INTRODUCTION
- A high dietary
intake of Sodium is associated with elevated blood pressure, a major risk
factor for cardiovascular disease.
- The United Nations
(UN), World Health Organization (WHO), Centers for Disease Control and
Prevention (CDC) and other organizations have emphasized the relationship
between dietary sodium and cardiovascular outcomes.
- As part of the
Global Burden of Diseases Nutrition and Chronic Diseases Expert Group
(NUTRICODE), we
i) Systematically
identified and analyzed data on sodium consumption worldwide and calculated
the dose-response effects of sodium on blood pressure in a new meta-analysis
of trials.
ii) Compiled data to
calculate the effects of blood pressure on cause-specific cardiovascular mortality
and to characterize current blood-pressure levels and numbers of cause-specific
deaths according to country, age, and sex
iii) Used data
relating levels of sodium intake to blood pressure and cardiovascular events, as
well as data on the lowest current levels of sodium intake according to
country, to define a reference range for sodium consumption
iv) Used data (Table
S1 in the Supplementary Appendix) to estimate the impact of current
levels of sodium intake on cardiovascular mortality throughout the world
METHODS
Assessment of Global Sodium Consumption
- Search Period:
March 2008 to December 2011
- Systematic
searches were conducted for previously conducted national or subnational
surveys on individual-level sodium consumption based on urinary excretion,
estimated dietary intake, or both
- Data Included:
142 surveys with data from 24-hour urine collections and 91 with estimates of
dietary intake, including 28 with both types of data (Table S2 in the
Supplementary Appendix).
- These surveys
included data from 66 countries, accounting for 74.1% of adults in
the world.
- Using a
hierarchical Bayesian model, we estimated the mean level of sodium consumption
and statistical uncertainty according to age, sex, and calendar year in 187
nations.
- An article with
detailed results of these analyses has been published previously (Powles et al.
BMJ Open 2013; 3(12): e003733)
- Our model estimated
sodium consumption with the use of 24-hour urine collections as the
reference standard.
- To make our data
comparable to data from prior regional surveys and blood pressure trials in
which urinary sodium levels were measured, we did not adjust our analyses
for sodium loss due to factors other than urinary excretion (e.g., sweat).
Effects of Reduced Sodium Intake on Blood Pressure
- Two recent
Cochrane meta-analyses evaluated randomized trials of the effect of reduce
sodium intake on blood pressure. (He et al. Cochrane Database Syst Rev
2013; 4: CD004937;
Graudal et al. Cochrane Database Syst Rev 2011;11: CD004022)
- These
meta-analyses did not determine whether blood-pressure lowering was linear
across a range of sodium intakes and did not simultaneously quantify heterogeneity
according to age, race, and the presence or absence of hypertension
- We performed a new
meta-analysis evaluating all randomized interventions identified in these articles
(Section S1 in Supplementary Appendix).
- Using data from these
trials, we evaluated whether the effects of reduced sodium intake on blood
pressure were linear.
- We evaluated
the potential heterogeneity in this effect by taking into account
population characteristics, including age, the presence or absence of hypertension,
and race, as well as the duration of the intervention.
- We also assessed
whether, apart from the presence or absence of hypertension, the effects
of reduced sodium intake on blood-pressure lowering were blunted by the use of
antihypertensive medication.
Effects of Blood-Pressure Levels on Cardiovascular
Mortality
- To calculate
the effects of systolic blood pressure on deaths from cardiovascular causes,
we combined results from two large international projects (totaling 99
cohorts, 1.38 million participants, and 65,000 cardiovascular events) that
pooled individual-level data, consistently adjusted for confounding.
- We accounted
for regression dilution bias based on serial blood-pressure measures over
time.
- We interpolated
and extrapolated age-specific proportional effects (relative risks) of
systolic blood pressure on cardiovascular mortality in 10-year age groups across
the pooling projects (see Section S2 and Fig. S3 in the Supplementary
Appendix).
- We used the same
estimates of relative risk according to sex and race, on the basis of evidence
of generally similar proportional effects of blood pressure on cardiovascular
events according to sex and race in trials of antihypertensive drugs and
observational studies of blood pressure and cardiovascular events.
Reference Levels of Sodium Consumption
- To define
reference levels of sodium consumption, we conducted a search of
published survey data, cohort studies, controlled trials, and dietary
recommendations.
- We determined levels of sodium consumption that were associated with the
lowest blood-pressure levels in ecologic studies and in randomized trials and with the lowest risk of disease
in meta-analyses of prospective cohort studies
- We also considered
at least theoretical feasibility based on the lowest national mean levels of
consumption globally.
- Finally, we considered
the consistency of our identified reference intake levels with major dietary
guidelines.
