Achieving blood pressure goals globally: five core actions for health-care professionals. A worldwide call to action.

The prevalence of hypertension continues to rise across the world, and most patients who receive medical intervention are not adequately treated to goal. A Working Group including representatives of nine international health-care organizations was convened to review the barriers to more effective blood pressure control and propose actions to address them. The group concluded that tackling the global challenge of hypertension will require partnerships among multiple constituencies, including patients, health-care professionals, industry, media, health-care educators, health planners and governments. Additionally, health-care professionals will need to act locally with renewed impetus to improve blood pressure goal rates. The Working Group identified five core actions, which should be rigorously implemented by practitioners and targeted by health systems throughout the world: (1) detect and prevent high blood pressure; (2) assess total cardiovascular risk; (3) form an active partnership with the patient; (4) treat hypertension to goal and (5) create a supportive environment. These actions should be pursued with vigour in accordance with current clinical guidelines, with the details of implementation adapted to the economic and cultural setting.

Development of explicit criteria to measure adherence to hypertension guidelines.

Measures of adherence to hypertension guidelines have historically been based on prescription data or physician survey data regarding treatment practices. These methods have limitations that decrease their accuracy. As part of a randomized controlled study testing the effects of pharmacist/physician collaboration on adherence to hypertension guidelines, the investigators and an expert panel developed a JNC 7 measurement tool. The final guideline adherence measurement tool includes 22 explicit criteria in four domains of care. An exploratory factor analysis, conducted to assess the structure of the tool, suggests three underlying treatment dimensions in hypertension care. The adherence measurement tool will allow researchers to link specific elements of care to improved blood pressure control. In addition, use of the tool will provide clinicians with a taxonomy for evaluating practice and describing the effect of improved patient care on patient outcomes.

Resistant hypertension in a tertiary care clinic.

STUDY OBJECTIVE: --To determine the prevalence of resistant hypertension in a tertiary care facility, the frequency of its various causes, and the results of treatment. DESIGN: --Review of clinic records of all patients seen for the first time between January 1, 1986, and December 31, 1988. METHODS: --Patients meeting criteria for resistant hypertension were examined for appropriateness of their medical regimen, presence of secondary causes of hypertension, noncompliance, interfering substances, drug interactions, office resistance (elevated blood pressure in the office only while receiving treatment), and other potential causes of resistance. RESULTS: --Of the 436 charts reviewed, 91 were those of patients who met criteria for resistant hypertension and were seen more than once. The most common cause was a suboptimal medical regimen (39 patients), followed by medication intolerance (13 patients), previously undiagnosed secondary hypertension (10 patients), noncompliance (nine patients), psychiatric causes (seven patients), office resistance (two patients), an interfering substance (two patients), and drug interaction (one patient). Blood pressure control, defined as diastolic blood pressure of 90 mm Hg or less and systolic blood pressure of 140 mm Hg or less for patients aged 50 years or less (less than or equal to 150 mm Hg for those aged 51 to 60 years and less than or equal to 160 mm Hg for those aged greater than 60 years), was achieved in 48 (53%) of those 91 patients. Another 10 had significant improvement in their blood pressure (greater than or equal to 15% decrease in diastolic blood pressure). Of patients whose blood pressure was controlled after they had been on a suboptimal regimen, the two most frequently used therapeutic strategies were to add (50%) or modify (24%) diuretic therapy or to add (50%) or increase the dose of (12%) a newer drug, either a calcium entry blocker or angiotensin-converting enzyme inhibitor. CONCLUSION: --We conclude that resistant hypertension is common in a tertiary care facility and that a suboptimal regimen is the most common reason. Furthermore, in the majority of these patients, the elevated blood pressures can be controlled or significantly improved.

Cough and ACE inhibitors.

