High Blood Pressure / Hypertension

The National Health and Nutrition Examination Survey III

By Cardiologist on August 13th, 2011

How Are We Doing with Blood Pressure Control?

Untreated and uncontrolled hypertension is a major health problem in the United States. Findings from the Third National Health and Nutrition Examination Survey (NHANES III, phase 2), conducted from 1991 to 1994, indicate that this problem may be worsening. Major decreases in awareness, treatment, and control rates for hypertension have been recorded in the past decade despite extensive educational programs directed toward patients and health care providers, the widespread availability of facilities for diagnosis and treatment, and the development of effective management strategies. Because of the high prevalence of hypertension in the United States, the observed decline in control rates is estimated to put more than 1 million hypertensive patients at increased risk for target organ damage and cardiovascular disease-related morbidity and mortality. Although a causal relationship has not been established, the decline in hypertension detection, treatment, and control rates has coincided with an increase in morbidity and mortality owing to cardiovascular disease. Since 1993, age-adjusted stroke rates have risen, the slope of the age-adjusted rate of decline in coronary heart disease has leveled off, and the incidence of end-stage renal disease and the prevalence of heart failure have increased. These trends support an urgent need for greater emphasis on public awareness of the problem of high blood pressure  and on more aggressive approaches to antihypertensive treatment and blood pressure control by caregivers.

Strategies for enhancing awareness of hypertension

Hypertension can be detected only by measuring blood pressure. This procedure should be carried out at each encounter between a patient and a health care provider. In addition, community screening at health fairs, schools, churches, sporting events, and other gathering places for persons who may not be engaged in the health care system may be useful in identifying previously undiagnosed hypertensive patients. Blood pressure should be measured in a standardized fashion using equipment that meets certification criteria. Repeated blood pressure measurements made at intervals are needed to determine whether initial elevations persist and require prompt attention or whether only periodic surveillance is needed. It is critical that persons in whom a diagnosis of hypertension has been considered not be lost to follow-up, since labile or intermittent hypertension in some people, particularly the young, may lead to fixed hypertension later in life.

Table Recommendations for Follow-up Based on Initial blood pressure Measurements for Adults”

Initial blood pressure (mmHg)
Systolic	Diastolic	Follow-up recommended
<130	<85	Recheck in 2 yr
130-139	85-59	Recheck in 1 yr
140-159	90-99	Confirm within 2 mo
160-179	100-109	Evaluate or refer to source of care within 1 mo
al80	allO	Evaluate or refer to source of care immediately or within 1 wk depending on clinical situation

Furthermore, people with high normal blood pressure (130-139/85-89 mmHg) are at greater risk of developing definite hypertension and of experiencing cardiovascular events than the general population. These increased risks should be clearly explained to patients in order to reinforce the need for periodic remeasurement of blood pressure.

Measurement of blood pressure outside of the health care setting by the patient or a friend, relative, or coworker is useful in making or ruling out a diagnosis of hypertension and in following the course of the blood pressure, whether or not antihypertensive treatment is administered. Self-measurement of blood pressure has the particular advantages of distinguishing sustained hypertension from “white coat” hypertension and of enhancing the active role of the patient in his or her own care, thus fostering adherence to treatment. The upper limit of normal for home blood pressure is generally set at 135/85 mmHg.

Strategies for enhancing adherence to antihypertensive treatment

Despite its obvious benefits, antihypertensive treatment, whether by lifestyle modification and/or drug administration, is frequently not embraced with enthusiasm by the patient. The reasons for nonadherence to antihypertensive treatment are many, and include the asymptomatic and chronic nature of high blood pressure; the adverse effects of many antihypertensive drugs; the sense of deprivation engendered by lifestyle modification, particularly when dietary restrictions are involved; the cost of medication and other aspects of care, e.g., clinic visits and special diet and exercise programs; and failure of the provider to communicate the benefits of successful treatment and the risks of nonadherence to prescribed therapy. Other barriers to care, such as changes in provider, long waiting times, and restrictions in reimbursement for diagnostic procedures, also contribute to the problem of nonadherence.

