Geographic Variations in Stroke Incidence and Mortality
Among Older Populations in Four US Communities
Aiman El-Saed, MD, PhD, MPH; Lewis H. Kuller, MD, DrPH; Anne B. Newman, MD, MPH;
Oscar Lopez, MD; Joseph Costantino, DrPH; Kathleen McTigue, MD, MS, MPH;
Mary Cushman, MD, MSc; Richard Kronmal, PhD
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Background and Purpose—Stroke is a leading cause of death and disability in the US. There is limited data on geographic
variations in stroke incidence among older US populations who experience the majority of stroke burden. The purpose
of this study was to compare stroke incidence and mortality rates in 4 US communities.
Methods—Participants in the Cardiovascular Health Study (CHS) who had no history of stroke at baseline (n⫽5639) were
followed for 10 or 7 years in predominantly white (n⫽5002) and black (n⫽637) participants, respectively. Incident
stroke was validated by a stroke adjudication committee after ascertainment at annual visits, interim telephone contacts,
and review of Medicare hospitalization data.
Results—The 2000 US population age and sex standardized total stroke incidence rate for all CHS participants was 17.7
per 1000 person-years (95% CI: 15.9, 19.5). The rate was significantly lower in Allegheny County, Pennsylvania
9.6/1000 person-years (95% CI: 7.7, 11.5) than Forsyth County, North Carolina 19.2/1000 person-years (95% CI: 15.6,
22.8), Sacramento County, California 20.7/1000 person-years (95% CI: 16.9, 24.5), and Washington County, Maryland
19.8/1000 person-years (95% CI: 16.1, 23.5). The lower stroke incidence rate in Allegheny County was consistent in
gender, race, and age groups. Though not statistically significant, stroke mortality was also lower in Allegheny County
than other 3 sites. The 1-month case fatality rate was similar in the 4 sites for all strokes, and by stroke types.
Conclusions—Understanding geographic variations in stroke incidence may be an important step in improving preventive
practices of stroke. (Stroke. 2006;37:000-000.)
Key Words: epidemiology 䡲 incidence 䡲 geography 䡲 mortality 䡲 stroke
G
eographic disparities in stroke have been persistent over
long periods of time in the US.1 Excess stroke mortality
risk (relative risk⫽1.3 to 1.5) in the Southeastern region of
the US versus the remainder of the nation, the “stroke belt”,
was first documented in 1965 and has existed at least since
1940. Geographic or secular comparisons of stroke incidence
or mortality are most meaningful if they are based on studies
that use similar definitions, methods, and data presentation.2,3
A number of studies assessing stroke incidence in different
US regions were published in the last decade, with ⬎2-fold
variations described in stroke incidence.4 –10 In these studies
older adults, who experience the majority of strokes, were
either not included4,6 or included together with a wide range
of age groups.5,7–10 Selective survival in older individuals that
significantly alter the importance of some stroke risk factors11
may alter geographic variations in stroke incidence. Moreover, different methodologies used for case ascertainment in
prior studies and different population characteristics (race and
time periods of data collection) further complicate any
attempt to study geographic variations in stroke incidence.
Whereas Atherosclerosis Risk In Communities (ARIC)
study6 used a prospective design to study stroke risk on the 45
to 64 age group, the Cardiovascular Health Study (CHS) used
a similar design for individuals 65 years or more. In this
report, older CHS men and women from 4 geographically
separated US communities were examined for stroke incidence using a standardized prospective design for case
ascertainment and validation.
Methods
Study Population
The CHS design, including recruitment techniques, definitions of
risk factors and outcomes, has been described in detail.12,13 CHS is
a population-based, longitudinal study of coronary heart disease and
stroke in adults aged 65 years and older. Participants of the CHS
were recruited from a random sample of Health Care Financing
Administration (HCFA) Medicare Part B eligibility lists in 4 US
Received April 7, 2006; accepted April 24, 2006.
