Hypertension affects about 30% of adults in the United States. Most cases are due to essential hypertension, i.e., hypertension without an identifiable cause. But, about 5 to 10% of cases of hypertension are due to secondary hypertension.
Secondary hypertension is elevated blood pressure (BP), which is secondary to an identifiable cause. Since its prevalence is relatively low, performing routine evaluations in every case of hypertension is not cost effective and is also time-consuming. However, one must be aware of clinical clues that could suggest a secondary cause of hypertension. The clinical clues to look out for that could be suggestive of a secondary cause of hypertension are as follows:
The etiology of secondary hypertension is varied. The causes subdivide into the following four categories:
A. Renal causes: Among these, the major categories are renal parenchymal disease (which includes chronic kidney disease and polycystic kidney disease) and reno-vascular disease (which includes renal artery stenosis and fibromuscular dysplasia).
B. Endocrine causes: Primary aldosteronism, Cushing syndrome/disease, hyperthyroidism, hypothyroidism, hyperparathyroidism, pheochromocytoma including drug-mediated pheochromocytoma crisis, acromegaly, congenital adrenal hyperplasia.
C. Vascular: Coarctation of the aorta.
D. Other: Obstructive sleep apnea, drug-induced hypertension, pregnancy, scleroderma.
Drug-induced hypertension is a significant cause of secondary hypertension. Hence, it is essential to look at the patient's medication list. Following are the drugs that can cause hypertension:
As stated above, about 5 to 10% of hypertension in adults results from secondary hypertension. The prevalence of secondary hypertension varies with age, being most prevalent at the extremes of age, accounting for 70 to 85 percent of hypertension cases in children less than 12 years of age, and approximately 17 percent of cases in adults age 65 and older. The prevalence of secondary hypertension is lowest amongst hypertensive patients who are 19 to 39 years of age at 5 percent. The prevalence in adolescents (12 to 18 years) is 10 to 15%.
Obtaining a complete history and performing a good physical exam is very important when trying to find the underlying cause of hypertension. The following history and physical exam findings point towards a specific cause of secondary hypertension:
Laboratory tests and imaging modalities also help in diagnosing secondary hypertension. Some of the findings on common tests that can create suspicion for an underlying cause of hypertension are as follows:
Upon establishing suspicion for a particular cause based on history, physical exam findings, and common laboratory tests, certain tests can be used to specifically rule out or rule in a cause of secondary hypertension. They are as follows:
Management of secondary hypertension comprises of adequate control of blood pressure with antihypertensive drugs and addressing the secondary causes mentioned above. This section briefly discusses the management of the more common causes of secondary hypertension, viz: renal parenchymal disease, renovascular hypertension, primary hyperaldosteronism, obstructive sleep apnea, drug-induced hypertension, and pregnancy.
A. Renal parenchymal disease:
Renal parenchymal disease-causing hypertension mainly involves chronic kidney disease (CKD) and autosomal dominant polycystic kidney disease (ADPKD).
i. Management of chronic kidney disease comprises of treating the reversible causes responsible for causing CKD (e.g., treating hypovolemia with fluids, avoid nephrotoxin use, relieve urinary tract obstruction) and slowing the rate of progression of the disease. To slow the rate of progression, adequate blood pressure control, decreasing urine protein, glycemic control, lifestyle changes like dietary protein restriction, and smoking cessation help. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are the best anti-hypertensives to use in proteinuric CKD. Bicarbonate use in patients with chronic metabolic acidosis slows progression to end-stage renal disease.
ii. Patients with ADPKD eventually require renal replacement therapy. Before that stage reached, hypertension management is with anti-hypertensives: ACE inhibitors or ARBs and sodium restriction. Tolvaptan is an option in patients who are at high risk for progression to CKD. It decreases the rate of estimated glomerular filtration rate decline.
