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Wasan Udayachalerm, MA, FAPSIC!
Overview!
When a patient’s systolic and diastolic blood pressures fall into different categories,
the higher category should apply for quantification of CV risk, decisions about drug ESH/ESC Guidelines 2007. !
2008 update treatment and estimation of treatment efficacy!
Eur Heart J 2007;28:1462-1536!
Definition and classification of
hypertension: ESH/ESC 2007!
Women
40
Total
20
Ong LK, et al. Hypertension 2007;49:69-75; Tu K, et al. CMAJ 2008;178:1429-1435; World Health Organization Global
2008 update Infobase; Macedo ME, et al. J Hypertens 2005;23:1661-1666; CÍfková R, et al. J Hypertens 2004;22:1479-1485 !
Prevalence of hypertension*: Asia!
* BP ≥140/90 mmHg or treatment with antihypertensive medication !
60
Prevalence (%)
Men Women
40
20
# Data for Hong Kong are crude prevalence; all other data are age-adjusted prevalence!
Dates in square brackets are publication date, all others are survey date !
Martiniuk ALC, et al. J Hypertens 2007;25:73–79; National Health Survey 2004, Singapore. Epidemiology and Disease
Department, Ministry of Health, Singapore.; Rampal L, et al. Public Health 2008;122:11-18; Philippines Facts and
2008 update Figures 2003. Part I. Clinical Facts and Figures. National Nutrition and Health Survey (NNHes 2003-2004)!
Prevalence of hypertension:
Other countries!
60
Men
Women
Prevalence (%)
40 Total
20
Ordunez P, et al. Pan Am J Public Health 2001;10:226-231; Cubillos-Garzon LA, et al. Am Heart J 2004;147:412-417;
Israel Centre for Disease Control. MABAT: First Israeli National Health and Nutrition Survey 1999-2001, 2003,
2008 update Personal communication: Dorit Nitzan Kaluski!
Projected increase in hypertension by 2025!
India!
China!
Sub-Saharan Africa!
Ong LK, et al. Hypertension 2007;49:69-75 ; Wang YR, et al. Arch Intern Med 2007;167:141-147; Choi KM, et al. J Hypertens
2006;24:1515-1521; Wang Z, et al. Hypertens Res 2004;27:703-709; CÍfková R, et al. J Hypertens 2004;22:1479-1485;
Aekplakorn W, et al. J Hypertens 2008 ;26:191-198; Rampal L, et al. Public Health 2008 ;122:11-18; !
2008 update Hathial M. J Indian Med Assoc 2007;105:401-402, 404, 410 !
National Health and Nutrition
Examination Survey (NHANES) !
Trends in awareness, treatment and control of
high blood pressure in adults aged 18-74*!
II! III! III ! ! ! !
(1976-80)! (Phase 1 (Phase 2 1999-2000! 2001-2002! 2003-2004!
1988-91)! 1991-94)!
! ! ! ! ! ! !
Awareness! 51%! 73%! 68%! 63%! 63%! 67%!
! ! ! ! ! ! !
Treatment! 31%! 55%! 54%! 47%! 50%! 54%!
! ! ! ! ! ! !
Control†! 10%! 29%! 27%! 25%! 30%! 33%!
59
60 55 54
51
%
40 34
31 29
27
20
10
0
1976-1980 1988-1991 1991-1994 1999-2000
BP, blood pressure; CVD, cardiovascular disease! JNC VII. JAMA 2003;289:2560-2572!
Hypertension: A risk factor for
cardiovascular disease!
Coronary
Stroke! Peripheral artery
Cardiac
disease! disease! failure!
50
45.5
45
Biennial age-adjusted rate !
40
per 1,000 subjects!
35 Normotensive
30 Hypertensive
25 22.7
21.3
20
13.9
15 12.4
9.5 9.9
10 7.3 6.3
6.2 5.0
5 3.3 2.4 3.5
2.0 2.1
0 Men Women Men Women Men Women Men Women
Risk
ratio:! 2.0! 2.2! 3.8! 2.6! 2.0! 3.7! 4.0! 3.0!
0.0
β(SBP)
- -0.5 p=0.008!
β(DBP)
* Favours
-1.0
DBP!
