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Blood pressure management in patients with atherosclerotic
cardiovascular disease
Last literature review version 18.2: May 2010 | This topic last updated: June 17, 2010
INTRODUCTION — Hypertension is the most frequent major risk factor for premature
cardiovascular disease (CVD), being more common than cigarette smoking, dyslipidemia, and
diabetes, the other major risk factors. In the INTERHEART study of patients from 52 countries,
hypertension accounted for 18 percent of the population attributable risk of a first myocardialinfarction (MI) [1]. (See "Cardiovascular risks of hypertension".)
The impact of hypertension on the risk of the development of a cardiovascular event such as
myocardial infarction, stroke or cardiovascular death is directly related to the level of blood
pressure. In addition, the majority of individuals with hypertension have one or more other risk
factors [2,3], which augment the cardiovascular risk at any level of blood pressure (figure 1) [4].
The excess risk of a future cardiovascular event attributable to hypertension is greater in
individuals with established CVD, diabetes mellitus, or chronic kidney disease compared to those
at lower risk. The 2003 Seventh Joint National Committee (JNC 7) report on high blood pressure
cited ischemic heart disease, heart failure, diabetes, chronic kidney disease, and cerebrovascular
disease as "compelling indications" for the treatment of hypertension [5]. Other considerations
include peripheral arterial disease and traditional major coronary risk factors such as cigarette
smoking and family history (table 1).
For those patients in whom a decision is made to lower blood pressure, the two most important
issues are the choice of antihypertensive agent(s) and the goal blood pressure (BP). The goal BP
in patients at increased risk for a cardiovascular event will be reviewed here. Goal BP in the
general population and in the specific settings of diabetes, proteinuric chronic kidney disease, and
heart failure are discussed separately. (See "What is goal blood pressure in the treatment of
hypertension?" and "Treatment of hypertension in patients with diabetes mellitus" and
"Antihypertensive therapy and progression of nondiabetic chronic kidney disease" and "Treatment
of hypertension in patients with heart failure".)
The choice of antihypertensive drug, assuming that the patient does not have an indication for a
particular class of drugs, are presented elsewhere. (See "Choice of therapy in essential
hypertension: Recommendations", section on 'Importance of attained blood pressure' and
"Indications and contraindications to the use of specific antihypertensive drugs".)
CLINICAL TRIALS — The benefit of BP reduction in patients at increased risk of a cardiovascular
event has been investigated in a number of major clinical trials. Some of these trials compared an
ACE inhibitor or ARB to placebo, while other trials compared two or more antihypertensive agents,
at least one of which was usually an ACE inhibitor or an ARB.
Based upon trial design, inclusion criteria, and patient population, the degree of blood pressure
lowering varied significantly in these trials. The findings in the major trials will be briefly reviewed
followed by recommendations for the goal BP.
Trials comparing blood pressure goals — Only three large trials, ACCORD BP, Cardio-Sis, and
Official reprint from UpToDate®
www.uptodate.com
©2010 UpToDate®
AuthorsGeorge L Bakris, MDGuy S Reeder, MD
Section EditorsJuan Carlos Kaski, MD, DM,DSc, FRCP, FESC, FACC
Norman M Kaplan, MD
Deputy EditorGordon M Saperia, MD, FACC
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HOT have directly compared blood pressure goals to test the hypothesis that lower attained blood
pressures (below the usual goal of less than 140/90 mmHg) improves patient outcomes. ACCORD
BP and Cardio-Sis, but not HOT, were limited to patients at increased cardiovascular risk other
than hypertension itself. In addition, HOT did not achieve systolic pressures below the usual goal
since the mean attained BP was 140/81 mmHg in the lowest group. As a result, the HOT trial will
not be further discussed here. The best data come from the ACCORD BP trial. (See "What is goal
blood pressure in the treatment of hypertension?", section on 'HOT trial' and "Treatment of
hypertension in patients with diabetes mellitus", section on 'HOT trial'.)
ACCORD BP trial — The ACCORD BP trial randomly assigned 4733 patients with type 2
diabetes who had cardiovascular disease or at least two additional risk factors for cardiovascular
disease to systolic blood pressure targets of either less than 120 mmHg or less than 140 mmHg
[6]. The mean attained blood pressures were 119 and 134 mmHg, respectively, compared to
139/76 mmHg at baseline.
