4. Causes of Hypertension
• Primary – 90-95% of cases – also termed “essential”
of “idiopathic”
• Secondary – about 5% of cases
– Renal or renovascular disease
– Endocrine disease
•
•
•
•
Pheochomocytoma
Cushing’s syndrome
Conn’s syndrome
Acromegaly and hypothyroidism
– Coarctation of the aorta
– Iatrogenic
• Hormonal / oral contraceptive
• NSAIDs
5.
6.
7.
8.
9.
10. Prevalence
•
•
•
•
•
Children - 4% mostly secondary
Middle age - 11-21%
50-59 years - 44%
60-69 years old - 54 %
>70 years old - ≥ 64 %
11. Risk Factors
• Age is the major risk factor
– Blood pressure increases with age in both men and women
– The lifetime risk for hypertension is nearly 90%
– The risks for high blood pressure increases in men over age
45 and women over age 55
• Family History
– People with parents or other close relatives who have high
blood pressure have an increased risk of developing it
themselves
12. Risk Factors
• Obesity
– About a third of patients with high blood pressure are
overweight
– BMI ≥ 35kg/m2 double the risk of hypertension than people
with normal weights
• Obstructive Sleep Apnea
• Lifestyle Factors
–
–
–
–
–
Smoking
High Salt (Na) and low Potassium intake
Chronic Alcohol intake
Physical Inactivity
Stress
13. Mortality Due to CHD per Quartile
of Usual SBP
USA
Japan
van den Hoogen et al. N Engl J Med 2000;342:1.
15. Key Message
Above 115/75 mmHg, CVD risk doubles
with each BP increase of 20/10 mmHg
Role of blood pressure in cardiovascular morbidity and mortality. Prog Cardiovasc Dis. 1974;17:5-2.
16.
17. Blood Pressure Classification
and Management
BP
Indications
Classification
Normal
SBP
DBP
Lifestyle
mm Hg
mm Hg
Changes
<120
and <80
Initial Drug Therapy
Compelling
Without
With
Encourage
Pre HTN
120-139 or 80-89
Yes
No
Yes*
Stage 1 HTN
140-159 or 90-99
Yes
Yes
Yes
Yes
Yes
Yes
Stage 2 HTN
>160
or >100
* Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mm Hg
JNC VII. JAMA 2003;289:2560.
18. Factors Contributing to Poor Blood Pressure
Control
18%
Took no action
Increased dose
Changed drug
Prescribed
add-on therapy
Taylor Nelson Healthcare, Epson, Surrey England - Cardiomonitor 1992
19. Goals of the Hypertensive Evaluation
• Does the patient have primary or
secondary (reversible) hypertension?
• Is target organ damage present?
• Are other cardiovascular (CV) risk
factors present?
20. Routine Work-up
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
21. "The Goal is to Get to Goal!”
Hypertension
< 140/90 mmHg
-PLUSDiabetes or Renal Disease
< 130/80 mmHg
24. Impact of a 5 mmHg Reduction
Overall Reduction
Stroke
14%
Coronary Heart Disease
9%
All Cause Mortality
7%
Hypertension 2003;289:2560-2572.
25. Dietary
Approaches to
Stop
Hypertension
• Lowers systolic BP
– In normotensive patients
by an average of 3.5
mm Hg
– In hypertensive patients
by 11.4 mm Hg
http://www.nhlbi.nih.gov/health/public/heart/hbp/dash/
26. DASH Eating Plan
• Low in saturated fat, cholesterol, and total fat
• Emphasizes fruits, vegetables, and low fat
diary products
• Reduced red meat, sweets, and sugar
containing beverages
• Rich in magnesium, potassium, calcium,
protein, and fiber
• 1.5-3 gm sodium per day
• Can reduce BP in 2 weeks
Sacks FM. NEJM. 2001; 344:3-10.
32. Loop Diuretics
Loop diuretics
bumetanide)
(furosemide,
etacrynic
acid,
– Strong short-lasting effect
– 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 as antihypertensive – only furosemide in low
dosage – if simultaneously is very much reduced Glomerular
filtration
– They aren´t suitable for long-lasting application
33. Thiazide Diuretics
Thiazide
diuretics
chlorthalidone, clopamide)
(hydrochlorothiazide,
– Block reabsorption of Na+ and Cl- from distal tubulus
– Effect is weaker then loop diuretics – they excrete about 5 %
from Na+ filtrate
– Most suitable diuretics for long–lasting treatment of
hypertension
– The most is used hydrochlorothiazide – daily dose 12.5 – 25
mg
34. K+ Sparing Diuretics
K-sparing diuretics - Spironolactone (aldosterone
antagonist), Amiloride, Triamterene
– Only in resistant hypertension and to assistant
drugs in combinations to correct hypokalemia
40. β-blockers – Side Effects
1. Tendency to bronchoconstriction
–
Use with caution in patients with asthma and reactive
airway disease
1. Negative chronotropic effects
–
Slowing of the resting heart rate and the development of
sinus bradycardia - relatively contraindicated in patients
with symptomatic bradycardia
1. Heart Block
–
By blocking AV node resulting in serious bradyarrhythmia
complete or partial AV conduction defect (i.e., second or
third degree AV block)
41. β-blockers – Side Effects
4. Metabolic Effects
– Worsening of lipid profile
– Mask symptoms of hypoglycemia and can impair glucose
tollerance – more at non-selective agents
– 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
42. β-blockers
!Selectivity of action is only relative!
• At higher doses selectivity is dissapearing even among β1-selective agents appear β2lytic effects
• Should not be combined with verapamil or a
diltiazem
• Treatment can´t be stopped abruptly –
rebound effect!
44. CCB – Mechanism of Action
• Block influx of calcium to cell through slow L-type
channels, lower its intracellular concentration what
causes relaxation of smooth muscle in vessel wall,
decrease of contractility, decrease of electrical
irritability and conductivity
45. CCB in Hypertension
• Most commonly used Calcium channel blockers in
treatment of hypertension are:
– Dihydropyridines – especially Amlodipine (Norvasc)
– Non dihydropyridines – Verapamil and Diltiazem only in
presence of tachycardia
– Prototype short-acting DHP nifedipine is contraindicated!
• It reduces BP too rapidly, so induces reflex activation of
sympathatic stimulation with subsequent increase of BP and
such a repeated BP fluctuation causes worse vessel damage
as untreated hypertension → instead of mortality decrease its
increase!
46. CCB in Hypertension
• Ca++ blockers are suitable for
– Patients with DM
– Metabolic syndrome
– Peripheral vascular disease
• It has of particularly advantageous in
treatment of isolated systolic hypertension
• Nimodipine (1st generation) affinity to brain
vasculature → effectively relieves spasms of
cerebral arteries → used in subarachnoid
bleeding
47. CCB – Side Effects
• Side effects of CCB are:
–
–
–
–
–
–
–
–
Dizziness
Headache
Redness in the face
Fluid buildup in the legs and ankle – dependent
edema
Rapid heart rate
Slow heart rate
Constipation
Gingival overgrowth
50. ACE Inhibitors
• It block the conversion of angiotensin I to angiotensin
II and at the same time block inactivation of
bradykinin
– Vasodilation in both resistant and capacitance vessels
• Indication:
– Hypertensive patients with heart failure
– In acute myocardial infarction
– In diabetes and diabetic nephropathy with or without
microalbuminuria
54. ACE Inhibitors – Side Effects
• A persistent dry cough is a relatively common
adverse effect believed to be associated with
the increases in bradykinin levels produced
by ACE inhibitors
• Patients who experience this cough are often
switched
to
angiotensin
II
receptor
antagonists
55. ACE Inhibitors - Contraindications
•
•
•
•
•
•
Previous angioedema associated with ACE inhibitor therapy
Renal artery stenosis (bilateral or unilateral with a solitary
functioning kidney)
Hypersensitivity to ACE inhibitors
Hyperkalemia (>5.5mmole/L)
Creatinine >2.5mg/dl
ACE inhibitors should be used with caution in patients with:
– Impaired renal function
– Aortic valve stenosis or cardiac outflow obstruction
– Hypovolemia or dehydration
56. ACE Inhibitors - Contraindications
• In pregnancy - category D
– Should be avoided in women who are likely to become
pregnant
– Taken during the first trimester have been reported to cause
major congenital malformations, stillbirths, and neonatal
deaths
– Commonly reported fetal abnormalities include hypotension,
renal
dysplasia,
anuria/oliguria,
oligohydramnios,
intrauterine growth retardation, pulmonary hypoplasia,
patent ductus arteriosus, and incomplete ossification of the
skull
– Overall, about half of newborns exposed to ACE inhibitors
are adversely affected
57. Angiotensin Receptor Blockers
• Most often replacement of ACEI in case of cough
– Losartan
– Valsartan
– Candesartan
– Irbesartan
• Sometimes 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
• Side effect profile (except cough) and contraindications
are same as that of ACEI
58. α1- Blockers
• Along with BP reduction they reduce the size of
prostate
→ Indicated mainly in older man with simultaneous
benign prostate hyperplasia (BPH)
• Other indications:
– In combination for severe resistant hypertension
– strong 1st dose phenomenon! → postural
hypotension, syncopes
59. α1- Blockers
• Prazosin
• Doxazosin
• Terazosin
Side effects
– Hypotension
– Orthostatic hypotension (postural hypotension) –
thus alpha blockers should be taken at bedtime
– First dose phenomenon may be reduced by
starting at a low dose and titrating upwards as
needed
60. α2 - Agonists
• Centraly acting – stimulation of central α2
receptors
• Through negative feedback inhibit release of
norepinephrine on periphery → reflex BP
reduction
– α-metyldopa
– Clonidine
• S/E:
– Central depression – sleepiness, bad dreams
– Clonidine has significant rebound phenomenon
63. Relative Efficacy of Each group
These observations are secondary to the plasma Renin activity, older and
blacks have less activity than younger and white population
N Engl J Med. 1993;328(13):914-21.
64. Meta Analysis
14
12
10
SBP Reduction 8
(mmHg)
6
4
2
0
1/2 Standard
Standard
2x Standard
Thiazides
BB
ACEI
ARB
CCB
• All five drug categories produced similar BP
reductions
• Blood pressure reduction achieved with half
standard dose was only 20% lower than standard
dose
Law MR et al. BMJ. 2009;338:b1665.
65. • The ASCOT trial found a lower rate of
cardiovascular disease and death with
a calcium channel blocker (Amlodipine)
compared to a beta blocker (Atenolol)
– Patients in the Amlodipine arm had a
significantly lower mean blood pressure at
the end of the study (3/2 mmHg)
Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): Lancet.
2005;366(9489):895-906.
66. Ramipril1 and
Perindopril2 produced
better outcomes than placebo in the
HOPE and EUROPA trials of patients at
increased cardiovascular risk, but the
blood pressure was significantly lower
in the treated patients: 3.3/1.4 mmHg
(with a greater difference overnight) in
HOPE and 5/2 mmHg in EUROPA
1. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342(3):145-53.
2. EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators.
Lancet. 2003;362(9386):782-8.
67. When differences in outcomes have
been noted in trials comparing different
antihypertensive
drugs,
the
drug
producing better outcomes had better
blood pressure control
68. AHA statement on the treatment of blood pressure in
ischemic heart disease, and European Society of
Hypertension/ESC guidelines on the management of
hypertension all concluded that the amount of blood
pressure reduction is the major determinant of reduction
in cardiovascular risk in both younger and older patients
with hypertension, NOT the choice of antihypertensive
drug
69. Is it appropriate to start multiple antihypertensive?
Administering two drugs as initial therapy should be
considered when the blood pressure is more than
20/10 mmHg above goal
Fixed dose combinations can be used as it increased
patient compliance
The JNC 7 report. JAMA. 2003;289(19):2560-72.
70. Is it appropriate to start 2 agents?
• In ALLHAT, 60% of patients achieved SBP control
• The mean number of drugs to achieve BP control
was 1.6
• Inadequate titration of drug regimens is a primary
reason patients do not reach BP goal
• Patients and providers should be educated that
more than one antihypertensive is the norm not
the exception
71. Low Dose Combinations
• Meta-analysis of 354
• n=56,000 patients
randomized trials of
• Placebo adjusted
antihypertensives: BB,
reductions in SBP and
ACEI, ARB, & CCB
DBP
• Dose of each agent
• Prevalence in adverse
expressed as a multiple
effects based on dose
of a standard dose
Law MR et al. BMJ. 2009;338:b1665.
72. Low Dose Combinations
19.9
20
SBP
Reduction 10
(mmHg)
0
13.3
6.7
1 Drug
2 Drug
3 Drugs
BP lowering effects from different drug
categories were additive
Law MR et al. BMJ. 2009;338:b1665.
73. Low Dose Combinations
• Adverse effects in all drug categories, except
ACEI, were dose related
• Prevalence of adverse effects in combination
was less than additive
Conclusion:
Utilization of low dose combination therapy
can effectively reduce blood pressure while
limiting the incidence of side effects
Law MR et al. BMJ. 2009;338:b1665.
76. "The Goal is to Get to Goal!”
Hypertension
-PLUSDiabetes or Renal Disease
< 140/90 mmHg
Patients should return for
< 130/80 mmHg
follow-up and adjustment of
medications every 1-2 months
until the BP goal is reached
77. When a Patient is Still Not at Goal?
Optimize dosages or add additional
drugs until goal blood pressure is
achieved
78. When a Patient is Still Not at Goal?
What do you do when you are using
several effective medications?
Consider causes of resistant
hypertension
79. Causes of Resistant Hypertension
Improper BP measurement
Dietary and medicine non compliance
Inadequate diuretic therapy
Medication
• Inadequate doses
•Drug actions and interactions:
Nonsteroidal anti-inflammatory 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
80. 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
81. Other Medications
(1) Aspirin:
•
Use 75mg daily if patient is aged ≥50 years with blood pressure
controlled to <150/90 mm Hg and either; target organ damage,
diabetes mellitus, or 10 year risk of cardiovascular disease of
≥20%
(2) Statin:
•
Use when 10 year risk of cardiovascular disease of ≥20% and with
total cholesterol concentration ≥200mg/dl
(3) Vitamins—no benefit shown, do not prescribe
84. Chinese Menu Approach
Veins
Heart
Thiazides
Loops
Aldosterone Ant.
