1. TATALAKSANA HIPERTENSI OPTIMAL UNTUK MENCEGAH STROKE
Dr. Sapto Priatmo, Sp.PD
RS BETHESDA YOGYAKARTA
4 November 2017

2. HIPERTENSI
Suatu keadaan klinis dimana tekanan darah seseorang lebih tinggi daripada tekanan darah normal (>140/90 mmHg)
Epidemiologi :
Jumlah penderita hipertensi di seluruh dunia : 1 milyar
USA : 65 juta
Indonesia: 27,6% (SKRT, 2004)
Conlin PR, Int J Clin Pract 2005; 59(2):214-24

3. Klasifikasi tekanan darah (JNC VII)
BP category
SBP (mmHg)
DBP (mmHg)
Normal
<120
and
<80
Pre-hypertension
120–139
and/or
80–89
Stage 1
140–159
90–99
Stage 2
> 160
> 100
This slide shows the categories of BP and the DBPs/SBPs (mmHg) associated with them, as defined by the US treatment guidelines: JNC VII.1
According to these guidelines, hypertension is defined as a systolic pressure of 140 mmHg or higher and/or a DBP of 90 mmHg or higher (for an extended time).1
In contrast to the JNC VI guidelines, a new category designated ‘pre-hypertension’ has been added and stages 2 and 3 hypertension have been combined.1 Patients with pre-hypertension are at increased risk of progression to hypertension.2
References
Chobanian AV, et al. Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. JAMA. 2003;289:2560−2572.
Schunkert H. Pharmacotherapy for prehypertension − mission accomplished? N Engl J Med. 2006;354:1742−1744.
Chobanian et al. JAMA. 2003;289:2560−2572.

4. Definitions and classification of office BP levels (mmHg)*
Hypertension:
SBP >140 mmHg ± DBP >90 mmHg
Category
Systolic
Diastolic
Optimal
<120
and
<80
Normal
120–129
and/or
80–84
High normal
130–139
85–89
Grade 1 hypertension
140–159
90–99
Grade 2 hypertension
160–179
100–109
Grade 3 hypertension
≥180
≥110
Isolated systolic hypertension
≥140
<90
* The blood pressure (BP) category is defined by the highest level of BP, whether systolic or diastolic. Isolated systolic hypertension should be graded 1, 2, or 3 according to systolic BP values in the ranges indicated.

5. JNC 8 No definition of HT <120 a ./or 80-84 120-139 o r 90-99
CLASSIFICATION HYPERTENSION BP
SBP
DBP
Optimal
<120
and
<80 BP
SBP
DBP
Normal
<120 a
nd <80
Pre HT o
r 80-89
Stg 1 o
r 90-99
Stg 2
≥160 o
r ≥100
Normal
and
./or 80-84
High Normal
85-89
HT stg 1
90-99
HT stg 2
HT stg 3
≥180
≥110
ISH
≥140
<90
and BP
SBP
DBP
JNC 8
No definition of HT
Optimal
<120
and
<80
Normal
<130 and
<85
High Nml o r
85-89
HT stg 1 o
r 90-99
HT stg 2 o r
HT stg 3
≥180 or
≥110

6. Prevalensi hipertensi dunia
This slide shows the high prevalence of hypertension, indicating the substantial need for both prevention and better pharmacologic control of hypertension.
Data from national sample surveys were analyzed to provide age- and sex-adjusted estimates of BP and prevalence of hypertension at the standard threshold (BP ≥ 140/90 mmHg or treatment with antihypertensive medication) by country and region (Europe compared with North America).1
The prevalence of hypertension was highest in Germany (55%), followed by Finland (49%), Spain (47%), England (42%), Sweden (38%) and Italy (38%). Prevalence in the United States was half of the rate in Germany (28%; as was the rate in Canada [27%; Canada data not shown on slide]). The prevalence of hypertension for the European average was markedly higher at 44.2% compared to 27.6% in North America.1 Another study in Japan found the prevalence to be high at 49% across the adult population over the age of 30 years.2
The pattern of higher BP measurements and hypertension prevalences is strongly correlated with death rates from stroke, the CV condition with the highest RR from hypertension.1
References
Wolf-Maier K, et al. Hypertension prevalence and blood pressure levels in 6 European countries, Canada, and the United States. JAMA. 2003;289:2363–2369.
Sekikawa A, Hayakawa T. Prevalence of hypertension, its awareness and control in adult population in Japan. J Hum Hypertens. 2004; 2004;18:911–912.
Prevalence of hypertension (%) US
Italy
Sweden
England
Spain
Finland
Japan*
Germany
Adults aged 35–64 years (data are age- and sex-adjusted), except* (adults aged ≥ 30 years)
Hypertension defined as BP ≥ 140/90 mmHg or on treatment
Wolf-Maier et al. JAMA. 2003;289:2363−2369; Sekikawa, Hayakawa. J Hum Hypertens. 2004; 2004;18:911–912.

