Lifestyle factors
Observational studies have identified several environmental factors associated with hypertension, and prospective studies have demonstrated BP lowering with manipulation of these factors [see Table 8].4849 51,54,55,57-6" In addition to lowering BP, lifestyle recommendations are designed to reduce overall CV risk. These measures should be advised for all patients with BP above the normal level. Tobacco use should be discouraged because, in addition to being a powerful CV risk factor, each cigarette smoked elevates BP for 15 to 30 minutes, and multiple cigarettes can raise BP for most of the day. A new device that facilitates deep-breathing exercises (Desperate) has been shown to low-er BP and can be considered as an adjunct to lifestyle and drug treatments.61
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Table 8 Lifestyle Modifications for Hypertension Prevention and Management |
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Lose weight if overweight |
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Reduce sodium intake to s 100 mmol/day (2.4 g sodium, 6 g salt) |
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Increase aerobic exercise (30-45 min/day) |
|
Limit alcohol intake to no more than 1 oz (30 ml; e.g., 24 oz of beer, 10 oz of wine, 2 oz of 100-proof whiskey) or to 0.5 oz for women and lighter-weight people |
|
Maintain adequate intake of potassium (90 mmol/day) |
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Ingest a diet rich in fruits and vegetables and low-fat dairy products but reduced in saturated and total fat (e.g., Dietary Approaches to Stop Hypertension [DASH] diet) |
|
Discontinue tobacco use |
Pharmacologic treatment
The JNC 7 report recommends thiazide diuretics as initial drugs of choice for most patients; this recommendation is based on the totality of data from randomized trials, including the An-tihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).8,62-64 Critics of diuretics have cited evidence suggesting that diuretic-based treatment does not provide protection from coronary artery disease events to the degree predicted from epidemiologic studies. The ALLHAT was designed to determine whether treatment with a diuretic would be inferior to treatment with an alpha blocker, a calcium antagonist, or an ACE inhibitor in preventing fatal and nonfatal coronary artery disease events in a high-risk group of adults with essential hypertension. The study showed no difference among the drugs for the outcome of fatal and nonfatal coronary artery disease or total mortality. Moreover, diuretic treatment was superior to alpha blocker, calcium antagonist, or ACE inhibitor treatment with some CV disease outcomes. The alpha-blocker arm of the trial was terminated early because of an almost twofold increase in the risk of heart failure compared with the diuretic group. On the basis of these results, alpha blockers are no longer considered an appropriate initial therapy for hypertension. Compared with the diuretic group, the calcium antagonist group also had a higher risk of heart failure. Compared with the diuretic group, the ACE inhibitor group had an increased risk of stroke and combined CV disease, but much of the increased risk occurred in blacks, in whom BP control with the ACE inhibitor was inferior to the control achieved with the diuretic.
Alternative medications should be considered if diuretics are contraindicated or are poorly tolerated or there is a compelling indication for a drug from a different class. Alternative drug choices are beta blockers, ACE inhibitors, ARBs, and calcium antagonists.
A subsequent study contradicted the results of ALLHAT and suggested that ACE inhibitors are superior to diuretics in older men.65 In truth, differences in outcomes by drug choice likely reflect differences in achieved BP rather than unique effects of specific agents.66 Therefore, achieving the BP goal is more important than the specific agents used to achieve it.
Randomized clinical trials suggest that the presence of certain comorbid conditions constitutes a so-called compelling indication for selection of specific drugs [see Table 9]. Other considerations that should influence drug selection include concomitant conditions for which some agents may be beneficial and others contraindicated [see Tables 9 and 10], potential drug-drug interactions, concerns about quality of life, cost (generic formulations are available for diuretics, beta blockers, calcium antagonists, and ACE inhibitors), and, finally, demographics (in general, older patients and blacks respond better to diuretics and calcium antagonists, whereas younger patients and whites respond better to beta blockers, ACE inhibitors, and ARBs). In general, the drug chosen should have a long half-life (once-daily dosing is preferable). It should be continued only if the patient tolerates it and is comfortable with its cost, because these are important factors in long-term compliance. To achieve currently recommended goal BP levels, many patients will require more than one drug; this possibility should be discussed at the outset with the patient. Regardless of the agent chosen, BP should be reassessed after 2 to 4 weeks of treatment [see Figure I].