To assess the prevalence of cough as a side effect of angiotensin-converting enzyme inhibitor antihypertensive therapy, we reviewed 300 consecutive patient charts from a private practice and 200 consecutive patient charts from a university-based referral center for hypertension. Incidence of definite angiotensin-converting enzyme inhibitor-induced cough in the private practice was 25% and in the university practice, 7%, with an additional 6% of university-practice patients reporting a possible angiotensin-converting enzyme-inhibitor induced cough. This incidence is considerably greater than listed in the Physicians' Desk Reference. Reasons for the variability in incidence as reported in the literature are explored. Clinicians must be aware of this potentially disturbing side effect of angiotensin-converting enzyme inhibitors to avoid expensive and unnecessary diagnostic evaluations.

Cost-effectiveness of the lower treatment goal (of JNC VI) for diabetic hypertensive patients. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

BACKGROUND: The recommendation of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) to lower blood pressure (BP) in diabetic patients to less than 130/85 mm Hg may have negative economic consequences. A formal cost-effectiveness analysis was therefore performed, comparing the costs and potential benefits of a BP goal of less than 140/90 mm Hg (as recommended by JNC V) vs less than 130/85 mm Hg (as inJNC VI). METHODS: A 24-cell computer model was populated with costs (1996 dollars), relative risks, and age-specific base-line rates for death and 4 nonfatal adverse events (stroke, myocardial infarction, heart failure, and end-stage renal disease), derived from published data. Costs and benefits were discounted at 3%. RESULTS: For 60-year-old diabetic persons with hypertension, treating to the lower BP goal increases life expectancy by 0.48 (discounted) years and lowers (discounted) lifetime medical costs by $1450 compared with treating BP to less than 140/90 mm Hg. The lower treatment BP goal results in an overall cost savings over a wide range of initial conditions, and for nearly all analyses for patients older than 60 years. CONCLUSIONS: Any incremental treatment for 60-year-olds that costs less than $414 annually and successfully lowers BP from below 140/90 to below 130/85 mm Hg would be cost saving in the long term, due to the reduction in attendant costs of future morbidity. The lower treatment goal recommended for high-risk hypertensive patients compares favorably in cost-effectiveness with many other frequently recommended treatment strategies, and saves money overall for patients aged 60 years and older.

Implications of a health lifestyle and medication analysis for improving hypertension control.

BACKGROUND: National Health and Nutritional Examination surveys have documented poor rates of hypertension treatment and control, leading to preventable morbidity and mortality. OBJECTIVES: To examine covariation in the medication and health lifestyle beliefs and behaviors of persons with hypertension to identify and profile distinct subgroups of patients. METHODS: A sample of 727 patients with hypertension, weighted to match the 1992 National Health Interview Survey age and sex distribution of patients with hypertension, was interviewed by telephone about their beliefs and behaviors regarding hypertension and its management. Cluster analysis of key variables was used to identify 4 patient types. RESULTS: Subgroups differed significantly. Group A members use an effective mix of medication and health lifestyle regimens to control blood pressure. Group B members are most likely to depend on medication and have high adherence rates. Yet they also have high rates of smoking (29%) and alcohol use (average, 104 times per year) and are less likely to exercise regularly. Group C members are most likely to forget to take medication, are likely to be obese, and find it most difficult to comply with lifestyle changes (except for very low rates of smoking and alcohol use). Group D members are least likely to take medication, most likely to change or stop medication without consulting their physician (20%), most likely to smoke (40%), and least likely to control diet (29%). Group A and B members have better health outcomes than group C and D members. CONCLUSIONS: Optimal management strategies are likely to differ for the 4 patient types. Further research should be conducted to validate these findings on a separate sample and to devise and test tailored management algorithms for hypertension compliance and control.

Garlic powder and plasma lipids and lipoproteins: a multicenter, randomized, placebo-controlled trial.

