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Background Benefits of elevated high-density lipoprotein cholesterol (HDL-C) levels are challenged by reports demonstrating U-shaped relations between HDL-C levels and all-cause mortality; the association with cause-specific mortality is less studied. Methods A total of 344 556 individuals (20–79 years, 52 % women) recruited from population-based health screening during 1985–2003 were followed until the end of 2018 for all-cause and cause-specific mortality by serum HDL-C level at inclusion of 99 mg/dl (< 0.78, 0.78–1.01, 1.04–1.27, 1.30–1.53, 1.55–1.79, 1.81–2.04, 2.07–2.31, 2.33–2.56, >2.56 mmol/L). Hazard ratios (HRs) were adjusted for sex, age, calendar period, smoking, total cholesterol, triglycerides, systolic blood pressure, physical activity, educational length, body mass index and ill health. Results During a mean follow-up of 22 years, 69 505 individuals died. There were U-shaped associations between HDL-C levels and all-cause, cancer and non-cardiovascular disease/non-cancer mortality (non-CVD/non-cancer), whereas for CVD there was increased risk of death only at lower levels. With HDL-C stratum 50–59 mg/dl (1.30–1.53 mmol/L) as reference, HRs [95% confidence intervals (CIs)] for levels >99 mg/dl (>2.56 mmol/L) were 1.32 (1.21–1.43), 1.05 (0.89–1.24), 1.26 (1.09–1.46) and 1.68 (1.48–1.90) for all–cause, CVD, cancer and non–CVD/non–cancer mortality, respectively. For HDL-C levels Conclusions Higher HDL-C levels were associated with increased mortality risk of several diseases which also have been associated with heavy drinking, and lower HDL-C levels were associated with increased mortality from IHD, other CVDs, gastric cancer and diabetes.

Background Several studies have shown that women and men with two children have lower mortality than the childless, but there is less certainty about mortality, including CVD mortality, at higher parities and meagre knowledge about factors underlying the parity–mortality relationship. Methods The association between parity and CVD mortality was analyzed by estimating discrete-time hazard models for women and men aged 40–80 in 1975–2015. Register data covering the entire Norwegian population were used, and the models included a larger number of relevant sociodemographic control variables than in many previous studies. To analyze the relationship between parity and seven CVD risk factors, logistic models including the same variables as the mortality models were estimated from the CONOR collection of health surveys, linked to the register data. Results Men (but not women) who had four or more children had higher mortality from CVD than those with two, although this excess mortality was not observed for the heart disease sub-group. Overweight, possibly in part a result of less physical activity, seems to play a role in this. All CVD risk factors except smoking and alcohol may contribute to the relatively high CVD mortality among childless. Conclusions Childbearing is related to a number of well-known CVD risk factors, and becoming a parent or having an additional child is, on the whole, associated with lower—or at least not higher—CVD mortality in Norway. However, for men family sizes beyond three children are associated with increased CVD mortality, with risks of overweight one possible pathway.

Aims Alcohol consumption has been linked to colorectal cancer (CRC) and also to the high-density lipoprotein cholesterol level (HDL-C). HDL-C has been associated with the incidence of CRC. The aim of this study was to investigate the association between self-reported alcohol consumption, HDL-C and incidence of CRC, separately for the two sites. Methods Altogether, 250,010 participants in Norwegian surveys have been followed-up for an average of 18 years with respect to a first-time outcome of colon or rectal cancer. During follow-up, 3023 and 1439 colon and rectal cancers were registered. Results For men, the HR per 1 drink per day was 1.05 with 95% confidence interval (0.98–1.12) for colon and 1.08 (1.02–1.15) for rectal cancer. The corresponding figures for women were 1.03 (0.97–1.10) and 1.05 (1.00–1.10). There was a positive association between alcohol consumption and HDL-C. HDL-C was inversely associated with colon cancer in men (0.74 (0.62–0.89) per 1 mmol/l) and positively associated with rectal cancer, although not statistically significant (1.15 (0.92–1.44). A robust regression that assigned weights to each observation and exclusion of weights ≤ 0.1 increased the HRs per 1 drink per day and decreased the HR per 1 mmol/l for colon cancer. The associations with rectal cancer remained unchanged. Conclusion Our results support a positive association between alcohol consumption and colon and rectal cancer, most pronounced for rectal cancer. Considering the positive relation between alcohol consumption and HDL-C, the inverse association between HDL-C and colon cancer in men remains unsettled., Short Summary: This study showed that the relation between alcohol consumption is somewhat stronger for rectal cancer than for colon cancer. Although there is a positive relation between levels of HDL and alcohol consumption, the relation between HDL and colon cancer in men is inverse. This finding warrants further studies.

AimsWhile investigators have typically quantified the health risk of passive smoking by utilising self-reported exposure, prospective studies with objective ascertainment, which are less liable to measurement error, are rare. Using data pooling, we examined the relation of a biochemical assessment of passive smoking, salivary cotinine, with mortality from a range of causes.MethodsWe combined data from twelve cohort studies from England and Scotland initiated between 1998 and 2008. Study members were linked to national death registries. A total of 36 584 men and women aged 16 to 85 years of age reported that they were non-smoking at baseline, provided baseline salivary cotinine, and consented to mortality record linkage.ResultsA mean of 8.1 years of mortality follow-up of 36 584 non-smokers (16 792 men and 19 792 women) gave rise to 2367 deaths (775 from cardiovascular disease, 780 from all cancers, and 289 from smoking-related cancers). After controlling for a range of covariates, a 10 ng/ml increase in salivary cotinine level was related to an elevated risk of total (hazard ratios; 95% confidence interval: 1.46; 1.16, 1.83), cardiovascular (1.41; 0.96, 2.09), cancer (1.49; 1.00, 2.22) and smoking-related cancer mortality (2.92; 1.77, 4.83).ConclusionsPassive smoking assessed biomedically was a risk factor for a range of health outcomes known to be causally linked to active smoking.

Aim The aim of this study was to investigate whether the coffee brewing method is associated with any death and cardiovascular mortality, beyond the contribution from major cardiovascular risk factors. Methods and results Altogether, 508,747 men and women aged 20–79 participating in Norwegian cardiovascular surveys were followed for an average of 20 years with respect to cause-specific death. The number of deaths was 46,341 for any cause, 12,621 for cardiovascular disease (CVD), 6202 for ischemic heart disease (IHD), and 2894 for stroke. The multivariate adjusted hazard ratios (HRs) for any death for men with no coffee consumption as reference were 0.85 (082–0.90) for filtered brew, 0.84 (0.79–0.89) for both brews, and 0.96 (0.91–1.01) for unfiltered brew. For women, the corresponding figures were 0.85 (0.81–0.90), 0.79 (0.73–0.85), and 0.91 (0.86–0.96) for filtered, both brews, and unfiltered brew, respectively. For CVD, the figures were 0.88 (0.81–0.96), 0.93 (0.83–1.04), and 0.97 (0.89–1.07) in men, and 0.80 (0.71–0.89), 0.72 (0.61–0.85), and 0.83 (0.74–0.93) in women. Stratification by age raised the HRs for ages ≥60 years. The HR for CVD between unfiltered brew and no coffee was 1.19 (1.00–1.41) for men and 0.98 (0.82–1.15) for women in this age group. The HRs for CVD and IHD were raised when omitting total cholesterol from the model, and most pronounced in those drinking ≥9 of unfiltered coffee, per day where they were raised by 9% for IHD mortality. Conclusion Unfiltered brew was associated with higher mortality than filtered brew, and filtered brew was associated with lower mortality than no coffee consumption.

