Urinary excretion of 13 dietary flavonoids and phenolic acids in free-living healthy subjects - variability and possible use as biomarkers of polyphenol intake.

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.

Prevalences of hyperhomocysteinemia, unfavorable cholesterol profile and hypertension in European populations.

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.

Evidence for a protective (synergistic?) effect of B-vitamins and omega-3 fatty acids on cardiovascular diseases.

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.

[Missing data mechanisms of the questionnaire SF-36's items in the SU.VI.MAX study]. / Non-réponses aux questionnaires de qualité de vie SF-36 dans un échantillon de l'étude SU.VI.MAX.

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.

The use of computerised 24 h dietary recalls in the French SU.VI.MAX Study: number of recalls required.

OBJECTIVE: The 24 h dietary recall is a widely used method to estimate nutritional intakes in epidemiological studies. The objective of the present study was to estimate the number of recalls necessary for an accurate estimation of nutrient intake in French adults followed for 4 y. SUBJECTS AND METHODS: Participants of the SU.VI.MAX study (intervention study on the effects of antioxidant supplementation on chronic diseases) who completed a 24 h dietary recall every 2 months for at least 1 y. Inter- and intra-individual variance ratios (S(w)/S(b)) were calculated by analysis of variance for two time periods: year 1 and 2 (n=4955) and year 3 and 4 (n=1458). The number of recalls necessary was calculated using an accuracy of 0.9. RESULTS: The highest intra-individual/inter-individual variance ratio in the first period was seen for beta-carotene and the lowest for carbohydrate. The number of recalls necessary was five for carbohydrate and calcium intake and 16 for beta-carotene. For proteins, total and saturated fat, fibre, vitamin C and iron eight recalls were required, while nine, 11 and 10 recalls were necessary for mono- and polyunsaturated fat and vitamin E, respectively. The variance ratios in the second period were all lower and fewer recalls were therefore required. The same difference in number of recalls required between the two time periods was observed when only those subjects were included who completed at least 18 recalls (n=727). CONCLUSION: These results indicate that for an accurate estimation of carbohydrate intake only, already five recalls are necessary. Fewer recalls may be needed during long-time follow-up. SPONSORSHIP: The SU.VI.MAX Study has support from public and private sectors: Fruit d'Or Recherche, Candia, Lipton, Kellogg's, Céréal, CERIN, Estée Lauder, L'Oréal, Peugeot, Jet Service, RP Scherer, Sodexho, France Telecom, Santogen, Becton Dickinson, Fould Springer, Boehringer Diagnostic, Seppic Givaudan Lavirotte, Le grand Canal, Danone and Knorr.

Alcohol intake and fasting insulin in French men and women. The D.E.S.I.R. Study.

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.

Habitual diet in four populations of African origin: a descriptive paper on nutrient intakes in rural and urban Cameroon, Jamaica and Caribbean migrants in Britain.

BACKGROUND: The prevalence of chronic diseases is increasing in West Africa, the Caribbean and its migrants to Britain. This trend may be due to the transition in the habitual diet, with increasing (saturated) fat and decreasing fruit and vegetable intakes, both within and between countries. OBJECTIVE: We have tested this hypothesis by comparing habitual diet in four African-origin populations with a similar genetic background at different stages in this transition. DESIGN: The study populations included subjects from rural Cameroon urban Cameroon Jamaica and African-Caribbeans in Manchester, UK all aged 25-74 years. Habitual diet was assessed by a food-frequency questionnaire, specifically developed for each country separately. RESULTS: Total energy intake was greatest in rural Cameroon and lowest in Manchester for all age/sex groups. A tendency towards the same pattern was seen for carbohydrates, protein and total fat intake. Saturated and polyunsaturated fat intake and alcohol intake were highest in rural Cameroon, and lowest in Jamaica, with the intakes in the UK lower than those in urban Cameroon. The percentage of energy from total fat was higher in rural and urban Cameroon than in Jamaica and the UK for all age/sex groups. The opposite was seen for percentage of energy from carbohydrate intake, the intake being highest in Jamaica and lowest in rural Cameroon. The percentage of energy from protein increased gradually from rural Cameroon to the UK. CONCLUSIONS: These results do not support our hypothesis that carbohydrate intake increased, while (saturated) fat intake decreased, from rural Cameroon to the UK.

