1 defining chronic diseases chronic diseases are difficult to define by using the well-known...

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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.

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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.

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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

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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.

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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?

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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.

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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.

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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.

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Examples of Geographical studies of CVD

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

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

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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 0–121.2).

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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.

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• 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.

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• 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.

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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

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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.

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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.

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• 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.

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• 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.

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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.

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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.

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• 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.

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• 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.

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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.

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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.

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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.

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Weight at one year ( pounds)Ischemic heartDisease (deaths)

All non-circulatorydisease

≤ 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

Standardized mortality ratios for IHD according to weight at one year in 6500 men during 1911-1930 in Hertfordshire, England.

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• 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.

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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

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

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• 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

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• 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.

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• 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.


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• 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.


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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.


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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.


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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.

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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

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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

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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

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Geography of Cancer …

• Malignant melanoma of the skin

• Female rates showed a significant clustering

• Elevated risk in a group of counties north of Toronto

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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

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• Corpus uteri cancer

• Significant spatial pattern with persistence over time

• Rates were low in northern Ontario and generally high in the southwest

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• 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

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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

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• 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.

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