Surprisingly few attempts have been made to quantify the simultaneous contribution of well-established risk factors to CVD mortality differences between countries. We aimed to develop and critically appraise an approach to doing so, applying it to the substantial CVD mortality gap between Russia and Norway using survey data in three cities and mortality risks from the Emerging Risk Factor Collaboration. We estimated the absolute and relative differences in CVD mortality at ages 40–69 years between countries attributable to the risk factors, under the counterfactual that the age- and sex-specific risk factor profile in Russia was as in Norway, and vice-versa. Under the counterfactual that Russia had the Norwegian risk factor profile, the absolute age-standardized CVD mortality gap would decline by 33.3% (95% CI 25.1–40.1) among men and 22.1% (10.4–31.3) among women. In relative terms, the mortality rate ratio (Russia/Norway) would decline from 9–10 to 7–8. Under the counterfactual that Norway had the Russian risk factor profile, the mortality gap reduced less. Well-established CVD risk factors account for a third of the male and around a quarter of the female CVD mortality gap between Russia and Norway. However, these estimates are based on widely held epidemiological assumptions that deserve further scrutiny.

Background and Aims The time post-release from prison involves elevated mortality, especially overdose deaths. Variations in overdose mortality both by time since release from prison and time of release has not been investigated sufficiently. Our aims were to estimate and compare overdose death rates at time intervals after prison release and to estimate the effect on overdose death rates over calendar time. Design, Setting, Participants, Measurements This 15-year cohort study includes all individuals (n = 91 090) released from prison (1 January 2000 to 31 December 2014) obtained from the Norwegian prison registry, linked to the Norwegian Cause of Death Registry (2000–14). All-cause and cause-specific mortality were examined during different time-periods following release: first week, second week, 3–4 weeks and 2–6 months, and by three different time intervals of release. We calculated crude mortality rates (CMRs) per 1000 person-years and estimated incidence rate ratios (IRR) by Poisson regression analysis adjusting for time intervals after prison release, release periods and time spent in prison. Findings Overdose deaths accounted for 85% (n = 123) of all deaths during the first week following release (n = 145), with a peak during the 2 days immediately following release. Compared with week 1, the risk of overdose death was more than halved during week 2 [IRR = 0.43; 95% confidence interval (CI) = 0.31–0.59] and reduced to one-fifth in weeks 3–4 (IRR = 0.22; 95% CI = 0.16–0.31). The risk of overdose mortality during the first 6 months post-release was almost twofold higher in 2000–04 compared with 2005–09 (IRR = 0.53; 95% CI = 0.43–0.65) and 2010–14 (IRR = 0.47; 95% CI = 0.37–0.59). The risk of overdose death was highest for those incarcerated for 3–12 months compared with those who were incarcerated for shorter or longer periods, and recidivism was associated with risk of overdose death. Conclusions There is an elevated risk of death from drug overdose among individuals released from Norwegian prisons, peaking in the first week. The risk has reduced since 2000–04, but is greatest for those serving 3–12 months compared with shorter or longer periods.

Purpose To study the association between coffee and alcoholic beverage consumption and alcoholic liver disease mortality. Methods In total, 219,279 men and women aged 30–67 years attended cardiovascular screening in Norway from 1994 to 2003. Linkage to the Cause of Death Registry identified 93 deaths from alcoholic liver disease. Coffee consumption was categorized into four levels: 0, 1–4, 5–8, and greater than or equal to 9 cups/d and alcohol consumption as 0, greater than 0 to less than 1.0, 1.0 to less than 2.0, and greater than or equal to 2.0 units/d, for beer, wine, liquor, and total alcohol consumption. Results The hazard ratios per one category of consumption were 2.06 (95% confidence interval 1.62–2.61), 0.68 (0.46–1.00), and 2.54 (1.92–3.36) for beer, wine, and liquor, respectively. Stratification at 5 cups/d (the mean) revealed a stronger association between alcohol consumption and alcoholic liver disease at less than 5 versus 5 or more cups/d. With less than 5 cups/d, 0 alcohol units/d as reference, the hazard ratio reached to 25.5 (9.2–70.5) for greater than or equal to 2 units/d, whereas with greater than or equal to 5 cups/d, it reached 5.8 (1.9–17.9) for greater than or equal to 2 units/d. A test for interaction was significant (P = .01). Conclusions Coffee and wine consumption were inversely associated with alcoholic liver disease death. Total alcohol consumption was adversely associated with alcoholic liver disease mortality and the strength of the association varied with the level of coffee consumption.

OBJECTIVE To quantify concentrations of cartilage oligomeric matrix protein (COMP) and fibromodulin in synovial fluid from the tarsocrural joints (TCJs) of horses with osteochondritis dissecans (OCD) of the distal intermediate ridge of the tibia and determine whether concentrations would change following arthroscopic removal of osteochondral fragments. ANIMALS 115 client-owned horses with OCD of the TCJ and 29 control horses euthanized for unrelated reasons. PROCEDURES COMP and fibromodulin concentrations were measured in synovial fluid from the TCJs of the affected horses before and after osteochondral fragments were removed arthroscopically and in synovial fluid from the TCJs of the control horses after euthanasia. Synovial biopsy specimens from the TCJs of affected and control horses were examined histologically for evidence of inflammation. RESULTS Synovial fluid COMP and fibromodulin concentrations prior to surgery in horses with OCD were not significantly different from concentrations in control horses. Fibromodulin, but not COMP, concentration in horses with OCD was significantly decreased after surgery, compared with the concentration before surgery. Fibromodulin concentration was significantly correlated with joint effusion score but not with lameness score or results of a flexion test and was correlated with histologic score for number of synoviocytes on the surface of the synovium but not with score for degree of infiltration of inflammatory cells in the synovium. Synovial fluid COMP concentration was not significantly correlated with clinical or histologic findings. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that fibromodulin, but not COMP, could potentially be a biomarker of joint inflammation in horses with OCD of the TCJ.

Background: There is insufficient epidemiological evidence on the relationship between type of coffee and the risk of prostate cancer. Methods: The risk of prostate cancer by use of boiled vs not boiled coffee were assessed in a prospective study of 224,234 men 20–69 years. 5740 incident prostate cancers were identified. Results: With no coffee as reference group the hazard ratios of

A potential link between intimate partner violence (IPV) and cardiovascular disease (CVD) has been suggested, yet evidence is scarce. We assessed cardiovascular risk and incident prescription of cardiovascular medication by lifetime experiences of physical and/or sexual IPV and psychological IPV alone in women.A population-based cohort study of women aged 30-60 years was performed using cross-sectional data and clinical measurements from the Oslo Health Study (2000-2001) linked with prospective prescription records from the Norwegian Prescription Database (January 1, 2004 to December 31, 2009). We used age-standardized chi-square analyses to compare clinical characteristics by IPV cross-sectionally, and Cox proportional hazards regression to examine cardiovascular drug prescription prospectively.Our study included 5593 women without cardiovascular disease or drug use at baseline. Altogether 751 (13.4%) women disclosed IPV experiences: 415 (7.4%) physical and/or sexual IPV and 336 (6.0 %) psychological IPV alone. Cross-sectional analyses showed that women who reported physical and/or sexual IPV and psychological IPV alone were more often smokers compared with women who reported no IPV. Physical and/or sexual violence was associated with abdominal obesity, low high-density lipoprotein cholesterol, and elevated triglycerides. The prospective analysis showed that women who reported physical and/or sexual IPV were more likely to receive antihypertensive medication: incidence rate ratios adjusted for age were 1.27 (95% confidence interval 1.02-1.58) and 1.36 (CI 1.09-1.70) after additional adjustment for education and systolic and diastolic blood pressure, respectively. No significant differences were found for cardiovascular drugs overall or lipid modifying drugs.Our findings indicate that clinicians should assess the cardiovascular risk of women with a history of physical and/or sexual IPV, and consider including CVD prevention measures as part of their follow-up.

