Patients with uncontrolled hypertension or concomitant hypertension and benign prostatic hyperplasia

At optimal doses, individual antihypertensive agents lower blood pressure (BP) by an average of 10 mmHg. Many patients with hypertension, including those with stage 3 hypertension, target organ damage, or those at high risk for cardiovascular events and/or adverse effects of high-dose monotherapy, are likely to require combination antihypertensive drug treatment to achieve the recommended systolic/diastolic BP (< 140/90 mmHg). Two studies, a placebo-controlled, double-blind trial (n = 70) and a community-based, open-label trial (n = 491) investigated the antihypertensive efficacy of doxazosin, a long-acting selective alpha1-adrenoceptor blocker, as add-on therapy for uncontrolled hypertension with other antihypertensive medications and in patients with concomitant benign prostatic hyperplasia (BPH) and treated but inadequately controlled hypertension, respectively. The addition of doxazosin to baseline antihypertensive medication(s) significantly lowered BP and had a significantly positive effect on the serum lipid profile. In patients with concomitant BPH, doxazosin significantly improved all BPH symptom scores, regardless of initial symptom severity. Add-on doxazosin sufficiently reduced systolic/diastolic BP such that many patients whose hypertension was previously uncontrolled by other antihypertensive medications were able to reach goal BP (< 140/90 mmHg). Doxazosin as add-on therapy was well tolerated. In conclusion, doxazosin as add-on therapy improves BP control in hypertensive patients not at goal BP and improves lower urinary tract symptoms in patients with concomitant BPH.     

Improving blood pressure control and clinical outcomes through initial use of combination therapy in stage 2 hypertension

Poor control of clinic and 24-h blood pressure (BP) is associated with enhanced risk of all cardiovascular disease events. Certain patient groups including the elderly, African-Americans, and those with hypertension and comorbid disease are difficult to control, as are patients with stage 2 hypertension (systolic BP>or=160 mmHg or diastolic BP>or=100 mmHg). It has been estimated that more than two-thirds of high-risk hypertensive patients with stage 2 hypertension and all hypertensive patients with diabetes mellitus or kidney disease will require two or more antihypertensive agents from different therapeutic classes to reach BP goals. Combining agents with distinct and complementary modes of action can address different pathophysiologic mechanisms involved in hypertension and may lead to more complete and prompt reductions in BP. Tolerability may also improve, as certain classes of antihypertensive agents ameliorate adverse effects associated with other agents. Patients may benefit from fixed-dose combinations of drugs as this simplifies the regimen and may improve adherence with therapy, control of BP, and ultimately lead to reductions in cardiovascular events. Recent data and treatment guidelines support the use of a combination strategy as 'initial' antihypertensive therapy in high-risk patients with stage 2 hypertension.     

Exercise training in the management of patients with resistant hypertension

Hypertension is a very prevalent risk factor for cardiovascular disease. The prevalence of resistant hypertension, i.e., uncontrolled hypertension with 3 or more antihypertensive agents including 1 diuretic, is between 5% and 30% in the hypertensive population. The causes of resistant hypertension are multifactorial and include behavioral and biological factors, such as nonadherence to pharmacological treatment. All current treatment guidelines highlight the positive role of physical exercise as a non-pharmacological tool in the treatment of hypertension. This paper draws attention to the possible role of physical exercise as an adjunct non-pharmacological tool in the management of resistant hypertension. A few studies have investigated it, employing different methodologies, and taken together they have shown promising results. In summary, the available evidence suggests that aerobic physical exercise could be a valuable addition to the optimal pharmacological treatment of patients with resistant hypertension.     

Refractory hypertension: definition, prevalence, and patient characteristics

Among patients with resistant hypertension (RHTN), there are those whose blood pressure (BP) remains uncontrolled in spite of maximal medical therapy. This retrospective analysis aims to characterize these patients with refractory hypertension. Refractory hypertension was defined as BP that remained uncontrolled after ≥3 visits to a hypertension clinic within a minimum 6-month follow-up period. Of the 304 patients referred for RHTN, 29 (9.5%) remained refractory to treatment. Patients with refractory hypertension and those with controlled RHTN had similar aldosterone levels and plasma renin activity (PRA). Patients with refractory hypertension had higher baseline BP (175±23/97±15 mm Hg vs 158±25/89±15 mm Hg; P=.001/.005) and heart rate, and higher rates of prior stroke and congestive heart failure. During follow-up, the BP of patients with refractory hypertension remained uncontrolled (168.4±14.8/93.8±17.7 mm Hg) in spite of use of an average of 6 antihypertensive medications, while those of patients with controlled RHTN decreased to 129.3±11.2/77.6±10.8 mm Hg. Spironolactone reduced the BP by 12.9±17.8/6.6±13.7 mm Hg in patients with refractory hypertension and by 24.1±16.7/9.2±12.0 mm Hg in patients with controlled RHTN. In patients with RHTN, approximately 10% remain refractory to treatment. Similar aldosterone and PRA levels and a diminished response to spironolactone suggest that aldosterone excess does not explain the treatment failure.     

