• Review the family history of patients who do not respond to appropriate antihypertensive therapy, targeting hypertension and inherited disorders associated with high blood pressure (BP). B
• Include obstructive sleep apnea in the differential diagnosis of patients with resistant hypertension, particularly if they’re obese. B
• Include a thorough medication history in a work-up for resistant hypertension, as a number of drugs can cause or exacerbate high BP. A
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
What to include in the workup
Whether you’re doing an initial evaluation of a patient with high blood pressure (BP) or examining a patient with resistant hypertension, the history should focus on the duration of hypertension, previous BP levels, and comorbid conditions. It is also important to take a targeted family history, inquiring about hypertension as well as genetic disorders that increase the likelihood of secondary hypertension.
Inherited diseases associated with secondary hypertension include polycystic kidney disease, multiple endocrine neoplasia type 2 (MEN2), and von Hippel-Lindau syndrome.12,13 All are inherited in an autosomal dominant pattern. Patients with von Hippel-Lindau syndrome may present with multiple tumors, which can develop in the eyes, brain, adrenal glands, pancreas, liver, spinal cord, kidneys, or other parts of the body. Pheochromocytoma is a manifestation of both MEN2 and von Hippel-Lindau syndrome, and some specialists recommend that everyone with a family history of either condition undergo screening for pheochromocytoma.14
|Secondary cause*||Signs and symptoms||Screening tests|
|Renal disease||Depends on underlying cause (eg, diabetes, polycystic kidney disease, glomerulonephritis)||Serum creatinine, urinalysis, renal ultrasound|
|Renal artery stenosis||Abdominal or flank bruits||Renal ultrasound, MRA, CT angiography|
|Primary hyperaldosteronism||Muscle cramps||PA/PRA|
|Pheochromocytoma||Paroxysms of palpitations, diaphoresis, headaches||Plasma metanephrine and normetanephrine|
|Cushing’s syndrome||Rapid weight gain, truncal obesity, abdominal striae||Measurement of 24-hour urinary free cortisol|
|OSA†||Obesity, daytime somnolence, nighttime snoring||Overnight polysomnography|
|Coarctation of the aorta‡||Murmur of anterior and posterior thorax; claudication and weak femoral pulses||Echocardiography|
|CT, computed tomography; MRA, magnetic resonance angiography; OSA, obstructive sleep apnea; PA/PRA, plasma aldosterone-plasma renin activity. |
*Secondary hypertension may also be drug-induced, related to pregnancy (hypertension complicates up to 15% of pregnancies), or associated with inherited syndromes.
†Highly prevalent in obese patients.
‡Higher prevalence in childhood hypertension; rarely diagnosed in adulthood.
BP measurement is key
The physical examination should start with a calculation of body mass index, as well as a careful measurement of BP. The patient should be seated quietly in a chair for ≥5 minutes, with both feet on the floor and the arm being tested supported at heart level.
Unfortunately, reliability on the office BP measurement can be a confounding factor in the diagnosis of hypertension. “White coat hypertension”—in which BP is persistently elevated in the office and persistently normal in nonclinical settings—should be considered in patients who have high BP but no other signs or symptoms, and ambulatory monitoring used to rule out hypertension.15,16
Physicians also need to consider the opposite effect: Masked hypertension, characterized by normal office readings and elevated ambulatory readings, is more serious, of course, with patients at higher risk for end organ damage from unrecognized hypertension.17,18 Asking patients who self-monitor what type of BP readings they’re getting can be helpful in identifying masked hypertension. Ambulatory monitoring may be used to identify this condition, as well.
Other components in the physical workup include a fundoscopic exam; assessment of the thorax for murmurs and the abdomen for enlarged kidneys, masses, and abnormal aortic pulsation; auscultation for abdominal and carotid bruits; palpation of the thyroid gland; and palpation of the lower extremities for edema and pulses.
Include these tests in the workup
Routine tests for a patient with hypertension include:
- blood glucose and hematocrit
- serum potassium, creatinine, and fasting lipid profiles
- urinalysis with measurement of microalbumin.
Microalbuminuria, a sensitive marker of early renal disease, is defined as a urinary albumin excretion between 30 and 300 mg/d.19 The albumin-creatinine ratio (30-300 mcg/mg), measured in spot urine specimens, is a more convenient way to detect it.20
Suspicious findings prompt further testing. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends specific testing—much of it detailed below—if any aspect of the initial evaluation raises suspicion of a secondary cause or the patient has hypertension that’s of sudden onset or hard to control.21 (According to the National Heart, Lung, and Blood Institute, JNC 8 is due for release later this year.)