Combination Therapy
The JNC 7 report suggests initiation of therapy with two drugs (combination therapy) rather than a single agent if BP is more than 20 mm Hg systolic or 10 mm Hg diastolic above the treatment goal.8 Generally, a two-drug regimen should include a diuretic appropriate for the level of renal function. An increasing number of antihypertensive combination products are available in a number of dosing options.8 Although combination products may be more convenient, it is often less expensive to use individual agents, because generic drugs are frequently available. In addition, titration of doses of the two agents may be easier when the two drugs are prescribed separately. Once BP control is achieved with given doses of two agents, switching to the same therapy in combination form can be considered.
The advantages and disadvantages of using combination products have been reviewed.67 Caution is advised when using combination therapy in older persons and diabetic patients, because of the increased risk of precipitous declines in BP or aggravation of orthostatic hypotension.
Improving Control Rates
In general, significant progress has been made in lowering BP in patients with hypertension. Although the proportion of patients with BP lower than 160/95 mm Hg has increased significantly since the 1970s, the percentage of patients with controlled hypertension (defined as systolic BP maintained below 140 mm Hg and diastolic BP, below 90 mm Hg) remains low. It is estimated that control of hypertension was accomplished in 31% of patients for the period from 1999 to 2000.1 This is well below the Healthy People 2010 goal of at least 50% of patients achieving control. It is commonly believed that the major factors responsible for lower control rates are lack of access to health care and patient noncompliance and believed that the population of patients with uncontrolled hypertension comprises disproportionately large numbers of ethnic and racial minorities. However, studies suggest that other factors are also important. Analyses of the Third National Health and Nutrition Examination Survey (NHANES III) identified factors associated with the likelihood both of attaining control of hypertension and of failing to attain control.68 Factors associated with an increased likelihood of controlling hypertension included being married (greater social support), having private health insurance, visiting the same health care facility or having the same provider over time, having had BP measured within the previous 6 to 11 months, and using lifestyle modifications in the treatment program. On the other hand, factors associated with an increased likelihood of uncontrolled hypertension included being 65 years or age or older, being male, being black, and failing to see a physician in the preceding year. Interestingly, not having health insurance or not having a source of health care was not predictive of uncontrolled hypertension.
Most cases of uncontrolled hypertension occur in older persons and represent mild ISH (systolic BP, 140 to 160 mm Hg).69 In a study of self-reported treatment practices among primary care physicians, 43% of physicians would neither start drug therapy for a patient whose systolic BP is between 140 and 160 mm Hg nor intensify treatment for a patient whose systolic BP is 158 mm Hg.70 In this same study, 41% of the care givers were unfamiliar with national hypertension guidelines. In a further analysis, familiarity with the guidelines lowered the provider’s BP treatment threshold. Other studies of physician practices have shown similar results.