Microalbuminuria and markers of the atherosclerotic process: the D.E. S.I.R. study.

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.

Underreporting of energy intake in four populations of African origin.

OBJECTIVE: To investigate the frequency of dietary underreporting in four African populations in different geographic and cultural settings. SUBJECTS: Seven-hundred and forty three men and women from rural Cameroon, 1042 men and women from urban Cameroon, 857 men and women from Jamaica and 243 male and female African Caribbeans from the UK. Subjects who reported dieting or weight control were excluded. MEASUREMENTS: Habitual dietary intake was estimated with a quantitative food frequency questionnaire, developed specifically for each country. Underreporting was defined using three cut-off levels for energy intake/estimated basic metabolic rate (EI/BMRest), based on age, sex and weight, in each site. RESULTS: The EI/BMRest was highest in rural Cameroonian men at 3.07 (95% confidence interval: 2.97, 3.17) and women at 2.84 (2.74, 2.94), intermediate in urban Cameroon and Jamaica and lowest in the UK men and women at 1.44 (1.26, 1.62) and 1.41 (1.21, 1.61). This trend existed even after adjustment for age, BMI and education (P for trend<0.0001). The trend in the frequency of underreporting using the lowest cut-off level for EI/BMRest of 1.15 was 6% and 6% in rural Cameroon for women and men, respectively, 4% and 5% in urban Cameroon, 24% and 19% in Jamaica and 28% and 39% in the UK. With higher cut off levels this trend was similar. CONCLUSION: The results suggest that the frequency of dietary underreporting differs between societies and that Westernization may be one of the factors underlying this phenomenon.

The -323Ins10 polymorphism for factor VII is not associated with coronary atherosclerosis in symptomatic men. The REGRESS study group.

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.

The habitual diet in rural and urban Cameroon.

OBJECTIVE: To evaluate the habitual diet of a rural and urban population in Cameroon, Central Africa. SETTING: An urban area-Cité Verte Housing District, Yaoundé (1058 subjects); and a rural area-three villages in Evodoula, Cameroon (746 subjects). SUBJECTS: Cameroonian men and women of African origin (1058 urban, and 746 rural), aged 24-74 y. METHODS: The habitual diet was estimated with an interviewer-administered food frequency questionnaire. MAIN OUTCOME MEASURES: Macro- and micronutrient intake. RESULTS: The intake of energy, fat and alcohol was higher in rural men and women than in urban subjects. In rural women, the intake of carbohydrates and protein was also higher. The intakes of fibre, iron, carotene, zinc, potassium, and of the vitamins C, D and E were all higher in rural men and women than in their urban counterparts. The intake of retinol was lower in rural subjects than in urban subjects. Eight of the 10 foods eaten in the highest amount and contributing most to energy intake differed between the rural and urban population. CONCLUSION: The habitual diet in rural Cameroon contains more fat and alcohol than the diet in urban Cameroon. The high physical activity in the rural area may explain the lower levels of the cardiovascular risk factors in this area compared to those of the urban dwellers. SPONSORSHIP: This work was supported by a grant from the European Union (contract no. TS3*CT92-0142) and by the Conseil Régional d'Ile de France and INSERM. European Journal of Clinical Nutrition (2000) 54, 150-154

Gender differences in the relation between fibrinogen, tissue-type plasminogen activator antigen and markers of insulin resistance: effects of smoking. D.E.S.I.R. Study Group. Data from an Epidemiological Study on Insulin Resistance Syndrome.

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.

Postprandial response of activated factor VII in elderly women depends on the R353Q polymorphism.

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.

Tissue-type plasminogen activator antigen and consumption of dairy products. The DESIR study. Data from an Epidemiological Study on Insulin Resistance Syndrome.

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.

Fibrinogen: a possible link between alcohol consumption and cardiovascular disease? DESIR Study Group.

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.

Dietary effects on coagulation factor VII vary across genotypes of the R/Q353 polymorphism in elderly people.

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, serum-triglycerides and the R/Q353 polymorphism: differences between older men and women.

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.

The association of dietary fat and fiber with coagulation factor VII in the elderly: the Rotterdam Study.

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.