This comprehensive article highlights the significance of identifying secondary causes of hypertension and outlines a detailed approach to diagnosing and managing these underlying conditions.

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Definition

Secondary hypertension is defined as elevated blood pressure (BP), secondary to an identifiable cause.

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Aetiology

1. Renal parenchymal disease

2. Endocrine disorders

• Primary aldosteronism
• Pheochromocytoma
• Cushing syndrome
• Thyroid disorders

3. Renovascular disorders: Renal artery stenosis

4. Vascular disorders

• Coarctation of the aorta
• Vasculitides of medium or large-sized arteries

5. Obstructive sleep apnea

6. Polycystic ovarian syndrome

7. Preeclampsia

8. Drugs

• NSAIDS
• Methylphenidate, anti-depressants like SNRI, atypical antipsychotics like clozapine
• Decongestants that have phenylephrine or pseudoephedrine
• Steroids like dexamethasone, methylprednisolone, prednisone, prednisolone, and fludrocortisones
• Estrogens, androgens, and oral contraceptives
• Immunosuppressants like cyclosporine and tacrolimus
• Erythropoietin

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Approach to the patient

History and physical

The common clinical signs which warrant investigations for a secondary cause of hypertension may include:

1. Resistant hypertension, i.e., persistent blood pressure greater than 140/90 mm Hg despite using optimal doses of at least three anti-hypertensive from different classes, that includes a diuretic.
2. An acute rise in blood pressure in a patient who had previously stable pressures.
3. Hypertension develops before the age of 30 years, who do not have any other risk factors for hypertension.
4. Patients with severe hypertension with end-organ damage like acute kidney injury, neurological manifestations, flash pulmonary oedema, and hypertensive retinopathy.
5. Hypertension is associated with electrolyte disorders like hypokalemia or metabolic alkalosis.
6. Non-dipping or reverse dipping patterns while monitoring 24-hour ambulatory blood pressure.
7. Snoring, obesity and daytime sleepiness could be indicative of obstructive sleep apnea.
8. History of renal insufficiency, atherosclerotic cardiovascular disease, and oedema may warrant further evaluation of chronic kidney disease.
9. History of recurrent urinary tract infections, kidney stones, acute/chronic abdominal/flank pain, hematuria, and progressive renal failure may point towards autosomal dominant polycystic kidney disease.
10. Worsening renal function with angiotensin-converting enzyme inhibitors (ACEi) and a systolic/ diastolic abdominal bruit point towards the reno-vascular disease.
11. Episodic hypertension, headache, and palpitation, associated with acute stress, in a perioperative setting, could be the signs of pheochromocytoma or paragangliomas.
12. Decreased or delayed femoral pulses, radio femoral delay, and differences in the blood pressure in the arms are seen in the coarctation of the aorta and vasculitic causes of secondary hypertension.
13. Weight gain, fatigue, weakness, hirsutism, amenorrhea, moon facies, dorsal hump, purple striae, and truncal obesity are present in Cushing syndrome/disease.
14. Fatigue, weight loss, hair loss, diastolic hypertension, and muscle weakness are seen in hypothyroidism.
15. Heat intolerance, weight loss, palpitations, systolic hypertension, exophthalmos, tremor, and tachycardia will occur in hyperthyroidism.

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Investigations

Laboratory

• S.creatinine
• S.electrolytes
• Urine examination
• Plasma aldosterone/Renin ratio
• Urinary or plasma metanephrine
• S.TSH, free T4

Radiology

1. Ultrasound renal Doppler is the initial recommended test for the screening and diagnosis of renal artery stenosis. Computed tomographic angiogram (CTA) and magnetic resonance angiogram (MRA) can be considered in a selected group of patients. Renal ultrasound also helps in knowing the kidney size and cortico-medullary differentiation.
2. An echocardiogram is the best screening as well as a diagnostic test for the coarctation of the aorta. Computed tomographic aortogram (CTA) and magnetic resonance angiogram (MRA) are recommended for the diagnosis and confirmation of coarctation of the aorta as well as vasculitis.

Polysomnography: For diagnosis of OSA.

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Treatment

Renal parenchymal disease

Guidelines recommend ACEi/ARB as the preferred drug therapy for the treatment of hypertension in CKD. The RAAS-blocking drugs not only control hypertension but also prevent the progression of CKD, especially in patients with proteinuria.

Renovascular hypertension

Management of renovascular hypertension (renal artery stenosis) is divided into medical therapy and revascularization.

Medical therapy involves the use of anti-hypertensive drugs to control blood pressure and in the case of atherosclerotic disease, the use of antiplatelet, statins, diet, and lifestyle changes.

ACE inhibitors and ARBs are the anti-hypertensive drugs of choice in patients with unilateral renal artery stenosis, however, these drugs are contraindicated in bilateral renal artery stenosis due to the risk of rapid renal dysfunction.

Other pharmacologic treatment options are calcium channel blockers and thiazide diuretics. Percutaneous revascularization is recommended, along with medical therapy in selective patients, especially those with fibromuscular dysplasia.

In the following patients, revascularization may be more beneficial than medical therapy alone:

• Patients with recurrent flash pulmonary oedema
• Failure or intolerance to optimal medical treatment
• Refractory hypertension
• Unexplained, progressive decline in renal function
• Recent initiation of dialysis in a patient with suspected renal artery stenosis
• An acute increase in creatinine after medical therapy and in patients with a renal resistive index of less than 80 mmHg on Doppler

Endocrine hypertension

1. Unilateral primary aldosteronism (e.g., unilateral adrenal hyperplasia or aldosterone-producing adenoma) is treated with unilateral laparoscopic adrenalectomy.
2. If the patient is not a surgical candidate or a patient has bilateral adrenal disease, then medical management with a mineralocorticoid receptor antagonist is recommended and spironolactone is the drug of choice for primary aldosteronism.
3. For Cushing Syndrome or Cushing Disease, an open surgical or laparoscopic resection of the lesion/tumour is the treatment of choice.
4. The definite treatment of pheochromocytoma is surgical resection of the hormone-producing lesion; however preoperative alpha and beta-adrenergic blocking drugs are an essential part of pheochromocytoma management. It is recommended to start alpha-adrenergic blocking drugs first and then add beta blockers for the treatment of tachyarrhythmias.
5. The specific treatment of patients with hypothyroidism includes thyroid replacement therapy, while hyperthyroidism is treated with antithyroid drugs.

Vascular hypertension

The definite treatment is the percutaneous or surgical correction of the coarctation. Correction of coarctation at an early age provides better long-term outcomes, but one-third of the patients remain hypertensive even after surgical correction of the coarctation of the aorta.

Vasculitides of the large vessels (e.g. Takayasu Arteritis) may also lead to hypertension due to a significant rise in systemic vascular resistance. Corticosteroids or other immunosuppressant agents along with antihypertensive drugs are recommended for the treatment of secondary hypertension due to vasculitides.

Obstructive sleep apnea

Continuous positive airway pressure (CPAP) therapy is the mainstay of treatment for OSA. To note, however, lifestyle modifications like weight loss, along with the usage of CPAP have a synergistic effect on lowering blood pressure and are better than either intervention alone.

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Bhavin Mandowara is a practising nephrologist at Zydus Hospital, Ahmedabad.