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  • Blood pressure above the recommended values (140/90 mm Hg) despite the use of greater than or equal to 3–4 antihypertensive agents, each belonging to a different class.
  • Insufficient treatment prescription and lack of adherence to prescribed drugs, dietary restrictions, and lifestyle recommendations are the most frequent causes.
  • Associated with obesity, sleep apnea, diabetes, chronic kidney disease, advanced age, high dietary salt intake, and black race.

As the 21st century unfolds, hypertension remains a challenging medical problem. Hypertension continues to be a common reason for office, urgent care center, and emergency room visits. If not properly controlled, hypertension can lead to blindness, renal failure, heart disease, and stroke. In spite of the establishment of extensive health action programs, blood pressure (BP) values remain above the recommended objectives in the majority of patients with hypertension. Data from the National Health and Nutrition Examination Survey 1999–2000 showed that in only 34% of all persons with hypertension in the United States was blood pressure controlled to meet recommended values. Similar data come from different countries.

Common factors associated with the development of resistant hypertension include obesity, sleep apnea, diabetes, chronic kidney disease, advanced age, high dietary salt intake, and black race. Interfering substances such as nonsteroidal anti-inflammatory drugs and excessive alcohol consumption can worsen blood pressure control. However, an insufficient treatment prescription and the lack of adherence to the prescribed drug and lifestyle recommendations (eg, the moderation of alcohol consumption, the restriction of salt intake, the reduction of body weight) seem to be the most frequent causes of uncontrolled BP. Other causes of resistance to treatment include cases of spurious hypertension, such as isolated office (white-coat) hypertension, and failure to use large cuffs on large arms. Nevertheless, a significant number of patients adequately diagnosed and treated still have uncontrolled BP. The real prevalence of refractory hypertension is difficult to determine. Published studies describe a prevalence that oscillates between 3% and 30% in hypertension units. Further, the existence of different diagnostic and therapeutic strategies makes a comparison between different published studies difficult.

This review focuses on those causes of resistance to treatment that can be evaluated in the outpatient setting. These include a search for nonadherence, assessing the adequacy of the treatment regimen, and ruling out drug interactions and associated conditions. In the absence of the above factors, assessment for secondary causes of hypertension is appropriate. This careful stepwise evaluation is not only cost effective, but also capable of identifying the contributing factors in the vast majority of patients with apparently resistant hypertension.

The recent joint directives of the European Society of Hypertension/European Society of Cardiology (ESH-ESC) define the treatment of refractory hypertension as a therapeutic plan that includes attention to lifestyle measures and the prescription of at least three drugs (including a diuretic); however, in adequate doses this has failed to lower systolic and diastolic BP sufficiently. Moreover, the VII Joint National Committee report further notes the exclusion of ...

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