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PATIENT WITH HYPERTENSION

2004-2005
Case presentation 1

•D.A. 45 years
•Female
•Risk factors:
•Family history: mother - HT
•smoker
•Obesity (BMI = 30)
•Asymptomatic
•BP= 135/85 mmHg, HR= 62 b/min (medicated)
Associated risk factors
Dislipidemia

•Total Colesterol = 220 mg/dL

•LDL = 152 mg/dL

•HDL = 32 mg/dL
A. What is the risk of a 45 year old woman
with high normal hypertension?

Cumulative cardiovascular incidents (%)


•45 years
10
– high normal HT, obesity High normal
8
– High normal HTN is
associated with an increased 6

cardiovascular risk 4
Normal

2
Optimal
•The risk for 1o years? 0

0 2 4 6 8 10 12 14
HIGH
HIGH RISK!
RISK!
Time
(years))
10 years cardiovascular events rate in women
with obesity and HT

Vasan RS, Larson MG, Leip EP, et al. N Engl J Med. 2001;345:1291-1297.
Vasan RS, Beiser A, Seshadri S, et al. JAMA. 2002;287:1003-1010.
B. Does BP normally increase with aging?

• BP increases with aging


• diastolic BP increases with aging, but reaches maximal values between 55
and 60 years
• Arterial stiffness: leads to high systolic BP, but also low diastolic BP

Diastolic Systolic
95 175
• Cohort study
90 165
BP (mm Hg)

155

BP (mm Hg)
85
4
3 145
80
135
75 2
125
1
70
115
65 105
30-34

40-44

50-54

60-64

70-74
75-79
80-84

30-34

40-44

80-84
50-54

60-64
35-39

65-69
45-49

55-59

75-79
70-74
35-39

45-49

55-59

65-69
Age Age
(years) (years)

Franklin SS, Fustin W 4th, Wong ND, et al. Circulation. 1997;96:308-315.


C. What is the proper treatment?

Does she need associated medication?

1. Lifestyle change:
- diet (low sodium, low cholesterol intake,
hypocaloric)
- daily exercise

2. ACEI (or Dihydropirydine or Sartan or Diuretic)

3. Aspirin 100 mg /zi

4. Dislipidemia - Statin
CASE PRESENTATION 2

• B.P. 50 years
• Male
• Type 2 DM (for 8 years, treated with gliclazid and
metformin)
• HbA1C 8.2% 1 month ago
• no retinopathy or neuropathy
• Obesity (BMI 32)
• BP 140/85 mm Hg, HR 64 b/ min (treated with
dihydropirydine)
Associated risk factors

• Cholesterol 220 mg/dL, HDL 32 mg/dL, LDL 144 mg/dL

• TG 200 mg/dL

• Albuminuria
A. Connection between HT and DM

Excessive Inherited
• HT is more frequent in caloric intake genetic
disorders
type 2 diabetes
Obesity Diabetes (NIDDM)

Insulin
resistance

HIGH RISK!
Hyperinsulinemia

Atherosclerosis
Hypertension

HyperTG
Hyper CT
LowHDL

Grundy SM, Benjamin IJ, Burke GL, et al. Circulation. 1999;100:1134-1146.


B. Which risk factor should be monitored?

• High incidence of vascular diseases


(stroke, CAD, peripheric vascular Metabolic syndrome
disease) in type 2 diabetes • Obesity
• Does the patient have metabolic • Hypertension
syndrome?
• Glucose tolerance
impairment

• Dislipidemia

• Insulinresistance

UK Prospective Diabetes Study Group. BMJ. 1998;317:703-713.


C. Comments regarding the assessment and
management

• HT treatment reduces CV death


in diabetics
• Goals of treatment:

– Lifestyle changes
- diet
- exercise
– control glycemia (HbA1C <7%):
hypoglycemic drugs + diet, insulin
being often necessary
– BP<130/80 mm Hg
– LDL below 100 mg/dL
- statins
C. Comments regarding the assessment
and management

•The proper therapy should consider ACEI or


AT1 blockers
•ACEI are superior to calcium channel blockers
in elderly and in diabetics (they decrease
morbidity and mortality)
•ACEI and AT1 blockers: renoprotective effects
CARDIOVASCULAR RISK FACTORS

Smoking HT

x 1.6 x 4.5 x3

x 16
x6 x9

x4

Cholesterol
DIAGNOSTIC STEPS IN HT

(1) ASSESS BP

HT should be defined depending on the way of BP assessing


(mmHg)

