Resistant hypertension is being increasingly recognized and discussed, not because of its escalating prevalence but because of improved diagnostic and treatment modalities. The term “resistant hypertension” is often applied casually and without proper criteria despite the reasonable definition provided in the last Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC) document.1 In this issue of The Journal of Clinical Hypertension, Acelajado and colleagues2 analyzed the prevalence and attributes of resistant hypertension in a referral hypertension clinic. While the authors provide some factors defining resistant hypertension, the data may not be applicable to the experiences in the community nonreferral primary care clinical practices. Nonetheless, the findings reported by Acelajado and colleagues have implications in the management of hypertension in the speciality clinics as well as in primary care practice. Despite careful clinical assessment, there remains a group of patients with hypertension who show refractoriness to maximum and intensive antihypertensive drug therapy.3–5 These patients do not “look” different nor do they have an up regulated renin-angiotensin-aldosterone system. In the study reported by Acelajado and colleagues, patients with resistant hypertension who responded to drug therapy (including an aldosterone antagonist) and those who did not respond to the same treatment had similar levels of aldosterone and plasma renin activity (PRA). This observation then suggests that obtaining aldosterone/PRA levels in patients with resistant hypertension (who do not have hypokalemia) is not helpful and is not a predictor of therapeutic response to specific classes of antihypertensive drugs. The authors use a new descriptive treatment—refractory resistant hypertension—to characterize resistant hypertension that remains unresponsive to aggressively titrated polypharmacy. So, the patients with resistant hypertension who achieve the treatment goal lose the term “resistant” in their diagnosis and those whose blood pressure remains uncontrolled gain the term “refractory” in their diagnosis. The terminology surely would attract the attention of hypertension guideline committees.
We noted some additional interesting observations in this report. Resting heart rate was high in patients with refractory resistant hypertension despite the concomitant use of β-blockade indicating persistent stimulation of sympathetic nervous system. It is worth speculating, therefore, that such patients may be appropriate candidates for the emerging novel invasive sympatholytic therapies: renal denervation6,7 and carotid baroceptor activation.8–10 A substantial number (50%) of patients with controlled resistant hypertension who had obstructive sleep apnea (OSA) achieved the treatment goals with antihypertensive therapy. It is not clear whether these patients were also on oxygen therapy with continuous positive airway pressure (CPAP); indeed, if they were not on CPAP therapy, it appears likely that aggressively applied antihypertensive therapy is effective in patients with OSA irrespective of their oxygenation status! The authors suggest that approximately 10% of patients treated vigorously in a specialty clinic have refractory resistant hypertension. This prevalence may not be accurate in the routine (nonreferral) clinical settings where an overwhelming number of patients are evaluated and treated generally under hurried and busy circumstances. In the authors’ clinic, the blood pressure was measured in “both arms” by “two hypertension specialists” 5 minutes apart in the well-rested, seated patients with the arm properly supported. It is guaranteed that such a scenario does not exist in the busy practitioners’ clinics. Hence, we will never know the true prevalence and persistence of resistant or refractory resistant hypertension in the real world. Of note, the prevalence of chronic kidney disease was similar in the refractory and controlled groups. A conclusion here is that chronic kidney disease does not explain “refractory” resistant hypertension. Should we reserve the diagnosis of refractory resistant hypertension for patients requiring 5 to 8 antihypertensive drugs? Future research efforts should be directed to investigate the possible pathophysiologic mechanism(s) underlying refractory resistant hypertension so that rationally tailored treatment modalities can be utilized to reduce the chronic disease burden in patients with uncontrolled systemic hypertension.