"Secondary Hypertension: Causes, Diagnosis, and Management"

1. Introduction to Secondary Hypertension

Definition and Classification

• Definition: Secondary hypertension refers to elevated blood pressure (BP) caused by an identifiable, underlying, and often correctable condition, such as kidney disease, endocrine disorders, or vascular abnormalities.
• It contrasts with primary (essential) hypertension, which has no identifiable cause and accounts for the majority (90-95%) of hypertension cases.
• Stages of Hypertension (based on 2017 ACC/AHA Guidelines):
• Normal: <120/<80 mmHg
• Elevated: 120–129/<80 mmHg
• Hypertension Stage 1: 130–139/80–89 mmHg
• Hypertension Stage 2: ≥140/≥90 mmHg

Epidemiology and Prevalence of secondary hypertension

• Secondary hypertension accounts for 5-10% of all hypertension cases in adults and up to 80% in children.
• It is more commonly diagnosed in:
• Younger individuals (ages <40) with severe or resistant hypertension.
• Patients with abrupt onset or accelerated hypertension.
• Certain conditions causing secondary hypertension are regionally more prevalent. For instance:
• Renovascular hypertension is more common in elderly individuals in Western countries.
• Endocrine causes (e.g., primary aldosteronism) are increasingly recognized globally.

 

2. Etiology and Pathophysiology of secondary hypertension

Common Causes of Secondary Hypertension

1. Renal Causes:
• Chronic kidney disease (CKD): Reduced renal function leads to fluid retention and activation of the renin-angiotensin-aldosterone system (RAAS).
• Renovascular hypertension: Narrowing of the renal artery (e.g., due to atherosclerosis or fibromuscular dysplasia) causes hypoperfusion and RAAS activation.
2. Endocrine Causes:
• Primary hyperaldosteronism (Conn’s syndrome): Excess aldosterone causes sodium retention, hypokalemia, and hypertension.
• Cushing's syndrome: Elevated cortisol levels increase blood pressure via mineralocorticoid receptor activation and vascular sensitivity to catecholamines.
• Pheochromocytoma: Tumors of the adrenal medulla cause episodic surges in catecholamines, leading to hypertension.
• Hypothyroidism and hyperthyroidism: Alter vascular resistance and cardiac output, contributing to hypertension.
• Acromegaly: Excess growth hormone increases vascular tone and cardiac output.
3. Vascular Causes:
• Coarctation of the aorta: A congenital narrowing of the aorta, leading to upper body hypertension and diminished lower body perfusion.
4. Drug-Induced Hypertension:
• Medications like NSAIDs, oral contraceptives, corticosteroids, and sympathomimetics can raise BP.
5. Obstructive Sleep Apnea (OSA):
• Recurrent nocturnal hypoxia leads to sympathetic nervous system activation and vascular dysfunction.
6. Miscellaneous:
• Hyperparathyroidism: Elevated calcium increases vascular tone.
• Excess alcohol intake.

Pathophysiology of secondary hypertension

• Secondary hypertension often involves dysregulation of one or more BP control systems, such as:
• Renin-angiotensin-aldosterone system (RAAS): Overactivation leads to vasoconstriction and fluid retention.
• Sympathetic nervous system (SNS): Increased sympathetic activity can elevate heart rate and vascular tone.
• Hormonal imbalances: Disorders of cortisol, aldosterone, and catecholamines directly increase BP.

 

3. Clinical Presentation of secondary hypertension 

History

• Patients often present with signs or symptoms of the underlying condition:
• Abrupt or severe onset of hypertension.
• Hypertension resistant to ≥3 antihypertensive medications, including a diuretic.
• Worsening BP control after previously stable readings.
• Symptoms such as headache, palpitations, sweating (pheochromocytoma), muscle weakness, and polyuria (hyperaldosteronism).

Physical Examination

• Look for clues suggesting secondary causes:
• Abdominal bruits: Renovascular hypertension.
• Cushingoid appearance: Cushing's syndrome.
• Upper-lower extremity BP gradient: Coarctation of the aorta.
• Signs of hyperthyroidism or hypothyroidism: Tachycardia, exophthalmos, or bradycardia.

