Dr.

Ika Prasetya Wijaya SpPD-KKV, FINASIM, FACP, FICA

www.ipwijaya@gmail.com Samarinda: 5 Januari 1968

Pendidikan :
S1 : FKUI 1992
Spesialis 1 : FKUI 2003
Spesialis 2 : KIPD/FKUI 2011
Fellow INASIM : PAPDI 2010
Fellow ACP : ACP, AS 2015
FELLOW ICA : ICA, 2015
Pekerjaan:
KETUA Divisi Kardiologi, Departemen Ilmu Penyakit Dalam FKUI-RSUPNCM 2014
Editor Acta Medica Indonesiana/Indonesian Journal of Internal Medicine

Organisasi:
WAKIL KETUA UMUM PB PAPDI 2015-sekarang
Wakil Ketua PAPDI Cabang Jakarta 2010- sekarang
Ketua I PB IKKI 2009-sekarang

CRE/062/Aug10-Aug11/MF
Peneliti dan Pengembangan:
Tim Karotis FKUI RSCUPNCM
Anggota Tim Stem Cell FKUI RSUPNCM
Tim Transplan Ginjal RSCM
Clinical Mentor

HIPERTENSI

Ika Prasetya W
Divisi Kardiologi,
Departemen Ilmu Penyakit Dalam
FKUI/RSCM

PDUI 2013
Outline
• Hipertensi
• Hipertensi pada Lansia
• Kombinasi terapi Hipertensi
• Hipertensi pada DM dan CKD
• Hipertensi dengan Gangguan Jantung
• Hipertensi pada Stroke
• Pencegahan Komplikasi
• Krisis Hipertensi
• Hipertensi pada Kehamilan
Hipertensi
Kasus 1:
Laki-laki, 32 tahun, tanpa keluhan, datang
karena dikatakan menderita tekanan darah
tinggi saat menjalani “medical check up”.
TD 150/100 mmHg, pada pemeriksaan fisik tidak
ditemukan kelainan, foto torak tidak ada
pembesaran jantung, EKG saat “check up” tak
ada kelainan
Pertanyaan:
1. Masalah pasien?
2. Tatalaksana yang akan diberikan?
3. Pemeriksaan apa yang sebaiknya dikerjakan?
 Blood Pressure Classification
BP Classification SBP mmHg DBP mmHg

Normal <120 and <80

Prehypertension 120–139 or 80–89

Stage 1 Hypertension 140–159 or 90–99

Stage 2 Hypertension >160 or >100

 ESH 2007 & JNC VII
ESH-ESC BP BP JNC VII
BP Classification Bp Classification
Optimal <120 / <80 <120/<80 Normal

Normal 120-129 / 80-84 120-129 /80-84 Prehypertension

High normal 130-139 / 85-89 130-139 / 85-89 Prehypertension

Grade 1 Hypertension 140-159 / 90-99 140-159 / 90-99 Stage 1

(mild) Hypertension
Grade 2 Hypertension 160-179 /100-109 Stage 2
(moderate) >160 / >100 Hypertension
Grade 3 Hypertension > 180 / >110
(severe)
Isolated Systolic Isolated Systolic
Hypertension > 140 < 90 Hypertension
 BP Measurement and
Clinical Evaluation
 Classification of BP
 CVD Risk
 Benefits of Lowering BP
 BP Control Rates
 BP Measurement Techniques
• In-office
• Ambulatory BP Monitoring
• Self-measurement
 Patient Evaluation
• Laboratory Tests and Other Diagnostic Procedures
 CVD Risk

 HTN prevalence ~ 50 million people in the United States.

 The BP relationship to risk of CVD is continuous, consistent, and

independent of other risk factors.

 Each increment of 20/10 mmHg doubles the risk of CVD across the
entire BP range starting from 115/75 mmHg.

 Prehypertension signals the need for increased education to reduce

BP in order to prevent hypertension.
 Cardiovascular Mortality Risk Doubles with Each
20/10 mmHg Increment in Systolic/Diastolic BP*

Cardiovascular mortality risk

8
8X
risk
6

4
4X
risk
2
2X
1X risk risk
0
115/75 135/85 155/95 175/105
Systolic BP/Diastolic BP (mmHg)

*Individuals aged 40–69 years Lewington et al. Lancet 2002;360:1903–13

 Benefits of Lowering BP
In clinical trials, antihypertensive therapy has been associated with:

•35% to 40% mean ÓTakeda Chemical Industries, 1998

Treating hypertension reduces cardiovascular

reductions in stroke morbidity and mortality
Major
incidence; Relative risk (%)
0
CHF Stroke
CV
mortality
coronary
event All deaths

