Karen Margrete Due

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.

Added Predictive Ability of the CHA2DS2VASc Risk Score for Stroke and Death in Patients With Atrial Fibrillation The Prospective Danish Diet, Cancer, and Health Cohort Study

Background— The objective of this study was to evaluate the added predictive ability of the CHA2DS2VASc prediction rule for stroke and death in a nonanticoagulated population of patients with atrial fibrillation. Methods and Results— We included 1603 nonanticoagulated patients with incident atrial fibrillation from a Danish prospective cohort study of 57 053 middle-aged men and women. The Net Reclassification Improvement was calculated as a measure to estimate any overall improvement in reclassification with the CHA2DS2VASc sore as an alternative to the CHADS2 score. After 1-year follow-up, crude incidence rates were 3.4 per 100 person-years for stroke and 13.6 for death. After a mean follow-up of 5.4 years (±3.7 years), the crude incidence rates for stroke and death were 1.9 and 5.6, respectively. During the entire observation period, the c-statistics and negative predictive values were similar for both risk scores. The Net Reclassification Improvement analysis showed that 1 of 10 reclassified atrial fibrillation patients would have been upgraded correctly using the CHA2DS2VASc score. Conclusions— Both the CHADS2 as well as the CHA2DS2VASc risk score can exclude a large proportion of patients from having high risk of stroke or death. However, using the CHA2DS2VASc risk score, fewer patients will fulfill the criterion for low risk (and are truly low risk for thromboembolism). For every 10 extra patients transferred to the treatment group at 5 years, using the CHA2DS2VASc risk score, 1 patient would have had a stroke that might have been avoided with effective treatment.

Impact of vascular disease in predicting stroke and death in patients with atrial fibrillation: the Danish Diet, Cancer and Health cohort study.

Summary.  Background: The presence of vascular disease (peripheral artery disease [PAD] and/or myocardial infarction [MI]) may impact on the risk of stroke and death among patients with incident atrial fibrillation (AF). To test this hypothesis, we analyzed data from a large Danish prospective cohort, the Danish Diet, Cancer and Health (DCH) study, to assess the risk of stroke or death among those who developed AF according to concomitant presence of vascular disease. Methods: A prospective cohort study of 57 053 persons (27 178 men and 29 876 women, respectively), aged between 50 and 64 years. The risk of stroke or death for patients with vascular disease was assessed amongst 3315 patients with incident AF (mean age, 67.1 years; 2130 men, 1185 women) using Cox proportional hazard models, after a median follow‐up of 4.8 years. Results: Of the subjects with AF, 417 (12.6%) had ‘vascular disease’ (PAD and/or prior MI). The risk of the primary endpoint (stroke or death) was significantly higher in patients with vascular disease at 1‐year follow‐up (crude hazard ratio [HR] 2.51 [1.91–3.29]), with corresponding crude HRs for PAD and MI being 3.51 (2.40–5.13), and 1.99 (1.46–2.72), respectively. For the secondary endpoints of death or stroke individually, these risk estimates were similar (crude HR 2.48 [1.89–3.26] and 1.77 [1.18–2.66], respectively). After adjustment for risk factors within the CHADS2 score, the adjusted HR for the primary endpoint (stroke or death) in patients with vascular disease was 1.91 (1.44–2.54), which was also significant for death (1.97 [1.48–2.62]). Conclusion: Vascular disease (prior MI and PAD) is an independent risk factor for the primary endpoint of ‘stroke or death’ in patients with AF, even after adjustment for the CHADS2 risk score, although this is driven by the impact on mortality. This reaffirms that patients with vascular disease represent a ‘high‐risk’ population, which necessitates proactive management of all cardiovascular risk factors and effective thromboprophylaxis (i.e. oral anticoagulation), which has been shown to significantly reduce the risk of stroke and death in AF.

Nationwide fluoroscopic screening of recalled riata defibrillator leads in Denmark

