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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. [ABSTRACT FROM AUTHOR]

Abstract. Moerman CJ, van Hout BA, Bonneux L, Witteman JCM (University of Amsterdam, Amsterdam, and Erasmus University Medical School, Rotterdam, the Netherlands). Postmenopausal hormone therapy: less favourable risk–benefit ratios in healthy Dutch women. J Intern Med 2000; 248: 143–150. Objectives. To estimate the health effects of postmenopausal hormone therapy used for 10 or 20 years in a population of intermediate cardiovascular risk. Design. Using existing estimates of the effect of hormone therapy on rates of myocardial infarction, hip fracture and breast cancer, a proportional multistage life table was generated to calculate the effects of use for 10 and 20 years in a synthetic cohort of Dutch women aged 55 with an average and a high-risk profile for cardiovascular disease. Results. A woman of the general population who starts hormone therapy at age 55 for 10 years can prolong her life by 1 month and may postpone the occurrence of first incidence of one of the diseases under consideration by 2.4 months. One excess breast cancer case is likely to occur per 5–6 averted cases of first myocardial infarction or hip fracture. If she prolongs her use to 20 years, the gain of life expectancy and disease-free life expectancy is doubled. The risk–benefit ratio worsens to one extra breast cancer per 3–4 averted cases of the preventable diseases. For a woman with a high-risk profile, the gains in health are about twice as high as for her counterpart in the general population, and her risk–benefit ratio is also more favourable. Yet, the risk–benefit ratio still worsens for 20 as compared with 10 years of use. Conclusions. Women from the general population in the Netherlands and similar populations can achieve only a modest gain in life expectancy by using hormones during 10 or 20 years following menopause. This is a consequence of the low incidence of myocardial infarction and hip fracture and the relatively high incidence of breast cancer before the age of 75. Women at increased cardiovascular risk can benefit more from hormone therapy. But even amongst these women, the risk of breast cancer incurred with long-term use offsets much of the benefit that could accrue from changing the risk of heart disease and hip fracture. [ABSTRACT FROM AUTHOR]

Background Previous studies found an association between osteoarthritis (OA) and risk of cardiovascular disease (CVD) and therefore suggested intensive treatment of cardiovascular risk factors in OA patients. However, prospective population-based data is lacking. Objectives To investigate the association between OA and CVD longitudinally in a general population and examine the role of disability in this association. Methods This study was embedded in the Rotterdam Study, a prospective population-based cohort study in Rotterdam, the Netherlands that started in 1989. At baseline 4648 persons aged ≥55, free of CVD were classified into those with and those without radiographic or clinical OA. HRs adjusted for traditional cardiovascular risk factors for developing CVD (a composite of fatal and non-fatal coronary heart disease and stroke) were calculated. Results During a median follow-up of 14.4 years, 1230 cardiovascular events occurred, of which 101 were in participants with clinical OA. Presence of radiographic OA at baseline was not related to future CVD (HR 0.99, 95% CI 0.86 to 1.15), neither was presence of clinical OA (HR 1.09, 95% CI 0.88 to 1.34). However, persons with increasing disability were more likely to suffer a cardiovascular event compared with non-disabled persons (HR 1.26, 95% CI 1.12 to 1.42); this was independent of the presence of OA. Conclusions In this large population-based study, participants with OA were not at increased risk of CVD. The close relation between disability and osteoarthritis may explain previous findings. Further studies are required in order to clarify whether OA patients need more intensive treatment of their cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Objectives: Changes in cardiovascular risk factors with menopausal status are difficult to study, owing to the high correlation of menopausal status with age. Therefore we examined cardiovascular risk factors in a meticulously selected population in which the contrast in oestrogen status between pre- and postmenopausal women of the same age was maximized.Design: Risk factors were compared in 93 premenopausal and 93 postmenopausal women who were matched on age (range 43-55 years).Setting: The women were selected from respondents to a mailed questionnaire about the menopause, which was sent to all women aged 40-60 years in the Dutch town of Zoetermeer (n = 12 675; response 54%).Subjects: Postmenopausal women who were at least 3 years after menopause or whose menses had stopped naturally before age 48 were age-matched with premenopausal women with regular menses and without menopausal complaints.Results: Compared to premenopausal women, postmenopausal women had significantly increased levels of total cholesterol (10.0%, 95% confidence interval 5.1-14.0), low density lipoprotein (LDL) cholesterol (14.0%, 6.9-19.9), and apolipoprotein B (8.2%, 0.6-15.5). The difference was present within 3 years after onset of menopause and did not show a trend towards an increase with the number of postmenopausal years. No differences were found in high density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein A1, blood glucose, insulin, body mass index, waist-to-hip ratio, and systolic and diastolic blood pressure.Conclusions: The results of this study add to the evidence that total cholesterol, LDL cholesterol and apolipoprotein B are the primary cardiovascular risk factors affected by menopause. [ABSTRACT FROM AUTHOR]

Objective: To investigate the associations of serum total and HDL cholesterol with the risk of myocardial infarction in men and women of 55 years and over.Design: The Rotterdam Study is a population-based prospective cohort study. In total 2453 men and 3553 women of 55 years and older were included in this study. The mean duration of follow-up was 4 years.Main Outcome Measures: Relative risks were estimated with Cox's proportional-hazard analysis. Cholesterol was analysed as a continuous variable and in sex-specific quartiles.Results: In subjects aged 55 years and older the relative risk of myocardial infarction was 1.9 in men (95% confidence interval 1.1-3.3) and 3.2 in women (1.5-6.4) in the highest compared to the lowest serum total cholesterol quartile (Q4 vs. Q1). In men and women of 70 years and older, total cholesterol remained an important risk factor for myocardial infarction (Q4 vs. Q1 relative risk 3.2; 1.3-7.7 and 2.9; 1.3-6.6, respectively). For HDL cholesterol, the relative risk in the highest compared to the lowest quartile (Q4 vs. Q1) was 0.5 in men (0.3-0.9) and 0.4 in women (0.2-0.9). HDL cholesterol was a weaker predictor in men after the age of 70 (Q4 vs. Q1 0.8; 0.3-2.1). In women of 70 years and older the relative risk was also not significant (Q4 vs. Q1 0.6; 0.3-1.3), although the trend over the quartiles was still significant.Conclusion: Serum total cholesterol remains an important risk factor for myocardial infarction in men and women aged 70 years and older, whilst HDL cholesterol at older age remains important in women only. [ABSTRACT FROM AUTHOR]

