Defining chronic diseases

1
Defining chronic diseases

• Chronic diseases are difficult to define by using
  the well-known criteria of
• causation,
• acuteness,
• age of onset,
• activity restriction,
• period of illness and
• premature mortality.

2
Defining chronic diseases

• They are mostly characterized by
• complex causality,
• multiple risk factors,
• a long latency period,
• a prolonged course of illness, and
• functional impairment or disability.

3
Arrival of the chronic disease epidemic

• Chronic diseases are not new to human societies.
  Prehistorical and historical evidence clearly
  shows that our ancestors suffered from a variety
  of chronic diseases including osteoarthritis and
  diabetes (Hinkle 1987).
• However, it was not until the twentieth century
  that chronic diseases began to dominate the
  health scene their prevalence is now greater
  than at any earlier period in human history

4
Arrival of the chronic disease epidemic

• Up until the nineteenth century, infectious
  diseases and injury dominated the health of all
  populations even though descriptions of chronic
  diseases and conditions such as coronary heart
  disease, atherosclerosis and diabetes among
  affluent sections of the society were beginning
  to accumulate (Cohen 1989).
• The growing impact of chronic diseases and
  conditions such as stroke, cancer, renal disease
  and high blood pressure was not fully appreciated
  until the early part of the twentieth century.

5
Geography of Chronic Disease

• What are the determinants/risk factors of chronic
  diseases such as heart disease, cancer, asthma?
• Why a geography of chronic disease?

6
Why a Geography of Chronic Disease?

• Examining chronic disease at the lowest available
  level of data aggregation (local level) is
  beneficial in highlighting localized rate
  variations.
• Geographic patterns that remain after variations
  due to known factors have been extracted can be
  used to suggest new factors responsible for the
  remaining variations in measures of chronic
  disease e.g., cancer
• Such information enable public health officials
  to target additional resources to specific
  locations.

7
Coronary Heart Disease (CHD)

• One in five men and women have some form of CVD.
• Although the odds for men to develop a CVD before
  the age of 60 exceed that of women (one in three
  for men and 1 in 10 for women), women develop CVD
  at a higher rate in the postmenopausal years.

8
Coronary Heart Disease (CHD)

• Coronary heart disease (CHD) mortality is
  associated with social and material deprivation,
  though the principle feature of sudden and
  unexpected coronary heart disease mortality, is
  uncertain.
• In general, instances of mortality from CHD is
  not uniformly distributed throughout regions, as
  distinct geographical hot spots exist where
  mortality is usually greater than expected.

9
Examples of Geographical studies of CVD

• Soo et al. (2001 Nottinghamshire, England)
• Barker and Martyn, (1991 England Wales)

10
Geography of Coronary Heart Disease
Nottinghamshire, England

• Soo et al. 2001 conducted a population based,
  retrospective study in the County of
  Nottinghamshire, England
• County has 191 electoral areas. In the 4 years
  from 1 January, 1991 to 31 December, 1994
• 1634 patients sustained a cardiac arrest
  attributed to a cardiac cause
• The overall crude mean incidence rate of
  community cardiac arrest per electoral area was
  40.2 per 100 000 population (range 0121.2).

11
Geography of Coronary Heart Disease
Nottinghamshire, England

• Thirteen electoral areas, relatively deprived
  according to the Townsend score, had a
  significantly greater than expected incidence
  rate of cardiac arrest (median of 75.6100 000
  per electoral area interquartile range (IQR)
  65.3, 83.8).
• Twelve relatively affluent electoral areas had a
  significantly lower than expected incidence rate
  (median of 18.5100 000 per area (IQR 13.0,
  28.7).
• See map below.

12
Geography of Coronary Heart Disease
Nottinghamshire, England
13
Geography of Coronary Heart Disease
Nottinghamshire, England

• After adjusting for deprivation index, there were
  no differences in coronary heart disease (CHD)
  mortality and community cardiac arrest in urban
  and rural electoral areas.
• Apart from response times by ambulance crews, the
  events that follow the cardiac arrest such as
  bystander resuscitation, ventricular fibrillation
  found as the presenting rhythm and survival were
  similar in all electoral areas.

14
Geography of Coronary Heart Disease
Nottinghamshire, England

• Conclusions
• Increasing level of deprivation is associated
  with areas of increased incidence of
  out-of-hospital cardiac arrest in
  Nottinghamshire, and the effect is apparently
  different from that on CHD mortality.
• Strategies should aim at improving survival in
  areas identified as having high rates of
  community cardiac arrest.

