Low dietary sodium in heart failure: time for a re-evaluation of guidelines?
- The George Institute for Global Health, The University of Sydney, Sydney, New South Wales, Australia
- Correspondence to Dr Min Jun, The George Institute for Global Health, The University of Sydney, PO Box 201, Missenden Road, Sydney, NSW 2050, Australia;
There is much evidence that higher sodium intake is associated with elevated blood pressure and there is a strong likelihood that the relationship between excess dietary sodium intake and hypertension is causal.1–3 Corresponding evidence from clinical trials shows that significant reductions in blood pressure can be achieved by lowering dietary sodium consumption in groups with hypertension as well as among normotensive individuals.4 With high blood pressure identified as the leading cause of cardiovascular disease in the world, responsible for more than 60% of stroke events and almost 50% of coronary heart disease,5 efforts to control blood pressure levels have been a global priority for decades. In addition to very well established clinical hypertension control programmes, many of the world's leading scientific and health organisations recommend the widespread reduction of sodium intake for blood pressure lowering. In the USA, the US dietary guidelines recommend reducing the daily intake of sodium to less than 2300 mg/day for the general population, which equates to about one teaspoon or 6 g of salt.6 The US dietary guidelines also advise that higher risk individuals, such as African Americans or people with hypertension, diabetes, or chronic kidney disease, should aim for a daily intake of 1500 mg/day or less.6
A key challenge for these guidelines has been the absence of definitive evidence that reduced dietary sodium translates into lower risks of ‘hard’ clinical outcomes such as stroke and heart attack. This has been the focus of much recent debate. On the one hand, investigators have projected that population-wide reductions in dietary sodium intake will deliver very large benefits because the blood pressure reductions that would ensue would produce substantial reductions in cardiovascular disease.7 It is estimated that reducing population salt intake in the USA by 3 g/day could prevent between 60 000 and 120 000 new cases of coronary heart disease a year, translating into healthcare savings of US$10–24 billion. The converse view arises from research suggesting that the blood pressure reductions achieved by reducing salt intake will not actually translate into lower risks of hard outcomes. A recent meta-analysis of the randomised trials of sodium reduction reported no evidence of benefit from low sodium diets on clinical outcomes including all-cause mortality and cardiovascular morbidity.8 Another reported a ‘J-curve’ relationship between sodium intake and cardiovascular events, suggesting that low sodium intake, in addition to high sodium intake, is harmful.9 The problem is that all these studies have their weaknesses and their standalone interpretation conveys confusion rather than clarity. The meta-analysis of trials had very limited statistical power to address the question posed, particularly when findings were reported separately for hypertensive and normotensive individuals. Combination of the data10 by contrast suggests a 20% reduction in cardiovascular events, although this result in turn is heavily dependent on the findings of two large trials with very incomplete follow-up.11 ,12 Likewise, the recent observational epidemiology is plagued by issues of reverse causation, and the selective reporting of studies with positive, neutral, or negative findings has provided an opportunity for those of all different persuasions to put forward their particular viewpoint. It remains the case that the best approximation to truth is to be had from a balanced, critical and systematic review of the totality of the evidence. Several highly reputable organisations have made such assessments and the recommendation continues to be that most individuals should try to eat less salt.13–15
There may, however, be a group for which this advice is no longer sound. DiNicolantonio and colleagues16 assessed, in a systematic review and meta-analysis, the effects of low sodium diets (1.8 g/day) compared to normal sodium diets (2.8 g/day) in patients with systolic heart failure (defined as left ventricular ejection fraction <40%). The authors systematically searched the literature for randomised controlled trials including participants with heart failure, and identified over 10 000 abstracts from which 51 potentially eligible studies were recovered and reviewed in full text. Six trials ultimately satisfied the inclusion criteria of the review. The clinical outcomes extracted from the studies included all-cause mortality, heart failure readmissions, sudden death and death due to heart failure. The authors report that only two trials were double-blinded, but all trials had outcomes assessed by blinded adjudicators and used intention-to-treat analyses. The results of this overview provide strong evidence of harm caused by low dietary sodium intake in this setting, showing an almost doubling in the risk of all-cause mortality (RR 1.95, 95% CI 1.66 to 2.29) and a more than twofold increase in the risk of death due to heart failure (RR 2.23, 95% CI 1.77 to 2.81). The findings were consistent across the contributing trials results with no evidence of heterogeneity (I2=0% for both). The low sodium diet was also associated with a similarly elevated risk of hospital admissions for heart failure (RR 2.10, 95% CI 1.67 to 2.64), although for this outcome there was some evidence of heterogeneity between the individual trial results (I2=59%, p=0.03).