In usual medical practice, low patient adherence seriously undermines the effectiveness of antihypertensive therapy. At each step, from detection through long-term follow-up, large numbers of patients drop out of care: up to 50% fail to follow through with referral advice, more than 50% of those who begin treatment drop out of care within 1 yr, and 50-70% of new treatments are changed or discontinued within the first 6 mo in most practices. The initial choice of antihypertensive drug is an important determinant of adherence to therapy, independent of the cost of the medication. For example, examination of all outpatient prescriptions (more than 3 million) for antihypertensive drugs filled in the Canadian province of Saskatchewan over the period 1989-1994 revealed that 41% of 27,364 newly diagnosed hypertensive patients stopped treatment during the study period. The likelihood of stopping was significantly related to the class of the initial agent — greatest for diuretics and smallest for angiotensin-converting enzyme inhibitors. Even for those who remained compliant, fewer than half remained on the initial agent throughout the period of the study (4+ yr). Because Saskatchewan Health funds the prescription drug plan for the province, the cost of medications did not appear to play a role in either the physician’s choice of drug or the patient’s decision about whether or not to continue therapy. What was important was the number of changes in the drug regimen and the class of initial agent chosen. Patients whose prescriptions were changed frequently were less likely to adhere to the regimens prescribed. Further, angiotensin-converting enzyme inhibitors performed better than diuretics, β-blockers, or calcium channel blockers, presumably because they were better tolerated. The angiotensin receptor blockers, which appear to have an even better tolerabil-ity profile, were not available at the time of this study.

The Losartan Effectiveness and Tolerability (LET) study was a 16-wk prospective, open label, randomized study that compared a three-step losartan/hydrochlorothiazide (hydrochlorothiazide) regimen (50 mg of losartan titrated to 50 mg of losartan + 12.5 mg of hydrochlorothiazide and to 50 mg of losartan + 25 mg of hydrochlorothiazide) plus additional medications, as needed, to a usual care regimen. Enrollees included 2616 outpatients in community care sites who required a switch in antihypertensive therapy owing to either uncontrolled blood pressure (82%) or intolerable adverse effects (18%). Primary end points included the percentage of patients reaching goal blood pressure (< 140/90 mmHg) and the frequency of medication switches. Secondary end points were the percentage of patients reaching goal blood pressure without a switch and the frequency of adverse effects for each treatment group. Blood pressure control rates were identical (66%) in both groups, but medication switches were significantly less frequent in the losartan group (113/1303, 9%) than in the usual care group (303/1313, 23%) (p < 0.001). Figure 32-3 summarizes the adverse effects of medications for the two treatment groups. Note that the antihypertensive drugs used by the usual care group after the initial switch included calcium channel blockers (35%), angiotensin-converting enzyme inhibitors (25%), β-blockers (9%), diuretics (±another agent) (8%), and other classes (22%); twenty-six percent of patients taking losartan received other medications, and only 9% were switched to another class. The investigators concluded that the losartan regimen was as effective as usual care in controlling blood pressure, required fewer switches, and had fewer adverse effects. They hypothesized that if better tolerabil-ity translates into better compliance and persistency, a losartan regimen may result in better long-term hypertension control than usual care with the older classes of drugs. Further study is needed to determine whether the hypothesis is correct and whether the benefits seen with the losartan regimens are also seen with other members of the ARB class. When selecting antihypertensive drug therapy, it is extremely important to consider tolerability and the likelihood that the patient will adhere to the prescribed regimen over time. The cost of poorly tolerated therapy, which often involves changes in the drug program, includes payments for additional clinic visits and laboratory tests, supplemental/ alternative drugs, and treatment of adverse effects. These costs tend to be higher for patients treated with diuretics and β-blockers than with the newer classes of antihypertensive drugs. In one study conducted in a tertiary care hypertension clinic, charges generated for 1 yr after an antihypertensive drug was changed were recorded.

Table Suggestions for Increasing Patient Compliance with Antihypertensive Therapy

Educate patient about hypertension and the importance of following prescribed drug regimen.

Schedule follow-up appointment during office visit and reconfirm by telephone.

Prescribe the drug regimen least likely to result in adverse effects.

Choose the least costly regimen likely to be effective.

Prescribe a once-a-day regimen, if feasible.

Simplify drug regimen by using a fixed-dose combination product.

Track attendance.

Monitor for achievement of blood pressure goal.

Reward/acknowledge progress toward goal.

Inquire about compliance obstacles.

Collaborate with patient in devising new treatment strategies.

Diuretic or β-blocker therapy was changed in 122 of 357 patients, compared with 44 of the 270 given the newer classes of drugs during 4+ yr of follow-up. Per-patient charges generated in switching from diuretic or β-blocker therapy were $1333 ± 130 (mean ± SEM) over the next year, compared with $1017 ± 126 for patients switching from other antihypertensive drugs (p < 0.001). Most of the charges were the result of additional clinic visits to monitor blood pressure and laboratory parameters. Additional expenses such as the cost of time off from work and transportation were not included in the analysis. Thus, the cost of antihypertensive therapy includes much more than that of drug acquisition alone. The economic burden of poor blood pressure control, with attendant target organ damage and cardiovascular events, may ultimately involve disability payments, hospital costs, and payments to physicians and other health care providers for the treatment of advanced cardiovascular disease.

