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Article ; Online: Author Correction: Characterization of the genetic architecture of infant and early childhood body mass index.

Helgeland, Øyvind / Vaudel, Marc / Sole-Navais, Pol / Flatley, Christopher / Juodakis, Julius / Bacelis, Jonas / Koløen, Ingvild L / Knudsen, Gun Peggy / Johansson, Bente B / Magnus, Per / Kjennerud, Ted Reichborn / Juliusson, Petur B / Stoltenberg, Camilla / Holmen, Oddgeir L / Andreassen, Ole A / Jacobsson, Bo / Njølstad, Pål R / Johansson, Stefan

Nature metabolism

2024 Volume 6, Issue 2, Page(s) 378

Language	English
Publishing date	2024-02-09
Publishing country	Germany
Document type	Published Erratum
ISSN	2522-5812
ISSN (online)	2522-5812
DOI	10.1038/s42255-024-01004-z
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Article ; Online: Temporal Changes in Cardiac Troponin I Are Associated with Risk of Cardiovascular Events in the General Population: The Nord-Trøndelag Health Study.

Lyngbakken, Magnus N / Røsjø, Helge / Holmen, Oddgeir L / Dalen, Håvard / Hveem, Kristian / Omland, Torbjørn

Clinical chemistry

2019 Volume 65, Issue 7, Page(s) 871–881

Abstract: Background: Cardiac troponins are associated with cardiovascular risk in the general population, but whether temporal changes in cardiac troponin I provide independent prognostic information remains uncertain. Using a large community-based cohort with ... ...

Abstract	Background: Cardiac troponins are associated with cardiovascular risk in the general population, but whether temporal changes in cardiac troponin I provide independent prognostic information remains uncertain. Using a large community-based cohort with follow-up close to the present day, we aimed to investigate the associations between temporal changes in cardiac troponin and cardiovascular events. Methods: We measured cardiac troponin I with a high-sensitivity assay (hs-cTnI) in 4805 participants attending both the second (HUNT 2, 1995-97) and third wave (HUNT 3, 2006-2008) of the prospective observational Nord-Trøndelag Health (HUNT) Study. We constructed statistical models with both relative and absolute changes of hs-cTnI from HUNT 2 to HUNT 3. A composite end point of cardiovascular death or first admission for myocardial infarction or heart failure was generated. Results: Participants with relative decrease in hs-cTnI were more frequently younger and female and had lower blood pressure and body mass index. Participants with relative increase in hs-cTnI more frequently were older and male, with higher systolic blood pressure. The adjusted hazard ratio (HR) for relative increase in hs-cTnI was 1.68 (95% CI, 1.16-2.42) and the adjusted HR for relative decrease was 1.19 (95% CI, 0.84-1.68). Absolute increases in hs-cTnI exhibited similar prognostic properties as relative increases in hs-cTnI. The most recent measurement of hs-cTnI outperformed the change variables in discrimination and reclassification models. Conclusions: Both relative and absolute increases in hs-cTnI are independently associated with cardiovascular risk. For refinement of risk prediction models, the most recent measurement of hs-cTnI should be preferred in clinical practice.
MeSH term(s)	Adult ; Aged ; Biomarkers/blood ; Biomarkers/metabolism ; Cohort Studies ; Female ; Heart Failure/diagnosis ; Heart Failure/mortality ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Myocardial Infarction/diagnosis ; Myocardial Infarction/mortality ; Prognosis ; Proportional Hazards Models ; Prospective Studies ; Regression Analysis ; Risk Factors ; Troponin I/blood ; Troponin I/metabolism
Chemical Substances	Biomarkers ; Troponin I
Language	English
Publishing date	2019-04-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80102-1
ISSN	1530-8561 ; 0009-9147
ISSN (online)	1530-8561
ISSN	0009-9147
DOI	10.1373/clinchem.2018.301069
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Article ; Online: Characterization of the genetic architecture of infant and early childhood body mass index.

