HYPERTENSION MORE THAN BLOOD PRESSURE ALONE!. Richard Bright( 1789-1858) the First Nephrologist*...

HYPERTENSIONHYPERTENSION

MORE THAN BLOOD MORE THAN BLOOD PRESSURE ALONE!PRESSURE ALONE!

Richard Bright( 1789-1858)Richard Bright( 1789-1858) the First Nephrologist* the First Nephrologist*

First observation of “hardened pulse”and

renal damage at autopsy (1827)

* Source: Richard Bright Web-page Internet

First observation association of

cardiac hypertrophy and shrunken kidneys (1836)

Hypertension: classical Hypertension: classical conceptsconcepts

Causal factors hypertension

Target organ damageBrainHeart Kidney




HYPERTENSION FOLLOWS THE KIDNEY




HYPERTENSION FOLLOWS THE KIDNEY

EpidemiologyEpidemiology

Prevalence of hypertension very different between populations

Hypertension is associated with end organ damage

Relationship between sodium intake and Relationship between sodium intake and blood pressure around the world: population blood pressure around the world: population studiesstudies

0

5

10

15

20

25

30

0 10 20 30 40 50

% hypertensives

mea

n s

od

ium

in

take

(g

ram

s)

Northern Japan

Southern JapanUS

Marshall islands

Inuit

Meneely & Dahl, 1961

Low salt and high salt populations Low salt and high salt populations

Relationship between sodium intake Relationship between sodium intake and end-organ damageand end-organ damage

500

700

900

1100

1300

1500

1700

1900

2100

7,5 8 8,5 9 9,5 10 10,5

UNaV (g/day)

dea

ths

stro

ke p

er 1

00.0

00/y

r portugal

hollandgermany

spain

italy

malta

finland

UKdenmarkiceland

Hypertension and CV Hypertension and CV mortalitymortality

Domanski, JAMA 2002

Higher BP: worse outcomeSBP and DBP are independent risk factors

There is NO clearcut lower treshold!

Hypertension and end stage renal Hypertension and end stage renal failurefailure

Brancati, NEJM 1996

Higher BP: worse outcomeSBP and DBP are independent risk factors

There is NO clearcut lower treshold!

The remedyThe remedy

Lower blood pressureLower blood pressure


Lifestyle intervention; Drug treatment

Lower blood pressure

Reduction target organ damage > Better outcome





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 !








Meta Analysis: Lower SBP Results in Less GFR Meta Analysis: Lower SBP Results in Less GFR Decline in Diabetics and Non-DiabeticsDecline in Diabetics and Non-Diabetics

95 98 101 104 107 110 113 116 119

r = 0.69; P <0.05

MAP (mm Hg)

GFR

(mL/min/year)

Untreatedhypertension

0

-2

-4

-6

-8

-10

-12

-14Parving HH et al. Br Med J. 1989Viberti GC et al. JAMA. 1993Klahr S et al. N Eng J Med. 1993*Hebert L et al. Kidney Int. 1994Lebovitz H et al. Kidney Int. 1994

Maschio G et al. N Engl J Med. 1996*Bakris GL et al. Kidney Int. 1996Bakris GL. Hypertension. 1997GISEN Group. Lancet. 1997*

*:Studies in nondiabetic nephropathy. Bakris GL et al. Am J Kidney Dis. 2000;36:646-661.

140/90130/85

PROTECTIVE EFFECT OF LOWER BLOOD PROTECTIVE EFFECT OF LOWER BLOOD PRESSURE ON LONG TERM RENAL OUTCOME PRESSURE ON LONG TERM RENAL OUTCOME

DEPENDS ON PROTEINURIA !DEPENDS ON PROTEINURIA !

• Effect of poor BP control on Effect of poor BP control on GFR decline is larger in GFR decline is larger in proteinuriaproteinuria

• Need for lower target Need for lower target blood pressure in blood pressure in proteinuric proteinuric patients !!!patients !!!

