Publications by authors named "Grethe S Tell"

235 Publications

Assessment of Dietary Choline Intake, Contributing Food Items and Associations with One-carbon and Lipid Metabolites in Middle-aged and Elderly Adults: The Hordaland Health Study.

J Nutr 2021 Oct 13. Epub 2021 Oct 13.

Centre for Nutrition, Department of Clinical Science, University of Bergen, Bergen, Norway.

Background: Choline is an essential nutrient for humans and is involved in various physiological functions. Through its metabolite betaine, it is closely connected to the one-carbon metabolism and the fat-soluble choline form phosphatidylcholine is essential for very-low-density-lipoprotein synthesis and secretion in the liver connecting choline to the lipid metabolism. Dietary recommendations for choline are not available in the Nordic countries primarily due to data scarcity.

Objective: The aim of this study was to investigate the dietary intake of total choline and individual choline forms, dietary sources, and the association of total choline intake with circulating one-carbon metabolites and lipids.

Methods: We included 5746 participants in the Hordaland Health Study (HUSK), a survey including community-dwelling adults born in 1925-1927 (mean age 72 years, 55% women) and 1950-1951 (mean age 48 years, 57% women). Dietary data was obtained using a 169-item food frequency questionnaire and choline content was calculated using the USDA Database for Choline Content of Common Foods, release 2. Metabolites of the one-carbon and lipid metabolism were measured in a non-fasting blood sample obtained at baseline and association with total choline intake were assessed using polynomial splines.

Results: The geometric mean (95% prediction interval) energy-adjusted total choline intake was 260 (170, 389) mg/d with phosphatidylcholine being the main form (44%). The major food items providing dietary choline were eggs, low-fat milk, potatoes, and leafy vegetables. Dietary total choline was inversely associated with circulating concentrations of total homocysteine, glycine and serine and positively associated with choline, methionine, cystathionine, cysteine, trimethyllysine, trimethylamine-N-oxide and dimethylglycine. A weak association was observed between choline intake and serum lipids.

Conclusion: Phosphatidylcholine was the most consumed choline form in community-dwelling adults in Norway. Our findings suggest that choline intake is associated with the concentration of most metabolites involved in the one-carbon and lipid metabolism.
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http://dx.doi.org/10.1093/jn/nxab367DOI Listing
October 2021

Associations of overweight, obesity and osteoporosis with ankle fractures.

BMC Musculoskelet Disord 2021 Aug 23;22(1):723. Epub 2021 Aug 23.

Department of Rheumatology, Division of Medicine, District General Hospital of Førde, Førde, Norway.

Background: Studies exploring risk factors for ankle fractures in adults are scarce, and with diverging conclusions. This study aims to investigate whether overweight, obesity and osteoporosis may be identified as risk factors for ankle fractures and ankle fracture subgroups according to the Danis-Weber (D-W) classification.

Methods: 108 patients ≥40 years with fracture of the lateral malleolus were included. Controls were 199 persons without a previous fracture history. Bone mineral density of the hips and spine was measured by dual-energy x-ray absorptiometry, and history of previous fracture, comorbidities, medication, physical activity, smoking habits, body mass index and nutritional factors were registered.

Results: Higher body mass index with increments of 5 gave an adjusted odds ratio (OR) of 1.30 (95% confidence interval (CI) 1.03-1.64) for ankle fracture, and an adjusted OR of 1.96 (CI 0.99-4.41) for sustaining a D-W type B or C fracture compared to type A. Compared to patients with normal bone mineral density, the odds of ankle fracture in patients with osteoporosis was 1.53, but the 95% CI was wide (0.79-2.98). Patients with osteoporosis had reduced odds of sustaining a D-W fracture type B or C compared to type A (OR 0.18, CI 0.03-0.83).

Conclusions: Overweight increased the odds of ankle fractures and the odds of sustaining an ankle fracture with possible syndesmosis disruption and instability (D-W fracture type B or C) compared to the stable and more distal fibula fracture (D-W type A). Osteoporosis did not significantly increase the odds of ankle fractures, thus suffering an ankle fracture does not automatically warrant further osteoporosis assessment.
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http://dx.doi.org/10.1186/s12891-021-04607-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381556PMC
August 2021

Effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in atrial fibrillation: a scandinavian population-based cohort study.

Eur Heart J Qual Care Clin Outcomes 2021 Jul 9. Epub 2021 Jul 9.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Aims: Using Scandinavian population-based registries, we assessed risk of stroke/systemic embolism (SE) and bleeding with non-vitamin K antagonist oral anticoagulants compared with warfarin in oral anticoagulation-naïve patients with atrial fibrillation (AF).

Methods And Results: This historical cohort study included 219,545 AF patients (median age, 74 years; 43% women; mean CHA2DS2-VASc score 3.3) initiating apixaban, dabigatran, rivaroxaban, or warfarin in Denmark, Norway, and Sweden 01JAN2013-31DEC2016. The primary endpoints were stroke/SE and major bleeding. The median follow-up times were 9.7 (3.9-21.5) months for stroke/SE and 9.6 (3.8-21.3) months for bleeding. Apixaban and warfarin initiators were older and had higher CHA2DS2-VASc scores compared with dabigatran and rivaroxaban initiators. After 1:1 propensity score matching, three cohorts were created: apixaban-warfarin (n = 111,162), dabigatran-warfarin (n = 56,856), and rivaroxaban-warfarin (n = 61,198). Adjusted hazard ratios (HRs) were estimated using a Cox regression. For stroke/SE, adjusted HRs against warfarin were 0.96 (95% confidence interval [CI], 0.87-1.06) for apixaban; 0.89 (95% CI, 0.80-1.00) for dabigatran; and 1.03 (95% CI, 0.92-1.14) for rivaroxaban. For major bleeding, the HRs against warfarin were 0.73 (95% CI, 0.67-0.78) for apixaban; 0.89 (95% CI, 0.82-0.97) for dabigatran; and 1.15 (95% CI, 1.07-1.25) for rivaroxaban. The results in the dabigatran cohort did not hold in all dosedefined subgroups.

Conclusions: In this large Scandinavian study among AF patients initiating oral anticoagulation, those initiating dabigatran, apixaban, and rivaroxaban had similar rates of stroke/SE as patients initiating warfarin. Rates of major bleeding were lower with apixaban and dabigatran and higher with rivaroxaban, each compared with warfarin.
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http://dx.doi.org/10.1093/ehjqcco/qcab048DOI Listing
July 2021

Association of markers of inflammation, the kynurenine pathway and B vitamins with age and mortality, and a signature of inflammaging.

J Gerontol A Biol Sci Med Sci 2021 Jun 12. Epub 2021 Jun 12.

Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia.

Background: Inflammation is a key feature of aging. We aimed to i) investigate the association of 34 blood markers potentially involved in inflammatory processes with age and mortality, ii) develop a signature of 'inflammaging'.

Methods: Thirty-four blood markers relating to inflammation, B vitamin status and the kynurenine pathway were measured in 976 participants in the Melbourne Collaborative Cohort Study at baseline (median age=59 years) and follow-up (median age=70 years). Associations with age and mortality were assessed using linear and Cox regression, respectively. A parsimonious signature of inflammaging was developed and its association with mortality was compared with two marker scores calculated across all markers associated with age and mortality, respectively.

