S??????? ?e?ape?t??? p??s????s? ?p??tas?? ??????

1
S??????? ?e?ape?t??? p??s????s? ?p??tas??
??????µ????

• ??d??a? ??tta???
• ?a?d???????
• Hypertension specialist ESH
• ?pe?tas??? ?at?e??? ????e?? ??s???µe??
• ?pe?????a?d????af??? e??ast???? ???? ???

2

• ?? ??????µ???? (gt65 et??) pa??st??? t? ta??te?a
  a??a??µe?? p?s?st? t?? p????sµ??
• ? ?????a?? ?at?????a ??? t?? 65 et?? a??????e
  ?at? 14 se pa???sµ?? ep?ped? ap? 1990-1995
• ?? ?a? ap?te???? t? 12 t?? p????sµ??, ap????f???
  gt1/3 t?? ???d????? ??a t?? ??e?a
• St??? ??????µ????? ? ?? ap?te?e? t?? sp??da??te??
  t??p?p???s?µ? pa?????ta ???d???? ??a ???, S?,
  ?a?d?a?? a?ep???e?a

3
Framingham Study ?? ?a? ?????a
Kannel et al 1978
4
NHANES III ?????a?? ?ata??µ? t?? ?pe?tas????
46
54
47.4 million hypertensives 26.0 of US population
Franklin S J Hypertens 1999 17 (suppl 5)S29-S36
5
??????S ??????S??S ??S ??????S S?? ??????GG?????
S?S????

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

• ??at?µ????
• ????s? a??t???? d?aµ?t???
• ????s? a??ste??? ???p??
• ????s? a??ste??? ?????t?ta?
• ?sß?st?s? da?t????? µ?t??e?d???/a??t??
• ?p?µ????s? a??t??

6
???????G???S ??????S??S ??S ??????S S??
??????GG????? S?S????

• ???t?
• ?e??µ??? e?ast???t?ta
• ????µ??? S??
• ????µ??? p?es? sf??µ??

• ???ste?? ?????a
• F?s???????? ??
• ?e??µ??? d?atas?µ?t?ta
• ?a???????? d?ast????? p????s?

7
?a??f?s??????a ?? ??t???a?? ?p??tas? ?? a??e?a??
??s??

• ????µ??e? pe??fe????? a?t?st?se??
• ??s?e?t?????a t?? e?d???????
• ????µ??? ta??t?ta a????? sf??µ???? ??µat??
• ????µ? ep?st??f? t?? a?a???µ???? ??µ?t??
• ?e??µ??? d?atas?µ?t?ta t?? µe????? a?t?????

8
?????a ?a? a?a???µe?a ??µata
9
Prevalence of isolated SBP and DBP by age and sex
in the Framingham Heart Study
American Heart Journal Sept. 1999
10
?a????µ?s? t?? ?? (mmHg)
St?d?? S?? ???
?da???? lt 120 lt 80
F?s???????? 120-129 80-84
????? F?s???????? 130-139 85-89
St?d?? 1 ?? (?p?a) 140-159 90-99
St?d?? 2 ?? (µ?t??a) 160-179 100-09
St?d?? 3 ?? (s?ßa??) ? 180 ? 110
?eµ???µ??? s?st????? ?? ? 140 lt 90

ESC/ESH 2003
11
?a????µ?s? t?? ?? (mmHg)
St?d?? S?? ???
F?s???????? lt 120 ?a? lt 80
????p??tas? 120-139 ? 80-89

St?d?? 1 ?? (?p?a) 140-159 ? 90-99
St?d?? 2 ?? (µ?t??a) ? 160-179 ? ? 100-09

?eµ???µ??? s?st????? ?? ? 140 lt 90

JNC VII
12
Kaplan-Meier Event Curves for Ischemic and
Hemorrhagic Strokes by Treatment Group
Perry HM, JAMA 2000
13
K??d???? ??a ??? epe?s?d?a ap? ?? se ?t?µa
?????a? 35-64 ??????, µet? ap? pa?a???????s? 36
?????? sta p?a?s?a t?? µe??t?? Framingham
JAMA 19962751571-1576
14
Framingham Study Isolated Systolic Hypertension
?a? ?a?d?a??e?a??? ???d????
ISH BP ?160/lt95 mmHg BP lt140/95 mmHg
2.5
2.4
Age-adjusted annual CVD event rate per 1000
ISHisolated systolic hypertension Plt0.001 for
difference between both men and women with ISH
and BPlt140/95 mmHg
Wilking SV et al. JAMA 19882603451-3455.
15
MRFIT ?p?d?as? S?? ?a? ??? st?? ???t?t?ta ap? S?
CHD death rateper 10,000 person-years
81
44
40
38
37
35
25
25
25
24
23
17
24
17
160
14
13
13
12
21
140-159
12
10
9
9
9
120-139
SBP(mm Hg)
lt120
100
90-99
80-89
75-79
70-74
lt70
DBP (mm Hg)
Neaton JD, Wentworth D. Arch Intern Med.
199215256-64.
16
???S? SF?G??? ??? ??? ?e??t? MRFIT

