Search

Objective: Estimation of dietary intake of polyphenols is difficult, due to limited availability of food composition data and bias inherent to dietary assessment methods. The aim of the present study was to evaluate whether we could detect polyphenols and their metabolites in a spot urine sample in a free-living human population and whether it was related to those observed in 24-h urine samples, for potential use as a biomarkers of polyphenol intake.Subjects: Four 24-h urine samples and two spot urine samples were collected from 154 participants of the SU.VI.MAX cohort (a randomized primary-prevention trial evaluating the effect of daily antioxidant supplementation on chronic diseases) in two separate studies over, respectively, a 7- and 2-day periods. Thirteen polyphenols and metabolites (chlorogenic acid (CGA), caffeic acid (CA), m-coumaric acid (mCOU), gallic acid (GA), 4-O-methylgallic acid (MeGA), quercetin (Q), isorhamnetin (MeQ), kaempferol (K), hesperetin (HESP), naringenin (NAR), phloretin (PHLOR), enterolactone (ENL) and enterodiol (END) were measured using HPLC-ESI-MS-MS.Results: Correlations between the urinary excretion levels were observed. The most significant were explained by metabolic filiations (CGA/CA, CA/mCOU, GA/MeGA, Q/MeQ, NAR/PHLOR, ENL/END) or co-occurrence in a same food source (NAR/HESP). Concentrations in spot samples correlated with those in 24-h urine sample (P<0.02, except for CA and for MeQ). Intra-individual variations were smaller than inter-individual variations for all polyphenols (P<0.01) except for MeGA and for PHLOR.Conclusion: These results show that these polyphenols and metabolites are useful biomarkers for polyphenol intake. [ABSTRACT FROM AUTHOR]

Objective: Alcohol consumption may play a role in the development of obesity but the relationship between alcohol and weight is still unclear. The aim of our study was to assess the cross-sectional association of intakes of total alcohol and of specific alcoholic beverages (wine, beer and spirits) with waist-to-hip ratio (WHR) and body mass index (BMI) in a large sample of adults from all over France.Design: Cross-sectional.Setting: Participants were free-living healthy volunteers of the SU.VI.MAX study (an intervention study on the effects of antioxidant supplementation on chronic diseases).Subjects: For 1481 women aged 35-60 years and 1210 men aged 45-60 years, intakes of total alcohol and specific alcoholic beverages were assessed by six 24-hour dietary records. BMI and WHR were measured during a clinical examination the year after.Results: A J-shaped relationship was found between total alcohol consumption and WHR in both sexes and between total alcohol consumption and BMI in men only (P<0.05). The same relationships were observed with wine (P<0.05); men and women consuming less than 100 g day(-1) had a lower BMI (men only) and WHR than non-drinkers or those consuming more. Spirits consumption was positively associated with BMI (linear regression coefficient beta=0.21, 95% confidence interval (CI): 0.09-0.34 and beta=0.22, 95% CI: 0.06-0.39 for men and women, respectively) and WHR (beta=0.003, 95% CI: 0.001-0.005 and beta=0.003, 95%CI: 0.0002-0.006) in both sexes in a linear fashion. No relationship between beer consumption and BMI or WHR was found.Conclusion: If confirmed in longitudinal studies, our results indicate that consumption of alcoholic beverages may be a risk factor for obesity. [ABSTRACT FROM AUTHOR]