7. Prevalensi hipertensi meningkat dengan pertambahan usia
Women
This slide shows the results of an analysis of worldwide data (from published literature dated 1980 to 2002) on the prevalence of hypertension (age- and gender-specific).1
Hypertension was defined as SBP ≥ 140 mmHg, or DBP ≥ 90 mmHg or the use of antihypertensive medication. Only data for the established market economies (i.e., Australia, Canada, England, Germany, Greece, Italy, Japan, Spain, Sweden, USA) are given on this slide. Other data (not shown) are available for former socialist economies (Slovakia), India, Latin America and the Caribbean, Middle East, Asia and sub-Saharan Africa.1
As illustrated, the prevalence of hypertension increases with advancing age. At young ages, the prevalence was higher in males than in females; from age 60 years; however, the trend was reversed, with prevalence higher in women than in men. The reasons for gender differences in BP are not known, although it has been suggested (but not proven) that oestrogen may be responsible for lower BP in younger women.2
References
Kearney PM, et al. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365:217−223.
August P, et al. Hypertension in women. J Clin Endocrinol Metab. 1999;84:1862–1866.
Prevalence of hypertension (%)
20-29
30-39
40-49
50-59
60-69 70
Age (Years)
Data for established market economies: Australia, Canada, England, Germany, Greece, Italy, Japan, Spain, Sweden, USA
Kearney et al. Lancet. 2005;365:217−223.

8. Komplikasi hipertensi
Eyes
retinopathy
Brain
stroke
Target Organ damage!!
Damages depend on:
How high of the blood pressures
How long the uncontrolled and untreated high blood presure
Heart
ischaemic heart disease
Kidneys
left ventricular hypertrophy
renal failure
heart failure
Peripheral arterial disease

9. © Continuing Medical Implementation …...bridging the care gap

10. Fold increase in relative CV risk
Risiko mortalitas meningkat 2x dengan peningkatan tekanan darah 20/10 mmHg
SBP/DBP (mmHg)
8 X
8-fold
Fold increase in relative CV risk
This slide shows that if hypertension is left uncontrolled, patients are at a higher risk for CV death.1
A meta-analysis of individual data from 1 million adults without previous vascular disease from 61 prospective observational studies of BP and mortality addressed the cause-specific death rate during a 10-year period among people who were initially aged 40, 50, 60, 70 or 80 years.1
The findings indicated that the risk for CV mortality doubles with each 20/10 mmHg increase in BP. Furthermore, the rise in CV mortality was directly related to higher initial BP in every group. With a 20 mmHg higher SBP or a 10 mmHg higher DBP, mortality from ischaemic heart disease was two-fold higher and mortality from stroke was greater than two-fold higher.1
These results indicate that both SBP and DBP were strongly related to vascular mortality in middle and old age.
Reference
Lewington S, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903−1913.
4 X
2 X
1 X
115/75
135/85
155/95
175/105
Meta-analysis of 61 prospective, observational studies
1 million adults aged 40–69 years with BP > 115/75 mmHg
12.7 million person–years
Lewington et al. Lancet. 2002;360:1903–1913.

11. 2 mmHg decrease in mean SBP
Penurunan tekanan darah sistolik 2 mmHg menurunkan risiko mortalitas 7-10%
Meta-analysis of 61 prospective, observational studies
1 million adults aged 40–69 years with BP > 115/75 mmHg
12.7 million person-years
7% reduction in risk of ischaemic heart disease and other vascular disease mortality
This slide shows that lowering BP reduces the risk of CV disease.1
A meta-analysis of 61 prospective, observational studies has shown that a 10 mmHg lower SBP would be associated over the long term with a 40% lower risk of stroke death and a 30% lower risk of death from IHD or other vascular causes.1
Even a small, 2 mmHg fall in mean SBP would be associated with large reductions in stroke mortality (10%) and death due to IHD and other vascular diseases (7%) in middle age.1
The reduction in risk associated with a given reduction in mean BP was approximately constant down to at least an SBP of 115 mmHg and a DBP of 75 mmHg – well beyond what is normally achieved.1
There was no evidence of a threshold level of SBP (at about 140−160 mmHg) below which lower BP levels are not associated with lower disease risks.1
The reduction in risk holds for all age groups assessed from 40 up to 89 years old.1
Reference
Lewington S, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903−1913.
2 mmHg decrease in mean SBP
10% reduction in risk of stroke mortality
Lewington et al. Lancet. 2002;360:1903–1913.

