Comprehensive evaluation of the impact of workplace exposures on physician-certified sick leave in the general working population.

BACKGROUND: Our objective was to quantify the prospective associations between work factors across chemical, physical, mechanical, and psychosocial domains and the onset of medically certified sick leave. METHODS: Eligible respondents were interviewed in 2009, 2013, or 2016 and were registered in the national sick leave register with an employee relationship lasting more than 50 working days during the year of the survey interviews and the following year (n = 15,294 observations). To focus on the onset of high-level sick leave (HLSL; >16 days a year), we excluded individuals with HLSL during the survey year (baseline). We then used mixed-effect logistic regression models to assess prospective associations between self-reported work conditions and the occurrence of doctor-certified HLSL in the following year. RESULTS: The average occurrence of HLSL was 13.1%. After adjusting for sex, age, level of education, chronic health problems, and smoking, we observed an exposure-response relationship between cumulative exposure to work factors within all domains and the occurrence of HLSL. When evaluating the impact of combined exposures, predicted odds ratios (OR) for employees exposed to 1, 2, and 3 or more work factors within all domains were 1.60 (95%CI 1.32 - 1.94), 2.56 (95%CI 1.73 - 3.74) and 4.09 (95%CI 2.28 - 7.25), compared to those not exposed. CONCLUSIONS: The results support the notion that exposure to multiple work factors in various domains, including psychosocial, mechanical, chemical, and physical work conditions, is associated with an increased risk of high-level sick leave. Employers and occupational health professionals should consider the joint impact of these domains when designing interventions.

Alcohol consumption and lower risk of cardiovascular and all-cause mortality: the impact of accounting for familial factors in twins.

BACKGROUND: A moderate to high alcohol consumption is associated with a lower risk of cardiovascular disease (CVD) mortality in comparison with low consumption. The mechanisms underlying this association are not clear and have been suggested to be caused by residual confounding. The main objective of this study was to separate the familial and individual risk for CVD mortality and all-cause mortality related to alcohol consumption. This will be done by estimating the risk for CVD mortality and all-cause mortality in twin pairs discordant for alcohol consumption. METHODS: Alcohol consumption was assessed at two time points using self-report questionnaires in the Norwegian Twin Registry. Data on CVD mortality was obtained from the Norwegian Cause of Death Registry. Exposure-outcome associations for all-cause mortality and mortality due to other causes than CVD were estimated for comparison. RESULTS: Coming from a family with moderate to high alcohol consumption was protective against cardiovascular death (HR = 0.54, 95% CI 0.65-0.83). Moderate and high alcohol consumption levels were associated with a slightly increased risk of CVD mortality at the individual level (HR = 1.33, 95% CI 1.02-1.73). There was no association between alcohol consumption and all-cause mortality both at the familial nor at the individual level. CONCLUSIONS: The protective association of moderate to high alcohol consumption with a lower risk of CVD mortality was accounted for by familial factors in this study of twins. Early life genetic and environmental familial factors may mask an absence of health effect of moderate to high alcohol consumption on cardiovascular mortality.

Adverse social behaviour at work and health-related employment exit: a prospective population-based four-wave survey.

BACKGROUND: The level of evidence for various aspects of adverse social behaviour (ASB) at work as risk factors for exit from employment due to health problems or diseases is inconclusive. METHODS: We obtained data from four consecutive surveys (2006/09/13/16) of the general population of Norway. Respondents who were interviewed in two consecutive surveys and employed at the first survey time point constituted the sample (n = 17 110 observations). We investigated associations of self-reported exposure to ASB (i.e. experiencing sexual harassment, bullying or violence/threats in the first survey) and health-related employment exit (i.e. individuals reporting exit from employment due to health problems or disease between two consecutive surveys) by means of mixed-effect logistic regression. RESULTS: The prevalence of ASB and health-related employment exit was 10.8% (n = 1853) and 2.6% (n = 440), respectively. Adjusted for age, sex, level of education, occupation and weekly work hours, sexual harassment, bullying and violence/threats were associated with an increased risk of exit from employment. The odds ratios (ORs) for the association between exposure to any of the three aspects of ASB and employment exit was 1.78 [95% confidence interval (CI) 1.33-2.38]; the estimated corresponding population attributable risk was PAR% = 7.32 [95% CI 2.67-12.27]. Further adjustment of mental distress attenuated the observed association between exposure to any ASB and exit from employment (OR = 1.45 [95% CI 1.07-1.95], i.e. a reduction of 42% in the OR). CONCLUSIONS: ASB at work increases the risk of health-related exit from employment in the Norwegian workforce.

