Dr.

Heru Prasanto, SpPD-KGH, FINASIM

Divisi Nefrologi, Departemen Ilmu Penyakit Dalam FK UGM/
RSUP DR Sardjito, Yogyakarta

Tujuan pengobatan pada hipertensi
mengurangi risiko
dan kerusakan organ demi kualitas hidup pasien

Prevalensi hipertensi di Indonesia tergolong tinggi, namun

masih banyak penderita penyakit ini yang tidak terdeteksi
dan tertangani dengan baik.

masih banyak masyarakat kurang paham dengan

penyakit hipertensi dan pemahaman tentang bahayanya.
Hasil Riset Kesehatan Dasar Depkes (Riskesdas) 2007:


76 persen kasus hipertensi di masyarakat belum
terdiagnosis.

Hal ini terlihat dari hasil pengukuran tekanan darah pada
usia 18 tahun ke atas ditemukan prevalensi hipertensi di
Indonesia sebesar 31,7%.


dari 31,7% tsb yang sudah mengetahui memiliki
tekanan darah tinggi (hipertensi) berdasarkan diagnosis
tenaga kesehatan adalah 7,2%.

Sementara dari kasus tersebut yang sadar dan menjalani
pengobatan hipertensi hanya 0,4%.
Hasil Riset Kesehatan Dasar Depkes (Riskesdas) 2013

Prevalensi hipertensi di Indonesia sebesar 25,8 persen,
tertinggi di Bangka Belitung (30,9%), diikuti Kalimantan Selatan
(30,8%), Kalimantan Timur (29,6%) dan Jawa Barat (29,4%).

Responden yang mempunyai tekanan darah normal tetapi

sedang minum obat hipertensi sebesar 0.7 persen.

 prevalensi hipertensi di Indonesia sebesar 26,5 persen
(25,8% + 0,7 %).
Prevalence of Hypertension

Province

• Prevalence of HTN on people ≥ 18 y.o based on measurement

• Decrease in the prevalence can be due to :
• Difference in measurement technique from 2007 and 2013
• Awareness increase to check their condition to Healthcare Professional
RISKESDAS 2013
 Hypertension is an important
public health challenge worldwide
Population (in millions) with
hypertension globally
In 2000, 2000
> quarter of global Predicted
population with increase
hypertension
60%
1500

26.4%
1000

500

0
Yr 2000 Yr 2025

Kearney PM, et al. Lancet. 2005;365:217-223.

Hypertension is most important risk factor for global disease burden
DALY: The disability-adjusted life year
www.worldlifeexpectancy.co
m, 2014
BP Elevation or HTN Remains One of the Most Important
Multipliers for CV Risk

BP >140/90 mmHg associated with:

69% of first MIs

74% of cases of CHD

77% of first strokes

91% of cases of HF

277,000 deaths in 2003

$63.5 billion annually

(direct/indirect)  2005 Anatomical Travelogue Inc.
Underwritten by Novartis.

BP=blood pressure; HTN=hypertension; MI=myocardial infarction;

CHD=coronary heart disease; HF=heart failure.

Adapted from Thom T et al. Circulation. 2006;113:e85–e151.

 Stroke and IHD mortality linked to BP levels

Systolic Blood Pressure Age at risk:

Systolic Blood Pressure
Age at risk:
256 80-89 years 80-89 years
256
(Floating Absolute Risk and 95% CI)

(Floating Absolute Risk and 95% CI)

128 70-79 years 128 70-79 years

64 60-69 years 64 60-69 years

Stroke Mortality

32

IHD Mortality
50-59 years 32
50-59 years
16 16
40-49 years
8 8
4 4
2 2
1 1
0 0
120 140 160 180 120 140 160 180
Usual Systolic BP (mm Hg) Usual Systolic BP (mm Hg)

Prospective Studies Collaboration. Lancet. 2002;360:1903-1913.

Reducing BP prevents CV outcomes
in patients with hypertension

There is an undoubted and well-proven benefit in reducing
mean BP in patients with hypertension to prevent CV events1-3

BP goals for patients with hypertension with or without added

CV risk are well established in the hypertension guidelines1-3

Each 2
mmHg rise 7% 10%
in SBP4

Risk of mortality from Risk of mortality

ischemic heart disease from stroke

BP, blood pressure; CV, cardiovascular.

