Explaining declining hip fracture rates in Norway: a population-based modelling study.

Background: Although age-standardised hip fracture incidence has declined in many countries during recent decades, the number of fractures is forecast to increase as the population ages. Understanding the drivers behind this decline is essential to inform policy for targeted preventive measures. We aimed to quantify how much of this decline could be explained by temporal trends in major risk factors and osteoporosis treatment. Methods: We developed a new modelling approach, Hip-IMPACT, based on the validated IMPACT coronary heart disease models. The model applied sex- and age stratified hip fracture numbers and prevalence of pharmacologic treatments and risk/preventive factors in 1999 and 2019, and best available evidence for independent relative risks of hip fracture associated with each treatment and risk/preventive factor. Findings: Hip-IMPACT explained 91% (2500/2756) of the declining hip fracture rates during 1999-2019. Two-thirds of the total decline was attributed to changes in risk/preventive factors and one-fifth to osteoporosis medication. Increased prevalence of total hip replacements explained 474/2756 (17%), increased body mass index 698/2756 (25%), and increased physical activity 434/2756 (16%). Reduced smoking explained 293/2756 (11%), and reduced benzodiazepine use explained (366/2756) 13%. Increased uptake of alendronate, zoledronic acid, and denosumab explained 307/2756 (11%), 104/2756 (4%) and 161/2756 (6%), respectively. The explained decline was partially offset by increased prevalence of type 2 diabetes and users of glucocorticoids, z-drugs, and opioids. Interpretation: Two-thirds of the decline in hip fractures from 1999 to 2019 was attributed to reductions in major risk factors and approximately one-fifth to osteoporosis medication. Funding: The Research Council of Norway.

Cause-specific excess mortality after hip fracture: the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS).

BACKGROUND: Information on cause of death may help appraise the degree to which the high excess mortality after hip fracture reflects pre-existing comorbidities or the injury itself. We aimed to describe causes of death and cause-specific excess mortality through the first year after hip fracture. METHODS: For studying the distribution of causes of death by time after hip fracture, we calculated age-adjusted cause-specific mortality at 1, 3, 6 and 12 months in patients hospitalized with hip fracture in Norway 1999-2016. Underlying causes of death were obtained from the Norwegian Cause of Death Registry and grouped by the European Shortlist for Causes of Death. For estimating excess mortality, we performed flexible parametric survival analyses comparing mortality hazard in patients with hip fracture (2002-2017) with that of age- and sex matched controls drawn from the Population and Housing Census 2001. RESULTS: Of 146,132 Norwegians with a first hip fracture, a total of 35,498 (24.3%) died within one year. By 30 days post-fracture, external causes (mainly the fall causing the fracture) were the underlying cause for 53.8% of deaths, followed by circulatory diseases (19.8%), neoplasms (9.4%), respiratory diseases (5.7%), mental and behavioural disorders (2.0%) and diseases of the nervous system (1.3%). By one-year post-fracture, external causes and circulatory diseases together accounted for approximately half of deaths (26.1% and 27.0%, respectively). In the period 2002-2017, cause-specific one-year relative mortality hazard in hip fracture patients vs. population controls ranged from 1.5 for circulatory diseases to 2.5 for diseases of the nervous system in women, and correspondingly, from 2.4 to 5.3 in men. CONCLUSIONS: Hip fractures entail high excess mortality from all major causes of death. However, the traumatic injury of a hip fracture is the most frequently reported underlying cause of death among older patients who survive less than one year after their fracture.

Inflammation, sex, blood pressure changes and hypertension in midlife: the Hordaland Health Study.

Our aim was to test sex-specific associations of circulating markers of inflammation with blood pressure (BP) and incident hypertension in midlife. Participants in the Hordaland Health study (n = 3280, 56% women, mean age 48 years) were examined at baseline and followed for 6 years. Circulating levels of inflammatory markers including high-sensitive C-reactive protein (hs-CRP), neopterin, and pyridoxic acid ratio (PAr) index were measured at follow-up. The associations with systolic/diastolic BP and incident hypertension were tested in sex-specific linear- or logistic-regression analyses adjusted for body mass index, serum triglycerides, creatinine, physical activity, smoking and diabetes. At follow-up, women had lower mean BP than men (124/72 vs. 130/78 mmHg, p < 0.001). Higher hs-CRP was significantly associated with greater systolic and diastolic BP (standardized ß = 0.07 and ß = 0.09, both p < 0.01) in women, but not in men. Higher neopterin was associated with higher diastolic BP in women and higher PAr index was associated with higher diastolic BP in women and higher systolic and diastolic BP in men (all p < 0.01). Compared to hs-CRP < 1 mg/l, higher levels of hs-CRP 1-<3 mg/l and hs-CRP ≥ 3 mg/l were associated with new-onset hypertension only in women (odds ratio (OR) 1.74, 95% CI 1.20-2.53 and OR 1.87, 95% CI 1.20-2.90). Sex-interactions were found for hs-CRP and neopterin in models on incident hypertension and diastolic BP, respectively (both p < 0.05). Higher levels of circulating markers of inflammation were associated with higher BP and incident hypertension in a sex-specific manner. Our results suggest a sex-specific interaction between cardiovascular inflammation and BP in midlife.

Association of Markers of Inflammation, the Kynurenine Pathway and B Vitamins with Age and Mortality, and a Signature of Inflammaging.