Work-life interference and physician-certified sick leave: a prospective study of a general working population.

BACKGROUND: Work-life interference has been associated with adverse health outcomes. Here, we quantify the association between work-life interference and subsequent sick leave. METHODS: Respondents from a randomly drawn cohort of the general working Norwegian population were interviewed in 2009, 2013 and/or 2016. Mixed-effects logistic regression models were used to assess prospective associations of self-reported work-life interference and risk of subsequent physician-certified sick leave of 1-16 days (low-level) and >16 days (high-level) in strata of men and women. To quantify the importance of work-life interference as risk factors for sick leave, we estimated the population attributable risk (PAR). RESULTS: Both low- and high-level sick leave were most prevalent among women while the prevalence of work-life interference was similar between sexes. Risk of sick leave was higher among women reporting work-life interference sometimes or often in comparison with seldom or never {low- and high-level sick leave odds ratio (OR) = 1.21 [95% confidence interval (CI) = 1.07-1.37] and 1.30 (95% CI = 1.14-1.49), respectively}. The associations for high-level sick leave progressively increased with the level of work-life interference [highest OR = 1.44 (95% CI = 1.19-1.75)]. In men, there was no consistent higher risk of sick leave according to more frequent work-life interference [low- and high-level sick leave OR = 1.00 (95% CI = 0.87-1.14) and 0.98 (95% CI = 0.84-1.16), respectively], but the risk of high-level sick leave tended to be higher among men reporting work-life interference often (OR = 1.21, 95% CI = 0.98-1.50). Estimating PAR, 6.69% (95% CI = 1.52-11.74) of low-level and 9.94% (95% CI = 4.22-15.45) of high-level sick leave could be attributed to work-life interference among women. CONCLUSIONS: Self-reported work-life interference was associated with a higher risk of sick leave, with the most consistent results among women.

Onset of Work-Life Conflict Increases Risk of Subsequent Psychological Distress in the Norwegian Working Population.

We aimed to assess whether the onset of work-life conflict is associated with a risk of subsequent onset of psychological distress. Respondents from a randomly drawn cohort of the general Norwegian working population were interviewed in 2009 (T1), 2013 (T2), and 2016 (T3) (gross sample n = 13,803). Participants reporting frequent work-life conflict at T1 and/or psychological distress (five-item Hopkins Symptom Checklist mean score ≥ 2) at T2 were excluded to establish a design that allowed us to study the effect of the onset of work-life conflict at T2 on psychological distress at T3. Logistic regression analysis showed that the onset of frequent work-life conflict more than doubled the risk of the onset of psychological distress at T3 (OR = 2.55; 95% CI 1.44-4.51). The analysis of the association between occasional work-life conflict and psychological distress was not conclusive (OR = 1.21; 95% CI 0.77-1.90). No differential effects of sex were observed (log likelihood ratio = 483.7, p = 0.92). The calculated population attributable risk (PAR) suggests that 12.3% (95% CI 2.84-22.9%) of psychological distress onset could be attributed to frequent work-life conflict. In conclusion, our results suggest that the onset of frequent work-life conflict has a direct effect on the future risk of developing symptoms of psychological distress in both male and female workers.

The Relationship between Workplace Conflicts and Subsequent Physician-Certified Sick Leave: A Prospective Population Study.

The impact of workplace conflicts on sick leave is largely unknown. We studied the associations between conflicts and physician-certified sick leave in a randomly drawn general working population sample. Eligible respondents were interviewed in 2009, 2013, and 2016 and were registered with an employee relationship ≥50 working days in the national sick-leave register the year following the survey interviews (n = 22,088 observations/13,731 respondents). We used mixed-effects logistic regression models (adjusted for sex, age, education level, occupation and sick leave days) to assess the associations of self-reported conflicts with superiors or colleagues and subsequent physician-certified sick leave of 1-16 days (i.e., low-level sick leave (LLSL)) and more than 16 days (i.e., high-level sick leave (HLSL)). Conflicts with superiors were associated with LLSL (OR = 1.73 95% CI 1.15-2.62) and HLSL (OR = 1.84 95% CI 1.15-2.94). The corresponding ORs for conflicts involving colleagues were weaker and largely non-significant. The population risks of LLSL and HLSL attributable to conflicts with superiors were 1.95% (95% CI 0.55-3.41) and 3.98% (95% CI 2.08-5.91), respectively. Conflicts with superiors appear to be an important risk factor for sick leave among employees. Organizations are well-advised to develop policies and competencies to prevent and manage conflicts at work.