Nature metabolism

2022 Volume 4, Issue 3, Page(s) 344–358

Abstract: Early childhood obesity is a growing global concern; however, the role of common genetic variation on infant and child weight development is unclear. Here, we identify 46 loci associated with early childhood body mass index at specific ages, matching ... ...

Abstract	Early childhood obesity is a growing global concern; however, the role of common genetic variation on infant and child weight development is unclear. Here, we identify 46 loci associated with early childhood body mass index at specific ages, matching different child growth phases, and representing four major trajectory patterns. We perform genome-wide association studies across 12 time points from birth to 8 years in 28,681 children and their parents (27,088 mothers and 26,239 fathers) in the Norwegian Mother, Father and Child Cohort Study. Monogenic obesity genes are overrepresented near identified loci, and several complex association signals near LEPR, GLP1R, PCSK1 and KLF14 point towards a major influence for common variation affecting the leptin-melanocortin system in early life, providing a link to putative treatment strategies. We also demonstrate how different polygenic risk scores transition from birth to adult profiles through early child growth. In conclusion, our results offer a fine-grained characterization of a changing genetic landscape sustaining early childhood growth.
MeSH term(s)	Adult ; Body Mass Index ; Child ; Child, Preschool ; Cohort Studies ; Female ; Genome-Wide Association Study ; Humans ; Infant ; Mothers ; Pediatric Obesity
Language	English
Publishing date	2022-03-21
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2522-5812
ISSN (online)	2522-5812
DOI	10.1038/s42255-022-00549-1
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Article ; Online: Prediction of Ankylosing Spondylitis in the HUNT Study by a Genetic Risk Score Combining 110 Single-nucleotide Polymorphisms of Genome-wide Significance.

Rostami, Sina / Hoff, Mari / Brown, Matthew A / Hveem, Kristian / Holmen, Oddgeir L / Fritsche, Lars G / Videm, Vibeke

The Journal of rheumatology

2019 Volume 47, Issue 2, Page(s) 204–210

Abstract: Objective: The genetic component of ankylosing spondylitis (AS) development is ∼90%. Of the known heritability, ∼20% is explained by HLA-B27, and 113 identified AS-associated single-nucleotide polymorphisms (SNP) account for ∼7.4%. The objectives were ... ...

Abstract	Objective: The genetic component of ankylosing spondylitis (AS) development is ∼90%. Of the known heritability, ∼20% is explained by HLA-B27, and 113 identified AS-associated single-nucleotide polymorphisms (SNP) account for ∼7.4%. The objectives were to construct a weighted genetic risk score (wGRS) using currently known genome-wide susceptibility SNP, and to evaluate its predictive ability for AS in the Norwegian population-based Nord-Trøndelag Health Study (HUNT). Methods: AS cases (n = 164) and controls (n = 49,032) were from the second (1995-1997) and third (2006-2008) waves of the HUNT study, to which the entire adult population of the northern region of Trøndelag was invited. A wGRS based on 110 SNP weighted by published OR for AS was constructed, representing each person's carriage of all risk variants. Logistic regression models including the wGRS alone or in combination with HLA-B27 carrier state and other adjustment variables (sex, age, smoking, body mass index, and hypertension) were developed. Discrimination among models was compared using area under the curve (AUC). Results: The wGRS was associated with AS (OR 1.7, 95% CI 1.4-2.1), but showed low discrimination (AUC 0.62, 95% CI 0.58-0.67). HLA-B27 was significantly associated with AS (OR 50, 95% CI 32-81), showing high discrimination (AUC 0.88, 95% CI 0.85-0.90). Combining the wGRS and HLA-B27 improved prediction (AUC 0.90, 95% CI 0.87-0.92; p < 0.001 vs wGRS alone, p < 0.01 vs HLA-B27 alone). Further inclusion of adjustment variables gave a small improvement (AUC 0.91, 95% CI 0.89-0.94; p = 0.03). Conclusion: Prediction in a population-based setting based on all currently known AS susceptibility SNP was better than HLA-B27 carrier state alone, although the improvement was small and of uncertain clinical value.
MeSH term(s)	Adult ; Aged ; Area Under Curve ; Case-Control Studies ; Cohort Studies ; Female ; Genetic Predisposition to Disease ; Genome-Wide Association Study/methods ; Genotype ; HLA-B27 Antigen/genetics ; Humans ; Logistic Models ; Male ; Middle Aged ; Norway/epidemiology ; Polymorphism, Single Nucleotide ; Prognosis ; Risk ; Spondylitis, Ankylosing/epidemiology ; Spondylitis, Ankylosing/genetics
Chemical Substances	HLA-B27 Antigen
Language	English
Publishing date	2019-04-01
Publishing country	Canada
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	194928-7
ISSN	1499-2752 ; 0315-162X
ISSN (online)	1499-2752
ISSN	0315-162X
DOI	10.3899/jrheum.181209
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Article ; Online: Relative Prognostic Value of Cardiac Troponin I and C-Reactive Protein in the General Population (from the Nord-Trøndelag Health [HUNT] Study).

