2) Read this article. Write a 1- 2-page max SUMMARY of the article in your own words. In your summary include why the ratio between sodium and potassium is important? According to the article, what other factor(s) are greater contributors to high sodium than table salt? What limitations(weaknesses) did this study have? Use facts from the article to support your argument.
ORIGINAL INVESTIGATION
HEALTH CARE REFORM
Sodium and Potassium Intake and Mortality
Among US Adults
Prospective Data From the Third National Health and Nutrition Examination Survey
Quanhe Yang, PhD; Tiebin Liu, MSPH; Elena V. Kuklina, MD, PhD; W. Dana Flanders, MD, ScD;
Yuling Hong, MD, PhD; Cathleen Gillespie, MS; Man-Huei Chang, MPH; Marta Gwinn, MD;
Nicole Dowling, PhD; Muin J. Khoury, MD, PhD; Frank B. Hu, MD, PhD
Background: Several epidemiologic studies suggested
that higher sodium and lower potassium intakes were associated with increased risk of cardiovascular diseases
(CVD). Few studies have examined joint effects of dietary sodium and potassium intake on risk of mortality.
Methods: To investigate estimated usual intakes of sodium
and potassium as well as their ratio in relation to risk of allcause and CVD mortality, the Third National Health and
Nutrition Examination Survey Linked Mortality File (19882006), a prospective cohort study of a nationally representative sample of 12 267 US adults, studied all-cause, cardiovascular, and ischemic heart (IHD) diseases mortality.
Results: During a mean follow-up period of 14.8 years,
we documented a total of 2270 deaths, including 825 CVD
deaths and 443 IHD deaths. After multivariable adjustment, higher sodium intake was associated with increased all-cause mortality (hazard ratio [HR], 1.20; 95%
R
Author Affiliations: Office
of Public Health Genomics
(Drs Yang, Gwinn, Dowling,
and Khoury, Mr Liu, and
Ms Chang) and Division for
Heart Disease and Stroke
Prevention (Drs Kuklina and
Hong and Ms Gillespie),
Centers for Disease Control and
Prevention, and Department
of Epidemiology, Rollins School
of Public Health, Emory
University (Dr Flanders)
Atlanta, Georgia; and
Departments of Nutrition and
Epidemiology, Harvard School
of Public Health, Boston,
Massachusetts (Dr Hu).
confidence interval [CI], 1.03-1.41 per 1000 mg/d), whereas
higher potassium intake was associated with lower mortality risk (HR, 0.80; 95% CI, 0.67-0.94 per 1000 mg/d).
For sodium-potassium ratio, the adjusted HRs comparing
the highest quartile with the lowest quartile were HR, 1.46
(95% CI, 1.27-1.67) for all-cause mortality; HR, 1.46 (95%
CI, 1.11-1.92) for CVD mortality; and HR, 2.15 (95% CI,
1.48-3.12) for IHD mortality. These findings did not differ significantly by sex, race/ethnicity, body mass index, hypertension status, education levels, or physical activity.
Conclusion: Our findings suggest that a higher sodium-
potassium ratio is associated with significantly increased risk of CVD and all-cause mortality, and higher
sodium intake is associated with increased total mortality in the general US population.
Arch Intern Med. 2011;171(13):1183-1191
ANDOMIZED CONTROLLED
trials (RTCs) and epidemiologic studies have shown
that individuals with higher
sodium or lower potassium
intakes have increased risk for elevated
blood pressure and hypertension.1-8 Although elevated blood pressure and hypertension are associated with increased
CME available online at
www.jamaarchivescme.com
and questions on page 1144
risk for cardiovascular diseases (CVDs), the
observed association between sodium or potassium intake and CVD incidence or mortality has been inconsistent.4,9-12 Recently,
several studies suggested that the ratio of sodium to potassium intakes represented a
more important risk factor for hypertension and CVD than each factor alone.3,11-14
Examining the joint effects of sodium
and potassium intakes on CVD risk is par-
ARCH INTERN MED/ VOL 171 (NO. 13), JULY 11, 2011
1183
ticularly important because most of the
US population consumes more sodium and
See Invited Commentary
at end of article
less potassium daily than recommended.15-18
Herein, we report an analysis of the association between the estimated usual intakes of sodium and potassium, as well as
their ratio, with all-cause and CVD mortality among persons 20 years of age and
older in the Third National Examination
and Nutritional Health Survey (NHANES
III) Linked Mortality File.