• Se ???e?e? ?pe?tas????? ?????a? 35-44 et??, ? ?
  ??? s?et??eta? µe ta ????? ep?peda S?? ?a? ???
• Se ?t?µa ?????a? 44-57 et?? , ? ? ??? s?et??eta?
  µe
• ????? ?S (? S?? ?a? ? ???)
• ????s? t?? S?? ?a? t?? ???
• ?p???sd?p?te s??d?asµ?? t?? 2 ap? t?? 3 t?µ?? ??
  (S??, ???, ?S), pa???e? pe??ss?te?e? p????f???e?
  ??a t?? e?t?µ?s? t?? ??? s?????t??? µe µ?t??s?
  µ??? µ?a? t?µ??
• JAMA 20022872677-2683

17
S?? ? ??? st?? p?????s? t?? S? ? ????? t??
?????a?
?????a 20-79 et?? (5 groups lt 40, 40-49, 50-59,
60-69, 70-79)
ß(SBP)-ß(DBP)
?????a (?t?)
Adjusted for age, sex and other risk factors
Franklin SS et al. Circulation 20011031245-1249
18
?p?pt?s? s???pa????s?? ?a?d?a??e?a??? pa??se??
se ??????µ????? ?pe?tas????? as?e?e?? 65 - 89
et?? (Framingham)
ep?pt?s?
??d?e? G??a??e?
St?????? 27.4 27.9 ?µf?a?µa
µ???a?d??? 23.7 9.4 ?a?d?a??
a?ep???e?a 4.4 7.9 ???
16.0 8.9 ???
15.9
10.0
19
??? st??? ??????µ????? ?pe?tas?????

• ? ?????a e??a? ? p?? ?s????? p??d?a?es????
  pa?????ta? ???
• ?et? ta 55 ?t?, ? s????t?ta ??? d?p?as???eta?
  a?? 10et?a
• ?a d?? t??ta ???? t?? ??? s?µßa????? se as?e?e??
  gt 65 et??
• ? a???s? t?? ??? ??a t?? ?????a?? ?at?????a gt 65
  et?? ?p??????eta? se 82 µeta?? 1996-2020 se
  pa???sµ?? ep?ped?

1 Thompson, D.W,, Furlan, A.J. Neurologic
Clinics 199614(2)309-3152 1998 Heart and
Stroke Statistical Update, American Heart
Association3 Guide to Stroke, 1997, National
Stroke Association4 Executive Summary, World
Health Report 1997
20
?????? ?a?????te? ???d???? ??a ???
?a?????ta? ???d???? S?et????
???d???? S????t?ta ??s??
?p??tas? 6X 35 ?a?d?a?? p???s? 2-6X
10-20 ?????. ???efa???? 10X 2 ??s??
?a??t?d?? 3X 4 ??aß?t??
2-4X 4-6 ??p??sµa 2X 25
Stroke Clinical Updates 1991I(5)17-20
21
S?? ?a? ??? ?a? S? (MRFIT)
??? (n1233)
S? (n11,149)
32
16
16
8
8
4
S?et???? ???d???? ???t?t?ta? ap? S?
S?et???? ???d???? ???t?t?ta? ap? ???
4
2
2
1
135
168
lt120
125
135
148
168
120
125
148
??s? S?? (mm Hg)
22
?? ??? e??a? p?? p??a?? ap? t? ???

• Se µeta-a????s? µe?et?? p??? t? 1990 se 37,000
  as?e?e?? ?ate???f?sa? 773 e??efa???? ?a? 1442
  eµf???µata.
• Se µeta-a????s? µe?et?? µet? t? 1990 se 59,650
  as?e?e?? ?ate???f?sa? 2233 e??efa???? ?a? 1627
  eµf???µata.
• ? a???t??? a?t? t?s? pa?at??????e t?s? µ????te?e?
  ?s? ?a? se µe?a??te?e? ?????e?.
• ?? ????? ??a a?t? t?? eµfa?? a??a?? pa?aµ?????
  ????st??.

Kjeldsen et al, Blood Pressure 2001 10 190-2
23
StrokeMI Ratio in Hypertension Trials Kjeldsen
SE, Julius S, Hedner T, Hansson L. Blood Pressure
200110190-2
24
??????µ???? s?et???? ???d???? ??a ??? a?????a µe
ta ep?peda t?? ?? se 6545 ?t?µa t?? Copenhagen
City Heart Study
25
?a?????te? p?? ep??e????? t?? p?????s? t??
??????µ???? ?pe?tas???? at?µ??

• ?p?peda ISH
• S???p?????te? pa?????te? ???d????
• ???ße? ??????? st????
• Sa??a??d?? d?aß?t??
• S?et???µe?e? ???????? ?atast?se??