-1.5
25 35 45 55 65 75
Age (years)
* The difference between SBP and DBP proportional hazard regression
coefficients, ie, β(SBP) - β(DBP), was estimated for each age group!
!
SBP, systolic blood pressure; DBP, diastolic blood pressure;
CHD, coronary heart disease! Franklin SS, et al. Circulation 2001;103:1245-1249!
Impact of high-normal BP on CV risk!
16!
14! Men! High-normal BP!
Cumulative 12!
10! Normal BP!
incidence of 8!
CV events
6! Optimal BP!
(%)! 4!
2!
0!
12!
Women!
Cumulative 10! High-normal BP!
incidence of 8!
CV events
6!
4! Normal BP!
(%)!
2!
Optimal BP!
0!
0! 2! 4! 6! 8! 10! 12!
Years!
Optimal BP: <120/80 mmHg; normal BP: 120-129/80-84 mmHg;
high-normal BP: 130-139/85-89 mmHg!
!
BP, blood pressure; CV, cardiovascular! Vasan RS, et al. N Engl J Med 2001;345:1291-1297!
Implications of small reductions in DBP
for primary prevention!
DBP reduction
-10 -6
Risk reduction (%)
-16 -15
-20
-21
-30
-40 CHD
-38
Stroke
-50 -46
DBP, diastolic blood pressure; CHD, coronary heart disease Cook NR, et al. Arch Intern Med 1995;155:701-709!
Comparison of tight BP vs tight glucose
control in UKPDS!
Any diabetes-! Microvascular! Diabetes-related!
Stroke! related endpoint! endpoints! deaths!
0!
-10!
Risk reduction (%)!
†!
-20!
*! †!
-30!
*!
-40! *!
Tight glucose control!
*! Tight BP control!
-50!
* p<0.02, tight BP control (achieved BP 144/82 mmHg) vs less tight control (achieved BP 154/87 mmHg).!
† p<0.03, intensive glucose control (achieved HbA 7.0%) vs less intensive control (achieved HbA 7.9%).!
1c 1c
BP, blood pressure; UKPDS, United Kingdom Prospective Diabetes Study! UKPDS 38. BMJ 1998;317:703-713;!
UKPDS 33. Lancet 1998;352:837-853!
Steno-2: Patients who reached intensive-
treatment goals at a mean of 7.8 years!
80 Good BP control
Intensive reduces risk of
p=0.21!
p<0.001!
70 therapy cardiovascular events
Conventional p=0.19!
60
Patients (%)
therapy
50 p=0.001!
40
30
20 p=0.06!
10
0
HbA1c! Cholesterol! Triglycerides! Systolic BP! Diastolic BP!
<6.5%! <175 mg/dL! <150 mg/dL! <130 mmHg! <80 mmHg!
BP, blood pressure! Gaede P, et al. N Engl J Med 2003;348:383-393!
Steno-2: Composite CV endpoints!
60
p=0.007 Conventional therapy
50 BP 146/78 mmHg
Primary composite
endpoint* (%)
Hazard ratio=0.47
40 (95% CI, 0.24 to 0.73; p=0.008)
30
20
Intensive therapy
10 BP 132/73 mmHg
0
0 12 24 36 48 60 72 84 96
Months of follow-up
* Primary composite endpoint = composite of death from cardiovascular (CV) causes,
nonfatal myocardial infarction, nonfatal stroke, revascularization and amputation! Gaede P, et al. N Engl J Med 2003;348:383-393!
Section 5: Treatment Guidelines!
Treatment guidelines!
2008 update
Treatment initiation: ESH/ESC 2007!
Blood pressure!
SBP !140 or! SBP <140 or! SBP !150 or! SBP <150 or!
DBP !90 –! DBP <90 –! DBP !95 –! DBP <95!
Begin drug! Continue to ! Begin drug! (borderline) –!
treatment! monitor! treatment! Continue to !
monitor!
SBP, systolic blood pressure; DBP, diastolic blood pressure;
TOD, target organ damage; ACC, associated clinical conditions, 1999 WHO/ISH Guidelines for the Management of Hypertension.!
including cardiovascular disease and renal disease! J Hypertens 1999;17:151-183!
Treatment guidelines!
2008 update
Goals of treatment: ESH/ESC 2007!
