Urinary sodium excretion, blood pressure, cardiovascular disease, and mortality: a community-level prospective epidemiological cohort study

Summary

Background

WHO recommends that populations consume less than 2 g/day sodium as a preventive measure against cardiovascular disease, but this target has not been achieved in any country. This recommendation is primarily based on individual-level data from short-term trials of blood pressure (BP) without data relating low sodium intake to reduced cardiovascular events from randomised trials or observational studies. We investigated the associations between community-level mean sodium and potassium intake, cardiovascular disease, and mortality.

Methods

The Prospective Urban Rural Epidemiology study is ongoing in 21 countries. Here we report an analysis done in 18 countries with data on clinical outcomes. Eligible participants were adults aged 35–70 years without cardiovascular disease, sampled from the general population. We used morning fasting urine to estimate 24 h sodium and potassium excretion as a surrogate for intake. We assessed community-level associations between sodium and potassium intake and BP in 369 communities (all >50 participants) and cardiovascular disease and mortality in 255 communities (all >100 participants), and used individual-level data to adjust for known confounders.

Findings

95 767 participants in 369 communities were assessed for BP and 82 544 in 255 communities for cardiovascular outcomes with follow-up for a median of 8·1 years. 82 (80%) of 103 communities in China had a mean sodium intake greater than 5 g/day, whereas in other countries 224 (84%) of 266 communities had a mean intake of 3–5 g/day. Overall, mean systolic BP increased by 2·86 mm Hg per 1 g increase in mean sodium intake, but positive associations were only seen among the communities in the highest tertile of sodium intake (p<0·0001 for heterogeneity). The association between mean sodium intake and major cardiovascular events showed significant deviations from linearity (p=0·043) due to a significant inverse association in the lowest tertile of sodium intake (lowest tertile <4·43 g/day, mean intake 4·04 g/day, range 3·42–4·43; change –1·00 events per 1000 years, 95% CI –2·00 to –0·01, p=0·0497), no association in the middle tertile (middle tertile 4·43–5·08 g/day, mean intake 4·70 g/day, 4·44–5.05; change 0·24 events per 1000 years, –2·12 to 2·61, p=0·8391), and a positive but non-significant association in the highest tertile (highest tertile >5·08 g/day, mean intake 5·75 g/day, >5·08–7·49; change 0·37 events per 1000 years, –0·03 to 0·78, p=0·0712). A strong association was seen with stroke in China (mean sodium intake 5·58 g/day, 0·42 events per 1000 years, 95% CI 0·16 to 0·67, p=0·0020) compared with in other countries (4·49 g/day, –0·26 events, –0·46 to –0·06, p=0·0124; p<0·0001 for heterogeneity). All major cardiovascular outcomes decreased with increasing potassium intake in all countries.

Interpretation

Sodium intake was associated with cardiovascular disease and strokes only in communities where mean intake was greater than 5 g/day. A strategy of sodium reduction in these communities and countries but not in others might be appropriate.

Funding

Population Health Research Institute, Canadian Institutes of Health Research, Canadian Institutes of Health Canada Strategy for Patient-Oriented Research, Ontario Ministry of Health and Long-Term Care, Heart and Stroke Foundation of Ontario, and European Research Council.

Introduction

Reduction of sodium intake as a population-level intervention to reduce cardiovascular disease and mortality is recommended by WHO.¹ The recommended mean population-level sodium intake is 2 g/day (equivalent to 5 g/day salt), but has not been achieved in any country.¹ The rationale, however, is based on the association between sodium intake and blood pressure (BP) and the assumption that any approach to reducing BP will translate into fewer clinical cardiovascular outcomes.2, 3, 4, 5 Nevertheless, the claim that the effects of salt on cardiovascular disease are exclusively mediated through its effects on BP has never been proven.6, 7 Increased mean sodium intake was associated with a modestly raised mean BP at the community level in one study,⁵ but the study cohort was too small to assess the association at all levels of sodium intake. Additionally, no study has reported on the association between community-level sodium intake and cardiovascular disease or mortality. The effect of sodium on BP is small and, therefore, only slight reductions in cardiovascular disease could be expected.3, 4, 5 However, sodium affects numerous physiological processes and, therefore, its net effects on cardiovascular events cannot be predicted solely from its effects on BP.6, 8, 9 Thus, direct data are lacking for population-level effects of mean sodium intake on cardiovascular disease or death.

Research in context

Systematic review

We searched PubMed for papers published between Jan 1, 1960, and April 1, 2018, using the term “(‘sodium’ OR ‘salt’ AND ‘mortality’ OR ‘cardiovascular’ OR ‘myocardial’ OR ‘stroke’ OR ‘heart failure’ OR ‘sudden cardiac death’)”. We screened papers by title and abstract to identify full-text reports that were relevant to the study aims. We also screened citation lists from retrieved papers to identify further relevant research. We considered papers if they assessed the relation between sodium intake and at least one of the outcomes of interest. The papers cited in this Article were selected to be representative of the existing evidence base but do not comprise an exhaustive list of relevant research. WHO recommends that all populations consume less than 2 g/day sodium as a preventive measure against cardiovascular disease, but the target has not been achieved in any country. This recommendation is based on individual-level data from short-term trials of blood pressure, with no data from randomised trials or observational studies showing significantly lower rates of clinical cardiovascular events or mortality with sodium intake less than 3 g/day compared with 3–5 g/day. J-shaped or inverse associations between sodium and cardiovascular events or mortality have been observed in cohort studies estimating sodium intake by 24 h urine collection, morning fasting urine, or diet.

Added value of the study

We investigated community-level mean sodium intake and associations with cardiovascular disease and mortality among individuals enrolled from the general population in a large number and range of communities in 18 different countries followed up for around 8 years. We recorded standardised and detailed data on exposure, confounders, and outcomes, which allowed individual-level and group-level analyses.

Implications of all the available data

We found a positive association between sodium intake and systolic blood pressure across communities. Sodium intake and stroke were associated, but only significantly among communities in the upper third of sodium intake, which were largely confined to China. By contrast we found an inverse relation with myocardial infarction and mortality. The rates of stroke, cardiovascular death, and total mortality decreased with increasing potassium intake in all communities. A strategy of sodium reduction that targets communities and countries with high mean sodium intake (eg, >5 g/day) might be preferable to a global strategy. By contrast, a strong case can be made for increasing the consumption of potassium-rich foods (eg, fruits and vegetables) worldwide.

The Prospective Urban Rural Epidemiology (PURE) study¹⁰ provides a unique opportunity to assess associations between community-level mean sodium intake and cardiovascular disease and mortality in a large sample of individuals from the general population in different countries and communities. Standardised and detailed data on exposure, confounders, and outcomes have been recorded to permit both individual-level and group-level analyses. Here we report an analysis of PURE data on sodium intake and outcomes at the community (or centre) level and extend our previous analyses with greater numbers of cardiovascular events obtained with additional follow-up.