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Free iron has been implicated in lipid peroxidation and ischemic myocardial damage, and it has been suggested that iron is an independent risk factor for myocardial infarction. The authors investigated whether dietary iron is associated with an increased risk of fatal and nonfatal myocardial infarction in the Rotterdam Study, a community-based prospective cohort study of 7,983 elderly subjects in Rotterdam, the Netherlands. The study sample consisted of 4,802 participants who at baseline had no known history of myocardial infarction and for whom dietary data were available. From 1990 to 1996, 124 subjects had a myocardial infarction. No association was observed between total iron intake and risk of myocardial infarction after adjustment for age and sex (relative risk for the highest vs. the lowest tertile of intake=0.89, 95% confidence interval (CI) 0.55-1.45, p for trend=0.640). Heme iron intake was positively associated with risk of myocardial infarction (relative risk for the highest vs. the lowest tertile of intake=1.83, 95% Cal 1.16-2.91, p for trend=0.008) after adjustment for age and sex, and this association persisted after multivariate adjustment (relative risk=1.86, 95% Cal 1.14-3.09, p for trend=0.010). A distinction between fatal and nonfatal cases of myocardial infarction indicated that the association of heme iron with myocardial infarction was more pronounced in fatal cases. The results suggest that a high dietary heme iron intake is related to an increased risk of myocardial infarction and that it may specifically affect the rate of fatality from myocardial infarction.

Background: Mild metabolic acidosis, which can be caused by diet, may result in elevated blood pressure (BP). Objective: The objective was to examine whether dietary acid load was associated with incident hypertension in a cohort of older Dutch adults from the Rotterdam Study. Design: The analyses included 2241 participants aged ≥55 y who were free of hypertension at baseline (1990-1993) and who had complete dietary and BP data. Dietary data were obtained from a 170-item food-frequency questionnaire. We used 2 measures to characterize dietary acid load: 1) potential renal acid load (PRAL) by using an algorithm including protein, phosphorus, potassium, calcium, and magnesium, and 2) estimated net endogenous acid production (NEAP) based on protein and potassium. HRs for 6-y incidence of hypertension were obtained in tertiles of PRAL and NEAP with adjustment for age, sex, BMI, smoking, education, and intakes of alcohol, fiber, and total energy. Results: We identified 1113 incident cases of hypertension during 8707 person-years of follow-up. The median dietary acid load ranged from -14.6 to 19.9 mEq/d across categories of PRAL. Hypertension risk was not significantly associated with dietary acid load. The multivariate HRs (95% CIs) in consecutive tertiles of PRAL were 1.00 (reference), 1.01 (0.87, 1.17), and 1.02 (0.88, 1.18) (P trend = 0.83). The median dietary acid loads were 30.4, 36.7, and 43.7 mEq/d, respectively, in consecutive tertiles of NEAP. Corresponding HRs for NEAP were 1.00 (reference), 0.92 (0.80, 1.07), and 0.94 (0.81, 1.10) (P-trend = 0.46). Conclusion: The findings from this prospective cohort study provided no evidence of an association between dietary acid load and risk of hypertension in older adults. © 2012 American Society for Nutrition.

Objective: The epidemiological evidence for the association between sleep duration and obesity in the elderly is inconsistent and has not been investigated with objective measures. Furthermore, the role of sleep fragmentation in this relationship is unknown. Our aim was to investigate the association of sleep measures with body mass index (BMI) and obesity in a normal elderly population. Design: Cross-sectional study. Subjects: A total of 983 community-dwelling elderly (mean age 68.4±6.9 years, range, 57-97). Measurements: Weight and height were measured, and sleep duration and fragmentation were assessed with on average six nights of actigraphy. Results: A quadratic model adequately described the association between continuous measures of sleep duration and BMI. Actigraphic sleep duration had a significant U-shaped relationship with BMI (β of quadratic term=0.30, 95% confidence interval (CI): 0.08, 0.52). Both short sleepers (<5 h: OR, 2.76 (95% CI: 1.38, 5.49), 5 to <6 h: OR, 1.97 (95% CI: 1.26, 3.08)) and long sleepers (≥8 h: OR, 2.93 (95% CI: 1.39, 6.16)) were more likely to be obese, compared to participants who slept 7 to <8 h. BMI increased with 0.59 kg m -2 per standard deviation of sleep fragmentation (95% CI: 0.34, 0.84). After adjustment for sleep fragmentation, the association between short sleep and obesity was no longer significant. Exclusion of participants with probable sleep apnea only marginally changed these associations. Self-reported habitual sleep duration was not associated with BMI or obesity. Conclusions: Sleep duration, as measured with actigraphy, had a U-shaped relationship with BMI and obesity in an elderly population. A highly fragmented sleep is associated with a higher BMI and a higher risk of obesity, and may explain why short sleep is related to obesity. To preclude bias that can be introduced by self-report measures of sleep duration, using multiple measures of sleep parameters is recommended in future research. © 2008 Macmillan Publishers Limited All rights reserved.

