Tracy Wolff, MD, MPHa, and Therese Miller, DrPH.a
Address correspondence to: Drs. Wolff and Miller, U.S. Preventive Services Task Force Program, Agency for Healthcare Research and Quality, 540 Gaither Road, Rockville, MD 20850.
This article was first published in the Annals of Internal Medicine. Select for copyright and source information.
Contents
Abstract
Introduction
Methods
Results
Conclusion
References
Notes
Background: High blood pressure is common, and screening is
a well-established evidence-based standard of current medical
practice.
Purpose: To perform a literature search for new, substantial evidence
on screening for high blood pressure that would inform the
reaffirmation of the U.S. Preventive Services Task Force recommendation
on screening for high blood pressure.
Data Sources: The PubMed® and Cochrane databases were
searched. The searches were limited to English-language articles on
studies of adult humans (age >18 years) that were published
between 1 October 2001 and 31 March 2006 in core clinical
journals.
Study Selection: For the literature on benefits, meta-analyses; systematic
reviews; and randomized, controlled trials were included.
For harms, meta-analyses; systematic reviews; randomized, controlled
trials; cohort studies; case–control studies; and case series of
large, multisite databases were included. Two reviewers independently
reviewed titles, abstracts, and full articles for inclusion.
Data Extraction: No new evidence was found on benefits or harms
of screening. Two reviewers extracted data from studies on the
harms of early treatment, including adverse effects of drug therapy
and adverse quality-of-life outcomes.
Data Synthesis: No new evidence was found for the benefits of
screening for high blood pressure. New evidence on the harms of
treatment of early hypertension shows that pharmacologic therapy
is associated with common side effects; serious adverse events are
uncommon.
Limitations: The nonsystematic search may have missed some
smaller studies on the benefits and harms of screening and treatment
for high blood pressure.
Conclusion: No new evidence was found on the benefits of
screening. Pharmacotherapy for early hypertension is associated
with common side effects.
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Introduction
Hypertension is usually defined in adults as systolic
blood pressure of 140 mm Hg or higher or diastolic
blood pressure of 90 mm Hg or higher.1 Data from
NHANES III (Third National Health and Nutrition Examination
Survey) suggest that an estimated 43 million
U.S. adults older than 25 years have hypertension and that
hypertension is more common in African American and
elderly persons than in other groups. In the United States,
hypertension is responsible for 35% of myocardial infarctions
and strokes, 49% of episodes of heart failure, and
24% of premature deaths. Additional complications of
hypertension include end-stage renal disease, retinopathy,
and aortic aneurysm.2-4
In 2006, the U.S. Preventive Services Task Force
(USPSTF) decided to reexamine the evidence in order to
reaffirm its 2003 recommendation on screening for high
blood pressure (or hypertension). The Task Force issues a
reaffirmation update for a topic that the USPSTF decides
to keep current because the topic is one of its priorities, is
within its scope, and is a topic for which there is a compelling
reason to make a recommendation. Topics in this
category are well-established evidence-based standards of
current medical practice. The USPSTF decided to perform
a reaffirmation update because the evidence base on hypertension
is strong and only large, high-quality studies would
overturn such a recommendation. Such recommendations
would previously have been an A or D recommendation.
Therefore, we performed a literature search for new, substantial
evidence that would be sufficient to change the
2003 recommendation.
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Methods
The USPSTF developed 2 key questions to be addressed:
1) What are the benefits of screening for high
blood pressure in adults? 2) What are the harms of screening
and/or early treatment of high blood pressure? To determine
whether the benefits of screening for hypertension
continue to outweigh the harms, the USPSTF included
new information on the adverse effects of drug therapy for
"early hypertension" as part of the question on harms.
Data Sources and Searches
We performed nonsystematic literature searches of
PubMed® and the Cochrane Library. We used the following
search terms: hypertension, mass screening, adverse effects,
and false positive results. We limited the searches to English-language
studies of adult humans (age >18 years) that
were published in core clinical journals between 1 October
2001 and 31 March 2006. "Core clinical journals" are a
subset of 120 English-language journals defined by the National Library of Medicine; it was previously known as the
Abridged Index Medicus. We also checked reference lists of
systematic reviews and other studies for possibly relevant
studies.
Study Selection
We included studies on benefits and harms of screening
and treatment of "early hypertension." We understood
"early hypertension" to be blood pressure elevation that
screening could reasonably identify. We defined "early hypertension"
as prehypertension (systolic blood pressure of
120 to 139 mm Hg or diastolic blood pressure of 80 to 89
mm Hg), hypertension detected through screening, or untreated
or newly diagnosed mild to moderate hypertension
(systolic blood pressure of 140 to 180 mm Hg or diastolic
blood pressure of 90 to 110 mm Hg, when information
was not given about how hypertension was detected). We
excluded studies in very high-risk or special populations,
including patients with preexisting cardiovascular disease.