Sigurdardottir, Fjola D / Lyngbakken, Magnus N / Holmen, Oddgeir L / Dalen, Håvard / Hveem, Kristian / Røsjø, Helge / Omland, Torbjørn

The American journal of cardiology

2018 Volume 121, Issue 8, Page(s) 949–955

Abstract: C-reactive protein and cardiac troponin I measured with high-sensitivity assays (high-sensitivity C-reactive protein [hs-CRP] and high-sensitivity troponin I [hs-TnI]) have been associated with risk of fatal and nonfatal cardiovascular events in the ... ...

Abstract	C-reactive protein and cardiac troponin I measured with high-sensitivity assays (high-sensitivity C-reactive protein [hs-CRP] and high-sensitivity troponin I [hs-TnI]) have been associated with risk of fatal and nonfatal cardiovascular events in the general population. The relative prognostic merits of hs-CRP and hs-TnI, and whether these markers of inflammation and subclinical myocardial injury provide incremental information to established cardiovascular risk prediction models, remain unclear. hs-CRP and hs-TnI were measured in 9,005 participants from the prospective observational Nord-Trøndelag Health (HUNT) study. All study subjects were free from known cardiovascular disease at baseline. During a median follow-up period of 13.9 years, 733 participants reached the composite end point of hospitalization for acute myocardial infarction or heart failure, or cardiovascular death. In adjusted models, increased hs-TnI concentrations (>10 ng/L for women and >12 ng/L for men) were associated with the incidence of the composite end point (hazard ratio 3.61, 95% confidence interval [CI] 2.89 to 4.51]), whereas the risk associated with increased hs-CRP concentrations (>3 mg/L for both genders) appeared to be weaker (HR 1.71, 95% CI 1.40 to 2.10). The addition of hs-TnI to established cardiovascular risk prediction models led to a net reclassification improvement of 0.35 (95% CI 0.27 to 0.42), superior to that of hs-CRP (0.21, 95% CI 0.13 to 0.28). The prognostic accuracy of hs-TnI, assessed by C-statistics, was significantly greater than that of hs-CRP (0.753, 95% CI 0.735 to 0.772, vs 0.644, 95% CI 0.625 to 0.663). In conclusion, in subjects from the general population without a history of cardiovascular disease, hs-TnI provides prognostic information superior to that provided by hs-CRP and may therefore be a preferred marker for targeted prevention.
MeSH term(s)	Adult ; Aged ; C-Reactive Protein/metabolism ; Cardiovascular Diseases/metabolism ; Cardiovascular Diseases/mortality ; Cohort Studies ; Female ; Heart Failure/epidemiology ; Heart Failure/metabolism ; Hospitalization ; Humans ; Incidence ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Myocardial Infarction/epidemiology ; Myocardial Infarction/metabolism ; Norway/epidemiology ; Prognosis ; Proportional Hazards Models ; Prospective Studies ; Risk Assessment ; Troponin I/metabolism
Chemical Substances	Troponin I ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2018-02-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80014-4
ISSN	1879-1913 ; 0002-9149
ISSN (online)	1879-1913
ISSN	0002-9149
DOI	10.1016/j.amjcard.2018.01.004
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Article ; Online: Association between the G protein β3 subunit C825T polymorphism and the occurrence of cardiovascular disease in hypertensives: The Nord-Trøndelag Health Study (HUNT).