12. FAKTA HIPERTENSI PADA STROKE

13. AHA Stroke Statistics 2016
Approximately 77% of those who had first stroke have BP >140/90 mmHg (ARIC, CHS, and FHS Cohort and Offspring studies)
For each 10 mm Hg increase in levels of SBP, the increased stroke risk in whites is ≈8%; however, a similar 10 mm Hg increase in SBP in African Americans is associated with a 24% increase in stroke risk, an impact 3 times greater than in whites.
Diabetic subjects with BP <120/80 mm Hg have appx half the lifetime risk of stroke of subjects with hypertension.
Large accelerated reductions in stroke mortality due to Median SBP decline (16 mmHg) between 1959 and 2010 for different age groups
Average 41% reduction in stroke incidence with SBP reductions of 10 mm Hg with anti-HTN therapy

14. AHA Stroke Statistics 2016
Several studies have shown significantly lower rates of recurrent stroke with lower BPs.
Most recently, the BP- reduction component of the SPS3 trial showed that targeting an SBP <130 mmHg was likely to reduce recurrent stroke by ≈20% (P=0.08) and significantly reduced ICH by two thirds.

15. What is the goal BP?

16. Group BP Goal (mm Hg) General DM* CKD** Goal BP JNC 8:
<60 yr: <140/90
< 140/90
>60 yr: <150/90
ESH/ESC:
< 140/85
Elderly
/90
(SBP < 130 if proteinuria)
(<80 yr: SBP<140)
ASH/ISH
>80 yr: <150/90
(Consider < 130/80 if proteinuria)
AHA/ACC
Goal BP
**KDIGO: <140/90 w/o albuminuria
<130/80 if >30 mg/24hr
*ADA: < 140/80 or lower

17. Comparison of Recent Guideline Statements
JNC 8
ESH/ESC
AHA/ACC
ASH/ISH
>140/90
Threshold
>140/90 < 60 yr
Eldery SBP >160
>140/90 <80 yr
for Drug Rx
>150/90 >60 yr
Consider SBP
>150/90 >80 yr
if <80 yr
B-blocker No
Yes
First line Rx
Initiate Therapy
>160/100
"Markedly
w/ 2 drugs
elevated BP"
Comparison of Recent Guideline Statements

18. TATALAKSANA HIPERTENSI

19. Recommendations to reduce BP and/or CV risk factors
Lifestyle changes for hypertensive patients
Recommendations to reduce BP and/or CV risk factors
Salt intake
Restrict 5-6 g/day
Moderate alcohol intake
Limit to g/day men, g/day women
Increase vegetable, fruit, low-fat dairy intake
BMI goal
25 kg/m2
Waist circumference goal
Men: <102 cm (40 in.)*
Women: <88 cm (34 in.)*
Exercise goals
≥30 min/day, 5-7 days/week
(moderate, dynamic exercise)
Quit smoking
* Unless contraindicated. BMI, body mass index.

20. Lifestyle Modification

21. CHS January 2004 Considerations for individualization of anti-hypertensive therapy
Indication
Initial Therapy
Second line Rx
Notes/Cautions
DM with nephropathy
ACE-i or ARB
addition thiazide, * -blockers , LA-CCB, ACE/ARB combo
*Cardioselective  -blockers
If CR >150 mmol/l use loop diuretic for volume control
DM without
nephropathy
or thiazide
Combo1st line Rx or *-blockers, LA-CCB
Angina
 -blockers + strongly consider ACE-i
LA-CCB
Avoid short acting nifedipine
Prior MI
 -blockers + ACE-i
Combine additional Rx
CHF
 -blockers + ACE-i + spironolactone (ARB if ACE-i intolerant )
Hydralazine /ISDN: thiazide or loop diuretics as additive therapy
Avoid non DHP-CCB
(diltiazem, verapamil)
Prior CVA or TIA
ACE-i/diuretic combination
BP reduction  recurrent events
Renal Disease
ACE-i/diuretic as additive Rx
ARB if ACE-i intolerant
Combo other agents
Avoid ACE-i if bilateral Renal artery stenosis
LVH
ACE-I, ARBs, DHP-CCB, thiazide,  -blockers < 55 yr
Avoid hydralazine and minoxidil

22. JNC 8

24. Strategies to Dose Antihypertensive Drugs
Description
Details A
Mulai 1 obat naikan sp
Jika target BP blm tercapai naikkan dosis
dosis
obat 1 sp
maksimum
sblm
maksimum,kemudian
menambahkan obat ke-2 dan ke-3.
tambahkan obat ke-2 B
Mulai 1 obat kemudian tambahkan obat ke-2 sblm dosis maksimum
Tambahkan obat ke-2 sblm obat 1 mencapai dosis maks.Jk Target BP blm tercapai,tambahkan obat ke-3 dan titrasi sp dosis maks. C
Mulai dengan 2 obat (separate or single combination)
Mulai dg 2 obat
Bbrp committee merekomendasi:
≥2 obat SBP >160 dan/atau DBP
>100, atau SBP >20 mmHg diatas target dan/atau DBP >10 mmHg
Jika target BP tdk tercapai (2 drugs),
tambahkan obat ke-3 dan titrasi.