ESC/ESH 2003
26
??????µ???? s?et???? ???d???? ??a te???? ?ef????
a?ep???e?a ?? p??? ta peµpt?µ???a ?? se ??d?e?
st? MRFIT.
5
S?? ???
4
3
Relative risk
2
1
0
1
2
3
4
5
Quintile (highest 20)
(lowest 20)
SBP lt 117 117-123 124-130 131-140 gt 140
DBP lt 75 75-79 80-85 86-91 gt 91
27
???d???? S? s?et???µe??? µe t?? S?? ?a? t??
µ????a?ß??µ??????a
N2,085 10 year follow-up
Borch-Johnsen K, et al. Arterioscler Thromb Vasc
Biol 1999191992-1997.
28
Isolated ambulatory hypertension predicts
cardiovascular morbidity in elderly men

• K.Björklund, L.Lind, B. Zethelius, B.Andrea,
  H.Lithell
• Circulation 2003 107 1297-1302

29
Isolated ambulatory hypertension

• In a multivariate model with continuous BP
  variables, ambulatory day time systolic BP was
  associated with an adverse outcome independently
  of office systolic BP.
• Björklund et al. 2003

30
Morning surge in blood pressure as a predictor
of cerebrovascular disease in elderly
hypertensives

• K.Kario, T.Pickering et al.
• Circulation 2003 107 1401-1406

31
Morning surge in blood pressure

• In older hypertensives, a higher morning BP
  surge is associated with stroke risk
  independently of ambulatory BP, nocturnal falls
  and silent infarct
• K.Kario, T.Pickering et al.
• Circulation 2003 107 1401-1406

32
??ast??µ?t?s? ?a?d?a??e?a??? ???d????
?? (mmHg) ?? (mmHg) ?? (mmHg) ?? (mmHg) ?? (mmHg) ?? (mmHg)
????? ?? ?a? at?µ??? ?st????? F?s???????? S?? 120-129 ? ??? 80-84 ????? F?s???????? S?? 130-139 ? ??? 85-89 St?d?? 1 S?? 140-159 ? ??? 90-99 St?d?? 2 S?? 160-179 ? ??? 90-99 St?d?? 3 S?? ?180 ? ??? ?110
??e? ???p?? ?? ?aµ???? ???d???? ?aµ???? ???d???? ?p??? ???d???? ??t???? ???d???? ?????? ???d????
1-2 ?? ?p??? ???d???? ?p??? ???d???? ??t???? ???d???? ??t???? ???d???? ???? ?????? ???d????
3 ?? ? ??S ? D?aß?t?? ??t???? ???d???? ?????? ???d???? ?????? ???d???? ?????? ???d???? ???? ?????? ???d????
S?? ?????? ???d???? ???? ?????? ???d???? ???? ?????? ???d???? ???? ?????? ???d???? ???? ?????? ???d????
ESC/ESH 2003
33
????? pe?? t?? ?? t?? ??????µ????

• ????s? t?? S?? µet? ta 60 ?t? e??a? f?s????????
  fa???µe??
• ?? ??????µ???? de? a?????ta? t?? a?t??pe?tas???
  fa?µa?e?t??? a????
• ?? ??????µ???? de? s?µµ??f????ta? µe t?? ?d???e?
  t?? ?at???
• ?a ?f??? t?? a?t??pe?tas???? ?e?ape?a? st???
  ??????µ????? de? e??a? epa???? te?µ????µ??a

34
S?µe?a p??s???? ?p??tas?? ??????µ????

• ????fa?µa??a (µ? ste??e?d?, ????at????)
• ?ef???? ?e?t?????a
• ?ste?p???s?
• ???
• ??at/?? ??e?t????t??, ???????
• ??ata?a??? ???p??????a??? a????µ?t?t??
• ????a??t?ta
• ???µ??, ????a, ??a???µa, ???stat?sµ??
• ??e???sµa a??t??, ßa?ß?d?p??e?e?

35
??t??s? ?? st?? ??????µ???

• ?p?f??? a???ast???? ??sµat?? (?p?e?t?µ?s? S??,
  ?pe?e?t?µ?s? ???, s?µe?? ßa????
  a?t????s??????s??, ?pe?te?e? ? ta?a?t?s?µet????
  µ???d?? ??a?t? t?? a???ast????)
• ??t?µ?s? ?e?d??p??tas?? (te????? Osler,
  e?da?t???a?? µ?t??s?)
• ??e???? ????stat???? ?p?tas?? (t?????????
  a?t??ata???pt???, a-a?ast??e?? ??p)

36
??t?µet?p?s? ?? st?? ??????µ???

• ??e???? ?? ?e???? µp????a?
• ??att?µ??? p??sa?µ?st???t?ta t?? tase??p?d?????
  µe ap?t??esµa a???µ??? ap????s? t?? S?? se
  ?at?stas? st??? ?a? ?p?tas??? ap????s? µet? ap?
  ?s??s? ? ap? ?e?µa
• S????te?? µ??f? ? ?d??pa??? ?? a??? de?
  ap???e?eta? ?a? ? de?te??pa??? ?? (p?
  ?ef?a??e?a?? ?? a????s??????t???? a?t??????a?)
• ???? µe µ????te?e? d?se?? p?? ?a a??????ta?
  stad?a??
• ?a?t???te?? e?t?µ?s? t?? ?ef????? ?e?t?????a?
• ??t?µet?p?s? s???pa????t?? pa?a???t?? ???d????

