• Clinical science

Hypertension

Abstract

Hypertension is a common condition that affects one in every three adults in the United States. It is defined by the JNC 8 criteria as a blood pressure of ≥ 140/90 mm Hg and by the AHA/ACC guideline as ≥ 130/80 mm Hg. Hypertension can be classified as either primary (essential) or secondary. Primary hypertension accounts for approx. 95% of cases of hypertension and has no detectable cause, whereas secondary hypertension is due to a specific underlying condition. Typical underlying conditions include renal, endocrine, or vascular diseases (e.g., renal failure, primary hyperaldosteronism, or coarctation of the aorta). Clinically, hypertension is usually asymptomatic until organ damage occurs, which then commonly affects the brain, heart, kidneys, or eyes (e.g., retinopathy, myocardial infarction, stroke). Common early symptoms of hypertension include headache, dizziness, tinnitus, and chest discomfort. Hypertension is diagnosed if blood pressure is persistently elevated on two or more separate measurements. Further diagnostic measures include evaluation of possible organ damage (e.g., kidney function tests) and additional tests if an underlying disease is suspected. Treatment of primary hypertension includes lifestyle changes (e.g., diet, weight loss, exercise) and pharmacotherapy. Commonly prescribed antihypertensive medications includes ACE inhibitors, angiotensin receptor blockers, thiazide diuretics, and calcium channel blockers. To treat secondary hypertension, the underlying cause needs to be addressed. In cases of hypertensive emergency, a condition with a sudden and severe increase in blood pressure and impending end-organ damage, immediate treatment with intravenously administered antihypertensives is required to prevent serious consequences such as cerebral hemorrhage.

Definition

  • JNC 8 definition: systolic blood pressure of ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg
  • AHA/ACC definition (2017): systolic blood pressure of ≥ 130 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg

JNC 8

BP category Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg)
Normal blood pressure < 120 and < 80
Prehypertension 120–139 or 80–89
Stage 1 hypertension 140–159 or 90–99
Stage 2 hypertension ≥ 160 or ≥ 100

AHA/ACC 2017

BP catergory Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg)
Normal blood pressure < 120 and < 80
Elevated 120–129 and <80
Stage 1 hypertension 130–139 or 80–89
Stage 2 hypertension ≥ 140 or ≥ 90

References:[1][2][3]

Epidemiology

  • Most common risk factor for cardiovascular disease
  • One in three US adults is affected (∼ 65% among those ≥ 60 years of age)
  • African American populations are more commonly affected than white or Asian populations.
  • 60–75% of obese and overweight patients are affected.

References:[4][5][1][6][7][8][9][10]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Primary (essential) hypertension

  • Accounts for 85–95% of cases of hypertension in adults
  • No specific cause; multifactorial etiology including epigenetic/genetic and environmental factors
  • Non-modifiable risk factors
    • Positive family history
    • Ethnicity
    • Advanced age
  • Modifiable risk factors
    • Obesity
    • Diabetes
    • Smoking; , excessive alcohol or caffeine intake
    • Diet high in sodium, low in potassium
    • Physical inactivity
    • Psychological stress

Secondary hypertension

References:[11][11][12][1][13][14][15][16][17]

Clinical features

Hypertension is usually asymptomatic until complications of end-organ damage arise or an acute increase in blood pressure occurs (see hypertensive urgency below). Possible symptoms include:

  • Headaches, esp. early morning or waking headache
  • Dizziness; , tinnitus, blurred vision
  • Flushed appearance
  • Epistaxis
  • Chest discomfort, palpitations; strong, bounding pulse on palpation
  • Nervousness
  • Fatigue, sleep disturbances
  • Additional symptoms of an underlying disease in secondary hypertension (see “Etiology” above)
  • Symptoms of end-organ damage (see “Complications” below)

Since hypertension is often asymptomatic, regular screening is necessary to prevent end-organ damage!

