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Evidence-Based Treatment of Hypertension

By Sandra Lookinland, PhD, RN, and Renea L. Beckstrand, PhD, RN


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Objectives: The purpose of this article is to educate nurse practitioners about new guidelines for the diagnosis and
treatment of hypertension. After reading this article, the nurse practitioner should be able to:
Describe the incidence of uncontrolled and controlled hypertension in the United States and the desired end
point for systolic and diastolic pressures.
Compare and contrast lifestyle modifications as a nonpharmacologic treatment for hypertension.
Identify antihypertensive drugs that should be chosen for specific conditions or situations (compelling
reasons).
Discuss the treatment rationales for older patients, African Americans and patients with diabetes.
Hypertension (HTN) is considered a disease of civilization because of the higher incidence of blood pressure
elevation in developed countries. In non-urban areas, people ingest less salt, lead less sedentary lifestyles and are
less obese. With geographical shifts from small, cohesive, supportive groups to a larger and disorganized urban
environment, the incidence of HTN increases. As people age, systolic blood pressure (SBP) continues to rise and
diastolic blood pressure (DBP) decreases and then plateaus, contributing to the development of isolated systolic
hypertension.
1
A systolic pressure higher than 140 mm Hg contributes more to cardiovascular disease (CVD) risk
than diastolic pressure in people older than 50. With aging, a normal decline in glomerular filtration rate occurs.
Lowering blood pressure is the most important intervention to slow the renal consequences.
2

Incidence
Even though HTN is the most common reason for an office visit, only 53% of patients with identified HTN are being
treated with prescription medications today.
3
Of those being treated, only 29% have their blood pressure under
control (< 140/90 mm Hg ).
4
Patients with a systolic pressure between 120 mm Hg and 139 mm Hg and a diastolic
pressure of 80 mm Hg to 89 mm Hg are now considered prehypertensive. More than 50 million hypertensive
Americans are thus at increased risk for cardiovascular disease, with many more poised to enter that category
because they are prehypertensive.
5
As blood pressure rises above 115/75 mm Hg, the risk of CVD doubles for every
increment of 20/10 mm Hg.
What End Point?
For years, a myth persisted that an elevated SBP (100 + the patient's age) was a normal response to aging and was
necessary to perfuse vital organs.
6
The belief probably originated because of the adverse side effects associated with
the rapid, pharmacologically-induced lowering of blood pressure in the elderly compared to today's method of "start
low, go slow." During aging, elastin is replaced, causing increased arterial stiffness and decreased vascular
compliance and resulting in higher mortality in patients with untreated isolated systolic hypertension. Currently the
emphasis for management has shifted to pulse pressure (> 60 mm Hg to 70 mm Hg) as a better indicator of arterial
stiffening.
7,8
Whether a decreased blood pressure (intermediate measure) translates into a lower cardiac morbidity
and mortality (health outcome) over time remains unknown.
JNC 7 Guidelines
A committee representing the National Heart, Lung and Blood Institute has published treatment guidelines every few
years to guide providers who treat hypertensive patients. The seventh JNC report (JNC 7), originally scheduled for
release in 2001, was suspended until the ALLHAT trial (Antihypertensive and Lipid-Lowering treatment to prevent
Heart Attacks) was completed in 2002 and includes evidence from hypertension outcome studies published between
January 1997 and April 2003.
9

The report from the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood
Pressure was published in May.
10
These latest guideline changes were prompted by the findings of recent clinical
trials and observational studies, as well as the need to simplify the classification of blood pressure. Research
continues to demonstrate that providers are not using past JNC guidelines to the fullest when controlling blood
pressure. The most startling recommendation based on evidence from clinical trials is that patients with blood
pressures between 120/80 mm Hg and 139/89 mm Hg are considered prehypertensive and should be encouraged to
make lifestyle modifications to reduce their CVD risk. This modification in the guidelines was based on findings from
the Framingham study.
11
Subjects in the prehypertensive blood pressure range were twice as likely to become
hypertensive as subjects with lower values.
11
This article summarizes the evidence-based recommended goals for
hypertension contained in JNC 7.
Measurement of Blood Pressure
To reduce the high morbidity and mortality associated with cardiovascular disease, elevated blood pressure must be
identified and treated. Adequately controlled blood pressure has recently been associated with a 50% reduction in
heart failure, 25% reduction in myocardial infarction, and a 35% reduction in stroke incidence.
12
The blood pressure
classification system recommended in JNC 7 is shown in Table 1. Blood pressure measurement on a routine basis
offers the best "view" of a patient's typical vascular pressure.
The recommended technique for measuring blood pressure assures the recording of valid information upon which to
base clinical decisions. Patients should not ingest caffeine or smoke cigarettes for at least 30 minutes prior to an
office visit. They should sit quietly in a chair for 5 minutes with an arm at heart level before blood pressure is
measured. After waiting 2 minutes, the provider should take a second reading and average the result with the first. If
the two measurements differ by more than 5 mm Hg, additional measurements need to be taken and averaged. JNC
7 states that the goal for uncomplicated hypertension remains at < 140/90 mm Hg. The American Diabetes
Association and the National Kidney Foundation have set a goal for patients with diabetes or renal disease at <
130/80 mm Hg.
13,14

