CLINICAL RESEARCH STUDY
Systolic Blood Pressure and Cardiovascular Outcomes
During Treatment of Hypertension
Michael A. Weber, MD,a George L. Bakris, MD,b Allen Hester, PhD,c Matthew R. Weir, MD,d Tsushung A. Hua, PhD,c
Dion Zappe, PhD,c Bjorn Dahlof, MD,e Eric J. Velazquez, MD,f Bertram Pitt, MD,g Kenneth Jamerson, MDg
a
SUNY Downstate College of Medicine, Brooklyn, NY; bThe University of Chicago Medicine, Chicago, Ill; cNovartis Pharmaceuticals,
East Hanover, NJ; dUniversity of Maryland, Baltimore; eSahlgrenska University Hospital, Goteborg, Sweden; fDuke University School
of Medicine, Durham, NC; gUniversity of Michigan, Ann Arbor.
ABSTRACT
OBJECTIVE: Randomized controlled trials in hypertension demonstrate cardiovascular benefits when systolic
blood pressures are reduced from higher values to ⬍ 160 mm Hg. The value of lower targets has not been fully
defined, although major guidelines recommend achieving systolic blood pressures of ⬍ 140 mm Hg. This study
was conducted to explore cardiovascular outcomes at differing on-treatment blood pressure levels.
METHODS: On the basis of a prespecified plan to explore relationships between clinical outcomes and systolic
blood pressures, the pooled cohort of high-risk hypertensive patients (N ⫽ 10,705) in the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension trial were divided into
4 strata of systolic blood pressure levels: ⬎140 mm Hg, 130 to ⬍140 mm Hg, 120 to ⬍130 mm Hg, and 110
to ⬍120 mm Hg. The primary end point was cardiovascular death or nonfatal myocardial infarction or stroke.
Outcomes comparisons between the blood pressure groups were by Cox regression.
RESULTS: The mean patient age was 68 years, and the study duration was 35.7 months. The primary end point
occurred in 171 of 3429 patients (5.0%) with systolic blood pressure in the 10 mm Hg range ⬍ 140 and in 179
of 2354 patients (7.6%) with systolic blood pressure ⱖ 140 mm Hg (hazard ratio [HR], 0.62; 95% CI, 0.50-0.77;
P ⫽ .0001). Likewise, cardiovascular death decreased by 36% (P ⫽ .0147), total myocardial infarction
(fatal ⫹ nonfatal) decreased by 37% (P ⫽ .0028), and stroke decreased by 47% (P ⫽ .0002). Cardiovascular
event rates in those with systolic blood pressure ⬍ 130 mm Hg were not different from those with systolic blood
pressure ⬍ 140 mm Hg. However, compared with systolic blood pressure ⬍ 130 mm Hg, stroke incidence in
those with systolic blood pressure ⬍ 120 mm Hg was lower (HR, 0.60; 95% CI, 0.35-1.01; P ⫽ .0529), but
myocardial function was higher (HR, 1.52; 95% CI, 1.00-2.29; P ⫽ .0437), as were composite coronary events
(myocardial infarction, hospitalized angina, or sudden death) (HR, 1.63; 95% CI, 1.18-2.24; P ⫽ .0023). The
renal end point of a sustained ⬎ 50% increase in serum creatinine was significantly lower in those with systolic
blood pressure ⬍ 140 mm Hg than in any of the other higher or lower blood pressure ranges.
CONCLUSIONS: In high-risk hypertensive patients, major cardiovascular events are significantly lower in
those with systolic blood pressures ⬍ 140 mm Hg and ⬍ 130 mm Hg than in those with levels ⬎ 140 mm
Hg. There are stroke benefits at levels ⬍ 120 mm Hg, but they are offset by increased coronary events.
Renal function is best protected in the 130 to 139 mm Hg range.
© 2013 Elsevier Inc. All rights reserved. • The American Journal of Medicine (2013) 126, 501-508
KEYWORDS: Blood pressure control; Cardiovascular events; Hypertension; Renal function; Stroke
The underlying assumption in treating hypertension is that
reduction of blood pressure decreases the incidence of cardiovascular events, strokes, and chronic kidney disease. The
strongest evidence for this has come from clinical trials in
which patients with untreated systolic blood pressure values
of ⱖ 160 mm Hg had significant decreases in major clinical
Funding: Novartis (Basel, Switzerland).
Conflict of Interest: See last page of article.
