Migration within Great Britain and cardiovascular disease: early life and adult environmental factors

S Goya Wannametheea, A Gerald Shapera, Peter H Whincupb and Mary Walkera

a Department of Primary Care and Population Sciences, Royal Free and University College Medical School, London, UK.
b Department of Public Health Sciences, St George’s Hospital Medical School, London, UK.

Dr S Goya Wannamethee, Department of Primary Care and Population Sciences, Royal Free and University College Medical School, Rowland Hill St, London NW3 2PF, UK. E-mail: goya{at}pcps.ucl.ac.uk

Abstract

Aim To examine the relative contributions of early life and adult life factors to risk of cardiovascular disease (CVD) in middle-aged men using migration within Great Britain (GB).

Methods Prospective study of 7735 men (40–59 years) drawn from one group practice in each of 24 British towns. Zones of birth and/or examination: South of England and rest of GB (Midlands and Wales, North of England, and Scotland).

Results There were 1392 coronary heart disease (CHD) events and 1154 cardiovascular deaths during 21.8 years mean follow-up. Regardless of birth zone, men examined in the South showed lower risk of CHD events and CVD mortality than those examined in the rest of GB. Migrants from South to rest of GB showed a small increase in cardiovascular risk. Men born and examined in the rest of GB showed the highest adjusted risk of CHD events (RR = 1.15, 95% CI: 0.96–1.38) and CVD mortality (RR = 1.28, 95% CI: 1.04–1.57). Men born in the rest of GB who moved to the South showed adjusted risks of CHD events and CVD mortality similar to those born and examined in the South. Zone of examination was more strongly associated with CHD events and CVD mortality than zone of birth (RR = 1.23 versus 0.95 for CHD; RR = 1.26 versus 1.04 for CVD mortality). Smokers, irrespective of zone of birth or examination, showed higher risk than non-smokers.

Conclusion Factors in adult life appear to be dominant in determining cardiovascular risk in middle and older age although this does not exclude early life effects on cardiovascular risk.

Keywords Migration, cardiovascular disease, place of birth, risk factors

Accepted 26 April 2002

There is a well-established geographical gradient in cardiovascular mortality in Great Britain (GB) with the highest rates in Scotland and the lowest rates in the south.1 Studies of migration within GB have been used to investigate the relative contribution of circumstances in childhood and adult life to cardiovascular disease risk.2 The logic in these studies is that if the risk of cardiovascular disease (CVD) among people migrating from a low incidence to a high incidence area increases with time, or the risk among people migrating from a high incidence area to one of low incidence decreases with time, it is likely that factors acting in later life are of key importance. If the migrants retain the risk of their area of origin, it is likely that genetic or early life factors exert the major influence. However, previous studies of migrants within GB have produced conflicting results.2–4 In an earlier report from the British Regional Heart Study (BRHS) the geographical area of adult residence appeared to be of greater importance in determining the risk of coronary heart disease (CHD) incidence than place of birth,2 whereas a national study of proportional mortality ratios in England and Wales suggested a significant influence from birthplace for deaths from CHD and stroke.3 In a later study of migrants within England and Wales, mortality rates from CHD were found to be related in almost equal measures to region of origin and to region of residence in later life.4 The conclusion from the earlier BRHS report was based on 8 years follow-up and relatively few cardiovascular events, and none of these three internal migration studies assessed the role of social class or individual adult lifestyle factors on the findings observed. The purpose of this paper is to examine the role of early life environment and adult life factors in determining the risk of cardiovascular disease, a subject of current debate.5 We aim to (1) examine the relationship between migration and risk of CHD events in the BRHS using 22 years follow-up data, (2) to extend the outcome to CVD mortality, and (3) to examine the effect of individual adult risk factors on migration status and cardiovascular risk.

