Grethe Tell | University of Bergen (original) (raw)

Papers by Grethe Tell

International Journal of Epidemiology, 2008

Journal of Diabetes and its Complications

Aim To prospectively examine whether depressive symptoms increase the risk of diabetes and a diab... more Aim To prospectively examine whether depressive symptoms increase the risk of diabetes and a diabetic foot ulcer. Methods The Nord-Trøndelag Health Study (HUNT) is a community-based longitudinal study. The Hospital Anxiety and Depression Scale (HADS-D subscale) assessed depressive symptoms. We followed individuals with complete HADS-D data from HUNT2 (1995–97) and assessed whether they reported diabetes with or without a history of diabetic foot ulcer (DFU) in HUNT3 (2006–08) (n = 36,031). Logistic regression was used to investigate the effect of depressive symptoms on subsequent development of diabetes and of DFU. Results Unadjusted odds for reporting diabetes at follow-up was higher among individuals who reported a HADS-D score ≥ 8 at baseline (OR 1.30 95% CI, 1.07 – 1.57) than among those reporting a lower score. After adjusting for age, gender and BMI, this association was no longer significant. The odds of developing a DFU was almost two-fold (OR = 1.95 95% CI, 1.02 – 3.74) for...

Choline, obtained from diet and formed by biosynthesis, is the immediate precursor of betaine. An... more Choline, obtained from diet and formed by biosynthesis, is the immediate precursor of betaine. Animal studies suggest an impact of choline on bone metabolism. We examined the associations of plasma choline and betaine with bone mineral density (BMD), the risk of hip fractures, and possible effect-modification by nicotine exposure. The Hordaland Health Study (1998 to 2000) included 7074 women and men (ages 46 to 49 or 71 to 74 years). In 5315, BMD was measured. The oldest (n ¼ 3311) were followed for hip fractures through 2009. Risk associations were studied by logistic and Cox regression by comparing the lowest and middle tertiles with the highest, as well as trends across tertiles of plasma choline and betaine. In analyses adjusted for sex and age, participants in the lowest (odds ratio [OR] ¼ 2.00, 95% confidence interval [CI] 1.69-2.37) and middle (OR ¼ 1.39, CI 1.17-1.66) tertiles of plasma choline had an increased risk of low BMD (lowest quintile) (p trend < 0.001). Separate analyses for sex and age groups revealed the strongest relations in elderly women (lowest tertile: OR ¼ 2.84, CI 1.95-4.14; middle tertile: OR ¼ 1.80, CI 1.22-2.67, p trend < 0.001), and highest OR among those in the lowest tertile who were exposed to nicotine (OR ¼ 4.56, CI 1.87-11.11). Low plasma choline was also associated with an increased risk of hip fracture in elderly women and men (lowest tertile: hazard ratio [HR] ¼ 1.45, CI 1.08-1.94; middle tertile: HR ¼ 1.13, CI 0.83-1.54, p trend ¼ 0.012). In elderly women, the HR for hip fracture was 1.90 (CI 1.32-2.73) and 1.36 (CI 0.92-1.99) (p trend < 0.001) for lowest and middle tertiles of choline, and the highest HR was found among women in the lowest tertile exposed to nicotine (HR ¼ 2.68, CI 1.16-6.19). Plasma betaine was not related to BMD or hip fracture. Low plasma choline was associated with low BMD in both sexes and increased the risk of hip fracture in elderly women. These results should motivate further studies on choline, nicotine exposure, and bone metabolism.

American Journal of Clinical Nutrition

Few population-based studies have assessed relations between plasma or serum total homocysteine (... more Few population-based studies have assessed relations between plasma or serum total homocysteine (tHcy) and all-cause mortality. Our goal was to study associations between plasma tHcy and all-cause, cardiovascular, and noncardiovascular mortality. This was a prospective cohort study of 2127 men and 2639 women aged 65-67 y in 1992-1993 when they were recruited as part of a population-based national cardiovascular screening program carried out in Hordaland County, Norway. During a median of 4.1 y of follow-up, 162 men and 97 women died. A strong relation was found between plasma tHcy and all-cause mortality. The association was highly significant for noncardiovascular and for cardiovascular causes of death. In a comparison of individuals having tHcy concentrations of 9.0-11.9, 12.0-14.9, 15.0-19.9, or > or = 20 micromol/L with individuals having a tHcy concentration < 9 micromol/L, adjusted mortality ratios were 1.4, 1.9, 2.3, and 3.6 (P for trend = 0.0002) for noncardiovascular ...

American Journal of Clinical Nutrition

The lean phenotype of cystathionine beta-synthase-deficient homocystinuria and the positive assoc... more The lean phenotype of cystathionine beta-synthase-deficient homocystinuria and the positive association of plasma total cysteine (tCys) with body mass index (BMI) suggest that total homocysteine (tHcy) and tCys are associated with body composition. We aimed to study associations of tCys and tHcy with body composition in the general population. Using data from 7038 Hordaland Homocysteine Study participants, we fitted regression models and dose-response curves of tCys and tHcy with BMI. In 5179 participants, we investigated associations of tCys and tHcy with fat mass and lean mass and examined whether changes in these aminothiols predicted body composition 6 y later. tCys showed positive associations with BMI (partial r = 0.28, P < 0.001), and fat mass (partial r = 0.25, P < 0.001), independent of diet, exercise, and plasma lipids. Women in the highest tCys quintile had fat mass 9 kg (95% CI: 8, 10 kg; P < 0.001) greater than that of women in the lowest quintile. The correspo...