From the Department of Epidemiology (A.E., L.H.K., A.B.N.), University of Pittsburgh, Pa; the Department of Neurology (O.L), University of
Pittsburgh, Pa; the Department of Biostatistics (J.C.), University of Pittsburgh, Pa; the Department of General Medicine (K.M.), University of Pittsburgh,
Pa; the Department of Medicine (M.C.), University of Vermont, Colchester, Vt; and the Department of Biostatistics (R.K.), University of Washington,
Seattle, Wash.
Correspondence to Aiman El-Saed, MD, PhD, MPH, Department of Epidemiology, University of Pittsburgh, 130 N Bellefield Ave, Rm 405, Pittsburgh,
PA 15213. E-mail [email protected]
© 2006 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org
DOI: 10.1161/01.STR.0000231453.98473.67
1
2
Stroke
TABLE 1.
August 2006
CHS Participant Characteristics at Baseline by Site
Forsyth
County, NC n (%)
Sacramento
County, CA n (%)
Washington
County, MD n (%)
Allegheny
County, PA n (%)
Total n (%)
1488 100.0%
1471 100.0%
1251 100.0%
1429 100.0%
5639 100.0%
1266 85.1%
1267 86.1%
1251 100.0%
1218 85.2%
5002 88.7%
222 14.9%
204 13.9%
NA
211 14.8%
637 11.3%
65–74 years
997 67.0%
989 67.2%
801 64.0%
972 68.0%
3759 66.7%
75–84 years
443 29.8%
420 28.6%
394 31.5%
411 28.8%
1668 29.6%
48 3.2%
62 4.2%
56 4.5%
46 3.2%
212 3.8%
Males
900 60.5%
850 57.8%
726 58.0%
811 56.8%
3287 58.3%
Females
588 39.5%
621 42.2%
525 42.0%
618 43.2%
2352 41.7%
Whites
1154 78.0%
1228 84.6%
1238 99.1%
1123 79.0%
4743 84.7%
Blacks
326 22.0%
224 15.4%
11 0.9%
299 21.0%
860 15.3%
Total No. of those at risk
for stroke at baseline
Cohort
Original cohort
New cohort
Baseline Age
85⫹ years
Gender
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Race
NA indicates not applicable.
communities: Forsyth County, NC; Sacramento County, CA; Washington County, MD; and Allegheny County, PA. Potentially eligible
participants were excluded if they were institutionalized, wheelchairbound in the home, or were receiving cancer treatment. The Allegheny
County site population was entirely urban, and the other 3 centers
recruited a mixture of urban and rural populations. 5888 men and
women were recruited in 2 waves. A total of 5201 participants were
recruited in 1989 to 1990 in the first wave (original cohort). Because
blacks were under-represented in the first wave of the study,
additional 687 black participants were recruited in 1992 to 1993 in a
second wave (new cohort), to improve the racial representativeness
of the study. Differences between those recruited and those not
recruited have been presented elsewhere.13
Outcome Assessment
Ascertainment methods of incident and prevalent stroke in CHS have
been described.14,15 Extensive historical, physical and laboratory
evaluations were performed at baseline for each cohort to identify
prevalent strokes, and these were validated by a committee.12
ICD-9-CM codes 430 to 438 were investigated for possible stroke
events. Ascertainment of new stroke events was carried out by
interview at annual visits and interim telephone contacts, from
notification of events by participants, and reviewing Medicare
hospitalization data. For suspected stroke events, clinical records
were sought, and copies including admission and discharge notes,
results of pertinent tests, and copies of any brain images (CT and
MRI) were obtained.14,15
Provisional diagnoses of stroke were reviewed and adjudicated at
periodic meetings of a cerebrovascular disease end-point committee.
The committee also classified the stroke subtype and determined
whether death was caused by stroke.14 Information for classification
of death was obtained from death certificates, autopsy and coroner’s
reports (if available), hospital records, and interviews with attending
physicians, next-of-kin, and witnesses.12
Stroke incidence rates per 1000 person-years were calculated by
dividing the number of new stroke events by the person-years at risk.
