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 ± 1282 mg/d. The average estimated sodium over-estimated the intake by 1297 mg/d (95% confidence interval: 1267-1326). The average estimated value was systematically biased with over-estimation at lower levels and under-estimation at higher levels. The average measured sodium showed a linear relationship with mortality. The average estimated sodium appeared to show a J-shaped relationship with mortality. The first measured and the first estimated sodium both flattened the relationship.

Conclusions: Accurately measured sodium intake showed a linear relationship with mortality. Inaccurately estimated sodium changed the relationship and could explain much of the paradoxical J-shaped findings reported in some cohort studies.

Figure 1

Box plots showing the distributions of sodium intake estimated by various methods. The lower and upper hinges correspond to the first and third quartiles (i.e. the 25th and 75th percentiles, respectively). The upper whisker extends from the hinge to the highest value no further than 1.5 × IQR from the hinge (where IQR is the inter-quartile range, or distance between the first and third quartiles). The lower whisker extends from the hinge to the lowest value no further than 1.5 × IQR of the hinge. Data beyond the end of the whiskers are ‘outlying’ points and are plotted individually. P < 0.001, N = 3010 for comparison of average measured vs average estimated. P < 0.001, N = 2656 for comparison of first measured vs first estimated.

Figure 2

Bland-Altman plot comparing average estimated with average measured 24-h urinary sodium excretion during the trial periods.

Figure 3

Bland-Altman plot comparing first estimated with first measured 24-h urinary sodium excretion at the beginning of each trial.

Figure 4

Spline plots for the association between different estimates of 24-h urinary sodium excretion and all-cause mortality adjusted for age, sex, race/ethnicity, clinic, treatment assignment, education status, baseline weight, alcohol use, smoking, exercise, 24-h urinary potassium excretion and family history of cardiovascular disease. Rug plot indicates distribution of sodium excretion. (a) P (Linear) = 0.047; P (Nonlinear) = 0.87. (b) P (Linear) = 0.006; P (Nonlinear) = 0.26. (c) P (Linear) = 0.82; P (Nonlinear) = 0.71. (d) P (Linear) = 0.15; P (Nonlinear) = 0.088.