PubMed Health⌕ Search

Biomedical subjects

R Luben

Publications and source records attributed to R Luben.

At least 19 recordsLinked to original sources
PubMed2006

Tissue factor serum levels and the risk of future coronary artery disease in apparently healthy men and women: the EPIC-Norfolk prospective population study.

INTRODUCTION: Tissue factor (TF) has been implicated in coronary artery disease (CAD). High levels of circulating TF are found in patients with acute atherothrombotic events. Whether high serum TF levels predict risk of future CAD independent of known risk factors remains unknown. METHODS: We conducted a prospective case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk population study. Cases (n=1037) were apparently healthy men and women, aged 45-79 years, who developed fatal or non-fatal CAD during follow-up. Controls (n=2005) were matched by age, sex, and enrolment time. Serum TF levels were measured using high-affinity antibodies. RESULTS: In men, median TF levels were not significant higher in cases than in controls (59.0 pg mL-1, range: 16.7-370.4 vs. 54.9 pg mL-1, range: 16.2-452.4). In women, median TF levels were not significant higher in controls than in cases (73.4 pg mL-1, range: 16.7-492.3 vs. 50.5 pg mL-1, range: 16.5-376.7). The incidence of smoking was about double in the lowest compared with the highest TF quartile. Correcting for sex, age, body mass index, smoking, diabetes, systolic blood pressure, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and C-reactive protein levels, the risk of future CAD was 1.05 (95% CI: 0.81-1.36) for people in the highest TF quartile, compared with those in the lowest (P-value for linearity=0.8). CONCLUSION: High levels of serum TF were not independently associated with an increased risk of future CAD in apparently healthy individuals.

Aged↗
PubMed2006

Fibrinogen plasma levels modify the association between the factor XIII Val34Leu variant and risk of coronary artery disease: the EPIC-Norfolk prospective population study.

BACKGROUND: The factor (F) XIII Val34Leu variant has been implicated in coronary artery disease (CAD). In vitro evidence suggests an interaction between this variant and fibrinogen concentrations in determining thrombus structure. OBJECTIVES: To test whether this interaction is relevant in influencing coronary risk in apparently healthy individuals. METHODS: In an 8-year prospective population study of 25 663 men and women, we compared 898 apparently healthy men and women developing incident CAD with 1580 matched controls. RESULTS: Overall, the FXIII Val34Leu variant was not associated with the risk of future CAD. However, a significant interaction existed between the Val34Leu variant and fibrinogen levels for the risk of future CAD (P = 0.004). Among people in the lowest tertile of fibrinogen concentrations, LeuLeu carriers had an odds ratio (OR) of 2.88 (95% confidence interval; CI 1.24-6.74) compared to wild-type individuals (P for linearity = 0.003). By contrast, among those in the highest fibrinogen tertile, LeuLeu carriers were had a lower risk than wild-type individuals (OR 0.47, 95% CI 0.18-1.17, P for linearity = 0.1). CONCLUSIONS: Our results suggest that a significant gene-covariate interaction exists between the FXIII Val34Leu variant and fibrinogen levels. Relationships between genotype and disease risk may be altered by biological covariates. Simplistic paradigms of gene or biomarker associations are unlikely to fully characterize disease risk in populations.

Adult↗
PubMed2006

Single-nucleotide polymorphisms in the RB1 gene and association with breast cancer in the British population.

A substantial proportion of the familial risk of breast cancer may be attributable to genetic variants each contributing a small effect. pRb controls the cell cycle and polymorphisms within it are candidates for such low penetrance susceptibility alleles, since the gene has been implicated in several human tumours, particularly breast cancer. The purpose of this study was to determine whether common variants in the RB1 gene are associated with breast cancer risk. We assessed 15 tagging single-nucleotide polymorphisms (SNPs) using a case-control study design (n< or = 4474 cases and n < or = 4560 controls). A difference in genotype frequencies was found between cases and controls for rs2854344 in intron 17 (P-trend = 0.007) and rs198580 in intron 19 (P-trend = 0.018). Carrying the minor allele of these SNPs appears to confer a protective effect on breast cancer risk (odd ratio (OR) = 0.86 (0.76-0.96) for rs2854344 and OR = 0.80 (0.66-0.96) for rs198580). However, after adjusting for multiple testing these associations were borderline with an adjusted P-trend = 0.068 for the most significant SNP (rs2854344). The RB1 gene is not known to contain any coding SNPs with allele frequencies > or = 5% but several intronic variants are in perfect linkage disequilibrium with the associated SNPs. Replication studies are needed to confirm the associations with breast cancer.