Mechanisms and treatment of resistant hypertension

Resistant hypertension is defined as blood pressure (BP) that remains uncontrolled in spite of the use of >/=3 antihypertensive medications. Stricter BP goals, higher obesity rates, older age, and increased use of exogenous BP-elevating substances are related to an increasing prevalence of resistant hypertension. The evaluation of patients with resistant hypertension is focused on identifying contributing and secondary causes of hypertension, including hyperaldosteronism, obstructive sleep apnea, chronic kidney disease, renal artery stenosis, and pheochromocytoma. Hyperaldosteronism is now recognized as the most common cause of resistant hypertension, and all patients with resistant hypertension should be screened with a plasma aldosterone/renin ratio even if the serum potassium level is normal. Treatment includes removal of contributing factors, appropriate management of secondary causes, and use of effective multidrug regimens. Recent studies indicate that the addition of spironolactone to standard treatment induces significant BP reduction in most patients with resistant hypertension.     

Systolic blood pressure is the main etiology for poorly controlled hypertension

BACKGROUND: Isolated systolic hypertension is an important risk factor for cardiovascular events. The purpose of this study was to detect the prevalence of and to evaluate the effectiveness of currently available medications in the treatment of uncontrolled isolated systolic hypertension. METHODS: We randomly selected a total of 585 patients with hypertension from our database. The two most recent blood pressure (BP) readings and other data were obtained by chart review. RESULTS: Of 585 patients, 340 (58%) had controlled BP. Of 245 patients with uncontrolled hypertension, 77.1% had uncontrolled isolated systolic hypertension and the remaining 22.9% had uncontrolled diastolic hypertension. Patients with uncontrolled systolic hypertension were on average taking more antihypertensive medications than patients with controlled BP (2.10 +/- 0.09; P = .034). CONCLUSIONS: Systolic hypertension is the etiology of uncontrolled hypertension in the majority of patients. Currently available antihypertensive medications are less effective in controlling systolic hypertension.     

Management of morning hypertension: a consensus statement of an Asian expert panel

Morning blood pressure (BP) surge is an important aspect of hypertension research. Morning BP monitoring could be a clinically relevant concept in the therapeutic management of hypertension and in the prevention of cardiovascular complications by defining and treating morning hypertension. Because antihypertensive medication is often taken in the morning, uncontrolled morning BP during the trough effect hours could be a hallmark of inadequate choice of antihypertensive regimen, such as the use of short‐ or intermediate‐acting drugs, underdosing of drugs, or no use or underuse of combination therapy. To improve the management of hypertension in general and morning hypertension in particular, long‐acting antihypertensive drugs should be used in appropriate, often full dosages and in proper combinations. The clinical usefulness of antihypertensive drugs with specific mechanisms for morning BP or split or timed dosing of long‐acting drugs in controlling morning BP remains under investigation.     

Intensive Monitoring of Adherence to Treatment Helps to Identify "True" Resistant Hypertension

Intensive monitoring of adherence in patients with uncontrolled hypertension was evaluated over a 6-month period. After that period, only patients well characterized as having resistant hypertension were followed for 12 months. The goal of this study was to evaluate whether adherence to a drug regimen helps to identify patients with resistant hypertension. Forty-four hypertensive patients resistant to a 3-drug regimen (average blood pressure [BP] mm Hg, mean ± standard deviation) were studied prospectively. Each patient was followed for a 12-month period. Adherence to treatment was evaluated through self-report, applying Morisky's questionnaire and the pill count method. Ambulatory BP monitoring and office BP measures were performed. By pill count, 63.6% of the patients were adherent to treatment at the start of the survey and 94% at the end, although 59% of the patients still did not reach normal BP levels. We found that non-adherence was not associated with resistance to antihypertensive treatment. Therefore, after investigation, we concluded that patients who presented with uncontrolled arterial BP may be truly resistant hypertensive to treatment.     