SBP DBP

Hospital 140 90

Holter monitor 125 80

At home (self) 135 85


DIAGNOSTIC STEPS

(2) Personal and family history


- Duration of high BP
- Possible secondary HT:
- family history of polycystic kidney
- personal history of kidney disorder: hematuria, urinary infections,
analgetics abuse
- intake of: oral contraceptives, amphetamines, cocaine, steroids,
NSAIDS etc.
- episodes of headache-anxiety-palpitations (feocromocitoma)
- episodes of muscular fatigue, tetany (hyperaldosteronism)
- Risk Factors : High lipid level
Smoking
Diabetes mellitus
Obesity-Sedentary life
Eating habits
- Signs that suggest target organ damage
- Use of BP lowering medication (type/doses/effectiveness /adverse reactions)
DIAGNOSTIC STEPS

(3) Investigations

Routine tests: fasting glycemia


CT
HDL
TG
creatinin
K++
Hb, Ht
urine exam
ECG
DIAGNOSTIC STEPS

(3) Investigations

Specific tests: Echocardiography


Carotid / femural ultrasound
C reactive protein
Microalbuminuria (D.M.)
Quantitative proteinuria
Funduscopy
DIAGNOSTIC STEPS

(3) Investigations

Extended evaluation (specialist)

- Complicated HT: tests to assess cardiac function


renal function
cerebral function
- secondary HT: measurement of renin
aldosterone
catecholamines
arteriography
renal and adrenal ultrasound
CT / MRI
DIAGNOSTIC STEPS

(4). Target organ damage (TOD)

- LVH: ECG – Sokolow-Lyon > 38mm


ECHO – LV mass index
- IVS – LVPP
- LV dysfunction
- Ultrasound evidence of arterial wall thickening (carotid IMT
≥0.9 mm) or atherosclerotic plaque
- Serum creatinine 1,0-1,2 mg/dl
- microalbuminuria 30-300 mg/24 hours
DIAGNOSTIC STEPS
(5). Associated clinical conditions (ACC)-complications

- Cerebrovascular disease: - ischemic stroke


- transient ischemic attack
- cerebral haemorrhage
- Heart disease - myocardial infarction
- angina
- coronary revascularization
- congestive heart failure
- Renal d. - diabetic nephropathy
- renal impairment: serum creatinine > 1,5mg/dl
- proteinuria > 300mg/24 hours
- Peripheral vascular disease
- Advanced retinopathy
CLASSIFICATION OF BP LEVELS (mm Hg)

Category SBP DBP

Optimal < 120 < 80


Normal 120-129 80-84
High normal 130-139 85-89
Grade 1 HT (mild) 140-159 90-99
Grade 2 HT (moderate) 160-179 100-109

Grade 3 HT (severe) ≥ 180 ≥ 110

Isolated systolic HT ≥ 140 < 90

ESH-ESC Guidelines, 2003


STRATIFICATION OF RISK

BP (mmHg)
RF
Normal High normal Grade 1 Grade 2 Grade 3
SBP 120-129 or SBP 130-139 or SBP 140-159 or SBP 160-179 or SBP ≥ 180 or
DBP80-84 DBP 85-89 DBP 90-99 DBP 100-109 DBP ≥ 110

No other RF Average risk Average risk Low added risk Moderate added High added risk
risk

1-2 RF Low added risk Low added risk Moderate added Moderate added Very high added
risk risk risk

3 or more RF or TOD Moderate added High added risk High added risk High added risk Very high added
or diabetes risk risk

ACC High added risk Very high added Very high added Very high added Very high added
risk risk risk risk

ACC – associated clinical conditions; TOD – target organ damage; SBP – systolic blood pressure; DBP –
diastolic blood pressure
“White-coat” HT

- Diagnosis : BP ≥ 140/90 mmHg (at several visits)


BP < 125/80 mmHg (Holter)

- Investigation - possible metabolic syndrome


- possible target organ damage (TOD)

- Prescription: - lifestyle changes


- pharmacological treatment (TOD)
THERAPEUTIC APPROACH

(1) High normal BP

STRATIFY ABSOLUTE RISK

- very high  drug treatment


- high  drug treatment
- moderate  monitor BP frequently
- low  lifestyle change
THERAPEUTIC APPROACH

(2) Grades 1 and 2 HT

- STRATIFY ABSOLUTE RISK

(a) very high: drug treatment promptly


(b) high : drug treatment promptly
(c) moderate : monitor BP and RF (3 months)
-SBP ≥ 140 or TAD ≥ 90 drug treatment
-SBO < 140 and DBP < 90 continue to monitor
(d) low : monitor BP and RF (3-12 months)
-SBP ≥ 140-159 and DBP ≥ 90-93 consider drug treatment
-SBP < 140 and DBP < 90 continue to monitor
THERAPEUTIC APPROACH

(3) Grade 3 HT

• BEGIN DRUG TREATMENT IMMEDIATELY!