•20% to 25% in –20

*** **

myocardial infarction; –40

***
***
‘Older’ patients (mean >65 years)
***

and…….
–60 ‘Younger’ patients (<65 years)
* p<0 .05; ** p<0.01; *** p<0.00 1

–80

• more than 50% in HF. Gueyffier e t al (1996)

The JNC 7 Report 2003

JAMA. 2003;289:(DOI 10.1001/jama.289.19.2560).
Blood Pressure Reduction of 2 mmHg Decreases the
Risk of Cardiovascular Events by 7–10%
• Meta-analysis of 61 prospective, observational
studies
• 1 million adults
• 12.7 million person-years
7% reduction in risk of
ischaemic heart
disease mortality
2 mmHg
decrease in mean
SBP
10% reduction in risk of
stroke mortality

Lewington et al. Lancet 2002;360:1903–13

 Algorithm for Treatment of Hypertension
Lifestyle Modifications

Not at Goal Blood Pressure (<140/90 mmHg)

(<130/80 mmHg for those with diabetes or chronic kidney disease)

Initial Drug Choices

Without Compelling With Compelling

Indications Indications

Stage 1 Hypertension Stage 2 Hypertension Drug(s) for the compelling

(SBP 140–159 or DBP 90–99 mmHg) (SBP >160 or DBP >100 mmHg) indications
Thiazide-type diuretics for most. 2-drug combination for most (usually Other antihypertensive drugs
May consider ACEI, ARB, BB, CCB, thiazide-type diuretic and (diuretics, ACEI, ARB, BB, CCB)
or combination. ACEI, or ARB, or BB, or CCB) as needed.

Not at Goal
Blood Pressure

Optimize dosages or add additional drugs

until goal blood pressure is achieved.
Consider consultation with hypertension specialist.
 Classification and Management
of BP for adults
Initial drug therapy
BP SBP* DBP* Lifestyle
classification mmHg mmHg modification Without compelling With compelling
indication indications
Normal <120 and <80 Encourage
Prehypertension 120–139 or 80–89 Yes No antihypertensive drug Drug(s) for compelling
indicated. indications. ‡
Stage 1 140–159 or 90–99 Yes Thiazide-type diuretics for
Drug(s) for the
Hypertension most. May consider ACEI,
compelling
ARB, BB, CCB, or
indications.‡
combination.
Other antihypertensive
Stage 2 >160 or >100 Yes Two-drug combination for
drugs (diuretics, ACEI,
Hypertension most† (usually thiazide-type
ARB, BB, CCB) as
diuretic and ACEI or ARB or
needed.
BB or CCB).
*Treatment determined by highest BP category.
†Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension.
‡Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmHg.
NICE/BHS algorithm: June 2006
Hipertensi pada Lansia
Kasus 2:
Perempuan, 65 tahun, dengan keluhan sering
cepat lelah saat belanja di pasar. Tidak ada
keluhan kaki membengkak, hanya kadang-
kadang merasakan kurang nafsu makan.
Pada pemeriksaan fisik TD 170/80 mmHg
dengan batas jantung melebar ke lateral.
Terdapat bising sistolik dengan grade III/6,
tanpa gallop.
• Bagaimana tatalaksana?
• Perhatian khusus apa yang sebaiknya
dilakukan?
Hypertension in the Very Old
(Bulpitt J Hum Hyp 1994; 8:603)

Four Reasons why Hypertension may be Different in the Elderly

1. They are survivors

2. Many have taken years to become ‘hypertensive’
3. Some have atheromatous renal artery stenosis
4. Diastolic pressure falls in the elderly
 BP and Survival in the Very Old
(Mattila et al, BMJ 1988:296; 887)

561 Finns aged 84-102 (mean 88)

50

40 Systolic Pressure
30 mmHg
20

10

5 year 0
<120 120-139 140-159 160-179 180-199 >200
survival 50

40
Diastolic Pressure
30 mmHg
20

10

0
<70 70-79 80-89 90-99 100-109 >110
Hypertension in the Very Elderly Trial (HYVET)

• 2100 hypertensives aged >80 randomised to No

treatment, ACEI, or diuretic
• 5 year F/U
• Endpoint is a 40% reduction in stroke
 HYVET: Results of Pilot Study (Bulpitt et al, J
Hypertens 2003: 21: 2409)

• 1283 hypertensive patients aged >80 randomized to

Diuretic, ACEI, or no treatment
• Target BP <150/80; follow-up 13 months
• Results:
– Total mortality: no effect
– CV mortality: no effect
– Stroke events: Diuretics RR 0.313, p<0.01
ACEI RR 0.629, p= 0.21
Tanpa Medikamentosa?
 JNC 7: Lifestyle Modification
Modification Approximate SBP reduction
(range)

