The participants were part of a prospective population study of 25,639 men and women aged 45–79 y, 99.5% white (as self-defined on questionnaire), resident in Norfolk, UK, first surveyed in 1993–1997. (Norfolk is a county in the UK encompassing a wide socioeconomic and urban-rural distribution.) They were recruited from age-sex registers of general practices as part of a ten-country collaborative study, the European Prospective Investigation into Cancer and Nutrition (EPIC). As virtually 100% of people in the UK are registered with general practitioners through the National Health Service, the age-sex registers form a population-based sampling frame. From the inception of the EPIC-Norfolk cohort, data collection was broadened to enable the examination of a wider range of determinants of chronic diseases. The Norfolk cohort was comparable to national population samples with respect to characteristics including anthropometry, blood pressure, and lipids, but with a lower prevalence of current smokers [21
At the 1993–1997 baseline survey, participants completed a detailed health and lifestyle questionnaire. They were asked about medical history with the question “Has a doctor ever told you that you have any of the following?” followed by a list of conditions that included heart attack, stroke, and cancer. Smoking history was derived from yes/no responses to the questions “Have you ever smoked as much as one cigarette a day for as long as a year?” and “Do you smoke cigarettes now?” Alcohol consumption derived from the question “How many alcoholic drinks do you have each week?” with four separate categories of drinks. A unit of alcohol (approximately 8 g) was defined as a half pint of beer, cider, or lager; a glass of wine; a single unit of spirits (whisky, gin, brandy, or vodka); or a glass of sherry, port, vermouth, or liqueurs. Total alcohol consumption was estimated as the total units of drinks consumed in a week. For these analyses, a moderate drinker was defined as someone who drank one or more units a week (that is, not a nondrinker), but not more than 14 units a week.
Habitual physical activity was assessed using two questions referring to activity during the past year. The first question asked about usual physical activity at work, classified as four categories: sedentary, standing (e.g., hairdresser or guard), physical work (e.g., plumber or nurse), and heavy manual work (e.g., construction worker). The second question asked about the amount of time spent, in hours per week, in winter and summer in other physical activity. The average time spent daily in recreational activity was estimated as the total hours spent per week (average of winter and summer) in cycling and other physical activity such as swimming or jogging, divided by seven. A simple index allocated individuals to four ordered categories: inactive (sedentary job and no recreational activity); moderately inactive (sedentary job with <0.5 h recreational activity per day, or standing job with no recreational activity); moderately active (sedentary job with 0.5–1 h recreational activity per day, or standing job with <0.5 h recreational activity per day, or physical job with no recreational activity); and active (sedentary job with >1 h recreational activity per day, or standing job with >1 h recreational activity per day, or physical job with at least some recreational activity, or heavy manual job). This index was validated against heart rate monitoring with individual calibration in two independent studies [22
]. We have also previously reported that this four-point index is inversely related to all-cause mortality and cardiovascular disease incidence in the EPIC-Norfolk population in men and women across a wide age and social class range [20
]. For the purposes of the current study, we dichotomised the population into physically inactive (sedentary job and no recreational activity) and not physically inactive (any category with activity levels above the latter).
Social class was classified according to the Registrar General's occupation-based classification scheme into five main categories, with social class I representing professionals, social class II managerial and technical occupations, social class III subdivided into nonmanual and manual skilled workers, social class IV partly skilled workers, and social class V unskilled manual workers. We also recategorized social class into manual and nonmanual social classes. Social classes I, II, and III nonmanual were classified as nonmanual, whereas social classes III manual, IV, and V were classified as manual.[24
Trained nurses carried out a health examination at a clinic. Height and weight were measured with subjects in light clothing without shoes. Body mass index was estimated as weight in kilograms divided by height in meters squared. Blood was taken by venepuncture into plain and citrate bottles. After overnight storage in a dark box in a refrigerator at 4–7 °C, they were spun at 2,100g
for 15 min at 4 °C, and plasma and serum samples obtained. Six months after the start of the study, when funding became available, samples from participants were additionally taken for vitamin C assays. Plasma vitamin C was measured from blood drawn into citrate bottles. Plasma for vitamin C was stabilized in a standardized volume of metaphosphoric acid stored at −70 °C. Plasma vitamin C concentration was estimated using a fluorometric assay within 1 wk of sampling [25
]. The coefficient of variation was 5.6% at the lower end of the range (mean, 33.2 μmol/l) and 4.6% at the upper end (mean, 102.3 μmol/l). We have previously reported that high plasma vitamin C level is inversely associated with mortality from all causes. Because humans do not manufacture vitamin C and have to rely on exogenous sources, plasma vitamin C is a good biomarker of plant food intake; previous studies have reported that a blood value of 50 mmol/l or more indicates an intake of at least five servings of fruit and vegetables daily [19
We constructed a simple pragmatic health behaviour score. Participants scored one point for each of the following health behaviours: current nonsmoking, not physically inactive, moderate alcohol intake (1 to 14 units a week), and plasma vitamin C level >50 mmol/l, indicating fruit and vegetable intake of at least five servings a day. Participants could therefore have a total health behaviour score ranging from zero to four (). These particular health behaviours and their categorization were chosen based on extensive previous evidence on the relationship between these lifestyle factors and health endpoints.
Health Behaviour Score: Score One Point for Each of the Health Behaviours Below for a Total Score of Zero to Four
All participants are followed up for health events. We report results for follow-up to July 2006, an average of 11 y. All participants are flagged for death certification at the Office of National Statistics, United Kingdom which is virtually complete. Death certificates for decedents are coded by trained nosologists according to the International Classification of Disease (ICD). Cardiovascular death was defined as those who had ICD 400–438 (ICD9) or ICD I10–I79 (ICD 10) as underlying cause of death and encompasses stroke and coronary heart disease as well as other vascular causes. Cancer death was defined as those who had ICD 140–208 (ICD9) or ICD C00–C97 (ICD 10) as underlying cause of death. Deaths not due to cardiovascular or cancer were classified as deaths from other causes. The study was approved by the Norwich District Health Authority Ethics Committee, and all participants gave signed informed consent.
The present analysis included all men and women aged 45–79 y who completed the health and lifestyle questionnaire and attended the health examination, who had complete data for physical activity, alcohol intake, and plasma vitamin C. Of the 22,301 with available data, 2,057 had a history of heart disease, stroke, or cancer at the baseline visit and were excluded from the main analyses, leaving 20,244 individuals.
We examined risk factor distributions in men and women. The Cox proportional hazards model was used to determine the relative risks of all-cause and cause-specific mortality by each of the individual health behaviours: current smoking, physical activity, moderate alcohol intake, and plasma vitamin C category after adjusting for age, sex, body mass index, and social class. We then examined mortality rates and relative risks of all-cause and cause-specific mortality by health score, adjusted for age, sex, body mass index, and social class. We estimated the difference in survival between those with health behaviour score of four compared to zero in age-equivalent terms by comparing the beta coefficient for mortality associated with each year of age with the beta coefficient difference in mortality for those with a score of four compared to zero [27
]. We also examined relative risks in subgroups, stratified by sex, age group (<65 y and ≥65 y), body mass index category (<27 kg/m2
), and manual and nonmanual social class, and also after excluding those who died within 2 y of follow-up. We additionally examined the relationship between health behaviour score and mortality in the 2,057 individuals with prevalent disease excluded from the main analyses.