Transcript Risk generally refers to the probability of some untoward

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 of
Cohort 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 AND
COMPARE 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.