CHAPTER TWO Defining and aSsessing Risks to Health This chapter offers a detailed explanation of the report s approach to health risks. It argues that while much scientific effort and most health resources today are directed towards treating disease, rather than preventing it, focusing on risks to health is the key to prevention. Such risks do not occur in isolation so both proximal and distal causes of adverse health outcomes need to be considered Population-based strategies aim to make healthy behaviour a social norm, thus lowering risk in the entire population. Small shifts in some risks in the population can translate into major public health benefits. Therefore this chapter strongly advocates the assessment of population-wide risks as wellas high-risk individuals in strategies for risk reductio to find theright balance between the to approaches. Risk assessment has emerged in recent years from its roots in the study of environmental problems, and th steps generally involved in environmental risk assessment can be adapted to apply more specifically to the analysis of health risks. This chapter explains the benefits of comparing different risks to health and defines and explains risk assessment
Defining and Assessing Risks to Health 7 CHAPTER TWO efining and ssessing isks to ealth 7 This chapter offers a detailed explanation of the report’s approach to health risks. It argues that while much scientific effort and most health resources today are directed towards treating disease, rather than preventing it, focusing on risks to health is the key to prevention. Such risks do not occur in isolation, so both proximal and distal causes of adverse health outcomes need to be considered. Population-based strategies aim to make healthy behaviour a social norm, thus lowering risk in the entire population. Small shifts in some risks in the population can translate into major public health benefits. Therefore this chapter strongly advocates the assessment of population-wide risks as well as high-risk individuals in strategies for risk reduction. The key challenge is to find the right balance between the two approaches. Risk assessment has emerged in recent years from its roots in the study of environmental problems, and the steps generally involved in environmental risk assessment can be adapted to apply more specifically to the analysis of health risks. This chapter explains the benefits of comparing different risks to health and defines and explains risk assessment.
DEFINING AND ASSESSING RISKS TO HEALTH WHAT ARE RISKS TO HEALTH? 2 isk can mean different things to different people, as summarized in Box 2.1.The two most common meanings will be used in this report risk as a probability of an adverse outcome, or a factor that raises this probability WHY FOCUS ON RISKS TO HEALTH? Focusing on risks to health is key to preventing disease and injury. The most emotive ind tangible images in health are of people suffering from disease, but preventing disease and injury occurring in the first place requires systematic assessment and reduction of their causes Much scientific effort and most health resources are directed towards treating disease the"rule of rescue"still dominates(3). Data on disease or injury outcomes, such as death or hospitalization, tend to focus on the need for palliative or curative services. In contrast, assessments of burden resulting from risk factors will estimate the potential of prevention One notable exception concerns communicable diseases, since treating infected individuals can prevent further spread of infection, and hence treatment can be a method of prevention in itself Even when the focus is on causes as well as disease outcomes, much scientific activity as been directed to assessing whether a risk exists at all. Does electromagnetic frequency radiation cause leukaemia? Do certain infections predispose to heart attacks? These assessments are usually accompanied by estimates of how much higher the risk is in individuals who are exposed compared with those who are not. It has been much less common to assess impact at a population level by asking"of all the disease burden in this population, how much could be caused by this risk? Many factors are relevant in prioritizing strategies to reduce risks to health: the extent of the threat posed by different risk factors, the availability of cost-effective interventions, and societal values and preferences are particularly important. These factors are also key for research priorities- if major threats exist without cost-effective solutions, then these must be placed high on the agenda for research. Governments are also likely to place particular value on ensuring their main efforts focus on the largest threats to health in their countries Reliable, comparable and locally relevant information on the size of different risks to health is therefore crucial to prioritization, especially for governments setting broad directions for health policy and research. However, such information has typicall ery limited, cre-
Defining and Assessing Risks to Health 9 2 DEFINING AND ASSESSING RISKS TO HEALTH WHAT ARE RISKS TO HEALTH? isk can mean different things to different people, as summarized in Box 2.1. The two most common meanings will be used in this report – risk as a probability of an adverse outcome, or a factor that raises this probability. WHY FOCUS ON RISKS TO HEALTH? Focusing on risks to health is key to preventing disease and injury. The most emotive and tangible images in health are of people suffering from disease, but preventing disease and injury occurring in the first place requires systematic assessment and reduction of their causes. Much scientific effort and most health resources are directed towards treating disease – the “rule of rescue” still dominates (3). Data on disease or injury outcomes, such as death or hospitalization, tend to focus on the need for palliative or curative services. In contrast, assessments of burden resulting from risk factors will estimate the potential of prevention. One notable exception concerns communicable diseases, since treating infected individuals can prevent further spread of infection, and hence treatment can be a method of prevention in itself. Even when the focus is on causes as well as disease outcomes, much scientific activity has been directed to assessing whether a risk exists at all. Does electromagnetic frequency radiation cause leukaemia? Do certain infections predispose to heart attacks? These assessments are usually accompanied by estimates of how much higher the risk is in individuals who are exposed compared with those who are not. It has been much less common to assess impact at a population level by asking “of all the disease burden in this population, how much could be caused by this risk?” Many factors are relevant in prioritizing strategies to reduce risks to health: the extent of the threat posed by different risk factors, the availability of cost-effective interventions, and societal values and preferences are particularly important. These factors are also key for research priorities – if major threats exist without cost-effective solutions, then these must be placed high on the agenda for research. Governments are also likely to place particular value on ensuring their main efforts focus on the largest threats to health in their countries. Reliable, comparable and locally relevant information on the size of different risks to health is therefore crucial to prioritization, especially for governments setting broad directions for health policy and research. However, such information has typically been very limited, cre-