Weight reduction 5–20 mmHg/10 kg weight loss

Adopt DASH eating plan 8–14 mmHg

Dietary sodium reduction 2–8 mmHg

Physical activity 4–9 mmHg

Moderation of alcohol 2–4 mmHg

consumption
Lifestyle Modification: PREMIER
(JAMA 2003: 289; 2083)

Baseline 3 mo 6 mo
 Hypertension in the Elderly

1. An increasing problem with the ageing of the US

population
2. Related to increased stiffness of arteries
3. Importance of white coat HTN, and out-of-office
monitoring
4. Diuretics drugs of choice, with addition of others-
emphasis on combination Rx
5. BP control is more important than drugs used
6. Include lifestyle modifications
7. Benefits of treatment in very old (>85) are unproven,
but diuretics may be protective
Kombinasi terapi Hipertensi
Kasus 3:
Perempuan, profesi sekretaris, 45 tahun. Keluhan
badan tidak terasa nyaman, riwayat tekanan
darah tinggi sudah 7 tahun. Diketahui setelah
melahirkan anak ke-3. Berobat tidak teratur
karena kesibukannya. Obat: Amlodipin 10 mg
sekali sehari
Pada pemeriksaan fisik: TD 170/100 mmHg, batas
jantung sulit diperiksa, mur-mur tak terdengar,
gallop S4 terdengar.
 Algorithm for Treatment of Hypertension
Lifestyle Modifications

Not at Goal Blood Pressure (<140/90 mmHg)

(<130/80 mmHg for those with diabetes or chronic kidney disease)

Initial Drug Choices

Without Compelling With Compelling

Indications Indications

Stage 1 Hypertension Stage 2 Hypertension Drug(s) for the compelling

(SBP 140–159 or DBP 90–99 mmHg) (SBP >160 or DBP >100 mmHg) indications
Thiazide-type diuretics for most. 2-drug combination for most (usually Other antihypertensive drugs
May consider ACEI, ARB, BB, CCB, thiazide-type diuretic and (diuretics, ACEI, ARB, BB, CCB)
or combination. ACEI, or ARB, or BB, or CCB) as needed.

Not at Goal
Blood Pressure

Optimize dosages or add additional drugs

until goal blood pressure is achieved.
Consider consultation with hypertension specialist.
ESHESC Recommendations for Combining BP-lowering
Drugs and Availability as Single-pill Combinations
Diuretics

Angiotensin
b-blockers receptor blockers
(ARBs)

Calcium channel
a-blockers
blockers (CCBs)

Angiotensin-converting enzyme (ACE) inhibitors

Available as a single-pill combination

Less frequently used/combination used as necessary

Task Force for ESH–ESC. J Hypertens 2007;25:1105–87

 Pharmacologic Sites of Action
Veins Heart
Arteries

Thiazides Beta Blockers Dihydropyridine

Loops Diltiazem CCBs
Aldosterone Ant. Verapamil Hydralazine
Nitrates Minoxidil
Via Central Alpha1 Blockers
ACEI Mechanism: ACEI
ARB Clonidine ARB
 Chinese Menu Approach
Veins Heart
Arteries

Thiazides Beta Blockers Dihydropyridines

Loops Diltiazem Hydralazine
Aldosterone Ant. Verapamil Minoxidil
Nitrates Alpha1 Blockers
Via Central ACEI
ACEI Mechanism: ARB
ARB Clonidine

Choose one agent from each category

Hipertensi dengan DM dan CKD
Kasus 4:
Laki-laki, 56 tahun, dengan riwayat DM 10 tahun
dan tekanan darah tinggi 12 tahun. Sudah
menjalani cuci darah seminggu 2 kali sejak 8
tahun yl.
Pada pemeriksaan fisik: tampak sakit sedang, sesak,
JVP 5 – 0 cm H2O. Nadi 98 x/menit, ronkhi basah
halus di bagiuan bawah paru, edema tungkai
minimal. Kulit di kedua tungkai baewah tampak
kehitaman.
PHARM-RX OF HTN IN DIABETES: I
Accurate Dx of HTN:
• BP ≥ 130/80 in office, and/or
• BP ≥ 125/75 out-of-office

• ACE-I or ARB
• Lifestyle ’s
• If BP ≥ 150/90:
- ACE-I or ARB  Diuretic (or CCB?)