MDRD studyMDRD study

-16

-12

-8

-4

0

86 92 98 107

obtained MAP mmHg

GFR d

ecline m

l/m

in/y

r

0 >0,25 >1 >3Peterson, Ann Int Med 1995; 123:745

Uprot:

Patients with vulnerable Patients with vulnerable kidneys need a lower kidneys need a lower

blood pressure !blood pressure !

ProteinuriaProteinuria

DiabetesDiabetes

No specific vulnerability:No specific vulnerability:

More liberal regimen jusitifiedMore liberal regimen jusitified








Control of sodium status improves response Control of sodium status improves response to RAAS-blockadeto RAAS-blockade

0

1

2

3

4

5

6

7

80

85

90

95

100

105

110

Uprot, g/dMAP, mmHG

Heeg, Kidney Int 1989; 36,272

0

0.5

1

1.5

2

2.5

3

3.5

4

80

85

90

95

100

105

Vogt en Waanders, JASN 2008

ACEi

AIIA








Effect of high salt intake on long term Effect of high salt intake on long term outcome outcome

500

700

900

1100

1300

1500

1700

1900

2100

7,5 8 8,5 9 9,5 10 10,5

UNaV (g/day)

dea

ths

stro

ke p

er 1

00.0

00/y

r

Is it all blood pressure??

Salt intake: effects on mortality in general Salt intake: effects on mortality in general populationpopulation

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

haza

rd ratio

low salt high salt

• Increased mortality risk Increased mortality risk per 6 gr rise in salt intakeper 6 gr rise in salt intake

• Interaction with BMI > 27Interaction with BMI > 27– HR normal weight: 0,98 nsHR normal weight: 0,98 ns– HR overweight : 1,56 HR overweight : 1,56

– Effect ONLY present in Effect ONLY present in overweight subjectsoverweight subjects

Tuomilehto, Lancet 2001; 357:848-51

Sodium-sensitivity in obesity hypertension is Sodium-sensitivity in obesity hypertension is reversible by weight lossreversible by weight loss

-15

-10

-5

0

5

mm

Hg by low salt

leanobeseafter weight loss

• 250 vs 30 mmol Na+; 2-250 vs 30 mmol Na+; 2-weeksweeks

• Weight loss > 1 kg by 20-Weight loss > 1 kg by 20-week programweek program

• Weight excess is a main Weight excess is a main determinant of sodium-determinant of sodium-sensitivity of blood sensitivity of blood pressurepressure

Rocchini AP, NEJM 1989: 322: 476-7

Salt intake: effects on mortality in general Salt intake: effects on mortality in general populationpopulation

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

haza

rd ratio

low salt high salt

• Increased mortality Increased mortality risk per 6 gr rise in risk per 6 gr rise in salt intakesalt intake

– Effect Effect INDEPENDENT OF INDEPENDENT OF BLOOD PRESSURE! BLOOD PRESSURE!

Tuomilehto, Lancet 2001; 357:848-51

High salt increases albuminuria in High salt increases albuminuria in healthy subjects, independent of blood healthy subjects, independent of blood

pressurepressure

6

6.5

7

7.5

8

8.5

3 g/day 12 g/day

UAlb, m

g/24h

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

JA Krikken, Kidney Int 2007: 71: 260-265

Salt status: associated with albuminuria independent of BP, but dependent on BMI

(n=7913, Prevend population)

Urinary sodium excretion (mmol/24h)

50 100 150 200 250 300

UA

E (

mg

/24

h)

6

7

8

9

10

11

12

BMI third tertileBMI second tertileBMI first tertile

JC Verhave, Eur J Clin Invest 2004: 256: 324-30

27,3-67

24-27,3

16,3-24

BMI:

INTERACTION SODIUM STATUS-WEIGHT INTERACTION SODIUM STATUS-WEIGHT EXCESSEXCESS

• Sodium sensitivity of blood pressureSodium sensitivity of blood pressure

• Blood pressureBlood pressure

• CV outcomes – BP dependent AND BP CV outcomes – BP dependent AND BP independentindependent

• Risk markers (NT-proBNP, UAE)Risk markers (NT-proBNP, UAE)

SODIUM EXCESS AND WEIGHT EXCESSSODIUM EXCESS AND WEIGHT EXCESS

Deadly twins! Deadly twins!