Stroke mortality rate was calculated as the number of adjudicated
stroke deaths within a month after stroke divided by the person-years
at risk. Incidence rates were compared across the sites for all
participants and by race, gender, and baseline age groups (65 to 74,
75 to 84, and 85 years and older). Stroke rates were either
age-specific or age-standardized. Rates were also sex-standardized
when applicable. Age standardization was done using the 2000 US
census population distribution16 using the direct method. Stroke case
fatality rates were calculated by dividing the number of fatal strokes
by all new strokes. Fatal and nonfatal cumulative stroke hazards over
the total follow-up period were calculated using a Cox regression
with adjustment for age, race and gender. The models were then
stratified by site.
Results
Demographics
The total number of participants at risk for incident stroke at
baseline in the 4 sites was 5639. Of these, 5002 (88.7%) were
recruited between 1989 and 1990 (original cohort) and 637
(11.3%) recruited between 1992 and 1993 (new cohort). The
mean age at baseline was 72.8 years (median 72 years, range
65 to 100 years); 3759 (66.7%) participants were aged 65 to
74 years, 1668 (29.6%) were 75 to 84 years, and 212 (3.8%)
were 85 or more years old. 58% of the participants were
women. There were no significant age or gender differences
between sites. Approximately 85% of the participants were
white and 15% were black with a lower percentage of blacks
at the Washington County site (Table 1).
Statistical Analysis
Stroke Incidence Rates
Participants with prebaseline stroke were excluded from all analyses.
Incident stroke cases were adjudicated from the baseline examination
for each cohort through June 30, 2000. Years of follow-up were
defined as the time from the baseline visit to occurrence of stroke for
those who had a stroke and as the time from the baseline visit to
censoring (death or drop out) for those who did not have a stroke.
Over an average of 8.6 years of follow-up (median 10.2) in
the original cohort and 6.3 years (median 7.2) in the new
cohort (total 46 976 person-years), there were 665 incident
strokes in the 4 sites combined. The 2000 US population ageand sex-standardized total stroke incidence rate for all CHS
El-Saed et al
TABLE 2.
and Site
Gender:
Males
Females
Race:
Whites
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Blacks
Total*
Geographic Variations in Stroke Incidence
3
Age Standardized Total Stroke Incidence Rates per 1000 Person-Years of CHS Participants by Gender, Race
Forsyth County, NC
Events
P-Y
Rate
95% CI
Sacramento County, CA
Events
P-Y
Rate
95% CI
Washington County, MD
Events
P-Y
Rate
95% CI
Allegheny County, PA
Events
P-Y
Rate
95% CI
Total
Events
P-Y
Rate
95% CI
71
4583.5
17.8
11.6, 24.0
114
7638.4
19.7
15.2, 24.2
79
4998.9
16.0
12.1, 19.9
121
7325.5
22.8
17.5, 28.0
74
4015.4
21.1
15.4, 26.8
96
6374.2
18.8
14.1, 23.5
50
4925.7
12.2
8.3, 16.1
60
7113.7
8.4
6.1, 10.6
274
18 523.6
16.4
14.1, 18.8
391
28 452.0
18.1
15.7, 20.5
143
9930.8
18.4
14.3, 22.5
41
2233.3
21.4
13.7, 29.1
185
12 221.9
19.1
15.5, 22.7
172
10 667.5
19.8
16.1, 23.4
27
1491.4
20.2
11.1, 29.4
200
12 324.5
19.5
16.2, 22.8
168
10 292.1
19.4
15.8, 23.0
2
84.7
24.4
0, 59.4
170
10 389.7
19.7
16.0, 23.3
91
9905.9
10.7
7.7, 13.6
19
2084.3
12.0
5.6, 18.4
110
12 039.4
10.8
8.2, 13.3
574
40 796.4
17.3
15.4, 19.1
89
5893.8
18.2
13.7, 22.8
665
46 975.7
17.3
15.6, 18.9
P-Y indicates person-years.
*Age- and sex-standardized.
participants was 17.7 per 1000 person-years (95% CI: 15.9,
19.5). The rates were significantly lower in Allegheny
County (9.6; 95% CI: 7.7, 11.5) than Forsyth County (19.2;
95% CI: 15.6, 22.8), Sacramento County (20.7; 95% CI: 16.9,
24.5), and Washington County (19.8; 95% CI: 16.1, 23.5).
