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Hypertension
Case 1
• A 31 year old Burmese male presents with
shortness of breath x2 weeks. His blood
pressure is 210/130 and he has evidence of
volume overload. The creatinine is 2.0 and he
has severe LV dysfunction on an echo.
Case 1
• After initiating appropriate therapy, which of
the following studies should you consider
ordering next?
– MRI of the renal arteries
– 24 hour urine for catecholamines and
metanephrines
– 24 urine for cortisol
– Plasma renin activity and aldosterone levels
Case 1
• What is the best first choice for management
of this patients hypertension?
– Hydrochlorothiazide
– Lisinopril
– Hydralazine, isosorbide mononitrate and
furosemide
– Carvedilol and lisinopril
– Diltiazem and furosemide
Case 2
• A 55 year old male smoker recently diagnosed
with diabetes presents for a follow-up office
visit. His blood pressure on the last 3 visits has
been 148/85, 152/89 and 148/92. He is
asymptomatic. Laboratory studies and a
urinalysis are unremarkable. An EKG shows
sinus rhythm.
Case 2
• What is the next best step in management of
this patient?
– Council him to loose weight, stop smoking and
exercise more
– Start lisinopril 10 mg daily
– Start hydrochlorothiazide 25 mg daily
– Start metoprolol tartrate 25 mg BID
– Order an echocardiogram for LV function
HTN Is A Common And Costly
Problem
• Most common reason for non-pregnant patients to
visit MD office
• Most common reason for use of prescription drugs
• 29-31% incidence in population > age 18
• 56-65 million hypertensives vs 43.3 million in 1990
• Only 34% have controlled blood pressure
• Costs: 37 billion annually, 15.5 billion for Rx
• Projected to affect 1.5 billion worldwide by 2025
Cutler. Hypertension. 2008.
ALLHAT. JAMA. 2002.
Kearny. Lancet. 2005.
HTN Is Associated With Significant Morbidity
• Estimated lifetime risk of HTN is 90%
• Most common modifiable risk factor for
– MI
– Stroke
– Aortic dissection
– Heart failure
– Atrial fibrillation
– Peripheral arterial disease
Vasan. JAMA. 2002.
Definitions
• Normal blood pressure
– SBP < 120 and DBP < 80
• Prehypertension
– SBP 120-139 or DBP 80-90
• Hypertension
– Stage I: SBP 140-159 or DBP 80-89
– Stage 2: SBP > 160 or DBP > 100
Age Related Changes in Blood Pressure
Burt. Hypertension. 1995.
HTN Is A Risk Factor For
Death Worldwide
http://www.who.int/healthinfo/global_burden_disease/GlobalHealthRisks_report_full.pdf
HTN Is A Top Risk Factor For
Death At Every Income Level
http://www.who.int/healthinfo/global_burden_disease/GlobalHealthRisks_report_full.pdf
Global Mortality and Disease and Risk Factor Burden: Age 30
HTN Compounds Risk Regardless Of The Presence Of Other Risk Factors
Chobanian. JAMA. 2003.
Heart Disease Risk Increases With Minimal BP Elevation
Chobanian. JAMA. 2003.
Stroke Risk Increases With Minimal BP Elevation
Chobanian. JAMA. 2003.
Minimal BP Elevation Is Associated With Increased
Mortality
Chobanian. JAMA. 2003.
HTN Treatment And Awareness In the
US Has Improved
Kotchen. Circulation. 2010
Reduction Blood Pressure Leads to Clinical Benefits
Law. BMJ. 2009.
Physiology of Vascular Control
• Goal: Maintain blood flow to important organs
– Local tissue controls and overall adjustments of cardiac
pumping and vascular tone
• Short term blood pressure control
– Cardiac output=Stroke volume x HR
– Mechanisms
• Arterial baroreceptors, chemoreceptors, CNS (brain ischemia)
• Fluid shifts, RAS activation, vasodilator systems
• Long term blood pressure control
– Pressure natriuresis and diuresis
– Infinite gain feedback control
– All hypertension somehow alters this mechanism
Determinant of Blood Pressure
Klabunde. CV Physiology Concepts. 2005.
Time Dependence of BP Control
Fuster. Hurst’s the Heart. 12th Ed.
Mechanisms of HTN
Kaplan. Lancet. 2006.
Sympathetic Nervous System
Libby. Braunwald’s Heart Disease. 8th Ed.
Short Term BP Control
Mohrman. Cardiovascular Physiology. 6th Ed.
Long Term BP Control: Volume
Mohrman. Cardiovascular Physiology. 6th Ed.