This article gives an overview of the potential hazards of polyphenol consumption, as reported during the round-table discussion at the 1st International Conference on Polyphenols and Health, held in Vichy, France, November 2003. Adverse effects of polyphenols have been evaluated primarily in experimental studies. It is known, for example, that certain polyphenols may have carcinogenic/genotoxic effects or may interfere with thyroid hormone biosynthesis. Isoflavones are of particular interest because of their estrogenic activity, for which beneficial as well as detrimental effects have been observed. Furthermore, consumption of polyphenols inhibits nonheme iron absorption and may lead to iron depletion in populations with marginal iron stores. Finally, polyphenols may interact with certain pharmaceutical agents and enhance their biologic effects. It is important to consider the doses at which these effects occur, in relation to the concentrations that naturally occur in the human body. Future studies evaluating either beneficial or adverse effects should therefore include relevant forms and doses of polyphenols and, before the development of fortified foods or supplements with pharmacologic doses, safety Copyright © 2005 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Scope: The dietary fatty acid cis9,trans11 conjugated linoleic acid (cis9,trans11 CLA) has been shown to modify the function of endothelial cells, monocytes, and platelets, all of which are involved in the development of atherosclerosis. Potential mechanisms for the platelet effects have not been assessed previously. In this study, we assessed how supplementation of the diet with an 80:20 cis9,trans11 CLA blend affects the platelet proteome., Methods and Results: In a double-blind, randomized, placebo-controlled, parallel-group trial, 40 overweight but apparently healthy adults received either 4 g per day of cis9,trans11 CLA-enriched oil or placebo oil, consisting of palm oil and soybean oil, for 3 months. Total platelet proteins were extracted from washed platelets, separated using two-dimensional gel electrophoresis and differentially regulated protein spots were identified by LC-ESI-MS/MS. Supplementation with the CLA blend, compared with placebo, resulted in significant alterations in levels of 46 spots (p < 0.05), of which 40 were identified. Network analysis revealed that the majority of these proteins participate in regulation of the cytoskeleton and platelet structure, as well as receptor action, signaling, and focal adhesion., Conclusion: The platelet proteomics approach revealed novel insights into regulation of cellular biomarkers of atherogenic and thrombotic pathways by an 80:20 cis9,trans11 CLA blend., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Animal studies suggest that dietary cis-9,trans-11 (c9,t11) conjugated linoleic acid (CLA) may inhibit or regress the development of atherosclerosis. The effect of CLA on atherosclerosis has not been assessed in humans., Objective: We investigated the effect of c9,t11 CLA supplementation on aortic pulse wave velocity (a marker of atherosclerosis) and on cardiovascular risk factors in overweight and obese but otherwise apparently healthy subjects., Design: In a double-blind, randomized, placebo-controlled, parallel-group trial, we randomly assigned 401 subjects, aged 40-70 y and with a body mass index (in kg/m(2)) > or = 25, to receive either 4 g CLA/d (2.5 g c9,t11 CLA/d and 0.6 g trans-10,cis-12 CLA/d) or placebo supplements for 6 mo. Aortic pulse wave velocity, blood pressure, anthropometric characteristics, and concentrations of fasting lipid, glucose, insulin, and C-reactive protein were measured before and after supplementation., Results: During the intervention, mean (+/-SE) pulse wave velocity did not change in the c9,t11 CLA group (Delta0.00 +/- 0.07) compared with the placebo group (Delta0.09 +/- 0.06). There was no effect of c9,t11 CLA supplementation on blood pressure, body composition, insulin resistance, or concentrations of lipid, glucose, and C-reactive protein., Conclusion: This study does not support an antiatherosclerotic effect or an effect on cardiovascular risk factors of c9,t11 CLA. This trial was registered at www.clinicaltrials.gov as NCT00706745.

Appetite suppressants may be one strategy in the fight against obesity. This study evaluated whether Korean pine nut free fatty acids (FFA) and triglycerides (TG) work as an appetite suppressant. Korean pine nut FFA were evaluated in STC-1 cell culture for their ability to increase cholecystokinin (CCK-8) secretion vs. several other dietary fatty acids from Italian stone pine nut fatty acids, oleic acid, linoleic acid, alpha-linolenic acid, and capric acid used as a control. At 50 muM concentration, Korean pine nut FFA produced the greatest amount of CCK-8 release (493 pg/ml) relative to the other fatty acids and control (46 pg/ml). A randomized, placebo-controlled, double-blind cross-over trial including 18 overweight post-menopausal women was performed. Subjects received capsules with 3 g Korean pine (Pinus koraiensis) nut FFA, 3 g pine nut TG or 3 g placebo (olive oil) in combination with a light breakfast. At 0, 30, 60, 90, 120, 180 and 240 minutes the gut hormones cholecystokinin (CCK-8), glucagon like peptide-1 (GLP-1), peptide YY (PYY) and ghrelin, and appetite sensations were measured. A wash-out period of one week separated each intervention day.CCK-8 was higher 30 min after pine nut FFA and 60 min after pine nut TG when compared to placebo (p < 0.01). GLP-1 was higher 60 min after pine nut FFA compared to placebo (p < 0.01). Over a period of 4 hours the total amount of plasma CCK-8 was 60% higher after pine nut FFA and 22% higher after pine nut TG than after placebo (p < 0.01). For GLP-1 this difference was 25% after pine nut FFA (P < 0.05). Ghrelin and PYY levels were not different between groups. The appetite sensation "prospective food intake" was 36% lower after pine nut FFA relative to placebo (P < 0.05). This study suggests that Korean pine nut may work as an appetite suppressant through an increasing effect on satiety hormones and a reduced prospective food intake.