Holmen, Oddgeir L / Romundstad, Solfrid / Melien, Oyvind

American journal of hypertension

2010 Volume 23, Issue 10, Page(s) 1121–1127

Abstract: Background: Several studies examining the C825T polymorphism of the G protein β3 subunit (GNB3) have shown inconsistent results regarding susceptibility to hypertension. With twice the length of earlier studies, the aim of our study was to further ... ...

Abstract	Background: Several studies examining the C825T polymorphism of the G protein β3 subunit (GNB3) have shown inconsistent results regarding susceptibility to hypertension. With twice the length of earlier studies, the aim of our study was to further investigate this association with a cross-sectional design over an 11.5-year follow-up period in a Norwegian population. Methods: Two randomized selected population samples from the Nord-Trøndelag Health Study 1995-1997 (HUNT 2) were genotyped. One sample included individuals reporting use of antihypertensive medication (n = 969), and the other did not report use of antihypertensive medication, cardiovascular disease (CVD), or diabetes (n = 1,867). Of those genotyped, 2,254 participants (79.5%) also attended HUNT 1 in 1984-1986. Results: There was no significant higher prevalence of hypertension (blood pressure ≥140/90 mm Hg and/or antihypertensive medication) in T-allele carriers than in C allele carriers. However, TT homozygous men with treated hypertension showed statistical significant association with self-reported CVD compared to the CC genotype (odds ratio (OR) 3.19, P = 0.001). No statistical significant association between hypertension and the C825T polymorphism was found during the follow-up. Conclusions: No association was found between the C285T polymorphism of the GNB3 and hypertension. However, CVD was more common among treated hypertensive men with the TT genotype compared to men with the CC genotype. Thus, further studies are needed to explore whether this finding could be caused by other mechanisms than elevated blood pressure.
MeSH term(s)	Aged ; Alleles ; Antihypertensive Agents/therapeutic use ; Blood Pressure/physiology ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/genetics ; DNA/genetics ; Female ; Genetic Association Studies ; Genotype ; Heterotrimeric GTP-Binding Proteins/genetics ; Humans ; Hypertension/drug therapy ; Hypertension/epidemiology ; Hypertension/genetics ; Logistic Models ; Male ; Middle Aged ; Norway/epidemiology ; Polymorphism, Genetic/genetics ; Reverse Transcriptase Polymerase Chain Reaction
Chemical Substances	Antihypertensive Agents ; G-protein beta3 subunit ; DNA (9007-49-2) ; Heterotrimeric GTP-Binding Proteins (EC 3.6.5.1)
Language	English
Publishing date	2010-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	639383-4
ISSN	1941-7225 ; 1879-1905 ; 0895-7061
ISSN (online)	1941-7225 ; 1879-1905
ISSN	0895-7061
DOI	10.1038/ajh.2010.121
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Article ; Online: Hypertension after preeclampsia and relation to the C1114G polymorphism (rs4606) in RGS2: data from the Norwegian HUNT2 study.

Kvehaugen, Anne Stine / Melien, Øyvind / Holmen, Oddgeir L / Laivuori, Hannele / Dechend, Ralf / Staff, Anne Cathrine

BMC medical genetics

2014 Volume 15, Page(s) 28

Abstract: Background: Preeclampsia is associated with an increased risk of hypertension later in life. The regulator of G protein signaling 2 negatively regulates several vasoconstrictors. We recently demonstrated an association between preeclampsia and the CG or ...

