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Urinary Sodium Excretion and Cardiovascular Disease Mortality

Urinary Sodium Excretion and Cardiovascular Disease Mortality To the Editor: Dr Stolarz-Skzypek and colleagues reported that lower urinary sodium excretion was associated with higher cardiovascular disease (CVD) mortality.1 These findings contradict a large body of evidence that established elevated sodium consumption as a risk factor for CVD and shed doubts on the worldwide efforts to implement population-based sodium reduction strategies.2 We have a number of concerns that suggest their findings should be interpreted cautiously. First, the volume of urine collected during 24 hours was significantly higher among people with high sodium excretion compared with those with low sodium excretion. It is not clear whether these differences reflect true urinary volume output or problematic completeness of urine collections. The authors assessed the accuracy of urine collection based on 24-hour urinary volume and creatinine excretion. However, these parameters are not reliable markers for completeness; instead, the proposed standard criterion in nutritional epidemiology studies is the use of para-aminobenzoic acid.3 Furthermore, the lowest levels of 24-hour urinary volume and sodium excretion were found in people with low educational attainment, which is in contradiction with observations from earlier studies that found sodium excretion to be higher in people with low educational level.4 Lower education level is also associated with unfavorable CVD risk profile and higher risk of developing CVD.5 Thus, although the authors adjusted for educational attainment, the findings may have been caused by misclassifying people with low socioeconomic status but higher CVD risk as having low 24-hour sodium excretion. Second, although the authors used the same study protocol, the baseline examinations in the cohorts that were combined for analysis were conducted in different time periods (a gap of roughly 10 years between recruitment) and in geographically and culturally different regions of Europe. In addition, nearly all cardiovascular deaths (81/84) occurred in FLEMENGHO (Flemish Study on Environment, Genes, and Health Outcomes; eTable 6 in the article), and mean sodium excretion was substantially lower in this cohort compared with the other study. Simple pooling of the FLEMENGHO cohort with the cohort in EPOGH (European Project on Genes in Hypertension) raises concern that ecological or temporal differences between cohorts may account for the observed association of sodium excretion with CVD mortality. It would be informative to see stratified results based on study-specific tertiles of sodium excretion. Back to top Article Information Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. References 1. Stolarz-Skrzypek K, Kuznetsova T, Thijs L, et al; European Project on Genes in Hypertension (EPOGH) Investigators. Fatal and nonfatal outcomes, incidence of hypertension, and blood pressure changes in relation to urinary sodium excretion. JAMA. 2011;305(17):1777-178521540421PubMedGoogle ScholarCrossref 2. Appel LJ, Frohlich ED, Hall JE, 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(10):1138-114321233236PubMedGoogle ScholarCrossref 3. Margetts B, Nelson N. Design Concepts in Nutritional Epidemiology. New York, NY: Oxford University Press; 1997:248 4. Stamler R, Shipley M, Elliott P, Dyer A, Sans S, Stamler J. Higher blood pressure in adults with less education: some explanations from INTERSALT. Hypertension. 1992;19(3):237-2411548050PubMedGoogle ScholarCrossref 5. Manrique-Garcia E, Sidorchuk A, Hallqvist J, Moradi T. Socioeconomic position and incidence of acute myocardial infarction: a meta-analysis. J Epidemiol Community Health. 2011;65(4):301-30920841371PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

Urinary Sodium Excretion and Cardiovascular Disease Mortality

JAMA , Volume 306 (10) – Sep 14, 2011

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Publisher
American Medical Association
Copyright
Copyright © 2011 American Medical Association. All Rights Reserved.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.2011.1291
Publisher site
See Article on Publisher Site

Abstract

To the Editor: Dr Stolarz-Skzypek and colleagues reported that lower urinary sodium excretion was associated with higher cardiovascular disease (CVD) mortality.1 These findings contradict a large body of evidence that established elevated sodium consumption as a risk factor for CVD and shed doubts on the worldwide efforts to implement population-based sodium reduction strategies.2 We have a number of concerns that suggest their findings should be interpreted cautiously. First, the volume of urine collected during 24 hours was significantly higher among people with high sodium excretion compared with those with low sodium excretion. It is not clear whether these differences reflect true urinary volume output or problematic completeness of urine collections. The authors assessed the accuracy of urine collection based on 24-hour urinary volume and creatinine excretion. However, these parameters are not reliable markers for completeness; instead, the proposed standard criterion in nutritional epidemiology studies is the use of para-aminobenzoic acid.3 Furthermore, the lowest levels of 24-hour urinary volume and sodium excretion were found in people with low educational attainment, which is in contradiction with observations from earlier studies that found sodium excretion to be higher in people with low educational level.4 Lower education level is also associated with unfavorable CVD risk profile and higher risk of developing CVD.5 Thus, although the authors adjusted for educational attainment, the findings may have been caused by misclassifying people with low socioeconomic status but higher CVD risk as having low 24-hour sodium excretion. Second, although the authors used the same study protocol, the baseline examinations in the cohorts that were combined for analysis were conducted in different time periods (a gap of roughly 10 years between recruitment) and in geographically and culturally different regions of Europe. In addition, nearly all cardiovascular deaths (81/84) occurred in FLEMENGHO (Flemish Study on Environment, Genes, and Health Outcomes; eTable 6 in the article), and mean sodium excretion was substantially lower in this cohort compared with the other study. Simple pooling of the FLEMENGHO cohort with the cohort in EPOGH (European Project on Genes in Hypertension) raises concern that ecological or temporal differences between cohorts may account for the observed association of sodium excretion with CVD mortality. It would be informative to see stratified results based on study-specific tertiles of sodium excretion. Back to top Article Information Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. References 1. Stolarz-Skrzypek K, Kuznetsova T, Thijs L, et al; European Project on Genes in Hypertension (EPOGH) Investigators. Fatal and nonfatal outcomes, incidence of hypertension, and blood pressure changes in relation to urinary sodium excretion. JAMA. 2011;305(17):1777-178521540421PubMedGoogle ScholarCrossref 2. Appel LJ, Frohlich ED, Hall JE, 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(10):1138-114321233236PubMedGoogle ScholarCrossref 3. Margetts B, Nelson N. Design Concepts in Nutritional Epidemiology. New York, NY: Oxford University Press; 1997:248 4. Stamler R, Shipley M, Elliott P, Dyer A, Sans S, Stamler J. Higher blood pressure in adults with less education: some explanations from INTERSALT. Hypertension. 1992;19(3):237-2411548050PubMedGoogle ScholarCrossref 5. Manrique-Garcia E, Sidorchuk A, Hallqvist J, Moradi T. Socioeconomic position and incidence of acute myocardial infarction: a meta-analysis. J Epidemiol Community Health. 2011;65(4):301-30920841371PubMedGoogle ScholarCrossref

Journal

JAMAAmerican Medical Association

Published: Sep 14, 2011

References