Background: To study the association between the total plasma homocysteine (tHcy) concentration and the carotid artery intima-medial wall thickness (IMT), pulse wave velocity (PWV) and the presence of arterial plaques in a French population., Methods: Cross-sectional analysis of data from 556 male and 559 female middle-aged participants (mean (+/-SD) age 59.6+/-4.7 years) provided by an ongoing intervention trial., Results: Mean geometric tHcy concentration was higher for men than for women (10.6 vs. 8.5 micromol/L, p<0.001) and was associated in the expected direction with known determinants. The mean IMT was 0.71+/-0.1 mm for men and 0.69+/-0.1 mm for women (p<0.001), the mean PWV was, respectively, 12.0+/-2.8 and 10.9+/-2.2 m/sec (p<0.001), and the percentages of subjects with plaques were, respectively, 40.8% and 22.7% (p<0.001). In men only, the age-adjusted mean IMT and PWV increased with an increasing tHcy concentration: the IMT was 0.71 mm in the first tHcy-quartile and 0.73 mm in the fourth tHcy-quartile (p for linear trend=0.03), the PWV values were, respectively, 11.6 and 12.4 m/sec (p for linear trend=0.01). These associations disappeared after adjustment for conventional cardiovascular disease risk factors., Conclusion: In this population, the tHcy concentration was not associated with measures of arterial thickness and stiffness.

Purpose: The objective of the study is to evaluate the relation between antioxidant-rich beverages and the incidence of breast cancer., Methods: This prospective study consisted of 4396 women without a history of cancer who were participants in the French Supplémentation en Vitamines et Minéraux Antioxydants Study. Beverage consumption was estimated by using three nonconsecutive 24-hour recalls. Incident cancer cases were identified through clinical examinations performed every other year, including, e.g., a screening mammogram, and through a monthly health questionnaire., Results: During the median 6.6 years of follow-up, 95 breast cancers were diagnosed. In a multivariate model, an inverse association between herbal tea consumption and risk for breast cancer was observed (compared with nondrinkers, drinking 1 to 149 mL/d; relative risk [RR], 0.93; 95% confidence interval [CI], 0.48-1.80, and for > or =150 mL/d; RR, 0.43; 95% CI, 0.20-0.94; p for trend = 0.04). Consumption of coffee, tea, fruit juices, or wine was not associated with risk for breast cancer., Conclusion: Results of this study suggest that consumption of herbal tea may have a role in the prevention of breast cancer.

Background: Hyperhomocysteinemia (HHCY) is a risk factor for cardiovascular diseases (CVD). HHCY may interact with hypertension (HTEN) and an unfavorable cholesterol profile (UNFAVCHOL) to alter the risk of CVD., Objectives: To estimate the prevalences of HHCY (1) isolated and (2) in combination with UNFAVCHOL and/or HTEN in different age categories. To provide information that may improve the screening and treatment of subjects at risk of CVD., Design: Cross-sectional data on 12,541 men and 12,948 women aged 20 + y were used from nine European studies., Results: The prevalence of isolated HHCY was 8.5% in subjects aged 20-40 y, 4.7% in subjects aged 40-60 y and 5.9% in subjects aged over 60 y. When combining all age groups, 5.3% had isolated HHCY and an additional 5.6% had HHCY in combination with HTEN and/or UNFAVCHOL. The combinations of risk factors increased with age and, except for HHCY&UNFAVCHOL, were more prevalent than predicted by chance. Of the young subjects (20-40 y), 24% suffered from one or more of the investigated CVD risk factors. This figure was 75.1% in the old subjects (60+ years)., Conclusions: A substantial number of subjects in selected European populations have HHCY (10.9%). In half of these cases, subjects suffer also from other CVD risk factors like UNFAVCHOL and HTEN. Older people in particular tend to have more than one risk factor. Healthcare professionals should be aware of this when screening and treating older people not only for the conventional CVD risk factors like UNFAVCHOL and HTEN but also HHCY, as this can easily be reduced through increased intake of folic acid via supplement or foods fortified with folic acid.

The results of dietary intervention trials favor the hypothesis that higher intakes of B-vitamins (folate, vitamin B(6) and B(12)), and subsequently lower total homocysteine (tHcy) concentrations, are causally associated with a decreased risk of vascular disease in patients with cardiovascular diseases (CVD). The same is true for a higher intake of omega-3 fish fatty acids. Yet, the lack of hard end points and/or appropriate study designs precludes a definitive conclusion about causality. In the future, intervention trials with hard end points and randomized double-blind placebo-controlled designs should be able to elucidate the causality problem. There are several pathways by which B-vitamins and omega-3 fatty acids may exert their protective effect on CVD, a common pathway is a beneficial effect on the endothelial function and hemostasis. With respect to synergy between B-vitamins and omega-3 fatty acids, there is no evidence that fish oils have a tHcy-lowering effect beyond the effect of the B-vitamins. Nevertheless, animal studies clearly illustrate that vitamin B(6)- as well as folate-metabolism are linked with those of long-chain omega-3 fatty acids. Furthermore, a human study indicated synergistic effects of folic acid (synthetic form of folate) and vitamin B(6) together with omega-3 fatty acids on the atherogenic index and the fibrinogen concentration. Although these results are promising, they were produced in very small selective study populations. Thus, confirmation in large well-designed intervention trials is warranted.