Abstract	Background: Preeclampsia is associated with an increased risk of hypertension later in life. The regulator of G protein signaling 2 negatively regulates several vasoconstrictors. We recently demonstrated an association between preeclampsia and the CG or GG genotype of the C1114G polymorphism (rs4606) of the regulator of G protein signaling 2 gene. Here, we examined the polymorphism with respect to the development of hypertension after pregnancy. Methods: We genotyped 934 women on average 15.1 years after preeclampsia and 2011 age matched women with previous normotensive pregnancy. All women in this study were retrospectively recruited from the Nord-Trøndelag Health Study (HUNT2). Information from HUNT2 was linked to the Medical Birth Registry of Norway to identify women with a history of preeclampsia and women without a history of preeclampsia. Results: No significant association was found between hypertension (blood pressure ≥140/90 mmHg and/or taking antihypertensive drugs) and the polymorphism in crude analysis (OR (95% CI): CG genotype: 1.07 (0.90-1.27); GG genotype: 1.23 (0.90-1.67)). However, in a minimally adjusted model (age and BMI adjusted), a significant association between the GG genotype and hypertension was found (OR (95% CI): 1.49 (1.05-2.11)). This association remained significant also after adjustment for a history of preeclampsia (OR (95% CI): 1.46 (1.02-2.09)), but not in a model adjusted for multiple other variables (OR (95% CI): 1.26 (0.82-1.94)). In multivariate, but not in crude, analysis, the GG genotype of rs4606 (OR (95% CI): 1.93 (1.05-3.53)) was significantly and independently associated with severe hypertension later in life, defined as systolic blood pressure ≥160 mmHg (stage 2 hypertension) and/or taking antihypertensive drugs. A significant association was also found for the merged CG and GG genotypes (OR (95% CI): 1.43 (1.02-2.00)). Moreover, an interaction with physical activity was found. A history of preeclampsia was a significant and independent predictor of either definition of hypertension, both in crude and adjusted analyses. Conclusion: Women carrying the rs4606 CG or GG genotype are at elevated risk for developing hypertension after delivery. Physical activity may interact with the association. Preeclampsia remains an independent risk factor for subsequent hypertension after adjusting for this polymorphism and classical CVD risk factors.
MeSH term(s)	Adult ; Case-Control Studies ; Exercise ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hypertension/epidemiology ; Hypertension/genetics ; Norway ; Polymorphism, Single Nucleotide ; Pre-Eclampsia/epidemiology ; Pre-Eclampsia/genetics ; Pregnancy ; Prevalence ; RGS Proteins/genetics ; Risk Factors
Chemical Substances	RGS Proteins ; RGS2 protein, human
Language	English
Publishing date	2014-03-05
Publishing country	England
Document type	Journal Article
ISSN	1471-2350
ISSN (online)	1471-2350
DOI	10.1186/1471-2350-15-28
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Article ; Online: Gender, High-Sensitivity Troponin I, and the Risk of Cardiovascular Events (from the Nord-Trøndelag Health Study).

Lyngbakken, Magnus Nakrem / Røsjø, Helge / Holmen, Oddgeir L / Nygård, Ståle / Dalen, Håvard / Hveem, Kristian / Omland, Torbjørn

The American journal of cardiology

2016 Volume 118, Issue 6, Page(s) 816–821

Abstract: Gender is an important determinant of cardiovascular risk, and men generally develop cardiovascular disease earlier than women. Increased levels of high-sensitivity cardiac troponin I (hs-TnI) have been shown to be predictive of cardiovascular death, ... ...

