1

Personal View
Lifetime risk of stroke and dementia: current concepts, and
estimates from the Framingham Study
Sudha Seshadri, Philip A Wolf
Lancet Neurol 2007; 6: 1106–14
Department of Neurology,
Boston University School of
Medicine, Boston,
Massachusetts and the NHLBI’s
Framingham Heart Study,
Framingham, MA, USA
(S Seshadri MD, PA Wolf MD)
Correspondence to:
S Seshadri, Department of
Neurology, Boston University
School of Medicine,
715 Albany Street, B-602,
Boston, MA 02118-2526, USA
[email protected]
1106
The main neurological causes of morbidity and mortality are stroke and dementia. We contend that the most relevant
and readily communicated risk estimate for stroke and dementia is lifetime risk, which is the probability of someone
of a given age and sex developing a condition during their remaining lifespan. Lifetime risk estimates describe the
population burden; however, they can be refined with risk-stratified models to enable individual risk prediction.
Community-based data on a group of North Americans of European descent indicate that the lifetime risk of stroke
for a middle-aged woman is 1 in 5 and for a middle-aged man is 1 in 6. The lifetime risk of stroke was equal to the
lifetime risk of dementia and equal to or greater than the lifetime risk of Alzheimer’s disease (1 in 5 and 1 in 10 for
women and men, respectively), and the lifetime risk of stroke or dementia was greater than 1 in 3. Thus, the lifetime
burden attributable to common neurological disease is immense.
Introduction
In the past century, the worldwide average life expectancy
at birth rose sharply from less than 40 years in 1900 to
more than 65 years in 1975; more of the population now
live to be 80 years or older. A corollary of increased life
expectancy is an increase in the individual and population
burden of age-related diseases. Stroke and dementia are
the most widely feared age-related neurological diseases,
and are also the only neurological disorders listed in the
ten leading causes of disease burden.1 Stroke is the third
highest cause of mortality and the highest neurological
cause of disability-adjusted life-years lost in the developed
world; in developing countries that have a low overall
mortality rate, stroke ranks second in disability-adjusted
life-years lost.1 The 2007 statistical update from the
American Heart Association estimates the lifetime risk
of stroke and other cardiovascular diseases on the basis
of data from the Framingham Heart Study.2 But what is
the lifetime risk of a disease, and do we need this
additional descriptive statistic for stroke when we already
have the widely used measures of incidence, prevalence,
relative risk, and cause-specific mortality?
People should be aware of the risk of a disease at some
point in their life; similarly, such statistics are essential
for public health planners to estimate the projected
disease burden in a population during its expected
lifespan. The estimation of lifetime risk enables a longterm perspective, which is particularly important for
conditions such as stroke where exposure to risk factors
in midlife can alter the incidence of disease later.3
The lifetime risk of a condition can be defined as
the probability that a person who is currently free of the
condition will acquire it at some time during
the remainder of their expected lifespan. The concept of
lifetime risk was pioneered by cancer epidemiologists4–6
and later extended to chronic bone7 and mental health
disorders.8 The term lifetime risk was used to describe
the diagnosis of a specific disease (such as breast cancer5
or Alzheimer’s disease [AD]9), a specific disease event
(such as hip fracture10 or stroke11), or the development of
a risk factor (such as hypertension12 or obesity13). Lifetime
risk was used to define risk from birth14 or, more
frequently, to define the residual or remaining lifetime
risk from an age when that risk becomes of relevance
and of concern to a person or to a society, such as the
remaining lifetime risk (or the lifetime risk) of breast
cancer in adults, the risk of stroke from age 55 years, or
the risk of dementia from age 65 years.
The concept of lifetime risk is underused. Most
neuroepidemiological papers address disease incidence
and prevalence but do not provide any estimate of the
lifetime risk of the condition in their study samples. In
this Personal View, we present a conceptual definition of
lifetime risk and distinguish it from measures of
cumulative incidence and prevalence. We describe how
the lifetime risk can be operationally defined and
computed, and discuss data on the lifetime risks of
stroke, dementia, and AD from one well characterised,
community-based sample. In addition, we discuss the
use of such estimates for health planning, public
education, and the prediction of a person’s risk. We also
set out the reasons and preliminary evidence for the
expected regional and temporal differences in lifetime
risk, and summarise some of the available data on the
lifetime risk of various neurological diseases. The lifetime
risk estimates for other common age-related diseases,
such as cancer and cardiovascular disease, are compared
with the lifetime risk of neurological disorders. With this
Personal View, we aim to persuade more investigators to
use lifetime risk estimates.
