Please note: In 2003, the CTF updated its Grades of Recommendations to include an "I Recommendation" for situations where insufficient evidence exists to allow a recommendation to be made. (Formerly, these situations were captured under a "C Recommendation".) This change is not retroactive, and all "C Recommendations" made prior to 2003 have not been reevaluated in light of the new "I" recommendation grade. For a discussion of these recommendation grades, please link to the 2003 article in the Canadian Medical Association Journal here.
Overview
In 1984 the Task Force recommended that all
persons aged 25 or over should receive a blood pressure (BP) measurement
during any visit to the physician and that antihypertensive therapy should
be limited largely to those with a diastolic pressure of 100 mmHg or greater.<
1> These recommendations were based principally on the results of several
large scale randomized controlled treatment trials of persons with mild
to moderate diastolic hypertension.<2> Since then new data concerning
the diagnosis and treatment of hypertension have been published including
several randomized controlled trials in the elderly.<3> Important gaps
in our knowledge still exist nonetheless; there are, for example, no clinical
trial data on the efficacy of treating diastolic hypertension in persons
under 2 1 years of age or isolated systolic hypertension in those under
60 or over 84 years of age. Hypertension in the elderly is addressed in
Chapter 79 and prevention of preeclampsia in Chapter 13.
Accurate BP measurement by sphygmomanometer in the physicians’ office remains the principal method of diagnosis. There is insufficient evidence to recommend the routine use of echocardiography, self-measurement of BP or ambulatory BP monitoring in diagnosis.<4> While there is good evidence to recommend antihypertensive therapy for young and middle-aged adults with diastolic pressures of 90 mmHg or over, the clinical decision to initiate pharmacologic treatment should take into account the individual’s absolute risk for cardiovascular disease, particularly when the average diastolic pressure is in the range of 90 to 99 mmHg and there is no hypertensive target organ damage or other concomitant diseases.<4,5>
Burden of Suffering
Estimates from several BP surveys over the past
decade suggest that up to 15% of the adult population have definite or
established hypertension and that an almost equal percentage have labile
hypertension characterized by elevations of BP on some, but not all, occasions.<6>
Epidemiological and actuarial studies have repeatedly demonstrated that
cardiovascular morbidity and mortality are substantially higher in hypertensives,
compared with normotensives at all ages and in both sexes. Also, the presence
of mild hypertension is a powerful predictor of progression to more severe
elevations of BP.<7,8> Because hypertension is an important contributor
to the principal cardiovascular diseases which account for more than 40%
of all deaths in Canada,<9> good BP control will have a major beneficial
effect on health care costs.
Epidemiological investigations indicate that with increasing BP levels the excess risk of cardiovascular events in adult men and women increases in a curvilinear manner.<7,8> Hypertension is a major contributor to pressure-related events such as stroke, congestive heart failure and ruptured aortic aneurysm, and a significant risk factor for atheromatous complications such as coronary heart disease and occlusive peripheral arterial disease. Cardiovascular events are as closely linked to systolic as to diastolic pressure elevations, and possibly more so. The absolute risk of cardiovascular disease amongst equally hypertensive individuals varies substantially, depending upon a history of previous cardiovascular disease or the presence of associated risk factors including hypercholesterolemia, cigarette smoking, glucose intolerance, left ventricular hypertrophy, older age, and male gender. Except for individuals with extremely high BP levels, absolute risk is influenced more by these factors than BP level per se.<7> This spectrum of risk is increasingly being taken into account in making treatment decisions,<4,5> since greater benefits in absolute terms are observed among those at higher risk.