METHODS
THE THIRD NATIONAL HEALTH
AND NUTRITION EXAMINATION
SURVEY (NHANES III, 1988-1994)
NHANES III used a stratified, multistage probability design to obtain a nationally represen-
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tative sample of the civilian, noninstitutionalized US population.19 In NHANES III, each survey participant completed a
household interview and underwent a physical examination.20
Of the 16 562 nonpregnant adults 20 years or older who attended the medical examination center (MEC) and for whom
complete mortality follow-up information was available, we excluded, sequentially, 879 participants with incomplete data on
the first or second 24-hour dietary recall; 2693 participants who
were on a reduced salt diet for hypertension at baseline; and 723
participants who reported a history of heart attack, stroke, or congestive heart failure. After these exclusions, 12 267 NHANES III
participants were available for the present analysis.
ESTIMATING USUAL INTAKES
OF SODIUM AND POTASSIUM
Dietary information was obtained from in-person 24-hour dietary recalls with use of a personal computer–based, automated,
interactive data collection and coding system.19 All MEC participants provided a single 24-hour dietary recall, and a subsample
of about 8% adult participants (?20 years) provided a second 24hour dietary recall. Among 12 267 NHANES III participants who
were eligible for this analysis, 912 (7.4%) provided reliable second 24-hour dietary recalls. The US Department of Agriculture
Survey Nutrient Database (http://www.cdc.gov/nchs/nhanes
/nh3data.htm) was used to calculate nutrient intakes.
Because dietary data from a single 24-hour recall do not represent usual intake owing to day-to-day variations,21,22 we used
the method developed by the National Cancer Institute (NCI)
to estimate the usual intakes of sodium, potassium, and total
energy (calorie) intake.23 The NCI methods for estimating usual
intake involve 2 steps. The first step is a 2-part model for repeated measures of nutrient data with correlated random effects. Because sodium and potassium were consumed by nearly
every participant daily, we used only the second part of the 2-part
model (MIXTRAN macro). The data on amount were transformed to approximate normality using Box-Cox transformation.23 The second step in the NCI methods (using the INDIVINT
macro) calculates the individual’s estimated usual intakes using
parameters from the first step.24 The NCI method requires that
at least some of the respondents have multiple days of nutrient values to estimate the within- and between-individual variations.23,24 In our study, we included 912 participants who provided reliable second-day dietary recalls. For each nutrient, the
models included the following covariates: an indicator of sequence number (first- vs second-day recall); day of the week
when the 24-hr recall was collected (weekday vs weekends [Friday-Sunday]); race/ethnicity (non-Hispanic white, nonHispanic black, Mexican American, and others); and age groups
(20-30, 31-50, 51-70, and ?70 years).17 We estimated the usual
intakes of sodium, potassium, and total calorie intake for men
and women separately. We present the median, interquartile
range, and sodium-potassium ratio of day 1 and day 2 and the
estimated usual intakes of sodium and potassium for total population and by sex (eTable 1; http://www.archinternmed.com).
BASELINE COVARIATES
Race/ethnicity was classified as non-Hispanic white, nonHispanic black, Mexican American, or other. Educational attainment was classified as less than 12 years, 12 to 15 years, or
more than 15 years of formal education. Body mass index (BMI)
was calculated as weight in kilograms divided by height in meters squared. Smoking status was categorized as never, former, or current. Alcohol consumption was classified as 0, 1 to
2, or 3 or more drinks per week. Physical activity was categorized as 0, 1 to 4, or 5 or more times per week of moderate in-
tensity to vigorous activities including walking, jogging or running, bicycling, swimming, aerobics or aerobic dancing, other
dancing, calisthenics, and gardening or yard work. Hypertension was defined as systolic blood pressure of 140 mm Hg or
higher or diastolic blood pressure of 90 mm Hg or higher or
taking hypertension medication. Family history of CVD was
classified into 3 mutually exclusive groups as average risk (absence of family history or, at most, 1 second-degree relative with
CVD), moderate risk (only 1 first-degree and 1 second-degree
relative with CVD, or only 1 first-degree, or at least 2 seconddegree relatives with CVD), and high risk (at least 2 firstdegree relatives or 1 first-degree and at least 2 second-degree
relatives).25 We included total serum cholesterol (milligrams
per deciliter) and high-density lipoprotein cholesterol (HDL-C)
as continuous variables in our analysis.