37
S????? T???????S S?S??????S ??????S?S S???S
?????O?????S

• lt 140mmHg ??a t??? pe??ss?te???? ?pe?tas?????
• lt 130mmHg ??a t??? d?aß?t????? ?a? t??? ????te?
  ?????a ?ef???? ??s?
• 2 to 4 f??µa?a ?a apa?t????? ??a t?? ep?te???
  a?t?? t?? t?µ?? st????

38
?f??? ap? t?? ?e?ape?a t?? ?? st??? ??????µ?????

• ??a??s?µe? ap?de??e??

39
(No Transcript)
40
?pa?t?se?? ??t??pe?tas???? Te?ape?a?

• ?p?te?esµat??? µe??s? ??
• 24-??? d??s?
• ?????ste? pa?e????e?e?
• ??d?te?? µetaß?????
• ???a??p??stas?a
• ?e??s? ???t?t?ta?

?pe?t??f?a
Stefa??a?a ??s??
?a?d??
?a?d?a?? a?ep???e?a
???te??????a
?ef???
Spe??aµat?s??????s?
??ast???t?ta,??d?t???t?ta
??d??????, ?????µ?t?s?
???e?a
?a??? ?s?-µ?s?? ??t??a
???
????fa???
41
M? Fa?µa?e?t??? ??sa
Fa?µa?e?t??? ??sa

• ap??e?a ß?????
• d?a??p? ?ap??sµat??
• e?att?µ??? p??s???? ?e?µ?d??
• pe?????sµ?? p??s????? ?at????
• pe?????sµ?? ????p?e?µat?d??
• s?µat??? d?ast????t?ta
• p??s???? ?a????

• d?????t???
• s?µpa????t???

• ß-ap???e?st??
• a- ap???e?st??
• ?e?t????? d???ta

• a?ta????st?? asßest???
• a-???
• a?ta?.a??e??tas???? ??
• aµ?s?? d???ta a??e??d?asta?t???

42
TONE STUDYTrial of Nonpharmacologic
Interventions in the Elderly

• 2gr a??t? (30 µ??e?)
• S??, ???
• 40 d?a??p? ?e?ape?a?
• µe??s? ß????? ltlt?? 50

43

• Increased physical activity lowers resting BP and
  LVMI in hypertensive patients.

Kokkinos,Pittaras, et al., NEJM, 1995
44
?p?d?as? µetaß???? t?? t??p?? ???? st?? ??
?etaß??? ?e??s? t?? S??
?e??s? S? 520 mmHg/10 kg µe??s?? S?
?p?d??? d?a?ta? DASH 814 mmHg
?e??s? ??at?? 28 mmHg
?s??s? 49 mmHg
?e?????sµ?? a????? 24 mmHg
JNC VII
ESC/ESH 2003
45
?f??? ap? t?? µe??s? t?? ??

??s? µe??s? ??? 3540 ?µf?a?µa
µ???a?d??? 2025 ?a?d?a?? a?ep???e?a 50
JNC VII
46
?f??? ap? t?? µe??s? t?? ??
Se as?e?e?? µe st?d?? 1 ?? ?a? ep?p??s?et???
pa?????te? ???d????, µe µ?a µe??s? t?? S?? ?at?
12 mmHg ??a 10 ?t?, ?a p????ß??µe 1 ???at? ??a
???e 11 ?e?ape??µ????? as?e?e??.
JNC VII
47
?e??te? µe ISH (vs. Placebo)
?e??s?
?e??t?
F??µa??
???
S?
????? ???t?t?ta
SHEP
Chlorthalidone,
-36
-27
-13 (n.s.)
Atenolol
(n4736)
Syst-Eur
Nitrendipine,
-42
-30 (n.s.)
-22 (n.s.)
(n4695)
Enalapril,
HCTZ
Syst-China
Nitrendipine,
-38
6 (n.s.)
-39
(n2394)
Captopril, HCTZ
SHEP, JAMA 1991 Syst-Eur, Lancet 1997
Syst-China, J Hypertens 1998
48
Effects of Therapy in Older Person With
Hypertension
CLINICAL TRIAL NAME
EWPHE SHEP SYST-EUR SYST-EUR STOP-HYPERTENSION MRC STONE
No. of patients 840 4736 4695 4695 1627 4396 1632
Age range,y gt60 gt60 gt60 gt60 70-84 65-74 60-79
Mean BP at entry, mm/Hg 182/101 170/77 174/86 174/86 195/102 185/91 188/98
Relative risk of event (treated vs control) Relative risk of event (treated vs control) Relative risk of event (treated vs control) Relative risk of event (treated vs control) Relative risk of event (treated vs control)
Stroke 0.64 0.67 0.67 0.58 0.53 0.75 0.43
CAD 0.80 0.73 0.73 0.74 0.87 0.81
CHF 0.78 0.45 0.45 0.71 0.49 0.32
All CVD 0.71 0.68 0.68 0.69 0.60 0.83 0.40
49
??t??pe?tas??? a???? ??a?t? e???????? fa?µ????
S?st?????-??ast????? ?? ??a?t? ISH
ESC/ESH 2003
S?st?????-??ast????? ?? S?st?????-??ast????? ?? ?eµ???µ??? S?st????? ?? ?eµ???µ??? S?st????? ??
?e??s? ???d???? P ?e??s? ???d???? P
T??s?µ?t?ta
S??????? -14 lt0.01 -13 0.02
?a?d?a??e?a?? -21 lt0.001 -18 0.01
??-?a?d?a??e?a?? -1 NS NS
Ta?at?f??a ?a? µ? s?µß?µata Ta?at?f??a ?a? µ? s?µß?µata
???efa???? -42 lt0.001 -30 lt0.001
Stefa??a?a -14 lt0.01 -23 lt0.001
50
??a f??µa?a vs pa?a?? f??µa?a
Primary Endpoint (RR 95 CI)
CAPPP captopril p0.52 (n10.985) Lancet
1999 STOP-2 ACEIs/CCBs p0.89 (n6.614) Lancet
1999 NORDIL diltiazem p0.97 (n10.948) Lancet
2000 INSIGHT nifedipine GITS p0.34 (n6.321)
Lancet 2000 ALLHAT doxazosin p0.71 (n24.335)
JAMA 2000 Favours Diuretics / ß-Blockers
Favours New Drugs
0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0
Kjeldsen SE, Westheim A, Os I. Lancet
20003561929-30.
51
A comparison of outcomes with ACE- I and
diuretics for hypertension in the elderly