We included studies of nonpregnant adults older than
18 years. We included studies from the United States and
from countries with patient populations that are generalizable
to the United States. For the literature on benefits, we
included meta-analyses; systematic reviews; and randomized,
controlled trials. For harms, we included meta-analyses;
systematic reviews; randomized, controlled trials; cohorts;
case– control studies; and case series of large,
multisite databases. We excluded editorials, case reports,
nonsystematic reviews, and guideline reports.
Data Extraction
No studies were included for data abstraction on the
benefits or harms of screening. For harms of early treatment,
2 reviewers abstracted information on sample size,
entry criteria, demographic characteristics, comorbid conditions,
study design, treatment group allocation, reports
of adverse effects of drug therapy, and quality-of-life outcomes.
Data Synthesis and Analysis
Data from the included studies were synthesized qualitatively
in tabular and narrative formats.
Role of the Funding Source
The work of the USPSTF is supported by the Agency
for Healthcare Research and Quality. No separate funding
was used specifically for this study.
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Results
The search returned 378 potentially relevant titles,
which we entered into a reference database. A total of 341
studies were excluded after title review, 19 studies were
excluded after abstract review, and 13 were excluded after
full article review. We excluded 253 studies that were not
on hypertension, 62 that included a high-risk population,
31 that did not meet study design criteria, 12 that were not
from a U.S. population, 8 that were not done in adults,
and 7 that had no relevant outcomes.
No new studies on the benefits or harms of screening
for high blood pressure met our inclusion criteria. Five
studies evaluated the harms of early treatment of hypertension
and met our inclusion criteria (Table); these are discussed
below.
Three studies presented data on adverse effects related
to antihypertensive drugs. These studies compared outcomes
from treatment of one type of drug versus another
type of drug or placebo. In general, they were multicenter
studies in the United States, Canada, and United Kingdom;
included a predominantly white, male patient sample;
and excluded persons with multiple comorbid conditions
or manifest cardiovascular disease. In addition, 2
studies examined the effects of antihypertensive medications
on quality of life. In these 2 studies, participants with
untreated hypertension were randomly allocated to different
treatment regimens (the second study also included a
placebo group) and followed for effects on quality of life:
sexual dysfunction in one study, and "symptom distress" in
the other study. The study on sexual dysfunction included
men 40 to 49 years of age, and the study on symptom
distress included men and women 50 years of age or older.
In 1 study that gathered data on adverse effects, White
and colleagues studied the effect of bedtime dosing on
early-morning blood pressure in 261 persons who were
randomly allocated to 10 weeks of extended-release diltiazem
or ramipril.5 Adverse effects were reported in 50%
of the diltiazem group and 40% of the ramipril group.
Serious adverse effects were uncommon, and 2 of the 3
reported events were probably not related to the drug: 1
event occurred during placebo run-in, and 1 was associated
with infection. The most common reasons for withdrawal
from the study were lower-extremity edema associated with
diltiazem (3%) and cough associated with ramipril (2%).
Headache was commonly reported in both groups. The
main finding of the study was that diltiazem at bedtime
reduced early-morning blood pressure to a greater extent
than ramipril.
Julius and colleagues compared candesartan with placebo
in participants with systolic blood pressure of 130 to
139 mm Hg and diastolic blood pressure of 89 mm Hg or
less.6 Serious adverse effects were uncommon, occurring
in 3.5% of candesartan recipients and 5.9% of placebo
recipients. However, other, less serious adverse effects were
very common, occurring in approximately 89% of participants
in both the candesartan and placebo groups. Commonly
reported adverse effects in the candesartan group
were headache (22%), upper respiratory infection (14%),
nasopharyngitis (10%), and dizziness (10%).
A third study evaluated the effectiveness in reducing
clinic-measured and ambulatory blood pressure of 4 antihypertensive
agents (doxazosin, amlodipine, enalapril, and
bendrofluazide) in 204 persons with diastolic blood pressure
of 95 to 110 mm Hg.7 The authors reported that
clinic-measured and ambulatory blood pressure decreased in all groups, with no significant differences among them;
the authors did not report data that allowed us to determine
the statistical significance of this comparison. Adverse
effects were very common and did not statistically significantly
differ among treatment groups (overall rate, 74%
[range among groups, 68% to 81%]). Serious adverse effects
were uncommon (overall rate, 11% [range, 6% to
14%]), and the rate of withdrawals due to adverse events
was 11%. The most commonly reported adverse effect was
headache (overall rate, 20% [range, 16% to 25%]).
