Resistant hypertension: Diagnostic strategies and management
ABSTRACTBlood pressure that remains above target levels despite drug therapy is an increasingly common problem. The evaluation of resistant hypertension includes confirming blood pressure measurements with an automated device that works without the clinician present and with 24-hour ambulatory monitoring; assessing for target-organ damage; and determining if kidney disease is present or if the hypertension is secondary to another condition. The goal of management should be to optimize drug therapy by using different classes of appropriate drugs.
KEY POINTS
- Resistant hypertension is arbitrarily divided into two categories: apparent resistance (pseudoresistant hypertension) and true resistance. Apparent resistance is much more common.
- Common causes of true resistant hypertension are volume overload, excessive alcohol use, some drugs (eg, nonsteroidal anti-inflammatory drugs), and some over-the-counter supplements.
- Volume overload commonly results from excess sodium intake, kidney disease, or a counterregulatory response to arterial vasodilation.
- To address volume overload, an appropriate diuretic at an adequate dosage is a cornerstone of therapy, along with potassium supplementation.
- Hospitalization may be needed to monitor drug intake if poor compliance is suspected.
EXPERIMENTAL NONPHARMACOLOGIC THERAPIES
Electrical stimulation of carotid sinus baroreceptors is being tried under the assumption that a high sympathoexcitatory state contributes to resistant hypertension. Devices are placed around the carotid artery bifurcation, and stimulation is believed to increase the depressor influences that modulate blood pressure. Large-scale trials are under way, but it is too early to tell if the approach will be useful. Patients complain of neck pain from the device.
Renal denervation is another experimental approach.12 The kidney has a central role in blood pressure regulation: efferent nerves regulate renal vascular resistance, renal blood flow, and renin release from the juxtaglomerular apparatus; afferent nerves modulate sympathetic output from the central nervous system. The results of the Renal Denervation in Patients With Uncontrolled Hypertension (Symplicity HTN) trials 1 and 2 have been encouraging. The Symplicity HTN-3 trial will begin soon in the United States.
OUR PATIENT UNDERGOES ADDITIONAL STUDIES
To rule out the white-coat effect in our patient, we measured her blood pressure with an automated device that takes several readings without the clinician in the room. (This topic has been reviewed by Vidt et al in this journal13). The average of the automated readings was 183/113 mm Hg, and her average pulse was 109 beats per minute, arguing against a white-coat effect.
Her blood pressure was also markedly elevated (average 198/129) during 24-hour ambulatory blood pressure monitoring.
Findings on physical examination were unremarkable except for grade III hypertensive retinopathy. She had no carotid or abdominal bruits. Her peripheral pulses were strong and synchronous bilaterally.
Laboratory testing found the patient had normal serum electrolyte levels and good renal function but relatively low urinary sodium, 90 mmol/day (normal 40–220), and very low renin activity, 0.7 μg/L/h (normal up-right 0.8–5.8 μg/L/h, supine 0.5–1.8 μg/L/h), calling into question the wisdom of treatment with an angiotensin receptor blocker.
Hemodynamic studies were performed using impedance cardiography and found very high systemic vascular resistance with normal cardiac output, indicating that the patient had a high preload, which could be from hypervolemia or intense venous constriction. It is especially interesting that her vascular resistance was high despite her treatment regimen that included an angiotensin receptor blocker and a vasodilator, perhaps an indication of nonadherence with her medications.
Diuresis reduces her blood pressure
The patient was admitted to the hospital, and because her laboratory results indicated that plasma renin activity was suppressed, the angiotensin receptor blocker valsartan was discontinued.
On day 1, her weight was 162 lb and average blood pressure was 194/128 mm Hg. After 4 days of diuresis with escalating doses of furosemide, her weight was 153 lb and blood pressures ranged from 140 to 158 over 82 to 98 mm Hg. Her heart rate was 90 beats per minute. The hospital stay showed that volume overload was one of the factors maintaining her hypertension. She was discharged on metoprolol succinate (Toprol-XL) 100 mg twice daily and furosemide 80 mg twice daily.
Her blood pressure fluctuates widely after discharge
Over the next 5 days after discharge, the patient’s blood pressure rose steadily to 180/122 mm Hg, her heart rate was in excess of 100 beats per minute, and her weight increased to 158 lb. Blood screening found that the level of metoprolol was undetectable, and a diuretic screen showed no furosemide in the urine. Both the patient and her husband were adamant that she was taking her medications.
Hydrochlorothiazide 25 mg daily was added, and nadolol (Corgard) 80 mg once daily was started in place of metoprolol. On a return visit, her blood pressure and heart rate were finally good at 138/86 mm Hg and 60 beats per minute (sitting) and 134/92 and 63 (standing).
On 24-hour monitoring, some fluctuations of elevated blood pressure were still evident, with an average of 142/91 mm Hg, so nifedipine (Procardia) 60 mg daily was added.
Her final list of medications is hydrochlorothiazide 25 mg, nadolol 80 mg, and nifedipine XL 60 mg, all taken once daily.
Volume overload complicated by nonadherence
In summary, the main pathogenetic mechanism that sustained this patient’s hypertension was volume overload. Her urinary sodium level indicated that she was not taking excessive amounts of sodium. The volume overload may have been a compensatory response to the concomitant use of peripheral vasodilators plus sympatholytic agents.
In addition, she was not adherent to her antihypertensive regimen. The fact that her heart rate was 109 beats per minute despite having a drug regimen that included five sympathetic blocking agents was a strong clue. She eventually admitted that she did not like taking diuretics because they made her skin wrinkle.
In general, in a case like this, I try to minimize the number of drugs and give a diuretic as well as different classes of appropriate drugs.
