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Abstract
The objective of this review was to provide a synthesis of the evidence on the effect of dietary salt and
potassium intake on population blood pressure, cardiovascular disease, and mortality. Dietary guidelines
and recommendations are outlined, current controversies regarding the evidence are discussed, and rec-
ommendations are made on the basis of the evidence. Designed search strategies were used to search
various databases for available studies. Randomized trials of the effect of dietary salt intake reduction or
increased potassium intake on blood pressure, target organ damage, cardiovascular disease, and mortality
were included. Fifty-two publications from January 1, 1990, to January 31, 2013, were identified for
inclusion. Consideration was given to variations in the search terms used and the spelling of terms so that
studies were not overlooked, and search terms took the following general form: (dietary salt or dietary
sodium or [synonyms]) and (dietary potassium or [synonyms]) and (blood pressure or hypertension or vascular
disease or heart disease or chronic kidney disease or stroke or mortality or [synonyms]). Evidence from these
studies demonstrates that high salt intake not only increases blood pressure but also plays a role in
endothelial dysfunction, cardiovascular structure and function, albuminuria and kidney disease progres-
sion, and cardiovascular morbidity and mortality in the general population. Conversely, dietary potassium
intake attenuates these effects, showing a linkage to reduction in stroke rates and cardiovascular disease
risk. Various subpopulations, such as overweight and obese individuals and aging adults, exhibit greater
sensitivity to the effects of reduced salt intake and may gain the most benefits. A diet that includes modest
salt restriction while increasing potassium intake serves as a strategy to prevent or control hypertension and
decrease cardiovascular morbidity and mortality. Thus, the body of evidence supports population-wide
sodium intake reduction and recommended increases in dietary potassium intake as outlined by current
guidelines as an essential public health effort to prevent kidney disease, stroke, and cardiovascular disease.
ª 2013 Mayo Foundation for Medical Education and Research n Mayo Clin Proc. 2013;88(9):987-995
D
uring the past century, medical costs of hypertension at more than $93.5
research in the United States has billion per year.3
undergone a classic epidemiologic Population studies have reported an associ- From the Department of
transition,1 with the focus shifting from public ation between dietary sodium chloride (termed Medicine/Nephrology,
University of Alabama at
health issues related to childhood infectious salt in this review) intake as well as dietary po- Birmingham (K.J.A.,
diseases, nutrient deficiencies, and epidemics tassium intake and blood pressure (BP).4-9 P.W.S.), and Department
of Veterans Affairs Medical
to noncommunicable diseases, including car- Because of the increasing prevalence of hyper-
Center, Birmingham, AL
diovascular disease (CVD), hypertension, dia- tension and CVD, nonpharmacological dietary (P.W.S.).
betes mellitus, and chronic kidney disease guidelines designed to promote the health of
(CKD). Although these diseases may have a the public have, therefore, been instituted.10
genetic predisposition, there is a strong associ- Although these programs have an impact,
ation with environmental influences, suggest- most Americans consume well above the mini-
ing that they are lifestyle related. The problem mum daily requirement for dietary salt and,
is enormous: in 2009-2010, for example, further, have inadequate potassium intake. To
23.1% of adult Americans had prehyperten- emphasize the excess salt in the American
sion, and an additional 29.5% had hyperten- diet, the US Department of Health and Human
sion.2 Estimates projected by the American Services/US Department of Agriculture 2010
Heart Association place the direct and indirect Dietary Guidelines advise Americans to reduce
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DIETARY SALT AND POTASSIUM INTAKE IN VASCULAR HEALTH
outcomes for diastolic BP15-22,24-38; 3 studies in BP was greater at a lower level of salt intake
with 640 participants receiving an intervention, (ie, from 6 to 4 g/d compared with that from 8
715 controls, and approximate median follow- to 6 g/d).27 Other large, well-designed RCTs,
up of 2 months reported outcomes for mean including the Trials of Hypertension Preven-
arterial pressure 21,39,40; 3 studies with 273 par- tion I and II56,59,65 and the Trial of Nonphar-
ticipants receiving an intervention, 228 con- macologic Interventions in the Elderly,16,36
trols, and approximate median follow-up of have reinforced the important role of salt
1.5 months reported outcomes for ambulatory intake in determining the levels of BP in the
BP.26,28,37 Of the 12 publications in which di- populations under study. Additional RCTs
etary salt and potassium were adjusted, 11 have also lent support to reduction of salt
studies with 2713 participants receiving an intake in specific populations.19,22,30,32,38,55,58
intervention, 2430 controls, and approximate Eighteen studies involving 3470 participants
median follow-up of 12 months reported out- receiving the intervention and 3171 controls
comes for systolic and diastolic BP55-65 documented the effect of changes in dietary so-
(Table 3). The most compelling evidence of dium intake on laboratory parameters, markers
the dose-response relationship between salt of CVD or CKD progression, and CVD events or
and BP came from rigorously controlled trials CVD mortality over median follow-up of 3.5
in which more than 2 levels of salt diets months.15,16,19,20,22,25,29-34,36,37,39-42 In addi-
were implemented, such as the seminal work tion, 3 studies with 803 participants receiving
