Camilla Plambeck Hansen

Adherence to a Healthy Nordic Food Index Is Associated with a Lower Risk of Type-2 Diabetes—The Danish Diet, Cancer and Health Cohort Study

Background: Type-2 diabetes (T2D) prevalence is rapidly increasing worldwide. Lifestyle factors, in particular obesity, diet, and physical activity play a significant role in the etiology of the disease. Of dietary patterns, particularly the Mediterranean diet has been studied, and generally a protective association has been identified. However, other regional diets are less explored. Objective: The aim of the present study was to investigate the association between adherence to a healthy Nordic food index and the risk of T2D. The index consists of six food items: fish, cabbage, rye bread, oatmeal, apples and pears, and root vegetables. Methods: Data was obtained from a prospective cohort study of 57,053 Danish men and women aged 50–64 years, at baseline, of whom 7366 developed T2D (median follow-up: 15.3 years). The Cox proportional hazards model was used to assess the association between the healthy Nordic food index and risk of T2D, adjusted for potential confounders. Results: Greater adherence to the healthy Nordic food index was significantly associated with lower risk of T2D after adjusting for potential confounders. An index score of 5−6 points (high adherence) was associated with a statistically significantly 25% lower T2D risk in women (HR: 0.75, 95%CI: 0.61–0.92) and 38% in men (HR: 0.62; 95%CI: 0.53–0.71) compared to those with an index score of 0 points (poor adherence). Conclusion: Adherence to a healthy Nordic food index was found to be inversely associated with risk of T2D, suggesting that regional diets other than the Mediterranean may also be recommended for prevention of T2D.

Plasma Elaidic Acid Level as Biomarker of Industrial Trans Fatty Acids and Risk of Weight Change: Report from the EPIC Study.

Background Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow-up, age, energy, alcohol, smoking status, physical activity, and region. Results In women, doubling elaidic acid was associated with a decreased risk of weight loss (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.55-0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5-year follow-up (OR = 1.23, 95% CI = 0.97-1.56, p = 0.082) (p-trend<.0001). In men, a trend was observed for doubling elaidic acid level and risk of weight loss (OR = 0.82, 95% CI = 0.66-1.01, p = 0.062) while no significant association was found with risk of weight gain during the 5-year follow-up (OR = 1.08, 95% CI = 0.88-1.33, p = 0.454). No association was found for saturated and cis-monounsaturated fatty acids. Conclusions These data suggest that a high intake of industrial trans fatty acids may decrease the risk of weight loss, particularly in women. Prevention of obesity should consider limiting the consumption of highly processed foods, the main source of industrially-produced trans fatty acids.

Adherence to a Healthy Nordic Diet and Risk of Stroke: A Danish Cohort Study

Background and Purpose— Specific dietary patterns, including the Mediterranean diet, have been associated with stroke prevention. Our aim was to investigate whether adherence to a healthy Nordic diet, including fish, apples and pears, cabbages, root vegetables, rye bread, and oatmeal, was associated with risk of stroke. Methods— Incident cases of stroke among 55 338 men and women from the Danish Diet, Cancer and Health cohort were identified from the Danish National Patient Register and verified by review of records. Cases of ischemic stroke were further subclassified based on etiology according to the TOAST classification system (Trial of Org 10172 in Acute Stroke Treatment). Information on diet was collected at baseline (1993–1997) using a semiquantitative food-frequency questionnaire. Cox proportional hazards models were used to estimate hazards ratios of total stroke and subtypes of ischemic and hemorrhagic stroke. Results— During a median follow-up of 13.5 years, 2283 cases of incident stroke were verified, including 1879 ischemic strokes. Adherence to a healthy Nordic diet, as reflected by a higher Healthy Nordic Food Index score, was associated with a lower risk of stroke. The hazards ratio comparing an index score of 4 to 6 (high adherence) with an index score of 0 to 1 (low adherence) was 0.86 (95% confidence interval 0.76–0.98) for total stroke. Inverse associations were observed for ischemic stroke, including large-artery atherosclerosis. No trend was observed for hemorrhagic stroke; however, a statistically insignificant trend was observed for intracerebral hemorrhage. Conclusions— Our findings suggest that a healthy Nordic diet may be recommended for the prevention of stroke.