The World Health Report 2002 nting a gap in which interest groups may seek either to downplay or to overestimate some risks. In addition there is an inherent imbalance in media information about risks: com mon, major threats to health are usually not reported beca luse thev are area whereas rare or unusual threats to health are highly newsworthy Stewardship is one of the key functions of government, necessitating a broad overview, a long-term horizon and an evidence-based approach, and requiring information from reliable, comparable assessments of the magnitude of different major risks to health. This report helps to redress the dearth of such information. The report recognizes that risk analysis is a political enterprise as well as a scientific one, and that public perception of risk also plays a role in risk analysis, bringing issues of values, process, power and trust into the picture. The roles and contributions of risk assessment, communication, risk management, ost-effectiveness and policy development form the focus of the report. DEVELOPMENT OF RISK ASSESSMENT People have been interested in risks to health throughout history. During the past sev eral decades, this interest has intensified and has also begun to include many new perspec tives.The field of risk analysis has grown rapidly, focusing on the identification, qu aton and characterization of threats to human health and the environment - a set of activities broadly called risk assessment While clearly there has been very long interest in comparing risks posed by different threats to health, formal frameworks have been developed only relatively recently. Risk assessment has its roots in the environmental sector, where it was developed as a systematic vay of comparing environmental problems that pose different types and degrees of health risk. Such environmental risk assessment exercises generally comprise four elements Hazard identification identifies the types of health effect that can be caused, based on toxicological data from laboratory or epidemiological studies: for example, chemical X causes liver damage Exposure assessment combines data on the distribution and concentrations of pollution in the environment with information on behaviour and physiology to estimate the amount of pollutant to which humans are exposed. Biomarkers have been used to gauge levels of some exposures, such as lead and dioxin Dose-response assessment relates the probability of a health effect to the dose of pol mutant or amount of exposure Risk characterization combines the exposure and dose-response assessments to alculate the estimated health risks, such as the number of people predicted to experience a particular disease, for a particular population. This typically includes estimation and communication of uncertainties Environmental risk assessments of likely health effects, together with consideration of costs, technical feasibility and other factors, can be used to set priorities for environmental management. Environmental risk assessment has analogies to the strategies developed in epidemiology for assessing population attributable risks, that is, the proportion of disease in a population that results from a particular hazard. A more general approach based on nese frameworks can be extended to many other areas. a key part of this report outlines such methods and provides an illustrative analysis of burden caused by a variety of different risks to health Risk assessment can be defined here as a systematic approach to estimating and omparing the burden of disease and injury resulting from different risks. The work pre
10 The World Health Report 2002 ating a gap in which interest groups may seek either to downplay or to overestimate some risks. In addition, there is an inherent imbalance in media information about risks: common, major threats to health are usually not reported because they are already known, whereas rare or unusual threats to health are highly newsworthy. Stewardship is one of the key functions of government, necessitating a broad overview, a long-term horizon and an evidence-based approach, and requiring information from reliable, comparable assessments of the magnitude of different major risks to health. This report helps to redress the dearth of such information. The report recognizes that risk analysis is a political enterprise as well as a scientific one, and that public perception of risk also plays a role in risk analysis, bringing issues of values, process, power and trust into the picture. The roles and contributions of risk assessment, communication, risk management, cost-effectiveness and policy development form the focus of the report. DEVELOPMENT OF RISK ASSESSMENT People have been interested in risks to health throughout history. During the past several decades, this interest has intensified and has also begun to include many new perspectives. The field of risk analysis has grown rapidly, focusing on the identification, quantification and characterization of threats to human health and the environment – a set of activities broadly called risk assessment. While clearly there has been very long interest in comparing risks posed by different threats to health, formal frameworks have been developed only relatively recently. Risk assessment has its roots in the environmental sector, where it was developed as a systematic way of comparing environmental problems that pose different types and degrees of health risk. Such environmental risk assessment exercises generally comprise four elements. • Hazard identification identifies the types of health effect that can be caused, based on toxicological data from laboratory or epidemiological studies: for example, chemical X causes liver damage. • Exposure assessment combines data on the distribution and concentrations of pollution in the environment with information on behaviour and physiology to estimate the amount of pollutant to which humans are exposed. Biomarkers have been used to gauge levels of some exposures, such as lead and dioxin. • Dose–response assessment relates the probability of a health effect to the dose of pollutant or amount of exposure. • Risk characterization combines the exposure and dose–response assessments to calculate the estimated health risks, such as the number of people predicted to experience a particular disease, for a particular population. This typically includes estimation and communication of uncertainties. Environmental risk assessments of likely health effects, together with consideration of costs, technical feasibility and other factors, can be used to set priorities for environmental management. Environmental risk assessment has analogies to the strategies developed in epidemiology for assessing population attributable risks, that is, the proportion of disease in a population that results from a particular hazard. A more general approach based on these frameworks can be extended to many other areas. A key part of this report outlines such methods and provides an illustrative analysis of burden caused by a variety of different risks to health. Risk assessment can be defined here as a systematic approach to estimating and comparing the burden of disease and injury resulting from different risks. The work pre-
Defining and Assessing Risks to Health Box 2.1 What does risk mean? Risk can mean a probability, for example, the answer to the question: Relative risk- the likelihood of an adverse health outcome in people What is the risk of getting HIV/AIDS from an infected needle? exposed to aparticular risk, compared with people who are not exposed Risk can mean a factor that raises the probability of an adverse outcome. For example, if people who smoke for a certain time are, on average, 15 For example, major risks to child health include malnutrition, unsafe water times more likely to develop lung cancer than those who do not smoke, and indoor air pollution. their relative risk is 15 Risk can mean a consequence. For example, what is the risk from driving Hazard-an inherent property, for example of a chemical, that provides hile drunk? (answer: being in a car crash) the potential for harm. Risk can mean a potential adversity or threat. For example, is there risk in Population attributable risk-the proportion of disease in a popula riding a motorcycle? tion that results from a particular risk to health. In this report, the first two meanings are used Risk is defined as a probabil- Attributable burden-the proportion of current disease or injury bur- ity of an adverse health outcome, or a factor that raises this probability. Other.Avoidable burden-the proportion of future disease or injury burden important risk-related definitions are outlined below Prevalence of risk-the proportion of the population who are exposed at is avoidable if current and future exposure levels are reduced to to a particular risk. For example, the prevalence of smoking might be those specified by some altemative, or counterfactual, distribution 25% in a particular population. Sources: (1, 2) sented in this report builds on several similar estimates conducted in recent years. The first global estimates of disease and injury burden attributable to a set of different risk factors were reported in the initial round of the global burden of disease study (4, 5). These esti mates add to the many others made for selected risk factors in specific populations, for example, tobacco(6), alcohol and other drugs (7), environmental factors(8), blood pressure (9), and selected risk factors for certain regions (10-12) In the first round of the