1. Mancia G, et al. Eur Heart J. 2007;28:1462-1536.

2. NICE Hypertension guidelines 2011 http://publications.nice.org.uk/hypertension-cg127.
3. Chobanian AV, et al. JAMA. 2003;289:2560-2572.
4. Lewington S, et al. Lancet. 2002;360:1903-1913
 Rationale for Combination Therapy
• Monotherapy is the standard initial treatment for reducing BP, with stepwise
increases in dose if the desired decrease in BP is not achieved 1
• Combining antihypertensive drugs from different classes provides
synergistic benefits and is the preferred initial strategy in the treatment of
high BP1,2
• Increasing the dose of a single antihypertensive agent to achieve an adequate
response may increase AEs, which can lead to noncompliance2
• At low doses, fixed-dose combinations may have better tolerability than the
respective high-dose monotherapies2

1. Wald DS, et al. Am J Med 2009;122:290–300;

2. Kreutz R. Vasc Health Risk Manag 2011;7:183-192
Preferred Drug Combinations
Beberapa pola hidup sehat yang dianjurkan

Penurunan berat badan.

Mengganti makanan tidak sehat dengan memperbanyak
asupan sayuran dan buah-buahan.

Mengurangi asupan garam.

makanan tradisional daerah  tinggi garam dan lemak.

makanan cepat saji, makanan kaleng, daging olahan dll.

asupan garam tidak melebihi 2 gr/ hari
Beberapa pola hidup sehat yang dianjurkan

Olah raga.

 teratur sebanyak 30 – 60 menit/ hari, minimal 3 hari/
minggu

berjalan kaki, mengendarai sepeda atau menaiki
tangga dalam aktifitas rutin mereka di tempat kerjanya.

Mengurangi konsumsi alcohol.

Konsumsi alcohol lebih dari 2 gelas per hari pada pria
atau 1 gelas per hari pada wanita, dapat meningkatkan
tekanan darah.
Beberapa pola hidup sehat yang dianjurkan

Berhenti merokok.

Walaupun hal ini sampai saat ini belum terbukti berefek
langsung dapat menurunkan tekanan darah, tetapi
merokok merupakan salah satu faktor risiko utama
penyakit kardiovaskular, dan pasien sebaiknya
dianjurkan untuk berhenti merokok.
Another target to consider
 SPRINT: Study design
• Age ≥50 years
• SBP 130–180 mmHg (treated or untreated)
• Additional CV risk factors (≥1)
− Clinical or subclinical CVD (excluding stroke)
− CKD (eGFR 20–<60 mL/min/1.73 m2)
− Framingham 10-year risk score ≥15%
− Age ≥75 years

Intensive treatment Standard treatment

Target SBP <120 mmHg Target SBP <140 mmHg
Exclusion criteria: stroke; diabetes; polycystic kidney disease; symptomatic HF or
LVEF <35%; proteinuria >1 g/d; CKD with eGFR <20 mL/min/1.73 m2 (MDRD);
adherence concerns
eGFR, estimated glomerular filtration rate; HF, heart failure; LVEF, left ventricular ejection fraction; MDRD, Modification of Diet in Renal Disease
SPRINT Research Group. N Engl J Med 2015;373:2103–2116

35
 SPRINT: SBP in standard- versus
intensive-treatment groups
150
Throughout 3.26 years’
Standard treatment follow-up, mean SBP
140 was 121.5 mmHg in the
intensive-treatment
SBP (mmHg)

group versus 134.6 mmHg in

130 the standard-treatment
Intensive treatment group, and the mean number
of BP medications was 2.8 and
120 1.8, respectively

110
0 1 2 3 4 5
No. with data Time (years)
Standard treatment 4683 4345 4222 4092 3997 3904 3115 1974 1000 274
Intensive treatment 4678 4375 4231 4091 4029 3920 3204 2035 1048 286
Mean No. of medications
Standard treatment 1.9 1.8 1.8 1.8 1.8 1.8 1.8 1.8 1.8 1.9
Intensive treatment 2.3 2.7 2.8 2.8 2.8 2.8 2.8 2.8 2.8 3.0

Mean number of medications is the number of BP medications administered at the exit of each visit
I Bars represent 95% CI
SPRINT Research Group. N Engl J Med 2015;373:2103–2116

36
 SPRINT: Primary outcome – time to first CV event
(composite endpoint)
Hazard ratio with intensive treatment
0.10 0.75 (95% CI, 0.64–0.89)
p<0.001 319/4683 = 6.8%
Cumulative hazard

0.08
Standard treatment 243/4678 = 5.2%
0.06
ARR 1.6%
0.04 Intensive treatment
NNT = 61
0.02

0.00
0 1 2 3 4 5
Time (years)

