS: For all cohorts, bifactor models established that despite some multidimensionality the total sum score of the BDS checklist adequately reflected physical symptom burden and illness severity. The BDS checklist had acceptable convergent validity with measures of overall health (r=0.25-0.58), physical functioning (r=0.22-0.58), emotional distress (r=0.47-0.62) and illness worry (r=0.36-0.55). Acceptability was good with a low number of missing responses to items (<3%). Internal consistency was high (α ≥0.879). BDS score means varied and reflected symptom burden across cohorts (13.03-46.15). We provide normative data for the Danish general population. CONCLUSIONS: The BDS checklist total sum score can be used as a measure of symptom burden and FSD illness severity across settings. These findings establish the usefulness of the BDS checklist in clinics and in research, both as a diagnostic screening tool and as an instrument to assess illness severity.

4.
J Psychosom Res ; 138: 110245, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32950761

RESUMO

OBJECTIVE: The Whiteley Index (WI) is the most widely used screening tool for health anxiety/illness worry. Diverse versions (different number of items and factors) have been used. We aimed to examine psychometric properties of 7 items of the WI besides adding a new item on obsessive illness rumination for better future detection of health anxiety. METHODS: Data from a large population-based study in Denmark (N = 9656). Construct validity was examined by exploratory (EFA) and confirmatory factor analysis (CFA) plus hypothesis testing. Criterion validity was evaluated via Receiver Operating Characteristic curves and area under the curve (AUC) using a diagnostic criterion as gold standard. RESULTS: Factor loadings of EFA revealed viable one-factor models (6, 7, or 8 items) and two-factor models (7 or 8 items). Factor one indicated a dimension of illness worry. Factor two indicated a somatic symptoms dimension. The new item on obsessive illness rumination merged well with the existing items. EFA of two-factor models and one-factor 6-item model showed good fit. CFA resembles these findings. A one-factor 6-item model (including the item on obsessive illness rumination and excluding two items concerning somatic symptoms) was chosen as the optimal model and presented good criterion validity: AUC 0.88 (95%CI(0.84;0.92)). Main hypotheses concerning associations with somatic symptoms, anxiety, and depression were met. CONCLUSIONS: We found good psychometric properties for a new one-factor 6-item version of the WI. Through elimination of items concerning somatic symptoms and inclusion of obsessive illness rumination, we propose a clear, unidimensional and improved measure of illness worry: Whiteley-6-R.

5.
Stroke ; 51(9): 2770-2777, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32811388

RESUMO

BACKGROUND AND PURPOSE: Stroke is a common cause of death and a leading cause of disability and morbidity. Stroke risk assessment remains a challenge, but circulating biomarkers may improve risk prediction. Controversial evidence is available on the predictive ability of troponin concentrations and the risk of stroke in the community. Furthermore, reports on the predictive value of troponin concentrations for different stroke subtypes are scarce. METHODS: High-sensitivity cardiac troponin I (hsTnI) concentrations were assessed in 82 881 individuals (median age, 50.7 years; 49.7% men) free of stroke or myocardial infarction at baseline from 9 prospective European community cohorts. We used Cox proportional hazards regression to determine relative risks, followed by measures of discrimination and reclassification using 10-fold cross-validation to control for overoptimism. Follow-up was based upon linkage with national hospitalization registries and causes of death registries. RESULTS: Over a median follow-up of 12.7 years, 3033 individuals were diagnosed with incident nonfatal or fatal stroke (n=1654 ischemic strokes, n=612 hemorrhagic strokes, and n=767 indeterminate strokes). In multivariable regression models, hsTnI concentrations were associated with overall stroke (hazard ratio per 1-SD increase, 1.15 [95% CI, 1.10-1.21]), ischemic stroke (hazard ratio, 1.14 [95% CI, 1.09-1.21]), and hemorrhagic stroke (hazard ratio, 1.10 [95% CI, 1.01-1.20]). Adding hsTnI concentrations to classical cardiovascular risk factors (C indices, 0.809, 0.840, and 0.736 for overall, ischemic, and hemorrhagic stroke, respectively) increased the C index significantly but modestly. In individuals with an intermediate 10-year risk (5%-20%), the net reclassification improvement for overall stroke was 0.038 (P=0.021). CONCLUSIONS: Elevated hsTnI concentrations are associated with an increased risk of incident stroke in the community, irrespective of stroke subtype. Adding hsTnI concentrations to classical risk factors only modestly improved estimation of 10-year risk of stroke in the overall cohort but might be of some value in individuals at an intermediate risk.