Strategies that enhance adherence and improve patient outcomes must involve both patient education and behavioral modification. Evidence-based approaches that have been shown to be helpful in maximizing long-term adherence to antihypertensive regimens include educating the patient and his or her family about high blood pressure and its treatment, individualizing the regimen, providing feedback to the patient, and promoting social support. With respect to medications, it is reasonable to individualize antihypertensive treatment based on each patient’s personal needs with respect to tolerability, convenience, and quality of life. Initiation of treatment with a drug that is expected to be well tolerated and therefore likely to be effective in lowering blood pressure over time is prudent. Long-acting agents are preferable because adherence to therapy and consistency of blood pressure control are superior with once daily dosing. Low-dose, fixed-dose combination therapy can be used in place of monotherapy as initial treatment or as an alternative to adding a second agent of a different therapeutic class to unsuccessful monotherapy. The advantage of this approach is that low doses of drugs that act by different mechanisms may have additive or synergistic effects on blood pressure with minimal dose-dependent adverse effects. Single-tablet dosing provides an additional benefit. The pairing of pill taking with daily habits, such as brushing teeth or shaving, helps minimize missed medication. Furthermore, compliance packaging such as blister packaging helps patients remember when to take their medication and to note errors in pill taking. Self-monitoring of blood pressure at home and/or at work increases patient involvement and ties adherence to a successful treatment outcome — blood pressure lowering.

Whenever possible, multidisciplinary teams that address patients’ specific needs and concerns and provide follow-up and feedback should be utilized. This multilevel approach, in which patients, providers, and health care organizations/systems take part, is needed to optimize adherence. Provision of reminders, outreach, and follow-up services is useful. Many of these functions can be carried out by nurses and/or office assistants and by the pharmacists who dispense the patients’ medications. Vigilant counseling and surveillance by an interested pharmacist concerning timeliness of prescription refills and possible drug-drug interactions can greatly enhance the quality of antihypertensive treatment.

Strategies for improving blood pressure control

Data from NHANES III indicate that approx 50% of patients under treatment for hypertension are uncontrolled (blood pressure > 140/90 mmHg). When the more stringent blood pressure goals recommended for diabetics (<130/ 85 mmHg) and patients with renal dysfunction and proteinuria (125/ 75 mmHg) are taken into account, control rates are even lower. The reasons are complex, but are most commonly related to patient nonad-herence to therapy (previously discussed), and inadequate and inappropriate therapy. Secondary hypertension is a less common (<5% of cases overall) but nevertheless important cause of uncontrolled hypertension, and it is potentially curable.

Table  Reasons for Lack of Responsiveness to Hypertension Therapy²

Nonadherence to therapy	Drug-related causes	Associated conditions	Volume overload
Cost of medication and related care	Doses too low	Increasing obesity	Inadequate diuretic therapy
	Inappropriate combinations (e.g., two centrally acting adrenergic inhibitors)	Alcohol intake >1 oz of ethanol/d
Instructions not clear and/or not given to the patient in writing			Excess sodium intake
		Sedentary lifestyle	Fluid retention from reduction of blood pressure
	Rapid inactivation (e.g., hydralazine, oral clonidine [Catapres], captopril [Capoten], short-acting calcium channel blockers	Sleep apnea
Failure of physician to increase or change therapy to achieve blood pressure goals			Progressive renal damage
			Secondary hypertension
Inadequate or no patient education	Drug interactions: glucocorticoids, mineralocorticoids, NSAIDS, tyramine and Monamine oxidase inhibitors, appetite suppressants, phenothiazines, oral contraceptives, sympathomimetics, antidepressants, adrenal steroids, nasal decongestants, cocaine, cyclosporine (Sandimmune, neoral), erythropoietin
Lack of involvement of the patient in the treatment plan
Side effects of medication
Organic brain syndrome (e.g., memory deficit)
Inconvenient dosing schedule

Because definitive diagnosis and treatment of these conditions can be technically difficult and operator dependent, referral to a hypertension specialist is recommended in cases of suspected secondary hypertension.

Most hypertensive patients are undertreated; that is, they are receiving inappropriately low doses of individual antihypertensive drugs or too few drugs. For example, in the Hypertension Optimal Treatment (Hypertension Optimal Treatment) study, mean blood pressure on enrollment was 161/98 mmHg on a one-(-60% of participants) or two- (-30% of participants) drug regimen, whereas at the end of the study, blood pressure was well controlled (mean = 142/ 83 mmHg) on a regimen that required two or more drugs in 52% of cases. Clearly, the choice of initial monotherapy, which receives so much attention in the literature and in commercial promotions, is less important than administering appropriate drug combinations in adequate doses because (1) blood pressure can be controlled with monotherapy in fewer than 50% of patients, and (2) all of the major classes of antihypertensive drugs appear to be similarly effective in lowering blood pressure in persons with stage 1 hypertension and without target organ damage.