Why define the lifetime risk of a condition?
A brief historical perspective that describes the
development and application of lifetime risk in the
context of the Framingham database might be helpful.
We realised the usefulness of the concept of lifetime risk
in the early 1990s when neurologists were grappling with
a simultaneously exciting and yet disappointing
observation. An unexpected new risk factor—the
apolipoprotein E (APOE) ε4 allele—was found to have a
powerful effect on the age of onset and risk of AD in
familial and apparently sporadic late-onset variants of the
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Personal View
What is the lifetime risk of a disease?
The lifetime risk of a disease is clearly not synonymous
with the age-specific annual incidence of the disease
because lifetime risk is the risk over a long period rather
than the risk over a year. The lifetime risk differs from
conventional estimates of cumulative incidence (or
cumulative risk) whenever we regard a disease that is
common—with a prevalence greater than 10%—or a
group in which there is a high risk of competing events
(typically death by a different cause) that remove people
from the at-risk group.17 Although estimates of the
theoretical cumulative risk assume that people who die
of alternative causes would have developed the disease at
the same rate as those who survive, estimates of the
actual lifetime risk recognise that the risk of disease after
death is zero. Therefore, people who are free of a disease
when they die have, essentially, escaped the condition.
The cumulative incidence or risk not adjusted for
mortality is frequently appropriate when regarding the
role of an aetiological factor in the cause of a disease,
whereas the experienced lifetime risk is appropriate
when regarding individual or population risk. The
lifetime risk of a disease is not synonymous with the
prevalence of a condition in the population, because
people with the trait or disease commonly live for a
shorter time than people without the condition; therefore,
if a condition shortens life expectancy, estimates of
disease prevalence in a community underestimate the
true lifetime risk. Finally, the lifetime risk does not
assume that all people live to the upper age limit used in
the risk calculation; rather, it weights each age interval on
the basis of the actual probability that a person will live
for that period.
How can we estimate the lifetime risk?
Operationally, the lifetime risk or, more accurately, the
mortality-adjusted residual or remaining lifetime risk at
any age is the conditional probability of developing a
disease when a person has reached the baseline (index)
age and is free of that disease. The conditional probability
can be estimated on the basis of the mean age-adjusted
incidence of the disease and the average residual life
expectancy for each sex at a particular age. In 1994, when
we first approached this question, there were lifetime
risk estimates for breast cancer5 and hip fracture10 but
http://neurology.thelancet.com Vol 6 December 2007
25
Men: all causes
Men: ischaemic stroke
Women: all causes
Women: ischaemic stroke
20
Lifetime risk (%)
disease.15 However, the allele is neither necessary nor
sufficient to cause AD; rather, the APOE ε4 allele
multiplied the underlying risk of the disease. A definition
of a meaningful baseline or a priori risk—ie, the risk in
all people before they were genotyped for APOE—is
needed to put this risk in perspective. But what is an
appropriate a priori risk estimate? Clearly, someone who
is disease-free but feels at risk (eg, a 65 year old) would
not want to know his or her risk only during the next
year, or even during the next 5 years; rather, they would
want to know the risk of ever getting the disease.4,16
15
10
5
0
55
65
75
Age (years)
85
95
Figure 1: Lifetime risk of all-cause stroke and ischaemic stroke from age 55 years
Lifetime risk of first-ever stroke in Framingham Study participants (women and men) who were stroke-free at
55 years old and were followed during their lifespan. Adapted with permission from the American Heart
Association.11
few reports of the lifetime risk for any of the common
neurological diseases. Two notable exceptions were
reports that estimated the lifetime risk of AD in high-risk
families18 and a single report on the remaining morbid
lifetime risk of AD in a community-based group.19 These
and other studies that address the lifetime risk of nonneurological disorders used a double-decrement life-table
method, which combined published life-expectancy data
(mostly comprising national rather than group-specific
data) and group-specific, observed disease-incidence data
to estimate the lifetime risk.