Assuntos
Miocárdio/metabolismo , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/metabolismo , Troponina I/metabolismo , Biomarcadores , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sistema de Registros , Fatores de Risco
6.
J Am Heart Assoc ; 9(9): e015218, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32351154

RESUMO

Background Differences in risk factors for atrial fibrillation (AF) and heart failure (HF) are incompletely understood. Aim of this study was to understand whether risk factors and biomarkers show different associations with incident AF and HF and to investigate predictors of subsequent onset and mortality. Methods and Results In N=58 693 individuals free of AF/HF from 5 population-based European cohorts, Cox regressions were used to find predictors for AF, HF, subsequent onset, and mortality. Differences between associations were estimated using bootstrapping. Median follow-up time was 13.8 years, with a mortality of 15.7%. AF and HF occurred in 5.0% and 5.4% of the participants, respectively, with 1.8% showing subsequent onset. Age, male sex, myocardial infarction, body mass index, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) showed similar associations with both diseases. Antihypertensive medication and smoking were stronger predictors of HF than AF. Cholesterol, diabetes mellitus, and hsCRP (high-sensitivity C-reactive protein) were associated with HF, but not with AF. No variable was exclusively associated with AF. Population-attributable risks were higher for HF (75.6%) than for AF (30.9%). Age, male sex, body mass index, diabetes mellitus, and NT-proBNP were associated with subsequent onset, which was associated with the highest all-cause mortality risk. Conclusions Common risk factors and biomarkers showed different associations with AF and HF, and explained a higher proportion of HF than AF risk. As the subsequent onset of both diseases was strongly associated with mortality, prevention needs to be rigorously addressed and remains challenging, as conventional risk factors explained only 31% of AF risk.

7.
Eur J Psychotraumatol ; 11(1): 1717824, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32128043

RESUMO

Background: Negative life events are a predictor for mental illness. However, most research has focused on selected domains, e.g. childhood or recent adversity. The Cumulative Lifetime Adversity Measure (CLAM), a newly introduced questionnaire not yet validated, examines cumulative effect of a range of events including number of exposure to the same event. This measure gives opportunity to collect detailed data on lifetime adversity in large cohort studies. Objective: The aim of this study was translation of the CLAM into Danish and validation of the CLAM in a large general population cohort. Secondly, we aimed to describe the occurrence of adverse life events in a large representative sample of the general population in Denmark. Methods: Translation and validation followed the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) for formative models. Content and construct validity were evaluated including hypothesis testing of accumulated lifetime adversity having a U-shaped pattern with low levels of cumulated lifetime adversity as opposed to no or high levels being associated with lower emotional distress, functional impairment, and pain impairment. The field testing sample was the DanFunD cohort (n = 7493) randomly drawn in a Danish population and examined between 2012 and 2015. Results: Pilot interviews showed that the questions were confronting but not offensive, straight forward, and easy to answer. Acceptability was good. U-shaped patterns between accumulated lifetime adversity and the outcome measures were found. Quadratic term: Emotional distress (ß(95%CI) 0.007(0.002;0.012), p < 0.007), functional impairment (ß(95%CI) -0.002(-0.003;-0.001), p < 0.001), and pain impairment (ß(95%CI) 0.004(0.002;0.006), p = 0.001). Field testing provided basic numbers for adverse life events for the Danish general population, with a cumulated lifetime adversity mean (SD), 5.9 (3.7). Compared to the US there were lower rates of violence, social/environmental stress, and disaster. Conclusions: The results from the original version were replicated, indicating high construct validity. Furthermore, content validity was good.