Abstract	Gender is an important determinant of cardiovascular risk, and men generally develop cardiovascular disease earlier than women. Increased levels of high-sensitivity cardiac troponin I (hs-TnI) have been shown to be predictive of cardiovascular death, with stronger effects in women. However, it remains unclear whether the stronger association between hs-TnI and cardiovascular death in women is based on the ability of hs-TnI to predict myocardial infarction (MI) or heart failure (HF). Accordingly, we aimed to assess the influence of gender on the association between levels of hs-TnI and incident MI and HF. hs-TnI was measured in 5,060 women and 4,054 men participating in the prospective observational Nord-Trøndelag Health Study using the Architect STAT High-Sensitive Troponin assay. All subjects were free from known coronary heart disease at baseline. After a median follow-up of 5,105 and 6,169 days, 292 MIs and 209 admissions for HF were registered, respectively. In our total cohort, hs-TnI was associated with the incidence of both end points, with adjusted hazard ratio per 1 SD in log hs-TnI 1.19 (95% CI 1.02 to 1.39) for MI and 1.58 (1.38 to 1.82) for HF. The corresponding values for women and men were 1.35 (1.02 to 1.78) versus 1.13 (0.93 to 1.38) for MI and 1.55 (1.26 to 1.91) versus 1.61 (1.36 to 1.90) for HF. The C-index for hs-TnI was stronger for women than men for MI (p <0.001), and no such difference was observed for HF (p = 0.06). In conclusion, in the general population, the association between hs-TnI concentrations and MI is stronger in women than in men. For HF, the impact of gender on the prognostic value of hs-TnI is less pronounced. Increased levels of troponin I in women may thus reflect an adverse phenotype more prone to the development of cardiovascular disease.
MeSH term(s)	Adult ; Biomarkers/blood ; Cohort Studies ; Female ; Heart Failure/blood ; Heart Failure/epidemiology ; Humans ; Incidence ; Male ; Middle Aged ; Myocardial Infarction/blood ; Myocardial Infarction/epidemiology ; Norway/epidemiology ; Prognosis ; Proportional Hazards Models ; Prospective Studies ; Sex Factors ; Troponin I/blood
Chemical Substances	Biomarkers ; Troponin I
Language	English
Publishing date	2016-09-15
Publishing country	United States
Document type	Journal Article ; Observational Study
ZDB-ID	80014-4
ISSN	1879-1913 ; 0002-9149
ISSN (online)	1879-1913
ISSN	0002-9149
DOI	10.1016/j.amjcard.2016.06.043
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Article ; Online: The HUNT study: A population-based cohort for genetic research.

Brumpton, Ben M / Graham, Sarah / Surakka, Ida / Skogholt, Anne Heidi / Løset, Mari / Fritsche, Lars G / Wolford, Brooke / Zhou, Wei / Nielsen, Jonas Bille / Holmen, Oddgeir L / Gabrielsen, Maiken E / Thomas, Laurent / Bhatta, Laxmi / Rasheed, Humaira / Zhang, He / Kang, Hyun Min / Hornsby, Whitney / Moksnes, Marta Riise / Coward, Eivind /

Melbye, Mads / Giskeødegård, Guro F / Fenstad, Jørn / Krokstad, Steinar / Næss, Marit / Langhammer, Arnulf / Boehnke, Michael / Abecasis, Gonçalo R / Åsvold, Bjørn Olav / Hveem, Kristian / Willer, Cristen J

Cell genomics

2022 Volume 2, Issue 10, Page(s) 100193

Abstract: The Trøndelag Health Study (HUNT) is a population-based cohort of ∼229,000 individuals recruited in four waves beginning in 1984 in Trøndelag County, Norway. Approximately 88,000 of these individuals have available genetic data from array genotyping. ... ...