Aged↗
PubMed2005

The CAFE computer program for nutritional analysis of the EPIC-Norfolk food frequency questionnaire and identification of extreme nutrient values.

BACKGROUND: Food frequency questionnaires (FFQs) are widely used in nutritional epidemiology but no papers detail the development of the supporting programs and nutritional databases. The principles involved in data collection, processing and treatment of the European Prospective Investigation into Cancer Study (EPIC)-Norfolk Study FFQ and development of the structure and content of the Compositional Analyses from Frequency Estimates (CAFE) program for calculating nutrient intakes are described. Extreme nutrient values and derivation of cut-points for data exclusion are also discussed. METHODS: The FFQ was sent to 25,637 participants. To exclude extreme (nonphysiological) outliers of nutrient intakes, the extreme top and bottom 0.5% of the ratio of energy intake to estimated basal metabolic rate was used. RESULTS: The CAFE computer program modifies nutrient intake according to specific fats used in food preparation and the amount of visible fat on meat. It incorporates different breakfast cereals and distinguishes between text for brands and types. After exclusion of outliers of nutrient intake some extreme values remained for energy, carbohydrate, protein, fat and alcohol, because of high reported frequencies of certain foods. CONCLUSIONS: The features of CAFE include flexible, updateable, databases and a novel method for matching text. The effect of extreme nutrient values on the accuracy of the FFQ in estimating diet in nutritional epidemiology should be investigated further.

Adult↗
PubMed2004

Correlated measurement error--implications for nutritional epidemiology.

BACKGROUND: In nutritional epidemiology, it is common to fit models in which several dietary variables are included. However, with standard instruments for dietary assessment, not only are the intakes of many nutrients often highly correlated, but the errors in the estimation of the intake of different nutrients are also correlated. The effect of this error correlation on the results of observational studies has been little investigated. This paper describes the effect on multivariate regression coefficients of different levels of correlation, both between the variables themselves and between the errors of estimation of these variables. METHODS: Using a simple model for the multivariate error structure, we examine the effect on the estimates of bivariate linear regression coefficients of (1) differential precision of measurement of the two independent variables, (2) differing levels of correlation between the true values of the two variables, and (3) differing levels of correlation between the errors of measurement of the two variables. As an example, the prediction of plasma vitamin C levels by dietary intake variables is considered, using data from the European Prospective Investigation of Cancer (EPIC) Norfolk study in which dietary intake was estimated using both a food frequency questionnaire (FFQ) and a 7-day diary (7DD). The dietary variables considered are vitamin C, fat, and energy, with different approaches taken to energy adjustment. RESULTS: When the error correlation is zero, the estimates of the bivariate regression coefficients reflect the precision of measurement of the two variables and mutual confounding. The sum of the observed regression coefficients is biased towards the null as in univariate regression. When the error correlation is non-zero but below about 0.7, the effect is minor. However, as the error correlation increases beyond 0.8 the effect becomes large and highly dependent on the relative precision with which the two variables are measured. At the extreme, the bivariate estimates can become indefinitely large. In the example, the error correlation between fat and energy using the FFQ appears to be over 0.9, the corresponding value for the 7DD being approximately 0.85. The error correlation between vitamin C and fat, and vitamin C and energy, appears to be below 0.5 and smaller for the 7DD than for the FFQ. The impact of these error correlations on bivariate regression coefficients is large. The effect of energy adjustment differs widely between vitamin C and fat. CONCLUSION: High levels of error correlation can have a large effect on bivariate regression estimates, varying widely depending on which two variables are considered. In particular, the effect of energy adjustment will vary widely. For vitamin C, the effect of energy adjustment appears negligible, whereas for fat the effect is large indicating that error correlation close to one can partially remove regression dilution due to measurement error. If, for fat intake, energy adjustment is performed by using energy density, the partial removal of regression dilution is achieved at the expense of substantial reduction in the true variance.

