혈압의 효과적인

조절방법(저항성 고혈압과 임

신성 고혈압 중심으로)-2013 대한고혈압학회 진료지침을 중심으로-

(2016년 2월 개정 교육표준슬라이드)

연세의대 내과학교실심장내과박성하

Initiation of antihypertensive drug treatment

고혈압약 선택의 원칙 (1)

• 약을 처음 투여할 때는 부작용을 피하기 위해 저용량으로 시작함.

• 약효가 24시간 지속되어 1일 1회 복용이 가능한 약을 선택함.

• 최저/최대효과(trough/peak ratio) 0.5

• 1일 1회 투여로 부족하면 2회 이상 나누어 투여함.

• 일차 고혈압약으로 ACE 억제제, 안지오텐신 수용체 차단제

(ARB), 베타차단제, 칼슘차단제, 이뇨제 중에서 선택하며 적응증,

금기사항, 환자의 동반질환, 무증상 장기 손상 등을 고려함.

고혈압약 선택의 원칙 (2)

• 동반질환에 대한 효과를 우선적으로 고려함.

• 노인에서 베타차단제는 치료 이득에 대한 논란이 있음.

• 베타차단제와 이뇨제의 병용투여는 당뇨병 발생의 위험이 높

은 환자에게는 주의가 필요함.

• 혈압이 160/100 mmHg 이상이거나, 목표 혈압 보다 20/10

mmHg 이상 높은 경우는 처음부터 병용 투여가 가능함.

• 병용요법은 강압 효과를 상승시키고 부작용을 줄이고, 환자의

약 순응도를 증가시켜, 심혈관 질환과 무증상 장기손상을 방

지하는데 도움이 됨.

동반질환에 따른 추천 고혈압약

동반질환 ACE 억제제또는 ARB

베타차단제 칼슘통로차단제

이뇨제

심부전 O O O

좌심실비대 O O

관상동맥질환 O O O

당뇨병성 콩팥병 O

뇌졸중 O O O

노인성수축기 고혈압

O O O

심근경색 후 O O

심방세동 예방 O

당뇨병 O

권장 병용요법

(굵은선: 우선 권장되는 병용요법, 가는선: 가능한 병용요법)

ACE, 안지오텐신전환효소; ARB, 안지오텐신 차단제.

혈압과 심혈관 위험에 따른

단일약제-병용요법의 선택

고혈압 단계심혈관 위험

1-2기 고혈압저~중위험

2기 고혈압고위험

단일약 소량 두 가지 복합약

기전이 다른 약으로 변경

용량 증가두가지 약용량 증가 셋 째 약 추가

소량의 두 가지 복합약기전이 다른

두 가지 약으로복합

세 가지 약용량 증가

ACEI/ARB or BB CCB/Diuretics

ACEI/ARB + CCB or ACEI/ARB + Diuretics

ACEI/ARB + CCB + thiazide like Diuretics

Add

Low dose spironolactone K < 4.5mmole/L

Further diuretics

Alpha blockers

Beta blockers

Age < 55 years Age ≥ 55 years

Blacks of any age

NICE Clinical guideline

Outcome Relative risk with atenolol 95% CI

Stroke 1.26 1.15–1.38

MI 1.05 0.91–1.21

All-cause mortality 1.08 1.02–1.14

Lindholm LH, et al. Lancet 2005

Atenolol vs. other

antihypertensives

160

150

140

130

120

110

100

90

80

70

60

BP

(mmHg)

and

Heart Rate

In 34 young (28-55yrs) hypertensives, Bisoprolol 5mg was

more effective than Amlodipine 5mg, Doxazosin 104mg,

Bendrofluazide 2.5mg, Lisinopril 2.5-10mg (double blind,

crossover,1 month each)

Deary; Brown et al J. Hypert. 2002

Brief history• F/56

• Chief complain

– Refer for palpitation and high blood pressure

• Clinical diagnosis

– Pancreatic cyst, Mucinous cystadenoma of

pancreas, s/p Laparoscopic distal

pancreatectomy with splenectomy [2011-03-21]

– DM

– Fatty liver, Liver hemangioma

24 ABPM (2016-6-29)

non dipper (diff. -3%)Full mean BP 174/85

Awake mean BP 175/87Sleep mean BP 169/79

OPD (2016-7-12)

• 180/100mmHg

• Blood Chemistry

– BUN/Cr 21.0/0.67 mg/dL

– T-cholesterol/HDL/TG/LDL 204/59/112/122.6

mg/dL

– HbA1C 7.7%

• kanarb 30mg + norvasc 5mg start

OPD f/u (2016-7-19)

• 120/70mmHg

• Palpitation, anxiety : 심장 뛰는 것이 느껴진다.