BACKGROUND The natural history of insulation defects with inside-out conductor externalization in recalled St Jude Medical Riata defibrillator leads is not well understood. OBJECTIVES To determine the prevalence of externalization in a nationwide screening. Secondary aims were to examine time dependence and location of externalization, association with electrical failure, and fluoroscopic diagnostic performance. METHODS All 299 patients with recalled Riata leads in Denmark were identified, and all except one underwent fluoroscopy and device interrogation. Externalizations were confirmed by multiple investigators. RESULTS The prevalence of externalization was 32 of 298 (11%) at a mean dwell time of 5.1 years. The prevalence was 21 of 98 (21%) for 8-F leads and 11 of 200 (6%) for 7-F leads; however, 8-F leads had longer dwell times. The degree of externalization was correlated with dwell time (Spearmans ρ = .37; P = .03). Externalization more often included the lead segment below the tricuspid annulus in dual coil leads than in single coil leads (69% vs 16%; P = .004). No association was observed between externalization and electrical function. Fluoroscopic diagnostic performance was good with positive and negative predictive values of 88% and 99%, respectively. CONCLUSIONS The prevalence of externalization in a nationwide screening is at the same level as reported in previous studies with similar lead dwell times. The degree of externalization is time dependent, and location seems to differ between single and dual coil leads. Long-term lead performance and association with electrical failure need further clarification. Fluoroscopy has a good diagnostic performance in clinical practice.

Alcohol drinking and risk of subsequent hospitalisation with pneumonia.

The dose–response relationship between alcohol consumption and pneumonia risk in healthy individuals is poorly understood. We examined 22,485 males and 24,682 females from Denmark who were aged 50–64 yrs. Subjects were without major chronic diseases at baseline and had a median follow-up of 12 yrs for first-time hospitalisation with pneumonia. 1,091 (males) and 944 (females) had pneumonia-related hospitalisation. Among males, the risk of pneumonia was increased for alcohol abstainers and those who drank large weekly amounts. The adjusted hazard ratios (HRs) for 0, 7–20, 21–34, 35–50 and >50 drinks·week−1 were 1.49 (95% CI 1.00–2.21), 0.88 (95% CI 0.76–1.03), 0.87 (95% CI 0.72–1.05), 1.15 (95% CI 0.93–1.44) and 1.81 (95% CI 1.40–2.33), respectively, compared with 1–6 drinks·week−1. The association between high alcohol intake and pneumonia persisted after controlling for subsequent chronic diseases. Among females, HRs for 0, 7–20, 21–35 and >35 drinks·week−1 were 1.26 (95% CI 0.89–1.79), 1.01 (95% CI 0.88–1.17), 1.10 (95% CI 0.88–1.37) and 0.54 (95% CI 0.29–1.01), respectively. For the same moderate to high weekly alcohol amount, infrequent intake yielded higher pneumonia HRs than more regular intake in both sexes. Regular moderate alcohol intake is not associated with increased risk of hospitalisation for pneumonia. High weekly alcohol consumption in males and infrequent heavy drinking in both sexes may increase pneumonia risk.

Fish consumption and subsequent change in body weight in European women and men

Fish consumption is the major dietary source of EPA and DHA, which according to rodent experiments may reduce body fat mass and prevent obesity. Only a few human studies have investigated the association between fish consumption and body-weight gain. We investigated the association between fish consumption and subsequent change in body weight. Women and men (n 344,757) participating in the European Prospective Investigation into Cancer and Nutrition were followed for a median of 5.0 years. Linear and logistic regression were used to investigate the associations between fish consumption and subsequent change in body weight. Among women, the annual weight change was 5.70 (95 % CI 4.35, 7.06), 2.23 (95 % CI 0.16, 4.31) and 11.12 (95 % CI 8.17, 14.08) g/10 g higher total, lean and fatty fish consumption per d, respectively. The OR of becoming overweight in 5 years among women who were normal weight at enrolment was 1.02 (95 % CI 1.01, 1.02), 1.01 (95 % CI 1.00, 1.02) and 1.02 (95 % CI 1.01, 1.04) g/10 g higher total, lean and fatty consumption per d, respectively. Among men, fish consumption was not statistically significantly associated with weight change. Adjustment for potential over- or underestimation of fish consumption did not systematically change the observed associations, but the 95 % CI became wider. The results in subgroups from analyses stratified by age or BMI at enrolment were not systematically different. In conclusion, the present study suggests that fish consumption has no appreciable association with body-weight gain.

Adipose tissue arachidonic acid content is associated with the expression of 5-lipoxygenase in atherosclerotic plaques