global burden of disease study, risk factors were assessed that were either exposures in the environment(for example, unsafe water), human behaviour (for example, tobacco smoking) or physiological states(for example, hypertension). However, in such early risk assessments, there was a lack of comparability between different risk factor assessments arising, in part, from a lack of standard comparison groups and different degrees of reliability in assessing risk factors. Also, the relevance of varying time lags between exposure and outcome-for example, short for alcohol and injuries and long for smoking and cancer-was not captured. A key aim of this ar therefore to increase comparability between the estimates of the impact of different risk factors and characterize the timing of these impacts Risk assessment estimates burden of disease resulting from different risk factors, each of which may be altered by many different strategies; it can provide an overall picture of the relative roles of different risks to human health. Specific strategies for identifying the appropriate sets of interventions, and the crucial roles of cost-effectiveness analyses in choosing from among them, are outlined in Chapter 5. KEY GOALS OF GLOBAL RISK ASSESSMENT An effective risk assessment must have a well-defined scope, which in tum depends on the purpose of the analysis. For example, an evaluation of emissions from a particular industrial facility is likely to concentrate on their health effects on local populations. In contrast, a project to set national environmental priorities may be much broader in scope, covering such factors as emissions of greenhouse gases and ozone-depleting substances Some trade-offs will inevitably be required. Governments and ministries of health oversee
Defining and Assessing Risks to Health 11 sented in this report builds on several similar estimates conducted in recent years. The first global estimates of disease and injury burden attributable to a set of different risk factors were reported in the initial round of the global burden of disease study (4, 5). These estimates add to the many others made for selected risk factors in specific populations, for example, tobacco (6), alcohol and other drugs (7), environmental factors (8), blood pressure (9), and selected risk factors for certain regions (10–12). In the first round of the global burden of disease study, risk factors were assessed that were either exposures in the environment (for example, unsafe water), human behaviour (for example, tobacco smoking) or physiological states (for example, hypertension). However, in such early risk assessments, there was a lack of comparability between different risk factor assessments arising, in part, from a lack of standard comparison groups and different degrees of reliability in assessing risk factors. Also, the relevance of varying time lags between exposure and outcome – for example, short for alcohol and injuries and long for smoking and cancer – was not captured. A key aim of this analysis is therefore to increase comparability between the estimates of the impact of different risk factors and characterize the timing of these impacts. Risk assessment estimates burden of disease resulting from different risk factors, each of which may be altered by many different strategies; it can provide an overall picture of the relative roles of different risks to human health. Specific strategies for identifying the appropriate sets of interventions, and the crucial roles of cost-effectiveness analyses in choosing from among them, are outlined in Chapter 5. KEY GOALS OF GLOBAL RISK ASSESSMENT An effective risk assessment must have a well-defined scope, which in turn depends on the purpose of the analysis. For example, an evaluation of emissions from a particular industrial facility is likely to concentrate on their health effects on local populations. In contrast, a project to set national environmental priorities may be much broader in scope, covering such factors as emissions of greenhouse gases and ozone-depleting substances. Some trade-offs will inevitably be required. Governments and ministries of health oversee Box 2.1 What does risk mean? • Risk can mean a probability, for example, the answer to the question: “What is the risk of getting HIV/AIDS from an infected needle?” • Risk can mean a factor that raises the probability of an adverse outcome. For example, major risks to child health include malnutrition, unsafe water and indoor air pollution. • Risk can mean a consequence. For example, what is the risk from driving while drunk? (answer: being in a car crash). • Risk can mean a potential adversity or threat. For example, is there risk in riding a motorcycle? In this report, the first two meanings are used. Risk is defined as a probability of an adverse health outcome, or a factor that raises this probability. Other important risk-related definitions are outlined below. • Prevalence of risk – the proportion of the population who are exposed to a particular risk. For example, the prevalence of smoking might be 25% in a particular population. • Relative risk – the likelihood of an adverse health outcome in people exposed to a particular risk, compared with people who are not exposed. For example, if people who smoke for a certain time are, on average, 15 times more likely to develop lung cancer than those who do not smoke, their relative risk is 15. • Hazard – an inherent property, for example of a chemical, that provides the potential for harm. • Population attributable risk – the proportion of disease in a population that results from a particular risk to health. • Attributable burden – the proportion of current disease or injury burden that results from past exposure. • Avoidable burden – the proportion of future disease or injury burden that is avoidable if current and future exposure levels are reduced to those specified by some alternative, or counterfactual, distribution. Sources: (1, 2)
The World Health Report 2002 overall population health and so, at the broadest level, need information from risk assess- ments that are comprehensive as well as being reliable, relevant and timely. Because the range of risks to health is almost limitless, it is essential for govemments to have a quanti tative approach to gauging their importance. Risks need to be defined and studied compre hensively irrespective of factors such as their place in a causal chain or the methods used (from the disciplines of the physical, natural, health, and social sciences) for their analysis. The following sections outline some of the different dimensions that should be considered. STANDARDIZED COMPARISONS AND COMMON OUTCOME MEASURES Ideally, the impact of eachrisk factor should be assessed in terms of a"common currency that incorporates loss of quality of life as well as loss of life years. The principal metric used this report is the daLy (disability-adjusted life year)-one DALY being equal to the loss ne healthy life year(13) a key initial question when assessing the impact of a risk to health is to ask"compared to what? " This report employs an explicit counterfactual approach, in which current distributions of risk factors are compared with some alternative, or counterfactual, distribu tion of exposure. Many different counterfactuals are potentially of interest To enhance com parability across risk factors, the basis for the results in Chapter 4 is the theoretical min risk distribution, that is exposure levels that would yield the lowest population risk(for example, no tobacco use by any members of a population). For the analysis of the costs and effects of interventions to reduce risk in Chapter 5, a related counterfactual is used-based on the burden that would exist in the absence of relevant interventions risk factor distri butions that are plausible, feasible and cost-effective will lie somewhere between the cur- rent risk factor levels and the related theoretical minimum. The envisaged shift from current to counterfactual scenarios has been termed the distributional transition(see Figure 2.1) In many instances, the counterfactual of most relevance will involve small to moderate distributional transitions(for example, 10%, 20%or 30%), as these are most likely to be feasible and cost-effective. These estimates are also less susceptible to the influence of arbitrary choices of theoretical minima, and are likely to be the most reliable, as the dose- response is often least certain at low exposure levels Figure 2. 1 Example of distributional transitions for blood pressure and for tobacco smoking Tobacco smoking Current level After 10%6 distributional transition e After 20%o distributional transition After 30%6 distributional transition 160170 Systolic blood pressure(mmHg Cigarettes per day
