Response to letter by Campbell et al. regarding the results of the COSTICK trial

We thank Cambpell et al. for taking the time to read our trial report1Smyth A. Judge C. Kerins C. et al.Dietary counselling to reduce moderate sodium intake: effects on cardiovascular and renal biomarkers: primary findings of the COSIP and STICK phase II feasibility randomised controlled trials.eClinicalMedicine. 2023; 57101856https://doi.org/10.1016/j.eclinm.2023.101856Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar and pleased to respond to their comments and queries.2Campbell N.R.C. MacGregor G.A. He F.J. Dietary counseling to reduce moderate sodium intake. Concerns about the methods, evidence and feasibility of lowering sodium intake.eClinicalMedicine. 2023; Summary Full Text Full Text PDF Google Scholar Cambpell et al. cite the SODIUM-HF trial as evidence to support the feasibility of reducing sodium intake below 2.0 g/day (salt intake of below 5 g/day).3Ezekowitz J.A. Colin-Ramirez E. Ross H. et al.Reduction of dietary sodium to less than 100 mmol in heart failure (SODIUM-HF): an international, open-label, randomised, controlled trial.Lancet. 2022; 399: 1391-1400https://doi.org/10.1016/S0140-6736(22)00369-5Summary Full Text Full Text PDF PubMed Scopus (36) Google Scholar However, the SODIUM-HF trial measured sodium intake using 3-day food records, which may underestimate sodium intake (compared to 24-h urine assessments). In the COSTICK trial, participants reported a change in their discretionary use of salt, which did not translate into reductions in 24-h urinary excretion, possibly related to compensatory changes in non-discretionary salt intake. Moreover, dietary intake in patients with heart failure is not expected to be representative of the general population. Patients with heart failure are often heavily counselled to reduce dietary sodium intake as part of routine clinical care, and, those with more advanced disease are likely to have a lower caloric intake and, by extension, lower sodium intake. In contrast, our trials included a population with less morbidity and a more heterogenous population of free-living adults, with high quality diets (as evidenced by high diet quality scores and high potassium excretion). In measuring 24-h sodium excretion, which was not a primary outcome of our trial, we chose a threshold of at least 50% predicted creatinine clearance for inclusion in our sensitivity analysis. Our choice was based on a literature review on the accuracy and usefulness of different methods to assess the completeness of 24 h urine, including the systematic review4John K.A. Cogswell M.E. Campbell N.R. et al.Accuracy and usefulness of select methods for assessing complete collection of 24-hour urine: a systematic review.J Clin Hypertens. 2016; 18: 456-467https://doi.org/10.1111/jch.12763Crossref Scopus (81) Google Scholar cited in the letter by Cambpell et al. We selected a cut-off of 50% (observed:predicted creatinine) for pragmatic reasons, as we were keen to include a larger sample size in our analysis, while considering the purpose of the measurement in the setting of a randomised controlled trial. Other studies report a greater sensitivity using a cut-off of 70%.4John K.A. Cogswell M.E. Campbell N.R. et al.Accuracy and usefulness of select methods for assessing complete collection of 24-hour urine: a systematic review.J Clin Hypertens. 2016; 18: 456-467https://doi.org/10.1111/jch.12763Crossref Scopus (81) Google Scholar The purpose of estimating 24-h urine excretion of sodium, in a parallel randomized controlled trial, is primarily to gain an estimate of mean change in sodium excretion between groups, unlike an observational research study designed to estimate mean intake in a population. In the case of randomised controlled trials, the measurement error incurred will be distributed equally between treatment groups, thereby providing a comparative estimate of relative change. In response to this comment, we have completed an analysis confined to participants with 24 h collections with observed: predicted creatinine ratios ≥0.7; the mean sodium intake in the intervention group (n = 67) from 3.70 ± 1.43 g/day to 3.41 ± 1.57 g/day, over two years, and increased from 3.27 ± 1.26 to 3.32 ± 1.30 g/day in the usual care group (n = 61), with an adjusted mean difference of −0.22 (95% CI −0.66 to 0.21)g/day (p = 0.31, n = 128). Therefore, our conclusions are unchanged by the analytical approach employed. Cambpell et al. reference a meta-analysis of randomized controlled trials of sodium reduction trials reporting a mean reduction of sodium intake from 3.65 g/day to 2.69 g/day. However, the majority of clinical trials included were short-term in duration, and we provide a detailed discussion of our findings in the context of other longer-term trials. While no long-term trial has achieved sustained low sodium intake, extended observational follow-up of the Trials of Hypertension Prevent (TOHP) suggests that reducing intake, within a population with moderate intake, may be associated with reduced cardiovascular disease.5Cook N.R. Appel L.J. Whelton P.K. Lower levels of sodium intake and reduced cardiovascular risk.Circulation. 2014; 129: 981-989https://doi.org/10.1161/CIRCULATIONAHA.113.006032Crossref PubMed Scopus (194) Google Scholar We agree with Cambpell et al. that ‘it is difficult for individuals to sustain lower salt intake long-term’, which is a primary conclusion of our trial. The reasons underlying the challenge with reducing sodium intake to sustained low levels is controversial, and may relate to the food environment, but may also relate to physiological drivers related to salt thirst.6Kotchen T.A. Cowley Jr., A.W. Frohlich E.D. Salt in health and disease--a delicate balance.N Engl J Med. 2013; 368: 1229-1237https://doi.org/10.1056/NEJMra1212606Crossref PubMed Scopus (105) Google Scholar The inability to sustain low sodium intake raises a practical issue of whether guidelines should recommend an individual-level target that is considered unfeasible. AS and MOD drafted and finalised this letter in response to a letter received by the journal. The authors (AS and MOD) access and verified the underlying data for the statistical analysis presented in this letter. We declare no competing interests. Dietary counselling to reduce moderate sodium intake: effects on cardiovascular and renal biomarkers: primary findings of the COSIP and STICK phase II feasibility randomised controlled trialsAmong individuals with moderate sodium intake, intensive dietary counselling resulted in small short-term reductions in sodium intake and BP, but no significant effect on sodium intake, BP, or cardiorenal biomarkers at two years. Our trial suggests that it may not feasible to reduce sodium sustainably in those with a sodium intake around 3.0 g/day, through an intensive dietary counselling intervention. Full-Text PDF Open AccessDietary counseling to reduce moderate sodium intake. Concerns about the methods, evidence and feasibility of lowering sodium intakeSmyth et al. performed a 2-year randomized controlled trial (RCT) examining the impact of 6.5 h of dietary advice to reduce sodium intake on blood pressure and biological markers of cardiovascular (CVD) and renal disease.1 However, there are concerns about their methods for assessing urinary sodium and some statements regarding the feasibility of reducing dietary sodium and the evidence supporting sodium reduction. Full-Text PDF Open Access