BACKGROUND: Garlic powder tablets have been reported to lower serum cholesterol levels. There is widespread belief among the general public that garlic powder tablets aid in controlling cholesterol levels. However, much of the prior data demonstrating the cholesterol-lowering effect of garlic tablets involved studies that were inadequately controlled. OBJECTIVE: To determine the lipid-lowering effect of garlic powder tablets in patients with hypercholesterolemia. METHODS: This was a randomized, double-blind, placebo-controlled, 12-week, parallel treatment study carried out in 2 outpatient lipid clinics. Entry into the study after 8 weeks of diet stabilization required a mean low-density lipoprotein cholesterol level on 2 visits of 4.1 mmol/L (160 mg/dL) or lower and a triglyceride level of 4.0 mmol/L (350 mg/dL) or lower. The active treatment arm received tablets containing 300 mg of garlic powder (Kwai) 3 times per day, given with meals (total, 900 mg/d). This is equivalent to approximately 2.7 g or approximately 1 clove of fresh garlic per day. The placebo arm received an identical-looking tablet, also given 3 times per day with meals. The main outcome measures included levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol after 12 weeks of treatment. RESULTS: Twenty-eight patients (43% male; mean +/- SD age, 58 +/- 14 years) received garlic powder treatment and 22 (68% male; mean +/- SD age, 57 +/- 13 years) received placebo treatment. There were no significant lipid or lipoprotein changes in either the placebo- or garlic-treated groups and no significant difference between changes in the placebo-treated group compared with changes in the garlic-treated patients. CONCLUSION: Garlic powder (900 mg/d) treatment for 12 weeks was ineffective in lowering cholesterol levels in patients with hypercholesterolemia.

Relation of low body mass to death and stroke in the systolic hypertension in the elderly program. The SHEP Cooperative Research Group.

BACKGROUND: There are scant data on the effect of body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters) on cardiovascular events and death in older patients with hypertension. OBJECTIVE: To determine if low body mass in older patients with hypertension confers an increased risk of death or stroke. PATIENTS: Participants were 3975 men and women (mean age, 71 years) enrolled in 17 US centers in the Systolic Hypertension in the Elderly Program trial, a randomized, double-blind, placebo-controlled clinical trial of lowdose antihypertensive therapy, with follow-up for 5 years. MAIN OUTCOME MEASURES: Five-year adjusted mortality and stroke rates from Cox proportional hazards analyses. RESULTS: There was no statistically significant relation of death or stroke with BMI in the placebo group (P = .47), and there was a U- or J-shaped relation in the treatment group. The J-shaped relation of death with BMI in the treated group (P = .03) showed that the lowest probability of death for men was associated with a BMI of 26.0 and for women with a BMI of 29.6; the curve was quite flat for women across a wide range of BMIs. For stroke, men and women did not differ, and the BMI nadir for both sexes combined was 29, with risk increasing steeply at BMIs below 24. Those in active treatment, however, had lower death and stroke rates compared with those taking placebo. CONCLUSIONS: Among older patients with hypertension, a wide range of BMIs was associated with a similar risk of death and stroke; a low BMI was associated with increased risk. Lean, older patients with hypertension in treatment should be monitored carefully for additional risk factors.

Influence of long-term, low-dose, diuretic-based, antihypertensive therapy on glucose, lipid, uric acid, and potassium levels in older men and women with isolated systolic hypertension: The Systolic Hypertension in the Elderly Program. SHEP Cooperative Research Group.