12 The World Health Report 2002 overall population health and so, at the broadest level, need information from risk assessments that are comprehensive as well as being reliable, relevant and timely. Because the range of risks to health is almost limitless, it is essential for governments to have a quantitative approach to gauging their importance. Risks need to be defined and studied comprehensively irrespective of factors such as their place in a causal chain or the methods used (from the disciplines of the physical, natural, health, and social sciences) for their analysis. The following sections outline some of the different dimensions that should be considered. STANDARDIZED COMPARISONS AND COMMON OUTCOME MEASURES Ideally, the impact of each risk factor should be assessed in terms of a “common currency” that incorporates loss of quality of life as well as loss of life years. The principal metric used in this report is the DALY (disability-adjusted life year) – one DALY being equal to the loss of one healthy life year (13). A key initial question when assessing the impact of a risk to health is to ask “compared to what?” This report employs an explicit counterfactual approach, in which current distributions of risk factors are compared with some alternative, or counterfactual, distribution of exposure. Many different counterfactuals are potentially of interest. To enhance comparability across risk factors, the basis for the results in Chapter 4 is the theoretical minimum risk distribution, that is exposure levels that would yield the lowest population risk (for example, no tobacco use by any members of a population). For the analysis of the costs and effects of interventions to reduce risk in Chapter 5, a related counterfactual is used – based on the burden that would exist in the absence of relevant interventions. Risk factor distributions that are plausible, feasible and cost-effective will lie somewhere between the current risk factor levels and the related theoretical minimum. The envisaged shift from current to counterfactual scenarios has been termed the distributional transition (see Figure 2.1). In many instances, the counterfactual of most relevance will involve small to moderate distributional transitions (for example, 10%, 20% or 30%), as these are most likely to be feasible and cost-effective. These estimates are also less susceptible to the influence of arbitrary choices of theoretical minima, and are likely to be the most reliable, as the dose– response is often least certain at low exposure levels. Blood pressure 0 4 5 6 1 2 3 7 8 90 110 150 170 100 120 140 160 Systolic blood pressure (mmHg) Population (%) Theoretical miminum Distributional transitions Current level Tobacco smoking 0 20 40 60 80 100 0 1-14 15-24 25-34 35+ Cigarettes per day Population (%) Current level After 10% distributional transition After 20% distributional transition After 30% distributional transition Theoretical minimum Figure 2.1 Example of distributional transitions for blood pressure and for tobacco smoking 130
Defining and Assessing Risks to Health ASSESSING PROTECTIVE AS WELL AS HAZARDOUS FACTORS Factors that affect risk of disease or injury are, of course, not all harmful Risk factor does have a negative connotation, but ideally a risk assessment should include a range of protective as well as hazardous risk factors. For example, this report considers the protective benefits of fruit and vegetable intake and physical activity by assessing people with low levels of these factors. The important role of protective factors in adolescent health is outlined in INCLUDING PROXIMAL AND DISTAL CAUSES isks to health do not occur in isolation. The chain of events leading to an adverse health outcome includes both proximal and distal causes- proximal factors act directly or almost directly to cause disease, and distal causes are further back in the causal chain and act via a number of intermediary causes(see Figure 2.2). The factors that lead to someone developing disease on a particular day are likely to have their roots in a complex chain of environmental events that may have begun years previously, which in turn were shaped by broader socioeconomic determinants. For example, society and culture are linked to certain drinking patterns, which in turn influence outcomes such as coronary heart disease via physiological processes such as platelet aggregation. Clearly, there are risks over which an individual has at least some control (for example, inactivity) and risks that mostly or entirely rest at a population or group level(for example, ambient air pollution). It is essential that the whole of the causal chain is considered in the assessment of risks to health. Indeed many risks cannot be disentangled in order to be considered in isolation, as they act at Box 2.2 Protective factors A growing body of cross-cultural evidence indi- health behaviours(e. g, proper diet and adequate Evidence from 25 developing countries, 25 cates that various psychological, social and be- exercise, and avoiding cigarettes, drugs, excessive European countries, Canada, Israel and the havioural factors are protective of health in alcohol and risky sexual practices) are also influ- United States shows that adolescents who re- adolescence and later life. Such protection facili- enced by psychosocial factors port having a positive connection to a trusted tates resistance to disease, minimizes and delays The presence of psychosocial factors in under- adult (parent or teacher) are committed to the emergence of disabilities, and promotes standing positive human health points to new di- school, have a sense of spirituality and exhibit a more rapid recovery from illness rections for research and practice. The biological significantly lower prevalence of risky behav- Among the psychosocial factors that have mechanisms through which psychosocial and be- iours. This is in addition to being more socially been linked to protection in adults are: an opti- havioural factors influence health are a flourish- competent and showing higher self-esteem mistic outlook on life with a sense of purpose and ing area of scientific inquiry: investigations in than adolescents without such a connection. direction, effective strategies for coping with affective neuroscience are relating emotional ex- Studies in the Us have shown that these pro- challenge, perceived control over life outcomes, perience to neural structures, function, dynamics tective factors also predict positive outcomes and expressions of positive emotion Epidemio- and their health consequences. There is a need for (remaining connected to school, engaging in logical studies have shown reduced morbidity greater emphasis in policy and practice on inter- more exercise and having healthy diets) while and delayed mortality among peoplewho are so- ventions built around the growing knowledge that diminishing negative behaviour(problem drink cially integrated. The quality of social relation- psychosocial factors protect health. ing, use of marijuana and other illicit drugs, and ships in the home(parent-child relations and Adolescence is a critical life stage when life- delinquent behaviour) spousal ties) and the workplace (employer- style choices are established, induding health- Protective factors promote positive behav- mployee relations and coworker connections) related behaviours with impacts throughout life. iours and inhibit risk behaviours, hence mitigat are now recognized as key influences on physi- Recent research has begun to focus on the role of ing the impacts of exposure to risk. Current cal and mental health. A growing literature un- protective factors in youth behaviour, comple- efforts to reduce risks in the lives of adolescents derscores the protective health benefits menting previous approaches concerned only with should be broadened to include the strength ssociated with persistently positive and emo- problems and risk taking ening of protective factors. tionally rewarding social relationships. Positive Sources: (14-19)