After a mean follow up of 4.7 years, there was no significant difference in the annual rate of the
primary composite endpoint of nonfatal myocardial infarction, nonfatal stroke, or death from
cardiovascular causes (1.87 versus 2.09 percent, hazard ratio 0.88, 95% CI 0.73-1.06). The
annual rate of stroke, a prespecified secondary outcome, was significantly lower in those with a
lower targeted BP (0.32 and 0.53 respectively; hazard ratio 0.59, 95% CI 0.39-0.89). Significantadverse events occurred in significantly more patients in the group assigned to the lower blood
pressure goal (3.3 versus 1.3 percent). ACCORD BP is discussed in detail elsewhere. (See
"Treatment of hypertension in patients with diabetes mellitus", section on 'ACCORD BP trial'.)
Cardio-Sis trial — Cardio-Sis evaluated different blood pressure goals in 1111 patients with a
systolic pressure ≥150 mmHg and at least one additional cardiovascular risk factor but without
diabetes [7]. The patients were randomly assigned to a systolic target of less than 130 mmHg
(tight-control) or less than 140 mmHg (usual-control). The mean attained blood pressures were
132/78 versus 135/79 mmHg. Although the composite secondary outcome occurred significantly
less often in the tight-control group (4.8 versus 9.4 percent; hazard ratio 0.50, 95% CI
0.31-0.79), the benefit was primarily due to a reduction in rates of new onset atrial fibrillation orcoronary revascularization.
Cardio-Sis has important limitations, including a short duration of follow-up (two years), a weak
primary end point that assessed a risk marker (electrocardiographic left ventricular hypertrophy)
not cardiovascular events, and a composite secondary end point that included unusual end points
for a hypertension trial.
Placebo-controlled trials with a mean baseline BP less than 140/90
mmHg — Placebo-controlled trials, such as HOPE, EUROPA, PEACE, CAMELOT, TRANSCEND, and
NAVIGATOR evaluated the hypothesis that ACE inhibitors or ARBs might have a direct and
clinically significant cardiovascular benefit in patients with a mean baseline BP less than 140/90
mmHg. In addition, CAMELOT and ACTION compared long-acting dihydropyridine calcium channel
blockers to placebo.
Some, but not all, of these trials demonstrated benefit from active therapy. However, patients
treated with active therapy also had lower attained blood pressures, which provided another
mechanism than angiotensin inhibition to explain any observed benefits. Some support for the
attained blood pressure being most important came from the CAMELOT trial in which
enalapril and amlodipine produced similar outcomes that were nonsignificantly better than
placebo [8].
The following provides a brief summary of the results of the major trials. In the ACCORD BP trial
described above, an attained systolic pressure of 119 mmHg provided no significantcardiovascular benefit and more drug-induced side effects compared to an attained systolic
pressure of 134 mmHg [6]. This finding is not inconsistent with the following trials that suggest
that an attained systolic pressure between 130 and 134 mmHg may provide better cardiovascular
outcomes than an attained systolic pressure between 135 and 139 mmHg.
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Trials demonstrating benefit — Significant benefit was demonstrated with active therapy
compared to placebo in the following trials:
HOPE trial — The HOPE trial evaluated 9297 patients over the age of 55 who were at high risk
due to prior cardiovascular disease and/or diabetes mellitus with one other coronary risk factor:
at 4.5 years, cardiovascular mortality occurred in 8.1 percent and nonfatal MI in 4.8 percent [9].
The mean BP at entry was 139/79 mmHg. The patients were randomly assigned to ramipril (10
mg once daily) or placebo, given before sleep.
The primary end point was any cardiovascular event (cardiovascular death, MI, or stroke). The
trial was prematurely terminated after a 4.5-year follow-up because ramipril therapy was
associated with the following significant benefits:
- A reduction in the primary end point (14.0 versus 17.8 percent for placebo, relative risk [RR]
0.78, 95% CI 0.70-0.86) (figure 2) and in each of the individual components of the primary end
point, including cardiovascular mortality (6.1 versus 8.1 percent) [9].