References:[5][17]

Subtypes and variants

White coat hypertension (white coat effect)

  • Definition: arterial hypertension detected only in clinical settings or during blood pressure measurement at a physician's practice
  • Etiology: anxiety experienced by the patient
  • Clinical features: consistently normal blood pressure measurements and normalization of elevated blood pressure outside of a clinical setting
  • Diagnostics: 24-hour blood pressure monitoring

Isolated systolic hypertension (ISH)

  • Definition: increase in systolic blood pressure (≥ 140 mm Hg) with diastolic BP within normal limits (≤ 90 mm Hg)
  • Etiology
  • Clinical features:
    • Often asymptomatic
    • Signs of increased pulse pressure: e.g., head pounding; , rhythmic nodding, or bobbing of the head in synchrony with heartbeats
    • Symptoms of hypertension (see “clinical features” above)
  • Diagnostics: See “diagnosis of hypertension” below.
  • Treatment: thiazide diuretics or dihydropyridine calcium antagonists
  • Prognosis: high risk of cardiovascular events (MI, stroke, renal dysfunction)

References:[4][11][12][18][19][20][21][22][23][24][25][26][27][28][29][30][3][31][32]

Diagnostics

General approach

  • Blood pressure monitoring
    • Repeated measurements on both arms Hypertension is diagnosed if the average blood pressure of ≥ 2 readings obtained on ≥ 2 separate visits is elevated
    • Long-term measurement of blood pressure (24 hours)
    • Basic measurement approach: See “Blood pressure measurement” for details.
  • Initial evaluation of newly diagnosed hypertensive patients:
    • Stratification of cardiovascular risk: fasting blood glucose, lipid profile (HDL, LDL, and triglycerides levels)
    • Evaluation of end-organ damage and underlying causes
  • Evaluation of secondary hypertension if an underlying condition is suspected (see below)

Approach to diagnosing secondary hypertension

  • General indicators of secondary hypertension
    • Young age (< 30 years) at onset of hypertension or onset of diastolic hypertension at an older age (> 55 years)
    • Abrupt onset of hypertension
    • End-organ damage that is disproportionate to the degree of hypertension
    • Recurrent hypertensive crises
    • Resistant hypertension: hypertension that is resistant to treatment with ≥ 3 antihypertensives of different classes
  • Specific indicators (for details on individual diagnostic procedures, see the individual learning cards.)
Diagnostic findings Underlying condition
  • Hypokalemia
  • Difference in blood pressure
  • In both arms
  • Of upper and lower limbs
  • Day time sleepiness (Epworth scale, Berlin questionnaire)
  • Nondipping in 24-hour blood pressure monitoring
  • Increased 24-hour urinary metanephrines

References:[33][12][18][1][17][34][3][35][36][37][38]

Treatment

Nonpharmacologic measures (lifestyle changes)

Intervention Target Approximate systolic BP reduction in hypertensive patients
Decrease dietary sodium
  • Daily sodium intake < 1500 mg/day
5-6 mm Hg
Increase dietary potassium
  • Daily potassium intake < 3.5–5 g
4-5 mm Hg
DASH diet
  • Diet rich in fruits, vegetables, whole grains and low in staturated and trans fats
11 mm Hg
Weight loss
  • Ideal body weight
1 mm Hg per kg reduction in body weight in overweight individuals
Exercise Aerobic
  • 90–150 minutes per week
  • 65–75% of maximum heart rate (e.g., brisk walk)
5–8 mm Hg
Dynamic resistance (e.g., weight training)
  • 50–80% of maximum strength
  • 6 exercises with 3 sets per exercise and 10 repetitions per set
  • 90–150 minutes per week
4 mm Hg
Isometric resistance (e.g., hand grip exercise)
  • 30–40% of maximum strength
  • 4 repetitions/session, 3 sessions/week for 8–10 weeks
5 mm Hg
Decreased alcohol intake
  • : ≤ 2 drink daily
  • : ≤ 1 drink daily
4 mm Hg
Smoking cessation
  • Completely quit smoking

3–5 mm Hg after 1 year; 6–7 mm Hg after 3 years [39]

Non-pharmcological measures should be implemented in any patient with a systolic BP > 120 mm Hg or a diastolic BP > 80 mm Hg!

Pharmacologic treatment

Guideline JNC 8 AHA/ACC 2017
Indication for pharmacological therapy
Treatment goal
  • BP less than threshold for initiating pharmacological therapy
  • Age < 65: BP < 130/80 mm Hg
  • Age ≥ 65: systolic BP < 130 mm Hg
  • Specific recommendations
  • Initiation of treatment and follow-up
    1. Number of antihypertensives
      • Newly diagnosed hypertension with BP < 150/90 mm Hg: begin therapy with one primary antihypertensive
      • Newly diagnosed hypertension with BP > 150/90 mm Hg: begin therapy with two primary antihypertensives
    2. Reassess within one month of initiating or changing pharmacological therapy.
      • If treatment goal is not reached with one drug: Increase the dose of the initial drug or add a second drug
      • If treatment goal cannot be reached with two drugs
        • Add a third drug.
        • Evaluate for secondary causes of hypertension
      • If blood pressure is controlled: reassess after 3–6 months and annually thereafter