Results: The majority of markers (30/34) were associated with age, with stronger associations observed for neopterin, cystatin C, IL-6, TNF-α, several markers of the kynurenine pathway and derived indices KTR (kynurenine/tryptophan ratio), PAr index (ratio of 4-pyridoxic acid and the sum of pyridoxal 5´-phosphate and pyridoxal), and HK:XA (3-hydroxykynurenine/xanthurenic acid ratio). Many markers (17/34) showed an association with mortality, in particular IL-6, neopterin, CRP, quinolinic acid, PAr index, and KTR. The inflammaging signature included ten markers and was strongly associated of mortality (HR per SD=1.40, 95%CI:1.24-1.57, P=2x10 -8), similar to scores based on all age-associated (HR=1.38, 95%CI:1.23-1.55, P=4x10 -8) and mortality-associated markers (HR=1.43, 95%CI:1.28-1.60, P=1x10 -10), respectively. Strong evidence of replication of the inflammaging signature association with mortality was found in the Hordaland Health Study.

Conclusion: Our study highlights the key role of the kynurenine pathway and vitamin B6 catabolism in aging, along with other well-established inflammation-related markers. A signature of inflammaging based on ten markers was strongly associated with mortality.
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http://dx.doi.org/10.1093/gerona/glab163DOI Listing
June 2021

Examining the lower range of the association between alcohol intake and risk of incident hospitalization with atrial fibrillation.

Int J Cardiol Heart Vasc 2020 Dec 29;31:100679. Epub 2020 Nov 29.

Department of Community Medicine and Global Health, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway.

Background: Evidence is sparse on the association between alcohol intakes in the lower range and risk of atrial fibrillation (AF). We aimed to investigate self-reported low and moderate alcohol intakes and subsequent risk of incident AF among current drinkers.

Methods: Norwegian population-based health examination surveys assessing self-reported daily alcohol intake (mean grams per day) were linked to health and population registers. Hazard ratios (HR) (95% confidence interval) for time to incident (first) hospitalization with AF by alcohol intake level were assessed by Cox regression, with adjustment for educational level and cardiovascular risk factors except blood pressure.

Results: The study population included 234,392 participants (49% men). Incident hospitalization with AF was identified in 5043 (2.2%) persons during a mean follow-up of 9 years. Compared to a very low alcohol intake of <1 unit weekly, a moderate consumption in the range of 1 to <2 units daily increased the risk of incident AF by 18% (HR 1.18 [1.06-1.32]). The average risk of incident AF increased by 9% per daily alcohol unit of 12 g (HR 1.09 [1.03, 1.14]). In sex-stratified analyses significant associations were found in men only.

Conclusions: We found that less than two alcohol units/day significantly increased the risk of incident AF, however, in men only. Reduction of even a moderate alcohol intake may thus reduce the risk of AF at the population level.
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http://dx.doi.org/10.1016/j.ijcha.2020.100679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164130PMC
December 2020

Primary cardiovascular risk prediction by LDL-cholesterol in Caucasian middle-aged and older adults: a joint analysis of three cohorts.

Eur J Prev Cardiol 2021 Jun 1. Epub 2021 Jun 1.

Zora Biosciences Oy, Tietotie 2C, 02150 Espoo, Finland.

Aims: Low-density lipoprotein cholesterol (LDL-C) is an established causal driver of atherosclerotic cardiovascular disease (ASCVD), but its performance and age-dependency as a biomarker for incident events and mortality arising from ASCVD is less clear. The aim was to determine the value of LDL-C as a susceptibility/risk biomarker for incident coronary heart disease (CHD), ASCVD, and stroke events and deaths, for the age groups <50 and ≥50 years.

Methods And Results: The performance of LDL-C was evaluated in three cohorts, FINRISK 2002 (n = 7709), HUSK (n = 5431), and ESTHER (n = 4559), by Cox proportional hazards models, C-statistics, and net reclassification index calculations. Additionally, the hazard ratios (HRs) for the three cohorts were pooled by meta-analysis. The most consistent association was observed for CHD [95% confidence interval (CI) for HRs per standard deviation ranging from 0.99 to 1.37], whereas the results were more modest for ASCVD (0.96-1.18) due to lack of association with stroke (0.77-1.24). The association and discriminatory value of LDL-C with all endpoints in FINRISK 2002 and HUSK were attenuated in subjects 50 years and older [HRs (95% CI) obtained from meta-analysis 1.11 (1.04-1.18) for CHD, 1.15 (1.02-1.29) for CHD death, 1.02 (0.98-1.06) for ASCVD, 1.12 (1.02-1.23) for ASCVD death, and 0.97 (0.89-1.05) for stroke].

Conclusion: In middle-aged and older adults, associations between LDL-C and all the studied cardiovascular endpoints were relatively weak, while LDL-C showed stronger association with rare events of pre-mature CHD or ASCVD death among middle-aged adults. The predictive performance of LDL-C also depends on the studied cardiovascular endpoint.
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http://dx.doi.org/10.1093/eurjpc/zwab075DOI Listing
June 2021

Stage 1 hypertension, sex, and acute coronary syndromes during midlife: the Hordaland Health Study.

Eur J Prev Cardiol 2021 May 16. Epub 2021 May 16.

Department of Clinical Science, University of Bergen, PO Box 7804, 5020 Bergen, Norway.

Aims: Hypertension has been suggested as a stronger risk factor for acute coronary syndromes (ACS) in women than men. Whether this also applies to stage 1 hypertension [blood pressure (BP) 130-139/80-89 mmHg] is not known.

Methods And Results: We tested associations of stage 1 hypertension with ACS in 12 329 participants in the Hordaland Health Study (mean baseline age 41 years, 52% women). Participants were grouped by baseline BP category: Normotension (BP < 130/80 mmHg), stage 1 and stage 2 hypertension (BP ≥140/90 mmHg). ACS was defined as hospitalization or death due to myocardial infarction or unstable angina pectoris during 16 years of follow-up. At baseline, a lower proportion of women than men had stage 1 and 2 hypertension, respectively (25 vs. 35% and 14 vs. 31%, P < 0.001). During follow-up, 1.4% of women and 5.7% of men experienced incident ACS (P < 0.001). Adjusted for diabetes, smoking, body mass index, cholesterol, and physical activity, stage 1 hypertension was associated with higher risk of ACS in women [hazard ratio (HR) 2.18, 95% confidence interval (CI) 1.32-3.60], while the association was non-significant in men (HR 1.30, 95% CI 0.98-1.71). After additional adjustment for systolic and diastolic BP, respectively, stage 1 diastolic hypertension was associated with ACS in women (HR 2.79 [95% CI 1.62-4.82]), but not in men (HR 1.24 [95% CI 0.95-1.62]), while stage 1 systolic hypertension was not associated with ACS in either sex.

Conclusion: Among subjects in their early 40s, stage 1 hypertension was a stronger risk factor for ACS during midlife in women than in men.
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http://dx.doi.org/10.1093/eurjpc/zwab068DOI Listing
May 2021

Use of patient-reported outcome measures (PROMs) in clinical diabetes consultations: the DiaPROM randomised controlled pilot trial.

BMJ Open 2021 04 14;11(4):e042353. Epub 2021 Apr 14.

Department of Health and Caring Sciences, Western Norway University of Applied Sciences, Bergen, Norway.

Objective: To pilot test the proposed DiaPROM trial components and address uncertainties associated with conducting a full-scale randomised controlled trial (RCT) to evaluate whether such a trial is feasible.

