?????

1
?????µ???? ?a? ??µ?????????? ??e???? t??
?p??tas?? st?? ??????? p????
??d??a? ??tta??? MD
2
?????µ???? ??e???? t?? ?p??tas??

• ?????s? ?????
• ??t??? ????
• ????? ????
• ??eat????? ????
• ??µat????t??
• G?????? ????
• ?sß?st??
• T-Chol, HDL-Chol, LDL-Chol, TGL

The JNC 7 Report , JAMA 2003
3
???ast???a??? ??et?se?? ???t??a? st? ?pe?tas???
?t?µ?

• G?????? p??sµat?? (?at? p??t?µ?s? ??ste?a?)
• ????? ????ste???? ????
• HDL
• ???????e??d?a ???? ??ste?a?
• ?????? ???
• ??eat????? ????
• ????? ????
• ??µ?sfa????? ?a? ??µat????t??
• Ge???? e??tas? ?????
• ??G

• LDL
• ?sß?st?? ????
• - ?????? ???

JNC VII
ESC/ESH 2003
4
???te???µe?e? e??ast???a??? e?et?se?? st??
?pe?tas???

• Echo ?a?d???
• U/S ?a??t?d?? ?a? µ???a??? a?t?????
• C-a?t?d??sa p??te???
• ?????a?ß??µ??????a (apa?a?t?t? e??tas? se
  d?aß?t????? as?e?e??)
• ??s?t???? p??sd????sµ?? p??te??????a? (e?? t?
  stick ????? e??a? ?et???)
• ????s??p?s? (se s?ßa??? ßa?µ?? ??)

ESC/ESH 2003
5
?????µ???? ??e???? ?????

• ???te??????a ( gt300mg/24??? ? gt200µg/min)
  d?aß?t??? ?ef??p??e?a ?a? se ?ef???? ??s?
• ?????s??p??? ??µat????a ?a????? ?p??tas?,
  ?pe?tas??? ?ef??s??????s?
• G?????????a sa??a??d?? d?aß?t??

6
?????a?ß??µ??????a
???sµ?? 30-300 mg/day ? 20-200 µg/min

• ??d?????a?? d?s?e?t?????a sta spe??aµat???
  t????e?d?
• (J Cardiovascular Pharmacol 1999)
• ????s? t?? µeta???p??te???s??-9, ?????? st???
  d?aß?t????? (Am J Kidney Dis 1998)
• ????s? t?? pa?????ta t?? Von Willebrand, t??
  ???µß?µ?d??????? ?a? t?? ???d??????
• ( Diabetes 1994, Arterioscler Thromb Vasc Biol
  1995)

7
???sµ?? ??????e???µat??????a?
?e???µat??????a?
?a??µet??? F.? M?????e???µat??????a ?e???µat?- ?????a
Urine AER (?g/min) lt 20 20 - 200 gt200
Urine AER (mg/24h) lt 30 30 - 300 gt300
Urine albumin/ Cr ratio (mg/gm) lt 30 30 - 300 gt300
AERAlbumin excretion rate CR creatinine
8
???a??sµ?? ?ef????? ß??ß?? st?? ?p??tas?

• Spe??aµat??? ?p??tas?
• ?pe?d????s?
• ??s?e?t?????a spe??aµat???? ??µ??
• ???te??????a
• ?pe?p?as?a µesa??e?a??? ??tt????
• ??d??ef???? f?e?µ???d?? d?e??as?a
• ??d?????a?? d?s?e?t?????a
• S?????t??s? ?e??? µ????? ??tt????

F?s????????? ?ef???
??t???a?? ??es?
9
?ef???? ß??ß? st?? ?p??tas?
?pa??????a

• ?e?t???????
• ?e??s? GFR
• ???te??????a
• ??µ???
• Glomular basement membrane changes
• Expanded mesangial matrix
• Glomerulosclerosis
• Tubulo-interstitial fibrosis

Renal Failure
?p??tas?
10
(No Transcript)
11
? ?????a?ß??µ??????a e??a? de??t?? ß??ß?? ???????
st????