Overview of antihypertensive drugs

Drug class Comments Side effects
Primary drugs
ACE inhibitors (e.g., lisinopril, captopril, enalapril)
Angiotensin-receptor blockers (ARB) (e.g., losartan, valsartan)
  • ↑ K+
  • Teratogenic
Thiazide diuretics (e.g., hydrochlorothiazide, chlorthalidone)
Calcium channel blockers Dihydropyridines (e.g., nifedipine, amlodipine)
Non-dihydropyridines (e.g., diltiazem, verapamil)
Secondary drugs
Beta blockers (e.g., propranolol, metoprolol, labetalol)
Aldosterone antagonists (e.g., eplerenone, spironolactone)
Direct renin inhibitors (e.g., aliskiren)
  • Should not be used in combination with ACEi or ARBs
  • ↑ K+
Alpha-1 blockers (e.g., prazosin, doxazosin)
Alpha-2 agonists (e.g., clonidine)
  • Rarely used
  • CNS depression
  • Bradycardia
  • Rebound hypertension
Direct arteriolar vasodilators (e.g., hydralazine)

Pharmacologic treatment in pregnancy

References:[33][11][12][1][34][40][41][42][3]

Complications

Arterial hypertension leads to changes in the vascular endothelium, particularly of the small vessels, and can therefore affect any organ system.

Cardiovascular system

Brain

Kidneys

  • Hypertensive nephrosclerosis
    • Pathophysiology: chronic hypertension → narrowing of afferent and efferent arterioles → reduction of glomerular blood flow → glomerular and tubular ischemiaarteriolonephrosclerosis and fibrosis (focal segmental glomerulosclerosis) end-stage renal disease
    • Typical findings
      • Initially microalbuminuria and microhematuria
      • With disease progression, nephrosclerosis with macroalbuminuria (usually < 1 g/day) and progressive renal failure occur
      • Biopsy: sclerosis in capillary tufts, arterial hyalinosis

Eyes

  • Hypertensive retinopathy
    • Arteriosclerotic and hypertension-related changes of the retinal vessels
    • Fundoscopic examination: cotton-wool spots, retinal hemorrhages (i.e., flame-shaped hemorrhages), arteriovenous nicking; , marked swelling and prominence of the optic disk with indistinct borders due to papilledema and optic atrophy (end-stage disease)

Local treatment of the eye is not possible; therefore, systemic reduction of blood pressure is critical!

Classification system according to Keith-Wagener-Barker Findings Symptoms
Grade I Vessel diameter variation: arteriolar constriction and tortuosity Usually asymptomatic
Grade II Gunn's sign and marked constriction of vessels and sclerosis of arterioles
Grade III Cotton-wool exudates, hard exudates, retinal hemorrhage, retinal edema, macular star formation Decreased and/or blurred vision, headaches
Grade IV Papilledema, optic atrophy

Hypertensive crisis (acute severe hypertension)

  • Definition: acute increase in blood pressure > 180/120 mm Hg

Classification

Diagnostics [43]

Treatment

Hypertensive urgency

Hypertensive emergency

Rate of blood pressure reduction
  • General goal
    • Reduce BP by max. 25% within the first hour; to prevent coronary insufficiency and to ensure adequate cerebral perfusion!
    • Reduce BP to 160/100–110 mm Hg over next 2–6 hours
    • Reduce BP to normal over 24–48 hours
  • Special cases
Choice of intravenous antihypertensive drug
  • The selection of an intravenous antihypertensive and its dosing is based on the desired rate of BP decrease, the presence or absence of certain co-morbidities, and the drug's pharmacodynamic properties
Associated co-morbidity Preferred intravenous antihypertensive Comments
Aortic dissection
Pulmonary edema
Acute coronary syndrome
Acute renal failure
Catecholamine excess
Acute ischemic stroke
Acute intracerebral hemorrhage
Eclampsia/severe pre-eclampsia
Intravenous antihypertensives

The most commonly used drugs to treat hypertensive emergency are nitroprusside, labetalol, and nicardipine.

Prognosis

  • If left untreated, hypertensive emergencies are associated with a 1-year death rate > 80% and a median survival of 10–11 months [3]

References:[19][20][21][22][23][24][25][26][27][28][29][30][3][31][32]

References:[11][12][1][17][44][45][46][47]

We list the most important complications. The selection is not exhaustive.