BACKGROUND: Previous studies often of short duration have raised concerns that antihypertensive therapy with diuretics and beta-blockers adversely alters levels of other cardiovascular disease risk factors. METHODS: The Systolic Hypertension in the Elderly Program was a community-based, multicenter, randomized, double-blind, placebo-controlled clinical trial of treatment of isolated systolic hypertension in men and women aged 60 years and older. This retrospective analysis evaluated development of diabetes mellitus in all 4736 participants in the Systolic Hypertension in the Elderly Program, including changes in serum chemistry test results in a subgroup for 3 years. Patients were randomized to receive placebo or treatment with active drugs, with the dose increased in stepwise fashion if blood pressure control goals were not attained: step 1, 12.5 mg of chlorthalidone or 25.0 mg of chlorthalidone; and step 2, the addition of 25 mg of atenolol or 50 mg of atenolol or reserpine or matching placebo. RESULTS: After 3 years, the active treatment group had a 13/4 mm Hg greater reduction in systolic and diastolic blood pressure than the placebo group (both groups, P<.001). New cases of diabetes were reported by 8.6% of the participants in the active treatment group and 7.5% of the participants in the placebo group (P=.25). Small effects of active treatment compared with placebo were observed with fasting levels of glucose (+0.20 mmol/L [+3.6 mg/dL]; P<.01), total cholesterol (+0.09 mmol/L [+3.5 mg/dL]; P<.01), high-density lipoprotein cholesterol (-0.02 mmol/L [-0.77 mg/dL]; P<.01) and creatinine (+2.8 micromol/L [+0.03 mg/dL]; P<.001). Larger effects were seen with fasting levels of triglycerides (+0.9 mmol/L [+17 mg/dL]; P<.001), uric acid (+35 micromol/L [+.06 mg/dL]; P<.001), and potassium (-0.3 mmol/L; P<.001). No evidence was found for a subgroup at higher risk of risk factor changes with active treatment. CONCLUSIONS: Antihypertensive therapy with low-dose chlorthalidone (supplemented if necessary) for isolated systolic hypertension lowers blood pressure and its cardiovascular disease complications and has relatively mild effects on other cardiovascular disease risk factor levels.

Drug treatment of hypertension in patients with diabetes mellitus.

Patients with diabetes mellitus have an increased prevalence of hypertension and its vascular consequences, including coronary and cerebrovascular disease. Drug treatment of hypertension in diabetic subjects is fraught with potential difficulties, including the altered efficacy of medications, the increased risk of side effects, and the possibility of worsening glycemic control and increasing serum lipid levels. Despite these difficulties, treatment is an important part of reducing morbidity and mortality from vascular events. Antihypertensive therapy may also have the potential to prevent or retard the development of diabetic nephropathy. In this article, we discuss the efficacy and metabolic and nonmetabolic side effects of the various classes of antihypertensive agents in patients with diabetes mellitus and suggest a stepped-care approach to the drug treatment of patients with hypertension and diabetes.

Choosing initial therapy for hypertension. A personal view.

With numerous safe and effective antihypertensive drugs now available, the clinician should no longer choose only diuretic agents or beta-adrenergic receptor blockers (beta-blockers) as initial therapy. Five classes of agents, including angiotensin converting enzyme inhibitors, beta-blockers, calcium entry blockers, peripheral alpha 1-adrenergic receptor blockers, and thiazide diuretic agents, are all appropriate monotherapy in properly selected patients. The choice depends on efficacy, side effects, demography, comorbidity, dosage schedule, cost, mechanism of drug action, and the pathophysiology of the patient's hypertension. Extensive data are now available that will assist the clinician in choosing an agent that has the greatest probability of success without the need for extensive biochemical or hemodynamic evaluation.

A new classification scheme for hypertension based on relative and absolute risk with implications for treatment and reimbursement.

Classification schemes for hypertension are necessary. They provide us with definitions for when hypertension begins and help us to assess risk, determine prognosis, and guide management. Systems in current use rely on either the level of blood pressure (diastolic, systolic, or both) and classify patients based on the level of relative risk (the proportional likelihood of cardiovascular events occurring as blood pressure rises), absolute risk (the actual odds that a patient or a population will develop an event), or both. Absolute risk reflects the sum of all the factors that contribute to the likelihood that a patient will experience cardiovascular disease. The system we propose stages hypertensive individuals on the basis of blood pressure level (as does the Fifth Joint National Committee report on the detection, evaluation, and treatment of high blood pressure [JNC-V] and the World Health Organization/International Society of Hypertension guidelines) but uses different levels for each stage than do the previous systems and then modifies the numerical stage with the subscript "c" for complicated (when target-organ damage and/or other cardiovascular risk factors are present) or "u" for uncomplicated (when they are absent). The data obtained from a complete medical history and physical examination and a few inexpensive laboratory tests provide the information a provider needs to classify an individual as being complicated or uncomplicated. This system also provides a guide to treatment, as drug therapy would be used sooner in individuals with complicated hypertension, and we propose that compensation for providers be higher when they are caring for a patient with complicated rather than uncomplicated hypertension.