Prediagnostic Intake of Dairy Products and Dietary Calcium and Colorectal Cancer Survival—Results from the EPIC Cohort Study

Background: We investigated whether prediagnostic reported intake of dairy products and dietary calcium is associated with colorectal cancer survival. Methods: Data from 3,859 subjects with colorectal cancer (42.1% male; mean age at diagnosis, 64.2 ± 8.1 years) in the European Investigation into Cancer and Nutrition cohort were analyzed. Intake of dairy products and dietary calcium was assessed at baseline (1992–2000) using validated, country-specific dietary questionnaires. Multivariable Cox regression models were used to calculate HR and corresponding 95% confidence intervals (CI) for colorectal cancer–specific death (n = 1,028) and all-cause death (n = 1,525) for different quartiles of intake. Results: The consumption of total dairy products was not statistically significantly associated with risk of colorectal cancer–specific death (adjusted HR Q4 vs. Q1, 1.17; 95% CI, 0.97–1.43) nor that of all-cause death (Q4 vs. Q1, 1.16; 95% CI, 0.98–1.36). Multivariable-adjusted HRs for colorectal cancer–specific death (Q4 vs. Q1) were 1.21 (95% CI, 0.99–1.48) for milk, 1.09 (95% CI, 0.88–1.34) for yoghurt, and 0.93 (95% CI, 0.76–1.14) for cheese. The intake of dietary calcium was not associated with the risk of colorectal cancer–specific death (adjusted HR Q4 vs. Q1, 1.01; 95% CI, 0.81–1.26) nor that of all-cause death (Q4 vs. Q1, 1.01; 95% CI, 0.84–1.21). Conclusions: The prediagnostic reported intake of dairy products and dietary calcium is not associated with disease-specific or all-cause risk of death in patients diagnosed with colorectal cancer. Impact: The impact of diet on cancer survival is largely unknown. This study shows that despite its inverse association with colorectal cancer risk, the prediagnostic intake of dairy and dietary calcium does not affect colorectal cancer survival. Cancer Epidemiol Biomarkers Prev; 23(9); 1813–23. ©2014 AACR.

Intake of ruminant trans fatty acids and changes in body weight and waist circumference

Background/Objectives:Follow-up studies have suggested that total intake of trans fatty acids (TFA) is a risk factor for gain in body weight and waist circumference (WC). However, in a cross-sectional study individual TFA isomers in adipose tissue had divergent associations with anthropometry. Our objective was to investigate the association between intake of TFA from ruminant dairy and meat products and subsequent changes in weight and WC. Furthermore, potential effect modification by sex, age, body mass index and WC at baseline was investigated.Subjects/Methods:Data on weight, WC, habitual diet and lifestyle were collected at baseline in a Danish cohort of 30 851 men and women aged 50–64 years. Follow-up information on weight and WC was collected 5 years after enrolment. The associations between intake of ruminant TFA (R-TFA) and changes in weight and WC were analysed using multiple linear regression with cubic spline modelling.Results:Intake of R-TFA, both absolute and energy-adjusted intake, was significantly associated with weight change. Inverse associations were observed at lower intakes with a levelling-off at intakes >1.2 g/day and 0.4 energy percentage (E %). Absolute, but not energy-adjusted, intake of R-TFA was significantly associated with WC change. An inverse association was observed at lower intakes with a plateau above an intake of 1.2 g/day.Conclusions:The present study suggests that intake of R-TFA is weakly inversely associated with changes in weight, whereas no substantial association with changes in WC was found.

