No evidence for a J-curve for association between sodium intake and CVD

Cook NR, Appel LJ, Whelton PK
Circulation. January 10, 2014 doi: 10.1161/​CIRCULATIONAHA.113.006032

Background

Although the American Heart Association recommends lowering sodium intake to <1500 mg/24h [1,2], and the World Health Organization recommends <2000 mg/24hr [3], there is not enough data to support a lowering to below 1500 mg/24 hr, according to the Institute of Medicine (IOM) in a review of the effects of sodium intake on health effects other than blood pressure.
Recently data from the FLEMENGHO and EPOGH cohorts have shown adverse cardiovascular disease (CVD) outcomes with very low sodium intake [4], although the IOM concluded that the quality of the data was insufficient. All studies that have reported a paradoxical inverse or J-shaped association between sodium intake and CVD have been based on secondary analyses of studies that were not specifically designed to evaluate this relationship. Suboptimal measurements of sodium  are also a major concern.
Mulitiple 24-hour urine specimens were collected over either 18 months [5] or 3-4 years [6] in the phase I and II of the Trials of Hypertension Prevention (TOHP). In participants not on active sodium intervention, these measures were averaged to represent long-term usual intake of sodium. This report sheds more light on the relationship of sodium to CVD, specifically around the low absolute sodium intake levels, based on follow-up data of after the TOHP 1 and 2 trials, including 4526 healthy participants (prehypertensive).

Main results

• Median sodium excretion averaged across the trial period among participants with follow-up data was 3630 mg/24hr, with only 1.4% of participants having <1500 and 10% <2300 mg/24hr. Men (median 3934 mg/24hr) had higher sodium levels than women (3078 mg/24hr).
• During the post-trial follow-up, 193 CV events or CVD deaths were documented.
  In different statistical models with increasing adjustments, a non-significant trend of increasing risk with increasing sodium level was seen. In the fully adjusted model, in comparison to those with sodium of 3600-4800 mg/24hr, participants with sodium <2300 mg/24hr had a 32% lower risk (P for trend=0.13). When regarding sodium as a continuous term, risk increased linearly with 17% per 1000 mg/24hr increase in sodium (P=0.054) in the fully adjusted model.
• In a non-linear spline plot curve estimate HR for participants consuming 2300 and 1500 mg/24hr in comparison to those 3600 mg/24hr, were 0.78 and 0.69 respectively.
• In sensitivity analyses excluding those with coefficient of variation of creatinine/weight (Cr/Wt )>20%, the associations of sodium with CVD were slightly stronger, albeit not statistically significant.
• CVD risk increased by 20% per SD of the first baseline measure of Cr/Wt, but not its average over the trial period. Also, the risk of CVD increased by 21% per SD of average sodium excretion (P=0.05) and decreased by 15% per SD of average potassium excretion (P=0.12). Adjustment of Cr/Wt did not change these relationships.

Conclusion

This TOHP Follow-up Study used an average of multiple 24-hour urine collections as a more accurate measure of sodium exposure than previously applied in studies evaluating the association between sodium and CVD. A continued decrease in CVD events was seen among those with sodium levels as low as 1500 mg/day, thus no evidence of a J-shape in a spline curve. The 32% risk reduction in those excreting less than 2300 mg/day was substantial, although not statistically significant due to the small size of the subgroup.
Thus, these results are consistent with overall health benefits and current guidelines of reducing sodium intake to the 1500 to 2300 mg/day range in the majority of the population. The practical implementation of such targets is challenging, but even a small reduction in the average intake of dietary sodium could yield improved CVD health.

Editorial comment [7]

Based on the findings of Cook et al., the ideal level of sodium intake to reduce CVD risk was below 2300 mg/day (less than one teaspoon of salt. Despite public health efforts to encourage lower sodium consumption in the United States, Americans consume over an average 3400 mg/day. It has been estimated that 12% of sodium intake occurs naturally in food, 11% is added while preparing food or at the table, and 77% of sodium comes from processed/packaged food or restaurant food.
The low availability of lower sodium choices makes lower sodium consumption challenging. Individuals should use the information on the Nutrition Facts panel on package labels, to be informed on the sodium content, among other measures that can reduce sodium intake.
Cooperation from the food an restaurant industries to lower sodium in manufactured and restaurant foods would assist Americans in meeting the lower sodium recommendations, as well as public health nutrition strategies to help people select lower sodium foods for better CV health.

Find this article online

References

1. Lloyd-Jones DM, Hong Y, Labarthe D, et al., on behalf of the American Heart Association Strategic Planning Task Force and Statistics Committe. Defining and setting national goals for cardiovascular health promotion and disease reduction: The American Heart Association’s Strategic Impact Goal Through 2020 and Beyond. Circulation. 2010;121:586-613.
2. Appel LJ, Frohlich ED, Hall JE, et al. The importance of population-wide sodium reduction as a means to prevent cardiovascular disease and stroke: a call to action from the American Heart Association. Circulation. 2011;123:1138-1143.
3. WHO. Guideline: Sodium intake for adults and children. Geneva: World Health Organization (WHO); 2012.
4. Stolarz-Skrzypek K, Kuznetsova T, Thijs L, et al. for the 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;305:1777-1785.
5. The Trials of Hypertension Prevention Collaborative Research Group. The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels. Results of the Trials of Hypertension Prevention, Phase I. J Amer Med Assoc. 1992;267:1213-1220.
6. The Trials of Hypertension Prevention Collaborative Research Group. Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high- normal blood pressure. The Trials of Hypertension Prevention, Phase II. The Trials of Hypertension Prevention Collaborative Research Group. Arch Intern Med. 1997;157:657-667.
7. Steffen LM. Lower Levels of Sodium Intake and Reduced Cardiovascular Risk: The Challenge to Achieve Lower Sodium Recommendations. Circulation. Online January 10, 2014