• Change medication

Kanarb stop

Concor 1.25mg startRBBB, HR 90

OPD f/u (2016-7-28)

• 130/80mmHg

• Palpitation much improved

• Reduce norvasc dose

– Concor 1.25mg + Norvasc 2.5mg

• Low salt diet

OPD f/u (2016-10-6)

• 120/70mmHg

• Comfortable and well controlled BP

• Keep concor 1.25mg monotherapy

• Low salt diet, exercise

Progress

7/12 7/19 7/28 8/18 10/6

Kanarb 30mg + norvasc

5mgConcor 1.25mg + norvasc

5mgConcor 1.25mg + norvasc

2.5mg Concor 1.25mg

• After initiating anti-HT drug therapy, it is important to see the

patient at 2- to 4-week intervals to evaluate the effects on BP

and the possible side effects.

• Once the target is reached, a visit interval between 3- and 6-

month is evidenced to be not different.

• It is nevertheless advisable to assess risk factors and

asymptomatic OD at least every 2 years.

• Subjects with high normal BP or white-coat HT without

medication should be regularly follow-up (at least annually) to

measure office and out-of-office BP as well as CV risk profile.

Follow-up of hypertensive patients: ESH/ESC

Hypertensive emergency

• Large elevations in BP > 180/120mmHg

with impending or progressive organ

damage

• Large elevation in BP > 180/120mmHg

without organ damage urgent HT

• HT emergencies 25% reduction within

the first few hours

2013 ESH/ESC guidelines J Hypertens 2013;31:1281-1357

Drugs for hypertensive emergencies:

Malignant HT, Hypertensive retinopathy,

Acute MI, aortic dissection, acute renal

failure, hypertensive encephalopathy, ICH

Drugs for hypertensive urgencies:

Severe elevation in BP without evidence of

major organ damage

Treat with rapid acting oral agents

Resistant Hypertension

• Patients prescribed 3 or more

antihypertensive medications at optimal

doses including if possible diuretics

• Office blood pressure at goal but patients

requiring 4 or more antihypertensives

Calhoun DA et al. Circulation 2008;117:e510-e526

Pseudoresistance

• Non-adherence may account for up to 50% of resistant cases

• Pseudohypertension/White coat hypertension

• Interfering medicines and substances also need to be considered– NSAIDs

– Excessive Alcohol, Caffeine, or Tobacco

– Excessive Salt Intake

– Oral contraceptives

• Inadequate Regimen

– Especially inadequate diuretic component

• M/67

• CC : poor controlled BP

• Present Illness

– 상기 67세 남환 2014년 10월 Primary hyperaldosteronism

으로 진단받고 medication후 well-controlled BP 로 OPD

f/u

중 2달전부터 갑자기 poor controlled BP(180/90)소견보여내원

• Past Hx

– HTN

– Primary hyperaldosteronism (2014.10월 진단후 po medi)

• Office Vital Sign BP: 180/90 mmHg

• 160cm, 66kg

• BUN 16.8 / Cr 1.06, eGFR 70, Na 141 / K 4.4 / Cl 102

Current Medication

Aldactone 25mg qd

Norvasc 10mg qd

BP Trend

Aldactone 25mg qd

Norvasc 10mg qd

죽염 중단

Fludex 1.5mg qd

Cardura-XL 4mg qd

Aldactone 25mg qd

Norvasc 10mg qd

4월 7일 8월 19일 9월 5일 11월 1일

7월부터

죽염 7g/day 복용

100

200

Approach to Resistant Hypertension

Exclude pseudoresistance, white coat

hypertension

Identify and reverse contributing factor

Discontinue and/or minimize interfering substance

Screen for Secondary causes of Hypertension

Calhoun DA et al. Circulation 2008;117:e510-e526

Truly idiopathic resistant Hypertension

• M/77

• CC : Referred from Rheumatology clinic for resistant

HTN

• Present Illness

– 상기 77세 남환 RA 로 본원 류마티스내과 f/u 하던 분으로local clinic 에서 고혈압 medication 중이나 poor BP control