- Details are
provided in Section S4 in the Supplementary Appendix
Current Blood-Pressure Levels and Cause-Specific
Mortality
- Data on current
blood-pressure levels and cardiovascular mortality, each according to
country, age, and sex, were compiled as part of the Global Burden of Disease
Study 2010
- Data on blood pressure (from 786 country-years and 5.4 million participants) were obtained from
published and unpublished health examination surveys and epidemiologic studies
from around the world.
- Data on causes
of death were obtained for 187 countries from 1980 through 2010; these data
were obtained from vital-registration systems, verbal autopsies, mortality
surveillance, census data, surveys, hospitals, police records, and mortuaries.
- Details of data
collection and the statistical modeling used to estimate mean systolic blood pressure
and causespecific mortality are provided in Table S1 and Sections S5 and S6 in
the Supplementary Appendix
Cardiovascular Mortality Associated with Sodium
Consumption above the Reference Level
- We estimated
disease burdens using comparative risk assessment, capturing geographic and
demographic variations in sodium intake, blood pressure, cardiovascular
mortality, and corresponding uncertainties (details are provided in Table S1
and Section S7 in the Supplementary Appendix).
- We incorporated age-specific and sex-specific sodium intake,
blood-pressure level, relative risk, and mortality data for each country to
model the fraction and numbers of deaths estimated to be attributable to sodium
intake above the reference level.
- The population-attributable
fraction was estimated in a two-step
process.
- First, we used the effects of sodium consumption on blood
pressure according to age, the presence or absence of hypertension, and race to
calculate the change in mean systolic blood pressure that would be expected from
reducing sodium consumption to reference levels as defined above.
- Second, we used the age-specific effects of blood pressure
on cardiovascular mortality to calculate the resulting change in risk.
- Estimated numbers of deaths attributable to sodium intake
above the reference level were calculated by multiplying the
population-attributable fraction by the absolute number of deaths in each
country, age, and sex stratum.
RESULTS
Global Sodium
Consumption
- We estimated that in
2010, the mean level of consumption
of sodium worldwide was 3.95 g per
day, and regional means ranged from
2.18 to 5.51 g per day (Fig. S1 in the Supplementary Appendix).
- Overall, 181 of 187 countries — 99.2% of the adult population in the world — had estimated mean
levels of sodium intake exceeding the
World Health Organization recommendation of 2.0 g per day, and 119
countries — 88.3% of the adult
population in the world — exceeded
this recommended level by more than 1.0 g per day.
Effects of Reduced
Sodium Intake on Blood Pressure
- In our primary analysis of reduced sodium intake and blood
pressure, we found strong evidence of a
linear dose–response relationship (P < 0.001 for linearity and P = 0.58
for nonlinearity) (Fig. 1A).
- When the data were evaluated with the use of inverse-variance
weighted meta-regression, each reduction
of 2.30 g of sodium per day was associated with a reduction of 3.82 mm Hg
(95% confidence interval [CI], 3.08 to 4.55) in blood pressure (Fig. 1B).
- The effects of
dietary sodium on blood pressure were modified according to population
characteristics, with larger
reductions in blood pressure among (Fig. S2 in the Supplementary Appendix):
i) older persons > younger persons
ii) blacks > whites,
iii) hypertensive > normotensive persons.
- For a white, normotensive population at 50 years of age,
each reduction of 2.30 g per day in sodium intake lowered systolic blood
pressure by 3.74 mm Hg (95% CI, 2.29 to 5.18).
- We did not find
evidence of substantial blunting of the blood-pressure–lowering effects of
sodium restriction by antihypertensive drugs, although the data available to address this question
were limited. Further details are
provided in Section S1 in the Supplementary Appendix
Effects of Blood Pressure on Cardiovascular Mortality
- The pooled
analyses of blood pressure and cardiovascular mortality showed a log-linear (proportional)
dose–response relationship, with no evidence of a threshold as low as a
systolic blood pressure of at least 115 mm Hg (see Section S2 and Fig. S3 in
the Supplementary Appendix).
- The relative
magnitude of the effect on blood pressure decreased with age, in a manner
similar to that seen with other cardiovascular risk factors.
Reference Levels of Sodium Consumption
- Potential
reference levels of sodium consumption according to various definitions are
shown in Table S3 in the Supplementary Appendix
- The lowest mean
intake associated with both lower systolic blood pressure and a lower positive
relationship between higher age and blood pressure in ecologic studies was 614
mg of sodium per day.
- In large,
well-controlled, randomized feeding trials, the lowest tested
sodium intake for which reductions in blood-pressure levels were clearly
documented was 1500 mg per day.
- In prospective
observational studies, the lowest mean sodium intake associated with a lower
risk of cardiovascular events ranged from 1787 to 2391 mg per day.