Thallium-201 stress imaging in hypertensive patients.

To assess the potential effect of hypertension on the results of thallium-201 stress imaging in patients with chest pain, 272 thallium-201 stress tests performed in 133 hypertensive patients and 139 normotensive patients over a 1-year period were reviewed. Normotensive and hypertensive patients were similar in age, gender distribution, prevalence of cardiac risk factors (tobacco smoking, hyperlipidemia, and diabetes mellitus), medications, and clinical symptoms of coronary disease. Electrocardiographic criteria for left ventricular hypertrophy were present in 16 hypertensive patients. Stepwise probability analysis was used to determine the likelihood of coronary artery disease for each patient. In patients with mid to high likelihood of coronary disease (greater than 25% probability), abnormal thallium-201 stress images were present in 54 of 60 (90%) hypertensive patients compared with 51 of 64 (80%) normotensive patients. However, in 73 patients with a low likelihood of coronary disease (less than or equal to 25% probability), abnormal thallium-201 stress images were present in 21 patients (29%) of the hypertensive group compared with only 5 of 75 (7%) of the normotensive patients (p less than 0.001). These findings suggest that in patients with a mid to high likelihood of coronary artery disease, coexistent hypertension does not affect the results of thallium-201 exercise stress testing. However, in patients with a low likelihood of coronary artery disease, abnormal thallium-201 stress images are obtained more frequently in hypertensive patients than in normotensive patients.

Comparison of nifedipine alone and with diltiazem or verapamil in hypertension.

Receptor binding studies suggest that combinations of calcium channel blockers may result in either enhanced or diminished pharmacological effects, but clinical data in hypertension are incomplete. In this study, we compared blood pressure reductions using nifedipine alone, nifedipine plus diltiazem, and nifedipine plus verapamil and determined whether combinations alter nifedipine pharmacokinetics. After determination of baseline blood pressures. 16 subjects with essential hypertension (12 men, 4 women; mean age, 48 years) received 30 mg/d open-label, sustained release nifedipine for 2 weeks. If still hypertensive (n = 16), they were randomized (double-blind) to receive either additional sustained release diltiazem or sustained release verapamil, both 180 mg/d, for 2 weeks and were then crossed-over for the final 2 weeks of the study. All medications were once-daily, extended-release formulations. Blood pressures and nifedipine plasma concentrations were measured during the final day of each treatment. Overall, each combination lowered mean systolic and diastolic pressures more than nifedipine alone. Mean supine diastolic pressures were significantly lower at 8 hours (77.6 versus 84.6 mm Hg, P = .001) and 12 hours (81.5 versus 87.1 mm Hg, P = .04) with nifedipine plus diltiazem than nifedipine plus verapamil. Mean nifedipine concentrations were inversely correlated with mean blood pressures. Mean nifedipine area under the curve values were greater with diltiazem than verapamil (1430 versus 1134 ng.h/mL, P = .026), with each greater than nifedipine alone (957 ng.h/mL). Nifedipine plus diltiazem had a greater antihypertensive effect than nifedipine plus verapamil. Diltiazem caused greater increases in nifedipine plasma concentrations than did verapamil. These data suggest that combined calcium channel blockers result in additive antihypertensive effects, perhaps because of a pharmacokinetic interaction.

Prostaglandin E2 analogue elicits renal and hormonal compensatory mechanisms in human hypertension.