6083 HTN pts, Age 65-84 yrs, follow-up 4 yrsBP reduction 26/12 mm Hg in both groups 6083 HTN pts, Age 65-84 yrs, follow-up 4 yrsBP reduction 26/12 mm Hg in both groups 6083 HTN pts, Age 65-84 yrs, follow-up 4 yrsBP reduction 26/12 mm Hg in both groups 6083 HTN pts, Age 65-84 yrs, follow-up 4 yrsBP reduction 26/12 mm Hg in both groups 6083 HTN pts, Age 65-84 yrs, follow-up 4 yrsBP reduction 26/12 mm Hg in both groups
Event ACE-I Diuretic RR plt
All CV event or death 695 736 0.89 .05
First CV event or death 490 529 0.89 .06
MI 58 82 0.68 .04
HF 69 78 0.85 NS
Stroke 112 107 1.02 NS
Wing LM, et al. N Engl J Med 2003 Feb 13
52
??t??pe?tas??? a???? ?e??s? ???d???? ??a
???efa????

• St?? µe??te?
• Blood Pressure, Stroke and Coronary Heart Disease
  II 1
• µe??s? t?? ??ast?????? ?? ?at? 5-6 mm Hg e??e
  ?? ap?t??esµa
• 42 µe??s? t?? s?µßaµ?t?? ???efa????? epe?s?d???
• 45 µe??s? t?? ?a?at?f???? ???efa????? epe?s?d???
• Swedish Trial in Old Patients with Hypertension
  (STOP) 2
• 47 µe??s? t?? ???efa????? epe?s?d??? se as?e?e??
  gt70 ??????
• Systolic Hypertension in the Elderly Program
  (SHEP) 3
• 11 mm Hg µe??s? t?? S?st?????? ?? ?a? 3-4 mm Hg
  µe??s? t?? ??ast?????? ?? e??e ?? ap?t??esµa
• 36 µe??s? sta s?µß?µata ???efa????? epe?s?d???

1 Collins, et al. Lancet 1990 335827-838 2
Dahlof, et al. Lancet 1991 338 1281-85 3 SHEP
JAMA 1991 2653255-3264
53
?e????a a??e?a?? s?µß?µata ???, ??? ? ???at??
?a?d?a??e?a??? a?t??????a?
26 risk reduction
p lt 0.0001
54
AEE s?µf??a µe t?? a????? ??
(s??d?asµ??)
??ast??? placebo
?e??s?
106 87 62
47 42 39
57 54 39
S?? gt 160 S?? 140-160 S?? lt 140
27 65 56
60 99 89
62 36 37
??? gt 95 ??? 85-94 ??? lt 85
150
255
43
S?????
55
LIFE ISH Fatal/Nonfatal Stroke
40
Risk Reduction 40 Adjusted p-value 0.020
SE Kjeldsen et al data on file.
56
Cumulative Event Rates for the Primary Outcome
(Fatal CHD or Nonfatal MI) by ALLHAT Treatment
Group
RR (95 CI) p value
A/C 0.98 (0.90-1.07) 0.65
L/C 0.99 (0.91-1.08) 0.81
Chlorthalidone Amlodipine Lisinopril
57
BP Results by Treatment Group
Compared to chlorthalidone SBP significantly
higher in the amlodipine group (1 mmHg) and the
lisinopril group (2 mmHg).
Compared to chlorthalidone DBP significantly
lower in the amlodipine group (1 mm Hg).
58
Cumulative Event Rates for Strokeby ALLHAT
Treatment Group
RR (95 CI) p value
A/C 0.93 (0.81-1.06) 0.28
L/C 1.15 (1.02-1.30) 0.02
59
?a?a?? vs ??a a?t??pe?tas??? ep?d?as? sta ???

