Showing papers by "Diederick E. Grobbee published in 2004"

A randomized trial comparing conventional and endovascular repair of abdominal aortic aneurysms

Abstract: Background Although the initial results of endovascular repair of abdominal aortic aneurysms were promising, current evidence from controlled studies does not convincingly show a reduction in 30-day mortality relative to that achieved with open repair. Methods We conducted a multicenter, randomized trial comparing open repair with endovascular repair in 345 patients who had received a diagnosis of abdominal aortic aneurysm of at least 5 cm in diameter and who were considered suitable candidates for both techniques. The outcome events analyzed were operative (30-day) mortality and two composite end points of operative mortality and severe complications and operative mortality and moderate or severe complications. Results The operative mortality rate was 4.6 percent in the open-repair group (8 of 174 patients; 95 percent confidence interval, 2.0 to 8.9 percent) and 1.2 percent in the endovascular-repair group (2 of 171 patients; 95 percent confidence interval, 0.1 to 4.2 percent), resulting in a risk ratio ...

Dietary Intake of Menaquinone Is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study

Abstract: Vitamin K-dependent proteins, including matrix Gla-protein, have been shown to inhibit vascular calcification. Activation of these proteins via carboxylation depends on the availability of vitamin K. We examined whether dietary intake of phylloquinone (vitamin K-1) and menaquinone (vitamin K-2) were related to aortic calcification and coronary heart disease (CHD) in the population-based Rotterdam Study. The analysis included 4807 subjects with dietary data and no history of myocardial infarction at baseline (1990-1993) who were followed until January 1, 2000. The risk of incident CHD, all-cause mortality, and aortic atherosclerosis was studied in tertiles of energy-adjusted vitamin K intake after adjustment for age, gender, BMI, smoking, diabetes, education, and dietary factors. The relative risk (RR) of CHD mortality was reduced in the mid and upper tertiles of dietary menaquinone compared to the lower tertile [RR = 0.73 (95% CI: 0.45, 1.17) and 0.43 (0.24, 0.77), respectively]. Intake of menaquinone was also inversely related to all-cause mortality [RR = 0.91 (0.75, 1.09) and 0.74 (0.59, 0.92), respectively] and severe aortic calcification [odds ratio of 0.71 (0.50, 1.00) and 0.48 (0.32, 0.71), respectively]. Phylloquinone intake was not related to any of the outcomes. These findings suggest that an adequate intake of menaquinone could be important for CHD prevention.

Endogenous sex hormones and progression of carotid atherosclerosis in elderly men.

Abstract: Background— The burden of atherosclerosis especially afflicts the increasing older segment of the population. Recent evidence has emphasized a protective role of endogenous sex hormones in the deve...

Effect of Moderate Alcohol Consumption on Adiponectin, Tumor Necrosis Factor-α, and Insulin Sensitivity

Abstract: OBJECTIVE - Epidemiological studies suggest that moderate alcohol consumers have enhanced insulin sensitivity and a reduced risk of type 2 diabetes. Adiponectin, an adipocyte-derived plasma protein, has been found to be negatively associated with adiposity and positively associated with insulin sensitivity. Moderate alcohol consumption may increase adiponectin, which in turn causes a decrease of tumor necrosis factor (TNF)-α. A decreased TNF-α level may consequently increase insulin sensitivity. RESEARCH DESIGN AND METHODS - To test this hypothesis, we performed a randomized crossover partially diet-controlled study. A total of 23 healthy middle-aged male subjects consumed daily four glasses of whisky (40 g ethanol) or tap water with dinner during two successive periods of 17 days. RESULTS - Moderate alcohol consumption increased plasma adiponectin level (11%; P = 0.002) but did not affect plasma TNF-α level. An increase in insulin sensitivity index was observed in an insulin-resistant subgroup (21%; P = 0.11), which positively correlated with the relative alcohol-induced increase in plasma adiponectin level (r = 0.73, P = 0.02). CONCLUSIONS - The experimental results are in agreement with observational data. Moderate alcohol consumption improved insulin sensitivity in relatively insulin-resistant middle-aged men, an effect that may be mediated through alcohol-induced increases in adiponectin.