Overweight-obesity and smoking are two main preventable causes of premature death. Because the relationship between smoking and body mass index (BMI) complicates the interpretation of associations between BMI and death risks, direct estimates of risks associated with joint exposures are helpful. We have studied the relationships of BMI and smoking to middle age (40-69 years) death risk-overall and by causes-in a Norwegian cohort of 32,727 women and 33,475 men who were 35-49 years old when baseline measurements and lifestyle information were collected in 1974-1988. Individuals with a history of cancer, cardiovascular disease or diabetes at baseline were excluded. Mortality follow-up was through 2009. The relationship between BMI and middle age death risk was U-shaped. Overall middle age death risks were 11% in women and 21 % in men. The combination of obesity and heavy smoking resulted in fivefold increase in middle age death risks in both women and men: For women middle age death risk ranged from 6 % among never smokers in the 22.5-24.9 BMI group to 31% (adjusted 28%) in obese (BMI > 30 kg/m(2)) heavy smokers (≥20 cigarettes/day). The corresponding figures in men were 10% and 53% (adjusted 45%). Obese never smokers and light (1-9 cigarettes/day) smokers in the 22.5-24.9 BMI groups both experienced a twofold increase in middle age risks of death. For women, cancer (56%) was the most common cause of death followed by cardiovascular disease (22%). In men, cardiovascular disease was most common (41%) followed by cancer (34%). Cardiovascular disease deaths were more strongly related to BMI than were cancer deaths.

Background: While hypertension still is a major health problem worldwide, some studies have indicated that the blood pressure level has decreased in some populations. This population based cohort study aims at analysing blood pressure changes in a large Norwegian population over a 22 year period. Methods: Data is acquired from three comprehensive health surveys of the HUNT Study conducted from 1984–86 to 2006–08. All citizens of Nord-Trøndelag County, Norway, >20 years were invited: 74,549 individuals participated in 1984–86; 64,523 in 1995–97; and 43,905 in 2006–08. Results: Both systolic and diastolic blood pressure levels decreased substantially from mid 1980s to mid 2000s, with the most pronounced decrease from 1995–97 to 2006–08 (from 136.0/78.9 to 128.3/70.9 mmHg in women and from 140.1/82.1 to 133.7/76.5 mmHg in men). Although the use of blood pressure lowering medication increased, there was a considerable decrease even in those who reported never use of medication (mean decrease 6.8/7.2 mmHg in women and 6.3/5.3 mmHg in men), and the decrease was most pronounced in the elderly (mean decrease 16.1/12.4 mmHg in women and 14.7/10.4 mmHg in men aged 80+). Mean heart rate, total cholesterol and daily smoking decreased, self-reported hard physical activity increased, while body weight and the prevalence of diabetes increased during the same period. Conclusions: The BP decrease might seem paradoxically, as body weight and prevalence of diabetes increased during the same period. Salt consumption might have decreased, but no salt data is available. The parallel decrease in mean heart rate might indicate reduction in the white-coat phenomenon, or increased use of beta blockers or calcium channel blockers for other diagnosis than hypertension. Additionally, the data could support the “healthy obese” hypothesis, i.e., that subgroups in the population can sustain obesity without serious health consequences. © 2016 Holmen et al. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Declining incidences of hip fractures are reported from western countries. Norway has among the highest rates in the world. The aim of this study was to investigate trends in total hip fracture rates in Norway between 1999 and 2008 and risk of second hip fractures. All hospitalizations given a hip fracture diagnosis code (International Classification of Diseases (ICD) 9 or ICD 10) (cervical, trochanteric or subtrochanteric) in Norwegian hospitals were retrieved with accompanying surgical procedure codes and additional diagnoses. A total of 93,123 hip fractures were identified between 1999 and 2008 in persons ≥50 years. Annual incidences of hip fractures were calculated and tested for trends. Rates of first and second hip fractures (2006-2008) were compared. The age-standardized total incidence of hip fracture decreased by 13.4 % (95 % confidence interval (CI): 11.0-15.6) in women and 4.8 % (95 % CI: 0.7, 8.7) in men. Age-adjusted rates of second hip fractures did not change in the observation period. In those with a prior hip fracture, the age-standardized risk of a subsequent hip fracture was 2.5-fold (95 % CI: 2.5, 2.6) in women, and 4.6-fold (95 % CI: 4.5, 4.7) in men. Total hip fracture rates declined in both genders during 1999-2008, whereas rates of second hip fractures did not change.

Background: The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain. Methods: We calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies. Results: For people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators. Conclusion: Adult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2012; all rights reserved.

BACKGROUND Many studies have demonstrated that a low socioeconomic status is associated with poor health. The aim of the study was to investigate whether use of prescription drugs, generally and within selected categories, varies with education. MATERIAL AND METHOD Data on education from the 2001 Population and Housing Census for 645,023 men and women born in the period 1960-1969 and living in Norway in 2001 were linked to data from the Norwegian Prescription Database on drugs dispensed in the period 2004-2009. The overall frequency of drug dispensing was compared with six levels of education. The relative risk associated with limited education (≤ 10 years) compared with long education (> 10 years) of having at least one drug dispensed during the period was calculated for 42 selected drug categories. RESULTS There was a dose-response relationship between education and the number of drug prescriptions dispensed. Subjects with lower secondary education collected prescription drugs about three times as often on average as subjects with researcher education. The average relative risk of drug dispensing for subjects with short education (≤ 10 years) compared with long (>10 years) for the 42 selected drug categories was 1.29 for men and 1.31 for women. INTERPRETATION Given that dispensing of drugs is an expression of state of health, our findings support earlier studies that have shown that there is social inequality in the health of the adult population.

Purpose To examine the occurrence of chronic diseases and antimicrobial treatment in an asthma population 8–29 years old, compared with the general population. Methods In this cross-sectional study, the asthma population was identified from the general population (retrieved from a census covering the entire Norwegian population) using filled prescriptions on asthma drugs as a proxy measure of current asthma. The outcome was excess occurrence of specific diseases (comorbidity) among people with asthma, compared with the age-specific general population. Diseases were defined by filled prescriptions with specific diagnostic codes (International Classification of Primary Care 2nd edition [ICPC-2] or International Classification of Diseases 10th revision [ICD-10]) during a 1-year period in the Norwegian Prescription Database. Nine chronic diseases were examined: attention deficit/hyperactivity disorder, epilepsy, migraine, mental illness, cardiovascular disease, diabetes, autoimmune disorders, gastro-oesophageal reflux disease (GORD), and allergy. Additionally, antibacterials recommended for respiratory tract infections and antivirals were examined (defined by Anatomical Therapeutic Chemical codes). Standardized morbidity ratios (SMR) for each disease were calculated. Results Fifty-nine percent of the population with asthma had at least one of nine chronic diseases examined, compared with 18% in the general population. Few individuals with asthma had more than one additional chronic disease (6% of male subjects and 8% of female subjects). SMRs were increased for all diseases except diabetes, implying higher than expected occurrence of the specific diseases in people with asthma. This pattern was observed in both age groups (8–19 and 20–29 years) and genders. Allergy and GORD had highest SMR (range 3.2–4.8), whereas the other diseases were in the range 1.2–2.5. Conclusions An excess occurrence of comorbidities was found in the population with asthma. A majority of people with asthma had one additional chronic disease, and few had more than one. Copyright © 2011 John Wiley & Sons, Ltd.