15
Geographical studies of CVD

• Barker and Martyn, (1991 England Wales)
• A possible explanation for the geographical
  differences in mortality from cardiovascular
  disease in England and Wales is that its causes
  begin to operate not in adult life but during
  fetal development and infancy.
• Infant mortality
• Animal studies
• Studies in Humans

16
Infant mortality and CVD

• Infant mortality is, of course, no more than a
  general indicator of adverse environmental
  conditions
• Records of infant mortality dating from the
  beginning of the century allow current death
  rates in the 212 local authority areas of England
  and Wales to be compared with infant mortality
  rates in the same places 60 or more years ago.

17
Infant mortality and CVD

• The correlation between past infant mortality and
  current mortality from cardiovascular disease (r
  0.73) is strikingly close.
• This relationship implies that some aspect of
  poor living conditions in early childhood
  determines risk of cardiovascular disease in
  adult life.

18
Infant mortality and CVD

• The records of infant mortality in England and
  Wales are sufficiently detailed to allow neonatal
  mortality (i.e., deaths before one month of age)
  to be distinguished from post-neonatal mortality
  (i.e., deaths between the ages of one month and
  one year).
• A further analysis using these separate
  categories showed that adult cardiovascular
  mortality is more closely linked to neonatal
  mortality 60 years earlier than to post-neonatal
  mortality
• Neonatal mortality in the past was high in places
  where many babies were born with low birth
  weight.

19
Infant mortality and CVD

• Neonatal mortality is also known to have been
  associated with high maternal mortality.
• High rates for both neonatal and maternal
  mortality were found in places where the physique
  and health of women were poor.
• Cardiovascular disease is therefore associated
  more strongly with poor maternal physique and
  health and poor fetal growth than with
  conditions, such as overcrowding, that predispose
  to high post-neonatal death rates.

20
Animal studies and CVD

• Ideas about the importance of early life in
  determining risk of disease in adulthood are
  reinforced by studies in animals
• Transient events in prenatal or early postnatal
  life have permanent and profound effects on
  physiology though such effects may remain latent
  until the animal is mature.

21
Animal studies and CVD

• A female rat injected with a few micrograms of
  testosterone propionate during the first four
  days of life develops normally until puberty.
• Only then does it become apparent that the
  hypothalamic neuronal substrate that mediates the
  cyclic release of gonadotrophins has been
  irreversibly altered to a male pattern when,
  despite adequate ovarian and pituitary function,
  the animal fails to ovulate or show normal
  patterns of female sexual behaviour.
• The same injection of androgen given when the
  animal is 10 days old has no effect on
  reproductive function.

22
Animal studies and CVD

• In another example, the nutrition of pregnant and
  lactating rats was manipulated.
• The adult body size of these rats was more
  powerfully determined by their mothers' nutrition
  during pregnancy and lactation than by their
  genetic constitutions.
• Under-nutrition during pregnancy stunted the
  growth of the offspring and this effect could not
  be reversed by an optimal diet after birth.

23
Animal studies and CVD

• Nutritional deprivation in early life affects the
  size and DNA content of different organ systems,
  depending on the precise time at which it occurs.
• In rats, a brief period of energy restriction
  immediately after birth caused a profound
  reduction in the weight of the liver, spleen, and
  thymus, while brain and skeletal muscle were
  spared.
• Energy restriction immediately after weaning
  reduced only the weight of the thymus.

24
Studies in Humans and CVD

• The question explored is whether the programming
  effect of the early environment applicable to the
  pathogenesis of cardiovascular disease in humans
• This was done by studying adults in middle and
  old age whose growth and development in infancy
  was recorded in Hertfordshire, UK.
• From 1911 onwards, every baby born in the county
  of Hertfordshire was weighed at birth, visited
  periodically by a health visitor throughout the
  first year, and weighed again at one year of age.

25
Studies in Humans and CVD

• The records of these visits have survived so that
  it is possible to trace men and women born about
  60 years ago and to relate these measurements to
  the later occurrence of illness and death and to
  the level of known risk factors for
  cardiovascular disease.
• In the first study, 6500 men born in eight
  districts of the county between 1911 and 1930
  were followed up.

26
Studies in Humans and CVD

• Table I shows their standardized mortality ratios
  for ischemic heart disease according to weight at
  one year the ratios fall steeply as weight at
  one year increases. There are similar trends with
  increasing birth weight, though the relation is
  not as strong as with weight at one year.
• These findings prompt questions about mechanism.
• There is now evidence that haemostatic variables,
  glucose tolerance, blood pressure, and lipid
  metabolism are all susceptible to the programming
  effects of the environment in early life.