Subjects and Methods

The BRHS is a prospective study of cardiovascular disease involving 7735 men aged 40–59 years selected from the age-sex registers of one group general practice in each of 24 towns in England, Wales and Scotland. The criteria for selecting the town, the general practice and the subjects as well as the methods of data collection have been reported.6 In brief, towns were chosen that reflected known geographical variations in cardiovascular mortality and, wherever possible, were representative of their region in socioeconomic terms. In 1978–1980 research nurses administered to each man a standard questionnaire which included questions on smoking habits, alcohol intake and medical history. Physical measurements were made, and blood samples (non-fasting) were taken for measurement of biochemical and haematological variables. Details of the classification of smoking habits, alcohol intake, social class and physical activity have been reported.6–8 The longest held occupation of each man was recorded at screening and the men were grouped into one of seven social classes: I, II and III non-manual, III manual, IV, V and the Armed Forces. The men were classified according to their current smoking status: those who had never smoked, ex-cigarette smokers and current smokers at four levels (1–19, 20, 21–39, and >=40 cigarettes/day). Heavy drinking was defined as drinking >6 alcoholic drinks daily or most days of the week (1 drink = 8–10 g of alcohol). Physical activity status was determined for each man on the basis of their total physical activity score: inactive, occasional, light, moderate, moderately-vigorous and vigorous.7 ‘Active men’ were those graded as moderate or more active. Body mass index (BMI) calculated as weight/height2 was used as an index of relative weight. Obesity was defined as BMI >=28 kg/m2, the top fifth of the BMI distribution in all men.

Migration status
All men were asked their place of birth and for how long they had lived in the town where they were examined. With this information the men were allocated to three groups.

Non-migrants
Men who were born in the town in which they were examined (n = 3144). These men had lived in the same town for most, if not all, of their lives.

Internal migrants
Men born in GB but not in the town of examination (n = 4147). On average, these men had lived in their town of examination for 24 years.2

International migrants
This small group consisted of men who were born outside GB (n = 422). They had lived in their town of examination for 20 years on average.

No information was available on the migration status of 22 men.

Geography
We divided GB into four zones according to the established geographical trend in cardiovascular mortality (Figure 1Go). The four geographical zones are the South of England (2280 men; 30%), Midlands and Wales (1208 men; 16%), the North (3285 men; 42%) and Scotland (962 men; 12%). Men born in GB were classified by their geographical zone of birth and their geographical zone of examination.



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Figure 1 Geographical location of study towns

 
1992 questionnaire (Q92)
In 1992, 12–14 years after screening, a postal questionnaire, similar to but more comprehensive than the one administered at screening, was sent to the surviving men and information was obtained on father’s social class. The questionnaire (Q92) was completed by 5934 (91%) of the available survivors. The men were asked to describe their father’s longest held occupation and to classify it as manual or non-manual.9 Their classification was validated by comparison of the description of the father’s occupation against the Office of Population Censuses and Surveys Classification of Occupations (1980) social class coding index manual.10 Validated father’s social class was used and was available for 5643 of the 7713 men in the present study. Overall 71.1% of fathers were definitively classified as manual, 26.8% as non-manual and 2.1% as being in the Armed Forces.9

Follow-up
All men, whether or not they showed evidence of CHD at initial examination, were followed up for all-cause mortality and cardiovascular morbidity.10 Information on death was collected through the established ‘tagging’ procedures provided by the NHS registers. Fatal CHD events were defined as death from CHD (International Classification of Diseases Ninth Revision [ICD-9] codes 410–414) as the underlying cause. All events and deaths occurring up to December 2000 have been included (average follow-up of 21.8 years [range 20.5–23 years]) and follow-up has been achieved for 99% of the cohort. A non-fatal myocardial infarction was diagnosed according to World Health Organization criteria which included any report of myocardial infarction accompanied by at least two of the following: a history of severe chest pain, electrocardiographic evidence of myocardial infarction and cardiac enzyme changes associated with myocardial infarction. Major CHD events included myocardial infarction (heart attack) and sudden cardiac death. Cardiovascular mortality comprised ICD-9 codes 410–439.

Statistical methods

Cox’s proportional hazards model was used to assess the relationship between migration status and risk of major CHD events adjusting for potential confounders.11 In the adjustment, social class (I, II, III non-manual, III manual, IV, V Armed Forces), smoking (never, ex-smokers, 1–19/day, 20/day, >20/day), physical activity (none, occasional, light, moderate, moderately-vigorous, vigorous), evidence of CHD on WHO (Rose) chest pain questionnaire (yes/no), diabetes (yes/no), zone of residence (South, Midlands/Wales, North, Scotland), and alcohol intake (none, occasional, light, moderate or heavy) were fitted as categorical variables. Age, BMI and height were fitted as continuous variables. ‘Full’ adjustment includes age, social class, smoking, BMI, physical activity and height.