Antibacterial prescribing is driving antibiotic resistance. We aimed to analyse whether smoking habits are associated with susceptibility to be prescribed antibacterials in primary care and to examine whether patients' smoking habits influence physicians' choice of therapy.Information on smoking habits from health surveys in 1985-99 was related to use of antibacterials 5-25 years later by linkage to the Norwegian Prescription Database. The study population included 365 117 men and women, 40-45 years old. Individuals likely to have chronic obstructive airway disease were excluded. Relative risk (RR) of being dispensed antibacterials for systemic use was calculated for five levels of smoking intensity with never smokers as reference. Adjustments were made for age, education, marital status, household size, body mass index and residence (rural/urban).Fifty-six percent of the male and 69% of the female never smokers received at least one antibacterial prescription in the whole period, increasing to 68% and 82%, respectively, in heavy smokers (19 cigarettes/day) (adjusted RR 1.17 and 1.16). The percentage receiving at least one antibacterial prescription every year was 0.5% in male and 1.9% in female never smokers, increasing to 1.1% and 4.0%, respectively, in heavy smokers (adjusted RR 2.07 and 1.89). The proportion of antibacterial users who were prescribed broad-spectrum antibacterials increased with increasing cigarette consumption.Smoking habits influenced the usage of antibacterials years later with a dose-response relationship. Prescribers seem to acknowledge smoking as a risk factor for resistant bacteria since broad-spectrum antibacterials are more frequently prescribed to smokers than never smokers.

The association between nonfasting triglycerides and cardiovascular disease (CVD) has recently been actualized. The aim of the present study was to investigate nonfasting triglycerides as a predictor of CVD mortality in men and women. A total of 86,261 participants in the Norwegian Counties Study 1974–2007, initially aged 20–50 years and free of CVD were included. We estimated hazard ratios (HRs) for deaths from CVD, ischemic heart disease (IHD), stroke and all causes by level of nonfasting triglycerides. Mean follow-up was 27.0 years. A total of 9,528 men died (3,620 from CVD, 2,408 IHD, 543 stroke), and totally 5,267 women died (1,296 CVD, 626 IHD, 360 stroke). After adjustment for CVD risk factors other than HDL-cholesterol, the HRs (95% CI) per 1 mmol/l increase in nonfasting triglycerides were 1.16 (1.13–1.20), 1.20 (1.14–1.27), 1.26 (1.19–1.34) and 1.09 (0.96–1.23) for all cause mortality, CVD, IHD, and stroke mortality in women. Corresponding figures in men were 1.03 (1.01–1.04), 1.03 (1.00–1.05), 1.03 (1.00–1.06) and 0.99 (0.92–1.07). In a subsample where HDL-cholesterol was measured (n = 40,144), the association between CVD mortality and triglycerides observed in women disappeared after adjustment for HDL-cholesterol. In a model including the Framingham CHD risk score the effect of triglycerides disappeared in both men and women. In conclusion, nonfasting triglycerides were associated with increased risk of CVD death for both women and men. Adjustment for major cardiovascular risk factors, however, attenuated the effect. Nonfasting triglycerides added no predictive information on CVD mortality beyond the Framingham CHD risk score in men and women.

Background Meta-analysis of individual participant time-to-event data from multiple prospective epidemiological studies enables detailed investigation of exposure–risk relationships, but involves a number of analytical challenges. Methods This article describes statistical approaches adopted in the Emerging Risk Factors Collaboration, in which primary data from more than 1 million participants in more than 100 prospective studies have been collated to enable detailed analyses of various risk markers in relation to incident cardiovascular disease outcomes. Results Analyses have been principally based on Cox proportional hazards regression models stratified by sex, undertaken in each study separately. Estimates of exposure–risk relationships, initially unadjusted and then adjusted for several confounders, have been combined over studies using meta-analysis. Methods for assessing the shape of exposure–risk associations and the proportional hazards assumption have been developed. Estimates of interactions have also been combined using meta-analysis, keeping separate within- and between-study information. Regression dilution bias caused by measurement error and within-person variation in exposures and confounders has been addressed through the analysis of repeat measurements to estimate corrected regression coefficients. These methods are exemplified by analysis of plasma fibrinogen and risk of coronary heart disease, and Stata code is made available. Conclusion Increasing numbers of meta-analyses of individual participant data from observational data are being conducted to enhance the statistical power and detail of epidemiological studies. The statistical methods developed here can be used to address the needs of such analyses.

Studies of clinical cohorts and retrospective reports have identified psychiatric disorders as paramount risk factors for suicide. Much less is known about how self-reported mental health is related to completed suicide. To study the relation between self-reported mental health and risk of completed suicide, the authors prospectively followed a population-based Norwegian cohort of 61,588 men and 69,774 women aged 39-44 years for an average of 10.4 years between 1994 and 2007. Self-reported mental health was measured using an instrument based on the Hopkins Symptom Checklist and the General Health Questionnaire. Completed suicides were registered in the official Norwegian Cause of Death Registry. Females reported higher levels of mental distress than males. In comparison with persons reporting the fewest mental health symptoms, the adjusted hazard ratio for suicide increased from 1.8 (95% confidence interval (CI): 1.1, 2.9) in the moderately depressed group to 8.9 (95% CI: 4.4, 18.2) in the most depressed group. The risk difference was greatest in males. At each level of the mental health index, males had double the risk of suicide of females (hazard ratio = 2.3, 95% CI: 1.5, 3.3). This study shows a dose-response effect of self-reported mental health problems on completed suicide and replicates the gender paradox observed in the general population with prospective data.

The original publication is available at: http://dx.doi.org/10.1016/j.socscimed.2009.11.015 The proportion of Norwegians on disability pensions has doubled since the 1980s. The Norwegian Government wants action to stimulate the working capacity in those disability pensioners who have the potential to work. Information on factors that may impair rehabilitation efforts, including the unfavourable use of benzodiazepines, may be useful in this context. A longitudinal design, including data on 40–42 year old participants in Norwegian health surveys (year 1985–1989) linked to a prescription database (year 2004–2006), was used to describe risk of long-term use of benzodiazepines among disability pension recipients. The study population constituted benzodiazepine users at baseline. More than half of those on disability pensions, 57% of all men and 65% of all women, retrieved benzodiazepine prescriptions 20 years later, a span covering a large part of the potential active workforce period. Further, the observed amount of benzodiazepines dispensed over a three-year period indicated more than sporadic use e.g. half of the female disability pensioners were dispensed an amount of benzodiazepines corresponding to the use of a daily dose every second day over a three year period (median 450 daily doses). The majority of those who were dispensed benzodiazepines, were dispensed opioids as well: half of all men and 3 out of four women. And last, being on a disability pension was a predictor of benzodiazepine use 20 years later. Our study suggests that benzodiazepines are extensively and unfavourably used among disability pensioners, and that disability pension may have an independent effect on long-term use. Improved management of benzodiazepine use may be one alternative to get disability pensioners with the potential to work back into employment.