Defining and Assessing Risks to Health 13 ASSESSING PROTECTIVE AS WELL AS HAZARDOUS FACTORS Factors that affect risk of disease or injury are, of course, not all harmful. Risk factor does have a negative connotation, but ideally a risk assessment should include a range of protective as well as hazardous risk factors. For example, this report considers the protective benefits of fruit and vegetable intake and physical activity by assessing people with low levels of these factors. The important role of protective factors in adolescent health is outlined in Box 2.2. INCLUDING PROXIMAL AND DISTAL CAUSES Risks to health do not occur in isolation. The chain of events leading to an adverse health outcome includes both proximal and distal causes – proximal factors act directly or almost directly to cause disease, and distal causes are further back in the causal chain and act via a number of intermediary causes (see Figure 2.2). The factors that lead to someone developing disease on a particular day are likely to have their roots in a complex chain of environmental events that may have begun years previously, which in turn were shaped by broader socioeconomic determinants. For example, society and culture are linked to certain drinking patterns, which in turn influence outcomes such as coronary heart disease via physiological processes such as platelet aggregation. Clearly, there are risks over which an individual has at least some control (for example, inactivity) and risks that mostly or entirely rest at a population or group level (for example, ambient air pollution). It is essential that the whole of the causal chain is considered in the assessment of risks to health. Indeed, many risks cannot be disentangled in order to be considered in isolation, as they act at Box 2.2 Protective factors A growing body of cross-cultural evidence indicates that various psychological, social and behavioural factors are protective of health in adolescence and later life. Such protection facilitates resistance to disease, minimizes and delays the emergence of disabilities, and promotes more rapid recovery from illness. Among the psychosocial factors that have been linked to protection in adults are: an optimistic outlook on life with a sense of purpose and direction, effective strategies for coping with challenge, perceived control over life outcomes, and expressions of positive emotion. Epidemiological studies have shown reduced morbidity and delayed mortality among people who are socially integrated. The quality of social relationships in the home (parent–child relations and spousal ties) and the workplace (employer– employee relations and coworker connections) are now recognized as key influences on physical and mental health. A growing literature underscores the protective health benefits associated with persistently positive and emotionally rewarding social relationships. Positive health behaviours (e.g., proper diet and adequate exercise, and avoiding cigarettes, drugs, excessive alcohol and risky sexual practices) are also influenced by psychosocial factors. The presence of psychosocial factors in understanding positive human health points to new directions for research and practice. The biological mechanisms through which psychosocial and behavioural factors influence health are a flourishing area of scientific inquiry: investigations in affective neuroscience are relating emotional experience to neural structures, function, dynamics and their health consequences. There is a need for greater emphasis in policy and practice on interventions built around the growing knowledge that psychosocial factors protect health. Adolescence is a critical life stage when lifestyle choices are established, including healthrelated behaviours with impacts throughout life. Recent research has begun to focus on the role of protective factors in youth behaviour, complementing previous approaches concerned only with problems and risk taking. Evidence from 25 developing countries, 25 European countries, Canada, Israel and the United States shows that adolescents who report having a positive connection to a trusted adult (parent or teacher) are committed to school, have a sense of spirituality and exhibit a significantly lower prevalence of risky behaviours. This is in addition to being more socially competent and showing higher self-esteem than adolescents without such a connection. Studies in the US have shown that these protective factors also predict positive outcomes (remaining connected to school, engaging in more exercise and having healthy diets) while diminishing negative behaviour (problem drinking, use of marijuana and other illicit drugs, and delinquent behaviour). Protective factors promote positive behaviours and inhibit risk behaviours, hence mitigating the impacts of exposure to risk. Current efforts to reduce risks in the lives of adolescents should be broadened to include the strengthening of protective factors. Sources: (14–19)
The World Health Report 2002 different levels, which vary over time. An appropriate range of policies can be generated only if a range of risks is assessed There are many trade-offs between assessments of proximal and distal causes. As one moves further from the direct, proximal causes of disease there can be a decrease in causal certainty and consistency, often accompanied by increasing complexity. Conversely, distal causes are likely to have amplifying effects- they can affect many different sets of proximal causes and so have the potential to make very large differences(20). In addition, many distal risks to health, such as climate change or socioeconomic disparity, cannot ppropriately be defined at the individual level. A population s health may also reflect more than a simple aggregation of the risk factor profile and health status of its individual members, being a collective characteristic and a public good that in turn affects the health status of its Research into the different levels of risks should be seen as complementary. There is considerable importance in knowing the population-level determinants of major proximal risks to health such as smoking. Similarly, there is value in knowing the mechanisms through which distal determinants operate. Understanding both proximal and distal risks requires contributions from different scientific traditions and different areas of health impact environmental, communicable, noncommunicable, injury, and so on, and as a result different intellectual tools and methods, including those of health, physical and social sciences. This in turn requires consideration of the context of particular risks: some are likely always to have negative health effects (for example, tobacco use) while others may have a role that changes from setting to setting(for example, breastfeeding protects against diarrhoeal isease, to an extent that depends on the prevalent patterns of diarrhoea). Also, the same risk can be measured and quantified at various levels depending on measurement technology Figure 2.2 Causal chains of exposure leading to disease socioeconomIc physiological Outcomes causes Causes Prevention Treatment Treatment of infectious disease can lead to prevention of further cases if it interrupts transmission. nomic causes include income, education and occupation, all of which affect levels of proximal factors such as and alcohol intake; these interact with physiological and pathophysiological causes, such pressure, cholesterol levels and glucose metabolism, to cause cardiovascular disease such as stroke or coronary heart disease. The sequelae include death and disability, such as angina or hemiplegia
14 The World Health Report 2002 different levels, which vary over time. An appropriate range of policies can be generated only if a range of risks is assessed. There are many trade-offs between assessments of proximal and distal causes. As one moves further from the direct, proximal causes of disease there can be a decrease in causal certainty and consistency, often accompanied by increasing complexity. Conversely, distal causes are likely to have amplifying effects – they can affect many different sets of proximal causes and so have the potential to make very large differences (20). In addition, many distal risks to health, such as climate change or socioeconomic disparity, cannot appropriately be defined at the individual level. A population’s health may also reflect more than a simple aggregation of the risk factor profile and health status of its individual members, being a collective characteristic and a public good that in turn affects the health status of its members (21). Research into the different levels of risks should be seen as complementary. There is considerable importance in knowing the population-level determinants of major proximal risks to health such as smoking. Similarly, there is value in knowing the mechanisms through which distal determinants operate. Understanding both proximal and distal risks requires contributions from