• Hypertension 1999, Am J Kidney Dis 1995 ?
  µ????a?ß??µ??????a s?s?et??eta? µe t? µ??a t??
  a??ste??? ?????a? se ?pe?tas????? as?e?e??
• Stroke 1997, J Hum Hypertens 1995, Curr Opin
  Nephrol Hypertens 1995 ? µ????a?ß??µ??????a
  s?s?et??eta? µe a???s? t?? p????? ?s?-µ?s??
  ??t??a t?? ?a??t?da? se ?pe?tas????? as?e?e??
• J Hypertens 1993 ? ep?pt?s? t?? ?a?d?a??e?a???
  ??s?? e??a? ?at? 47 µe?a??te?? se ?pe?tas?????
  as?e?e?? µe µ????a?ß??µ??????a

12
? ?????a?ß??µ??????a e??a? p?????st???? de??t??
???t?t?ta? se ?pe?tas????? µe ???
T??t?t?ta
?pe?tas???? µe ??? 1
?pe?tas???? µe ????????a?ß??µ??????a (t?? 1? ?µ??a) 25
?pe?tas???? µe ????????a?ß??µ??????a (t?? 3? ?µ??a) 35
J Hypertens 1998
13
?????a?ß??µ??????a ?a? Sa??a??d?? ??aß?t??

• Am J Cardiol 1997
• ?????e?a µe??t?? 6,3 ?t?
• ?????sµ?? ?pe?tas????
• 94 as?e?e?? µe Sa??a??d? ??aß?t? ?a?
• 345 as?e?e?? ????? Sa??a??d? ??aß?t?

• ? ?????a?ß??µ??????a ap?te?e? a?e???t?t?
  p?????st??? pa?????ta ???? st??? d?aß?t?????

14
??e???? ??e?t????t?? ?a? ?ef????? ?e?t?????a?

• ??t??? ? p??t?pa?? ?pe?a?d?ste????sµ?
• ????? ? ???? d?????t???? a????? ?a? st??
  p??t?pa?? ?pe?a?d?ste????sµ?
• ?sß?st?? ? st?? p??t?pa?? ?pe?pa?a???e?e?d?sµ?
• ??eat????? ? se ?ef???? ß??ß?

15
(No Transcript)
16
? ?p??tas? st??? d?aß?t????? t?p?? ?

• ? ?p??tas? st??? ??aß?t????? t?p?? ? s?s?et??eta?
  µe t? d?aß?t??? ?ef??p??e?a

J Hypertension 1992
17
??t?stas? st?? ??s??????

• ? a?t?stas? st?? ??s?????? e??a? pa???sa st???
  µ?s??? as?e?e?? µe ?p??tas? p?? de? ?????
  pa??sa???a
• Diabet Care 1991
• ???µ?tas???? as?e?e?? µe s??d??µ? a?t?stas?? st??
  ??s?????? ????? ?????te?? a?t???a?? p?es? se
  s??s? µe t??? ???µ?tas????? p?? ????? f?s????????
  ep?peda ??s???????
• N Engl J Med 1987
• ?a ep?peda ??s??????? e??a? ?????te?a se
  ???µ?tas??? pa?d?? ?pe?tas???? as?e???
• Hypertension 1987

18
? ?p??tas? st??? ??aß?t????? t?p?? ??
19
?????? ???

• ?? ?????? ??? ??e? a?t???e?d?t???? ?d??t?te?

• ?? ?????? ??? p???a?e? e?d?????a?? d?s?e?t?????a

Circulation 2002 Hypertension 2000 Circulation
2001 JAMA 2000
Proc Natl Acad Sci USA 1981 Bioch J. 1986 J Am
Chem Soc 1989 Arch Biochem Biophys 2000
20
?? ?????? ??? a????eta? se as?e?e?? µe
?a?d?a??e?a?? ???d???
Hypertension 2003
21
(No Transcript)
22
?? ?????? ??? s?s?et??eta? µe t?? a?t???a??
?p??tas?

• ?? 25 t?? ?pe?tas???? as?e??? ????? a???µ??e?
  t?µ?? ??????? ?????
• 50 t?? as?e??? p?? ?aµß????? d?????t??? ?????
  a???µ??e? t?µ?? ??????? ?????
• 75 t?? as?e??? µe ?a????? ?p??tas? eµfa??????
  a???µ??e? t?µ?? ??????? ?????

Hypertension 2003
23
???a??sµ?? d??s?? t?? ??????? ?????

• ?TXA
• ?MCP-1
• ?TNF-a
• ?IL-6

Hypertension 2003
24
?a ep?peda t?? ??????? ????? s?s?et????ta? µe t??
a?t???a?? p?es?

