Original Contributions
Geographic Patterns in Overall and Specific Cardiovascular
Disease Incidence in Apparently Healthy Men in the
United States
David Q. Rich, ScD, MPH; J. Michael Gaziano, MD, MPH; Tobias Kurth, MD, ScD
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Background and Purpose—Residence in the Southeastern United States (US) has been linked to increased stroke
incidence and mortality. However, data on regional variability in overall cardiovascular disease (CVD) and specific
coronary heart disease incidence are sparse.
Methods—We assessed the risk of major CVD (nonfatal stroke, nonfatal myocardial infarction, or death from CVD) and
specific CVD associated with region of residence (Northeast, Southeast, Midwest, and West) in 17 927 apparently
healthy male participants of the Physicians’ Health Study. Subjects were aged 40 to 84, most were white (93%), and
had no previous CVD at baseline. We used residence in the Northeast as the reference group and proportional hazards
models to adjust for potential confounding.
Results—We found no difference in risk of major CVD between regions of residence. Further, we found no consistent
association between myocardial infarction and CVD death and region of residence. In contrast, we found a significantly
increased risk of total stroke (HR, 1.22; 95% CI, 1.02 to 1.47) associated with residence in the Southeast compared with
the Northeast. This relative risk was further increased for ischemic stroke (HR, 1.30; 95% CI, 1.06 to 1.58). We saw
no difference in risk of any outcome when categorizing state of residence into tertiles based on mean winter temperature,
mean summer temperature, or into 2 groups based on latitude.
Conclusions—In this homogenous and well-characterized cohort of US male physicians, we found greater incidence of
ischemic stroke, but not other vascular events among those living in the Southeastern US, compared with other regions.
(Stroke. 2007;38:2221-2227.)
Key Words: cardiovascular disease 䡲 epidemiology 䡲 ischemic stroke 䡲 myocardial infarction
I
n 1980, the National Heart Lung and Blood Institute
classified the 11 states (Indiana, Kentucky, Tennessee,
Mississippi, Alabama, Georgia, South Carolina, North Carolina, Virginia, Arkansas, and Louisiana) with stroke mortality
rates 10% higher than the national average (ie, ⱖ65 deaths/
100 000 persons) as the “Stroke Belt,” and has since funded
research to reduce the risk of stroke in this region.1 Others
have also identified the Stroke Belt, reporting similar disparities in stroke mortality rates.2– 4 Howard et al5 documented a
national decline in stroke mortality, predicting regional variability to persist with other regions emerging with high stroke
rates. The National Health and Nutrition Examination Survey
I Epidemiologic Follow-up Study found the highest stroke
incidence rates in the Southeast United States (US) compared
with other regions.6 In white males 45 to 74 years of age, risk
associated with the Southeastern US was not attenuated after
adjusting for conventional stroke risk factors. Further, there
was no difference in incidence rates between subjects resid-
ing inside and outside standard metropolitan statistical areas.6
However, stroke subtype was not assessed and the only
control for socioeconomic status was education level.
The Southeast has also been associated with higher mortality rates from congestive heart failure,7 higher prevalence
of self-reported heart disease,8 and greater prevalence of
hypertension among black females,9 white men, as well as
black men and women,10 compared with other regions. In
contrast, the West has been associated with increased incidence of ischemic heart disease, compared with the Southeast, Northeast, and Midwest regions.11
Increased stroke incidence has been reported in several
studies in the colder months and in other studies during the
warmer months. Others have found no seasonal differences in
stroke rates.12 Seasonal variation in ischemic stroke incidence, if real, may reflect the influence of acute changes in
temperature on known stroke risk factors (eg, blood pressure,
blood clotting time, fibrinogen levels, etc).12 Other potential
Received January 25, 2007; final revision received March 29, 2007; accepted April 4, 2007.
