Management Of Resistant Hypertension Research Articles

Management of Resistant Hypertension

“Resistant” hypertension has been variously defined, but most authors accept a definition that includes a blood pressure ≥140/90 mm Hg after prescription of a diuretic and typically two other appropriately chosen antihypertensive drugs at near-maximal doses. Patients with resistant hypertension are of great public health importance because they have a high absolute cardiovascular and renal risk, greater health care expenditures, a higher prevalence of secondary hypertension and target-organ damage, and are, by definition, more “difficult to control” than hypertensive patients who are controlled with only one or two medications. Centers that specialize in these patients report that more than 90% can be diagnosed with a specific cause of their treatment resistance, and more than 50% can be controlled in a relatively short time after an appropriate intervention. This article reviews the differential diagnosis, evaluation, and outcomes of treatment paradigms for such patients, and emphasizes the role of hypertension specialists in their management.

Is It Ethical to Perform Irreversible Renal Denervation Before a Trial of Low Sodium Intake for Treatment-Resistant Hypertension?

To the Editor: Current guidelines emphasize the importance of identification and reversal of lifestyle factors in the management of resistant hypertension.1 This position is supported by evidence that dietary modification, particularly a decrease in salt intake, is effective not only in mild-to-moderate hypertension2 but also in resistant hypertension.3 A recent study in which renal sympathetic innervation was irreversibly disrupted by radiofrequency ablation is, therefore, of concern.4 We believe that, before heroic measures are taken to control resistant hypertension, it is appropriate not only to attempt dietary modification but also to provide assurance that …

Long-term effects of aldosterone blockade in resistant hypertension associated with chronic kidney disease

Hypertension is a major risk factor for the development and progression of chronic kidney disease (CKD). Mineralocorticoid receptor antagonists (MRAs) are effective in the management of resistant hypertension but are not widely used in CKD because of the risk of hyperkalemia. We retrospectively evaluated the long-term effects and safety of MRAs added to a pre-existing antihypertensive regimen in subjects with resistant hypertension associated with stage 3 CKD. In all, 32 patients were treated with spironolactone and 4 with eplerenone for a median follow-up of 312 days. MRAs induced a significant decrease in systolic blood pressure from 162±22 to 138±14 mm Hg (P<0.0001) and in diastolic blood pressure from 87±17 to 74±12 mm Hg (P<0.0001). Serum potassium increased from 4.0±0.5 to 4.4±0.5 mEq l(-1) (P=0.0001), with the highest value being 5.8 mEq l(-1). The serum creatinine increased from 1.5±0.3 to 1.8±0.5 mg dl(-1) (P=0.0004) and the estimated glomerular filtration rate decreased from 48.6±8.7 to 41.2±11.5 ml min(-1) per 1.73 m(2) (P=0.0002). One case of acute renal failure and three cases of significant hyperkalemia occurred. MRAs significantly reduced blood pressure in subjects with resistant hypertension associated with stage 3 CKD, although close biochemical monitoring is recommended because of an increased risk of hyperkalemia and worsening of renal function.

What is new in the management of resistant hypertension?

Resistant hypertension, generally defined as blood pressure that remains above goal in spite of the use of three antihypertensive medications prescribed at optimal dose amounts, is an increasingly common medical problem, and patients with this condition are at high risk of cardiovascular events. Recent studies have shown that new technologies, such as carotid stimulation and renal denervation, and more established approaches, such as low dietary salt and mineralocorticoid receptor blockers, effectively reduce blood pressure in patients with resistant hypertension. In this article, we discuss the background, safety and effectiveness of these and other treatment approaches.

Papel de la MAPA en el manejo de la hipertensión arterial resistente

Hypertension is considered to be resistant when blood pressure goals (<140/90 mmHg in general, <130/80 mmHg in hypertensive patients with diabetes or renal disease) are not achieved by means of a triple-drug combination including a diuretic at full doses. In this situation, lack of therapeutic adherence, and causes of secondary hypertension must be excluded. The importance of ambulatory blood pressure monitoring (ABPM) in the management of resistant hypertension can be summarized in three points: a) ABPM-confirmation of true resistant hypertension allows false (“white-coat”) resistant hypertension (25–30% of cases with apparent resistant hypertension) to be excluded and consequently these patients do not required new antihypertensive agents to be added or complex complementary investigations to exclude secondary hypertension; b) as in other types of hypertension, the prognosis of patients with resistant hypertension is closely related to ambulatory blood pressure levels, as confirmed by several prospective studies, and c) a non-dipper pattern of nocturnal blood pressure confers a worse outcome profile.

