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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- WWW.ARCHINTERNMED.COM ©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 08/04/2019 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 (ⱖ20 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- ARCH INTERN MED/ VOL 171 (NO. 13), JULY 11, 2011 1184 WWW.ARCHINTERNMED.COM ©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 08/04/2019 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 ⱖ60 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 ⱖ16 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) ⱖ3 (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 ⱖ25), hypertension, physical activity (nonactive vs active), and educational attainment (⬍12 vs ⱖ12 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). ARCH INTERN MED/ VOL 171 (NO. 13), JULY 11, 2011 1185 WWW.ARCHINTERNMED.COM ©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 08/04/2019 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 ⱖ5 P value for trend BMI ⬍25 25-30 ⬎30 P value for trend Total serum cholesterol, mg/dL ⬍240 ⱖ240 P value Total HDL-C level, mg/dL ⬍60 ⱖ60 P value Systolic BP, mm Hg ⬍125 ⱖ125 P value Diastolic BP, mm Hg ⬍85 ⱖ85 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 ARCH INTERN MED/ VOL 171 (NO. 13), JULY 11, 2011 1186 WWW.ARCHINTERNMED.COM ©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 08/04/2019 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. ARCH INTERN MED/ VOL 171 (NO. 13), JULY 11, 2011 1187 WWW.ARCHINTERNMED.COM ©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 08/04/2019 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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