What are the primary (essential) and secondary causes of hypertension (HTN)?

Causes of Hypertension

The vast majority (approximately 90-95%) of hypertension cases are primary (essential) hypertension with no identifiable single cause, while secondary hypertension accounts for 5-10% of cases in the general population but increases to 10-35% in patients with resistant hypertension. 1, 2, 3

Primary (Essential) Hypertension

Primary hypertension results from complex interactions between genetic predisposition and environmental factors, involving multiple interconnected physiological systems. 3

Key Pathophysiologic Mechanisms

• Overactivation of the renin-angiotensin-aldosterone system (RAAS) drives sustained blood pressure elevation through increased peripheral vascular resistance 3
• Endothelial dysfunction impairs normal vascular regulation and contributes to vascular remodeling 3
• Dysregulation of renal sodium handling and impaired pressure natriuresis play fundamental roles, with dietary sodium acting as a direct vascular toxin 3
• Vascular remodeling with fibrosis and inflammation in the microcirculation perpetuates hypertension 3

Major Risk Factors

• Obesity is responsible for 40% of hypertension cases overall and up to 78% in men and 65% in women, with a continuous linear relationship between BMI and blood pressure 3
• Excessive dietary sodium intake far exceeds the physiologic requirement of <10 mmol/day and accounts for much of the age-related blood pressure increase 3
• Physical inactivity and sedentary lifestyle combined with caloric excess lead to steep rises in blood pressure, particularly systolic 3
• Excessive alcohol consumption (≥3 standard drinks per day) shows a strong direct relationship with blood pressure elevation 3
• Family history of hypertension is commonly present in individuals with primary hypertension 3

Secondary Hypertension

Secondary hypertension has identifiable, potentially reversible causes with specific pathophysiologic mechanisms, and should be aggressively pursued because treating the underlying cause can lead to cure or dramatic improvement. 1, 2

Common Secondary Causes in Adults

Renal Parenchymal Disease (Prevalence: 1-2%)

• Clinical clues: History of urinary tract infections, obstruction, hematuria, urinary frequency, nocturia, analgesic abuse, family history of polycystic kidney disease, elevated serum creatinine, abnormal urinalysis 1, 2
• Physical exam: Palpable abdominal mass (polycystic kidney disease), skin pallor 1
• Screening test: Renal ultrasound 1, 2

Renovascular Disease (Prevalence: 5-34% in resistant hypertension)

• Clinical clues: Resistant hypertension, abrupt onset or worsening hypertension, flash pulmonary edema (atherosclerotic), early-onset hypertension especially in women (fibromuscular dysplasia), ≥50% rise in serum creatinine within one week after starting ACE inhibitor or ARB 1, 2, 4
• Physical exam: Abdominal systolic-diastolic bruit, bruits over carotid or femoral arteries 1, 2
• Screening test: Renal Duplex Doppler ultrasound 1, 2
• Confirmatory test: CT or MR renal angiography, bilateral selective renal intra-arterial angiography 1, 2

Primary Aldosteronism (Prevalence: 8-20% in resistant hypertension)

• Clinical clues: Resistant hypertension, spontaneous or diuretic-induced hypokalemia, muscle cramps or weakness, incidentally discovered adrenal mass, obstructive sleep apnea, family history of early-onset hypertension or stroke at age <40 years 1, 2, 5
• Physical exam: Arrhythmias (especially atrial fibrillation with hypokalemia) 1
• Screening test: Plasma aldosterone-to-renin ratio (ARR) under standardized conditions—the 2024 European Society of Cardiology guidelines now recommend measuring ARR in all adults with confirmed hypertension (Class IIa) 2, 5
• Confirmatory tests: Oral sodium loading test or IV saline infusion test, adrenal CT scan, adrenal vein sampling 1, 2

Obstructive Sleep Apnea (Prevalence: 25-50% in resistant hypertension)

• Clinical clues: Snoring, fitful sleep, breathing pauses during sleep, daytime sleepiness, non-dipping or reverse-dipping nocturnal blood pressure pattern 1, 2, 5
• Physical exam: Obesity, Mallampati class III-IV, neck circumference >40 cm, loss of normal nocturnal BP fall 1, 2, 5
• Screening test: Berlin Questionnaire, home sleep apnea testing 2
• Confirmatory test: Polysomnography 2, 5