different scientific traditions and different areas of health impact: environmental, communicable, noncommunicable, injury, and so on, and as a result different intellectual tools and methods, including those of health, physical and social sciences. This in turn requires consideration of the context of particular risks: some are likely always to have negative health effects (for example, tobacco use) while others may have a role that changes from setting to setting (for example, breastfeeding protects against diarrhoeal disease, to an extent that depends on the prevalent patterns of diarrhoea). Also, the same risk can be measured and quantified at various levels depending on measurement technology Distal socioeconomic causes Proximal causes Physiological and pathophysiological causes Outcomes Sequelae Prevention Treatmenta Figure 2.2 Causal chains of exposure leading to disease a Treatment of infectious disease can lead to prevention of further cases if it interrupts transmission. D1 P1 Pa1 O1 S1 D2 P2 Pa2 O2...n S2 D3...n P3...n Pa3...n S3...n An example: Distal socioeconomic causes include income, education and occupation, all of which affect levels of proximal factors such as inactivity, diet, tobacco use and alcohol intake; these interact with physiological and pathophysiological causes, such as blood pressure, cholesterol levels and glucose metabolism, to cause cardiovascular disease such as stroke or coronary heart disease. The sequelae include death and disability, such as angina or hemiplegia
Defining and Assessing Risks to Health and policy needs. For example, measuring iodine levels in food and in the environment requires different tools and the results have different implications When distal exposures operate through different levels of risk factors, their full impact hay not be captured in traditional regression analysis methods in which both proximal and distal variables are included. More complex multilevel models and characterization of causal webs of interactions among risk factors may lead to more appropriate estimates, as well facilitating estimation of the effect of simultaneous changes in two or more risk factor distributions. Some examples are shown later in the report. Risk factors can also be separated from outcomes in time, sometimes by many decades. ox 2.3 shows how disadvantage can be accumulated across the life course ASSESSING POPULATION-WIDE RISKS AS WELL AS IGH-RISK INDIVIDUALI Many risks to health are widely distributed in the population, with individuals differing the extent of their risk rather than whether they are at risk or not. Binary categorization into"exposed"and"unexposed"can substantially underestimate the importance of continuous risk factor-disease relationships Consequently, much of this report estimates the effects of shifting distributions of exposures by applying a counterfactual approach, that is, by comparing the burden caused by the observed risk factor distribution with that expected from some alternative, or counterfactual, distribution. This approach allows assessment of population-wide interventions(see Box 2.4 and Figure 2.3) INCLUDING RISKS THAT ACT TOGETHER TO CAUSE DISEASE Many risks to health act jointly to cause disease or injury, and this has important imp cations for prevention opportunities, as outlined in Box 2.5. This report presents estimates of the individual effects of different selected risks to health, followed by analyses of the joint effect of selected clusters of risks Box 2.3 Risks to health across the life course In recent years, a life-course approach to the cognitive development, which in turn may affect effects of premature birth. The associations may study of health and illness-which suggests that health and labour-market success later in life. The be a consequence of "programming, whereby exposure to disadvantageous experiences and impact of living and working environments-and a stimulus or insult at a critical, sensitive period iironments accumulates throughout life and lifestyle factors such as smoking -on health in- of early life has permanent effects on structure, increases the risk of illness and premature death equalities has long been recognized Cumulative physiology and metabolism. Programming of has helped to explain the existence of wide differential lifetime exposure to health-damaging the fetus may result from adaptations invoked socioeconomic differentials in adult morbidity or health-promoting environments appears to be when the maternal-placental nutrient supply and mortality rates. the main explanation for observed variations in fails to match the fetal nutrient demand. Al- Chronic illness in childhood, more common health and life expectancy by socioeconomic status. though the influences that impair fetal devel- among children of manual workers, can have Disadvantage may begin even before birth: low opment and programme adult cardiovascul long-term consequences both for health and birth weight is associated with increased rates of disease remain to be defined, there are strong socioeconomic circumstances in later life. Slow coronary heart disease, stroke, hypertension and pointers to the importance of maternal growth in childhood (short stature for age and non-insulin-dependent diabetes. These associa- body composition and dietary balance during sex) is an indicator of early disadvantage. Early tions extend across the normal range of birth pregnancy material and psychosocial disadvantage may also weight and depend on lower birth weights in re- have an adverse impact on psychological and lation to the duration of gestation rather than the Sources: (22-24)
Defining and Assessing Risks to Health 15 and policy needs. For example, measuring iodine levels in food and in the environment requires different tools and the results have different implications. When distal exposures operate through different levels of risk factors, their full impact may not be captured in traditional regression analysis methods in which both proximal and distal variables are included. More complex multilevel models and characterization of causal webs of interactions among risk factors may lead to more appropriate estimates, as well as facilitating estimation of the effect of simultaneous changes in two or more risk factor distributions. Some examples are shown later in the report. Risk factors can also be separated from outcomes in time, sometimes by many decades. Box 2.3 shows how disadvantage can be accumulated across the life course. ASSESSING POPULATION-WIDE RISKS AS WELL AS HIGH-RISK INDIVIDUALS Many risks to health are widely distributed in the population, with individuals differing in the extent of their risk rather than whether they are at risk or not. Binary categorization into “exposed” and “unexposed” can substantially underestimate the importance of continuous risk factor–disease relationships. Consequently, much of this report estimates the effects of shifting distributions of exposures by applying a counterfactual approach, that is, by comparing the burden caused by the observed risk factor distribution with that expected from some alternative, or counterfactual, distribution. This approach allows assessment of population-wide interventions (see Box 2.4 and Figure 2.3). INCLUDING RISKS THAT ACT TOGETHER TO CAUSE DISEASE Many risks to health act jointly to cause disease or injury, and this has important implications for prevention opportunities, as outlined in Box 2.5. This report presents estimates of the individual effects of different selected risks to health, followed by analyses of the joint effect of selected clusters of risks. In recent years, a life-course approach to the study of health and illness – which suggests that exposure to disadvantageous experiences and environments accumulates throughout life and increases the risk of illness and premature death – has helped to explain the existence of wide socioeconomic differentials in adult morbidity and mortality rates. Chronic illness in childhood, more common among children of manual workers, can have long-term consequences both for health and socioeconomic circumstances in later life. Slow growth in childhood (short stature for age and sex) is an indicator of early disadvantage. Early material and psychosocial disadvantage may also have an adverse impact on psychological and cognitive development, which in turn may affect health and labour-market success later in life. The impact of living and working environments – and lifestyle factors such as smoking – on health inequalities has long been recognized. Cumulative differential lifetime exposure to health-damaging or health-promoting environments appears to be the main explanation for observed variations in health and life expectancy by socioeconomic status. Disadvantage may begin even before birth: low birth weight is associated with increased rates of coronary heart disease, stroke, hypertension and non-insulin-dependent diabetes. These associations extend across the normal range of birth weight and depend on lower birth weights in relation to the duration of gestation rather than the effects of premature birth. The associations may be a consequence of “programming”, whereby a stimulus or insult at a critical, sensitive period of early life has permanent effects on structure, physiology and metabolism. Programming of the fetus may result from adaptations invoked when the maternal–placental nutrient supply fails to match the fetal nutrient demand. Although the influences that impair fetal development and programme adult cardiovascular disease remain to be defined, there are strong pointers to the importance of maternal body composition and dietary balance during pregnancy. Sources: (22–24). Box 2.3 Risks to health across the life course