BP ≥ 130/80 after 1 mo

Add Diuretic
• Thiazide for most patients
• Loop diuretic if eGFR < 30-50 (Cr ≥ 1.6-1.9 mg%)
- BID furosemide, bumetanide or QD torsemide

Am J Kid Dis 2007; 49(Suppl 2):S74 Diabetes Care 2007; 30(Suppl 1):S4
 PHARM-RX OF HTN IN DIABETES: II
ACE-I or ARB  Diuretic

BP ≥ 130/80 after 1 mo

Add non-DHP CCB: Verapamil or Diltiazem

BP ≥ 130/80 after 1 mo

Add DHP CCB Add aldosterone blocker IF • Stop Non-DHP CCB

(amlodipine or other) eGFR > 50 (Cr ≤ 1.5 mg%) and K+ < 4.5
• Add:
• Spironolactone or amiloride
- DHP CCB
• Monitor K+ carefully
(amlodipine or other)
- BB (esp., carvedilol)

BP ≥ 130/80 after 1 mo

Consultation

Am J Kid Dis 2007; 49(Suppl 2):S74 Diabetes Care 2007; 30(Suppl 1):S4
 RENOPROTECTION IN DIABETES
Normoalbuminuria (ACR < 30)

Θ
Type 2 DM: ACE-I BENEDICT:
49%  vs verapamil

Microalbuminuria (ACR 30-299)

Type 2 DM: ARBs, ACE- Θ IRMA-2, MARVAL: 44-70%  vs
Is other, p

Type 2 DM: ARBs = DETAIL

ACE-Is
Macroalbuminuria (ACR ≥ 300)
Type 2 DM: ARBs Θ IDNT, RENAAL: 23-28%  vs
other
Type 1 DM: ACE-Is Collab. Study: 50%  vs other
Progressive Kidney Failure
 RENOPROTECTION: DOSE MATTERS
% Progressing to
Microalbuminuria Rx Final BP Macroalbuminuria
Placebo 144/83 14.9%

Irbesartan 150 mg/d 143/83 9.7%

Irbesartan 300 mg/d 141/83 5.2%

NEJM 2001; 345:870

 RENOPROTECTION: DOSE MATTERS
• Titrate ARB/ACE-I to  study dose in CKD, if
tolerated:

ACE-I (mg/d) ARB (mg/d)

Lisinopril, 20-40 Candesartan, 16-32
Benazepril, 30-40 Irbesartan, 300
Ramipril, 10-20 Telmisartan, 80
Perindopril, 4-16 Valsartan, 160-320
Trandolapril, 3-4 Losartan, 100

NEJM 2004; 351:1952 Am J Kid Dis 2004; 43(May Suppl):S142

 Case 1
45 yo female with 3 years of type II DM, BP
145/87, hyperlipidemia, smoker, no
microalbuminuria
 Case 1
Case 1: HCTZ and ACE or Beta Blocker
Why?
HCTZ because of benefits shown in ALLHAT specifically
CV mortality in CHF and inexpensive
In UKPDS, no significant difference in outcomes
between ACE and beta-blockers in patients without
microalbuminuria and not post-MI, however, her
diuretic may be more effective in combo with an ACE
b/c it cranks up the renin, ACEII that gets shut down
by the diuretic
 Case 2
56 yo with Hyperlipidemia and DM, BP 132/74.
Besides starting an aspirin and a statin, do you
wish to begin anything else?
 Case 2
Case 2: YES, you do! ACE inhibitor- over 55 with
more than DM as a risk factor for CVD, ACE
inhibitors decrease risk for events- i.e. HOPE
trial. Remember, patients entered into HOPE
trial were NORMOtensive!
Also should be on an Aspirin daily
 Case 3
74 yo DM, recent MI and hyperchol, LVH on
ECHO and EKG, BP 156/58, quit all meds since
making him sick… Actually, what was making
him sick was his big widow maker MI. He now
concedes that it was his heart attack that was
making him feel terrible. What BP meds do
you restart?
 Case 3
Case 3: Old guy, start beta blocker first because
mortality data with CVD and recent MI. Then
ACE again because of mortality data (ie. HOPE
trial) and finally HCTZ if increased risk for CHF.
Start slowly and always check orthostatics at
each visit. ACE or ARB (LIFE and HOPE show
regression of LVH)
 Case 4
64 yo 3 mo ago diagnosed with DM. BP at that
time 143/78 and now 149/82. Also with
Hypercholesterolemia. Would you
recommend anything at this point?
 Case 4
• Case 4: Technically 3 months of lifestyle is
past, pt is over 55, has another RF, and has 2
BP over goal. In addition, there is no
threshold at which there isn’t greater benefit,
so GO FOR IT. Give pt an ACE or HCTZ!
Hipertensi pada gangguan Jantung
Kasus 5:
Laki-laki, 48 tahun, riwayat tekanan darah tinggi
sejak 12 tahun yl. Menderita sesak saat
aktifitas sejak 3 tahun lalu. Sesak berkurang
dengan istirahat. Tidur berbantal 2-3 buah.
Pemeriksaan Fisik: TD 158/93 mmHg< JVP 5+1
cm H2O. Terdapat ronkhi basah halus di kedua
lapang bawah paru. Asites minimal dengan
edema tungkai.
 Effects of Hypertension on The Heart