From Department of Epidemiology (D.Q.R.), University of Medicine and Dentistry of New Jersey–School of Public Health, Piscataway, NJ; Division
of Aging (D.Q.R., J.M.G., T.K.) and Division of Preventive Medicine (J.M.G., T.K.), Brigham & Women’s Hospital, Boston, Mass; Massachusetts
Veterans Epidemiology Research and Information Center (J.M.G.), Boston VA Healthcare System, Boston, Mass; Department of Epidemiology (T.K.),
Harvard School of Public Health, Boston, Mass.
Correspondence to Tobias Kurth, MD, ScD, Brigham and Women’s Hospital, Division of Aging, 1620 Tremont Street, Boston, MA 02120. E-mail
[email protected]
© 2007 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org
DOI: 10.1161/STROKEAHA.107.483719
2221
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Stroke
August 2007
explanations for this increased stroke risk associated with
residence in the Southeast include residual confounding
caused by lifestyle factors and factors correlated with weather
conditions. We therefore aimed to prospectively evaluate the
association between geographic region of residence and
incidence of overall and specific cardiovascular disease
(CVD), using data from a well-characterized cohort of mostly
white, apparently healthy, US male physicians, aged 40 to 84
years, and free of CVD at baseline.
Materials and Methods
Study Population
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The Physicians Health Study is a completed randomized trial
designed to test the benefits and risks of aspirin (325 mg every other
day) or beta-carotene (50 mg every other day) in the primary
prevention of cardiovascular disease and cancer among 22 071
apparently healthy men aged 40 to 84 at baseline in 1982. The
methods and results of the Physicians Health Study have been
described in detail previously.13,14 Post-trial follow-up is continuing.15 All participants gave informed consent. The Institutional
Review Board of Brigham and Women’s Hospital approved the
Physicians Health Study. For this analysis, we included follow-up
information through February 28, 2004 (maximum of 22.5 years of
follow-up). As of that date, follow-up was 97% complete.
At baseline, subjects completed a questionnaire detailing information on cardiovascular risk factors and lifestyle habits. Of the original
trial cohort, we excluded 702 participants who did not reside within
the 50 US states or in Washington DC. Of these 21 369 subjects, we
retained only those subjects with complete information on age at
baseline, frequency of smoking, exercise, and alcohol intake, height,
weight, previous diagnoses of hypertension (diagnosis of hypertension or systolic blood pressure ⱖ140 mm Hg or diastolic blood
pressure ⱖ90 mm Hg), elevated cholesterol (diagnosis of high
cholesterol or cholesterol ⱖ240 mg/100 mL), diabetes, and family
history of myocardial infarction (MI) before age 60, and those
without a coronary revascularization procedure before receiving the
baseline questionnaire procedure. This left 17 927 subjects for
analysis.
Geographic Region
Using the state listed in subjects’ baseline mailing address, we
categorized subjects into the 4 geographic regions Northeast, Southeast, Midwest, and West (Table 1) according to the 2000 US
Census.16
Outcome Ascertainment
Every 6 months in the first year and annually thereafter, participants
self-reported incidence of study outcomes, including CVD events.
Medical records were obtained for all reported cardiovascular
end points and reviewed by an Endpoints Committee of physicians,
except coronary revascularization procedures. The occurrence of MI
was confirmed if symptoms met World Health Organization criteria
and if the event was associated with abnormal levels of cardiac
enzymes or diagnostic electrocardiograms. Nonfatal stroke was
confirmed if the participant had a new focal–neurologic deficit of
vascular origin and sudden onset that persisted for ⬎24 hours.
Strokes were classified as ischemic, hemorrhagic, or unknown after
review of all available information including diagnostic testing, such
as brain scans. This classification had a high interrater agreement
(␬⫽0.82).17 Cardiovascular deaths were confirmed by autopsy reports, death certificates, medical records, and information obtained
from next of kin or family members. We evaluated the following
outcome events: major CVD (a combined end point composed of
nonfatal stroke, nonfatal MI, or death from CVD), total MI, total
stroke, ischemic stroke, death from CVD, and reports of coronary
revascularization procedures (bypass surgery or percutaneous coronary angioplasty). There were too few hemorrhagic strokes to create
a separate category for this analysis.