8.
Endocrine ; 68(2): 358-367, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32040823

RESUMO

PURPOSE: Thyroid dysfunction may affect the risk of cardiovascular disease and mortality through effects on myocardial and vascular tissue and metabolism. Levels of thyroid stimulating hormone (TSH) indicates thyroid function. We aimed to assess the association between TSH-levels and incident ischemic heart disease (IHD), incident stroke, and all-cause mortality. METHODS: We included 13,865 participants (18-71 years, 51.6% women) from five cohort studies conducted during 1974-2008 were included. TSH was measured at the baseline examination and classified as <0.4; 0.4-2.5 (ref.); 2.5-5.0; 5.0-10, or >10 mU/l. Incident IHD, incident stroke, and all-cause mortality were identified in registries until ultimo 2013. Data were analysed by multivariate Cox regression with age as underlying time axis. Results from the individual cohorts were pooled by random-effects meta-analysis. RESULTS: The crude incidence rate was for IHD 7.8 cases/1000 person years (PY); stroke 5.4 cases/1000 PY; and all-cause mortality 11.3 deaths/1000 PY (mean follow-up: 14 years). Analyses showed no statistically significant associations between TSH-levels and incident IHD or incident stroke in the partly or fully adjusted models. There was a statistically significant association between TSH of 2.5-5 mU/l and all-cause mortality (hazard ratio 1.145 (95% CI 1.004-1.306) compared with TSH of 0.4-2.5 mU/l in the fully adjusted model. CONCLUSION: The results do not provide evidence of a harmful effect of decreased or increased TSH on IHD or stroke in the general population. However, there is some indication of an elevated risk for all-cause mortality with TSH 2.5-5 mU/l compared with 0.4-2.5 mU/l.

9.
Sci Rep ; 10(1): 3273, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32094442

RESUMO

Prevalence of functional somatic syndromes (FSS) in the general population varies with observed overlap between syndromes. However, studies including a range of FSS are sparse. We investigated prevalence and characteristics of various FSS and the unifying diagnostic construct bodily distress syndrome (BDS), and identified mutual overlap of the FSS and their overlap with BDS. We included a stratified subsample of 1590 adults from a randomly selected Danish general population sample (n = 7493). Telephonic diagnostic interviews performed by three trained physicians were used to identify individuals with FSS and BDS. Prevalence of overall FSS was 9.3%; 3.8% for irritable bowel, 2.2% for chronic widespread pain, 6.1% for chronic fatigue, 1.5% for whiplash associated disorders, and 0.9% for multiple chemical sensitivity. Prevalence of BDS was 10.7% where 2.0% had the multi-organ type. FSS were highly overlapping with low likelihood of having a "pure" type. Diagnostic agreement of FSS and BDS was 92.0%. Multi-syndromatic FSS and multi-organ BDS were associated with female sex, poor health, physical limitations, and comorbidity. FSS are highly prevalent and overlapping, and multi-syndromatic cases are most affected. BDS captured the majority of FSS and may improve clinical management, making the distinction between multi- and mono-syndromatic patients easier.

11.
J Psychosom Res ; 128: 109868, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759195

RESUMO

OBJECTIVES: Bodily distress syndrome (BDS) has been shown to encompass a range of functional somatic syndromes (FSS) such as irritable bowel syndrome (IBS), fibromyalgia (FM), and chronic fatigue syndrome (CFS) in clinical samples. This study aimed to explore symptom clusters and test classification of individuals with illness similar to the BDS criteria in a general population sample. METHODS: A stratified subsample of 1590 individuals from the DanFunD part two cohort was included. Symptoms were assessed with the Research Interview for Functional somatic Disorders, performed by trained physicians. In 44 symptoms pooled from criteria of IBS, FM, CFS, and BDS, symptom clusters were explored with explorative factor analysis. Confirmation of symptom clusters of BDS in the previously described 25- and 30-item BDS checklists was performed with confirmatory factor analysis. Classification of individuals into illness groups was investigated with latent class analysis. RESULTS: Four symptom clusters (cardiopulmonary, gastrointestinal, musculoskeletal, general symptoms/fatigue) corresponding to the BDS subtypes and their corresponding FSS were identified and confirmed. A three-class model including 25 BDS items had the best fit for dividing participants into classes of illness: One class with low probability, one class with medium probability, and one class with high probability of having ≥4 symptoms in all symptom clusters. CONCLUSION: The BDS concept was confirmed in the general population and constitutes a promising approach for improved FSS classification. It is highly clinical relevant being the only diagnostic construct defining the complex multi-organ type.


