Transcript Sodium sensitivity - Zuivel en gezondheid

HYPERTENSION
MORE THAN BLOOD PRESSURE
ALONE!
Richard Bright( 1789-1858)
the First Nephrologist*
First observation of
“hardened pulse”and
renal damage at autopsy
(1827)
First observation
association of cardiac
hypertrophy and
shrunken kidneys
(1836)
* Source: Richard Bright Web-page Internet
Hypertension: classical concepts
Causal factors
hypertension
Target organ damage
Brain
Heart
Kidney
Hypertension: classical concepts
Causal factors
hypertension
Target organ damage
Brain
Heart
Kidney
HYPERTENSION FOLLOWS THE KIDNEY
Hypertension: classical concepts
Causal factors
hypertension
Target organ damage
Brain
Heart
Kidney
HYPERTENSION FOLLOWS THE KIDNEY
Epidemiology
Prevalence of hypertension very different
between populations
Hypertension is associated with end organ
damage
mean sodium intake (grams)
Relationship between sodium intake and blood
pressure around the world: population studies
30
25
Northern Japan
20
15
Southern Japan
US
10
Marshall islands
5
Inuit
0
0
10
20
30
% hypertensives
Meneely & Dahl, 1961
40
50
Low salt and high salt populations
deaths stroke per 100.000/yr
Relationship between sodium intake and
end-organ damage
portugal
2100
1900
1700
malta
1500
1300
spain
finland
1100
italy
denmark
iceland
900
700
UK
germany
holland
500
7,5
8
8,5
9
UNaV (g/day)
9,5
10
10,5
Hypertension and CV mortality
Higher BP: worse outcome
SBP and DBP are independent risk factors
There is NO clearcut lower treshold!
Domanski, JAMA 2002
Hypertension and end stage renal failure
Higher BP: worse outcome
SBP and DBP are independent risk factors
There is NO clearcut lower treshold!
Brancati, NEJM 1996
The remedy
Lower blood pressure
The remedy
Lifestyle intervention; Drug treatment
Lower blood pressure
Reduction target organ damage > Better outcome
BENEFIT OF TREATMENT IS NOT EQUAL FOR ALL
PATIENTS !
The remedy
LIFESTYLE INTERVENTION & DRUG TREATMENT CAN
POTENTIATE EACH OTHER !
Lifestyle intervention; Drug treatment
INTERVENTION CAN IMPROVE OUTCOME ALSO
INDEPENDENT OF EFFECT ON BLOOD PRESSURE !
Lower blood pressure
Reduction target organ damage > Better outcome
BENEFIT OF TREATMENT IS NOT EQUAL FOR ALL
PATIENTS !
The remedy
LIFESTYLE INTERVENTION & DRUG TREATMENT CAN
POTENTIATE EACH OTHER !
Lifestyle intervention; Drug treatment
INTERVENTION CAN IMPROVE OUTCOME ALSO
INDEPENDENT OF EFFECT ON BLOOD PRESSURE !
Lower blood pressure
Reduction target organ damage > Better outcome
Meta Analysis: Lower SBP Results in Less GFR Decline
in Diabetics and Non-Diabetics
MAP (mm Hg)
95
98
101
104
107
110
113
116
119
0
GFR
(mL/min/year)
-2
r = 0.69; P <0.05
-4
-6
Untreated
hypertension
-8
-10
-12
130/85
140/90
-14
Parving HH et al. Br Med J. 1989
Viberti GC et al. JAMA. 1993
Klahr S et al. N Eng J Med. 1993*
Hebert L et al. Kidney Int. 1994
Lebovitz H et al. Kidney Int. 1994
*:Studies in nondiabetic nephropathy.
Maschio G et al. N Engl J Med. 1996*
Bakris GL et al. Kidney Int. 1996
Bakris GL. Hypertension. 1997
GISEN Group. Lancet. 1997*
Bakris GL et al. Am J Kidney Dis. 2000;36:646-661.