• Left Ventricular Hypertrophy

• Vascular Disease:
-Atherosclerosis
-Arteriosclerosis
 Prevalence of Systolic and Diastolic Dysfunction by
Age
60
45-54
50 55-64
65-74
40
% of >75
Population ALL
30

20

10

0
Mild Moderate Severe EF<50% EF<40%
Diastolic Dysfunction Systolic Dysfunction

Redfield MM et al. JAMA. 2003;289:194-202.

Hipertensi pada Stroke
Kasus 6:
Laki-laki, 43 tahun tanpa diketahui riwayat
tekanan darah tinggi. Ditemukan terjatuh saat
mengikuti rapat organisasi.
Pada pemeriksaan fisik: TD 210/110 mmHg
Kesadaran menurun, GCS 11. Ditemukan sisi
kanan melemah, dan ngorok.
 Khusus Strok
• Pada Strok Iskemik, pemberian anti hipertensi
menunggu setelah 5 hari kondisi pasien stabil
kecuali TD > 200/100 mmHg
• Pada Strok Perdarahan: pemberian
antihipertensi dilakukan bila TD > 180/100
mmHg
Pencegahan Komplikasi
Kasus 7:
Perempuan 28 tahun, belum menikah, diketahui
sudah menderita tekanan darah tinggi sejak 1
tahun yl. Obat yang diminum adalah
Amlodipin 5 mg sekali sehari.
Pada pemeriksaan fisik : TD 118/78 mmHg.
Tidak ditemukan kelainan pada organ lain.
 BP Control Rates
Trends in awareness, treatment, and control of high
blood pressure in adults ages 18–74

National Health and Nutrition Examination Survey, Percent

II II
II (Phase 1) (Phase 2)
1976–80 1988–91 1991–94 1999–2000
Awareness 51 73 68 70
Treatment 31 55 54 59
Control 10 29 27 34

Sources: Unpublished data for 1999–2000 computed by M. Wolz, National Heart, Lung, and Blood Institute; JNC 6.
 Laboratory Tests
 Routine Tests
• Electrocardiogram
• Urinalysis
• Blood glucose, and hematocrit
• Serum potassium, creatinine, or the corresponding estimated GFR,
and calcium
• Lipid profile, after 9- to 12-hour fast, that includes high-density and
low-density lipoprotein cholesterol, and triglycerides
 Optional tests
• Measurement of urinary albumin excretion or albumin/creatinine ratio
 More extensive testing for identifiable causes is not generally indicated
unless BP control is not achieved
 When a Patient is Still Not at Goal?
• Optimize dosages or add additional drugs until
goal blood pressure is achieved
• What do you do when you are using several
effective medications?
– Consider causes of resistant hypertension
– Assure drug therapy is rational
– “Tricks of the trade”
 Identifiable Causes of Hypertension
 Sleep apnea
 Drug-induced or related causes
 Chronic kidney disease
 Primary aldosteronism
 Renovascular disease
 Chronic steroid therapy and Cushing’s syndrome
 Pheochromocytoma
 Coarctation of the aorta
 Thyroid or parathyroid disease

JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314

 Causes of Resistant Hypertension
 Improper BP measurement
 Excess sodium intake
 Inadequate diuretic therapy
 Medication
• Inadequate doses
•Drug actions and interactions:
Nonsteroidal antiinflammatory drugs (NSAIDs), illicit
drugs, sympathomimetics, oral contraceptives
• Over-the-counter (OTC) drugs and herbal supplements
 Excess alcohol intake
 Identifiable causes of HTN

JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314

 Drug-Induced Hypertension: Prescription
Medications
• Steroids • Ketamine
• Estrogens • Desflurane
• NSAIDS • Carbamazepine
• Phenylpropanolamines • Bromocryptine
• Cyclosporine/tacrolimus • Metoclopramide
• Erythropoietin • Antidepressants
• Sibutramine – Venlafaxine
• Methylphenidate • Buspirone
• Ergotamine • Clonidine
 COX-2 Inhibitors and NSAIDs
• Inhibition of cyclooxygenase, inhibits
prostaglandin synthesis that normally maintains
afferent arteriole vasodilatation
• Afferent vasoconstriction decreases renal
perfusion → increased BP
– Increasing salt and water retention
– Increasing rennin release
• COX-1 is thought to be primary enzyme
responsible for renal vasodilatory
prostaglandins
 COX-2 Inhibitors and NSAIDs
• However, COX-2 inhibitors are no less likely to
increase BP than other NSAIDS
• Case reports of severe increases in BP exists in
patients after one dose or more typically after
4 weeks for regular usage
• Consider scheduled acetaminophen as an
alternative to NSAIDs in patients with difficult
to manage hypertension