A high consumption of flavonoids may lower cardiovascular risk through their antioxidant capacity. This study evaluated the relation between consumption of foods rich in flavonoids and estimated cardiovascular risk. A cross-sectional analysis was performed in 1286 women and 1005 men of the SU.VI.MAX Study (an 8-y trial evaluating the effect of antioxidant supplementation on the incidence of major chronic diseases). Dietary intakes were estimated using six 24-h dietary records collected during the year between the clinical measurement of blood pressure, weight and height and the biological measurement of total serum cholesterol and fasting plasma glucose. The relation between flavonoid rich food consumption and cardiovascular risk factors was evaluated with analyses of covariance and the effect on cardiovascular risk with logistic regression analyses. In women, flavonoid-rich food consumption was inversely related to systolic blood pressure (P = 0.005). No relation between risk factors and flavonoid-rich food consumption was seen in men. Women in the highest tertile of flavonoid-rich food consumption were at lower risk for cardiovascular disease [odds ratio (OR): 0.31; 95%CI: 0.14, 0.68], whereas a positive tendency was seen in men (OR: 1.38; 95%CI: 0.96, 2.00). These results indicate that in women, a high consumption of flavonoid-rich foods may prevent cardiovascular disease.

Background: Health related quality of life is becoming of greater importance in the medical field. Nevertheless, methodological problems persist, and particularly when it comes to processing missing data on quality of life questionnaires. In fact, this leads to three difficulties: (i) loss of power; (ii) bias; (iii) choice of the most adequate method for treating missing data. Prevention is the best recommendation in order to avoid unanswered questions. Unfortunately, this does not guarantee the absence of missing data. Therefore, the treatment of missing data depends on: i) identification of the missing data mechanism and ii) choice of the most appropriate method to correct the data. The main objective of this article is to illustrate the identification of non-response items as described in the SF-36 questionnaire items in the SU.VI.MAX study., Methods: A logistic regression on the characteristics of the subjects was used to distinguish between two missing data mechanisms: missing completely at random (MCAR) and missing at random (MAR). Two global Chi-2 tests on MCAR mechanism were proposed. The missing data not at random (MNAR) mechanism was also analysed considering the questionnaire features., Results: The percentage of non-responses was small (1.7%), with a maximum equal to 3% for four questions of the General Health dimension (GH2 to GH5). Both global Chi-2 tests rejected the hypothesis that all SF-36 non-responses were MCAR. As to the 32 items with less than 2.3% of non-responses, the mechanisms were: MCAR for 29 items, MAR for 2 items, and probably MNAR for 1 item. The logistic regression indicates that the factors related to non-responses were gender (female), age (> or =50 years), attention problem, and number of children (> or =3). The hierarchical feature of item PF5 (climb one flight of stairs) in relation to PF4 (climb several flights of stairs) would be a generator MNAR non-responses. The "I don't know" response modality of bloc GH2 to GH5 would also be generator of non-responses of the MNAR type., Conclusion: The identification of missing data mechanisms through statistical analysis and through further reflection on the questionnaire's features is a necessary preliminary in the treatment of non-responses.

Background: Previous studies on the effects of alcohol consumption on total plasma homocysteine (tHcy) concentrations showed contradictory results. The conflicting results may derive in part from confounding by the type of alcoholic beverage consumed., Objective: The objective of the study was to evaluate in a predominantly wine-drinking French population whether the relation between alcohol consumption and homocysteine concentrations is dependent on the type of alcoholic beverage consumed., Design: In 1996, a cross-sectional study measuring tHcy and red blood cell folate concentrations was conducted in 1196 middle-aged women and men from the French Supplementation with Antioxidant Vitamins and Minerals Study. Intakes of alcohol, energy, coffee, and B vitamins were assessed by 6 separate 24-h dietary records from the previous year., Results: tHcy concentrations were positively associated with wine intake (P = 0.01) in the women and with beer intake in the men (P = 0.002). No association with the consumption of spirits was observed. The association between beer consumption and tHcy concentrations in the men was modified by the consumption of wine; the association was positive in wine drinkers, whereas an inverse trend was seen in those who drank no wine., Conclusion: Wine consumption may increase tHcy concentrations, whereas beer consumption seems to have no effect (or even an inverse effect) on tHcy.

