HYPERTENSION

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HYPERTENSION

• MORE THAN BLOOD PRESSURE ALONE!

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Richard Bright( 1789-1858) the First
Nephrologist
First observation of hardened pulseand renal
damage at autopsy (1827)
First observation association of cardiac
hypertrophy and shrunken kidneys (1836)
Source Richard Bright Web-page Internet
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Hypertension classical concepts
Causal factors
hypertension
Target organ damage Brain Heart Kidney
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Hypertension classical concepts
Causal factors
hypertension
Target organ damage Brain Heart Kidney
HYPERTENSION FOLLOWS THE KIDNEY
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Hypertension classical concepts
Causal factors
hypertension
Target organ damage Brain Heart Kidney
HYPERTENSION FOLLOWS THE KIDNEY
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Epidemiology
Prevalence of hypertension very different between
populations Hypertension is associated with end
organ damage
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Relationship between sodium intake and blood
pressure around the world population studies
Northern Japan
Southern Japan
US
Marshall islands
Inuit
Meneely Dahl, 1961
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Low salt and high salt populations
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Relationship between sodium intake and end-organ
damage
portugal
malta
spain
finland
italy
denmark
UK
iceland
germany
holland
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Hypertension and CV mortality
Higher BP worse outcome SBP and DBP are
independent risk factors There is NO clearcut
lower treshold!
Domanski, JAMA 2002
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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
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The remedy

• Lower blood pressure

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The remedy
Lifestyle intervention Drug treatment
Lower blood pressure
Reduction target organ damage gt Better outcome
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The remedy
BENEFIT OF TREATMENT IS NOT EQUAL FOR ALL
PATIENTS ! LIFESTYLE INTERVENTION DRUG
TREATMENT CAN POTENTIATE EACH OTHER
! INTERVENTION CAN IMPROVE OUTCOME ALSO
INDEPENDENT OF EFFECT ON BLOOD PRESSURE !
Lifestyle intervention Drug treatment
Lower blood pressure
Reduction target organ damage gt Better outcome
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The remedy
BENEFIT OF TREATMENT IS NOT EQUAL FOR ALL
PATIENTS ! LIFESTYLE INTERVENTION DRUG
TREATMENT CAN POTENTIATE EACH OTHER
! INTERVENTION CAN IMPROVE OUTCOME ALSO
INDEPENDENT OF EFFECT ON BLOOD PRESSURE !
Lifestyle intervention Drug treatment
Lower blood pressure
Reduction target organ damage gt Better outcome
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Meta Analysis Lower SBP Results in Less GFR
Decline in Diabetics and Non-Diabetics
MAP (mm Hg)
0
-2
GFR (mL/min/year)
r 0.69 P lt0.05
-4
-6
Untreated hypertension
-8
-10
140/90
130/85
-12
-14
Studies in nondiabetic nephropathy.
Bakris GL et al. Am J Kidney Dis.
200036646-661.
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PROTECTIVE EFFECT OF LOWER BLOOD PRESSURE ON LONG
TERM RENAL OUTCOME DEPENDS ON PROTEINURIA !

• Effect of poor BP control on GFR decline is
  larger in proteinuria
• Need for lower target blood pressure in
  proteinuric patients !!!
• MDRD study

Peterson, Ann Int Med 1995 123745
Uprot
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Patients with vulnerable kidneys need a lower
blood pressure !

