Classification of Hypertension
The relationship between blood pressure
levels and cardiovascular risk is continuous and direct, and this makes any
numerical definition and classification of hypertension arbitrary, the
guidelines committee has stressed. Any numerical definitions must be flexible,
resulting from evidence of risk and availability of effective and well-tolerated
drugs. Since no new epidemiologic evidence has emerged since 1999, the WHO/ISH
classification (also that of JNC 6, but not JNC 7) has been retained (Table 1),
with the reservation that the threshold for hypertension must be considered as
flexible -- ie, higher or lower based on the total (global) cardiovascular risk
profile of each individual. Accordingly, the definition of high-normal blood
pressure includes values that may be considered as high (ie, hypertensive) in
high-risk individuals or acceptable in those at lower risk.
Table 1. WHO/ISH Definition and
Classification of Blood Pressure Levels
Category
|
Systolic (mm Hg)
|
Diastolic (mm Hg)
|
Optimal
|
< 120
|
< 80
|
Normal
|
120-129
|
80-94
|
High-normal
|
130-139
|
85-89
|
Hypertension:
|
|
|
Grade 1 (mild)
|
140-159
|
90-99
|
Grade 2 (moderate)
|
150-179
|
100-109
|
Grade 3 (severe)
|
>/= 180
|
>/= 10
|
Isolated systolic hypertension
|
>/= 140
|
< 90
|
According to the guidelines, when a
patient's SBP and DBP levels fall into different categories, the higher
category should apply. Moreover, in older patients with isolated systolic
hypertension, the blood pressure can also be assessed as grades 1, 2, and 3,
according to SBP values in the ranges indicated, provided diastolic values are
< 90 mm Hg.
In another departure, the ESH committee believes
that use of the term "hypertension" should be avoided in classifying
blood pressure, and instead used only to promote the case for tight blood
pressure control. Notably, they avoid and do not support the term
"prehypertension," as used in JNC 7, although they point out that
they were not aware of the term when the new European guidelines were prepared.
Total Cardiovascular Risk
Total (global) cardiovascular risk makes
up an important part of the new guidelines. The committee points out that
hypertension is often accompanied by other risk factors. Total cardiovascular
risk quantification allows more accurate prognostic evaluation of the patient.
The timing and type of antihypertensive treatment depend on this profile, and
the blood pressure threshold and targets for therapy are modified, and the need
for accompanying antihypertensive treatment modulated, by it.
Because of this, the classification using
stratification for total cardiovascular risk has been expanded from the scheme
in the 1999 WHO/ISH guidelines to indicate the added risk in some groups of
individuals with normal or high blood pressure (Table 2).
Table 2 Stratification of Risk to
Quantify Prognosis
Other Risk Factors and Disease History
|
Blood Pressure
|
|
Normal
|
High-normal
|
Grade 1
|
Grade 2
|
Grade 3
|
No other risk factors
|
Average risk
|
Average risk
|
Low added risk
|
Moderately added risk
|
High added risk
|
1-2 risk factors
|
Low added risk
|
Low added risk
|
Moderate added risk
|
Moderate added risk
|
Very high added risk
|
>/= 3 risk factors, TOD, or diabetes
|
Moderate added risk
|
High added risk
|
High added risk
|
High added risk
|
Very high added risk
|
ACC
|
High added risk
|
Very high added risk
|
Very high added risk
|
Very high added risk
|
Very high added risk
|
ACC = associated clinical conditions; TOD
= target organ damage
The total level of risk is the main
indication for intervention, but lower or higher pressure values are also more
or less stringent indicators for blood pressure-lowering intervention. The
terms "low added," "moderate added," "high
added," and "very high added" risk are calibrated to indicate an
approximate absolute 10-year risk of cardiovascular disease of < 15%, 15% to
20%, 20% to 30%, and > 30% added risk, respectively, according to Framingham
criteria, or an absolute risk of fatal cardiovascular disease of < 4%, 4% to
5%, 5% to 8%, and > 8%, respectively, according to the SCORE (Systemic
Coronary Risk Evaluation) chart. The word "added" is used because it
accounts for an increase in relative risk and, for example, could negate the
misleading impression that patients at "low risk" are below average
risk (they are actually at low added risk).
The most common risk factors for
cardiovascular disease used for stratification are:
1.
Levels of SBP/DBP
2.
Men aged > 55 years
3.
Women aged > 65 years
4.
Smoking
5.
Dyslipidemia
Total cholesterol > 6.5 mmol/L (> 250 mg/dL)
or
LDL-cholesterol > 4.0 mmol/L (> 155 mg/dL)
or
HDL-cholesterol :
Men: < 1.0 mmol/L (< 40 mg/dL);
Women: < 1.2 mmol/L (< 48 mg/dL)
6.
