Clinical Sciences

Clinical Sciences
Dietary Sodium and Risk of Stroke in the Northern
Manhattan Study
Hannah Gardener, ScD; Tatjana Rundek, MD; Clinton B. Wright, MD;
Mitchell S.V. Elkind, MD; Ralph L. Sacco, MD
Downloaded from http://stroke.ahajournals.org/ by guest on September 18, 2016
Background and Purpose—The American Heart Association recommends limiting sodium intake to ⱕ1500 mg/day for
ideal cardiovascular health. Although sodium intake has been linked to vascular disease by direct relationship with
hypertension, few studies have supported an association with stroke risk.
Methods—Participants were from the Northern Manhattan Study (mean age 69⫾ 10 years, 64% women, 21% white, 53%
Hispanic, 24% black), a population-based cohort study of stroke incidence. Sodium intake was assessed with a food
frequency questionnaire at baseline and evaluated continuously and categorically: ⱕ1500 mg/day (12%), 1501 to 2300
mg/day (24%), 2301 to 3999 mg/day (43%), and ⱖ4000 mg/day (21%). Over a mean follow-up of 10 years, we
examined the association between sodium consumption and 235 strokes using Cox models adjusting for sociodemographics, diet, behavioral/lifestyle, and vascular risk factors.
Results—Of 2657 participants with dietary data, the mean sodium intake was 3031⫾1470 mg/day (median, 2787;
interquartile range, 1966 –3815 mg/day). Participants who consumed ⱖ4000 mg/day sodium had an increased risk of
stroke (hazard ratio, 2.59; 95% CI, 1.27–5.28) versus those who consumed ⱕ1500 mg/day with a 17% increased risk
of stroke for each 500-mg/day increase (95% CI, 1.07–1.27).
Conclusions—High sodium intake was prevalent and associated with an increased risk of stroke independent of vascular risk
factors. The new American Heart Association dietary sodium goals will help reduce stroke risk. (Stroke. 2012;43:12001205.)
Key Words: diet 䡲 epidemiology 䡲 sodium 䡲 stroke
potential exposure misclassification and a relatively young
population resulting in a small number of outcome events, it
raised some doubts about the association of sodium and
cardiovascular events. Limited research has been conducted
within ethnically heterogeneous populations, including blacks
and Hispanics, who are at an increased risk for hypertension
and stroke.5,6 The controversial findings of this recent report
and gaps in the literature regarding the association between
sodium consumption and risk of cardiovascular disease and
stroke among blacks and Hispanics underscore the need for
further research.
We examined the association between sodium consumption and risk of stroke and combined vascular events, stroke,
myocardial infarction (MI), and vascular death, in a multiethnic population-based prospective cohort study.
See related article, pages 1195–1196
he American Heart Association (AHA) lowered its recommended level of sodium consumption to ⱕ1500
mg/day for all Americans. This recommendation is based
largely on the well-established relationship between excess
sodium intake and hypertension.1 Although hypertension is a
risk factor for vascular disease, and is associated with an
approximately 3-fold increased risk of stroke,2 studies on the
relationship between sodium consumption and risk of stroke
and cardiovascular disease have shown inconsistent results. A
recent meta-analysis suggested that elevated salt intake was
associated with an increased risk of stroke and, to a lesser
extent, with an increased risk of cardiovascular disease.3
However, there was significant heterogeneity in effect estimates across studies, and the majority of included studies did
not show an association between high sodium intake and risk
of stroke or cardiovascular disease or did so only for certain
population subsets. In fact, a recent cohort study of white
Europeans even showed a higher rate of cardiovascular
disease mortality among those with lower sodium excretion.4
Although the latter study had several limitations, including
T
Methods
Study Population
The Northern Manhattan Study (NOMAS) is a cohort study designed
to determine stroke incidence, risk factors, and prognosis in a
Received October 6, 2011; final revision received December 19, 2011; accepted December 22, 2011.
From the Evelyn F. McKnight Brain Institute and Department of Neurology (H.G., T.R., C.B.W., R.L.S.), and the Department of Epidemiology and
Public Health (T.R., C.B.W., R.L.S.), University of Miami, Miami, FL; and the Department of Neurology (M.S.V.E.), Columbia University Medical
Center, New York, NY.
Correspondence to Hannah Gardener, ScD, 1120 NW 14th Street, Miami, FL 33136. E-mail [email protected]
© 2012 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.111.641043
1200
Gardener et al
multiethnic urban population. Study details have been published
previously.7
Eligible participants were: (1) stroke-free; (2) ⬎40 years old; and
(3) resided in northern Manhattan for ⱖ3 months with a household
telephone. Participants were identified by random-digit dialing (91%
telephone response rate) and recruited to have an in-person baseline
interview and assessment between 1993 and 2001. The enrollment
response rate was 75%, and 3298 participants were enrolled. For our
analysis, we excluded participants without a completed diet questionnaire (N⫽132), with improbable total daily kilocalories or
sodium consumption based on food frequency responses (⬍500 or
⬎4000 kcal/day or ⬎10 000 mg/day sodium, N⫽272), and those
with an MI before baseline (n⫽237). The study was approved by the
Columbia University and University of Miami Institutional Review
Boards and all participants provided informed consent.