In normotensive AND in hypertensive subjects

SODIUM EXCESS AND WEIGHT EXCESSSODIUM EXCESS AND WEIGHT EXCESS

Deadly twins! Deadly twins!

MECHANISM?

Effect of overweight on extracellular Effect of overweight on extracellular volume during low vs high sodium volume during low vs high sodium

intakeintake

17

18

19

20

21

22

23

low sodium high sodium

ECV, liter

s

BMI 22 BMI 25

• In slightly overweight In slightly overweight young men, ECV is higher young men, ECV is higher than in lean subjects, ONLY than in lean subjects, ONLY during high sodiumduring high sodium

• This is NOT accompanied This is NOT accompanied by higher blood pressure.by higher blood pressure.

• It IS accompanied by a rise It IS accompanied by a rise in NT-proBNP: marker of in NT-proBNP: marker of CV risk CV risk

Visser en Krikken et al, Obesity, in press

Weight excess/obesityWeight excess/obesity

• Volume expanded during high sodiumVolume expanded during high sodium

• In hypertensives: > rise in blood In hypertensives: > rise in blood pressurepressure

• In young normotensives: no signs at In young normotensives: no signs at the outsidethe outside

SODIUM SENSITIVITY = HIGHER ECVSODIUM SENSITIVITY = HIGHER ECV

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

14

16

18

20

22

low sodium high sodiumEC

V, liter

s

SR SS

F.Visser, Am J Hyp 2008,21:323

Weight excess and high sodiumWeight excess and high sodium

A sodium-induced rise in BP may be the tip of the Iceberg, the ECV expansion

underneath being the true pathogenetic factor

hypothesis

Low Na+ diet reduces CV events and Low Na+ diet reduces CV events and mortality on long term follow up (TOHP I and mortality on long term follow up (TOHP I and II)II)

0

0,01

0,02

0,03

0,04

0,05

years

c um

ula

tive m

ort

alit

y

intervention control

• Prehypertensive subjectsPrehypertensive subjects

• Dietary counseling Dietary counseling n=327/1191, control 417/1191 n=327/1191, control 417/1191

• Baseline sodium excreton Baseline sodium excreton 150/182 mmol/d150/182 mmol/d

• Reduction 50-40 mmol/dReduction 50-40 mmol/d

• Blood pressure effect during Blood pressure effect during trial hardly presenttrial hardly present

• Most subjects overweightMost subjects overweight

Cook, BMJ, april 20, 2007

TOHP I





Do you know the sodium intake of your Do you know the sodium intake of your patients?patients?

Do you know the sodium intake of your Do you know the sodium intake of your patients?patients?

24-hour urine: unbiased and cheap assessment of sodium intake

Allows unbiased feedback for patients

Do you know the Do you know the PROTEINPROTEIN intake of your intake of your patients?patients?

24-hour urine: unbiased and cheap assessment of protein intake (urea excretion)

Allows unbiased feedback for patients

Recommendations Recommendations GezondheidsraadGezondheidsraad• limited effect of lowering sodium intake on limited effect of lowering sodium intake on

prevention of hypertension on population levelprevention of hypertension on population level

• use modest amounts of sodium (max 6 g)use modest amounts of sodium (max 6 g)

• combine these diet changes with combine these diet changes with low fat and high low fat and high fruit intakefruit intake

• hypertensives: replace other minerals for sodiumhypertensives: replace other minerals for sodium

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HYPERTENSION MORE THAN BLOOD PRESSURE ALONE!. Richard Bright( 1789-1858) the First Nephrologist*...

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