Drugs Aging. 2004; 21:479-84; JAMA. 2001; 286:954-59

Drug-Induced Hypertension: Street Drugs
and Herbal Products
• Cocaine
• Ma huang “herbal ecstasy”
• Nicotine
• Anabolic steroids
• Narcotic withdrawal
• Methylphenidate
• Phencyclidine
• Ketamine
• Ergot-containing herbal products
• St John’s wort
 Substances Associated with HTN
• Food Substances • Chemicals
– Sodium Chloride – Lead
– Ethanol – Mercury
– Licorice – Thallium and other
– Tyramine-containing heavy metals
foods (with MAOI) – Lithium salts
Rational Combination Therapy:

Chinese Menu Approach

Krisis Hipertensi
Kasus 8:
Perempuan, 42 tahun, dikonsulkan dari Spesialis
mata karena perdarahan di mata dengan TD
240/120 mmHg.
Pada pemeriksaan fisik: tampak cemas, TD
240/140 mmHg, tak ditemukan suara jantung
abnormal, tak ditemukan edema.
 Hypertensive Urgencies
and Emergencies
 Patients with marked BP elevations and acute TOD (e.g.,
encephalopathy, myocardial infarction, unstable angina, pulmonary
edema, eclampsia, stroke, head trauma, life-threatening arterial
bleeding, or aortic dissection) require hospitalization and parenteral
drug therapy.

 Patients with markedly elevated BP but without acute TOD usually do

not require hospitalization, but should receive immediate combination
oral antihypertensive therapy.
Hipertensi pada Kehamilan
Kasus 9:
 Hypertension in Women

 Oral contraceptives may increase BP, and BP should be checked

regularly. In contrast, HRT does not raise BP.

 Development of HTN—consider other forms of contraception.

 Pregnant women with HTN should be followed carefully. Methyldopa,

BBs, and vasodilators, preferred for the safety of the fetus. ACEI and
ARBs contraindicated in pregnancy.
 The Case
• 34 year old G2P1 at 28 weeks gestation
• Sent to you for a BP of 160/98 mm Hg in GP’s office
the previous day
• No previous medical problems
• No smoking and on no meds
• Review of antenatal record shows her BP was 145/90
at 14 and 18 weeks gestation
From this information alone you conclude:

A) She has pre-eclampsia

B) She likely has pre-existing hypertension
C) She needs immediate delivery
D) She has underlying renal disease
BP 15 mm Hg

0 wks ~20 wks

Weeks
 Grading of
Recommendations
• Grade A – Very strong evidence
• Grade B – Fair evidence
• Grade C – Poor studies
• Grade D – Expert opinion
 Back to the Case
• She remains asymptomatic and states there are good
fetal movements
• Exam shows her to be overweight
• BP is 155/98
• No pitting edema, reflexes are brisk, but no clonus
• There is no evidence of any secondary cause of HTN
• Urinary dipstick is negative for protein
Appropriate measures at this point include:

A) Laboratory investigations
B) 24 hour urine collection for protein
C) Admission to hospital
D) All of the above
E) A and B
 Definitions
• HTN defined as DBP > 90 mm Hg (D)
• Severe HTN is > 110 mm Hg (D)
• All reading > 90 mm Hg must be confirmed 4
hours later with 2nd reading (D)
– Except when > 110 mm Hg
• Significant proteinuria defined as > 0.3 g/day
using a 24 hr urine collection (increased from 0.15
g/day in non-pregnancy) (A)
• Severe proteinuria is > 3 g/day
• Edema and weight gain no longer used to
diagnosis of PET
 Classification of Hypertensive Disorders in
Pregnancy
CHS classification Interpretation

Pre-existing HTN Pre-existing HTN

Essential hypertension Essential hypertension
Secondary Secondary causes
Gestational HTN without proteinuria “Pregnancy-Induced” HTN

Gestational HTN with proteinuria Pre-eclampsia

Pre-existing HTN + superimposed Pre-existing HTN with superimposed

gestational HTN with proteinuria pre-eclampsia
Unclassifiable
 When do you initiate therapy?
(Grade D)
• Immediately:
SBP > 169 or DBP > 109 symptomatic

• After 1-2 hrs:

SBP > 169 or DBP >109 asymptomatic

• After few days observation:

SBP > 139 or DBP > 89 if PET/underlying problems
SBP > 149 or DBP > 94 if otherwise
 When do you admit to hospital?

