Resistant Hypertension Workup and Approach to Treatment

Resistant Hypertension Workup and Approach to Treatment Anastasios Makris, Maria Seferou, and Dimitris P. Papadopoulos European Excellent Center of Hypertension, Laiko University Hospital, 24 Agiou Ioannou Theologou Street, 155-61 Athens, Greece Received 30 September 2010; Accepted 18 November 2010 Academic Editor: Konstantinos Tsioufis Copyright © 2011 Anastasios Makris et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Resistant hypertension is defined as blood pressure above the patient's goal despite the use of 3 or more antihypertensive agents from different classes at optimal doses, one of which should ideally be a diuretic. Evaluation of patients with resistive hypertension should first confirm that they have true resistant hypertension by ruling out or correcting factors associated with pseudoresistance such as white coat hypertension, suboptimal blood pressure measurement technique, poor adherence to prescribed medication, suboptimal dosing of antihypertensive agents or inappropriate combinations, the white coat effect, and clinical inertia. Management includes lifestyle and dietary modification, elimination of medications contributing to resistance, and evaluation of potential secondary causes of hypertension. Pharmacological treatment should be tailored to the patient's profile and focus on the causative pathway of resistance. Patients with uncontrolled hypertension despite receiving an optimal therapy are candidates for newer interventional therapies such as carotid baroreceptor stimulation and renal denervation. 1. Introduction Hypertension is the most common chronic disease in the developed world affecting up to 25% of the adult population [1]. It remains the most important modifiable risk factor for coronary heart disease, stroke, congestive heart failure, renal disease, and peripheral vascular disease. Suboptimal blood pressure control is responsible for 62% of cerebrovascular disease, 49% of ischemic heart disease, and an estimated 7.1 million deaths a year [2]. Because of the associated morbidity, mortality and economic cost to society early diagnosis and treatment within the established guidelines is imperative. A sizeable percentage of the hypertensive population does not manage to achieve adequate control in spite of receiving 3 or more antihypertensive medications. These are the patients with resistant hypertension. Resistant hypertension is defined by the Joint National Committee 7 as blood pressure that is above the patient’s goal despite the use of 3 or more antihypertensive agents from different classes at optimal doses, one of which should ideally be a diuretic [3]. Patients whose blood pressure is controlled but require 4 or more medications to do so should also be considered resistant to treatment. However, the definition does not include newly diagnosed hypertensives. Resistant hypertension is not synonymous with uncontrolled hypertension. The latter includes both patients with inadequately treated blood pressure due to poor adherence or inadequate treatment, as well as those with true resistant hypertension [3, 4]. The importance of resistant hypertension lies in the identification of patients who are at high risk of suffering complications from reversible causes of hypertension and patients who may benefit from a particular diagnostic or therapeutic approach [3]. The exact prevalence of resistant hypertension is unknown, in part because of its arbitrary definition. However, small studies estimate prevalence from 5% in general medical practice up to 50% in nephrology clinics [5]. In a prospective analysis of Framingham study data, a higher baseline systolic blood pressure along with older age, the presence of LVH and obesity (BMI > 30 kg/m2) were the strongest predictors of lack of blood pressure control [6, 7]. Results were similar in ALLHAT where the older, obese patients with higher baseline systolic blood pressure and LVH required 2 or more antihypertensive agents [8]. The strongest predictor however was serum creatinine over 1.5 mg/dL. Other patient characteristics associated with resistant hypertension include excessive salt ingestion, diabetes, black race, and female gender. Both studies showed greater difficulty in controlling systolic blood pressure compared to diastolic. Up to 92% of patients achieved target diastolic blood pressure while only 60%–67% achieved systolic blood pressure goals [6, 8]. It is likely that this condition will become increasingly common because of the aging population and a progressive increase in obesity and comorbidities such as diabetes. There are also a few studies implicating gene mutations. A Finnish study found that certain variants of the β and γ subunits of the epithelial sodium channel gene ENaC were significantly more prevalent in patients with (...truncated)