Objective: To relate cross-sectionally assessed indicators of carotid atherosclerosis measured in participants of the Rotterdam Study to absolute 10-12 year risks of stroke, coronary heart disease and death estimated by risk functions available from other studies.Setting: General population living in the suburb of Ommoord in Rotterdam, The Netherlands.Subjects: A sample of men and women (n = 1683), aged 55 years or over, drawn from participants from the Rotterdam Study (n = 7983).Main Outcomes Measures: Three risk scores were used to estimate for each individual the absolute risk of stroke, coronary heart disease and death within 10-12 years as a function of their cardiovascular risk factor profile. Cross-sectionally measured indicators of carotid atherosclerosis (presence of atherosclerotic lesions and common carotid intima-media thickness) were subsequently related to these risk scores.Results: The 10-year absolute risk of stroke increased linearly from 4.8% (95% CI = 3.8, 5.8) for subjects in the lowest quintile to 16.1% (12.3, 21.9) for subjects in the highest quintile of common carotid intima-media thickness distribution. Similarly, the 10-year absolute risk for coronary heart disease rose from 13.1% (95% CI = 12.0, 14.2) to 23.4% (95% CI = 21.4, 25.4), whereas the risk of death within 11.5 years rose from 15.0% (95% CI = 12.8, 17.4) in the lowest quintile to 46.0% (42.8, 49.3) in the upper quintile. The absolute risks of stroke, coronary heart disease or death rose from 8.8, 15.8 and 26.9% to 14.3, 19.8 and 40.9%, respectively, when plaques in the common carotid artery were present. Similar findings were observed for plaques in the carotid bifurcation.Conclusion: Common carotid intima-media thickness and carotid plaques are markers for increased risk of stroke, coronary heart disease and death within 10-12 years. [ABSTRACT FROM AUTHOR]

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 irOCfree levels. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background/Objectives:The nutrient-rich food (NRF) index assesses nutrient quality of individual food items by ranking them according to their nutrient composition. The index reflects the nutrient density of the overall diet. We examined the associations between the NRF9.3 index-a score on the basis of nine beneficial nutrients (protein, fiber, vitamins and minerals) and three nutrients to limit (saturated fat, sugar and sodium)-incidence of cardiovascular disease (CVD) events and all-cause mortality.Subjects/Methods:A total of 4969 persons aged 55 and older from the Rotterdam Study, a prospective cohort study in the Netherlands, were studied. First, all foods were scored on the basis of their nutrient composition, resulting in an NRF9.3 score on food item level. Subsequently, they were converted into individual weighted scores on the basis of the amount of calories of each food item consumed by the subjects and the total energy intake. The hazard ratios (HRs) of the NRF9.3 index score were adjusted for age, gender, body mass index, smoking history, doctor-prescribed diet, alcohol consumption and education.Results:Food groups that contributed most to the NRF9.3 index score were vegetables, milk and milk products, fruit, bread and potatoes. A high NRF9.3 index score was inversely associated with all-cause mortality (HR Q4 versus Q1: 0.84 (95% confidence interval: 0.74, 0.96)). Associations were stronger in women than in men. The NRF9.3 index score was not associated with incidence of CVD.Conclusion:Elderly with a higher NRF9.3 index score, indicating more beneficial components and/or less limiting components, had a lower risk of all-cause mortality. Consuming a nutrient-dense diet may improve survival. [ABSTRACT FROM AUTHOR]

There are indications that in persons of older age, systolic blood pressure (SBP) is no longer associated with mortality. This raises the question whether the predictive value of SBP changes from younger to older age groups. Analysis in the Rotterdam Study, a population-based prospective cohort study among 4,612 participants aged ≥55 years without previous cardiovascular disease and with a median follow-up of 14.9 (interquartile range, 11.1-15.8) years. Within four age groups (55-64, 65-74, 75-84, ≥85 years), the predictive value of baseline SBP for mortality was studied. From age 55 to ≥85 years, risk of all-cause mortality associated with SBP ≥160 mmHg decreased from HR 1.7 (95%CI 1.2-2.2) to HR 0.7 (95%CI 0.4-1.1), p for trend <0.001. For participants with SBP 140-159 mmHg, the risk decreased from HR 1.2 (95%CI 0.9-1.5) to HR 0.7 (95%CI 0.5-1.1), p for trend <0.001. Analyses in the 5-year age groups showed an increased risk with higher SBPs up to age 75 years. After 75 years, a trend towards SBP no longer being associated with an increased mortality risk was seen in our study. These findings need to be considered with recently reported beneficial effects of antihypertensive treatment in this age group. [ABSTRACT FROM AUTHOR]

We present a method for carotid vessel wall volume quantification from magnetic resonance imaging (MRI). The method combines lumen and outer wall segmentation based on deformable model fitting with a learning-based segmentation correction step. After selecting two initialization points, the vessel wall volume in a region around the bifurcation is automatically determined. The method was trained on eight datasets (16 carotids) from a populationbased study in the elderly for which one observer manually annotated both the lumen and outer wall. An evaluation was carried out on a separate set of 19 datasets (38 carotids) from the same study for which two observers made annotations. Wall volume and normalized wall index measurements resulting from the manual annotations were compared to the automatic measurements. Our experiments show that the automatic method performs comparably to the manual measurements. All image data and annotations used in this study together with the measurements are made available through the website http://ergocar.bigr.nl. [ABSTRACT FROM AUTHOR]

