Hypertension

Learning Objectives
• Identify the different stages of elevated blood pressure
• Recognize the various risk factors for developing hypertension
• Describe standard of care approach to treatment of
hypertension
• Summarize the major adverse effects of different
antihypertensive classes
• Define resistant hypertension, hypertensive urgency, and
hypertensive emergency
Definitions

Blood Pressure Systolic Pressure (mm Diastolic Pressure (mm

Classification Hg) Hg)
Normal <120 and <80

Elevated 120-129 and <80

Stage 1 Hypertension 130-139 or 80-89

Stage 2 Hypertension ≥140 or ≥90

Harrison’s Manual of Medicine Chapter 119; adapted from J Am Coll Cardiol 71:e127-e248. 2017.
Some Definitions

• Primary “Essential” Hypertension

• Accounts for up to 95% of cases of hypertension
• No clear cause

• Secondary Hypertension
• Accounts for 5-10% of cases of hypertension
• Hypertension with an identifiable underlying cause which is generally
correctable

Harrison’s Manual of Medicine Chapter 119

Epidemiology & Risk Factors
• 1 in 3 people worldwide have elevated blood
pressure
• Incidence and prevalence hypertension depends on:
• Age
• Sex (men until age 64, then women afterward)
• Race (black > white > Asian)
• Diet, sodium intake
• Obesity
• Family history
• Diabetes
• Alcohol use
• Mortality and Morbidity
• Hypertension is a major cause of premature death
• Heart disease (heart failure, coronary artery disease,
arrhythmias)
• Stroke
• Renal disease
• Peripheral Arterial Disease CDC. Hypertension. | Harrison’s Chapter 271
Epidemiology: Hypertension in Vietnam
• The prevalence of hypertension in Vietnam is estimated to be
21.1% based on a recent study

• Only 9.3% of those with hypertension were aware of their

diagnosis

• Awareness and treatment of hypertension were much lower in

rural settings compared to urban settings in Vietnam

Asia Pac J Public Health. 2019 Mar;31(2):101-112. doi: 10.1177/1010539518824810. Epub 2019 Jan 24.
Etiology and Pathophysiology
• Arterial pressure is determined by
cardiac output and peripheral resistance
• Intravascular Volume
• Sodium is the main determinant of
extracellular fluid volume
• During increased sodium intake,
extracellular fluid volume increases and
cardiac output increases
• Autonomic Nervous System
• Increased sympathetic tone (epinephrine
and norepinephrine)increases arterial
pressure
• Ex: pheochromocytoma
Harrison’s Chapter 271
Etiology and Pathophysiology
• Activation of Renin-Angiotensin
Aldosterone System
• Angiotensin II: causes vasoconstriction
• Aldosterone: causes sodium retention
• Ex: reno-vascular hypertension (causes
increased renin release)
• Vascular Mechanisms
• Remodeling of vessels in patients with
hypertension is seen (stiff vessels)

Harrison’s Chapter 271

Case Discussions
Case 1
• 45 year-old man with Type 2 diabetes presents to your clinic for
an annual visit. He has no concerns.
• He is on metformin and atorvastatin.
• Vital Signs: T 37C, pulse 88, BP 138/80, respirations 12
• Physical exam is normal.
What are your next steps?

• Does this patient meet criteria for hypertension?

• Would you treat this patient’s blood pressure?

• Are any other tests needed?

