Risk: Looking Forward

Risk generally refers to the probability of some untoward event. In this chapter, the term risk is used in a more restricted sense to indicate the probability that people who are exposed to certain "risk factors" will subsequently develop a particular disease more often than similar people who are not exposed

• This chapter• describes how investigators obtain estimates

of risk by observing the relationship between exposure to possible risk factors and the subsequent incidence of disease.

• To describe methods that determine risk by following groups into the future.

• To discuss several ways of comparing risks as they affect individuals and populations

RISK FACTORS

• Characteristics associated with an increased risk of becoming diseased are called risk factors.

• Exposure to a risk factor means that a person, before becoming ill, has come in contact with or has manifested the factor in question.

• Exposure can take place at a single point in time, as when a community is exposed to radiation during a nuclear accident.

• Contuct with risk factor for chronic disease

• For example,• having the haplotype HLA-B27 greatly increases

one's risk of acquiring the spondylarthropathies. Work on the Human Genome Project has identified many other diseases for which specific genes are risk factors, including colon and breast cancer, osteoporosis, and amyotropic lateral sclerosis.

• Other risk factors, such as infectious agents, drugs, and toxins, are found in the physical environment

• Still others are part of the social environment. For example, bereavement after the loss of a spouse, change in daily routines, and crowding all have been shown to increase rates of disease-not only emotional illness but physical illness as well.

• Some of the most powerful risk factors are behavioral; examples are smoking, drinking alcohol to excess, driving without seat belts, engaging in unsafe sex, eating too much, and exercising too little.

• Exposure to a risk factor means that a person, before becoming ill, has come in contact with or has manifested the factor in question

• Exposure can take place at a single point in time• contact with risk factors for chronic disease

takes place over a period of time• Although the various measures of dose tend to

be related to one another, some may show an exposure-disease relationship, whereas others may not

RECOGNIZING RISK

• Large risks associated with effects that occur rapidly after exposure are easy for anyone to recognize:Chikenpox, sunborn… because

• These conditions follow exposure relatively rapidly and with obvious effects.

• Most morbidity or mortality is caused by chronic diseases for which the relationships between exposure and disease are far less obvious

Long Latency

• Many chronic diseases have long latency periods between exposure to a risk factor and the first manifestations of disease

• When patients experience the consequence of exposure to a risk factor years later, the original exposure may be all but forgotten and the link between exposure and disease obscured

Common Exposure to Risk Factors

• Many risk factors, such as cigarette smoking or eating a diet high in cholesterol and saturated fats, have become so common in western societies that for many years it was difficult to discern their dangers.

• Using cross-national studies or investigating special subgroups- Mormons

Low Incidence of Disease

• The onset of most diseases. even ones thought to be "common," is actually uncommon. Thus, although lung cancer is the most common cause of cancer deaths in Americans, the yearly incidence of lung cancer, even in people who have smoked heavily for 25 years, is 2 to 3 in 1000

• To draw conclisions about risks from such infrequent events.

Small Risk

• Most chronic diseases are caused by several risk factors acting together. The risk associated with any one of them, taken alone, is small. To detect this risk, a large number of people must be studied to observe a difference in disease rates between exposed and unexposed persons. This is true even when both the risk factor and the disease occur relatively frequently

Common Risk

• When a disease is common such as heart disease, cancer, or stroke and some of the risk factors for it are already known,

• it becomes difficult to distinguish a new risk factor from the others.

• There may be less incentive to look for new risk factors

Multiple Causes and Effects

• There is usually not a close, one-to-one relationship between a risk factor and a particular disease

• There relationship between hypertension and congestive failure

• For all these reasons, individual clinicians are rarely in a position to recognize, let alone confirm, associations between exposure and chronic diseases

• The medical literature

USES OF RISK

• In clinical medicine, knowledge of risk factors can be used in several different ways

• Risk Factors Predict Future Disease• Risk Factors May or May Not Be Causal• Risk Factors Help Establish Pretest Disease

Probability for Diagnostic Testing• Risk Stratification for Screening Programs• Removing Risk Factors May Prevent Disease

Risk Factors Predict Future Disease

• Risk factors are used, first and foremost, to predict the occurrence of disease. The best available information for predicting disease in an individual person is past experience with a large number of people who have a similar risk factor. How well the prediction applies to the individual depends on the similarity of the individual person to the group and is, in any case, never perfect.

Risk Factors May or May Not Be Causal

• The search for risk factors usually is a search for causes of disease. In clinical medicine, physicians are more comfortable with immediate causes of disease infectious, physiologic, or anatomic changes leading to sickness such as a coronavirus causing SARS or hypocalcemia leading to seizures. But distant causes, more remote from a condition, may be important in the causal pathway.

• Low birth- weight infants

Risk Factors May or May Not Be Causal

• It is important to remember that just because risk factors predict disease, it does not necessarily follow that they cause disease. A risk factor may predict a disease outcome indirectly, by virtue of an association with some determinant of disease

• A risk factor that is not a cause of disease is called a marker of disease, because it "marks" the increased probability of disease

Risk Factors Help Establish Pretest Disease

Probability for Diagnostic Testing• Knowledge of risk can be used in the

diagnostic process, since the presence of a risk factor increases the pretest probability of disease among patients, which is one way of improving the positive predictive value of a diagnostic test. However, in individual patients, risk factors usually are not as strong a predictor of disease as are clinical findings of early disease

• The absence of a very strong risk factor may help to rule out disease. Thus, it is reasonable to consider mesothelioma in the differential diagnosis of a pleural mass in a parient who is an asbestos worker. But mesothelioma is a much less likely diagnosis for the patient who has never been exposed to asbestos.

