Improved Blood Pressure Control in the Hands of the Hypertension Specialist: Method, Magic, or Something in Between?

In this issue of the Journal, Denker and colleagues provide details about their successful approach to the management of patients referred to a hypertension specialist at the University of Pennsylvania Hypertension Program (“Blood Pressure Control One Year After Referral to a Hypertension Specialist”).1 In essence, they were able to achieve an average blood pressure (BP) reduction of 20 mm Hg systolic BP and 8 mm Hg diastolic BP by following a treatment pathway based on pathophysiologic profiling. Using measurements of renin and aldosterone, patients were characterized into 1 of 4 categories: normal renin‐aldosterone profile, high renin profile, salt‐sensitive, or hyperaldosteronism. Pharmacotherapy choices were made that were intended to address the specific pathophysiologic derangement identified, such that, for instance, “salt‐sensitive” patients would preferentially receive enhancement of diuretics.

Overall, almost 90% of patients had better BP control using their approach, with the exception of patients identified as having high renin. At the same time, better BP control did not require more medication, but instead seemed to be associated with better chosen medication, since the average number of medications necessary to achieve the improved levels of BP control was unchanged from baseline. Do results like those reported by Denker and colleagues corroborate the essential value of including the expertise of hypertension specialists in hypertension management, implying that hypertension specialists simply “do it better”? Can aspirations of the hypertension specialist to be seen as a Statue of Liberty–like figure with a beacon of light shining upon those beleaguered by hypertension suggesting, along the lines of Emma Lazarus poem “…send us your weak, your tired, your hypertensive, and we will fix them…” be bolstered by sanguine outcomes such as these? We health professionals designated as Hypertension Specialists would all like to think that a justification for the existence of Specialists in Hypertension is that we possess special knowledge, skills, or insights that can lead to better identification, treatment, and control of hypertension than provided by nonspecialists in hypertension. Proving that specialized knowledge leads to improved outcomes, however, is often a difficult task. While we have every reason to celebrate the success seen in the hypertensive population retrospectively reviewed by Denker and colleagues, and congratulate the authors on the application of their method to the benefit of their patients, much remains to be elucidated. Is the success demonstrated in this article the result of method, magic, or something in between?

A number of unknowns should give reason for pause before making simplistic assumptions about the successes reported by Denker and colleagues. First, at the point of initial consultation with a hypertension specialist, the status of the patients was not clear, other than that all were hypertensive. For instance, it is not even clearly defined whether all the patients had resistant hypertension at the initial referral. The fact that patients were referred to the Hypertension Program implies difficult to control hypertension, but perhaps some patients were referred to a center of excellence simply because of the preference of the provider: might a psychiatrist, OB‐GYN, or orthopedic physician refer to a hypertension specialist simply because they feel it is beyond the boundaries of their specialty, or that they are “out of their league” when BP management becomes at all complicated? If a substantial number of patients in Denker's study group were referred by clinicians who simply defer to experts by default, then it is not at all difficult to anticipate excellent results.

All patients in this trial were given advice about diet, exercise, salt intake, alcohol moderation, and weight management. How can we know whether such advice had been given prior and, if so, had it been given effectively or at a point in the Stages of Change progression where patients might effectively employ such advice? For the sake of discussion, what if the advice of the University of Pennsylvania Hypertension Program about lifestyle change is the best and most effective imaginable, and patients referred to this site make important lifestyle changes they did not make in the hands of the referring provider? Could that not account, in large part, for similar reductions in BP?

It is also not stated whether white‐coat hypertensive patients were either identified or de‐selected from the study population. The most recent United Kingdom recommendations on hypertension (National Institute for Health and Care Excellence) suggest that ambulatory BP monitoring (ABPM) is indicated prior to initiating hypertension treatment, recognizing that as many as 30% of patients initially designated as hypertensive do not, on ABPM, have that impression confirmed. How do we know the proportion of patients referred to the University of Pennsylvania's Hypertension Program who had underlying white‐coat hypertension, whose BP might have spontaneously regressed to normotension?

Resistant hypertension (r‐HTN), according to current definitions, exists when a patient has not reached goal BP despite utilization of 3 drugs, at least one of which is a diuretic and each of which is used at appropriate doses2 That Denker colleagues ultimately found about 10% of patients to be “refractory” is consistent with other reports in the Journal; for instance, Acelajado colleagues reviewed data on more than 300 patients referred for r‐HTN, of which 9.5% remained refractory at 6‐month follow‐up.3 In contrast to the findings of Denker and associates, however, plasma renin activity and aldosterone levels were not associated with refractory hypertension in the population studied by Acelajado and colleagues.

The mechanistic algorithm approach to treating hypertension—resistant or not—is not new. Mann and colleagues used a simple two‐channel pathway to classify r‐HTN patients as belonging to “volume excess” or “neurogenic” categories, diuretic optimization being selected for the former, and α‐ and/or β‐blockade utilized for the latter.4 They, too, achieved an almost 90% success rate.

Yet, there remains doubt that taking sophisticated steps to discriminate putative underlying pathophysiology—and making the additional investment in dollars or laboratory investigation—is really necessary. In a world where hypertension is consistently in the top 10 diagnostic categories for which patients see primary care clinicians, there is something to be said in support of simplicity and cost‐consciousness. For instance, in a recently published trial of patients with r‐HTN, simply adding 25 mg/d to 50 mg/d of spironolactone, regardless of underlying pathophysiology, provided a remarkably similar net mean reduction of BP: 26.0/10.7 mm Hg.5 Despite the intellectual appeal of identifying r‐HTN patients whose underlying pathologic derangement is related to aldosterone excess, the success of aldosterone blockade in r‐HTN may even be independent of aldosterone status.6 In a trial of 76 r‐HTN patients treated with spironolactone 12.5 mg/d to 50 mg/d, 6 months of treatment reduced BP by 25/12 mm Hg, a number surprisingly similar to that reported by Denker and coworkers. Aldosterone status in this trial did not affect spironolactone efficacy.

Hypertension specialists will, hopefully, continue to be viewed as important contributors to the well‐being of patients with hypertension. Our nonspecialist colleagues do rely on us to problem‐solve for them for a variety of reasons, not the least of which is the repeatedly demonstrated successful BP control attainment seen in referral populations to hypertension specialty clinics. The results reported by Denker and colleagues are gratifying and corroborate the functionality of incorporating hypertension specialists in the management of difficult to treat hypertension. Characterization of putative underlying pathophysiology as a method of choosing antihypertensive treatment has been demonstrated to be effective in their hands. In the absence of a large, prospective randomized controlled trial to compare methodologies, one cannot say with certainty whether pathophysiologically determined hypertension treatment choices are superior to, the same as, or even less effective than unsophisticated rational use of agents such as aldosterone antagonists (barring appropriate contraindications). So, whether the success of Denker and colleagues is due to method, magic, or everything in between remains to be determined. Clinicians who find their methods appealing are certainly justified to consider employing them.