Before instituting an extensive evaluation for secondary causes of hypertension, the clinician must be certain that the blood pressure readings obtained are indicative of
the patient’s “true” blood pressure during the majority of the day. It is of foremost importance first to establish that the blood pressure-measurement methods are valid and accurate per established guidelines (5). Lack of attention to proper measurement techniques, even by trained medical staff (6) and cardiologists alike (7), can lead to false diagnoses of resistant hypertension. Among many common errors, careful attention should be given to using an appropriate arm-cuff size (particularly in obese patients), keeping the upper arm at heart level (mid-sternal), and allowing for a full 5-minute resting in a seated position before obtaining duplicate or triplicate readings (5). Physicians must confirm nonemergency hypertension by corroborating readings on several occasions and should not be overly concerned by intermittent, isolated, or a few sporadic asymptomatic high values.

Although office blood pressures are most commonly used, a sizable subset of patients have significant hypertension only in the physician’s office (“white-coat” hypertension). Recognizing the continued debate, white-coat hypertension (home daytime blood pressures less than 135/85 mm Hg) is generally considered a comparatively benign condition and does not usually require (more) treatment (8). Patients receiving multidrug treatment with elevated office readings, yet with controlled 24-hour ambulatory blood pressures, are at markedly lower cardiovascular risk than are those with sustained true hypertension out of the medical office setting (9). On the contrary, true labile, or “borderline” hypertension carries an increased risk of cardiovascular events (10) and generally warrants treatment. Home blood pressure readings or 24-hour ambulatory monitoring can be important in distinguishing a patient with true severe hypertension from one who simply has controlled hypertension that is significantly augmented in the physician’s office (i.e., “pseudoresistance”). A workup for secondary causes in a patient with near-normal home blood pressure readings is likely to be unrevealing, and the cost of home blood pressure monitoring is low in comparison with most secondary evaluations. Moreover, home blood pressure readings can prevent overtreatment in patients with labile blood pressure, decrease drug side effects, and increase the patient’s ability to adhere to prescribed medical regimens. Basing treatment decisions on home blood pressure values leads to adequate blood pressure control without compromising clinical outcomes (11). Therefore all patients with refractory office hypertension should have the diagnosis corroborated by ruling out “white-coat resistance” with either proper home blood pressure or 24-hour ambulatory monitoring or both.

The confounding presence of pseudohypertension also is important to consider before undergoing a secondary hypertension evaluation (12). In elderly patients and those with renal insufficiency, conventional arm blood pressure measurement in a calcified and noncompressible brachial artery can lead to falsely elevated systolic cuff readings and to subsequent overtreatment. In these patients, alternative blood pressure-measuring devices such as wrist and finger monitors, or even arterial lines, can be useful to establish the “true” blood pressure. In addition, a number of patients with labile refractory hypertension actually have “paroxysmal hypertension syndrome.” During most times, blood pressure levels and variability are normal. However, frequent seemingly unprovoked paroxysms involve large blood pressure elevations, most often associated with somatic symptoms (e.g., headache, panic, skin flushing). In an attempt to find an organic cause of their problems, patients often blame the blood pressure increase as the cause of the symptoms. In actuality, the reverse relation is almost always the true one. This syndrome may also overlap with significant white-coat hypertension as well. This increasingly recognized phenomenon may be caused by underlying intermittent anxiety, stress, pain, or psychosocial problems such as
a previous traumatic life event (13). Most individuals will deny an obvious precipitant of the frequent, often very severe intermittent hypertensive episodes. This often leads to repeated negative evaluations for pheochromocytoma. Ambulatory blood pressure monitoring, calming nonjudgmental reassurance, focused testing to rule out worrisome diseases, and treatment of the underlying disorder (e.g., antidepressants, anxiolytics) can result in improved blood pressure control, less frequent paroxysms, and a reduction in the associated symptoms. Finally, a recently described phenomenon in young patients, termed pseudohypertension of the youth, should be considered in young patients who otherwise have no apparent cause for their hypertension (14). These individuals are typically tall, athletic young men between 15 and 30 years old with isolated systolic hypertension. Evaluation of central aortic blood pressures may demonstrate normal values despite an elevated brachial systolic pressure, possibly due to enhanced peripheral pressure amplification. However, the precise etiology, prevalence, and prognosis associated with this syndrome remains to be determined.

In addition, the health care provider must assess a patient’s adherence to and persistence with prescribed treatment plans before embarking on an extensive workup for secondary causes of hypertension. This can often be a difficult task, and many clinicians overestimate the degree of adherence of their patients. In very rare circumstances, an admission to the hospital for observed therapy is even required. More commonly, a detailed history with a noncombative questioning style and an assessment of the patient’s knowledge of the medical regimen can reveal the level of adherence. Most patients do not consciously disregard medical advice. It is more common that incomplete adherence to the full drug regimen or misunderstandings or both are responsible for medical nonadherence (15). Moreover, medication side-effect profiles and ease of adherence should be assessed. Moderate to severe hypertension is often treated with multiple drugs that are expensive and have adverse side-effect profiles. Because of their power in reducing blood pressure, drugs such as clonidine, hydralazine, and minoxidil are often prescribed without regard for the patient’s ability to tolerate the combined side effects. In short, patients are often not eager to spend money each month to feel miserable, particularly when they generally seem well despite their elevated blood pressure. Assessing medical adherence to treatment of an asymptomatic disease such as hypertension is absolutely essential for successful treatment.

Finally, all of the numeric and physical data from a patient should be consistent before a secondary evaluation is considered. A patient with years of extremely elevated blood pressure but no evidence of any target-organ damage (microalbuminuria, left ventricular hypertrophy, retinal abnormalities) is unlikely to have sustained levels of blood pressure elevation out of the physician’s office and would be a poor candidate for a workup for secondary hypertension. Similarly, a patient with modestly elevated readings in the physician’s office but evidence of target-organ damage should be evaluated more aggressively. This may be a sign of “masked” hypertension (elevated ambulatory blood pressures significantly higher than office readings), which carries a poor prognosis (16).

Once the accuracy of the blood pressure measurements and pattern is confirmed and the patient’s history of medical compliance is reasonably documented, an evaluation for secondary causes of hypertension can proceed. A vast number of rare causes for secondary hypertension have now been identified. However, this chapter focuses on the evaluation and treatment of several of the more common secondary causes of hypertension that may be encountered in a general medical or cardiology outpatient practice (Table 13.1). Clinicians should be aware that the credentialed discipline of a Hypertension Specialist now exists and not delay in referring patients to such expert care as required.