White-Coat Hypertension
Patients should routinely monitor their blood pressure outside the office to diagnose so-called white-coat
hypertension. White-coat hypertension exists when a patient's out-of-clinic or ambulatory blood pressure is normal
but his or her in-clinic blood pressure is persistently high. This definition is used to delineate a group of clinically
hypertensive patients with normal blood pressures outside the office setting.
15

White-coat hypertension is more common in the elderly, and particularly in older women who have been diagnosed
as hypertensive. The office blood pressure of elderly patients is, on average, 5 mm Hg higher than their ambulatory
blood pressure. Further, with increasing age, the mean difference between office and ambulatory blood pressure
readings continues to increase. This trend in elderly patients suggests that white-coat hypertension may not be the
benign condition it was once thought to be.
16

Other indications for ambulatory blood pressure monitoring include unexplained drug resistance, hypotensive
episodes while on antihypertensive medications, episodic hypertension, and autonomic dysfunction. Remember that
ambulatory readings are usually lower than those recorded in the office, even though they have been associated with
target organ damage.
17

Preventive Measures
Lifestyle modifications are necessary for patients with documented hypertension to lower blood pressure, enhance
the action of antihypertensive medications, and decrease cardiovascular risk. In light of the current epidemic of
obesity, encourage weight reduction in the general population to prevent future hypertension in these patients.
Nonpharmacologic Treatments
Dietary Sodium. Higher amounts of ingested sodium chloride have been associated with elevated blood pressure in
salt-sensitive patients. These include older patients, African Americans and patients with diabetes. Current
international guidelines recommend limiting salt intake to 2,400 mg sodium daily. Most people in industrialized
countries ingest at least twice that amount.
The hypotensive effects of angiotensin-converting enzyme (ACE) inhibitors and diuretics are dependent on lowered
sodium intake.
18
The Dietary Approaches to Stopping Hypertension (DASH) study demonstrated that decreasing
sodium intake (1,600 mg daily) and eating a diet rich in fruit, vegetables and low-fat dairy products can lower blood
pressure equivalent to antihypertensive monotherapy.
19

Alcohol Ingestion. Excessive ingestion of alcohol can cause patients to be resistant to therapy and greatly increase
the risk for stroke. JNC 7 recommends that hypertensive patients limit their intake to no more than 1 ounce (30 mL) of
ethanol daily. This translates into 2 ounces of 100-proof whiskey, 10 ounces of wine or 24 ounces of beer. Women or
lightweight people should not exceed 0.5 ounces of alcohol intake daily because of their susceptibility to the
detrimental effects of alcohol.
Electrolytes. Diets high in potassium, calcium and magnesium are associated with lower blood pressure
levels.
20
Diets rich in vegetables, fresh fruits and low-fat dairy products are recommended. The JNC 7 panel
recommends maintaining an adequate dietary intake of calcium but found no rationale for recommending calcium or
magnesium supplementation as a means to lower blood pressure.
Miscellaneous Dietary Factors. JNC 7 places much less emphasis on diet than the previous JNC report. However,
other studies have suggested that Omega-3 fatty acids, ingested in large amounts, can lower blood pressure.
Caffeine may acutely raise blood pressure, but tolerance develops quickly and most studies report no direct
relationship between hypertension and caffeine ingestion.
Smoking. Each smoked cigarette produces significant elevations in blood pressure, so strongly encourage all patients
to stop smoking. Hypertensive patients who continue to smoke while taking antihypertensive therapy may not be as
protected from cardiovascular disease as those who do not smoke.
Exercise. Blood pressure decreases with regular aerobic exercise. Hypertension risk is 20% to 50% higher in
sedentary people. Daily brisk walking for 30 minutes on most days of the week is recommended to lower blood
pressure.
10

