Maria Czarina Acelajado

REFRACTORY HYPERTENSION: DEFINITION, PREVALENCE AND PATIENT CHARACTERISTICS

J Clin Hypertens (Greenwich).

REFRACTORY HYPERTENSION: EVIDENCE OF HEIGHTENED SYMPATHETIC ACTIVITY AS A CAUSE OF ANTIHYPERTENSIVE TREATMENT FAILURE

Refractory hypertension is an extreme phenotype of treatment failure defined as uncontrolled blood pressure in spite of ≥5 classes of antihypertensive agents, including chlorthalidone and a mineralocorticoid receptor antagonist. A prospective evaluation of possible mechanisms of refractory hypertension has not been done. The goal of this study was to test for evidence of heightened sympathetic tone as indicated by 24-hour urinary normetanephrine levels, clinic and ambulatory heart rate (HR), HR variability, arterial stiffness as indexed by pulse wave velocity, and systemic vascular resistance compared with patients with controlled resistant hypertension. Forty-four consecutive patients, 15 with refractory and 29 with controlled resistant hypertension, were evaluated prospectively. Refractory hypertensive patients were younger (48±13.3 versus 56.5±14.1 years; P=0.038) and more likely women (80.0 versus 51.9%; P=0.047) compared with patients with controlled resistant hypertension. They also had higher urinary normetanephrine levels (464.4±250.2 versus 309.8±147.6 µg per 24 hours; P=0.03), higher clinic HR (77.8±7.7 versus 68.8±7.6 bpm; P=0.001) and 24-hour ambulatory HR (77.8±7.7 versus 68.8±7.6; P=0.0018), higher pulse wave velocity (11.8±2.2 versus 9.4±1.5 m/s; P=0.009), reduced HR variability (4.48 versus 6.11; P=0.03), and higher systemic vascular resistance (3795±1753 versus 2382±349 dyne·s·cm5·m2; P=0.008). These findings are consistent with heightened sympathetic tone being a major contributor to antihypertensive treatment failure and highlight the need for effective sympatholytic therapies in patients with refractory hypertension.Refractory hypertension is an extreme phenotype of treatment failure defined as uncontrolled blood pressure in spite of ≥5 classes of antihypertensive agents, including chlorthalidone and a mineralocorticoid receptor antagonist. A prospective evaluation of possible mechanisms of refractory hypertension has not been done. The goal of this study was to test for evidence of heightened sympathetic tone as indicated by 24-hour urinary normetanephrine levels, clinic and ambulatory heart rate (HR), HR variability, arterial stiffness as indexed by pulse wave velocity, and systemic vascular resistance compared with patients with controlled resistant hypertension. Forty-four consecutive patients, 15 with refractory and 29 with controlled resistant hypertension, were evaluated prospectively. Refractory hypertensive patients were younger (48±13.3 versus 56.5±14.1 years; P =0.038) and more likely women (80.0 versus 51.9%; P =0.047) compared with patients with controlled resistant hypertension. They also had higher urinary normetanephrine levels (464.4±250.2 versus 309.8±147.6 µg per 24 hours; P =0.03), higher clinic HR (77.8±7.7 versus 68.8±7.6 bpm; P =0.001) and 24-hour ambulatory HR (77.8±7.7 versus 68.8±7.6; P =0.0018), higher pulse wave velocity (11.8±2.2 versus 9.4±1.5 m/s; P =0.009), reduced HR variability (4.48 versus 6.11; P =0.03), and higher systemic vascular resistance (3795±1753 versus 2382±349 dyne·s·cm5·m2; P =0.008). These findings are consistent with heightened sympathetic tone being a major contributor to antihypertensive treatment failure and highlight the need for effective sympatholytic therapies in patients with refractory hypertension. # Novelty and Significance {#article-title-44}

Resistant Hypertension, Secondary Hypertension, and Hypertensive Crises: Diagnostic Evaluation and Treatment