Abstract	The Trøndelag Health Study (HUNT) is a population-based cohort of ∼229,000 individuals recruited in four waves beginning in 1984 in Trøndelag County, Norway. Approximately 88,000 of these individuals have available genetic data from array genotyping. HUNT participants were recruited during four community-based recruitment waves and provided information on health-related behaviors, self-reported diagnoses, family history of disease, and underwent physical examinations. Linkage via the Norwegian personal identification number integrates digitized health care information from doctor visits and national health registries including death, cancer and prescription registries. Genome-wide association studies of HUNT participants have provided insights into the mechanism of cardiovascular, metabolic, osteoporotic, and liver-related diseases, among others. Unique features of this cohort that facilitate research include nearly 40 years of longitudinal follow-up in a motivated and well-educated population, family data, comprehensive phenotyping, and broad availability of DNA, RNA, urine, fecal, plasma, and serum samples.
Language	English
Publishing date	2022-10-12
Publishing country	United States
Document type	Journal Article
ISSN	2666-979X
ISSN (online)	2666-979X
DOI	10.1016/j.xgen.2022.100193
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Article ; Online: Impact of sex on the prognostic value of high-sensitivity cardiac troponin I in the general population: the HUNT study.

Omland, Torbjørn / de Lemos, James A / Holmen, Oddgeir L / Dalen, Håvard / Benth, Jūratė Šaltytė / Nygård, Ståle / Hveem, Kristian / Røsjø, Helge

Clinical chemistry

2015 Volume 61, Issue 4, Page(s) 646–656

Abstract: Background: A new, high-sensitivity assay for cardiac troponin I (hs-cTnI) permits evaluation of the prognostic value of cardiac troponins within the reference interval. Men have higher hs-cTnI concentrations than women, but the underlying ... ...

Abstract	Background: A new, high-sensitivity assay for cardiac troponin I (hs-cTnI) permits evaluation of the prognostic value of cardiac troponins within the reference interval. Men have higher hs-cTnI concentrations than women, but the underlying pathophysiological mechanisms and prognostic implications are unclear. The aim of this study was to assess the potential impact of sex on the association between hs-cTnI and cardiovascular death. Methods: By use of the Architect STAT High-Sensitive Troponin assay, we measured hs-cTnI in 4431 men and 5281 women aged ≥20 years participating in the prospective observational Nord-Trøndelag Health Study (HUNT). Results: hs-cTnI was detectable in 98.5% of men and 94.7% of women. During a mean follow-up period of 13.9 years, 708 cardiovascular deaths were registered. hs-cTnI was associated with the incidence of cardiovascular death [adjusted hazard ratio (HR) per 1 SD in log hs-cTnI 1.23 (95% CI 1.15-1.31)], with higher relative risk in women than men [HR 1.44 (1.31-1.58) vs 1.10 (1.00-1.20); Pinteraction < 0.001]. This finding was mediated by both lower risk associated with low hs-cTnI concentrations in women than in men and higher risk associated with high concentrations of hs-cTnI in women than in men. Male sex was associated with a higher risk of cardiovascular death [HR 1.28 (1.11-1.49)], but after adjustment for hs-cTnI, this association disappeared [HR 0.87 (0.75-1.02)]. Conclusions: The prognostic value of hs-cTnI concentrations in the general population is stronger in women than in men. Subtle impairment of cardiovascular status may contribute to higher hs-cTnI concentrations in men, reflecting sex-dependent differences in cardiovascular risk.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Biomarkers/blood ; Cardiovascular Diseases/mortality ; Cohort Studies ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Norway/epidemiology ; Predictive Value of Tests ; Proportional Hazards Models ; Prospective Studies ; ROC Curve ; Sex Factors ; Troponin I/blood ; Young Adult
Chemical Substances	Biomarkers ; Troponin I
Language	English
Publishing date	2015-02-18
Publishing country	England
Document type	Journal Article ; Observational Study
ZDB-ID	80102-1
ISSN	1530-8561 ; 0009-9147
ISSN (online)	1530-8561
ISSN	0009-9147
DOI	10.1373/clinchem.2014.234369
Database	MEDical Literature Analysis and Retrieval System OnLINE

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