Ascorbic Acid↗
PubMed2004

Abdominal obesity and respiratory function in men and women in the EPIC-Norfolk Study, United Kingdom.

Poor respiratory function and obesity are associated with all-cause and cardiovascular disease mortality. Obese persons may also have impaired lung function, but the mechanism is unclear. The authors investigated the relation between abdominal pattern of obesity and respiratory function in the European Prospective Investigation into Cancer and Nutrition-Norfolk (EPIC-Norfolk) cohort in Norfolk, United Kingdom. This analysis included 9,674 men and 11,876 women aged 45-79 years with no known preexisting serious illness who had complete anthropometric and respiratory function measures obtained at a health visit between 1993 and 1997. Waist:hip ratio was used to assess abdominal obesity, and forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), obtained by spirometry, were used to assess respiratory function. Both FEV1 and FVC were linearly and inversely related across the entire range of waist:hip ratio in both men and women. This relation persisted after adjustment for age, body mass index, cigarette smoking, social class, physical activity index, prevalent bronchitis/emphysema, and prevalent asthma. The association remained significant among nonobese nonsmokers without preexisting respiratory disease. In the general adult population, abdominal fat deposition may play a role in the impairment of respiratory function among the abdominally obese.

Abdomen↗
PubMed2004

Traditional cardiovascular risk factors measured prior to the onset of inflammatory polyarthritis.

BACKGROUND: Cardiovascular mortality is increased in patients with seropositive inflammatory polyarthritis (IP). We tested the hypothesis that the increased risk of cardiovascular disease (CVD) can be explained by elevated traditional CVD risk factor levels in persons prior to development of IP. METHODS: In a population-based, prospective nested case-control study, 25 600 people aged 45-75 yr participated in a health survey, including standard CVD risk factor assessment, between the years 1993 and 1997. There were 91 incident IP cases (one-third were seropositive at presentation) identified during follow-up to the end of July 2001. Baseline CVD risk factors in the IP cases were compared with those in two age/gender-matched controls. RESULTS: Current smokers had an odds ratio of 2.0 (95% CI 1.0-4.0) for IP. Other risk factors, including total and LDL cholesterol, systolic and diastolic blood pressure and obesity, did not differ significantly between cases and controls. Importantly, in combination, using a standard coronary disease risk score, these factors only had a modest association with future IP, and no association when analysis was restricted to the smaller number of cases who were seropositive. CONCLUSION: Of the traditional cardiovascular risk factors, only smoking increases CVD risk prior to the onset of IP. Therefore the increased CVD observed in these patients is likely to be a consequence of factors operating after the onset of the arthritis.

Aged↗
PubMed2004

Occupational social class, educational level and area deprivation independently predict plasma ascorbic acid concentration: a cross-sectional population based study in the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk).

OBJECTIVE: To investigate the independent association between three different measures of socioeconomic status and plasma ascorbic acid level. DESIGN: Cross-sectional population based study. SETTING AND PARTICIPANTS: 20 292 men and women aged 39-79 y who participated in the EPIC-Norfolk study. RESULTS: Individuals in manual social classes, who had no educational qualifications or those who lived in the most deprived areas had significantly lower levels of plasma ascorbic acid compared to those in nonmanual social classes, with at least O-level qualifications or who lived in less deprived areas. The magnitude of effect for each measure of socioeconomic status was greater in current smokers compared to current nonsmokers. CONCLUSION: Education and social class were stronger predictors of differences in ascorbic acid levels, an indicator of dietary health behaviour, than a deprivation index based on the Townsend score. This suggests that education could be particularly important in influencing large socioeconomic differentials in health related behaviours and potentially, health outcomes in the UK.

Adult↗
PubMed2004

Microalbuminuria and stroke in a British population: the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) population study.

