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Background/Objectives:: The Dutch guidelines for a healthy diet aim to reduce major chronic diseases. However, supporting evidence on their overall association with all-cause and cause-specific mortality is limited. Recently, the Dutch Healthy Diet-index (DHD-index) has been developed to assess adherence to these guidelines. The aim was to examine the association between the DHD-index and all-cause mortality and deaths from cardiovascular disease (CVD), coronary heart disease (CHD), stroke and cancer. Subjects/Methods:: We followed 3593 men and women aged 55 years and older enrolled in the Rotterdam Study, a population-based prospective cohort study, from baseline in 1990–1993 to 2011. A validated 170-item food frequency questionnaire at baseline was used to calculate the DHD-index score (maximum 90 points). Cox proportional hazard models were used to estimate hazard ratios (HRs) adjusting for age, sex, total energy intake, smoking and educational level. Results:: During the 20-year follow-up, 1831 (51%) deaths were reported. Mean DHD-index score was 60.6 (s.d. 10.6). The score was inversely associated with all-cause mortality (highest vs lowest quartile HR 0.77; 95% confidence interval (CI) 0.67, 0.89). Inverse but non-significant associations were observed for mortality due to CVD (HR 0.74; 95% CI 0.55, 1.01), CHD (HR 0.60; 95% CI 0.34, 1.06) and stroke (HR 0.67; 95% CI 0.36, 1.22), whereas no association was observed with cancer mortality (HR 0.99; 95% CI 0.90, 1.11). Conclusions:: A higher level of adherence to the Dutch dietary guidelines, as assessed with the DHD-index, was associated with a lower risk of all-cause mortality, probably due to an inverse association with cardiovascular causes of death.

To investigate the relationship between unrecognized myocardial infarction and the risk of stroke in a population-based cohort study.

Increased homocysteine levels might accelerate dopaminergic cell death in Parkinson disease (PD), through neurotoxic effects. Higher dietary intakes of folate, vitamin B12, and vitamin B6(cofactors in homocysteine metabolism) might decrease the risk of PD through decreasing plasma homocysteine. Moreover, vitamin B6might influence the risk of PD through antioxidant effects unrelated to homocysteine metabolism and through its role in dopamine synthesis.

Interleukin-6 (IL-6) is a growth factor involved in many processes including carcinogenesis. The C allele of the G−174 C promoter single nucleotide polymorphism (SNP) in the IL-6 gene decreases levels of IL-6 expression and it has been studied in the context of breast cancer progression yielding contradicting results. Furthermore a recent study found that carriers of the C allele were at an increased risk for this disease. We aim to evaluate the association between this variant and breast cancer risk in Caucasian postmenopausal women. Women participating in the Rotterdam Study (N=3822), including 171 patients with breast cancer were genotyped for this polymorphism. In order to assess the relationship between this SNP and breast cancer we carried out a logistic regression in relation to the incidence of breast cancer. The C allele frequency was 41.3% and the genotypes followed Hardy–Weinberg distribution (p=0.3). The logistic regression analysis showed a slight increase of risk for C allele carriers (odds ratio=1.24, 95% CI: 0.8–1.9), compared to non-carriers of this allele. This increased risk was not statistically significant. Our data suggest that the IL-6 G−174 C polymorphism does not seem to play a role in breast cancer risk, although its role as a prognostic factor remains to be studied.Interleukin-6 (IL-6) is a growth factor involved in many processes including carcinogenesis. The C allele of the G−174 C promoter single nucleotide polymorphism (SNP) in the IL-6 gene decreases levels of IL-6 expression and it has been studied in the context of breast cancer progression yielding contradicting results. Furthermore a recent study found that carriers of the C allele were at an increased risk for this disease. We aim to evaluate the association between this variant and breast cancer risk in Caucasian postmenopausal women. Women participating in the Rotterdam Study (N=3822), including 171 patients with breast cancer were genotyped for this polymorphism. In order to assess the relationship between this SNP and breast cancer we carried out a logistic regression in relation to the incidence of breast cancer. The C allele frequency was 41.3% and the genotypes followed Hardy–Weinberg distribution (p=0.3). The logistic regression analysis showed a slight increase of risk for C allele carriers (odds ratio=1.24, 95% CI: 0.8–1.9), compared to non-carriers of this allele. This increased risk was not statistically significant. Our data suggest that the IL-6 G−174 C polymorphism does not seem to play a role in breast cancer risk, although its role as a prognostic factor remains to be studied.