Educational attainment and mortality in schizophrenia.

BACKGROUND: Individuals suffering from schizophrenia have a reduced life expectancy with cardiovascular disease (CVD) as a major contributor. Low educational attainment is associated with schizophrenia, as well as with all-cause and CVD mortality. However, it is unknown to what extent low educational attainment can explain the increased mortality in individuals with schizophrenia. AIM: Here, we quantify associations between educational attainment and all-cause and CVD mortality in individuals with schizophrenia, and compare them with the corresponding associations in the general population. METHOD: All Norwegian citizens born between January 1, 1925, and December 31, 1959, were followed up from January 1, 1990, to December 31, 2014. The total sample included 1,852,113 individuals, of which 6548 were registered with schizophrenia. We estimated hazard ratios (HR) for all-cause and CVD mortality with Cox models, in addition to life years lost. Educational attainment for index persons and their parents were included in the models. RESULTS: In the general population individuals with low educational attainment had higher risk of all-cause (HR: 1.48 [95% CI: 1.47-1.49]) and CVD (HR: 1.59 [95% CI: 1.57-1.61]) mortality. In individuals with schizophrenia these estimates were substantially lower (all-cause: HR: 1.13 [95% CI: 1.05-1.21] and CVD: HR: 1.12 [95% CI: 0.98-1.27]). Low educational attainment accounted for 3.28 (3.21-3.35) life years lost in males and 2.48 (2.42-2.55) years in females in the general population, but was not significantly associated with life years lost in individuals with schizophrenia. Results were similar for parental educational attainment. CONCLUSIONS: Our results indicate that while individuals with schizophrenia in general have lower educational attainment and higher mortality rates compared with the general population, the association between educational attainment and mortality is smaller in schizophrenia subjects than in the general population.

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

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

Adverse social behaviour at the workplace and subsequent physician certified sick leave: a three-wave prospective study of the general working population in Norway.

OBJECTIVES: We aimed to provide an integrated picture of the relationship between different facets of adverse social behaviour (ASB) at the workplace and sick leave. METHODS: Data from a randomly drawn prospective cohort of the general working population. Eligible respondents were interviewed in 2009, 2013 or 2016, and were registered with an employee relationship of at least 50 working days in the national register the year following the survey interviews (n=21 674 observations/13 470 respondents). We investigated the prospective associations of self-reported exposure to ASB, including threats/acts of violence, bullying and sexual harassment, with physician-certified sick leave of 1-16 days (ie, low level of sick leave (LLSL)) and >16 days (ie, high level of sick leave (HLSL)) by means of mixed effects logistic regression. RESULTS: The prevalence of sick leave was 18.4% (n=3986 observations) for LLSL and 16.1% (n=3492 observations) for HLSL. The different facets of ASB were independently associated with higher odds of sick leave, with stronger associations for HLSL than for LLSL. Adjusted for sex, age, education level, occupation, previous sickness absence level, OR (95% CI) for HLSL was 1.97 (1.61 to 2.35) for threats/acts of violence, 1.97 (1.53 to 2.54) for bullying and 1.41 (1.10 to 1.79) for sexual harassment. The population risks of LLSL and HLSL attributable to ASB were 5.27 (95% CI 1.85 to 8.81) and 8.27% (95% CI 4.01 to 12.48), respectively. CONCLUSIONS: Threats/acts of violence, bullying and sexual harassment were all independent predictors of sick leave, with threats/acts of violence appearing as the single most important factor.

Association of coincident self-reported mental health problems and alcohol intake with all-cause and cardiovascular disease mortality: A Norwegian pooled population analysis.