Results

During the mean follow-up period of 21.8 years there were 1392 major CHD events (838 fatal and 554 non-fatal) and 1154 deaths due to cardiovascular causes (CHD = 838, stroke = 156, other = 160) in the 7713 men with information on migration status.

Geographical variation in CHD and CVD mortality
Coronary heart disease incidence and CVD mortality rates were lowest in the South, with higher but similar CHD rates in all the other three zones and with the highest CVD mortality rates in Scotland (Table 1Go). Overall, the rest of GB had higher risk than the South even after adjustment for age, social class, smoking, BMI and physical activity. Additional adjustment for height made little difference to the findings. This pattern was seen in both non-migrants and internal migrants (data not shown).


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Table 1 Major coronary heart disease (CHD) events and cardiovascular disease (CVD) mortality rates/1000 person-years (number of cases/ number of men) by zone of examination and relative risks (rest of GB versus South)
 
Internal migrants who change zones
In order to compare zone of birth (proxy for early life factors) and zone of examination (proxy for adult life factors) in determining risk of major CHD events and CVD mortality in adult life, we focus on the internal migrants and examine the effects of changes in zones from birth to examination between the South and the rest of GB (Table 2Go). Men examined in the South had lower risk of CHD and CVD mortality than men examined in the rest of GB irrespective of place of birth. Men born in the rest of GB and who remained in the rest of GB showed the highest risks. Men born in the South who moved to the rest of the country showed lower CHD events and CVD mortality than those born and examined in the rest of GB. Men born in the rest of GB who moved to the South showed risks similar to those who were born and examined in the South.


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Table 2 Zone of birth and examination and risk of major coronary heart disease (CHD) events and cardiovascular disease (CVD) mortality in internal migrants (N = 4111)a. Born in South and remain in South used as referent group
 
However, men born in the South who moved to the rest of GB had a worse risk factor profile than those who remained in the South (Table 3Go). They had higher smoking rates, more heavy drinking and higher systolic blood pressure (SBP). On the other hand, they were of higher social class (adult and father’s) than men born and examined in the rest of GB. Men born in the rest of GB who moved South showed a better risk factor profile than those who remained in the rest of GB. They had lower smoking rates, less obesity, lower mean SBP, more physical activity and less heavy drinking. They also had a higher percentage of men in higher social class (adult and father’s). The mean height in men born in the South is greater than men born in the rest of GB, irrespective of zone of examination, indicating the persisting effect of early life experience.


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Table 3 Characteristics of internal migrants who change zones
 
Adjustment for age and social class had little effect on the relationships seen (Table 2Go, row A). Additional adjustment for risk factor status (smoking, BMI and physical activity) and height produced greater reduction in the risk of major CHD events and CVD mortality in men born and examined in the rest of GB but these men still showed increased risk of CHD events, although the increased risk was no longer significant (row B). Cardiovascular disease mortality risk remained significantly increased even after adjustment. Those who moved to the South still showed lower risk of CHD events and CVD mortality than those who remained in the rest of GB, and CVD mortality risk was similar to those who were born and remained in the South. Men born in the South who moved to the rest showed similar CHD events to those examined in the rest of GB but showed lower CVD mortality. Men born in the rest who moved to the South showed lower risk of both CHD and CVD mortality than those born and examined in the rest of the country. However, a test for interaction between zone of birth and zone of examination was not significant (P = 0.48 for major CHD events, P = 0.34 for CVD mortality).

When cardiovascular mortality was divided into CHD deaths (n = 442) and non-CHD deaths (stroke and other cardiovascular causes; n = 162) the pattern for CHD deaths and non-CHD deaths was broadly similar to the overall pattern for cardiovascular mortality.