Because factors that affect disease incidence might also
affect the risk of death by other causes, we concluded that
disease incidence and mortality estimates from the same
population would be preferable. The computational
technique used to run these analyses has been described
in detail.20 We were able to use these methods to estimate
the lifetime risk of dementia and AD during 1997 and,
more recently, we have estimated the lifetime risk of
stroke and compared this with updated estimates of the
lifetime risk of dementia and AD.9,11
What is the lifetime risk of stroke?
The Framingham Study has prospectively screened
participants for incident stroke since the original group
was enrolled in 1948–50.21–23 With data from the 4897
original participants in the Framingham Study who were
stroke-free and dementia-free at 55-years-old, 875 incident
strokes were recorded during a follow-up period of up to
51 years (115 146 person-years); therefore, we estimated
that the average 55-year-old man has a 1 in 6 risk of stroke
during his lifetime, whereas the risk for an average
55-year-old woman is 1 in 5 (figure 1, table 1).11 Thus,
women are more likely to have a stroke because of their
greater life-expectancy: women had an 18% lifetime risk
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Personal View
N*
First stroke all-causes (875)
First ischaemic stroke (749)
Short-term and intermediate-term risks
10 year
20 year
Lifetime risk
Short-term and intermediate-term risks
30 year
10 year
20 year
Lifetime risk
30 year
Women
55
522 (448)
2·3 (1·7–2·9)
6·5 (5·6–7·5)†
14·3 (13·0–15·6)
21·1 (19·4–22·7)†
1·8 (1·3–2·3)
5·4 (4·5–6·2)†
12·1 (10·9–13·4)
18·1 (16·6–19·7)†
65
462 (400)
4·6 (3·8–5·5)†
13·2 (11·8–14·5)
19·5 (17·8–21·1)‡
20·6 (19·0–22·3)†
3·9 (3·1–4·7)†
11·3 (10·1–12·6)
16·9 (15·4–18·5)‡
17·9 (16·2–19·5)†
75
347 (303)
10·5 (9·1–11·9)
18·3 (16·5–20·1)†
··
19·7 (17·8–21·6)†
9·1 (7·8–10·4)
16·0 (14·3–17·8)†
85
140 (123)
13·4 (11·1–15·6)†
··
15·8 (13·3–18·2)†
11·9 (9·8–14·0)†
··
··
··
17·2 (15·4–19·0)†
··
13·8 (11·5–16·2)†
Men
55
353 (301)
2·9 (2·2–3·6)
8·7 (7·5–9·9)†
14·7 (13·2–16·2)
16·9 (15·3–18·6)†
2·4 (1·7–3·1)
7·3 (6·2–8·4)†
12·6 (11·2–14·1)
14·5 (12·9–16·0)†
65
293 (251)
7·0 (5·8–8·2)†
14·1 (12·5–15·8)
16·5 (14·7–18·3)‡
16·8 (15·1–18·6)†
5·8 (4·7–6·9)
12·3 (10·7–13·8)
14·1 (12·4–15·7)‡
14·4 (12·8–16·1)†
75
166 (145)
10·4 (8·6–12·1)
12·0 (10·1–13·8)†
85
38 (30)
8·5 (5·7–11·3)†
13·8 (11·8–15·8)‡
··
··
14·3 (12·2–16·4)†
9·3 (7·7–11·0)
··
9·8 (6·7–12·8)†
6·6 (4·1–9·0)†
··
··
12·5 (10·6–14·4)†
··
7·8 (5·0–10·6)†
*All-cause stroke (ischaemic stroke). Risks shown as percentages (95% CI). Comparison of risks in men and women with z-test. †=p<0·01. ‡=p<0·05.