Key Diagnostic Clues by Cause

Cause	Clinical Clues
Renovascular hypertension	Abdominal bruit, worsening BP with ACE inhibitors, asymmetry in kidney size on imaging.
Primary hyperaldosteronism	Hypokalemia, muscle weakness, metabolic alkalosis.
Pheochromocytoma	Paroxysmal symptoms (headache, palpitations, sweating), episodic hypertension.
Cushing’s syndrome	Moon face, central obesity, purple striae, easy bruising.
Obstructive sleep apnea	Snoring, excessive daytime sleepiness, morning headaches.
Coarctation of the aorta	Delayed/weak femoral pulses, murmur, higher BP in arms vs. legs.

Complications

• Secondary hypertension, if untreated, can lead to:
• Cardiovascular diseases: Heart failure, myocardial infarction, stroke.
• Renal damage: Progression of CKD.
• End-organ damage: Retinopathy, vascular damage.

 

Secondary Hypertension: History Taking, Understanding Patient Complaints, Examination, and Diagnosis

1. History Taking for secondary hypertension 

Comprehensive history taking is crucial to identify the underlying cause of secondary hypertension. Focus on:

1.1. Presenting Complaints

• Symptoms of Hypertension Itself:
• Often asymptomatic.
• May present with headaches, particularly occipital (often in severe hypertension).
• Dizziness, blurred vision, fatigue, or epistaxis in cases of severe hypertension.
• Symptoms of hypertensive crisis: Chest pain, dyspnea, or neurologic deficits.
• Symptoms Suggesting Underlying Causes:
• Primary aldosteronism: Muscle weakness, cramps, polyuria (from hypokalemia).
• Pheochromocytoma: Episodic headache, palpitations, diaphoresis, and paroxysmal hypertension.
• Renovascular hypertension: Sudden worsening of BP, refractory to treatment.
• Cushing's syndrome: Weight gain, muscle weakness, easy bruising, and striae.
• Obstructive Sleep Apnea (OSA): Snoring, daytime sleepiness, morning headaches.

1.2. Risk Factors and History

• Age of Onset:
• Hypertension onset before age 30 or after age 50 suggests secondary hypertension.
• Family History:
• Look for hereditary conditions (e.g., polycystic kidney disease, pheochromocytoma, or hyperaldosteronism).
• Drug History:
• Use of NSAIDs, oral contraceptives, corticosteroids, sympathomimetics, or illicit drugs (e.g., cocaine, amphetamines).
• Lifestyle Factors:
• Alcohol intake, smoking, or high-sodium diet.
• Past Medical History:
• Known kidney disease, diabetes, or other endocrine disorders.
• Pregnancy History:
• History of preeclampsia or eclampsia.

 

2. Understanding Patient Complaints

2.1. Red Flags

Patients with the following complaints or signs should be evaluated for secondary hypertension:

• Severe or resistant hypertension (BP uncontrolled despite ≥3 drugs, including a diuretic).
• Abrupt onset or worsening of hypertension.
• Hypertension in younger individuals or non-obese patients.
• Symptoms of target organ damage:
• Neurologic symptoms: Confusion, stroke, or transient ischemic attack.
• Cardiac symptoms: Chest pain, dyspnea, palpitations.
• Renal symptoms: Hematuria, nocturia, or decreased urine output.

2.2. Symptom Patterns by Cause

• Renovascular Hypertension:
• Refractory hypertension and symptoms of volume overload (e.g., edema).
• Worsening BP with ACE inhibitors or ARBs.
• Endocrine Causes:
• Pheochromocytoma: Episodes of headache, sweating, and tachycardia.
• Hyperaldosteronism: Fatigue, muscle weakness, and polyuria.
• Cushing’s Syndrome: Gradual onset of weight gain, hirsutism, and proximal muscle weakness.