Endogenous prostaglandin E2 appears to play an important role in cardiovascular homeostasis. When administered exogenously, it is a potent vasodilator, but the requirement for intravenous administration and its short duration of action have limited studies to its acute effects. A novel prostaglandin E2 analogue, CL 115347, can be administered transdermally on a long-term basis. The cardiovascular responses to the chronic administration of CL 115347 were studied in a double-blind, placebo-controlled trial in 26 subjects with essential hypertension (16 given drug, 10 placebo) maintained on a 100-mEq sodium diet. Administration of CL 115347 produced a fall in diastolic blood pressure of 7.8 +/- 1.3 mm Hg, compared with a 2.3 +/- 1.7 mm Hg fall in controls (p = 0.02), with no change in heart rate. The direct vascular effect of the drug was confirmed by attenuation of the vasoconstrictor response to angiotensin II infusion (13.4 +/- 3.1 vs 21 +/- 2 mm Hg at 3.0 ng/kg/min; p less than 0.05). However, the chronic blood pressure effect of CL 115347 was modest. Subjects receiving active drug showed significant compensatory increases in plasma renin, aldosterone, and norepinephrine levels accompanied by sodium retention and kaliuresis. In summary, chronic administration of this prostaglandin E2 analogue resulted in a modest decrease in blood pressure and antagonism of angiotensin II-mediated vasoconstriction. However, its effects were largely offset by compensatory increases in vasoconstrictor hormones and sodium retention.

Simplified captopril renography in diagnosis and treatment of renal artery stenosis.

To improve the diagnosis and forecast the response to surgery or renal angioplasty in patients with hypertension and renal artery stenosis, we employed a simplified captopril renography protocol in conjunction with renal arteriography in 94 clinically selected patients. Fifty hypertensive patients (group 1) with a high clinical likelihood of renovascular hypertension were evaluated using a simplified captopril renography protocol and renal angiography on the arterial side. Criteria for normal captopril renal scintigrams were established based on this original cohort and validated in an additional 44 clinically comparable patients (group 2). Renal revascularization or nephrectomy was performed in 39 patients, and success of the procedure was determined in the 34 patients for whom 3-month follow-up was available. In the 94 patients, 44 (47%) had renal artery stenosis. Simplified captopril renography was 91% sensitive and 94% specific in identifying or excluding renal artery stenosis in the combined group, with no difference in the diagnostic utility between groups 1 and 2, or in those with renal insufficiency (n = 38) or those with bilateral disease (n = 17). Scintigraphic abnormalities induced by captopril were strongly associated with cure or improvement in blood pressure control following revascularization or nephrectomy (15 of 18), while the lack of captopril-induced changes was associated with failure of such intervention (13 of 16) (p = 0.0004). We conclude that simplified captopril renography is highly sensitive and specific in the diagnosis of renal artery stenosis in a clinically selected high-risk population and that the test accurately predicts the success or failure of therapeutic intervention.

Diurnal blood pressure in patients with mild-to-moderate hypertension treated with once-daily benazepril hydrochloride.

This study evaluated the blood pressure effects of administration of once daily oral benazepril hydrochloride, a new angiotensin-converting enzyme (ACE) inhibitor, for mild-to-moderate hypertension. After a 2 to 4 week placebo baseline period, patients with diastolic blood pressure between 95 and 114 mm Hg, were randomized to receive either placebo or benazepril hydrochloride, 5, 10, 20, or 40 mg, once daily in double-blind fashion for 28 days. Blood pressure was measured predose and at 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours after the dose during inpatient observation days at the end of the placebo baseline period, and on the first and last day of the double-blind treatment period; and 24 hours after the dose at weekly outpatient visits. All doses of benazepril hydrochloride resulted in clinically important reductions in diastolic and systolic blood pressures that lasted between 12 and 24 hours after both the first dose, and following the last dose after 4 weeks of treatment. The findings indicate that benazepril hydrochloride may be clinically useful as once-daily monotherapy in many patients with hypertension.

A simplified diagnostic approach to pheochromocytoma. A review of the literature and report of one institution's experience.