- A reduction in nonfatal MI (5.6 versus 7.2 percent) and stroke (3.1 versus 4.5 percent) that
was independent of other therapies, including beta blockers, lipid lowering agents, and
aspirin [10,11].
- These benefits were seen in all subgroups, including women and men and patients with
diabetes [12,13].
(See "Treatment of hypertension in patients with diabetes mellitus".)
The benefit of ramipril in the HOPE trial was initially thought to be independent of its
antihypertensive activity, as the difference between the two groups during the course of the trial
was only 3.3/1.4 mmHg (average 135/76 mmHg with ramipril) [14]. However, the actual
difference in BP was probably substantially greater. Ramipril was given before bedtime and the
office BP was measured about 10 to 18 hours later. In a subset of 38 patients with peripheral
arterial disease, ambulatory monitoring was performed at baseline and at one year [15]. The
24-hour ambulatory pressure was significantly reduced with ramipril, largely due to a more
prominent fall in BP during the night (17/8 mmHg compared to placebo).
EUROPA trial — The EUROPA trial of 13,655 patients with stable coronary heart disease and no
heart failure was similar in design to HOPE except that the patients were at lower risk, with lower
rates of hypertension (27 versus 47 percent), diabetes, and cerebrovascular and peripheral
arterial disease [16]. The mean BP at entry was 137/82 mmHg and only 27 percent had a history
of hypertension.
The patients were randomly assigned to perindopril (8 mg once daily) or placebo. The primary
end point was cardiovascular death, MI, or cardiac arrest. At a mean of 4.2 years, there was a
significant reduction in the primary end point with perindopril therapy (8 versus 10 percent,
relative risk reduction 20 percent, 95% CI 9-29 percent). There was at least a trend toward a
similar benefit in each of the components of the primary end point and the effect was consistent
in all predefined subgroups [17,18]. Perindopril therapy was associated with a BP ofapproximately 128/78 mmHg, a value that was a mean of 5/2 mmHg lower than seen with
placebo.
CAMELOT trial — The CAMELOT trial compared amlodipine (10 mg/day) or enalapril (20
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mg/day) to placebo in 1991 patients with known coronary disease [8]. The primary endpoint was
a composite of cardiovascular death and cardiovascular events. The mean baseline BP was 129/78
mmHg and both amlodipine and enalapril produced greater average reductions in BP than placebo
(4.8/2.5 and 4.9/2.4 versus 0.7/0.6 mmHg). (See "Choice of therapy in essential hypertension:
Recommendations", section on 'Importance of attained blood pressure'.)
Most of the events comprising the primary end point were due to coronary revascularization or
hospitalization for angina, and only these components were significantly reduced by
amlodipine (an antianginal drug) compared to enalapril and placebo. There was a nonsignificant
difference in the rate of "hard" cardiovascular end points (all-cause mortality, nonfatal MI, or
stroke) with amlodipine or enalapril compared to placebo (hazard ratio 0.70 and 0.71,
respectively, compared to placebo, 95% CI 0.41-1.21). A benefit this large, if real, would be
clinically important. However, the upper limit of the confidence interval indicates the possibility of
harm.
Trials showing no benefit — The following trials showed no benefit from active therapy
compared to placebo even though lower blood pressures were attained.
PEACE trial — In the PEACE trial, 8290 patients with stable coronary disease were randomly
assigned to trandolapril (4 mg daily) or placebo [19]. The patients were at lower cardiovascular
risk and were more likely to have been treated with blood pressure and lipid lowering therapy
than the HOPE and EUROPA cohorts. The mean baseline BP in the PEACE trial was 133/78 mmHg.
The primary end point was a composite of cardiovascular death, nonfatal MI, or revascularization.
At 4.8 years, there was no difference in the incidence of the primary end point with
trandolapril compared to placebo (21.9 versus 22.5 percent, hazard ratio 0.96; 95% CI
0.88-1.06) even those there was a greater reduction in mean BP with trandolapril (4.4/3.6 versus
1.4/2.4 mmHg in the placebo group, mean difference 3.0/1.2 mmHg).