Background: Moderate alcohol consumption has been shown to protect against cardiovascular disease. Aortic stiffness can be regarded as a marker of cardiovascular disease risk. Previously we have shown an inverse to J-shaped association between alcohol intake and aortic stiffness in middle-aged and elderly men and postmenopausal women. Objective: In the present study we examined whether a relation between alcohol intake and aortic stiffness is already present at a younger age. Design: Cross-sectional data of a cohort study in men and women aged 28 years were analysed stratified by gender (240 men and 283 women). Measurements: Alcohol intake was derived from a questionnaire and aortic stiffness was assessed by pulse-wave velocity measurement. Results: In women an alcoholic beverage intake of ≥1 glass/day is associated with a 0.36 m/s (95% confidence interval, -0.58 to -0.14) lower pulse-wave velocity compared with non-drinkers. In men alcohol intake is also inversely related to pulse-wave velocity, but this was not significant. These findings were independent of age, blood pressure and heart rate. Conclusions: These findings suggest that moderate intake of alcohol may affect vascular stiffness at an early age, notably in women. These findings may be viewed as compatible with a vascular protective effect of alcohol that expresses well before the occurrence of symptomatic cardiovascular disease. © 2005 Lippincott Williams & Wilkins.

Objective: Description and application of an adapted semiquantitative food frequency questionnaire (SFFQ) for dietary assessment in the elderly population of the Rotterdam Study. Design: Dietary assessment consisting of a two-step approach was performed in 5434 participants (2225 men, 3029 women) of the Rotterdam Study from 1990 to 1993, a population-based prospective cohort of 7983 subjects aged 55-95 years (participation rate 78%). Statistical analysis: Nutrient intake was calculated for men and women in four age groups (55-64 years, 65-74 years, 75-84 years, 85-95 years) and linear trend analysis for differences in mean nutrient intake across age groups (55-64 gears 65-74 years, 75-95 years) by regression analysis was conducted. The influence of baseline characteristics on energy and nutrient intakes adjusted by age and sex was investigated by one-way-analysis of variance. Results: The adapted SFFQ made it possible to measure nutrient intake in the elderly within a limited time frame (2 x 20 min) across a wide age range (55-95 years). For nutrient intake we observed a general decline in mean intake of energy and most nutrients with age in men. In women the relation with age was not consistent: for most nutrients mean intake showed a decrease with age (e.g. water, magnesium, potassium), for some an increase (e.g. total fat, saturated fat, mono/disaccharides), and some nutrients showed no substantial change (e.g. calcium, retinol). Reported nutrient intake was influenced by body mass index, smoking status, socioeconomic status and activities of daily living. A prescribed diet was reported by 12.9% of participants and 34.6% used supplements on a regular basis. Conclusions: The described two-step approach for dietary assessment in the elderly facilitated collection of data on dietary habits across a wide age range and within a limited time frame making it a suitable instrument for application in large-scale epidemiological studies in the elderly.

