Claus Dethlefsen

Intake of carbohydrates compared with intake of saturated fatty acids and risk of myocardial infarction: importance of the glycemic index

BACKGROUND Studies have suggested that replacing saturated fatty acids (SFAs) with carbohydrates is modestly associated with a higher risk of ischemic heart disease, whereas replacing SFAs with polyunsaturated fatty acids is associated with a lower risk of ischemic heart disease. The effect of carbohydrates, however, may depend on the type consumed. OBJECTIVES By using substitution models, we aimed to investigate the risk of myocardial infarction (MI) associated with a higher energy intake from carbohydrates and a concomitant lower energy intake from SFAs. Carbohydrates with different glycemic index (GI) values were also investigated. DESIGN Our prospective cohort study included 53,644 women and men free of MI at baseline. RESULTS During a median of 12 y of follow-up, 1943 incident MI cases occurred. There was a nonsignificant inverse association between substitution of carbohydrates with low-GI values for SFAs and risk of MI [hazard ratio (HR) for MI per 5% increment of energy intake from carbohydrates: 0.88; 95% CI: 0.72, 1.07). In contrast, there was a statistically significant positive association between substitution of carbohydrates with high-GI values for SFAs and risk of MI (HR: 1.33; 95% CI: 1.08, 1.64). There was no association for carbohydrates with medium-GI values (HR: 0.98; 95% CI: 0.80, 1.21). No effect modification by sex was observed. CONCLUSION This study suggests that replacing SFAs with carbohydrates with low-GI values is associated with a lower risk of MI, whereas replacing SFAs with carbohydrates with high-GI values is associated with a higher risk of MI.

Obesity, Behavioral Lifestyle Factors, and Risk of Acute Coronary Events

Background— Whether physical activity reduces the impact of obesity on the risk of acute coronary events is much debated. However, little is known about the role of other potentially modifiable lifestyle factors in combination with obesity. Methods and Results— We followed up 54 783 women and men from the prospective Danish Diet, Cancer and Health study who were 50 to 64 years at baseline (1993 to 1997) and free of coronary artery disease and cancer. During a median of 7.7 years, 1127 incident cases of acute coronary syndrome (ACS) occurred. After multivariable adjustments, each unit of body mass index was associated with a 5% and 7% higher risk of ACS among women and men, respectively (both P<0.0001 for trend). Overweight (body mass index, 25 to 29.9 kg/m2) and obesity (body mass index ≥30 kg/m2) were associated with a higher risk of ACS among the physically active and inactive, in nonsmokers and smokers, and among those who adhered more or less to a heart-healthy dietary pattern. Obese individuals who were active 1 to 3.5 h/wk had a lower risk than sedentary, obese individuals. In addition, obese nonsmokers had a lower risk than obese smokers. Adherence to a healthy diet was associated with a lower risk of ACS; however, the relative risk was not different among obese individuals with the most healthy diet versus obese individuals with a less healthy diet. Conclusions— Obesity confers an elevated risk of ACS in both healthy and less healthy subgroups of lifestyle behaviors. Adherence to healthy lifestyle behaviors was associated with a lower risk even among obese individuals.

Smoking and venous thromboembolism: a Danish follow‐up study

Summary.  Background: Large‐scale prospective studies are needed to assess whether smoking is associated with venous thromboembolism (VTE) (i.e. deep venous thrombosis and pulmonary embolism) independently of established risk factors. Objective: To investigate the association between smoking and the risk of VTE among middle‐aged men and women. Methods: From 1993 to 1997, 27 178 men and 29 875 women, aged 50–64 years and born in Denmark, were recruited into the Danish prospective study ‘Diet, Cancer and Health’. During follow‐up, VTE cases were identified in the Danish National Patient Registry. Medical records were reviewed and only verified VTE cases were included in the study. Baseline data on smoking and potential confounders were included in gender stratified Cox proportional hazard models to asses the association between smoking and the risk of VTE. The analyses were adjusted for alcohol intake, body mass index, physical activity, and in women also for use of hormone replacement therapy. Results: During follow‐up, 641 incident cases of VTE were verified. We found a positive association between current smoking and VTE, with a hazard ratio of 1.52 (95% CI, 1.15–2.00) for smoking women and 1.32 (95% CI, 1.00–1.74) for smoking men, and a positive dose‐response relationship. Former smokers had the same hazard as never smokers. Conclusions: Smoking was an independent risk factor for VTE among middle‐aged men and women. Former smokers have the same risk of VTE as never smokers, indicating acute effects of smoking, and underscoring the potential benefits of smoking cessation.