Maneuver
The diagnosis of hypertension is the essential
starting point in its management. Methods for accurate diagnosis were set
out in a consensus report of the Canadian Hypertension Society.<2> The
mercury sphygmomanometer is the instrument of choice because of its accuracy
and dependability. The aneroid type should be calibrated twice yearly using
mercury as the standard. Guidelines for sphygmomanometry include: selection
of appropriate cuff size (the rubber bladder should encircle at least 2/3
of the upper arm); measurement should be taken after five minutes of quiet
rest, and with the arm bared, supported and positioned at heart level;
for screening and diagnosis the seated position should be used; if hypertension
is established, subsequent readings should include a lying and standing
measurement. The patient should have refrained from smoking or ingesting
caffeine 30 minutes before measurement. Two or more readings should be
averaged; if the first two differ by more than 5 mm additional readings
should be obtained. If an initial BP is mildly elevated in a person not
previously known to have hypertension, the BP should be reassessed on at
least three occasions over a period of six months. For patients with more
severely elevated pressure readings the interval between repeat assessments
should be shortened.
Echocardiography, self-measured BP and ambulatory BP monitoring are increasingly being used in the evaluative process and may provide useful information in special circumstances. Nonetheless there is insufficient evidence at the present time to warrant their routine use in diagnosis.<3>
Effectiveness of Prevention
The results of many randomized clinical trials
of antihypertensive drug therapy on morbidity and mortality from cardiovascular
disease in patients with hypertension of varying severity have been published
over the past 30 years.<10> The early trials of antihypertensive therapy
demonstrated the efficacy of treating hypertension with initial diastolic
BPs of 90 mmHg or higher.<11-15> Detailed analysis of these trials indicated
that the benefits of active drug treatment accrued principally to those
with more severe hypertension (diastolic pressures of 105 mmHg or over),
those with a cardiovascular or renal abnormality at entry, or those who
were 50 years of age or older.<16> Consensus recommendations at the
time<17> favoured treatment of such individuals and close observation
of those with uncomplicated diastolic pressures of 90 to 104 mmHg, initiating
drug therapy only when there was clear evidence of a trend of rising BP
or of disease progression as demonstrated by adverse changes in target
organs (heart, kidneys, and brain).
More recent studies have focused principally on milder forms of diastolic hypertension in young and middle-aged adults,<18-20> the topic of this chapter, and on hypertension in the elderly.<21-24> The major therapeutic trials in mild hypertension were the American Hypertension Detection and Follow-up Program (HDFP), the Australian National Blood Pressure Study (ANBPS), and the British Medical Research Council (MRC) trial.
The HDFP was a community-based, randomized controlled trial that compared the effectiveness of an intensive, supervised program of specified antihypertensive drug treatment ("stepped care" (SC)) with that of routine therapy obtained by referral of patients to their customary source of medical care in the community ("referred care" (RC)).<18> The 10,940 hypertensive men and women, of whom more than 40% were black, were stratified by BP level, with the majority (71.5%) being in the baseline diastolic BP stratum of 90 to 104 mmHg (stratum 1). The age range of participants was 30 to 69 years. Almost one-quarter of stratum 1 participants were receiving antihypertensive medication at the time of stratum designation, indicating that many had a more severe form of hypertension, and a small percentage at entry had left ventricular hypertrophy (3.5%), history of stroke (2.1%), myocardial infarction (4.8%), or diabetes mellitus (7.0%). The difference in mean diastolic BP of 5 mmHg between the SC and RC groups at the end of this 5-year study was associated with a significant reduction in total mortality, the primary end-point, and deaths from all cardiovascular causes. Secondary analyses revealed similar outcomes in stratum 1 participants including those free of end-organ damage and not taking antihypertensive drugs on entry. White women, however, did not appear to benefit from therapy although the difference in the percentage of individuals receiving treatment between the SC and RC groups was smallest in this subgroup. Because the HDFP did not include an untreated control group, some maintain that the source of care and other factors unrelated to hypertension control were largely responsible for the difference in outcomes. This viewpoint was supported by the marked reduction in deaths from non-cardiovascular causes in the SC group, a finding not observed in the actively treated group in other similar trials.<19,20>
The ANBPS was a randomized, placebo-controlled, single-blind trial involving 3,427 white men and women aged 30 to 69 years with untreated diastolic BPs (phase V) of 95 to 109 mmHg and systolic BPs under 200 mmHg.<19> Participants were virtually free of any cardiovascular disease at entry (0.4% had previous myocardial infarction) and had no diabetes mellitus, stroke history or electrocardiographic evidence of myocardial ischemia. The in-trial average diastolic BP was 5.6 mmHg lower in the actively treated than in the control group and this difference resulted in a significant reduction in trial end-points (death from any cause and non-fatal cardiovascular events). Actively treated women had significantly fewer trial end-points than those in the control group.<25> The number needed to treat for 5 years to prevent one cardiovascular event was 44.
