Arterial hypertension continues to represent a major risk factor for heart disease, stroke, and kidney disease in the United States. Hypertension is the most common public health problem affecting one in five Americans. Prevalence increases progressively with age. The effective management of hypertension is therefore a primary health care objective in the management of cardiovascular disease.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-VII)¹ recommended that clinicians reduce blood pressure below 140/90 mm Hg or even lower if tolerated. In high-risk populations such as those with diabetes mellitus or renal disease a treatment goal of <130/80 mm Hg is recommended. The primary goal in the treatment of hypertension is to reduce morbidity and mortality by lowering blood pressure and by modifying other cardiovascular risk factors. The current classification of hypertension is shown in Table 1.

Current hypertension control rates [systolic blood pressure (SBP) <140 mm Hg and diastolic blood pressure (DBP) <90 mm Hg] while improved, are still far below the Healthy People 2010 Goal of 50%. At this point, 30% are still unaware they have hypertension; and while 59% are reportedly receiving treatment, only 34% are maintained at or below goal blood pressure. In the majority of patients, it is the SBP that drives the disappointing control rates. Recent clinical trials have shown that effective BP control can be achieved in most hypertensive patients, but to do so requires two or more antihypertensive drugs for most patients. Patients and providers must share responsibility for the poor control rates. Long-term adherence to treatment is always a problem in any chronic disease condition, and hypertension is no exception. More than 50% of patients prescribed antihypertensive medications actually discontinue therapy within 12 months. A primary reason given for stopping medications relates to adverse effects, although the patient's knowledge about the disease, attitudes regarding treatment of an often asymptomatic condition, and personal health beliefs together with cost of medications and health care availability are major contributors. The health care delivery system may not facilitate an appropriate frequency of patient visits and follow up for missed appointments. It must also be recognized that poor control rates are not limited to indigent populations. In fact, a majority of persons whose hypertension is inadequately controlled have health insurance coverage and have seen a physician at least 3 times in the prior year.²

Physicians often have a misguided belief that blood pressure can be controlled with a single drug and demonstrate reluctance to change or to add medications in those patients whose blood pressures are not at recommended goals. Many physicians are inclined to practice sequential monotherapy with individual agents as opposed to recognizing the additive benefits of agents in combination. It is well recognized that no more than 50% of a hypertensive population will be controlled by a single drug, even when used in maximal recommended dosages. On the other hand, the skillful use of two or more agents in combination can improve hypertension control rates to well above 80%. Physicians are particularly reluctant to treat systolic hypertension aggressively for fear of doing harm.

Myths such as "a SBP of 100 plus your age is normal in the elderly" must be cast aside with the recognition that SBP is a more accurate predictor of cardiovascular risks than DBP.

Clinicians are more inclined at office visits to increase antihypertensive medications for elevated DBP than for elevated SBP. A recent report focusing on hypertensive veterans showed that increases in drug therapy were most common at office visits when the patient had a DBP of >90 mm Hg, whereas increases were less common when the patient had an SBP of >165 mm Hg and a DBP of <90 mm Hg.³ Yet, it is precisely the older patients who are at highest risk of developing sequelae of uncontrolled hypertension and in whom drug therapy has been demonstrated to reduce risks. In a community-based sample of middle-aged and older patients in the Framingham Heart Study, poor blood pressure control was overwhelmingly attributed to lack of SBP control.⁴ Among treated subjects, 85% had DBP <90 mm Hg while fewer than 50% of participants had SBPs controlled <140 mm Hg. In general, poor control rates for hypertension are driven by our failure to adequately treat and control systolic blood pressure to recommended goals (Figure 1).