Baseline Evaluation
Downloaded from http://stroke.ahajournals.org/ by guest on September 18, 2016
Data were collected through interviews with trained research assistants in English or Spanish. Study physicians conducted physical
examinations. Race– ethnicity was based on self-identification using
questions modeled after the US census and conforming to standard
definitions outlined by Directive 15.8 Standardized questions were
adapted from the Behavioral Risk Factor Surveillance System by the
Centers for Disease Control and Prevention regarding hypertension,
diabetes, smoking, and cardiac conditions.9 Measurement of blood
pressure (BP) and fasting blood specimens for glucose and lipids and
the definitions of hypercholesterolemia, diabetes, moderate to heavy
physical activity, and moderate alcohol use were described previously.10,11 Hypertension was defined as BP ⱖ140/90 mm Hg, antihypertensive medication use, or the participant’s self-report of
hypertension.
Diet
At baseline, participants were administered a modified Block National Cancer Institute food frequency questionnaire by trained
research assistants in English or Spanish.12 This questionnaire
assesses dietary patterns over the previous year and was modified to
include specific dietary items commonly consumed among Hispanics. Sodium intake was calculated based on self-reported food
consumption using DIETSYS software (Block Dietary Data System:
Dietsys⫹ analysis software, Version 59, 1999).
Average sodium consumption was examined continuously with
500 mg/day as the unit of measurement and in prespecified categories: ⱕ1500 mg/day (reference, AHA recommendation), 1501 to
2300 mg/day (consistent with US Department of Agriculture recommendation of ⱕ2300 mg for those at standard risk), 2301 to 3999
mg/day, and 4000 to 10000 mg/day (approximately the top quintile).
Outcomes
The primary outcome was confirmed incident stroke of all subtypes
(infarcts, intracerebral hemorrhage, and subarachnoid hemorrhage).
Secondary outcomes were confirmed (1) incident combined vascular
event (stroke, MI, or vascular death); (2) incident MI; and (3)
vascular death. Follow-up procedures and outcome classifications
were detailed previously.10,13 Subjects were screened annually by
telephone to determine changes in vital status, detect neurological
events, document interval hospitalizations, and review risk factor
status, medication changes, and changes in functional status. Persons
who screened positive were scheduled for in-person assessment,
including chart review and examination by study neurologists.
Ongoing hospital surveillance of admission and discharge data,
including screening of International Classification of Diseases, 9th
Revision codes, was reviewed to detect outcome events. The
outcome surveillance network includes screening of all daily admissions, daily contacts with the neurology consult residents, reviewing
bimonthly hospital discharge lists, emergency room visits, and visits
to the ambulatory care network. All hospitalizations for suspected
stroke or MI were reviewed thoroughly and trigger more extensive
data collection for outcome adjudication. Medical records of all
hospitalizations were reviewed to verify the details of suspected
Dietary Sodium and Stroke Risk
1201
events. Outcome events were reviewed by a specially trained
research assistant and, when available, medical records were reviewed for all outcome events, including death, by the study
neurologists and cardiologists.
Stroke was defined by the first symptomatic occurrence of any
type of stroke including infarct, intracerebral hemorrhage, and
subarachnoid hemorrhage. Stroke was defined based on World
Health Organization criteria as “rapidly developing clinical signs of
focal (at times global) disturbance of cerebral function, lasting more
than 24 hours or leading to death with no apparent cause other than
that of vascular origin.” Strokes were classified as intracerebral
hemorrhage, subarachnoid hemorrhage, and cerebral infarction (atherosclerotic extracranial vessel, atherosclerotic intracranial vessel,
lacunar small vessel, cardioembolic, cryptogenic, and other determined cause). MI was defined by criteria adapted from the Cardiac
Arrhythmia Suppression Trial and the Lipid Research Clinics Coronary Primary Prevention Trial and requires at least 2 of the 3
following criteria: (1) ischemic cardiac pain determined to be typical
angina; (2) cardiac enzyme abnormalities defined as abnormal
creatine–phosphokinase MB isoenzyme fraction or troponin values;
and (3) electrocardiographic abnormalities. Stroke events were
adjudicated by the study neurologists and cardiac events by the study
cardiologists. The cause of death was classified as vascular or
nonvascular and based on information obtained from the family,
medical records, and death certificates. Vascular death included
death due to stroke, MI, heart failure, pulmonary embolus, cardiac
arrhythmia, or other vascular cause. These are International Classification of Diseases, 9th Revision codes 390 to 459.
Statistical Analysis
We examined the unadjusted associations of categories of sodium
consumption with sociodemographics and vascular risk factors using
analysis of variance and ␹2 tests.
We used Cox proportional hazards models to examine the association between sodium consumption (continuously and categorically) and vascular events. Person-time of follow-up was accrued
from baseline to the end of follow-up (March 2011), the time of
outcome event, death, or loss to follow-up, whichever came first. We
constructed the following models sequentially: (1) adjusted for
demographics: age, sex, race/ethnicity, and high school completion;
(2) adjusted for demographics and behavioral risk factors: smoking
(never, former, current), moderate to heavy physical activity, moderate alcohol consumption, daily consumption of total kcal, protein,
total fat, saturated fat, and carbohydrates; and (3) adjusted for
demographics, behavioral risk factors, and vascular risk factors:
diabetes, hypercholesterolemia, hypertension, previous cardiac disease, and body mass index. We assessed potential effect modification
by age, sex, race/ethnicity, hypertension status, and continuous BP
measurements (in the overall sample and among those not taking
antihypertensive medications) by including interaction terms between sodium consumption and these variables in Model 3.
