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BASICS

Description

  • Resistant hypertension (HTN): BP remains above target despite use of 3 different antihypertensives at optimal doses, including a diuretic.
  • Secondary HTN: BP elevation with identifiable underlying cause.
  • Diagnosis excludes pseudoresistance, medication nonadherence, white coat HTN.

Geriatric Considerations

  • Onset >60 years suggests secondary cause.
  • Target SBP ≥150 mm Hg for patients >80 years; avoid excessive diastolic lowering.
  • Common secondary causes in elderly: sleep apnea, renal disease, atherosclerotic renal artery stenosis (ARAS), primary aldosteronism.
  • Osler phenomenon: noncompressible arteries in elderly with arteriosclerosis.

Alerts

  • Pseudoresistance: Inaccurate BP measurement, poor adherence.
  • White coat effect: common (20-40% prevalence).
  • Use home BP monitoring (HBPM), ambulatory BP monitoring (ABPM) to confirm diagnosis.

EPIDEMIOLOGY

  • Onset usually between ages 30-50.
  • Resistant HTN prevalence ~10-15%; secondary HTN 5-10%.
  • Resistant HTN more common in males, older adults, diabetics.
  • Secondary HTN prevalence in children ~3.7%.

ETIOLOGY AND PATHOPHYSIOLOGY

Common Causes

  • Obstructive sleep apnea (25-50%)
  • Primary hyperaldosteronism (8-20% of resistant HTN)
  • Chronic renal disease (1-2%)
  • Renovascular disease (0.2-0.7%; up to 35% in elderly)
  • Cushing syndrome (<0.1%)
  • Pheochromocytoma (0.04-0.1%)
  • Others: hyperthyroidism, hyperparathyroidism, aortic coarctation, intracranial tumors

Drug-Induced

  • NSAIDs (may blunt ACEi effects)
  • Decongestants, stimulants, anorectic agents, herbals (guarana, ma huang, bitter orange)
  • Licorice-containing products
  • Glucocorticoids
  • Oral contraceptives (cessation may normalize BP)

Lifestyle Factors

  • Obesity
  • High dietary salt
  • Excessive alcohol
  • Physical inactivity

Genetics

  • Variants account for <3% BP variance in resistant HTN.

RISK FACTORS

  • Male sex
  • Caucasian ethnicity
  • Older age
  • Diabetes mellitus
  • Obesity
  • Stage 2 HTN (SBP >160 or DBP >100)
  • Renal disease
  • Alcohol or drug use
  • Lack of family history of HTN
  • Significant target organ damage

GENERAL PREVENTION

  • DASH diet
  • Low sodium intake
  • Weight loss in obese patients
  • Regular exercise
  • Alcohol moderation
  • Smoking cessation
  • Relaxation techniques

DIAGNOSIS

History

  • Use mnemonic SANS:
  • Salt intake
  • Alcohol use
  • NSAID use
  • Sleep (sleep apnea)
  • Medication adherence assessment essential.
  • Review home BP or ambulatory monitoring.

Physical Exam

  • Correct BP measurement technique:
  • Patient seated quietly 5 min
  • Proper cuff size
  • Measure in both arms
  • Standing BP for orthostasis
  • Look for signs of specific etiologies:
  • Renovascular HTN: abdominal bruit
  • Pheochromocytoma: tachycardia, diaphoresis
  • Cushing syndrome: moon face, purple striae
  • Thyroid disease: goiter, tremor
  • Coarctation: diminished femoral pulses

Differential Diagnosis

  • Pseudoresistance

Diagnostic Tests

  • ECG for LVH
  • Sleep study if indicated (Epworth Sleepiness Scale)
  • Initial labs: urinalysis, CBC, electrolytes, glucose, creatinine, lipids, TSH, calcium, microalbuminuria
  • Imaging:
  • Abdominal US for renal disease
  • Duplex US for renovascular disease
  • MR angiography or CT angiography if needed
  • Specialized tests:
  • Plasma aldosterone-renin ratio (ARR) for hyperaldosteronism
  • 24-hour urine/plasma metanephrines for pheochromocytoma
  • Dexamethasone suppression, urine toxicology as indicated
  • ABPM and HBPM recommended for diagnosis and monitoring.

TREATMENT

General

  • Treatment depends on underlying cause.
  • Empiric aldosterone antagonist trial (spironolactone, eplerenone) often helpful.
  • Lifestyle modifications per guidelines.
  • Obese and elderly patients often respond well to diuretics.
  • Diuretic tolerance (“braking effect”) may necessitate dose increase or addition of aldosterone antagonist.

Specific Etiology Treatments

  • Primary aldosteronism: aldosterone receptor antagonists.
  • Cushing syndrome: aldosterone receptor antagonists.
  • Obstructive sleep apnea (OSA): CPAP, weight loss, mandibular advancement devices.
  • Renovascular disease: medical therapy preferred; stenting for fibromuscular dysplasia.
  • Resistant HTN: combination therapies, referral to HTN specialist.

Medications

  • Follow JNC 8/AHA/ACC guidelines.
  • First-line: ARBs, ACEi, thiazides.
  • Avoid race-based prescribing bias but recognize differential responses.
  • Second-line: combine thiazide with ACEi/ARB/CCB or add aldosterone antagonist.
  • Beta blockers for specific indications.
  • Third-line: add other agents if BP uncontrolled, investigate secondary causes.

ISSUES FOR REFERRAL

  • Uncontrolled hypertension despite therapy
  • Complex secondary causes
  • Resistant hypertension

COMPLEMENTARY & ALTERNATIVE MEDICINE

  • University of Wisconsin Integrative Medicine offers patient resources.

ONGOING CARE

Follow-Up

  • Encourage aerobic exercise (~30 minutes daily).
  • Remote BP monitoring can be useful.
  • Sodium restriction and Mediterranean or DASH diet recommended.
  • Patient education on home BP monitoring (HBPM).

REFERENCES

  1. James PA, Oparil S, Carter BL, et al. 2014 Evidence-based guideline for management of high blood pressure: JNC 8. JAMA. 2014;311(5):507-520.
  2. Carey RM, Calhoun DA, Bakris GL, et al. Resistant hypertension: detection, evaluation, and management. Hypertension. 2018;72(5):e53-e90.
  3. Chen RJ, Suchard MA, Krumholz HM, et al. Comparative first-line effectiveness and safety of ACE inhibitors and ARBs. Hypertension. 2021;78(3):591-603.

Clinical Pearls

  • Consider aldosterone antagonists in all resistant hypertension cases.
  • Home BP monitoring predicts outcomes better than office BP.