Statistical Analysis
Incidence Rates
Within each region, we calculated crude CVD incidence rates. Next,
we calculated age standardized CVD incidence rates by region, using
the age distribution of the Northeast as the standard.
Main Analyses
We used Cox proportional hazards models to estimate the risk of
major CVD, specific major CVD, as well as ischemic stroke and
coronary revascularization procedures associated with geographic
region, adjusting for potential confounding factors. Indicator variables were generated for age at baseline (40 to 49, 50 to 69, and
ⱖ70), frequency of alcohol intake (once per day or more, once per
month through 6 times per week, rarely/never), smoking (never, past,
current 1 to 19 cigarettes per day, or current ⱖ20 cigarettes per day),
exercise frequency (once per day or more, 1 to 6 per week, 1 to 3 per
month, rarely/never), body mass index (weight in kg divided by
height in meters squared; ⬍25, 25 to 29, ⱖ30), history of cholesterol
ⱖ240 mg/dL, history of hypertension (defined as before), and
parental history of MI before age 60.
Sensitivity Analyses
In a first sensitivity analysis, we re-categorized geographic region
into 2 groups (Stroke Belt versus non-Stroke Belt). Additionally, we
re-categorized geographic region into 2 groups based on latitude.
Second, we gathered the monthly mean ambient temperature measurements from all monitoring stations in the US that were in
operation every year from 1982 to 2002 (Earth Info, Boulder, Colo).
We then computed winter mean (December to February) and
summer mean (June to August) temperatures for each state. We then
re-categorized geographic region into 3 groups based on winter mean
temperature, and then again into 3 groups based on summer mean
temperature (Table 1).
Results
Study subjects were predominantly white (93%). At baseline,
the 17 927 subjects were middle aged (mean⫾SD, 53.5⫾9.0),
predominantly never smokers (51%), and past smokers
(39%), with a mean body mass index of 24.8⫾2.8 kg/m2. A
large proportion was classified as overweight (38%) or obese
(4%). Subjects generally exercised to sweat at least once per
week (73%), and 25% drank daily whereas 15% drank rarely
or never. Some subjects were previously diagnosed with
elevated cholesterol (12%), hypertension (24%), diabetes
(2%), or had a family history of MI before age 60 (10%).
There appeared to be little difference in the prevalence of
these risk factors and cardiovascular events by geographic
region (Table 2). During a mean follow-up time (⫾SD) of
20.4⫾4.2 years, subjects experienced 2607 major CVD
events, 1018 strokes of which 846 were classified as ischemic
stroke, 1247 MIs, 2479 coronary revascularization procedures, and 995 CVD deaths.
Incidence Rates by Region
The Southeast and Midwest had higher crude and agestandardized major CVD, total stroke, ischemic stroke, coronary revascularization, and CVD death incidence rates
compared with the Northeast (Table 3). MI age-standardized
incidence rates were lowest in the Southeast, whereas major
CVD, stroke, ischemic stroke, and coronary revascularization
rates were highest in that region (Table 3).
Rich et al
TABLE 1.
