Classification and treatment

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 7) ¹ has recommended that clinicians reduce blood pressure to 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 lower than 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) lower than 140 mm Hg and diastolic blood pressure (DBP) lower than 90 mm Hg—although improved, are still far below the Healthy People 2010 Goal of 50%. At present, 30% are still unaware they have hypertension and even though 59% are reportedly receiving treatment, only 34% are maintained at or below goal blood pressure. In most patients, it is the SBP that drives the disappointing control rates. Clinical trials have shown that effective BP control can be achieved in most hypertensive patients, but this requires two or more antihypertensive drugs for most patients. Patients and health care 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 who are 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 the 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, most of those whose hypertension is inadequately controlled have health insurance coverage and have seen a physician at least three times in the previous year. ²

Physicians often have a misguided belief that blood pressure can be controlled with a single drug and demonstrate reluctance to change or add medications for 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 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. However, 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 older adults” 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 report focusing on hypertensive veterans showed that increases in drug therapy were most common at office visits when the patient had a DBP higher than 90 mm Hg, whereas increases were less common when the patient had an SBP of 165 mm Hg or higher and a DBP of lower than 90 mm Hg. ³ However, 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 a DBP lower than 90 mm Hg but fewer than 50% of participants had SBPs controlled to lower than 140 mm Hg. In general, poor control rates for hypertension are driven by the failure to treat and control systolic blood pressure adequately to recommended goals (Fig. 1).

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Prevalence

Aggressive lifestyle modification is strongly encouraged for all patients. Major lifestyle modifications shown to lower blood pressure (BP) include weight reduction for obese individuals, 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 BP similar to those from single-drug therapy ( Table 2 ). Patients with prehypertension are at increased risk for progression to sustained hypertension; those in the BP range of 130 to 139/80 to 89 mm Hg are at twice the risk of developing hypertension as those with lower values. The risk stratification in JNC 7 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 would seem appropriate for most. Drugs from the other classes can be added as needed for combination therapy. For those with stage 2 hypertension, the use of a two-drug combination 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 a separate prescription or fixed-dose combination.

The patient with hypertension and select comorbidities (compelling indications) will require special attention and follow-up. Table 4 describes select compelling indications that would benefit from certain hypertensive drug classes for these high-risk conditions. The drugs selected 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.

Summary

• Lifestyle modification interventions are dose- and time-dependent.
• Older and newer drugs reduce cardiovascular morbidity and mortality.
• Use of a thiazide-type diuretic is considered the initial treatment of choice.
• Most patients will require two or three medications to achieve optimal blood pressure control.

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 clinical trials have also made it clear that treating to lower BP goals can be associated with further risk reduction. A report using data from the National Health and Nutrition Examination Survey (NHANES) Epidemiologic Follow-up Study has estimated the absolute benefit associated with a 12-mm Hg reduction in systolic BP (SBP) over 10 years. For the patient with stage 1 hypertension (SBP, 140 to 159 mm Hg and/or diastolic BP [DBP], 90 to 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. Because most persons with hypertension, particularly those older than 50 years, 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, diabetes mellitus, and/or renal disease. The disappointing control rates can be significantly improved when both health care providers and patients can be encouraged 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 access to and regular visits with their health care providers.

Thus, it seems apparent that current poor control rates for hypertension relate largely 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 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 regard to effects on select secondary end points. Clinical trials have also provided evidence that poor control rates can be improved by the use of aggressive dose titration, particularly by the use of two or more agents in combination.

To summarize, steps must be taken to achieve better control rates, facilitate lower target blood pressures, and optimize cardiovascular risk reduction in the hypertensive population.