Table 1: Age-specific and sex-specific mortality-adjusted 10-year, 20-year, 30-year, and lifetime risk estimates for the development of all-cause stroke and ischaemic stroke. Adapted
with permission from the American Heart Association11
All-type dementia (400)
Alzheimer’s disease (292)
Short-term and intermediate-term risks
10 year
20 year
Lifetime risk
30 year
Short-term and intermediate-term risks
10 year
20 year
Lifetime risk
30 year
Women
65
1·0 (0·4–1·5)
7·6 (6·3–9·0)
75
7·4 (6·0–8·8)
20·6 (18·2–22·9)
85
20·3 (17·2–23·5)
··
19·4 (17·2–21·6)
21·7 (19·3–24·0)
0·6 (0·1–1·0)*
5·4 (4·3–6·6)*
··
23·1 (20·5–25·7)
5·4 (4·2–6·6)*
16·3 (14·2–18·5)
··
24·3 (20·7–27·8)
16·9 (13·9–19·8)
··
15·2 (13·2–17·2)*
17·2 (15·0–19·4)†
··
18·5 (16·2–20·9)
··
20·3 (17·0–23·6)†
Men
65
1·6 (0·8–2·4)
7·7 (6·1–9·3)
75
7·6 (5·8–9·3)
14·2 (11·7–16·8)
85
13·8 (9·9–17·7)
··
13·1 (10·9–15·3)
14·3 (12·0–16·7)
0·9 (0·3–1·5)*
4·4 (3·2–5·7)*
··
15·8 (13·0–18·5)
4·4 (3·0–5·7)*
9·2 (7·1–11·3)*
··
16·9 (12·5–21·4)
10·0 (6·6–13·4)
··
8·3 (6·5–10·2)*
9·1 (7·2–11·1)*
··
10·2 (7·9–12·5)*
··
12·1 (8·2–15·9)
Risks shown as percentages (95% CI). Comparison of risk of AD in corresponding age and sex categories with z-test. *=p<0·01. †=p<0·05.
Table 2: Age-specific and sex-specific mortality-adjusted 10-year, 20-year, 30-year, and lifetime risk estimates for dementia and Alzheimer’s disease at index ages 65 years, 75 years, and
85 years. Adapted with permission from the American Heart Association.11
of ischaemic stroke at age 55, whereas the corresponding
risk in men was 14% (p<0·01). Only one other report on
the lifetime risk of stroke has been published, with
estimates based on a 6-year follow-up of the Rotterdam
Study sample. The investigators’ results were similar to
ours: the lifetime risk of stroke was about 1 in 5 for men
and women at age 55 years.24 These two studies had
several strengths, including the prospective ascertainment
of end-points with standardised clinical diagnostic
criteria (the Framingham data were gathered over a
period of 50 years) and the complete ascertainment of
stroke and mortality in the same community-based
group. However, these estimates are based on only the
risk of overt stroke and not the additional burden of silent
(covert) stroke.25 Consequently, the lifetime risk of stroke
that we report might be an underestimate of the true
burden of cerebrovascular disease.
The severity of stroke can vary, and our lifetime risk
estimates do not distinguish between the lifetime risk of
disabling stroke and the lifetime risk of any stroke.
1108
However, we found no published data on this important
question. Furthermore, when we tried to analyse stroke
severity in our database, the answer was complex:
disability after stroke depends on age at stroke, prestroke
disability, the presence or absence of comorbid disorders
(such as arthritis and heart disease), and how long after
stroke the disability was assessed (30 days or 6 months).26,27
Moreover, the answer varied with the definition of
disability and how it was measured. These complex
issues are beyond the scope of this Personal View, but the
lifetime risk of disabling stroke must be studied within
population samples such as the Framingham Heart
study.
Lifetime risks of stroke versus dementia
We compared the lifetime risks of stroke and dementia
and noted that lifetime risk of stroke is greater than
lifetime risk of AD until people reach an advanced age
(~85 years old). We made this comparison because
dementia, which is mostly due to AD, is the only other
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Personal View
Lifetime risks in women
The greater life expectancy for women translates into a
greater lifetime risk of several diseases, which is true not
only for disorders that are known to affect women at least
as frequently as men (such as AD) but is also true for
vascular diseases (such as stroke), where premenopausal,
endogenous oestrogen concentrations might protect
women. The mean age of first stroke is later in women
than it is in men;29–31 however, because the average adult
now spends more than 25% of their life in the sixth or
subsequent decades, and during this time the average
woman is postmenopausal, the survival advantage
translates into a higher lifetime burden of AD and stroke.