로 본원 refer 된 분임

• Past Hx

– HTN(+), DM(-), Tb(-), smoking (-), FHx (-)

– Rheumatoid arthritis (3yrs) : celebrex, solodo, leflunomide

• Vital Sign BP: 190~180/90 mmHg

• 168cm, 70kg

Lab

• WBC 8900(56.6%) / Hb 13.7 / PLT 229k

• ESR 14 / CRP 0.6

• BUN 22.5 / Cr 0.92 / Na 143 / K 4.6 / Cl 27

• GOT 24 / GPT 32 / T. Bil 0.9 / Alb 4.2

• LDL 97 / HDL 84 / Triglyceride 121

• Random sugar 113 / HbA1c 6.4%

Medication from local clinic

Telmisartan 40 /

Amlodipine 2.5mg qd

Adalat oros 30mg qd

Carvedilol 25mg qd

BP Trend

Micardis 40mg qd

amlodipine 5mg bid

carvedilol 25mg bid

indapamide SR 1.5mg

Telmisartan 40mg qd

amlodipine 5mg qd

carvedilol 25mg qd

indapamide SR 1.5mg

• M/81

• CC : for resistant HTN

• Present Illness

–상기 81세 남환 local clinic 에서 내원 1년 전부터 고혈압 조절 중이던 분으로 혈압 조절되지 않아 본원 외래 refer 됨

• Past Hx

– HTN(+, 1yr), DM(-), Old Pul Tbc (+),

Smoking (-), FHx (-)

• BP: 195/94 mmHg

• 164cm, 55kg

Lab

• WBC 5450(69.3%) / Hb 11.2 / PLT 210k

• ESR 14 / CRP 0.6

• BUN 41.5 / Cr 2.32 / Na 138 / K 6.7 / Cl 09

• GOT 15 / GPT 13 / T. Bil 0.3 / Alb 3.6

• Urine Albumin-Creatinine Ratio 250 mg/g

• LDL 111 / HDL 34 / Triglyceride 92

• Random sugar 82

Felodipine 5mg qd

Candesartan 8mg qd

Torasemide 5mg qd

Carvedilol 12.5mg qd

BP Trend

Felodipine 10mg qd

Carvedilol 25mg qd

Torasemide 10mg qd

Medication from local clinic

Felodipine 5mg bid

Fimasartan 120mg

hydrochlorothiazide 25mg

Carvedilol 25mg

Critical Importance of

Adequate Diuretic Therapy

• Control improved in patients treated with potent

thiazide diuretics (indapamide, chlorthalidone,

or larger doses of hctz, etc.) or given multiple

daily doses of loop diuretics

• NICE/BHS guideline recommends the use of

chlorthalidone or indapamide

• Patients with co-existent renal disease may

require more intensive diuretic therapy

Comparison of thiazide and

thiazide like diuretics

Hydrochlorothiazide Indapamide Chlorthalidone

Bioavailability 65-75% 93% 64%

Half life 2.5 hours 15-25 hours 24-55 hours

24hour coverage No Yes Yes

Peak/Trough ratio > 50% No Yes Yes

Hypokalemia ++ + +++

Hyperglycemia ++ + +++

Dyslipidemia ++ + +++

CV event reduction evidence No Yes Yes

Black & Elliott. Hypertension: a companion to Braunwald’s Heart Disease. 2007; page 214

저항성 고혈압 환자가 refer 되면

– 이뇨제를 사용하지 않고 있으면 이뇨제 추가

– 이미 이뇨제를 사용하고 있었던 경우hydrochlorothiazide를 chlorthalidone이나indapamide로 바꿔본다

– 크레아티닌 청소율이 분당 30 mL 이하인 경우는thiazide 계열 이뇨제 보다는 loop 이뇨제(furosemide 혹은 torsemide (long-acting)을 사용한다

• M/65

• CC : Referred for resistant HTN

• Present Illness

상기 65세 남환 Rectal cancer s/p op (1992), Vitreous

hemorrhage (2006), CKD, DM 있는 분으로 local clinic 에서 고혈압 medication 중 poor BP control 로 본원 refer 된분임.