Anthropometry, Body Fat, and Venous Thromboembolism A Danish Follow-Up Study

Background— Obesity, measured as body mass index, is associated with venous thromboembolism (VTE). Body mass index is a marker of excess weight and correlates well with body fat content in adults; however, it fails to consider the distribution of body fat. We assessed the association between anthropometric variables and VTE. Methods and Results— From 1993 to 1997, 27 178 men and 29 876 women 50 to 64 years of age were recruited into a Danish prospective study (Diet, Cancer, and Health). During 10 years of follow-up, the outcome of VTE events was identified in the Danish National Patient Registry and verified by review of medical records. Body weight, body mass index, waist circumference, hip circumference, and total body fat were measured at baseline. We used Cox proportional hazard models to assess the association between anthropometry and VTE. Age was used as a time axis, with further adjustment for smoking, physical activity, height, hypertension, diabetes mellitus, cholesterol, and, among women, use of hormone replacement therapy. We verified 641 incident VTE events and found monotonic dose-response relationships between VTE and all anthropometric measurements in both sexes. In mutually adjusted analyses of waist and hip circumference, we found that hip circumference was positively associated with VTE in women but not in men, whereas waist circumference was positively associated with VTE in men but not in women. Conclusions— All measurements of obesity are predictors of the risk for VTE. Positive associations were found between VTE and body weight, body mass index, waist circumference, hip circumference, and total body fat mass.

Temporal Changes in the Incidence and 30-Day Mortality associated with Bacteremia in Hospitalized Patients from 1992 through 2006: A Population-based Cohort Study

BACKGROUND Little is known about temporal trends in the incidence and mortality associated with bacteremia in the general population. METHODS We conducted a population-based cohort study in Northern Denmark to examine changes in bacteremia occurrence and 30-day mortality from 1992 through 2006. All patients who received a diagnosis of bacteremia were identified in a population-based bacteremia database and followed up for mortality through the Danish Civil Registry System. We determined the overall annual age- and sex-standardized rates of bacteremia episodes, the incidence of first-time episodes, and the adjusted 30-day mortality by place of acquisition and study period. RESULTS We identified 14,303 bacteremia episodes, 11,703 (81.8%) of which were incident. The age- and sex-standardized overall rate of bacteremia increased by 68% from 1992 through 2006, and the incidence increased by 46% (from 114 to 166 episodes per 100,000 person-years). Community-acquired and nosocomial bacteremia incidence rates peaked at 92.1 and 77.2 episodes per 100,000 person-years in 2004 and 2002, respectively, whereas the incidence of health care-associated bacteremia increased steadily from 2.9 to 39.8 episodes per 100,000 person-years. Total number of deaths increased from 742 during 1992-1996 to 926 during 2002-2006. The 30-day mortality decreased in patients with community-acquired bacteremia (19.0% during 1992-1996 vs 15.4% during 2002-2006) but remained nearly unchanged for health care-associated (23.4% and 22.0%, respectively) and nosocomial bacteremia (27.9% and 27.7%, respectively). CONCLUSIONS The occurrence of bacteremia in Northern Denmark, regardless of the place of acquisition, increased considerably in the past 15 years, and bacteremia was associated with persistently high 30-day mortality. Thus, bacteremia remains a clinical and public health concern.