The lack of benefit of trandolapril in PEACE may have been due in part to a lower average
baseline BP than in HOPE or EUROPA and more aggressive baseline management of other aspectsof coronary risk (such as coronary revascularization and lipid lowering) that may have mitigated
the benefit of further BP reduction. The net effect was that the rate of cardiovascular death,
nonfatal myocardial infarction, or stroke in the placebo group in PEACE was lower than in the
ramipril and placebo groups in HOPE and in the placebo group in EUROPA and the rate of
all-cause mortality in PEACE was similar to that of an age- and sex-matched cohort from the
general population.
TRANSCEND trial — The TRANSCEND trial randomly assigned 5926 high-risk patients who
were similar to those in HOPE but did not tolerate ACE inhibitors to either telmisartan 80 mg/day
or placebo; the mean baseline blood pressure was 141/82 mmHg [20]. At a median follow-up of
56 months, the mean blood pressure was 4.0/2.2 mmHg lower in the telmisartan group. Despite
this, there was no statistically significant difference between the two groups in the primary
composite outcome of cardiovascular death, myocardial infarction, stroke, or hospitalization for
heart failure (15.7 versus 17.0 percent, hazard ratio 0.92, 95% CI 0.81-1.05). Compared to
HOPE, there was a significantly higher rate of use of statins, beta blockers, and antiplatelet
agents in TRANSCEND.
NAVIGATOR trial — In the NAVIGATOR trial, 9306 patients with impaired glucose tolerance
and either established cardiovascular disease (24 percent) or one or more risk factors for
cardiovascular disease were randomly assigned to valsartan (160 mg/day) or placebo [21]. In
addition, all patients participated in a lifestyle intervention program. The mean blood pressure at
baseline was 140/83 mmHg.
After a median follow-up of five years, there was no significant difference in the incidence of
either an extended composite outcome of death from cardiovascular causes, nonfatal MI, nonfatal
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stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable
angina (14.5 versus 14.8 percent respectively) or a core composite outcome that excluded
unstable angina and revascularization (8.1 percent in both groups). The mean blood pressure
decreased significantly more in the valsartan group (6.3/4.4 versus 3.8/3.0 mmHg).
ACTION trial — In the ACTION trial, 7665 patients with chronic stable angina (52 percent had
a prior MI) were randomly assigned to long-acting nifedipine 60 mg daily or placebo [22]. The
mean baseline blood pressure of 137/80 mmHg, and at study end was significantly lower in the
nifedipine group (130/75 versus 136/78 mmHg).
The primary end point was survival free of major cardiovascular events, including death of any
cause, acute MI, refractory angina, new overt HF, debilitating stroke, and peripheral
revascularization. At a mean follow-up of 4.9 years, nifedipine therapy had no effect on the
incidence of the primary end point (4.60 versus 4.75 percent per year, hazard ratio 0.97) or
all-cause mortality alone (1.64 versus 1.53 percent per year, hazard ratio). Nifedipine did reduce
the need for coronary angiography and interventions.
Meta-analysis and limitations — Cardiovascular outcomes were evaluated in a 2009
systematic review of seven trials that compared either an ACE inhibitor or an angiotensin receptor
blocker to placebo in patients with ischemic heart disease and preserved left ventricular systolic
function [23]. Six trials of ACE inhibitor therapy (including HOPE, EUROPA, CAMELOT, and PEACE)
significantly reduced both total mortality (risk ratio 0.87, 95% CI 0.81-0.94) and nonfatal MI (risk
ratio 0.83, 95% CI 0.73-0.94).
However, two important trials described above, both of which showed no benefit, were not
included in the meta-analysis:
TRANSCEND used the ARB telmisartan [20]. When TRANSCEND was included with the ACE
inhibitor trials in the meta-analysis, the total mortality benefit was less prominent but still
statistically significant (risk ratio 0.91)
NAVIGATOR, which used valsartan, was published after the meta-analysis [21]. If this trial
were included in the meta-analysis, it would make the mortality benefit even smaller and perhaps
no longer statistically significant. However, a potentially important limitation to NAVIGATOR is
that the difference in blood pressure between the two groups was only 2.5/1.4 mmHg, which may
be insufficient to affect cardiovascular risk.