Carotid Artery Plaque Burden, Stiffness, and Mortality Risk in Elderly Men A Prospective, Population-Based Cohort Study

Abstract: Background— Indicators of carotid atherosclerosis may confer additional prognostic value and guide clinicians in cardiovascular risk assessment. Carotid artery morphology (plaque burden) and function (stiffness indexes) as predictors of all-cause and cardiovascular mortality were prospectively evaluated in elderly men. Methods and Results— Cardiovascular risk profile was measured in 367 independently living men (mean± SD age, 78±4 years). The number of carotid plaques was assessed by B-mode ultrasound, and arterial stiffness was quantified with a wall tracker system. During 48 months of follow-up, 70 deaths (28 cardiovascular) occurred. The total number of carotid plaques was the parameter most closely related to prognosis. In the age-adjusted multivariate Cox model, all-cause mortality was predicted by number of plaques (hazard ratio [HR] per 1-unit increase, 1.35; 95% confidence interval [CI], 1.12 to 1.64). Predictors of cardiovascular mortality in the respective model were number of plaques (HR, 1.18;...

Impact of dietary and lifestyle factors on the prevalence of hypertension in Western populations

Abstract: Background: Data on the impact of the many dietary and lifestyle factors on the prevalence of hypertension in Western societies are lacking. This study quantified the contributions of body weight, physical inactivity and dietary factors to the prevalence of hypertension in Finland, Italy, the Netherlands, United Kingdom (UK) and USA. Methods: Distributions of blood pressure (BP) and risk factors in Western populations were obtained from nationwide surveys. The effect of risk factors on BP was assessed by meta-regression analysis of randomized trials, published between 1966 and March 2001. Population attributable risk percentages (PAR%) for hypertension (i.e. systolic BP ≥140 mmHg) were computed for all risk factors in the five countries. Results: Being overweight made the largest contribution to hypertension, with PAR% between 11% (Italy) and 25% (USA). PAR% were 5–13% for physical inactivity, 9–17% for high sodium intake, 4–17% for low potassium intake and 4–8% for low magnesium intake. The impact of alcohol was small (2–3%) in all populations. PAR% varied among populations for inadequate intake of calcium (2–8%), magnesium (4–8%), coffee (0–9%) and fish fatty acids (3–16%). Conclusions: Diet and lifestyle have a substantial impact on hypertension in Western societies, with being overweight, physical inactivity, high sodium intake and low potassium intake being the main contributors. The relative significance of different risk factors varies among populations, which is important for preventative strategies.

Test research versus diagnostic research

Abstract: The diagnostic workup starts with a patient presenting with symptoms or signs suggestive of a particular disease. The workup is commonly a consecutive process starting with medical history and physical examination and simple tests followed by more burdensome and costly diagnostic procedures. Generally, after each test all available results are converted (often implicitly) to a probability of disease, which in turn directs decisions for additional testing or initiation of appropriate treatment. Setting a diagnosis is a multitest or multivariable process of estimating and updating the diagnostic probability of disease presence given combinations of test results. Each test may be more or less burdensome to the patient, time-consuming, and/or costly. Different tests often provide to various degrees the same information because they are all associated with the same underlying disorder. Relevant for physicians is to know which tests are redundant and which have true, independent predictive value for the presence or absence of the target disease. Accordingly, studies of diagnostic accuracy should demonstrate which (subsequent) test results truly increase or decrease the probability of disease presence as estimated from the previous results, and to what extent. Various reviews have demonstrated that the majority of published studies of diagnostic accuracy still have methodologic flaws in design or analysis or provide results with limited practical applicability (1)(2)(3). This has been attributed to the absence of a proper methodologic framework for diagnostic test evaluations as, for example, exists for studies of therapies and etiologic factors and has motivated various researchers to establish frameworks for studies of diagnostic accuracy, such as the recent STARD Initiative (4)(5)(6)(7)(8)(9)(10)(11)(12). In our view, an issue that has received too little attention in most of these methodologic essays is the …