• Effect of poor BP control on
GFR decline is larger in
proteinuria
• Need for lower target
blood pressure in
proteinuric patients !!!
GFR decline ml/min/yr
PROTECTIVE EFFECT OF LOWER BLOOD PRESSURE ON
LONG TERM RENAL OUTCOME DEPENDS ON
PROTEINURIA !
0
-4
-8
-12
-16
MDRD study
86
92
98
107
obtained MAP mmHg
Peterson, Ann Int Med 1995;
123:745
Uprot:
0
>0,25
>1
>3
Patients with vulnerable
kidneys need a lower blood
pressure !
Proteinuria
Diabetes
No specific vulnerability:
More liberal regimen jusitified
BENEFIT OF TREATMENT IS NOT EQUAL FOR ALL
PATIENTS !
The remedy
LIFESTYLE INTERVENTION & DRUG TREATMENT CAN
POTENTIATE EACH OTHER !
Lifestyle intervention; Drug treatment
INTERVENTION CAN IMPROVE OUTCOME ALSO
INDEPENDENT OF EFFECT ON BLOOD PRESSURE !
Lower blood pressure
Reduction target organ damage > Better outcome
Control of sodium status improves response to
RAAS-blockade
Uprot, g/d
ACEi
7
MAP, mmHG
105
4
110
3.5
6
105
AIIA
100
3
5
100
4
2.5
95
2
95
3
90
1.5
90
2
1
85
85
1
0
s
ba
80
e
eli n
lo
alt
s
w
h
hig
lt
sa
lo
alt
s
w
Heeg, Kidney Int 1989; 36,272
0.5
0
Pl
80
S
aH
Pl
S
aL
S
sH
o
L
S
sL
Lo
C
sH
o
L
S
TH
C
sH
o
L
S
TL
Vogt en Waanders, JASN 2008
BENEFIT OF TREATMENT IS NOT EQUAL FOR ALL
PATIENTS !
The remedy
LIFESTYLE INTERVENTION & DRUG TREATMENT CAN
POTENTIATE EACH OTHER !
Lifestyle intervention; Drug treatment
INTERVENTION CAN IMPROVE OUTCOME ALSO
INDEPENDENT OF EFFECT ON BLOOD PRESSURE !
Lower blood pressure
Reduction target organ damage > Better outcome
deaths stroke per 100.000/yr
Effect of high salt intake on long term
outcome
2100
1900
1700
1500
1300
1100
900
700
500
7,5
8
8,5
9
9,5
10
UNaV (g/day)
Is it all blood pressure??
10,5
Salt intake: effects on mortality in general
population
• Increased mortality risk
per 6 gr rise in salt intake
1.6
1.4
• Interaction with BMI > 27
1.2
1
– HR normal weight: 0,98 ns
– HR overweight : 1,56
0.8
0.6
low salt
al
l
da
th
s
at
h
de
D
CV
CH
D
de
at
0.4
h
hazard ratio
1.8
high salt
Tuomilehto, Lancet 2001; 357:848-51
– Effect ONLY present in
overweight subjects
mmHg by low salt
Sodium-sensitivity in obesity hypertension is
reversible by weight loss
5
• 250 vs 30 mmol Na+; 2-weeks
0
• Weight loss > 1 kg by 20-week
program
-5
• Weight excess is a main
-10
determinant of sodiumsensitivity of blood pressure
-15
lean
obese
after weight loss
Rocchini AP, NEJM 1989: 322: 476-7
Salt intake: effects on mortality in general
population
• Increased mortality risk
per 6 gr rise in salt intake
1.6
1.4
1.2
– Effect INDEPENDENT
OF BLOOD PRESSURE!
1
0.8
0.6
low salt
al
l
da
th
s
at
h
de
D
CV
CH
D
de
at
0.4
h
hazard ratio
1.8
high salt
Tuomilehto, Lancet 2001; 357:848-51
High salt increases albuminuria in healthy
subjects, independent of blood pressure
• A rise in salt intake
UAlb, mg/24h
8.5
leads to a 25 % rise
in UAE in healthy
volunteers without
even a rise in BP !
