혈압의효과적인 조절방법 ( 저항성고혈압과임 신성고혈압중심으로 ) -2013 대한고혈압학회진료지침을중심으로 - (2016 년 2 월개정교육표준슬라이드 ) 연세의대내과학교실심장내과박성하
Initiation of antihypertensive drug treatment
고혈압약선택의원칙 (1) 약을처음투여할때는부작용을피하기위해저용량으로시작함. 약효가 24시간지속되어 1일 1회복용이가능한약을선택함. 최저 / 최대효과 (trough/peak ratio) 0.5 1일 1회투여로부족하면 2회이상나누어투여함. 일차고혈압약으로 ACE 억제제, 안지오텐신수용체차단제 (ARB), 베타차단제, 칼슘차단제, 이뇨제중에서선택하며적응증, 금기사항, 환자의동반질환, 무증상장기손상등을고려함.
고혈압약선택의원칙 (2) 동반질환에대한효과를우선적으로고려함. 노인에서베타차단제는치료이득에대한논란이있음. 베타차단제와이뇨제의병용투여는당뇨병발생의위험이높은환자에게는주의가필요함. 혈압이 160/100 mmhg 이상이거나, 목표혈압보다 20/10 mmhg 이상높은경우는처음부터병용투여가가능함. 병용요법은강압효과를상승시키고부작용을줄이고, 환자의약순응도를증가시켜, 심혈관질환과무증상장기손상을방지하는데도움이됨.
동반질환에따른추천고혈압약 동반질환 ACE 억제제또는 ARB 베타차단제 칼슘통로차단제 이뇨제 심부전 O O O 좌심실비대 O O 관상동맥질환 O O O 당뇨병성콩팥병 O 뇌졸중 O O O 노인성수축기고혈압 심근경색후 O O 심방세동예방 당뇨병 O O O O O
권장병용요법 ( 굵은선 : 우선권장되는병용요법, 가는선 : 가능한병용요법 ) ACE, 안지오텐신전환효소 ; ARB, 안지오텐신차단제.
혈압과심혈관위험에따른 단일약제 - 병용요법의선택 고혈압단계심혈관위험 1-2 기고혈압저 ~ 중위험 단일약 2 기고혈압고위험 소량두가지복합약 기전이다른약으로변경 용량증가 두가지약용량증가 셋째약추가 소량의두가지복합약 기전이다른두가지약으로복합 세가지약용량증가
Age < 55 years ACEI/ARB or BB Age 55 years Blacks of any age 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 NICE Clinical guideline
Atenolol vs. other antihypertensives 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
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) BP (mmhg) and Heart Rate 160 150 140 130 120 110 100 90 80 70 60 Deary; Brown et al J. Hypert. 2002
F/56 Brief history 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 175/87 Sleep 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 : 심장뛰는것이느껴진다. Change medication Kanarb stop Concor 1.25mg start RBBB, 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 5mg Concor 1.25mg + norvasc 5mg Concor 1.25mg + norvasc 2.5mg Concor 1.25mg
Follow-up of hypertensive patients: ESH/ESC 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.
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 67 세남환 2014 년 10 월 Primary hyperaldosteronism 으로진단받고 medication 후 well-controlled BP 로 OPD f/u 중 2 달전부터갑자기 poor controlled BP(180/90) 소견보여내원 Past Hx HTN Primary hyperaldosteronism (2014.10 월진단후 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
BP Trend 200 4 월 7 일 8 월 19 일 9 월 5 일 11 월 1 일 100 7 월부터죽염 7g/day 복용 Current Medication Aldactone 25mg qd Norvasc 10mg qd Fludex 1.5mg qd Cardura-XL 4mg qd Aldactone 25mg qd Norvasc 10mg qd Aldactone 25mg qd Norvasc 10mg qd 죽염중단
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 Truly idiopathic resistant Hypertension Calhoun DA et al. Circulation 2008;117:e510-e526
M/77 CC : Referred from Rheumatology clinic for resistant HTN Present Illness 상기 77 세남환 RA 로본원류마티스내과 f/u 하던분으로 local clinic 에서고혈압 medication 중이나 poor BP control 로본원 refer 된분임 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%
BP Trend Medication from local clinic Telmisartan 40 / Amlodipine 2.5mg qd Adalat oros 30mg qd Carvedilol 25mg qd Telmisartan 40mg qd amlodipine 5mg qd carvedilol 25mg qd indapamide SR 1.5mg Micardis 40mg qd amlodipine 5mg bid carvedilol 25mg bid indapamide SR 1.5mg
M/81 CC : for resistant HTN Present Illness 상기 81 세남환 local clinic 에서내원 1 년전부터고혈압조절중이던분으로혈압조절되지않아본원외래 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
