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HYPERTENSION

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).

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HYPERTENSION

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  1. HYPERTENSION MORE THAN BLOOD PRESSURE ALONE!

  2. 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

  3. Hypertension: classical concepts Causal factors hypertension Target organ damage Brain Heart Kidney

  4. Hypertension: classical concepts Causal factors hypertension Target organ damage Brain Heart Kidney HYPERTENSION FOLLOWS THE KIDNEY

  5. Hypertension: classical concepts Causal factors hypertension Target organ damage Brain Heart Kidney HYPERTENSION FOLLOWS THE KIDNEY

  6. Epidemiology Prevalence of hypertension very different between populations Hypertension is associated with end organ damage

  7. Relationshipbetweensodium intake and bloodpressurearound the world: population studies Northern Japan Southern Japan US Marshall islands Inuit Meneely & Dahl, 1961

  8. Low salt and high saltpopulations

  9. Relationshipbetweensodium intake and end-organdamage portugal malta spain finland italy denmark UK iceland germany holland

  10. Hypertension and CV mortality Higher BP: worse outcome SBP and DBP are independent risk factors There is NO clearcut lower treshold! Domanski, JAMA 2002

  11. 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

  12. The remedy Lower blood pressure

  13. The remedy Lifestyle intervention; Drug treatment Lower blood pressure Reduction target organ damage > Better outcome

  14. 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 ! The remedy Lifestyle intervention; Drug treatment Lower blood pressure Reduction target organ damage > Better outcome

  15. 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 ! The remedy Lifestyle intervention; Drug treatment Lower blood pressure Reduction target organ damage > Better outcome

  16. 95 98 101 104 107 110 113 116 119 • Parving HH et al. Br Med J. 1989 • VibertiGC 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 • Maschio G et al. N Engl J Med. 1996* • Bakris GL et al. Kidney Int. 1996 • Bakris GL. Hypertension. 1997 • GISEN Group. Lancet. 1997* 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 <0.05 -4 -6 Untreated hypertension -8 -10 130/85 140/90 -12 -14 *:Studies in nondiabetic nephropathy. Bakris GL et al. Am J Kidney Dis. 2000;36:646-661.

  17. PROTECTIVE EFFECT OF LOWER BLOOD PRESSURE ON LONG TERM RENAL OUTCOME DEPENDS ON PROTEINURIA ! • Effect of poor BP controlon GFR decline is larger in proteinuria • Needforlower target bloodpressure in proteinuricpatients !!! MDRD study Peterson, Ann Int Med 1995; 123:745 Uprot:

  18. Patients with vulnerable kidneys need a lower blood pressure ! Proteinuria Diabetes

  19. No specific vulnerability: More liberal regimen jusitified

  20. 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 ! The remedy Lifestyle intervention; Drug treatment Lower blood pressure Reduction target organ damage > Better outcome

  21. 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

  22. 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 ! The remedy Lifestyle intervention; Drug treatment Lower blood pressure Reduction target organ damage > Better outcome

  23. Effect of high salt intake on long term outcome Is it all blood pressure??

  24. Salt intake: effectsonmortality in generalpopulation • Increasedmortality risk per 6 gr rise in salt intake • Interactionwith BMI > 27 • HR normalweight: 0,98 ns • HR overweight : 1,56 • Effect ONLY present in overweight subjects Tuomilehto, Lancet 2001; 357:848-51

  25. Sodium-sensitivity in obesityhypertension is reversiblebyweight loss • 250 vs 30 mmol Na+; 2-weeks • Weight loss > 1 kg by 20-week program • Weightexcess is a main determinant of sodium-sensitivity of bloodpressure Rocchini AP, NEJM 1989: 322: 476-7

  26. Salt intake: effectsonmortality in generalpopulation • Increasedmortality risk per 6 gr rise in salt intake • Effect INDEPENDENT OF BLOOD PRESSURE! Tuomilehto, Lancet 2001; 357:848-51

  27. High saltincreasesalbuminuria in healthysubjects, independent of bloodpressure • A rise in salt intake leads to a 25 % rise in UAE in healthyvolunteers without even a rise in BP ! JA Krikken, Kidney Int 2007: 71: 260-265

  28. Salt status: associated with albuminuria independent of BP, but dependent on BMI(n=7913, Prevend population) BMI: 27,3-67 24-27,3 16,3-24 JC Verhave, Eur J Clin Invest 2004: 256: 324-30

  29. INTERACTION SODIUM STATUS-WEIGHT EXCESS • Sodium sensitivity of blood pressure • Blood pressure • CV outcomes – BP dependent AND BP independent • Risk markers (NT-proBNP, UAE)

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

  31. SODIUM EXCESS AND WEIGHT EXCESS Deadly twins! MECHANISM?

  32. Effect of overweightonextracellular volume during low vs high sodium intake • In slightlyoverweightyoung men, ECV is higherthan in leansubjects, ONLY during high sodium • This is NOT accompaniedbyhigherbloodpressure. • It IS accompaniedby a rise in NT-proBNP: marker of CV risk Visser en Krikken et al, Obesity, in press

  33. Weightexcess/obesity • Volume expanded during high sodium • In hypertensives: > rise in blood pressure • In young normotensives: no signs at the outside

  34. 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 2008,21:323

  35. Weightexcess 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

  36. Low Na+ diet reduces CV events and mortality on long term follow up (TOHP I and II) • Prehypertensivesubjects • Dietary counseling n=327/1191, control 417/1191 • Baseline sodiumexcreton 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

  37. The remedy Lifestyle intervention; Drug treatment Lower blood pressure Reduction target organ damage > Better outcome

  38. Do youknow the sodium intake of yourpatients?

  39. Do youknow the sodium intake of yourpatients? 24-hour urine: unbiased and cheap assessment of sodium intake Allows unbiased feedback for patients

  40. Do youknow the PROTEIN intake of yourpatients? 24-hour urine: unbiased and cheap assessment of protein intake (urea excretion) Allows unbiased feedback for patients

  41. 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

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