OUTCOME MEASURES
For the linked mortality study, eligible NHANES III participants were matched, using a probabilistic matching algorithm,
to the National Death Index through December 31, 2006, to determine their mortality status. A complete, detailed description
of the method can be found at http://www.cdc.gov/nchs/data
/datalinkage/matching_methodology_nhanes3_final.pdf. The International Statistical Classification of Diseases, 10th Revision (ICD10), was used to identify patients for whom cardiovascular diseases
(CVD) (ICD-10 codes I00-I78) or ischemic heart disease (IHD)
(ICD-10 codes I20-I25) were listed as the underlying cause of
death. Follow-up of survival time continued until death due to
CVD and was censored at the time of death among those who
died from causes other than CVD. Participants who were not
matched with a death record were considered to have remained
alive through the entire follow-up period.
STATISTICAL ANALYSIS
We calculated the weighted mean (SE) of the estimated usual
intakes of sodium, potassium, and sodium-potassium ratio across
categories of selected covariates. We used Cox proportional hazards regression to estimate the hazard ratios (HRs) and 95%
confidence intervals (CIs) for all-cause, CVD, and IHD mortality. We used the estimated usual intakes as continuous variables in the nutrient-diseases association. Because the relationships between the estimated usual intakes and all-cause and
CVD mortality were approximately linear, we calculated the
percentile distributions of the estimated usual intakes as the
middle value of each quartile: 87.5, 62.5, 37.5, and 12.5. To
present the results, we used the parameters from the continuous models and estimated the adjusted HRs comparing the middle
values of each quartile with the lowest quartile (Q4, Q3, Q2, vs
Q1).26,27 We used the attained age as the timescale in Cox proportional hazards models.28 Multivariable models were adjusted for sex, race/ethnicity, educational attainment, BMI, smoking status, alcohol intake, total cholesterol level, HDL-C level,
family history of CVD, and total calorie intake. For the sensitivity analysis, we adjusted for the Healthy Eating Index (HEI).
The HEI score ranges from 0 to 100 and contains information
on consumption of 10 subcomponents of the diet: fruits, vegetables, grains, dairy, meats, fats, saturated fat, cholesterol, sodium, and dietary variety.29 A higher HEI score indicates a
healthier eating pattern. We did not adjust for hypertension or
blood pressure in the main analysis because they are intermediate variables on the pathway. However, the results did not
alter materially after adjusting for hypertension and blood pressure. To examine the association between estimated usual intakes of sodium, potassium, and sodium-potassium ratio and
all-cause and CVD mortality, we used the standard multivar-
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Table 1. Estimated Usual Intakes of Sodium, Potassium, and Calories and Sodium-Potassium Ratio at Baseline by Sex,
NHANES IIII Linked Mortality File a
Mean (SE) b
Sample, No. (%) b
Characteristic c
All
Age, y
?60
?60
P value
Race/ethnicity
Non-Hispanic white (1)
Non-Hispanic black (2)
Mexican American (3)
Other (4)
P value (1 vs 2)
P value (1 vs 3)
P value (1 vs 4)
P value overall
Education, y
0-11
12-15
?16
P value for trend
Smoking status
Never (1)
Current (2)
Former (3)
P value (1 vs 2)
P value (1 vs 3)
P value overall
Alcohol intake, drinks/wk d
None (1)
?3 (2)
?3 (3)