It has been demonstrated that aortic stiffness is an independent predictor of cardiovascular disease. We investigated whether this measure is of use in cardiovascular risk stratification in clinical practice for elderly subjects (mean age 71.5 years). Within the framework of the Rotterdam Study, we stratified subjects free of coronary heart disease (CHD) at baseline into categories of low (<10%), intermediate (10-20%) and high (>20%) 10-year risk of CHD based on Framingham risk factors. Within each risk category, we determined the percentages of subjects moving into a higher or lower risk category when adding aortic stiffness to the Framingham risk factors. Among 2849 participants, 223 CHD events occurred during a median follow-up of 7.9 years. In the low risk group, 5% of the subjects could be reclassified and in the high-risk group, 6% of the subjects could be reclassified to the intermediate-risk group. In the intermediate-risk group 3% could be reclassified to the high-risk group and 6% to the low-risk group. In a population of elderly subjects, aortic stiffness measurement in addition to Framingham risk factors leads to a limited reclassification of subjects in 10-year cardiovascular disease-risk categories. Therefore, aortic stiffness is associated with the risk of CHD in elderly, but provides no additional value in cardiovascular risk stratification. [ABSTRACT FROM AUTHOR]

ims/hypothesis: An APOC3 promoter haplotype has been previously associated with type 1 diabetes. In this population-based study, we investigated whether APOC3 polymorphisms increase type 2 diabetes risk and need for insulin treatment in lean participants. Methods: In the Rotterdam Study, a population-based prospective cohort ( n = 7,983), Cox and logistic regression models were used to analyse the associations and interactive effects of APOC3 promoter variants (−482C > T, −455T > C) and BMI on type 2 diabetes risk and insulin treatment. Analyses were followed by replication in an independent case-control sample (1,817 cases, 2,292 controls) and meta-analysis. Results: In lean participants, the −482T allele was associated with increased risk of prevalent and incident type 2 diabetes: OR −482CT 1.47 (95% CI 1.13-1.92), −482TT 1.40 (95% CI 0.83-2.35), p = 0.009 for trend; HR −482CT 1.35 (95% CI 0.96-1.89), −482TT 1.68 (95% CI 0.91-3.1), p = 0.03 for trend, respectively. These results were confirmed by replication. Meta-analysis was highly significant (−482T meta-analysis p = 1.1 × 10). A borderline significant interaction was observed for insulin use among participants with type 2 diabetes (−482CT*BMI p = 0.06, −455TC*BMI p = 0.02). Conclusions/interpretation: At a population-based level, the influence of APOC3 promoter variants on type 2 diabetes risk varies with the level of adiposity. Lean carriers of the −482T allele had increased type 2 diabetes risk, while such an effect was not observed in overweight participants. Conversely, in overweight participants the −455C allele seemed protective against type 2 diabetes. The interaction of the variants with need for insulin treatment may indicate beta cell involvement in lean participants. Our findings suggest overlap in the genetic backgrounds of type 1 diabetes and type 2 diabetes in lean patients. [ABSTRACT FROM AUTHOR]

Objectives: The incidence of heart failure increases with aging. Aim of the present, study was to determine whether measures body composition predict incident heart failure in older adults. Selling: Prospective community-based cohort study. 5, 868 men and women aged 55 years and older participating the Rotterdam study. Measures of body mass index and waist circumference were obtained at baseline. Information on incident heart failure was obtained during follow-up. Cox regression analyses were performed to investigate the possible association between measure of body composition and incident heart failure. Results: During a mean follow up of 10.9 (SD ±4.4) years, 765 participants had heart failure. After adjustment for age and gender, 1-standard deviation of body mass index, waist circumference and the waist-hip ratio predicted heart failure (HR 1.25; 95% CI 1.17-1.34; HR 1.26; 95% CI 1.18-1.36; and HR 1.17; 95% CI 1.08-1.27), respectively. In age-stratified analyses, 1-standard deviation of body mass index (1.17; 95% CI 1.06-1.29) and waist circumference (1.16; 95% CI 1.05-1.29) were still associated with the risk of heart failure in the oldest participants, whereas the waist-hip ratio was not (1.06; 95% CI 0.945-1.18). Conclusion: Although estimates decrease with age, measures of overall and central adiposity predict incident heart failure among community dwelling older adults. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate whether common variation in genes involved in lipid metabolism modify the effect of statins on serum total cholesterol concentration. Statin users were identified in the Rotterdam Study, a prospective population-based cohort study of subjects >55 years of age. We studied the association between single nucleotide polymorphisms (SNPs) in genes involved in lipid metabolism and total cholesterol response to statin therapy, using linear regression analysis and adjusting for potential confounders. Replication was performed in an independent extended cohort of the Rotterdam Study. Genotype data and total cholesterol concentrations after start of statin therapy were available for 554 newly started statin users. Two SNPs were associated with a significantly higher cholesterol concentration under statin therapy: SNP rs1532624 in the CETP gene (β: 0.141 mmol l−1, P=0.004 per additional allele) and SNP rs533556 in the APOA1 gene (β: 0.138 mmol l−1, P=0.005 per additional allele). In the replication sample, only the CETP rs1532624 SNP again showed a significant association. The SNPs were not related to baseline total cholesterol in non-statin users. In conclusion, we found that the CETP rs1532624 polymorphism is associated with cholesterol response to statin therapy in a cohort of elderly subjects in the general population. [ABSTRACT FROM AUTHOR]