Geographic Patterns and Cardiovascular Disease
2223
States in Each Geographic Classification Grouping
States
Main Analysis
2000 United States Census
Northeast
Maine, New Hampshire, Vermont, Massachusetts, Connecticut, Rhode Island, New York, New Jersey, Pennsylvania
Southeast
Delaware, Maryland, Washington DC, Virginia, West Virginia, Kentucky, Tennessee, North Carolina, South Carolina,
Georgia, Florida, Alabama, and Mississippi
Midwest
Ohio, Michigan, Indiana, Illinois, Wisconsin, Minnesota, North Dakota, South Dakota, Nebraska, Kansas, Iowa,
Missouri, Oklahoma, Arkansas, Louisiana, Texas
West
Montana, Idaho, Wyoming, Colorado, New Mexico, Arizona, Utah, Nevada, Washington, Oregon, California, Alaska,
Hawaii
Sensitivity analyses
1980 National Heart Lung and Blood
Institute Report
Stroke belt
Indiana, Kentucky, Tennessee, Virginia, North Carolina, South Carolina, Georgia, Alabama, Mississippi, Louisiana,
Arkansas
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Not stroke belt
Other 39 states plus Washington DC
Latitude
North
Washington, Oregon, Idaho, Montana, Wyoming, Colorado, Utah, North Dakota, South Dakota, Nebraska, Kansas,
Missouri, Alaska, Iowa, Minnesota, Wisconsin, Michigan, Illinois, Indiana, Ohio, Pennsylvania, New Jersey, New
York, Connecticut, Rhode Island, Massachusetts, New Hampshire, Vermont, Maine
South
Hawaii, California, Nevada, Arizona, New Mexico, Oklahoma, Texas, Arkansas, Louisiana, Tennessee, Mississippi,
Alabama, Georgia, Florida, South Carolina, North Carolina, Kentucky, West Virginia, Virginia, Maryland, Washington
DC, Delaware
Mean winter temperature
Lowest (region 1)
Alaska, Colorado, Iowa, Illinois, Maine, Michigan, Minnesota, Montana, North Dakota, Nebraska, New Hampshire,
New York, Ohio, South Dakota, Vermont, Wisconsin, Wyoming
Middle (region 2)
Connecticut, Delaware, Idaho, Indiana, Kansas, Kentucky, Massachusetts, Maryland, Missouri, New Jersey,
Nevada, Pennsylvania, Rhode Island, Utah, Washington, Washington DC, West Virginia
Highest (region 3)
Alabama, Arkansas, Arizona, California, Florida, Georgia, Hawaii, Louisiana, Mississippi, North Carolina, New
Mexico, Oklahoma, Oregon, South Carolina, Tennessee, Texas, Virginia
Mean summer temperature
Lowest (region 1)
Alaska, Colorado, Idaho, Massachusetts, Maine, Michigan, Minnesota, Montana, North Dakota, New Hampshire,
New York, Oregon, Rhode Island, Vermont, Washington, Wisconsin, Wyoming
Middle (region 2)
California, Connecticut, Delaware, Iowa, Illinois, Indiana, Kentucky, Maryland, Nebraska, New Jersey, Nevada,
Ohio, Pennsylvania, South Dakota, Utah, Washington DC, West Virginia
Highest (region 3)
Alabama, Arkansas, Arizona, Florida, Georgia, Hawaii, Kansas, Louisiana, Missouri, Mississippi, North Carolina,
New Mexico, Oklahoma, South Carolina, Tennessee, Texas, Virginia
Main Analyses
Sensitivity Analyses
In unadjusted analyses, the Southeast was associated with
significantly decreased risk of MI, and marginally significant
(P⬍0.10) increased risk of coronary revascularization, and
ischemic stroke, compared with the Northeast. The Midwest
was also associated with significantly increased risk of
coronary revascularization procedures compared with the
Northeast. There were no other significant associations between geographic region and other CVD outcomes (Table 4).
After adjustment for potential confounding factors, the Southeast was no longer associated with significantly decreased
risk of MI compared with the Northeast. However, the
Southeast was associated with significantly increased risks of
total stroke (HR, 1.22; 95% CI, 1.02 to 1.47) and ischemic
stroke (HR, 1.30; 95% CI, 1.06 to 1.58) compared with the
Northeast (Table 4). Furthermore, we found significantly
increased risk of coronary revascularization with residence in
the Southeast and the Midwest.