Objective—To develop a scoring system for histopathologic changes in the synovium of tarsocrural joints (TCJs) of horses with osteochondritis dissecans (OCD) and to test for association between histopathologic changes and joint effusion or lameness. Animals—93 horses with OCD of the intermediate ridge of the tibia of 1 or both TCJs (134 joints) and 38 control horses without disease of TCJs (38 joints). Procedures—For OCD-affected horses, pretreatment lameness, TCJ effusion, and results of pelvic limb flexion test were scored. Synovial biopsy specimens were obtained from TCJs of OCD-affected horses during arthroscopy, and similar postmortem tissue specimens were obtained from control horses through a small arthrotomy. Histologic signs of synovitis in 172 biopsy specimens were scored by 2 pathologists (A and B) by use of 2 criteria: synoviocyte proliferation and cellular infiltration. Results—Analysis of scoring revealed good to very good intraobserver agreement within pathologist A (weighted kappa [WK], 0.76 to 0.81), and moderate to good agreement within pathologist B (WK, 0.56 to 0.63). Interobserver agreement for synoviocyte proliferation (WK, 0.34 to 0.52) and cellular infiltration (WK, 0.38 to 0.48) scores was fair to moderate. Joint effusion and synoviocyte proliferation were significantly associated, as were joint effusion and cellular infiltration. There was no association between histopathologic changes and the other clinical signs evaluated. Conclusions and Clinical Relevance—The scoring system was helpful for evaluating synovial inflammation caused by OCD of the intermediate ridge of the tibia in horses. Histopathologic signs of synovial inflammation were associated with effusion but not with lameness.

BACKGROUND From 1948 to 1975, Norway had a mandatory tuberculosis (TB) screening programme with Pirquet testing, X-ray examinations and BCG vaccination. Electronic data registration in 1963-75 enabled the current study aimed at revealing (i) the relations between socioeconomic factors and tuberculosis infection and (ii) differences in later all-cause mortality according to TB infection status. METHODS TB screening data were linked to information from the Norwegian Cause of Death Registry (1975-98) and the National Population and Housing Censuses (1960, 1970 and 1980). Analyses were done for 10 years cohorts born 1910-49, separately for men (approximately 534,000 individuals) and women (608,000), using logistic and Cox regressions. RESULTS TB infection and X-ray data confirmed the strong regional pattern seen for TB mortality, with the highest rates in the three northernmost counties and higher rates in urban than rural areas. High socioeconomic status relates to lower odds both for TB infection and TB-related chest X-ray findings (odds ratios 0.6-0.7 for highest vs lowest educational groups). Those infected by TB, and especially those with chest X-ray findings, have increased all-cause mortality in at least a 20 years period following determination of tuberculin status (hazard ratios approximately 1.15 and 1.30, respectively, higher for late than early cohorts). CONCLUSIONS TB particularly affected lower socioeconomic strata, but even those in higher strata were at high risk. The differences in all-cause mortality could partly be attributed to socioeconomic factors, but we hypothesize that developing TB infection may also indicate biological frailness.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Use of statins reduces cardiovascular morbidity and mortality. • Little is known about educational inequalities in use of statins. WHAT THIS STUDY ADDS • In Norway in patients with no history of cardiovascular disease or diabetes, start of statin treatment was not associated with educational level after adjustment for cardiovascular risk factors. • In patients with a history of cardiovascular disease or diabetes, especially highly educated women tended to start statin treatment more often than women of low educational level. • Persistence of statin treatment did not vary by educational level. AIMS To study the influence of patients' education and cardiovascular risk factors on the probability of statin treatment. METHODS A prospective cohort study of participants in regional health surveys in Norway 2000–2002 with statin use recorded in the Norwegian Prescription Database 2004–2006 as outcome measure. Information on history of cardiovascular disease (CVD) and diabetes, lipid levels, blood pressure, use of cardiovascular drugs, body mass index, family history, smoking, physical activity, marital status and place of residence was obtained at baseline. A total of 20 212 men and women aged 40–41, 45–46 and 59–61 years who reported never use of statins were included. Educational level was retrieved from Statistics Norway. Adjusted relative risks (RR) were estimated by Poisson regression. RESULTS Whereas 655 participants reported a history of CVD or diabetes, 19 557 reported no such history. In the non-CVD/diabetes group 1620 persons (8%) became statin users and 222 persons (34%) in the CVD/diabetes group. RR of becoming a statin user for high vs. low education increased from 0.64 [95% confidence interval (CI) 0.55, 0.73] to 0.91 (95% CI 0.79, 1.05) after adjustment in the non-CVD/diabetes group and from 0.94 (95% CI 0.70, 1.26) to 1.35 (95% CI 1.00, 1.81) in the CVD/diabetes group. CONCLUSIONS Patients with no history of CVD/diabetes were prescribed statins according to cardiovascular risk independent of education. There was a tendency to a higher probability of statin treatment among highly educated compared with people of lower educational level in the group with a history of CVD or diabetes, after adjustment for other CVD risk factors, particularly in women.

Objectives: To estimate the risk of dying from all causes and from specified smoking-related diseases in people who were ex-smokers at two consecutive examinations, compared with never smokers and with people who were ex-smokers at the first examination but who had resumed smoking at the following examination. Design: A prospective cohort study. Setting: Three counties in Norway. Participants: A total of 23 560 men and 25 122 women, aged 20–49, screened for cardiovascular disease risk factors in the mid 1970s, rescreened after 3–13 years and followed throughout 2005 participated in this study. Outcomes: Absolute mortality and relative risks adjusted for confounding variables, of dying from all causes, cardiovascular disease, ischaemic heart disease, stroke, lung cancer and other smoking-related cancer. Results: With sustained never smokers as reference, the sustained ex-smokers had adjusted relative risk (95% CI), of dying from any cause, for men 0.97 (0.80 to 1.18), for women 0.98 (0.65 to 1.48). Corresponding risk for ex-smokers who resumed smoking was for men 1.59 (1.32 to 1.91), for women 1.40 (1.08 to 1.81). For the specified smoking-related diseases, the risk in sustained ex-smokers was not significantly different from the risk in sustained never-smokers, except for lung cancer in men. For ex-smokers who resumed smoking, the corresponding risk was on the whole significantly higher. Conclusions: A more valid and favourable picture of ex-smokers’ risk will be obtained if exposure is being based upon people with two consecutive examinations, years apart. The study confirms clearly the large health benefit of quitting smoking for good.

BACKGROUND 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. OBJECTIVES We aimed to study associations of tCys and tHcy with body composition in the general population. DESIGN 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. RESULTS 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 corresponding values for men were 6 kg (95% CI: 5, 7 kg; P < 0.001; P < 0.001 in both sexes, ANOVA across quintiles). The rise in tCys over 6 y was associated with greater fat mass at follow-up (P < 0.001), but there was no effect on lean mass. tHcy was not associated with lean mass, and it became significantly inversely associated with BMI and fat mass only after adjustment for tCys. The association between tHcy and lean mass was not significant. CONCLUSIONS tCys concentrations show a strong positive association with BMI, mediated through fat mass. The link between cysteine and lipid metabolism deserves further investigation.

Aim To study the relationship between heart rate and (a) all deaths and (b) cardiovascular deaths in a large cohort of middle-aged Norwegian men and women. Methods and results A prospective study of participants in cardiovascular surveys that were carried out in 1985–1999 and covered men and women aged 40–45 years in all counties except the capital, Oslo. In total, 180 353 men and 199 490 women aged 40–45 years without cardiovascular history or diabetes accrued 4 775 683 years of follow-up. There was a positive and graded association between heart rate and mortality from all causes, as well as between heart rate and deaths from cardiovascular disease (CVD), ischaemic heart disease, and stroke. However, these associations were greatly reduced when we adjusted for the main risk factors of disease. The hazard ratios for any death were reduced from 3.14 to 1.82 for men (95% CI, 1.62–2.04) and from 2.14 to 1.37 for women (95% CI, 1.19–1.59), when we compared ≥95 b.p.m. with

