Download of Na

Salt and Hypertension
M.R.ABBASI
MD,Nephrologist
NRC
TUMS
1993
Natrium=Sodium(Na)
a metalic element with
mol.Wt. 23gr
Chloride(Cl)
a light green toxic gas with
mol. Wt. of 35.5gr
TUMS-Nephrology Research Center
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TUMS-Nephrology Research Center
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Forms of Sodium
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90% of sodium consumed as
sodium chloride (salt, common
salt, table salt,Halite)
Other forms:
– sodium bicarbonate
– sodium in processed foods, such as
sodium glutamate, sodium
benzoate, sodium phosphate
Sodium Balance
The human body contains 1 gr Na / Kg of
BW
• 70 gr Νa = ~ 3000 mmol = 3000 meq Na
• Sodium is located to 95% extracellularly
and to 5% intracellularly.
Every 6 gr salt contains 2.3 gr(
100mmol=100meq ) of Na
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NaCl
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Salt is composed of 40% Na and 60% Cl.
Sodium together with potassium is an
essential mineral for regulating body fluid
balance.
It is also essential for the transmission of
the nerve and muscle impulses.
Physiologic need of salt is only about 0.5
gr/day(current use is 9-12gr).
High salt using is an acquired addiction
for salt by consumption of processed
foods.
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Adverse Effects of
Excess
Salt
Intake
Established relationship
– Increased blood pressure → CVD and Stroke
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Probable relationship
– Gastric and Colorectal cancer
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Suggestive relationship
– Increased risk of osteoporosis
– Increased risk of nephrolithiasis
– Increased left ventricular mass
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Hypothesized relationship
– Overweight/obesity
– asthma
P. A. Gilbert* and G. Heiser: Salt and health
British Nutrition Fundation
The association between a
high salt intake and
hardened pulse was
already known 4500 years
ago .
Cirillo M, Capasso G, Di Leo VA, De Santo NG
Research
. A history ofTUMS-Nephrology
salt. Am J Nephrol
1994;14:426Center
431.
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Magnitude of BP Problem:
Population Perspective
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Worldwide, cardiovascular disease
(heart disease and stroke) is the leading
cause of death
62% of strokes and 49% of CAD events
attributed to elevated BP*
26% of adults worldwide (972 million)
have hypertension**
*WHO, World Health Report 2002: Reducing Risks, Promoting Healthy Life,
**Kearney Lancet 2005;305:217
Leading Causes of Death,
Worldwide in 2002
Cardiovascular diseases
Infectious and parasitic diseases
Cancer
Respiratory infections
Respiratory diseases
Unintentional injuries
Perinatal conditions
Digestive diseases
Intentional injuries
Neuropsychiatric conditions
Diabetes mellitus
Genitourinary diseases
Maternal conditions
Congenital anomalies
Nutritional deficiencies
Others
0
2000
4000 Research
6000
8000
10000 12000 14000
TUMS-Nephrology
Center
Number of deaths (x1000)
16000
18000
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Major Underlying Factors causing Death - Worldwide
Raised Blood Pressure
7 million
Tobacco
High cholesterol
Underweight
Unsafe sex
Low fruit &
vegetables intake
High BMI
Developed region
Physical inactivity
Developing region
Alcohol
Unsafe water, sani & hygiene
0
1
2
3
4
5
TUMS-Nephrology Research
Millions of Deaths
Ezzati et al. Lancet 2002:360:1347-60.
Center
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Types of Evidence Relating Salt Intake
to Blood Pressure
Epidemiology
Over 50 population studies
Migration
Several
Genetic
All defects identified so far impair the ability
of the kidney to excrete salt.
Animal
All forms of hypertension are caused or
aggravated by salt [rats, chimpanzees]
Trials
Children: ~10 trials, one trial in infants
Adults: > 50 trials
Population
Interventions
several
TUMS-Nephrology Research
Center
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Primary hypertension is seen primarily in societies
with average sodium intakes above 100 meq/day (2.3
g sodium(
• HTN is rare in societies with average sodium intakes
of less than 50 meq/day (1.2 g sodium)
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• HTN requires a threshold level of sodium intake.
• This effect appears to be independent of other risk
factors for hypertension, such as obesity.
SBP Slope with Age (mmHg/yr) by Median Na
Excretion in 52 Communities Worldwide
Systolic blood pressure slope with age
(mm Hg/year)
1.4
1.2
1.0
Populations with No
Rise in SBP with Age
0.8
0.6
0.4
0.2
0.0
-0.2
-0.4
0
1,150
2,300
3,450
Research
MedianTUMS-Nephrology
sodium excretion
(mg/24h)
INTERSALT BMJ 1988;297:319
Center
4,600
5,750
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Predicted Benefits of Reducing Sodium
on Stroke and Heart Attack Deaths
• Reducing sodium by 400 mg/day would reduce
 strokes by 5%
 heart attacks by 3%
• Reducing sodium by 2,400 mg/day would reduce
 strokes by 24%
 heart attacks by 18%
Hypertension
TUMS-Nephrology Research
Center
2003;42:1093-99
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Effects of Reduced Na on CVD Events:
Results from 3 Randomized Trials
INTERVENTION OUTCOME
TONE1 (2001)
639 Elderly
Veterans2
Taiwan
(2006) 1,981 Elderly
TOHP Follow-up3 (2007)
3,126 Prehypertensives
↓ Na
↓ Na /↑ K
Salt
↓ Na
21% ↓
CVD events
2.3 yrs
41%* ↓
CVD
Mortality
2.6 yrs
30%* ↓
10-15 yrs
CVD events
*p<0.05
1Appel,
FU
Arch Int Med, 2001; 2Chang, AJCN, 2006; 3Cook, BMJ, 2007
Meta-Analyses of the Effect of Salt Reduction on Blood Pressure.