Untreated,Uncontrolled, and Apparent Resistant Hypertension: Results of the German Health Examination Survey 2008–2011

The prevalence and associated factors of untreated, uncontrolled, and apparent‐resistant hypertension (RH) in Germany are unknown. Based on European Society of Hypertension criteria, apparent RH was defined as blood pressure (BP) ≥140/90 mm Hg (≥140/85 mm Hg in diabetics) under treatment with three different classes of antihypertensive agents including a diuretic. Data from the German Health Examination Survey (2008–2011; n=7115, age 18–79 years) including standardized BP measurements and Anatomical Therapeutic Chemical–coded taken medications were analyzed. Among patients aware of their hypertensive status (n=2205), 37.9% were uncontrolled and, among those, 33.4% were untreated. Being aware and having untreated and uncontrolled BP was associated with male sex, young age, not having cardiovascular disease, not performing BP self‐measurement, not being obese, and not smoking. Apparent RH occurred in 6.8% of treated aware hypertensive patients and was positively associated with having diabetes. The proportion of uncontrolled BP is still high. Not having “obvious risk factors” has become a risk itself for having untreated and uncontrolled hypertension.     

Primary hyperaldosteronism associated with hypertensive emergencies

There is growing awareness of primary hyperaldosteronism as a cause of secondary hypertension. Usually, it manifests as hypertension and hypokalemia, or as resistant hypertension. Much less often, primary hyperaldosteronism may be detected after a hypertensive emergency has developed. We highlight this association by reporting on eight patients with a clinical diagnosis of primary hyperaldosteronism whose course was complicated by a hypertensive crisis. In all patients, an elevated serum aldosterone, was accompanied by a suppressed plasma renin activity despite the presence of a hypertensive crisis. A good outcome was obtained either with laparoscopic adrenalectomy (1 patient) or with an antihypertensive drug regimen that included an antialdosterone agent (7 patients). The differential diagnosis of hypertensive emergencies should include primary hyperaldosteronism.     

Controversies in hypertension: mild hypertension, isolated systolic hypertension, and the choice of a step one drug

The realization that cardiovascular morbidity and mortality increases in patients with mild elevation of either systolic or diastolic blood pressure has led to a consideration to treat millions of patients with mild diastolic or isolated systolic hypertension. The cost of administering a successful antihypertensive treatment program and the potential adverse effects of pharmacologic agents is of great concern. It has been emphasized that the risk of premature mortality differs in individual patients according to the number of associated cardiovascular risk factors at any level of blood pressure. This has led to a suggestion that only high risk patients be treated. However, a significant number of low risk patients with mild hypertension develop a more severe or complicated form of their disease even over a follow-up period of five to ten years. There is no good way to identify these patients. Trials of antihypertensive therapy suggest a beneficial effect of blood pressure lowering in mild hypertension. No trials of antihypertensive therapy in elderly patients with isolated systolic hypertension have been reported, but the elevation in systolic blood pressure appears to be an independent risk factor for cardiovascular mortality. Even the choice of the first step agent in treatment is debatable. Diuretics or beta blockers effectively lower blood pressure in the majority of hypertensive patients, particularly if modest dietary sodium restriction is achieved. The incidence of side effects, either symptomatic or biochemical, is similar but diuretics are unquestionably cheaper and probably more effective. Successful application of an antihypertensive treatment program may continue to reduce our unacceptably great incidence of cardiovascular disease.     

Improving patient compliance: a major goal in the management of hypertension

The primary goal in the treatment of hypertension is to reduce the incidence of cardiovascular events in hypertensive patients. Studies performed to assess the impact of treating hypertension have revealed very disappointing reductions in the incidence of coronary heart disease. There are several reasons for these poor reductions in the incidence of cardiovascular disease; however, the most important is related to the fact that worldwide less than one quarter of hypertensive patients are adequately controlled for hypertension. Again, there are multiple reasons for these poor blood pressure (BP) control rates; however, most physicians would agree that patient compliance with their antihypertensive treatment is a major contributing factor. This is an area that we need to re focus on in our management of hypertensive patients. Issues such as safety, convenience, polypharmacy, cost, and education in the selection of antihypertensive agents are all critically important issues in the treatment of hypertensive patients. In addition, the level of patient involvement in their treatment seems to be essential in obtaining goal BP. Newer approaches to the management of hypertension such as earlier control of BP and the more aggressive use of low-dose combination therapy as first-line treatment of hypertension also need to be considered in our effort to improve BP control rates. Achieving goal BP in hypertensive patients is one of the most important clinical dilemmas facing physicians. There is little doubt that an improvement in control rates will result in substantial reductions in cardiovascular disease.     