Treatment Recommendations
If a patient does not reach goal blood pressure using lifestyle modifications, initiate pharmacologic treatment. Start
younger patients at the lowest recommended dose and older adults at half the normal dose. Research shows that
once-daily dosing improves adherence and decreases costs. More recent evidence suggests that twice-daily dosing
may provide for smoother blood pressure control and offer protection for the early waking hours, when an increased
risk of heart attack, stroke and sudden death occur. Perhaps one of the reasons that so few hypertensive patients
have their blood pressure under control is that most require two or more antihypertensive medications to achieve
blood pressure goals. In fact, if a patient's initial blood pressure is 20/10 mm Hg above goal, treatment with two drugs
is now the recommended initial therapy.
Before initiating therapy, order lab tests to evaluate the possibility of target organ damage. The recommended tests
are listed in Table 2. The Figure 1 accompanying this article provides suggested initial drug choices (Algorithm for the
Treatment of Hypertension on page 38).
How Low Should You Go?
Although research has shown that lowering SBP to less than 160 mm Hg is markedly beneficial, no trial has directly
measured the degree of additional benefit associated with lowering SBP to less than 140 mm Hg.
21
A DBP of 70 mm
Hg may be necessary to reach the needed reduction in SBP. In elderly patients, the lowered level of DBP is not
associated with an increase in cardiovascular risk as long as blood pressure is lowered slowly.
Treatment of Older Adults
A stepped care regimen is recommended for older patients. The question of which elderly need to be treated was
answered recently. Even patients older than 79 benefit strongly from antihypertensive drug therapy, dispelling the
myth that therapy should be withheld in this age group.
22-26

Diuretics are considered the initial drug of choice for uncomplicated hypertension in all patients, since they reduce the
numbers of cardiac events (27%), heart failure (55%) and stroke (37%) in both sexes.
21
In clinical trials evaluating the
prevention of cardiovascular complications, diuretics surpassed other expensive drugs.
23
In fact, the JNC 7 guidelines
suggest that thiazide diuretics be used as first-line therapy for most patients with hypertension, either alone or in
combination with other antihypertensive drugs. JNC 7 offered a list of other antihypertensive drugs that could be used
as initial therapy for patients who had compelling reasons to add other antihypertensive drugs.
In a comparison of three major classes of antihypertensive drugs, elderly diabetic patients treated with ACE inhibitors
had lower rates of both coronary disease and heart failure (Table 3).
27
Recently, the angiotensin receptor blocker
losartan (Cozaar, Hyzaar) outperformed the gold standard combination of diuretic and beta-blocker in reducing
cardiovascular morbidity and mortality even though the blood pressure was reduced to the same level in both
groups.
28

Lowering DBP to 80 mm Hg had the most profound effect in older diabetics. The group who took low-dose aspirin
reduced their risk of an acute myocardial infarction by 36%.
29
Monotherapy with beta-blockers is not recommended
since the ALLHAT study found that doxazosin (Cardura) was associated with a 25% greater risk of a cardiac
events.
30
Target both SBP and DBP when treating elderly patients up to the age of 85. Unfortunately, prescribing
practices do not follow the latest evidence-based guidelines.
31

Patients with Diabetes
The JNC 7 guidelines target hypertensive patients with particular co-morbidities for special treatment. Patients at
higher risk for CVD are considered to have compelling indications for use of certain antihypertensive drug classes
(Table 4). One of these special targeted groups is patients with diabetes.
The target blood pressure goal for diabetics has been lowered to 130/80 mm Hg to prevent macrovascular
complications through maintenance of tight blood pressure control.
32-34
The best choice of drug therapy is still under
investigation, but enough evidence is available to guide practice. Thiazide diuretics, beta-blockers, ACE inhibitors,
angiotensin-receptor blockers and calcium-channel blockers all reduce CVD and strokes in diabetics.
23,35-36
Lowering
the DBP to a goal of 80 mm Hg through the administration of a dihydropyridine calcium channel blocker (CCB) with
the addition of one or two other drugs as needed results in significant reduction in cardiovascular events and overall
mortality.
29

Regardless of the drug chosen, diabetic patients seem to benefit more from blood pressure control than their non-
diabetic counterparts.
35-37
Low doses of diuretics (12.5 mg to 25 mg) are safe and useful for diabetics since they act
synergistically with other drugs, minimize electrolyte abnormalities and reduce the fluid retention common in
diabetics.
35
When researchers compared ACE inhibitors to other drugs prescribed for type 2 diabetics, reductions in
blood pressure were similar, but ACE inhibitors were superior at reducing acute coronary events and being
renoprotective.
27,35,38
Researchers recently concluded that an angiotensin-receptor blocker (irbesartan, marketed as
Avapro) was superior to a calcium channel antagonist (amlodipine, marketed as Lotrel and Norvasc) in slowing the
progression of nephropathy in type 2 diabetics even though target blood pressures were similar among groups.
39