Efficacy of Spironolactone Therapy in Patients With True Resistant Hypertension

The role of spironolactone in resistant hypertension management is unclear. The aim of this prospective trial was to evaluate the antihypertensive effect of spironolactone in patients with true resistant hypertension diagnosed by ambulatory blood pressure monitoring. A total of 175 patients had clinical and complementary exams obtained at baseline and received spironolactone in doses of 25 to 100 mg/d. A second ambulatory blood pressure monitoring was performed after a median interval of 7 months. Paired Student t test was used to assess differences in blood pressure before and during spironolactone administration, and multivariate analysis adjusted for age, sex, and number of antihypertensive drugs to assess the predictors of blood pressure fall. There were mean reductions of 16 and 9 mm Hg, respectively, in 24-hour systolic and diastolic blood pressures (95% CIs: 13 to 18 and 7 to 10 mm Hg; P<0.001). Office systolic blood pressure and diastolic blood pressure also decreased (14 and 7 mm Hg). Controlled ambulatory blood pressure was reached in 48% of patients. Factors associated with better response were higher waist circumference, lower aortic pulse wave velocity, and lower serum potassium. No association with plasma aldosterone or aldosterone:renin ratio was found. Adverse effects were observed in 13 patients (7.4%). A third ambulatory blood pressure monitoring performed in 78 patients after a median of 15 months confirmed the persistence of the spironolactone effect. In conclusion, spironolactone administration to true resistant hypertensive patients is safe and effective in decreasing blood pressure, especially in those with abdominal obesity and lower arterial stiffness. Its addition to an antihypertensive regimen as the fourth or fifth drug is recommended.

Resistant Hypertension: Identifying Causes and Optimizing Treatment Regimens

Management of resistant hypertension (RH), defined as uncontrolled blood pressure on three or more antihypertensive medications including a diuretic, begins initially with identifying and addressing contributors such as medication adherence, lifestyle factors and the use of interfering substances. Evaluation for the "white-coat" phenomenon, or associated conditions and secondary causes such as sleep apnea, primary aldosteronism, chronic kidney disease or renovascular disease may be indicated. Inadequate dosing, lack of using long-acting diuretics, and suboptimal combinations are observed as causes in nearly half of patients with RH. Appropriate pharmacotherapy of RH begins first with insuring the patient is receiving appropriate therapy for compelling indications, as outlined by the JNC-7 guidelines. Specific regimen enhancements to achieve blood pressure control include the addition of aldosterone antagonists, dual renin-angiotensin system blockade, and dual calcium channel blockade. Addition of centrally acting agents, alpha blockers, or vasodilators may also be necessary.

Low-dose spironolactone in the management of resistant hypertension: a surveillance study

We have conducted an open observational study of the use of spironolactone 25-50 mg in the management of patients with resistant hypertension. This drug was recommended in 133 patients who were already receiving an angiotensin-blocking drug in addition to other therapies. Of these, three defaulted from follow-up and 11 could not tolerate spironolactone. We therefore have outcome data on 119 patients. The addition of spironolactone (median dose 25 mg) was associated with a mean (SD) fall in systolic blood pressure of 21.7 mmHg (24.0; P < 0.001) and diastolic blood pressure of 8.5 mmHg (14.9; P < 0.001). In two patients spironolactone had to be discontinued on account of a rise of serum potassium to above 6.0 mmol/l, whereas overall the mean increase in serum potassium was 0.3 mmol/l. With careful monitoring of plasma electrolytes, spironolactone at a low dose is an effective add-in drug in patients with hypertension resistant to a regime that includes an angiotensin-blocking agent.

Resistant Hypertension: Prevalence and Evolving Concepts

Resistant hypertension is a common medical disorder. Although the exact incidence of resistant hypertension is not established, estimates derived from recent outcome studies including the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), Valsartan Antihypertensive Long-term Use Evaluation (VALUE), and Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) emphasize that this condition may be more common than previously thought. A major advance in our understanding of the pathogenesis and management of resistant hypertension is the recognition of the importance of aldosterone. Several investigators have postulated a direct role of aldosterone excess as an important mechanism for drug resistance in hypertension. The mechanisms whereby aldosterone elevates BP are complex. It was previously thought that aldosterone produced hypertension primarily by promoting sodium retention with consequent hypervolemia. Recent studies of the effects of aldosterone on vascular smooth muscle have, however, delineated several extrarenal mechanisms whereby aldosterone produces hypertension-primarily by its direct vasoconstrictor effects and by altering vascular compliance. Consequently, aldosterone blockade constitutes an effective intervention for treating resistant hypertension.

