Cardiovascular Therapeutics

Hypertension

A comprehensive lecture note covering diagnosis, pathophysiology, lifestyle intervention, pharmacologic treatment, special populations, hypertensive crises, and exam-focused review.

Core Identity
The "Silent Killer"
Key Formula
BP = CO x SVR
Foundation
Lifestyle for all patients
First-Line Set
Thiazide, ACEI, ARB, CCB

1. Learning Objectives

  1. Define hypertension and classify blood pressure categories based on current guidelines.
  2. Explain the pathophysiology of primary (essential) hypertension.
  3. Identify major risk factors for hypertension and its target organ damage.
  4. List non-pharmacological interventions and their expected impact.
  5. Select appropriate pharmacotherapy based on patient-specific factors using a stepwise approach.
  6. Identify major drug classes, their mechanisms, key side effects, and monitoring parameters.
  7. Recognize and manage hypertensive emergencies and urgencies.
  8. Provide patient-centered counseling points to improve adherence and outcomes.

2. Introduction: The Silent Killer

Hypertension (HTN), or high blood pressure, is a chronic medical condition where the force of blood against the artery walls is persistently elevated. It is often called the "silent killer" because it is largely asymptomatic until significant organ damage has already occurred.

Clinical Significance

Hypertension is a primary risk factor for cardiovascular disease, including myocardial infarction, heart failure, stroke, and chronic kidney disease. It is one of the most common conditions managed in pharmacy practice.

Why Guidelines Matter

Treatment decisions are guided by evidence-based recommendations from the ACC/AHA and the ESC/ESH. Their treatment thresholds and targets may vary slightly, but the major drug classes and treatment logic are closely aligned.

3. Classification of Blood Pressure

Blood pressure is measured in millimeters of mercury (mmHg) and recorded as systolic blood pressure (SBP) over diastolic blood pressure (DBP). This note primarily uses the 2017 ACC/AHA classification.

BP Category Systolic BP Connector Diastolic BP Management Approach
Normal < 120 mmHg AND < 80 mmHg Promote healthy lifestyle.
Elevated 120 - 129 mmHg AND < 80 mmHg Non-pharmacologic therapy.
Stage 1 HTN 130 - 139 mmHg OR 80 - 89 mmHg Assess ASCVD risk; lifestyle plus consider drug therapy.
Stage 2 HTN >= 140 mmHg OR >= 90 mmHg Lifestyle modification plus pharmacotherapy.
Hypertensive Crisis > 180 mmHg and/or > 120 mmHg Immediate medical assessment.

4. Pathophysiology: Why Does BP Rise?

Core formula: Blood pressure = Cardiac Output x Systemic Vascular Resistance.

In primary (essential) hypertension, the exact cause is unknown, but blood pressure rises through a combination of increased cardiac output, increased systemic vascular resistance, or both.

Major Drivers

  • Sympathetic nervous system overactivity: increases heart rate and vasoconstriction.
  • RAAS activation: angiotensin II causes vasoconstriction and aldosterone promotes sodium and water retention.
  • Endothelial dysfunction: less nitric oxide, more vasoconstrictors.
  • Sodium and water retention: expands plasma volume and raises cardiac output.

5. Risk Factors and Target Organ Damage

Risk Factors

Non-modifiable Modifiable
Age High sodium diet
Family history Low potassium diet
Genetics Physical inactivity
Male sex or post-menopausal female Obesity, alcohol, tobacco, dyslipidemia, diabetes

Target Organ Damage

Organ Damage
Heart LVH, myocardial infarction, heart failure
Brain Stroke, TIA, vascular dementia
Kidneys CKD, ESRD
Eyes Hypertensive retinopathy
Arteries Atherosclerosis, PAD, aneurysm

6. Non-Pharmacological Therapy (Lifestyle Modification)

S-ABCDE: Sodium, Alcohol, Body weight, Cigarette cessation, Dietary change, Exercise.
Intervention Recommendation Expected SBP Reduction
Sodium restriction < 1500 mg/day; avoid processed foods. 5-10 mmHg
Alcohol limitation <= 2 drinks/day for men, <= 1 drink/day for women. 3-5 mmHg
Body weight reduction Aim for BMI < 25 kg/m². 5-20 mmHg per 10 kg loss
Cigarette cessation Complete cessation. Indirect BP benefit, major CV benefit
DASH diet High in fruits, vegetables, whole grains, low-fat dairy. 10-15 mmHg
Exercise 90-150 minutes/week of aerobic activity. 5-8 mmHg