• 120.574 ?pe?tas????
• 15 µe??te?
• ??s? ??a µe?a??te?? p??stas?a µe t???
  a?ta????st?? asßest???
• Staessen et al, J Hypertens 2003211005-1076

60
SCOPE ?p??µ?da µe ISH Ta?at?f??a(/-)
???
Proportion of patients ()
7
6
Control
5
Candesartan
4
3
2
Un-adjusted risk reduction42.3,
p0.050 Adjusted risk reduction42.5, p0.049
1
0
0
6
12
18
24
30
36
42
48
60
54
Months
Numbers at risk
Cand (n) 754 752 722 696 488 126Control (n)
764 753 731 701 474 132
61
Hypertensive subgroup analysis
ACTION
Significant reductions in composite endpoints (2)
Primary efficacy endpoint
Primary safety endpoint
Any CV event
All patients
Death, any CV event or procedure
Normotensive
Hypertensive
Any vascular event or procedure
0.6
1
1.2
1.4
0.8
Hazard ratio (95 CI)
Favours nifedipine GITS
Favours placebo
62
???a e??a? ? asfa??? t?µ? t?? ??? ?e?ape???ta?
t?? ISH

• ?p???e? ?aµp??? J?
• SHEP St??? as?e?e?? p?? e??µßa?a? e?e???
  ?e?ape?a ? ?aµ??? ??? (lt55mmHg) s??d???ta? µe
  a???µ??? ep?pt?s? ??? ?a? S? µet? ap? d?????s?
  ??a µ?a se??? d?µ???af???? ?a? ????????
  ?a?a?t???st????.
• St??? as?e?e?? p?? de? e??µßa?a? e?e??? ?e?ape?a
  de? pa?at??????e t?t??a s?s??t?s?
• Somes et al, Arch Intern Med 19991592004-2009

63
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64
??t??pe?tas??? a???? ?pe?tas???? ?ap??st?? JHH
200321697-700
??? Study
Se µ? ?ap??st?? µ? pa?at???s? J ?aµp????
Se ?ap??st?? ? ?a?d?a??e?a??
???t?t?ta ? a?f??d??? ???at?? ? ??? st?? ?µ?da
t?? ?aµ???te??? ??? (lt80-85mmHg)
65
??de??e?? ?a? a?te?de??e?? ??a t?? ?at?????e?
a?t??pe?tas???? fa?µ????
??te?de??e?? ??te?de??e??
?at?????a ??de??e?? p?? e??????t? ???s? ?p???e?t???? ???a???
??????t??? (?e?a??d???) S?µf???t??? ?a?d?a?? a?ep???e?a,??????µ????, µeµ???µ??? s?st????? ?p??tas?, ?pe?tas???? ?f???a????? ?ata????? ?????? a????t?da
??????t???(t?? a??????) ?ef???? a?ep???e?a, s?µf???t??? ?a?d?a?? a?ep???e?a
??????t???(??t.a?d/?????) S?µf???t??? ?a?d?a?? a?ep???e?a, µet? ap? ?µf?a?µa µ???a?d??? ?ef???? a?ep???e?a,?pe??a??a?µ?a
66
??de??e?? ?a? a?te?de??e?? ??a t?? ?at?????e?
a?t??pe?tas???? fa?µ????
??te?de??e?? ??te?de??e??
?at?????a ??de??e?? p?? e??????t? ???s? ?p???e?t???? ???a???
ß-ap???e?st?? St??????, µet? ap? ?µf?a?µa µ???a?d???, s?µf???t??? ?a?d?a?? a?ep???e?a (t?t??p???s?), ta??a????µ?e? ?s?µa, ?????a ap?f?a?t??? p?e?µ???p?-?e?a, ???p?-?????a??? ap???e?sµ?? (ßa?µ?? 2 ? 3) ?e??fe???? a??e??p??e?a, d?sa?e??a st? ???????, ?a? s?µat??? d?ast????? as?e?e??
67
??de??e?? ?a? a?te?de??e?? ??a t?? ?at?????e?
a?t??pe?tas???? fa?µ????
??te?de??e?? ??te?de??e??
?at?????a ??de??e?? p?? e??????t? ???s? ?p???e?t???? ???a???
??ta????st?? asßest???(d??d??p???d??e?) ??????µ???? as?e?e??, µeµ???µ??? s?st????? ?p??tas?, st??????, pe??fe???? a??e??p??e?a, ?a??t?d??? a????s??????s? ?a??a????µ?e?, s?µf???t??? ?a?d?a?? a?ep???e?a
68
??de??e?? ?a? a?te?de??e?? ??a t?? ?at?????e?
a?t??pe?tas???? fa?µ????
??te?de??e?? ??te?de??e??
?at?????a ??de??e?? p?? e??????t? ???s? ?p???e?t???? ???a???
??ta????st?? asßest???(verapamil, diltiazem) St??????, ?a??t?d??? a????s??????s?, ?pe??????a?? ta???a?d?a ???p??????a??? ap???e?sµ?? (ßa?µ?? 2 ? 3), s?µf???t??? ?a?d?a?? a?ep???e?a
69
??de??e?? ?a? a?te?de??e?? ??a t?? ?at?????e?
a?t??pe?tas???? fa?µ????
??te?de??e?? ??te?de??e??
?at?????a ??de??e?? p?? e??????t? ???s? ?p???e?t???? ???a???
??ast??e?? µetat?ept???? e???µ?? a??e??tas???? (????) S?µf???t??? ?a?d?a?? a?ep???e?a, d?s?e?t?????a a??ste??? ?????a?, µet? ap? ?µf?a?µa µ???a?d???, µ? d?aß?t??? ?ef??p??e?a, d?aß?t??? t?p?? 1 ?ef??p??e?a, p??te??????a Ype??a??a?µ?a, aµf?p?e??? st???s? ?ef????? a?t???a?
70
??de??e?? ?a? a?te?de??e?? ??a t?? ?at?????e?
a?t??pe?tas???? fa?µ????
??te?de??e?? ??te?de??e??
?at?????a ??de??e?? p?? e??????t? ???s? ?p???e?t???? ???a???
??ta????st?? ?p?d????? a??e??tas???? II (AT1-ap???e?st??) ??aß?t??? t?p?? 2 ?ef??p??e?a, d?aß?t??? µ????a?ß??µ??????a, p??te??????a, ?pe?t??f?a a??ste??? ?????a?, ß??a? ???? a?ast???a t?? ??? Ype??a??a?µ?a, aµf?p?e??? st???s? ?ef????? a?t???a?
71
??de??e?? ?a? a?te?de??e?? ??a t?? ?at?????e?
a?t??pe?tas???? fa?µ????
??te?de??e?? ??te?de??e??
?at?????a ??de??e?? p?? e??????t? ???s? ?p???e?t???? ???a???
a-ap???e?st?? ?pe?p?as?a p??st?t? (BPH), ?pe???p?da?µ?a ????stat??? ?p?tas? S?µf???t??? ?a?d?a?? a?ep???e?a
72
????t??? e?e??et???? d??se?? t?? a?t??pe?tas????