Thus, women typically need more long-term disability
care than men. A similar effect was shown when
comparing the lifetime burden of cardiovascular disease
in smokers and non-smokers; the latter developed
cardiovascular disease at a later age but had an overall
greater lifetime risk of these diseases.32
Patterns in lifetime risk estimates of disease
During the past decade several investigators have
extended the concept of estimating lifetime risks to
various cardiac disorders, such as coronary heart disease,33
congestive heart failure,34 and atrial fibrillation.35 Lifetime
risk estimates fall into two broad categories on the basis
of the pathophysiology of the underlying disease. One
group of diseases has a peak incidence within a given age
group, with decreased age-specific incidence in older
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Dementia
Delayed dementia
Lifetime risk (%)
20
15
10
5
0
65
70
75
80
85
90
95
Age (years)
Figure 2: Lifetime risk of dementia for women aged 65 years
Actual (blue line) lifetime risk in 65-year-old, dementia-free women in the Framingham Heart Study11 who were
followed up throughout their remaining life compared with projected lifetime risk (red line) of incident dementia
if it could be delayed in all cases by 5 years (arrows).
25
Stroke all-causes
Alzheimer’s disease
20
Lifetime risk (%)
neurological disorder listed in the ten leading causes of
total disease burden in developed countries, and these
are the two most widely feared age-related neurological
disorders in the public perception. A group of 2794
participants without dementia in the Framingham Study
who were 65 years or older were followed up for a
maximum of 29 years (42 233 person-years). There were
400 cases of incident dementia of all types and 292 cases
of incident AD. We estimated the lifetime risk of any
dementia at more than 1 in 5 in women and 1 in 6 in
men, and the lifetime risk of AD at about 1 in 5 for
women and 1 in 10 for men (table 2).11 A greater risk of
dementia in women was also noted in the Rotterdam
study, which reported a 33% lifetime risk of dementia in
women compared with a 16% lifetime risk in men.28 Our
projections suggest that, assuming a constant life
expectancy, if the age at onset of clinical dementia could
be delayed in all cases by just 5 years, the lifetime risk of
dementia could be drastically reduced (figure 2). The
lifetime risk of stroke was greater than the lifetime risk
of AD for men and women at ages 55 years, 65 years, and
75 years; only men and women aged 85 years or older
had a greater lifetime risk of AD than stroke (figure 3).11
The realisation that the lifetime risk of stroke or dementia
was more than 1 in 3 in both sexes, which is higher than
the lifetime risk of coronary heart disease in women, is
sobering.7
15
10
5
0
Women
65 years
Women
75 years
Women
85 years
Men
65 years
Men
75 years
Men
85 years
Figure 3: Comparison of lifetime risks for stroke and Alzheimer’s disease
Simple educational charts of the lifetime risks of developing stroke and dementia in men and women at ages
65 years, 75 years, and 85 years on the basis of data from the Framingham Heart Study.11
people. For these diseases, the lifetime risk estimates
also peak at a specific age (not always the age with the
greatest annual age-specific incidence) and either flatten
or decline thereafter.36,37 This levelling of risk appears to
occur for breast cancer, coronary artery disease, and
stroke, although a definite decline might not always be
reported. For other diseases and traits that are thought to
be related to ageing, per se, such as congestive heart
failure and AD, current life expectancies are associated
with an increase in age-specific incidence with increasing
age, which almost exactly matches and counterbalances
the decline in remaining life expectancy. Hence, the
estimated lifetime risk is fairly constant, which enables
the generation of a single risk estimate that is applicable
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25
HTN stage 2
HTN stage 1
preHTN
Normal BP
Lifetime risk (%)
20
15
10
5
0
65
70
75
80
Age (years)
85
90
95
Figure 4: Lifetime risk of stroke for men, stratified by JNC7 blood pressure categories
Lifetime risk of stroke for men aged 65 years by baseline blood pressure category. Four blood pressure categories
were defined, with SBP and DBP values measured in mm Hg and cut-off points similar to those used by JNC7. Green
line: normal BP=SBP <120 and DBP <80. Dark blue line: preHTN=SBP >120 but <140 and/or DBP >80 but <90. Red
line: HTN stage 1=SBP >140 but <160 and DBP >90 but <100. Light blue line: HTN stage 2=SBP >160 and/or DBP
>100. HTN=hypertension. SBP=systolic blood pressure. DBP=diastolic blood pressure. preHTN=prehypertension.
JNC=Joint National Committee on Prevention, Detection, and Evaluation of Treatments of High Blood Pressure.
