Feb 8 Geography of Chronic Diseases.ppt - Instruct Uwo

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Feb 8 Geography of Chronic Diseases.ppt - Instruct Uwo Powered By Docstoc
					            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.

        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.

  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

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.
        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?

 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.
      Coronary Heart Disease (CHD)

• One in five men and women have some form of

• 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.

       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

• 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.

  Examples of Geographical studies of CVD

• Soo et al. (2001 – Nottinghamshire, England)

• Barker and Martyn, (1991 – England & Wales)

      Geography of Coronary Heart Disease
           Nottinghamshire, England
• Soo et al. 2001 conducted a population based,
  retrospective study in the County of Nottinghamshire,

• 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 0–121.2).                          10
      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
  75.6:100 000 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 18.5:100 000 per area (IQR 13.0, 28.7).
• See map below.

Geography of Coronary Heart Disease
   Nottinghamshire, England …

   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.

    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
        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
           Infant mortality and CVD

• Infant mortality is, of course, no more than a
  general indicator of adverse environmental

• 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.

         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.

         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.
         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.
           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.

        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
• The same injection of androgen given when the animal
  is 10 days old has no effect on reproductive function.
          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.

         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.

         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.

       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

• In the first study, 6500 men born in eight districts
  of the county between 1911 and 1930 were
  followed up.

       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.
                        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.

                                        Ischemic heart           All non-circulatory
     Weight at one year ( pounds)
                                        Disease (deaths)         disease

     ≤ 18                               100(36)                  74(39)
      -20                               84(90)                   99 (157)
      -22                               92 (180)                 74 (215)
      - 24                              70 (109)                 67 (155)
      - 26                              55(44)                   84(99)
     ≥27                                34(10)                   72(31)
     All                                78(469)                  78(696)
Source: Barker & Martyn 1991
      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.

                     Studies in Humans and CVD …
      •Table II shows that concentrations are inversely related to
      weight at one year of age.

       Table II: Mean plasma fibrinogen in mm aged 59 to 70 years

       Weight at one year (pounds)            Number of men     Fibrinogen (g/litre )*

      ≤ 18                                    37                3.21
       -20                                    91                3.08
       -22                                    177               3.14
       -24                                    173               2.98
       - 26                                   80                2.95
      ≥27                                     33                2.93
       All                                    591               3.05
                    *Geometric mean values adjusted for age and cigarette smoking

Source: Barker & Martyn 1991
                        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

         Birthweight ( pounds)        Number of men           Systo!ic pressure
         -55                          31                      169
         - 65                         95                      166
         -75                          251                     165
         -85                          233                     163
         -95                          125                     162
         >95                          56                      162
         All                          791                     164

Source: Barker & Martyn 1991
     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.

                        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
                   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
                               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
                               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
    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.

    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

                   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
             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

                Geography of Cancer …

• Malignant melanoma of
  the skin

• Female rates showed a
  significant clustering

• Elevated risk in a group of
  counties north of Toronto

               Geography of Cancer
• Cervical Cancer

• Weak and dispersed
  geographic pattern with
  strong persistence over

• High rates tended to occur
  in northern Ontario and
  around Georgian Bay

• Rates in the southwest
  were generally low
                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

                 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

                      Geography of Cancer …
Major Known Risk Factors for Cancer Sites/Types with Evidence of Spatial Aggregation
Site/Type               Risk Factor(s)
Lip                     Sunlight, tobacco
Esophagus               Tobacco, alcohol, diet low in fresh fruits and vegetables, low; socioeconomic
                        status (SES)
Stomach                 Diet low in fresh fruits and vegetables, high intake of nitrates/ nitrites (e,g., in
                        water and preserved foods), low SES
Colon/Rectum            Diet high in fat, diet low in the fiber, high SES (colon)
Pancreas                Tobacco
Lung                    Tobacco, occupational exposures (radon, asbestos, etc.), low SES
Bone                    Ionizing radiation
Malignant melanoma      Ultraviolet radiation, susceptible phenotype (fair hair/eyes/ skin), high SES
Cervix uteri            Tobacco, sexual promiscuity (early age at coitus, multiple sex partners),
                        viruses (human papilloma virus, herpes simplex virus type 2), low SES
Corpus uteri            High levels of unopposed endogenous estrogens, use of exogenous estrogens,
                        use of combination of oral contraceptives, high SES
Prostate                Diet (possibly high in fat), high levels of androgens
Kidney                  Tobacco, obesity
           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


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