Alternations In Sodium Handling Result In HTN
Fuster. Hurst’s the Heart. 12th Ed.
Risk Factors: Essential Hypertension
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Black race
Family history
Salt intake
Excess alcohol intake
Obesity
Dyslipidemia
Personality traits
Diagnosis
• Screening
– Every two years in normal
– Every year in SBP > 120
– Diagnose after 3-6 measurements
• “White coat hypertension”
– 20-25% of mild office hypertension
• Ambulatory BP monitoring
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White coat HTN
Episodic HTN
Resistant to increasing medication
Hypotensive symptoms on treatment
Autonomic dysfunction
Initial Assessment
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Extent of target organ damage
Assess overall cardiovascular risk
Rule out modifiable causes of HTN
History and physical
Studies
– EKG
– Labs: UA, Hgb, Gluc, Cr, K+, Na+, lipids
Suspect Secondary Causes of HTN
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Suggested by: age, history, exam, severity,
lab findings
Poor response to drug therapy
Previously controlled becomes resistant
Sudden onset
Secondary Hypertension
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Renal disease
Drugs and alcohol
Pheochromocytoma
Primary hyperaldosteronism
Renovascular
Cushings
Thyroid and parathyroid disease
Sleep disordered breathing
Coarctation of the aorta
Hints to Secondary Causes
• Renal disease
– Increased creatinine or abnormal UA
• OCPs, NSAIDS, diet pills, decongestants, stimulants, stroids,
herbals, calcineurin inhbitors, antidepressants
• Pheochromocytoma
– HTN (paroxysmal), HA, palpitations, sweating
• Primary aldosteronism
– Hypokalemia
• Cushings
– Cushingoid facies, central obesity, proximal muscle weakness,
ecchymosis
• Sleep apnea
– Snoring and apnea, daytime somnolence, morning confusion ,
depression
• Coarctation
– UE HTN, brachial-femoral delay, LW hypotension
• Hypothyroidism and hyperparathyroidism
Screening Tests for Secondary Causes
Pheochromocytoma
• Paroxysmal hypertension
in 50% of pheo patients
• Present in about 0.2% of
patients with HTN
• Headache, palpitations,
perspiration, pallor
• Screen with 24 urine
– Metanephrines
– Epinepherine
• Treat with surgery
Verrijcken. Am J Card. In Press.
Renal Artery Stenosis
• Most common after obesity and
EtOH
• Rare in mild HTN, 10-45% of
severe HTN
• Renal artery stenosis
– HTN age < 30 without family
history, severe HTN with onset
after 55
– Abdominal bruit
– Accelerated HTN
– Progressively resistant HTN
– Flash pulmonary edema
– RF of uncertain etiology
– ARF after ACE-I
– Asymmetric kidney size
• Screen with RA CT, US or MRI
• Treatment
– Medical
– Angioplasty or stenting
Zhang. Progress in CV disease. 2009
Hyperaldosteronism
• 10-20% in resistant HTN
• 50% normokalemic
• Screen
– Plasma renin activity (low)
– Plasma aldo/renin (high)
• Confirmatory test
• Surgery
• Medical
– Mineralocorotoid antagonist
Kumar. Robbins and Cotran Pathologic Basis of Disease. 8th Ed.
Coarctation Of The Aorta
• 6-8% of all congenital heart defects
• More common in males
• Associated with bicuspid valve,
Turners syndrome, other
congenital heart disease and
intracranial aneurysms
• BP and pulse variation
• 75% mortality at 46 years if
uncorrected
• CT, echo diagnosis
• Surgical or percutaneous repair
Libby. Braunwald’s Heart Disease. 8th Ed.
Sleep Apnea
• 15 million Americans
affected
• Increased CV mortality
• 50% of OSA have HTN
• 30% of HTN have OSA
• BP improves with OSA Tx
Somers. JACC, 2008.
Goals of Therapy
• Reduce cardiovascular and renal morbidity
and mortality
• Treat to goal < 140/90
• For diabetics and heart disease, <130/80
Benefits of Blood Pressure Lowering
• For stage I HTN (140159/90-99) and one risk
factor, sustained 12
mmHg lowering over 10
years prevents one
death per 11 patients
Outcome
Reduction
Stroke
35-40%
Heart failure >50%
Myoocardial 20-25%
infarction
Chobanian. JAMA. 2003.
Lifestyle Modification
Intervention
Recommendation
SBP Reduction
Weight reduction Normal body weight
(BMI 18.5-24.9)
5-20 mmHg/10 kg
DASH Diet
High fruit/veg, low fat
8-14 mmHg
Low salt diet
Less than 6 g NaCl
2-8 mmHg
Physical activity
30 min daily
4-9 mmHg
Moderate
alcohol
≤2/1 drink/day M/F
2-4 mmHg
Chobanian. JAMA. 2003.
