Taking Aim at Resistant Hypertension

Drug trials, noninvasive tests part of treatment effort

By George Thomas, MD

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Hypertension is a leading cause of increased cardiovascular morbidity and mortality. Although hypertension control has improved during the past two decades, population-based studies indicate that it remains suboptimal despite the availability of a variety of anti-hypertensive medications.

Resistant hypertension is defined in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) as the failure to reach goal blood pressure (BP) in patients who are adhering to maximally tolerated doses of an appropriate three-drug regimen that includes a diuretic. The use of four or more anti-hypertensive medications, irrespective of BP level, is also considered by the American Heart Association to constitute resistant hypertension.

Morbidity, Mortality Risks

While the actual prevalence of resistant hypertension is unclear, epidemiologic analyses and clinical trials suggest that it is not uncommon, involving at least 15 to 20 percent of hypertensives. Likewise, the prognosis of resistant hypertension is unknown, but long-standing severe hypertension associated with other risk factors portends higher cardiovascular morbidity and mortality. JNC 7 recommends consultation with a hypertension specialist if goal BP cannot be achieved.

A hypertension specialist is certified by the American Society of Hypertension (ASH). The certification recognizes physicians with expert skills and knowledge in the management of clinical hypertension and related disorders. These physicians are identified as consultants for complex and difficult cases, and also can advise regarding guidelines and process improvement.

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Resistant Hypertension Clinic

The Department of Nephrology and Hypertension within Cleveland Clinic’s Glickman Urological & Kidney Institute has a rich history of innovation and research in hypertension.  The Resistant Hypertension Clinic has been established to provide specific expertise in this area and will be staffed by ASH-certified hypertension specialists, with a dedicated hypertension lab that contains space and equipment for evaluation and testing. Besides the standardized use of automated blood pressure devices in our outpatient clinics, we employ 24-hour ambulatory blood pressure measurement in a large cohort of patients to help with diagnosis of white coat hypertension, masked hypertension, labile hypertension, nocturnal dipping, and to assess efficacy of therapy.

Noninvasive Tools

We also use noninvasive impedance cardiography to help guide treatment decisions and tailor therapy by assessing neuro-humoral profiles and hemodynamic parameters in our hypertension lab. Central blood pressures have been shown to correlate more strongly with vascular disease than do routine peripheral blood pressure measurements, and we assess central blood pressure indices using applanation tonometry, including measures of pulse wave velocity and augmentation index. We also have the capability to study endothelial function noninvasively, which could aid early detection of endothelial dysfunction for assessment of cardiovascular risk. The Department of Nephrology and Hypertension also has expertise in the field of secondary hypertension management, specifically related to the diagnosis and management of primary aldosteronism, pheochromocytoma and renal artery stenosis.

Clinical Trials Evaluate Interventions

Our department, in collaboration with Cleveland Clinic’s Sydell and Arnold Miller Family Heart & Vascular Institute, is participating in large clinical trials involving renal denervation for resistant hypertension, including SYMPLICITY HTN-3, the largest randomized clinical trial to date examining the effect of renal denervation. Hyperactivation of the sympathetic nervous system has a major role in the initiation, development and maintenance of hypertension. Renal denervation (Figure 1) is a potential nonpharmacologic treatment adjunct for resistant hypertension. The renal sympathetic nerves are accessed through the femoral artery, and a novel, catheter-based percutaneous ablation device deliversradio frequency energy to the luminal surface of the renalartery. Thermal energy is applied selectively to renal sympatheticnerves without affecting abdominal, pelvic or other lower extremity nerves.


Figure 1. In the renal denervation procedure, a specially designed catheter is positioned in the renal artery and radiofrequency energy is applied to the indoluminal surface.

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Prior studies conducted outside the United States (SYMPLICITY HTN-1 and SYMPLICITY HTN-2) have shown that patients undergoing selective renal denervation have substantial decreases in blood pressure. Small pilot studies conducted outside the U.S. also indicate that hypertensive patients with chronic kidney disease and other conditions such as sleep apnea, left ventricular hypertrophy and diabetes may also respond favorably to the procedure. The procedure currently is available in the U.S. only as part of clinical trials.

Our department also is involved in a large National Institutes of Health study (SPRINT) that is evaluating intensive blood pressure control vs. standard blood pressure control, and subsequent outcomes as far as cardiovascular events, chronic kidney disease and cognitive ability. Patients older than 50 with risk factors for cardiovascular disease or chronic kidney disease are randomized into one of the above groups, and blood pressure medication changes are made by the study team to attain blood pressure targets in each group, with follow-up to five years. The study has completed recruitment and is in the follow-up phase. Results will provide more insight into optimal blood pressure targets for patients.

Dr. Thomas is a staff physician in Cleveland Clinic Glickman Urological & Kidney Institute’s Department of Nephrology and Hypertension.