Transcript The Use of Electronic Recorders for Evaluating the

EPIDEMIOLOGY OF
SALT AND HYPERTENSION
Arun Chockalingam
Professor & Director of Global Health
Secretary General, World Hypertension League
HTA 2008, 4th International Symposium of Hypertension
Santa Clara, Cuba
May 27, 2008
Historical Information
 As long ago as 2,000 B.C.,
when the famous Chinese
“Yellow Emperor” Huang
Ti recorded salt’s
association with a
“hardened pulse”, we
have known of a
relationship between salt
and blood pressure.
Hemodynamics of Early
Essential Hypertension
Hemodynamics of Established
Essential Hypertension
Overall Scheme for Pathogenesis
of Essential Hypertension
Cardiovascular Events and
Sodium Sensitivity
Kaplan-Meier plots showing the relationship between total CV
events in hypertensive patients and sodium sensitivity. p < 0.05
Morimoto et al, Lancet 1997; 350: 1734
Urinary Salt Excretion and Death
From strokes in 12 European countries
Adapted from Perry, IJ et al. J Hum Hypertens, 1992; 6:23-25
Hazard Ratios
association of a 6 g/day increase in salt intake with 24-h
urinary Na+ excretion
Increased risk of death related to a 6 g/day
increase in salt intake (N=2436)
1.75
¶ Adjusted for age, study
year, smoking, serum total
and HDL cholesterol,
systolic blood pressure,
and body mass index
CVD
Death
1.50
Hazard Ratio ¶
*** P<0.001 compared to
lower salt intake
CHD
Death
All
Death
High salt
intake
1.25
1.00
1.75
0.50
He FJ, MacGregor GA. a meta-analysis of randomized trials.
Implications for public health. J Hum Hyptens 2002;16:761-770
Lower salt
intake
Relationship between the net
change in urinary Na+ and SBP
The yellow circles
represent normotensives
and the blue circles
represent hypertensives.
The slope is weighted by
the inverse of the variance
of the net change in
systolic blood pressure.
The size of the circle is in
proportion to the weight
of the trial.
Change in Systolic Blood Pressure
(mmHg)
4
2
0
-2
-4
Normotensives
-6
-8
Hypertensives
-10
-12
-30
-50
-70
-90
-110
Change in Urinary Sodium
(mmol/24h)
-130
He FJ, MacGregor GA. a meta-analysis of randomized trials. Implications for public health.
J Hum Hyptens 2002;16:761-770
Dose-response relation between 24-h
urinary Na+ and BP in two studies
Double-blind salt reduction study & the DASH-Sodium study
DASH: Dietary Approaches to Stop Hypertension 79 Vs 81 HT/116 Vs 121 HT
Double-blind study: 3 salt intakes, each 4 wks 19 HT
He, FJ et al. Hypertension 2003; 42:1093-10
Comparison of the dose-response
relation among 3 studies
•Double-blind salt reduction study
He, FJ et al. Hypertension 2003; 42:1093-109
•DASH-Sodium study
•Metal-analysis of modest salt reduction > 4 wks
Weekly group ave. SBP at lower Na+
level compared with group ave. SBP
measured at end of higher Na+ level
(SBP mean 95% CI), (n=188); 60% NT
Age> 45: 65%; 55% F; 58% Black
Obarzanek, E et al. Hypertension 2003; 42:459-467
Mean SBP changes in the
DASH-Na+ trial
Solid lines indicate the effects of
sodium reduction in the 2 diets;
hatched lines, the effects of the
DASH diet at each sodium level
Adapted from Sacks, FM et al. N Engl J Med 2001; 344:3-10
BP by week during the DASH
feeding study in 3 diets
N=379
▲Na+
(mmol/24h)
▲ K+
(mmol/24h)
▲
Na+/K+
Control
Diet
+ 142
+ 146
0.972
Fruit/Veg
Diet
-232
+1298
-0.179
DASH
Diet
-73
-1500
-0.049
Adapted from Appel, LJ et al. N Engl J Med 1997; 336:1117-1124
% change in MAP in normotensive
subjects receiving incremental
increases in Na+
Blood pressure at the
end of 7 days of low (10
mmol/d) salt intake was
taken as baseline. All
subjects demonstrated an
increase in blood
pressure with salt
loading.