Overview of resistant hypertension: A glimpse of the cardiologist��s current standpoint

Hypertension is a major risk factor for cardiovascular disease,resulting in increased incidence of cerebrovascular events,ischaemic heart disease,heart failure,and renal impairment.Thus,it is one of the most important preventable causes of premature morbidity and mortality.Despite current knowledge on the management of hypertension and the availability of several effective antihypertensive medications,uncontrolled hypertension remains a common and challenging clinical problem.Resistant hypertension is a complex condition with multiple contributing factors and overlapping comorbidities.Although there is limited hard evidence regarding resistant hypertension,our understanding of this condition has improved recently.This article will present an overview of resistant hypertension and highlight recent publications about this topic.     

Hypertension management in patients with stable coronary disease

AIMS: To assess hypertension control in patients with stable coronary disease in France. DESIGN: A cross sectional study was conducted in a representative sample of 794 cardiologists. PARTICIPANTS: The first 6 patients with coronary disease received at practitioner's office were included. MAIN OUTCOME MEASURES: Cardiovascular risk factors, antihypertensive drugs, cardiovascular history were reported. BP was measured. Patients considered as hypertensive by his cardiologist and receiving antihypertensive drugs were considered as hypertensive. Controlled hypertension was defined as a blood pressure < 140/90 mmHg. Uncontrolled hypertension was defined as blood pressure > or = 140/90 mmHg. Among the uncontrolled hypertensives we distinguished patients with isolated systolic hypertension: diastolic blood pressure < 90 mmHg and systolic blood pressure > or = 140 mmHg. RESULTS: All variables were available in 6,349 patients who form the basis of this report. 3,161 patients were hypertensive. Of them, 1,846 (58.4%) were uncontrolled hypertensives, whom 1,280 (69.3%) were uncontrolled on the basis of systolic blood pressure alone. CONCLUSION: This study conducted in a representative sample of French cardiologists indicates that there is a considerable potential to further reduce cardiovascular morbidity in patients in secondary prevention.     

Cardiovascular outcome in treated hypertensive patients with responder, masked, false resistant, and true resistant hypertension

BACKGROUND: The aim of this study was to evaluate the cardiovascular outcome in apparently responder hypertensive patients with responder and masked hypertension, and in apparently resistant hypertensive patients with false and true resistant hypertension. METHODS: The occurrence of fatal and nonfatal cardiovascular events was evaluated in 340 patients with responder hypertension (clinic blood pressure [BP] <140/90 mm Hg and daytime BP <135/85 mm Hg), 126 with masked hypertension (clinic BP <140/90 mm Hg and daytime BP >135 or 85 mm Hg), 146 with false resistant hypertension (clinic BP >or=140 or 90 mm Hg and daytime BP <135/85 mm Hg), and 130 with true resistant hypertension (clinic BP >or=140 or 90 mm Hg and daytime BP >135 or 85 mm Hg). RESULTS: During follow-up period (4.98 +/- 2.9 years), the event-rate per 100 patient-years was 0.87, 2.42, 1.2, and 4.1 in patients with responder, masked, false resistant, and true resistant hypertension, respectively. After adjustment for several covariates, including clinic BP (forced into the model), Cox regression analysis showed that cardiovascular risk was significantly higher in masked hypertension (masked versus responder hypertension, relative risk [RR] 2.28, 95% confidence interval [CI] 1.1-4.7, P < .05) and in true resistant hypertension (true resistant versus responder hypertension, RR 2.94, 95% CI 1.02-8.41, P < .05), whereas there was no significant difference between false resistant and responder hypertension. CONCLUSIONS: This study shows that patients with masked hypertension are at higher risk than those with responder hypertension, and that those with false resistant hypertension are at lower risk than those with true resistant hypertension. Ambulatory BP monitoring should be performed in treated hypertensive patients to obtain a better prognostic stratification.     

The association between medication adherence and treatment intensification with blood pressure control in resistant hypertension