In 1 study with quality-of-life outcomes, Fogari and
colleagues followed 160 married men 40 to 49 years of age
with newly diagnosed hypertension (diastolic blood pressure
of 95 to 110 mm Hg) who had never been treated for
hypertension and had no symptoms of sexual dysfunction.8 One hundred twenty men were randomly assigned to
receive an angiotensin II receptor antagonist (valsartan) or
a beta-blocker (carvedilol) for 16 weeks, and, after a placebo
washout period, were crossed over to the alternative regimen
for another 16 weeks; 40 men were randomly assigned
to receive placebo. Results indicated that carvedilol caused
a decline in sexual function (the rate of sexual intercourse
decreased by 50%, and 13.5% of patients experienced sexual
dysfunction). Valsartan produced a temporary and
non–statistically significant decline in sexual function, and
function improved with ongoing treatment: By 16 weeks,
the rate of sexual intercourse had increased by 19%. The 2
drugs did not differ in control of blood pressure.
The other study with quality-of-life outcomes evaluated
symptom distress associated with a calcium-channel
blocker (amlodipine) and an aldosterone receptor antagonist
(eplerenone).9 A total of 269 men and women 50
years of age or older with untreated seated systolic blood
pressure of 140 to 190 mm Hg were randomly assigned to
receive 1 of the study drugs after a placebo run-in period.
On average, participants were approximately 68 years of
age, and 89% were white. Participants were followed for
24 weeks; quality-of-life measures were collected at randomization,
14 weeks, and 24 weeks. At 24 weeks, the
groups did not statistically significantly differ in blood
pressure control or scores on the Short Form-36 Health
Survey. However, there was a statistically significant difference
among treatment groups on a summary measure of
symptom distress in favor of eplerenone (P = 0.03). The
amlodipine group experienced symptoms commonly associated
with the drug, including ankle swelling, headache,
facial flushing, and constipation. Twenty-five percent of
amlodipine recipients and 5% of eplerenone recipients experienced
edema. Other adverse events were hyperkalemia
in 2 eplerenone recipients and 1 amlodipine recipient, and
hypokalemia in 2 amlodipine recipients. Erectile dysfunction
was reported by 2 of 61 eplerenone recipients and no
amlodipine recipients.
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Conclusion
In summary, there is no new evidence on the benefits
of screening for high blood pressure. New evidence on the
harms of treatment of early hypertension shows that pharmacologic
therapy is associated with common side effects;
serious adverse events are uncommon.
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References
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5. White WB, Lacourciere Y, Gana T, Pascual MG, Smith DH, Albert KS.
Effects of graded-release diltiazem versus ramipril, dosed at bedtime, on early
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6. Julius S, Nesbitt SD, Egan BM, Weber MA, Michelson EL, Kaciroti N, et
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8. Fogari R, Zoppi A, Poletti L, Marasi G, Mugellini A, Corradi L. Sexual
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Am J Hypertens 2001;14:27-31. [PMID: 11206674]
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Notes
Author Affiliation
a. Drs. Wolff and Miller: U.S. Preventive Services Task Force Program, Agency for Healthcare Research and Quality.
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Disclaimer
The authors of this article are responsible for its contents, including any clinical or treatment recommendations. No statement in this article should be construed as an official position of the Agency for
Healthcare Research and Quality or the U.S. Department of Health and Human Services.
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Copyright and Source Information
This document is in the public domain within the United States. For information on reprinting, contact Randie Siegel, Director, Division of Printing and Electronic Publishing, Agency for Healthcare Research and Quality,
540 Gaither Road, Rockville, MD 20850.
Requests for linking or to incorporate content in electronic resources should be sent to: info@ahrq.gov.
Reprints are available from the USPSTF
Web site (www.preventiveservices.ahrq.gov).
Source: U.S. Preventive Services Task Force. Evidence for the reaffirmation of the U.S. Preventive Services Task Force recommendation on screening for high blood pressure. Ann Intern Med 2007:147(11):787-91.
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Current as of December 2007
Internet Citation:
U.S. Preventive Services Task Force. Evidence for the Reaffirmation of the U.S. Preventive Services Task Force Recommendation on Screening for High Blood Pressure. December 2007. First published in Ann Intern Med 2007:147(11):787-91. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/uspstf07/hbp/hbparticle.htm
540 Gaither Road Rockville, MD 20850