Download Arterial hypertension

Arterial hypertension
Taras V. Chendey
MD, PhD, Associate Professor
Chair of Hospital Therapy
Definition
• A systolic blood pressure (SBP) >139
mmHg and/or
• A diastolic (DBP) >89 mmHg.
• Based on the average of two or more
properly measured, seated BP readings.
• On each of two or more office visits
• i.e. hypertension is a persistent elevation
of office BP
• Isolated systolic hypertension
• increased systolic blood pressure at normal or
decreased diastolic BP
• pseudohypertension ← rigid arteries in old age
• “white coat hypertension “ – induced by stress at
physical examination
• „masked hypertension“ - false finding of normal
blood pressure during the examination; opposite
of white coat hypertension
Normal course
of blood pressure over age
Mean SBP
Female
Male
Mean DBP
age
male
female
age
HTN: prevalence in Europe in 2008
Розповсюдженість, %
adults ≥25 y/o
5
BP and ischemic heart disease mortality
BP and stroke mortality
Relationship between BP and CVD (cardiovascular disease) risk is continual, consistent and not
dependent on other risk factors
AH classification (1)
primary hypertension(essential AH,
hypertensive disease) (95-97%) –
unknown cause
secondary (symptomatic) hypertension (35%) – symptom (sign) of other disease or
state (renal, endocrine, drug-induced etc.)
AH classification (2)
Prehypertension
AH classification (3)
•
•
-
Stage I – no target organ damage (TOD)
Stage II – subclinical TOD:
left ventricular hypertrophy (as assessed by ECG or Echo)
microalbuminuria (30-300 mg/day)
moderate serum creatinine increase (133 mcmol/L in male, 124
mcmol/L in female)
- generalized narrowing of retinal arteries
• Stage III – clinically significant TOD with symptoms and impaired
function:
- MI
- Stroke or TIA
- Renal failure
- Retinal haemorrhages and exudated with/without papilledema
AH classification (4)
Factors inducing Hypertension
•
•
•
•
•
•
•
•
Renin-angiotensin system RAS, RAAS
Sympathetic nervous system
Insuline resistance
Overweight
Stiff vessel walls (endothelial dysfunction)
Vasoactive substances (NO, Endotheline)
Kallikrein secretion
Natriuretic peptides
Pathophysiology of Hypertension
Heart Rate
x
Stroke volume
cardiac output
x
Peripheral resistance
=
Blood pressure
Basic equation according to
Law of OHM:
Current I
x
Resistance R
=
Voltage U
Neuro-humoral Regulation of
Hypertension
Heart rate x stroke volume
x
beta1
Norepinephrine
Nervous system
Peripheral resistance
=
Blood pressure
alpha1
Angiotensin II
Humoral RAAS*
*RAAS or RAS: renine angiotensine aldosterone system
Pathophysiology of Hypertension
prorenine, katecholamines
Angiotensinogene
Pathway of RAAS in the
organism (kidney, heart,
Vessels) to maintain
Fluid volume control,
Adjustment of CO and
Resistance.
If regulation fails, high
blood pressure occurs
Renin
Angiotensin I
ACE
Angiotensin II
receptor
AT1
AT2
Pathway of RAAS in the
Tissues: e.g.
Vessel wall
Competition of receptors:
AT1 vasoconstriction
AT2 vasodilatation
Pathophysiology of Hypertension:
Angiotensin II Stimulation
Sodium, renine
Kidney
Ang II*
Hypophysis
Hormone release
*Ang II effects mediated by AT1
Adrenal gland
Aldosterone, katecholamines
Pathophysiology of Hypertension:
Angiotensin II Effects
Brain
synaptic conduction
vasoconstriction
vessels
Ang II
Heart
constriction
AT1 mediated effects of
Angiotensin II
Uterus
contraction
hypertrophy
Pathophysiology of Hypertension
Heart rate x stroke volume
x
Peripheral resistance
=
Blood pressure
Conclusion:
n.sympathicus
RAAS*
Primary Hypertension
is a target disease mainly
of the RAAS - intima - endothelium system!
Stress
social
familial
*renine angiotensine aldosterone system
Genetic/Familial
ethnic
Hereditary
salt sensitivity
Vasoconstriction
Endothelial
dysfunction
Pathophysiology of Hypertension
time course of hypertension development
no symptoms
Onset,Trigger
3
Chronic stage
4
Nonspecific Symptoms:
Head ache,
Palpitation,
Exertional dyspnea
5
accelerated course
April 2013
ghennersdorf SES FESC DGK
target organ damage
death
6
6+ (x10th years)
HTN: clinical findings
• HTN is usually completely asymptomatic, unless
BP ≥230/120 Hg, when cerebral edema occurs
• Headaches, dizziness, blurred vision, vertigo,
palpitations, chest pain or discomfort may be
associated with concomitant stess/neurosis
rather than HTN
• History: search for stress (anxiety/depression),
smoking, alcohol and salt excess, family Hx,
drugs (e.g., NSAIDs, corticosteroids), obesity,
diabetes, renal disease, thyrotoxicosis
HTN: physical exam
• Most cases – no abnormalities
• Proper BP measurements are essential
• LVH may be suspected when point of maximum impulse
is brisk, enhanced and resistant
• Abdominal bruit may be suggestive for renovascular
HTN
• Palpable abdominal mass may be in fact enlarged
polycystic kidney
• Low BP on legs – major screening test for coarctation of
aorta
• Fundoscopy – search for hypertensive retinopathy
Retina Normal and Hypertensive
Retinopathy
A
B
C
Normal Retina
Hypertensive Retinopathy
A: Hemorrhages
B: Exudates (Fatty Deposits)
C: Cotton Wool Spots (Micro
Strokes)
Stage I- Arteriolar Narrowing
Arteriolar Narrowing
Stage II- AV Nicking
AV
AVNicking
Nicking
AV Nicking
AV Nicking
Stage III- Hemorrhages (H), Cotton
Wool Spots and Exudats (E)
H
E
Stage IV- Stage III+Papilledema
Left ventricular hypertrophy
– To diagnose LVH you can use the following criteria:
• R in V5 (or V6) + S in V1 (or V2) > 35 mm (Sokolow criterion), or
• R in avL + S in V3 > 28 mm (men), 20 mm (women) – Cornell criterion
S = 13 mm
* There are several
other criteria for the
diagnosis of LVH.
R = 25 mm
A common cause of LVH
is hypertension.
Circadian rythm of BP (dippers vs. non-dippers)
HTN: work-up
• Urinalysis.
• Blood glucose and hematocrit; serum potassium,
creatinine (or estimated GFR), and calcium.
• HDL cholesterol, LDL cholesterol, and
triglycerides.
• Optional tests
urinary albumin excretion.
albumin/creatinine ratio
• Echocardiography
Goals of Treatment
• Treating SBP and DBP to targets that are
<140/90 mmHg
• Patients with diabetes or renal disease, the BP
goal is <130/80 mmHg
• The primary focus should be on attaining the
SBP goal in older patients and DBP in younger
patients.
• To reduce cardiovascular and renal morbidity
and mortality
Benefits of Treatment
• Reductions in stroke incidence, averaging
35–40 percent
• Reductions in MI, averaging 20–25
percent
• Reductions in HF, averaging >50 percent.
Lifestyle modifications
www.nhlbi.nih.gov
Pharmacologic treatment
Antihypertensives
1st choice drugs:
1. diuretics
2. β-blockers
3. inhibitors of ACE
4. blockers of AT1 receptors (ARB)
5. calcium channel blockers
2nd choice drugs – mainly to drug combinations:
α1-sympatholytics; α2-sympathomimetics; direct
vasodilators; kallium channel openers;
agonists of I1 receptors in CNS; other mechanisms of action
Diuretics
Diuretics
• increase sodium excretion
1. loop diuretics (mainly long-acting lowdose torasemide) ability to excrete to 25 %
of Na+ from filtrate
• block active reabsorption of Na+, Cl-, K+
from ascending limb of Henle´s loop
• rarely used in treatment of hypertension
2. thiazide diuretics (hydrochlorothiazide, chlorthalidone,
•
•
clopamide)
• block reabsorption of Na+ and Cl- from distal tubulus
• effect is weaker as at loop diuretics – they excrete about
5 % from Na+ filtrate
• most suitable diuretics for long–lasting treatment of
hypertension
• effect also in vessel wall (↓ volume of Na and ↓reactivity to norepinephrine;
regression of media hypertrophy)→ this effect is characteristic for indapamid
and xipamid
(increase of diuresis is negligible) → also called „diuretics without diuretic
effect“ 
• the most is used hydrochlorothiazide – daily dose 12,5 – 25 mg
diuretics are preferred for older patients with ISH, concomitant chronic heart
failure. They could be combined with any other first-line medication
Side effects of thiazide diuretics - hypokalemia, hypovolemia, hyperuricemia,
metabolic ADRs (impaired glucose tolerance and dyslipidemia - mostly after
high doses), erectile dysfunction
Main Benefits of ACE inhibition
AC enzyme inhibitors