Non-pharmacologic Interventions
Health care providers are frequently remiss in educating their patients regarding the importance of non-pharmacologic interventions as an important component of reducing cardiovascular risk, both in the general population, and particularly in the hypertensive patient. Disappointing long-term success rates should not deter providers from aggressively urging their hypertensive patients to undertake selected lifestyle modifications that have proven benefits on blood pressure. However, aggressive efforts will be needed to ensure optimal compliance. Lifestyle modifications include limiting alcohol intake, increasing physical activity, and reducing sodium intake to <6 gms of sodium chloride daily. Weight reduction of as little as 10-12 pounds in the obese hypertensive can have an impact on elevated blood pressure. Appropriate nutritional counseling can also encourage a diet with reduced total fat and cholesterol intake, as well as one providing adequate daily intake of potassium, calcium, and magnesium. The dietary approaches to stop hypertension (DASH Trial) have provided data showing that a diet rich in fruits, nuts and vegetables, low-fat dairy products, with emphasis on fish and chicken rather than red meat, lowered blood pressure even without weight reduction and was particularly effective in those who also restricted sodium chloride intake.⁵ Recommendations must be individualized and well supported with educational and counseling efforts. Cigarette smoking is a recognized accelerator of cardiovascular disease and smoking cessation should be strongly encouraged. Education, counseling, and medications should be provided as needed. Table 2 lists lifestyle modifications for which evidence-based data are available to support BP reductions. The effects of implementing these modifications are dose- and time-dependent and could be greater for some individuals. And a combination of two or more lifestyle modifications can achieve even better results. Lifestyle modifications not only reduce BP, they also enhance antihypertensive drug efficacy, and decrease cardiovascular risk.

Recent clinical trials have provided new information dealing with: 1) more aggressive lowering of blood pressure versus higher blood pressures; 2) the efficacy of newer classes of drugs versus diuretics and beta-blockers; and 3) the issue relating to whether lower blood pressures reduce morbidity and mortality regardless of the agent utilized.

More Aggressive Lowering of Blood Pressure
The Hypertension Optimal Treatment (HOT) Trial was a forced titration study of more than 18,000 patients who received a calcium antagonist-based treatment regimen. Patients were randomized to three target DBPs <90, <85, or <80 mm Hg. A primary goal of the study was to determine if a lower achieved DBP was associated with greater reduction in cardiovascular events.⁶ Unfortunately, the distribution of DBP from 6-month follow-up to the end of the trial at 4.5 years was not sufficient to show a significant difference in major cardiovascular events, or cardiovascular mortality for the entire treatment group. However, a subgroup of 1500 patients with Type II diabetes mellitus clearly derived benefit when treated to a DBP of <80 mm Hg, compared to those treated to a "traditional" DBP of <90 mm Hg.

By using predefined goal blood pressures and sufficient efforts by the study group, more than 90% of patients in the study achieved and maintained a DBP <90 mm Hg, and 57% maintained a DBP <80 mm Hg. The HOT Study also demonstrated the importance of combination therapy to achieve target blood pressures. Overall, 60% of patients were on monotherapy at baseline, with a mean BP of 161/98 mm Hg. At the end of the study, 70% were receiving combination therapy to a mean achieved BP of 142/93 mm Hg. Increasing requirements for combination therapy were also observed in the three DBP treatment groups.

The United Kingdom Prospective Diabetes Study (UKPDS) Group showed that tighter control of BP (144/82 mm Hg) compared to less tight control (154/87 mm Hg) in Type II diabetes was associated with fewer myocardial infarctions, strokes, cases of microvascular disease, and diabetes-related deaths. It was of particular interest that tight BP control provided greater beneficial effects on these endpoints than did tight glucose control.

Risk Reduction with Newer Agents
The Captopril Primary Prevention Project (CAPPP) compared the ACE inhibitor captopril to standard therapy with diuretics or beta-blockers and revealed similar efficacy in preventing cardiovascular morbidity and mortality, the primary endpoints of the study.⁷ In a similar trial, the STOP HYPERTENSION II Trial, an ACE inhibitor and a dihydropyridine calcium antagonist provided similar reductions in mortality and major events when compared with standard therapy.⁸ The Nordic Diltiazem (NORDIL) Study compared the effectiveness of diltiazem with that of diuretics, beta blockers, or both, and again revealed comparable effects in preventing combined primary endpoints of all strokes, myocardial infarction, and other cardiovascular deaths.⁹ Of interest was the superior effectiveness of diltiazem in lowering the rate of all strokes while the rates of fatal and non-fatal myocardial infarction tended to be lower with diuretics and/or beta blockers. In the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT), nifedipine gastro-intestinal therapeutic system (GITS) vs. hydrochlorothiazide/amiloride-based regimens proved equally effective in preventing overall cardiovascular or cerebrovascular complications.¹⁰ In each of these studies, achievement of goal blood pressures required the addition of other medications to the regimen and clearly emphasized the importance of combination therapy for the achievement of lower blood pressure goals.