Given the very strong relationship between high blood pressure and the development of heart failure,17–19 and the known adverse effects that excess sodium has on cardiovascular function, an adverse effect of sodium restriction in these heart failure trials may appear counterintuitive. However, patients with heart failure receive aggressive ongoing diuretic therapy for the control of congestive symptoms. For many, a direct consequence of this is chronic depletion of sodium, with hyponatraemia reported to be present in over 20% of patients admitted to hospital with this diagnosis.20 ,21 Hyponatraemia is a sensitive marker of mortality risk in patients with heart failure20 ,22 ,23 as well as in other populations, such as those undergoing surgery.24
In the studies included in the meta-analysis by DiNicolantonio and colleagues,16 the trial participants all received very high doses of the diuretics furosemide and spironolactone. The 125–1000 mg of these agents administered twice daily as part of the trial regimens exceeds the dosages normally used in clinical practice and the maximum recommended doses provided for by most heart failure management guidelines.25 In addition, three of the six studies placed all patients on 1 l/day fluid restriction and it is thus likely that many trial participants were both hyponatraemic and hypovolaemic when dietary sodium restrictions were applied. When viewed in this light the harmful effects reported in this meta-analysis are much less surprising, and the authors themselves suggest hyponatraemia as a possible explanation for their findings.
All of the trials included in the systematic review appear to have been conducted by the same group of researchers using the same aggressive diuretic therapy in conjunction with fluid restriction as a background standard of care. The haemodynamic and biochemical effects resulting from the combination of high-dose diuretics, fluid restriction and low dietary sodium diet are likely to have pushed large numbers of patients beyond the usual homeostatic limits, and this is the most plausible explanation for the observed harmful effects. The intensity of therapy used in these studies is not, however, typical of clinical practice and as such the study findings have very limited generalisability. The results do, however, highlight the need for a careful evaluation of total body sodium status among patients with heart failure requiring diuretic therapy and a more nuanced approach to recommendations about dietary sodium intake in this population group. Current guidelines for heart failure management recommend universal dietary sodium restriction of between 2000 and 3000 mg for patients with clinical syndromes of heart failure and preserved or depressed left ventricular ejection fraction. In patients with moderate to severe heart failure, further restrictions below 2000 mg daily are recommended.25 The results reported by DiNicolantonio and colleagues16 suggest that an amendment to these guidelines may be warranted when patients with heart failure are using high doses of diuretics and are at risk of hyponatraemia.
For the great majority of the world's population the message is, however, unchanged. Preventive action will be a more effective long-term solution than any management strategy for cardiovascular disease. To this end, the development and implementation of better strategies to achieve population-wide reductions in sodium intake to lower cardiovascular risk and heart failure remains an imperative.
Contributors MJ wrote the first draft of the manuscript and performed critical revision of the manuscript as the corresponding author. BN contributed to critical revision and improvements to the manuscript.
Competing interests MJ reports no conflicts of interest. BN reports, over the past 5 years, receiving grant support from the Australian Food and Grocery Council, Baxter, Bupa Australia, Johnson and Johnson, Medtronic, Merck Shering Plough, Novartis, Respironics, Roche, Servier; consulting fees from Roche and Takeda; and lecture fees or reimbursements of travel expenses from Abbott, AstraZeneca, Novartis, Pepsico, Pfizer, Pharmacy Guild of Australia, and Roche. He is also the chair of the Australian Division of World Action on Salt and Health.
Provenance and peer review Commissioned; internally peer reviewed.