Zone of birth and zone of examination
We have compared the effects of zone of birth and zone of examination (rest of GB versus South) on CHD event risk and CVD mortality in internal migrants (Table 4Go). Zone of birth showed a small and non-significant increase in age-adjusted risk of major CHD events which was attenuated after adjustment for social class and lifestyle factors (row C). Zone of examination remained significantly associated with risk of major CHD events even after adjustment (C). For CVD mortality zone of birth and zone of examination were both significantly associated (marginal for place of birth) with risk of CVD mortality even after adjustment (C). There is a high degree of correlation between zone of birth and zone of examination and when both geographical zone of birth and zone of examination were entered into the multivariate model (row D) zone of examination appeared to be a more important determinant of major CHD events and CVD mortality than zone of birth.


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Table 4 Adjusted relative risk of major coronary heart disease (CHD) events and cardiovascular disease (CVD) mortality in internal migrants (n = 4111) according to zone of birth and zone of examination. Rest of GB versus South
 
Smoking effects
We have used smoking as an example of a major environmental determinant of risk for major CHD events and CVD mortality in order to compare the impact of an environmental factor and early life influence (zone of birth) on risk. Within both non-smokers and smokers those examined in the rest of GB had higher risk of CHD events and CVD mortality than those examined in the South although the difference was more apparent in non-smokers (Table 5Go). Irrespective of zone of birth or examination all smokers have higher risk of CHD events and CVD mortality than non-smokers. In smokers there was virtually no difference between those born and examined in the South and those born and examined in the rest of GB, suggesting that cigarette smoking is a dominant factor in determining risk, overwhelming any underlying advantageous characteristics.


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Table 5 Internal migrants: adjusted relative risk of major coronary heart disease (CHD) events and cardiovascular disease (CVD) mortality by zone of birth and zone of examination in non-smokers and smokers (n = 4111). Non-smoking men born and examined in South used as referent group
 
Discussion

There is considerable evidence that events occurring in early life may influence the risk of adult cardiovascular disease.9,12,13 However, the relative importance of early life factors as against adult environmental factors in the development of CVD in middle-aged subjects remains an issue.5 Migration within GB has been used to investigate the relative contribution of circumstances in childhood and adult environmental factors to risk of cardiovascular disease. Zone of birth and zone of examination have been used as proxy measures for relevant environmental exposures at different points in time. In the present study of migration effects within GB, zone of examination appears to be a stronger determinant of adult cardiovascular risk than zone of birth. This finding, based on 22 years follow-up and a substantially larger number of cardiovascular events than our earlier report adds weight to our earlier suggestion that zone of examination is a more important determinant of risk than zone of birth.2 Compared to men born and examined in the rest of GB, men born in the South who moved to the rest of GB showed similar CHD (fatal and non-fatal) risk but lower risk of CVD mortality, suggesting that some early life advantages might continue into later life. Those born in the rest who moved South showed lower risk of CHD and CVD mortality than those who remained in the rest of GB, and their risk was similar to those born and examined in the South. Migrants who moved South tended to be of higher socioeconomic status and to come from more advantageous family background than those who remained, and it is perhaps not surprising that these men showed lower risk than those who remained. However, despite their higher social classes the mean height in these men (a marker of early life experience) was less than in those born in the South, reflecting some earlier life disadvantage. The fact that they showed similar risk to those born and examined in the South even after adjustment for adult social class and adult lifestyle risk factors, suggests that changes in environment in later life can modify the effects of early life experiences.

Previous studies
Previous studies of migration within GB have produced results that are difficult to compare directly with the present study because of methodological differences. In an analysis involving almost 2 million deaths at all ages in 153 areas in England and Wales in 1969–1972, people born in the northern counties, in industrial towns and in Wales had increased risk of ischaemic heart disease (IHD) and stroke which persisted whether or not they had moved to another area.3 Although there was a significant effect of birthplace on both mortality from IHD and stroke, the influence of area of death (as assessed from the {chi}2 value) was greater.14 However, this study was based on proportional mortality ratios which depend as much on the geographical patterns of mortality from other causes of death as on cardiovascular mortality. The authors point out that the value of the place of birth effects did not necessarily reflect the strength of their effect on disease risk and the conclusions from this large study must be interpreted with caution.