- We also considered
observed mean levels of sodium intake that have been associated with the lowest
risk of stomach cancer (1245 mg per day).
- Levels of
sodium intake associated with the lowest risk ranged from 614 to 2391 mg per day,
depending on the type of evidence and the outcome.
- According to
national data on sodium consumption, the estimated lowest observed mean
national intake level was approximately 1500 mg per day.
- The maximum
level of sodium intake recommended in major dietary guidelines
ranged from 1200 to 2400 mg per day
Estimated Cardiovascular Mortality Attributed to Sodium
Consumption
- On the basis of the correlations between sodium intake and
blood pressure and between blood pressure and cardiovascular mortality that are
described above, and using a reference
level of sodium intake of 2.0±0.2 g per day, we found that 1.65 million deaths from cardiovascular
causes (95% uncertainty interval, 1.10 million to 2.22 million) worldwide in 2010 were attributable to
sodium consumption above the reference level (Table 1, and Table S4 in the
Supplementary Appendix).
Of these deaths,
- 687,000 (41.7%) were due to coronary heart disease,
- 685,000 (41.6%) were due to stroke, and
- 276,000 (16.7%) were due to other cardiovascular disease.
- Globally, 40.4% of
these deaths occurred prematurely (i.e.,
in persons younger than 70 years of age) (see Section S8 and Fig. S4 in the
Supplementary Appendix).
- Four of every 5
sodium-associated deaths from cardiovascular causes (84.3%) occurred in
low-income and middle-income countries.
- In sum, approximately 1
of every 10 deaths from cardiovascular causes worldwide (9.5%) (95%
uncertainty interval, 6.4 to 12.8) and
nearly 1 of every 5 (17.8%) premature deaths from cardiovascular causes were
attributed to sodium consumption above the reference level.
- Across nine regions of the world, the absolute rate of sodium-associated deaths
from cardiovascular causes was highest
in Central Asia and Eastern and Central Europe (Fig. 2A, and Fig. S5 and
Table S4 in the Supplementary Appendix).
- Proportional cardiovascular mortality was high in all
regions: among younger adults, it exceeded 10% in nearly all regions and it
exceeded 20% in Central Asia and Eastern and Central Europe, East Asia, and
Southeast Asia (Fig. 2B).
- Among older adults, who have a higher absolute risk and more
competing risk factors, proportional sodium-associated cardiovascular mortality
approached or exceeded 10% in Central Asia and Eastern and Central Europe, East
Asia, and Southeast Asia.
- Most sodium-associated cardiovascular deaths were due to
coronary heart disease, except in East Asia, Southeast Asia, and sub-Saharan
Africa, where most deaths from cardiovascular causes were due to stroke,
especially hemorrhagic and other nonischemic strokes (Table S4 and Fig. S5 in
the Supplementary Appendix).
- Across individual nations, substantial variation was
evident.
- Sodium-associated
cardiovascular mortality was highest in the country of Georgia (1967 deaths
per 1 million adults per year; 95% uncertainty interval, 1321 to 2647) and lowest in Kenya (4 deaths per 1 million
adults per year; 95% uncertainty interval, 3 to 6) (Fig. 3).
- Proportional cardiovascular mortality ranged from 27.4% in
Mauritius (95% uncertainty interval, 18.8 to 35.9) to 0.3% in Kenya (95%
uncertainty interval, 0.2 to 0.4) (Fig. 4).
-Among the 30 most populous nations (Fig. S6 in the
Supplementary Appendix), the highest
sodium-associated cardiovascular mortality was in Ukraine (1540 deaths per
1 million adults per year; 95% uncertainty interval, 1017 to 2099), and the highest proportional mortality was in China
(15.3% of all cardiovascular deaths; 95% uncertainty interval, 10.5 to 20.2).
- Detailed information about individual nations is provided in
Section S9 and Table S5 in the Supplementary Appendix.
- In sensitivity
analyses, lowering the definition of the reference intake level from 2.0 to 1.0 g of sodium per day increased the number of deaths from
cardiovascular causes in the world that were attributed to sodium consumption by approximately 40%, to 2.30 million
(95% uncertainty interval, 1.55 million to 3.07 million) (Tables S6 and S7 and
Fig. S7 and S8 in the Supplementary Appendix).
- When we estimated effects attributable only to sodium
intake above 4.0±0.4 g per day, 512,901 worldwide deaths from cardiovascular causes
(95% uncertainty interval, 333,710 to 704,773) were attributed to such
consumption (Tables S8 and S9 in the Supplementary Appendix).
- This was the estimated number of deaths that were
potentially preventable if only the nations with the highest level of sodium
consumption lowered their intake to just the current mean intake in the world.