8
7.5
7
6.5
6
3 g/day
12 g/day
JA Krikken, Kidney Int 2007: 71: 260-265
Salt status: associated with albuminuria
independent of BP, but dependent on BMI
(n=7913, Prevend population)
BMI:
1
2
1
1
27,3-67
B
M
I
t
h
i
r
d
t
e
r
t
i
l
e
B
M
I
s
e
c
o
n
d
t
e
r
t
i
l
e
B
M
I
f
i
r
s
t
t
e
r
t
i
l
e
1
0
9
UAE(mg/24h)
24-27,3
8
16,3-24
7
6
5
0
1
0
0
1
5
0
2
0
0
2
5
0
U
r
i
n
a
r
y
s
o
d
i
u
m
e
x
c
r
e
t
i
o
n
(
m
m
o
l
/
2
4
h
)
JC Verhave, Eur J Clin Invest 2004: 256: 324-30
3
0
0
INTERACTION SODIUM STATUS-WEIGHT EXCESS
• Sodium sensitivity of blood pressure
• Blood pressure
• CV outcomes – BP dependent AND BP
independent
• Risk markers (NT-proBNP, UAE)
SODIUM EXCESS AND WEIGHT EXCESS
Deadly twins!
In normotensive AND in hypertensive subjects
SODIUM EXCESS AND WEIGHT EXCESS
Deadly twins!
MECHANISM?
Effect of overweight on extracellular volume
during low vs high sodium intake
23
• In slightly overweight young
ECV, liters
22
men, ECV is higher than in
lean subjects, ONLY during
high sodium
21
20
• This is NOT accompanied by
19
higher blood pressure.
18
17
low sodium high sodium
BMI 22
BMI 25
Visser en Krikken et al, Obesity, in press
• It IS accompanied by a rise in
NT-proBNP: marker of CV risk
Weight excess/obesity
• Volume expanded during high sodium
• In hypertensives: > rise in blood pressure
• In young normotensives: no signs at the
outside
SODIUM SENSITIVITY = HIGHER ECV
• In young healthy
ECV, liters
volunteers ECV is
higher in SS
individuals, in
particular, but not
only, during high
sodium
22
20
18
16
14
low sodium high sodium
SR
SS
F.Visser, Am J Hyp 2008,21:323
Weight excess and high sodium
hypothesis
A sodium-induced rise in BP may be the tip of the
Iceberg, the ECV expansion underneath being the
true pathogenetic factor
Low Na+ diet reduces CV events and mortality
on long term follow up (TOHP I and II)
• Prehypertensive subjects
cumulative mortality
0,05
0,04
• Dietary counseling
TOHP I
n=327/1191, control 417/1191
0,03
• Baseline sodium excreton
0,02
150/182 mmol/d
0,01
• Reduction 50-40 mmol/d
13
10
7
4
1
0
• Blood pressure effect during
years
intervention
Cook, BMJ, april 20, 2007
control
trial hardly present
• Most subjects overweight
The remedy
Lifestyle intervention; Drug treatment
Lower blood pressure
Reduction target organ damage > Better outcome
Do you know the sodium intake of your patients?
Do you know the sodium intake of your patients?
24-hour urine: unbiased
and cheap assessment
of sodium intake
Allows unbiased
feedback for patients
Do you know the PROTEIN intake of your patients?
24-hour urine: unbiased
and cheap assessment
of protein intake (urea
excretion)
Allows unbiased
feedback for patients
Recommendations
Gezondheidsraad
• limited effect of lowering sodium intake on
prevention of hypertension on population level
• use modest amounts of sodium (max 6 g)
• combine these diet changes with low fat and high
fruit intake
• hypertensives: replace other minerals for sodium