Table 9 Patient Condition and Choice of Antihypertensive Drugs
|
Conditions |
Drug Choice |
|
No comorbid conditions |
Diuretics |
|
Isolated systolic hypertension (elderly patients) |
Diuretics (preferred), calcium antagonists (DHP)* |
|
Angina |
Beta blockers,* calcium antagonists (non-short-acting DHP) |
|
Angina (with diabetes or LV dysfunction) |
ACE inhibitors’ (in addition to beta blockers and calcium antagonists) |
|
Atrial fibrillation |
Beta blockers,* calcium antagonists (rate limiting)*’ |
|
Cough with ACE inhibitors |
ARBs* |
|
Diabetes mellitus type 1 with proteinuria |
ACE inhibitors*; calcium antagonists (non-DHP); diuretics, beta blockers’ |
|
Diabetes mellitus type 2 with proteinuria |
ARBs*‘; calcium antagonists (non-DHP)‘; diuretics, beta blockers‘ |
|
High risk of type 2 diabetes |
ACE inhibitors‘ |
|
Essential tremor |
Beta blockers (noncardioselective)‘ |
|
Heart failure, LV dysfunction |
ACE inhibitors, beta blockers, diuretics, aldosterone antagonists*; ARBs‘; generally, an ACE inhibitor is first choice, ± a beta blocker in asymptomatic patients; diuretic used to treat congestion; aldosterone antagonist used only in advanced disease in combination with other agents; ARB should not be used in patients on an ACE inhibitor and beta blocker [see 1:II Heart Failure] |
|
High risk of cardiovascular disease or type 2 diabetes |
ACE inhibitor‘ |
|
Hyperlipidemia |
Alpha blockers (not considered first-line therapy)‘ |
|
Intolerance to other antihypertensive drugs |
ARBs‘ |
|
Left ventricular hypertrophy (by ECG) |
ARBs‘ |
|
Migraine |
Beta blockers (noncardioselective), calcium antagonists (non-DHP)‘ |
|
Myocardial infarction |
Beta blocker (non-ISA) most often drug of choice, with ACE inhibitor added if LV function impaired*; aldosterone antagonist can be added to standard therapy in patients with LV dysfunction*; diltiazem (non-Q wave infarction)’; verapamil’ |
|
Osteoporosis |
Thiazide diuretics‘ |
|
Peripheral vascular disease |
Calcium antagonists‘ |
|
Preoperative hypertension if at increased cardiovascular risk |
Beta blockers‘ |
|
Previous stroke |
Diuretic + ACE inhibitor*; ACE inhibitor as monotherapy had no effect on BP or outcome; benefit noted only with combination that lowered BP |
|
Prostatism |
Alpha blockers (not considered first-line therapy)‘ |
|
Renal insufficiency with proteinuria from any cause |
ACE inhibitors, ARBs, calcium antagonists (non-DHP)‘ |
^Compelling indication.
+Specific indication.
ACE—angiotensin-converting enzyme
ARB—angiotension II receptor blocker
DHP—dihydropyridine
ISA—intrinsic sympathomimetic activity
LV—left ventricle
Emerging from these studies is the realization that a major factor in continued poor control rates for hypertension is a tolerance by the health care provider of elevated systolic BP, especially in older patients. On the basis of these study results, health care providers should consider steps to improve control rates in their practice [see Table 11].
Refractory/resistant hypertension
Studies conducted to determine what causes resistant hypertension have used different definitions of the term. In most studies, hypertension was considered resistant or refractory if control was not achieved with a combination of lifestyle modifications and the rational use of full therapeutic doses of two or three anti-hypertensive medications, one of which was a diuretic appropriate for the level of renal function. Studies suggest five issues to consider when evaluating patients with resistant hypertension42: noncompliance with therapy, interfering substances, an inappropriate drug regimen, office hypertension or pseudohypertension, and secondary hypertension. In most cases, causative factors will be identified if these five issues are given careful attention.
Noncompliance
Lack of BP control often results from noncompliance with the drug regimen or diet. Common reasons for noncompliance with drug therapy include drug costs, side effects, complex dosing schedules, and inadequate follow-up. Patients are reluctant to admit noncompliance with drug treatment, so a high degree of vigilance is required. Asking an open-ended question such as, "Many people have problems remembering their drug schedule; do you?" is occasionally effective.