PloS one, 2015

Persons with diabetes have increased risk of depression, however, studies addressing whether the ... more Persons with diabetes have increased risk of depression, however, studies addressing whether the risk varies by age and type of antidiabetic treatment have yielded conflicting results. The aim of this study was to investigate if the association between diabetes and depression varied by type of antidiabetic treatment in a large community based sample of middle-aged (40-47 years) and older adults (70-72 years). Data from 21845 participants in the Hordaland Health Study (HUSK) were analyzed in a cross-sectional design. Diabetes was assessed by self-report and classified as un-medicated, treated by oral antidiabetic agents or by insulin. Depression was defined as a score ≥8 on the depression subscale of the Hospital Anxiety and Depression Scale and/or self-reported use of antidepressant agents. Associations between diabetes and depression were estimated using logistic regression. Persons in their forties with diabetes had a doubled prevalence of depression (OR: 1.96 (95% C.I.: 1.35, 2.8...

European journal of preventive cardiology, Jan 3, 2015

Estimation of cardiovascular disease risk, using SCORE (Systematic COronary Risk Evaluation) is r... more Estimation of cardiovascular disease risk, using SCORE (Systematic COronary Risk Evaluation) is recommended by European guidelines on cardiovascular disease prevention. Risk estimation is inaccurate in older people. We hypothesized that this may be due to the assumption, inherent in current risk estimation systems, that risk factors function similarly in all age groups. We aimed to derive and validate a risk estimation function, SCORE O.P., solely from data from individuals aged 65 years and older. 20,704 men and 20,121 women, aged 65 and over and without pre-existing coronary disease, from four representative, prospective studies of the general population were included. These were Italian, Belgian and Danish studies (from original SCORE dataset) and the CONOR (Cohort of Norway) study. The variables which remained statistically significant in Cox proportional hazards model and were included in the SCORE O.P. model were: age, total cholesterol, high-density lipoprotein cholesterol, s...

Journal of Bone and Mineral Research, 2015

Hip fractures are associated with high excess mortality. Education is an important determinant of... more Hip fractures are associated with high excess mortality. Education is an important determinant of health, but little is known about educational inequalities in post-hip fracture mortality. To investigate educational inequalities in post-hip fracture mortality, and examine whether comorbidity or family composition could explain any association. Register-based population study of Norwegians aged 50+ years during 2002-2010 OUTCOME MEASUREMENTS: Total mortality according to educational attainment in 56,269 hip fracture patients (NORHip) and in the general Norwegian population. Both absolute and relative educational inequalities in mortality in people with and without hip fracture were compared. There was an educational gradient in post-hip fracture mortality in both genders. Compared to those with primary education only, the age-adjusted relative risk (RR) of mortality in hip fracture patients with tertiary education was 0.82 (95% CI: 0.77-0.87) in men and 0.79 (95% CI: 0.75-0.84) in women. Additional adjustments for Charlson comorbidity index, marital status and number of children did not materially change the estimates. Regardless of educational attainment, the one-year age-adjusted mortality was 3-5 fold higher in hip fracture patients compared to peers in the general population without fracture. The absolute differences in one-year mortality according to educational attainment were considerably larger in hip fracture patients than in the population without hip fracture. Absolute educational inequalities in mortality were higher after hip fracture compared to the general population without hip fracture, and were not mediated by comorbidity or family composition. Investigation of other possible mediating factors might help to identify new targets for interventions, based on lower educational attainment, to reduce post-hip fracture mortality. This article is protected by copyright. All rights reserved.

Circulation. Cardiovascular quality and outcomes, Jan 9, 2015

In studies using patient administrative data, the identification of the first (incident) acute my... more In studies using patient administrative data, the identification of the first (incident) acute myocardial infarction (AMI) in an individual is based on retrospectively excluding previous hospitalizations for the same condition during a fixed time period (lookback period [LP]). Our aim was to investigate whether the length of the LP used to identify the first AMI had an effect on trends in AMI incidence and subsequent survival in a nationwide study. All AMI events during 1994 to 2009 were retrieved from the Cardiovascular Disease in Norway project. Incident AMIs during 2004 to 2009 were identified using LPs of 10, 8, 7, 5, and 3 years. For each LP, we calculated time trends in incident AMI and subsequent 28-day and 1-year mortality rates. Results obtained from analyses using the LP of 10 years were compared with those obtained using shorter LPs. In men, AMI incidence rates declined by 4.2% during 2004 to 2009 (incidence rate ratio, 0.958; 95% confidence interval, 0.935-0.982). The us...

International Journal of Cardiology, 2015

To investigate self-reported family history (FH) of premature myocardial infarction (MI) in first... more To investigate self-reported family history (FH) of premature myocardial infarction (MI) in first-degree relatives as a risk factor for coronary heart disease (CHD) mortality, and assess whether any observed effect could be explained by current or life course socioeconomic position. 130,066 participants from Cohort of Norway were examined during 1994-2003. A subgroup (n=84,631) had additional life course socioeconomic data. Using Cox proportional hazard analyses, we calculated hazard ratios (HR) for CHD mortality, assessed by linkages to the Norwegian Cause of Death Registry through 2009. For subgroup analyses, we created an index of life course socioeconomic position, and assessed its role as a potential confounder in the association of FH with CHD. For men, MI in parents and siblings were both a significant risk factor for CHD mortality after adjusting for established risk factors and current socioeconomic conditions; the highest risk was with MI in siblings (HR: 1.44 [1.19-1.75]). For women, FH constituted significant risk after similar adjustment only for those with MI in parents plus siblings (HR: 1.78 [1.16-2.73]). Adjusting for current and life course socioeconomic conditions only marginally lowered the estimates, and those with FH did not have worse life course socioeconomic position than those without. FH of premature MI is an independent risk factor for CHD mortality that differs in magnitude of effect by the sex of the index person and type of familial relationship. Life course socioeconomic position has little impact on the association between FH and CHD, suggesting the effect is not confounded by this.