• Assess - other RF
- Diabetes mellitus
- Target organ damage
- Associated clinical conditions

• Add: lifestyle changes and correction of other RF and diseases


GOALS of treatment

a) Maximum reduction in the long-term total risk:


* CV morbidity reduction
* CV mortality reduction
Treatment of all reversible RF
Treatment of ACC

b) Recommended BP:
BP < 140/90 mmHg
BP < 130/80 mmHg (diabetics)
DIURETICS

(A) THIAZIDES AND ANALOGS


Hydroclorothiazid Butizid Chlortalidon Clopamid
Mefrusin Metazolon Xipamid Indapamid

(B) LOOP DIURETICS


Furosemid Piretanid Torasemid Bumetanid

(C) ANTI-ALDOSTERONE DIURETICS


Spironolacton Triamteren Amilorid

(D) FIX COMBINATIONS


 Triamteren + Butizid or/Hydroclorothiazid or/Xipamid or/Furosemid
 Amilorid + Hydroclorothiazid or/Furosemid or/Trichlormethiazid
 Spironolacton + Furosemid or/Hydroclorothiazid or/Butizid
BETA-BLOCKERS
(A
(A )NON-SELECTIVE:
)NON-SELECTIVE:
Alprenolol
Alprenolol •Bopindolol
•Bopindolol •Bupranolol
•Bupranolol •Carazolol
•Carazolol •Carteolol
•Carteolol
Carvedilol
Carvedilol •Mepindolol
•Mepindolol •Nadolol
•Nadolol •Oxprenolol
•Oxprenolol •Penbutolol
•Penbutolol
Pindolol
Pindolol •Sotalol
•Sotalol •Tertataolol
•Tertataolol
(B)
(B) SELECTIVE:
SELECTIVE:
Acebutolol
Acebutolol •Atenolol
•Atenolol •Betaxolol
•Betaxolol •Bisoprolol
•Bisoprolol •Celiprolol
•Celiprolol
Metoprolol
Metoprolol •Nebivolol
•Nebivolol •Talinolol
•Talinolol
(C)
(C) FIX
FIX COMBINATIONS:
COMBINATIONS:
DIRETICS
DIRETICS ++ BETA-BLOCKERS
BETA-BLOCKERS
C1
C1 SELECTIVE:
SELECTIVE: Hydrochlorothiazid
Hydrochlorothiazid ++ Metoprolol
Metoprolol
Hydrochlorothiazid + Bisoprolol
Hydrochlorothiazid + Bisoprolol
Chlortalidon
Chlortalidon + Metoprolol
Metoprolol
Chlortalidon
Chlortalidon + Atenolol
Atenolol
C2
C2 NON-SELECTIVE:
NON-SELECTIVE: Hydrochlorothiazid
Hydrochlorothiazid ++ Mepindolol
Mepindolol
Piretanid
Piretanid ++ Penbutolol
Penbutolol
Furosemid
Furosemid + Penbutolol
Penbutolol
Hydrochlorothiazid
Hydrochlorothiazid ++ Propranolol
Propranolol
Bendroflumethiazid
Bendroflumethiazid ++ Propranolol
Propranolol
Butizid
Butizid + Metipranolol
Chlortalidon
Chlortalidon + Oxprenolol
Clopamid
Clopamid ++ Pindolol
Pindolol
Hydrochlorothiazid
Hydrochlorothiazid ++ Triamteren
Triamteren ++ Propranolol
Propranolol
Hydrochlorothiazid
Hydrochlorothiazid ++ Amilorid
Amilorid ++ Timolol
Timolol
BETA-BLOCKER
BETA-BLOCKER ++ CALCIUM-BLOCKER
CALCIUM-BLOCKER
Metoprolol + Phelodipin
Metoprolol + Phelodipin SRSR Metoprolol
Metoprolol + Nifedipin
Atenolol
Atenolol ++ Nifedipin
Nifedipin retard
retard Acebutolol
Acebutolol + Nifedipin
BETA-BLOCKER
BETA-BLOCKER ++ DIURETIC
DIURETIC ++ DIHYDRALAZIN
DIHYDRALAZIN
C3
C3 SELECTIVE:
SELECTIVE: Metoprolol
Metoprolol + Hydrochlorothiazid + Hydralazin
Hydralazin
Atenolol
Atenolol ++ Chlortalidon
Chlortalidon ++ Hydralazin
Hydralazin
C4
C4 NON-SELECTIVE:
NON-SELECTIVE: Propranolol
Propranolol + Dihydralazin
Propranolol
Propranolol + Bendroflumethaizid
Bendroflumethaizid ++ Hydralazin
Hydralazin
Oxprenolol
Oxprenolol ++ Hydralazin
Hydralazin ++ Chlortalidon
Chlortalidon
ANGIOTENSIN-CONVERTING ENZYME
INHIBITORS
(A) •Captopril •Enalapril •Lisinopril •Cilazapril •Perindopril
•Ramipril •Trandolapril •Fosinopril •Benazepril •Quinapril
•Moexipril •Spirapril
(B) FIX COMBINATIONS:
ACE + DIURETICS
Hydroclorothiazid + Captopril or/Enalapril or/Cilazapril or/Lisinopril or/Ramipril
or/Quinapril or/Benazepril or/Fosinopril or/Moexipril
ACE + CALCIUM-BLOCKERS
Trandolapril + Verapamil •Ramipril + Phelodipin