One could consider the possibility that ACE inhibitors are beneficial in patients at increased
cardiovascular risk and that ARBs might not be. However, this has not been proven to be true in
patients with other disorders, such as heart failure and proteinuric chronic kidney disease.
Additional support for the lack of a specific beneficial effect of ACE inhibitors comes from the
CAMELOT trial in which enalapril and amlodipine produced identical outcomes compared toplacebo [8].
While the meta-analysis provides some support for the use of ACE inhibitors in patients with
stable ischemic heart disease or those at very high risk, our authors and reviewers believe that
any benefit achieved comes from blood pressure lowering. Thus, we do not recommend the
preferential use of ACE inhibitors or angiotensin receptor blockers in patients with cardiovascular
disease unless there is a specific indication such as heart failure, prior myocardial infarction, or
proteinuric chronic kidney disease.
Are lower blood pressures harmful? — There is a blood pressure threshold for all patients
below which tissue perfusion is reduced to vital organs. As long as the blood pressure is lowered
gradually, this threshold does not appear to occur at current blood pressure goals. The ACCORD
BP trial of patients with type 2 diabetes who had cardiovascular disease or at least two additional
risk factors for cardiovascular disease found that cardiovascular outcomes at 4.7 years were
similar in patients with attained systolic pressures of 119 and 134 mmHg [6]. (See 'ACCORD BP
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trial' above.)
Coronary heart disease without heart failure — For patients with coronary heart disease
without heart failure, it is possible that a lower limit exists for desirable diastolic pressure
because much of coronary filling occurs during diastole. Observations from the Framingham study
and a post hoc analysis from the INVEST trial suggested an increase in risk for patients with
cardiovascular at a diastolic pressure below 70 to 75 mmHg [24,25].
Other analyses from placebo-controlled trials of hypertension found a similar J-shaped curve for
diastolic and systolic pressures in both treated and untreated groups and for both cardiovascular
and noncardiovascular mortality (figure 3A-B) [26,27]. These findings indicate that the worse
outcomes at lower pressures are independent of antihypertensive therapy as long as the BP is
lowered slowly. This issue is discussed in detail elsewhere. (See "What is goal blood pressure in
the treatment of hypertension?", section on 'J-shaped diastolic curve' and "What is goal blood
pressure in the treatment of hypertension?", section on 'J-shaped systolic curve'.)
Heart failure — For patients with heart failure due to systolic dysfunction, many experts
consider the goal of therapy to be the lowest blood pressure that is not associated with symptoms
of hypotension or evidence of hypoperfusion (eg, worsening prerenal azotemia). In some patients
with severe HF, this may be a systolic pressure as low as 90 mmHg.
Most patients with systolic HF are treated with inhibition of the renin-angiotensin system (eg,
angiotensin converting enzyme inhibitors or angiotensin II receptor blockers), beta blockers, and,
in selected patients, an aldosterone antagonist. These agents have favorable effects on survival in
HF that are independent of their effects on blood pressure. (See "Treatment of hypertension in
patients with heart failure".)
Isolated systolic hypertension — Although there are no convincing data, there may be a
threshold diastolic BP below which adverse cardiovascular outcomes might increase in elderly
patients with isolated systolic hypertension. When treating such patients, we and others
(including JNC 7 [5]) suggest a minimum posttreatment diastolic pressure of 60 mmHg overall or
perhaps 65 mmHg in patients with known coronary artery disease unless symptoms that could beattributable to hypoperfusion occur at higher pressures. (See "Treatment of hypertension in the
elderly, particularly isolated systolic hypertension", section on 'Goal blood pressure'.)
Prior stroke — The efficacy of lowering the BP with antihypertensive therapy has been
evaluated in patients with a prior stroke, many of whom have a history of prior hypertension. This
issue is discussed in detail separately. (See "Treatment of hypertension in patients who have had
a stroke".)