European journal of cardiovascular nursing : journal of the Working Group on Cardiovascular Nursing of the European Society of Cardiology, Jan 17, 2015

While the overall incidence of acute myocardial infarction in Norway decreased in 2001-2009, this... more While the overall incidence of acute myocardial infarction in Norway decreased in 2001-2009, this was not observed for younger adults. Smoking cessation, physical activity and healthy diet are associated with reduced risk of recurrent cardiovascular events and mortality among individuals with established coronary heart disease (CHD). We investigated whether adults in their 40s with or without CHD had 1) attempted to improve their health behaviour during the previous year, and 2) had confidence in their ability to improve their health behaviour over the next five years. Study participants were 22,019 40-49 year olds from the Hordaland Health Study. Associations between improvements and intentions regarding health behaviours and prevalent CHD were assessed with logistic regression analyses. One hundred and seventy-five (0.8%) participants reported to have CHD. After controlling for demographic, lifestyle and psychosocial variables, attempts to improve health behaviour during the prior...

International Journal of Cardiology, 2015

Background: The kynurenine pathway, the main metabolic route of tryptophan degradation, has been ... more Background: The kynurenine pathway, the main metabolic route of tryptophan degradation, has been related to inflammatory responses. Some of its metabolites, referred to as kynurenines, have been associated with prevalence of coronary heart disease (CHD) in cross-sectional studies. This prospective study aims to investigate whether increased concentrations of kynurenines are associated with risk of acute coronary events, defined as unstable angina pectoris, acute myocardial infarction, and/or sudden death in community-dwelling elderly. Methods: The baseline examinations included 2819 individuals aged 71-74 years recruited into the Hordaland Health Study. Participants with known CHD at baseline were excluded from analyses. Baseline plasma concentrations of tryptophan, kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, xanthurenic acid, and 3-hydroxyanthranilic acid were measured by LC-MS/MS. During a median follow-up period of 10.8 years, with linkage to acute coronary event endpoints through the CVDNOR project, hazard ratios (HRs) for acute coronary events (n = 376) were estimated using Cox proportional hazard analyses. Results: After adjustment for established cardiovascular risk factors, HRs (95% CI) comparing the 4th vs 1st quartile were 1.86 (1.19-2.92) for kynurenine and 1.72 (1.19-2.49) for 3-hydroxykynurenine. Tryptophan, kynurenic acid, anthranilic acid, xanthurenic acid and 3-hydroxyanthranilic acid were not associated with acute coronary events. Conclusions: Kynurenine and 3-hydroxykynurenine were associated with increased risk of acute coronary events in community-dwelling elderly without a known history of CHD. These results suggest the involvement of the kynurenine pathway in the early development of CHD, and their potential usefulness to estimate CHD risk.

American heart journal, 2014

The reasons for decreasing birth prevalence of congenital heart defects (CHDs) in several Europea... more The reasons for decreasing birth prevalence of congenital heart defects (CHDs) in several European countries and Canada are not fully understood. We present CHD prevalence among live births, stillbirths, and terminated pregnancies in an entire nation over a period of 16 years. Information on all births in the Medical Birth Registry of Norway, 1994-2009, was updated with information on CHD from the hospitals' Patient Administrative Systems, the National Hospital's clinical database for children with heart disease, and the Cause of Death Registry. Individuals with heart defects were assigned specific cardiac phenotypes. Among 954,413 births, 13,081 received a diagnosis of CHD (137.1 per 10,000 births, 133.2 per 10,000 live births). The prevalence per 10,000 births was as follows: heterotaxia, 1.6; conotruncal defects, 11.6; atrioventricular septal defects, 5.6; anomalous pulmonary venous return, 1.1; left outflow obstructions, 8.7; right outflow obstructions, 5.6; septal defec...

Scandinavian journal of public health, 2014

This paper describes the history, purpose, data collection and contributions in the research coll... more This paper describes the history, purpose, data collection and contributions in the research collaboration Norwegian Osteoporosis Epidemiologic Studies (NOREPOS). NOREPOS encompasses almost 85,000 bone mineral density measurements within Cohort of Norway and data on almost 140,000 hip fractures in Norway 1994-2008. Included are anthropometric measurements, blood pressure, lipids and glucose, and 50 standard questions on sociodemographic factors, diseases and risk factors. Blood samples/DNA are stored. The main research question posed in NOREPOS is why hip fracture rates in Norway are the highest in the world. Data on hip fractures 2009-2013 will be added in 2014. Main findings include: Every hour a Norwegian suffers a hip fracture; hip fracture incidence rates declined after 1999; only 16% of patients used anti-osteoporosis drugs 1 year after hip fracture; 25% of patients died within 1 year after the fracture; 12% suffered a new hip fracture within 10 years; rural dwellers had lower...

European journal of preventive cardiology, 2014

Acute myocardial infarction (AMI) incidence reflects levels of risk factors in the general popula... more Acute myocardial infarction (AMI) incidence reflects levels of risk factors in the general population and influences coronary heart disease mortality rates. We examined trends in AMI incidence in Norway during 2001-2009 and potential differences between sex and age groups. All AMI hospitalizations (ICD9 410; ICD10 I21, I22) and coronary out-of-hospital deaths (ICD9 410-414; ICD10 I20-I25) in Norway for individuals ≥25 years were obtained during 1994-2009. Incident AMI was defined as a hospitalization or out-of-hospital death due to AMI with no prior hospitalization for AMI during the previous 7 years. Age-standardized and age-group specific rates were calculated and expressed per 100,000 persons. The annual changes in rates were obtained from Poisson regression analyses. The total change in incidence rates during 2001-2009 were then calculated based on the estimated annual change. We identified 148,522 incident AMIs (41% women; 21% out-of-hospital deaths) during 2001-2009. Incidence...