Patients with resistant hypertension are at risk for poor outcomes. Medication adherence and intensification improve blood pressure (BP) control; however, little is known about these processes or their association with outcomes in resistant hypertension. This retrospective study included patients from 2002 to 2006 with incident hypertension from 2 health systems who developed resistant hypertension or uncontrolled BP despite adherence to ≥3 antihypertensive medications. Patterns of hypertension treatment, medication adherence (percentage of days covered), and treatment intensification (increase in medication class or dose) were described in the year after resistant hypertension identification. Then, the association between medication adherence and intensification with 1-year BP control was assessed controlling for patient characteristics. Of the 3550 patients with resistant hypertension, 49% were male, and mean age was 60 years. One year after resistance hypertension determination, fewer patients were taking diuretics (77.7% versus 92.2%; P<0.01), β-blockers (71.2% versus 79.4%; P<0.01), and angiotensinogen-converting enzyme inhibitor/angiotensin receptor blocker (64.8% versus 70.1%; P<0.01) compared with baseline. Rates of BP control improved over 1 year (22% versus 55%; P<0.01). During this year, adherence was not associated with 1-year BP control (adjusted odds ratio, 1.18 [95% CI: 0.94-1.47]). Treatment was intensified in 21.6% of visits with elevated BP. Increasing treatment intensity was associated with 1-year BP control (adjusted odds ratio, 1.64 [95% CI, 1.58-1.71]). In this cohort of patients with resistant hypertension, treatment intensification but not medication adherence was significantly associated with 1-year BP control. These findings highlight the need to investigate why patients with uncontrolled BP do not receive treatment intensification.     

The heart,kidney, and brain as target organs in hypertension

The heart, kidney, brain, and arterial blood vessels are prime targets of hypertensive damage. Uncontrolled hypertension accelerates the damage to these organs and results in eventual organ failure and cardiovascular death and disability. Current guidelines for the appropriate treatment and control of hypertension requires an assessment of the presence of target organ damage. When present, evidence of target organ damage determines the urgency and intensity of drug treatment and may also dictate the choice of initial antihypertensive drug class. Thus, evaluation of persons with suspected or established hypertension must include a meticulous search for evidence of target organ damage. Fortunately, treatment with all antihypertensive medications that results in significant BP reductions also reduces fatal and nonfatal hypertensive complications and significantly slows down the progression to organ failure. Because of the important role that adverse activation of the renin-angiotensin-aldosterone system plays in target organ damage, drugs that antagonize this system have provided consistent and compelling proof of organ protection in both primary and secondary prevention of adverse outcomes. The challenge now is to use these and all other antihypertensive agents effectively to control BP to target levels in patients with hypertension. Continued emphasis on the adoption of lifestyle changes for prevention of hypertension in the first place or as adjunctive therapy in hypertensive patients is essential.     

The heart,kidney, and brain as target organs in hypertension

The heart, kidney, brain, and arterial blood vessels are prime targets of hypertensive damage. Uncontrolled hypertension accelerates the damage to these organs and results in eventual organ failure and cardiovascular death and disability. Current guidelines for the appropriate treatment and control of hypertension requires an assessment of the presence of target organ damage. When present, evidence of target organ damage determines the urgency and intensity of drug treatment and may also dictate the choice of initial antihypertensive drug class. Thus, evaluation of persons with suspected or established hypertension must include a meticulous search for evidence of target organ damage. Fortunately, treatment with all antihypertensive medications that results in significant BP reductions also reduces fatal and nonfatal hypertensive complications and significantly slows down the progression to organ failure. Because of the important role that adverse activation of the renin-angiotensin-aldosterone system plays in target organ damage, drugs that antagonize this system have provided consistent and compelling proof of organ protection in both primary and secondary prevention of adverse outcomes. The challenge now is to use these and all other antihypertensive agents effectively to control BP to target levels in patients with hypertension. Continued emphasis on the adoption of lifestyle changes for prevention of hypertension in the first place or as adjunctive therapy in hypertensive patients is essential.     

How should we treat a hypertensive emergency?

Hypertensive emergencies are life-threatening situations caused by acute blood pressure elevation. They require immediate treatment with antihypertensive drugs. Such emergencies include hypertensive crisis, acute left ventricular heart failure or intracranial bleeding in patients with hypertension, malignant hypertension resistant to treatment, and serious blood pressure elevations after vascular surgery. A hypertensive crisis may be defined as a sudden increase in systolic and diastolic blood pressure that causes functional disturbances of the central nervous system, the heart or the kidneys. In patients with hypertensive crisis, treatment should be started with an alpha receptor-blocking agent if pheochromocytoma has not been excluded by previous workup. Antihypertensive agents with a rapid onset of action--nifedipine, clonidine, dihydralazine, diazoxide and sodium nitroprusside--are being used.     

Resistant hypertension

Resistant hypertension is most often due to insufficient medical therapy. With a patient history, physical examination and focused laboratory tests, sufficient information can be gathered to lead to further directed medical therapy, which most often includes a diuretic as part of the drug regimen. Patients may require four or more classes of antihypertensives, some at high doses to achieve control. The clinician must be prepared to use sufficient medications at sufficient doses to achieve blood pressure targets. Referral to a hypertension specialist is appropriate if blood pressure remains uncontrolled despite therapy with three antihypertensive medications.