GOAL BLOOD PRESSURE — Regardless of the goal BP, blood pressure reduction should be
gradual in all patients in the absence of a hypertensive emergency. In addition, patients with
isolated systolic hypertension or stenotic arterial lesions (carotid or coronary) may be at increased
risk for ischemic manifestations at lower blood pressure goals. Thus, such patients should be
monitored carefully for possible signs of hypoperfusion, such as angina or neurologic dysfunction,
and for elevations in serum creatinine, which are more likely to occur in patients with bilateral
renal artery stenosis. (See "Treatment of hypertension in the elderly, particularly isolated systolic
hypertension", section on 'Goal blood pressure' and "Treatment of bilateral atherosclerotic renal
artery stenosis", section on 'Medical therapy'.)
Patients with known atherosclerotic cardiovascular disease — As many of the relevant
studies included patients with atherosclerotic cardiovascular disease (CVD) other than coronary
heart disease, such as those with peripheral arterial or cerebrovascular disease, our
recommendations are for all patients with atherosclerosis.
The 2003 JNC 7 report recommended a goal BP of less than 140/90 mmHg in patients with
coronary heart disease (CHD), similar to that in the general hypertensive population [5]. In
contrast, guidelines published in 2007 by the American Heart Association and the European
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Society of Hypertension/European Society of Cardiology set a goal of less than 130/80 mmHg for
patients with atherosclerotic CVD [2,28,29].
However, there is no compelling evidence supporting a goal of less than 130/80 mmHg in
patients with atherosclerotic CVD as evidenced from the clinical trial data presented above:
In the ACCORD BP trial, there was no significant difference in cardiovascular outcomes at a
mean attained systolic pressure of 119 compared to 134 mmHg [6]. It is theoretically possible
that outcomes were better at a blood pressure between 125 and 129 mmHg and then becameworse at lower pressures. Subgroup analyses in the future may address this issue. (See 'ACCORD
BP trial' above.)
The placebo-controlled trials cited above provide some (HOPE, EUROPA, and possibly
CAMELOT trials) but not consistent support (PEACE, TRANSCEND, ACTION, NAVIGATOR, and
ACCORD BP trials) for administering additional antihypertensive therapy in patients with a
baseline blood pressure already below 140/90 mmHg. A meta-analysis of most of these trials
showed significant benefit from angiotensin inhibition compared to placebo [23]. (See
'Placebo-controlled trials with a mean baseline BP less than 140/90 mmHg' above.)
It is difficult to reach a confident conclusion about the optimal goal blood pressure in patientswith atherosclerotic CVD from the above observations. Patients in the two major positive trials
(HOPE and EUROPA) had baseline systolic pressures of 139 and 137 mmHg, respectively, whereas
a major negative trial PEACE had a baseline pressure of 133 mmHg.
Based upon these observations:
We recommend a goal blood pressure of less than 140/90 mmHg compared to higher values
in all patients with atherosclerotic CVD.
In patients with a systolic pressure of 135 to 139 mmHg, we suggest (a weaker
recommendation) an attempt to lower the systolic pressure below 135 mmHg by either adding
one antihypertensive drug or increasing the dose of a drug already being given (that is not at
maximal recommended dose) without producing significant side effects. However, given the
available data, it would not be wrong to stop at a goal less than 140 mmHg.
Antihypertensive therapy should be accompanied by management of other risk factors. (See
"Secondary prevention of cardiovascular disease: Risk factor reduction".)
Patients at high risk for atherosclerotic cardiovascular events — A separate issue related to
goal blood pressure, is whether the recommendations in the preceding section on patients with
atherosclerotic cardiovascular disease apply to patients who are at risk (eg, smoker,
hyperlipidemia) but do not have documented disease. No studies have been performed to assess
goal blood pressure in these patients [2] and, given the weak evidence supporting of goal of lessthan 135/85 mmHg in patients who already have cardiovascular disease, we recommend a goal
blood pressure equivalent to that in the general hypertensive population (less than 140/90
mmHg) in patients at increased cardiovascular risk. (See "What is goal blood pressure in the
treatment of hypertension?".)
Patients with diabetes mellitus or chronic kidney disease — Patients with diabetes mellitus
and chronic kidney disease are also at increased cardiovascular risk. Issues related to goal blood
pressure in these disorders are discussed separately. (See "Treatment of hypertension in patients
with diabetes mellitus", section on 'Goal blood pressure' and "Antihypertensive therapy and
progression of nondiabetic chronic kidney disease", section on 'Goal blood pressure'.)