Inflammatory mediators and soluble cell adhesion molecules predict cardiovascular events. It is not clear whether they reflect the severity of underlying atherosclerotic disease. Within the Rotterdam Study, we investigated the associations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 with noninvasive measures of atherosclerosis. Levels of CRP were assessed in a random sample of 1317 participants, and levels of IL-6 and soluble cell adhesion molecules were assessed in a subsample of 714 participants. In multivariate analyses, logarithmically transformed CRP (regression coefficient [β]=-0.023, 95% CI -0.033 to -0.012) and IL-6 (β=-0.025, 95% CI -0.049 to -0.001) were inversely associated with the ankle-arm index. Only CRP was associated with carotid intima-media thickness (β=0.018, 95% CI 0.010 to 0.027). Compared with the lowest tertile, the odds ratio for moderate to severe carotid plaques associated with levels of CRP in the highest tertile was 2.0 (95% CI 1.3 to 3.0). Soluble intercellular adhesion molecule-1 levels were strongly associated with carotid plaques (odds ratio 2.5, 95% CI 1.5 to 4.4 [highest versus lowest tertile]). Soluble vascular cell adhesion molecule-1 was not significantly associated with any of the measures of atherosclerosis. This study indicates that CRP is associated with the severity of atherosclerosis measured at various sites. Associations of the other markers with atherosclerosis were less consistent. Chemicals/CAS: C-Reactive Protein, 9007-41-4; Cell Adhesion Molecules; Inflammation Mediators; Intercellular Adhesion Molecule-1, 126547-89-5; Interleukin-6

Several large studies have shown that both short and long average sleep durations increase the risk of hypertension in adults. We investigated whether sleep duration is also associated with hypertension in the elderly. This cross-sectional study was conducted in 5058 participants of the population-based Rotterdam Study, aged 58 to 98 years. Blood pressure was measured at the research center. Hypertension was defined as a systolic blood pressure of ≥160 mm Hg and/or a diastolic blood pressure of ≥100 mm Hg or current use of antihypertensive medication. In all of the participants, sleep duration was assessed by self-report. In a subsample of 975 subjects, it was additionally measured with actigraphy, a validated method that infers wakefulness and sleep from the presence or absence of limb movement. After adjustment for age and gender and additionally for body mass index, smoking, depressive symptoms, sleep medication use, diabetes mellitus, myocardial infarction, and stroke, none of the odds ratios (varying from 0.54; 95% CI: 0.27 to 1.08; to 1.19; 95% CI: 0.89 to 1.58) reflected a significant association between sleep duration and hypertension, whether measured by self-report or actigraphy. This study strongly suggests that sleep duration is not associated with hypertension in the elderly. © 2007 American Heart Association, Inc. Chemicals / CAS: Antihypertensive Agents

The objective of this study was to evaluate the association of factor VII with dietary factors while also considering the R/Q353 polymorphism. Nutrition is an important determinant of coagulation factor VII, which is also genetically determined by the R/Q353 polymorphism. High levels of coagulation factor VII clotting activity (FVII:C) are associated with the risk of myocardial infarction; nutrition may have an effect on these levels if people are genetically susceptible to dietary changes. FVII:C was measured in 3005 elderly subjects, and the extreme quintiles of the FVII:C distribution were selected for measurement of the R/Q353 genotype and FVII:Chr (reflects total factor VII). In these 1158 subjects, habitual diet was assessed with a semiquantitative food-frequency questionnaire. The frequency of the Q353 allele was 0.24 in the lowest and 0.09 in the highest quintile. The quintiles were combined for linear regression analyses. FVII:C was inversely associated with fiber [β = -0.64 % pooled plasma (PP)/g, confidence interval (CI): -1.07,-0.21] and protein intake (β = -0.16 % PP/g, CI: -0.31,-0.01) and positively with saturated fat intake (β = 0.19 % PP/g, CI: -0.10,0.48). FVII:Chr was inversely associated with fiber (β = -0.38 % PP/g, CI: -0.71 ,-0.05). No other associations with diet were observed. The inverse association of FVII:C with fiber was stronger in subjects with the RR genotype (β = -0.76 % PP/g, CI: -1.23,-0.29), than in those with the RQ/QQ genotypes (β = -0.19 % PP/g, CI: -0.97,0.59). The same was found for FVII:Chr. The association of FVII:C with saturated fat was positive in those with the RR allele and inverse in those carrying the Q allele. These findings suggest that the strength of the association between coagulation factor VII and diet varies across the genotypes of the R/Q353 polymorphism.