BackgroundThe content of arachidonic acid in adipose tissue is positively associated with the risk of myocardial infarction, whereas the content of eicosapentaenoic acid in adipose tissue has been reported to be negatively associated with the risk of myocardial infarction. Both arachidonic acid and eicosapentaenoic acid are substrates for the synthesis of pro-inflammatory leukotrienes and leukotrienes derived from eicosapentaenoic acid are generally much less potent. In this study we hypothesized that a high content of arachidonic acid in adipose tissue would reflect a high formation of arachidonic acid derived leukotrienes and a high expression of 5-lipoxygenase in atherosclerotic plaques. Likewise, we hypothesized that a high content of eicosapentaenoic acid in adipose tissue would reflect a low formation of arachidonic acid derived leukotrienes and a low expression of 5-lipoxygenase in plaques.MethodsIn a cross sectional study we included 45 consecutive subjects undergoing femoral thrombendarterectomy. The expression of 5-lipoxygenase in plaques was assessed by a semi-automated image analysis computer programme after immunohistochemical staining with mono-clonal 5-lipoxygenase antibodies. Leukotriene B4 and cysteinyl leukotriene formation from stimulated femoral artery plaques was quantified using ELISA methods. The fatty acid content of adipose tissue biopsies from the thigh was analyzed using gas chromatography. Associations between variables were assessed by Pearson correlations and were further explored in a multivariable linear regression model adjusting for potential confounders.ResultsA high content of arachidonic acid in adipose tissue was associated with a higher expression of 5-lipoxygenase in plaques (r = 0.32, p = 0.03), but no significant associations with leukotriene B4 (r = 0.22, p = 0.14) and cysteinyl leukotriene (r = −0.11, p = 0.46) formation was seen. No significant associations were found between the content of eicosapentaenoic acid in adipose tissue and 5-lipoxygenase expression or leukotriene formation in plaque.ConclusionsAdipose tissue arachidonic acid contents correlated positively with the expression of 5-lipoxygenase in plaques. This association might represent a causal link between adipose tissue arachidonic acid and the risk of myocardial infarction but confirmatory studies are needed.

Plasma phospholipid long-chain n-3 polyunsaturated fatty acids and body weight change

Objective: We investigated the association between the proportion of long-chain n-3 polyunsaturated fatty acids (PUFA) in plasma phospholipids from blood samples drawn at enrollment and subsequent change in body weight. Sex, age, and BMI were considered as potential effect modifiers. Method: A total of 1,998 women and men participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a median of 4.9 years. The associations between the proportion of plasma phospholipid long-chain n-3 PUFA and change in weight were investigated using mixed-effect linear regression. Results: The proportion of long-chain n-3 PUFA was not associated with change in weight. Among all participants, the 1-year weight change was –0.7 g per 1% point higher long-chain n-3 PUFA level (95% confidence interval: –20.7 to 19.3). The results when stratified by sex, age, or BMI groups were not systematically different. Conclusion: The results of this study suggest that the proportion of long-chain n-3 PUFA in plasma phospholipids is not associated with subsequent change in body weight within the range of exposure in the general population.

Reply: Dabigatran's ‘Real-World’ Data About Risk of Myocardial Infarction and Gastrointestinal Bleeding Contradicts With Randomized Trials

Dr. Sipahi and colleagues express concern about the discrepancy of our observational study with randomized controlled studies, and point to residual confounding as a possible explanation. We have already discussed these issues in the paper [(1)][1], but will expand on our discussion in the following

Dietary n-6 PUFA, carbohydrate:protein ratio and change in body weight and waist circumference: a follow-up study.

OBJECTIVE To investigate the association between the intake of n-6 PUFA and subsequent change in body weight and waist circumference at different levels of the carbohydrate:protein ratio. DESIGN Follow-up study with anthropometric measurements at recruitment and on average 5·3 years later. Dietary intake was determined at recruitment by using an FFQ that was designed for the study and validated. We applied linear regression models with 5-year change in weight or waist circumference as outcome and including a two-way interaction term between n-6 PUFA and carbohydrate intakes, lower-order terms, protein intake, long-chain n-3 PUFA intake and other potential confounders. Due to adjustment for intake of protein, levels of carbohydrate indirectly reflect levels of the carbohydrate:protein ratio. SETTING Diet, Cancer and Health follow-up study, Denmark. SUBJECTS Women and men (n 29 152) aged 55 years. RESULTS For a high intake of n-6 PUFA (6·9 % of energy) v. a low intake of n-6 PUFA (3·4 % of energy), the difference in 5-year weight change was -189·7 g (95 % CI -636·8, 257·4 g) at a low carbohydrate:protein ratio and -86·7 g (95 % CI -502·9, 329·6 g) at a high carbohydrate:protein ratio; the differences in 5-year waist circumference change were 0·26 cm (95 % CI -0·47, 0·98 cm) and -0·52 cm (95 % CI -1·19, 0·15 cm), respectively. Inclusion of the dietary glycaemic index did not change the results. CONCLUSIONS No consistent associations between the intake of n-6 PUFA and change in body weight or waist circumference at different levels of the carbohydrate:protein ratio were observed.