Results
This study included 2657 NOMAS participants. The mean
age at baseline was 69⫾10 years, 36% of participants were
men, 21% white, 24% black, and 53% Hispanic. Over a mean
follow-up of 10 years, 615 vascular events accrued, including
235 strokes (202 ischemic strokes), 209 MIs, and 371
vascular deaths. The mean sodium consumption was
3031⫾1470 mg/day (median, 2787 mg/day; interquartile
range, 1966 –3815). Only 12% consumed the AHArecommended level of ⱕ1500 mg/day sodium, whereas 24%
consumed 1501 to 2300, 43% 2301 to 3999, and 21% 4000 to
10 000 mg/day.
Table 1 shows the risk factor profile of the study population overall and in relation to sodium consumption. In
unadjusted analyses, lower sodium consumption was associ-
1202
Stroke
May 2012
Table 1.
Demographics and Vascular Risk Factors and Sodium Consumption
Sodium Consumption, mg/d
Full Cohort
ⱕ1500
1501–3999
ⱖ4000
(N⫽2657)
(N⫽320)
(N⫽1779)
(N⫽558)
965 (36)
68 (21)
622 (35)
275 (49)
Categorical factors, no. (%)
Male sex*
Race/ethnicity*
White
552 (21)
49 (15)
397 (22)
106 (19)
Black
637 (24)
104 (33)
418 (24)
115 (21)
1407 (53)
160 (50)
925 (52)
322 (58)
61 (2)
7 (2)
39 (2)
15 (3)
1124 (46)
140 (44)
836 (47)
248 (44)
Current
452 (17)
54 (17)
298 (17)
100 (18)
Former
946 (36)
92 (29)
625 (35)
229 (41)
Never
229 (41)
Hispanic
Other
High school completion
Smoking*
Downloaded from http://stroke.ahajournals.org/ by guest on September 18, 2016
1259 (47)
174 (54)
856 (48)
Moderate to heavy physical activity
232 (9)
18 (6)
163 (9)
51 (9)
Moderate alcohol use*
895 (34)
84 (26)
610 (34)
201 (36)
Previous cardiac disease
482 (18)
58 (18)
310 (17)
114 (20)
Hypertension
1928 (73)
244 (76)
1276 (72)
408 (73)
Antihypertensive use*
1139 (43)
161 (50)
751 (42)
227 (41)
Diabetes
Hypercholesterolemia
552 (21)
64 (20)
364 (20)
124 (22)
1501 (56)
193 (60)
1008 (57)
300 (54)
Continuous factors, mean (SD)
Age*
69 (10)
70 (10)
69 (10)
68 (9)
1561 (648)
814 (238)
1429 (401)
2413 (594)
Total fat, g/d*
61 (31)
31 (12)
54 (20)
99 (32)
Saturated fat, g/d*
20 (12)
9 (4)
18 (8)
34 (13)
Protein, g/d*
62 (28)
30 (11)
57 (18)
96 (28)
Carbohydrates, g/d*
187 (80)
100 (37)
175 (57)
277 (79)
Systolic blood pressure
143 (21)
144 (20)
143 (21)
144 (21)
Total kilocalories/d*
Diastolic blood pressure
83 (11)
83 (11)
83 (11)
84 (11)
Low-density lipoprotein
128 (36)
131 (35)
129 (36)
126 (36)
High-density lipoprotein*
47 (15)
49 (16)
47 (15)
45 (14)
Body mass index*
28 (6)
28 (5)
28 (5)
29 (6)
*P⬍0.05 across categories of sodium consumption (␹2 test for categorical variables, analysis of variance for continuous variables).
ated with older age, female sex, black race, never smoking,
and antihypertensive use, whereas higher sodium consumption was associated with Hispanic ethnicity, moderate alcohol
use, increased body mass index, and consumption of total
kilocalories, protein, carbohydrates, total fat, and saturated fat
(P⬍0.05). There was no significant association between
sodium consumption and continuous BP measurements or
hypertension status at baseline.
We observed an increased risk of stroke with greater
sodium consumption, and this relationship became stronger
after adjusting for behavioral and vascular risk factors (Table
2). The analysis of sodium as a continuous variable showed a
17% increase in stroke risk for each 500-mg/day increase in
sodium consumption (Model 3; 95% CI, 1.07–1.27). Those
who consumed ⱖ4000 mg/day sodium had a 2.6-fold increase in stroke risk versus those who consumed ⱕ1500
mg/day (Model 3; 95% CI, 1.27–5.28). Intake of sodium
⬎1500 but ⬍4000 mg/day had a hazard ratio of 1.3 for
stroke, which did not reach significance. We did not observe
an interaction between sodium and age (interaction P⫽0.68),
sex (interaction⫽0.84), race/ethnicity (interaction P⫽0.47
black versus white, P⫽0.73 Hispanic versus white), hypertension status (interaction P⫽0.99), or BP (interaction
P⫽0.98 for systolic BP and P⫽0.73 for diastolic BP) at
baseline in relation to stroke risk. When the outcome was
restricted to ischemic stroke, the results remained consistent.