Data adapted from Luft et al. Circulation 1979; 60:697-706
Key Messages From Intersalt Study
 Strong positive associations of 24 hr urinary Na excretion to BP of
individuals, to median BP across its 52 population samples, and to
differences in BP with age.
 The within population association of Na to BP in Intersalt are
concordant with the cross population findings for 52 samples.
 Estimates of the effect of median Na excretion higher by 100
mmol/day over a 30 year period (age 55 minus age 25) were a
greater difference of 10-11 mm Hg in SBP and 6 mm Hg in DBP.
 These results lend further support to recommendations for mass
reduction of high salt intake for the prevention and control of
adverse blood pressure levels and high blood pressure in
populations.
Elliott, P et al. BMJ 1996; 312:1249-1253
TONE Study
Baseline BP and Change From Baseline to Last
Visit Prior to Attempted Medication Withdrawal
TONE: Trial of
Nonpharmacologic
Interventions in the Elderly
*Change in BP calculated
For 953 participants who
attended at least 1 study visit
after Randomization.
p<.001 bet UC & IG for
SBP or DBP
Age: 60-80 yrs;
BP < 145/85 + 1 Rx
Whelton, PK et al. JAMA 1998, 279(11):839-846
CV Events During Follow-up of
TONE Participants According to
Intervention Assignment
Trial of Nonpharmacologic Interventions in the Elderly
Whelton, PK et al. JAMA 1998, 279(11):839-846
TONE Study - Mean change in 24-h
urinary Na+ excretion
Na+ reduction group: n=487
No Na+ reduction group: n=488
Error bars indicate SEMs.
The numbers used in the
figure are given in mmol/d
Trial of Nonpharmacologic
Interventions in the Elderly
Whelton, PK et al. JAMA 1998, 279(11):839-846
Trial of Nonpharmacologic
Interventions in the Elderly (TONE):
Mean change in Body weight
Weight loss group: n= 291
No weight loss group: n= 291
Error bars indicate SEMs. The numbers
used in the figure are given in kg
Whelton, PK et al. JAMA 1998, 279(11):839-846
TONE: % of people free of CV
events and HBP and did not have
antihyp. therapy during follow-up
Whelton, PK et al. JAMA 1998, 279(11):839-846
Change in SBP & DBP (mm Hg) achieved
in trials of 13 to 60 months
Systematic review of LT effects of advice to reduce
dietary salt in adults: Meta analysis of RCTs
Hooper at al. BMJ 2002; 325:628-636
Change in urinary Na+ (mmol Na/24 hours)
achieved in trials of 6 to 12 months, 13 to 60
months, and >60 months
Hooper at al. BMJ 2002; 325:628-636
Systematic review of LT effects of advice to reduce
dietary salt in adults: Meta analysis of RCTs
 Intensive interventions, unsuited to 1o care or
pop. prevention pgms, provide ONLY a
small reduction in BP and Na+ excretion.
 Effects on deaths and CV events are unclear.
 Advice to reduce Na+ intake may HELP
people on antihypertensive drugs to stop their
meds. while maintaining good BP control.
Hooper at al. BMJ 2002; 325:628-636
Correlation between salt intake and LV
mass in subjects with SBP >121 mm Hg
 M-mode echocardiographic LV
mass
 Pop-based study focused on
lifestyle & salt intake
 Random sample (51F+ 42M)
 7-day food record
 Conclusion: Synergistic
interaction of dietary salt with BP
suggests high Na+ intake may
sensitize the heart to the
hypertrophic stimulus of pressure
load
Adapted from Kupari P et al J. Circulation, 1994; 89:1041 – 1050
The relation of urinary salt excretion
to cancer of the stomach (CaS)
 Background: High salt and
nitrate intake are RFs for CaS.
Little is known of their possible
interaction.
 Methods: Randomly selected
24-hr urine from 39 pop (5756
for Na+ and 3303 for nitrate)
from INTERSALT study.