Background: An elevated plasma total homocysteine (tHcy) concentration seems to increase the risk of cardiovascular disease., Objective: We evaluated the determinants of tHcy in healthy French adults., Design: tHcy was measured by HPLC and fluorometric detection in 1139 women and 931 men aged 35-60 y. Subjects were participants of the Supplementation with Antioxidant Vitamins and Minerals Study, which investigates the effects of antioxidant supplementation on chronic diseases. Red blood cell folate (RBCF), plasma vitamins B-6 and B-12, and cardiovascular disease risk factors were also measured. The habitual diet was assessed in 616 subjects. Cross-sectional analyses were adjusted for age, smoking, energy intake, and concentration or intake of folate and vitamin B-6, where appropriate., Results: The mean (+/-SD) tHcy concentration was 8.74 +/- 2.71 micro mol/L in women and 10.82 +/- 3.49 micro mol/L in men. In women, tHcy was positively related to age (P = 0.001), apolipoprotein B (P < 0.01), serum triacylglycerol (P < 0.01), fasting glucose (P = 0.02), and coffee and alcohol consumption (both P < 0.01) and inversely related to RBCF (P = 0.11) and plasma vitamin B-12 (P = 0.08) and vitamin B-6 (P = 0.01) intakes. In men, tHcy was positively associated with body mass index (P = 0.03), blood pressure (P < 0.02), serum triacylglycerol (P < 0.01), fasting glucose (P = 0.01), and energy intake (P < 0.01) and inversely associated with physical activity (P = 0.04), RCBF (P = 0.02), plasma vitamin B-12 (P = 0.09), and dietary fiber (P < 0.01), folate (P = 0.03), and vitamin B-6 (P = 0.09) intakes., Conclusion: To control tHcy, decreasing coffee and alcohol consumption may be important in women, whereas increasing physical activity, dietary fiber, and folate intake may be important in men.

Background: To study the relation between alcohol consumption and the fasting insulin concentration in a French population with a range of alcohol intakes., Methods: 2.406 men and 2.500 women, aged 30 to 65 years who were not known as diabetic and with a non-diabetic fasting plasma glucose<7.0 mmol/l were studied. Insulin was assayed by a specific micro-enzyme immunoassay and alcohol intake was from a self-questionnaire., Results: Fasting insulin concentration showed an inverse linear association with alcohol consumption, after adjustment for age and possible confounding factors (p for trend<0.0001 men; p<0.002 women), with a 29% higher insulin in non-drinkers compared to very heavy drinkers (> 80 g/day) in men (p<0.0001) and a 23% and 26% difference when compared to heavy drinkers (41-80 g/day) in men and women respectively (p<0.0001, p<0.003). This relation did not differ significantly according to whether the alcohol was consumed as wine, beer/cider or spirits. Fasting plasma glucose modified the relation between alcohol and insulin in men: while the negative relation alcohol-insulin was strong for fasting plasma glucose<6.0 mmol/l (p<0.0001), there was no association above 6.0 mmol/l (p=0.4)., Conclusion: There is an inverse relation between alcohol consumption and fasting insulin concentrations. Some studies have found a U shaped relation, and this is probably due to the inclusion of diabetic subjects. As hyperinsulinemia has been shown to be positively associated with cardiovascular disease, it may be one of the variables that explains the protective effect of moderate alcohol consumption on cardiovascular disease.

Hormone replacement therapy (HRT) may reduce atherosclerosis among postmenopausal women, partly by reducing vascular endothelium damage. We have tested this hypothesis by evaluating the association of HRT with firstly, carotid intima media thickness (IMT) and plaques, and secondly, with endothelial cell damage, indicated by soluble thrombomodulin (sTM). Then, we tested the association between the two markers of atherosclerosis and the levels of sTM. Among 747 postmenopausal women included into the EVA study, we compared 154 HRT users (including 80% transdermal treatment) with 593 never users. Carotid IMT and plaques were measured with B-mode ultrasonography and sTM with ELISA. At least one plaque was detected among 13.6% of HRT users and 27.3% of never users. After adjustment for confounding factors, the odds ratio for the presence of plaque was 0.45 (95% confidence interval, 0.25-0.78, P=0.005) in HRT users in comparison with nonusers. HRT users had a slightly lower crude mean IMT than nonusers, but the difference was not significant. sTM was positively associated with mean IMT (P for trend=0.001) but not with plaques. Finally, estrogen users had a lower sTM level than nonusers (difference 0.14 ng/ml, P=0.03). As HRT was associated with sTM and plaques, but not with IMT, while sTM was only associated with IMT, our hypothesis was not confirmed. This suggests that the possible beneficial effects of HRT on atherosclerosis may not go through the endothelial cell damage assessed by plasma thrombomodulin.