Breast Cancer Risk After Caloric Restriction During the 1944–1945 Dutch Famine

Abstract: Background: Data from animal models suggest that caloric restriction may reduce the risk of breast cancer, although not all dietary regimens produce similar effects. We examined whether caloric restriction imposed as a consequence of the 1944 –1945 Dutch famine reduced the risk of breast cancer in women participating in a Dutch breast cancer screening program. Methods: Between 1983 and 1986, approximately 15 000 women, aged 2 to 33 years during the 1944 –1945 Dutch famine, responded to a questionnaire about their famine experience. A famine exposure score, graded as absent, moderate, or severe exposure, was derived from answers regarding hunger, cold, and weight loss. During follow-up until January 2000, 585 women with incident breast cancer were identifi ed by the regional cancer registry. The relationship between famine exposure and breast cancer risk was assessed by weighted Cox regression models, in which person-years lived for the entire cohort was extrapolated from data from a random sample of 15% of the cohort. Results: Women who were severely exposed to the famine had a statistically signifi cantly higher risk of breast cancer (hazard ratio [HR] 1.48, 95% confi dence interval [CI] 1.09 to 2.01) than women who were not exposed. Women who were moderately exposed to the famine had a 13% increased risk of breast cancer (HR 1.13, 95% CI 0.92 to 1.38; Ptrend 0.016). The association between famine exposure and breast cancer risk was stronger for women who were exposed between the ages of 2 and 9 years (severely exposed versus unexposed: HR 2.01, 95% CI 0.92 to 4.41) than for women who were exposed at older ages. Conclusions: The risk of breast cancer was increased in women who were severely exposed to a short but severe famine decades earlier. This result is compatible with data from the few animal studies investigating effects of shortterm, transient caloric restriction. [J Natl Cancer Inst 2004; 96:539 – 46]

Effect of Moderate Alcohol Consumption on Plasma Dehydroepiandrosterone Sulfate, Testosterone, and Estradiol Levels in Middle‐Aged Men and Postmenopausal Women: A Diet‐Controlled Intervention Study

Abstract: Background: Moderate alcohol consumption is inversely associated with cardiovascular diseases. Changes in hormone levels might in part help explain the positive health effect. This study was performed to examine the effect of moderate alcohol consumption on plasma dehydroepiandrosterone sulfate (DHEAS), testosterone, and estradiol levels. Methods: In a randomized, diet-controlled, crossover study, 10 middle-aged men and 9 postmenopausal women, all apparently healthy, nonsmoking, and moderate alcohol drinkers, consumed beer or no-alcohol beer with dinner during two successive periods of 3 weeks. During the beer period, alcohol intake equaled 40 and 30 g per day for men and women, respectively. The total diet was supplied and had essentially the same composition during these 6 weeks. Before each treatment there was a 1 week washout period, in which the subjects were not allowed to drink alcoholic beverages. At the end of each of the two experimental periods, fasting blood samples were collected in the morning. Results: Moderate alcohol consumption increased plasma DHEAS level by 16.5% (95% confidence interval, 8.0-24.9), with similar changes for men and women. Plasma testosterone level decreased in men by 6.8% (95% confidence interval, -1.0 - -12.5), but no effect was found in women. Plasma estradiol level was not affected. Serum high-density lipoprotein cholesterol level increased by 11.7% (95% confidence interval, 7.3-16.0), with similar changes for men and women. The overall alcohol-induced relative changes in DHEAS, testosterone, and estradiol correlated positively with the relative increase in high-density lipoprotein cholesterol (adjusted for the relative change in body weight); however, findings were only borderline significant for DHEAS and estradiol (r =0.44, p = 0.08; r = 0.32, p = 0.21; and r = 0.46, p = 0.06, respectively). Conclusions: A protective effect of moderate alcohol consumption for cardiovascular disease risk may in part be explained by increased plasma DHEAS level.