In a longitudinal study of a 1% sample of residents of England and Wales born before 1939, IHD and stroke deaths during 1971–1988 were analysed by area of residence at the censuses in 1939 (area of origin) and 1971, focussing on the 16% of deaths in those who moved between 14 areas in England and Wales (migrants).4 The aim was to differentiate the effects on mortality of factors operating in childhood and early adult life from those operating in middle and old age, using the area of origin (1939) and the area of residence in 1971 as proxy measures. Standardized mortality ratios were calculated with adjustment for sex, age, calendar period at risk and socioeconomic measures. For IHD mortality, the results suggested that the south-east and north-west gradient in England and Wales is related in almost equal measure to region of origin and region of later adult residence. While consistent with IHD risk being partly determined by fetal and early life experiences it could also reflect genetic factors or lifestyles acquired early in life. In the migrants, IHD risk was significantly influenced by region of residence in later life, implying that changes associated with migration can modify earlier effects whatever their nature. For stroke mortality, the study suggested that the low risk associated with living in Greater London was acquired by individuals who lived there and was not a consequence of early life factors or selective migration.

Both of these large mortality studies suggest that the area of residence during the latter part of life has a greater influence on the risk of CVD than the place of birth or early life, as seen in the present study.

By contrast, a study of migration between East Finland (high CHD mortality), Middle Finland (average) and West Finland (low) suggests that while both being born in East Finland and living there increase the risk of CHD, being born there is a more important factor than living there.15 Socioeconomic status appeared to have no effect on the regional differences in CHD mortality. No data were available on the risk factors of the various migrant groups. Indeed, none of these earlier migrant studies were able to examine the incidence of CVD and/or to take into account lifestyle characteristics such as smoking, body weight or physical activity. This makes it impossible to determine whether changes in lifestyle variables were involved in the determination of CHD risk status.

In the present study, zone of birth showed increased risk of CHD incidence and CVD mortality among internal migrants but this was attenuated upon adjustment for age and lifestyle factors and was abolished after further adjustment for zone of examination. By contrast, zone of examination remained significantly associated with increased risk of major CHD and CVD mortality although risk was attenuated after adjustment including birthplace.

Zone of birth is a crude measure of early life experience and the present study cannot exclude the presence of modest early life effects. Moreover we cannot exclude the possibility that selective migration, related to early life factors (e.g. birthweight) has contributed to the observed pattern of CHD events and CVD mortality. However, to produce even a modest increase in relative risk a very strong selective migration effect would need to be present with respect to birthweight.16

Adult lifestyle risk factors
Adjustment of relative risk estimates for various risk factors is an imprecise procedure but it provides some measure of the extent to which the relative risk estimate is conditioned by the risk factors used in the adjustment procedure. Adjustment for lifestyle factors considerably reduced cardiovascular risk in men born and examined in the rest of GB compared with men born and examined in the South, while it did not appear to affect the risk of men born in the South who moved to the rest of GB. This suggests that lifestyle factors play a considerable role in increasing the risk of both CHD events and CVD mortality in the internal migrants who are born and remain in the rest of GB. When analyses were stratified by cigarette smoking status, smokers had higher risk of major CHD events and CVD mortality than non-smokers irrespective of where they were born or examined even after adjustment for height (a marker of early life influence). Although early life advantages may play a role in determining the risk of CVD, these findings suggest that environmental factors in adult life may overwhelm these early life influences.

Public health implications
There are a number of well-established risk factors for CVD which have been identified as being strongly and causally associated with risk of CVD such as serum lipid abnormalities, cigarette smoking, raised blood pressure, overweight and obesity, diabetes and physical inactivity.17 It has been shown in this cohort that much of the variation in CHD incidence between the 24 towns in this study can be accounted for by these established risk factors.18 Preventive action at both population and individual levels has been directed towards these factors and modification of many of these has been associated with diminution in the risk of CVD.17 The present study suggests that the dominant effect on risk of CVD in middle and older age is associated with exposure to risk factors during the third to the sixth decades of life. These findings support Susser’s contention that ‘while early programming could create predisposition and vulnerability to life course experience, the contribution, if any, of such early experience must surely be complementary to the development of chronic cardiovascular disease’.19 Until we have more precise information regarding the nature of the effects operating in fetal life and early childhood, it would seem reasonable to direct our preventive actions towards those factors already established as critical to the development of CVD and capable of modification.17


KEY MESSAGES

  • In this study of migration effects within Great Britain, zone of examination appears to be a stronger determinant of adult cardiovascular risk than zone of birth.
  • Factors in adult life appear to be dominant in determining cardiovascular risk in middle and older age although this does not exclude early life effects on cardiovascular risk.

