After reviewing this handout, students should be able to: 1. Classify hypertension stages and understand measurement standards 2. Describe the role of out-of-office blood pressure monitoring in diagnosis 3. Identify first-line antihypertensive medications and their mechanisms 4. Apply evidence-based blood pressure targets based on patient risk 5. Recognize and manage special populations (diabetes, CKD, pregnancy, resistant HTN) 6. Interpret 2025 ACC/AHA guideline recommendations for treatment decisions
| Category | Office BP | Home BP | ABPM 24-hr |
|---|---|---|---|
| Elevated | 120-129/<80 | <130/80 | <130/80 |
| Stage 1 HTN | 130-139/80-89 | ≥130/80 | ≥130/80 |
| Stage 2 HTN | ≥140/90 | ≥140/90 | ≥140/90 |
Critical elements for accurate office BP measurement: - Patient seated 5 minutes with back supported, feet flat, arm at heart level - Proper cuff size (bladder encircles 80-100% of arm circumference) - Avoid caffeine, exercise, smoking for 30 minutes pre-measurement - Empty bladder before measurement - Take 2-3 readings 1-2 minutes apart; average the readings
Oscillometric vs. Auscultatory Methods: - Automated oscillometric devices preferred over manual auscultatory methods (Class 2a) - Oscillometric advantages: reproducibility, eliminates terminal digit bias, standardization - Disadvantage: algorithms are proprietary; only MAP directly measured, SBP/DBP are derived
Home Blood Pressure Monitoring (HBPM): - Recommended: 7 consecutive days, 2 readings morning/evening, discard day 1 - Threshold for hypertension: ≥130/80 mmHg (home average) - Preferred timing: morning pre-medication (captures trough effect) - Advantages: multiple readings, eliminates white coat effect, superior prognostic value
Ambulatory Blood Pressure Monitoring (ABPM) - Gold Standard: - 24-hour monitoring with readings every 15-30 min (day) and 30-60 min (night) - Diagnostic thresholds: ≥130/80 mmHg (24-hr), ≥135/85 mmHg (daytime), ≥120/70 mmHg (nighttime) - Captures nocturnal dipping patterns, morning surge, and true BP variability - Most predictive of cardiovascular outcomes
| Phenotype | Office BP | ABPM/Home BP | Prevalence | Cardiovascular Risk |
|---|---|---|---|---|
| Normotension | <130/80 | <130/80 | 60-70% | Baseline |
| White Coat HTN | 130-159/80-99 | <130/80 | 15-30% | 1.2× baseline (low) |
| Masked HTN | <130/80 | ≥130/80 | 10-15% | 1.6× baseline (significant) |
| Sustained HTN | ≥130/80 | ≥130/80 | ~20% | 2-3× baseline |
Clinical Pearl: Always exclude white coat hypertension before treating Stage 1 HTN. Masked hypertension carries significant risk—screen patients with normal office BP but target organ damage.
The 2025 guidelines introduce PREVENT (Predicting Risk of CVD Events and Nonfatal Talk) equations—more accurate than older Pooled Cohort Equations by incorporating contemporary preventive therapies.
Treatment Thresholds: - Stage 1 HTN (130-139/80-89) + PREVENT risk <7.5%: Lifestyle modification for 3-6 months; consider meds if lifestyle fails - Stage 1 HTN + PREVENT risk ≥7.5%: Initiate pharmacotherapy - Stage 2 HTN (≥140/90): Initiate pharmacotherapy regardless of risk (Class 1)
| Population | Target SBP | Special Considerations |
|---|---|---|
| General/Diabetes/CKD | <130 mmHg | Intensive: consider <120 if tolerated |
| Coronary artery disease | <130 mmHg | Avoid J-curve (DBP <60 increases coronary risk) |
| Heart failure | <130 mmHg | RAAS inhibitors mandatory |
| Acute stroke | 140 mmHg (ICH) | Avoid aggressive reduction post-ischemic stroke |
| Resistant HTN | <130 mmHg | Often requires 4+ agents |
| Elderly (>75 yrs) | <130 mmHg | Monitor for orthostasis; avoid <110 SBP |
Evidence Summary (SPRINT Trial): - Intensive SBP <120 mmHg vs. standard <140 mmHg - 25% relative risk reduction in major CV events (absolute reduction ~2.5% over 5 years) - 27% reduction in mortality - Absolute NNT = 40-60 to prevent one event; requires careful patient selection