 Treatment of Hypertension

• It is reasonable to start with

lifestyle modifications in
patients with blood pressure
<140/80.
• Lifestyle Modifications:
• Weight loss
• Sodium restriction
• Exercise
• Decrease alcohol
consumption

Adapted from JNC7 guidelines

Treatment of Hypertension
• 2017 Hypertension Guidelines recommend starting antihypertensive
drug therapy when systolic BP ≥140 mmHg or diastolic BP ≥90
• The goal is to reduce blood pressure to 130/80 or less.
• Exception: elderly (>65) patients with many comorbidities require personalized
approach and less conservative treatment goal to be determined by their doctor
• Initial first-line therapy for stage 1 hypertension includes:
• Thiazide diuretics
• CCBs (calcium channel blockers)
• ACE inhibitors or ARBs (ACE-inhibitors or angiotensin receptor blockers)

• Two first-line drugs of different classes are recommended with stage 2

hypertension and average BP of 20/10 mm Hg above the BP target.
2017 ACC/AHA Hypertension Guidelines
Most Commonly Used Antihypertensives
Blue = first-line

Drug Class Example Pros Cons

ACE-I Lisinopril, Well tolerated, improves Dry cough common (up to 15%), angioedema (<1%),
Benazepril proteinuria hyperkalemia, azotemia
ARB Losartan Well tolerated, improves Hyperkalemia, azotemia
proteinuria
Calcium Channel Amlodipine Once a day, well tolerated, no Peripheral edema, constipation
Blocker monitoring of renal function
(dihydropyridine) needed, effective in black
patients
Thiazide Diuretic Chlorthalidone, Effective in black and elderly Can cause hypokalemia, hyperglycemia,
HCTZ patients hyponatremia and hyperuricemia
Calcium Channel Verapamil Complete heart block, bradycardia, edema,
Blocker Diltiazem constipation
(non-dihydropyridine)
Aldosterone Antagonists Spironolactone Cheap, well tolerated Gynecomastia (in spironolactone), hyperkalemia
Eplerenone

Harrison’s Chapter 271.

Less Commonly Used Antihypertensives
Drug Class Example Pros Cons
Beta Blocker Metoprolol Good for concomitant tachy- Avoid in bradycardia
(cardioselective) arrhythmias
Nonselective beta Propranolol Well tolerated, good for Not very effective for hypertension
blockers concomitant performance
anxiety
Loop Diuretic Furosemide Effective in black and elderly Hypokalemia, hypouricemia
Bumetanide patients, works better than
Torsemide thiazides when creatinine
>2.5 mg/dL
Direct Vasodilators Hydralazine Well tolerated Three times a day dosing, can cause drug-induced
Minoxidil lupus
Alpha-1 blockers Terazosin Works well in patients with Can cause orthostatic hypotension
benign prostatic hyperplasia
Central alpha-2 agonists Clonidine Quick onset Can cause severe rebound hypertension if missed
Methyldopa doses
Potassium-sparing Amiloride Generally well tolerated Expensive
diuretics Triamterene Hyperkalemia

Harrison’s Chapter 271.

Which agent should I choose to start?
Indication
Does the patient have diabetes with albuminuria?
Does the patient have chronic kidney disease?
Does the patient have heart failure with reduced
ejection fraction?
Is the patient of African descent?
Does the patient have hypokalemia?
Does the patient have hyponatremia?
Does the patient have renovascular disease (ex:
renal artery stenosis)?
Best Choice
ACE-I or ARB
ACE-I or ARB
ACE-I or ARB (avoid dihydropyridine calcium channel
blockers as can worsen leg edema, and non-
dihydropyridine calcium channel blockers are
associated with increased mortality in patients with
heart failure)
Thiazide or calcium channel blocker
Avoid loop and thiazide diuretics
Avoid thiazide diuretics
Avoid ACE-Is and ARBs, as can cause significant
acute kidney injury
UpToDate: Hypertension Treatment. Accessed April 20, 2020.
Monitoring of Antihypertensive Therapy

• After diagnosis of hypertension, patient should return in 1 month for

a blood pressure check.
• In general, the following lab work should obtained at time of
diagnosis:
• Basic metabolic panel (monitoring potassium, sodium, creatinine)
• Lipid profile
• Urinalysis to check for proteinuria
• Thyroid-stimulating hormone
• ECG to evaluate for left ventricular hypertrophy
• Patients should generally have a basic metabolic panel checked
every 3-6 months after diagnosis, especially if taking a thiazide or
ACE-I/ARB.
2017 ACC/AHA Hypertension Guidelines
Case 2
• A 31 year-old healthy female presents to your clinic for an annual
visit. He got routine blood work prior to this visit. She has no
concerns.
• She is not taking any medications.
• Vital Signs: T 37C, pulse 68, BP 162/90, respirations 10
• She has a normal physical exam.