Unsaturated fatty acids are important constituents of neuronal cell membranes and have neuroprotective, antioxidant, and anti-inflammatory properties.

To examine whether high intake of total fat, saturated fatty acids (saturated fat), trans fatty acids (trans fat), and cholesterol and low intake of monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), n-6 PUFA, and n-3 PUFA are associated with increased risk of dementia and its subtypes.

White matter lesions are frequently found on cerebral MRI scans of elderly people and are thought to be important in the pathogenesis of dementia. Hyper tension has been associated with the presence of white matter lesions but this has been investigated almost exclusively in cross-sectional studies. We studied prospectively the association of these lesions with the duration and treatment of hypertension. We randomly sampled 1077 subjects aged between 60 and 90 years from two prospective population-based studies. One-half of the study subjects had their blood pressure measured between 1975 and 1978 and the other half between 1990 and 1993. All subjects underwent 1.5 T MRI scanning; white matter lesions in the subcortical and periventricular regions were rated separately. Subjects with hypertension had increased rates of both types of white matter lesion. Duration of hypertension was associated with both periventricular and subcortical white matter lesions. This relationship was influenced strongly by age. For participants with >20 years of hypertension and aged between 60 and 70 years at the time of follow-up, the relative risks for subcortical and periventricular white matter lesions were 24.3 [95% confidence interval (CI) 5.1-114.8] and 15.8 (95% CI 3.4-73.5), respectively, compared with normotensive subjects. Subjects with successfully treated hypertension had only moderately increased rates of subcortical white matter lesions and periventricular white matter lesions (relative risk 3.3, 95% CI 1.3-8.4 and 2.6, 95% CI 1.0-6.8, respectively) compared with normotensive subjects. For poorly controlled hypertensives, these relative risks were 8.4 (95% CI 3.1-22.6) and 5.8 (95% CI 2.1-16.0), respectively. In conclusion, we found a relationship between long-standing hypertension and the presence of white matter lesions. Our findings are consistent with the view that effective treatment may reduce the rates of both types of white matter lesion. Adequate treatment of hypertension may therefore prevent white matter lesions and the associated cognitive decline.

White matter lesions are frequently found on cerebral MRI scans of elderly people and are thought to be important in the pathogenesis of dementia. Hyper tension has been associated with the presence of white matter lesions but this has been investigated almost exclusively in cross‐sectional studies. We studied prospectively the association of these lesions with the duration and treatment of hypertension. We randomly sampled 1077 subjects aged between 60 and 90 years from two prospective population‐based studies. One‐half of the study subjects had their blood pressure measured between 1975 and 1978 and the other half between 1990 and 1993. All subjects underwent 1.5 T MRI scanning; white matter lesions in the subcortical and periventricular regions were rated separately. Subjects with hypertension had increased rates of both types of white matter lesion. Duration of hypertension was associated with both periventricular and subcortical white matter lesions. This relationship was influenced strongly by age. For participants with >20 years of hypertension and aged between 60 and 70 years at the time of follow‐up, the relative risks for subcortical and periventricular white matter lesions were 24.3 [95% confidence interval (CI) 5.1–114.8] and 15.8 (95% CI 3.4–73.5), respectively, compared with normotensive subjects. Subjects with successfully treated hypertension had only moderately increased rates of subcortical white matter lesions and periventricular white matter lesions (relative risk 3.3, 95% CI 1.3–8.4 and 2.6, 95% CI 1.0–6.8, respectively) compared with normotensive subjects. For poorly controlled hypertensives, these relative risks were 8.4 (95% CI 3.1–22.6) and 5.8 (95% CI 2.1–16.0), respectively. In conclusion, we found a relationship between long‐standing hypertension and the presence of white matter lesions. Our findings are consistent with the view that effective treatment may reduce the rates of both types of white matter lesion. Adequate treatment of hypertension may therefore prevent white matter lesions and the associated cognitive decline.