The impact of comorbidity and stage on ovarian cancer mortality: A nationwide Danish cohort study

BackgroundThe incidence of ovarian cancer increases sharply with age, and many elderly patients have coexisting diseases. If patients with comorbidities are diagnosed with advanced stages, this would explain the poor survival observed among ovarian cancer patients with severe comorbidity. Our aims were to examine the prevalence of comorbidity according to stage of cancer at diagnosis, to estimate the impact of comorbidity on survival, and to examine whether the impact of comorbidity on survival varies by stage.MethodsFrom the Danish Cancer Registry we identified 5,213 patients (> 15 years old) with ovarian cancer diagnosed from 1995 to 2003. We obtained information on comorbidities from the Danish National Hospital Discharge Registry. Vital status was determined through linkage to the Civil Registration System. We estimated the prevalence of comorbidity by stage and computed absolute survival and relative mortality rate ratios (MRRs) by comorbidity level (Charlson Index score 0, 1–2, 3+), using patients with Charlson Index score 0 as the reference group. We then stratified by stage and computed the absolute survival and MRRs according to comorbidity level, using patients with Charlson score 0 and localized tumour/FIGO I as the reference group. We adjusted for age and calendar time.ResultsComorbidity was more common among patients with an advanced stage of cancer. One- and five-year survival was higher in patients without comorbidity than in patients with registered comorbidity. After adjustment for age and calendar time, one-year MRRs declined from 1.8 to 1.4 and from 2.7 to 2.0, for patients with Charlson scores 1–2 and 3+, respectively. After adjustment for stage, the MRRs further declined to 1.3 and 1.8, respectively. Five-year MRRs declined similarly after adjustment for age, calendar time, and stage. The impact of severe comorbidity on mortality varied by stage, particularly among patients with tumours with regional spread/FIGO-stages II and III.ConclusionThe presence of severe comorbidity was associated with an advanced stage of ovarian cancer. Mortality was higher among patients with comorbidities and the impact of comorbidity varied by stage.

Storage time of allogeneic red blood cells is associated with risk of severe postoperative infection after coronary artery bypass grafting

OBJECTIVE The storage time of allogeneic red blood cells (RBCs) has been linked with the risk of severe postoperative infections following cardiac surgery. However, existing data are sparse and inconsistent. We therefore examined the association between the age of transfused RBCs and development of severe postoperative infection following coronary artery bypass grafting (CABG) in a large population-based cohort study. METHODS The study included patients undergoing CABG with or without concomitant cardiac surgery between June 2003 and July 2008 in the North and Central Denmark regions. Data on demography, perioperative variables, allogeneic blood transfusion and severe postoperative infections (deep sternal wound infection, bacteremia or septicemia) were retrieved from medical databases and medical records. We used logistic regression analyses to compute the crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for the association between storage time of transfused RBCs and the risk of severe infection. RESULTS A total of 4240 patients were included in the final analyses, and 1748 of these patients (41%) were transfused with RBCs. Among transfused patients, 953 were exclusively transfused with RBC stored for < 14 days and 548 were exclusively transfused with RBC stored for ≥ 14 days. Severe infection was identified in 165 patients (3.9%). The adjusted ORs for severe infection among all transfused patients and patients transfused with RBCs stored exclusively for either < 14 days or ≥ 14 days were 1.6 (95% CI: 0.9-2.8), 1.1 (95% CI: 0.6-2.1), and 2.3 (95% CI: 1.2-4.2), respectively, when compared with non-transfused patients. There was a dose-response relationship between the number of transfused RBC units and the risk of severe infection among patients exclusively transfused with RBCs stored for ≥ 14 days. CONCLUSION Although the risk of possible confounding could not be eliminated entirely in this observational study, the findings add further support for the hypothesis that storage time of RBCs is positively associated with the risk of transfusion-related severe postoperative infection in patients undergoing CABG.