BACKGROUND: The disease burden attributable to mental health problems and to excess or harmful alcohol use is considerable. Despite a strong relationship between these 2 important factors in population health, there are few studies quantifying the mortality risk associated with their co-occurrence in the general population. The aim of this study was therefore to investigate cardiovascular disease (CVD) and all-cause mortality according to self-reported mental health problems and alcohol intake in the general population. METHODS AND FINDINGS: We followed 243,372 participants in Norwegian health surveys (1994-2002) through 2014 for all-cause and CVD mortality by data linkage to national registries. The mean (SD) age at the time of participation in the survey was 43.9 (10.6) years, and 47.8% were men. During a mean (SD) follow-up period of 16.7 (3.2) years, 6,587 participants died from CVD, and 21,376 died from all causes. Cox models estimated hazard ratios (HRs) with 95% CIs according to a mental health index (low, 1.00-1.50; high, 2.01-4.00; low score is favourable) based on the General Health Questionnaire and the Hopkins Symptom Checklist, and according to self-reported alcohol intake (low, <2; light, 2-11.99; moderate, 12-23.99; high, ≥24 grams/day). HRs were adjusted for age, sex, educational level, marital status, and CVD risk factors. Compared to a reference group with low mental health index score and low alcohol intake, HRs (95% CIs) for all-cause mortality were 0.93 (0.89, 0.97; p = 0.001), 1.00 (0.92, 1.09; p = 0.926), and 1.14 (0.96, 1.35; p = 0.119) for low index score combined with light, moderate, and high alcohol intake, respectively. HRs (95% CIs) were 1.22 (1.14, 1.31; p < 0.001), 1.24 (1.15, 1.33; p < 0.001), 1.43 (1.23, 1.66; p < 0.001), and 2.29 (1.87, 2.80; p < 0.001) for high index score combined with low, light, moderate, and high alcohol intake, respectively. For CVD mortality, HRs (95% CIs) were 0.93 (0.86, 1.00; p = 0.058), 0.90 (0.76, 1.07; p = 0.225), and 0.95 (0.67, 1.33; p = 0.760) for a low index score combined with light, moderate, and high alcohol intake, respectively, and 1.11 (0.98, 1.25; p = 0.102), 0.97 (0.83, 1.13; p = 0.689), 1.01 (0.71, 1.44; p = 0.956), and 1.78 (1.14, 2.78; p = 0.011) for high index score combined with low, light, moderate, and high alcohol intake, respectively. HRs for the combination of a high index score and high alcohol intake (HRs: 2.29 for all-cause and 1.78 for CVD mortality) were 64% (95% CI 53%, 74%; p < 0.001) and 69% (95% CI 42%, 97%; p < 0.001) higher than expected for all-cause mortality and CVD mortality, respectively, under the assumption of a multiplicative interaction structure. A limitation of our study is that the findings were based on average reported intake of alcohol without accounting for the drinking pattern. CONCLUSIONS: In the general population, the mortality rates associated with more mental health problems and a high alcohol intake were increased when the risk factors occurred together.

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

BACKGROUND: Evidence is sparse on the association between alcohol intakes in the lower range and risk of atrial fibrillation (AF). We aimed to investigate self-reported low and moderate alcohol intakes and subsequent risk of incident AF among current drinkers. METHODS: Norwegian population-based health examination surveys assessing self-reported daily alcohol intake (mean grams per day) were linked to health and population registers. Hazard ratios (HR) (95% confidence interval) for time to incident (first) hospitalization with AF by alcohol intake level were assessed by Cox regression, with adjustment for educational level and cardiovascular risk factors except blood pressure. RESULTS: The study population included 234,392 participants (49% men). Incident hospitalization with AF was identified in 5043 (2.2%) persons during a mean follow-up of 9 years. Compared to a very low alcohol intake of <1 unit weekly, a moderate consumption in the range of 1 to <2 units daily increased the risk of incident AF by 18% (HR 1.18 [1.06-1.32]). The average risk of incident AF increased by 9% per daily alcohol unit of 12 g (HR 1.09 [1.03, 1.14]). In sex-stratified analyses significant associations were found in men only. CONCLUSIONS: We found that less than two alcohol units/day significantly increased the risk of incident AF, however, in men only. Reduction of even a moderate alcohol intake may thus reduce the risk of AF at the population level.

The association between obesity and cardiovascular disease mortality in different strata of socioeconomic position: evidence from pooled Norwegian health surveys.