Adapted with permission from the American Heart Association.11
to the entire population of adults at risk. A relatively
constant risk estimate for the lifetime risk of stroke is
also found over a specified age range, for example
55–75 years (table 1, figure 3).11
Individualised risk prediction
People who are apprehensive about the risk of a disabling
and potentially fatal condition, such as a stroke, should
be rightly concerned with not just the annual or 5-year
risk, although these short-term risks are important, but
also with the risk that they will develop the condition at
any time in their life. Someone who is worried about the
risk of stroke could use a predictive scale, such as the
Framingham stroke risk profile, to predict the 10-year risk
of stroke.31 However, risk prediction for the remaining
lifespan of a 45–75 year old would certainly require
estimation of risk over a period longer than 10 years; the
lifetime risk estimates that we generated on this basis
have been included in the most recent statistical update
of the American Heart Association.2
However, there are several caveats with lifetime risk
estimates for individual risk prediction. First, these
estimates are, by design, population estimates; for any
individual risk, the estimated lifetime risk would vary
with remaining life expectancy (eg, a family history of
longevity or other underlying diseases), risk factor profile,
and the success of risk factor management. Because
disorders that increase the risk of stroke, such as atrial
fibrillation or congestive heart failure, might alter overall
life expectancy and increase the risk of dying by other
causes, the change in lifetime risk of stroke associated
with these risk factors is not intuitively predictable.
1110
Second, lifetime risk estimates do not distinguish
between immediate and remote risks and, hence, should
be combined with short-term risk estimates when
counselling young people. Finally, the lifetime risk
estimates we have generated tend to be unstable for
people in the tenth decade and beyond because estimates
for people older than 90 years are based on small
numbers.
Nevertheless, lifetime risk estimates are useful for
individual and mass-media education campaigns because
they are easier to comprehend than alternative measures,
such as incidence, prevalence, or relative risk. For
example, when presented with information on annual
stroke risk “many subjects struggled to understand the
concept of cumulative risks”.38 Conversely, in the 1990s
the American Cancer Society effectively used a single
lifetime risk estimate of 1 in 9 to raise awareness of the
risk of breast cancer in women.39 Bayesian techniques
can be used to compute risk-factor-specific estimates of
the lifetime risk of a disease: having one APOE ε4 allele
doubled the age-specific and sex-specific risk of AD,
whereas being APOE ε4 negative halved the basal agespecific and sex-specific risks.3 Individualised estimates
of the lifetime risk of AD were presented to participants
in the REVEAL (Risk Evaluation and Education for AD)
study,40 and nearly half the participants could recall the
figure a year later. The results of research into effective
health communication suggest that patients prefer health
risks to be framed in absolute terms, with bar graphs,
and calculated over their expected lifetime.17 Risk-factorspecific lifetime risk estimates can also minimise
psychological distress18 by directly linking risk estimates
to an intervention that can favourably modify the
estimates.
Stroke risk prediction can be refined by including
individual risk factors. For example, our data showed
dramatic differences in the lifetime risk of stroke
according to blood pressure level: lifetime risk of stroke
in men with normal blood pressure (<120 mm Hg systolic
and <80 mm Hg diastolic) is about half that of men with
a baseline blood pressure in the hypertensive range
(≥140 mm Hg systolic or ≥90 mm Hg diastolic), as
assessed by the Seventh Joint National Committee on the
Prevention, Detection, Evaluation, and Treatment of
High Blood Pressure (figure 4).41 For women, the
corresponding risk fell from 1 in 4 in pateints with
hypertension to 1 in 6 in patients who were normotensive.
These data have been used to create simple and
educational bar diagrams (figure 5).
