Errors in estimating usual sodium intake by the Kawasaki formula alter its relationship with mortality: implications for public health†

Abstract

Background: Several cohort studies with inaccurate estimates of sodium reported a J-shaped relationship with mortality. We compared various estimated sodium intakes with that measured by the gold-standard method of multiple non-consecutive 24-h urine collections and assessed their relationship with mortality. Methods: We analysed the Trials of Hypertension Prevention follow-up data. Sodium intake was assessed in four ways: (i) average measured (gold standard): mean of three to seven 24-h urinary sodium measurements during the trial periods; (ii) average estimated: mean of three to seven estimated 24-h urinary sodium excretions from sodium concentration of 24-h urine using the Kawasaki formula; (iii) first measured: 24-h urinary sodium measured at the beginning of each trial; (iv) first estimated: 24-h urinary sodium estimated from sodium concentration of the first 24-h urine using the Kawasaki formula. We included 2974 individuals aged 30-54 years with pre-hypertension, not assigned to sodium intervention. Results: During a median follow-up of 24 years, 272 deaths occurred. The average sodium intake measured by the gold-standard method was 3769 6 1282 mg/d. The average estimated sodium overestimated the intake by 1297 mg/d (95% confidence interval: 1267-1326). The average estimated value was systematically biased with overestimation at lower levels and underestimation at higher levels. The average measured

The International Consortium for Quality Research on Dietary Sodium/Salt (TRUE) position statement on the use of 24‐hour, spot, and short duration (<24 hours) timed urine collections to assess dietary sodium intake

“…When Olde Engberink et al assessed multiple 24‐hour urine collections over 1‐5 years, there were substantially different estimates of individual sodium intake, and the risk of cardiovascular disease increased progressively with intake. Similarly, in the Trials of Hypertension Prevention (TOHP), estimates of sodium intake from an average of multiple 24‐hour urine collections had a statistically significant linear relationship with death, while the association was relatively flat, and not statistically significant when sodium intake, was measured by a single 24‐hour urine collection . Further, in the TOHP studies, when the Kawasaki equation was used to estimate 24‐hour urine sodium from the sodium concentration in 24‐hour urine collections, the association with death was not statistically significant and appeared to take on a J‐shaped curve.…”

“…Weaver et al found that ten 24‐hour urine collections were required to have a 75% reliability to estimate an individual's sodium intake when on a constant sodium diet and this number is likely higher when there is substantial day‐to‐day variation in sodium intake. The strength of the association between dietary sodium and health outcomes is highly influenced by the number of urine collections . The issues relating to current, short‐term, and long‐term estimates of sodium intake for populations also apply to individuals.…”

“…Several formulae used to estimate 24‐hour urine sodium from spot collections have relatively small systematic errors in estimating average population sodium intake; however, some formulae used in different settings result in more substantive systematic error (>400 mg sodium) . Currently, all commonly used formulae systematically overestimate sodium intake at lower 24‐hour urine sodium and underestimate intake at higher 24‐hour urine sodium . Thus, changes in dietary sodium intake at the population level (both increases and decreases) will be systematically underestimated when assessed by spot urine samples.…”

“…The associations between sodium intake estimated by formulae and disease are likely to be affected by the known and strong confounding variables in the formulae. Recently, the use of such formulae has been found to alter the relationship of estimated sodium intake to death compared to an average of multiple days of 24‐hour urine sodium collections …”

Outcome of public consultations on the Scientific Opinions of the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) on Dietary Reference Values for sodium and chloride

“…This study, despite having been judged by the Panel to be at low risk of bias (tier 1), has important limitations. There is strong evidence for a linear dose-response relationship of salt with blood pressure (He 2002(He , 2003, and also with cardiovascular events (Cook, 2014) and mortality (He, 2018), within the range of 3 to 12 grams of salt per day. In addition, we have concern over the possibility of undercollection of 24h urine samples in this study, which could have led two problematic findings, i.e.…”