The American journal of clinical nutrition, 2004

Elevated plasma concentrations of total homocysteine (tHcy) are a risk factor for cardiovascular ... more Elevated plasma concentrations of total homocysteine (tHcy) are a risk factor for cardiovascular disease. tHcy is a marker of folate and cobalamin deficiencies and is also related to several lifestyle factors. We examined whether changes in lifestyle influence tHcy over time. A population-based, prospective study was conducted in 7031 subjects from western Norway who constituted 2 age groups (41-42 and 65-67 y) at baseline (1992-1993). The subjects were reinvestigated in 1997-1999 ( follow-up: 6 y). During follow-up, median tHcy concentrations decreased 0.10 (25th and 75th percentiles: -1.24, 1.00) micromol/L in the younger subjects and increased 0.39 (25th and 75th percentiles: -0.99, 1.79) micromol/L in the older subjects. Changes in plasma vitamin status and vitamin supplement use were the strongest determinants of changes in tHcy over time. Each unit increase in plasma folate (nmol/L) and vitamin B-12 (pmol/L) was associated with reductions in tHcy concentrations of 0.2 and 0.1 ...

European journal of preventive cardiology, Jan 9, 2014

to prospectively evaluate the risk of acute myocardial infarction (AMI) associated with non-fasti... more to prospectively evaluate the risk of acute myocardial infarction (AMI) associated with non-fasting triglyceride levels. a health survey of 140,790 Norwegians free of known coronary heart disease at baseline (1994-2003) were followed through December 2009 via record linkages to the Cause of Death Registry and hospital discharge diagnoses in the CVDNOR project, and evaluated in Cox proportional hazards analyses. a total of 3219 (4.8%) men and 1434 (1.9%) women developed an AMI. Women had a steeper gradient risk with increasing triglyceride decile than men, where the highest (≥2.88 mmol/l) compared to the lowest decile (<0.7 mmol/l) was associated with an age-adjusted 4.7-fold excess risk in women in contrast to a 2.8-fold excess risk in men (interaction term, p < 0.001). A significant at-risk HDL-C (<1.0 mmol/l for men and <1.3 mmol/l for women) by triglyceride interaction term was observed. HRs increased with increasing triglyceride quartile in participants with a favour...

European journal of preventive cardiology, 2014

To analyse the impact of four different definitions of acute myocardial infarction (AMI) on numbe... more To analyse the impact of four different definitions of acute myocardial infarction (AMI) on number of events and all-cause mortality after AMI. We retrospectively examined number of AMI events and mortality according to four different definitions of AMI, among 1494 patients admitted to Haukeland University Hospital in Norway from March 2002 to February 2003. Eligible for analysis were 815 patients with a discharge diagnosis of an AMI, and 679 patients without any AMI discharge diagnosis but with elevated cardiac troponin I level during admission. Applying the WHO 1979 definition resulted in 566 definite AMIs among the 1494 patients and was used as reference. According to the other definitions, there were 455 (-20%) definite AMIs by the original troponin 'rise and fall' version of the ESC/ACC 2000 definition, 729 (+29%) by the troponin 'rise or fall' interpretation of the ESC/ACC 2000 definition, 761 (+34%) by the AHA 2003 definition, and 743 (+31%) by the Universal 2...

British Journal of Nutrition, 2014

Vitamins B 2 and B 6 are cofactors in the kynurenine pathway. Many of the kynurenines are neuroac... more Vitamins B 2 and B 6 are cofactors in the kynurenine pathway. Many of the kynurenines are neuroactive compounds with immunomodulatory effects. In the present study, we aimed to investigate plasma concentrations of vitamins B 2 and B 6 as determinants of kynurenines and two markers of interferon-g-mediated immune activation (kynurenine:tryptophan ratio (KTR) and neopterin). We measured the concentrations of vitamins B 2 and B 6 vitamers, neopterin, tryptophan and six kynurenines (i.e. kynurenine, anthranilic acid, kynurenic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and xanthurenic acid) in plasma from 7051 individuals. Dietary intake of vitamins B 2 and B 6 was assessed using a validated FFQ. Associations were investigated using partial Spearman's correlations, generalised additive models, and segmented or multiple linear regression. The B 2 vitamer, riboflavin, was positively associated with 3-hydroxyanthranilic acid and xanthurenic acid, with correlation coefficients, as obtained by segmented regression, of 0·20 (95 % CI 0·16, 0·23) and 0·24 (95 % CI 0·19, 0·28), at riboflavin concentrations below the median value (13·0 nmol/l). The vitamin B 6 vitamer, pyridoxal 5 0 -phosphate (PLP), was positively associated with most kynurenines at PLP concentrations ,39·3-47·0 nmol/l, and inversely associated with 3-hydroxykynurenine with the association being more prominent at PLP concentrations ,18·9 nmol/l. Riboflavin and PLP were associated with xanthurenic acid only at relatively low, but normal concentrations of both vitamers. Lastly, PLP was negatively correlated with neopterin and KTR. These results demonstrate the significant and complex determination of kynurenine metabolism by vitamin status. Future studies on B-vitamins and kynurenines in relation to chronic diseases should therefore integrate data on relevant biomarkers related to B-vitamins status and tryptophan metabolism.

The Journal of nutrition, 2015

Data from recent meta-analyses question an association between dietary intake of saturated fatty ... more Data from recent meta-analyses question an association between dietary intake of saturated fatty acids (SFAs) and risk of cardiovascular disease (CVD). Moreover, the prognostic effect of dietary SFA in patients with established CVD treated with modern conventional medication has not been extensively studied. We investigated the associations between self-reported dietary SFA intake and risk of subsequent coronary events and mortality in patients with coronary artery disease (CAD). This study included patients who participated in the Western Norway B-Vitamin Intervention Trial and completed a 169-item semiquantitative food-frequency questionnaire after coronary angiography. Quartiles of estimated daily intakes of SFA were related to risk of a primary composite endpoint of coronary events (unstable angina pectoris, nonfatal acute myocardial infarction, and coronary death) and separate secondary endpoints (total acute myocardial infarction, fatal coronary events, and all-cause death) wi...