Risk Stratification for Screening Programs

• Knowledge of risk factors can be used to improve the efficiency of screening programs by selecting subgroups of patients at substantially increased risk.

• screening for colorectal cancer is recommended for the general population starring at age 50. However, people with a first-degree relative with a history of colorectal cancer are at increased risk for the disease, and several expert groups suggest that screening these people should begin at age 40.

Removing Risk Factors May Prevent Disease

• If a risk factor is also a cause of disease, removing it can prevent disease whether or not the mechanism by which the disease develops is known. Some of the classic successes in the history of epidemiology illustrate this point.

• Chlera• HIV

STUDIES OF RISK

• The most powerful way to determine whether exposure to a potential risk factor results in an increased risk of disease is to conduct an experiment in which the researcher determines who is exposed. People currently without disease are divided into groups of equal susceptibility to the disease in question. One group is exposed to the purported risk factor and the other is not, but the groups otherwise are treated the same

When Experiments Are Not Possible

• The effects of most risk factors in humans cannot be studied with experimental studies. Consider some of the risk questions that concern us today:……

• Are inactive people at increased risk for cardiovascular disease, everything else being equal? Do cellular phones cause brain cancer?

• Does a high-fat diet increase the risk of breast cancer?• it is usually not possible to conduct an experiment.• Unethical, having their diets and behaviors, difficult

and expensive

• Clinical studies in which the researcher gathers data by simply observing events as they happen, without playing an active part in what takes place, are called observational studies. Most studies of risk are observational studies and are either cohort studies

Cohorts

• the term cohort is used to describe a group of people who have something in common when they are first assembled and who are then observed for a period of time to see what happens to them

• 1. They do not have the disease in question at the time they are assembled.

• 2. They should be observed over a meaningful period of time in the natural history of the disease in question. This is so that there will be sufficient time for the risk to be expressed.

• 3. Members of the cohort should be observed over the full period of follow-u p. To the extent that people drop our of the study and their reasons for dropping out are related in some way to the outcome, the information provided by an incomplete cohort can misrepresent the true stare of affairs

Cohort Studies

• In a cohort study , a group of people is assem bled, none of whom has experienced the outcome of interest, but all of whom could experience it.

• Upon entry into the study, people in the cohort are classified according to those

characteristics that might be related to outcome

• For each possible risk factor, members of the cohort are classified either as exposed or not exposed

• Other names for cohort studies are longitudinal studies, which emphasize that patients are followed over time, prospective studies, which imply the forward direction in which the patients are pursued, and incidence studies, which call attention to the basic measure of new disease events over time.

Prospective and Historical Cohort Studies

• The cohort can be assembled in the present and followed into the future (a prospective cohort study)

• or it can be identified from past records and followed forward from that time up to the present (a historical cohort study or retrospective cohort study).

Case-Cohort Studies• In a case-cohort study, all exposed people are

included in the study and followed for some outcome of interest.

• Only a small random sample of unexposed people is studied.• For efficiency, the group of unexposed people is

"enriched" with chose who subsequently suffer the outcome of interest.

• The results are then adjusted to reflect the sampling fractions used to obtain the sample.

Advantages and Disadvantages ofCohort Studies

• The potential for difficulties with The quality of data is different for the Two.

• data for historical cohorts are often gathered for other purposes-usually as part of medical

records for patient care.• The data in historical cohort studies may• not be of sufficient quality for rigorous research.

WAYS TO EXPRESS ANDCOMPARE RISK

• The basic expression of risk is incidence• In cohort studies, the incidence of disease is

compared in two or more groups that differ in exposure to a possible risk factor

• To compare risks, several measures of the association between exposure and disease, called measures of effect, are commonly used.

Absolute Risk

• Absolute risk is the probability of an event in a population under study.

• Absolute risk is the best way for individual patients and clinicians to understand how risk factors may affect their lives.

Attributable Risk• One might ask, "What is the additional risk

(incidence) of disease following exposure, over and above that experienced by people who are not exposed?"

• The answer is expressed as attributable risk,• Attributable risk is the additional incidence of disease related to exposure, taking into account the

background incidence of disease from other causes.• attributable risk is also called risk difference,• the differences between two absolute risks.• Risk difference

Relative Risk

• one might ask, "How many times are exposed persons more likely to get the disease relative to nonexposed persons?“

• relative risk or risk ratio, is the ratio of incidence in exposed persons to incidence in nonexposed persons.

• Because relative risk indicates the suength of the association between exposure and disease, it is a useful measure of effect for studies of disease etiology.

• Relative risk says nothing about the magnitude of the attributable risk, which depends on absolute as well as relative risk.

• with a large relative risk, the attributable risk might be quite small if the disease is uncommon

Interpreting Estimates of Individual Risk

• The appropriate expression of risk depends on what question is being asked

• attributable risk represents the additional probability of disease in those exposed, it is a more meaningful expression of risk for individ uals than is relative risk.

• relative risk is more useful for expressing the strength of a causal relationship.

Population Risk

• Another way of looking at risk is to ask, "How much does a risk factor contribute to the overall rates of disease in groups of people, ra ther than individuals?“

• This information is useful for deciding which risk factors are particularly important and which are trivial to the overall health of a community

• This can inform those in policy positions about how to choose priorities for the deployment of health-care resources

• If a relatively weak risk factor is very prevalent in a community, it could account for more disease than a very strong, bur rare, risk factor

• Population attributable risk is the product of the attributable risk and the prevalence of exposure to the risk factor in a population

• the fraction of disease occurrence in a population associated with a particular risk factor: the population-attributable fraction

• the population-attributable fraction obtained by dividing the population-attributable risk by the total incidence of disease in the population.