Is Risk Reduction the Same
Regardless of the Agent Selected?
It has already been noted that in the NORDIL Study, despite comparable reduction in total cardiovascular events, the calcium antagonist, diltiazem, appears to be more effective in reducing the risk of strokes while fatal and non-fatal myocardial infarctions were more effectively reduced with diuretics or beta blockers. Of particular interest in this regard was the Antihypertensive and Lipid Lowering to Reduce Heart Attack Trial (ALLHAT).¹¹ This trial was designed to compare an angiotensin converting enzyme inhibitor, a dihydropyridine calcium antagonist, and an alpha-blocker vs. treatment with an oral diuretic as the standard of therapy. The alpha-blocker arm of this study was discontinued due to the observation that patients receiving an alpha-blocker as monotherapy demonstrated twice the risk of congestive heart failure when compared to those treated with an oral diuretic. The diuretic, calcium antagonist, and lisinopril groups were continued to an average follow-up of 4.9 years, at which time there were no differences noted among groups in the primary outcome (fatal coronary disease or nonfatal myocardial infarction) or in all-cause mortality. However, compared with the diuretic group (chlorthalidone), the calcium antagonist group (amlodipine) had a significantly higher cumulative incidence of heart failure and the ACE inhibitor group (lisinopril) had significantly higher incidences of heart failure, stroke, and angina pectoris.¹² There were trial design issues which have generated significant debate regarding these results, particularly the magnitude of the differences noted. Nevertheless, it was apparent that the diuretic was as effective as therapy with a calcium channel blocker or an ACE inhibitor from the standpoint of the primary outcome of the trial and superior for selected subgroup analyses. The trial concluded that diuretics should be the initial treatment of choice for most hypertensive patients.

What Is Prehypertension?
The fact that the relationship between BP and risk of cardiovascular disease events is continuous, consistent, and independent of other risk factors is well-known. The higher the BP, the greater the risk of heart attack, stroke, and kidney disease. In fact, for individuals 40-70 years of age, each increment of 20 mm Hg SBP or 10 mm Hg of DBP actually doubles the risk of cardiovascular disease across the entire range of BP from 115/75 to 185/115 mm Hg. In an effort to highlight this relationship, the revised classification of hypertension has been provided by JNC VII (Table 1). BPs below 120 and 80 mm Hg are now considered "normal," while the previous categories of "normal" and "high-normal" BP have been combined to the new classification of "prehypertension" (SBP 120 to 139 mm Hg/ or DBP 80 to 89 mm Hg). It is hoped that this new classification of prehypertension will serve as an educational tool to signal the need for increased education of health care providers and the public to use all efforts to reduce BP levels and prevent the development of hypertension. In a further effort to simplify the new classification, Stage 3 hypertension has been folded into Stage 2 since the management of patients with Stage 2 or higher BP is the same and requires two or more drugs in combination for optimal BP control.

Aggressive lifestyle modification is strongly encouraged for all patients. Major lifestyle modifications shown to lower BP include weight reduction among the obese, dietary sodium reduction, increased physical activity and moderation of alcohol consumption. Adoption of a diet rich in potassium and calcium, and with increased servings of fruits and vegetables, low saturated fats, and using the DASH eating plan may all have effects on BPs similar to single drug therapy (Table 2). Patients with prehypertension are at increased risk for progression to sustained hypertension; those in the 130-139/80-89 mm Hg BP range are at twice the risk of developing hypertension as those with lower values. The risk stratification in JNC VII has been simplified for initial therapy to include those hypertensive patients with and without compelling indications (Table 3).

For the patient with Stage 1 hypertension and without compelling indications, initial therapy with a thiazide-type diuretic for most would seem appropriate. Obviously, drugs from the other available classes can be added as needed for combination therapy. For those with Stage 2 hypertension, the use of two-drug combinations is recommended—usually a thiazide-type diuretic combined with an agent from another class. When BP is more than 20/10 mm Hg above goal, consideration should be given to initiating therapy with two drugs, either as separate prescriptions or fixed-dose combinations.