SUMMARY AND RECOMMENDATIONS — Trials of antihypertensive therapy in patients with
different levels of risk for a cardiovascular event have shown benefit, particularly in individuals
with atherosclerotic cardiovascular (CVD) disease or those at very high risk, such as patients with
diabetes or chronic kidney disease. The higher the starting blood pressure, the more likely benefit
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from treatment will be seen. For patients with hypertension, the minimum goal of therapy (less
than 140/90 mmHg) is well established. (See "What is goal blood pressure in the treatment of
hypertension?".)
However, whether there is benefit from a lower goal blood pressure (such as less than 135/85 or
even 130/80 mmHg) for those with atherosclerotic CVD (coronary artery disease, peripheral
arterial disease, abdominal aortic aneurysm, diabetes, and/or cerebrovascular disease) has not
been well defined.
For hypertensive patients with established atherosclerotic CVD (see 'Patients with known
atherosclerotic cardiovascular disease' above:
We recommend antihypertensive therapy to lower the blood pressure to less than 140/90
mmHg compared to higher pressures (Grade 1B).
We suggest a goal blood pressure of less than 135/85 mmHg, rather than less than 140/90
mmHg, for patients in whom this goal can be attained by either adding one antihypertensive drug
or increasing the dose of a drug already being given (that is not at maximal recommended dose)
without producing significant side effects (Grade 2C). However, a goal blood pressure of less
than 140/90 mmHg is reasonable for patients who do not want to increase the intensity of
antihypertensive therapy.
For hypertensive patients at high risk for atherosclerotic CVD (see 'Patients at high risk for
atherosclerotic cardiovascular events' above:
We recommend a goal blood pressure less than 140/90 mmHg compared to higher values,
similar to that in the general hypertensive population (Grade 1C).
Use of UpToDate is subject to the Subscription and License Agreement.
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Sleight, P, Yusuf, S, Pogue, J, et al. Blood-pressure reduction and cardiovascular risk inHOPE study. Lancet 2001; 358:2130.
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Svensson, P, de Faire, U, Sleight, P, et al. Comparative effects of ramipril on ambulatory andoffice blood pressures: a HOPE Substudy. Hypertension 2001; 38:E28.
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Fox, KM. Efficacy of perindopril in reduction of cardiovascular events among patients with
stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentretrial (the EUROPA study). Lancet 2003; 362:782.
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Daly, CA, Fox, KM, Remme, WJ, et al. The effect of perindopril on cardiovascular morbidityand mortality in patients with diabetes in the EUROPA study: results from the PERSUADEsubstudy. Eur Heart J 2005; 26:1369.
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Brugts, JJ, Boersma, E, Chonchol, M, et al. The cardioprotective effects of theangiotensin-converting enzyme inhibitor perindopril in patients with stable coronary arterydisease are not modified by mild to moderate renal insufficiency: insights from the EUROPAtrial. J Am Coll Cardiol 2007; 50:2148.
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Braunwald, E, Domanski, MJ, Fowler, SE, et al. Angiotensin-converting-enzyme inhibition instable coronary artery disease. N Engl J Med 2004; 351:2058.
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Yusuf, S, Teo, K, Anderson, C, et al. Effects of the angiotensin-receptor blocker telmisartanon cardiovascular events in high-risk patients intolerant to angiotensin-converting enzymeinhibitors: a randomised controlled trial. Lancet 2008; 372:1174.
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McMurray, JJ, Holman, RR, Haffner, SM, et al. Effect of valsartan on the incidence ofdiabetes and cardiovascular events. N Engl J Med 2010; 362:1477.
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and cardiovascular morbidity in patients with stable angina requiring treatment (ACTIONtrial): randomised controlled trial. Lancet 2004; 364:849.
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Baker, WL, Coleman, CI, Kluger, J, et al. Systematic review: comparative effectiveness ofangiotensin-converting enzyme inhibitors or angiotensin II-receptor blockers for ischemicheart disease. Ann Intern Med 2009; 151:861.
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D'Agostino, RB, Belanger, AJ, Kannel, WB, Cruickshank, JM. Relation of low diastolic bloodpressure to coronary heart disease death in presence of myocardial infarction: TheFramingham study. BMJ 1991; 303:385.