25. JNC 7

26. Guideline Population Goal BP Initial drugs 2014 HT ESH/ESC CHEP
General ≥60 y
General <60 y DM
CKD
<150/90
<140/90
Non Black: thiazide type diuretic, ACEI, ARB or ARB
Black: thiazide type-diuretic or CCB Thiazide type diuretic, ACEI, ARB or CCB
ACEI or ARB
ESH/ESC
General (non
elderly)
General elderly
<80 y
General ≥ 80 y DM
CKD (no proteinemia)
CKD + proteinemia
βBocker, diuretic, CCB, ACEI, ARB
<140/85
<130/90
CHEP
General <80 y
Thiazide, βBlocker (<60y), ACEI (nonblack) or
ARB
General >80 y
<130/80
Add CVD risk: ACEI or ARB
No CVD risk: ACEI/ARB/Thiazide/DHPCCB
G U I D E L I N E
C 0 M P A R I S O N
GOAL BP INITIAL TX

27. Guideline Population Goal BP Initial drugs ADA KDIGO NICE ISHIB JNC 7DM
<140/80
ACEI or ARB
KDIGO
DM and CKD alb exc <30 mg/d
DM and CKD alb exc >30 mg/d
≤140/90
≤130/80
NICE
General <80 y General ≥80 y
<140/90
<150/90
<55 y; ACEI or ARB
≥55 y or black; CCB
ISHIB
Black, lower risk TOD or CVD risk
<135/85
<130/80
Diuretic or CCB
JNC 7
General CKD

28. Important Variables For HTN RecommendationsBP
NICE
ESC/ESH ASH/ISH AHA/AC
JNC 7
JNC 8
C/CDC
Definition HTN
≥140/90
and
Pre HT
or 80-89
Stg 1 HT
Not addressed
daytime
or 90-
ABPM 99
≥135/85
Stg 2 HT
≥160 or ≥100
Drug th/ in
≥160/100 •
<60 y,
low risk
or daytime
pts after
≥60 y,
non pharm
≥150/95
≥150/90
th/
βBlocker No
Yes
as 1st line

29. NICE ESH/ESC ASH/ISH AHA/ACC /CDC JNC 7 JNC 8 Diuretic Chorthali-
Thiazides
THZ
done
(THZ),
CTD
(CTD)
IND
IDP
Indapami- ND
de (IND)
Initiate
Not
Pts w/
≥160/90
≥160/100
th/ with
mentio-
markedly
mentioned
2 drugs
ned
elevated BP BP
<140/90
<160/90
target
≥80 y,
Elderly <80
(<60 y)
<150/90
SBP 140-
150, in fit
≥60 y,
pts SBP
<140
Elderly ≥80
y SBP 140-
150

30. Under JNC 8, in all cases, targets BP should be reached within a month of starting treatment either by increasing the dose or by using a combination drugs
In patients ≥60 yrs who do not have DM or CKD, the goal BP level is <150/90 mm Hg
In pts yrs without major comorbidities target BP
<140/90, and in patient ≥ 60 yrs without DM, CKD, or both, the new goal BP is <150/90 mm Hg
JNC 8 panel recommended thiazide-type diuretics as initial
therapy for most patients (include newly diagnosed HTN)

31. JNC 8. also recommend lifestyle interventions include use of the DASH
JNC 8 also recommend lifestyle interventions include use of the DASH eating plan, weight loss, reduction in sodium intake to
<2.4 gr/day, and at least 30 minutes of aerobic activity most days of the week
Under the JNC 8 guidelines, patients would receive a dosage adjustment and combinations of the 4 first-line & later line therapies ACEI/ARB, CCB, and thiazide-type diuretic
The JNC 8 does not recommend β-blockers and α-blockers as 1st therapy due to 1 trial that showed a higher rate of CV events with use of βB compared with use of an ARB, and another trial in which αB resulted in inferior CV outcomes compared with use of a diuretic

32. When initiating therapy, patients of African descent without CKD should use CCBs and thiazides instead of ACE inhibitors
ACE inhibitors and ARBs should not be used in the same patient simultaneously