- If we altered our model so that the estimated benefits of
blood-pressure lowering did not continue below 125 mm Hg, 1.55 million deaths
from cardiovascular causes in the world (95% uncertainty interval, 1.10 million
to 2.10 million) were attributed to sodium consumption above a level of 2.0 g
per day.
DISCUSSION
Main Findings
- Globally, 1.65 million deaths from cardiovascular causes
in 2010 — about 1 of 10 deaths from cardiovascular causes — were attributed to sodium
consumption of more than 2.0 g per day.
- Notably, 4 of 5 of these deaths occurred in low and middle-income
countries, and 2 of 5 of these deaths occurred prematurely (before the age of 70
years).
Regional Findings
- Our findings also show and quantify the heterogeneity in
disease burden attributed to sodium according to region, age, and type of
cardiovascular disease.
- Yet, we also found that no region and few countries were spared.
- Whereas estimated sodium-associated cardiovascular
mortality was highest in Central Asia, it was high (more than 750 deaths per 1
million adults who were 70 years of age or older) in all regions.
- The estimated number of proportional sodium-associated
deaths was also high, approaching or exceeding 15% of premature deaths from
cardiovascular causes in most regions
Dose-response
relationship between sodium intake and blood pressure
- Our meta-analysis of 107 randomized interventions in 103
trials showed a linear dose–response
relationship between reduced sodium intake and blood pressure, jointly
modified according to age, race, and the presence or absence of hypertension.
- These findings are consistent with the findings of a meta-analysis,
published after submission of this article, that included fewer trials (34
trials).
- Larger effects in
older adults and hypertensive persons would be consistent with decreasing vascular
compliance and renal filtration; in blacks, larger effects would be consistent
with differences in renal handling of sodium.
- We used randomized trials of reduced sodium intake and
blood pressure to estimate the more conceptually appropriate effect of lifetime
differences in intake, because direct evidence on lifetime effects, which may
be larger, is available only from ecologic comparisons and experiments
involving nonhuman primates
Possible controversy
- Some researchers have argued that it may not be possible
to directly extrapolate the effects of sodium on blood pressure to
cardiovascular risk.
- However, the effect on cardiovascular disease is supported
by extensive experimental and ecologic evidence, data on cardiovascular events
from some trials of reduced sodium intake, and evidence of the cardiovascular
benefits of blood-pressure lowering across multiple interventions (see Section S3
in the Supplementary Appendix).
- A meta-analysis of prospective cohort studies showed that
higher sodium consumption was associated with a higher rate of death from
coronary heart disease (relative risk, 1.32; 95% CI, 1.13 to 1.53) and death
from stroke (relative risk, 1.63; 95% CI, 1.27 to 2.10), the two main end
points in our analysis.
- Although concerns have been raised that reduced sodium
intake may cause physiological harm, a meta-analysis of 37 trials showed no significant
adverse effects on blood lipid levels, catecholamine levels, or renal function
Results from
observational studies
- There is mixed
evidence from observational data on the relationship between very low
sodium intake and cardiovascular events.
- A recent Institute of Medicine report concluded that, if
restricted to studies of clinical cardiovascular events, there is insufficient
evidence that lowering sodium intake further beyond 2.30 g per day either
increases or decreases the occurrence of cardiovascular disease.
- Yet the report further concluded that the entirety of the
evidence, “when considered collectively, indicates a positive relationship between
higher levels of sodium intake and [the] risk of cardiovascular disease.”
- Although precise targets for sodium reduction remain
controversial, various organizations tasked with reviewing all the evidence
have arrived at target levels ranging from 1200 to 2400 mg per day (Table S3 in
the Supplementary Appendix).
Limitations
- Causality cannot be proved, although every effort was made
to maximize validity, minimize error and bias, and incorporate heterogeneity
and uncertainty,
- Dietary sodium was estimated based on 24-hour urine
collections, which reflect approximately 90% of intake and also can be limited by
incomplete collection.
- Data on sodium intake were not available across all
countries or years - increased statistical uncertainty and the risk that some
data could reflect sampling bias.
- Dietary sodium is also associated with nonfatal cardiovascular
disease, kidney disease, and gastric cancer, the second-leading fatal cancer worldwide
– may underestimate the full global health effects of dietary sodium.
- No data on potassium consumption – also influences blood
pressure and the risk of stroke.
- Specific approaches or timelines for reduced sodium intake
was not incorporated.
CONCLUSION
- On
the basis of currently available data on sodium consumption, dose–response
effects on blood pressure and cardiovascular mortality, and cause-specific
deaths, we estimate that in 2010, a total of 1.65 million deaths from cardiovascular causes were attributable to
consumption of more than 2.0 g of sodium per day.
Correspondence (Comment by other experts and the authors' reply)
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