The relationship between microalbuminuria and tissue-type plasminogen activator antigen (tPA-ag) and fibrinogen was evaluated in non-diabetic subjects. Subjects were participants of the D.E.S.I. R. (Data from an Epidemiological Study on the Insulin Resistance syndrome) Study. Analyses were carried out on 2248 women and 2402 men for fibrinogen and on 272 women and 284 men for tPA-ag. Microalbuminuria was defined as urinary albumin concentration greater than 20 mg/l. Men with microalbuminuria had a 6% higher fibrinogen concentration than those without (3.07 g/l (95% confidence interval: 2.99,3.15) vs. 2.89 g/l (2.87,2.91), adjusted for age and smoking). This relationship existed in hypertensive as well as non-hypertensive subjects. The association between microalbuminuria and tPA-ag existed only in hypertensive men, those with microalbuminuria having a 21% higher tPA-ag than those without (4.39 ng/ml (3.70,5.08) vs. 3.63 ng/ml (3.32,3.94), adjusted for age and smoking). Adjustment for other risk markers for cardiovascular disease did not change the results. There was no relationship between microalbuminuria and these haemostatic factors in women. The results of this study suggest that in non-diabetic men, microalbuminuria is associated with fibrinogen, but with tPA-ag only when concomitant with hypertension.

Elevated factor VII coagulant activity (FVII:C) has been associated with an increased risk of ischaemic heart disease, particularly for fatal events. Results of studies on the association between FVII:C and atherosclerosis are not consistent. FVII:C levels are influenced by several environmental factors and by genetic factors. One of the genetic factors is the -323Ins10 polymorphism in the promoter region of the factor VII gene, which is strongly related to FVII:C, and thus may be associated with ischaemic heart disease. We studied the association of this polymorphism with the severity and progression of atherosclerosis. In 511 male patients of the Regression Growth Evaluation Statin Study, the genotype for the -323Ins10 polymorphism was determined. The minimum obstruction diameter and the mean segment diameter were determined at baseline and after a 2-year follow-up period, and new lesion formation was assessed as well. Cardiovascular events were recorded. No relationship was observed between the -323Ins10 polymorphism and angiographic measures of disease progression, nor on the risk of new cardiovascular events. The results suggest that there is no association between the -323Ins10 polymorphism for factor VII and the severity or progression of coronary atherosclerosis in male patients with symptomatic coronary artery disease.

Background: Activated factor VII (FVIIa) is a very potent coagulant and may be a key determinant of the outcome of a cardiovascular event. The main determinants of FVIIa are the R353Q polymorphism and dietary fat intake, which may have an interactive effect., Objective: The objective was to investigate whether the response of FVIIa to a fat-rich breakfast varies across genotypes of the R353Q polymorphism., Design: Ninety-one apparently healthy elderly women (>60 y of age), 56 with the RR genotype and 35 with the RQ or QQ genotype, participated in a randomized, controlled crossover study. Subjects received 5 breakfasts, each on a separate day: 1 low-fat control breakfast and 4 high-fat test breakfasts. Blood samples were taken for measurement of FVIIa at 0800 before each breakfast (fasting) and at 1300 and 1500., Results: The mean (+/-SD) fasting FVIIa concentration was 93.3 +/- 26.7 U/L in women with the RR genotype, 49.3 +/- 19.1 U/L in those with the RQ genotype and 39.5 +/- 17.2 U/L in those with the QQ genotype. The mean absolute response to all 4 test breakfasts was 37.0 U/L in those with the RR genotype and 16. 1 U/L in those carrying the Q allele (P < 0.001 for difference). Likewise, the FVIIa response relative to fasting FVIIa was significantly higher in women homozygous for the R allele., Conclusion: This observation may indicate a considerable difference in cardiovascular risk between genotype groups as a result of an increase in FVIIa after a fat-rich diet.

A stronger positive association between fibrinogen or tissue-type plasminogen activator antigen (tPA-ag) and fasting insulin is observed in women than in men. We investigated whether this effect could be explained by a difference in smoking habits. The relations between markers for insulin resistance [fasting insulin and insulin resistance as estimated by the homeostasis model assessment (HOMA-IR)] and fibrinogen and tPA-ag were examined cross-sectionally in 4976 (582 for tPA-ag) subjects from the D.E.S.I.R. (Data from an Epidemiological Study on the Insulin Resistance syndrome) study. The modifying effect of smoking habits were evaluated. Seventeen percent of women and 27% of men were smokers. Fibrinogen concentrations were higher in smokers than in non-smokers, in men only. Female smokers had lower concentrations of tPA-ag than non-smokers. In both women and men, fibrinogen was positively associated with fasting insulin [women: beta = 0.33 mg/U (95% confidence interval: 0.29, 0.37); men: beta = 0.15 mg/U (0.11, 0.19)] and with HOMA-IR [women: beta = 0.17 microg/microU mol/l (0.15, 0.19): men: beta = 0.06 (0.04, 0.08)]. For tPA-ag these associations were for insulin beta = 0.76 mg/U (0.54, 0.98) and beta = 0.89 mg/U (0.67, 1.11), and for HOMA-IR beta = 0.47 microg/microU mol/l (0.33, 0.61) and beta = 0.45 microg/microU mol/l (0.33, 0.57), women and men respectively. The associations of fibrinogen and tPA-ag with insulin and HOMA-IR were sharply reduced in male smokers compared to male non-smokers, however the strength of the associations in male non-smokers did not reach that in women. Fibrinogen and tPA-ag are independently related with markers of insulin resistance, with the relation with fibrinogen being stronger in women than in men. The strong modifying effect of smoking habits does not completely explain this gender difference.