OBJECTIVES: To examine the relationship between microalbuminuria and incident stroke in the general population. DESIGN: Population-based prospective cohort study. SETTING: Participants were recruited in a primary care setting from 35 participating general practice units in Norfolk, UK. SUBJECTS AND MAIN OUTCOME MEASURES: The study population consisted of 23,630 individuals aged 40-79 years recruited between 1993 and 1997 for the EPIC-Norfolk Study and followed up for an average of 7.2 years. Random spot urine specimens were collected at baseline and albumin-to-creatinine ratio measured. Participants were categorized into normoalbuminuria, microalbuminuria and macroalbuminuria groups. During follow-up, the main end point was stroke incidence (fatal and nonfatal), ascertained from the UK Office for National Statistics and from the National Health Service Health District database of all hospital admissions. RESULTS: A total of 246 stroke events occurred during follow-up [crude incidence rate of stroke, 1.5 per 1000 person years (pyrs)]. The age-adjusted incidence of stroke increased significantly across categories of baseline albuminuria (0.9, 1.1 and 1.4/1000 pyrs for tertiles of normoalbuminuria, 2.6/1000 pyrs for microalbuminuria, and 6/1000 pyrs for macroalbuminuria in the total population, P < 0.001 for trend). In all women and men, the multivariate hazard ratio [95% confidence interval (CI)] for stroke associated with microalbuminuria was 1.49 (1.13-2.14) and macroalbuminuria 2.43 (1.11-6.26). After stratifying by stroke subtype, microalbuminuria was only independently predictive of ischaemic stroke, with hazard ratio (95% CI) of 2.01 (1.29-3.31). CONCLUSION: Microalbuminuria is independently associated with approximately 50% increased risk of stroke in the general population. Microalbuminuria may be useful in identifying those at increased risk of stroke in the general population.

Adult↗
PubMed2004

Vitamin C and the risk of developing inflammatory polyarthritis: prospective nested case-control study.

OBJECTIVE: To investigate whether, there is an association between consumption of fruit and vegetables and dietary antioxidants and the risk of developing inflammatory polyarthritis (IP). METHODS: In a prospective, population based, nested case-control study of residents of Norfolk, UK, men and women aged 45-74 years were recruited, between 1993 and 1997 through general practice age-sex registers to the Norfolk arm of the European Prospective Investigation of Cancer (EPIC-Norfolk). Dietary intake was assessed at baseline using 7 day diet diaries. Seventy three participants who went on to develop IP between 1993 and 2001 and were registered by the Norfolk Arthritis Register (NOAR) were identified. Incident cases of IP, assessed by general practitioners, fulfilled the criteria of two or more swollen joints, persisting for a minimum of 4 weeks. Each case of IP was matched for age and sex with two controls free of IP. RESULTS: Lower intakes of fruit and vegetables, and vitamin C were associated with an increased risk of developing IP. Those in the lowest category of vitamin C intake, compared with the highest, increased their risk of developing IP more than threefold, adjusted odds ratio (OR) with 95% confidence intervals (CI) 3.3 (95% CI 1.4 to 7.9). Weak inverse associations between vitamin E and beta-carotene intake and IP risk were found. CONCLUSION: Patients with IP (cases) consumed less fruit and vitamin C than matched controls, which appeared to increase their risk of developing IP. The mechanism for this effect is uncertain. Thus similar studies are necessary to confirm these results.

Aged↗
PubMed2004

Area deprivation predicts lung function independently of education and social class.

The cross-sectional association between socioeconomic status (at both the individual and area-based level) and lung function, as measured by forced expiratory volume in one second, in a large population-based cohort was investigated. The study population consisted of 22,675 males and females aged 39-79 yrs. They were recruited from the general community in Norfolk, UK using general practice age/sex registers, as part of the European Prospective Investigation into Cancer (EPIC-Norfolk). It was found that being in a manual occupational social class, having no educational qualifications and living in a deprived area all independently predicted significantly lower lung function, even after controlling for smoking habit. The influence of area-deprivation on lung function, independent of individual socioeconomic status and of individual smoking habit, suggests that apart from targeting individuals who are at high-risk, such as smokers, environmental determinants also need to be examined when considering measures to improve respiratory health.

Adult↗
PubMed2003

Television viewing and low participation in vigorous recreation are independently associated with obesity and markers of cardiovascular disease risk: EPIC-Norfolk population-based study.