AT1-BLOCKERS

(A)•Candesartan •Eprosartan •Irbesartan


•Losartan •Telmisartan •Valsartan
(B) FIX COMBINATIONS:
Hydrochlorothiazid + Losartan or/Valsatran or/Irbesartan
CALCIUM CHANNEL BLOCKERS

(A) DIHYDROPYRIDINES:
GENERATION I •Nifedipin
•Nicardipin
GENERATION II •Phelodipin •Nimodipin
•Nifedipin SR
•Nisoldipin •Nitrendipin
GENERATION III •Lercanidipin
•Lacidipin •Amlodipin

(B) •Verapamil SR

(C) •Diltiazem
ALFA-1 BLOCKERS
(A) Alpha 1 selective: •Prazosin •Doxazosin •Terazosin
(B) Non-selective: •Phenoxybenzamin
•Urapidil

CENTRAL SYMPATHETIC INHIBITORS


(A) IMIDAZOLINIC RECEPTOR : •Moxonidin
(B) ALPHA-RECEPTOR: •Alpha-metil Dopa
(C) IMIDAZOLINIC RECEPTOR+ALPHA 2-AGONIST: •Clonidin

DIRECT VASODILATORS
(A) (Di)Hydralazin
(B) Minoxidil
(C) Diazoxid
(D) Sodium nitroprusside
(E) Nitroglycerine
Antihypertensive drugs with long-term action:

 24 hours effect in monodosis

 Better protection against major cardiovascular events and


against target organ damage.

 Calcium antagonists are effective in stroke prevention

 ACEI proved their efficiency in primary and/or secondary


prevention of myocardial infarction.
MONOTHERAPY vs. COMBINATION THERAPY

Consider untreated BP level


Assess the absence / presence of RF and target organ damage
Choose between

SINGLE AGENT TWO-DRUG COMBINATION


at low dose at low dose
Goal BP not achieved
Prev. agent Switch to Prev. combin Add a 3rdrd drug
(full dose) diff. agent (full dose) (at low dose)
(at low dose)

Goal BP not achieved


Two-three-drug Full dose THREE-DRUG COMBINATION
combination monotherapy at effective doses
POSSIBLE COMBINATIONS

Diuretics

BB AT1-receptor
blockers

α -Blockers Calcium antagonists

ACE inhibitors
CHOICE OF ANTIHYPERTENSIVE DRUGS

1. Previous experience (favourable/unfavourable) of the individual patient


with a given class of drugs

2. Cost of drugs

3. Cardiovascular risk profile of the individual patient

4. Presence of target organ damage

5. Presence of other coexisting disorders

6. Possibility of interactions with drugs used for other conditions present in


the patient
ANTIHYPERTENSIVE THERAPY IN
DIABETICS

 Goal BP: < 130/80 mmHg

 Type 1 DM
- without albuminuria : diuretics
beta-blockers
- with albuminuria : ACE inhibitors