A 16% increased risk of ischemic stroke was seen for each
500-mg/day sodium increase, and there was a 2.4-fold greater
risk among those who consumed ⱖ4000 versus ⱕ1500
mg/day of sodium.
Table 3 shows the relationship between sodium consumption and combined vascular events. Consumption of ⱖ4000
Gardener et al
Table 2.
Dietary Sodium and Stroke Risk
1203
Sodium Intake in Relation to Stroke Risk
Hazard Ratio (95% CI) for Stroke
Daily Dietary Sodium, mg
500-mg/d increase
Person-Years
Events
Model 1*
Model 2†
Model 3‡
1.17 (1.07–1.27)
27 048
235
1.08 (1.04 –1.13)
1.17 (1.07–1.27)
ⱕ1500
3408
24
1.0 (referent)
1.0 (referent)
1.0 (referent)
1501–2300
6620
56
1.24 (0.77–2.01)
1.33 (0.81–2.18)
1.38 (0.84–2.27)
2301–3999
11 752
89
1.15 (0.73–1.81)
1.31 (0.78–2.22)
1.32 (0.78–2.23)
5262
66
1.99 (1.24–3.20)
2.50 (1.23–5.07)
2.59 (1.27–5.28)
4000–10 000
*Adjusted for demographics (age, sex, race/ethnicity, education).
†Adjusted for demographics⫹behavioral risk factors (alcohol use, smoking, physical activity, total calories, total fat, saturated fat, carbohydrates, protein).
‡Adjusted for demographics⫹behavioral risk factors⫹vascular risk factors (diabetes, hypercholesterolemia, hypertension, previous cardiac disease, body mass
index).
Downloaded from http://stroke.ahajournals.org/ by guest on September 18, 2016
2300 mg/day compared with ⱕ1500 mg/day. Although we
found a 17% relative increase in the hazard of stroke for every
500-mg/day increase in dietary sodium intake, our data did
not suggest a linear dose–response relationship between
sodium consumption and stroke risk.
A meta-analysis supported a strong relationship between
sodium consumption and stroke risk,3 although many previous prospective cohort studies did not show an association or
did so only for a subset of the study population. Specifically,
a 23% increased risk of stroke was reported among those with
higher salt intake (approximately 5 g/day more salt than those
classified as consuming less salt). A 14% increased risk of
cardiovascular disease was also associated with higher salt
intake (P⫽0.07). Effect estimates across studies were heterogeneous as were the methods used. Some studies also used
food frequency questionnaires to assess sodium consumption,
whereas others used 24-hour dietary recall or urinary sodium
excretion analysis. The strength of the association with stroke
risk was often different for men versus women, but the
direction of this difference was inconsistent. In our study, we
did not observe effect modification by sex. Possible reasons
for the lack of association between sodium and stroke risk in
other studies include small sample size, misclassification of
sodium intake, and short follow-up.
Our results are consistent with the meta-analysis3 indicating a stronger association for sodium consumption with
stroke than with cardiovascular disease. The majority of
previous prospective studies also did not observe a significant
relationship with global cardiovascular disease risk. The
mg/day sodium was associated with an elevated risk of
combined vascular events versus ⱕ1500 mg/day. Intake
of 1501 to 2300 mg/day was associated with an increased risk
of stroke, MI, or vascular death compared with ⱕ1500
mg/day. There was no interaction between sodium consumption and age (interaction P⫽0.10), sex (interaction⫽0.30),
race/ethnicity (interaction P⫽0.19 black versus white,
P⫽0.18 Hispanic versus white), hypertension status (interaction P⫽0.28), or BP (interaction P⫽0.18 for systolic BP and
P⫽0.49 for diastolic BP) in relation to vascular events. No
association was observed between sodium consumption and
risk of MI or risk of vascular death (Table 3).
Discussion
Excessive sodium intake was prevalent in this populationbased multiethnic cohort with only 12% meeting the AHArecommended level of ⱕ1500 mg/day, only 36% meeting the
US Department of Agriculture-recommended level of ⱕ2300
mg/day, and 21% consuming ⱖ4000 mg/day based on
self-reported food consumption using a food frequency questionnaire. Excessive sodium intake was associated with an
increased risk of vascular events, but in our event-specific
analysis, sodium consumption ⱖ4000 mg/day was associated
mainly with stroke and less with MI or vascular death. There
was a slight increased risk of stroke among those in the 2
daily sodium consumption categories between 1501 to 3999
mg in comparison to ⱕ1500 mg, but this did not reach
statistical significance. For combined events, there was a
significantly increased risk among those consuming 1501 to
Table 3.
Sodium in Relation to Risk of Combined Vascular Events and of MI and Vascular Death Separately
Hazard Ratio (95% CI)
Stroke, MI, or Vascular Death
Daily Dietary
Sodium, mg
500-mg/d
increase
MI
Vascular Death
Person-Years
Events
Model 2*
Model 3†
Events
Model 2*
Model 3†
Events
Model 2*
Model 3†
26 278
615
1.06 (1.00 –1.12)
1.05 (0.99 –1.11)
209
0.95 (0.86 –1.04)
0.94 (0.85–1.04)
371
1.02 (0.95–1.10)
1.02 (0.95–1.10)
ⱕ1500
3306
67
1.0 (referent)
1.0 (referent)
29
1.0 (referent)
1.0 (referent)
41
1.0 (referent)
1.0 (referent)
1501–2300
6432
157
1.32 (0.98–1.78)
1.35 (1.00–1.82)
53
0.88 (0.55–1.43)
0.93 (0.58–1.51)
95
1.39 (0.95–2.04)
1.43 (0.97–2.11)
2301–3999
11 447
253
1.21 (0.87–1.67)
1.21 (0.87–1.67)
80
0.66 (0.39–1.11)
0.68 (0.40–1.15)
164
1.37 (0.91–2.07)
1.37 (0.90–2.07)
5095
138
1.70 (1.08–2.68)
1.68 (1.06–2.67)
47
0.79 (0.37–1.69)
0.78 (0.36–1.70)
71
1.49 (0.82–2.72)
1.49 (0.81–2.72)
4000–10 000
MI indicates myocardial infarction.