BACKGROUND: Socioeconomic position (SEP) is related to both obesity and cardiovascular disease (CVD). There is little evidence on whether SEP modifies the relation between obesity and CVD. The aim of the study was to investigate whether the association between obesity and CVD mortality is stronger among people with disadvantaged than among people with advantaged life course SEP. METHODS: Data from Norwegian population-based cardiovascular health surveys (1985-2003), including body mass index and CVD risk factors (cholesterol, blood pressure, smoking, current treatment for hypertension) were linked to socioeconomic indicators from register and census data (1960-90), and to the Cause of Death Registry (up until 2014). The total number of participants was 398 297. RESULTS: In comparison with normal weight, the age-adjusted hazard ratios and 95% confidence intervals of CVD mortality among obese participants were 2.39 (2.07-2.75) and 2.08 (1.70-2.53) among men and women with high SEP, respectively and 1.88 (1.60-2.21) and 1.75 (1.43-2.14) among men and women with low SEP. Adjustment for CVD risk factors attenuated the results in a similar manner in all SEP groups, and among both women and men. CONCLUSION: Obesity was consistently associated with a higher risk of CVD mortality, with only minor variation according to SEP. This means that preventing or treating obesity is, for the purpose of reducing CVD risk, equally important for an individual with high or low SEP.

The association between BMI and mortality using early adulthood BMI as an instrumental variable for midlife BMI.

The article aims to describe the association between midlife body mass index (BMI) and cardiovascular disease (CVD)- and all-cause mortality, and to use early adulthood BMI as an instrumental variable for midlife BMI, in order to obtain an estimate less distorted by midlife confounders and reverse causality. Data from Norwegian health surveys (1974-2003) (midlife BMI, smoking, blood pressure, total cholesterol, heart rate), Military Conscription Records, National Tuberculosis Screenings (early adulthood BMI), National Educational Registry and Cause of Death Registry were linked. Participants with data on BMI in early adulthood and midlife were included (n = 148.886). Hazard Ratio (HR) for CVD mortality was higher in men with midlife obesity relative to normal weight (HR = 1.46(95% CI 1.25, 1.70). For all-cause mortality, HR was higher in those with obesity or underweight in midlife relative to normal weight (Men:HR = 1.19(95% CI 1.09, 1.29), HR = 2.49(95% CI 1.81, 3.43) Women:HR = 1.33(95% CI 1.13, 1.56), HR = 1.61(95% CI 1.22, 2.13)). In instrumental variable analyses, increased BMI became more strongly associated with CVD and all-cause mortality, and the increased risk of all-cause mortality among the underweight attenuated.

Life course socioeconomic position, alcohol drinking patterns in midlife, and cardiovascular mortality: Analysis of Norwegian population-based health surveys.

BACKGROUND: Socioeconomically disadvantaged groups tend to experience more harm from the same level of exposure to alcohol as advantaged groups. Alcohol has multiple biological effects on the cardiovascular system, both potentially harmful and protective. We investigated whether the diverging relationships between alcohol drinking patterns and cardiovascular disease (CVD) mortality differed by life course socioeconomic position (SEP). METHODS AND FINDINGS: From 3 cohorts (the Counties Studies, the Cohort of Norway, and the Age 40 Program, 1987-2003) containing data from population-based cardiovascular health surveys in Norway, we included participants with self-reported information on alcohol consumption frequency (n = 207,394) and binge drinking episodes (≥5 units per occasion, n = 32,616). We also used data from national registries obtained by linkage. Hazard ratio (HR) with 95% confidence intervals (CIs) for CVD mortality was estimated using Cox models, including alcohol, life course SEP, age, gender, smoking, physical activity, body mass index (BMI), systolic blood pressure, heart rate, triglycerides, diabetes, history of CVD, and family history of coronary heart disease (CHD). Analyses were performed in the overall sample and stratified by high, middle, and low strata of life course SEP. A total of 8,435 CVD deaths occurred during the mean 17 years of follow-up. Compared to infrequent consumption (

Plasma 25-Hydroxyvitamin D and Mortality in Patients With Suspected Stable Angina Pectoris.