Authorship: All authors had access to the data and played a role in
writing this manuscript.
Requests for reprints should be addressed to Michael A. Weber, MD,
State University of New York, Downstate College of Medicine, 450 Clarkson Ave, Box 97, Brooklyn, NY 11203.
E-mail address: [email protected]
0002-9343/$ -see front matter © 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.amjmed.2013.01.007
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The American Journal of Medicine, Vol 126, No 6, June 2013
outcomes when their blood pressures were reduced to ⬍ 160
The present report is based on the randomized controlled
mm Hg.1 However, this information is of limited value in
trial Avoiding Cardiovascular Events through Combination
deciding how to manage patients diagnosed with hypertenTherapy in Patients Living with Systolic Hypertension
sion but whose systolic blood pressure levels are ⬍ 160
(ACCOMPLISH).12 We have measured and compared carmm Hg.
diovascular event rates in 4 patient groups: systolic blood
Epidemiologic data indicate
pressures ⱖ 140 mm Hg, 130
that the lowest incidence of carto ⬍ 140 mm Hg, 120 to ⬍ 130
diovascular and stroke events is at
mm Hg, and 110 to ⬍ 120 mm Hg.
CLINICAL SIGNIFICANCE
systolic blood pressures as low as
115 mm Hg.2 However, this infor● There is a clear cardiovascular benefit in
mation does not predict what
MATERIALS AND METHODS
achieving systolic blood pressures⬍140
might happen when therapeutic
The analysis in the current remm Hg compared with⬎140 mm Hg in
interventions are used to achieve
port is based on data from
treating high-risk hypertensive patients.
low blood pressure levels. Indeed,
ACCOMPLISH.12 The original
● Achieving a systolic blood presit has been reported that excessive
intention of ACCOMPLISH was
reductions can be associated with
sure ⬍ 130 mm Hg has similar benefits,
to compare the outcome effects of
increased coronary and other
the combination of an angiotensinbut reduced stroke rates at ⬍ 120 mm
events.3-6
converting enzyme inhibitor plus
Hg seem to be offset by increased corGuidelines for the treatment of
amlodipine with the effects of the
onary
events.
hypertension in the United States7
combination of the same angioten● Renal function in hypertensive patients
and Europe8 recommend that pasin-converting enzyme inhibitor
is best preserved with systolic blood
tients be treated to maintain sysplus hydrochlorothiazide. The
pressures from 130 to 139 mm Hg.
tolic blood pressure at ⬍ 140 mm
methods for this trial have been deHg; moreover, they recommend
Higher or lower blood pressures are
scribed.12-14 A prespecified analysis
that for patients with diabetes or
for ACCOMPLISH was the subject
associated with worsening renal
chronic kidney disease, a target
of the present report, in particular
outcomes.
of ⬍ 130 mm Hg should be conthe relationships of achieved blood
sidered. However, a recent reappressure levels to cardiovascular
praisal of the European guidelines
and other clinical end points.
recommends a target of ⬍ 140 mm Hg for these high-risk
patients.9
Conduct of the Study
Only 1 authoritative trial has prospectively explored
ACCOMPLISH was designed, supervised, analyzed, and
whether achieving low blood pressure targets is beneficial.
interpreted by an Executive Committee, all of whose memThe Action to Control Cardiovascular Risk in Diabetes
bers are among the academic authors of the current report
(ACCORD) trial10 randomized patients with diabetes to
(MW, GB, BP, EV, and KJ). The roles of key supporting
systolic blood pressure targets of ⬍ 140 or ⬍ 120 mm Hg.
committees for the trial and the role of the original sponsor
The primary end point of the study (cardiovascular death,
(Novartis) have been described.12-14 An institutional review
nonfatal myocardial infarction, or stroke) was not different
board at each participating site approved the study protocol.
The trial was officially registered (ClinicalTrials.gov, numbetween the 2 blood pressure targets. However, the event
ber NCT00170950).
rate for stroke as a single outcome was lower in patients
with systolic blood pressure ⬍ 120 mm Hg.