by MacGregor et al67 and the Dietary Ap- the intervention and 1248 controls documented
proaches to Stop Hypertension (DASH)- the effect of changes in dietary sodium and
Sodium trial.27 In adults with prehypertension potassium intakes on laboratory parameters,
or stage 1 hypertension in the DASH-Sodium markers of CVD or CKD progression, and
trial, a clear dose-response relationship was CVD events or CVD mortality over median
found in the general American diet and in follow-up of 6 months (Table 3).57,61,66 Die-
the DASH diet when salt intake was reduced tary salt contributed to vascular and target or-
from 8 to 6 and to 4 g/d; and, the decrease gan injury as established in studies in which
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DIETARY SALT AND POTASSIUM INTAKE IN VASCULAR HEALTH
Nevertheless, the trials reviewed in this study pro- and TRANSCEND (Telmisartan Randomized
vided high-quality evidence supporting a health Assessment Study in ACE Intolerant Subjects
benefit from restricting dietary sodium intake With Cardiovascular Disease), O’Donnell et al78
and increasing potassium intake. noted a J-shaped relationship between UNa
Most professional scientific organizations, excretion and risk of a composite outcome of
therefore, have agreed that the US/Western- CVD events and mortality. The J-shape is a
style diet contains excessive amounts of salt result of a contradictory inverse relationship
and that high levels of salt consumption in in 12% of participants with an estimated UNa
any population lead to higher rates of hyperten- excretion of less than 3000 mg/d. ONTARGET
sion, CVD, and CVD mortality. The debate was and TRANSCEND consisted of participants
rekindled when a high-profile prospective older than 55 years with a high risk of stroke
study reported an association between low and CVD during follow-up.78 At baseline,
baseline UNa excretion and higher CVD mor- 70% had hypertension, almost 40% had dia-
tality.71 Limitations in the strength of evidence betes, almost half had a history of myocardial
included the observational nature of the study infarction, and more than 1 in 5 had a history
and inherent flaws in design and methods as of stroke.78 The potential for an error in the
articulated in subsequent correspondence.72-74 assessment of salt intake is likely because a single
One issue of particular concern was the under- morning spot urine collection was used to deter-
collection of 24-hour urine samples in individ- mine the 24-hour UNa excretion estimate.
uals in the lowest tertile of UNa excretion, as Values obtained from spot urine specimens are
indicated by lower creatinine excretion, potas- not a suitable alternative for 24-hour collections,
sium levels, and 24-hour urine volume.75 especially in sick patients, such as those included
The conclusion of the present study also dif- in the study. Medications such as diuretics,
fers from that of a recent meta-analysis that eval- angiotensin-converting enzyme inhibitors, and
uated whether BP reduction was an explanatory angiotensin receptor blockers can greatly affect
factor in any effect of dietary salt interventions sodium levels in spot urine collections, and the
on mortality and CVD outcomes identified.76 use of these drugs is more likely in those at great-
In that report, the criteria for inclusion included est risk for CVD and is, thus, subsequently linked
(1) randomization with follow-up of at least 6 to a greater potential for measurement error.
months, (2) an intervention that reduced dietary Another study in patients with type 2 diabetes
salt intake (restricted salt dietary intervention or mellitus found that lower 24-hour UNa excre-
advice to reduce salt intake), (3) adults, and (4) tion was associated with increased all-cause
mortality or cardiovascular morbidity data and cardiovascular mortality.79 At baseline, par-
available.76 Of 7 trials identified, the authors ticipants with the lowest tertile of salt intake in
concluded that the combined experimental evi- that study were significantly older, had a longer
dence was insufficient to determine the health disease duration, and had a reduced estimated
effect of reducing salt intake.76 A weakness of glomerular filtration rate compared with the in-
that meta-analysis was the inclusion of a trial termediate and highest salt intake tertiles.79 In
on heart failure in which sick participants were addition, the methods used to ensure adequacy
receiving intensive drug regimens. Participants of urine sample collections were not detailed.
in that trial were treated with furosemide (250- Paradoxical findings, such as those described
500 mg twice daily) as well as spironolactone, by O’Donnell et al78 and Ekinci et al,79 can result
angiotensin-converting enzyme inhibitors, b- when illness is the cause rather than the conse-
blockers, and digitalis. In this heavily medicated quence of the level of salt intake. Sick individ-
population, a reduction in dietary salt intake was uals have a higher risk of disease progression
associated with an increase in mortality.77 and associated outcomes, and, as one becomes
Although the validity of that particular study more ill, caloric intake along with salt intake
was not doubted, it was not included in the pre- can decrease dramatically. Although severe
sent analysis because of the severity of illness of restrictions in dietary sodium intake might
the population in the study. contribute to adverse outcomes in patients
In an observational analysis of ONTARGET with multiple comorbidities, this classic frame-
(Ongoing Telmisartan Alone and in Combina- work, as noted by Whelton et al,80 is potentially
tion With Ramipril Global Endpoint Trial) one of reverse causality.
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DIETARY SALT AND POTASSIUM INTAKE IN VASCULAR HEALTH
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DIETARY SALT AND POTASSIUM INTAKE IN VASCULAR HEALTH
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