Measuring Effects on intima media Thickness: an Evaluation Of Rosuvastatin in subclinical atherosclerosis--the rationale and methodology of the METEOR study.

Abstract: Background: Increased carotid intima media thickness (IMT) is associated with established coronary heart disease (CHD) and is a marker of atherosclerosis. Statins are an effective treatment for dyslipidaemia, and have been shown to retard progression or promote carotid IMT regression in patients at high risk of CHD. Rosuvastatin is a highly efficacious statin, and the Measuring Effects on intima media Thickness: an Evaluation Of Rosuvastatin (METEOR) study is designed to assess the impact of rosuvastatin on carotid IMT progression in low risk subjects with signs of subclinical atherosclerosis. Methods: In this randomised, parallel-group study, asymptomatic subjects at low risk of cardiovascular disease, but with evidence of atherosclerosis (defined as carotid IMT ≥1.2 mm and <3.5 mm), will receive rosuvastatin (40 mg/day) or placebo for 104 weeks. The study will enrol 840 European and US subjects randomised 5:2 between rosuvastatin and placebo. The primary end point will be the change in carotid IMT from baseline to study end, measured using B-mode ultrasonography. Other efficacy end points include changes in the serum lipid profile and C-reactive protein. Safety parameters will also be assessed. Conclusion: The METEOR study will evaluate whether long-term rosuvastatin treatment promotes regression, or slows progression, of subclinical atherosclerosis in asymptomatic subjects at low risk of cardiovascular disease.

Meta-analysis on the effect of off-pump coronary bypass surgery

Abstract: Objective: To assess the effect of conventional coronary artery bypass surgery (CABG) compared to the off-pump procedure (OPCAB). Methods: Based on randomised trials found in PubMed and Science Citation Index, an overall odds ratio and 95% confidence interval was calculated for the combined endpoint of mortality, stroke and myocardial infarction. Results: The 18 randomised trials included 1584 patients (783 OPCAB, 801 CABG). The odds ratio was 0.73 (95% CI ¼ 0.26; 2.04) at 2-week post-surgery, 0.75 (0.39; 1.42) at 1-month post-surgery, 0.55 (0.28; 1.08) at 3-month post-surgery, and 0.66 (0.38; 1.15) at 1-year post-surgery. Conclusions: The outcome of this metaanalysis shows favourable results for OPCAB for the combined endpoint of mortality, stroke and myocardial infarction at short and long term follow-up. However, none of the risk reductions reach statistical significance at the conventional level. Based on our results OPCAB appears to be equivalent to CABG. q 2004 Elsevier B.V. All rights reserved.

Estrogen, inflammation and cardiovascular risk in women, a critical appraisal.

Abstract: The widely shared enthusiasm about the cardioprotective potential of estrogenic compounds has come to an abrupt halt since randomized trials failed to show a cardiovascular risk reduction in postmenopausal women. This was unexpected because observational studies had strongly suggested that hormone replacement therapy would reduce the incidence of cardiovascular disease. Inflammatory activity is considered central in atherogenesis and atherosclerosis progression. Thus, parts of the striking discrepancy between observational and randomized data have been attributed to an estrogen-mediated adverse effect on inflammation. Here, we review the current clinical evidence with respect to the inflammation-modulating effects of different estrogenic compounds as one potential explanatory factor for these divergent findings. We conclude that it is still unclear whether estrogen-modulated inflammation is an important biological factor determining clinical outcome or a mere epiphenomenon.