Retrospective analyses of clinical trials have explored
Patients
outcomes at different achieved blood pressures. In the ValThe study was performed in hypertensive patients at high risk
sartan Antihypertensive Long-Term Use Evaluation trial,
of cardiovascular events established by previously documented
there were significantly fewer events for cardiovascular
cardiovascular conditions, as described previously.14
mortality, heart failure, and stroke in patients with achieved
systolic blood pressure ⬍ 140 mm Hg compared with ⬎ 140
Study Procedures
mm Hg.11 The Ongoing Telmisartan Alone and in CombiThis was a randomized, controlled double-blind trial. Imnation with Ramipril Global EndPoint (ONTARGET) trial
mediately after entering the study, patients were randomly
demonstrated that optimal cardiovascular outcomes ocassigned to 1 of 2 treatment arms: benazepril plus hydrocurred in the systolic range from 130 to 140 mm Hg,
chlorothiazide or benazepril plus amlodipine, although data
although stroke events decreased further at lower blood
from these 2 arms were pooled for the present report. After
pressures.3 Likewise, the International VErapamil SR-Tranrandomization, all previous antihypertensive therapies were
dolapril Study found that cardiovascular events were sigdiscontinued completely and replaced immediately by one
nificantly lower at systolic blood pressures ⬍ 140 mm Hg
of the study’s fixed combination therapies. The starting
4
doses were benazepril 20 mg/d plus hydrochlorothiazide
than at ⬎ 140 mm Hg.
Weber et al
Blood Pressure and Cardiovascular Outcomes
503
12.5 mg/d or amlodipine 5 mg/d. The protocol then mandated an increase in benazepril to 40 mg/d in both treatment
arms at the following study visit. Thereafter, hydrochlorothiazide could be increased to 25 mg/d or amlodipine to
10 mg/d as required to achieve the target blood pressure
of ⬍ 140/90 mm Hg. For patients with diabetes or chronic
kidney disease, a target blood pressure of ⬍ 130/80 mm Hg
was recommended but not mandated. If needed, investigators could add other antihypertensive agents (except angiotensin-converting enzyme inhibitors, angiotensin receptor
blockers, calcium channel blockers, or thiazide diuretics).
After an initial 3-month period during which all treatment
intensifications were made, patients returned for visits after
a further 3 months and then at 6-month intervals until the
end of the trial. Blood pressure was measured by previously
described methods.12
regressions to obtain the hazard ratios and the 95% confidence intervals (CIs) between values being compared.
End Points
The primary study end point was the time to the first
recorded event. For the analyses reported, this was the
composite of the first occurrence of cardiovascular death,
nonfatal myocardial infarction, or nonfatal stroke. Death
from cardiovascular causes was defined as sudden death
from cardiac events or death from myocardial infarction,
stroke, coronary interventions, heart failure, or other cardiovascular causes. Only the first event in an individual
patient was counted toward the primary end point. In addition, there were analyses of secondary end points that were
counted without censoring for previous occurrence of other
end points. The secondary end points for this study were
cardiovascular death, total mortality, total stroke (fatal or
nonfatal), total myocardial infarction (fatal or nonfatal),
clinical coronary events (total myocardial infarction, hospitalized angina pectoris, or sudden cardiac death), coronary
revascularization, and increased serum creatinine (increase
from baseline of ⬎ 50%).
Analysis of Data
The study outcomes were adjudicated according to standard
criteria by a clinical end points committee.12 Interim statistical analyses were performed at 6-month intervals for the
trial’s Data Safety Monitoring Committee.12 This committee recommended early termination of the trial on the basis
of evidence that the criteria for satisfying the trial’s stopping
rules had been met.12
The principal observation in this analysis was the measurement of event rates in the pooled patient cohort of the
primary end point and secondary end points within each of
4 on-treatment systolic blood pressure ranges: ⬎140 mm
Hg, 130 to ⬍140 mm Hg, 120 to ⬍130 mm Hg, and 110 to
⬍120 mm Hg. We did not analyze data from patients with
systolic values ⬍ 110 mm Hg. Event rates in each of the
ranges were compared with those in the adjacent ranges. In
addition, event rates ⬎ 140 mm Hg were compared with
each of the other ranges. All patients were included according to the intention-to-treat principle. The analysis used Cox
Funding
The original ACCOMPLISH Trial was funded by Novartis.
Their role in the conduct of this trial has been described.12
Novartis did not provide funding for the present analysis,
although 3 authors (AH, TH, and DZ) are employees of the
company.
RESULTS
Patient Numbers
The mean duration of treatment in this trial was 35.7
months. A total of 11,506 patients were enrolled. As shown
in Figure 1, blood pressures after treatment titration were
not available in 564 patients. In addition, we did not report
outcomes in patients who achieved systolic blood pressures ⬍ 110 mm Hg because there were too few (237) to
permit meaningful analysis. Thus, there were 10,705 patients divided among the 4 groups of achieved systolic
blood pressures (Figure 1).
