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. 2021 May 17:8:645902.
doi: 10.3389/fcvm.2021.645902. eCollection 2021.

Long-Term Effect of Salt Substitute on All-Cause and Cardiovascular Disease Mortality: An Exploratory Follow-Up of a Randomized Controlled Trial

Hao Sun  1   2 , Bing Ma  1   2 , Xiaomei Wu  1   2 , Hailong Wang  1   2 , Bo Zhou  1   2
Affiliations

Long-Term Effect of Salt Substitute on All-Cause and Cardiovascular Disease Mortality: An Exploratory Follow-Up of a Randomized Controlled Trial

Hao Sun et al. Front Cardiovasc Med. .

Abstract

Background: Salt substitute, a strategy for salt reduction, has been shown to decrease blood pressure and the incidence of hypertension. However, whether its hypotensive effect will reduce long-term mortality remains unclear. Our study reported an exploratory follow-up of mortality outcomes from previous randomized controlled trial to assess the long-term effect of low-sodium salt on total and cardiovascular disease (CVD) mortality. Methods: Participants who completed a previous 3-year double-blind randomized controlled trial were followed up from 2009 to 2019 to collect mortality data. Multivariable Cox regression models were used to evaluate the association between low-sodium salt intervention and all-cause and CVD mortality. Results: Four hundred and forty participants completed the intervention trial, of which 428 participants had death outcome data recorded after 10 years follow-up: 209 in a salt substitute group and 219 in a normal salt group. Fifty participants died during follow-up, 25 died due to CVD. No significant differences in relative risks were found for all-cause mortality [HR = 0.81, 95% confidence interval (CI): 0.46-1.42] and CVD mortality (HR = 0.58, 95% CI: 0.26-1.32) in unadjusted analyses. After adjusted with age and alcohol drinking status, there were significant reductions for stroke mortality among all participants (HR = 0.26, 95% CI: 0.08-0.84) and for CVD mortality (HR = 0.38, 95% CI: 0.16-0.92) and stroke mortality (HR = 0.25, 95% CI: 0.08-0.82) among hypertensive participants. Conclusions: Compared to normal salt, salt substitute might reduce the risk of CVD death, especially stroke among hypertensive patients. Our exploratory follow-up results provide potential evidence that low-sodium salt may be an accessible and effective strategy for prevention of CVD events, but definitive randomized controlled trials are warranted.

Keywords: CVD mortality; all-cause mortality; hypertension; salt substitute; stroke mortality.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of study design and participant follow-up.
Figure 2
Figure 2
Survival curves of CVD and stroke mortality between groups among all participants or hypertensive participants. (A. Survival curve for CVD mortality among all participants; B. Survival curve for stroke mortality among all participants; C. Survival curve for CVD mortality among hypertensive participants; D. Survival curve for stroke mortality among hypertensive participants.) CVD, Cardiovascular disease.
Figure 3
Figure 3
Comparisons for urinary Na+, K+, and Na+/K+ ratios between salt substitute group and normal salt group.
See this image and copyright information in PMC

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