• block the conversion of angiotensin I to angiotensin II and at
the same time block inactivation of bradykinin
• vazodilation in both resistant and capacitance vessels
• most useful in:
- HTN with heart failure (vasodilating therapy
of cardial insuficiency), also after myocardial infarction
- hypertonic people with DM and different forms of diabetic
nephropathy starting with microalbuminuria
(nephroprotective effect of ACEI)
• reaction of airways is often irritating cough (bradykinin
cough) → intollerance of the whole group → replacement to
AT1 receptor blockers
• typical hydrophilic ACEI:
captopril (prototype substance – has SH-group; dosing q8
hrs – not suitable for chronic treatment)
enalapril (Renitec, Enap, Berlipril),
lisinopril (Diroton, Lipril)
• typical lipophilic ACEI:
perindopril (Prestarium)
ramipril (Tritace, Ampril)
• ADRs:
impaired renal function, hyperkalemia, hypotension, dry cough,
angioneurotic edema
• contraindications: pregnancy!, high concentration of
potassium and creatinine, bilateral stenosis of a. renalis,
severe aortal stenosis
Angiotensin-II receptor blockers (ARBs)
• antihypertensive efficacy comparable to ACEi
• the most often replacement of ACEI in case of cough
• losartan (prototype; Cozaar), valsartan (Diovan),
candesartan, irbesartan (Aprovel)
• often prescribed as 1st choice, even before ACEI
← clinical studies indicate that they have among patients
with HT and DM 2 slightly better protective effects than
ACEI
• ARBs are not associated with angioedema
• Absolutely contraindicated in pregancy
• Very few side effects – comparable to placebo
Calcium Channel Blockers (CCBs)
Classification:
CCB – Mode of Action
Block influx of calcium into cell through slow
L-type channels, lower its intracellular
concentration what causes relaxation of
smooth muscle in vessel wall, decrease
myocardial contractility, decrease of
electrical irritability and conductivity
Calcium channel blockers
• at treatment of hypertension dihydropyridines are mostly
used
• prototype short-acting DHP nifedipine is not indicated!
- it reduces BP too rapidly, so induces reflex sympathic
activation with subsequent increase of BP and HR
• the 2nd generation of DHPs (isradipine, felodipine,
nitrendipine) and 3rd generation (amlodipine, lacidipine,
lercanidipine) has no this side effect
• Ca2+ blockers are suitable to treat hypertonic patients with
DM, metabolic syndrome, at ischaemic disease of lower
extremities
• particularly advantageous are for isolated systolic
hypertension
• possibilities of combinations: ACEI, βB (only
dihydropyridines), diuretics
• ADRs: headache, red face, ankle edema, constipation,
tachycardia (dihydrop.), severe bradycardia (nondihydropyridins), steal phenomen
β-blockers
Classifications:
1. non-selective (β1- aj β2-effect – propranolol, metipranolol);
selective (β1-effect – metoprolol, bisoprolol, atenolol, ...);
hybrid substances (beside β-effect have also other effects,
additional, resp. β2-mimetic effect), through which they induce
vazodilation – labetalol, carvedilol, nebivolol, ...)
– the most important classification
2. β-blockers with ISA (intrinsic sympathomimetic activity –
pindolol, acebutolol, ...; ≈ parcial agonists) and without ISA
3. hydrophilic (atenolol, celiprolol, ...) and lipophilic β-blockers
(propranolol, metoprolol, carvedilol, ...)
4. classification according to generations
β-blockers
• preferenced are selective and hybrid substances before
nonselective
• don´t differ very much in antihypertensive effect, selection
according to adverse effect profile
• suitable for younger patients with ↑ sympathicoadrenal
activity, hyperkinetic circulation, patients under psychical
stress; patients with existent ischaemic heart disease and
mainly after myocardial infarction
• in our country are mainly prescribed :
metoprolol (Betaloc ZOK, Egilok)
bisoprolol (Concor)
carvedilol (Coryol, Cardiostad)
nebivolol (Nebitrend, Nebilet)
• β-blockers – possibilities of combinations:
diuretics, Ca2+ blockers – only dihydropyridines!, α1sympatholytics, ACEI, vazodilators
 ADRs:
• tendency to bronchoconstriction and to vasoconstriction
in the periphery – mainly at non-selective βB
• metabolic ADR – worsening of lipidogram; mask
symptoms of hypoglycemia and can impair glucose
tollerance – more at non-selective βB
• sleep disturbances, bad dreams → ... depression
• at very high doses can worsen heart failure; if indicated
at chronic heart failure, dose should be increased step by
step
• erectile dysfunction