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 and (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 2 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, interleukin (IL)-6, tumor necrosis factor alpha (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, C-reactive protein, quinolinic acid, PAr index, and KTR. The inflammaging signature included 10 markers and was strongly associated with mortality (hazard ratio [HR] per SD = 1.40, 95% CI: 1.24-1.57, p = 2 × 10-8), similar to scores based on all age-associated (HR = 1.38, 95% CI: 1.23-1.55, p = 4 × 10-8) and mortality-associated markers (HR = 1.43, 95% CI: 1.28-1.60, p = 1 × 10-10), 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 10 markers was strongly associated with mortality.

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

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.

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

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.

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.

BACKGROUND: Choline is an essential nutrient for humans and is involved in various physiologic functions. Through its metabolite betaine, it is closely connected to the one-carbon metabolism, and the fat-soluble choline form phosphatidylcholine is essential for VLDL 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. OBJECTIVES: 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, a survey including community-dwelling adults born in 1925-1927 (mean age 72 y, 55% women) and 1950-1951 (mean age 48 y, 57% women). Dietary data were obtained using a 169-item FFQ, 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 nonfasting blood sample obtained at baseline, and the association with total choline intake was 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. CONCLUSIONS: 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.

Associations of overweight, obesity and osteoporosis with ankle fractures.

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.

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

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.

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

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.

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

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.

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

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.

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

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 (Pint = 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.

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

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.

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

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 (HRQ4vsQ1 = 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 (HRQ4vsQ1 = 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 (HRQ4vsQ1 = 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.

Overall Treatment Satisfaction 5 Years After Bariatric Surgery.

INTRODUCTION: Up to 30 % of patients undergoing bariatric surgery are dissatisfied with treatment outcomes in the long term. The aim of this study was to examine overall satisfaction with treatment 5 years after bariatric surgery and its association with body mass index (BMI) and health-related quality of life (HRQOL). METHODS: Patients were surveyed 5 years after bariatric surgery; 108 patients had duodenal switch (DS) and 153 patients had laparoscopic sleeve gastrectomy (LSG). The main outcome was overall treatment satisfaction, assessed by a single question, and analyzed by multiple logistic regression. Estimates for continuous independent variables represent the odds ratios (OR) for a 2-standard deviation difference. RESULTS: Five years after surgery, 82.4 % of the patients were very satisfied or satisfied, whereas 17.6 % were unsure or dissatisfied. The following variables assessed at 5 years were associated with being dissatisfied/unsure: a higher BMI (OR = 6.1, 95 % CI = 2.7-14.0, p < 0.001), reduced obesity-specific HRQOL (OR = 3.0, 95 % CI = 1.1-7.8, p = 0.03), and reduced mental HRQOL (OR = 0.3, 95 % CI = 0.1-0.8, p = 0.02). We also found that a higher proportion of patients who underwent LSG, compared to DS, reported being dissatisfied/unsure (OR = 3.3, 95 % CI = 1.3-8.8, p = 0.01). CONCLUSION: Reduced mental HRQOL and obesity-related HRQOL, as well as higher BMI, were associated with less satisfaction with overall treatment outcomes 5 years after bariatric surgery. Differences in overall treatment satisfaction by type of operation warrant further investigation.

How should recruitment to public health surveys be conducted? / Hvordan bør rekrutteringen til folkehelseundersøkelsene gjennomføres?

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.

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

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.

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

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

Changes in quality of life 5 years after sleeve gastrectomy: a prospective cohort study.

OBJECTIVES: Sleeve gastrectomy (SG) is the most frequently performed bariatric surgery procedure worldwide, but reports on long-term quality of life (QOL) outcomes are scarce. We investigated 5-year trajectories in QOL and their associations with weight loss after SG. DESIGN: A prospective cohort study. SETTING: The study was conducted in a single Norwegian bariatric surgery centre. PARTICIPANTS: Out of 150 operated patients, 127 were included. Mean age was 41 years, 68% were women and the follow-up rate at 1 year was 85% and 64% at 1 and 5 years, respectively. OUTCOME MEASURES: Data were collected preoperatively, and 1 and 5 years after surgery assessing three different levels of QOL. The main exposure was weight loss after SG, assessed as per cent excess body mass index (kg/m2) loss (%EBMIL). The Obesity-Related Problem (OP) scale was used to measure obesity-specific health-related QOL (HRQOL). Physical (PCS) and mental (MCS) composite summary scores of the Short Form 36 Health Survey were used to capture generic HRQOL and Cantril Ladder was used to assess overall QOL. RESULTS: All HRQOL/overall QOL measures significantly improved at 1 year, followed by modest decline from 1 to 5 years after surgery. Greater %EBMIL 5 years after surgery was significantly associated with improvements in OP and PCS scores, but not with MCS and Cantril Ladder scores. Although significant (p<0.001) and clinically relevant improvements in HRQOL/overall QOL outcomes were observed at 5 years, scores were still below the general population norms. CONCLUSION: Most patients undergoing SG experience substantial weight loss accompanied by statistically significant and clinically relevant long-term improvements in HRQOL/overall QOL. However, an important minority of patients still report low HRQOL/overall QOL 5 years after SG. Further research should aim to identify other factors that contribute to impaired QOL after bariatric surgery, even in the presence of successful weight control.