P value (1 vs 2)
P value (1 vs 3)
P value overall
Men
Women
Usual Sodium
Intakes, mg/d
Men
Women
Usual Potassium
Intakes, mg/d
Men
Women
2918 (17)
3373 (14)
2433 (13)
1.31 (0.01)
1.23 (0.01)
2697 (14)
1785 (10)
4444 (85.2) 4904 (81.5) 4450 (20)
1455 (14.8) 1464 (18.5) 3593 (30)
?.001
3003 (18)
2546 (19)
?.001
3409 (17)
3165 (24)
?.001
2418 (15)
2501 (15)
?.001
1.34 (0.01)
1.16 (0.01)
?.001
1.27 (0.01)
1.03 (0.01)
?.001
2792 (14)
2147 (16)
?.001
1844 (10)
1524 (9)
?.001
2269 (76.1) 2631 (76.6) 4377 (23)
1540 (9.8) 1752 (10.6) 4098 (33)
1859 (6.1) 1702 (4.7) 3961 (27)
231 (8.0)
283 (8.1) 4367 (76)
?.001
?.001
.90
?.001
2914 (17)
2924 (20)
2781 (16)
3023 (75)
.66
?.001
.14
.04
3481 (18)
2794 (24)
3280 (21)
3116 (53)
?.001
?.001
?.001
?.001
2503 (13)
2020 (11)
2387 (17)
2331 (38)
?.001
?.001
?.001
?.001
1.28 (0.01)
1.50 (0.01)
1.23 (0.01)
1.43 (0.02)
?.001
?.001
?.001
?.001
1.19 (0.01)
1.48 (0.01)
1.19 (0.01)
1.31 (0.02)
?.001
.73
?.001
?.001
2735 (14)
2586 (20)
2654 (19)
2505 (43)
?.001
?.001
?.001
?.001
1789 (12)
1781 (12)
1787 (8)
1742 (35)
.59
.85
.18
.25
2391 (23.5) 2195 (20.9) 4101 (40)
2660 (52.3) 3316 (59.3) 4414 (28)
806 (24.2) 820 (19.8) 4350 (44)
?.001
2775 (22)
2950 (22)
2975 (26)
?.001
3213 (29)
3394 (26)
3488 (30)
?.001
2325 (13)
2424 (18)
2567 (22)
?.001
1.31 (0.01)
1.33 (0.01)
1.27 (0.01)
.07
1.22 (0.01)
1.25 (0.01)
1.18 (0.01)
.006
2531 (22)
2770 (21)
2705 (23)
?.001
1686 (12)
1802 (13)
1834 (18)
?.001
2211 (37.8) 3878 (54.2) 4395 (26.0) 2888 (22.0) 3377 (24.0) 2402 (14.0)
1959 (33.4) 1478 (26.8) 4403 (32.0) 2985 (28.0) 3353 (29.0) 2416 (23.0)
1728 (28.8) 1012 (19.0) 4136 (37)
2910 (22)
3389 (33)
2544 (22)
.84
.002
.55
.54
?.001
.49
.82
?.001
?.001
.003
.68
?.001
1.33 (0.01)
1.35 (0.01)
1.24 (0.01)
.39
?.001
?.001
1.23 (0.01)
1.27 (0.01)
1.16 (0.01)
?.001
?.001
?.001
2735 (17.0) 1754 (13.0)
2786 (23.0) 1854 (18.0)
2541 (22)
1773 (16)
.054
?.001
?.001
.35
?.001
?.001
590 (10.1) 1709 (30.4) 4172 (58)
1400 (36.2) 1398 (44.4) 4348 (42)
2208 (53.7) 810 (25.1) 4413 (32)
.01
.001
.01
1.37 (0.02)
1.32 (0.01)
1.32 (0.01)
.06
.07
.11
1.23 (0.01)
1.25 (0.01)
1.22 (0.02)
.15
.73
.16
2515 (34)
2709 (26)
2802 (23)
?.001
?.001
?.001
3135 (55)
3373 (38)
3420 (25)
?.001
?.001
.001
Women
Usual Calorie Intake
5899 (0.52) 6368 (0.52) 4323 (21)
2812 (29)
3009 (31)
2991 (35)
?.001
?.001
?.001
Men
Sodium-Potassium Ratio
2346 (24)
2466 (21)
2517 (20)
?.001
?.001
?.001
Men
Women
1684 (15)
1834 (17)
1884 (24)
?.001
?.001
?.001
(continued)
iate method adjusting for the total calorie intake.30 A P value
for trend across the HRs for the quintiles was calculated using
a Satterthwaite adjusted F test.31
We tested for interactions of estimated usual intakes of sodium, potassium, and sodium-potassium ratio with sex, race/
ethnicity, BMI (?25 vs ?25), hypertension, physical activity
(nonactive vs active), and educational attainment (?12 vs ?12
years of education) by including the interactions terms in the
Cox models using the Satterthwaite adjusted test.31 We conducted several sensitivity analyses. First, we restricted the participants to ages 25 to 74 years at baseline. Second, we conducted stratified analyses by sex, race/ethnicity, BMI, and
hypertension status. Third, we analyzed the associations between sodium, potassium intakes, and sodium-potassium ratio obtained from the first-day dietary recalls only and also tested
for departure from linearity. The results from these sensitivity
analyses are provided in eTables 2, 3, 4, 5, 6, and 7.