We investigated whether tissue-type plasminogen activator antigen (t-PA-Ag) was associated with intake of meat, fish, or dairy products. The study population comprised 295 women and 299 men aged 30-64 years, which was a random sample from the D.E.S.I.R. (Data from an Epidemiological Study on the Insulin Resistance syndrome) study comprising 5214 men and women in total. T-PA-Ag was measured in fasting blood samples and the habitual intake of foods was assessed by several questions on a food frequency questionnaire. Cross-sectional data were analyzed. The mean t-PA-Ag concentration was 3.28 ng/mL (SD, 1.26) in men and 2.52 ng/mL (SD, 1.22) in women. The concentration of t-PA-Ag was inversely associated with the consumption of milk and milk products in women (p for trend: 0.15) and in men (p for trend: 0.04). The difference between subjects with a low and a high milk consumption was 13% in women and 19% in men. Similar results were observed for consumption of cheese. The concentration of t-PA-Ag was 21 and 8% lower for women and men with a high cheese consumption, respectively, compared to those with a low consumption. Further analyses showed that the association of t-PA-Ag with milk and milk product consumption was independent of cheese consumption and vice versa. No association between meat or fish intake and t-PA-Ag was observed. The results of this study indicate that, if confirmed by others, a high intake of dairy products may influence fibrinolysis by an effect on t-PA-Ag.

The relation between alcohol consumption and fibrinogen concentration was evaluated in a French population to investigate whether fibrinogen could explain part of the relation between alcohol consumption and cardiovascular disease. Cross-sectional data on self-reported alcohol consumption and fibrinogen, measured by the immunonephelometric method, of 4967 men and women aged 30 to 64 years were used. These subjects were volunteers for a free health checkup in the western central part of France from 1994 to 1996 and participated in the DESIR Study (Data from an Epidemiological Study on the Insulin Resistance syndrome). Alcohol consumption was strongly associated with fibrinogen concentration, with higher concentrations in those who were nondrinkers or who drank >60 g of alcohol per day. This U-shaped association was stronger among men than women. Consumption of wine and spirits was associated with fibrinogen, whereas consumption of beer or cider was not. Furthermore, smoking was positively associated with fibrinogen concentration, and in men the difference between nondrinkers and drinkers with the lowest fibrinogen level was higher in nonsmokers and ex-smokers than in current smokers. We conclude that moderate drinking may lower fibrinogen concentration. If fibrinogen is a causal risk factor for cardiovascular disease, it may be 1 of the variables that explain the protective effect of moderate alcohol consumption on cardiovascular disease.

The objective of this study was to evaluate the association of factor VII with dietary factors while also considering the R/Q353 polymorphism. Nutrition is an important determinant of coagulation factor VII, which is also genetically determined by the R/Q353 polymorphism. High levels of coagulation factor VII clotting activity (FVII:C) are associated with the risk of myocardial infarction; nutrition may have an effect on these levels if people are genetically susceptible to dietary changes. FVII:C was measured in 3005 elderly subjects, and the extreme quintiles of the FVII:C distribution were selected for measurement of the R/Q353 genotype and FVII:Chr (reflects total factor VII). In these 1158 subjects, habitual diet was assessed with a semiquantitative food-frequency questionnaire. The frequency of the Q353 allele was 0.24 in the lowest and 0.09 in the highest quintile. The quintiles were combined for linear regression analyses. FVII:C was inversely associated with fiber [beta = -0.64 %pooled plasma (PP)/g, confidence interval (CI): -1.07,-0.21] and protein intake (beta = -0.16 %PP/g, CI: -0.31,-0. 01) and positively with saturated fat intake (beta = 0.19 %PP/g, CI: -0.10,0.48). FVII:Chr was inversely associated with fiber (beta = -0. 38 %PP/g, CI: -0.71,-0.05). No other associations with diet were observed. The inverse association of FVII:C with fiber was stronger in subjects with the RR genotype (beta = -0.76 %PP/g, CI: -1.23,-0. 29), than in those with the RQ/QQ genotypes (beta = -0.19 %PP/g, CI: -0.97,0.59). The same was found for FVII:Chr. The association of FVII:C with saturated fat was positive in those with the RR allele and inverse in those carrying the Q allele. These findings suggest that the strength of the association between coagulation factor VII and diet varies across the genotypes of the R/Q353 polymorphism.