27
Studies in Humans and CVD
Standardized mortality ratios for IHD according
to weight at one year in 6500 men during
1911-1930 in Hertfordshire, England.
Source Barker Martyn 1991
28
Studies in Humans and CVD

• High plasma concentration of fibrinogen is a
  strong predictor of increased risk of both
  ischemic heart disease and stroke.
• Fibrinogen concentrations have been measured in
  591 men aged 59 to 70 years still living in
  Hertfordshire.

29
Studies in Humans and CVD

• Table II shows that concentrations are inversely
  related to weight at one year of age.

Source Barker Martyn 1991
30
Studies in Humans and CVD

• The inverse relation between systolic blood
  pressure and birth weight present in the
  Hertfordshire men is shown in table IV.
• Table IV Mean systolic blood pressure in men
  aged 59 to 70 years

Source Barker Martyn 1991
31
Studies in Humans and CVD

• A similar relation has also been found in a
  national sample of men and women at the age of 36
  years.
• In contrast to plasma concentrations of
  fibrinogen and rates of glucose intolerance,
  blood pressure in these men is not related to
  weight at one year independently of birth weight,
  nor is it related to adult height.
• This may indicate that the critical period when
  blood pressure is sensitive to programming is
  during fetal life rather than infancy.

32
Studies in Humans and CVD

• These discoveries have implications both for the
  pathogenesis of cardiovascular and other
  diseases, and also for maternal and infant health
  at specific locations.
• The relations between early growth and risk
  factors and rates of disease are continuous.

Source Barker Martyn 1991
33
Studies in Humans and CVD

• Plasma levels of fibrinogen (table II), the
  prevalence of impaired glucose tolerance (table
  III), and levels of systolic blood pressure
  (table IV) fall progressively up to the highest
  values of weight at one year or birthweight.
• If the criterion for successful fetal and infant
  growth is adult health and longevity, we may no
  longer be entitled to assume that a baby of
  average birthweight and weight in infancy has
  necessarily achieved its optimum weight.

Source Barker Martyn 1991
34
Geography of CVD

• The results of these studies show that retarded
  growth in fetal life and infancy is strongly
  related both to mortality from cardiovascular
  disease and to adult levels of some of its known
  risk factors.
• Any argument concerns the extent to which this
  relation should be interpreted as being causal.
• In broad terms there are three possible
  explanations for our findings.
• The first is that birthweight is merely a marker
  for adverse environmental influences that act in
  later life.

Source Barker Martyn 1991
35
Geography of CVD

• Although this interpretation can just be
  sustained if one is prepared to view the
  ecological data in isolation, it cannot account
  for the results of follow up studies of
  individuals.
• In Hertfordshire birth weight was not associated
  with social class, either at birth or currently.

Source Barker Martyn 1991
36
The Geographic Variation of Cancer Incidence in
Ontario

• Walter et al. 1994
• Examination of the spatial pattern of cancer
  incidence in Ontario
• Cancer incidence were calculated for 22 cancer
  sites in 49 counties in Ontario during 1976-1986.

37
The Geographic Variation of Cancer Incidence in
Ontario

• The analysis reveal a number of cancers with
  significant patterning of risk
• Further work is needed to relate the cancer data
  to other information on potential life-style and
  environmental factors

38
Geography of Cancer

• Stomach cancer
• Strong spatial aggregation was apparent in both
  sexes.
• Northern Ontario and some areas near Lake Ontario
  had high rates, while central Ontario had lower
  rates
• Correlations between sexes and over time were
  high

39
Geography of Cancer

• Lung cancer.
• There were strong geographic patterns for both
  sexes, with high correlations between sexes and
  over time.
• High rates were found in large areas of the
  northeast and east and in some counties near Lake
  Ontario and in the southwest

40
Geography of Cancer

• Malignant melanoma of the skin
• Female rates showed a significant clustering
• Elevated risk in a group of counties north of
  Toronto

41
Geography of Cancer

• Cervical Cancer
• Weak and dispersed geographic pattern with strong
  persistence over time
• High rates tended to occur in northern Ontario
  and around Georgian Bay
• Rates in the southwest were generally low

42
Geography of Cancer

• Corpus uteri cancer
• Significant spatial pattern with persistence over
  time
• Rates were low in northern Ontario and generally
  high in the southwest

43
Geography of Cancer

• Prostatic cancer
• Strong spatial aggregation
• A risk gradient by latitude, with low rates in
  the north and high rates in the southwest
• Low correlation over time, suggesting a transient
  or recent effect

44
Geography of Cancer




45
Geography of Cancer

• Several cancers show regional variations, but the
  explanation for the variability requires an
  understanding of the possible impact of
  environmental factors
• However, migration and latency are major
  problems.