Drug-Induced Hypertension

• Common culprits: NSAIDs, oral contraceptives, decongestants, stimulants, corticosteroids, cyclosporine, erythropoietin, herbal supplements (licorice, ephedra) 1, 2, 5
• The American College of Cardiology recommends reviewing all medications before pursuing expensive workup 2

Uncommon Secondary Causes

Pheochromocytoma/Paraganglioma

• Clinical clues: Classic triad of episodic sweating, palpitations, and frequent headaches; labile or paroxysmal hypertension; pallor 1, 2, 5
• Screening test: 24-hour urinary catecholamines or metanephrines, or plasma free metanephrines 1, 2, 5
• Confirmatory test: Abdominal/adrenal CT or MRI 2, 5

Cushing Syndrome

• Clinical clues: Central obesity with thin extremities, wide (>1 cm) purple striae, easy bruising, proximal muscle weakness, moon facies, buffalo hump, fatty deposits 1, 2, 5
• Screening test: 24-hour urinary free cortisol or overnight dexamethasone suppression test, late-night salivary cortisol 1, 2, 5

Thyroid Disorders

• Clinical clues: Hyperthyroidism (heat intolerance, tremor, weight loss, tachycardia); Hypothyroidism (cold intolerance, weight gain, delayed reflexes) 1, 2, 5
• Screening test: Thyroid-stimulating hormone (TSH) 1, 2, 5

Aortic Coarctation

• Clinical clues: Young age, systolic BP difference >10 mmHg between arm and leg 2, 5
• Physical exam: Radio-femoral delay, diminished and delayed femoral pulses, precordial or chest murmurs 2, 5, 3
• Confirmatory test: Echocardiogram or thoracic/abdominal CT angiography or MRA 1, 2

Primary Hyperparathyroidism

• Clinical clues: Hypercalcemia 1
• Screening test: Serum calcium 1
• Confirmatory test: Serum parathyroid hormone 1

Red Flags Requiring Secondary Hypertension Work-Up

The American College of Cardiology recommends screening for secondary hypertension when any of the following are present: 1, 2, 5

• **Age of onset <30 years** (especially before puberty) or >50 years 2, 5, 6, 4
• Resistant hypertension (BP >140/90 mmHg despite optimal doses of ≥3 antihypertensive drugs including a diuretic) 2, 5, 7, 4
• Severe hypertension (systolic >180 mmHg or diastolic >110 mmHg) or hypertensive emergency 2, 5, 7
• Abrupt onset or sudden deterioration of previously controlled hypertension 2, 5, 7, 4
• Target organ damage disproportionate to duration or severity of hypertension 2, 5
• Absence of family history of hypertension in young patients 3, 7
• Unprovoked hypokalemia 1, 6

Initial Screening Approach

All patients with suspected secondary hypertension should undergo baseline laboratory screening before expensive imaging: 2, 5

• Serum electrolytes (sodium, potassium)—hypokalemia strongly suggests primary aldosteronism 2, 5
• Serum creatinine and eGFR 2, 5
• Urinalysis with albumin-to-creatinine ratio 2, 5
• Fasting glucose or HbA1c 2, 5
• Thyroid-stimulating hormone (TSH) 2, 5
• Fasting lipid panel 2, 5
• 12-lead ECG to assess for left ventricular hypertrophy 2, 5
• Plasma aldosterone-to-renin ratio (ARR) for all confirmed hypertension per 2024 ESC guidelines 2, 5

Common Pitfalls to Avoid

• Medication non-adherence accounts for a large share of apparent resistant hypertension—explicitly ask about missed doses, side effects, and cost barriers 5
• White-coat hypertension occurs in 20-30% of patients with apparent resistant hypertension—use ambulatory or home BP monitoring to exclude 5
• Failing to review all medications (including over-the-counter drugs and supplements) before pursuing expensive workup 2, 5
• Normal potassium levels do not exclude primary aldosteronism—hypokalemia is absent in the majority of cases 1, 2

Specialist Referral Indications

Refer to a hypertension specialist or endocrinologist when: 2, 5

• Positive screening tests require confirmatory evaluation (e.g., elevated ARR, elevated metanephrines) 2, 5
• Complex procedures are needed (e.g., adrenal vein sampling) 2, 5
• Surgical intervention is being considered (e.g., unilateral adrenalectomy for primary aldosteronism) 2, 5
• BP remains uncontrolled after ≥6 months of optimal medical therapy 5