The proportional hazards assumption of the Cox models was
evaluated with Schoenfeld residuals, which revealed no significant departure from proportionality in hazards over time.32
We compared the goodness of fit for models with sodium, potassium, or sodium-potassium ratio using Akaike information
criterion (AIC); a smaller AIC indicates a better fit.33 We conducted the Cox proportional hazards analyses using SUDAAN
statistical software (version 9.2; Research Triangle Park, North
Carolina) to take into account the complex sampling design.31
All tests were 2-sided, and P?.05 was considered statistically
significant.
RESULTS
Among the 12 267 participants meeting our eligibility criteria, 2270 deaths over 170 110 person-years of follow-up
(median follow-up, 14.8 years) were documented. There
were 825 deaths from CVD and 433 from IHD.
Table 1 shows the crude estimated usual intakes of
sodium, potassium, sodium-potassium ratio, and total
calorie intake by sex and selected characteristics. The sodium-potassium ratio was higher among males, the
younger age group, current smokers, minority groups,
and those with lower educational attainment (females
only), lower physical activity, higher BMI (females only),
lower total cholesterol or lower HDL-C (female only),
and lower systolic blood pressure.
After multivariable adjustment, higher sodium intake was associated with increased all-cause mortality (HR,
1.20; 95% CI, 1.03-1.41 per 1000 mg/d), whereas higher
potassium intake was associated with lower mortality risk
(HR, 0.80; 95% CI, 0.67-0.94 per 1000 mg/d) (Table 2).
The risk of all-cause deaths increased linearly with increasing sodium-potassium ratio: the adjusted HR comparing the highest quartile (Q4) with the lowest quartile
(Q1) was HR, 1.46 (95% CI, 1.27-1.67) (P value for
trend?.001).
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Table 1. Estimated Usual Intakes of Sodium, Potassium, and Calories and Sodium-Potassium Ratio at Baseline by Sex,
NHANES IIII Linked Mortality File a (continued)
Mean (SE) b
Sample, No. (%) b
Characteristic c
Physical activity, times/wk
None
?5
?5
P value for trend
BMI
?25
25-30
?30
P value for trend
Total serum cholesterol, mg/dL
?240
?240
P value
Total HDL-C level, mg/dL
?60
?60
P value
Systolic BP, mm Hg
?125
?125
P value
Diastolic BP, mm Hg
?85
?85
P value
Hypertension
Yes
No
P value
Familial risk of MI
Average
Moderate
High
P value for trend
Men
Women
Usual Sodium
Intakes, mg/d
Usual Potassium
Intakes, mg/d
Sodium-Potassium Ratio
Usual Calorie Intake
Men
Women
Men
Women
Men
Women
Men
Women
923 (10.4) 1580 (16.9)
2378 (42.6) 2762 (46.3)
2565 (47.0) 2005 (36.8)
4165 (48)
4357 (27)
4327 (26)
.003
2835 (29)
2968 (27)
2894 (21)
.08
3215 (40)
3358 (19)
3418 (20)
?.001
2334 (21)
2406 (14)
2511 (17)
?.001
1.33 (0.01)
1.33 (0.01)
1.30 (0.01)
.03
1.24 (0.01)
1.26 (0.01)
1.18 (0.01)
?.001
2580 (30)
2708 (18)
2711 (18)
?.001
1720 (16)
1815 (13)
1777 (14)
.001
2508 (43.3) 2825 (54.4)
2343 (40.2) 1843 (24.7)
1042 (16.6) 1685 (20.9)
4353 (30)
4305 (32)
4292 (36)
.12
2961 (23)
2846 (22)
2891 (25)
.03
3365 (23)
3388 (23)
3357 (33)
.85
2467 (16)
2424 (20)
2356 (22)
?.001
1.33 (0.01)
1.30 (0.01)
1.31 (0.01)
.18
1.23 (0.01)
1.20 (0.01)
1.26 (0.01)
.03
2747 (22)
2672 (19)
2625 (29)
?.001
1824 (16)
1731 (12)
1746 (14)
.001
4671 (83.7) 4938 (82.1)
952 (16.3) 1114 (17.9)
4367 (23)
4173 (39)
?.001
2961 (18)
2725 (24)