Nomograms and charts have been produced to present
the lifetime risk of several late-life diseases, such as hip
fractures, as a function of a risk factor estimate (bone
density).42 We have used Framingham data on the lifetime
risk of stroke and lifetime risk of all cardiovascular
disease to produce charts and nomograms that estimate
risk on the basis of individual risk factors, such as
hypertension and diabetes,43 but further development of
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30
Blood pressure ≥140/90 Hg
Blood pressure <120/80 Hg
25
20
Lifetime risk (%)
risk-factor-specific lifetime risk estimates for stroke, as
calculated for combined cardiovascular endpoints, is
needed.44 However, the use of our risk-specific lifetime
estimates compared with the older Framingham risk
prediction scores and the interactive nomograms that
have been widely used for years as effective educational,
prognostic, and risk-stratification tools has not yet been
directly assessed. We do not know how the presentation
of lifetime risks rather than 10-year risks will alter risk
perception and health-related behaviours. In theory, the
lifetime risk is a useful tool to give middle-aged adults a
long-term risk perspective. For this reason, a recent
update of the Evidence-based Guidelines for Cardiovascular
Disease Prevention in Women suggests an alteration to the
“approach to risk stratification of women” that places
“greater emphasis on lifetime risk than on short-term
absolute risk.”44
15
10
Population differences in lifetime risk estimates
Lifetime risk estimates are a useful public health tool
that can be estimated in any population for which we
have data on disease incidence and cause-specific
mortality. More estimates of lifetime risk from racially,
geographically,
and
socioeconomically
diverse
populations are needed because there are acknowledged
differences in stroke incidence and life expectancy among
ethnic groups, countries, and, possibly, socioeconomic
groups.45–47 Lifetime risk can vary with the differences in
life expectancy between developed and developing
countries. Lifetime risk estimates have been used to
categorise countries as high-risk or low-risk for hip
fractures, and such categorisation can help health
planning and budget allocation.48 Risk estimates are,
however, only as good as the data used to calculate them,
and under-reporting of events in developing countries
can lead to underestimation of risk.
Temporal trends in lifetime risk of stroke
Lifetime risk is not static over time. Temporal trends in
these risks should be expected because life expectancy
rises or falls, the number of risk factors change, and as
diagnostic criteria and the sensitivity of diagnostic tests
for a condition change. With the Framingham data,32 we
noted that there was a decreasing trend in the lifetime
risk of stroke at age 65 years across the three periods
analysed (1950–1977, 1978–1989, and later than 1990) that
did not reach statistical significance for men or women.32
Because the age-adjusted annual incidence and 10-year
cumulative incidence of stroke decreased over the same
three periods, the stable lifetime risk is likely to be due to
increases in life expectancy offsetting decreases in annual
and shorter-term risks of stroke.
Similar estimates are needed from other population
samples because temporal trends in the lifetime risk of
stroke can vary between countries and among different
ethnic groups within a country. Thus, increased lifetime
risk of stroke due to greater life expectancy is a particularly
http://neurology.thelancet.com Vol 6 December 2007
5
0
Men
Women
Figure 5: Lifetime risks of stroke for men and women according to baseline
blood pressure
Simple educational bar graphs that show the lifetime risks of stroke in men and
women with a BP of <120/80 mm Hg compared with the lifetime risks of stroke
in men and women with a BP of >140/90 mm Hg.11
important issue in countries that are currently undergoing
a rapid demographic transition, such as India and China.
The results of the Auckland stroke study, which gathered
incident stroke data through an ongoing stroke registry,
suggested that although there was an overall decline in
the incidence of first stroke of 14% (95% CI 12%–29%)
between 1981 and 2002, there was a considerable
(2·7-fold, 1·0-fold to 7·3-fold) increase in stroke incidence
in Pacific islanders, which the authors attributed to an
increase in the risk of obesity in this ethnic group.49,50
Lifetime risk of risk factors for stroke
Lifetime risk estimates are a useful measure of risk factor
burden in populations. For some of these reversible
disorders, such as obesity and hypertension, the
prevalence can change as people revert from a disease
condition to a healthy state. However, people who have
been exposed to these risk factors have an increased risk
even after they revert to a healthy state.3 Studying the
lifetime risk of developing risk factors for stroke and
vascular disease, such as hypertension,12 obesity,13
hypercholesterolaemia,51 and diabetes,52,53 has helped to
highlight the magnitude of the public health burden
associated with these disorders. The study of lifetime risk
has also shown the need to target societal factors and
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Personal View
Disease or risk factor
Index age (years)
Men
Women
Stroke11
55
1/6
1/5
Dementia11
65
1/7
1/5
Alzheimer’s disease11
65
1/10
1/5
Parkinsonism55
65
1/25
1/25
Parkinson’s disease55
65
1/50
1/75
Stroke or dementia11
65
1/3
1/2
All cardiovascular disease43
40
2/3
>1/2
Coronary heart disease
40
1/2
1/3
Congestive heart failure57
40
1/5
1/5
Atrial fibrillation35
40
1/4
1/4
Breast5
40
1/1000
1/8
Prostate59
40
1/6
··
Lung58
40
1/12
1/17
All58
40
1/4
1/5
50
1/20
1/6
Hypertension12
65
9/10
9/10
Type 2 diabetes
40
1/3
1/3
Obesity
40
1/3
1/3
Neurological
Cardiovascular
Cancers
Other diseases or injuries
Hip fracture10
Risk factors for stroke
Selection is illustrative rather than comprehensive. Lifetime risk estimates from the
Framingham study have been assessed with similar methods and are, therefore,
comparable. However, variations in the data and methods used in the studies
preclude a direct comparison of the lifetime risks of the other conditions listed.