Compared with the rest of the US, residence in the Southeast
was associated with marginally significantly increased risk of
total stroke (HR, 1.16; 95% CI, 1.00 to 1.34) and significantly
increased risk of ischemic stroke (HR, 1.20; 95% CI, 1.02 to
1.41). The Southeast was also associated with significantly
decreased risk of MI (HR, 0.86; 95% CI, 0.75 to 0.99), but not
coronary revascularization (HR, 1.08; 95% CI, 0.98 to 1.19),
compared with the rest of the US. Residence in the Southeast
was not associated with risk of major CVD or CVD death
(data not shown). Furthermore, compared with the rest of the
US, residence in the Midwest was not associated with any of
the evaluated outcomes (data not shown).
Because we found significantly increased risk of ischemic
stroke but not for MI and coronary revascularization, we
limited further sensitivity analyses to the ischemic stroke
outcome only. First, residence in the Stroke Belt was associated with marginally significantly increased risk of ischemic
2224
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August 2007
TABLE 2.
Distribution of Covariates by US Region
Characteristic
Northeast,
n (%)
Southeast,
n (%)
Midwest,
n (%)
West,
n (%)
Participants
4360 (24)
3734 (21)
5357 (30)
4476 (25)
Age, y (mean⫾SD)
53.9⫾9.2
53.3⫾9.1
53.4⫾8.8
53.3⫾9.0
Mean systolic blood pressure, mm Hg
126.7⫾11.8
125.4⫾11.8
125.6⫾11.6
125.7⫾11.7
Mean diastolic blood pressure, mm Hg
79.2⫾7.3
78.6⫾7.5
78.7⫾7.5
78.7⫾7.7
History of hypertension
1014 (23)
1085 (25)
897 (24)
1252 (23)
History of diabetes
112 (3)
93 (3)
130 (2)
85 (2)
Diagnosed cholesterol ⱖ240 mg/dL
576 (13)
396 (11)
611 (11)
530 (12)
Parental history of MI before age 60 y
407 (9)
390 (10)
486 (9)
426 (10)
Alcohol use
Daily
1153 (26)
865 (23)
1192 (22)
1204 (27)
1 per month to ⬍1 per day
2695 (62)
2278 (61)
3287 (61)
2531 (57)
512 (12)
591 (16)
878 (16)
741 (17)
Rarely or never
Smoking
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Never
2133 (49)
1827 (49)
2661 (50)
2454 (55)
Past
1789 (41)
1466 (39)
2064 (39)
1629 (36)
Current (1–19 per day)
166 (4)
136 (4)
205 (4)
167 (4)
Current (20⫹ per day)
272 (6)
305 (8)
427 (8)
226 (5)
Exercise to sweat
Daily
191 (4)
224 (6)
268 (5)
291 (7)
2629 (60)
2614 (70)
3707 (69)
3096 (69)
1–3 per month
714 (16)
490 (13)
733 (14)
587 (13)
Rarely or never
826 (19)
406 (11)
649 (12)
502 (11)
⬍25
2464 (57)
2126 (57)
3005 (56)
2756 (62)
25 to ⬍30
1710 (39)
1448 (39)
2113 (39)
1574 (35)
186 (4)
160 (4)
239 (4)
146 (3)
At least 1 per week
Body mass index, kg/m2
ⱖ30
Subgroup percentages may not sum to 100% because of rounding.
Physician’s Health Study (1982–2004) n⫽17 927.
stroke (HR, 1.17; 95% CI, 0.98 to 1.40) compared with the
rest of the US. When we categorized region of residence
based approximately on latitude, the South was not associated
with increased risk of ischemic stroke (HR, 1.00; 95% CI,
0.87 to 1.14) compared with the North.