Steps to Achieve Optimal Blood Pressure Control

1. Emphasize aggressive lifestyle modification.
   1. Emphasize the rationale and risk-benefit factors of lifestyle modification.
   2. Establish appropriate goals and monitor progress toward those goals at each office visit.
   3. Be prepared to resolve problems that block achievement of treatment goals.
   4. Offer praise for accomplishments.
   5. Use other health care professionals (e.g., nutritionists, exercise therapists) when needed.
2. Take steps to improve patient compliance.
   1. Establish the goal of therapy and ensure patient understanding and agreement.
   2. Contract with your patient never to miss a day of medication and to call with any questions before stopping medications.
   3. Involve family members in treatment.
   4. Encourage home blood pressure monitoring, and facilitate telephone or mail review of readings.
   5. Anticipate adverse effects and be prepared to adjust the treatment regimen appropriately to minimize symptoms.
   6. Have your patients bring their medications to each office visit.
   7. Interact with and listen to your patient.
   8. Encourage a positive attitude and offer praise for achievement of or progress toward treatment goals.
3. Enhance effectiveness of provider therapy.
   1. Provide a patient-friendly office environment and minimize waiting time.
   2. Increase the frequency of patient encounters (office, telephone, visit reminders).
   3. Appreciate language and cultural issues of your patients.
   4. Incorporate nurse management in the office when feasible.
   5. Consider the costs of treatment and simplify the regimen if feasible.
4. Treat to maximize risk reduction.
   1. Negotiate the goal blood pressure for each patient and treat aggressively to that goal.
   2. Individualize treatment on the basis of other risk factors and comorbid conditions.
   3. Use fixed-combination medications when feasible to reduce the number of pills.
   4. Be prepared to use multiple medications in titrating to goal.
   5. Aggressively manage other modifiable risk factors as well as blood pressure.

Summary

• Hypertension is the most common public health problem.
• Normal blood pressure is considered to be below 120/80 mm Hg.
• Target blood pressure should be below 140/90 mm Hg or lower if tolerated and lower than 130/80 mm Hg in high-risk populations (e.g., diabetics).

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Treatment

Nonpharmacologic Interventions

Health care providers are frequently remiss in educating their patients regarding the importance of nonpharmacologic interventions as an important component of reducing cardiovascular risk 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 select 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 less than 6 g of sodium chloride daily. Weight reduction of as little as 10 to 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 providing adequate daily intake of potassium, calcium, and magnesium. The dietary approaches to stop hypertension (DASH trial ⁵ ) have provided data showing that a diet rich in fruits, nuts, and vegetables, and 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. 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. Also, a combination of two or more lifestyle modifications can achieve even better results. Lifestyle modifications not only reduce BP but also enhance antihypertensive drug efficacy and decrease cardiovascular risk.

Pharmacologic Interventions

Clinical trials have provided new information dealing with the following: (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) whether lower blood pressures reduce morbidity and mortality regardless of the agent used.

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 diastolic blood pressures (DBPs)—lower than 90, 85, or 80 mm Hg. A primary goal of the study was to determine whether a lower achieved DBP is 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 2 diabetes mellitus clearly derived benefit when treated to a DBP lower than 80 mm Hg compared with those treated to a “traditional” DBP lower than 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 lower than 90 mm Hg, and 57% maintained a DBP lower than 90 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 with less tight control (154/87 mm Hg) in type 2 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 end points than tight glucose control.

Risk Reduction with Newer Agents

The Captopril Primary Prevention Project (CAPPP) compared the angiotensin-converting enzyme (ACE) inhibitor captopril with standard therapy with diuretics or beta blockers and revealed similar efficacy in preventing cardiovascular morbidity and mortality, the primary end points 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 end points of all strokes, myocardial infarction, and other cardiovascular deaths. ⁹ Of interest was the superior effectiveness of diltiazem in lowering the rates of all strokes, whereas the rates of fatal and nonfatal myocardial infarc-tions tended to be lower with diuretics, beta blockers, or both. In the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT), nifedipine gastrointestinal therapeutic system (GITS) versus 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, whereas fatal and nonfatal 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 ACE inhibitor, a dihydropyridine calcium antagonist, and an alpha blocker with treatment with an oral diuretic as the standard of therapy. The alpha blocker arm of this study was discontinued because of the observation that patients receiving an alpha blocker as monotherapy demonstrated twice the risk of congestive heart failure when compared with 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 regard to the primary outcome (fatal coronary disease or nonfatal myocardial infarction) or 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 that have generated significant debate regarding these results, particularly the magnitude of the differences noted. Nevertheless, it was apparent that the diuretic is as effective as a calcium channel blocker or an ACE inhibitor from the standpoint of the primary outcome of the trial and superior for select 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 relation 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 risks of heart attack, stroke, and kidney disease. In fact, for individuals 40 to 70 years of age, each increment of 20 mm Hg in systolic BP (SBP) or 10 mm Hg in 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 relation, the revised classification of hypertension has been provided by the JNC 7 ¹ (see Table 1 ). BPs below 120 and 80 mm Hg are now considered normal, whereas the previous categories of normal and high-normal BP have been combined into 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 can encourage 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 because 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.