International Journal of Epidemiology, 2008

Journal of Diabetes and its Complications

Aim To prospectively examine whether depressive symptoms increase the risk of diabetes and a diab... more Aim To prospectively examine whether depressive symptoms increase the risk of diabetes and a diabetic foot ulcer. Methods The Nord-Trøndelag Health Study (HUNT) is a community-based longitudinal study. The Hospital Anxiety and Depression Scale (HADS-D subscale) assessed depressive symptoms. We followed individuals with complete HADS-D data from HUNT2 (1995–97) and assessed whether they reported diabetes with or without a history of diabetic foot ulcer (DFU) in HUNT3 (2006–08) (n = 36,031). Logistic regression was used to investigate the effect of depressive symptoms on subsequent development of diabetes and of DFU. Results Unadjusted odds for reporting diabetes at follow-up was higher among individuals who reported a HADS-D score ≥ 8 at baseline (OR 1.30 95% CI, 1.07 – 1.57) than among those reporting a lower score. After adjusting for age, gender and BMI, this association was no longer significant. The odds of developing a DFU was almost two-fold (OR = 1.95 95% CI, 1.02 – 3.74) for...

Choline, obtained from diet and formed by biosynthesis, is the immediate precursor of betaine. An... more Choline, obtained from diet and formed by biosynthesis, is the immediate precursor of betaine. Animal studies suggest an impact of choline on bone metabolism. We examined the associations of plasma choline and betaine with bone mineral density (BMD), the risk of hip fractures, and possible effect-modification by nicotine exposure. The Hordaland Health Study (1998 to 2000) included 7074 women and men (ages 46 to 49 or 71 to 74 years). In 5315, BMD was measured. The oldest (n ¼ 3311) were followed for hip fractures through 2009. Risk associations were studied by logistic and Cox regression by comparing the lowest and middle tertiles with the highest, as well as trends across tertiles of plasma choline and betaine. In analyses adjusted for sex and age, participants in the lowest (odds ratio [OR] ¼ 2.00, 95% confidence interval [CI] 1.69-2.37) and middle (OR ¼ 1.39, CI 1.17-1.66) tertiles of plasma choline had an increased risk of low BMD (lowest quintile) (p trend < 0.001). Separate analyses for sex and age groups revealed the strongest relations in elderly women (lowest tertile: OR ¼ 2.84, CI 1.95-4.14; middle tertile: OR ¼ 1.80, CI 1.22-2.67, p trend < 0.001), and highest OR among those in the lowest tertile who were exposed to nicotine (OR ¼ 4.56, CI 1.87-11.11). Low plasma choline was also associated with an increased risk of hip fracture in elderly women and men (lowest tertile: hazard ratio [HR] ¼ 1.45, CI 1.08-1.94; middle tertile: HR ¼ 1.13, CI 0.83-1.54, p trend ¼ 0.012). In elderly women, the HR for hip fracture was 1.90 (CI 1.32-2.73) and 1.36 (CI 0.92-1.99) (p trend < 0.001) for lowest and middle tertiles of choline, and the highest HR was found among women in the lowest tertile exposed to nicotine (HR ¼ 2.68, CI 1.16-6.19). Plasma betaine was not related to BMD or hip fracture. Low plasma choline was associated with low BMD in both sexes and increased the risk of hip fracture in elderly women. These results should motivate further studies on choline, nicotine exposure, and bone metabolism.

American Journal of Clinical Nutrition

Few population-based studies have assessed relations between plasma or serum total homocysteine (... more Few population-based studies have assessed relations between plasma or serum total homocysteine (tHcy) and all-cause mortality. Our goal was to study associations between plasma tHcy and all-cause, cardiovascular, and noncardiovascular mortality. This was a prospective cohort study of 2127 men and 2639 women aged 65-67 y in 1992-1993 when they were recruited as part of a population-based national cardiovascular screening program carried out in Hordaland County, Norway. During a median of 4.1 y of follow-up, 162 men and 97 women died. A strong relation was found between plasma tHcy and all-cause mortality. The association was highly significant for noncardiovascular and for cardiovascular causes of death. In a comparison of individuals having tHcy concentrations of 9.0-11.9, 12.0-14.9, 15.0-19.9, or > or = 20 micromol/L with individuals having a tHcy concentration < 9 micromol/L, adjusted mortality ratios were 1.4, 1.9, 2.3, and 3.6 (P for trend = 0.0002) for noncardiovascular ...

American Journal of Clinical Nutrition

The lean phenotype of cystathionine beta-synthase-deficient homocystinuria and the positive assoc... more The lean phenotype of cystathionine beta-synthase-deficient homocystinuria and the positive association of plasma total cysteine (tCys) with body mass index (BMI) suggest that total homocysteine (tHcy) and tCys are associated with body composition. We aimed to study associations of tCys and tHcy with body composition in the general population. Using data from 7038 Hordaland Homocysteine Study participants, we fitted regression models and dose-response curves of tCys and tHcy with BMI. In 5179 participants, we investigated associations of tCys and tHcy with fat mass and lean mass and examined whether changes in these aminothiols predicted body composition 6 y later. tCys showed positive associations with BMI (partial r = 0.28, P < 0.001), and fat mass (partial r = 0.25, P < 0.001), independent of diet, exercise, and plasma lipids. Women in the highest tCys quintile had fat mass 9 kg (95% CI: 8, 10 kg; P < 0.001) greater than that of women in the lowest quintile. The correspo...