Design: Two-arm pilot RCT.

Participants: Adults aged ≥18-39 years, with minimum 1 year type 1 diabetes duration, attending outpatient follow-up. Exclusion criteria were pregnancy, severe cognitive, somatic or psychiatric conditions and impaired vision.

Randomisation And Intervention: All participants completed electronic Patient-Reported Outcome Measures (PROMs) prior to the annual diabetes consultation. Using computer-generated block-randomisation without blinding, we assigned participants in a 1:1 ratio stratified by sex to receive standard care or an intervention. Physicians reviewed diabetes distress scores () and referred individuals with scores ≥30 or single item(s) ≥3 to minimum two diabetes nurse consultations where reported problems were reviewed and discussed.

Outcomes: Recruitment and retention rates; participants perceptions about intervention components. Variance and estimated between-group differences in follow-up scores ( (DDS), , and ) and DDS correlation with baseline scores, to assist sample size calculations.

Results: We randomised 80 participants to the control or intervention arm (one participant was later excluded). 23/39 intervention arm participants qualified for additional consultations and 17 attended. 67/79 attended the 12-month follow-up (15.2% attrition); 5/17 referred to additional consultations were lost to follow-up (29.4% attrition). Participants reported PROMs as relevant (84.6%) and acceptable (97.4%) but rated the usefulness of consultations as moderate to low. Baseline mean±SD DDS score was 2.1±0.69; DDS SD was 0.71 (95% CI: 0.60 to 0.86) at follow-up; correlation between baseline and follow-up DDS scores was 0.8 (95% CI: 0.7 to 0.9).

Conclusions: The pilot trial revealed need for intervention modifications ahead of a full-scale trial to evaluate use of PROMs in diabetes consultations. Specifically, participant acceptability and intervention implementation need further investigation.
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http://dx.doi.org/10.1136/bmjopen-2020-042353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054082PMC
April 2021

Associations of Binge Drinking With the Risks of Ischemic Heart Disease and Stroke: A Study of Pooled Norwegian Health Surveys.

Am J Epidemiol 2021 08;190(8):1592-1603

Norwegian health survey data (1987-2003) were analyzed to determine if binge drinking increases the risk of incident major events from ischemic heart disease (IHD) and stroke. Among current drinkers reporting average alcohol intakes of 2.00-59.99 g/day (n = 44,476), frequent binge drinking (≥5 units at least once per month) was not associated with a greater risk of IHD (adjusted hazard ratio (HR) = 0.91, 95% confidence interval (CI): 0.76, 1.09) or stroke (adjusted HR = 0.98, 95% CI: 0.81, 1.19), in comparison with participants who reported that they never or only infrequently (less than once per month) had episodes of binge drinking. Participants with an average alcohol intake of 2.00-59.99 g/day had a lower risk of IHD in comparison with participants with very low intakes (<2.00 g/day), both among frequent binge drinkers (adjusted HR = 0.67, 95% CI: 0.56, 0.80) and among never/infrequent binge drinkers (adjusted HR = 0.75, 95% CI: 0.67, 0.84). The findings suggest that frequent binge drinking, independent of average alcohol intake, does not increase the risk of incident IHD or stroke events. However, the findings should be interpreted in light of the limitations of the study design.
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http://dx.doi.org/10.1093/aje/kwab063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489425PMC
August 2021

Association of fatal myocardial infarction with past level of physical activity: a pooled analysis of cohort studies.

Eur J Prev Cardiol 2021 Feb 10. Epub 2021 Feb 10.

Department of Cardiology, Bispebjerg Frederiksberg University Hospital, Bispebjerg Bakke 23, Building 67, 1st floor, DK-2400 Copenhagen, Denmark.

Aims: To assess the association between past level of physical activity (PA) and risk for death during the acute phase of myocardial infarction (MI) in a pooled analysis of cohort studies.

Methods And Results: European cohorts including participants with a baseline assessment of PA, conventional cardiovascular (CV) risk factors, and available follow-up on MI and death were eligible. Patients with an incident MI were included. Leisure-time PA was grouped as sedentary (<7 MET-hours), low (7-16 MET-hours), moderate (16.1-32 MET-hours), or high (>32 MET-hours) based on calculated net weekly energy expenditure. The main outcome measures were instant and 28-day case fatality of MI. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using multivariate random-effects models. Adjustments for age, sex, CV risk factors, alcohol consumption, and socioeconomic status were made. From 10 cohorts including a total of 1 495 254 participants, 28 140 patients with an incident MI comprised the study population. A total of 4976 (17.7%) died within 28 days-of these 3101 (62.3%) were classified as instant fatal MI. Compared with sedentary individuals, those with a higher level of PA had lower adjusted odds of instant fatal MI: low PA [OR, 0.79 (95% CI, 0.60-1.04)], moderate PA [0.67 (0.51-0.89)], and high PA [0.55 (0.40-0.76)]. Similar results were found for 28-day fatal MI: low PA [0.85 (0.71-1.03)], moderate PA [0.64 (0.51-0.80)], and high PA [0.72 (0.51-1.00)]. A low-to-moderate degree of heterogeneity was detected in the analysis of instant fatal MI (I2 = 47.3%), but not in that of 28-day fatal MI (I2 = 0.0%).

Conclusion: A moderate-to-high level of PA was associated with a lower risk of instant and 28-day death in relation to a MI.
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http://dx.doi.org/10.1093/eurjpc/zwaa146DOI Listing
February 2021

2.5-fold increased risk of recurrent acute myocardial infarction with familial hypercholesterolemia.

Atherosclerosis 2021 02 21;319:28-34. Epub 2020 Dec 21.

The Lipid Clinic, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Norway; Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway.

Background And Aims: A first-time acute myocardial infarction (AMI) is a severe diagnosis that leads to initiation or intensification of lipid-lowering medication to prevent recurrent events. Individuals with familial hypercholesterolemia (FH) already use high-intensity lipid-lowering medication at the time of an incident AMI due to their diagnosis. Hence, we hypothesized that compared with matched non-FH controls, individuals with genetically verified FH have increased mortality and risk of recurrent AMI after their first event.

Methods: The study population comprised 4871 persons with genetically verified FH, and 96,251 age and sex matched controls randomly selected from the Norwegian population. Data were obtained from the Cardiovascular Disease in Norway Project, the Norwegian Patient Registry and the Norwegian Cause of Death Registry. Incidence of AMI, all-cause mortality and recurrent AMI after incident AMI were analyzed for the period 2001-2017. Incidence and mortality were compared using hazard ratios (HR) from Cox regression. Risk of recurrent AMI was compared using sub-hazard ratios (SHR) from competing risk regression with death as a competing event.

Results: We identified 232 individuals with FH and 2118 controls with an incident AMI [HR 2.10 (95% CI 1.83-2.41)]. Among survivors ≥29 days after the incident AMI, both mortality [HR = 1.45 (95% CI: 1.07-1.95)] and recurrent AMI [SHR = 2.53 (95% CI: 1.88-3.41)] were significantly increased among individuals with FH compared with non-FH controls.

Conclusions: Individuals with FH have increased mortality and increased risk of recurrent AMI after the first AMI event compared with controls. These findings call for intensive follow-up of individuals with FH following an AMI.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.12.019DOI Listing
February 2021

Serum Galectin-3 and Subsequent Risk of Coronary Heart Disease in Subjects With Childhood-Onset Type 1 Diabetes: A Cohort Study.