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Risk-based classification of hypertension and treatment guidelines

It is critical that health practitioners must be aware of important, evolving changes in not only the definition of hypertension, but also take into consideration assessment of global risk of cardiovascular disease in the patient with high blood pressure. Despite decades of national and international educational efforts by organizations such as the National Institute of Health through a series of JNC guidelines, elevated blood pressure remains a leading cause of morbidity and mortality worldwide. Studies in a variety of countries, including the United States, consistently show that a significant proportion of hypertensive individuals remain unaware of their condition, and if aware, do not receive or accept treatment. Recommended goal blood pressure levels are achieved in a minority of patients, regardless of whether treatment is prescribed and/or patients are followed by a specialist or general practitioners. Control rates of systolic blood pressure are particularly disappointing, especially in patients with other cardiovascular risk factors, such as diabetes mellitus. The current JNC-7 report ¹ does incorporate the importance of elevated cardiovascular risk across a broad spectrum of blood pressure values as well as a high lifetime risk of developing hypertension. Yet, current treatment guidelines, which make up the body of this report are still largely based on threshold levels of blood pressure.

In 2005, a writing group of the American Society of Hypertension proposed an alternate classification system that would take into consideration not only threshold levels of blood pressure but also quantification of total (or global) cardiovascular risk. ¹³ It is recognized that only a minority of hypertensive patients have high blood pressure alone, in the absence of other cardiovascular risk factors. Recognition and management of other cardiac, vascular, renal and metabolic risk factors obviously play a significant role in the down-the-road cardiovascular risk of the hypertensive patient. This publication has generated significant discussion among the hypertensive community since their proposed guidelines suggested that the initiation of and aggressiveness of treatment should be individualized and guided by global cardiovascular risk as opposed to blood pressure thresholds.

Recently, the 2007 guidelines generated by the European Society of Hypertension and European Society of Cardiology ^14,15 have also embraced the concept of global cardiovascular risk in recommending that all patients should be classified not only in relation to the grades of hypertension but also in terms of their total cardiovascular risk which, of course, represents the risk from the co-existence of multiple risk factors and target organ damage. These guidelines stress that the threshold for hypertension and the subsequent drug therapy should remain flexible and should be a function of each patient's total cardiovascular risk.

I would urge referral to these documents to better understand the concept of hypertension diagnosis and treatment recommendations based on total cardiovascular risk. I fully expect that JNC-8, when published, will also give considerable attention to the concept and importance of global cardiovascular risk in its recommendations for prevention, detection, evaluation and treatment of hypertension.

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Suggested Readings

• ALLHAT Collaborative Research Group. Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). JAMA. 283: 2000; 1967-1975.
• ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial: Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 288: 2002; 2981-2997.
• Inadequate management of blood pressure in a hypertensive population. N Engl J Med. 339: 1998; 1957-1963.
• Morbidity and mortality in patients randomised to double-blind treatment with long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet. 356: 2000; 366-372.
• National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report. JAMA. 289: 2003; 2560-2571.
• Expanding the definition and classification of hypertension. J Clin Hypertens (Greenwich). 7: 2005; 505-512.
• Randomised trial of effects of calcium antagonists compared with diuretics and beta-blockers on cardiovascular morbidity and mortality in hypertension: The Nordic Diltiazem (NORDIL) study. Lancet. 356: 2000; 359-365.
• Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: The Captopril Prevention Project (CAPPP) randomised trial. Lancet. 353: 1999; 611-616.
• Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study. Lancet. 354: 1999; 1751-1756.
• Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: Principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet. 351: 1998; 1755-1762.
• Characteristics of patients with uncontrolled hypertension in the United States. N Engl J Med. 45: 2001; 479-486.
• Differential control of systolic and diastolic blood pressure: Factors associated with lack of blood pressure control in the community. Hypertension. 36: 2000; 594-599.
• 2007 ESH-ESC Practice Guidelines for the Management of Arterial Hypertension: ESH-ESC Task Force on the Management of Arterial Hypertension. J Hypertens. 25: 2007; 1751-1762.
• 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 25: 2007; 1105-1187.
• Effects of diet and sodium intake on blood pressure: subgroup analysis of the DASH-sodium trial. Ann Intern Med. 135: 2001; 1019-1028.