Cardiovascular diseases (CVDs) are the leading causes of morbidity and mortality worldwide, accounting for 17.8 million deaths and 35.7 million years lived with disability in 2017.[1] Ischemic heart disease (IHD) alone is estimated to have caused 8.9 million deaths and 5.3 million years lived with disability in 2017.[2] Currently, IHD and stroke are expected to remain the leading causes of CVD deaths well into 2040.[3] The economic burden of CVD is considerable and continues to increase in prevalence. Adopting cost-effective and cost-saving programs to reduce CVD is imperative. Notably, the development and implementation of public health campaigns that raise awareness of the determinantal effects of CVD on health have been a major focus of both high- and low/middle-income countries.
High blood pressure is the leading risk factor for CVD-related morbidity and mortality and is one of the most important modifiable risk factors for CVD prevention.[4] Previous animal models and epidemiological studies have demonstrated a dose-dependent reduction in blood pressure with salt intake reduction. There is also a direct effect of salt reduction on reducing the risk of stroke and improving left ventricular function.[4,5] As previously noted, salt effect on target organs is multifactorial and involves an interplay of blood pressure regulation, microbiome, hormonal, inflammatory, and immunological responses.[5] It is anticipated that lowering sodium intake could prevent CVD by modifying the sympathetic activity and autonomic neuronal modulation of the cardiovascular system, thereby reducing blood pressure and end-organ damage (Figure 1). Nonetheless, the effect of salt reduction on CVD risk has been challenged by some observational studies in which investigators reported J-shaped or U-shaped associations, suggesting that both low and high salt intake were associated with increased risk of CVD.[4] However, these studies had severe methodological limitations and were subsequently challenged by working groups from several organizations. The SSaSS (Salt Substitute and Stroke Study) was the largest clinical trial of salt reduction in cardiovascular events that evaluated the effect of replacing regular salt with salt substitute during cooking in Chinese participants.[6] This study showed a reduced risk of stroke, major cardiovascular events, and even death from any cause in the study group using salt substitute compared with those using regular salt. For this reason, there has been a greater interest in whether the frequency of adding salt to food has direct implication on CVD events and/or CVD subtypes. In addition, several recent studies have also demonstrated that the frequency of adding salt to food may not only represent the discretionary sodium intake of some individuals, but can also reflect the person's long-term taste preference. In that regard, the frequency of adding salt to foods maybe considered a surrogate marker for long-term sodium intake in some individuals eating a Western diet.
Figure 1.
Effects of Excess Salt Intake on Health
Excess salt intake leads to end-organ damage by an interplay of multiple mechanisms. Pathological elevations in blood pressure lead to endothelial dysfunction. Aberrant hormonal and inflammatory signaling result in dysregulated immunological responses and alterations in gut microbiome. The bidirectional interaction between these pathways result in target organ damage and an estimated 3 million deaths per year and 70 million disability-adjusted life years. Reproduced with permission from He FJ, Tan M, Ma Y, MacGregor GA. Salt reduction to prevent hypertension and cardiovascular disease: JACC state-of-the-art review. J Am Coll Cardiol. 2020;75(6):632–647.
In this issue of the Journal of the American College of Cardiology, Ma et al[7] sought to investigate the association between the frequency of adding salt to foods and CVD risk in the first prospective cohort of 176,570 participants from the UK biobank who were initially free from CVD. Participants answered questions at baseline to collect information on the frequency of adding salt to food. They also completed a 24-hour dietary recall that asked about the consumption of several types of food and drinks in the previous 24 hours. A Dietary Approaches to Stop Hypertension (DASH) diet score was calculated to examine the joint association of adding salt to food and diet in relation to CVD risk. The 24-hour sodium excretion was estimated from casual spot urinary concentrations collected from the participants. Cardiovascular events of interest were IHD, stroke, and total CVD events defined as a composite of IHD, stroke, and heart failure. During a median follow-up of 11.8 years, lower frequency of adding salt to foods was significantly related to lower risks of total CVD events after adjusting for covariates and DASH diet. The adjusted HRs were 0.81 (95% CI: 0.73–0.90), 0.79 (95% CI: 0.71–87), and 0.77 (95% CI: 0.70–84) across the groups that reported usually, sometimes, and never/rarely, respectively. Among the CVD subtypes, lower frequency of adding salt had the strongest association with heart failure. The adjusted HRs were 0.70 (95% CI: 0.57–0.86), 0.65 (95% CI: 0.54–0.79), and 0.63 (95% CI: 0.53–0.76) across the groups of usually, sometimes, and never/rarely, respectively. This was followed by a lower risk of IHD (P < 0.001) but not associated with stroke (P = 0.32). With relation to the DASH diet, participants with the lowest salt intake with highest adherence to the DASH diet had the lowest risk of total CVD events.
The findings of this study are promising. In a previous study, Ma et al[8] reported higher frequency of adding salt to foods was associated with higher risk of all-cause premature mortality and lower life expectancy. The present study builds on what was previously reported and eludes to the possible role that long-term salt preferences may have on the risks of total CVD events and major subtypes of CVD.[9] The strongest association between salt intake frequency and CVD was seen with heart failure. A recent clinical trial demonstrated that sodium reduction had a specific effect on N-terminal pro–brain-type natriuretic peptide but no other cardiac biomarkers involved in inflammation and cardiac injury.[10] Furthermore, a recent study from the Million Veteran Program showed a strong association of sodium intake and IHD risk.[11] As expected, participants who combined the lowest frequency of salt addition and the highest level of DASH diet adherence had the lowest risk of CVD, suggesting the additive role of lower salt preferences and a healthier diet may have on CVD prevention. A major limitation of the study is the self-reported frequency of adding salt to foods and the enrollment of participants only from the United Kingdom, limiting generalizability to other populations with different eating behaviors. Randomized trials are warranted to ascertain the results of this study. Nonetheless, the findings of the present study are encouraging and are poised to expand our understanding of salt-related behavioral interventions on cardiovascular health.
J Am Coll Cardiol. 2022;80(23):2168-2170. © 2022 American College of Cardiology Foundation
