AS525 - Assessing sodium and potassium in 24-h and spot urines: feasibility of calibrating self-reported diet for use in WHI CVD association studies
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Investigator Names and Contact Information
Lesley Tinker [ltinker@whi.org]
Introduction/Intent
Strong evidence exists that higher sodium intake is associated with increased blood pressure, whereas evidence is moderate for higher sodium intake increasing the risk of cardiovascular disease (CVD) and evidence is insufficient regarding an association between potassium and blood pressure 1,2. The US Dietary Guidelines 2010 3, and similarly the 2013 American Heart Association (AHA)/ American College of Cardiology (ACC) Guidelines on Lifestyle Management to Reduce Cardiovascular Risk 4 called for reducing daily sodium intake to less than 2,300 milligrams (mg) and further reducing intake to 1,500 mg among older persons and persons at risk of hypertension. The recent NEJM report of elevated CVD risk elevation, not only at higher sodium excretion levels, but to an even greater extent at very low excretion levels has opened a major question concerning public health recommendations to reduce sodium intake on a population level 5-7.
Potassium may be related inversely to hypertension or heart disease acting as a single nutrient or as a modulator to sodium, although the evidence is low or insufficient 4. Strong evidence does exist, however, for risk reduction of hypertension by consuming the Dietary Approach to Stop Hypertension (DASH) dietary pattern 4, a pattern that offers potassium-rich food choices as one component of the eating plan.
Assessing the association of dietary sodium and potassium with CVD risk is hampered by biases in dietary self-report 8 and participant burden and cost of collecting suitable biomarkers, which can be derived from 24-hour urine collections. With 90% of sodium absorbed then excreted in the urine, 24-hour urine collections have been considered reliable as a reliable biomarker of sodium intake 2 and similarly, 24-hour urinary excretion of potassium is considered reliable as a biomarker of dietary potassium 9, thus eliminating reliance on dietary self-report.
More recently, spot urine collections have been evaluated as a source of estimates for 24-hour excretions of sodium and potassium 9. Methods have been detailed 10,11 and applied in the international Prospective Urban Rural Epidemiology (PURE) Study 9. The International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) has also investigated the utility of spot urine estimates 12. Although assessed in select studies as described above, the use of spot urines for estimating 24-hour sodium collections in CVD association studies, as in the recent PURE Study 5 is not without controversy and has been debated through letters to the editors 7, suggesting a strong need for greater study 5.
In the Women's Health Initiative (WHI), methodologic investigations into biomarkers of dietary intake have been ongoing for the past decade through the Nutrition Biomarkers Study (NBS), a WHI core-sponsored study (W8) 13, the Nutrition and Physical Activity Assessment Study (NPAAS), a grant and WHI-core funded study (W27, AS218) 14, and the NPAAS competing renewal (NPAAS-Feeding Study, AS272), a currently active grant-funded feeding study (R01 CA119171-04A1). Within the NBS, NPAAS, and NPAAS-Feeding Study (NPAAS-FS), participants collected 24-hour urines and within the NPAAS-FS, participants (n=153) collected both a morning first void spot urine followed immediately by a 24-hour urine collection. Separately from the dietary biomarker research, the WHI Bone Mineral Density (BMD, n=11,020) cohort collected morning first void spot urines.
The NPAAS-FS spot and 24-hour urine collections provide the opportunity to examine the relationship between spot urine and 24-hour urine for assessing sodium and potassium intake. In the immediacy, this knowledge will be used to help interpret the PURE Study findings. As a feasibility study, we hope to follow this pilot work with an R01 grant proposal to use spot urine, corrected to estimate 24-hour urine in the WHI population for CVD association studies in a nested case-control study within the WHI BMD Cohort. These later analyses would not rely on dietary self-report in any way, and would provide a direct comparison to the provocative PURE Study results, in a setting with excellent control over specimen and data collection and well characterized outcomes.
Specific Aims
1. Utilize spot and 24-hour urinary collections from the NPAAS-FS (AS272; n=153) to assess the association between spot and 24-hour urinary sodium and potassium.
a. Conduct laboratory analysis of the spot and 24-hour urine collections for (1) sodium, (2) potassium and (3) creatinine (used as an adjustment factor linking the spot and 24-hour sodium and potassium concentrations)
b. Conduct statistical analyses to estimate calibration equations for estimating 24-hour estimates of sodium and potassium excretions from corresponding spot urine excretions and study subject characteristics. Examine the variance of the calibrated estimates as a function of the 24-hour excretion levels.