• ?a ?e?a??d??? d?????t??? e??a? ???s?µa st??
  ?a??st???s? t?? ?ste?p???s??
• ?? BBs ???s?µ?? se pe??pt?se?? ???p????
  ta??a????µ???, ?µ???a??a?, ?pe????e?e?d?sµ??,
  ?d??pa???? t??µ??, pe??e??e???t???? ??
• ?? CCBs ???s?µ?? se pe??pt?se?? s??d??µ??
  Raynauds ?a? a????µ???
• ?? Alpha-blockers ???s?µ?? se ?pe?t??f?a p??st?t?

JNC VII
73
???µ?s? t?? ??
??se?? st?? ep????s?, ?e?ape?a ?a? ???µ?s? t??
?????? ?? se e?????e? 18-74 et??
National Health and Nutrition Examination Survey, Percent National Health and Nutrition Examination Survey, Percent National Health and Nutrition Examination Survey, Percent National Health and Nutrition Examination Survey, Percent
II 197680 II (Phase 1) 198891 II (Phase 2) 199194 19992000
?p????s? 51 73 68 70
Te?ape?a 31 55 54 59
???µ?s? 10 29 27 34
Sources Unpublished data for 19992000 computed
by M. Wolz, National Heart, Lung, and Blood
Institute JNC 6.
JNC VII
74
SCOPE Subgroup with ISH Fatal/non-fatal strokes
Proportion of patients ()
7
6
Control
5
Candesartan
4
3
2
Un-adjusted risk reduction42.3,
p0.050 Adjusted risk reduction42.5, p0.049
1
0
0
6
12
18
24
30
36
42
48
60
54
Months
Numbers at risk
Cand (n) 754 752 722 696 488 126Control (n)
764 753 731 701 474 132
Papademetriou et al
75
Differential Control of SBP and DBP
100
P0,013
80
60
P0,049
P0,034
Controlled
40
20
0
DBP Goal
SBP Goal
DBP Goal
SBP and
Men Women
Lloyd Jones Hypertension 2000
76
CONTROL OF SYSTOLIC BLOOD PRESSURE

• MRFIT, HOT DBP gt 90 SBP lt 60
• Neaton JD. Arch Intern Med 1992
• Hannson L. Lancet 1998
• Value 2000 DBP gt 91 SBP lt 50
• 2001 DBP gt 92 SBP 62

77
???µ?s? ??
Lloyd Jones D et al. Hypertension
200036594-599
78
?????? s??d?asµ???? ?e?ape?a? ??a ep?te??? t??
t?µ?? st????
?e??t? ?? st???? (mm Hg)
UKPDS ??? lt85
ABCD ??? lt75
MDRD MAP lt92
HOT ??? lt80
AASK MAP lt92
DBP Diastolic Blood Pressure MAP Mean
Arterial Pressure.
Bakris GL et al. Am J Kidney Dis. 200036646-661
79
??t??pe?tas??? a???? st??? ??????µ?????