Assuntos
Síndrome de Fadiga Crônica/diagnóstico , Fibromialgia/diagnóstico , Síndrome do Intestino Irritável/diagnóstico , Estudos de Coortes , Análise Fatorial , Feminino , Humanos , Análise de Classes Latentes , Masculino , Pessoa de Meia-Idade
12.
Scand J Public Health ; 48(5): 567-576, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31409218

RESUMO

Aims: Little is known about the prevalence and characteristics of functional somatic syndromes (FSS) such as irritable bowel syndrome (IBS), fibromyalgia (FM), chronic fatigue syndrome (CFS), whiplash associated disorders (WAD), multiple chemical sensitivity (MCS), and bodily distress syndrome (BDS) in the general population when they are investigated simultaneously. Method: This cross-sectional study is based on the Danish Study of Functional Disorders (DanFunD) cohort consisting of 9656 adults from the general population. FSS and BDS were identified by questionnaires and characterized by age, sex, vocational training, physical health and comorbidity with physical and psychiatric disease. Results: In total, 16.3% (95% CI: 15.6-17.1) of the participants fulfilled the criteria for at least one FSS, ranging from 1.7% for WAD to 8.6% for CFS, and 16.1% (95% CI: 15.4-16.9) fulfilled the criteria for BDS. Cases had a high risk of poor self-perceived health, limitations in daily activities, and a high psychiatric comorbidity, all increasing with the number of syndromes in each individual. However, the associations differed across the various FSS. Mutual overlaps of IBS, FM and CFS were greater than could be expected by chance. Conclusions: FSS and BDS are prevalent in the adult Danish population, and cases have high risk of poor self-perceived health, limitation in daily activities, and psychiatric comorbidity. These associations were particularly strong for cases with multiple FSS and multi-organ BDS.


Assuntos
Transtornos Somatoformes/epidemiologia , Adulto , Idoso , Estudos Transversais , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Síndrome
13.
Eur J Clin Nutr ; 74(4): 581-587, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31316172

RESUMO

OBJECTIVES: The objective of the present study was to investigate the relationship between price and sales volume of non-alcoholic sugar-sweetened beverages (SSBs), diet drinks, sweets and chocolates, including own and cross price elasticity to further quantify the potential impact of price. METHODS: The study was based on retail scanner data for grocery sales from retail outlet chains in Denmark during the year 2008-2015. A fixed-effects model was used to estimate the association between price and sales volume, using own price and cross price elasticity. RESULTS: Sales volume of all sugary products except for chocolates were significantly negatively associated with price. Own price elasticity varied from -0.3 to -0.4 for drinks and sweets indicating that a 10% increase in price would cause a reduction in sales by 3 or 4%. A 10% increase in price of carbonated SSBs would increase sales of diet drinks by 7%. Cross price elasticities for other products were not significant. CONCLUSIONS: The results of the present study demonstrated significant negative associations between changes in price and changes in the sale of SSBs, diet drinks and sweets.

14.
Europace ; 22(4): 522-529, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31740944

RESUMO

AIMS: Limited evidence is available on the temporal relationship between atrial fibrillation (AF) and ischaemic stroke and their impact on mortality in the community. We sought to understand the temporal relationship of AF and ischaemic stroke and to determine the sequence of disease onset in relation to mortality. METHODS AND RESULTS: Across five prospective community cohorts of the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project we assessed baseline cardiovascular risk factors in 100 132 individuals, median age 46.1 (25th-75th percentile 35.8-57.5) years, 48.4% men. We followed them for incident ischaemic stroke and AF and determined the relation of subsequent disease diagnosis with overall mortality. Over a median follow-up of 16.1 years, N = 4555 individuals were diagnosed solely with AF, N = 2269 had an ischaemic stroke but no AF diagnosed, and N = 898 developed both, ischaemic stroke and AF. Temporal relationships showed a clustering of diagnosis of both diseases within the years around the diagnosis of the other disease. In multivariable-adjusted Cox regression analyses with time-dependent covariates subsequent diagnosis of AF after ischaemic stroke was associated with increased mortality [hazard ratio (HR) 4.05, 95% confidence interval (CI) 2.17-7.54; P < 0.001] which was also apparent when ischaemic stroke followed after the diagnosis of AF (HR 3.08, 95% CI 1.90-5.00; P < 0.001). CONCLUSION: The temporal relations of ischaemic stroke and AF appear to be bidirectional. Ischaemic stroke may precede detection of AF by years. The subsequent diagnosis of both diseases significantly increases mortality risk. Future research needs to investigate the common underlying systemic disease processes.