OBJECTIVE--To examine the effect of a reduced sodium and increased potassium and magnesium intake on blood pressure. DESIGN--Randomised double blind placebo controlled trial. SETTING--General population of a suburb of Rotterdam. SUBJECTS--100 men and women between 55 and 75 years of age with untreated mild to moderate hypertension. INTERVENTIONS--During 24 weeks the intervention group received a mineral salt (sodium: potassium: magnesium 8:6:1) and foods prepared with the mineral salt. Controls received common salt and foods. MAIN OUTCOME MEASURE--Change in blood pressure. RESULTS--Complete follow up was achieved for 97 of the 100 randomised subjects. Systolic blood pressure (mean of measurements at weeks 8, 16, and 24) fell by 7.6 mm Hg (95% confidence interval 4.0 to 11.2) and diastolic blood pressure by 3.3 mm Hg (0.8 to 5.8) in the mineral salt group compared with the controls, with a 28% decrease in urinary sodium excretion and a 22% increase in urinary potassium excretion. Twenty five weeks after the study the difference in blood pressure between the groups was no longer detectable. CONCLUSION--Replacing common sodium salt by a low sodium, high potassium, high magnesium mineral salt could offer a valuable non-pharmacological approach to lowering blood pressure in older people with mild to moderate hypertension.

To examine the relation between physical activity, calcium intake, and bone mineral content in children.

Gammacarboxyglutamate (Gla) is an uncommon amino acid formed by vitamin K action. Increasing evidence indicates that Gla-proteins are involved in the regulation of calcification processes in both bone tissue and atherosclerotic vessel wall. In a population-based study we have previously shown that in a group of 113 postmenopausal women the presence of abdominal aortic calcifications is associated with a reduced vitamin K status. In the present study we investigated whether this reduced vitamin K status was also associated with differences in bone mass or circulating calciotropic hormone levels. Serum immunoreactive osteocalcin with low affinity for hydroxyapatite (irOCfree) was used as a marker for vitamin K status. After correction for age it was found that women with atherosclerotic calcifications had a 7% lower bone mass as measured by metacarpal radiogrammetry (mean difference: 3.2 mm2, 95% CI: −0.2–6.5, P= 0.06). No differences between both groups of women were observed for serum intact parathyroid hormone (PTH) and serum 25-hydroxyvitamin D levels. In the atherosclerotic women (n = 34), markers for vitamin K status were inversely associated with bone mass (r =−0.47, P= 0.013), whereas no such association was found in the nonatherosclerotic women (n = 79). It is concluded that the atherosclerotic women in this study may be at higher risk for osteoporotic fractures as evidenced by their lower bone mass and higher serum irOCfreelevels. The finding that in atherosclerotic women vitamin K status is associated with bone mass supports our hypothesis that vitamin K status affects the mineralization processes in both bone and in atherosclerotic plaques.

The APOEgenotype is involved in atherosclerosis, and atherosclerosis increases the risk of dementia, in particular among carriers of the APOE-4 allele. We studied, in a population-based setting (244 dementia cases; 1,002 nondemented controls), whether APOEis associated with dementia through atherosclerosis. As neither adjusting nor stratification for atherosclerosis altered the association of APOEwith dementia, our study suggests that atherosclerosis is not an intermediate factor.

Aim: We investigated whether aortic stiffness and central pulse pressure were predictors of coronary heart disease in apparently healthy subjects. Methods and Results: We included 2024 subjects participating the third examination phase of the Rotterdam Study, a large ongoing population-based study. Aortic stiffness was measured as the carotid-femoral pulse wave velocity. Finger blood pressure was measured (Finapres) and central pulse pressure was calculated using upper arm level correction and a generalized transfer function. Information on smoking habits and previous cardiovascular disease were obtained. Body mass index was calculated. Serum total cholesterol and HDL cholesterol values were determined and diabetes mellitus was defined. The carotid IMT was assessed. Subjects with previous coronary heart disease were excluded from the analyses. Cox’s proportional hazard regression analysis, adjusted for cardiovascular risk factors was carried out. To facilitate comparisons among central pulse pressure and aortic stiffness each measure was divided by its standard deviation. The mean age of the participants was 71.4 years, 39.5% were men. During a mean follow-up time of 6.1 years, 109 subjects developed coronary heart disease. Hazard ratios and corresponding 95%CI of coronary heart disease for change of 1 standard deviation of aortic stiffness and central pulse pressure were 1.27 (1.06–1.51) and 1.20 (1.00–1.44), respectively. When both measures were included in the same statistical model, the prognostic value of aortic stiffness remained significant [1.22 (1.02–1.47)] whereas estimates of pulse pressure were slightly decreased [1.13 (0.93–1.37)]. Conclusions: Aortic stiffness is an independent predictor of coronary heart disease in apparently healthy subjects.