Dietary fiber, carbohydrate quality and quantity, and mortality risk of individuals with diabetes mellitus

Background Dietary fiber, carbohydrate quality and quantity are associated with mortality risk in the general population. Whether this is also the case among diabetes patients is unknown. Objective To assess the associations of dietary fiber, glycemic load, glycemic index, carbohydrate, sugar, and starch intake with mortality risk in individuals with diabetes. Methods This study was a prospective cohort study among 6,192 individuals with confirmed diabetes mellitus (mean age of 57.4 years, and median diabetes duration of 4.4 years at baseline) from the European Prospective Investigation into Cancer and Nutrition (EPIC). Dietary intake was assessed at baseline (1992–2000) with validated dietary questionnaires. Cox proportional hazards analysis was performed to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality, while adjusting for CVD-related, diabetes-related, and nutritional factors. Results During a median follow-up of 9.2 y, 791 deaths were recorded, 306 due to CVD. Dietary fiber was inversely associated with all-cause mortality risk (adjusted HR per SD increase, 0.83 [95% CI, 0.75–0.91]) and CVD mortality risk (0.76[0.64–0.89]). No significant associations were observed for glycemic load, glycemic index, carbohydrate, sugar, or starch. Glycemic load (1.42[1.07–1.88]), carbohydrate (1.67[1.18–2.37]) and sugar intake (1.53[1.12–2.09]) were associated with an increased total mortality risk among normal weight individuals (BMI≤25 kg/m2; 22% of study population) but not among overweight individuals (P interaction≤0.04). These associations became stronger after exclusion of energy misreporters. Conclusions High fiber intake was associated with a decreased mortality risk. High glycemic load, carbohydrate and sugar intake were associated with an increased mortality risk in normal weight individuals with diabetes.

Obesity and risk of subsequent hospitalisation with pneumonia

Obesity may be associated with increased risk of pneumonia, but available data on this relationship are sparse and inconsistent. We followed a prospective cohort of 22,578 males and 25,973 females from the Danish Diet, Cancer and Health Study, aged 50–64 yrs and free from major chronic diseases at baseline (1993–1997), for first-time hospitalisation with pneumonia (median follow-up 12 yrs). Compared with males of normal weight, adjusted hazard ratios (HRs) for pneumonia were 1.4 (95% CI 1.2–1.7) for males with moderate obesity (body mass index (BMI) 30.0–34.9 kg·m−2), and 2.0 (95% CI 1.4–2.8) for males with severe obesity (BMI ≥35.0 kg·m−2), controlling for lifestyle and educational variables. Among females the associations were weaker, with adjusted HRs of 0.8 (95% CI 0.6–1.0) for moderate obesity, and 1.2 (95% CI 0.8–1.6) for severe obesity. Adjustment for major chronic diseases diagnosed during follow-up eliminated the associations between obesity and pneumonia risk. Obesity is associated with higher risk of hospitalisation with pneumonia among males but not among females, which is apparently explained by occurrence of other chronic diseases.

Marine n-3 Polyunsaturated Fatty Acids in Adipose Tissue and the Risk of Acute Coronary Syndrome

Background— Marine n-3 polyunsaturated fatty acids may reduce coronary mortality. Previous data in relation to nonfatal coronary disease, however, have been inconsistent, which may be explained by the use of heterogeneous methods to assess the intake of marine n-3 polyunsaturated fatty acids. We investigated the hypothesis that the content of total and individual marine n-3 polyunsaturated fatty acids in adipose tissue is negatively associated with the incidence of acute coronary syndrome (ACS), including both fatal and nonfatal coronary disease. Methods and Results— In the Diet, Cancer and Health, a Danish cohort study, 57 053 subjects were enrolled and had an adipose tissue biopsy taken at inclusion. During a mean follow-up period of 7.6 years, we identified and verified all cases (n=1012) with an incident acute coronary syndrome diagnosis, and a random sample of the cohort (n=1630) had their fatty acid composition in adipose tissue determined by gas chromatography. We found negative dose-response associations between the content of total marine n-3 polyunsaturated fatty acids and individual n-3 polyunsaturated fatty acids in adipose tissue and the risk of acute coronary syndrome. Comparing men in the highest and lowest quintiles gave a hazard ratio of 0.65 (95% confidence interval, 0.45 to 0.95) for total n-3 polyunsaturated fatty acids and 0.51 (95% confidence interval, 0.36 to 0.73) for docosahexaenoic acid. Nonfatal cases constituted >86% of cases, and the association was driven primarily by a reduction in the risk of nonfatal acute coronary syndrome. No consistent associations were found among women. Conclusion— Intake of marine n-3 polyunsaturated fatty acids may protect against acute coronary syndrome in men.