Next, we ranked states into tertiles based on each state’s
mean winter temperature. Compared with the region with the
lowest mean winter temperatures (region 1: mean, 4.6°C;
state’s mean winter temperature ranged from ⫺9.0°C to
⫺0.9°C), neither the region with the next highest mean winter
temperatures (region 2: 1.3°C; range, ⫺0.6°C to 3.5°C; HR,
1.00; 95% CI, 0.85 to 1.17) nor the region with the highest
mean winter temperatures (region 3: 9.0°C; range, 4.3°C to
22.6°C; HR, 0.88; 95% CI, 0.74 to 1.06) was associated with
increased risk of ischemic stroke.
Last, we ranked states into tertiles based on each state’s
mean summer temperature. Compared with the region with
the lowest mean summer temperatures (region 1: mean,
19.7°C; state’s mean summer temperature ranged from
11.4°C to 21.6°C), neither the region with the next highest
mean summer temperatures (region 2: 23.0°C; range, 21.7°C
to 24.5°C; HR, 0.97; 95% CI, 0.81 to 1.15) nor the region
with the highest mean summer temperatures (region 3:
26.1°C; range, 24.6°C to 27.6°C; HR, 0.90; 95% CI, 0.77 to
1.06) was associated with increased risk of ischemic stroke.
Discussion
In this well-characterized cohort of mostly white, apparently
healthy, US male physicians, aged 40 to 84, with no CVD or
cancer at baseline, we did not find increased risk of major
CVD associated with region of residence in any analysis.
When we examined individual CVD events, we found significantly increased risk of total stroke and ischemic stroke
associated with the Southeast that was not attenuated after
adjusting for conventional CVD risk factors. We were also
able to replicate the pattern of increased stroke in the
Southeastern US (ie, Stroke Belt) seen in previous mortality
and incidence studies, as well as when using an alternative
definition of Stroke Belt (North Carolina, South Carolina,
Georgia, Alabama, Tennessee, Mississippi, Louisiana, Arkansas; data not shown), but not with any region when
classified by latitude or mean seasonal temperature. In
contrast, we found no consistent association between geographic region and risk of MI or CVD death. Our data
suggested an association between residence in the Southeast
and Midwest with coronary revascularization procedures,
Rich et al
TABLE 3.
Geographic Patterns and Cardiovascular Disease
2225
Crude and Age-Standardized Incidence Rates (per 1000 person-years) by Region
Outcome
Major cardiovascular disease* (n⫽2607)
Total stroke (n⫽1018)
Ischemic stroke (n⫽846)
MI (n⫽1247)
Coronary revascularization† (n⫽2479)
CVD death (n⫽995)
Type
Northeast
n⫽4360
Southeast
n⫽3734
Midwest
n⫽5357
West
n⫽4476
7.34
Crude
7.72
7.91
7.84
Age-standardized
7.72
8.38
8.30
7.75
Crude
2.78
3.14
2.90
2.55
Age-standardized
2.78
3.35
3.16
2.76
2.09
Crude
2.25
2.68
2.42
Age-standardized
2.25
2.86
2.65
2.25
Crude
3.75
3.12
3.50
3.59
Age-standardized
3.75
3.23
3.62
3.68
6.83
Crude
6.79
7.64
7.64
Age-standardized
6.79
7.79
7.72
6.98
Crude
2.62
2.81
2.87
2.55
Age-standardized
2.62
3.10
3.17
2.82
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*A major cardiovascular event was defined as any first of the following events: nonfatal stroke, nonfatal MI, or death from
cardiovascular cause.
†Includes reports of bypass surgery or percutaneous coronary angioplasty.
Physician’s Health Study (1982–2004) n⫽17 927.
which were, however, attenuated and no longer statistically
significant in our sensitivity analyses. The increased risk of
ischemic stroke in the Southeast region may be attributable to
differences in other regional environmental conditions or
lifestyle factors not included in this analysis.