In the British MRC trial, 17,354 men and women, aged 35 to 64 years, having an untreated mean phase vs. diastolic BP of 90 to 109 mmHg and systolic BP under 200 mmHg and free of significant cardiovascular disease (about 2% had left ventricular hypertrophy, electrocardiographic Q wave abnormalities or stroke history) or diabetes mellitus, were randomized in a single-blind fashion to receive active treatment or placebo.<20> The extent of separation between average diastolic pressures in actively treated and control groups was 5 to 6 mmHg. Active treatment significantly reduced the trial end-points (death from any cause and non-fatal cardiovascular events). The rates of stroke and of all cardiovascular events were significantly reduced but treatment had no effect on coronary events. Deaths from all causes were reduced in men on treatment but slightly increased in women. There were no other differences in outcomes by gender. The number needed to treat for 5 years to prevent one cardiovascular event was 141.
Quantitative meta-analyses of the results of these and other smaller trials of anti-hypertensive therapy have been reported<10,26> and the findings compared with data from several prospective observational studies on the effects on stroke and on coronary heart disease of prolonged BP differences of the same size.<10> A reduction in diastolic BP of 5 to 6 mmHg, the observed effect of active treatment in the randomized trials, resulted in a 42% reduction in fatal and nonfatal strokes (95% confidence interval (CI): 33% to 50%) and a 14% reduction in all coronary heart disease (95% CI: 4% to 22%). The expected decline in stroke incidence based on observational data for such a BP reduction was estimated to be 35% to 40%; thus the benefits of therapy were fully realized within three years, the average duration of the clinical trials. In sharp contrast the benefits for coronary heart disease were less than the predicted reduction of 20% to 25% from prospective observational studies. Several explanations for this apparent discrepancy have been posited including a delay in the full attainment of benefit of sustained BP reduction on a predominantly atherosclerotic disease process, adverse effects of treatment, and chance. New data suggest that the type of drug therapy is not responsible for the failure to obtain full coronary heart disease benefit from BP lowering.<22>
Treatment of Hypertension
Diuretics and beta-adrenergic blockers were the
two major classes of drugs used as first-line treatment in most of the
major outcome trials. Medications were generally given in a stepwise sequence
with maximum dosage of a drug being prescribed at each step before the
agent at the next step was added to achieve the treatment goal. A variety
of antihypertensive agents was introduced as additional therapy including
reserpine, alpha-methyldopa, guanethidine, hydralazine and clonidine, agents
which are no longer commonly prescribed.
Fortunately the incidence of serious or life-threatening drug reactions in these trials was rare. Less serious side effects, however, were common, resulting in discontinuation of randomized treatment (almost 20% by the fifth year in the British MRC trial<20>) or a substantial increase in patient discomfort (difference in subjective complaints of approximately 15% between active treatment and placebo groups<12>). In some instances the symptoms were predictable adverse effects associated with a particular class of drug but more often they represented a patient’s idiosyncratic reaction to a drug.