Objective: The study was conducted to assess the relative validity of a 170-item semiquantitative food frequency questionnaire (SFFQ) adapted for use in the elderly. Design and subjects: The study was carried out in a sample of 80 men and women aged 55-75 y participating in a community based prospective cohort study in Rotterdam, The Netherlands. The two-step dietary assessment comprised a simple self-administered questionnaire (20 min) followed by a structured interview with trained dietitians (20 min) based on the completed questionnaire. Multiple food records (FR) collected over a one year period served as reference method. 24 h urine urea was used as indirect marker for protein intake. Results: Compared with FR, the SFFQ generally overestimated nutrient intake as reflected by difference in means and the ratio of SFFQ to FR. Energy adjustment reduced the observed overestimation. Pearson's correlation coefficients varied from close to 0.5 to about 0.9 for crude data, and after adjustment for age, sex, total energy intake, and for within-person variability in daily intake for 0.4-0.8. Cross-classification into quintiles resulted in correct classification into the same or adjacent quintile of 75.8% for crude and 76.8% for energy adjusted data. Validation of protein intake estimated by SFFQ with protein excretion from 24 h urine urea indicated overestimation of protein intake by SFFQ. Spearman correlation coefficient between protein intake estimated from urea excretion and SFFQ was 0.67. Conclusions: Adaptation of a SEFQ for use in the elderly resulted in a valid and time-efficient dietary assessment instrument. Its ability to adequately rank study subjects according to their dietary intake support its application in epidemiological studies in the elderly.

Setting: Coronary angiography departments of four central general hospitals in the Netherlands. Patients: 80 sons (mean age, 24.8 years) of men with severe coronary artery disease and 55 sons (mean age, 23.2 years) of controls. Measurements: Postprandial levels of serum triglycerides, retinyl palmitate, and total cholesterol were measured during a 12-hour period after a standardized oral lipid load. Results: Both groups showed a marked increase in levels of serum triglyceride and retinyl palmitate after lipid loading, reaching a maximum 4 to 6 hours postprandially. No changes in postprandial total cholesterol levels were observed in either group. Sons of men with coronary artery disease had prolonged postprandial hypertriglyceridemia when compared with sons of controls. Significant differences in postprandial triglyceride levels were found at 8 hours (difference, 0.35 mmol/L; 95% CI, 0.07 to 0.62 mmol/L), at 10 hours (difference, 0.21 mmol/L; CI, 0.06 to 0.36 mmol/L), and at 12 hours after lipid loading (difference, 0.13 mmol/L; CI, 0.01 to 0.26 mmol/L). Levels of postprandial retinyl palmitate were also slightly, but not statistically, different (mainly after 6 hours). Conclusions: Healthy young adult sons, whose fathers have established coronary artery disease, have prolonged postprandial hypertriglyceridemia. Changes in postprandial lipoprotein metabolism appear to be associated with familial risk for coronary atherosclerosis.

Aims: Modulation of dopamine receptor D2 (DRD2) activity affects insulin secretion in both rodents and isolated pancreatic β-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ANKK1 locus may affect susceptibility to Type 2 diabetes in humans. Methods: Four potentially functional variants in the coding region of the DRD2/ANKK1 locus (rs1079597, rs6275, rs6277, rs1800497) were genotyped and analysed for Type 2 diabetes susceptibility in up to 25 000 people (8148 with Type 2 diabetes and 17687 control subjects) from two large independent Dutch cohorts and one Danish cohort. In addition, 340 Dutch subjects underwent a 2-h hyperglycaemic clamp to investigate insulin secretion. Since sexual dimorphic associations related to DRD2 polymorphisms have been previously reported, we also performed a gender-stratified analysis. Results: rs1800497 at the DRD2/ANKK1 locus was associated with a significantly increased risk for Type 2 diabetes in women (odds ratio 1.14 (1.06-1.23); P = 4.1*10-4) but not in men (odds ratio 1.00 (95% CI 0.93-1.07); P = 0.92) or the combined group. Although rs1800497 was not associated with insulin secretion, we did find another single nucleotide polymorphism in this locus, rs6275, to be associated with increased first-phase glucose-stimulated insulin secretion in women (P = 5.5*10-4) but again not in men (P = 0.34). Conclusion: The present data identify DRD2/ANKK1 as a potential sex-specific Type 2 diabetes susceptibility gene. What's new?: The rs1800497 single nucleotide polymorphism at the DRD2/ANKK1 locus was associated with a significantly increased risk for Type 2 diabetes in women but not in men. The rs6275 single nucleotide polymorphism in the DRD2 gene is associated with increased first-phase glucose-stimulated insulin secretion in women only. Our data identify DRD2/ANKK1 as a potential sex-specific Type 2 diabetes susceptibility gene. © 2014 Diabetes UK. Chemicals/CAS: glucose, 50-99-7, 84778-64-3; insulin, 9004-10-8