Context and Objective: Vitamin D status may affect cardiovascular disease (CVD) development and survival. We studied the relationship between concentrations of the circulating biomarker 25-hydroxyvitamin D (25OHD) and all-cause and cardiovascular mortality risk. Design, Setting, Participants, and Main Outcome Measures: 25OHD, the sum of 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2, was analyzed in plasma samples from 4114 white patients suspected of having stable angina pectoris and was adjusted for seasonal variation. Hazard ratios (HRs) for all-cause and cardiovascular mortality were estimated by using multivariable Cox models with 25OHD as the main exposure variable, with adjustment for study site, age, sex, smoking, body mass index, estimated glomerular filtration rate, and systolic blood pressure. Results: A total of 895 (21.8%) deaths, including 407 (9.9%) from CVD causes, occurred during a mean ± standard deviation follow-up of 11.9 ± 3.0 years. Compared with the first 25OHD quartile, HRs in the second, third, and fourth quartiles were 0.64 [95% confidence interval (CI), 0.54 to 0.77], 0.56 (95% CI, 0.46 to 0.67), and 0.56 (95% CI, 0.46 to 0.67) for all-cause mortality and 0.70 (95% CI, 0.53 to 0.91), 0.60 (95% CI, 0.45 to 0.79), and 0.57 (95% CI, 0.43 to 0.75) for cardiovascular mortality, respectively. Threshold analysis demonstrated increased all-cause and CVD mortality in patients with 25OHD concentrations below ∼42.5 nmol/L. Moreover, analysis suggested increased all-cause mortality at concentrations >100 nmol/L. Conclusion: Plasma 25OHD concentrations were inversely associated with cardiovascular mortality and nonlinearly (U-shaped) associated with all-cause mortality.

Bioavailability of iron, vitamin A, zinc, and folic acid when added to condiments and seasonings.

Seasonings and condiments can be candidate vehicles for micronutrient fortification if consumed consistently and if dietary practices ensure bioavailability of the nutrient. In this review, we identify factors that may affect the bioavailability of iron, vitamin A, zinc, and folic acid when added to seasonings and condiments and evaluate their effects on micronutrient status. We take into consideration the chemical and physical properties of different forms of the micronutrients, the influence of the physical and chemical properties of foods and meals to which fortified seasonings and condiments are typically added, and interactions between micronutrients and the physiological and nutritional status of the target population. Bioavailable fortificants of iron have been developed for use in dry or fluid vehicles. For example, sodium iron ethylenediaminetetraacetic acid (NaFeEDTA) and ferrous sulfate with citric acid are options for iron fortification of fish and soy sauce. Furthermore, NaFeEDTA, microencapsulated ferrous fumarate, and micronized elemental iron are potential fortificants in curry powder and salt. Dry forms of retinyl acetate or palmitate are bioavailable fortificants of vitamin A in dry candidate vehicles, but there are no published studies of these fortificants in fluid vehicles. Studies of zinc and folic acid bioavailability in seasonings and condiments are also lacking.

Vitamin D status was not associated with 'one-year' progression of coronary artery disease, assessed by coronary angiography in statin-treated patients.

BACKGROUND: Low vitamin D status is associated with increased risk of cardiovascular disease and may be involved in atherosclerosis. Our aim was to assess the association between vitamin D status and the progression of coronary artery disease (CAD). METHODS AND RESULTS: We measured 25-hydroxyvitamin D3 (25OHD3) by liquid chromatography tandem mass spectrometry (LC-MS/MS) in plasma from 348 participants with established CAD (84% males, mean ± standard deviation (SD) age 60 ± 10 years) of the Western Norway B-vitamin Intervention Trial (WENBIT, 1999-2006). The patients underwent invasive coronary angiography (CA) and percutaneous coronary intervention at baseline and a second CA after 302 ± 79 days of follow-up. From the angiograms, minimal lumen diameter (MLD) and diameter stenosis (DS) of atherosclerotic lesions were obtained. Significant CAD in non-intervened vessels was found in 309 coronary arteries from 183 participants either at baseline and/or at follow-up. To assess the association between levels of 25OHD3 and CAD progression in non-intervened vessels, we applied a linear quantile fitted mixed effects model with MLD or DS measured at follow-up as a function of continuous 25OHD3 concentrations. There were no statistically significant associations between plasma 25OHD3 concentrations (median: 63.9, 95% confidence interval (CI): 48.1-78.5 nmol/l) measured at baseline and the follow-up measures of either MLD (estimated effect per 10 nmol/l increase of 25OHD3 and 95% CI: -0.015 (-0.032-0.002) mm, p = 0.088) or DS (0.225 (-0.354-0.804) percentage points, p = 0.444). Multivariate adjustment did not alter these results. CONCLUSION: Plasma 25OHD3 levels were not associated with 'one-year' progression of CAD, assessed by CA in statin-treated patients.