• Achieve maximum reduction in total
cardiovascular risk !
• Treat all reversible risk factors and associated
clinical conditions in addition to treating raised
blood pressure!
• Target blood pressure <140/90 mmHg and to
lower values, if tolerated!
• For those with diabetes or a history of
cerebrovascular disease, target blood pressure
is <130/80 mmHg!
– this target should also be considered in
patients with coronary disease!
Mancia G, et al. Eur Heart J 2007;28:1462-1563!
2008 update
Goals of treatment: JNC VII!
2008 update
Hypertension treatment strategy: ESH/
ESC 2007!
Consider:!
Untreated BP level!
Presence or absence of TOD and risk factors!
Mild BP elevation Marked BP elevation
Low/moderate CV risk High/very high CV risk
Conventional BP target Choose between:! Lower BP target
Optimize dosages or add additional drugs until goal blood pressure is achieved.!
Consider consultation with hypertension specialist.!
SBP, systolic blood pressure; DBP, diastolic blood pressure; ACE-I,
angiotensin-converting enzyme inhibitor; ARB, angiotensin II JNC VII. JAMA 2003;289:2560-2572!
receptor blocker; BB, beta-blocker; CCB, calcium-channel blocker!
Hypertension treatment strategy:
WHO/ISH 2003!
!
Step 1 A
C or D
Step 2 A + C or A + D
Step 3 A + C + D
AT1! AT2!
êBP!
• Vasoconstriction! • Vasodilation!
• Aldosterone secretion! • Inhibition of cell growth!
• Catecholamine release! • Cell differentiation!
• Proliferation! • Injury response!
• Hypertrophy! • Apoptosis!
Ellis ML, et al. Pharmacotherapy 1996;16:849-860;!
BP, blood pressure Carey RM, et al. Hypertension 2000;35:155-163!
Inhibition of the RAAS by ACE inhibitors!
ACE
Angiotensinogen!
(-)! inhibitor!
Renin!
Angiotensin I! Bradykinin!
Non- Angiotensin-!
Non-
renin! converting !
ACE! enzyme!
Angiotensin II! Inactive kinins!
AT1! AT2!
!B
• Vasoconstriction! • Vasodilation!
P! • Aldosterone secretion! • Inhibition of cell growth!
• Catecholamine release! • Cell differentiation!
• Proliferation! • Injury response!
• Hypertrophy! • Apoptosis!
RAAS, renin-angiotensin-aldosterone system; Ellis ML, et al. Pharmacotherapy 1996;16:849-860;!
ACE, angiotensin-converting enzyme; BP, blood pressure Carey RM, et al. Hypertension 2000;35:155-163!
Inhibition of the RAAS by ARBs!
Angiotensinogen
Renin
Angiotensin I Bradykinin
Angiotensin-!
converting !
enzyme!
ARB!
BP AT1 AT2
Efficacy!
+!
Adverse effects!
+!
Convenience!
Dose-related efficacy and
side-effect profile!
• Antihypertensive efficacy generally improves with
an increase in dose!
• Common side effects associated with:!
! ACE inhibitors – cough!
! CCBs – ankle oedema, flushing!
! Beta-blockers – tiredness, impotence!
• ARBs have demonstrated placebo-like tolerability
even at higher doses!
ACE, angiotensin-converting enzyme;
CCB, calcium-channel blocker; ARB, angiotensin II receptor blocker!
Compliance at 1 year with
antihypertensive treatment!
70!
64!
*
* p<0.007 vs ACE inhibitors
58!
Compliance at 1 year (%)!
60!
50!
50!
43!
40! 38!
30!
20!
10!
0!
Diuretics! Beta-blockers! CCBs! ACE inhibitors! ARBs!
60! *
* p<0.007 vs ACE inhibitors 51.9!
Treatment persistence (%)!
50! 48.0!
40.3!
40! 38.3!
29.9!
30!
20!
10!
0!
Diuretics (n=34,934)! CCBs (n=36,246)! Beta-blockers ACE inhibitors ARBs (n=10,245)!
(n=82,241)! (n=78,616)!
CKD
New risk factors
2008 update Ruilope L. ESH Annual Meeting 2007; June 15-19, 2007; Milan, Italy