• Past Hx

– HTN(+), DM(+), old Pul Tb (-), smoking (-), FHx (-)

– Rectal cancer s/p op (1992), Vitreous hemorrhage

(2006), CKD

• BP: 170/70mmHg

• 168cm, 71kg

Lab

• WBC 4670 / Hb 12.3 / PLT 133k

• BUN 26.3 / Cr 1.36 / Na 143 / K 4.8 / Cl

104

• GOT 18/ GPT 16 / T. Bil 0.7 / Alb 4.1

• Urine Albumin-Creatinine Ratio 593 mg/g

• LDL 53 / HDL 69 / Triglyceride 28

• Random sugar 102

Carvedilol 25mg bid

Amlodipine 5mg qd

Olmesartan 40mg qd

Doxazosin-XL 4mg bid

Minoxidil 2.5mg bid

Torasemide 2.5mg bid

BP Trend

Carvedilol 25mg bid

Amlodipine 5mg qd

Olmesartan 20mg qd

Doxazosin-XL 4mg bid

Minoxidil 2.5mg bid

Torasemide 2.5mg bid

Spironolactone 12.5mg

QOD

Medication from local

Carvedilol 25mg

Lercarnidipine 10mg

Losartan 100mg

Beventolol 100mg

Williams B et al. Lancet 2015;386:2059-2068

Spironolactone superior to beta blocker and alpha blocker

저항성 고혈압 환자가 refer 되면

–Primary aldosteronism 이 아니라도 금기가 없는 이상 spironolactone의 사용을 고려해야 한다

–Hyperkalemia 주의

– Chronic kidney disease에서는 주의해야한다.

Resistant hypertension 약물 치료

2) Thiazide 계열 이뇨제를사용하고 있는 지 확인

1) 작용시간이길고 혈압강하효과가 상대적으로큰칼슘통로차단제, RAS 길항제를 적절한 용량으로사용하고있는지 확인

3) Hydrochlorothiazide를 indapamide 나 chlorthalidone 으로 바꿀 것을 고려

4) 베타차단제 추가

Spironolactone 추가 (12.5~50mg) K < 4.5mmole/L

Doxazosin 추가

Minoxidil 추가 고려

Hypertension in Pregnancy

Etiology & Definition

• Complicates 10-20% of pregnancies

• Elevation of BP ≥140 mmHg systolic and/or ≥90

mmHg diastolic, on two occasions at least 6

hours apart.

• Evidence for treatment in severe HT ≥

160/110mmHg definitely beneficial(Class I)

• Treatment for < 160/110mmHg, not definite

• Increased risk of stroke with BP >

150/95mmHg(Class IIb)

2013 ESH/ESC guideline for management of arterial HT

Categories

• Chronic Hypertension

– Gestational Hypertension

• Preeclampsia

• Preeclampsia superimposed on Chronic Hypertension

Chronic Hypertension

• “Preexisting Hypertension”

• Definition

– Systolic pressure ≥ 140 mmHg, diastolic pressure ≥90 mmHg, or both.

– Presents before 20th week of pregnancy or persists longer then 12 weeks postpartum.

• Causes

– Primary = “Essential Hypertension”

– Secondary = Result of other medical condition (ie: renal disease)

Prenatal Care for Chronic

Hypertensives

– Electrocardiogram should be obtained in women

with long-standing hypertension.

– Baseline laboratory tests

– Urinalysis, urine culture, and serum creatinine, glucose,

and electrolytes

– Tests will rule out renal disease, and identify

comorbidities such as diabetes mellitus.

– Women with proteinuria on a urine dipstick should have

a quantitative test for urine protein.

– 2ndary HT should be ruled out

Treatment for Chronic Hypertension

1. Avoid treatment in women with uncomplicated

mild essential HTN as blood pressure may decrease in the 1st

and 2nd trimester

2. May taper or discontinue meds for women with blood

pressures less than 150/95mmHg in 1st and 2nd trimester.

3. Reinstitute or initiate therapy for persistent diastolic

pressures >95 mmHg, systolic pressures >150 mmHg

4. Start therapy > 140/90mmHg with gestational HT, organ

damage, symptoms, preeclampsia To prevent stroke

5. Medication choices = Oral methyldopa, labetalol,

nifedipine(IIa), 2nd line: oral hydralazine

6. Target SBP; 140-150mmHg

Preeclampsia superimposed on

Chronic Hypertension

• Affects 10-25% of patients with chronic

HTN

• Preexisting Hypertension with the

following additional signs/symptoms:

– New onset proteinuria

– Hypertension and proteinuria beginning prior

to 20 weeks of gestation.