• ?? t??a??p???µ??e? e?e???µe?e? µe??te? de?
  af????? p????? aµf?ß???e? ?t? ?? p?? ??????µ????
  as?e?e?? µe s?st?????-d?ast????? ? µeµ???µ???
  s?st????? ?p??tas? ep?fe????ta? ap? t??
  a?t??pe?tas??? a????, ?? p??? t? µe??µ???
  ?a?d?a??e?a?? ??s???t?ta ?a? ???s?µ?t?ta.
• ? ??a??? a?t??pe?tas???? a????? se ??????µ?????
  as?e?e?? p??pe? ?a a??????e? t?? ?e?????
  ?ate????t???e? ?d???e?, a??? ?a p??pe? ?a e??a?
  ?d?a?te?a stad?a??, ?????? se e?pa?? ?t?µa.
• ? µ?t??s? t?? ?? p??pe? ep?s?? ?a ???eta? se
  ????a ??s?, ??a ?a ap???e???ta? ?? as?e?e?? µe
  ??t??? ?p?tas? ??s?? ?a? ?a a??????e?ta? ?
  ep?d?as? t?? a????? a?????a µe t? ??s? t??
  s?µat??.

80
??t??pe?tas??? a???? st??? ??????µ?????

• ?????? ??????µ???? as?e?e?? ?a ????? ??????
  pa?????te? ???d????, ß??ß? ??????? st???? ?a?
  s???d?? ?a?d?a??e?a??? pa??se??, sta ?p??a p??pe?
  ?a p??sa?µ??eta? ? ep????? t?? p??t?? fa?µ????.
• ?????? ??????µ???? as?e?e?? ?a ??e?as???? d?? ?
  pe??ss?te?a f??µa?a ??a t?? ???µ?s? t?? ??,
  ?d?a?te?a af?? e??a? s???? d?s???? ?a µe???e? ?
  s?st????? ?? se ep?peda ??t? t?? 140 mmHg.
• Se ?,t? af??? ?t?µa ?????a? 80 et?? ?a? ???, µ?a
  p??sfat? µeta-a????s? ?at????e ?t? ta µ???a?a ?a?
  µ? µ???a?a ?a?d?a??e?a?? epe?s?d?a, a??? ??? ?a?
  ? ???s?µ?t?ta, µe?????ta? µe t?? a?t??pe?tas???
  a????.

81
???G?OSS?? ??F??????? ? ???????? ?O? ??
????G???O? ??

• Fa???µe?? ?p????p??
• ???ß??µat??? ??????s?
• a) St???s? ?a??t?d??
• ß) ?µf?a?µa µ???a?d???
• ?) LVH µe µ???? ?????t?ta a??ste??? ?????a?.

82
??t?µet?p?s? ?p??tas?? st??? ??????µ????? (I)

• ? a?t??pe?tas??? ?e?ape?a t?? ??????µ???? as?e???
  µe s?st?????-d?ast????? ?? ? µeµ???µ??? s?st?????
  ??, pa???s???e? s?µa?t??? ?f??? ?a??t? e?att??e?
  t?? ?a?d?a??e?a?? ??s???t?ta ?a? ???s?µ?t?ta.
• ? ??a??? t?? a?t??pe?tas???? ?e?ape?a? p??pe? ?a
  a??????e? t?? ?e????? ?d???e?, a??? ?? pe?a?t???
  µetaß???? st?? a???? p??pe? ?a ?????ta? stad?a??,
  e?d??? se e?as?e??µ??a ?t?µa.
• ?d?a?te?? p??s??? st?? a???ß? µ?t??s? t?? ??

83
??t?µet?p?s? ?p??tas?? st??? ??????µ????? (I?)

• ?e??s? t?? S?? se ep?peda lt140 mmHg p??pe? ?a
  e??a? ? p??ta?????? st????
• ?????? ??????µ???? as?e?e?? pa???s?????? ?a?
  ?????? pa?????te? ???d????, ??S ?a? S??. ?
  ep????? t?? p??t?? a?t??pe?tas???? s?e??sµat??
  p??pe? ?a ???eta? af?t?? ??f???? ?p???? ta
  p??????µe?a.
• ???et?? ??????µ???? as?e?e?? ??e?????ta? 2 ?
  pe??ss?te?a f??µa?a ??a t?? ??e??? t?? ??, af??
  e??a? s???? d?s???? ?a µe???e? ? S?? lt140 mmHg.
• .

84
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