Effects Of Lifestyle Interventions On HTN:
Premier Trial
Premier Collborative Group. JAMA, 2003.
Salt Reduction
Bibbins-Domingo. NEJM. 2010.
Approach to Medical Therapy
• Major drug categories
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Thiazide diuretics
ACE-I or ARB
Calcium channel blockers
Beta blockers
Direct Vasodilators
• Blood pressure reduction is important NOT agent used
• Wide interpatient variability in response to therapy
• Find regimen that is most effective with fewest side
effects
• Why we don’t succeed: lack of lifestyle modification,
inadequate drug dose, inappropriate drug combinations
ALL HAT Trial
• Designed to compare older cheaper agents
with newer ones
• 33,357 subjects 55 or older
• HTN and one additional cardiac RF
• Randomly assigned to chlorthalidone,
amlodipine, lisinopril or doxazosin
• Doxazosin stopped early for increased CHF
• Primary outcome: fatal heart disease or nonfatal MI
ALLHAT. JAMA. 2002.
Thiazide Diuretics First
Are Best: ALLHAT
• Chlorthalidone
– Lower heart failure than amlodipine and lisinopril
– Lower combined CV disease than lisinopril
– Benefits likely secondary to better BP control
• Chlorthalidone is different than HCTZ
– Different potency and duration of action
Blood Pressure Achieved: ALLHAT
ALLHAT. JAMA. 2002.
CAD Mortality and Non-Fatal MI: ALLHAT
ALLHAT. JAMA. 2002
Primary Endpoint: ACCOMPLISH
Jamerson. NEJM. 2008.
Initial Monotherapy
• Unlikely to be effective if BP > 20/10 over goal
• 60% of patients in ALLHAT required 2 drugs
Factors Affecting Choice of Initial
Therapy
Agent
Indication
Precautions
ACE-I
LV dysfunction, post MI,
DM, proteinuria
Diuretics (loop)
Heart failure
CCB (nondihydropyridine)
Rate control in AF, angina,
reactive airway disease
Beta Blockers
Post MI, HF, AF, Ishchemia
↑ stroke, CV events,
diabetes in age > 60
Alpha Blockers
Prostatism
Increased HF and CV
events
Hypokalemia
Sequential Monotherapy
• Largest benefit with initial low dose
• Higher doses with marginal increased benefit
and increase AEs
• Normalization with one drug in 30-50% of
patients with mild HTN
• If not responsive to one, 50% chance or
response to another
Comparison of Two Drug Regimens:
ACCOMPLISH
• 11, 506 patients
• Randomized to benez + HCTZ or amlodipine
Jamerson. NEJM. 2008.
Blood Pressure Control Achieved: ACCOMPLISH
Jamerson. NEJM. 2008.
ACCOMPLISH: ACE-I and CCB Was
Superior
Jamerson. NEJM. 2008.
Combination Therapy
• Long acting dihydropyridine + ACE-I/ARB
• Consider stopping thiazide
Strategy for HTN Management
Libby. Braunwald’s Heart Disease. 2007.
Thiazides
• Inhibits Na absorption in
DCT -> short term reduction
in plasma volume
• Vasodilation long term
• Adverse effects
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Erectile dysfunction
Hyperuricemia/gout
Hypo Na/K/Mg
Inc gluc or cholesterol
Sexual/sleep dysfunction
• Less effective with GFR <30
Libby. Braunwald’s Heart Disease. 2007.
Other Diuretics
• Loop diuretics
– Useful in volume overload
states
– Renal dysfunction
• Aldo antagonists
– Hyperaldo
• Amiloride
– K Sparing
• Adverse effects
– Dig and Li toxicity
– Inhibited by NSAIDS
Beta Antagonists
• Reduction in heart rate,
contractility, cardiac
output
• Reduction in renin
release
• Initial drop in cardiac
output, long term
reduction in peripheral
vascular resistance
Libby. Braunwald’s Heart Disease. 2007.
Calcium Channel Blockers
• Inhibit entry of calcium
into smooth muscle
through L-type channels
• DHP vs Non-DHP
• Non-DHP:
contrainidcations
– AV block
– LV dysfunction
Epstein. NEJM, 1982.
ACE-Inhibitors or Angiotensin Receptor Blockers
• Inhibit angiotensin II
or block its receptor
• Adverse effects
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Hyperkalemia
Angioedema
Cough (4-10%)
Renal dysfunction
Zaman. Nature Reviews, 2002.