The Data Show a U-Shaped Association of Sodium Intake With Cardiovascular Disease and Mortality

Extract

To the Editor: Whelton and Appel inaccurately state that we implied using Institute of Medicine (IOM) recommendations to derive “post hoc” cut points for low- and high-sodium intake.¹ However, we implied what the IOM recommendations might have been,² if the 2004 IOM committee had followed traditional IOM rules for assessing nutrients. As correctly stated, the 2013 IOM committee precluded deriving numerical definitions of low- and high-sodium intakes.¹ Consequently, we a priori (not “post hoc”) related the “low” and “high” definitions to the recently confirmed usual global sodium intake.³ Unfortunately, despite the 2013 IOM conclusion, the Centers for Disease Control and the American Heart Association insist that a sodium intake above 2,300mg is “high.”

The 2013 IOM committee’s a priori decision not to make meta-analyses was independent of the assessment of the cohort studies, of which many, as stated,¹ were not primarily designed to associate sodium intake with health outcomes. The unintended advantage of this is that they are free of preparation bias, which may have influenced the results of blood pressure trials used to estimate the present limits for sodium intake (trials of hypetension prevention (TOHP) 1 and 2, dietary approaches to stop hypertension (DASH)-sodium, and trial of nonpharmacologic interventions in the elderly). These trials were biased in favor of greater blood pressure reduction in the sodium-reduction group by including salt-sensitive overweight participants with high blood pressure. Furthermore, the reliability of the analysis of the DASH-sodium trial is limited, as external access to raw data from this trial has been refused.⁴ The repeated statistical analyses of post hoc subgroups of the original TOHP trials, unaccompanied by protocols, should not obscure that in the actual TOHP trials there was no difference in the most reliable outcome, all-cause mortality, between the low-sodium and normal-sodium group. Finally, these blood pressure trials provide no support that reduction of sodium intakes below 2,300mg/day is either safe or will result in health benefits. Importantly, the Prospective Urban Rural Epidemiology study,⁵ a large cohort study of more than 100,000 individuals, was prospectively designed to associate sodium intake with health outcomes. This study also documents the “U”-shaped association between sodium intake and health outcomes. The large-scale study in Northern China may show whether sodium reduction in a population is feasible and has effects on blood pressure. Although the data have been analyzed and results have been promised by August 2013,⁶ the study has not yet been published. It would be interesting to know whether the study is withheld or there is another reason for Whelton and Appel’s statement that these results will not be available for several years.