• 125 pa?d?? ?pe?tas???, 6-18 et??
• ???a?s? ??eat?????? gt80 ml/min.1,73 m2

• 63 pa?d?? ?d??pa?? ?p??tas?
• 40 pa?d?? de?te??pa?? ?p??tas?
• 22 ?p??tas? ?e???? µp????a?

Hypertension 2003
25
(No Transcript)
26

• ?????? ??? gt5,5 mg/dl se ?pe?tas??? pa?d??
  ?p?d????e? ?d??pa?? ?p??tas?

?????? ???gt5,5mg/dl
?d??pa??? ?p??tas? 89
?e?te??pa??? ?p??tas? 30
?p??tas? ?e???? µp????a? 0
?µ?da e?????? 0
Hypertension 2003
27
??d???????? ??s?µata ?a? ?p??tas?

• ???t?pa??? a?d?ste????sµ??
• Fa?????µ???t?µa
• S??d??µ? Cushing

28
???t?pa??? ??d?ste????sµ??

• ?????e? ad???µa
• ?µf?te??p?e??? ?pe?p?as?a ep??ef??d???
• Ca ep??ef??d???
• ???ep??ef??d?a??? ?????

29
???t?pa??? ??d?ste????sµ??
????S??????S??S
?pe??at??a?µ?a
?p??a??a?µ?a

1. ????? ad??aµ?a
2. ?etaß????? a?????s?
3. ????????a

????s? ????? p??sµat??
?p??tas?
?atast??? ?e?????-a??e??tas????
30
?p??tas? ?p??a??a?µ?a
? ?????
gt30meq/24h
lt30meq/24h

• ??????t???
• ?p??e?e? ap? t? pept???

??ast???t?ta ?e????? p??sµat??
?aµ???
????µ??? ??st?????a, ?ef?a??e?a??
?p??tas?, ?a?????? ?p??tas?
??d?ste????
?aµ???
????µ???
G????????a, S??d??µ? Liddle
???t?pa??? a?d?ste????sµ??
31
S??s? a?d?ste????? p??sµat??/ d?ast???t?ta?
?e????? p??sµat??

• ??d?ste???? p??sµat?? f.t.5-20 ng/dl
• ?e???? p??sµat??
• f.t. 1-3 ng/dl
• PA/PRA lt 10

• ???t?pa??? a?d?ste????sµ??
• PA/PRA gt20 ?a? p????? f???? PA/PRA gt50
  

32
?p?ßeßa??t???? d???µas?e? p??t?pa????
a?d?ste????sµ??

• ????µas?a ?atast???? t?? a?d?ste????? µe NaCl
  (Kem et al) - de? µe?????ta? ta ep?peda
  a?d?ste????? p??sµat?? ??t? ap? 10 ng/dl
• ????µas?a f??t?s?? µe ??t??? ?a? µ?t??s? t??
  a?d?ste????? t?? ????? 3 µ??e? µet?- ??d?ste????
  ????? gt 12-14 µg/24h
• (Bravo, 1994)
• ????µas?a ?atast???? µe ?apt?p???? S??s? PA/PRA
  gt30,p??? ?a? 90 ?ept? µet? t? ??????s? 50 mg
  ?apt?p????? (Rossi, 1996)

33
Fa?????µ???t?µa

• ????? ap? ???µ??f??a ??tta?a
• ??apt?ss??ta? se s?µe?a p?? ?p?????? ta ??tta?a
  a?t?
• 15 st??? e???????? ?a? 30 sta pa?d?? t?
  fa?????µ???t?µa ß??s?eta? e?t?? t?? ep??ef??d???

34
??t?p?s? t?? fa?????µ???t?µat??
??t?p?s?
????????????? 97-99
??????? ????? ep??ef??d??? 50-70
??????? e??ep??ef??d?a??? ????? 10-20
????ap??? ????? 15-40
?µf?te??p?e???? ????? ep??ef??d??? 5-25
????ap??? e??ep??ef??d?a??? ????? 5-15
??O????????? 1-3
??d????a????? 2
St?? t?????? lt1
35
??????s? t?? fa?????µ???t?µat??

• S???st?ta? ??e???? ??a fa?????µ???t?µa se
  ?pe?tas????? as?e?e?? µe e???µata e?de??t??? t??
  pa???s?a? t?? ?????
• ?p??tas?
• ?efa?a???a
• ?f?d??se??
• ?a???a?d?a
• ???µ?
• ???s???a, ?e?????t?ta

36
??????s? t?? fa?????µ???t?µat??