 Type 2 DM : AT1-receptor antagonists


THERAPY IN HYPERTENSIVES with
IMPAIRED RENAL FUNCTION

 1st choice therapy : ACE inhibitors or AT1-receptor blockers


 2nd choice therapy: combination
- loop diuretic (creatinine > 2 mg/dl)
- Calcium antagonist
 Recent evidence : in advanced stages of renal impairment
ACE inhibitors + AT1-receptor blockers
THERAPY IN HYPERTENSIVES with
CAD and CONGESTIVE HEART
FAILURE

 The risk of a recurrent event in patients with CAD is significantly


affected by the BP level

Usual antihypertensive agents:


- Beta-blockers
- ACE inhibitors
- Anti-aldosterones
Recent data:
- AT1-receptors (as an alternative to ACE inhibitors or
in combination)
- dihydropiridines with long-term action (coronary
events prevention)
ANTIHYPERTENSIVE THERAPY IN THE
ELDERLY

 Benefit in all types of HT (isolated systolic HT)


 Treated :
SBP = 140 mmHg
DBP < 60 mmHg – bad prognosis
 Choice:
- diuretics
- dihydropiridines
- ACE inhibitors or AT1-receptor blockers
- beta-blockers
Hypertension in pregnancy

1. PRE-EXISTING HT BP ≥ 140/90 mmHg ± proteinuria


- before week 20 of gestation
- persists > 40 days postpartum

2. GESTATIONAL HT
a) without proteinuria
b) with significant proteinuria (> 500 mg/day)
= PRE-ECLAMPSIA
- develops after 20 weeks of gestation
- it resolves within 40 days postpartum

3. PRE-EXISTING HT + SUPERIMPOSED GESTATIONAL HT with


proteinuria
THERAPY CHOICE IN PREGNANCY

- Normal diet, without salt restriction!


- Not recommended: weight reduction!
- Level of SBP ≥ 170 mmHg or DBP ≥ 110 mmHg
- emergency admission !
- pharmacological therapy - Labetalol I.V.
- MetilDOPA p.o.
- Nifedipin
- Pharmacological management
* Gestational HT without proteinurie
* Pre-existing HT before 20 weeks of gestation
* gestational HT with proteinuria

Used agents : - MetilDOPA


- Labetalol
- Calcium antagonists
- BB
HYPERTENSIVE EMERGENCIES

1. MALIGNANT HT
Onset : hypertensive encephalopathy
Convulsive crises
• DBP > 140 mmHg
• Severe hypertensive retinopathy
• Spontaneous evolution : death/ cerebral, cardiac , renal damage
• Assessment: clinic: BP, diuresis
lab: urea, creatinine, ions
• Therapy: loop diuretics
arteriolar vasodilators: Hydralazin/Diazoxid/Na nitoprusside
ACE inhibitors
haemodialysis
2. PAROXISTIC HT
Etiology: - Phaeochromocytoma
- Aortic dissection
- Abrupt cessation of antihypertensive agents
- Brainstem tumors
Therapy:
* Regitin
* Loop diuretic
* Diazoxid or - Na nitroprusside
- Labetalol
- Clonidin
3. HT CRISIS and ACUTE CORONARY SYNDROME
* Na nitroprusside
* ACE inhibitors
* Sympathetic central inhibitors (Guanfacine)
* Nitrates
Antihypertensive agents in HT
emergency - dosis

1. Nitroprusiat Na: 0.25 - 10 µ g/kg/min


2. Nitroglycerin: 5 - 100 µ g/min
3. Diazoxid: 10 - 30 mg/min/30 min
4. Hydralazin: 10 - 20 mg
5. Labetalol: 2 - 4 mg/min
6. Urapidil: 12.5 - 25 mg bolus
7. Regitin: 5 - 10 mg bolus
8. Enalapril: 0.625 - 1.25 mg
Resistant Hypertension
DEFINITION:
Lifestyle changes and three-combination agents fail to lower systolic and diastolic BP sufficiently

Causes of resistant HTN:


-Unsuspected secondary cause
-Poor adherence to therapeutic plan
-Continued intake of drugs that rise blood pressure
-Failure to modify lifestyle (weight gain, heavy alcohol intake)
-Volume overload due to:
-Inadequate diuretic therapy
-Progressive renal insufficiency
-High sodium intake