7. Pharmacological Therapy: A Stepwise Approach

7.1. First-Line Drug Classes (The "Big Five")

Class Examples High-Yield Points
Thiazide-like diuretics Chlorthalidone, HCTZ, Indapamide Hypokalemia, hyperglycemia, hyperuricemia; take in the morning.
ACE inhibitors Lisinopril, Enalapril, Ramipril Cough, angioedema, hyperkalemia, teratogenicity.
ARBs Losartan, Valsartan, Olmesartan No cough; still monitor potassium and pregnancy risk.
Dihydropyridine CCBs Amlodipine, long-acting nifedipine Peripheral edema, headache, flushing.
Non-dihydropyridine CCBs Verapamil, Diltiazem Bradycardia, heart block, constipation with verapamil.

7.2. Stepwise Treatment Algorithm

  • Step 1: Start one first-line drug for low-risk Stage 1 HTN, or a two-drug combination for Stage 2 HTN or high-risk patients.
  • Preferred combinations: ACEi/ARB + thiazide or ACEi/ARB + CCB.
  • Step 2: Titrate to full dose if not at goal after 2-4 weeks.
  • Step 3: Add a third complementary drug if still uncontrolled.
  • Step 4: Consider resistant hypertension; spironolactone is the classic fourth-line agent.
  • Avoid: ACE inhibitor + ARB combination due to hyperkalemia and kidney injury risk.

7.3. Other Drug Classes (Not First-Line)

  • Beta-blockers: still valuable post-MI, in HFrEF, angina, and AF, but not first-line for uncomplicated HTN.
  • Alpha-blockers: useful when BPH coexists.
  • Central alpha agonists: reserved for resistant cases; watch for rebound hypertension.
  • Aldosterone antagonists: especially useful in resistant HTN and HFrEF.

8. Hypertension in Special Populations (Compelling Indications)

Comorbidity Preferred Drug Class(es) Rationale
Diabetes mellitus ACEi or ARB Renoprotective and slows diabetic nephropathy progression.
Chronic kidney disease ACEi or ARB Reduces intraglomerular pressure; monitor creatinine and potassium.
HFrEF Beta-blocker, ACEi/ARB/ARNI, spironolactone Guideline-directed foundational therapy.
Post-myocardial infarction Beta-blocker, ACEi/ARB Reduces mortality and remodeling.
Black/African American patients Thiazide or CCB Often lower-renin hypertension; better monotherapy response.
Pregnancy Methyldopa, labetalol, long-acting nifedipine ACEi and ARBs are contraindicated.

9. Hypertensive Crises

Type Definition Key Feature Management
Hypertensive emergency BP > 180/120 mmHg with acute target organ damage End-organ damage is present. Admit, use IV antihypertensives, lower BP carefully by no more than 20-25% in the first hour.
Hypertensive urgency BP > 180/120 mmHg without acute target organ damage Severely elevated BP without emergency complications. Use oral therapy or reinitiate home therapy; lower BP over 24-48 hours.

10. Patient Counseling Points: The Key to Adherence

  • Hypertension is chronic: treatment is long-term even when the patient feels well.
  • Asymptomatic does not mean harmless: control prevents silent damage to the heart, brain, kidneys, and eyes.
  • Take medicines consistently: same time daily, do not stop abruptly.
  • ACEi cough: report it; switching to an ARB is often appropriate.
  • CCB edema: this is from vasodilation, not always fluid overload.
  • Home BP monitoring: measure after 5 minutes of rest with the arm supported at heart level.

11. Summary for Exam Preparation

High-yield memory anchors: memorize BP categories, know the "Big Five", remember ACEi cough versus ARB tolerance, thiazide metabolic effects, CCB edema, resistant hypertension on spironolactone, hypertensive emergency versus urgency, and pregnancy contraindications for ACE inhibitors and ARBs.
  • ABCD memory anchor: ACEi/ARB, Beta-blocker (only with compelling indication), CCB, Diuretic.
  • Preferred combinations: ACEi/ARB + CCB or ACEi/ARB + thiazide.
  • Do not combine: ACEi + ARB.
  • Black patients: thiazide or CCB is usually the best initial monotherapy.
  • Pregnancy: ACE inhibitors and ARBs are contraindicated.
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