The World Health Report 2002 USING BEST AVAILABLE EVIDENCE TO ASSESS CERTAIN AND PROBABLE RISKS TO HEALTH It is important in any risk assessment to review quantitatively the best available evi- dence for both"definite"and"probable"risks. Estimation of the potential impact of a health hazard can never wait until perfect data are available, since that is unlikely to occur. Timeli- ness is essential. This area can be a source of tension between scientists and policy-makers tainty or certainty when, in fact, there are different degrees of uncertainty and disage However, arguments are often clouded by the use of dichotomies -assertions of und ment about tolerable thresholds. Similarly, it may be asserted that there are no data when some indirect data are available, or at least the range of levels in other parts of the world is known. For example, in estimating fruit and vegetable intake for countries with no known surveys on this topic, upper and lower ranges can be estimated from surveys undertaken elsewhere, and food sales and agricultural data can be used to produce indirect estimates that occupy a narrower range. Internal consistency can help put ranges on uncertainty: for example, mortality rates, population numbers and birth rates should be internally consist ent, and reliable estimates for some of these components will put bounds on the uncer- tainty of the others. However, as outlined earlier, the sum of causes is unbounded and so internal consistency checks cannot be performed in assessments of different risks to health Strategies to minimize this problem include full documentation of data sources, methods and assumptions, extensive peer review, explicit assessments of causality, and quantitative estimates of other uncertainty Box 2. 4 Population-wide strategies for prevention It makes little sense to expect individuals to behave differently from their peers; it is more appropriate to seek a general change in behavioural norms and in the circumstances which facilitate their adoption. "gEoffrey Rose, 1992. population have major implications for strate- more cardiovascular events than the hypertensive might seek to identify and target individuals gies of prevention. Geoffrey Rose observed, like minority. While a high-risk approach may appear with three or more risk factors(such as a numbe others before and since, that for the vast major- more appropriate to the individuals and their phy- of moles, blonde or auburn hair, previous sun- o.of diseases"nature presents us with a process sicians, it can only have a limited effect at a burn, and a family history of skin cancer).How- or continuum, not a dichotomy. Risk typically in- population level. It does not alter the underlying ever, only 24% of cases of melanoma occur in creases across the spectrum of a risk factor. Use causes of illness, relies on having adequate power this 9% of the population, so a targeted ap- of dichotomous labels such as"hypertensive"and to predict future disease, and requires continued proach would succeed in identifying those at normotensive"are therefore not a description and expensive screening for new high-risk indi- high risk but would do little for population lev- of the natural order, but rather an operational viduals els of melanoma% of cases occur in the convenience. Following this line of thought, it In contrast, population-based strategies that 58%of the population with at least one risk fac- becomes obvious that the deviant minority(e.g. seek to shift the whole distribution of risk factors tor a population-wide strategy would seek to hypertensives)who are considered to be at high have the potential to control population incidence. make sun protection a social norm, so that the risk are only part of a risk continuum, rather than Such strategies aim to make healthy behaviours whole population is less exposed to risk. a distinct group. This leads to one of the most and reduced exposures into social norms and thus These approaches are complementary: a fundamental axioms in preventive medicine. "a lower the risk in the entire population. The poten- population approach can work to improve and large number of people exposed to a small risk tial gains are extensive, but the challenges are extend the coverage of a high-risk approach. A may generate many more cases than a small great as well -a preventive measure that brings key challenge is finding the right balance be- number exposed to high risk Rose pointed out large benefits to the community appears to offer tween population-wide and high-risk ap- that wherever this axiom applies, a preventive little to each participating individual. This may proaches Rose concluded that this will require rategy focusing on high-risk individuals will adversely affect motivation of the population at a wider world view of ill-health, its causes and deal only with the margin of the problem and large(known as the"prevention paradox? solutions, and will lead to acknowledgement will not have any impact on the large proportion Although most often applied to cardiovascu- that the primary determinants of disease are of disease occurring in the large proportion of lar disease prevention, a population-wide ap- mainly economic and social, and therefore rem- people who are at moderate risk. For example, proach is often relevant in other areas. For example, edies must also be economic and social
16 The World Health Report 2002 USING BEST AVAILABLE EVIDENCE TO ASSESS CERTAIN AND PROBABLE RISKS TO HEALTH It is important in any risk assessment to review quantitatively the best available evidence for both “definite” and “probable”risks. Estimation of the potential impact of a health hazard can never wait until perfect data are available, since that is unlikely to occur. Timeliness is essential. This area can be a source of tension between scientists and policy-makers. However, arguments are often clouded by the use of dichotomies – assertions of uncertainty or certainty when, in fact, there are different degrees of uncertainty and disagreement about tolerable thresholds. Similarly, it may be asserted that there are no data when some indirect data are available, or at least the range of levels in other parts of the world is known. For example, in estimating fruit and vegetable intake for countries with no known surveys on this topic, upper and lower ranges can be estimated from surveys undertaken elsewhere, and food sales and agricultural data can be used to produce indirect estimates that occupy a narrower range. Internal consistency can help put ranges on uncertainty: for example, mortality rates, population numbers and birth rates should be internally consistent, and reliable estimates for some of these components will put bounds on the uncertainty of the others. However, as outlined earlier, the sum of causes is unbounded and so internal consistency checks cannot be performed in assessments of different risks to health. Strategies to minimize this problem include full documentation of data sources, methods and assumptions, extensive peer review, explicit assessments of causality, and quantitative estimates of other uncertainty. Box 2.4 Population-wide strategies for prevention “It makes little sense to expect individuals to behave differently from their peers; it is more appropriate to seek a general change in behavioural norms and in the circumstances which facilitate their adoption.” – Geoffrey Rose, 1992. The distribution and determinants of risks in a