*Adjusted for demographics⫹behavioral risk factors.
†Adjusted for demographics⫹behavioral risk factors⫹vascular risk factors.
1204
Stroke
May 2012
Downloaded from http://stroke.ahajournals.org/ by guest on September 18, 2016
stronger relationship between sodium consumption and risk
of stroke as compared with MI is likely due to the fact that BP
is etiologically more important for stroke than MI.14 Our
findings do not support the conclusions of a recent study
suggesting an increased risk of cardiovascular events among
those with low sodium excretion levels in a predominantly
white, younger European cohort.4
The current study includes a large proportion of blacks and
Hispanics, who have been underrepresented in the literature.
Because dietary behavior may vary across race/ethnic groups,
even those living in the same community, and evidence
suggests that blacks and Hispanics are at an increased risk of
stroke and hypertension,5,6 examination of the relationship
between sodium consumption and stroke and cardiovascular
disease risk in an ethnically heterogeneous population was
needed. Sodium consumption differed by race/ethnicity in our
study with Hispanics consuming the most, and therefore the
attributable risk of sodium consumption for stroke among
Hispanics is likely to be higher. The power to detect effect
modification by race/ethnicity was modest, however, and we
did not observe a significant difference in the relationship
between sodium consumption and stroke risk across race/
ethnic groups.
Our study uses the new AHA-recommended sodium consumption guideline as its reference value. The results show
that a large proportion of our study population (88%) consumed more than the AHA recommendation of ⱕ1500
mg/day and that lowering their sodium consumption may
have a substantial effect on lowering their stroke risk.
Although the US Department of Agriculture level for the
general population is set at 2300 mg/day, a lower level of
ⱕ1500 mg/day has been recommended for certain population
groups including those aged ⬎51 years, all blacks, and all
patients who have hypertension, chronic kidney disease, or
diabetes. Our study supports the importance of reducing
sodium consumption to this level for most Americans. The
association between sodium consumption and stroke risk was
independent of behavioral and vascular risk factors, including
hypertension, at baseline, and was observed among those
with and without hypertension and across age groups, suggesting that lowering sodium consumption can have beneficial effects on stroke risk for all.
Although we controlled for hypertension at baseline, BP
may still be on a causal pathway underlying the association
between sodium consumption and stroke risk, because sodium consumption may influence changes in BP during
follow-up. Excess sodium intake is directly related to elevated BP, and dose–response trials have shown that the BP
response to sodium reduction is progressive and nonlinear.1
Likewise, elevated BP is an established risk factor for
cardiovascular disease and stroke, and primary and secondary
prevention strategies support BP reduction to decrease vascular events.15–19
Sodium consumption was not associated with systolic or
diastolic BP or defined hypertension in our study. In fact,
antihypertensive use was associated with lower sodium consumption. The lack of association between sodium consumption and BP was likely due to the cross-sectional nature of the
analysis, because BP and diet were both assessed at baseline.
Participants with hypertension, particularly those taking antihypertensive medication, may have been advised by their
physicians to limit sodium consumption. In addition, the
majority of our cohort (73%) had hypertension at baseline,
which could have inhibited our ability to detect an association
with sodium intake.
The biological mechanisms by which sodium might influence stroke risk independent of BP are speculative. Adverse
health effects of heavy sodium consumption, independent of
BP, include increased oxidative stress, impaired renal function, left ventricular hypertrophy, arterial fibrosis, increased
large elastic artery stiffness, vascular endothelial dysfunction,
and vascular remodeling, all of which are associated with
vascular disease risk.1
Strengths of our study include its population-based prospective design, multiethnic population, high follow-up, validated outcomes, and comprehensive collection of vascular
and other behavioral/lifestyle risk factors. However, despite
the use of a well-established valid and reliable food frequency
questionnaire12,20,21 to calculate sodium consumption, a potential for both random misclassification and recall bias
persists. We lacked independent verification of dietary sodium intake using an objective measurement such as urinary
sodium excretion. The prospective design suggests that most
misclassification would likely be random. We tried to limit
the effect of inaccurate recall of diet by excluding participants
with improbably low or high total daily kilocalories (⬍500 or
⬎4000) or sodium consumption ⬎10 000 mg. However,
possible underreporting of total diet is suggested by the low
mean caloric consumption, particularly in the ⱕ1500-mg
sodium category. In addition, the calculation of sodium
consumption using the food frequency questionnaire was not
able to fully capture the contribution of salt added to foods at
the table. Sodium consumption was based on self-reported
food consumption at a single time point, but participants were
asked to indicate their average food consumption over the last
year. Dietary patterns may change over time and possibly
during follow-up. Because our study population was all aged
⬎40 years at baseline food frequency assessment, we were
not able to examine the effect of sodium consumption before
enrollment at earlier stages in life.