Age-standardized rates were significantly lower in Allegheny
County for women and whites. The rates were also lower, but
not statistically significant, in Allegheny County for men and
blacks (Table 2). Age-specific stroke incidence rate steadily
increased with increasing age groups at all 4 sites. Allegheny
County had a lower total stroke incidence rate than the other
3 sites among all age groups; statistical significance of this
difference varied by age groups (Figure). The distribution of
incidence of different stroke types was similar among the 4
sites (P⫽0.68): overall 85% of strokes were ischemic, 10%
hemorrhagic and 5% undefined stroke type.
Age-specific stroke incidence rates per 1000
person-years of CHS participants by site.
4
Stroke
August 2006
Case Fatality and Mortality
For all CHS participants, the 1-month case fatality was 12.6%
for all strokes, 8.1% for ischemic strokes, and 44.6% for
hemorrhagic strokes. The 1-month case fatality percentages
were similar in the 4 sites for all strokes (P⫽0.95) and by
stroke types (P⫽0.87 for ischemic and P⫽0.23 for hemorrhagic). Though not statistically significant, age- and sexstandardized total stroke mortality rates per 1000 personyears were lower in Allegheny County (1.55; 95% CI: 0.77,
2.43) than Forsyth County (2.79; 95% CI: 1.34, 4.26),
Sacramento County (2.67; 95% CI: 1.16, 4.24), and Washington County (3.07; 95% CI: 1.37, 4.83).
Cumulative Incidence and Mortality
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The 10-year cumulative hazard for total incident stroke events
adjusted for age, gender and race was significantly lower
(P⬍0.001) in Allegheny County (156 per 1000; 95% CI: 144.2,
167.8) compared with Forsyth County (172; 95% CI: 148.5,
195.5), Sacramento County (175; 95% CI: 153.4, 196.6), and
Washington County (176; 95% CI: 150.5, 201.5). The 10-year
cumulative hazard for fatal stroke events was lower, but not
statistically significant, in Allegheny County compared with the
other 3 sites after adjusting for age, gender and race (P⫽0.47).
For all CHS participants, the cumulative hazard for fatal stroke
events was 19 deaths per 1000 (95% CI: 15.1, 22.9).
Discussion
Overall Total Stroke Incidence
The unadjusted overall stroke incidence rate in this study is
substantially higher than those reported in other similar stroke
incidence studies in the US4 –10 because of the older age group
in the CHS.17 In previous reports the overall estimated annual
stroke incidence rates among US whites ranged between 0.8
to 1.18 per 1000 in New York5 to 1.61 to 3.16 in South
Carolina4 compared with 17.3 per 1000 person-years in the
current report. The age-specific rates from this report, however, were not dramatically different than those reported in
other studies. For example, the overall stroke incidence for
those 75 to 84 years in the CHS was 21.9 per 1000
person-years compared with 12.2 (white) and 18.3 (black) per
1000 in Greater Cincinnati study8 and 18.2 (white men) and
11.9 (white women) per 1000 in Rochester, Minnesota study.7
In addition, using different overlapping ascertainment techniques in CHS14,15 may have yielded higher ascertainment of
stroke cases than other studies.4 –10
Age-specific rates in CHS were also comparable to those
reported in other western countries. For example, comparing
the CHS stroke incidence rates in those aged 85 years or older
(32.7 per 1000 person-years) to other countries, as reviewed
by Feigin et al,18 the CHS incidence was similar to Greece,
Italy and Norway (26.6 to 30.4 per 1000), higher than France,
the United Kingdom and Germany (18.2 to 21.2 per 1000),
and lower than Japan (38.5 per 1000 in females and 49.2 per
1000 in males).
We did not observe significant differences in stroke incidence based on race or gender. This may reflect sample age,
with older populations having less race and gender differences in stroke incidence. In previous reports, older age
groups have a smaller black/white difference5,8,19 and male/
female difference5,7,20 in stroke incidence compared with
younger age groups. For example, the black/white risk ratio
in the Greater Cincinnati study8 decreased from 2.2 in those
⬍35 years to 1.3 in those ⱖ85 years. The male/female risk in
the Northern Manhattan Stroke Study5 decreased steadily
from 2.5-fold in those aged 45 to 54 years, reversing in those
aged 85 years or older, when females had slightly higher
stroke incidence than males.