15.
Scand J Public Health ; 48(3): 294-302, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30813840

RESUMO

Aim: Heart failure is a serious complication of acute myocardial infarction leading to poor prognosis. We aimed at exploring time trends of heart failure and their impact on mortality among patients with an incident acute myocardial infarction. Methods: From the National Patient Danish Registry we collected data on all patients hospitalized with an incident of acute myocardial infarction during 2000-2009 and identified cases with in-hospital heart failure (presented on admission or developing heart failure during acute myocardial infarction hospitalization) or post-discharge heart failure (a hospitalization or outpatient visit following acute myocardial infarction discharge), and assessed in-hospital, 30-day and 1-year mortality. Results: Of the 78,814 patients included in the study, 10,248 (13.0%) developed in-hospital heart failure. The odds of in-hospital heart failure declined 0.9% per year (odds ratio=0.991, 95% confidence interval: 0.983-0.999). In-hospital heart failure was associated with 13% (odds ratio=1.13, 95% confidence interval: 1.06-1.20) and 14% (odds ratio=1.14, 95% confidence interval: 1.07-1.20) higher in-hospital and 30-day mortality, respectively. Of the 61,637 patients discharged alive without in-hospital heart failure, 5978 (9.7%) experienced post-discharge heart failure, 4116 (6.7%) were hospitalized and 1862 (3.0%) were diagnosed at outpatient clinics. The risk of heart failure requiring hospitalization declined 5.5% per year (hazard ratio=0.945, 95% confidence interval: 0.934-0.955) whereas the risk of heart failure diagnosed at outpatient clinics increased 13.4% per year (hazard ratio=1.134, 95% confidence interval: 1.115-1.153). Post-discharge heart failure was associated with 239% (hazard ratio=3.39, 95% confidence interval: 3.18-3.63) higher 1-year mortality. Conclusions: In-hospital and post-discharge heart failure requiring hospitalization decreased whereas post-discharge heart failure diagnosed at outpatient clinics increased among incident acute myocardial infarction patients during 2000-2009. The development of heart failure, especially after acute myocardial infarction discharge, indicates a poor prognosis.


Assuntos
Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Hospitalização/estatística & dados numéricos , Infarto do Miocárdio/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Prognóstico , Sistema de Registros , Fatores de Risco , Fatores de Tempo
17.
JAMA Cardiol ; 4(12): 1270-1279, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31664431