PURPOSE: The aim of the study was to evaluate the effect of the consumption of anxiolytic or hypnotic drugs on total mortality in a general population. METHODS: We followed a cohort of 7225 men and 7726 women aged 40-42 years who underwent health surveys in 1985-1989 in two Norwegian counties, with respect to deaths. Mean follow-up period was 18 years. The subjects were categorised according to frequency of anxiolytic or hypnotic drug use during the last month: daily, every week, less than every week and not used during the last month. RESULTS: The proportion of anxiolytic or hypnotic drug users was 6.6% among men and 16.2% among women. Altogether 402 men and 290 women died. There was an increase in risk of death with an increase in frequency of use. Crude hazard ratios for men and women daily using anxiolytics or hypnotics were 3.1 (95%CI 2.0, 4.8) and 2.7 (1.9, 4.0), respectively, as compared with non-users last month. After adjusting painkiller use and smoking the hazard ratios were lowered, being 2.4 (1.5-4.0) (men) and 2.1 (1.4-3.2) (women). After additional adjustments for other possible confounders the hazard ratios were further attenuated to 1.5 (0.9-2.7) for men and 1.7 (1.1-2.6) for women. CONCLUSIONS: Daily users of anxiolytic or hypnotic drugs in our study showed higher crude mortality than non-users. However, after adjusting lifestyle and socio-economic variables the difference was markedly reduced suggesting that the remaining excess mortality is due to residual confounding. Language: en

The aim of the study was to compare educational and gender specific trends in the classical cardiovascular risk factors body mass index (BMI), cholesterol, systolic blood pressure and smoking in a Norwegian population during a period when the coronary heart disease mortality had just reached its peak in the late 1970s and 1980s. We used The Norwegian Counties study: a longitudinal study with three screenings on the same individuals in Oppland, Sogn og Fjordane and Finnmark counties in Norway in the period 1974-1988. All residents aged 35-49 were invited and 48,422 participated (89%) in the baseline screening. To estimate the cardiovascular risk factor change in individuals over time longitudinal statistical methods were used. BMI, cholesterol and blood pressure levels increased with age, while the amount of daily smokers decreased. The higher the educational level the lower the level of BMI, blood pressure, smoking and cholesterol. This pattern persisted through the whole study period. In men, however, the educational gradient in cholesterol diminished in the last screening. Among women there was an increase in inequality in systolic blood pressure, and for smoking there was a steeper decrease for men than women across all educational groups. The educational differences in classical cardiovascular risk factors persisted, except for BMI, cholesterol and daily smokers in men which tended to decrease.

Objectives: To determine the risk in men and women smoking 1–4 cigarettes per day of dying from specified smoking related diseases and from any cause. Design: Prospective study. Setting: Oslo city and three counties in Norway. Participants: 23 521 men and 19 201 women, aged 35–49 years, screened for cardiovascular disease risk factors in the mid 1970s and followed throughout 2002. Outcomes: Absolute mortality and relative risks adjusted for confounding variables, of dying from ischaemic heart disease, all cancer, lung cancer, and from all causes. Results: Adjusted relative risk (95% confidence interval) in smokers of 1–4 cigarettes per day, with never smokers as reference, of dying from ischaemic heart disease was 2.74 (2.07 to 3.61) in men and 2.94 (1.75 to 4.95) in women. The corresponding figures for all cancer were 1.08 (0.78 to 1.49) and 1.14 (0.84 to 1.55), for lung cancer 2.79 (0.94 to 8.28) and 5.03 (1.81 to 13.98), and for any cause 1.57 (1.33 to 1.85) and 1.47 (1.19 to 1.82). Conclusions: In both sexes, smoking 1–4 cigarettes per day was associated with a significantly higher risk of dying from ischaemic heart disease and from all causes, and from lung cancer in women. Smoking control policymakers and health educators should emphasise more strongly that light smokers also endanger their health.

UNLABELLED BACKGROUND There are few long-term follow-up data on the relation between body mass index (BMI) in adolescence and in adulthood, and between adolescent BMI and adult mortality. The present study explores these relations. METHODS In Norwegian health surveys during 1963-1999, height and weight were measured for 128,121 persons in a standardized way both in adolescence (age 14-19 years) and 10 or more years later. Persons were followed for an average of 9.7 years after the adult measurement. Cox proportional hazard regression models were used to study the association between adolescent and adult BMI and mortality. RESULTS The odds ratio of obesity (BMI >/=30) in adulthood increased steadily with BMI in adolescence, from 0.2 for low BMI up to 16 for very high BMI. Very high adolescent BMI was associated with 30-40% higher adult mortality compared with medium BMI. Adjusting for adult BMI explained most of the association of adolescent obesity and mortality, especially among men. Adjustment for smoking did not change the results. CONCLUSIONS Obesity in adolescence tends to persist into adulthood. Adolescent obesity is also connected to excess mortality, but this excess seems to be explained mostly by obesity in adulthood. High BMI in adolescence seems to be predictive of both adult obesity and mortality.

Aims The SCORE project was initiated to develop a risk scoring system for use in the clinical management of cardiovascular risk in European clinical practice. Methods and results The project assembled a pool of datasets from 12 European cohort studies, mainly carried out in general population settings. There were 205 178 persons (88 080 women and 117 098 men) representing 2.7 million person years of follow-up. There were 7934 cardiovascular deaths, of which 5652 were deaths from coronary heart disease. Ten-year risk of fatal cardiovascular disease was calculated using a Weibull model in which age was used as a measure of exposure time to risk rather than as a risk factor. Separate estimation equations were calculated for coronary heart disease and for non-coronary cardiovascular disease. These were calculated for high-risk and low-risk regions of Europe. Two parallel estimation models were developed, one based on total cholesterol and the other on total

A large number of studies have explored the relation between body mass index (BMI) and mortality in adults. The relation between BMI in adolescence and mortality has been investigated to a lesser extent. It has been suggested that all-cause mortality is elevated among those who were overweight during adolescence, but the limitation of previous studies has been study size. The present study explored this relation in a Norwegian cohort of 227,003 boys and girls, aged 14-19 years, whose height and weight were measured during tuberculosis screening in 1963-1975. These persons were followed for an average of 31.5 years (about 7.2 million person-years). A total of 7,516 deaths were registered. Multivariate Cox proportional hazards regression models were used in the analyses. An increasing risk of death by increasing BMI in adolescence was observed. Mortality among males whose baseline BMI was between the 85th and 95th percentiles and above the 95th percentile in the US reference population was 30% and 80% higher, respectively, than that among those whose baseline BMI was between the 25th and 75th percentiles. The corresponding rates among females were 30% and 100%. The excess mortality among adolescents whose BMI was high was not clearly manifested before they reached their thirties. Hence, BMI in adolescence is predictive of adult mortality.

Purpose To study the association between body mass index (BMI) and mortality, and to evaluate the effect of physical activity during leisure time and smoking on this association in a general male population. Methods During 1974-1978, all men aged 35-49 yr living in three Norwegian counties were invited to a cardiovascular screening, and 87.1% attended and had their weight and height measured. Men with recognized cardiovascular diseases, diabetes mellitus, or cancer at screening were excluded. The cohort (N = 22,304) was followed for an average of 16.3 yr with respect to total and cause-specific mortality. Results During follow-up, 1909 men died. We found a J-shaped association between BMI and total mortality, and the form of association was similar for death from cardiovascular diseases. Although not statistically significant, a J-shaped association was also suggested in never-smokers. Irrespective of BMI level, ex- and never-smokers had lower mortality than current smokers. Obese smoking men had a relative risk of dying of 2.01 (95% CI: 1.29-3.11) compared with obese never-smokers, and a relative risk of 4.55 (95% CI: 3.34-6.20) compared with normal weight never-smokers (BMI 22-24.9 kg x m(-2)). Within each category of physical activity during leisure time, obese men had a similar increased relative risk of death compared with normal-weight individuals. However, the U- to J-shaped association between BMI and mortality seemed to disappear by increasing level of physical activity, but this finding was not significant. Conclusion This study suggests a J-shaped association between BMI and total mortality, also when stratified on smoking habits and physical activity. The suggested linear trend in the most physical active men needs to be reassessed.