Patient Characteristics
The principal clinical features of the patients in this trial are
summarized in Table 1. All patients had histories of stroke,
cardiovascular disease, chronic renal disease, or diabetes, or
both disease and diabetes. The mean age of the cohort was
68 years, and the mean body mass index was 31. More
detailed descriptions of the ACCOMPLISH cohort have
been reported.12,13
Blood Pressures
The baseline and on-treatment systolic and diastolic blood
pressures for each of the 4 study subgroups are listed in
Table 2. Of the total cohort, 97% were receiving antihypertensive treatment at baseline.12 Across the 4 subgroups
of ascending on-treatment blood pressures, a parallel trend
for increasing blood pressures was observed in the baseline
values. The differences in baseline systolic and diastolic
blood pressures between each of the groups were significant
(P ⬍ .0001 for all). In all 4 groups, blood pressures decreased significantly during the trial (P ⬍ .0001 for both
systolic and diastolic blood pressures).
Clinical Outcomes According to Systolic Blood
Pressure Groups
We compared the primary and secondary clinical end points
by Cox regression analysis between patients with achieved
systolic blood pressures ⬎ 140 mm Hg, 130 to ⬍ 140 mm
Hg, 120 to ⬍ 130 mm Hg, and 110 to ⬍ 120 mm Hg.
These data are shown in Figure 2. With the exception of
coronary revascularization, all end points were significantly
lower in the ⬍ 140 mm Hg group than in the ⬎ 140 mm Hg
group. However, there were no significant differences be-
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The American Journal of Medicine, Vol 126, No 6, June 2013
Figure 1 Disposition of patients in the ACCOMPLISH trial according to their achieved
systolic blood pressures. SBP ⫽ systolic blood pressure.
tween the ⬍ 130 mm Hg and ⬍ 140 mm Hg groups, except
for serum creatinine, which was higher in the ⬍ 130 mm Hg
group. In comparing the ⬍ 120 mm Hg group with
the ⬍ 130 mm Hg group, most outcomes tended to be higher
in the ⬍ 120 mm Hg group and were significantly different
for total myocardial infarction, clinical coronary events, and
serum creatinine. Only stroke was lower in the ⬍ 120 mm
Hg group.
The incidence of clinical events across the 4 systolic
blood pressure groups, expressed as events per 1000 patient
years, is shown in Figure 3 (primary end point, cardiovas-
Table 1 Baseline and Clinical Data of the Analyzed
ACCOMPLISH Cohort
No.
Age, y; mean (SD)
Male, n (%)
Diabetes mellitus, n (%)
Previous coronary disease, n (%)
Prior MI, n (%)
History of stroke, n (%)
Baseline eGFR ⬍ 60 mL/min, n (%)
Renal function (eGFR), mean (SD)
Body mass index, mean (SD)
Baseline SBP, mean (SD)
Baseline DBP, mean (SD)
Achieved SBP after 6 mo, mean (SD)
Achieved SBP after 6 mo, mean (SD)
10,705
68.35 (6.81)
6529 (61.0)
6459 (60.3)
4917 (45.9)
2503 (23.4)
1392 (13.0)
1906 (17.8)
79.04 (21.22)
30.90 (6.17)
145.9 (18.04)
80.2 (10.70)
132.7 (12.04)
74.0 (7.76)
ACCOMPLISH ⫽ Avoiding Cardiovascular Events through Combination
Therapy in Patients Living with Systolic Hypertension; DBP ⫽ diastolic
blood pressure; eGFR ⫽ estimated glomerular filtration rate;
MI ⫽ myocardial infarction; SBP ⫽ systolic blood pressure; SD ⫽
standard deviation.
cular death, all-cause mortality, and total stroke) and Figure
4 (total myocardial infarction, clinical coronary events, coronary revascularization, and increased serum creatinine). In
Figures 3 and 4, P values are shown for comparisons
between the ⬎ 140 mm Hg group and each of the other
systolic blood pressure groups, and P values (when significant) between adjacent groups also are shown.
