Hypertensive Woman With Labile Blood Pressure

At a routine blood pressure check, a 63-year-old woman has 2 readings of 165/100 mm Hg. The patient has had essential hypertension since age 41 years. For more than a decade, it was easily controlled with a β-blocker; however, in recent years, her blood pressure has been more variable, with occasional readings of higher than 150/90 mm Hg.

Two years ago, a diuretic was added to her regimen, and last year a calcium channel blocker was added. She has regularly kept her office appointments and states that she has been compliant with her antihypertensive regimen. However, she frequently comments on the number of medications she has to take and their cost.

HISTORY

The patient does not have diabetes or coronary artery disease. She drinks alcohol socially and has smoked 1 pack of cigarettes daily for 30 years. She has tried to stop smoking but with limited success.

PHYSICAL EXAMINATION

This slightly overweight woman has normal vital signs, except for her blood pressure. There are no carotid bruits. An S₄ gallop is audible, but there are no murmurs. Her abdomen is without bruits, tenderness, or masses. Trace pedal edema is evident.

LABORATORY AND IMAGING STUDIES

Hemogram is normal. A biochemistry profile reveals a random blood glucose level of 98 mg/dL, a creatinine level of 1.4 mg/dL, and a blood urea nitrogen level of 19 mg/dL. Electrolyte levels are normal. Her nonfasting total cholesterol level is 219 mg/dL, with a high-density lipoprotein cholesterol level of 42 mg/dL. A chest radiograph is normal. An ECG reveals mild left ventricular hypertrophy with no acute injury currents or Q waves.

Which of the following is least likely to be responsible for this patient's difficulty with blood pressure control?

A. Her adherence to her antihypertensive regimen.
B. Exogenous dietary and lifestyle factors, such as salt intake and alcohol intake.
C. The persistence of her smoking habit.
D. An underlying condition that is causing secondary hypertension.

CORRECT ANSWER: C

In the most recent cohort of the National Health and Nutrition Examination Surveys (1999-2000), rates of control of hypertension were significantly lower in women, Mexican Americans, and patients 60 years or older.^1-3 This patient's blood pressure had been well controlled until recent months. It now exceeds 140/90 mm Hg, even though her current regimen includes 3 antihypertensive agents (although the dosages are not given and may not be optimal). She vigorously avers that she adheres to her medication regimen; thus, she meets the criteria for resistant or refractory hypertension.³ A number of possible causes need to be considered in the evaluation of such patients.

Accuracy of blood pressure readings. First, blood pressure measurements must be technically accurate and obtained in an appropriate clinical setting. Use a properly fitting cuff and allow the patient ample relaxation time in the office. Drinking regular coffee or smoking a cigarette within 30 minutes of the reading can transiently raise systolic blood pressure from 1 to 20 mm Hg. However, chronic use of cigarettes or coffee does not cause sustained hypertension.⁴ Thus, assuming the patient's readings were obtained 30 minutes or more after her last cigarette, her continued smoking (choice C) is not the cause of her elevated blood pressure.

Problems with adherence. Poor adherence to an antihypertensive regimen is a very frequent cause of "refractory" hypertension (perhaps more than 50% of cases). This patient insists that she is adherent, but there are hints in the history—her comments regarding the number and cost of her medications—that suggest otherwise. Thus, choice A is a possible cause of her resistant hypertension. Nonadherence is always difficult to diagnose. Having the patient bring her medicines to the office (so that prescription dates and pill counts can be checked) and monitoring for the effects of medications (eg, heart rate, urinary frequency) can be helpful.

Exogenous factors. Interfering factors (choice B) are more often a problem in the current era of polypharmacy than they were years ago. Certain medications (eg, sympathomimetics, corticosteroids, appetite suppressants) can all cause previously well-controlled hypertension to become refractory. Excessive alcohol consumption (more than 3 or 4 drinks a day) and high dietary salt intake can also result in resistance. None of these factors is an obvious culprit here, based on the initial history taking, but such factors are often not volunteered, either because of lack of awareness (eg, of the effects of over-the-counter medications or appetite suppressants) or patient embarrassment (eg, about indiscretions in diet or alcohol consumption). Thus, such issues must be specifically investigated in patients with resistant hypertension.

When to suspect secondary hypertension. Finally, the possibility of secondary hypertension (choice D)—a routine diagnostic inquiry in many patients with hypertension in decades past—is still an appropriate avenue of investigation in patients with refractory hypertension. One study found secondary causes in 10% of patients with resistant hypertension overall and in 17% of those older than 60 years.⁵ Renal disease, hyperaldosteronism, renovascular hypertension, and pheochromocytoma are possibilities that can be tested for in appropriate situations. (This woman's stable, normal creatinine level at least rules out the first of these.)

Thus, all choices except C (the correct answer) are possible causes of this patient's resistant hypertension.

Outcome of this case. Detailed history taking about exogenous factors and adherence was nonrevealing. Dosages of all 3 antihypertensives were maximized, but blood pressure control remained tenuous. Magnetic resonance angiography and angiotensin-converting enzyme inhibitor renography revealed a disparity in renal size and function, with a physiologically significant renal artery stenosis on the right. Angioplasty with stenting was scheduled.