BACKGROUND Few population-based studies have assessed relations between plasma or serum total homocysteine (tHcy) and all-cause mortality. OBJECTIVE Our goal was to study associations between plasma tHcy and all-cause, cardiovascular, and noncardiovascular mortality. DESIGN 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. RESULTS 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 and 1.3, 2.1, 2.6, and 3.5 (P for trend = 0.0002) for cardiovascular causes of death. A tHcy increment of 5 micromol/L was associated with a 49% (95% CI: 28%, 72%) increase in all-cause mortality, a 50% (95% CI: 21%, 85%) increase in cardiovascular mortality (121 deaths), a 26% (95% CI: -2%, 63%) increase in cancer mortality (103 deaths), and a 104% (95% CI: 44%, 289%) increase in noncancer, noncardiovascular mortality (33 deaths). CONCLUSION Plasma tHcy is a strong predictor of both cardiovascular and noncardiovascular mortality in a general population of 65-72-y-olds. These results should encourage studies of tHcy in a wider perspective than one confined to cardiovascular disease.

An elevated circulating level of total homocysteine (tHcy) is a powerful and independent risk factor for vascular disease as well as an indicator of folate deficiency. Both infants with neural tube defects and their mothers have altered homocysteine metabolism, and numerous studies have pointed to a relation between plasma tHcy and both pregnancy complications and a compromised neonatal outcome. This analysis examined associations between tHcy and reproductive outcomes in 5883 women 40 to 42 years of age who were enrolled in the Hordaland Homocysteine Study conducted in Norway during 1992–1993. The findings were compared with those of 14,492 pregnancies in the same women during the years 1967–1996. Women with the highest tHcy levels smoked more than the others, drank more coffee, were less educated, and used fewer vitamin supplements. In addition, they tended to have their children at a younger age than women with lower tHcy values. Preeclampsia correlated with the tHcy level to a highly significant degree, particularly in women who delivered prematurely. Controlling for blood pressure weakened this association, but for pregnancies lasting less than 37 weeks, the odds ratio (OR) for preeclampsia in women with plasma tHcy in the upper quartile was 4.42. The risk of placental abruption was elevated in women with a high tHcy level (OR, 3.13), and elevations also correlated with premature deliveries before 37 weeks’ gestation and before 32 weeks’ gestation. Low birth weight correlated strongly with relatively high tHcy values. After 1970 the OR for very low birth weight ( Am J Clin Nutr 2000;71:962–968

A comparative cohort study of reproductive performance in organic and conventional dairy husbandry was conducted using longitudinal data from the Norwegian National Board of Animal Production Recording from January 1, 1994 to December 31, 1996. The present study is the first study comparing reproductive efficiency in organic and conventional husbandry in which characteristics such as herd size, breeding season, milk yield, parity, breed, use of artificial insemination (AI), and geographical distribution were taken into account. The organically managed cohort comprised 998 lactation periods, and the conventionally managed cohort comprised 3016 lactation periods. Both groups were similar in herd size and geographical distribution. The following reproduction variables were studied: days open, calving interval, calving to first AI interval, calving to last AI interval, and AI per cow. No consistent difference in reproductive performance was found between the cohorts before adjustments were made for milk yield, breeding season, service, and parity. After inclusion of these independent variables in the repeated measures, mixed-model analyses, reproductive efficiency of organically managed dairy cows was impaired compared with those under conventional management. In organic dairy farming, breeding efficiency was difficult to maintain in cows bred during winter. Organic husbandry proved more efficient than did conventional husbandry in converting roughage into milk. Furthermore, the average multiparity percentage was higher in organically managed cows.

The combination of an immunohistochemical technique and a panel of monoclonal antibodies was used to investigate the presence of leukocyte populations in the distal jejunal lymph node of 3–4 week old calves and adult cattle. The application of computer-assisted morphometric analysis enabled information to be obtained on the distribution of leukocyte populations in lymphoid compartments of the lymph node cortex. Semi-quantitative estimates of the areas of staining in histological sections showed that calves possessed significantly fewer B-cells and CD4+ cells in the outer cortex and significantly fewer T-cells (CD4+, CD8+ and γδ T-cells) in the deep cortex. These findings were interpreted to be a possible consequence of immunosuppression resulting from the passive transfer of maternal immunity in colostrum. The presence of some B-cell follicles in the region defined as the deep cortex suggested the on-going differentiation of this predominantly T-cell compartment. The larger presence of interdigitating cells (IDC) in the deep cortex of calves than adults was suggested by significantly larger CD1+ populations and it was argued that this could be the result of the confrontation with exogenous antigen faced by calves in early postnatal life. Antigen presenting populations, pan MHC II + and MHC II DQ + populations, were increased in all compartments of calf lymph nodes but were not significantly different from the populations in adult lymph nodes. Variance component analysis of the data generated in the present study showed that the image analysis technique was an effective and statistically powerful approach to investigate leukocyte populations within the specific microenvironments of the lymph node.

Background: The effects of systolic blood pressure (SBP), serum total cholesterol (TC), fasting plasma glucose (FPG), and body mass index (BMI) on the risk of cardiovascular diseases (CVD) have been established in epidemiological studies, but consistent estimates of effect sizes by age and sex are not available. Methods: We reviewed large cohort pooling projects, evaluating effects of baseline or usual exposure to metabolic risks on ischemic heart disease (IHD), hypertensive heart disease (HHD), stroke, diabetes, and, as relevant selected other CVDs, after adjusting for important confounders. We pooled all data to estimate relative risks (RRs) for each risk factor and examined effect modification by age or other factors, using random effects models. Results: Across all risk factors, an average of 123 cohorts provided data on 1.4 million individuals and 52,000 CVD events. Each metabolic risk factor was robustly related to CVD. At the baseline age of 55-64 years, the RR for 10 mmHg higher SBP was largest for HHD (2.16; 95% CI 2.09-2.24), followed by effects on both stroke subtypes (1.66; 1.39-1.98 for hemorrhagic stroke and 1.63; 1.57-1.69 for ischemic stroke). In the same age group, RRs for 1 mmol/L higher TC were 1.44 (1.29-1.61) for IHD and 1.20 (1.15-1.25) for ischemic stroke. The RRs for 5 kg/m 2 higher BMI for ages 55-64 ranged from 2.32 (2.04-2.63) for diabetes, to 1.44 (1.40-1.48) for IHD. For 1 mmol/L higher FPG, RRs in this age group were 1.18 (1.08-1.29) for IHD and 1.14 (1.01-1.29) for total stroke. For all risk factors, proportional effects declined with age, were generally consistent by sex, and differed by region in only a few age groups for certain risk factor-disease pairs. Conclusion: Our results provide robust, comparable and precise estimates of the effects of major metabolic risk factors on CVD and diabetes by age group.

Objective To study the impact of resting heart rate and leisure time physical activity at middle age on long term risk of drug treated lone atrial fibrillation (AF). Design Longitudinal cohort study of 309 540 Norwegian men and women aged 40–45 years examined during 1985–1999 followed from 2005 through 2009. Setting Data from a national health screening programme were linked to the Norwegian Prescription Database (NorPD). Patients The cohort comprised 162 078 women and 147 462 men; 575 (0.4%) men and 288 women (0.2%) received flecainide and 568 men and 256 women sotalol and were defined as patients with AF. Interventions No interventions. Main outcome measures The outcome was lone fibrillation defined by having at least one prescription of flecainide or sotalol registered in NorPD between 2005 and 2009. Cox proportional hazard regression models were used to assess time to first prescription. Results The risk for being prescribed these drugs increased with decreasing baseline resting heart. Adjusted hazard ratio (HR) per 10 beats/min decrease in resting heart rate for flecainide prescription was 1.26 in men (95% CI 1.17 to 1.35) and 1.15 (95% CI 1.05 to 1.27) in women. Similar effects were seen for sotalol in men, but not in women. Men who reported intensive physical activity were more often prescribed flecainide than those in the sedentary group (adjusted HR=3.14, 95% CI 2.17 to 4.54). Conclusions This population based study supports the hypothesis that the risk of drug treated lone AF increases with declining resting heart rate in both sexes, and with increasing levels of self-reported physical activity in men.