Our study provides evidence for a strong relationship
between excess sodium intake and increased stroke risk in a
multiethnic population. Our findings contribute to a body of
literature indicating the high sodium intake in the United
States has negative health consequences. The new AHA
strategic dietary goals for 2020, which include sodium
reduction to ⱕ1500 mg/day, will help promote ideal cardiovascular and brain health. Our findings underscore the need
for public health initiatives to reduce the sodium level in the
food supply.
Sources of Funding
This work is supported by a grant from the National Institute of
Neurological Disorders and Stroke (R37 NS 29993).
Disclosures
None.
Gardener et al
References
Downloaded from http://stroke.ahajournals.org/ by guest on September 18, 2016
1. Appel LJ, Frohlich ED, Hall JE, Pearson TA, Sacco RL, Seals DR, et al.
The importance of population-wide sodium reduction as a means to
prevent cardiovascular disease and stroke: a call to action from the
American Heart Association. Circulation. 2011;123:1138 –1143.
2. Stokes J III, Kannel WB, Wolf PA, D’Agostino RB, Cupples LA. Blood
pressure as a risk factor for cardiovascular disease. The Framingham
study—30 years of follow-up. Hypertension. 1989;13:I13–I18.
3. Strazzullo P, D’Elia L, Kandala NB, Cappuccio FP. Salt intake, stroke,
and cardiovascular disease: meta-analysis of prospective studies. BMJ.
2009;339:b4567.
4. Stolarz-Skrzypek K, Kuznetsova T, Thijs L, Tikhonoff V, Seidlerova J,
Richart T, et al. Fatal and nonfatal outcomes, incidence of hypertension,
and blood pressure changes in relation to urinary sodium excretion.
JAMA. 2011;305:1777–1785.
5. Sacco RL, Boden-Albala B, Gan R, Chen X, Kargman DE, Shea S, et al.
Stroke incidence among white, black, and Hispanic residents of an urban
community: the Northern Manhattan Stroke Study. Am J Epidemiol.
1998;147:259 –268.
6. White H, Boden-Albala B, Wang C, Elkind MS, Rundek T, Wright CB,
et al. Ischemic stroke subtype incidence among whites, blacks, and
Hispanics: the Northern Manhattan Study. Circulation. 2005;111:
1327–1331.
7. Sacco RL, Boden-Albala B, Abel G, Lin IF, Elkind M, Hauser WA, et al.
Race– ethnic disparities in the impact of stroke risk factors: the Northern
Manhattan Stroke Study. Stroke. 2001;32:1725–1731.
8. Wallman KK, Hodgdon J. Race and ethnic standards for federal statistics
and administrative reporting. Stat Report. 1977:450 – 454.
9. Gentry EM, Kalsbeek WD, Hogelin GC, Jones JT, Gaines KL, Forman
MR, et al. The behavioral risk factor surveys: II. Design, methods, and
estimates from combined state data. Am J Prev Med. 1985;1:9 –14.
10. Boden-Albala B, Cammack S, Chong J, Wang C, Wright C, Rundek T, et
al. Diabetes, fasting glucose levels, and risk of ischemic stroke and
vascular events: findings from the Northern Manhattan Study (NOMAS).
Diabetes Care. 2008;31:1132–1137.
Dietary Sodium and Stroke Risk
1205
11. Willey JZ, Paik MC, Sacco R, Elkind MS, Boden-Albala B. Social
determinants of physical inactivity in the Northern Manhattan Study
(NOMAS). J Community Health. 2010;35:602– 608.
12. Block G, Hartman AM, Dresser CM, Carroll MD, Gannon J, Gardner L.
A data-based approach to diet questionnaire design and testing. Am J
Epidemiol. 1986;124:453– 469.
13. Boden-Albala B, Sacco RL, Lee HS, Grahame-Clarke C, Rundek T,
Elkind MV, et al. Metabolic syndrome and ischemic stroke risk: Northern
Manhattan Study. Stroke. 2008;39:30 –35.
14. O’Donnell MJ, Xavier D, Liu L, Zhang H, Chin SL, Rao-Melacini P, et
al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22
countries (the Interstroke study): a case– control study. Lancet. 2010;376:
112–123.
15. Cook NR, Cohen J, Hebert PR, Taylor JO, Hennekens CH. Implications
of small reductions in diastolic blood pressure for primary prevention.
Arch Intern Med. 1995;155:701–709.
16. Dahlof B, Lindholm LH, Hansson L, Schersten B, Ekbom T, Wester PO.
Morbidity and mortality in the Swedish trial in old patients with hypertension (STOP-hypertension). Lancet. 1991;338:1281–1285.
17. Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhager WH,
et al. Randomised double-blind comparison of placebo and active
treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (SYST-EUR) trial investigators. Lancet.
1997;350:757–764.
18. Rashid P, Leonardi-Bee J, Bath P. Blood pressure reduction and secondary prevention of stroke and other vascular events: a systematic
review. Stroke. 2003;34:2741–2748.
19. Medical research council trial of treatment of hypertension in older
adults: principal results. MRC working party. BMJ. 1992;304:405– 412.