Diabetes Care 2021 03 6;44(3):810-816. Epub 2021 Jan 6.

Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.

Objective: To study whether serum galectin-3 and other biomarkers of inflammation predict coronary heart disease (CHD) in subjects with long-standing childhood-onset type 1 diabetes.

Research Design And Methods: A population-based nationwide cohort of 299 subjects with type 1 diabetes diagnosed in Norway at <15 years of age during 1973-1982 was examined in 2002-2003 at a mean age of 33 years (range 21-44), with mean diabetes duration of 24 years (range 19-30). Subjects were followed through 31 December 2017 for their first CHD event registered by a hospitalization or cause of death using nationwide registries. Stored serum samples were available for 296 subjects and analyzed for interleukin-6 (IL-6), IL-6 receptor, IL-18, hs-CRP, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), galectin-3, and high-sensitivity troponin T. Adjusted hazard ratios (aHRs) for CHD per SD increase in biomarker were estimated using Cox regression.

Results: Of 295 subjects, 40 (13.6%) had a documented CHD event during a mean follow-up of 14.4 years (range 0.5-16). IL-6 (aHR 1.32 [95% CI 1.07-1.63]), galectin-3 (aHR 1.44 [95% CI 1.09-1.80]), and TIMP-1 (aHR 1.37 [95% CI 1.04-1.81]) were significant predictors of CHD after adjustment for conventional risk factors.

Conclusions: Galectin-3 was significantly associated with future CHD in subjects with type 1 diabetes, and if the results are replicated in larger studies, it may aid in prediction together with conventional risk factors for CHD.
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http://dx.doi.org/10.2337/dc20-1712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896257PMC
March 2021

No association between osteoporosis and AO classification of distal radius fractures: an observational study of 289 patients.

BMC Musculoskelet Disord 2020 Dec 4;21(1):811. Epub 2020 Dec 4.

Department of Rheumatology, Division of Medicine, District General Hospital of Førde, Førde, Norway.

Background: It is mechanically plausible that osteoporosis leads to more severe peripheral fractures, but studies investigating associations between BMD and radiographically verified complexity of distal radius fractures are scarce. This study aims to study the association between osteoporosis, as well as other risk factors for fracture, and the AO classification of distal radius fractures.

Methods: In this observational study, 289 consecutive patients aged ≥40 years with a distal radius fracture were included. Bone mineral density (BMD) of the hips and spine was measured by dual-energy x-ray absorptiometry (DXA), and comorbidities, medication, physical activity, smoking habits, body mass index (BMI), and history of previous fracture were registered. The distal radius fractures were classified according to the Müller AO system (AO) (type B and C regarded as most complex).

Results: Patients with osteoporosis (n = 130) did not have increased odds of a more complex distal radius fracture (type B + C, n = 192)) (n = vs type A (n = 92) (OR 1.1 [95% CI 0.5 to 2.3]) compared to those with osteopenia /normal BMD (n = 159). Patients with AO fracture types A or C had a higher prevalence of osteoporosis than patients with type B fracture.

Conclusions: Distal radius fracture patients with osteoporosis did not sustain more complex fractures than those with osteopenia/normal BMD according to the AO classification system. The AO classification of distal radius fracture cannot be used to decide which patients should be referred to DXA scan and considered for secondary fracture prevention.
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http://dx.doi.org/10.1186/s12891-020-03842-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718704PMC
December 2020

Effect of a telemedicine intervention for diabetes-related foot ulcers on health, well-being and quality of life: secondary outcomes from a cluster randomized controlled trial (DiaFOTo).

BMC Endocr Disord 2020 Oct 21;20(1):157. Epub 2020 Oct 21.

Faculty of Health and Social Sciences, Department of Health and Caring Sciences, Western Norway University of Applied Sciences, N-5020, Bergen, Norway.

Background: Follow-up care provided via telemedicine (TM) is intended to be a more integrated care pathway to manage diabetes-related foot ulcers (DFU) than traditionally-delivered healthcare. However, knowledge of the effect of TM follow-up on PROMs including self-reported health, well-being and QOL in patients with DFUs is lacking and often neglected in RCT reports in general. Therefore, in this study of secondary outcomes from the DiaFOTo trial, the aim was to compare changes in self-reported health, well-being and QOL between patients with DFUs receiving telemedicine follow-up care in primary healthcare in collaboration with specialist healthcare, and patients receiving standard outpatient care.

Methods: The current study reports secondary endpoints from a cluster randomized controlled trial whose primary endpoint was ulcer healing time. The trial included 182 adults with diabetes-related foot ulcers (94/88 in the telemedicine/standard care groups) in 42 municipalities/districts, recruited from three clinical sites in Western Norway. Mean (SD) diabetes duration for the study population was 20.8 (15.0). The intervention group received care in the community in collaboration with specialist healthcare using an asynchronous telemedicine intervention. The intervention included an interactive web-based ulcer record and a mobile phone enabling counseling and communication between the community nurses and specialist healthcare; the control group received standard outpatient care. In total 156 participants (78/78) reported on secondary endpoints: self-reported health, well-being and quality of life evaluated by generic and disease-specific patient-reported outcome measures (e.g. Euro-QOL, the Hospital Anxiety and Depression Scale (HADS), Problem Areas in Diabetes (PAID), Neuropathy and Foot Ulcer-Specific Quality of Life Instrument (NeuroQOL)). Linear mixed-effects regression was used to investigate possible differences in changes in the scores between the intervention and control group at the end of follow-up.

Results: In intention to treat analyses, differences between treatment groups were small and non-significant for the health and well-being scale scores, as well as for diabetes-related distress and foot ulcer-specific quality of life.

Conclusions: There were no significant differences in changes in scores for the patient reported outcomes between the intervention and control group, indicating that the intervention did not affect the participants' health, well-being and quality of life.

Trial Registration: Clinicaltrials.gov , NCT01710774 . Registered October 19th, 2012.
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http://dx.doi.org/10.1186/s12902-020-00637-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580005PMC
October 2020

Socioeconomic Gradients in Mortality Following HF Hospitalization in a Country With Universal Health Care Coverage.

JACC Heart Fail 2020 11 7;8(11):917-927. Epub 2020 Oct 7.

Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Division of Mental and Physical Health, Norwegian Institute of Public Health, Bergen, Norway.

Objectives: This study explored the association between socioeconomic position (SEP) and long-term mortality following first heart failure (HF) hospitalization.

Background: It is not clear to what extent education and income-individually or combined-influence mortality among patients with HF.

Methods: This study included 49,895 patients, age 35+ years, with a first HF hospitalization in Norway during 2000 to 2014 and followed them until death or December 31, 2014. The association between education, income, and mortality was explored using Cox regression models, stratified by sex and age group (35 to 69 years and 70+ years).

Results: Compared with patients with primary education, those with tertiary education had lower mortality (adjusted hazard ratio [HR]: 0.89; 95% confidence interval [CI]: 0.78 to 0.99 in younger men; HR: 0.57; 95% CI: 0.43 to 0.75 in younger women; HR: 0.90; 95% CI: 0.84 to 0.97 in older men, and HR: 0.87; 95% CI: 0.81 to 0.93 in older women). After adjusting for educational differences, younger and older men and younger women in the highest income quintile had lower mortality compared with those in the lowest income quintile (HR: 0.63; 95% CI: 0.55 to 0.72; HR: 0.78; 95% CI: 0.63 to 0.96, and HR: 0.91; 95% CI: 0.86 to 0.97, respectively). The association between income and mortality was almost linear. No association between income and mortality was observed in older women.