Adherence to a healthy Nordic food index and risk of myocardial infarction in middle-aged Danes: the diet, cancer and health cohort study

Background/objectives:For decades, the Mediterranean diet has been in focus regarding healthy eating as it has been associated with reduced risk of non-communicable diseases. Less interest has been given to health benefits of other regional diets. The aim of the present study was to assess whether adherence to a healthy Nordic food index was associated with lower risk of myocardial infarction (MI) among middle-aged Danes.Subjects/methods:Data were obtained from the Danish Diet, Cancer and Health cohort study of 57 053 men and women aged 50−64 years recruited between 1993 and 1997. The healthy Nordic food index comprised healthy Nordic food items selected a priori (fish, cabbage, rye bread, oatmeal, apple and pears and root vegetables). Information on incident MI was ascertained through linkage with national registries. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated from sex-specific Cox proportional hazard models.Results:In total, 1669 men and 653 women developed MI during follow-up (13.6 median years). In adjusted models, those with an index score of 5−6 points (highest scores) had significantly lower MI risk (men: HR=0.77, 95% CI=0.62, 0.97; women: HR=0.55, 95% CI=0.37, 0.82) relative to those scoring 0 points in the index (lowest score). A significantly lower MI risk was found per 1-point increment in the index in both men (HR=0.95, 95% CI=0.92, 0.99) and women (HR=0.93, 95% CI=0.88, 0.98).Conclusions:A healthy Nordic diet is associated with lower MI risk among middle-aged Danes, suggesting that Nordic diets should be considered in recommendations for dietary changes in the promotion of coronary health.

Adipose tissue trans-fatty acids and changes in body weight and waist circumference

Previous studies have suggested that the intake of trans-fatty acids (TFA) plays a role in the development of obesity. The proportions of adipose tissue fatty acids not synthesised endogenously in humans, such as TFA, usually correlate well with the dietary intake. Hence, the use of these biomarkers may provide a more accurate measure of habitual TFA intake than that obtained with dietary questionnaires. The objective of the present study was to investigate the associations between the proportions of specific TFA in adipose tissue and subsequent changes in weight and waist circumference (WC). The relative content of fatty acids in adipose tissue biopsies from a random sample of 996 men and women aged 50-64 years drawn from a Danish cohort study was determined by GC. Baseline data on weight, WC and potential confounders were available together with information on weight and WC 5 years after enrolment. The exposure measures were total trans-octadecenoic acids (18:1t), 18:1 Δ6-10t, vaccenic acid (18:1 Δ11t) and rumenic acid (18:2 Δ9c, 11t). Data were analysed using multiple regression with cubic spline modelling. The median proportion of total adipose tissue 18:1t was 1.52% (90% central range 0.98, 2.19) in men and 1.47% (1.01, 2.19) in women. No significant associations were observed between the proportions of total 18:1t, 18:1 Δ6-10t, vaccenic acid or rumenic acid and changes in weight or WC. The present study suggests that the proportions of specific TFA in adipose tissue are not associated with subsequent changes in weight or WC within the exposure range observed in this population.

Adherence to national food-based dietary guidelines and incidence of stroke: A cohort study of Danish men and women

Background and purpose National dietary guidelines are intended to promote primary prevention of lifestyle-related diseases, but little is known about their effectiveness in prevention of stroke. Methods We used the Danish cohort Diet, Cancer and Health (n = 57 053) to investigate whether adherence to the Danish food-based dietary guidelines was associated with risk of stroke. Adherence was assessed by the Danish Dietary Guidelines Index, score 0 [no adherence] to 6 [complete adherence]. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals for stroke and subtypes of stroke in men and women separately. Results Incident stroke was determined in 1357 men and 900 women during follow-up (median 12.5 years and 13.0 years, respectively). A higher Danish Dietary Guidelines Index score was inversely associated with total stroke in men but not in women. In men, a high Index score (≥4) was also inversely associated with total ischemic stroke (hazard ratio 0.75, 95% confidence interval 0.65–0.86), large-artery atherosclerosis (hazard ratio 0.63, 95% confidence interval 0.44–0.92) and small artery occlusion (hazard ratio 0.68, 95% confidence interval 0.54–0.84) compared to a low Index score (<4). In women, inverse associations were found for total ischemic stroke (hazard ratio 0.84, 95% confidence interval 0.72–0.98) and intracerebral hemorrhage (hazard ratio 0.64, 95% confidence interval 0.43–0.96). Conclusions Our findings suggest that adherence to the Danish Dietary Guidelines is associated with a lower rate of stroke, and thus may be useful in primary prevention of disease.