Family history of premature cardiovascular
disease (men < 55 years, women < 65 years)
7.
Abdominal obesity (abdominal circumference
>/= 102 cm [40 in] in men, 88 cm [35 in] in women)
8.
C-reactive protein >/= 1 mg/dL
Obesity is defined as abdominal obesity
to draw attention to an important sign of the metabolic syndrome (carrying
extra weight may not be a problem, unless it is all carried around the
abdominal girth). C-reactive protein was added after increasing evidence
pointed to its value as a predictor of cardiovascular events; it has been shown
to be as reliable a predictor as LDL-cholesterol levels, and because of CRP's
association with the metabolic syndrome.
The importance of target organ damage
(TOD) for determining overall cardiovascular risk is also emphasized. The
practicing physician should seek evidence for organ involvement, including
electrocardiogram/echocardiogram investigations for left ventricular (LV)
hypertrophy, ultrasound evidence of arterial wall thickening or atherosclerotic
plaque, slight increase in serum creatinine, and microalbuminuria.
Other factors the guidelines points to as
influencing prognosis are the presence/absence of diabetes mellitus and of
associated clinical conditions, including cerebrovascular disease, heart
disease, renal disease, peripheral vascular disease, and advanced retinopathy.
Goals of Treatment
The primary goal of treatment is to
achieve the maximum reduction in the long-term total risk of cardiovascular
morbidity and mortality. On the basis of current evidence from trials, blood
pressures should be lowered to < 140/90 mm Hg at least, and, if tolerated,
to levels < 130/80 mm Hg in diabetic patients.
Therapeutic Approach
The guidelines for initiating
antihypertensive treatment are based on 2 criteria:
1.
The total level of cardiovascular risk
(Table 2), and
2.
SBP and DBP levels (Table 1).
The total level of cardiovascular risk is
the main indication for intervention, but lower or higher blood pressure values
are also less or more stringent indicators for blood pressure-lowering
intervention.
Recommendations for individuals with high
normal blood pressure (SBP 130-139 or DBP 85-89 mm Hg on several occasions)
include:
1.
Assess other risk factors, TOD
(particularly renal), diabetes, associated clinical conditions
2.
Initiate lifestyle measures and correction
of other risk factors or disease
3.
Stratify absolute risk:
Very high/high: begin drug treatment
Moderate: monitor blood pressure frequently
Low: no blood pressure intervention
Recommendations for individuals with grades
1 and 2 hypertension (SBP 140-179 mm Hg or DBP 90-109 mm Hg on several
occasions) include:
1.
Assess other risk factors (TOD, diabetes, associated
clinical conditions)
2.
Initiate lifestyle measures and correction
of other risk factors or disease
3.
Stratify absolute risk
Very high/high: begin drug treatment promptly
Moderate: monitor BP and other risk factors for >/=3 months:
-- SBP >/= 140 or DBP >/= 90 mm Hg: begin drug treatment
-- SBP < 140 or DBP < 90 mm Hg: continue to monitor
Low: monitor BP and other risk factors for 3-12 months:
-- SBP >/= 140 or DBP >/= 90 mm Hg: consider drug treatment and elicit
patient's preference
-- SBP < 140 or DBP < 90 mm Hg: continue to monitor
Recommendations for individuals with grade
3 hypertension (SBP >/= 180 or DBP >/= 110 mm Hg on repeated
measurements within a few days):
1.
Begin drug treatment immediately.
2.
Assess other risk factors, TOD, diabetes, associated
clinical conditions.
3.
Add lifestyle measures and correction of
other risk factors or diseases.
Lifestyle Changes
Lifestyle measures recommended include
smoking cessation, weight reduction, reduction of excessive alcohol intake,
physical exercise, reduction of salt intake, and increase in fruit and
vegetable intake and decrease in saturated and total fat intake.
Choice of Antihypertensive Agents
The guidelines stress that the main
benefits of antihypertensive therapy are due to the lowering of blood pressure
per se. They list the standard major classes of antihypertensive agents
suitable for the initiation and maintenance of therapy:
1.
Diuretics
2.
Beta-blockers
3.
Calcium channel blockers (CCBs)
4.
ACE inhibitors
5.
Angiotensin-receptor blockers (ARBs).
Regarding a final class, alpha-adrenergic
receptor blockers, the arm of the only trial testing an alpha-blocker (the
doxazosin arm of ALLHAT) was terminated early, for an excess of cardiovascular
events. Although the termination has been criticized, evidence favoring
alpha-blockers as antihypertensive therapy is more scanty than evidence of the
benefits of other antihypertensive agents. Nevertheless, alpha-blockers should
be considered as a therapeutic option, particularly for combination therapy.