BP Trend Medication from local clinic Felodipine 5mg bid Fimasartan 120mg hydrochlorothiazide 25mg Carvedilol 25mg Felodipine 5mg qd Candesartan 8mg qd Torasemide 5mg qd Carvedilol 12.5mg qd Felodipine 10mg qd Carvedilol 25mg qd Torasemide 10mg qd
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
저항성고혈압환자가 refer 되면 이뇨제를사용하지않고있으면이뇨제추가 이미이뇨제를사용하고있었던경우 hydrochlorothiazide 를 chlorthalidone 이나 indapamide 로바꿔본다 크레아티닌청소율이분당 30 ml 이하인경우는 thiazide 계열이뇨제보다는 loop 이뇨제 (furosemide 혹은 torsemide (long-acting) 을사용한다
M/65 CC : Referred for resistant HTN Present Illness 상기 65 세남환 Rectal cancer s/p op (1992), Vitreous hemorrhage (2006), CKD, DM 있는분으로 local clinic 에서고혈압 medication 중 poor BP control 로본원 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
BP Trend Medication from local Carvedilol 25mg Lercarnidipine 10mg Losartan 100mg Beventolol 100mg Carvedilol 25mg bid Amlodipine 5mg qd Olmesartan 40mg qd Doxazosin-XL 4mg bid Minoxidil 2.5mg bid Torasemide 2.5mg bid 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
Williams B et al. Lancet 2015;386:2059-2068
Spironolactone superior to beta blocker and alpha blocker
저항성고혈압환자가 refer 되면 Primary aldosteronism 이아니라도금기가없는이상 spironolactone 의사용을고려해야한다 Hyperkalemia 주의 Chronic kidney disease 에서는주의해야한다.
Resistant hypertension 약물치료 1) 작용시간이길고혈압강하효과가상대적으로큰칼슘통로차단제, RAS 길항제를적절한용량으로사용하고있는지확인 2) Thiazide 계열이뇨제를사용하고있는지확인 3) Hydrochlorothiazide 를 indapamide 나 chlorthalidone 으로바꿀것을고려 4) 베타차단제추가
Spironolactone 추가 (12.5~50mg) K < 4.5mmole/L Doxazosin 추가 Minoxidil 추가고려
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 20 th 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 1 st and 2 nd trimester 2. May taper or discontinue meds for women with blood pressures less than 150/95mmHg in 1 st and 2 nd 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), 2 nd 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
BMJ 2011;343:d5931 Majority of RAS inhibitor associated teratogenecity occur during 2 nd and 3 rd 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)
F/29 CC : poor controlled BP Present Illness 상기 29 세여환 2009 년 Preeclampsia 과거력있던분으로, 2014 년 renovascular HTN s/p PTRA at Rt. Renal artery 시행후 medication 하며 f/u 해오던중, 2015 년 10 월임신후발생된 uncontrolled HTN 으로내원함 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
BP Trend 15.9 월 ( 임신확인전 ) 15.10 월 (IUP 9w) 15.11 월 (IUP 12w) 15.12 월 (IUP 16w) 16.1 월 (IUP 19w) 16.1 월 13 일 (IUP 20w) 200 100 Labetalol 3 일복용못함 Dilatrend 25mg BID Sevikar 5/40 QD Adalat oros 30mg BID -stop- Dilatrend Sevikar Adalat oros 30mg BID Hydralazine 12.5mg TID Labetalol 50mg BID Adalat oros 30mg BID Hydralazine 12.5mg TID Labetalol 100mg BID Adalat oros 30mg BID Hydralazine 25mg TID Labetalol 100mg BID Adalat oros 60mg BID Hydralazine 25mg TID Admission
BP Trend 16.1 월 19 일퇴원시 16.2 월 (IUP 25w) 15.4 월 (IUP 32w) 16.5 월출산직후 16.6 월 16.11 월 200 100 Adalat oros 30mg BID Hydralazine 25mg TID Labetalol 200mg BID Adalat oros 30mg BID Hydralazine 25mg TID Labetalol 200mg BID Adalat oros 30mg BID Hydralazine 25mg TID Labetalol 200mg BID 5 월 10 일출산 Adalat oros 30mg BID Concor 2.5mg QD Aprovel 150mg QD Dichlozid 12.5mg QD Adalat oros 30mg BID Concor 2.5mg QD Aprovel 150mg QD Dichlozid 12.5mg QD Adalat oros 30mg BID Dilatrend 16mg QD Aprovel 300mg QD Fludex SR 1.5mg QD
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