population have major implications for strategies of prevention. Geoffrey Rose observed, like others before and since, that for the vast majority of diseases “nature presents us with a process or continuum, not a dichotomy”. Risk typically increases across the spectrum of a risk factor. Use of dichotomous labels such as “hypertensive” and “normotensive” are therefore not a description of the natural order, but rather an operational convenience. Following this line of thought, it becomes obvious that the “deviant minority” (e.g. hypertensives) who are considered to be at high risk are only part of a risk continuum, rather than a distinct group. This leads to one of the most fundamental axioms in preventive medicine: “a large number of people exposed to a small risk may generate many more cases than a small number exposed to high risk”. Rose pointed out that wherever this axiom applies, a preventive strategy focusing on high-risk individuals will deal only with the margin of the problem and will not have any impact on the large proportion of disease occurring in the large proportion of people who are at moderate risk. For example, people with slightly raised blood pressure suffer more cardiovascular events than the hypertensive minority. While a high-risk approach may appear more appropriate to the individuals and their physicians, it can only have a limited effect at a population level. It does not alter the underlying causes of illness, relies on having adequate power to predict future disease, and requires continued and expensive screening for new high-risk individuals. In contrast, population-based strategies that seek to shift the whole distribution of risk factors have the potential to control population incidence. Such strategies aim to make healthy behaviours and reduced exposures into social norms and thus lower the risk in the entire population. The potential gains are extensive, but the challenges are great as well – a preventive measure that brings large benefits to the community appears to offer little to each participating individual. This may adversely affect motivation of the population at large (known as the “prevention paradox”). Although most often applied to cardiovascular disease prevention, a population-wide approach is often relevant in other areas. For example, a high-risk strategy for melanoma prevention might seek to identify and target individuals with three or more risk factors (such as a number of moles, blonde or auburn hair, previous sunburn, and a family history of skin cancer). However, only 24% of cases of melanoma occur in this 9% of the population, so a targeted approach would succeed in identifying those at high risk but would do little for population levels of melanoma – 75% of cases occur in the 58% of the population with at least one risk factor. A population-wide strategy would seek to make sun protection a social norm, so that the whole population is less exposed to risk. These approaches are complementary: a population approach can work to improve and extend the coverage of a high-risk approach. A key challenge is finding the right balance between population-wide and high-risk approaches. Rose concluded that this will require a wider world view of ill-health, its causes and solutions, and will lead to acknowledgement that the primary determinants of disease are mainly economic and social, and therefore remedies must also be economic and social. Sources: (20, 25, 26)
Defining and Assessing Risks to Health 17 Figure 2.3 The importance of population distributions of exposure 5100121517520 Systolic blood pressure(mmHg) Total cholesterol(mmol/ Mean systolic blood pressure(mmHg) Mean cholesterol (mmol) Mean body mass index (kg/m2 Source: Asia Pacific Cohort Studies Collaboration od pressure, cholesterol and body mass ind a consequence, lower mean population levels are associated with dramatically reduced proportions of the population that are hypertensive, hypercholestero bese. Rose G. The strategy of preventive medicine. Oxford: Oxford University Press: 1992. Extrapolations and indirect methods are often justified where there are implications in laying estimates of health impacts and subsequent policy choices. If decisions await improved estimates, then not producing best current estimates(with appropriate indications of uncertainty) may mean inappropriate inaction. Altematively, decisions may be made with other even more uncertain information, where the uncertainty will often be implicit Nonetheless, there can be costs in making incorrect estimates and, ultimately, it is largely a matter of judgement to decide when data are adequate Whenever possible, the level of uncertainty should be reported explicitly in risk assessments. There is still considerable debate about how this is best done in a policy relevant way, given the inevitable play of chance and uncertainties in both the likelihood of causality and the validity of the estimation methods. Major uncertainty should result in calls for more data. In particular, data are often absent or scanty in the developing countries, where many risks are highest and more information could produce the greatest gains in knowledge. The management of highly uncertain risks and the use of the precautionary principle are discussed in Chapter 6 ASSESSING AVOIDABLE AS WELL AS ATTRIBUTABLE BURDEN o risk assessments to date have typically used only attributable risk estimates, basically Dressing the question"what proportion of current burden is caused by the accumulated effects of all prior exposure? "However, often a more policy-relevant question is"what are the likely future effects of partial removal of current exposure? "Two key developments are therefore needed: an explicit focus on future effects and on less-than-complete risk factor
Defining and Assessing Risks to Health 17 Extrapolations and indirect methods are often justified where there are implications in delaying estimates of health impacts and subsequent policy choices. If decisions await improved estimates, then not producing best current estimates (with appropriate indications of uncertainty) may mean inappropriate inaction. Alternatively, decisions may be made with other even more uncertain information, where the uncertainty will often be implicit. Nonetheless, there can be costs in making incorrect estimates and, ultimately, it is largely a matter of judgement to decide when data are adequate. Whenever possible, the level of uncertainty should be reported explicitly in risk assessments. There is still considerable debate about how this is best done in a policyrelevant way, given the inevitable play of chance and uncertainties in both the likelihood of causality and the validity of the estimation methods. Major uncertainty should result in calls for more data. In particular, data are often absent or scanty in the developing countries, where many risks are highest and more information could produce the greatest gains in knowledge. The management of highly uncertain risks and the use of the precautionary principle are discussed in Chapter 6. ASSESSING AVOIDABLE AS WELL AS ATTRIBUTABLE BURDEN Risk assessments to date have typically used only attributable risk estimates, basically addressing the question “what proportion of current burden is caused by the accumulated effects of all prior exposure?” However, often a more policy-relevant question is “what are the likely future effects of partial removal of current exposure?” Two key developments are therefore needed: an explicit focus on future effects and on less-than-complete risk factor 75 100 125 150 175 200 2 3 4 5 6 7 8 9 15 20 25 30 35 Mean systolic blood pressure (mmHg) Mean cholesterol (mmol/l) Mean body mass index (kg/m2) 0 5 10 15 20 25 30 35 40 45 110 120 130 140 150 0 5 10 15 20 25 4.0 4.5 5.0 5.5 6.0 0 5 10 15 20 25 30 21 22 23 24 25 26 27 Population with SBP > 160 mmHg (%) Population with cholesterol > 7 mmol/l (%) Population with BMI >30 kg2/m (%) Population (%) Population (%) Population (%) Systolic blood pressure (mmHg) Total cholesterol (mmol/l) Body mass index (kg/m2) Figure 2.3 The importance of population distributions of exposure Source: Asia Pacific Cohort Studies Collaboration. Note: The distributions of blood pressure, cholesterol and body mass index are plotted for 14 different populations in the top panel, showing that all are bell-shaped. As a consequence, lower mean population levels are associated with dramatically reduced proportions of the population that are hypertensive, hypercholesterolaemic or obese. Rose G. The strategy of preventive medicine. Oxford: Oxford University Press; 1992