1. ACE Inhibitors (ACEI) – Mechanism: Blocks angiotensin I→II conversion
| Agent | Mechanism | Unique Features | Cautions |
|---|---|---|---|
| Lisinopril | Renal elimination (100%) | Long half-life (40-50 hrs in CKD) | Cough 10.6%, angioedema 0.3% |
| Ramipril | Hepatic + renal | HOPE trial cardioprotection | Cough, hyperkalemia risk |
| Fosinopril | Hepatic (80%) | Preferred in CKD (short washout to ARNI) | Well tolerated |
| Perindopril | Active metabolite | Ultra-long acting | Extended washout if ARNI transition |
Side Effects (Absolute Risk): - Persistent cough: 10.6% (NNH 13 vs. ARBs) - Angioedema: 0.3% (serious, may recur years into therapy) - Hyperkalemia: 5.3% in general population; 9.7% in CKD stage 4-5
2. Angiotensin Receptor Blockers (ARB) – Mechanism: AT₁ receptor antagonism
| Agent | Unique Properties | Indication |
|---|---|---|
| Losartan | Uricosuric (0.6-1.1 mg/dL UA reduction); CYP2C9 pro-drug | Hyperuricemia/gout + HTN |
| Telmisartan | Longest half-life (24 hrs); ONTARGET trial | Once-daily dosing convenience |
| Valsartan | Used in ARNIs; well-studied CKD | Albuminuria reduction |
Advantages over ACEIs: - No cough (0.4% vs. 10.6%) - Lower angioedema risk (0.11% vs. 0.3%) - Similar BP reduction and CV outcomes - Better adherence (33% fewer discontinuations)
3. Calcium Channel Blockers (CCB) – Mechanism: L-type calcium antagonism → arteriolar vasodilation
| Subclass | Agent | Half-Life | Comments |
|---|---|---|---|
| Dihydropyridines | Amlodipine | 30-50 hrs | No reflex tachycardia; edema common |
| Extended-rel nifedipine | 24 hrs | Avoid immediate-release (excessive variability) | |
| Non-dihydropyridines | Diltiazem | 3-4 hrs | Negative inotrope; bradycardia risk |
| Verapamil | 3-7 hrs | Constipation; contraindicated in HFrEF |
Clinical Pearl: Dihydropyridine CCBs (e.g., amlodipine) maintain cardiac output and don’t cause reflex tachycardia—preferred in most patients.
4. Thiazide and Thiazide-Like Diuretics – Mechanism: Renal tubular sodium/chloride reabsorption block
| Agent | Potency Ratio | Half-Life | Use |
|---|---|---|---|
| Hydrochlorothiazide (HCTZ) | 1.0 | 5-14 hrs | Avoid if possible (less potent, shorter acting) |
| Chlorthalidone | 1.5-2.0× HCTZ | 40-60 hrs | Preferred (superior BP reduction, sustained effect) |
| Indapamide | 1.5-2.0× HCTZ | 14-18 hrs | Good alternative to chlorthalidone |
Key Metabolic Effects: - Hypokalemia: 5-10%, especially at doses >25 mg daily - Hyperglycemia: 2-3% new-onset diabetes - Hyperuricemia: may precipitate gout - Dyslipidemia: modest increases in total cholesterol
Renal Pearl: Despite metabolic effects, thiazides are still Class 1 for hypertension. Monitor electrolytes 4-12 weeks after initiation.
BP Target: <130/80 mmHg (Class 1)
Preferred Medications: 1. RAAS inhibitors (ACEI/ARB) – mandatory with any albuminuria (including <30 mg/g) 2. Add CCB if not at goal with RAAS inhibitor monotherapy 3. Thiazide diuretic as second/third agent 4. Avoid dual RAAS blockade (ACEI + ARB or DRI) – increased HK, AKI, hypotension without CV benefit (Class 3 Harm)
Synergistic Agents: - GLP-1 agonists: 3-5 mmHg reduction + CV protection - SGLT2 inhibitors: 2-3 mmHg reduction + renal/HF protection
BP Target: <130/80 mmHg systolic across all CKD stages (Class 1)
Obligatory Therapy: - RAAS inhibition for albuminuric patients (≥30 mg/g creatinine) – renoprotective (Class 1) - Acceptable 30% creatinine rise in first 2-4 weeks (hemodynamic response, not progressive) - Add SGLT2 inhibitor for additive renal protection
Monitoring Parameters: - Check K+, Cr 1-2 weeks after RAAS inhibitor initiation - If K+ >5.5 mEq/L or Cr rise >30%: confirm true progression (repeat, rule out dehydration) - Urine-ACR at baseline and annually to assess albuminuria response
Clinical Pearl: ABPM (24-hour) more strongly predicts renal outcomes than office BP in CKD.
Definition: SBP ≥140 mmHg despite 3+ optimally-dosed medications (including diuretic), or requiring ≥4 agents to achieve goal.