Our stroke risk estimates for the Southeast region for
predominantly white, male, physicians 40 to 84 years of age
(HR, 1.22; 95% CI, 1.02 to 1.47), were slightly lower than
those reported by Gillum and Ingram6 for white males 45 to
74 years of age (HR, 1.41; 95% CI, 1.02 to 1.92). Unadjusted
TABLE 4. Unadjusted and Adjusted HR and 95% CIs for Overall and Specific CVD Associated With
Residence in Each US Region
Outcome
Northeast
(n⫽4360)
Southeast
(n⫽3734)
Midwest
(n⫽5357)
West
(n⫽4476)
Major cardiovascular disease* (n⫽2607)
(n⫽633)
(n⫽557)
(n⫽793)
(n⫽624)
Unadjusted
1.00
1.02 (0.91–1.15)
1.01 (0.91–1.13)
0.95 (0.85–1.06)
Adjusted†
1.00
1.09 (0.97–1.22)
1.07 (0.97–1.19)
1.07 (0.95–1.19)
(n⫽243)
(n⫽234)
(n⫽311)
(n⫽230)
1.00
1.13 (0.94–1.35)
1.04 (0.88–1.23)
0.92 (0.77–1.10)
Total stroke (n⫽1018)
Unadjusted
Adjusted†
1.00
1.22 (1.02–1.47)
1.13 (0.95–1.34)
1.03 (0.86–1.24)
(n⫽197)
(n⫽200)
(n⫽260)
(n⫽189)
Unadjusted
1.00
1.19 (0.98–1.45)
1.07 (0.89–1.29)
0.93 (0.76–1.13)
Adjusted†
1.00
1.30 (1.06–1.58)
1.17 (0.97–1.41)
1.05 (0.86–1.29)
(n⫽323)
(n⫽232)
(n⫽372)
(n⫽320)
1.00
0.83 (0.70–0.98)
0.93 (0.80–1.08)
0.96 (0.82–1.12)
Ischemic stroke (n⫽846)
MI (n⫽1247)
Unadjusted
Adjusted†
1.00
0.86 (0.73–1.02)
0.96 (0.83–1.12)
1.05 (0.90–1.23)
(n⫽568)
(n⫽542)
(n⫽780)
(n⫽589)
Unadjusted
1.00
1.12 (1.00–1.26)
1.12 (1.01–1.25)
1.00 (0.89–1.13)
Adjusted†
1.00
1.17 (1.04–1.31)
1.15 (1.03–1.28)
1.08 (0.96–1.21)
(n⫽233)
(n⫽214)
(n⫽314)
(n⫽234)
Unadjusted
1.00
1.07 (0.89–1.29)
1.09 (0.92–1.30)
0.97 (0.81–1.17)
Adjusted†
1.00
1.15 (0.95–1.39)
1.20 (1.01–1.42)
1.14 (0.95–1.37)
Coronary revascularization† (n⫽2479)
CVD death (n⫽995)
*A major cardiovascular event was defined as any first of the following events: nonfatal stroke, nonfatal MI, or death from
cardiovascular cause.
†Adjusted for age, alcohol consumption, smoking status, exercise frequency, body mass index, history of elevated cholesterol
ⱖ240 mg/dL, previous diagnosis of hypertension, previous diagnosis of diabetes, and family history of MI before age 60.
Physician’s Health Study (1982–2004) n⫽17 927.
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August 2007
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stroke incidence rates were markedly lower in our study,
compared with Gillum and Ingram.6 This likely reflects that
our cohort only included physicians. On average, physicians
are considered to be of higher socioeconomic status, to have
healthier lifestyles, better diets, better access to health care
services, and more frequent use of preventive health care,
compared with nonphysicians. Another explanation why our
incidence rates are lower is that our study was conducted
from 1982 to 2004, whereas the study period in the study by
Gillum and Ingram6 was much earlier (1971 to 1987).
Because stroke mortality rates have declined over time,5 and
assuming incidence rates followed a similar pattern, we
would expect to see lower incidence rates in our study.