20. Coates RJ, Eley JW, Block G, Gunter EW, Sowell AL, Grossman C, et al.
An evaluation of a food frequency questionnaire for assessing dietary
intake of specific carotenoids and vitamin E among low-income black
women. Am J Epidemiol. 1991;134:658 – 671.
21. Harlan LC, Block G. Use of adjustment factors with a brief food frequency questionnaire to obtain nutrient values. Epidemiology. 1990;1:
224 –231.
Dietary Sodium and Risk of Stroke in the Northern Manhattan Study
Hannah Gardener, Tatjana Rundek, Clinton B. Wright, Mitchell S.V. Elkind and Ralph L. Sacco
Downloaded from http://stroke.ahajournals.org/ by guest on September 18, 2016
Stroke. published online April 12, 2012;
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2012 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://stroke.ahajournals.org/content/early/2012/04/12/STROKEAHA.111.641043
Data Supplement (unedited) at:
http://stroke.ahajournals.org/content/suppl/2013/10/02/STROKEAHA.111.641043.DC1.html
http://stroke.ahajournals.org/content/suppl/2013/10/08/STROKEAHA.111.641043.DC2.html
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published
in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office.
Once the online version of the published article for which permission is being requested is located, click
Request Permissions in the middle column of the Web page under Services. Further information about this
process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Stroke is online at:
http://stroke.ahajournals.org//subscriptions/
18
Stroke 日本語版 Vol. 7, No. 2
Abstract
Northern Manhattan Study における食事中のナトリウムと
脳卒中のリスク
Dietary Sodium and Risk of Stroke in the Northern Manhattan Study
Hannah Gardener, ScD1; Tatjana Rundek, MD1,2; Clinton B. Wright, MD1,2; Mitchell S. V. Elkind, MD3;
Ralph L. Sacco, MD1,2
1 Evelyn F. Mcknight Brain Institute and Department of Neurology and 2 Department of Epidemiology and Public Health, University of Miami,
Miami, FL; 3 Department of Neurology, Columbia University Medical Center, New York, NY.
背景および目的：米国心臓協会は，心血管を理想的な健康
状態に保つためにはナトリウム摂取量を≦ 1,500 mg/ 日に
制限することを推奨している。ナトリウム摂取は，高血圧
との直接的な関係によって血管疾患と関連づけて考えられ
てきたが，脳卒中リスクとの関連を裏づけた試験はほとん
ど存在しない。
方法：被験者は，脳卒中の発生率に関する地域住民を対象
としたコホート研究，Northern Manhattan Study（平均年齢
69 ± 10 歳，女性 64％，白人 21％，ヒスパニック 53％，
黒人 24％）から組み入れた。ナトリウム摂取量はベースラ
イン時に食物摂取頻度調査票を用いて評価し，連続的およ
びカテゴリー別に評価した：≦ 1,500 mg/kg 日
（12％）
，1,501
～ 2,300 mg/ 日
（24％）
，
2,301 ～ 3,999 mg/ 日
（43％）
および≧
4,000 mg/ 日（ 21％）
。平均 10 年間の追跡期間にわたり，ナ
トリウム摂取量と 235 件の脳卒中の関係を，社会人口統計
学的要素，食事，行動 / ライフスタイルおよび血管危険因
子について補正し，Cox モデルを用いて検討した。
結果：食事のデータが得られた 2,657 例の被験者では，平
均のナトリウム摂取量が 3,031 ± 1,470 mg/ 日（中央値：
2,787 mg/ 日，四分位範囲：1,966 ～ 3,815 mg/ 日）であっ
た。≧ 4,000 mg/ 日のナトリウムを摂取していた被験者は，
摂取量が≦ 1,500 mg/ 日の患者に比べて脳卒中のリスクが
高く（ハザード比＝ 2.59，95％ CI：1.27 ～ 5.28），脳卒中
の発現リスクは摂取量が 500 mg/ 日増加するごとに 17％
上昇した
（ 95％ CI：1.07 ～ 1.27 ）
。
結論：ナトリウムの多量摂取は多くみられ，血管危険因子