Beta-blockers are often not prescribed because they have been associated with decreased glucose tolerance.
However, beta-blockers may be more beneficial to diabetics than ACE inhibitors.
33
Remember, two or three drugs are
often necessary to achieve the target goal of 130/80 mm Hg in diabetics.
African Americans
African Americans are at high risk for hypertension-related complications. They have a higher prevalence of
hypertension, including stage 3 disease. African Americans with stage 3 hypertension have high levels of target
organ damage, resulting in a 59% higher mortality from cardiac events, 80% higher stroke mortality rate, and six
times greater risk for end-stage renal disease.
40
African Americans have physiologic characteristics that contribute to
this risk:
low circulating renin with excessive levels of angiotensin II
more likely to have the salt-sensitive gene
endothelial dysfunction as a result of reduced bradykinin and nitric oxide
abnormal sympathetic nervous system activation
higher levels of intracellular calcium stores
higher incidence of obesity (60% of African-American women).
41-43

With sodium restriction, hypertensive African Americans exhibit a greater decline in SBP than hypertensive
whites.
44
Salt sensitivity is an issue since sensitive patients require higher doses of ACE inhibitors, angiotensin-
receptor blockers and beta-blockers. Even though this effect is attenuated with calcium channel antagonists, higher
doses are required.
45-46

Because of a higher prevalence of stage 3 hypertension among African Americans, few can reach target blood
pressure with a single drug. All antihypertensive drugs lower blood pressure in this population if adequately dosed,
but JNC 7 recommends that diuretics and calcium channel antagonists be considered the first drugs of choice.
47
In
one study, ramipril (Altace), an ACE inhibitor, was better than amlodipine, a calcium channel antagonist, at retarding
renal disease in blacks with non-diabetic nephropathy and proteinuria, whereas a calcium channel antagonist was
more effective in patients with severe hypertension.
48
Drugs that block the renin-aldosterone-angiotensin system,
such as ACE inhibitors and angiotensin-receptor antagonists, offer a benefit by protecting target organs and slowing
disease progression in this at-risk population.
49

NSAID Use and Hypertension
Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently prescribed classes of medications for
the treatment of arthritis and other pain conditions. Approximately 30 million people use NSAIDs daily.
50
At least 12
million of the people who take NSAIDS for arthritis also concurrently receive treatment for hypertension.
51

NSAIDs work by inhibiting the enzyme cyclooxygenase (COX), thus limiting prostaglandin production. By inhibiting
prostaglandin production, the pathologic effects of inflammation, such as pain and fever, are relieved.
52

NSAIDs can cause hypertension and edema because of the inhibition of vasodilatory prostaglandin
production.
53
NSAIDs have been associated with blood pressure elevations of 3 mm Hg to 6 mm Hg.
54-55
JNC 7
identifies NSAIDs as one of the drug-induced causes of resistant hypertension. The effect of NSAID use on blood
pressure, however, is not consistent with all drugs in this class.
56
When the newer COX-2 inhibitors were studied,
rofecoxib (Vioxx) was associated with an increase in nighttime systolic and diastolic blood pressure. This pattern
caused the disappearance of the physiologic diurnal variation, however, daytime arterial blood pressure did not
change. Nabumetone (Relafen) was associated with an increase in both day and night blood pressure without any
effect on the diurnal variation.
56
Blood pressure increases to the greatest degree with use of indomethacin (Indocin)
and piroxicam (Feldene), but research shows that no increase in blood pressure occurs with ibuprofen use by
normotensive subjects.
57

Overall Recommendations
Rigorous control of blood pressure protects against left ventricular hypertrophy, which can result in heart failure.
Blood pressure burden is calculated as the percentage of blood pressure > 140/90 mm Hg during waking hours and
blood pressure > 120/90 mm Hg during sleeping hours. If the percentage exceeds 50%, the incidence of left
ventricular hypertrophy rises to 90%.
1

Nurse practitioners and other primary care providers need to become familiar with one or two drugs in each class of
antihypertensive medications and follow the recommended doses used in study trials cited in JNC 7. Since
monotherapy is effective in only 50% of patients with hypertension, many will require a regimen of two to three drugs.
The goal of treatment is to titrate drug dosages upward until either the blood pressure is under control or the
maximum dosage is reached (unless untoward side effects occur). At this point, add a drug from another class that
has synergistic effects.
The interval between dosage adjustments should not be shorter than 4 weeks, unless the patient has accelerated
hypertension. If a patient's blood pressure remains elevated after you have prescribed the maximum dose of three
classes of drugs, refer him or her to a hypertension specialist.
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Sandra Lookinland is a nurse with a PhD who is a professor in the College of Nursing at Brigham Young University in
Provo, Utah. She has taught pathophysiology to NP students for nearly 10 years. Renea Beckstrand is a nurse with a
PhD who is an associate professor in the College of Nursing at Brigham Young University. She is also certified in
critical care nursing. <% footer %>