SPRINT was terminated early (after mean follow-up of 3.26 years) on the
recommendation of the Data and Safety Monitoring Board because of a clear
benefit of intensive therapy

ARR, Absolute Risk Reduction; NNT, number needed to treat

SPRINT Research Group. N Engl J Med 2015;373:2103–2116

37
 SPRINT: All-cause mortality
Hazard ratio with intensive treatment
0.10 0.73 (95% CI, 0.60–0.90)
p=0.003 210/4683 = 4.5%
Cumulative hazard

0.08
155/4678 = 3.3%
0.06
Standard treatment ARR 1.2%
0.04
NNT = 90
0.02 Intensive treatment

0.00
0 1 2 3 4 5
Time (years)

SPRINT Research Group. N Engl J Med 2015;373:2103–2116

38
 Recent evidence suggests that reducing
BPV also prevents vascular outcomes

How BP reduction is achieved and sustained is clinically important

Reducing BP fluctuation over time as well as mean BP has recently been
recognized as a potential target for improved management of hypertension
to prevent vascular outcomes, particularly stroke1,2
220
200
180

Blood pressure
160

(mmHg)
140 Systolic BP
Aim to reduce
both BP and BPV 120
100
80
60 Diastolic BP
40
1 2 3
Weeks

1. Muntner P et al. Hypertension. 2011;57:160-166. BP, blood pressure;

2. Rothwell PM. Lancet. 2010;375:938-948. BPV, BP variability; CV, cardiovascular.
What is Blood Pressure Variability (BPV)?
• BP normally fluctuates during the day and can vary from day to day in response to
environmental challenges eg, stress, activity, carrying out tasks1
220 220

200 200

180 180 SBP

Blood pressure (mmHg)

Blood pressure (mmHg)

160 160

140 140 Higher

mean BP
120 120
overall
100 100
DBP
80 80

60 60

40 40
1 2 3 1 2 3
Weeks Weeks

Patient 1 with lower BPV Patient 2 with higher BPV

BP, blood pressure; BPV, BP variability.

1. Schillaci G, et al. Hypertension 2011;58:133-135. 2. Rothwell PM. Lancet 2010;375:938-948.

 BPV can be monitored in the short term
and in the long term
Short-term monitoring Longer-term monitoring

Beat-to- Second-to- Minute- Hour-to-hour Day-to-day Visit-to-visit

beat BPV second to-minute BPV BPV BPV
BPV BPV
Computer analysis of BP tracing 24-hour ABPM Home BP Clinic BP
monitoring measurements

Less commonly Less commonly Less commonly

through home through 24-hour through 24-hour
and clinic BP ABPM or clinic ABPM and home
measurements measurements BP
measurements

Level of assessment within a treatment group

Within-individual variability: multiple readings within each subject available

Inter/between-individual variability: single readings for each subject available

ABPM, ambulatory BP monitoring;

BP, blood pressure; BPV, BP variability.
 Pronounced BP fluctuations can occur over short- and
long-term observation periods
Different types of BP variability, their determinants and prognostic relevance

↓ Arterial compliance Inappropriate dosing or ↓ Adherence to AHT;

↑ Central sympathetic drive titration of AHT BP measurement errors
↓ Arterial or cardiopulmonary reflex;
humoral, rheological, behavioral and
emotional factors; activity or sleep

Seasonal
Ventilation change

↑ Very short-term BPV (beat-to-beat)* ↑ Short-term BPV (over 24 h) ↑ Mid-term BPV (day-to-day) ↑ Long-term BPV (visit-to-visit)

↑ Subclinical organ damage ↑ Subclinical organ damage
↑ Cardiovascular events and ↑ Cardiovascular events
mortality? ↑ Cardiovascular mortality
↑ Renal outcomes? ↑ All-cause mortality
↑ Progression of
microalbuminuria and proteinuria
↓ eGFR, progression to ESRD
↑ Subclinical organ damage
↑ Cardiovascular events
↑ Cardiovascular mortality
↑ All-cause mortality
↑ Microalbuminuria
↓ eGFR
↑ Subclinical organ damage
↑ Cardiovascular events
↑ All-cause mortality
↑ Microalbuminuria and
proteinuria
↓ eGFR

Parati G, et al. Nat Rev Cardiol 2013;10:143-155.

42
Ringkasan

Hipertensi merupakan masalah kesehatan global
maupun di Indonesia

Pencapaian target tekanan darah harus
memperhatikan faktor-faktor yang mempengaruhi
untuk mencegah kerusakan target organ.