Site-Specific Total Stroke Incidence
Despite similar total mortality and CHD morbidity (data not
shown), we report significantly lower stroke incidence rates in
Allegheny County than the other 3 CHS sites. The lower stroke
incidence rate in Allegheny County was consistent over time and
began as early as the fourth year of follow-up. It is possible that
site differences in stroke incidence become clearer with increasing overall stroke rates later in follow-up. Site differences in
stroke incidence may not be attributed to differential loss of
follow-up between Allegheny and non-Allegheny sites because
there was virtually no loss to follow-up in the CHS irrespective
of site and even among those who did not attend a certain clinic
visit, information was still obtained for clinical events mainly by
phone contact, home or nursery home visit, or reviewing HCFA
records. Moreover, both groups had similar mean stroke
follow-up years; in addition, our stroke rates were calculated per
1000 person-years and not 1000 persons. Lower stroke incidence
rates in Allegheny County were consistent with national vital
statistics (1991–1998) showing lower age-adjusted stroke mortality rates per 1000 Americans age 35 years or older in
Allegheny (1.10) compared with Forsyth (1.58), Sacramento
(1.36), and Washington (1.18) Counties.21 These differences in
stroke mortality could be a function of the lower incidence rates
or to differential case fatality. In another related manuscript22 and
after comparing many traditional and subclinical stroke risk
factors, site differences in stroke risk factors at baseline and
subsequent control through the follow-up period explained only
about 30% of site differences in stroke incidence.
Forsyth County, NC was the only CHS site located in the
“stroke belt” and according to national data,21 ranked the
highest for stroke mortality among the 4 studied counties.
However, the stroke incidence rate in Forsyth County was
similar to that in Sacramento County, CA and Washington
County, MD. Although the population studied in Forsyth
County is not representative of the whole stroke belt, this data
may support the hypothesis that the “stroke belt” is not a
static phenomenon, and could be related to temporal trends in
a variety of medical, socioeconomic, and behavioral factors
rather than the physical properties of southeastern US.23
Stroke Mortality and Case Fatality
The 1-month case fatality rate of stroke in CHS was comparable to other US studies (10% to 15%).4,5 The stroke
mortality rate per 1000 person-years was also lower in
Allegheny County (1.55) than the other 3 sites (2.79, 2.67,
3.07), although these differences were not statistically significant, probably because of limited power (84 fatal events).
The lower mortality rate in Allegheny County than the other
3 sites might be explained by the lower incidence and similar
case fatality and proportional frequencies of incident stroke
El-Saed et al
types in Allegheny County compared with the other 3 sites. In
addition, total mortality (unlike stroke mortality) was similar
between sites suggesting similar health care use.
Study Strengths and Limitations
This study has many strengths, including a prospective
population-based design, central adjudication of events from 4
geographically separated sites, large sample size, and long-term
follow-up. Nevertheless, the number of events was small for
fatal strokes and for incident strokes in some groups as blacks
and the very old (85 years and more). In addition, because CHS
sites were chosen based on methodological applicability rather
than geographic characteristics, it is difficult to generalize
conclusions from the 4 CHS sites to different parts of US.
Conclusions
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Stroke incidence rates increased with age at all 4 CHS sites,
with little or no race or gender differences in incidence. Total
stroke incidence rates were significantly lower in Allegheny
County than other 3 sites. Though not statistically significant,
the total stroke mortality rates were also lower in Allegheny
County than other 3 sites. Understanding variations in stroke
incidence may be an important step in improving preventive
practices. Further investigation in ongoing studies24 is needed
to clarify the undetermined causes of stroke incidence variation.
Disclosures
None.
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Geographic Variations in Stroke Incidence and Mortality Among Older Populations in
Four US Communities
Aiman El-Saed, Lewis H. Kuller, Anne B. Newman, Oscar Lopez, Joseph Costantino, Kathleen
McTigue, Mary Cushman and Richard Kronmal
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Stroke. published online June 22, 2006;
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