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Urinary Sodium Excretion and Cardiovascular Disease Mortality

Urinary Sodium Excretion and Cardiovascular Disease Mortality To the Editor: Low sodium excretion was associated with higher CVD mortality in a prospective study of 3681 participants from Europe.1 The results should be interpreted with caution considering several flaws in study design, analysis, and interpretation. A major source of bias in this study was misclassification of urinary sodium excretion. A single 24-hour urine sample, which was used for all the analyses, cannot represent usual sodium intake at the individual level. Nor can it be used to accurately classify individuals into categories as the authors did in analyzing 3 levels of sodium excretion with CVD mortality. It has been well documented that differential misclassification bias occurs when a continuous exposure variable with random measurement error is classified into multiple categories.2 Although the authors tried to exclude participants with inaccurate urine collection, it would have been helpful to examine the association of CVD mortality with sodium/creatinine ratio because this ratio is less affected by incompleteness of urine sample collection. Furthermore, their cohort appears to have included persons who followed a very low sodium diet (50 mmoL/day). Since dietary salt reduction is a common recommendation to patients with hypertension and other conditions that increase the risk of CVD, the inclusion of persons prescribed a low sodium diet in the low sodium excretion tertile could have biased the study findings. Previous studies have identified an interaction between sodium intake and obesity on the risk of CVD.3,4 Individuals with obesity or metabolic syndrome are more sensitive to dietary sodium intake.5 A stratified analysis by obesity or metabolic syndrome would provide additional insight on the sodium-CVD relationship. Finally, the authors' conclusion of lower sodium excretion with higher CVD mortality was based on an observed weak association (P = .04 for hazard ratio and P = .02 for trend across tertiles). A large number of statistical tests were conducted in this study, and observed statistical significance could be due to chance alone. If multiple comparisons were taken into account, these observed associations may not remain statistically significant. Back to top Article Information Conflict of Interest Disclosures: Both 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. Flegal KM, Keyl PM, Nieto FJ. Differential misclassification arising from nondifferential errors in exposure measurement. Am J Epidemiol. 1991;134(10):1233-12441746532PubMedGoogle Scholar 3. He J, Ogden LG, Vupputuri S, Bazzano LA, Loria C, Whelton PK. Dietary sodium intake and subsequent risk of cardiovascular disease in overweight adults. JAMA. 1999;282(21):2027-203410591385PubMedGoogle ScholarCrossref 4. Tuomilehto J, Jousilahti P, Rastenyte D, et al. Urinary sodium excretion and cardiovascular mortality in Finland: a prospective study. Lancet. 2001;357(9259):848-85111265954PubMedGoogle ScholarCrossref 5. Chen J, Gu D, Huang J, et al; GenSalt Collaborative Research Group. Metabolic syndrome and salt sensitivity of blood pressure in non-diabetic people in China: a dietary intervention study. Lancet. 2009;373(9666):829-83519223069PubMedGoogle 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.2011.1292
Publisher site
See Article on Publisher Site

Abstract

To the Editor: Low sodium excretion was associated with higher CVD mortality in a prospective study of 3681 participants from Europe.1 The results should be interpreted with caution considering several flaws in study design, analysis, and interpretation. A major source of bias in this study was misclassification of urinary sodium excretion. A single 24-hour urine sample, which was used for all the analyses, cannot represent usual sodium intake at the individual level. Nor can it be used to accurately classify individuals into categories as the authors did in analyzing 3 levels of sodium excretion with CVD mortality. It has been well documented that differential misclassification bias occurs when a continuous exposure variable with random measurement error is classified into multiple categories.2 Although the authors tried to exclude participants with inaccurate urine collection, it would have been helpful to examine the association of CVD mortality with sodium/creatinine ratio because this ratio is less affected by incompleteness of urine sample collection. Furthermore, their cohort appears to have included persons who followed a very low sodium diet (50 mmoL/day). Since dietary salt reduction is a common recommendation to patients with hypertension and other conditions that increase the risk of CVD, the inclusion of persons prescribed a low sodium diet in the low sodium excretion tertile could have biased the study findings. Previous studies have identified an interaction between sodium intake and obesity on the risk of CVD.3,4 Individuals with obesity or metabolic syndrome are more sensitive to dietary sodium intake.5 A stratified analysis by obesity or metabolic syndrome would provide additional insight on the sodium-CVD relationship. Finally, the authors' conclusion of lower sodium excretion with higher CVD mortality was based on an observed weak association (P = .04 for hazard ratio and P = .02 for trend across tertiles). A large number of statistical tests were conducted in this study, and observed statistical significance could be due to chance alone. If multiple comparisons were taken into account, these observed associations may not remain statistically significant. Back to top Article Information Conflict of Interest Disclosures: Both 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. Flegal KM, Keyl PM, Nieto FJ. Differential misclassification arising from nondifferential errors in exposure measurement. Am J Epidemiol. 1991;134(10):1233-12441746532PubMedGoogle Scholar 3. He J, Ogden LG, Vupputuri S, Bazzano LA, Loria C, Whelton PK. Dietary sodium intake and subsequent risk of cardiovascular disease in overweight adults. JAMA. 1999;282(21):2027-203410591385PubMedGoogle ScholarCrossref 4. Tuomilehto J, Jousilahti P, Rastenyte D, et al. Urinary sodium excretion and cardiovascular mortality in Finland: a prospective study. Lancet. 2001;357(9259):848-85111265954PubMedGoogle ScholarCrossref 5. Chen J, Gu D, Huang J, et al; GenSalt Collaborative Research Group. Metabolic syndrome and salt sensitivity of blood pressure in non-diabetic people in China: a dietary intervention study. Lancet. 2009;373(9666):829-83519223069PubMedGoogle ScholarCrossref

Journal

JAMAAmerican Medical Association

Published: Sep 14, 2011

References