A possible reason for the observed association between
residence in the Southeastern US and incidence of ischemic
stroke is diet. In the third National Health and Nutrition
Examination Survey, the Southeast region had the highest
blood pressures values, the highest intakes of monounsaturated and polyunsaturated fatty acids, cholesterol, and sodium, and the lowest intake of fiber and several vitamins and
minerals18 compared with the other three regions. We had no
detailed information on dietary intake at baseline in the
Physicians Health Study. However, statistical adjustment
using available information on vegetable and milk intake
made little difference (data not shown).
The National Health and Nutrition Examination Survey III
reported lower mean serum selenium levels among people
residing in the Southern US compared with the other 3 US
regions.19 Selenium levels have previously been inversely
associated with risk of nonfatal MI and fatal CHD,20 total,
cardiovascular, and stroke mortality,21 and directly associated
with coronary revascularization procedures.20
Studies of temperature and stroke incidence have been
inconsistent, with some finding no association, others reporting associations with cold months, and others with warm
months.12 One study found no difference in stroke incidence
rates between days with abrupt changes in weather conditions
and those without such changes.22 We ranked states based on
mean winter temperature, mean summer temperature and
latitude. Although we found no association with geographic
region based on either latitude or seasonal mean temperature,
other characterizations of the regional variability in temperature or other weather conditions may be associated with
increased risk of ischemic stroke.
Our study had several strengths, including the large number of outcome events and participants, prospective method
of data collection, and the homogenous nature of our cohort,
which reduced confounding by many sociodemographic factors. Furthermore, with the exception of coronary revascularization, all outcome events were confirmed after medical
record review.
Several limitations should be considered when interpreting
out results. The mailing address given by each subject at
baseline was used to classify each subject into US regions.
This mailing address could have been the subject’s home or
the subject’s work address. Some subjects may work and live
in different cities and states, which could be important if we
were examining local variability in CVD incidence. However, it
is unlikely that subjects worked and lived in different census
regions; therefore, this likely did not result in substantial
misclassification of census region. If a few cases of misclassification did in fact occur, this was likely nondifferential
with respect to outcome, resulting in underestimation of risk.
If subjects moved during follow-up from other regions
(cold weather states in the Northeast and Midwest) to the
Southeast (eg, Florida, South Carolina, etc), this would
have made the regions’ incidence rates more similar.
Therefore, this also would have led to an underestimate of
the risk of ischemic stroke associated with residence in the
Southeast.
These findings are directly generalizable to middle-aged to
older, white, US males of higher socioeconomic status.
However, gender and racial differences in stroke mortality3
and stroke incidence6,23 have been demonstrated. Therefore, it
is likely that different racial and gender groups may have
markedly different ischemic stroke incidence rates in the
same region of residence. Thus, these analyses should be
replicated in women and nonwhites.
In summary, in this large, prospective cohort of apparently
healthy, mostly white, US male physicians, we found no
evidence of regional differences in risk of major CVD. In
further analyses, we found consistent significantly increased
risk of total and ischemic stroke, but not other vascular events
associated with living in the Southeast compared with the
Northeast or the rest of the US, after adjustment for traditional CVD risk factors.
Acknowledgments
The authors are indebted to the participants of the Physician’s Health
Study for their outstanding commitment and cooperation, and to the
entire Physicians’ Health Study staff for their expert and
unfailing assistance.
Sources of Funding
The study was supported by NCI grants CA 34944 and CA 40360,
and NHLBI grants HL 26490 and HL 34595.
Disclosures
None.
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Geographic Patterns in Overall and Specific Cardiovascular Disease Incidence in
Apparently Healthy Men in the United States
David Q. Rich, J. Michael Gaziano and Tobias Kurth
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Stroke. 2007;38:2221-2227; originally published online June 28, 2007;
doi: 10.1161/STROKEAHA.107.483719
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