The role of aldosterone antagonists in the management of resistant hypertension

Resistant hypertension is an increasingly common problem faced by primary care physicians and specialists and will undoubtedly become even more common as the adult population ages and gains weight. In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), at least 8% of subjects were resistant to treatment based on the need for three or more antihypertensive agents. Characteristics of patients with resistant hypertension include being older, black, obese, and diabetic, and having chronic kidney disease as well as untreated sleep apnea. Hyperaldosteronism is common in patients with resistant hypertension, with a prevalence of approximately 20%. This, however, is likely an underestimation of the role aldosterone excess plays in causing drug resistance. In subjects with resistant hypertension, suppressed renin levels are common, exceeding 75% in our studies, suggesting aldosterone excess effects beyond cases of true primary hyperaldosteronism. Recent studies indicate that aldosterone antagonists provide significant blood pressure reduction when added to antihypertensive regimens of patients with resistant hypertension. Interestingly, the blood pressure reduction with use of spironolactone is not limited to patients with hyperaldosteronism, consistent with the concept of aldosterone excess as a continuum from low-renin hypertension with normal aldosterone levels to true primary hyperaldosteronism.

HYPERTENSION

The current JNC-VI criteria for diagnosis and classification of hypertension are discussed. The laboratory evaluation of both essential and secondary hypertension is examined, and recommendations are made in this regard. Finally, the complications and treatment of essential hypertension and the causes and management of resistant hypertension are discussed.

Management of Resistant Hypertension in Patients with Carotid Stenosis: High Prevalence of Renovascular Hypertension

Introduction: Patients with carotid stenosis are at high risk of vascular events and therefore require an optimal control of risk factors such as hypertension. As the treatment of hypertension differs according to the cause, we examined the prevalence of resistant hypertension, and the cause of hypertension, among patients with carotid stenosis followed closely in two randomized trials of carotid endarterectomy. Objective: The purpose of this study was to determine the prevalence of resistant hypertension and of secondary hypertension among patients with carotid stenosis. Methods: A chart review was performed of all patients from our center who participated in the North American Symptomatic Carotid Endarterectomy Trial or the Asymptomatic Carotid Artery Study to determine the prevalence of renovascular hypertension. Results: Among 170 patients with carotid stenosis followed in these two trials, 145 (83.5%) were hypertensive (systolic >160 or diastolic >90 mm Hg); at least 24 (14.1% overall, 16.6% of hypertensives) had renovascular hypertension based on either nuclear medicine renography, renal angiography or both; among the 79 patients with resistant hypertension (mean arterial pressure >130 mm Hg despite treatment), 20 (25.3%) had renovascular hypertension. Adrenocortical hyperplasia was the underlying cause of hypertension in 12 (7.1% of cases, 8.3% of hypertensives, 8.8% of resistant hypertensives). Blood pressures were significantly higher for patients with renovascular and adrenocortical hypertension (p < 0.0001 for systolic, p = 0.024 for diastolic pressures). Conclusion: Among patients with carotid stenosis, renovascular hypertension is unusually common. Resistant hypertension among such patients should lead to investigation and management directed at the cause of hypertension. Appropriate investigations might include plasma renin/aldosterone ratio, captopril renography and MRA of the renal arteries or renal angiography.

The ‘Birmingham Hypertension Square’ for the optimum choice of add-in drugs in the management of resistant hypertension

The ‘Birmingham Hypertension Square’ for the optimum choice of add-in drugs in the management of resistant hypertension

Management of Resistant Hypertension

Management of Resistant Hypertension

Resistant Hypertension: Diagnosis and Management

Fortunately, hypertension resistant to a good drug regimen is rare. When hypertension fails to respond to medical treatment there is usually another explanation, such as poor patient compliance, excessive salt ingestion, drug interactions, spuriously high office readings, or an unsuspected secondary cause for the hypertension. Management of resistant hypertension can be aided by identifying the hemodynamic and humoral mechanisms responsible for its resistance and redesigning the therapeutic regimens accordingly. When they become available, two investigational drugs, minoxidil and an oral converting enzyme inhibitor, both of which lower total peripheral resistance, will offer a new approach to controlling truly resistant hypertension.