Patients with heart failure used to have an increased risk of stroke, but this may have changed with current treatment regimens. We assessed the association between heart failure and the risk of stroke in a population-based cohort that was followed since 1990. The study uses the cohort of the Rotterdam Study and is based on 7,546 participants who at baseline (1990-1993) were aged 55 years or over and free from stroke. The associations between heart failure and risk of stroke were assessed using time-dependent Cox proportional hazards models, adjusted for cardiovascular risk factors (smoking, diabetes mellitus, BMI, ankle brachial index, blood pressure, atrial fibrillation, myocardial infarction and relevant medication). At baseline, 233 participants had heart failure. During an average follow-up time of 9.7 years, 1,014 persons developed heart failure, and 827 strokes (470 ischemic, 75 hemorrhagic, 282 unclassified) occurred. The risk of ischemic stroke was more than five-fold increased in the first month after diagnosis of heart failure (age and sex adjusted HR 5.79, 95% CI 2.15-15.62), but attenuated over time (age and sex adjusted HR 3.50 [95% CI 1.96-6.25] after 1-6 months and 0.83 [95% CI 0.53-1.29] after 0.5-6 years). Additional adjustment for cardiovascular risk factors only marginally attenuated these risks. In conclusion, the risk of ischemic stroke is strongly increased shortly after the diagnosis of heart failure but returns to normal within 6 months after onset of heart failure. [ABSTRACT FROM AUTHOR]

While type 2 diabetes is well-known to be associated with poorer cognitive performance, few studies have reported on the association of metabolic syndrome (MetS) and contributing factors, such as insulin-resistance (HOMA-IR), low adiponectin-, and high C-reactive protein (CRP)- levels. We studied whether these factors are related to cognitive function and which of the MetS components are independently associated. The study was embedded in an ongoing family-based cohort study in a Dutch population. All participants underwent physical examinations, biomedical measurements, and neuropsychological testing. Linear regression models were used to determine the association between MetS, HOMA-IR, adiponectin levels, CRP, and cognitive test scores. Cross-sectional analyses were performed in 1,898 subjects (mean age 48 years, 43% men). People with MetS had significantly higher HOMA-IR scores, lower adiponectin levels, and higher CRP levels. MetS and high HOMA-IR were associated with poorer executive function in women ( P = 0.03 and P = 0.009). MetS and HOMA-IR are associated with poorer executive function in women. [ABSTRACT FROM AUTHOR]

This study was performed to examine the association of cardiovascular risk factors with calcification in the coronary arteries, aortic arch and carotid arteries, assessed by multislice computed tomography (MSCT). This study was embedded in the Rotterdam Study, a population-based study in subjects aged 55 years and over. From October 2003 until December 2004, subjects were invited to undergo a MSCT scan. Coronary, aortic arch and carotid calcification were quantified according to the Agatston score. Analyses were performed in the first 1003 subjects. Age and current smoking were the strongest independent risk factors for arterial calcification. The odds ratio (OR) for age in women, irrespective of the vessel bed, was 1.1 (P<0.001) and in men it was 1.2 with aortic arch and 1.1 with carotid calcification (both P<0.001). Current smoking was associated with aortic arch calcification with an OR of 3.5 in women and of 4.7 in men (both P<0.001); and with carotid calcification with an OR of 2.1 in women (P<0.05) and of 4.1 in men (P<0.01). Hypertension, hypercholesterolemia and diabetes were also independently related to calcification, although not consistent across all vessel beds and for men and women. Obesity tended to be inversely related to arterial calcification in women, whereas low high-density lipoprotein-cholesterol showed no relation with arterial calcification. In conclusion, although associations were not completely consistent across the different vessel beds and for men and women, our results indicate that generally the same risk factors are present for atherosclerosis in the coronary, aortic arch and carotid circulation. [ABSTRACT FROM AUTHOR]

Objective We aimed to examine the associations of maternal anthropometrics with fetal weight measured in different periods of pregnancy and with birth outcomes. Design Population-based birth cohort study. Setting Data of pregnant women and their children in Rotterdam, the Netherlands. Population In 8541 mothers, height, prepregnancy body mass index (BMI) and gestational weight gain were available. Methods Fetal growth was measured by ultrasound in mid- and late pregnancy. Regression analyses were used to assess the impact of maternal anthropometrics on fetal weight and birth outcomes. Main outcome measures Fetal weight and birth outcomes: weight (grams) and the risks of small (<5th percentile) and large (>95th percentile) size for gestational age at birth. Results Maternal BMI in pregnancy was positively associated with estimated fetal weight during pregnancy. The effect estimates increased with advancing gestational age. All maternal anthropometrics were positively associated with fetal size ( P-values for trend <0.01). Mothers with both their prepregnancy BMI and gestational weight gain quartile in the lowest and highest quartiles showed the highest risks of having a small and large size for gestational age child at birth, respectively. The effect of prepregnancy BMI was strongly modified by gestational weight gain. Conclusions Fetal growth is positively affected by maternal BMI during pregnancy. Maternal height, prepregnancy BMI and gestational weight gain are all associated with increased risks of small and large size for gestational age at birth in the offspring, with an increased effect when combined. [ABSTRACT FROM AUTHOR]

Several β-blockers are metabolized by the polymorphic enzyme cytochrome P450 2D6 (CYP2D6). CYP2D6*4 is the main polymorphism leading to decreased enzyme activity. The clinical significance of impaired elimination of β-blockers is controversial, and most studies suffer from inclusion of small numbers of poor metabolizers (PMs) of CYP2D6. In this study, the association between CYP2D6*4 and blood pressure or heart rate was examined in 1,533 users of β-blockers in the Rotterdam Study, a population-based cohort study. In CYP2D6 *4/*4 PMs, the adjusted heart rate in metoprolol users was 8.5 beats/min lower compared with *1/*1 extensive metabolizers (EMs) (P < 0.001), leading to an increased risk of bradycardia in PMs (odds ratio = 3.86; 95% confidence interval 1.68–8.86; P = 0.0014). The diastolic blood pressure in PMs was 5.4 mm Hg lower in users of β-blockers metabolized by CYP2D6 (P = 0.017) and 4.8 mm Hg lower in metoprolol users (P = 0.045) compared with EMs. PMs are at increased risk of bradycardia.Clinical Pharmacology & Therapeutics (2008); 85, 1, 45–50 doi:10.1038/clpt.2008.172 [ABSTRACT FROM AUTHOR]