Adverse Events
The treatments used in this trial, benazepril plus hydrochlorothiazide and benazepril plus amlodipine, were well tolerated. Adverse events during ACCOMPLISH have been
described.12
DISCUSSION
The principal goal of this analysis was to explore the relationships between achieved systolic blood pressures and
clinical outcomes in hypertensive patients. There was clear
evidence that patients with a systolic blood pressure range
from 130 to 139 mm Hg had significantly fewer events than
those with a systolic blood pressure ⬎ 140 mm Hg. This
applied not only to the primary end point but also to the
secondary end points of cardiovascular death, all-cause
mortality, total stroke, total myocardial infarction, clinical
coronary events, and renal function. Only coronary revascularization was not different.
Systolic blood pressures ⬍ 130 mm Hg were not associated with lower event rates than pressures ⬍ 140 mm Hg. Our
findings are consistent with those from the ONTARGET trial
and International VErapamil SR-Trandolapril Study in
which the nadir for the same primary end point as in this
study was approximately 130 mm Hg.3,4 A further report
from ONTARGET describing patients with diabetes con-
Weber et al
Blood Pressure and Cardiovascular Outcomes
505
Table 2 Mean Baseline and On-treatment Systolic and Diastolic Blood Pressures for the Whole Study Cohort Divided into Subgroups
of Achieved Systolic Blood Pressure
Post-titration Mean SBP Subgroup
110 to ⬍120 mm Hg
120 to ⬍130 mm Hg
130 to ⬍140 mm Hg
⬎140 mm Hg
No.
Baseline SBP (mm Hg), mean (SD)
Baseline DBP (mm Hg), mean (SD)
On-treatment SBP (mm Hg), mean (SD)
On-treatment DBP (mm Hg), mean (SD)
1329
133.3
76.5
116.3
68.5
3593
140.7
79.2
125.5
72.1
3429
147.7
81.0
134.5
75.0
2354
158.3
82.8
150.2
78.8
(15.02)
(10.13)
(2.73)
(5.98)
(15.31)
(9.95)
(2.77)
(6.33)
(16.22)
(10.62)
(2.83)
(6.89)
(18.03)
(11.39)
(9.52)
(8.74)
DBP ⫽ diastolic blood pressure; SBP ⫽ systolic blood pressure; SD ⫽ standard deviation.
firmed that systolic blood pressures of approximately 130
mm Hg were associated with the fewest cardiovascular
events.15
Effects of Low Achieved Blood Pressures
We observed that systolic blood pressures in the 10 mm Hg
range ⬍ 120 mm Hg, with the exception of stroke, provided
no greater cardiovascular benefit than in the 10 mm Hg
range ⬍ 130 mm Hg. The event rates for total myocardial
infarction and major clinical coronary events (total myocardial infarction or unstable angina or sudden death) were
significantly higher in those with levels ⬍ 120 mm Hg.
These findings add emphasis to the ACCORD study, which
found that, for the same primary end point as reported in the
current article, a systolic blood pressure ⬍ 120 mm Hg was
not different than ⬍ 140 mm Hg.10
Figure 2 Comparisons of clinical outcomes among groups of patients categorized by their achieved systolic blood pressures in the
ACCOMPLISH trial. Hazard ratios were derived by Cox regression analysis. Definitions of the primary end point, clinical coronary
events, and increased serum creatinine are given in the “Materials and Methods” section. BP ⫽ blood pressure; CI ⫽ confidence interval;
CV ⫽ cardiovascular; HR ⫽ hazard ratio; MI ⫽ myocardial infarction.
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Figure 3 Event rates (per 1000 patient years) for major clinical outcomes in patients in ACCOMPLISH categorized according to their
achieved systolic blood pressures. The P values for differences between adjacent groups are shown only if they are significant, but are
shown for all comparisons between the ⬎ 140 mm Hg group and each of the other groups. The definition of the primary end point is given
in the “Materials and Methods” section.
It is not clear why some cardiovascular outcomes increased
at systolic blood pressures ⬍ 120 mm Hg in ACCOMPLISH.
Epidemiologic data indicate that the lowest cardiovascular
event rates occur at systolic blood pressures of approximately
115 mm Hg, but these findings are derived from relatively
healthy people compared with the high-risk patients in clinical
trials.2 There has been speculation that the so-called J-curve
effect seen in trials is due to low diastolic blood pressures
during treatment causing increased coronary events in patients
with preexisting disease,16 but in the present study it seems
doubtful that the mean diastolic blood pressure of 69 mm Hg
in patients with systolic blood pressures ