HYPERTENSION

Physiology of Blood Pressure I

Blood Pressure =
Cardiac Output (CO) X
Peripheral Vascular Resistance

Components of Blood Pressure

Systolic Pressure
Diastolic Pressure
Pulse Pressure
Mean Arterial Pressure
2
 Pathophysiology I
Primary Hypertension

Genetics

Environment

Neurohormonal
mediators

4
Pathophysiology II
Contributing factors for
Primary HTN:
Increased activity of:
sympathetic nervous system (SNS)
Renin-angiotensin-aldosterone system
(RAA)
Defects in natriuretic hormone
function
Inflammation
Obesity
Endothelial dysfunction
Insulin resistance

5
 Pathophysiology III

Secondary Hypertension
Causes
Complications
Treatment

6
 Pathophysiology IV

Other forms of HTN

Complicated HTN
Malignant HTN

Hypertensive Crisis

7
 Natural History of Hypertensive Disease

From endothelial dysfunction to target-organ damage

Endothelial Vascular Elevated Target organ

dysfunction dysfunction BP damage
LVH
Renal
Hypertension, dysfunction
Aging, Stroke
Smoking,
Dyslipidemia MI/CAD
Awareness, Treatment, and Control of Hypertension Have Not
Increased Significantly in the USA

80 73
68 70
70
US population (%)*

59
60 55 54
51
50
40 34
31 29
30 27

20
10
10
0
NHANES II NHANES III NHANES III NHANES IV
(1976-1980) (1988-1991) (1991-1994) (1999-2000)
[Phase I] [Phase II]

Aware Treated Controlled

*Adults with hypertension aged 18 to 74 years.

Controlled: BP <140/90 mm Hg.
BP Reductions as Little as 2 mm Hg
Reduce the Risk of CV Events by Up to 10%

Meta-analysis of 61 prospective, observational studies

1 million adults
12.7 million person-years

7% reduction in risk
of ischemic heart
disease mortality
2 mm Hg decrease
in mean SBP
10% reduction in
risk of stroke
mortality

Lewington S et al. Lancet 2002;360:1903-1913.

 Pulse Pressure
PP = SBP DBP
Increase in pulse pressure (PP) indicates
greater stiffness in large conduit arteries,
primarily the thoracic aorta.
PP, therefore, is a surrogate measure of
dynamic, cyclic stress during systole.
PP may be a better marker of increased CV risk
than either systolic BP or diastolic BP alone in
older persons.
New Guidelines for Hypertension
National Institute for Health and Clinical Excellence (NICE), 2011
Kidney Disease: Improving Global Outcome (KDIGO), 2012
European Society of Hypertension/European Society of Cardiology,
(ESH/ESC), 2013
American Diabetes Association (ADA), 2014
American Society of Hypertension and the International Society of
Hypertension (ASH/ISH), 2014
Eighth Joint National Committee (JNC8), 2013
 2013 ESH/ESC Guidelines for the management of arterial hypertension

Denitions and classication of office BP levels (mmHg)*

Hypertension:
SBP >140 mmHg DBP >90 mmHg

Category Systolic Diastolic

Optimal <120 and <80

Normal 120129 and/or 8084

High normal 130139 and/or 8589

Grade 1 hypertension 140159 and/or 9099

Grade 2 hypertension 160179 and/or 100109

Grade 3 hypertension 180 and/or 110

Isolated systolic hypertension 140 and <90

* The blood pressure (BP) category is defined by the highest level of BP, whether systolic or diastolic. Isolated systolic hypertension should be
graded 1, 2, or 3 according to systolic BP values in the ranges indicated.

The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357
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Recommendations for
General Population Age 60 Years
JNC 7 Evidence for JNC8
BP Goal < 140/90 mmHg HYVET Trial
(No age recommendations) SHEP Trial
JATOS Trial
JNC8 VALISH Trial
BP Goal < 150/90 mmHg
Rated Grade A
Recommendations for
General Population Age < 60 Years
JNC 7
BP Goal < 140/90 mmHg
JNC8
SBP Goal < 140 mmHg
Grade E
DBP Goal < 90 mmHg
Ages 30-59 years (Grade A)
Ages 18-29 years (Grade E)
Evidence for JNC8
HDFP Trial
Hypertension-Stroke
Cooperative Trial
MRC Trial
ANBP Trial
VA Cooperative Trial
Recommendations for
General Non-black Population (Including DM)
JNC 7 Evidence for JNC8
First-line: Thiazide diuretics
ALLHAT Trial
(no racial distinction made) BP control more important than
JNC8 medication used
Alpha blockers not recommended
First-line first-line
Thiazide diuretics LIFE Study
CCB Beta-blockers not recommended
ACE inhibitor first-line
ARB Insufficient evidence to
Grade B recommend other classes
Recommendations for
General Black Population (Including DM)
JNC 7
First-line: Thiazide diuretics
(no racial distinction made)
JNC8
Initial treatment for black
population (Grade B) with DM
(Grade C)
Thiazide diuretics
CCB
ALLHAT Trial
Pre-specified subgroup analysis
Thiazide more effective in
improving CV outcomes
compared to ACEi in black
patient subgroup
51% higher rate of stroke (RR 1.51;
95% CI 1.22-1.86) with use of ACEi
as initial therapy in black patients
(compared to CCB)
46% of patients in subgroup
analysis had DM
Recommendations for
General Population Age 18 with CKD
JNC 7 Evidence for JNC8
Goal BP: < 130/80 mmHg AASK Trial
First-line agent: ACEi or ARB MDRD Trial
Potential benefit of goal <130/80 for
JNC8 patients with proteinuria (>3g/24
Goal BP: < 140/90 mmHg hours)
Grade E REIN-2 Trial
Initial or add-on treatment: ACEi No trials showed goal
or ARB <130/80 mmHg significantly
Grade B lowered kidney or CV end points
Regardless of race or DM status compared to 140/90
Recommendations for
General Population Age 18 with DM
JNC 7 Evidence for JNC8
Goal BP: < 130/80 mmHg ACCORD-BP Trial
No difference in outcomes with SBP
< 140 vs. SBP < 120
JNC8 No good or fair quality trials to
Goal BP: < 140/90 mmHg support DBP < 80
Grade E
ADA Guidelines for 2014
Goal BP for patients with DM
Less than 140/80 mmHg
ACCORD-BP trial
HOT Trial
Showed 51% reduction in major CV events in patients with DM
Post-hoc analysis of small subgroup of the study (not pre-specified)
Evidence graded as low quality by JNC8
Preferred Agents
ACEi or ARB
HOPE Study
Included non-hypertensive patients
Decreased risk of stroke with ACEi
Despite conflicting evidence, continue to recommend ACE/ARB first-line
Cite high CVD risk and high prevalence of undiagnosed CVD in patients with DM
JNC8: Treatment Strategies (Grade E)
If goal BP not met after 1 month of treatment:
Increase dose of initial drug, or
Add a second drug (Thiazide, CCB, ACEi, or ARB)
If goal BP not met with 2 medications:
Add and titrate a third medication (Thiazide, CCB, ACEi, or ARB)
Do not use ACE and ARB together
Other classes may be used in the following scenarios:
Goal BP not met with 3 medications
Contraindication to thiazide, ACE/ARB, or CCB
Strategies to Dose Antihypertensive Drugs
Titrate to max dose, then add a second drug
Add a second drug before achieving max dose of the
initial drug
Start with 2 drugs at the same time
If SBP 160mmHg and/or DBP 100 mmHg
If SBP 20mmHg above goal and/or DBP 10mmHg above
goal
***Consider scheduling follow-up with the Enhanced
Care Clinic for titration of BP Meds
Guideline Population Goal BP, Initial Drug Treatment Options
mm Hg
JNC 8 General 60 y <150/90 Nonblack: thiazide-type diuretic, ACEI, ARB, or CCB
2014 Hypertension
guideline

General <60 y <140/90 Black: thiazide-type diuretic or CCB

Diabetes <140/90 Thiazide-type diuretic, ACEI, ARB, or CCB

CKD <140/90 ACEI or ARB

NICE 2011 General <80 y <140/90 <55 y: ACEI or ARB

General 80 y <150/90 55 y or black: CCB

KDIGO 2012 CKD no proteinuria 140/90 ACEI or ARB

CKD + proteinuria 130/80

JAMA. 2013;():. doi:10.1001/jama.2013.284427

 2013 ESH/ESC Guidelines for the management of arterial hypertension

Blood pressure goals in hypertensive patients

Recommendations
SBP goal for most <140 mmHg
Patients at lowmoderate CV risk
Patients with diabetes
Consider with previous stroke or TIA
Consider with CHD
Consider with diabetic or non-diabetic CKD

SBP goal for elderly 140-150 mmHg

Ages <80 years
Initial SBP 160 mmHg

SBP goal for fit elderly <140 mmHg

Aged <80 years

SBP goal for elderly >80 years with SBP 140-150 mmHg
160 mmHg

DBP goal for most <90 mmHg

DB goal for patients with diabetes <85 mmHg

SBP, systolic blood pressure; CV, cardiovascular; TIA, transient ischaemic attack; CHD, coronary heart disease; CKD, chronic kidney disease;
DBP, diastolic blood pressure.