This study investigates whether the interaction between angiotensin-converting enzyme (ACE) inhibitors or β-blockers and the ACE insertion/deletion (I/D) polymorphism or angiotensin receptor II type 1 (AGTR1) 573C/T polymorphism modifies the risk of myocardial infarction (MI) or stroke. In total, 4097 subjects with hypertension were included in this study. The drug–gene interaction on the risk of MI or stroke was determined with a Cox proportional hazard model. The risk of MI was reduced in current users of ACE inhibitors with the AGTR1 573CT or CC genotype compared to ACE inhibitors with the AGTR1 573TT genotype (synergy index (SI):0.32; 95% confidence interval (CI): 0.14–0.70). No significant drug–gene interaction was found on the risk of stroke (SI:0.82; 95% CI: 0.44–1.52) or in β-blocker users. Also, no significant drug–gene interaction was found with the ACE I/D polymorphism. In conclusion, subjects with at least one copy of the AGTR1 573C allele might have more benefit from ACE inhibitor therapy.The Pharmacogenomics Journal (2008) 8, 400–407; doi:10.1038/sj.tpj.6500493; published online 18 March 2008 [ABSTRACT FROM AUTHOR]

Retinol-binding protein 4 (RBP4), originally known for retinol transport, was recently identified as an adipokine affecting insulin resistance. The RBP4 −803GA promoter polymorphism influences binding of hepatic nuclear factor 1α and is associated with type 2 diabetes in case–control studies. We hypothesised that the RBP4 −803GA polymorphism increases type 2 diabetes risk at a population-based level. In addition, information on retinol intake and plasma vitamin A levels enabled us to explore the possible underlying mechanism. In the Rotterdam Study, a prospective, population-based, follow-up study, the −803GA polymorphism was genotyped. In Cox proportional hazards models, associations of the −803GA polymorphism and retinol intake with type 2 diabetes risk were examined. Moreover, the interaction of the polymorphism with retinol intake on type 2 diabetes risk was assessed. In a subgroup of participants the association of the polymorphism and vitamin A plasma levels was investigated. Homozygous carriers of the −803A allele had increased risk of type 2 diabetes (HR 1.83; 95% CI 1.26–2.66). Retinol intake was not associated with type 2 diabetes risk and showed no interaction with the RBP4 −803GA polymorphism. Furthermore, there was no significant association of the polymorphism with plasma vitamin A levels. Our results provide evidence that homozygosity for the RBP4 −803A allele is associated with increased risk of type 2 diabetes in the Rotterdam population. This relationship was not clearly explained by retinol intake and vitamin A plasma levels. Therefore, we cannot differentiate between a retinol-dependent or -independent mechanism of this RBP4 variant. [ABSTRACT FROM AUTHOR]

Objective: The ‘vascular depression’ hypothesis suggests that late-life depression results from vascular brain damage. We studied the longitudinal association between cerebrovascular risk factors and incident depression in a large population-based study. Method: Two thousand nine hundred and thirty-one persons with the age of ≥61 years were followed up. Data on a comprehensive set of cerebrovascular risk factors were collected at baseline. Participants received a psychiatric assessment 5 years later to establish DSM-IV diagnoses. Results: Only current smoking and antihypertensive drug use were independently associated with incident depressive symptoms. Diabetes mellitus and the Framingham stroke risk score were related to incident depressive disorder. No relation with depression was observed for cholesterol, diastolic and systolic blood pressure, history of cardiovascular disease, atrial fibrillation, left ventricular hypertrophy or the use of statins and anticoagulants. Conclusion: These results moderately support the ‘vascular depression’ hypothesis. [ABSTRACT FROM AUTHOR]

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.International Journal of Obesity (2008) 32, 1083–1090; doi:10.1038/ijo.2008.57; published online 15 April 2008 [ABSTRACT FROM AUTHOR]

Objectives:To examine the development and tracking of subcutaneous fat mass in the first 2 years of life and to examine which parental, fetal and postnatal characteristics are associated with subcutaneous fat mass.Design:This study was embedded in the Generation R Study, a prospective cohort study from early fetal life onward. Subcutaneous fat mass was measured by skinfold thickness (biceps, triceps, suprailiacal, subscapular) at the ages of 1.5, 6 and 24 months in 1012 children. Information about parental, fetal and postnatal growth characteristics was collected by physical and fetal ultrasound examinations and questionnaires.Results:Normal values of subcutaneous fat mass are presented. Total subcutaneous fat mass was higher in girls than in boys at the age of 24 months (P=0.01). Subjects in the lowest and highest quartiles at the age of 6 months tended to keep their position in the same quartile at the age of 24 months (odds ratios 1.86 (95% confidence interval (CI) 1.3, 2.7)) and 1.84 (95% CI: 1.3, 2.6), respectively). Maternal height and weight, paternal weight, fetal weight at 30 weeks, birth weight and weight at the age of 6 weeks were each inversely associated with subcutaneous fat mass at the age of 24 months after adjustment for current weight at 24 months.Conclusion:This study shows for the first time that subcutaneous fat mass tends to track in the first 2 years of life. Furthermore, the results suggest that an adverse fetal environment and growth are associated with increased subcutaneous fat mass at the age of 24 months. Further studies are needed to examine whether these associations persist in later life.International Journal of Obesity (2008) 32, 1050–1059; doi:10.1038/ijo.2008.76; published online 17 June 2008 [ABSTRACT FROM AUTHOR]

The article develops charts for ultrasound dating of pregnancy based on crown-rump length and biparietal diameter. It also derives reference curves for normal fetal growth based on biparietal diameter, head circumference, transverse cerebellar diameter, abdominal circumference and femur length from ten weeks of gestational age onwards.