In direct contrast to JNC 7, the European
guidelines refrain from recommending specific classes of drugs as initial
treatment; nevertheless, the guidelines recognize that there is evidence to
support variable effects of specific drug classes on special subsets of
patients. These include the elderly, pregnant women, diabetic patients;
patients with concomitant cerebrovascular disease, coronary heart disease, or
congestive heart failure; deranged renal function; or resistant hypertension.
Specific indications are given for the major classes of antihypertensive drugs
(Table 3).
Table 3. Indications for the Major
Classes of Antihypertensive Drugs
Drug
|
Conditions Favoring Use
|
Diuretics (thiazide)
|
CHF; elderly; ISH; hypertensives of
African origin
|
Diuretics (loop)
|
Renal insufficiency; CHF
|
Diuretics (antialdosterone)
|
CHF; post MI
|
Beta-blockers
|
Angina pectoris; post MI; CHF
(up-titration); pregnancy; tachyarrhythmias
|
CCBs (dihydropyridine)
|
Elderly; ISH; angina pectoris;
peripheral vascular disease; carotid atherosclerosis; pregnancy
|
CCBs (verapamil, diltiazem)
|
Angina pectoris, carotid
atherosclerosis; supraventricular tachycardia
|
ACE inhibitors
|
CHF; LV dysfunction; post MI;
nondiabetic nephropathy; type 1 diabetic nephropathy; proteinuria
|
ARBs
|
type 2 nephropathy; diabetic
microalbuminuria; proteinuria; LV hypertrophy; ACE inhibitor cough
|
Alpha-blockers
|
BPH; hyperlipidemia
|
ARBs, angiotensin receptor blockers; BPH,
benign prostatic hyperplasia; CCBs, calcium channel blockers; CHF, congestive
heart failure; ISH, isolated systolic hypertension; MI, myocardial infarction;
LV, left ventricular
Finally, if, in the judgment of the
physician, treatment can proceed with a single pharmaceutical agent, it is
recommended that monotherapy be started gradually in most patients.
Combination Therapy
In direct contrast to JNC 7, the European
guidelines state that emphasis on a preferred class of drugs for
"first-line therapy" is probably outdated, given the need to use 2 or
more drugs in combination in order to achieve goal blood pressure. Taking into
account baseline blood pressure and the presence or absence of complications,
the guidelines recommend initiating therapy either with an adequate dose of a single
agent or with a low-dose combination of 2 agents.
Drug combinations found to be effective
and well tolerated include:
1.
Diuretic and beta-blocker
2.
Diuretic and ACE inhibitor or ARB
3.
CCB (dihydropyridine) and beta-blocker
4.
CCB and ACE inhibitor or ARB
5.
CCB and diuretic
6.
Alpha-blocker and beta-blocker
7.
Other combinations (eg, with centrally
acting agents, including alpha2-adrenoceptor agonists and
imidazoline-I2 receptor modulators, or ACE inhibitors or ARBs) can
be used, if necessary.
8.
In many cases, 3 or 4 drugs may be
necessary.
There are advantages and disadvantages
associated with both monotherapy and combination therapy, the guidelines state.
A disadvantage of combination therapy is the potential exposure of patients to
unnecessary drugs, but control of blood pressure and its complications is more
likely. Use of low-dose combinations are more likely to be free of side
effects, and fixed-dose combinations available in Europe are likely to have the
practical advantage of optimizing compliance. The decision as to which approach
should be prescribed in which patients will likely depend on the initial blood
pressure, risk factors, and the presence or possibility of TOD.
Other Aspects of the Guidelines
As well as detailed sections on treatment
of special populations, other hypertension treatment areas covered in the
guidelines include the present status of genetic analysis, relative benefits of
ambulatory/home blood pressure, follow-up strategies, the importance of
long-acting agents, evaluation of adverse effects, and
implementation/compliance/adherence. Treatments for associated risk factors
include lipid-lowering agents, antiplatelet therapy, and glycemic control.
Implementation of Guidelines
The importance of closing the gap between
experts' recommendations and the poor blood pressure control seen in European
medical practice is emphasized in the new guidelines. It is hoped that
translations of the guidelines into the many European languages will be
sanctioned by the national hypertension societies and leagues, so that the
guidelines can be widely disseminated to improve blood pressure control in
Europe.
hemorrhagic fever (EHF)
which is a disease of humans and other primates. Symptoms start two days to
three weeks after contact with the virus. Symptoms area fever, sore throat, muscle
pain, and headaches. Typically nausea, vomiting, and diarrhea follow, along
with decreased functioning of the liver and kidneys. Around this time, affected
people may begin to bleed both within the body and externally.
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