PloS one, 2015

Persons with diabetes have increased risk of depression, however, studies addressing whether the ... more Persons with diabetes have increased risk of depression, however, studies addressing whether the risk varies by age and type of antidiabetic treatment have yielded conflicting results. The aim of this study was to investigate if the association between diabetes and depression varied by type of antidiabetic treatment in a large community based sample of middle-aged (40-47 years) and older adults (70-72 years). Data from 21845 participants in the Hordaland Health Study (HUSK) were analyzed in a cross-sectional design. Diabetes was assessed by self-report and classified as un-medicated, treated by oral antidiabetic agents or by insulin. Depression was defined as a score ≥8 on the depression subscale of the Hospital Anxiety and Depression Scale and/or self-reported use of antidepressant agents. Associations between diabetes and depression were estimated using logistic regression. Persons in their forties with diabetes had a doubled prevalence of depression (OR: 1.96 (95% C.I.: 1.35, 2.8...

European journal of preventive cardiology, Jan 3, 2015

Estimation of cardiovascular disease risk, using SCORE (Systematic COronary Risk Evaluation) is r... more Estimation of cardiovascular disease risk, using SCORE (Systematic COronary Risk Evaluation) is recommended by European guidelines on cardiovascular disease prevention. Risk estimation is inaccurate in older people. We hypothesized that this may be due to the assumption, inherent in current risk estimation systems, that risk factors function similarly in all age groups. We aimed to derive and validate a risk estimation function, SCORE O.P., solely from data from individuals aged 65 years and older. 20,704 men and 20,121 women, aged 65 and over and without pre-existing coronary disease, from four representative, prospective studies of the general population were included. These were Italian, Belgian and Danish studies (from original SCORE dataset) and the CONOR (Cohort of Norway) study. The variables which remained statistically significant in Cox proportional hazards model and were included in the SCORE O.P. model were: age, total cholesterol, high-density lipoprotein cholesterol, s...

Journal of Bone and Mineral Research, 2015

Hip fractures are associated with high excess mortality. Education is an important determinant of... more Hip fractures are associated with high excess mortality. Education is an important determinant of health, but little is known about educational inequalities in post-hip fracture mortality. To investigate educational inequalities in post-hip fracture mortality, and examine whether comorbidity or family composition could explain any association. Register-based population study of Norwegians aged 50+ years during 2002-2010 OUTCOME MEASUREMENTS: Total mortality according to educational attainment in 56,269 hip fracture patients (NORHip) and in the general Norwegian population. Both absolute and relative educational inequalities in mortality in people with and without hip fracture were compared. There was an educational gradient in post-hip fracture mortality in both genders. Compared to those with primary education only, the age-adjusted relative risk (RR) of mortality in hip fracture patients with tertiary education was 0.82 (95% CI: 0.77-0.87) in men and 0.79 (95% CI: 0.75-0.84) in women. Additional adjustments for Charlson comorbidity index, marital status and number of children did not materially change the estimates. Regardless of educational attainment, the one-year age-adjusted mortality was 3-5 fold higher in hip fracture patients compared to peers in the general population without fracture. The absolute differences in one-year mortality according to educational attainment were considerably larger in hip fracture patients than in the population without hip fracture. Absolute educational inequalities in mortality were higher after hip fracture compared to the general population without hip fracture, and were not mediated by comorbidity or family composition. Investigation of other possible mediating factors might help to identify new targets for interventions, based on lower educational attainment, to reduce post-hip fracture mortality. This article is protected by copyright. All rights reserved.

Circulation. Cardiovascular quality and outcomes, Jan 9, 2015

In studies using patient administrative data, the identification of the first (incident) acute my... more In studies using patient administrative data, the identification of the first (incident) acute myocardial infarction (AMI) in an individual is based on retrospectively excluding previous hospitalizations for the same condition during a fixed time period (lookback period [LP]). Our aim was to investigate whether the length of the LP used to identify the first AMI had an effect on trends in AMI incidence and subsequent survival in a nationwide study. All AMI events during 1994 to 2009 were retrieved from the Cardiovascular Disease in Norway project. Incident AMIs during 2004 to 2009 were identified using LPs of 10, 8, 7, 5, and 3 years. For each LP, we calculated time trends in incident AMI and subsequent 28-day and 1-year mortality rates. Results obtained from analyses using the LP of 10 years were compared with those obtained using shorter LPs. In men, AMI incidence rates declined by 4.2% during 2004 to 2009 (incidence rate ratio, 0.958; 95% confidence interval, 0.935-0.982). The us...

International Journal of Cardiology, 2015

To investigate self-reported family history (FH) of premature myocardial infarction (MI) in first... more To investigate self-reported family history (FH) of premature myocardial infarction (MI) in first-degree relatives as a risk factor for coronary heart disease (CHD) mortality, and assess whether any observed effect could be explained by current or life course socioeconomic position. 130,066 participants from Cohort of Norway were examined during 1994-2003. A subgroup (n=84,631) had additional life course socioeconomic data. Using Cox proportional hazard analyses, we calculated hazard ratios (HR) for CHD mortality, assessed by linkages to the Norwegian Cause of Death Registry through 2009. For subgroup analyses, we created an index of life course socioeconomic position, and assessed its role as a potential confounder in the association of FH with CHD. For men, MI in parents and siblings were both a significant risk factor for CHD mortality after adjusting for established risk factors and current socioeconomic conditions; the highest risk was with MI in siblings (HR: 1.44 [1.19-1.75]). For women, FH constituted significant risk after similar adjustment only for those with MI in parents plus siblings (HR: 1.78 [1.16-2.73]). Adjusting for current and life course socioeconomic conditions only marginally lowered the estimates, and those with FH did not have worse life course socioeconomic position than those without. FH of premature MI is an independent risk factor for CHD mortality that differs in magnitude of effect by the sex of the index person and type of familial relationship. Life course socioeconomic position has little impact on the association between FH and CHD, suggesting the effect is not confounded by this.