Objective To examine whether differences in birthweight of various ethnic groups residing in the Netherlands can be explained by determinants of birthweight. Design Population-based birth cohort study. Setting Data of pregnant women and their partners in Rotterdam, the Netherlands. Population We examined data of 6044 pregnant women with a Dutch, Moroccan, Turkish, Capeverdean, Antillean, Surinamese-Creole, Surinamese-Hindustani and Surinamese-other ethnic background. Methods Regression analyses were used to assess the impact of biomedical, socio-demographic and lifestyle-related determinants on birthweight differences. Main outcome measure Birthweight was established immediately after delivery in grams. Results Compared with mean birthweight of offspring of Dutch women (3485 g, SD 555), the mean birthweight was lower in all non-Dutch populations, except in Moroccans. Differences ranged from an 88-g lower birthweight in offspring of the Turkish women to a 424-g lower birthweight in offspring of Surinamese-Hindustani women. Differences in gestational age, maternal and paternal height largely explained the lower birthweight in the Turkish, Antillean, Surinamese-Creole and Surinamese-other populations. Differences in birthweight between the Dutch and the Capeverdean and Surinamese-Hindustani populations could only partly be explained by the studied determinants. Conclusions These results confirm significant differences in birthweight between ethnic populations that can only partly be understood from established determinants of birthweight. The part that is understood points to the importance of determinants that cannot easily be modified, such as parental height. Further study is necessary to obtain a fuller understanding. [ABSTRACT FROM AUTHOR]

This study investigates whether the interaction between diuretics and alpha-adducin (ADD1) G460W or G-protein β3-subunit (GNB3) rs2301339 polymorphism modifies the risk of myocardial infarction (MI) or stroke. Data were used from the Rotterdam Study. The drug–gene interaction was determined with a Cox proportional hazard model with adjustment for each drug class as time-dependent covariates. The risk of MI in current users of low-ceiling diuretics with one or two copies of the ADD1 W-allele (hazard ration (HR)=0.92) was similar compared to the expected joint effect of the W-allele and low-ceiling diuretics on a multiplicative scale (1.04 × 0.90=0.94) (synergy index (SI):0.99; 95% confidence interval (CI): 0.43–2.27). No drug–gene interaction was found on the risk of stroke (SI:0.66; 95% CI:0.43–1.27). In addition, a trend towards an interaction was found between current use and the GNB3 rs230119 G/A polymorphism on the risk of MI (SI: 0.51; 95% CI: 0.23–1.15), whereas no interaction on the risk of stroke was found (SI: 0.84; 95% CI: 0.46–1.56).The Pharmacogenomics Journal (2007) 7, 346–352; doi:10.1038/sj.tpj.6500428; published online 26 December 2006 [ABSTRACT FROM AUTHOR]

Background: The renin-angiotensin system is involved in the development of hypertension, atherosclerosis and cardiovascular disease. We studied the association between the M235T polymorphism of the angiotensinogen gene (AGI) and the C573T polymorphism of the angiotensin II type 1 receptor (AT1R) and blood pressure, carotid atherosclerosis and cerebrovascular disease. Methods: We genotyped over 6000 subjects from the Rotterdam Study and more than 1000 subjects from the Rotterdam Scan Study. We used logistic regression and univariate analyses, adjusting for age and sex with, for AGT, the MM and, for ATIR, the IT genotype as reference. Results: We found that AGT-235T increased systolic (p for trend =0.03) and diastolic blood pressure (p for trend = 0.04). The prevalence of carotid plaques was increased 1 .25-fold (95% CI 1.02-1.52) in AGT-U carriers. There was a significant increase in mean volume deep subcortical white matter lesions (WML) for AGT-1T carriers (1.78 ml vs 1.09 ml in the reference group; p=O.OO8). A significant interaction was found between AGT and ATIR, further increasing the effect on periventricular and subtotal WML (p for interaction =0.02). We found a non-significant increased risk of silent brain infarction for AGT-IT carriers and AT1R-CC carriers, but no effect on stroke. Conclusion: We found an association between AGT and blood pressure, atherosclerosis and WML. Also, we found synergistic effects between AGT and ATIR on the development of WML. These findings raise the question of whether the renin-angiotensin system may be a therapeutic target for the prevention of cerebral white matter pathology. [ABSTRACT FROM AUTHOR]

The insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene may be involved in determining blood pressure changes. The aim of the present study was to assess the relationship between the ACE I/D gene and the change of blood pressure levels during follow-up. We calculated the difference between mean levels of SBP, DBP and PP obtained during the two observations as follows: BP mean levels obtained at third phase minus the BP mean levels at baseline and subsequently we investigated the association of the ACE I/D polymorphism and the mean changes of SBP, DBP and PP levels. The study was conducted within the Rotterdam Study, a population-based cohort study including subjects aged 55 years and older. Information on the II, ID and DD genotypes of the ACE gene and mean change of blood pressure levels were available in 3966 subjects. In adjusted models, subjects with the D allele had higher mean changes of systolic and pulse pressure (PP) than subjects with the I allele. The mean changes of systolic blood pressure were 6.1 (4.7–7.5), 8.2 (7.5–9.3) and 7.4 (5.9–8.5) mm Hg in subjects with the II, ID and DD genotype, respectively. The corresponding mean changes of PP through genotypes were 4.3 (3.3–5.4), 6.0 (5.3–6.7) and 5.9 (4.9–6.9) mm Hg, respectively. No difference was found for mean change of diastolic blood pressure among genotypes. In conclusion, the results of this population-based study show that the ACE ID/DD genotypes are associated with increased mean changes of systolic and PP.Journal of Human Hypertension (2007) 21, 736–740; doi:10.1038/sj.jhh.1002229; published online 10 May 2007 [ABSTRACT FROM AUTHOR]