OBJECTIVE: This study describes the associations between sedentary behaviour (television viewing) and participation in vigorous recreational activity with obesity and with biomarkers of cardiovascular disease (CVD) risk profile. DESIGN: Cross-sectional analysis of the EPIC-Norfolk cohort study. SETTING: The study is a population-based study of participants living in Norfolk, UK. SUBJECTS: A total of 15 515 men and women aged between 45 and 74 y, recruited through General Practice lists, who completed the detailed physical activity questionnaire. RESULTS: Following exclusion of those with self-reported myocardial infarction, stroke and diabetes, 14 189 participants remained for the analysis. Self-reported television viewing was positively and participation in vigorous activity negatively associated with markers of obesity, blood pressure and plasma lipids. In multiple regression analysis, adjusting for age, alcohol, smoking, treatment for hypertension, vigorous and total physical activity, these associations remained significant. For women who participated in more than 1 h/week of vigorous activity and who watched fewer than 2 h of television each day, the adjusted mean body mass index was 1.92 kg/m(2) less than for women who reported participating in no vigorous activity and who watched more than 4 h of television each day (P<0.001). The equivalent figure for men was 1.44 kg/m(2) (P<0.001). In a similar analysis, with blood pressure as the outcome, mean diastolic blood pressure difference between the extreme groups of vigorous activity and television viewing was 3.6 mmHg in men (P<0.001) and 2.7 mmHg (P=0.001) in women. CONCLUSIONS: These data suggest that time spent participating in vigorous recreational physical activity and television viewing, an indicator of a sedentary lifestyle, are associated with obesity and markers of CVD disease risk independent of total reported physical activity. Whether these observations represent the true underlying aetiological relations or are a manifestation of the different precision with which the subdimensions of activity are measured remains uncertain.

Aged↗
PubMed2003

Residential area deprivation predicts smoking habit independently of individual educational level and occupational social class. A cross sectional study in the Norfolk cohort of the European Investigation into Cancer (EPIC-Norfolk).

OBJECTIVES: To investigate the independent association between individual and area based measures of socioeconomic status and cigarette smoking habit. DESIGN AND SETTING: Cross sectional, population based study. PARTICIPANTS AND METHODS: 12 579 men and 15 132 women aged 39-79 years living in the general community participating in the EPIC-Norfolk Study in 1993-1997. The association between social class, educational status, Townsend residential deprivation level, and cigarette smoking status was examined. MAIN OUTCOME MEASURES: Cigarette smoking status at baseline survey. RESULTS: Social class, educational level, and residential deprivation level independently related to cigarette smoking habit in both men and women. Multivariate age adjusted odds ratios for current smoking in men were 1.62 (95% CI 1.45 to 1.81) for manual compared with non-manual social class, 1.32 (95% CI 1.17 to 1.48) for those with educational level less than O level compared with those with O level qualifications or higher and 1.84 (95% CI 1.62 to 2.08) for high versus low area deprivation level. For women, the odds ratios for current smoking for manual social class were 1.14 (95% CI 1.03 to 1.27); 1.31 (95% CI 1.18 to 1.46) for low educational level and 1.68 (95% CI 1.49 to 1.90) for high residential deprivation respectively. CONCLUSIONS: Residential deprivation level using the Townsend score, individual social class, and educational level all independently predict smoking habit in both men and women. Efforts to reduce cigarette smoking need to tackle not just individual but also area based factors. Understanding the specific factors in deprived areas that influence smoking habit may help inform preventive efforts.

Adult↗
PubMed2002

Variability of fish consumption within the 10 European countries participating in the European Investigation into Cancer and Nutrition (EPIC) study.