Hypertension is a very common modifiable risk factor for cardiovascular morbidity and mortality. Patients with hypertension represent a diverse group. In addition to those with primary hypertension, there are patients whose hypertension is attributable to secondary causes, those with resistant hypertension, and patients who present with a hypertensive crisis. Secondary causes of hypertension account for less than 10% of cases of elevated blood pressure (BP), and screening for these causes is warranted if clinically indicated. Patients with resistant hypertension, whose BP remains uncontrolled in spite of use of 3 or more antihypertensive agents, are at increased cardiovascular risk compared with the general hypertensive population. After potentially correctible causes of uncontrolled BP (pseudoresistance, secondary causes, and intake of interfering substances) are eliminated, patients with true resistant hypertension are managed by encouraging therapeutic lifestyle changes and optimizing the antihypertensive regimen, whereby the clinician ensures that the medications are prescribed at optimal doses using drugs with complementary mechanisms of action, while adding an appropriate diuretic if there are no contraindications. Mineralocorticoid receptor antagonists are formidable add-on agents to the antihypertensive regimen, usually as a fourth drug, and are effective in reducing BP even in patients without biochemical evidence of aldosterone excess. In the setting of a hypertensive crisis, the BP has to be reduced within hours in the case of a hypertensive emergency (elevated BP with evidence of target organ damage) using parenteral agents, and within a few days if there is hypertensive urgency, using oral antihypertensive agents.

Hypertension in the Elderly

Hypertension is an important risk factor for cardiovascular morbidity and mortality, particularly in the elderly. Blood pressure elevation in the elderly is due to structural and functional changes that occur with aging. Treatment of hypertension reduces the risk of stroke, heart failure, myocardial infarction, all-cause mortality, cognitive impairment, and dementia in elderly patients with hypertension. A healthy lifestyle helps hypertension management, with benefits extending beyond lowering of blood pressure. Several classes of antihypertensive drugs are effective in preventing cardiovascular events. Treatment decisions should be guided by the presence of compelling indications such as diabetes or heart failure and by the tolerability of individual drugs or drug combinations in individual patients. The concomitant intake of certain medications that counter the effects of antihypertensive drugs and the frequent occurrence of orthostatic hypotension complicate treatment in older patients and drive down blood pressure control rates.

Aldosteronism and Resistant Hypertension

Resistant hypertension (RHTN) is defined as blood pressure (BP) that remains uncontrolled in spite of intake of ≥3 antihypertensive medications, ideally prescribed at optimal doses and one of which is a diuretic. The incidence of primary aldosteronism (PA) in patients with RHTN is estimated in prospective studies to be 14 to 23%, which is higher than in the general hypertensive population. Patients with PA are at an increased cardiovascular risk, as shown by higher rates of stroke, myocardial infarction, and arrhythmias compared to hypertensive individuals without PA. Likewise, RHTN is associated with adverse cardiovascular outcomes, and the contribution of PA to this increased risk is undetermined. Similar to PA, obstructive sleep apnea (OSA) is closely associated with RHTN, and a causal link between PA, OSA, and RHTN remains to be elucidated. The addition of MR antagonists to the antihypertensive regimen in patients with RHTN produces a profound BP-lowering effect, and this effect is seen in patients with or without biochemical evidence of PA, highlighting the role of relative aldosterone excess in driving treatment resistance in this group of patients.

Salt and aldosterone: A concert of bad effects

A very large number of experimental and human studies independently link high dietary salt intake and aldosterone excess to the development and progression of end-organ damage. Observational and dietary interventional studies clearly establish high diet salt intake as an important contributor to the development of hypertension, cardiac hypertrophy, and proteinuria. Likewise, observational data and studies of aldosterone blockade demonstrate that hyperaldosteronism significantly relates to level of blood pressure, intracardiac volumes, left ventricular mass, and urinary protein excretion. As such, these studies establish both high dietary salt intake and excess aldosterone to be important and independent mediators of cardiovascular risk.1,2 It is interesting, however, that animal models of hyperaldosteronism have consistently demonstrated that the unfavorable target-organ effects of aldosterone are in fact dependent on the concomitant dietary sodium intake. Beginning with landmark studies by Brilla and Weber,3 it has been repeatedly demonstrated that the proinflammatory and profibrotic effects of excess aldosterone induced in end organs, including the heart, vasculature, and kidney, do not manifest unless the dietary salt intake is also excessive.4,5 That is, the deleterious tissue effects of aldosterone could be largely avoided by maintaining the rats on a low-salt diet. Until recently, such an interaction between sodium and aldosterone in humans, while anticipated, had not been clearly observed. Now, however, a growing body of data, including the article by du Cailar et al6 in this edition of Hypertension , demonstrates that the blood …

Resistant hypertension: who and how to evaluate.