RESUMO

Importance: Risk stratification for coronary heart disease (CHD) remains challenging because of the complex causative mechanism of the disease. Metabolomic profiling offers the potential to detect new biomarkers and improve CHD risk assessment. Objective: To evaluate the association between circulating metabolites and incident CHD in a large European cohort. Design, Setting, and Participants: This population-based study used the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) case-cohort to measure circulating metabolites using a targeted approach in serum samples from 10 741 individuals without prevalent CHD. The cohort consisted of a weighted, random subcohort of the original cohort of more than 70 000 individuals. The case-cohort design was applied to 6 European cohorts: FINRISK97 (Finland), Monitoring of Trends and Determinants in Cardiovascular Diseases/Cooperative Health Research in the Region of Augsburg (MONICA/KORA; Germany), MONICA-Brianza and Moli-sani (Italy), DanMONICA (Denmark), and the Scottish Heart Health Extended Cohort (United Kingdom). Main Outcomes and Measures: Associations with time to CHD onset were assessed individually by applying weighted and adjusted Cox proportional hazard models. The association of metabolites with CHD onset was examined by C indices. Results: In 10 741 individuals (4157 women [38.7%]; median [interquartile range] age, 56.5 [49.2-62.2] years), 2166 incident CHD events (20.2%) occurred over a median (interquartile range) follow-up time of 9.2 (4.5-15.0) years. Among the 141 metabolites analyzed, 24 were significantly associated with incident CHD at a nominal P value of .05, including phosphatidylcholines (PCs), lysoPCs, amino acids, and sphingolipids. Five PCs remained significant after correction for multiple testing: acyl-alkyl-PC C40:6 (hazard ratio [HR], 1.13 [95% CI, 1.07-1.18]), diacyl-PC C40:6 (HR, 1.10 [95% CI, 1.04-1.15]), acyl-alkyl-PC C38:6 (HR, 1.11 [95% CI, 1.05-1.16]), diacyl-PC C38:6 (HR, 1.09 [95% CI, 1.04-1.14]) and diacyl-PC C38:5 (HR, 1.10 [95% CI, 1.05-1.16]). Lower levels of these metabolites were associated with increased risk of incident CHD. The strength of the associations competes with those of classic risk factors (C statistics: acyl-alkyl-PC C40:6, 0.756 [95% CI, 0.738-0.774], diacyl-PC C40:6, 0.754 [95% CI, 0.736-0.772], acyl-alkyl-PC C38:6, 0.755 [95% CI, 0.736-0.773], diacyl-PC C38:6, 0.754 [95% CI, 0.736-0.772]), diacyl-PC C38:5, 0.754 [95% CI, 0.736-0.772]). Adding metabolites to a base risk model including classic risk factors high-sensitivity C-reactive protein and high-sensitivity troponin I did not improve discrimination by C statistics. Conclusions and Relevance: Five PCs were significantly associated with increased risk of incident CHD and showed comparable discrimination with individual classic risk factors. Although these metabolites do not improve CHD risk assessment beyond that of classic risk factors, these findings hold promise for an improved understanding of the pathophysiology of CHD.


Assuntos
Aminoácidos/sangue , Doença das Coronárias/epidemiologia , Lipídeos/sangue , Metaboloma , Medição de Risco , Biomarcadores/sangue , Estudos de Coortes , Doença das Coronárias/sangue , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais
18.
Clin Endocrinol (Oxf) ; 91(5): 652-659, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31400012

RESUMO

OBJECTIVE: To investigate the impact of mandatory iodine fortification (IF) on the incidence of nosological subtypes of overt thyrotoxicosis and hypothyroidism. DESIGN: We identified and scrutinized all possible new cases of overt thyrotoxicosis and hypothyroidism in an open cohort in Northern Jutland (n = 309 434; 1 January 1997) during the years 2014-2016. Individual medical history was evaluated to verify and detail the incidence of overt thyroid dysfunction and for classification into nosological subtypes. A number of cases were excluded during final verification due to spontaneous normalization of thyroid function, as they had no medical history suggesting a known condition, which could transiently affect thyroid function (subacute/silent thyroiditis, PPTD and iatrogenic thyroid dysfunction). An identical survey was conducted in 1997-2000 prior to mandatory IF of salt (13 µg/g) that was in effect from year 2001. RESULTS: The standardized incidence rate (SIR) of verified overt thyrotoxicosis decreased markedly from 97.5/100 000/year in 1997-2000 to 48.8 in 2014-2016 (SIRR: 0.50 [95% CI: 0.45-0.56]). This was due to a distinct decrease in the SIR of multinodular toxic goitre (SIRR: 0.18 [0.15-0.23]), solitary toxic adenoma (SIRR: 0.26 [0.16-0.43]) and to a lesser degree Graves' disease (SIRR: 0.67 [0.56-0.79]). SIR for overt hypothyroidism was unaltered by 2014-2016 (SIRR: 1.03 [0.87-1.22]). However, age distribution shifted with more young and fewer elderly cases of verified overt hypothyroidism. CONCLUSION: Mandatory IF caused a substantial reduction in SIR of verified overt thyrotoxicosis (especially of nodular origin) while avoiding an increase in SIR of verified overt hypothyroidism.