Pheochromocytoma is an unusual but potentially devastating tumor. Although a high index of suspicion is necessary, the likelihood of a pheochromocytoma is lower in the absence of the typical symptoms and findings. Nonetheless, screening must be broadened to include patients with a lower risk of the disease, such as those with resistant or labile hypertension who are minimally symptomatic. Extensive diagnostic evaluations should be reserved for those whose clinical or laboratory findings are more suggestive. Symptoms in a group of patients in whom a pheochromocytoma was seriously considered but excluded overlap symptoms in patients with a pheochromocytoma. Certain symptoms are useful: flushing to suggest a non-pheochromocytoma illness; visual symptoms, flank pain, and pallor to suggest that a pheochromocytoma is more likely. Combinations of symptoms can be of value: 2 or more symptoms from the triad of headache, palpitations, and diaphoresis were present in the majority of pheochromocytoma patients, but in a smaller number of non-pheochromocytoma patients. The presence of the entire triad is more specific, but less sensitive. New hypertension, or hypertension associated with unexplained orthostatic hypotension, are suggestive of an underlying pheochromocytoma. Twenty-four-hour urine studies are consistently abnormal in patients with a pheochromocytoma, but are also elevated in a significant proportion of non-pheochromocytoma patients. Values greater then 1.5-2-fold above the upper limit of normal are very suggestive that a pheochromocytoma is present, and warrant a more intensive subsequent evaluation. Imaging studies are reliable in the diagnosis of pheochromocytoma, and can help to confirm or exclude the disease. Patients with a higher clinical likelihood and any elevated urinary testing, or with a lower clinical likelihood and persistently and/or significantly elevated urinary testing, should have imaging studies performed. This combination of clinical screening, 24-hour urinary testing, and imaging studies is a useful and reliable approach to patients suspected of harboring a pheochromocytoma.

The evolution of low-dose diuretic therapy: the lessons from clinical trials.

Safe and effective antihypertensive therapy became available in the 1950s with the introduction of thiazide diuretics. Prior to that time, we did have agents that lowered blood pressure but they often needed to be given parenterally and were too poorly tolerated to be used for the treatment of any but those with life-threatening elevations of blood pressure. When thiazide diuretics-first chlorothiazide and then hydrochlorothiazide-became available, it was possible to lower blood pressure in most hypertensives and assess whether that reduction would lead to a reduction in cardiovascular morbidity and mortality. The results of 17 large trials have now made it clear that antihypertensive therapy with regimens based on diuretics and beta blockers reduces cardiovascular events and saves lives. When first introduced, thiazide diuretics were prescribed at doses we now know are excessively high (100-200 mg of hydrochlorothiazide/day), and we have learned that much lower doses, even as little as 12.5 mg of hydrochlorothiazide, are effective. These lower doses will reduce blood pressure and do so with considerably less in the way of metabolic effects. This article will trace the development of antihypertensive therapy and review how data from clinical trials have influenced the recommendations of the Joint National Committees on the Detection, Evaluation and Treatment of Hypertension.

Blood pressure control.

Numerous studies have shown that effective control of elevated blood pressure has greatly reduced the risk of stroke and, to a lesser extent, the risk of coronary artery disease. Although the relationship between diastolic blood pressure and both stroke and coronary disease is significant, systolic blood pressure correlates more strongly with stroke, congestive heart failure, coronary artery disease, declining renal function, and left ventricular hypertrophy. Studies have also shown that the presence of a wide pulse pressure (>/=60-70 mm Hg) also has an independent and major impact on coronary disease mortality and is strongly correlated with increased risk for cardiovascular disease. Because many hypertensives have end-organ damage (cardiac, central nervous system, renal), and the majority also have a comorbid condition such as diabetes and hyperlipidemia, which also increases cardiovascular risk, it is necessary to view the risks and comorbidity of hypertension and antihypertensive therapy in light of these problems. Despite evidence that antihypertensive therapy reduces the risk of stroke and coronary events, and despite the availability of effective agents, roughly half of the hypertensives in the United States remain untreated and only 24% have blood pressure <140 mm Hg systolic and 90 mm Hg diastolic. To ensure that hypertensive patients receive adequate therapy, physicians should treat patients aggressively and appropriately, avoiding antihypertensive drugs that adversely affect comorbid conditions and selecting those that also exert favorable therapeutic effects on these conditions.