Purpose of review Resistant hypertension is found in an important and rapidly growing subset of the hypertensive population, and data characterizing this group of patients are limited. The purpose of this review is to present the latest evidence on resistant hypertension, its risk factors, patient characteristics, and approach to diagnosis. We focus on important associations between resistant hypertension and primary aldosteronism and with obstructive sleep apnea. Recent findings Resistant hypertension comprises 20–35% of the general hypertensive population. It is important to ascertain that a patient has true resistant hypertension and not merely uncontrolled hypertension. Twenty-four-hour ambulatory blood pressure monitoring can reliably rule out a white-coat effect and may have prognostic significance in patients with resistant hypertension. Patients should be screened for secondary causes of hypertension. Primary aldosteronism is common among patients with resistant hypertension, as is obstructive sleep apnea. A plasma aldosterone to renin ratio is a useful screening tool for primary aldosteronism. Aldosterone has been found to accelerate the increase in left ventricular mass in patients with hypertension. Summary Patients with resistant hypertension comprise a unique subset, with risk factors and associations that are distinct or pronounced compared with the general hypertensive population. It is important to bear these associations in mind when dealing with patients with true resistant hypertension.

Reduction of blood pressure in patients with treatment-resistant hypertension

Background: Resistant hypertension is a common clinical problem, and patients with resistant hypertension have increased cardiovascular risk. It is a subset of the hypertensive population that is little studied and poorly characterized. Objective: The purpose of this review is to discuss resistant hypertension, its recognition and diagnostic workup and management, and to present current data about the disease from the latest research. Methods: We define resistant hypertension and differentiate it from pseudoresistance. We identify diagnostic tests that may be done on patients with resistant hypertension. Last, we discuss therapeutic approaches to resistant hypertension, focusing on pharmacological treatment, and present an algorithm that may be used by the clinician in treating a patient with resistant hypertension. Conclusion: Resistant hypertension is a significant clinical problem commonly encountered by clinicians. Patients with resistant hypertension have increased cardiovascular risk. In evaluating for resistant hypertension, it is important to recognize elements that contribute to pseudoresistance to treatment. Secondary causes of hypertension are common in patients with resistant hypertension and should be included in the diagnostic workup. Pharmacological treatment for resistant hypertension entails choosing medications with complementary mechanisms of action, optimizing diuretic use, and considering the use of mineralocorticoid antagonists as an add-on agent to the antihypertensive regimen.

Antiplatelet Therapy for Transient Ischemic Attack

J Clin Hypertens (Greenwich).****;**:**–**. ©2011 Wiley Periodicals, Inc.

Optimal management of hypertension in elderly patients

Hypertension is a common and important modifiable risk factor for cardiovascular and kidney diseases. The prevalence of hypertension, particularly isolated systolic hypertension, increases with advancing age, and this is partly due to the age-related changes in the arterial tree, leading to an increase in arterial stiffness. Therapeutic lifestyle changes, such as reduced dietary sodium intake, weight loss, regular aerobic activity, and moderation of alcohol consumption, have been shown to benefit elderly patients with hypertension. Lowering blood pressure (BP) using pharmacological agents reduces the risk for cardiovascular morbidity and mortality, with no difference in risk reduction in elderly patients compared to younger hypertensives. Guidelines recommend a BP goal of <140/90 in hypertensive patients regardless of age and <130/80 in patients with concomitant diabetes or kidney disease, and lowering the BP further has not been shown to confer any additional benefit. Moreover, the choice of antihypertensive does not seem to be as important as the degree of BP lowering. Special considerations in the treatment of elderly hypertensive patients include cognitive impairment, dementia, orthostatic hypotension, and polypharmacy.