Assuntos
Hipotireoidismo/dietoterapia , Hipotireoidismo/patologia , Iodo/uso terapêutico , Tireotoxicose/dietoterapia , Tireotoxicose/patologia , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/metabolismo , Cloreto de Sódio na Dieta/uso terapêutico , Testes de Função Tireóidea
19.
N Engl J Med ; 380(26): 2529-2540, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31242362

RESUMO

BACKGROUND: Data regarding high-sensitivity troponin concentrations in patients presenting to the emergency department with symptoms suggestive of myocardial infarction may be useful in determining the probability of myocardial infarction and subsequent 30-day outcomes. METHODS: In 15 international cohorts of patients presenting to the emergency department with symptoms suggestive of myocardial infarction, we determined the concentrations of high-sensitivity troponin I or high-sensitivity troponin T at presentation and after early or late serial sampling. The diagnostic and prognostic performance of multiple high-sensitivity troponin cutoff combinations was assessed with the use of a derivation-validation design. A risk-assessment tool that was based on these data was developed to estimate the risk of index myocardial infarction and of subsequent myocardial infarction or death at 30 days. RESULTS: Among 22,651 patients (9604 in the derivation data set and 13,047 in the validation data set), the prevalence of myocardial infarction was 15.3%. Lower high-sensitivity troponin concentrations at presentation and smaller absolute changes during serial sampling were associated with a lower likelihood of myocardial infarction and a lower short-term risk of cardiovascular events. For example, high-sensitivity troponin I concentrations of less than 6 ng per liter and an absolute change of less than 4 ng per liter after 45 to 120 minutes (early serial sampling) resulted in a negative predictive value of 99.5% for myocardial infarction, with an associated 30-day risk of subsequent myocardial infarction or death of 0.2%; a total of 56.5% of the patients would be classified as being at low risk. These findings were confirmed in an external validation data set. CONCLUSIONS: A risk-assessment tool, which we developed to integrate the high-sensitivity troponin I or troponin T concentration at emergency department presentation, its dynamic change during serial sampling, and the time between the obtaining of samples, was used to estimate the probability of myocardial infarction on emergency department presentation and 30-day outcomes. (Funded by the German Center for Cardiovascular Research [DZHK]; ClinicalTrials.gov numbers, NCT00470587, NCT02355457, NCT01852123, NCT01994577, and NCT03227159; and Australian New Zealand Clinical Trials Registry numbers, ACTRN12611001069943, ACTRN12610000766011, ACTRN12613000745741, and ACTRN12611000206921.).


Assuntos
Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Medição de Risco/métodos , Troponina/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sensibilidade e Especificidade , Troponina I/sangue
20.
Eur Thyroid J ; 8(2): 70-78, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31192145

RESUMO

Objective: To investigate the association between reproductive history and later development of various nosological subtypes of overt hyperthyroidism. Study Design: From the Danish population, we included incident hyperthyroid women, and for each case we recruited 4 euthyroid age-sex-region-matched controls from the same sub-population. Hyperthyroid cases/controls were: Graves' disease (GD, n = 232/928), multinodular toxic goitre (MNTG, n = 91/364), solitary toxic adenoma (STA, n = 21/84). Patients diagnosed with hyperthyroidism within 1 year after delivery including post-partum GD were excluded. In multivariate conditional regression models (reference: no reproductive events), we analysed the association between development of GD/MNTG/STA and reproductive factors such as age at menarche/menopause, reproductive span, number of pregnancies/childbirths/abortions, investigations for infertility, and years on oral contraceptives. We adjusted for possible confounders such as alcohol intake, smoking, co-morbidity, and education. Age was studied as a potential effect measure modifier. Results: GD patients diagnosed before the age of 40 years had given births more often than control subjects (OR [95% CI] for 1/2/3+ births [ref.: nulliparous] were 1.57 [0.80-3.11]/2.06 [1.001-4.22]/3.07 [1.50-6.26]), and they had induced abortions performed more often (OR for 1/2+ induced abortions [ref.: no: events] were 0.99 [0.54-1.84]/2.24 [1.12-4.45]). No associations were observed between any reproductive factor and the development of MNTG or STA. Conclusions: Childbirths and induced abortions may be followed by development of Graves' hyperthyroidism after the post-partum period. This was not the case for the non-autoimmune subtypes of hyperthyroidism.

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