The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357
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 2013 ESH/ESC Guidelines for the management of arterial hypertension

Hypertension treatment for people with diabetes

Recommendations Additonal considerations
Mandatory: initiate drug treatment in patients with SBP Strongly recommended: start drug treatment when
160 mmHg SBP 140 mmHg

SBP goals for patients with diabetes: <140 mmHg

DBP goals for patients with diabetes: <85 mmHg

All hypertension treatment agents are recommended RAS blockers may be preferred
and may be used in patients with diabetes Especially in presence of preoteinuria or
microalbuminuria

Choice of hypertension treatment must take comorbidities into account

Coadministration of RAS blockers not recommended Avoid in patients with diabetes

SBP, systolic blood pressure; DBP, diastolic blood pressure; RAS, reninangiotensin system.

The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357
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 2013 ESH/ESC Guidelines for the management of arterial hypertension

Hypertension treatment for people with nephropathy

Recommendations Additonal considerations

Consider lowering SBP to <140 mmHg

Consider SBP <130 mmHg with overt proteinuria Monitor changes in eGFR

RAS blockers more effective to reduce albuminuria than Indicated in presence of microalbuminuria or overt
other agents proteinuria

Combination therapy usually required to reach BP goals Combine RAS blockers with other agents

Combination of two RAS blockers Not recommended

Aldosterone antagonist not recommended in CKD Especially in combination with a RAS blocker
Risk of excessive reduction in renal function,
hyperkalemia

SBP, systolic blood pressure; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; RAS, reninangiotensin system.

The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357
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 2013 ESH/ESC Guidelines for the management of arterial hypertension

Lifestyle changes for hypertensive patients

Recommendations to reduce BP and/or CV risk factors
Salt intake Restrict 5-6 g/day

Moderate alcohol intake Limit to 20-30 g/day men,

10-20 g/day women

Increase vegetable, fruit, low-fat dairy intake

BMI goal 25 kg/m2

Waist circumference goal Men: <102 cm (40 in.)*

Women: <88 cm (34 in.)*

Exercise goals 30 min/day, 5-7 days/week

(moderate, dynamic exercise)

Quit smoking

* Unless contraindicated. BMI, body mass index.

The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357
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 Pregnant Women

Chronic hypertension is high blood pressure present

before pregnancy or diagnosed before the 20th
week of gestation.
Preeclampsia is increased blood pressure that
occurs in pregnancy (generally after the 20th week)
and is accompanied by edema, proteinuria, or both.
ACE inhibitors and angiotensin II receptor blockers
are contraindicated for pregnant women.
Methyldopa is recommended for women diagnosed
during pregnancy.
 Antihypertensive Drugs
Used in Pregnancy
These agents* may be used with chronic hypertension
(DBP > 100 mm Hg) or acute hypertension (DBP > 105 mm Hg).

Central -agonists Methyldopa is the drug of choice.

-blockers and Atenolol, metoprolol, and labetalol appear safe and

effective in late pregnancy.
--blockers

Calcium antagonists Potential synergism with magnesium sulfate may lead to

precipitous hypotension.

*Limited or no controlled trials in pregnant women.

 Antihypertensive Drugs
Used in Pregnancy (continued)
These agents* may be used with chronic hypertension
(DBP > 100 mm Hg) or acute hypertension (DBP > 105).

Diuretics Diuretics are recommended for chronic

hypertension if prescribed before gestation, but
they are not recommended for preeclampsia.
Direct Hydralazine is the parenteral drug of choice
vasodilators based on its long history of safety and efficacy.

*Limited or no controlled trials in pregnant women.

ACE inhibitors and angiotensin II receptor blockers are contraindicated.

 Older Persons

Hypertension is common.
SBP is a better predictor of events than DBP.
Pseudohypertension and white-coat
hypertension may indicate a need for
readings outside the office.
Primary hypertension is the most common
cause, but common identifiable causes
(e.g., renovascular hypertension) should be
considered.
 Older Persons (continued)

Therapy should begin with lifestyle

modifications.
Starting doses for drug therapy should be lower
than those used in younger adults.
Goal of therapy is the same (< 140/90 mm Hg),
although an interim goal of SBP < 160 mm Hg
may be necessary.
 Referral
A patient should be referred
when:

BP remains uncontrolled after

three concurrent medications

Uncontrolled BP and signs and

symptoms of end-organ
damage

34
 Hospitalization
Hospitalization should be considered if:

Very high BP

Severe headache

Chest pain

Neurologic symptoms

Altered mental status

Acutely worsening renal failure

S & S of hypertensive emergency

35
Summary
Hypertension is a major factor responsible for
progression of atherosclerotic disease. Therefore,
a comprehensive treatment of hypertension should
aim at CV risk reduction strategies, including
management of all associated risk factors.