Conclusions: Despite the well-organized universal health care system in Norway, education and income were independently associated with mortality in patients with HF in a clear sex- and age group-specific pattern.
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http://dx.doi.org/10.1016/j.jchf.2020.05.015DOI Listing
November 2020

Intake of carbohydrates and SFA and risk of CHD in middle-age adults: the Hordaland Health Study (HUSK).

Public Health Nutr 2020 Sep 10:1-15. Epub 2020 Sep 10.

Department of Global Public Health and Primary Care, University of Bergen, Årstadveien 17, 5009Bergen, Norway.

Objective: Limiting SFA intake may minimise the risk of CHD. However, such reduction often leads to increased intake of carbohydrates. We aimed to evaluate associations and the interplay of carbohydrate and SFA intake on CHD risk.

Design: Prospective cohort study.

Setting: We followed participants in the Hordaland Health Study, Norway from 1997-1999 through 2009. Information on carbohydrate and SFA intake was obtained from a FFQ and analysed as continuous and categorical (quartiles) variables. Multivariable Cox regression estimated hazard ratios (HR) and 95 % CI. Theoretical substitution analyses modelled the substitution of carbohydrates with other nutrients. CHD was defined as fatal or non-fatal CHD (ICD9 codes 410-414 and ICD10 codes I20-I25).

Participants: 2995 men and women, aged 46-49 years.

Results: Adjusting for age, sex, energy intake, physical activity and smoking, SFA was associated with lower risk (HRQ4 v. Q1 0·44, 95 % CI 0·26, 0·76, Ptrend = 0·002). For carbohydrates, the opposite pattern was observed (HRQ4 v. Q1 2·10, 95 % CI 1·22, 3·63, Ptrend = 0·003). SFA from cheese was associated with lower CHD risk (HRQ4 v. Q1 0·44, 95 % CI 0·24, 0·83, Ptrend = 0·006), while there were no associations between SFA from other food items and CHD. A 5 E% substitution of carbohydrates with total fat, but not SFA, was associated with lower CHD risk (HR 0·75, 95 % CI 0·62, 0·90).

Conclusions: Higher intake of predominantly high glycaemic carbohydrates and lower intake of SFA, specifically lower intake from cheese, were associated with higher CHD risk. Substituting carbohydrates with total fat, but not SFA, was associated with significantly lower risk of CHD.
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http://dx.doi.org/10.1017/S1368980020003043DOI Listing
September 2020

Heart Failure in Women With Hypertensive Disorders of Pregnancy: Insights From the Cardiovascular Disease in Norway Project.

Hypertension 2020 11 24;76(5):1506-1513. Epub 2020 Aug 24.

Division of Women's Health, Department of Medicine, Brigham and Women's Hospital, Boston (J.W.R.-E.).

Hypertensive disorders of pregnancy (HDP) have been associated with heart failure (HF). It is unknown whether concurrent pregnancy complications (small-for-gestational-age or preterm delivery) or recurrent HDP modify HDP-associated HF risk. In this cohort study, we included Norwegian women with a first birth between 1980 and 2004. Follow-up occurred through 2009. Cox models examined gestational hypertension and preeclampsia in the first pregnancy as predictors of a composite of HF-related hospitalization or HF-related death, with assessment of effect modification by concurrent small-for-gestational-age or preterm delivery. Additional models were stratified by final parity (1 versus ≥2 births) and tested associations with recurrent HDP. Among 508 422 women, 565 experienced incident HF over a median 11.8 years of follow-up. After multivariable adjustment, gestational hypertension in the first birth was not significantly associated with HF (hazard ratio, 1.41 [95% CI, 0.84-2.35], =0.19), whereas preeclampsia was associated with a hazard ratio of 2.00 (95% CI, 1.50-2.68, <0.001). Among women with HDP, risks were not modified by concurrent small-for-gestational-age or preterm delivery (=0.42). Largest hazards of HF were observed in women whose only lifetime birth was complicated by preeclampsia and women with recurrent preeclampsia. HF risks were similar after excluding women with coronary artery disease. In summary, women with preeclampsia, especially those with one lifetime birth and those with recurrent preeclampsia, experienced increased HF risk compared to women without HDP. Further research is needed to clarify causal mechanisms.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544653PMC
November 2020

Initiation of anti-osteoporotic drugs in high-risk female patients starting glucocorticoid treatment: a population study in Norway.

Arch Osteoporos 2020 08 5;15(1):121. Epub 2020 Aug 5.

Department of Global Public Health and Primary Care, University of Bergen, Kalfarveien 31, N-5018, Bergen, Norway.

Glucocorticoid use is a risk factor for osteoporosis and fractures. We studied whether women initiating glucocorticoid treatment also started anti-osteoporotic treatment, according to clinical guidelines. Women with versus without previous fracture were twice as likely to start anti-osteoporotic treatment within 1 year after initiating glucocorticoid treatment, but the cumulative incidences were low 9.1% vs. 4.6%, respectively.

Purpose: Use of glucocorticoids (GC) is a risk factor for osteoporosis and fractures, and clinical guidelines suggest that preventive treatment with anti-osteoporotic drugs (AOD) should be considered when starting GC. Women with high risk of osteoporosis comprise those with previous fractures or a known inflammatory rheumatic disease, for whom the indication of AOD is even stronger. The purpose of these analyses was to investigate whether women initiating GC treatment also started AOD, especially those with high risk of osteoporosis.

Methods: We used data from the Norwegian Prescription Database to identify all women 55 years and older initiating GC treatment in Norway during 2010-2016 and to obtain information on use of AOD. Data from the Norwegian Patient Registry were used to obtain information on previous fractures and diagnoses.

Results: Among 105,477 women initiating GC treatment during 2010-2016, 3256 had started AOD and 79,638 had discontinued GC treatment after 1-year follow-up. Cumulative incidence of starting AOD after 1 year was 9.1% (95% CI: 7.9, 10.4) for women with vs. 4.6% (95% CI: 4.4%, 4.8%) for women without a previous fracture. Women with rheumatoid arthritis or another inflammatory rheumatic disease were more likely to start AOD than women with other indications. For the whole cohort, the probability of starting AOD treatment within 1 year after initiating GC increased on average 3% per year (HR = 1.03, CI: 1.01, 1.05) from 2010 to 2016.

Conclusions: Having had a previous fracture or an inflammatory rheumatic disease increased the probability of treatment with AOD. However, the proportions starting AOD were much lower than clinically indicated.
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http://dx.doi.org/10.1007/s11657-020-00783-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406535PMC
August 2020

3-Hydroxyisobutyrate, A Strong Marker of Insulin Resistance in Type 2 Diabetes and Obesity That Modulates White and Brown Adipocyte Metabolism.

Diabetes 2020 09 25;69(9):1903-1916. Epub 2020 Jun 25.

Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway

Circulating branched-chain amino acids (BCAAs) associate with insulin resistance and type 2 diabetes. 3-Hydroxyisobutyrate (3-HIB) is a catabolic intermediate of the BCAA valine. In this study, we show that in a cohort of 4,942 men and women, circulating 3-HIB is elevated according to levels of hyperglycemia and established type 2 diabetes. In complementary cohorts with measures of insulin resistance, we found positive correlates for circulating 3-HIB concentrations with HOMA2 of insulin resistance, as well as a transient increase in 3-HIB followed by a marked decrease after bariatric surgery and weight loss. During differentiation, both white and brown adipocytes upregulate BCAA utilization and release increasing amounts of 3-HIB. Knockdown of the 3-HIB-forming enzyme 3-hydroxyisobutyryl-CoA hydrolase decreases release of 3-HIB and lipid accumulation in both cell types. Conversely, addition of 3-HIB to white and brown adipocyte cultures increases fatty acid uptake and modulated insulin-stimulated glucose uptake in a time-dependent manner. Finally, 3-HIB treatment decreases mitochondrial oxygen consumption and generation of reactive oxygen species in white adipocytes, while increasing these measures in brown adipocytes. Our data establish 3-HIB as a novel adipocyte-derived regulator of adipocyte subtype-specific functions strongly linked to obesity, insulin resistance, and type 2 diabetes.
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http://dx.doi.org/10.2337/db19-1174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968520PMC
September 2020

A novel patient-reported outcome monitoring with clinical feedback system in bariatric surgery care: study protocol, design and plan for evaluation.

BMJ Open 2020 06 22;10(6):e037685. Epub 2020 Jun 22.

Faculty of Health and Social Sciences, Western Norway University of Applied Sciences-Forde Campus, Forde, Norway.

Background: Consultations before and after bariatric surgery should include structured assessments of patients' health-related quality of life (HRQOL) and mental health. One way to conduct this assessment is to implement patient-reported outcome monitoring with a clinical feedback system (PRO/CFS).

Aim: We will explore patients' and healthcare professionals' experiences when a PRO/CFS is an integrated part of bariatric surgery care.

Methods And Analyses: This is a design paper in which a PRO/CFS will be implemented in two bariatric outpatient clinics. All patients who have an appointment with a healthcare professional prior to, and 3 and 12 months after surgery, will be asked to complete six digital questionnaires measuring HRQOL, mental health, bowel symptoms and eating self-efficacy prior to each consultation. A digital summary report generated from the patient's responses will form the basis for the clinical consultation. A team of patient representatives, healthcare professionals and researchers will be involved in all phases of designing the PRO/CFS to ensure its relevance for clinical consultations. The patients' experiences will be explored with a generic 12-item questionnaire, developed for use in outpatient clinics, prior to and 12 months after bariatric surgery. We will conduct focus-group interviews with patients and healthcare professionals to explore their experiences when PRO/CFS is integrated into the consultations.

Ethics And Dissemination: Written informed consent will be obtained for all participants in the study. The project is approved by the Norwegian Centre for Research Data, Department of Data Protection Services (ref. no. 282738). The project has also undergone Data Protection Impact Assessments, both at Førde Hospital Trust and at St. Olav Hospital (registration no. 2016/3912). Data from the qualitative and quantitative studies will be kept in de-identified form in a secured research database, and the findings will be published in international peer-reviewed journals and presented at scientific conferences.
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http://dx.doi.org/10.1136/bmjopen-2020-037685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311033PMC
June 2020

Association of dietary vitamin K and risk of coronary heart disease in middle-age adults: the Hordaland Health Study Cohort.

BMJ Open 2020 05 21;10(5):e035953. Epub 2020 May 21.

Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.

Objective: The role of vitamin K in the regulation of vascular calcification is established. However, the association of dietary vitamins K1 and K2 with risk of coronary heart disease (CHD) is inconclusive.

Design: Prospective cohort study.

Setting: We followed participants in the community-based Hordaland Health Study from 1997 - 1999 through 2009 to evaluate associations between intake of vitamin K and incident (new onset) CHD. Baseline diet was assessed by a past-year food frequency questionnaire. Energy-adjusted residuals of vitamin K1 and vitamin K2 intakes were categorised into quartiles.

Participants: 2987 Norwegian men and women, age 46-49 years.

Methods: Information on incident CHD events was obtained from the nationwide Cardiovascular Disease in Norway (CVDNOR) Project. Multivariable Cox regression estimated HRs and 95% CIs with test for linear trends across quartiles. Analyses were adjusted for age, sex, total energy intake, physical activity, smoking and education. A third model further adjusted K1 intake for energy-adjusted fibre and folate, while K2 intake was adjusted for energy-adjusted saturated fatty acids and calcium.

Results: During a median follow-up time of 11 years, we documented 112 incident CHD cases. In the adjusted analyses, there was no association between intake of vitamin K1 and CHD (HR = 0.92 (95% CI 0.54 to 1.57), p for trend 0.64), while there was a lower risk of CHD associated with higher intake of energy-adjusted vitamin K2 (HR = 0.52 (0.29 to 0.94), p for trend 0.03). Further adjustment for potential dietary confounders did not materially change the association for K1, while the association for K2 was slightly attenuated (HR = 0.58 (0.28 to 1.19)).

Conclusions: A higher intake of vitamin K2 was associated with lower risk of CHD, while there was no association between intake of vitamin K1 and CHD.

Trial Registration Number: NCT03013725.
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http://dx.doi.org/10.1136/bmjopen-2019-035953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247390PMC
May 2020

Systemic Cardiac Troponin T Associated With Incident Atrial Fibrillation Among Patients With Suspected Stable Angina Pectoris.

Am J Cardiol 2020 07 12;127:30-35. Epub 2020 Apr 12.

Department of Heart Disease, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.

Higher concentrations of cardiac troponin T are associated with coronary artery disease (CAD) and adverse cardiovascular prognosis. The relation with incident atrial fibrillation (AF) is less explored. We studied this association among 3,568 patients evaluated with coronary angiography for stable angina pectoris without previous history of AF. The prospective association between high-sensitivity cardiac troponin T (hs-cTnT) categories (≤3 ng/L; n = 1,694, 4-9; n = 1,085, 10 to 19; n = 614 and 20 to 30; n = 175) and incident AF and interactions with the extent of CAD were studied by Kaplan-Meier plots and Cox regression. Risk prediction improvements were assessed by receiver operating characteristic area under the curve (ROC-AUC) analyses. During median (25 to 75 percentile) 7.3 (6.3 to 8.6) years of follow-up 412 (11.5%) were diagnosed with AF. In a Cox model adjusted for age, gender, body mass index, hypertension, diabetes mellitus, smoking, estimated glomerular filtration rate, and left ventricular ejection fraction, hazard ratios (HRs) (95% confidence intervals [CIs]) were 1.53 (1.16 to 2.03), 2.03 (1.49 to 2.78), and 2.15 (1.40 to 3.31) when comparing the second, third, and fourth to the first hs-cTnT group, respectively (P for trend <0.000001). The strongest association between hs-cTnT levels and incident AF was found among patients without obstructive CAD (P = 0.024) and adding hs-cTnT to established AF risk factors improved risk classification slightly (ΔROC 0.006, p = 0.044). In conclusion, in patients with suspected stable angina higher levels of hs-cTnT predicted increased risk of incident AF. This was most pronounced in patients without obstructive CAD suggesting an association not mediated by coronary disease.
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http://dx.doi.org/10.1016/j.amjcard.2020.03.036DOI Listing
July 2020

Factors associated with increase in blood pressure and incident hypertension in early midlife: the Hordaland Health Study.