None of the trials employed the newer classes of antihypertensive agents (calcium entry blockers, angiotensin converting enzyme inhibitors, or alpha-adrenergic blockers) or the now common treatment approach of sequential monotherapy. These therapeutic innovations were introduced to reduce drug-related side effects and to circumvent the adverse metabolic consequences of older classes of drugs. The newer agents have been shown to be as effective as diuretics and beta-blockers in lowering BP,<27,28> are well tolerated by most patients, and appear to provide substantial advantages in specific patient groups.<28,29> Nonetheless there are insufficient data on the long-term benefits and risks of these drugs and the comparative advantages over substantially less expensive ‘older’ agents to recommend them as first-line drug treatment. From available evidence it seems likely that the magnitude of benefit from treatment is related to lowering BP per se rather than to any specific property of the various antihypertensive agents. Given the importance of this issue, however, new information is urgently needed.
Several nonpharmacologic measures including weight reduction in overweight subjects, moderation in alcohol consumption, increased physical activity and sodium restriction particularly in sodium-sensitive individuals have been shown in relatively short studies to lower BP in hypertensive patients.<30> No data exist, however, on whether these short-term changes in BP translate into less cardiovascular morbidity and mortality. Generally non-pharmacologic interventions are less effective than drug treatment in lowering BP and their effects on quality of life is quite variable.<31,32> Some measures such as weight loss improve elements of quality of life, whereas others such as sodium restriction may make them worse.<32> Despite the absence of evidence on the long-term safety, acceptability and effectiveness of nonpharmacologic therapy, they are considered a useful starting point for treatment and viewed as important adjuncts to drug therapy.<30>
Decision to Initiate Drug Treatment
There is a continuum of cardiovascular risk associated
with level of BP that extends well down into the arbitrarily defined normal
BP range, beginning for systolic above 110 mmHg and for diastolic above
70 mmHg.<33> Evidence on the benefits of antihypertensive therapy comes
from clinical trials in which treatment categories were defined by BP level
alone.<11-15,18-24> The results indicate that young and middle-aged
patients (ages 21 to 64 years) with diastolic BPs of 90 mmHg or over will
benefit from antihypertensive drug therapy.<10> Despite this demonstration
there has been general reluctance to use BP level alone as the sole determinant
for drug treatment in persons whose average diastolic pressure is in the
range of 90 to 99 mmHg.<4,5,34-37> In these instances the presence of
other cardiovascular disease risk factors or concomitant diseases strongly
influences the decision to initiate drug therapy. Factors generally taken
into account include left ventricular hypertrophy, or cardiovascular, cerebrovascular
or peripheral vascular disease. In addition patients with renal disease,
diabetes mellitus, or hypercholesterolemia, or who smoke cigarettes are
at substantial risk for morbid or fatal cardiovascular events and should
be more aggressively treated. In low-risk individuals, on the other hand,
treatment has focused principally on non-pharmacologic measures to which
drug therapy is added in the event of progression to more severe hypertension
or the development of hypertension-related target organ damage.