Labs: Hb 12.5 gm/dL, Na 142 mEq/L, K 3.3 mEq/L, HCO3 - 29 mEq/L,

Urine pregnancy negative
What are your next steps?
• What could be the cause of the patient’s hypertension?
• Which laboratory or radiology tests could help determine diagnosis?
When to suspect secondary hypertension
• Suspect secondary hypertension in this
young patient with severe hypertension.

• The patient has hypertension, hypokalemia,

and a metabolic alkalosis.
• This is consistent with primary
hyperaldosteronism (Conn’s Syndrome). This is
usually caused by adrenal adenomas or
hyperplasia.
• Next steps in diagnosis are:
• Check plasma renin and plasma aldosterone
concentration

2017 ACC/AHA Hypertension Guidelines.

Causes of Secondary Hypertension
Common causes of secondary hypertension
Renal parenchymal disease
Renovascular disease
Primary hyperaldosteronism
• 5-10% of cases of Obstructive sleep apnea
hypertension are Drug or alcohol induced
Uncommon causes of secondary hypertension
classified as Pheochromocytoma/paraganglioma
secondary Cushing’s syndrome
hypertension Hypothyroidism
Hyperthyroidism
Aortic coarctation
Primary hyperparathyroidism
Congenital adrenal hyperplasia
Mineralocorticoid excess syndromes other than primary aldosteronism
Acromegaly

Harrison’s Chapter 271. | Whelton et al. Hypertens. 13 Nov 2017

Work-up in suspected secondary hypertension

• You may suspect secondary hypertension in a patient with severe

hypertension, who develops hypertension at a young age (<30), or
suddenly later on in life (>65). In these cases, consider checking:
• Doppler US of renal arteries (or MR angiogram)
• Aldosterone serum level and plasma renin activity. If PRA ratio >25 and aldo
>10, suggests primary hyperaldosteronism
• Serum free metanephrines/normetanephrines
• TSH
• Consider sleep study in appropriate context

UpToDate. Evaluation of Secondary Hypertension. Accessed April 25, 2020.

Case 3
• 73 year old man with hypertension comes to your office for a
follow-up visit. You started him on lisinopril at your last visit one
month ago. He is on no other medications.
• Vital Signs: T36.5, pulse 80, BP 105/70, respirations 12
• Physical exam is notable for bruits over the abdominal flanks
that you did not notice at last visit.
• Labs notable for Na 140 mEq/L, K 4.8 mEq/L, Creatinine 3.1
mEq/L (was 1.2 mEq/L when last checked)
What are your next steps?
• What could be the cause of his acute kidney injury?
• How would you manage this patient’s medication?
Renal Effects of ACE-Is in Hypertension
• An increase in serum creatinine up to 30% within 2 to 5 days can be
expected in most patients started on ACE-Is. This increase usually
stabilizes in 2 to 3 weeks and is reversible upon drug
discontinuation.
• This patient has a severe AKI, likely related to the ACE-I.
• Bilateral renovascular disease (ex: bilateral renal artery stenosis) is
one not-to-miss reason for the plasma creatinine concentration to
rise by more than 30% shortly after starting an ACE inhibitor.
• Stopping the medication will reverse the effect.

UpToDate. Renal Effects of ACE-Is in Hypertension. Accessed April 25, 2020.