• ?ate???aµ??e? p??sµat??
• gt2000pg/ml (11,8 nmol/L)
• ??a???st??? ???t????
• ?ate???aµ??e? p??sµat??
• gt950pg/ml (5,6 nmol/L)
• ????µas?a ?????d???? ??????s? 0,3 mg ?????d????.
• ?ate???aµ??e? p??sµat?? lt500 pg/ml
• (3,0 nmol/L) ????t???

Arch Intern Med 2000
37
??????s? t?? fa?????µ???t?µat??

• ?eta?ef???e? ????? 24???? gt 1,2mg/day

38
??????s? t?? fa?????µ???t?µat??study of Mayo
clinic

• ?eta?ef???e? p??sµat??
• (PLASMA 1999, JAMA 2002)
• ?eta?ef???e? ?a? ?ate???aµ??e? sta ???a 24????
• (Endocr Metabol Clin North Am 1997)

J Clin Endocrinol Metab 2003
39
?eta?ef???e? ?a? ???µeta?ef???e? p??sµat??
J Clin Endocrinol Metab 2003
40
?ate???aµ??e? ?a? µeta?ef???e? sta ???a 24????
J Clin Endocrinol Metab 2003
41
??????s? t?? fa?????µ???t?µat??
?eta?ef???e? p??sµat?? ?eta?ef???e? ?a? ?ate???aµ??e? ????? 24h
??a?s??s?a 97 90
??d???t?ta 85 98
J Clin Endocrinol Metab 2003
42
S??d??µ? Cushing
43
S??d??µ? Cushing
44
??????s? S??d??µ?? Cushing

• ???t????? ????? 24???? f.t 9.92.7 mg/24 h
• (277.5 µmol/24h)
• 12 to 40 µg (33 to 110 nmol) ???t??????
  ap?ß?????ta? sta ???a 24????
• ?a a??te?a f?s???????? ???a t?µ?? ???t??????
  ????? 24???? e??a? ta 90-100 µg

• ???t????? ????? 24???? gt100 µg /24 hours
• Cushings syndrome
• Pseudo-Cushings syndrome
• Major stress (trauma,infection)

N Engl J Med 1995
45
??????s? S??d??µ?? Cushing

• ????ap?? de??µata ????? 24/????
• ? p????t?ta t?? s??????? e?t?µ?ta? ap? t??
  e??????µe?? ??eat????? ?????
• ?? ? ??eat????? ????? sta de??µata 24????
  d?af??e? gt10 ep?ß???eta? ? s?????? 2 ? 3 ????
  de??µ?t??

46
????µas?a ?atast???? µe de?aµe?a????

• ????µas?a ??????t?a? ?atast????
• ?e?aµe?a???? 1 mg st?? 23.00
• ???t????? p??sµat?? st?? 08.00gt5 µg per
  deciliter (gt138 nmol per liter) st?? 08.00
• ?et??? d???µas?a

• ?atast??? µe µ????? d?se?? de?aµe?a?????
• ?e?aµe?a???? 0,5 mg/6??? ?a? ??a 48
  ??e?
• ???t????? ????? gt10µg/ 24???
• ?et??? d???µas?a

47
(No Transcript)
48
???e? ??d????????? ??ata?a???

• ?p????e?e?d?sµ??
• ?pe????e?e?d?sµ??
• ?pe?pa?a???e?e?d?sµ??
• ????µe?a??a

49
S?µpe??sµata

• Se a?ep?p?e?t? ?p??tas? ?a? p??? t?? ??a??? t??
  ?e?ape?a? apa?te?ta? pe?????sµ???? ß????µ???? ?a?
  a?µat???????? ??e????
• (Ht, s???a?? a?µat??, ??eat?????,
  ??e?t????te?, Chol, Chol HDL, Chol LDL,
  t??????e??d?a, a????s? ?????)
• ?? ?????? ??? fa??eta? ?a d?ad?aµat??e? s?µa?t???
  ???? st?? pa?????e?a t?? a?t???a??? ?p??tas??
  ?????? sta pad??

50
S?µpe??sµata

• ? e?d????????????? ??e???? ????eta?
  apa?a?t?t?? ?ta? de? ep?t?????eta? ? ??e???? t??
  a?t???a??? p?es?? ? ?ta? e?a???? ?p??????
  ???????? ?a? e??ast???a??? e?de??e?? p?? ?a
  ??t??? ß?s?µa t?? ?p???a e?d?????????????
  ??s?µat??