Alcohol Consumption in Relation to Aortic Stiffness and Aortic Wave Reflections: A Cross-Sectional Study in Healthy Postmenopausal Women

Abstract: Objective-Moderate alcohol consumption has been postulated to be cardioprotective. Such an effect might be reflected in large-artery properties, such as arterial stiffness and wave reflections. Methods and Results-Three hundred seventy-one healthy postmenopausal women aged 50 to 74 years were sampled from a population-based study. Alcohol intake was calculated from a standardized questionnaire. Applanation tonometry was applied to assess the augmentation index and aortic pulse-wave velocity. Those drinking 1 to 3, 4 to 9, 10 to 14, and 15 to 35 glasses of alcoholic beverages per week had a 0.044 (95% CI -0.47 to 0.56), -0.085 (95% CI -0.59 to 0.43), -0.869 (95% CI -1.44 to -0.29), and -0.225 (95% CI -0.98 to 0.53) m/s difference in mean pulse-wave velocity compared with nondrinkers, respectively, which indicates a J-shaped relationship. Adjustment for potential confounders of pulse-wave velocity or alcohol intake did not materially change the strength of the association. Adjustment for HDL further attenuated the relationship. The augmentation index was not related to alcohol consumption when adjustments were made for physiological determinants such as age, height, and ejection duration. Conclusions-Among postmenopausal women, alcohol consumption is inversely associated with pulse-wave velocity. This supports the presence of a decreased risk of cardiovascular disease with moderate alcohol consumption, which may be mediated in part by HDL cholesterol.

Interrupter Resistance and Wheezing Phenotypes at 4 Years of Age

Abstract: It is difficult to distinguish young children with respiratory symptoms who will develop asthma from those with transient symptoms only. Measurement of interrupter resistance may help to identify children at high risk of asthma. The aim of this study is to compare interrupter resistance in 4-year-old children with different wheezing phenotypes. All children participated in the Prevention and Incidence of Asthma and Mite Allergy cohort, a prospective birth cohort of more than 4,000 children. At 4 years of age, data on interrupter resistance plus wheezing phenotype were available for 838 children. Mean interrupter resistance values (95% confidence interval) were 0.95 (0.93, 0.97), 0.95 (0.92, 0.98), 0.96 (0.87, 1.05), and 1.08 (1.02, 1.14) kPa · L−1 · second for never (n = 482), early transient (n = 236), late-onset (n = 22), and persistent (n = 98) wheezing phenotypes, respectively. Additional analyses were performed for children with atopic and nonatopic mothers separately. Both in children with atopic an...

Long term consequences of the 1944-1945 Dutch famine on the insulin-like growth factor axis.

Abstract: The insulin-like growth factor axis is highly responsive to nutritional status and may be involved as one of the underlying mechanisms through which caloric restriction could affect cancer risk. High levels of circulating insulin-like growth factor (IGF)-I, or IGF-I relative to IGF binding protein (IGFBP)-3 have been related to various human cancer types. In a group of 87 postmenopausal women, we found that childhood exposure to the 1944-1945 Dutch famine was associated with increased plasma levels of IGF-I and IGFBP-3, whereas IGFBP-1 and -2 levels were weakly decreased. These results are opposite to immediate responses seen under starvation and we hypothesize that this could indicate a permanent overshoot upon improvement of nutritional status after the famine.

Do prothrombotic factors influence clinical phenotype of severe haemophilia? A review of the literature

Abstract: There is considerable variability in bleeding patterns of severe haemophilia (<1% factor VIII). Knowledge of the contribution of thrombophilic factors in these patterns may improve individually tailored treatment strategies. We reviewed the literature regarding the relation between prothrombotic factors and clinical phenotype of severe haemophilia. Medline and EMBASE were searched for relevant articles. 9369 articles published between 1963 and September 2003 were screened and seven relevant papers were retrieved. Each of these reported on a different combination of thrombophilic factors. Presence of the factor V Leiden mutation appears to decrease the severity of severe haemophilia most consistently. Findings on other thrombophilic factors were inconclusive. There is a clear need for additional research on potential determinants of phenotypes of severe haemophilia before such knowledge can be translated into individual care for severe haemophilia patients with confidence.

Linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative trait loci influencing variation in human menopausal age.