• Proteinuria
• Diabetes

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No specific vulnerability

• More liberal regimen jusitified

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The remedy
BENEFIT OF TREATMENT IS NOT EQUAL FOR ALL
PATIENTS ! LIFESTYLE INTERVENTION DRUG
TREATMENT CAN POTENTIATE EACH OTHER
! INTERVENTION CAN IMPROVE OUTCOME ALSO
INDEPENDENT OF EFFECT ON BLOOD PRESSURE !
Lifestyle intervention Drug treatment
Lower blood pressure
Reduction target organ damage gt Better outcome
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Control of sodium status improves response to
RAAS-blockade
Uprot, g/d
MAP, mmHG
ACEi
AIIA
Heeg, Kidney Int 1989 36,272
Vogt en Waanders, JASN 2008
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The remedy
BENEFIT OF TREATMENT IS NOT EQUAL FOR ALL
PATIENTS ! LIFESTYLE INTERVENTION DRUG
TREATMENT CAN POTENTIATE EACH OTHER
! INTERVENTION CAN IMPROVE OUTCOME ALSO
INDEPENDENT OF EFFECT ON BLOOD PRESSURE !
Lifestyle intervention Drug treatment
Lower blood pressure
Reduction target organ damage gt Better outcome
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Effect of high salt intake on long term outcome
Is it all blood pressure??
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Salt intake effects on mortality in general
population

• Increased mortality risk per 6 gr rise in salt
  intake
• Interaction with BMI gt 27
• HR normal weight 0,98 ns
• HR overweight 1,56
• Effect ONLY present in overweight subjects

Tuomilehto, Lancet 2001 357848-51
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Sodium-sensitivity in obesity hypertension is
reversible by weight loss

• 250 vs 30 mmol Na 2-weeks
• Weight loss gt 1 kg by 20-week program
• Weight excess is a main determinant of
  sodium-sensitivity of blood pressure

Rocchini AP, NEJM 1989 322 476-7
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Salt intake effects on mortality in general
population

• Increased mortality risk per 6 gr rise in salt
  intake
• Effect INDEPENDENT OF BLOOD PRESSURE!

Tuomilehto, Lancet 2001 357848-51
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High salt increases albuminuria in healthy
subjects, independent of blood pressure

• A rise in salt intake leads to a 25 rise in UAE
  in healthy volunteers without even a rise in BP !

JA Krikken, Kidney Int 2007 71 260-265
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Salt status associated with albuminuria
independent of BP, but dependent on BMI (n7913,
Prevend population)
BMI
27,3-67 24-27,3 16,3-24
JC Verhave, Eur J Clin Invest 2004 256 324-30
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INTERACTION SODIUM STATUS-WEIGHT EXCESS

• Sodium sensitivity of blood pressure
• Blood pressure
• CV outcomes BP dependent AND BP independent
• Risk markers (NT-proBNP, UAE)

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• SODIUM EXCESS AND WEIGHT EXCESS
• Deadly twins!

In normotensive AND in hypertensive subjects
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• SODIUM EXCESS AND WEIGHT EXCESS
• Deadly twins!

MECHANISM?
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Effect of overweight on extracellular volume
during low vs high sodium intake

• In slightly overweight young men, ECV is higher
  than in lean subjects, ONLY during high sodium
• This is NOT accompanied by higher blood pressure.
• It IS accompanied by a rise in NT-proBNP marker
  of CV risk

Visser en Krikken et al, Obesity, in press
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Weight excess/obesity

• Volume expanded during high sodium
• In hypertensives gt rise in blood pressure
• In young normotensives no signs at the outside

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SODIUM SENSITIVITY HIGHER ECV

• In young healthy volunteers ECV is higher in SS
  individuals, in particular, but not only, during
  high sodium

F.Visser, Am J Hyp 2008,21323
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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
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Low Na diet reduces CV events and mortality on
long term follow up (TOHP I and II)

• Prehypertensive subjects
• Dietary counseling n327/1191, control 417/1191
• Baseline sodium excreton 150/182 mmol/d
• Reduction 50-40 mmol/d
• Blood pressure effect during trial hardly present
• Most subjects overweight

TOHP I
Cook, BMJ, april 20, 2007
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The remedy
Lifestyle intervention Drug treatment
Lower blood pressure
Reduction target organ damage gt Better outcome
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(No Transcript)
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Do you know the sodium intake of your patients?
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Do you know the sodium intake of your patients?
24-hour urine unbiased and cheap assessment of
sodium intake Allows unbiased feedback for
patients
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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
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(No Transcript)
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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