Regression analyses in relation
to national CaS mortality rates.
 Conclusion: Salt intake is likely
the rate-limiting factor for CaS
mortality at population level.
Adapted from Joossens, JV et al. Int J Epidemiol, 1996; 25 494-504
Salt and Essential Hypertension
 Essential hypertension is seen primarily in societies with
average salt intakes of more than 50meq/day (2.3 g
sodium).
 Essential hypertension is rare in societies with average
salt intakes of less than 50meq/day (1.2 g sodium).
 These observations suggest that the development of
hypertension requires a threshold level of salt intake.
Elliott P, Stamler J, Nichols R et al. Intersalt revisited: Further analyses of 24 hour sodium excretion
and blood pressure within and across populations. BMJ 1996; 312:1249
Decrease in salt intake (g) calculated
from urinary Na+ excretion among Finns
Linear Regression Analyses
(adjusted by age & Survey area):
Annual decrease among
men: 0.14 g (p<0.001);
Women: 0.11 g (p<0.0001)
Only N.Karelia, Kuopio & SW
Finland are included in the analysis
Laatikainen, T et al. European Journal of Clinical Nutrition 2006; 60:965-970
National Policy Intervention
“The experience of Finland, which has had a salt
reduction program running since the late 1970s,
shows that population-wide reduction of dietary salt
leads to population-wide reductions in blood
pressure and parallel reductions in deaths from
stroke and heart disease.”
--- Professor Graham MacGregor, Chairman of WASH
Demographic Factors Influencing
Salt Sensitivity
 Race: Blacks have been consistently shown to
have a greater frequency of salt sensitivity than
Whites.
 Age: Increasing salt sensitivity has been noted
with increasing age. This relationship appears to
be stronger in hypertensive than in normotensive
individuals.
Weinberger, M.H. Hypertension 1996, 27:481-490
Familial and Genetic Factors
 Salt sensitivity was more likely to be observed
in individuals with the homozygous
haptoglobin 1-1 genotype than in those with
the 2-2 genotype and that individuals with the
heterozygotic 2-1 genotype had responses that
were intermediate between the other two
groups.
Weinberger, M.H. Hypertension 1996, 27:481-490
Physiological Factors Associated
with Salt Sensitivity








Renal Function
The Renin-Angiotensin-Aldosterone System
Atrial Natriuretic Factor
The Sympathetic Nervous System
Adrenergic Receptors
Endothelin and Nitric Oxide
Ion Transport
Insulin
Weinberger, M.H. Hypertension 1996, 27:481-490
Deaths averted by population-level
intervention
Asaria et al. Lancet 2007; 370: 2044-53
Salt & tobacco reduction: Estimated
Deaths averted/100K pop (2006-15)
Asaria et al. Lancet 2007; 370: 2044-53
Population older than 30 yrs of age
Cost to implement the package of
intervention
Asaria et al. Lancet 2007; 370: 2044-53
Key messages
 23 countries have 80% of burden of CNCD in
LMI regions of the world.
 In these countries 13.8 m deaths could be averted
over 10 yrs (8.5 m by salt reduction and 5.5 by
implementing FCTC)
 Most deaths averted would be from CVD 975.6%)
followed by Resp dis (15.4%) and cancer (8.7%).
 Cost to implement both strategies would be $ 0.4
in LMIC and $ 0.5-1.0 in UMIC (as of 2005).
Asaria et al. Lancet 2007; 370: 2044-53
SUMMARY
 Across populations, the level of blood pressure, the
incremental rise in blood pressure with age, and the
prevalence of hypertension are related to sodium intake.
 Observational studies and RCTs document a consistent effect
of sodium consumption on blood pressure. Modest
reduction in average sodium intake (from 31 to 44 mmol/d)
decreases the percentage of prehypertension.
 Blood pressure is also affected by many other variables, and
a reduced sodium intake is only ONE component of
recommended strategies to lower blood pressure.
Report of the AMA Council on Science and Public Health
Dickinson, B et al. Arch Intern Med 2007; 167(14):1460-1468