Case 4
• A 39 year-old man presents to your office for a blood pressure
check. He is currently taking maximum doses of
hydrochlorothiazide, lisinopril, and amlodipine. He denies
missing any doses. His blood pressures at home have been
running 150s-160s systolic over 90s-100s diastolic.
• Vital Signs: T 36.5, pulse 80, BP 155/70, respirations 12
• Physical exam is normal.
• Labs notable for Na 140 mEq/L, K 4.1 mEq/L, Creatinine 1.5
mEq/L, thyroid-stimulating hormone within normal limits
What are your next steps?
• Does this patient have resistant hypertension?
• How would you manage this patient’s medications?
Resistant Hypertension

• This patient has resistant hypertension:

• patient is on 3 antihypertensive medications (including a diuretic) and not at
blood pressure control or
• patient is on at least 4 medications and blood pressure is controlled

• In patients with resistant hypertension, diuretic therapy should be

maximized and a mineralocorticoid receptor antagonist (such as
spironolactone) should be added as the fourth agent.

2017 ACC/AHA Hypertension Guidelines. | PATHWAY-2 Trial The Lancet. Volume 386, ISSUE 10008, P2059-2068, November 21, 2015
A word on hypertensive urgency/emergency..
• Hypertensive Emergency
• Severe elevations in blood pressure (>180/120 mm Hg) associated with
evidence of new or worsening target organ damage.
• Examples of organ damage: stroke, heart attack, pulmonary edema,
hypertensive encephalopathy, unstable angina, eclampsia
• Requires ICU monitoring for blood pressure lowering

• Hypertensive Urgency
• Severe blood pressure elevation in otherwise stable patients without target
organ damage or dysfunction.
• Does not need hospital monitoring. Work on increasing home blood pressure
regimen and ensuring medication compliance.
 Hypertensive Emergency

• In general, blood pressure should not

be reduced by more than 25% in the
first hour except in aortic dissection,
eclampsia, or pheochromocytoma.

• This is because abrupt decrease in

blood pressure can worsen cerebral,
renal, or cardiac ischemia.

2017 ACC/AHA Hypertension Guidelines.

Prevention of Hypertension

• Healthy lifestyle with a focus on diet and exercise

• Diet: low sodium diet rich in fruits and vegetables
• Weight loss: goal body mass index <25
• Reduction in alcohol intake

UpToDate. Diet in the Treatment of Hypertension. Accessed April 25, 2020.

Take-Home Points: Hypertension
• Stage 1 hypertension is a systolic pressure ranging from 130 to
139 mm Hg or a diastolic pressure ranging from 80 to 89 mm Hg.

• Stage 2 hypertension is a systolic pressure of 140 mm Hg or

higher or a diastolic pressure of 90 mm Hg or higher.

• Modifiable risk factors for hypertension include diet, activity level,

alcohol consumption, and weight.

• The first-line agents for blood pressure treatment are

ACE-Is/ARBs, calcium channel blockers, or thiazide diuretics.
Take-Home Points: Hypertension
• Goal for treatment in most cases is to achieve blood pressure <130/80.
• Exception: elderly/frail patients with multiple comorbidities (use clinical
judgment)

• Secondary hypertension is hypertension with an identifiable cause.

The treatment aims at treating the underling cause.

• Hypertensive emergency requires ICU monitoring of blood pressure,

whereas hypertensive urgency can be addressed as an outpatient.

• Lifestyle modifications (diet, exercise, alcohol cessation) should be

addressed in all patients with hypertension.
Additional Reading/References
Chobanian AV et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure: The JNC 7 report. JAMA 2003 May 21; 289:2560-72.

Harrison’s Principles of Internal Medicine 17th Ed. Chapter 271: Hypertensive Vascular Disease.

Paul K. Whelton. Hypertension. 2017 ACC/AHA Guideline for the Prevention, Detection, Evaluation, and
Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart
Association Task Force on Clinical Practice Guidelines, Volume: 71, Issue: 6, Pages: e13-e115

Whelton et al, Hypertension. 2018 Jun;71(6):1269-1324. Epub 2017 Nov 13.

Williams et al, Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for
drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. The Lancet. Vol 386, Issue
10008. P2059-2068, November 21, 2015