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Boutitie, F, Gueyffier, F, Pocock, S, et al. J-shaped relationship between blood pressure andmortality in hypertensive patients: new insights from a meta-analysis of individual-patientdata. Ann Intern Med 2002; 136:438.
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Rosendorff, C, Black, HR, Cannon, CP, et al. Treatment of hypertension in the preventionand management of ischemic heart disease: a scientific statement from the American HeartAssociation Council for High Blood Pressure Research and the Councils on Clinical Cardiology
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and Epidemiology and Prevention. Circulation 2007; 115:2761.
Graham, I, Atar, D, Borch-Johnsen, K, et al. European guidelines on cardiovascular diseaseprevention in clinical practice: executive summary. Eur Heart J 2007; 28:2375.
29.
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GRAPHICS
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Cumulative absolute risk of CVD at five years
Cumulative absolute risk of cardiovascular disease (CVD) at five
years according to systolic blood pressure and specified levels ofother risk factors. The reference category is a nondiabetic,nonsmoking 50 year-old woman with a serum total cholesterol (TC)of 154 mg/dL (4.0 mmol/L) and HDL-cholesterol of 62 mg/dL (1.6mmol/L). The CVD risks are given for systolic blood pressure levelsof 110, 130, 150, and 170 mmHg. In the other categories, theadditional risk factors are added consecutively. As an example, thediabetes category is a 50-year-old diabetic man who is a smokerand has a total cholesterol (TC) of 270 mg/dL (7 mmol/L) andHDL-cholesterol of 39 mg/dL (1 mmol/L). Adapted from Jackson, R,Lawes, CM, Bennett, DA, et al, Lancet 2005; 365:434
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Components of cardiovascular risk factors in patients with hypertension
Major risk factors
Hypertension
Cigarette smoking
Obesity (BMI ≥30 kg/m2)
Physical inactivity
Dyslipidemia
Diabetes mellitus
Microalbuminuria or estimated GFR 55 years for men, >65 years in women
Family history of premature coronary disease
Men -
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Ramipril improves the outcome in high risk patients
The HOPE trial randomized 9541 patients at high risk for a
cardiovascular event to ramipril or placebo; after a 4.5 yearfollow-up, ramipril significantly reduced the incidence of thecomposite endpoint of death from cardiovascular causes,myocardial infarction, or stroke (14.1 versus 17.7 percent forplacebo, relative risk 0.78, p
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Lack of true J-shaped curve in diastolic pressure
Age- and sex-adjusted mortality rates (per 1000 patient years,
bars show the 95 percent confidence intervals) according toachieved diastolic pressure in active treatment and control groups
in a meta-analysis of seven randomized clinical trials ofhypertensive patients. The number of events is shown below eachbar. Among treated patients, cardiovascular mortality initially fallsat achieved diastolic pressures below 106 mmHg and then risesagain at low diastolic pressures (upper right panel). However, asimilar relationship is seen with noncardiovascular mortality(bottom right panel) and in the control groups (left panels). Thus,the increase in mortality at low diastolic pressures probablyreflects underlying poor health rather than an adverse effect of
antihypertensive therapy. Data from Boutitie, F, Gueyffier, F, Pocock, S,et al, Ann Intern Med 2002; 136:438.
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Lack of true J-shaped curve in systolic pressure
Age- and sex-adjusted mortality rates (per 1000 patient years, bars
show the 95 percent confidence intervals) according to achievedsystolic pressure in active treatment and control groups in ameta-analysis of seven randomized clinical trials of hypertensivepatients. The number of events is shown below each bar. Amongtreated patients, cardiovascular mortality initially falls at achievedsystolic pressures below 180 mmHg and then rises again at lowsystolic pressures (upper right panel). However, a similarrelationship is seen with noncardiovascular mortality (bottom rightpanel) and in the control groups (left panels). Thus, the increase inmortality at low diastolic pressures probably reflects underlyingpoor health rather than an adverse effect of antihypertensive
therapy. Data from Boutitie, F, Gueyffier, F, Pocock, S, et al, Ann Intern Med
2002; 136:438.
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