 

Acknowledgments

The British Regional Heart Study is a British Heart Foundation Research Group and is also supported by the Department of Health (England). The views expressed in this publication are those of the authors and not necessarily those of the Department of Health.

References

1 Britton M. Geographic variation in mortality since 1920 for selected causes. In: Britton M (ed.). Mortality and Geography. A Review in the Mid-1980s. The Registrar General’s Decennial Supplement for England and Wales. London: HMSO, 1990, pp. 28–30 (Series DS, No. 9).

2 Elford J, Phillips AN, Thomson AG, Shaper AG. Migration and geographic variations in ischaemic heart disease in Great Britain. Lancet 1989;i:343–46.[CrossRef]

3 Osmond C, Barker DJP, Slattery JM. Risk of death from cardiovascular disease and chronic bronchitis determined by place of birth in England and Wales. J Epidemiol Community Health 1990;44:139–41.[Abstract]

4 Strachan DP, Leon DA, Dodgeon B. Mortality from cardiovascular disease among interregional migrants in England and Wales. BMJ 1995;319:423–27.

5 Kuh D, Ben-Shlomo Y (eds). A Life Course Approach to Chronic Diseases Epidemiology. Tracing the Origins of Ill-health from Early to Adult Life. Oxford: Oxford University Press, 1997.

6 Shaper AG, Pocock SJ, Walker M, Cohen NM, Wale CJ, Thomson AG. British Regional Heart Study: cardiovascular risk factors in middle-aged men in 24 towns. BMJ 1981;283:179–86.[ISI][Medline]

7 Shaper AG, Wannamethee G. Physical activity and ischaemic heart disease in middle-aged British men. Br Heart J 1991;66:384–94.[Abstract]

8 Shaper AG, Wannamethee SG, Walker M. Alcohol and mortality: explaining the U-shaped curve. Lancet 1988;ii:1268–73.

9 Wannamethee SG, Whincup PH, Shaper AG, Walker M. Influence of father’s social class on cardiovascular disease in middle-aged men. Lancet 1996;348:1259–63.[CrossRef][ISI][Medline]

10 Walker M, Shaper AG, Lennon L, Whincup PH. Twenty years follow-up of a cohort based in general practices in 24 British towns. J Public Health Med 2000;22:479–85.[Abstract/Free Full Text]

11 Cox DR. Regression models and life tables. J Roy Stat Soc B 1972; 34:187–220.[ISI]

12 Barker DJP (ed.). Mothers, Babies and Health in Later Life. London: Churchill Livingstone, 1998.

13 Joseph KS, Kramer MS. Review of the evidence on fetal and early childhood antecedents of adult chronic disease. Epidemiol Rev 1996; 18:158–74.[ISI][Medline]

14 Osmond C, Slattery JM, Barker DJP. Mortality by place of birth. In: Britton M (ed.). Mortality and Geography. A Review in the Mid-1980s. The Registrar General’s Decennial Supplement for England and Wales. London: HMSO, 1990, pp. 96–100 (Series DS, No. 9).

15 Valkonen T. Male mortality from ischaemic heart disease in Finland: relation to region of birth and region of residence. Eur J Popul 1987;3:61–83.[ISI][Medline]

16 Fall CH, Vijayakur M, Barker DJP, Osmond C, Duggleby S. Weight in infancy and prevalence of coronary heart disease in adult life. BMJ 1995;310:17–19.[Abstract/Free Full Text]

17 National Heart Forum. In: Sharp I (ed.). Looking to the Future. Making Coronary Heart Disease an Epidemic of the Past. London: The Stationery Office, 1999.

18 Morris RW, Whincup PH, Lampe FC, Walker M, Wannamethee SG, Shaper AG. Geographic variation in incidence of coronary heart disease in Britain: the contribution of established risk factors. Heart 2001;86:277–283.[Abstract/Free Full Text]

19 Susser M. Foreword. In: Kuh D, Ben-Shlomo Y (eds). A Life Course Approach to Chronic Diseases Epidemiology. Tracing the Origins of Ill-health from Early to Adult Life. Oxford: Oxford University Press, 1997, pp. v–vii.





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