Consumption of individual saturated fatty acids and the risk of myocardial infarction in a UK and a Danish cohort

BACKGROUND The effect of individual saturated fatty acids (SFAs) on serum cholesterol levels depends on their carbon-chain length. Whether the association with myocardial infarction (MI) also differs across individual SFAs is unclear. We examined the association between consumption of individual SFAs, differing in chain lengths ranging from 4 through 18 carbons, and risk of MI. METHODS We used data from 22,050 and 53,375 participants from EPIC-Norfolk (UK) and EPIC-Denmark, respectively. Baseline SFA intakes were assessed through validated, country-specific food frequency questionnaires. Cox regression analysis was used to estimate associations between intakes of individual SFAs and MI risk, for each cohort separately. RESULTS During median follow-up times of 18.8 years in EPIC-Norfolk and 13.6 years in Denmark, respectively, 1204 and 2260 MI events occurred. Mean (±SD) total SFA intake was 13.3 (±3.5) en% in EPIC-Norfolk, and 12.5 (±2.6) en% in EPIC-Denmark. After multivariable adjustment, intakes of C12:0 (lauric acid) and C14:0 (myristic acid) inversely associated with MI risk in EPIC-Denmark (HR upper versus lowest quintile: 0.80 (95%CI: 0.66, 0.96) for both SFAs). Intakes in the third and fourth quintiles of C4:0-C10:0 also associated with lower MI risk in EPIC-Denmark. Moreover, substitution of C16:0 (palmitic acid) and C18:0 (stearic acid) with plant proteins resulted in a reduction of MI risk in EPIC-Denmark (HR per 1 energy%: 0.86 (95%CI: 0.78, 0.95) and 0.87 (95%CI: 0.79, 0.96) respectively). No such associations were found in EPIC-Norfolk. CONCLUSION The results from the present study suggest that the association between SFA and MI risk depends on the carbon chain-length of the SFA.

The Pseudo-Observation Analysis of Time-To-Event Data. Example from the Danish Diet, Cancer and Health Cohort Illustrating Assumptions, Model Validation and Interpretation of Results

Abstract Regression analyses for time-to-event data are commonly performed by Cox regression. Recently, an alternative method, the pseudo-observation method, has been introduced. This method offers new possibilities of analyzing data exploring cumulative risks on both a multiplicative and an additive risk scale, in contrast to the multiplicative Cox regression model for hazard rates. Hence, the pseudo-observation method enables assessment of interaction on an additive scale. However, the pseudo-observation method implies more strict model assumptions regarding entry and censoring but avoids the assumption of proportional hazards (except from combined analyses of several time intervals where assumptions of constant hazard ratios, risk differences and relative risks may be imposed). Only few descriptions of the use of the method are accessible for epidemiologists. In this paper, we present the pseudo-observation method from a user-oriented point of view aiming at facilitating the use of this relatively new analytical tool. Using data from the Diet, Cancer and Health Cohort we give a detailed example of the application of the pseudo-observation method on time-to-event data with delayed entry and right censoring. We discuss model control and suggest analytic strategies when assumptions are not met. The introductory model control in the data example showed that data did not fulfill the assumptions of the pseudo-observation method. This was caused by selection of healthier participants at older baseline ages and a change in the distribution of study participants according to outcome risk during the inclusion period. Both selection effects need to be addressed in any time-to-event analysis and we show how these effects are accounted for in the pseudo-observation analysis. The pseudo-observation method provides us with a statistical tool which makes it possible to analyse cohort data on both multiplicative and additive risk scales including assessment of biological interaction on the risk difference scale. Thus, it might be a relevant choice of method – especially if the focus is to investigate interaction from a public health point of view.