Blood Press 2020 10 13;29(5):267-275. Epub 2020 May 13.

Department of Clinical Science, University of Bergen, Bergen, Norway.

We aimed to identify sex-specific factors associated with increase in blood pressure (BP) and incident hypertension in early midlife. 2,008 women and 1,610 men aged 40-43 years were followed for six years in the Hordaland Health Study. Participants taking antihypertensive medication at baseline were excluded. High-normal BP was defined as baseline BP 130-139/85-89 mmHg, and incident hypertension as BP≥140/90 mmHg or use of antihypertensive medication at follow-up. During follow-up, an increase in systolic (SBP) and diastolic (DBP) BP was observed in 54% and 30% of women vs. 44% and 41% of men, respectively (both <0.001). In both sexes higher baseline body mass index (BMI) and increases in BMI and serum lipids were associated with increases in SBP and DBP during follow-up (all <0.05). Incident hypertension was more common in men (14 vs.11%, <0.01), and predicted by higher BMI and high-normal BP at baseline in both sexes, and by higher serum triglyceride level in women (all <0.01). In the Hordaland Health Study, BP development differed between women and men in early midlife. The main factors associated with BP increase in both sexes were higher BMI, weight gain and increases in serum lipids.
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http://dx.doi.org/10.1080/08037051.2020.1762070DOI Listing
October 2020

Lipid parameters and vitamin A modify cardiovascular risk prediction by plasma neopterin.

Heart 2020 07 12;106(14):1073-1079. Epub 2020 May 12.

Centre for Nutrition, Department of Clinical Science, University of Bergen, Bergen, Norway.

Objectives: Oxidised cholesterol metabolites are linked to increased production of the active vitamin A (Vit-A) form and monocyte/macrophage activation, which may be reflected by neopterin, a marker of both interferon-γ-mediated immune activation and coronary artery disease risk. We examined the influence of serum lipid parameters and Vit-A on the risk association between neopterin and incident acute myocardial infarction (AMI).

Methods: We included 4130 patients with suspected stable angina pectoris (SAP), of whom 80% received lipid-lowering treatment with statins. Risk associations between plasma neopterin and AMI are given as HRs per SD increase in log-transformed neopterin.

Results: During a median follow-up of 7.5 years, 530 (12.8%) patients experienced an AMI. In age-adjusted and sex-adjusted analysis, plasma neopterin was positively associated with incident AMI (HR (95% CI) per SD: 1.26 (1.17 to 1.35)). However, the estimates were most pronounced in patients with serum low-density lipoprotein cholesterol (LDL-C) or apolipoprotein (apo) B100 below-median (HR (95% CI) per SD: 1.35 (1.24 to 1.48) and 1.42 (1.27 to 1.58), respectively; both p ≤0.03). We also observed a particularly strong risk association in those with above-median Vit-A (HR (95% CI) per SD: 1.32 (1.21 to 1.44); p=0.03). The estimates were slightly modified after multivariable adjustment.

Conclusions: In patients with suspected SAP, the majority of whom receiving statin therapy, high plasma neopterin was associated with increased risk of AMI particularly among those with low LDL-C and apoB100 or high Vit-A levels. The particularly strong relationship of plasma neopterin with residual cardiovascular risk in patients with low lipid levels should be further investigated.
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http://dx.doi.org/10.1136/heartjnl-2019-316165DOI Listing
July 2020

Transsulfuration metabolites and the association with incident atrial fibrillation - An observational cohort study among Norwegian patients with stable angina pectoris.

Int J Cardiol 2020 Oct 8;317:75-80. Epub 2020 May 8.

Haukeland University Hospital, Dept of Heart Disease, Bergen, Norway; University of Bergen, Dept of Clinical Science, Bergen, Norway.

Background/aim: Plasma total homocysteine (tHcy) is elevated in patients with persistent vs. paroxysmal atrial fibrillation (AF), and has been related to increased risk of new-onset AF. Homocysteine is degraded to cystathionine (Cysta) and cysteine (Cys). All three metabolites have been linked to potential proarrhythmic traits such as inflammation and atrial fibrosis. We evaluated the prospective association between these metabolites and new-onset AF among patients with suspected stable angina pectoris.

Methods: Information regarding AF was obtained by linking patient data to national health registries. Risk associations were explored by Cox regression and potential improvements in risk reclassification were calculated by the continuous net reclassification index (NRI > 0).

Results: At baseline, 3535 patients without any prior history of AF were included. During median follow-up of 7.4 years, 392 patients (10.2%) were registered with incident AF. Higher plasma tHcy and tCys were associated with increased risk of incident AF [age and gender adjusted HRs (95% CI) per 1 log transformed SD 1.23 (1.12-1.35) and 1.23 (1.11-1.38)]; multivariate adjustment yielded similar results. Plasma tHcy and tCys also improved reclassification of patients (NRI > 0 (95% CI)) for tHcy 0.118 (0.02-0.22) and tCys 0.107 (0.002-0.21). No association was seen between plasma Cysta and incident AF.

Conclusion: Plasma tHcy and tCys, but not Cysta, were associated with, and improved risk classification of, new-onset AF among patients with stable angina pectoris. Our results motivate further studies to explore the relationship between homocysteine metabolism and cardiac arrhythmias.
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http://dx.doi.org/10.1016/j.ijcard.2020.05.010DOI Listing
October 2020

Urban-Rural Differences in Hip Fracture Mortality: A Nationwide NOREPOS Study.

JBMR Plus 2019 Nov 21;3(11):e10236. Epub 2019 Oct 21.

Institute of Health and Society, Department of Community Medicine and Global Health University of Oslo Oslo Norway.

Higher hip fracture incidence in urban than in rural areas has been demonstrated, but urban-rural differences in posthip fracture mortality have been less investigated, and the results are disparate. Hence, the aims of the present register-based cohort study were to examine possible urban-rural differences in short- and long-term mortality in Norwegian hip fracture patients and their potential associations with sociodemographic variables, and to investigate possible urban-rural differences in excess mortality in hip fracture patients compared with the general population. Data were provided from the NOREPOS hip fracture database, the 2001 Population and Housing Census, and the National Registry. The urbanization degree in each municipality was determined by the proportion of inhabitants living in densely populated areas (rural: <1/3, semirural: 1/3 to 2/3, and urban: >2/3). Age-adjusted mortality rates and standardized mortality ratios were calculated for hip fracture patients living in rural, semirural, and urban municipalities. A flexible parametric model was used to estimate age-adjusted average and time-varying HRs by category of urbanization with the rural category as reference. Among 96,693 hip fracture patients, urban residents had higher mortality than their rural-dwelling counterparts. The HR of mortality in urban compared with rural areas peaked during the first 1 to 2 years postfracture with a maximum HR of 1.20 (95% CI, 1.10 to 1.30) in men and 1.15 (95% CI, 1.08 to 1.21) in women. The differences were significant during approximately 5 years after fracture. Adjusting for sociodemographic variables did not substantially change the results. However, absolute 30-day mortality was not significantly different between urban and rural residents, suggesting that health-care quality immediately postfracture does not vary by urbanization. The novel findings of a higher long-term mortality in urban hip fracture patients might reflect disparities in health status or lifestyle, differences in posthip fracture health care or rehabilitation, or a combination of several factors. © 2019 The Authors. published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbm4.10236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874178PMC
November 2019

Heart failure in Norway, 2000-2014: analysing incident, total and readmission rates using data from the Cardiovascular Disease in Norway (CVDNOR) Project.