とは無関係に脳卒中のリスク上昇に関連していた。米国心
臓協会の食事中ナトリウムの新しい目標は，脳卒中のリス
ク軽減に役立つであろう。
Stroke 2012; 43: 1200-1205
表 2 ナトリウム摂取量と脳卒中リスクの関係
脳卒中のハザード比（95％ CI）
1 日あたりの食事中ナトリウム量，mg
人・年
イベント
モデル 1*
モデル 2 †
モデル 3 ‡
500 mg/ 日の増加
27,048
235
1.08（1.04 〜 1.13）
1.17（1.07 〜 1.27）
1.17（ 1.07 〜 1.27 ）
≦ 1,500
3,408
24
1,501 ～ 2,300
6,620
56
2,301 ～ 3,999
11,752
89
1.15（0.73 〜 1.81）
1.31（0.78 〜 2.22）
1.32（ 0.78 〜 2.23 ）
5,262
66
1.99（1.24 〜 3.20）
2.50（1.23 〜 5.07）
2.59（ 1.27 〜 5.28 ）
4,000 ～ 10,000
1.0（参照基準）
1.0（参照基準）
1.24（0.77 〜 2.01）
1.33（0.81 〜 2.18）
1.0（参照基準）
1.38（ 0.84 〜 2.27 ）
* 人口統計学的要素（年齢，性別，人種 / 民族，教育）について補正。
†
人口統計学的要素＋行動に関する危険因子（飲酒，喫煙，運動量，総摂取カロリー，総脂質，飽和脂肪，炭水化物，蛋白）について補正。
‡
人口統計学的要素＋行動に関する危険因子＋血管危険因子（糖尿病，高コレステロール血症，高血圧，心臓疾患の既往，肥満指数）について補正。
表 3 ナトリウムと複合血管イベントリスクとの関係ならびに心筋梗塞および血管死それぞれとの関係
ハザード比（95％ CI）
脳卒中，MI または血管死
1 日の食事中
ナトリウム量，mg
人・年イベント
500 mg/ 日の増加
モデル 2*
モデル 3 †
MI
イベント
モデル 3 †
615
67
1,501 ～ 2,300
6,432
157
1.32（ 0.98 〜 1.78）1.35（ 1.00 〜 1.82）
53
0.88（ 0.55 〜 1.43）0.93（ 0.58 〜 1.51）
95
1.39（ 0.95 〜 2.04）1.43（ 0.97 〜 2.11）
2,301 ～ 3,999
11,447
253
1.21（ 0.87 〜 1.67）1.21（ 0.87 〜 1.67）
80
0.66（ 0.39 〜 1.11）0.68（ 0.40 〜 1.15）
164
1.37（ 0.91 〜 2.07）1.37（ 0.90 〜 2.07）
5,095
138
1.70（ 1.08 〜 2.68）1.68（ 1.06 〜 2.67）
47
0.79（ 0.37 〜 1.69）0.78（ 0.36 〜 1.70）
71
1.49（ 0.82 〜 2.72）1.49（ 0.81 〜 2.72）
MI：心筋梗塞。
* 人口統計学的要素＋行動に関する危険因子について補正。
†
人口統計学的要素＋行動に関する危険因子＋血管危険因子について補正。
29
1.0（参照基準）
1.0（参照基準）
371
モデル 2*
3,306
1.0（参照基準）
0.95（ 0.86 〜 1.04）0.94（ 0.85 〜 1.04）
イベント
26,278
1.0（参照基準）
209
血管死
モデル 3 †
≦ 1,500
4,000 ～ 10,000
1.06（ 1.00 〜 1.12）1.05（ 0.99 〜 1.11）
モデル 2*
41
1.02（ 0.95 〜 1.10）1.02（ 0.95 〜 1.10）
1.0（参照基準）
1.0（参照基準）
25
Abstract 5
Clinical Sciences
소금 섭취량이 뇌졸중 위험에 미치는 영향: 북부 맨하탄 연구
Dietary Sodium and Risk of Stroke in the Northern Manhattan Study
Hannah Gardener, ScD; Tatjana Rundek, MD; Clinton B. Wright, MD; Mitchell S.V. Elkind, MD; Ralph L. Sacco, MD
(Stroke. 2012;43:1200-1205.)
Key Words: diet ■ epidemiology ■ sodium ■ stroke
배경과 목적
미국심장협회에서 이상적인 심혈관계 질환 예방을 위해 하루 소
금 섭취량을 1,500 mg 이하로 제한하는 것을 권고하였다. 소금
섭취량은 고혈압과의 직접적 관련을 통해 혈관질환의 발생과 관
련되어 있으나, 소금 섭취량과 뇌졸중 위험도에 대해서는 거의
알려진 바가 없다.
방법
뇌졸중 발생 코호트인 북부 맨하탄 연구에서 참여자(평균 연령
69±10, 64% 여성, 21% 백인, 53% 히스패닉, 24% 흑인)를 얻
었다. 소금 섭취량은 연구 참여 시 식품영양조사 설문지를 이용
하여 조사하였으며 연속형 및 범주형 변수(≤1,500 mg/일 [12%],
1,501~2,300 mg/일[24%], 2,301~3,999 mg/일[43%], 그리
고 ≥4,000 mg/일[21%])로 나누어 분석하였다. 평균 10년 동
안 추적관찰 기간 동안 소금 섭취량과 235건의 뇌졸중 발생에
대해서, 사회경제적인 요인, 식이, 생활패턴 및 심혈관계 위험
인자 등을 보정한 콕스 모델을 이용하여 분석하였다.
결과
2,657명의 식이자료를 분석하였고, 평균 소금 섭취량은 3,031
±1,470 mg/일(중앙값, 2,787; 사분위수, 1,966~3,815 mg/
일)이었으며, 하루 4,000 mg 이상을 섭취하는 사람들은
1,500 mg 이하를 섭취하는 사람들과 비교했을 때, 뇌졸중 위
험도가 높았다(HR, 2.59; 95% CI, 1.27~5.28). 또한 하루 소
금 섭취량이 500 mg씩 증가할 때마다 뇌졸중 위험도는 약
17% 증가하였다(95% CI, 1.07~1.27).
결론
소금 섭취량이 높은 경우가 일반적이었으며, 높은 소금 섭취량
은 심혈관계 위험인자와 무관하게 뇌졸중 위험도 증가와 관련
이 있었다. 미국심장학회에서 새롭게 제시한 소금 목표 섭취량
은 뇌졸중 위험도를 낮추는 데 기여할 것이다.

Download Report