– A sudden increase in blood pressure.

– Thrombocytopenia.

– Elevated aminotransferases.

Treatment of Preeclampsia

• Definitive Treatment = Delivery

• Major indication for antihypertensive therapy

is prevention of stroke.

– Diastolic pressure ≥90 mmHg or systolic

pressure ≥140 mmHg

• Choice of drug therapy:

– Acute – IV labetalol, IV hydralazine, SR

Nifedipine

– Long-term – Oral methyldopa, labetalol,

nifedipine

Gestational Hypertension

• Mild hypertension without proteinuria or other signs

of preeclampsia.

• Develops in late pregnancy, after 20 weeks gestation.

• Resolves by 12 weeks postpartum.

• Can progress onto preeclampsia.

• Often when hypertension develops <30 weeks gestation.

• Indications for and choice of antihypertensive therapy

are the same as for women with preeclampsia

Diastolic pressure ≥90 mmHg or systolic

pressure ≥140 mmHg

• Majority of RAS inhibitor associated teratogenecity occur

during 2nd and 3rd trimester

• Pregnant women and their live born offspring (465 754

mother-infant pairs) in the Kaiser Permanente Northern

California region from 1995 to 2008.

• However, compared with hypertension controls (those with a

diagnosis of hypertension but without use of

antihypertensives) (708/29 735 (2.4%) cases of congenital

heart defects), neither use of ACE inhibitors or of other

antihypertensives in the first trimester was associated

with increased congenital heart defects risk(odds ratios

1.14 (0.65 to 1.98) and1.12 (0.76 to 1.64) respectively)

BMJ 2011;343:d5931

• F/29

• CC : poor controlled BP

• Present Illness

– 상기 29세 여환 2009년 Preeclampsia 과거력 있던 분으로,

2014년 renovascular HTN s/p PTRA at Rt. Renal artery 시행후 medication하며 f/u해오던 중, 2015년 10월 임신후 발생된 uncontrolled HTN 으로 내원함

• Past Hx

– Preeclampsia

– Renovascular HTN d/t renal artery stenosis

s/p PTRA at Rt. Renal artery (2014.1.6)

• Office Vital Sign BP: 170/100 mmHg

• 163cm, 89kg

Dilatrend

25mg BID

Sevikar

5/40 QD

BP Trend

‘15.9월

(임신

확인전)

100

200

Adalat oros

30mg BID

-stop-

Dilatrend

Sevikar

‘15.10월

(IUP 9w)‘15.11월

(IUP 12w)

Adalat oros

30mg BID

Hydralazine

12.5mg TID

Labetalol

50mg BID

Adalat oros

30mg BID

Hydralazine

12.5mg TID

Labetalol

100mg BID

‘15.12월

(IUP 16w)

Adalat oros

30mg BID

Hydralazine

25mg TID

Labetalol

100mg BID

‘16.1월

(IUP 19w)

Adalat oros

60mg BID

Hydralazine

25mg TID

Admission

Labetalol 3일

복용 못함

‘16.1월 13일

(IUP 20w)

Adalat oros

30mg BID

Hydralazine

25mg TID

Labetalol

200mg BID

BP Trend

‘16.1월19일

퇴원시

100

200

Adalat oros

30mg BID

Hydralazine

25mg TID

Labetalol

200mg BID

‘16.2월

(IUP 25w)

Adalat oros

30mg BID

Hydralazine

25mg TID

Labetalol

200mg BID

Adalat oros

30mg BID

Concor

2.5mg QD

Aprovel

150mg QD

Dichlozid

12.5mg QD

‘15.4월

(IUP 32w)

Adalat oros

30mg BID

Concor

2.5mg QD

Aprovel

150mg QD

Dichlozid

12.5mg QD

‘16.5월

출산직후

Adalat oros

30mg BID

Dilatrend

16mg QD

Aprovel

300mg QD

Fludex SR

1.5mg QD

5월 10일

출산

‘16.11월‘16.6월

Thank you very muchfor your attention