European journal of cardiovascular nursing : journal of the Working Group on Cardiovascular Nursing of the European Society of Cardiology, Jan 17, 2015

While the overall incidence of acute myocardial infarction in Norway decreased in 2001-2009, this... more While the overall incidence of acute myocardial infarction in Norway decreased in 2001-2009, this was not observed for younger adults. Smoking cessation, physical activity and healthy diet are associated with reduced risk of recurrent cardiovascular events and mortality among individuals with established coronary heart disease (CHD). We investigated whether adults in their 40s with or without CHD had 1) attempted to improve their health behaviour during the previous year, and 2) had confidence in their ability to improve their health behaviour over the next five years. Study participants were 22,019 40-49 year olds from the Hordaland Health Study. Associations between improvements and intentions regarding health behaviours and prevalent CHD were assessed with logistic regression analyses. One hundred and seventy-five (0.8%) participants reported to have CHD. After controlling for demographic, lifestyle and psychosocial variables, attempts to improve health behaviour during the prior...

International Journal of Cardiology, 2015

Background: The kynurenine pathway, the main metabolic route of tryptophan degradation, has been ... more Background: The kynurenine pathway, the main metabolic route of tryptophan degradation, has been related to inflammatory responses. Some of its metabolites, referred to as kynurenines, have been associated with prevalence of coronary heart disease (CHD) in cross-sectional studies. This prospective study aims to investigate whether increased concentrations of kynurenines are associated with risk of acute coronary events, defined as unstable angina pectoris, acute myocardial infarction, and/or sudden death in community-dwelling elderly. Methods: The baseline examinations included 2819 individuals aged 71-74 years recruited into the Hordaland Health Study. Participants with known CHD at baseline were excluded from analyses. Baseline plasma concentrations of tryptophan, kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, xanthurenic acid, and 3-hydroxyanthranilic acid were measured by LC-MS/MS. During a median follow-up period of 10.8 years, with linkage to acute coronary event endpoints through the CVDNOR project, hazard ratios (HRs) for acute coronary events (n = 376) were estimated using Cox proportional hazard analyses. Results: After adjustment for established cardiovascular risk factors, HRs (95% CI) comparing the 4th vs 1st quartile were 1.86 (1.19-2.92) for kynurenine and 1.72 (1.19-2.49) for 3-hydroxykynurenine. Tryptophan, kynurenic acid, anthranilic acid, xanthurenic acid and 3-hydroxyanthranilic acid were not associated with acute coronary events. Conclusions: Kynurenine and 3-hydroxykynurenine were associated with increased risk of acute coronary events in community-dwelling elderly without a known history of CHD. These results suggest the involvement of the kynurenine pathway in the early development of CHD, and their potential usefulness to estimate CHD risk.

American heart journal, 2014

The reasons for decreasing birth prevalence of congenital heart defects (CHDs) in several Europea... more The reasons for decreasing birth prevalence of congenital heart defects (CHDs) in several European countries and Canada are not fully understood. We present CHD prevalence among live births, stillbirths, and terminated pregnancies in an entire nation over a period of 16 years. Information on all births in the Medical Birth Registry of Norway, 1994-2009, was updated with information on CHD from the hospitals' Patient Administrative Systems, the National Hospital's clinical database for children with heart disease, and the Cause of Death Registry. Individuals with heart defects were assigned specific cardiac phenotypes. Among 954,413 births, 13,081 received a diagnosis of CHD (137.1 per 10,000 births, 133.2 per 10,000 live births). The prevalence per 10,000 births was as follows: heterotaxia, 1.6; conotruncal defects, 11.6; atrioventricular septal defects, 5.6; anomalous pulmonary venous return, 1.1; left outflow obstructions, 8.7; right outflow obstructions, 5.6; septal defec...

Scandinavian journal of public health, 2014

This paper describes the history, purpose, data collection and contributions in the research coll... more This paper describes the history, purpose, data collection and contributions in the research collaboration Norwegian Osteoporosis Epidemiologic Studies (NOREPOS). NOREPOS encompasses almost 85,000 bone mineral density measurements within Cohort of Norway and data on almost 140,000 hip fractures in Norway 1994-2008. Included are anthropometric measurements, blood pressure, lipids and glucose, and 50 standard questions on sociodemographic factors, diseases and risk factors. Blood samples/DNA are stored. The main research question posed in NOREPOS is why hip fracture rates in Norway are the highest in the world. Data on hip fractures 2009-2013 will be added in 2014. Main findings include: Every hour a Norwegian suffers a hip fracture; hip fracture incidence rates declined after 1999; only 16% of patients used anti-osteoporosis drugs 1 year after hip fracture; 25% of patients died within 1 year after the fracture; 12% suffered a new hip fracture within 10 years; rural dwellers had lower...

European journal of preventive cardiology, 2014

Acute myocardial infarction (AMI) incidence reflects levels of risk factors in the general popula... more Acute myocardial infarction (AMI) incidence reflects levels of risk factors in the general population and influences coronary heart disease mortality rates. We examined trends in AMI incidence in Norway during 2001-2009 and potential differences between sex and age groups. All AMI hospitalizations (ICD9 410; ICD10 I21, I22) and coronary out-of-hospital deaths (ICD9 410-414; ICD10 I20-I25) in Norway for individuals ≥25 years were obtained during 1994-2009. Incident AMI was defined as a hospitalization or out-of-hospital death due to AMI with no prior hospitalization for AMI during the previous 7 years. Age-standardized and age-group specific rates were calculated and expressed per 100,000 persons. The annual changes in rates were obtained from Poisson regression analyses. The total change in incidence rates during 2001-2009 were then calculated based on the estimated annual change. We identified 148,522 incident AMIs (41% women; 21% out-of-hospital deaths) during 2001-2009. Incidence...