Table 3: Examples of lifetime risk for stroke and other disorders in
people without the disorder at index age
individual behaviours to reduce the lifetime risk of these
apparently ubiquitous disorders. We have recently
studied temporal trends in the prevalence and effect of
stroke risk factors as an explanation for the observed
decline in the age-specific incidence of stroke.54 The
effect was explained by a decrease in the prevalence of
some of the risk factors (such as high mean systolic blood
pressure) and a decrease in the effect of other risk factors
(such as atrial fibrillation).
Lifetime risk of other neurological disorders
The lifetime risks of other neurological conditions apart
from stroke and dementia have been reported; these
include Parkinson’s disease55 and carpal tunnel syndrome
in people with diabetes.56 The lifetime risks of common
neurological disorders have been compared with the
risks of coronary heart disease and all cardiovascular
diseases, the risks of common cancers (such as breast,
prostate, and lung cancer) and all deaths from cancer,
and with other age-related conditions, such as hip
fractures, atrial fibrillation, and congestive heart failure
(table 3).43,57–59 These data emphasise the enormity of the
burden associated with common neurological diseases
such as stroke and dementia.
1112
Search strategy and selection criteria
References for this Personal View were identified by searches
of PubMed from 1966 until August 25, 2007, with the terms
“lifetime risk” and either “stroke” or “dementia”, which found
151 and 119 articles, respectively. Articles were also found by
a review of all publications on the topics of “stroke” and
“lifetime risk” from the Framingham Heart Study, through a
review of citations in the primary articles and the Science
Citation Index, and a review of articles that cited the
identified articles. Finally, the authors searched their own
files. Abstracts of all English language papers that met these
criteria were reviewed to determine the relevance of their
content, and 60 articles were studied in detail.
Conclusions
The lifetime risk of stroke, AD, or other disorders is an
aggregate estimate of actual risk during the remaining
lifespan that is applicable to people of a particular age
and sex. The risk can be refined, however, for an
individual on the basis of their risk factor profile. For an
individual, the lifetinme risk is the appropriate a priori
risk estimate to determine the usefulness and costeffectiveness of additional prognostic tests and
algorithms. As multiple genetic, metabolic, imaging, and
functional biomarkers for stroke and other neurological
diseases are discovered we must understand their
individual and collective value in risk prediction. Lifetime
risk estimates for all cardiovascular diseases were
published on the basis of an aggregate measure of midlife
exposure to risk factors.60 Our future goals include the
use of the Framingham data to develop a stroke risk
profile that will provide lifetime risk estimates based on
aggregate risk factor scores, which is a useful step
towards evidence-based, personalised medicine.
The lifetime risk of a disease can also be used as a
population risk estimate to aid health economics and
public policy decisions, to compare geographically or
ethnically distinct populations, and to study temporal
trends in disease risk in a population. The lifetime risk of
stroke can be estimated for any population that has data
on stroke incidence and non-stroke mortality; therefore,
our recommendation is that studies that report stroke
incidence should also provide lifetime risk estimates
whenever possible.
Contributors
SS reviewed the literature, planned the outline of the Personal View, and
drafted and critically revised the manuscript. PAW planned the outline
of the Personal View and critically revised the manuscript. Both authors
have read and approved the final version.
Conflicts of interest
We have no conflicts of interest.
Acknowledgments
We are supported by grants from the National Institute of Neurological
Disorders and Stroke (NS17950), the National Institute of Aging
(AG08122, AG16495), and the National Heart, Lung and Blood Institute’s
Framingham Heart Study (NIH/NHLBI Contract # N01-HC-25195).
http://neurology.thelancet.com Vol 6 December 2007
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