What is already known about this subject • To our knowledge, there are no prior studies which investigate whether there is a drug–gene interaction between the three genes involved in the renin–angiotensin system and ACE-inhibitor therapy or β-blocker therapy with these subclinical measurements of atherosclerosis. • Some studies have found an effect on blood pressure or stroke/myocardial infarction, although the results are not conclusive. What this study adds • The results do not indicate the presence of a strong drug–gene interaction between the use of ACE-inhibitors or β-blockers and the ACE insertion/deletion, AGT M235T or AGTR1573C/T polymorphism on the overall risk of atherosclerosis. Aims To investigate whether the angiotensin-converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen M235T or angiotensin II receptor type 1 573C/T polymorphism modify the risk of atherosclerosis associated with β-blocker or ACE-inhibitor therapy. Methods Data were used from the Rotterdam Study, a population-based prospective cohort study in the Netherlands, which started in 1990 and included 7983 subjects of ≥ 55 years. In this study, 2216 subjects with hypertension were included. Three subclinical measurements were used for atherosclerosis, i.e. peripheral arterial disease, carotid atherosclerosis and aortic atherosclerosis. The interaction between antihypertensive drugs and genetic polymorphisms on the risk of atherosclerosis was determined with binary logistic regression analysis. Results The risk of aortic atherosclerosis associated with long-term (≥4 years) β-blocker treatment compared with no use of β-blockers was higher in subjects with the TT genotype than in subjects with the MM genotype of the AGT gene [synergy index (SI) = 3.36; 95% confidence interval (CI) 1.14, 9.97]. The risk of carotid atherosclerosis associated with long-term ACE-inhibitor treatment compared with no use of ACE-inhibitors was lower in subjects with the TT genotype than in subjects with the MM genotype of the AGT gene (SI = 0.20; 95% CI 0.04, 0.95). Conclusion Overall, the risk of atherosclerosis in hypertensives taking a β-blocker or ACE-inhibitor-based regimen was not strongly modified by any of the three candidate gene polymorphisms. [ABSTRACT FROM AUTHOR]

Arterial stiffness is a risk factor for cardiovascular disease. Transforming growth factor β1 is a pleiotropic cytokine, with many functions, including influence on the vascular wall (e.g., on angiogenesis, endothelial cells and the extracellular matrix). We investigated five functional polymorphisms in the transforming growth factor β1 gene (−800 G/A, −509 C/T, codon 10 Leu/Pro, codon 25 Arg/Pro and codon 263 Thr/Ile) in relation to arterial stiffness in a population-based study. A total of 3863 participants of the Rotterdam Study, a prospective population-based study, were included in the current study. The relations of the genotypes and haplotypes with arterial stiffness (pulse wave velocity (PWV), distensibility coefficient (DC) and pulse pressure (PP)) were studied using analyses of variance and linear regression. The analyses were adjusted for age, sex, mean arterial pressure, heart rate, conventional cardiovascular risk factors and measures of atherosclerosis. There were no associations between PWV and −800 G/A (P=0.56), −509 C/T (P=0.29), codon 10 (P=0.98) and, codon 25 (P=0.28). These polymorphisms were not associated with the DC or with PP. The haplotype-based analyses yielded similar results. The results of this study show that the TGF-β1 –800 G/A, −509 C/T, codon 10 Leu/Pro and codon 25 Arg/Pro polymorphisms are not associated with arterial stiffness.Journal of Human Hypertension (2007) 21, 431–437. doi:10.1038/sj.jhh.1002175; published online 15 March 2007 [ABSTRACT FROM AUTHOR]

Objectives The objectives of this study were to determine ethnic differences in prenatal growth and to examine their association with differences in maternal and fetal characteristics such as maternal height, weight, age, parity and fetal gender. Methods A total of 1494 women from Rotterdam, The Netherlands, with a low-risk pregnancy who participated in a population-based cohort study, the Generation R Study, were offered three ultrasound examinations during pregnancy. Multilevel modeling was applied to determine ethnic differences in (estimated) fetal weight (including birth weight) and in the separate biometric variables that were used to calculate the estimated fetal weight (abdominal circumference, head circumference and femur length). Additionally the association of ethnic differences with maternal and fetal characteristics (i.e. maternal weight, height, age, parity and fetal gender) was studied. Results Turkish, Cape Verdian, Surinamese-Creole and Surinamese-Hindustani women had on average smaller fetuses than the native Dutch women. The differences became more pronounced towards term. In the Turkish group the differences were no longer statistically significant when adjusted for maternal weight, height, age, parity and fetal gender. In the Cape Verdian, Surinamese-Creole and Surinamese-Hindustani groups the differences decreased after adjustment (31%, 16% and 39%, respectively). Conclusions This study shows that there are ethnic differences in fetal growth, which to a large extent may be attributed to differences in maternal weight, height, age and parity. For some ethnic groups, however, additional factors are involved, as differences remain significant after correction for fetal and maternal characteristics. [ABSTRACT FROM AUTHOR]

The genetic and environmental risk factors, which may influence longevity and mortality, have received much attention during more than one decade. One of the major risks for mortality is cardiovascular disease and the renin angiotensin system (RAS) plays a major role in maintaining blood pressure homeostasis. In this system, the Angiotensin Converting Enzyme (ACE) is one of the key regulators and has been studied in relation to cardiovascular disease and mortality. We aimed to evaluate if the ACE I/D polymorphism is related to total mortality in the elderly. Some 6968 elderly individuals from the Rotterdam study were genotyped for this polymorphism. Smoking was studied as a possible covariable or effect modifier. To examine the effect of the ACE genotype on mortality, a Cox proportional hazards model was fitted. Our results show an increased risk of total mortality in subjects with age at death below 65 years carriers of the DD genotype (HR 1·8, 95% CI 1·1–2·9, P = 0·016). This association was significant in total and cause specific mortality only in those who smoke ( P-value < 0·001 for gene–age interaction). Our findings suggest that the ACE gene is rather associated with early mortality than with late. Individuals who carry the DD genotype appear to be susceptible to early mortality if they smoke, suggesting a possible interaction between smoking and the ACE gene. Eur J Clin Invest 2005; 35 (7): 444 –449 [ABSTRACT FROM AUTHOR]