 

3. Examination for secondary hypertension 

3.1. General Physical Examination

• Vital Signs:
• Measure BP in both arms (difference >20 mmHg may suggest aortic coarctation).
• Check heart rate (tachycardia in pheochromocytoma, bradycardia in hypothyroidism).
• General Appearance:
• Signs of Cushing’s syndrome: Moon face, central obesity, purple striae.
• Thin body habitus in hyperthyroidism.

3.2. Cardiovascular System

• Heart Sounds:
• S4 gallop in left ventricular hypertrophy (from chronic hypertension).
• Pulses:
• Delayed or diminished femoral pulses in coarctation of the aorta.

3.3. Abdomen

• Renal Bruits:
• Indicative of renovascular hypertension.
• Palpable Kidneys:
• Seen in autosomal dominant polycystic kidney disease (ADPKD).

3.4. Neurologic and Ophthalmologic Exam

• Fundoscopy:
• Retinal changes such as hypertensive retinopathy (e.g., flame hemorrhages, papilledema).
• Neurologic Exam:
• Focal deficits in stroke or hypertensive encephalopathy.

3.5. Signs Suggesting Specific Causes

Condition	Examination Findings
Primary aldosteronism	Signs of hypokalemia (muscle weakness, hyporeflexia).
Pheochromocytoma	Episodic hypertension, diaphoresis, and tachycardia.
Cushing's syndrome	Moon face, truncal obesity, proximal muscle wasting, striae.
Coarctation of the aorta	BP disparity between arms and legs, diminished femoral pulses.

 

4. Diagnosis of secondary hypertension 

4.1. Initial Workup

1. Basic Investigations:
• Serum Electrolytes: Hypokalemia in primary aldosteronism.
• Renal Function Tests: Elevated creatinine or BUN in renal causes.
• Thyroid Function Tests: Hyperthyroidism or hypothyroidism.
• Urinalysis: Hematuria, proteinuria, or casts suggest kidney disease.
2. Hormonal Tests:
• Plasma aldosterone concentration (PAC) and plasma renin activity (PRA): Elevated aldosterone/renin ratio (>20:1) in primary hyperaldosteronism.
• 24-hour urinary cortisol or dexamethasone suppression test: Cushing’s syndrome.
• Plasma and urinary metanephrines: Pheochromocytoma.
3. Imaging Studies:
• Renal Doppler Ultrasound/CT/MRI Angiography: Renal artery stenosis.
• CT Adrenal Glands: Adenomas in hyperaldosteronism or pheochromocytoma.
• Chest X-ray or MRI: Coarctation of the aorta.
4. Specialized Tests:
• Polysomnography for obstructive sleep apnea.
• Genetic testing for hereditary causes (e.g., ADPKD).

 

 

Secondary Hypertension: Management and Treatment, Complications, Patient Education, and Special Considerations

 

1. Management and Treatment of secondary hypertension 

1.1 General Approach

Management of secondary hypertension focuses on:

1. Identifying and treating the underlying cause to normalize blood pressure.
2. Controlling blood pressure to prevent end-organ damage.

1.2. Cause-Specific Treatment

Cause	Treatment Options
Renovascular Hypertension	- Medications: ACE inhibitors or ARBs (use with caution if bilateral renal artery stenosis is present). - Procedures: Angioplasty, stenting, or surgical revascularization for severe stenosis or resistant hypertension.
Primary Aldosteronism	- Surgical Treatment: Adrenalectomy for unilateral aldosterone-producing adenoma. - Medical Management: Mineralocorticoid receptor antagonists (e.g., spironolactone or eplerenone).
Pheochromocytoma	- Surgical Removal: After alpha-blockade (e.g., phenoxybenzamine) to control BP and avoid hypertensive crisis. - Beta-blockers are added only after alpha-blockade to prevent unopposed alpha-adrenergic stimulation.
Cushing's Syndrome	- Surgical Treatment: Removal of cortisol-secreting tumors. - Medical Therapy: Ketoconazole or metyrapone if surgery is not an option.
Obstructive Sleep Apnea	- Lifestyle Modifications: Weight loss, positional therapy. - Continuous Positive Airway Pressure (CPAP): Improves BP and cardiovascular outcomes.
Coarctation of the Aorta	- Surgical Repair or balloon angioplasty with stenting.
Chronic Kidney Disease	- Blood Pressure Management: ACE inhibitors or ARBs to protect renal function. - Manage fluid overload with diuretics.