OBJECTIVE: To describe and compare the consumption of total fish (marine foods) and the fish sub-groups - white fish, fatty fish, very fatty fish, fish products and crustacea, in participants from the European Investigation into Cancer and Nutrition (EPIC) study. DESIGN: Cross-sectional analysis of dietary intake using a computerised standardised 24-hour recall interview. Crude means, means and standard errors adjusted by age, season and day of the week were calculated, stratified by centre and gender. SETTING: Twenty-seven redefined centres in the 10 European countries participating in the EPIC study. SUBJECTS: In total, 35 955 subjects (13 031 men and 22 924 women), aged 35-74 years, selected from the main EPIC cohort. RESULTS: A six- to sevenfold variation in total fish consumption exists in women and men, between the lowest consumption in Germany and the highest in Spain. Overall, white fish represented 49% and 45% of the intake of total fish in women and men, respectively, with the greatest consumption in centres in Spain and Greece and the least in the German and Dutch centres. Consumption of fatty fish reflected that of total fish. However, the greatest intake of very fatty fish was in the coastal areas of northern Europe (Denmark, Sweden and Norway) and in Germany. Consumption of fish products was greater in northern than in southern Europe, with white fish products predominating in centres in France, Italy, Spain, The Netherlands and Norway. Intake of roe and roe products was low. The highest consumption of crustacea was found in the French, Spanish and Italian centres. The number of fish types consumed was greater in southern than in northern Europe. The greatest variability in consumption by day of the week was found in the countries with the lowest fish intake. CONCLUSIONS: Throughout Europe, substantial geographic variation exists in total fish intake, fish sub-groups and the number of types consumed. Day-to-day variability in consumption is also high.

Adult↗
PubMed2002

Patterns of alcohol consumption in 10 European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) project.

OBJECTIVE: The aim of this study was to compare the quantities of alcohol and types of alcoholic beverages consumed, and the timing of consumption, in centres participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). These centres, in 10 European countries, are characterised by widely differing drinking habits and frequencies of alcohol-related diseases. METHODS: We collected a single standardised 24-hour dietary recall per subject from a random sample of the EPIC cohort (36 900 persons initially and 35 955 after exclusion of subjects under 35 and over 74 years of age). This provided detailed information on the distribution of alcohol consumption during the day in relation to main meals, and was used to determine weekly consumption patterns. The crude and adjusted (by age, day of week and season) means of total ethanol consumption and consumption according to type of beverage were stratified by centre and sex. RESULTS: Sex was a strong determinant of drinking patterns in all 10 countries. The highest total alcohol consumption was observed in the Spanish centres (San Sebastian, 41.4 g day-1) for men and in Danish centres (Copenhagen, 20.9 g day-1) for women. The lowest total alcohol intake was in the Swedish centres (Umeå, 10.2 g day-1) in men and in Greek women (3.4 g day-1). Among men, the main contributor to total alcohol intake was wine in Mediterranean countries and beer in the Dutch, German, Swedish and Danish centres. In most centres, the main source of alcohol for women was wine except for Murcia (Spain), where it was beer. Alcohol consumption, particularly by women, increased markedly during the weekend in nearly all centres. The German, Dutch, UK (general population) and Danish centres were characterised by the highest percentages of alcohol consumption outside mealtimes. CONCLUSIONS: The large variation in drinking patterns among the EPIC centres provides an opportunity to better understand the relationship between alcohol and alcohol-related diseases.

Adult↗
PubMed2001

Frequency of eating and concentrations of serum cholesterol in the Norfolk population of the European prospective investigation into cancer (EPIC-Norfolk): cross sectional study.

OBJECTIVES: To examine the relation between self reported eating frequency and serum lipid concentrations in a free living population. DESIGN: Cross sectional population based study. SETTING: Norfolk, England. PARTICIPANTS: 14 666 men and women aged 45-75 years from the Norfolk cohort of the European prospective investigation into cancer (EPIC-Norfolk). MAIN OUTCOME MEASURES: Concentrations of blood lipids. RESULTS: Mean concentrations of total cholesterol and low density lipoprotein cholesterol decreased in a continuous relation with increasing daily frequency of eating in men and women. No consistent relation was observed for high density lipoprotein cholesterol, body mass index, waist to hip ratio, or blood pressure. Mean cholesterol concentrations differed by about 0.25 mmol/l between people eating more than six times a day and those eating once or twice daily; this difference was reduced to 0.15 mmol/l after adjustment for possible confounding variables, including age, obesity, cigarette smoking, physical activity, and intake of energy and nutrients (alcohol, fat, fatty acids, protein, and carbohydrate). CONCLUSIONS: Concentrations of total cholesterol and low density lipoprotein cholesterol are negatively and consistently associated with frequency of eating in a general population. The effects of eating frequency on lipid concentrations induced in short term trials in animals and human volunteers under controlled laboratory conditions can be observed in a free living general population. We need to consider not just what we eat but how often we eat.

Aged↗