Nitrates
Beta Blockers
Diltiazem
Verapamil
ACEI
ARB
Via Central
Mechanism:
Clonidine
Arteries
Dihydropyridines
Hydralazine
Minoxidil
Alpha1 Blockers
ACEI
ARB
Choose one agent from each category
85. 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
Indications
Stage 1 HTN (SBP 140–159 or
DBP 90–99 mmHg)
Thiazide-type diuretics for most.
May consider ACEI, ARB, BB,
CCB, or combination.
With Compelling
Indications
Stage 2 HTN (SBP >160 or DBP
>100 mmHg)
2-drug combination for most
(usually thiazide-type diuretic
and
ACEI, or ARB, or BB, or CCB)
Drug(s) for the compelling
indications
Other antihypertensive drugs
(diuretics, ACEI, ARB, BB, 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.
JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314
86. Follow-up and Monitoring
Patients should return for follow-up and
adjustment of medications every 1-2 months
until the BP goal is reached
After BP at goal and stable, follow-up visits at 3to 6-month intervals
More frequent visits for stage 2 HTN or with
complicating comorbid conditions
Continue to encourage self BP monitoring
Serum potassium and creatinine monitored 1–2
times per year
JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314
87. Malignant Hypertension (HTN
Emergency)
• Hypertensive emergencies encompass a spectrum of
clinical presentations in which uncontrolled blood
pressures lead to progressive or impending endorgan dysfunction
• BP should be lowered aggressively over minutes to
hours
89. Malignant Hypertension (HTN
Emergency)
• The history and the physical examination determine
the nature, severity, and management of the
hypertensive event
• The history should focus on the presence of endorgan dysfunction, the circumstances surrounding the
hypertension, and any identifiable etiology
• The duration and severity of the patient’s preexisting
hypertension
90. Malignant Hypertension (HTN
Emergency)
• Patients may complain of specific symptoms
that suggest end-organ dysfunction
– Chest pain may indicate myocardial ischemia or
infarction
– Back pain may denote aortic dissection
– Dyspnea may suggest pulmonary edema or
congestive heart failure
– Presence of neurologic symptoms may include
seizures, visual disturbances, and altered level of
consciousness and may be indicative of
hypertensive encephalopathy
91. Malignant Hypertension (HTN
Emergency)
•
•
•
•
Physical examination should assess whether end-organ
dysfunction is present
BP should be measured in both the supine and standing
position as well as in both arms
The presence of new retinal hemorrhages, exudates, or
papilledema suggests a hypertensive emergency
Evaluate for the presence of heart failure
– Indicated jugular venous distention
– Crackles on auscultation
– Peripheral edema
•
•
CNS findings may include changes in the patient's level of
consciousness and visual fields, and/or the presence of focal
neurologic signs
Abdominal masses or bruits may be noted
92. Malignant Hypertension (HTN
Emergency)
•
•
•
•
Immediate admission
Close monitoring
Parentral antihypertensive
Selection of antihypertensive agent depends
upon target organ at risk
• Goal is to rapidly lower BP in minutes to
hours
93. Hypertensive Urgency
•
Severe hypertension (as defined by a Systolic BP >200mmHg
&/or diastolic blood pressure above 120 mmHg) in
asymptomatic patients without any evidence of target organ
damage
•
Don't require immediate reduction in BP
•
Don't require admission in monitored setup
•
Treat with oral medications
•
BP should be lower in hour to days
94. Take Home Message
For persons over age 50, SBP is a more important than DBP as CVD risk
factor
Starting at 115/75 mmHg, CVD risk doubles with each increment of
20/10 mmHg throughout the BP range
Persons who are normotensive at age 55 have a 90% lifetime risk for
developing HTN
Those with SBP 120–139 mmHg or DBP 80–89 mmHg should be
considered prehypertensive who require health-promoting lifestyle
modifications to prevent CVD
95. Take Home Message
• Start with one of CCB/ACEI/ARB/HCTZ
– All have equal efficacy in lowering BP
– Unless compelling indication
• Use two or more drugs or in combination if
needed – have additive effect
• And the goal is TO GET THE GOAL
Editor's Notes
This slide summarizes the classification of BP and the suggested treatment approaches from JNC 7 published in 2003.
Two important differences from JNC6
redefinition of BP goals such that we now talk about prehypertensive readings(those patients with BP 130-139/80-89 are at twice the risk to develop hypertension as those with lower values
stage 2 and 3 were combined
Weight reduction + DASH is equivalent to 1-2 antihypertensives