This modification of treatment decisions based on epidemiological risk is theoretically attractive and has been adopted in some manner or other by most groups formulating guidelines for clinical practice.<4,5,34-37> Nonetheless this treatment strategy has not been formally evaluated and past experiences with multifactorial intervention trials of primary prevention of cardiovascular disease in high risk subjects generally have been disappointing.<38-40>
Recommendations of Others
Guidelines of most other groups identify two
threshold pressures, one for the diagnosis of hypertension, which for diastolic
pressure is 90 mmHg or higher and for systolic pressure, 140 mmHg or higher,
and one for the initiation of drug treatment based on BP level alone.<4,5,30,34-37>
The drug treatment threshold for diastolic BP alone differs considerably
amongst the guidelines being 90,<30> 95,<35-37> or 100 mmHg.<4>
Most guidelines suggest that factors other than BP should influence the
decision to begin drug treatment of patients with pressures between the
thresholds for diagnosis and routine treatment of hypertension.<4,5,34-37>
There are few differences amongst the guidelines on factors that interact
with hypertension to increase the likelihood of cardiovascular risk and
include older age, male gender, smoking cigarettes, hypercholesterolemia,
diabetes, hypertensive target organ damage, and the presence of cardiovascular
disease. Most guidelines recommend diuretics or beta-blockers as initial
drug therapy for patients in whom there are no specific contradictions;<5,30,34-37,41>
the World Health Organization/International Society of Hypertension guidelines
suggest, however, that any particular class of antihypertensive agent may
be chosen.<35> The primary goal of treatment in most guidelines is a
diastolic BP below 90 mmHg,<4,30,34-37> and even lower levels in certain
situations such as the presence of renal disease in diabetic patients.<30,35,42>
All guidelines recommend a more individualized therapeutic approach in
special circumstances<4,5,30,34-37> although even here the American
Joint National Committee guidelines still tend to favour diuretics and
beta-blockers as initial therapy in most instances.<30>
The Preventive Services Task Force recommends that BP be measured regularly in all persons aged 3 and above.<43>
Conclusions and Recommendations
There is fair evidence to measure BP in young
and middle-aged adults (B Recommendation). Case-finding should be considered
in all persons aged 21 to 64 years; individual clinical judgment should
be exercised in all other cases. Accurate BP measurement by sphygmomanometer
in the physicians’ office remains the principal method of diagnosis. There
is insufficient evidence to recommend the routine use of echocardiography,
self-measurement of BP or ambulatory BP monitoring in diagnosis.
While there is good evidence to recommend antihypertensive therapy for young and middle-aged adults (ages 21 to 64 years) with diastolic pressures of 90 mmHg or over (A Recommendation), the clinical decision to introduce pharmacologic treatment should take into account a person’s absolute risk for cardiovascular disease, particularly when the average diastolic pressure is in the range of 90 to 99 mmHg and there is no hypertensive target organ damage or other concomitant diseases. There is insufficient evidence to evaluate therapy in persons 1) with elevated pressure aged under 21 years; or 2) with isolated systolic hypertension defined as a systolic pressure of 140 mmHg or higher and diastolic pressure less than 90 mmHg.
Unanswered Questions (Research
Agenda)
Important gaps in our knowledge on the management
of hypertension still exist. With respect to diagnosis, the role of echocardiography,
self-measurement of BP and ambulatory BP monitoring needs to be defined.
For example, if persons who demonstrate the ‘white-coat’ phenomenon were
found not to be at increased risk for cardiovascular disease events, treatment
of up to a quarter of the hypertensive population might be avoided. Equally
the early detection of left ventricular hypertrophy by echocardiography
or the demonstration of increasing left ventricular mass may enhance the
specificity of therapeutic intervention.
The benefits and risks of treating diastolic hypertension in persons under 21 years of age, or isolated systolic hypertension in those under 60 or over 80 years of age still needs to be demonstrated. Furthermore large-scale trials of non-pharmacologic measures with clinical endpoints need to be conducted both in persons with hypertension and in those at risk to develop hypertension in the future.
Future management approaches will likely involve genetic testing to detect persons at risk for hypertension. Identification of genetic susceptible individuals should enhance selectivity of primary prevention strategies and raises the possibility of gene therapy.
Evidence
A MEDLINE search was conducted using a MESH heading
hypertension and the subheadings complications, diagnosis, drug therapy,
epidemiology, prevention and control, and therapy for primary papers published
from January 1966 to March 1994. A search was also carried out for review
articles published between 1984 and 1994. References from these papers
were reviewed to identify relevant articles. This review was initiated
in October 1993 and recommendations were finalized by the Task Force in
March 1994.
Full Citation
Logan AG Screening for hypertension in young
and middle-aged adults. In: Canadian Task Force on the Periodic Health
Examination. Canadian
Guide to Clinical Preventive Health Care. Ottawa: Health Canada,
1994; 636-48.