Abstract: Age at natural menopause may be used as parameter for evaluating the rate of ovarian aging. Environmental factors determine only a small part of the large variation in menopausal age. Studies have shown that genetic factors are likely to be involved in variation in menopausal age. To identify quantitative-trait loci for this trait, we performed a genomewide linkage study with age at natural menopause as a continuous quantitative phenotype in Dutch sister pairs, through use of a selective sampling scheme. A total of 165 families were ascertained using extreme selected sampling and were genotyped for 417 markers. Data were analyzed by Haseman-Elston regression and by an adjusted variance-components analysis. Subgroup analyses for early and late menopausal age were conducted by Haseman-Elston regression. In the adjusted variance-components analysis, 12 chromosomes had a LOD score of ⩾1.0. Two chromosomal regions showed suggestive linkage: 9q21.3 (LOD score 2.6) and Xp21.3 (LOD score 3.1). Haseman-Elston regression showed rather similar locations of the peaks but yielded lower LOD scores. A permutation test to obtain empirical P values resulted in a significant peak on the X chromosome. To our knowledge, this is the first study to attempt to identify loci responsible for variability in menopausal age and in which several chromosomal regions were identified with suggestive and significant linkage. Although the finding of the region on the X chromosome comes as no surprise, because of its widespread involvement in premature ovarian failure, the definition of which particular gene is involved is of great interest. The region on chromosome 9 deserves further consideration. Both findings require independent confirmation.

Alcohol consumption and arterial stiffness in men.

Abstract: Objective: Moderate alcohol consumption has been proposed to be anti-atherogenic and protect against coronary heart disease. Arterial stiffness provides a summary measure of atherosclerotic arterial damage and cardiovascular risk. A vascular protective effect of moderate alcohol consumption would be reflected in an inverse association between alcohol intake and aortic stiffness. Design: A cross-sectional study. Setting: The male population of Utrecht. Participants: Of 370 men, aged 40-80 years, alcohol intake was calculated from a standardized questionnaire and aortic stiffness was non-invasively assessed by pulse-wave velocity (PWV) measurement of the aorta. Results: There were no non-drinkers; therefore the group consuming 0-3 glasses of alcoholic beverage per week was chosen as the reference group in the analyses. Those drinking 4-10, 11-21 and 22-58 glasses of alcoholic beverage per week had a -0.77 m/s (95% confidence interval, -1.26 to -0.28), -0.57 m/s (95% confidence interval, -1.07 to -0.08) and -0.14 m/s (95% confidence interval, -0.65 to 0.36) difference in mean PWV compared with those drinking 0-3 glasses per week. Adjustment for factors that correlated with PWV or alcohol consumption did not change the strength of the association. Conclusion Among men aged 40-80 years there is a J-shaped association between alcohol consumption and PWV. This further supports a decreased risk of cardiovascular disease with moderate alcohol consumption. © 2004 Lippincott Williams & Wilkins.

Current smoking at menopause rather than duration determines the onset of natural menopause.

Abstract: Background: Smoking has frequently been associated with early menopause. However, studies of this association have been inconclusive with regard to duration and intensity of smoking. A major problem in analyzing the effect of smoking duration on menopausal age is that both exposure and outcome are age-dependent. Methods: We calculated age-specific rates for categories of smoking duration and subsequently computed the rate ratios for occurrence of menopause. We were thus able to model the effect of smoking duration on 2 time scales without assumptions of linearity. We used data from a Dutch population-based cohort comprising 5544 women age 49-70 years who had experienced natural menopause. Results: The rate ratio (RR) for occurrence of menopause was increased in women who smoked in the year of menopause (RR = 1.41; 95% confidence interval = 1.32-1.50). The rate ratio of former smokers was similar to women who never smoked (0.95; 0.89-1.02). Prolonged exposure of smoking did not materially affect the risk of menopause, although the daily number of cigarettes currently smoked could increase the risk. Conclusion: Perimenopausal smoking is apparently more important than smoking history in explaining an earlier age of onset of menopause among women who smoke