The American journal of clinical nutrition, 2004

Elevated plasma concentrations of total homocysteine (tHcy) are a risk factor for cardiovascular ... more Elevated plasma concentrations of total homocysteine (tHcy) are a risk factor for cardiovascular disease. tHcy is a marker of folate and cobalamin deficiencies and is also related to several lifestyle factors. We examined whether changes in lifestyle influence tHcy over time. A population-based, prospective study was conducted in 7031 subjects from western Norway who constituted 2 age groups (41-42 and 65-67 y) at baseline (1992-1993). The subjects were reinvestigated in 1997-1999 ( follow-up: 6 y). During follow-up, median tHcy concentrations decreased 0.10 (25th and 75th percentiles: -1.24, 1.00) micromol/L in the younger subjects and increased 0.39 (25th and 75th percentiles: -0.99, 1.79) micromol/L in the older subjects. Changes in plasma vitamin status and vitamin supplement use were the strongest determinants of changes in tHcy over time. Each unit increase in plasma folate (nmol/L) and vitamin B-12 (pmol/L) was associated with reductions in tHcy concentrations of 0.2 and 0.1 ...

European journal of preventive cardiology, Jan 9, 2014

to prospectively evaluate the risk of acute myocardial infarction (AMI) associated with non-fasti... more to prospectively evaluate the risk of acute myocardial infarction (AMI) associated with non-fasting triglyceride levels. a health survey of 140,790 Norwegians free of known coronary heart disease at baseline (1994-2003) were followed through December 2009 via record linkages to the Cause of Death Registry and hospital discharge diagnoses in the CVDNOR project, and evaluated in Cox proportional hazards analyses. a total of 3219 (4.8%) men and 1434 (1.9%) women developed an AMI. Women had a steeper gradient risk with increasing triglyceride decile than men, where the highest (≥2.88 mmol/l) compared to the lowest decile (<0.7 mmol/l) was associated with an age-adjusted 4.7-fold excess risk in women in contrast to a 2.8-fold excess risk in men (interaction term, p < 0.001). A significant at-risk HDL-C (<1.0 mmol/l for men and <1.3 mmol/l for women) by triglyceride interaction term was observed. HRs increased with increasing triglyceride quartile in participants with a favour...

European journal of preventive cardiology, 2014

To analyse the impact of four different definitions of acute myocardial infarction (AMI) on numbe... more To analyse the impact of four different definitions of acute myocardial infarction (AMI) on number of events and all-cause mortality after AMI. We retrospectively examined number of AMI events and mortality according to four different definitions of AMI, among 1494 patients admitted to Haukeland University Hospital in Norway from March 2002 to February 2003. Eligible for analysis were 815 patients with a discharge diagnosis of an AMI, and 679 patients without any AMI discharge diagnosis but with elevated cardiac troponin I level during admission. Applying the WHO 1979 definition resulted in 566 definite AMIs among the 1494 patients and was used as reference. According to the other definitions, there were 455 (-20%) definite AMIs by the original troponin 'rise and fall' version of the ESC/ACC 2000 definition, 729 (+29%) by the troponin 'rise or fall' interpretation of the ESC/ACC 2000 definition, 761 (+34%) by the AHA 2003 definition, and 743 (+31%) by the Universal 2...

British Journal of Nutrition, 2014

Vitamins B 2 and B 6 are cofactors in the kynurenine pathway. Many of the kynurenines are neuroac... more Vitamins B 2 and B 6 are cofactors in the kynurenine pathway. Many of the kynurenines are neuroactive compounds with immunomodulatory effects. In the present study, we aimed to investigate plasma concentrations of vitamins B 2 and B 6 as determinants of kynurenines and two markers of interferon-g-mediated immune activation (kynurenine:tryptophan ratio (KTR) and neopterin). We measured the concentrations of vitamins B 2 and B 6 vitamers, neopterin, tryptophan and six kynurenines (i.e. kynurenine, anthranilic acid, kynurenic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and xanthurenic acid) in plasma from 7051 individuals. Dietary intake of vitamins B 2 and B 6 was assessed using a validated FFQ. Associations were investigated using partial Spearman's correlations, generalised additive models, and segmented or multiple linear regression. The B 2 vitamer, riboflavin, was positively associated with 3-hydroxyanthranilic acid and xanthurenic acid, with correlation coefficients, as obtained by segmented regression, of 0·20 (95 % CI 0·16, 0·23) and 0·24 (95 % CI 0·19, 0·28), at riboflavin concentrations below the median value (13·0 nmol/l). The vitamin B 6 vitamer, pyridoxal 5 0 -phosphate (PLP), was positively associated with most kynurenines at PLP concentrations ,39·3-47·0 nmol/l, and inversely associated with 3-hydroxykynurenine with the association being more prominent at PLP concentrations ,18·9 nmol/l. Riboflavin and PLP were associated with xanthurenic acid only at relatively low, but normal concentrations of both vitamers. Lastly, PLP was negatively correlated with neopterin and KTR. These results demonstrate the significant and complex determination of kynurenine metabolism by vitamin status. Future studies on B-vitamins and kynurenines in relation to chronic diseases should therefore integrate data on relevant biomarkers related to B-vitamins status and tryptophan metabolism.

The Journal of nutrition, 2015

Data from recent meta-analyses question an association between dietary intake of saturated fatty ... more Data from recent meta-analyses question an association between dietary intake of saturated fatty acids (SFAs) and risk of cardiovascular disease (CVD). Moreover, the prognostic effect of dietary SFA in patients with established CVD treated with modern conventional medication has not been extensively studied. We investigated the associations between self-reported dietary SFA intake and risk of subsequent coronary events and mortality in patients with coronary artery disease (CAD). This study included patients who participated in the Western Norway B-Vitamin Intervention Trial and completed a 169-item semiquantitative food-frequency questionnaire after coronary angiography. Quartiles of estimated daily intakes of SFA were related to risk of a primary composite endpoint of coronary events (unstable angina pectoris, nonfatal acute myocardial infarction, and coronary death) and separate secondary endpoints (total acute myocardial infarction, fatal coronary events, and all-cause death) wi...