B. Renovascular hypertension:
Management of renovascular hypertension (i.e., renal artery stenosis from either atherosclerotic disease or fibromuscular dysplasia) divides into medical therapy and revascularization. Medical therapy involves the use of anti-hypertensives to control blood pressure and in the case of atherosclerotic disease, the use of antiplatelets, statins, diet, and lifestyle changes. ACE inhibitors and ARBs are the anti-hypertensives of choice. Other anti-hypertensives that are treatment options are calcium channel blockers and thiazide diuretics.
Revascularization is usually done by percutaneous angioplasty with stenting of the renal artery. Surgery (which frequently includes aorto-renal bypass or sometimes removal of the ‘pressor’ kidney) is only for patients with complex anatomy.
In the following patients, revascularization may be more beneficial than medical therapy alone:
C. Primary hyperaldosteronism:
Unilateral primary hyperaldosteronism (e.g., unilateral adrenal hyperplasia or aldosterone-producing adenoma) gets treated with unilateral laparoscopic adrenalectomy. If the patient is not a surgical candidate or a patient has the bilateral adrenal disease, then medical management with a mineralocorticoid receptor antagonist is recommended- with spironolactone being the primary agent and eplerenone being the alternative.
D. 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 usage of CPAP have a synergistic effect on lowering blood pressure, and is better than either intervention alone.
An alternative to CPAP, are oral appliances, used in mild to moderate OSA, which are non-inferior to CPAP in the reduction of blood pressure and may even help with better compliance in patients. In patients refractory to the above treatment, few upper airway surgeries can be performed to help with symptoms and reduction in blood pressure, like uvulopalatopharyngoplasty (UPPP) in adults and tonsillectomy and adenoidectomy in children. Along with these, anti-hypertensive drugs also help, particularly the ones that modulate the renin-angiotensin system (ACE inhibitors, ARBs, aldosterone antagonists, and beta blockers are the best options).
E. Drug-induced hypertension: In drug-induced hypertension, upon identification of the culprit drug, the management is to withhold it and look for improvement.
F. Pregnancy: Hypertension in pregnancy comprises of chronic hypertension, gestational hypertension, pre-eclampsia, and eclampsia. Chronic hypertension is when hypertension occurs before pregnancy or before 20 weeks of gestation, whereas the other three occur after 20 weeks. Pre-eclampsia is associated with proteinuria, and eclampsia is associated with seizures.
Interventions for hypertension in pregnancy are lifestyle modifications and anti-hypertensives. The anti-hypertensives commonly used in pregnancy are labetalol, nifedipine, and methyldopa.
In cases of severe hypertension (severe preeclampsia, eclampsia, and HELLP syndrome), the standard of care is delivery, especially after 37 weeks of gestation. If an acute decrease in blood pressure is required, intravenous labetalol or intravenous hydralazine are options. Magnesium sulfate prevents seizures.
The differential diagnosis of secondary hypertension as stated above are: chronic kidney disease, autosomal dominant polycystic kidney disease, renal artery stenosis, fibromuscular dysplasia, primary aldosteronism, Cushing syndrome/disease, hyperthyroidism, hypothyroidism, hyperparathyroidism, pheochromocytoma, acromegaly, congenital adrenal hyperplasia, coarctation of aorta, obstructive sleep apnea, drug-induced hypertension, pregnancy, scleroderma.
The prognosis of secondary hypertension is good. With the treatment of the underlying condition, the blood pressure may decrease or even come back to normal.
The underlying medical condition that causes high blood pressure can be worsened by secondary hypertension. Some of the complications of secondary hypertension are atherosclerosis, aneurysm, heart failure, metabolic syndrome, chronic renal failure, and retinopathy.
The patient's primary care doctor and/or nurse practitioner may be the main person involved in diagnosing a secondary cause of hypertension. But an interprofessional team of specialists consisting of a nephrologist, cardiologist, endocrinologist, rheumatologist, and surgeons can help with diagnosing and managing the patient. Nurses also play an essential role in patient care, as do pharmacists. Hence, interprofessional communication and care coordination between physicians, nurses, and other health professionals are crucial to enhance patient outcomes. [Level V]
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