We studied the relations between body height, body mass index (BMI), and fatal hip fractures prospectively in a large, representative population. During the years 1963–1975, a nationwide compulsory mass x-ray examination including standardized height and weight measurements took place in Norway cove

Aims Cardiovascular diseases (CVDs) have been related to low birth weight, suggesting the foetal environment may program future risk. Alternatively, common genetic factors for both low birth weight and CVD could explain such associations. We investigated associations between offspring birth weight and paternal and maternal cardiovascular mortality and offspring birth weight and cardiovascular mortality among all four grandparents, and further assessed the mediating role of maternal smoking during pregnancy. Methods and results All births from 1967 to 2008 that could be linked to parents and grandparents comprised the population ( n = 1 004 255). The mortality follow-up among parents was from 1970 to 2008 and among grandparents from 1960 to 2008. The association of grandparental mortality with maternal smoking during pregnancy was analysed in a subpopulation of those born after 1997 ( n = 345 624). Per quintile higher in birth weight was related to 0.82 (0.75–0.89) hazard ratio from coronary heart disease in mothers and 0.94 (0.92–0.97) in fathers. For stroke, these were 0.85 (0.78–0.92) and 0.94 (0.89–1.00), respectively. In grandparents for cardiovascular causes, the effects were 0.95 (0.93–0.96) (maternal grandmother), 0.97 (0.96–0.98) (maternal grandfather), 0.96 (0.94–0.98) (paternal grandmother), and 0.98 (0.98–1.00) (paternal grandfather). Adjusting for maternal smoking in pregnancy in the subpopulation accounted for much of the effect on grandparental cardiovascular mortality in all categories of birth weight. For grandparental diabetes mortality, U-shaped associations were seen with grandchild birth weight for the maternal grandmother and inverse associations for all other grandparents. Conclusion Associations between CVD mortality in all four grandparents and grandchild birth weight exist, and while genetic and environmental factors may contribute to these, it appears that there is an important role for maternal smoking during pregnancy (and associated paternal smoking) in generating these associations. For diabetes, however, it appears that intrauterine environmental influences and genetic factors contribute to the transgenerational associations.

Objectives:To investigate the prescription of potentially addictive drugs, including analgesics and central nervous system depressants, to women who had experienced intimate partner violence (IPV). Design: Prospective population-based cohort study. Setting: Information about IPV from the Oslo Health Study 2000/2001 was linked with prescription data from the Norwegian Prescription Database from 1 January 2004 through 31 December 2009. Participants: The study included 6081 women aged 30–60 years. Main outcome measures: Prescription rate ratios (RRs) for potentially addictive drugs derived from negative binomial models, adjusted for age, education, paid employment, marital status, chronic musculoskeletal pain, mental distress and sleep problems. Results: Altogether 819 (13.5%) of 6081 women reported ever experiencing IPV: 454 (7.5%) comprised physical and/or sexual IPV and 365 (6.0%) psychological IPV alone. Prescription rates for potentially addictive drugs were clearly higher among women who had experienced IPV: crude RRs were 3.57 (95% CI 2.89 to 4.40) for physical/sexual IPV and 2.13 (95% CI 1.69 to 2.69) for psychological IPV alone. After full adjustment RRs were 1.83 (1.50 to 2.22) for physical/sexual IPV, and 1.97 (1.59 to 2.45) for psychological IPV alone. Prescription rates were increased both for potentially addictive analgesics and central nervous system depressants. Furthermore, women who reported IPV were more likely to receive potentially addictive drugs from multiple physicians. Conclusions: Women who had experienced IPV, including psychological violence alone, more often received prescriptions for potentially addictive drugs. Researchers and clinicians should address the possible adverse health and psychosocial impact of such prescription and focus on developing evidence-based healthcare for women who have experienced IPV. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

Trans-fatty acids (TFA) have adverse effects on blood lipids, but whether TFA from different sources are associated with risk of CVD remains unresolved. The objective of the present study was to evaluate the association between TFA intake from partially hydrogenated vegetable oils (PHVO), partially hydrogenated fish oils (PHFO) and ruminant fat (rTFA) and risks of death of CVD, CHD, cerebrovascular diseases and sudden death in the Norwegian Counties Study, a population-based cohort study. Between 1974 and 1988, participants were examined for up to three times. Fat intake was assessed with a semi-quantitative FFQ. A total of 71 464 men and women were followed up through 2007. Hazard ratios (HR) and 95 % CI were estimated with Cox regression. Energy from TFA was compared to energy from all other sources, carbohydrates or unsaturatedcis-fatty acids with different multivariable models. During follow-up, 3870 subjects died of CVD, 2383 of CHD, 732 of cerebrovascular diseases and 243 of sudden death. Significant risks, comparing highest to lowest intake category, were found for: TFA from PHVO and CHD (HR 1·23 (95 % CI 1·00, 1·50)) and cerebrovascular diseases (HR 0·65 (95 % CI 0·45, 0·94)); TFA from PHFO and CVD (HR 1·14 (95 % CI 1·03, 1·26)) and cerebrovascular diseases (HR 1·32 (95 % CI 1·04, 1·69)); and rTFA intake and CVD (HR 1·30 (95 % CI 1·05, 1·61)), CHD (HR 1·50 (95 % CI 1·11, 2·03)) and sudden death (HR 2·73 (95 % CI 1·19, 6·25)) in women. These associations with rTFA intake were not significant in men (Pinteraction ≥ 0·01). The present study supports that TFA intake, irrespective of source, increases CVD risk. Whether TFA from PHVO decreases risk of cerebrovascular diseases warrants further investigation.

with 1 mmol/l increase in total cholesterol was 1.31 (95% CI: 1.27‐1.34) among men and 1.39 (95% CI: 1.32‐1.47) among women, decreasing to 1.26 (95% CI: 1.23‐1.30) in men and 1.32 (95% CI: 1.24‐1.41) in women when adjusted for blood pressure and daily smoking (yes/no). Persons with more than one risk factor had a substantially increased risk of both cardiovascular and total mortality.

Many studies have found an inverse association between consumption of filtered coffee and incident type 2 diabetes. The effect of boiled coffee has been less studied.Information on self-reported coffee consumption was available from health surveys conducted from 1985 to 1999. We estimated type 2 diabetes incidences from redeemed prescriptions of oral antidiabetic drugs in the period 1 January 2004 to 1 January 2008.With less than 1 cup/day as the reference, the relative risks associated with 1-4, 5-8, and 9 or more cups of boiled coffee per day were 0.87 (95% confidence interval = 0.80-0.95), 0.65 (0.59-0.72), and 0.65 (0.57-0.74), respectively, after adjusting for confounders. The corresponding relative risks associated with other types of coffee (mainly filtered) were 0.84 (0.79-0.90), 0.67 (0.62-0.71) and 0.62 (0.56-0.68).A moderate inverse association was found between consumption of both boiled and other types of coffee at the age of 40-45 years and the risk of being prescribed oral antidiabetic drugs 5-20 years later.