?.001
3396 (16)
3322 (38)
.12
2438 (14)
2434 (20)
.85
1.32 (0.01)
1.29 (0.01)
.03
1.24 (0.01)
1.14 (0.01)
?.001
2729 (15)
2569 (24)
?.001
1817 (12)
1640 (13)
?.001
4660 (85.9) 4038 (65.1)
919 (14.1) 1984 (34.9)
4336 (22)
4325 (50)
.84
2919 (20)
2914 (21)
.84
3380 (15)
3408 (38)
.53
2406 (14)
2495 (17)
?.001
1.31 (0.01)
1.30 (0.01)
.39
1.24 (0.01)
1.20 (0.01)
?.001
2696 (15)
2745 (38)
.23
1782 (11)
1791 (14)
.47
3309 (62.6) 4397 (74.6)
2583 (37.4) 1959 (25.4)
4440 (24)
4129 (29)
?.001
3002 (19)
2670 (20)
?.001
3423 (22)
3294 (22)
?.001
2426 (15)
2454 (15)
.14
1.33 (0.01)
1.28 (0.01)
?.001
1.27 (0.01)
1.11 (0.01)
?.001
2776 (16)
2566 (21)
?.001
1841 (11)
1619 (11)
?.001
4823 (83.1) 5837 (93.1)
1069 (16.9) 519 (6.9)
4339 (20)
4249 (49)
.06
2925 (18)
2823 (40)
.03
3382 (15)
3339 (33)
.21
2437 (13)
2373 (31)
.06
1.31 (0)
1.30 (0.01)
.46
1.23 (0.01)
1.22 (0.01)
.55
2705 (14)
2660 (29)
.13
1790 (11)
1717 (21)
.01
1447 (20.6) 1449 (18.6)
4452 (79.4) 4919 (81.4)
4080 (45)
4387 (21)
?.001
2719 (25)
2963 (18)
?.001
3289 (29)
3394 (16)
.002
2421 (16)
2436 (14)
.47
1.27 (0.01)
1.32 (0)
?.001
1.15 (0.01)
1.25 (0.01)
?.001
2513 (28)
2744 (13)
?.001
1650 (15)
1815 (11)
?.001
4239 (75.8) 4172 (70.5)
1173 (19.0) 1530 (22.6)
386 (5.2)
574 (6.9)
4326 (25)
4306 (35)
4301 (75)
.76
2936 (20)
2881 (25)
2880 (46)
.27
3374 (17)
3369 (28)
3394 (77)
.81
2449 (16)
2393 (20)
2406 (36)
.32
1.31 (0.01)
1.31 (0.01)
1.30 (0.03)
.76
1.23 (0.01)
1.23 (0.01)
1.23 (0.02)
.84
2707 (16)
2667 (24)
2615 (42)
.04
1798 (13)
1757 (13)
1749 (24)
.10
Abbreviations: BP, blood pressure; HDL-C, high-density lipoprotein cholesterol; MI, myocardial infarction; NHANES III, Third National Health and Nutrition Examination
Survey.
SI conversion factor: To convert serum cholesterol to millimoles per liter, multiply by 0.0259.
a See study by the National Center for Health Statistics, Centers for Disease Control and Prevention.20
b Mean (SE) and population percentage presented by sex of estimated usual intakes of sodium, potassium, and calorie intake.
c For categories of the continuous variables in nature (eg, years of education and body mass index), P value for difference across the categories. For categorical
variables (eg, race/ethnicity), we presented pairwise and overall P values. All tests were 2-tailed and based on Satterthwaite adjusted F test.
d Approximately 25% of participants had missing information on frequency and amount of alcohol consumed.
Sodium intake was not statistically significantly associated with CVD or IHD mortality (Table 3). However, potassium intake was significantly inversely associated with the incidence of CVD or IHD death: the
adjusted HR, 0.39 (95% CI, 0.19-0.80), for CVD mortality and HR, 0.26 (95% CI, 0.10-0.71), for IHD mortality comparing the highest quartile with the lowest quartile of potassium intake. Higher sodium-potassium ratio
was significantly associated with risk of CVD and IHD
mortality: the adjusted HRs comparing the highest quartile with the lowest quartile were 1.46 (95% CI, 1.111.92) and 2.15 (95% CI, 1.48-3.12) for CVD and IHD
mortality, respectively. The models with the sodiumpotassium ratio had consistently smaller AIC compared
with the models with either sodium or potassium for allcause, CVD, and IHD mortality (AIC: 19199, 6244, and
3618 vs 19214, 6246, and 3623), suggesting a better fit
for the model with the sodium-potassium ratio.