Evaluation Algorithm: 1. Confirm true resistance: ABPM to rule out white coat effect (37.5% of apparent resistance) 2. Assess adherence: Pharmacy refill history, drug levels (lowest cost screening) 3. Exclude secondary causes: Primary aldosteronism (Class 1 universal screening regardless of K+ level—normokalemic phenotype common), RAS, OSA, hyperparathyroidism, hyperthyroidism 4. Address modifiable factors: Dietary sodium, NSAID/stimulant use, sleep apnea treatment
Fourth-Line Agent: - Spironolactone (MRA): 20-25 mmHg additional reduction in resistant HTN (Class 1) - Requires eGFR ≥45 mL/min (check K+ closely) - Typical dose: 12.5-25 mg daily
New Guideline: Universal screening in resistant HTN regardless of potassium status (Class 1)
Rationale: 70-80% of primary aldosteronism is normokalemic; old practice missed most cases.
Screening Test: Morning seated aldosterone-to-renin ratio (ARR)
Treatment: Mineralocorticoid receptor antagonist (spironolactone/eplerenone) reduces CV risk beyond BP control alone.
Classification: - Normal: <120/80 mmHg - Elevated: 120-129/<80 - Stage 1 HTN: 130-139/80-89 - Stage 2 HTN: ≥140/90 - Hypertensive crisis (urgent treatment): ≥160/110
Treatment Thresholds (CHAP Trial): - Treat chronic HTN ≥140/90 mmHg in pregnancy (Class 1) - Advantages: 25% reduction in preeclampsia, no increased fetal risk
Preferred Medications: 1. Methyldopa – gold standard (safest long-term) 2. Labetalol – excellent (avoid in asthma) 3. Extended-release nifedipine – safe alternative
Contraindicated (Teratogenic/Harmful): - ACE inhibitors, ARBs (2nd/3rd trimester teratogenesis) - Atenolol (intrauterine growth restriction) - Enalapril, lisinopril, etc. - Spironolactone (anti-androgenic)
Hypertensive Emergency in Pregnancy: - SBP ≥160/110 mmHg requires urgent IV treatment within 30-60 minutes - Goal: Reduce by 10-15% initially, then to 140-150 mmHg (avoid excessive reduction→placental hypoperfusion) - Agents: IV labetalol, IV hydralazine, sublingual nifedipine (NOT immediate-release)
Class 2a recommendation for agents containing 25% KCl / 75% NaCl
Evidence (SSaSS Trial): - 3.34 mmHg systolic reduction - 13% stroke risk reduction - Dual benefit: ↓ Na+, ↑ K+
Contraindications: - eGFR <30 mL/min (hyperkalemia risk) - Concurrent potassium-sparing diuretics or RAAS inhibitors (additive HK risk) - Baseline hyperkalemia
Candidates: - Office SBP 140-180 mmHg despite adherence - eGFR ≥40 mL/min - No significant renal artery abnormalities - Multidisciplinary team evaluation required
Efficacy: 5-10 mmHg office SBP reduction (modest); 30-40% non-responders; durability uncertain.
Clinical Pearl: Not a replacement for pharmacotherapy; combined with optimal medications for best outcomes.
Question 1: A 52-year-old woman has office BP 138/87 mmHg with no symptoms. She is not on medications. Home BP monitoring over 7 days (after discarding day 1) averages 127/78 mmHg. What is the most appropriate next step?
Answer: B – Office BP 138/87 with home BP <130/80 defines white coat HTN. Lifestyle modification with reassessment in 3-6 months is Class 2a recommended; ABPM is optional confirmatory testing.
Question 2: A 68-year-old man with type 2 diabetes (HbA1c 7.2%) and CKD stage 3b (eGFR 38) has BP 142/88 despite lisinopril 10 mg daily. Serum K+ 5.2 mEq/L. Which medication would you add next?
Answer: C – Amlodipine is appropriate second-line; avoids further K+ elevation (given borderline hyperkalemia and RAAS inhibitor). Spironolactone inappropriate here (baseline HK). HCTZ less preferred than chlorthalidone/indapamide. Increasing ACEI would worsen HK.
Question 3: A 44-year-old woman in her second trimester with chronic hypertension (BP 148/92 mmHg) is currently on lisinopril. What is the most appropriate management?
Answer: B – ACE inhibitors are teratogenic in 2nd/3rd trimester (enalapril-associated renal dysgenesis). Switch to methyldopa or labetalol. Treatment threshold is ≥140/90 per CHAP trial (Class 1), so treatment is indicated.
Created for PA/Medical Student Education Last Updated: 2026-02-12