1.3 General Antihypertensive Therapy

• First-Line Medications:
• ACE Inhibitors/ARBs: Effective for renovascular and endocrine causes.
• Calcium Channel Blockers (CCBs): Often used in resistant hypertension.
• Thiazide Diuretics: Manage volume overload.
• Resistant Hypertension:
• Consider spironolactone, clonidine, or alpha-blockers.

1.4 Lifestyle Modifications

• Dietary Approaches to Stop Hypertension (DASH) diet: High in fruits, vegetables, and low-fat dairy, with reduced sodium intake (<2,300 mg/day).
• Weight loss: Aim for a BMI <25 kg/m².
• Exercise: Moderate aerobic activity for 30 minutes, 5 days a week.
• Smoking cessation and limiting alcohol intake.

 

2. Complications and Comorbidities of secondary hypertension 

2.1. Complications of Secondary Hypertension

• Cardiovascular:
• Left ventricular hypertrophy, heart failure, myocardial infarction, arrhythmias.
• Aneurysms and peripheral arterial disease.
• Cerebrovascular:
• Stroke (ischemic or hemorrhagic) and transient ischemic attacks (TIA).
• Renal:
• Progression to chronic kidney disease (CKD) or end-stage renal disease (ESRD).
• Ophthalmologic:
• Hypertensive retinopathy, leading to vision loss.

2.2. Comorbidities

• Patients with secondary hypertension may have associated conditions, including:
• Metabolic Syndrome: Obesity, insulin resistance, dyslipidemia.
• Type 2 Diabetes Mellitus: Exacerbates hypertension and accelerates end-organ damage.
• Sleep Apnea: Aggravates resistant hypertension.

 

3. Patient Education about secondary hypertension 

3.1 Importance of Treating Secondary Hypertension

• Educate patients on the potential risks of untreated hypertension, including heart attack, stroke, and kidney failure.
• Stress the importance of adhering to treatment and follow-up appointments.

3.2 Lifestyle Modifications

• Dietary Advice:
• Reduce sodium, limit processed foods, and avoid alcohol overconsumption.
• Encourage potassium-rich foods (bananas, spinach) unless contraindicated.
• Physical Activity:
• Discuss an individualized exercise program appropriate for the patient’s age and comorbidities.
• Smoking Cessation:
• Provide resources or referrals to smoking cessation programs.

3.3 Drug Adherence

• Emphasize the importance of taking medications as prescribed.
• Educate patients about potential side effects and the importance of discussing them with their healthcare provider.

3.4 Self-Monitoring

• Encourage home BP monitoring to track progress and adjust treatments as needed.

 

4. Special Considerations

4.1. Pregnancy and Secondary Hypertension

• Certain causes, such as preeclampsia or renovascular hypertension, can worsen during pregnancy.
• Avoid medications contraindicated in pregnancy (e.g., ACE inhibitors, ARBs) and switch to safer alternatives like labetalol or methyldopa.

4.2. Pediatric Secondary Hypertension

• Secondary hypertension is more common in children, often due to renal parenchymal disease or coarctation of the aorta.
• Diagnosis often requires imaging (e.g., Doppler ultrasound, echocardiography).

4.3. Elderly Patients

• Secondary causes like renovascular hypertension and CKD are more common in older adults.
• Tailor treatment to avoid over-aggressive BP lowering, which can cause orthostatic hypotension and falls.

4.4. Resistant Hypertension

• Patients with BP not controlled by ≥3 drugs should be evaluated for secondary causes.
• Referral to a hypertension specialist may be necessary.

 

References

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