Kotchen TA et al. N Engl J Med 2013;368:1229-1237.
Projected Estimates of Comparative Effect of Various Population Interventions on Annual
Reductions in Cardiovascular Events.
Bibbins-Domingo K et al. N Engl J Med 2010;362:590-599.
Estimated Changes in Systolic Blood Pressure Associated with Reductions in Dietary Salt.
Bibbins-Domingo K et al. N Engl J Med 2010;362:590-599.
Estimated Changes in Systolic Blood Pressure Associated with Reductions in Dietary Salt.
Bibbins-Domingo K et al. N Engl J Med 2010;362:590-599.
Effects of Sodium Reduction in
Children: Results of a Meta-Analysis
• 10 Trials
• 966 Children
• Mean age=14
• Median duration
= 20wk
• 42% Reduction
in Na
He and MacGregor, HTN 2006
Salt sensitivity
BP responsiveness to
variations in salt intake is known as
salt sensitivity.
30-50% of hypertensives and a
smaller percentage of
normotensives are thought to have
salt sensitive BP.
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Factors Associated with Increased
Salt Sensitivity
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Fixed factors
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African-Americans
Middle and older-aged persons
Genetic Factors
Individuals with:
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Hypertension
Diabetes
Chronic Kidney Disease
Low birth Wt
Modifiable
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Low potassium intake
Low Calcium intake
Poor quality diet
Obesity and metabolic syndrom.
Na sensitivity associated
with:
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Insulin resistance
Dyslipidemia
Microalbuminuria
Subtle renal injury
The fundamental defect in all
hypertension is the kidneys' inability
to excrete the excessive sodium load
imposed by a high-salt diet.
(He & MacGregor, 2007).
Interrelated Salt-Induced Alterations That May Impair Sodium Excretion and Promote
Vasoconstriction.
Kotchen TA et al. N Engl J Med 2013;368:12291237.
Sodium
retention(mechanisms)
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Increase activity of the proximal NaH exchanger
Increase Na reabsorption in thick
ascending limb of henle loop by NaK-2Cl cotransporter
Increase Na reabsorption by distal
Na-Cl cotransporter
Increase Na reabsorption by ENaC
in the collecting tubule.
Effect of low potassium diet
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Low K intake may increase the effect
of Na on BP .
Urinary Na:K ratio is more important
than urinary sodium excretion only.
K excretion less than 50 mmol/day
was associated with rising 3.4
mmHg in SBP and 1.9 mmHg in
DBP.(INTERSALT study).
Sodium and Potassium in the Pathogenesis
of Hypertension
Horacio J. Adrogué, M.D., and Nicolaos E. Madias,
M.D.NEJM356;19. May10 2007
Hakuo Takahashi et al, The cntral mechanism underlyinh
HTN: a revew of the role of Na ions, ENaC, the R-A-A system,
oxidative stress and endogenous digitalis in the brain:HTN
research (1160-34,1147)2011
Sodium and Potassium in the Pathogenesis
of Hypertension
Horacio J. Adrogué, M.D., and Nicolaos E. Madias,
M.D.NEJM356;19. May10 2007
Sodium and Potassium in the Pathogenesis
of Hypertension
Horacio J. Adrogué, M.D., and Nicolaos E.
Madias, M.D.NEJM356;19. May10 2007
Vasodilation failure
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Na loading causes vasodilation in
Na insensitive subjects(by NO
release).
In Na sensitives Na loading causes
an increase in Asymmetrical
dimethylarginine which is
endogenous inhibitor of NO.
Sources of Dietary Sodium
(62 adults who completed 7 day dietary records)
Inherent
12%
Food
Processing
77%
At the Table
6%
During Cooking
5%
Mattes and Donnelly, JACN, 1991; 10: 383
Na/K cotent of food
Copyright 2005 Wadsworth Group, a division of Thomson Learning
Food labelling
Standard format :
--group 1(Big4): energy, protein,
carbohydrates and fat.
--group2(4+4): sugars, saturated fat, fiber
and sodium(and not salt).
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There is a significant variation in the
levels of salt consumption between
countries, and also significantly different
patterns of consumption. In
European and North American countries the
main sources of dietary salt
are processed foods, restaurant services,
and catering, while in Asian
and African countries the main sources are
the salt used in cooking and
sauces.
The food industry uses salt in every food
category to enhance flavor, condition
dough, preserve foods, and retain
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World Action on Salt and
Health(WASH)
-increasing public awareness of the harmful effects
of salt on health.
-Reduction of salt use to less than 5-6 gr
-getting food industry to decrease the amount of
salt added to foods and clearing labelling on food
products.
Recommendations for Sodium
Intake (mg/d): US and WHO
US 2005 Dietary Guidelines
General Population
Hypertensives, blacks, adults (45+)
World Health Organization
< 2,300
(6gr
salt)
<1,500
(4GR
salt)
<2,000
(5gr
Institute of medicine
recommends:
Na intake 65mmol(3.8gr
NaCl) for<50yrs old,
55mmol(3.2gr salt) for 5170yrs old,
50mmol(2.9gr)/day for>70
yrs old + 120 mmol K(4.7gr)
/day .
Sodium and Potassium in the Pathogenesis
of Hypertension
Horacio J. Adrogué, M.D., and Nicolaos E. Madias,
M.D.NEJM356;19. May10 2007
Thank You
Nephrology Research
Center