Chapter 7  ·  Module 2

Diagnosis, Evaluation & Secondary Causes

Blood pressure phenotypes, pharmacological implications of secondary causes, and treatment thresholds

The Four Blood Pressure Phenotypes

Office vs Out-of-Office Measurement

Why Out-of-Office Measurement Changes the Diagnosis

Phenotype Office BP Out-of-Office BP Prevalence Action
Normotension Normal Normal — No treatment
White Coat Hypertension Elevated Normal 15–30% Avoid premature treatment — monitor
Masked Hypertension Normal Elevated 10–15% Same CV risk as sustained HTN — treat
Sustained Hypertension Elevated Elevated — Confirmed — treat per stage and risk

Secondary Causes — Key Pharmacological Rules

Pheochromocytoma / Cocaine

Alpha Before Beta — Critical Rule

  • Never give beta-blocker first in pheochromocytoma: removes beta-2 vasodilation, leaves alpha-1 vasoconstriction unopposed → hypertensive crisis
  • Start alpha blocker (phenoxybenzamine or doxazosin) 10–14 days before surgery
  • Add beta-blocker for rate control only after alpha blockade confirmed
  • Same rule applies to cocaine-associated hypertension: use phentolamine or benzodiazepines, not beta-blockers

Renovascular Hypertension

RAAS Inhibitor Contraindication

  • Bilateral renal artery stenosis: angiotensin II maintains glomerular filtration via efferent arteriolar constriction
  • ACE inhibitors and ARBs remove this compensatory mechanism → acute kidney injury
  • Use calcium channel blockers, diuretics, or centrally acting agents instead
  • Clue: acute kidney injury shortly after starting ACE inhibitor or ARB in refractory hypertension

Primary Aldosteronism

Mineralocorticoid Receptor Antagonists

  • Autonomous aldosterone secretion: sodium retention, potassium wasting, renin suppression
  • Spironolactone: first-line medical therapy; non-selective (anti-androgenic side effects)
  • Eplerenone: selective MRA; preferred when gynecomastia or sexual dysfunction is a concern
  • Avoid thiazides: worsen existing hypokalemia

Drug-Induced Hypertension

Common Offenders & Mechanisms

  • NSAIDs: prostaglandin inhibition → sodium retention; blunt diuretics and RAAS inhibitors
  • Oral contraceptives: estrogen → angiotensinogen ↑ → RAAS activation
  • Calcineurin inhibitors: renal vasoconstriction; use amlodipine (avoid diltiazem/verapamil — raise drug levels)
  • Sympathomimetics: alpha-1 agonism → vasoconstriction

Treatment Thresholds & Blood Pressure Targets

When to Start and What to Aim For

Evidence-Based Treatment Framework

BP Stage When to Start Pharmacotherapy Target Key Evidence
Stage 1 (130–139/80–89) 10-year CV risk ≥10%, or established CVD / CKD / diabetes; otherwise lifestyle first Below 130/80 ACC/AHA 2017
Stage 2 (≥140/90) All patients; combination therapy if ≥160/100 Below 130/80 SPRINT (2015)
Diabetes All patients with Stage 1 or 2 Below 130/80 ACCORD (2010)
Chronic kidney disease with proteinuria All patients; ACE inhibitor or ARB first-line Below 130/80 KDIGO 2021

Lifestyle Modifications — Quantified BP Reductions

DASH diet: −11 mm Hg systolic  ·  Sodium restriction (<2.3 g/day): −5 to 6 mm Hg  ·  Aerobic exercise: −5 to 8 mm Hg  ·  Weight loss (per kg): −1 mm Hg  ·  Additive with pharmacotherapy at all stages