Additional adjustment for the HEI did not alter the
results substantially: the adjusted HRs were 1.38 (95%
CI, 1.14-1.67), 1.37 (95% CI, 0.99-1.89), and 1.94 (95%
CI, 1.36-2.76) comparing the highest quartile with the
lowest quartile of sodium-potassium ratio for all-cause,
CVD, and IHD mortality, respectively. After adjustment
for calorie intake by the residual method,30 the observed
associations were slightly strengthened (adjusted HRs:
1.50 [95% CI, 1.29-1.75], 1.52 [95% CI, 1.17-1.98], and
2.34 [95% CI, 1.53-3.58] comparing the highest quartile with the lowest quartile of sodium-potassium ratio
for all-cause, CVD, and IHD mortality, respectively).
The increased risk for all-cause, CVD, or IHD mortality associated with higher sodium-potassium ratio remained largely consistent across sex, race/ethnicity, BMI,
hypertension status, physical activity, and educational attainments (Figure). We tested statistical interactions between estimated usual intakes of sodium and potassium
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Table 2. Adjusted HRs of Estimated Usual Intakes of Sodium, Potassium, and Sodium-Potassium Ratio for All-Cause Mortality,a
NHANES III b
Midvalue of Quartile of Estimated Usual Intakes in Population, %
Characteristic
Q1: 12.5
Usual sodium intake, mg (range, 839-8555)
HR adjusted for sex and race/ethnicity only
Fully adjusted HR e
Usual potassium intake, mg (range, 609-8839)
HR adjusted for sex and race/ethnicity only
Fully adjusted HR e
Sodium-potassium ratio (range, 0.46-2.98)
Usual sodium intake (range, 839-8555)
Usual potassium intake (range, 609-8839)
HR adjusted for sex and race/ethnicity only
Fully adjusted HR e
2176
1 [Reference]
1 [Reference]
1793
1 [Reference]
1 [Reference]
0.98
2728
2940
1 [Reference]
1 [Reference]
Q2: 37.5
Q3: 62.5
Q4: 87.5
P Value c
Total d
3040
1.16 (1.02-1.30)
1.17 (1.13-1.33)
2476
.81 (.71-.91)
.86 (.77-.97)
1.17
3295
2936
1.15 (1.10-1.21)
1.13 (1.08-1.18)
3864
1.33 (1.05-1.68)
1.37 (1.28-1.74)
3108
0.66 (0.52-0.83)
0.75 (0.60-0.95)
1.33
3650
2918
1.30 (1.19-1.42)
1.25 (1.15-1.35)
5135
1.64 (1.08-2.49)
1.73 (1.54-2.63)
4069
0.49 (0.32-0.73)
0.61 (0.41-0.91)
1.57
3757
2699
1.55 (1.33-1.81)
1.46 (1.27-1.67)
NA
.02
.02
NA
?.001
.01
NR
NR
NR
?.001
?.001
NA
1.18 (1.03-1.36)
1.20 (1.03-1.41)
NA
0.73 (0.61-0.87)
0.80 (0.67-0.94)
NA
NA
NA
2.11 (1.63-2.74)
1.89 (1.50-2.37)
Abbreviations: CI, confidence interval; HR, hazard ratio; NA, not applicable; NHANES III, Third National Health and Nutrition Examination Survey Linked Mortality File;
NR, not reported.
a Total number of deaths, 2270; total person-years, 170 110.
b Unless otherwise reported, data are given as HRs (95% CIs) or milligrams per day. See study by the National Center for Health Statistics, Centers for Disease Control
and Prevention.20
c P value for trend across percentiles of estimated usual intakes of sodium, potassium, or sodium-potassium ratio based on Satterthwaite adjusted F test; all tests
were 2-tailed.
d For the estimated usual intakes of sodium or potassium, HRs are for per 1000 mg/d intake. For sodium-potassium ratio, HRs are per unit change.
e Adjusted for sex, race/ethnicity, educational attainment, body mass index, smoking status, alcohol intake, total cholesterol, high-density lipoprotein cholesterol,
physical activity, family history of cardiovascular disease, and total calorie intake.