Table 10 Contraindications to Antihypertensive Drugs
|
Class of Drug |
Possible Contraindications |
Compelling Contraindications |
|
Diuretics |
Dyslipidemia (high doses), allergy to sulfa-based antibiotics, patient is sexually active man, diabetes mellitus (high doses) |
Gout, allergy to sulfa-based diuretics |
|
Beta blockers |
Bronchospastic disease (asthma, COPD, noncardioselective agents), dyslipidemia (non-ISA agents), severe peripheral vascular disease, athletes |
Bronchospastic disease (noncardioselective agents) second- or third-degree heart block |
|
ACE inhibitors, ARBs |
Renovascular disease (bilateral renal artery stenosis), renal insufficiency |
Pregnancy, hyperkalemia |
|
Calcium antagonists |
Second- or third-degree heart block (non-DHP agents); heart failure (except amlodipine, felodipine) |
|
|
Alpha blockers |
Postural hypotension |
Urinary incontinence |
|
Reserpine |
Peptic ulcer, nasal allergy |
Depression |
|
Methlydopa |
Liver disease |
— |
|
Labetalol |
Liver disease |
— |
|
Central alpha agonists |
Depression, sleep disorders |
— |
ACE—angiotensin-converting enzyme
ARBs—angiotensin receptor blockers
COPD—chronic obstructive pulmonary disease
DHP—dihydropyridine
ISA—intrinsic sympathomimetic activity
Clues to noncom-pliance include failure to keep follow-up appointments or renew prescriptions, or complaints about the cost of drugs or side effects. Certain drugs are expected to cause findings on the physical examination or laboratory evaluation. An absence of these findings may indicate noncompliance. Examples are slowing of the heart rate with beta blockers, electrolyte changes with diuretics, or dry mouth with clonidine. Noncompliance with a low-salt diet can also be important. A high-salt diet can interfere with the effectiveness of almost all of the currently used antihypertensive drugs.
Interfering Substances
Certain prescription drugs, over-the-counter medications, herbals, and street drugs can raise BP or interfere with the BP-lowering effect of antihypertensive drugs [see Table 5]. Taking a complete medication history and asking patients to bring in all their medication bottles is essential for identifying interfering substances. Alcohol abuse should also be considered, because in addition to its physiologic effects, alcohol abuse is often associated with poor compliance and lack of BP control.
Inappropriate Drug Regimens
The drug regimen should be carefully reviewed. Full therapeutic doses of drugs should be employed. In general, it is preferable to use drugs that have complementary actions and that work by interfering with different BP regulatory pathways. In compliant patients, inadequate control of extracellular volume is the most common cause of resistant hypertension.71 Extracellular volume expansion tends to occur as BP is lowered and is a secondary effect of some drugs (e.g., centrally acting sympatholytics in modest doses and some direct vasodilators). In patients with renal dysfunction, impaired renal excretion of sodium often is an important factor in raising BP. Thiazide diuretics are often ineffective when serum creatinine is higher than 2.0 mg/dl or creatinine clearance is less than 30 ml/min. In such patients, loop diuretics are required.
Figure 1 Overview of drug treatment for hypertension.
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Table 11 Considerations for Improving Blood Pressure Control Rates |
|
Become familiar with national guidelines (set a BP goal with the patient) |
|
Schedule regular follow-up visits |
|
Recommend self-monitoring of BP (involve patients in the treatment process) |
|
Measure BP at every follow-up office visit and articulate a treatment recommendation if BP is above goal (be more aggressive, especially with systolic hypertension in older patients) |
|
Emphasize lifestyle factors as part of the treatment program (involve patients in the treatment process); review progress and barriers at each visit |
|
Use adequate doses of antihypertensive drugs; be willing to use multiple drugs |
|
Encourage communication regarding medication costs and side effects |
|
Be aware of poor control rates in men and African Americans |
For patients on multidrug regimens, the lack of a diuretic or the use of low doses of short-acting loop diuretics given only once daily may explain the resistant state. In some patients with renal disease, combinations of loop agents and thiazide diuretics are required to control volume.