Terapi kombinasi dan terapi jangka panjang
diperlukan dalam tatalaksana hipertensi.

Kepatuhan pasien untuk minum obat sangat
mempengaruhi keberhasilan terapi hipertensi.
Take home message

Blood Pressure Variability /BPV sebagai suatu topic aktual
yang perlu diketahui oleh kalangan medis.

Dalam penatalaksanaan hipertensi tidak hanya tekanan

darah sesaat saja yang diperhatikan akan tetapi perilaku
tekanan darah sepanjang waktu tertentu yang penting
untuk diperhatikan dimana hal tersebut berhubungan
dengan prognosa organ organ target yang dipengaruhi oleh
hipertensi.
Take home message

Tujuan pengobatan pada hipertensi adalah
mengurangi resiko dan kerusakan organ.


Hal ini demi kualitas hidup pasien melalui
kepatuhan pengobatan.

Menurunkan tekanan darah dan mengontrolnya

sesuai target penurunan darah adalah salah satu
cara mengurangi risiko kematian, dan penyakit
penyerta hipertensi, seperti penyakit jantung,
gagal ginjal, dan stroke.
 "Karena itu, pasien harus tetap mengonsumsi obat
untuk menurunkan tekanan darah, dan menjaga supaya
tetap sesuai target"
 Increased 24-hour BPV has been associated with
cardiovascular damage

In patients with mild to moderate hypertension, 24-hour BPV
has been related to the rate and severity of target organ damage (TOD)1

For nearly any level of 24-hour mean BP, subjects with low 24-hour BPV
had a lower prevalence and severity of TOD than those with high 24-hour
BPV (108 patients, P <0.05)

Increased awake systolic BPV over a 24-hour period correlates with

subclinical TOD

Carotid intima-media thickness and left ventricular mass index
progressively increased across tertiles of awake systolic BPV over a 24-hour
period (180 patients, P for trend 0.001 and 0.003, respectively)

Awake systolic BPV was identified as an independent predictor for these
endpoints2

1. Parati G, et al. J Hypertens. 1987;5:93-98. BP, blood pressure; BPV, BP variability;

2. Tatasciore A, et al. Hypertension. 2007;50:325-332. TOD, target organ damage.
 Ohasama study: Day-to-day BP variability predictive of
stroke and CV mortality

Japanese observational study (n=2,455) found that day-to-day BP variability,
measured by home BP monitoring, was an independent predictor of
mortality from stroke, cerebral infarction or cardiovascular causes after
adjusting for mean BP
Hazard ratio* p value
Prognostic effect of increase in systolic BP variability of +1 between-subject
standard deviation
Stroke mortality 1.41 ≤0.00143
Cerebral infarction mortality 1.46 ≤0.01
Cardiovascular mortality 1.27 ≤0.01

*After adjusting for systolic BP, heart rate, sex, age, obesity, smoking and drinking, history of cardiovascular disease, diabetes mellitus,
hyperlipidemia, and treatment with antihypertensive drugs.

51 Kikuya M, et al. Hypertension 2008;52:1045-1050.

 Visit-to-visit variability in systolic BP was a strong predictor of
stroke, independent of mean SBP
Hazard ratios for risk of any stroke by deciles of visit-to-visit SD systolic BP based
on the first 7 measurements
Hazard ration (95% CI)

Decile of SD SBP

52 Rothwell PM, et al. Lancet 2010;375:895-905.

Visit-to-visit variability in systolic BP was a strong predictor of
stroke, independent
UK-TIA trial of mean SBP

Rothwell PM, et al. Lancet 2010;375:895-905.

 Increased risk of cerebrovascular disease
• In the WHICAP study, cerebral WMH increased across 4 groups in a linear
with increased
fashion – BP and BPV
ie, the higher the mean/SD, the higher the WMH
• Increased mean BP and BPV were associated with increased risk of infarction
–4.55 45
–4.6 40

Percentage with infarct

relative WMH volume

–4.65 35
Log-transformed

–4.7 30
–4.75 25
–4.8 20
–4.85 15
–4.9 10
–4.95 5
–5 0
Low Low High High Low Low High High
mean, mean, mean, mean, mean, mean, mean, mean,
low SD high SD low SD high SD low SD high SD low SD high SD
BP, blood pressure; BPV, BP variability;
WMH, white matter hyperintensity
Brickman AM, et al. Arch Neurol. 2010;67:564-569.
 Guidelines on BPV

NICE 20111

Variability in SBP when measured visit-to-visit is a strong predictor of stroke,
independent of mean SBP

Whatever the underlying mechanisms, SBP variability appears to be an important
independent predictor of clinical outcomes

“Updated guidance recommends the best available evidence-based

treatment options to suppress BPV in people with hypertension”

ESC/ESH guidelines 20132

Consideration should be given to the evidence that visit-to-visit BPV may be a
determinant of CV risk, independently of the mean BP levels achieved during long-term
treatment, and that, thus, CV protection may be greater in patients with consistent BP
control throughout visits

BP, blood pressure; CV, cardiovascular; BPV, BP variability; SBP, systolic BP.