Coagulation factor VII activity (FVII:C) is a risk indicator for cardiovascular disease. It is related to serum-triglycerides and the R/Q353 polymorphism (alleles R and Q) in the gene coding for factor VII is strongly associated with factor VII. The association of serum-triglycerides with factor VII may differ between the genotypes, but the results of earlier studies were inconsistent and did not include older people. We studied FVII, triglycerides and the R/Q353 polymorphism in the Rotterdam Study. In 1158 older subjects (489 men and 669 women) FVII:C, factor VII:Chr, serum-triglycerides and the R/Q353-genotype were determined. In women triglycerides were positively associated with FVII:Chr and FVII:C (FVII:Chr: beta = 12.4% PP/mmol/L, CI: 10.3-14.5; FVII:C: beta = 13.1% PP/mmol/L, CI: 10.4-15.8). These associations varied by genotype (FVII:Chr: RR: beta = 11.7, CI: 9.6-13.8, RQ/QQ: beta = 7.9, CI: 4.6-11.2; FVII:C: RR: beta = 12.5, CI: 9.5-15.5, RQ/QQ: beta = 6.4, CI: 1.4-11.4). In men, the associations of FVII:Chr and FVII:C with triglycerides were weaker (FVII:Chr: beta = 5.9, CI: 4.1-7.7; FVII:C: beta = 8.7, CI: 6.2-11.2). There was no difference between the genotype groups. These results suggest that only in older women the strength of the association of factor VII with serum-triglycerides varies according to genotype of the R/Q353 polymorphism.

Considerable evidence suggests that a high concentration of coagulation factor VII is a risk factor for ischemic heart disease. Factor VII is known to be influenced by dietary fat and probably by dietary fiber in young and middle-aged people. There are no data available in elderly people and the effects of different types of fat are unclear. This study examines the relation of factor VII activity (factor VIIc) with dietary fat and fiber in The Rotterdam Study. The Rotterdam Study is a population-based study among 7983 men and women aged > or = 55 y. Factor VIIc was measured in 3007 subjects (1730 women and 1277 men aged 67.3 +/- 7.8 and 66.3 +/- 7.0 y, respectively). Measurements included cardiovascular risk factors and habitual diet was assessed by a semiquantitative food-frequency questionnaire. Associations that were significant or nearly significant differed for some nutrients between men and women. Total fat intake showed a direct association with factor VIIc only in women (beta = 0.1%/g; 95% CI: 0.01, 0.20). Saturated fat intake was associated with factor VIIc in women (beta = 0.18%/g; 95% CI: 0.001, 0.36) and in men (beta = 0.11%/g; 95% CI: -0.06, 0.27). Monounsaturated fat was positively related to factor VIIc in women (beta = 0.17%/g; 95% CI: -0.05, 0.39) and polyunsaturated fat was inversely associated with factor VIIc in men (beta = -0.15%/g; 95% CI: -0.33, 0.03). Fiber intake was inversely associated with factor VIIc in both men (beta = -0.31%/g; 95% CI: -0.57, -0.06) and women (beta = -0.36%/g; 95% CI: -0.63, -0.09). No associations were found for energy intake. In elderly persons, factor VIIc is associated with fat and fiber intake. This suggests that factor VIIc is influenced by nutritional factors, even in old age.

Objective: To determine the prevalence of risk factors for cardiovascular disease among elderly people., Design: Prospective cohort study., Setting: A district of Rotterdam, the Netherlands., Methods: As a part of the Rotterdam Study information about smoking habits, blood pressure, Quetelet index and serum cholesterol of 7,983 responding persons (78%) (3,105 men and 4,878 women) of 55 years and older was obtained by an interview and physical examination during two visits to a research center., Results: Among men and women there were 29.7% and 16.7% smokers and 60.1% and 25.9% ex-smokers, respectively. Among men the proportion of smokers decreased from 31.0% in the age category 55-59 years to 15.9% in de category > or = 85 years, among women from 28.0% to 2.7%. Systolic blood pressure increased with age in both sexes, while diastolic blood pressure hardly changed. Hypertension (systolic blood pressure 160 mmHg and/or diastolic blood pressure > or = 95 mmHg at a single measurement and/or use of antihypertensive drugs) occurred in 23.3% of men and 28.0% of women. In men, total serum cholesterol decreased gradually with age, whereas in women there was a slight increase up to the category 70-74 years. No evident change in HDL cholesterol with increasing age was observed in men, but in women a decrease was observed until the same level was reached as in men. Thirty-five per cent of men and 49.5% of women had an elevated level of serum cholesterol (> or = 6.5 mmol/l). The prevalence of obesity (Quetelet index > 25 kg/m2) was about 50% in both men and women but was less in the categories from 75 years onwards. Approximately 80% of men and women had at least one risk factor, while in almost half of them two or more risk factors were found., Conclusion: Risk factors for cardiovascular disease are common among elderly people.