The patient with hypertension and selected comorbidities (compelling indications) will require special attention and follow-up. Table 4 describes selected compelling indications that would benefit from certain hypertensive drug classes for these high-risk conditions. The drug selections for these compelling indications are derived from evidence-based data from clinical trials. A combination of agents will often be required. Another management consideration is the achievement of desired BP goals, and the tolerability of individual drug classes by the patient. An algorithm for the treatment of hypertension based on this new classification and treatment strategies is depicted in Figure 2.

The ultimate public health goal of antihypertensive therapy is the reduction of cardiovascular and renal morbidity and mortality. It is well established that lowering BP reduces cardiovascular risk. Numerous recent clinical trials have also made it clear that treating to lower BP goals can be associated with further risk reduction. A recent report using data from the National Health and Nutrition Examination Survey (NHANES) Epidemiologic Follow-up Study estimated the absolute benefit associated with a 12-mm Hg reduction in SBP over 10 years. For the patient with Stage 1 hypertension (SBP 140-159 mm Hg and/or DBP 90-99 mm Hg), and additional cardiovascular risk factors, one death would be prevented for every 11 patients treated. In the presence of cardiovascular disease with target organ damage only 9 patients would require BP reduction to prevent a death. Since most persons with hypertension, particularly those over age 50, reach their DBP goal once SBP is at goal, the primary focus should be on achieving the SBP goal. Treating SBP and DBP to a target below 140/90 mm Hg is associated with reduced cardiovascular disease complications. Data now support treatment to a BP goal below 130/80 mm Hg in patients with hypertension and diabetes mellitus and/or renal disease. Obviously, the disappointing control rates can be significantly improved when we can encourage both providers and patients to embrace lower target BPs suggested by recent clinical trials. Most cases of uncontrolled hypertension consist of isolated Stage 1 or 2 systolic hypertension in older adults, most of whom have both access to and regular visits with their health care providers.

Thus, it seems apparent that current poor control rates for hypertension relate in large part to patient and physician barriers to aggressive treatment as well as to shortcomings in the health care delivery system. The problem is confounded further by evidence from recent clinical trials suggesting that even lower blood pressure goals are desirable. It is now evident that existing classes of medications are all of comparable effectiveness in lowering blood pressure and reducing cardiovascular morbidity and mortality, although differences do exist in effects on selected secondary endpoints.

Recent clinical trials also provide evidence that poor control rates can be improved by the use of aggressive dose titration and particularly by the use of two or more agents in combination.

Let me summarize by addressing steps that must be taken to achieve better control rates, to facilitate lower target blood pressures, and to optimize cardiovascular risk reduction among the hypertensive population.

Steps to Achieve Optimal Blood Pressure Control:

I. Emphasize aggressive lifestyle modification

• Emphasize the rationale and risk benefits of lifestyle modification
• Establish appropriate goals and monitor progress toward those goals at each office visit
• Be prepared to resolve problems that block achievement of treatment goals
• Offer praise for accomplishments
• Utilize other health professionals (nutritionists, exercise therapists) when needed

II. Take steps to improve patient compliance

• Establish the goal of therapy and ensure patient understanding and agreement
• Contract with your patient to never miss a day of medication and to call with any questions before stopping medications
• Involve family members in treatment
• Encourage home blood pressure monitoring, and facilitate telephone or mail review of readings
• Anticipate adverse effects and be prepared to adjust the treatment regimen appropriately to minimize symptoms
• Have your patients bring their medications to each office visit
• Interact with and listen to your patient
• Encourage a positive attitude and offer praise for achievement of or progress toward treatment goals

III. Enhance effectiveness of provider therapy

• Provide a patient-friendly office environment and minimize waiting time
• Increase the frequency of patient encounters (office, telephone, visit reminders)
• Appreciate language and cultural issues of your patients
• Incorporate nurse management in the office when feasible
• Consider the costs of treatment and simplify the regimen where feasible.

IV. Treat to maximize risk reduction

• Negotiate the goal blood pressure for each patient and treat aggressively to that goal
• Individualize treatment on the basis of other risk factors and co-morbid conditions
• Use fixed combination medications when feasible to reduce the number of pills
• Be prepared to use multiple medications in titrating to goal
• Aggressively manage other modifiable risk factors as well as blood pressure

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