• Mandatory: SBP > 169, DBP > 109 symptomatic

• Strongly recommended:
– Pre-eclampsia
Note: for purposes of RC
– anyone with DBP > 99
exam, it is never wrong to
– anyone you can’t monitor closely as outpatient
admit for :a few days of
• Recommended
monitoring
– anyone with DBP 90-99 that you want to follow
closely
– to assess fetal well-being
 Back to the Case...
This woman likely had pre-existing hypertension given that she
had a diastolic blood pressure of 90 mm Hg prior to 20 weeks’
gestation (answer B).
• HTN at 28 weeks gestation raises the possibility of PET
• Should have appropriate initial investigations
• Admission is debatable, but most prudent thing to do
• Allows for fetal assessment, collection of urine to rule out PET,
and monitoring of blood pressure (answer D)
Note: Some centres have “Obstetric Day Units”, an acceptable
option
 Which investigations would be
appropriate on admission?
(mostly Grade C + D)
• CBC, blood film
• Lytes, BUN, Creat
• Uric acid (Grade B) – may reflect severity
• Liver enzymes
• Coags
• 24 hr urine for protein
• Urinalysis (Grade A)
• OB to see + BPP/NST/FMC/doppler flow…
 Back to the case
• Our patient is admitted to hospital and monitored
closely
• Fetal ultrasound is normal
• Bloodwork is normal
• 24 urinary protein excretion is 0.20 g/day
• Her DBP remains 95-105

You would like to begin treatment.

What would you prescribe?
 Management of Mild-Moderate HTN in
pregnancy
• First line drug: Methyldopa (grade A)

• Second line drugs:

Goal of therapy: DBP 80-
– Labetalol/Pindolol/Oxprenolol/Nifedipine(grade A/B)

•
90 mm
Third line drugs:
Hg (grade D)
– Hydralazine + clonidine (A)
– Hydralazine + metoprolol (A)
– Clonidine (B)

• Diuretics - only in specific situations

 Beyond the guidelines...
• Lancet, January 2000
– meta-analysis
– 45 trials including 3773 women
• Aggressive lowering of BP can cause LOW
BIRTH WEIGHT (100-200 grams!)
• Guidelines will likely be modified soon
• Most experts now aim to keep HTN’sive
pregnant women at BP 150-160/90-100
 Outcomes of treatment
Perinatal death

Methydopa - in women with pre-existing HTN

 Outcomes of treatment
Prevention of severe HTN

Methydopa in women with pre-existing HTN

Beta-blockers/Nifedipine/combination therapy
with hydralazine
 Outcomes of treatment
Superimposed PET

NO known pharmacologic prevention

 Outcomes of treatment
Preterm delivery

No good data
 Outcomes of treatment
IUGR

Poor evidence
?Maybe Beta blockers cause IUGR?
?Maybe Diuretics cause IUGR?
 What about Non-Parmacologic
Treatment and Prevention?
 Indicated for SBP> 140mmHg or DBP >
90mmHg
 “Non-pharmacologic Rx alone is
recommended for women with SBP of 140-
150 mmHg or DBP 90-99mmHg in the absence
of maternal or fetal risk factors (Grade D)”
 Possibly Promising therapies
 ASA
 no role for routine use (Grade B)
 BUT…low dose ASA reduces incidence of pre-term
delivery and early onset PET in women at risk
(Grade A)
 Calcium
 primary prevention of PET
 does not prevent development of more severe
GESTATIONAL HTN (Grade B) (NEJM 1991, NEJM
1997)
 Others...
 Bedrest
 no evidence for efficacy
 in fact, Grade B evidence that it is not advisable
 Exercise
 no evidence
 Stress control
 no evidence
 Increased energy and protein intake
 Grade B evidence that they are NOT beneficial
 Weight reduction
 not recommended (Grade C)
 Na restriction
 not recommended (Grade C)
 Alcohol restriction
 no evidence
 Magnesium
 not justified (Grade B)
 Zinc/iron/folate
 not beneficial (Grade B)
 Back to the Case
• Methyldopa, 250 mg BID is started
• BP drops to 140/88
• Pt. Discharged home

• 2 weeks later - presents to ER with epigastric pain, headache

and blurred vision
• BP 190/115
• 3+ protein on dipstick
Each of the following would be appropriate initial
therapy except:

A) Labetalol 5-10 mg IV
B) Nifedipine 5 mg PO
C) Metoprolol 50 mg PO
D) Hydralazine 5-10 mg IV
Management of Severe Hypertension in Pregnancy
(DBP> 110 mm Hg)
• First line drugs:
– Hydralazine (grade B)
– Labetalol (grade B)
– Nifedipine (grade B)
Treatment goal: 90-100 mm Hg
• Second line drugs: if refractory to above
– Diazoxide (grade D)
– Sodium nitroprusside (grade D)

• Note: need continuous fetal monitoring

 Back to the case...
This patient has severe hypertension in the setting of
pre-eclampsia, and is symptomatic

Her blood pressure needs to be lowered acutely, and so

oral metoprolol is NOT an appropriate initial choice
(Answer C)
 Pre-eclampsia
• Multi organ disorder

• Diagnosis after 20 wks gestation

– HTN
– significant proteinuria
 Burden of disease
• Affects 3-14 % of all pregnancies worldwide
• in 2nd pregnancy:
– 1 % if Normal 1st preg
– 5-7 % if mild PET in 1st preg
– 60-80 % if early severe PET in 1st preg
 Other Risk Factors
• HTN at start of preg
• FHx
• Multiple pregnancies
• Chronic maternal HTN
• DM
• APLAS
• CTD
• Increased maternal age
• New partner
• Note: smoking reduces the risk of PET
 Pre-eclampsia: Presentation
Clinical
• headache
• vision disturbances
• RUQ pain
• nausea and vomiting
• elevated blood pressure
• edema
• convulsions
• stroke
• cerebral edema
• pulmonary edema
• retinal detachment
Laboratory
• proteinuria >0.3 g/24 hr
• high uric acid (indicates
severity)
• HELLP syndrome
- hemolysis, high liver enzymes,
low platelets
• increased hematocrit
• elevated PTT, d-Dimers, low
fibrinogen (markers of DIC)
 Back to the Case
• She is treated with labetalol 10 mg IV
• BP drops to 160/97
• Fetal heart tracing is reassuring
• Lab tests are as follows: AST 520, ALT 480, platelets
200, creatinine 100, uric acid 500
• She is transferred to labour and delivery, and has a
tonic-clonic seizure
Which of the following is the MOST EFFECTIVE in
preventing further seizures?

A) Dilantin
B) Diazepam
C) Magnesium sulfate
D) Control of blood pressure
 Eclampsia

• Complicates about 1% of patients with PET

• Magnesium sulfate is the treatment of choice: more
effective than dilantin or diazepam in the prevention
of further seizures/status eclampticus
• Role of MgSO4 in the primary prevention of PET is
controversial, and not yet proven
• Typical loading is 4-6 g IV bolus followed by 1-2
g/hour
• should be continued 12-24 hrs postpartum
• Recent NEJM article comparing MgSO4 to
Calcium Channel blocker

• MgSO4 better
 Should MgSO4 have been initiated
before the seizure?
Probably…
MAGPIE trial
• Primary prevention of eclampsia for all
degrees of PET
• NNT = 63 in severe PET
• NNT = 109 in mild-moderate PET
 Back to the Case
• patient is treated with MgSO4
• BP controlled with labetalol IV
• She undergoes a STAT caesarean section and delivers
a healthy baby boy (taken to NICU…doing well)
• After 24 hrs of monitoring, she is transferred to the
ward, and discharged 6 days later
 GOAL : IDENTIFICATION OF SECONDARY (IDENTIFIABLE)
CAUSES OF HYPERTENSION
SUSPECTED DIAGNOSIS CLINICAL FEATURES DIAGNOSTIC TESTING

24-Hour urine creatinine and protein, renal ultrasound

Renal Elevated serum creatinine or abnormal
parenchymal urinalysis
hypertension
Captopril renogram, duplex Doppler sonography, magnetic
Renovascular New elevation in serum creatinine, marked resonance or CT angiogram, invasive angiogram
disease elevation in serum creatinine with initiation of
ACEI or ARB, refractory hypertension, flash
pulmonary edema, abdominal bruit

MRI, aortogram
Coarctation of the Arm pulses >leg pulses, arm BP >leg BP, chest
aorta bruits, rib notching on chest radiograph

Plasma renin and aldosterone, 24-hour urine potassium,

Primary Hypokalemia, refractory hypertension 24-hour urine aldosterone and potassium after salt loading,
aldosteronism adrenal CT scan

Plasma cortisol, urine cortisol after dexamethasone ,

Cushing's Truncal obesity, purple striae, muscle weakness adrenal CT scan
syndrome
Plasma metanephrine and normetanephrine, 24-hour urine
Pheochromocyto Spells of tachycardia, headache, diaphoresis, catechols, adrenal CT scan
ma pallor, and anxiety