Eur J Heart Fail 2020 02 23;22(2):241-248. Epub 2019 Oct 23.

Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.

Aims: To examine trends in heart failure (HF) hospitalization rates and risk of readmissions following an incident HF hospitalization.

Methods And Results: During 2000-2014, we identified in the Cardiovascular Disease in Norway Project 142 109 hospitalizations with HF as primary diagnosis. Trends of incident and total (incident and recurrent) HF hospitalization rates were analysed using negative binomial regression models. Changes over time in 30-day and 3-year risk of HF recurrences or cardiovascular disease (CVD)-related readmissions were analysed using Fine and Grey competing risk regression, with death as competing events. Age-standardized rates declined on average 1.9% per year in men and 1.8% per year in women for incident HF hospitalizations (both P  < 0.001) but did not change significantly in either men or women for total HF hospitalizations. In men surviving the incident HF hospitalization, 30-day and 3-year risk of a HF recurrent event increased 1.7% and 1.2% per year, respectively. Similarly, 30-day and 3-year risk of a CVD-related hospitalization increased 1.5% and 1.0% per year, respectively (all P  < 0.001). No statistically significant changes in the risk of HF recurrences or CVD-related readmissions were observed among women. In-hospital mortality for a first and recurrent HF episode declined over time in both men and women.

Conclusions: Incident HF hospitalization rates declined in Norway during 2000-2014. An increase in the risk of recurrences in the context of reduced in-hospital mortality following an incident and recurrent HF hospitalization led to flat trends of total HF hospitalization rates.
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http://dx.doi.org/10.1002/ejhf.1609DOI Listing
February 2020

How should recruitment to public health surveys be conducted?

Tidsskr Nor Laegeforen 2019 10 21;139(15). Epub 2019 Oct 21.

Background: The aim of the public health survey in the Norwegian counties is to obtain information that is useful for public health work. In 2018, two parallel data collection processes were undertaken in Hordaland county. Both samples were drawn randomly from the National Population Register, but one of these was limited to users of the helsenorge.no website. The purpose of this article is to investigate the degree to which limiting users to the helsenorge.no website leads to selection bias beyond the selection that occurs through ordinary non-participation.

Material And Method: Services for Sensitive Data (TSD) was used in the data collection for the sample drawn from the National Population Register (n = 36 000), and the helsenorge.no platform was used in the data collection for the sample limited to users of helsenorge.no (n = 30 000). The response rate was 40.8 % and 41.5 %, respectively.

Results: For some outcome measures, the differences between the two datasets were modest (gender distribution, age, education and health habits). For variables that were more directly related to health, the differences were greater. In the helsenorge.no sample a higher proportion reported generally poorer health (29.4 vs. 24.0 %), mental health problems (13.6 vs. 11.6 %), disability pension (10.5 vs. 7.8 %) and long-term illness (13.3 vs. 9.3 %). Analyses of subgroups showed more pronounced differences in the proportion with generally poorer health and mental health problems between those with low education in the helsenorge.no sample and the corresponding group in the sample from the National Population Register.

Interpretation: Systematic and pronounced differences between the samples show that limiting recruitment to users of helsenorge.no's services results in further selection problems.
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http://dx.doi.org/10.4045/tidsskr.19.0054DOI Listing
October 2019

Kynurenines, Neuropsychiatric Symptoms, and Cognitive Prognosis in Patients with Mild Dementia.

Int J Tryptophan Res 2019 29;12:1178646919877883. Epub 2019 Sep 29.

Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.

Introduction: Circulating tryptophan (Trp) and its downstream metabolites, the kynurenines, are potentially neuroactive. Consequently, they could be associated with neuropsychiatric symptoms and cognitive prognosis in patients with dementia.

Objective: The objective of this study was to assess associations between circulating kynurenines, cognitive prognosis, and neuropsychiatric symptoms.

Methods: We measured baseline serum Trp, neopterin, pyridoxal 5'-phosphate (PLP), and 9 kynurenines in 155 patients with mild dementia (90 with Alzheimer's disease, 65 with Lewy body dementia). The ratios between kynurenine and Trp and kynurenic acid (KA) to kynurenine (KKR) were calculated. The Mini-Mental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI) were administered at baseline and annually over 5 years. Associations between baseline metabolite concentrations with MMSE and the NPI total score were assessed using a generalized structural equation model (mixed-effects multiprocess model), adjusted for age, sex, current smoking, glomerular filtration rate, and PLP. Post hoc associations between KKRs and individual NPI items were assessed using logistic mixed-effects models. False discovery rate (0.05)-adjusted values ( values) are reported.

Results: Kynurenine had a nonlinear quadratic relationship with the intercept of the MMSE scores over 5 years ( < 0.05), but not with the slope of MMSE decline. Kynurenine was associated with a higher NPI total score over time ( < 0.001). Post hoc, both KKR and KA were associated with more hallucinations ( < 0.05).

Conclusions: Kynurenine has a complex relationship with cognition, where both low and high levels were associated with poor cognitive performance. A higher KKR indicated risk for neuropsychiatric symptoms, especially hallucinations.
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http://dx.doi.org/10.1177/1178646919877883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769202PMC
September 2019

Association of Low-Density Lipoprotein Cholesterol With Risk of Aortic Valve Stenosis in Familial Hypercholesterolemia.

JAMA Cardiol 2019 11;4(11):1156-1159

The Lipid Clinic, Oslo University Hospital, Oslo, Norway.

Importance: Aortic valve stenosis (AS) is the most common valve disease. Elevated levels of low-density lipoprotein (LDL) cholesterol are a risk factor; however, lipid-lowering treatment seems not to prevent progression of AS. The importance of LDL cholesterol in the development of AS thus remains unclear. People with familial hypercholesterolemia (FH) have elevated LDL cholesterol levels from birth and until lipid-lowering treatment starts. Thus, FH may serve as a model disease to study the importance of LDL cholesterol for the development of AS.

Objective: To compare the incidence of AS per year in all genetically proven patients with FH in Norway with the incidence of these diseases in the total Norwegian population of about 5 million people.

Design, Setting, And Participants: This is a registry-based prospective cohort study of all Norwegian patients with FH with regard to first-time AS between 2001 and 2009. All genotyped patients with FH in Norway were compared with the total Norwegian populations through linkage with the Cardiovascular Disease in Norway project and the Norwegian Cause of Death Registry regarding occurrence of first-time AS. Data were analyzed between January 1, 2018, and December 31, 2018.

Main Outcomes And Measures: Standardized incidence ratios.

Results: In total, 53 cases of AS occurred among 3161 persons (1473 men [46.6%]) with FH during 18 300 person-years of follow-up. Mean age at inclusion and at time of AS were 39.9 years (range, 8-91 years) and 65 years (range, 44-88 years), respectively. Total standardized incidence ratios were 7.9 (95% CI, 6.1-10.4) for men and women combined, 8.5 (95% CI, 5.8-12.4) in women, and 7.4 (95% CI, 5.0-10.9) in men, respectively, indicating marked increased risk of AS compared with the general Norwegian population.

Conclusions And Relevance: In this prospective registry study, we demonstrate a marked increase in risk of AS in persons with FH.
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http://dx.doi.org/10.1001/jamacardio.2019.3903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802245PMC
November 2019
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