Role of Coronary Collaterals in Off-Pump and On-Pump Coronary Bypass Surgery

Abstract: Background— Collaterals limit infarct size, preserve viability, and reduce mortality in patients with acute myocardial infarction. In patients with stable coronary disease, collaterals are associated with less angina and ischemia during angioplasty and fewer ischemic events during follow-up. The role of collaterals has not been studied in patients undergoing off-pump or on-pump bypass surgery. Methods and Results— The population consisted of the 281 patients randomized to off-pump or on-pump CABG in the Octopus Study. Collaterals were defined on the baseline angiogram with the Rentrop score and were present in 49% and 51% of the patients in the off-pump and on-pump group, respectively. Perioperative myocardial infarction was defined by a creatine kinase-MB to CK ratio >10% and occurred in 18.2% in the off-pump group and 32.5% in the on-pump group. The unadjusted OR of perioperative myocardial infarction in the presence of collaterals was 0.31 (95% CI 0.17 to 0.84) in the off-pump group and 1.06 (95% CI 0....

Carotid Stiffness Indicates Risk of Ischemic Stroke and TIA in Patients With Internal Carotid Artery Stenosis The SMART Study

Abstract: Background and Purpose— Patients with a carotid artery stenosis, including those with an asymptomatic or moderate stenosis, have a considerable risk of ischemic stroke. Identification of risk factors for cerebrovascular disease in these patients may improve risk profiling and guide new treatment strategies. We cross-sectionally investigated whether carotid stiffness is associated with previous ischemic stroke or transient ischemic attack (TIA) in patients with a carotid artery stenosis of at least 50%. Methods— Patients were selected from the Second Manifestations of ARTerial disease (SMART) study, a cohort study among patients with manifest vascular disease or vascular risk factors. Arterial stiffness, measured as change in lumen diameter of the common carotid arteries during the cardiac cycle, forms part of the vascular screening performed at baseline. The first 420 participants with a stenosis of minimally 50% in at least 1 of the internal carotid arteries measured by duplex scanning were included in t...

Dietary phytoestrogens and vascular function in postmenopausal women: a cross-sectional study.

Abstract: ObjectiveTo investigate the effects of low levels of intake of phytoestrogens in Western habitual diet on vascular function.DesignA cross-sectional study.SettingA population-based study.ParticipantsA total of 301 postmenopausal women aged 60–75 years living in The Netherlands.DeterminantDietary phyt

GSTM1 Null Genotype, Red Meat Consumption and Breast Cancer Risk (The Netherlands)

Abstract: Objective: We studied whether polymorphisms in N-acetyltransferase 1 and 2 and Glutathione S-transferase M1 and T1 genes modify the association between meat consumption and breast cancer. Methods: A nested case control was conducted in a Dutch prospective cohort. Breast cancer cases (229) and controls (264) were frequency matched on age, town and menopausal status. Results: There is no relation between any type of meat consumption (i.e., total meat, processed meat, fresh meat, red meat and white meat) and breast cancer risk. Neither presence of NAT1 or NAT2 rapid genotype, or GSTT1 null genotype, alone or in combination with meat consumption affects breast cancer risk. Absence of GSTM1 shows 46% increased breast cancer risk (OR = 1.46 (95% confidence interval, 95% CI = 1.02–2.09)). When stratifying according to combined ‘GSTM1 genotype-meat consumption’ categories, breast cancer risk is slightly increased with consumption of red meat both in women with genotype GSTM1 presence (OR = 1.49 and 1.75 for intermediate and high versus low consumption) and in GSTM1 null genotype (OR = 1.18 and 1.02). These increases are statistically not significant. In postmenopausal women a suggestion of an effect of red meat consumption is observed: effects are slightly stronger, although still not statistically significant and without a clear dose–response relation: OR = 1.79 (95% CI = 0.92–3.50) and 1.46 (1.46 (95% CI = 0.76–2.82) for intermediate and high compared to low red meat consumption respectively. Reliable evaluation of interaction is not possible due to the small number of cancers. Conclusion:GSTM1 null genotype increases breast cancer risk. Red meat consumption slightly increases breast cancer risk, but the relation is not statistically significant and GSTM1, NAT1, NAT2 and GSTT1 polymorphisms do not modify this relation.