Underdosing of antihypertensive drugs can be minimized if physicians become familiar with one or two drugs in each class and follow the manufacturer’s recommendations for their use. Doses should be titrated upward until blood pressure is controlled or the maximal recommended dose is reached, in the absence of dose-related adverse effects. A drug from another class that has additive or synergistic effects with the first drug should then be added. Addition of a diuretic, even in very low doses, potentiates most other classes of drugs, and adding an angiotensin-converting enzyme inhibitor to a calcium channel blocker both increases efficacy and reduces some of the dose-related adverse effects, principally peripheral edema, of the calcium channel blocker. In general, combining multiple drugs from the same class or drugs that share a common mechanism of action should be avoided. Angiotensin-converting enzyme inhibitor β-blocker combinations do not have additive antihypertensive effects, and β-blocker a-agonist combinations are undesirable because their antihypertensive effects are not additive and because of a potential for paradoxical hypertension and rebound hypertension on drug withdrawal. Unless the patient has symptoms or signs of accelerated hypertension, the interval between dose adjustments or addition of new drugs should be 4 wk or longer, because this much time is necessary for any dose of antihypertensive medication to reach its full therapeutic benefit.

Fixed-dose combination therapy offers the advantages of improved patient adherence, by decreasing the number of pills that must be taken, and enhanced tolerability, by reducing the dose-dependent adverse effects of individual components. To be combined in a single-dose form, each component in the combination must contribute to blood pressure lowering, and the dosage of each component must be such that the combination is safe and effective in a majority of the target population. The antihypertensive effects of individual components can be additive or synergistic. In some cases, one component of the combination attenuates the adverse effects of the other; for example, angiotensin-converting enzyme inhibitors blunt diuretic-induced metabolic abnormalities and calcium channel blocker-induced sympathetic nervous system activation. Furthermore, the cost of fixed-dose combination therapy is frequently less than that of individual components. Most fixed-dose combinations contain one or even two diuretics (one for natriuresis, the other for potassium sparing) since diuretics enhance the efficacy of the other classes of antihypertensive drugs.

Short-acting antihypertensive agents, including dihydropyridine calcium channel blockers such as capsular nifedipine (Adalat, Procardia), oral clonidine (Catapres), and captopril (Capoten) should be avoided because of the need for frequent dosing, leading to noncompliance. These agents, with the exception of captopril, also tend to activate the sympathetic nervous system, leading to unstable blood pressure control and periods of rebound hypertension at the end of the dosing interval.

Diuretics are a critical component of multidrug antihypertensive regimens, because volume overload is the most common cause of resistant hypertension in patients who adhere to prescribed therapy. Avoidance of foods high in salt and increased consumption of foods high in fruits, vegetables, and low-fat dairy products, which contain micronutrients that reduce the pressor effect of concomitant salt intake, are also helpful in reducing volume overload. Thiazide diuretics are more effective than loop diuretics in lowering blood pressure in patients with normal renal function, whereas loop diuretics are needed to control both blood pressure and volume in patients with renal dysfunction (serum creatinine > 3 mg/dL; glomerular filtration rate < 30 mL/min).

Comorbid conditions

The majority of hypertensive patients have comorbid conditions and other cardiovascular risk factors and/or target organ damage that may dictate their antihypertensive drug therapy. Compelling indications for initial drug choices from specific classes are based on randomized clinical trials. These recommendations indicate that a drug from a specific class should be included in the antihypertensive regimen unless contraindicated, not necessarily be administered as monotherapy. Because of the aggressive nature of target organ damage in these conditions, particularly diabetes and renal dysfunction, a multidrug regimen is usually needed to lower blood pressure and prevent the progression of renal disease and cardiovascular events. Furthermore, the level of blood pressure control appears to be more important than the choice of drug in determining outcome. For example, the United Kingdom Prospective Diabetes Study showed that tight blood pressure control was associated with a 24% reduction in diabetes-related end points compared to usual control, independent of the choice of antihypertensive drug (atenolol- and captopril-based regimens were equally effective).

In conditions in which angiotensin-converting enzyme inhibitors are recommended first-line agents, such as congestive heart failure, diabetes, and myocardial infarction, angiotensin receptor blockers are being tested in clinical trials as alternative or substitution therapies. In view of the excellent tolerability of this new class of antihypertensive drugs, they may add greatly to our ability to control blood pressure, even in hypertensive patients with TOD and comorbid conditions.

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