Table 3. Adjusted HRs of Estimated Usual Intakes of Sodium, Potassium, and Sodium-Potassium Ratio for CVD and IHD Mortality,a
NHANES III Linked Mortality File b
Midvalue of Quartiles of Estimated Usual Intakes
In Population, HR (95% CI)
Characteristic
Usual sodium intake, mg (range, 839-8555)
CVD mortality
HR adjusted for sex and race/ethnicity only
Fully adjusted HR e
IHD mortality
HR adjusted for sex and race/ethnicity only
Fully adjusted HR e
Usual potassium intake, mg (range, 609-8839)
CVD mortality
HR adjusted for sex and race/ethnicity only
Fully adjusted HR e
IHD mortality
HR adjusted for sex and race/ethnicity only
Fully adjusted HR e
Sodium-potassium ratio (range, 0.46-2.98)
Usual sodium intake (range, 839-8555)
Usual potassium intake (range, 609-8839)
CVD mortality
HR adjusted for sex and race/ethnicity only
Fully adjusted HR e
IHD mortality
HR adjusted for sex and race/ethnicity only
Fully adjusted HR e
Q1: 12.5
Q2: 37.5
Q3: 62.5
Q4: 87.5
P Value
for Trend c
Total/HR per
1000 mg/d d
2176
3040
3864
5135
NA
NA
1 [Reference]
1 [Reference]
1.02 (0.76-1.37) 1.04 (0.59-1.85) 1.08 (0.40-2.95)
0.95 (0.71-1.27) 0.90 (0.51-1.60) 0.83 (0.31-2.28)
.88
.72
1.03 (0.73-1.44)
0.94 (0.67-1.32)
1 [Reference]
1 [Reference]
1793
1.25 (.88-1.76) 1.54 (0.78-3.01) 2.12 (0.65-6.88)
1.17 (0.84-1.62) 1.36 (0.71-2.58) 1.70 (0.55-5.27)
2476
3108
4069
.21
.36
NA
1.29 (0.87-1.92)
1.20 (0.81-1.77)
NA
1 [Reference]
1 [Reference]
0.68 (0.55-0.84) 0.48 (0.32-0.72) 0.28 (0.14-0.56)
0.75 (0.61-0.94) 0.58 (0.38-0.88) 0.39 (0.19-0.80)

?.001
.005
0.57 (0.42-0.78)
0.63 (0.46-0.87)
1 [Reference]
1 [Reference]
0.98
2728
2940
0.58 (0.43-0.79) 0.35 (0.20-0.63) 0.16 (0.06-0.45)
0.67 (0.50-0.90) 0.46 (0.26-0.82) 0.26 (0.10-0.71)
1.17
1.33
1.57
3295
3650
3757
2936
2918
2699
?.001
.005
NR
NR
NR
0.45 (0.29-0.70)
0.51 (0.32-0.81)
NA
NA
NA
1 [Reference]
1 [Reference]
1.17 (1.08-1.27) 1.34 (1.15-1.56) 1.64 (1.27-2.13)
1.13 (1.03-1.23) 1.25 (1.07-1.47) 1.46 (1.11-1.92)
?.001
.01
2.32 (1.50-3.59)
1.90 (1.20-3.03)
1 [Reference]
1 [Reference]
1.33 (1.19-1.48) 1.69 (1.38-2.06) 2.41 (1.72-3.38)
1.28 (1.13-1.44) 1.57 (1.26-1.97) 2.15 (1.48-3.12)
?.001
?.001
4.45 (2.51-7.89)
3.66 (1.94-6.90)
Abbreviations: CI, confidence interval; CVD, cardiovascular disease; HR, hazard ratio; IHD, ischemic heart disease; NA, not applicable; NHANES III, Third
National Health and Nutrition Examination Survey; NR, not reported.
a Total number of CVD deaths, 825; total number of IHD deaths, 443; total person-years, 170 110.
b Unless otherwise reported, data are given as HRs (95% CIs) or milligrams per day. See study by the National Center for Health Statistics, Centers for Disease
Control and Prevention.20
c P value for trend across percentiles of estimated usual intakes of sodium, potassium, or sodium-potassium ratio based on Satterthwaite adjusted F test; all
tests were 2-tailed.
d For the estimated usual intakes of sodium or potassium, HRs are for per 1000 mg/d intake. For sodium-potassium ratio, HR are per unit change.
e Adjusted for sex, race/ethnicity, educational attainment, body mass index, smoking status, alcohol intake, total cholesterol, high-density lipoprotein
cholesterol, physical activity, family history of CVD, and total calorie intake.
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or sodium-potassium ratio and selected covariates in relation to all-cause or CVD mortality and found no evidence of significant interactions (P?.05 for all comparisons) (eTables 2-6).
A
Sex
Male
Female
Race/ethnicity
Non-Hispanic white
Non-Hispanic black
Mexican American
BMI

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