Background: Findings on the association between the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene and cardiovascular morbidity and mortality have been inconsistent. Considering the possible interaction between this polymorphism and smoking, we evaluated the association between ACE I/D polymorphism and myocardial infarction (MI), mortality due to coronary heart disease (CHD), and cardiovascular disease (CVD). Methods: The study was performed within the Rotterdam Study, a population based cohort study. The ACE I/D polymorphism was determined for 6714 participants and smoking status recorded at baseline. Fatal and non-fatal MIs and mortality events were regularly recorded. Cox proportional hazard analysis was performed separately for current smokers and non-smokers. We used age as the follow up time, presenting age specific survivals. Results: During follow up, 248 MIs and 301 and 482 deaths, respectively, due to CHD and CVD occurred. There were no significant differences between the genotypes as regards MI incidence. Among smokers, there was an increased risk of CHD and CVD mortality in carriers of the DD genotype compared to the II genotype, which diminished at later ages (p<0.01 for gene-age interaction). Subgroup analysis in a younger and older group (based on the median age of 68.2 years) showed a significantly increased risk of CVD mortality in the younger group (hazard ratio = 5.19; 95% confidence interval: 1.15 to 23.42). Conclusions: This study showed that the ACE I/D polymorphism is not a strong risk factor for MI but its interaction with smoking might play a role in cardiovascular mortality especially at younger ages. [ABSTRACT FROM AUTHOR]

The aim was to examine the risk profiles and prognosis of treated and untreated hypertensive subjects and examine to what degree confounding by indication was present in a population-based cohort study with up to 30-year follow-up. The study population consisted of 9328 men and 10?062 women, aged 33-87 years at the time of attendance from 1967 to 1996. The main outcome measures were myocardial infarction (MI), cardiovascular disease (CVD) mortality and all-cause mortality. Comparing the risk profiles between treated and untreated subjects entering the study showed significantly higher values for some risk factors for treated subjects. During the first 10 years, hypertensive men without treatment, compared with those treated, had a significantly lower risk of suffering MI, CVD and all-cause mortality, hazard ratio (HR) 0.72 (95% CI; 0.57, 0.90), 0.75 (95% CI; 0.59, 0.95) and 0.81 (95% CI; 0.61, 0.98), respectively. No significant differences in outcome were seen during the following 20 years. In identically defined groups of women, no significant differences in mortality were seen between groups. Subgroup analysis, at two stages of the study 5 years apart, revealed that some cardiovascular risk factors had a higher prevalence in hypertensive men who were treated at the later stage, compared with those who remained untreated (P=0.004). In conclusion, hypertensive treated men had a worse prognosis during the first 10 years of follow-up than untreated ones, which is most likely due to worse baseline risk profile. Hypertensive men that were treated at a later stage had a worse risk profile than those not treated at a later stage.Journal of Human Hypertension (2004) 18, 615-622. doi:10.1038/sj.jhh.1001725 Published online 8 April 2004 [ABSTRACT FROM AUTHOR]

Low estrogen exposure throughout life is thought to result in low bone mineral density (BMD) and an increased incidence of cardiovascular disease. In the Rotterdam Study we cross-sectionally examined the relation between BMD and peripheral arterial disease (PAD), as assessed by an ankle-arm index (AAI) of <0.9 in either leg. Data on BMD and PAD were available for 5268 individuals (3053 women, 2215 men). From the BMD, Z-scores were calculated and subsequently divided into tertiles. Logistic regression analysis was used to compute odds ratios (OR) for PAD in tertiles of BMD, using the upper tertile as a reference. When adjusting for age, women with a low femoral neck BMD had a significantly increased risk of PAD (OR = 1.49, 95% CI 1.16–1.91). This could not be found for men (1.14, 0.84–1.53). The mid-tertile did not differ from the reference in either men or women. In women, additional adjustment for several potential confounders resulted in a somewhat lowered risk estimate (1.35, 1.02–1.79). In contrast, no association between lumbar spine BMD and PAD could be observed in either men or women. Our study shows an association between low femoral neck BMD and PAD in women only, an association unlikely to be causal. Estrogen deficiency may be the common denominator in osteoporosis and PAD, resulting in clustering of these two major diseases in postmenopausal women. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare body mass index (BMI), waist-hip ratio (WHR) and waist circumference as predictors of all-cause mortality among the elderly. DESIGN: Population-based cohort study; mean follow-up was 5.4 y. SETTING: The Rotterdam Study. PARTICIPANTS: A total of 6296 men and women; baseline age 55-102 y. MEASUREMENTS: Sex-specific all-cause mortality was compared between quintiles of BMI, WHR and waist circumference and between predefined categories of BMI and waist circumference, stratified for smoking category. RESULTS: High quintiles of waist circumference, but not high quintiles of BMI and WHR were related to increased mortality among never smoking men, without reaching statistical significance. Only the highest category of BMI (BMI > 30 kg/m²) among never smoking men was related to increased mortality, compared to normal BMI (hazard ratio 2.6 (95% confidence interval: 1.3-5.3)). Waist circumference between 94 and 102 cm and waist circumference 102 cm and larger were related to increased mortality, compared to normal waist circumference (hazard ratios 1.7 (95% confidence interval 1.1-2.8) and 1.6 (95% confidence interval 1.0-2.8), respectively). The proportion of mortality attributable to large waist circumference among never smoking men was three-fold the proportion attributable to high BMI. Among never smoking women and ex- and current smokers, categories of large body fatness did not predict increased mortality. CONCLUSION: Among never smoking elderly men waist circumference may have more potential for detecting overweight than the BMI. [ABSTRACT FROM AUTHOR]