1. National Institute for Health and Clinical Excellence (NICE) Clinical Guideline 127. Available at: http://www.nice.org.uk/nicemedia/live/13561/56007/56007.pdf. 2. Mancia G, et al. Eur Heart J 2013;34:2159-2219.
 Association between CV events and early morning period

18:00 0:00 6:00 12:00

Time of day

CV, cardiovascular risk; EMBPS, early morning blood pressure surge.

1. Muller JE, et al. N Engl J Med 1985;313:1315–1322. 2. Marler JR, et al. Stroke 1989;20:473–476.
 MBP surge: What is it?

Patients with sleep-trough surge of >55 mm Hg

were classified in the MBP surge group
MBP, morning blood pressure.
Kario K, et al. J Cardiovasc Pharmacol 2003;42 Suppl 1:S87-S91.
 MBP surge as a cardiovascular risk

Morning surge Non-surge P-value

group (n=46) group (n=145)
Age (years) 76 76 NS
24-h systolic BP (mmHg) 142 142 NS
Baseline data
Silent cerebral infarct 70 49 0.02
prevalence (%)
Number (/person) 2.0 1.5 0.01
Multiple cerebral infarcts 54 37 0.04
prevalence (%)
Prospective data
Stroke incidence (%) 17 7.0 0.04
(relative risk = 2.7)

A 10 mm Hg increase in morning surge in SBP

increased clinical stroke risk by 22%
MBP, morning blood pressure; SBP, systolic blood pressure.
Kario K, et al. J Cardiovasc Pharmacol 2003;42 Suppl 1:S87-S91.
 IDACO: Morning BP surge was a significant and independent
predictor of mortality and CV events

Multivariable-adjusted hazard ratios (95% CIs) for all-cause mortality
and all fatal and nonfatal cardiovascular events by deciles of the
morning BP surge (n=5,645)

Sleep-trough morning BP surge (mmHg) Sleep-trough morning BP surge (mmHg)

59 Li Y, et al. Hypertension 2010;55:1040-1048.

 Morning BPArising
surge and stroke riskSilent
in elderly hypertensionStroke events
cerebral infarcts
(matching
Sleepfor ageAwake
and 24-hr(%)
systolic BP)detected by brain MRI）
（Prevalence, (Incidence)
(%)
70
25
p<0.05 p<0.05
Morning Morning BP 60
BP surge 57% 20
17% 2.7 times
(Sleep-trough)
Nighttime 50
15
Lowest
BP
40
10 7.0%
33%
30
5

20
0
Morning Non-surge Morning Non-surge
Surge group Surge group
group （n=145） group （n=145）
Morning Surge group (Top 10%: MS >55 mmHg) （n=46） （n=46）
Kario K, et al. Circulation 2003;107:1401-1406.

JMS ABPM Study Wave 1

60
Management of BPV

Drugs with 24h efficacy are preferred.

Long acting drug minimize BP Variability and offer
protection against progression of organ damage
and risk of CV events

Simplification of treatment improves adherence to
therapy

Tujuan pengobatan pada hipertensi adalah mengurangi resiko dan
kerusakan organ. Hal ini demi kualitas hidup pasien melalui
kepatuhan pengobatan.
"Menurunkan tekanan darah dan mengontrolnya sesuai target
penurunan darah adalah salah satu cara mengurangi risiko kematian,
dan penyakit penyerta hipertensi, seperti penyakit jantung, gagal
ginjal, dan stroke," ujarnya.
Dijelaskannya, didalam tubuh terdapat pembuluh darah mikro yang
mengalirkan darah. Bila tekanan darah tinggi, pembuluh darah ini bisa
rusak sehingga tidak mampu untuk menapis. Kerusakan ini justru
memicu tahanan perifer, yang bila rusak dapat mengeluarkan hormon
yang membuat tekanan darah menjadi lebih tinggi lagi.
"Karena itu, pasien harus tetap mengonsumsi obat untuk menurunkan
tekanan darah, dan menjaga ginjal supaya tetap terjaga," tambahnya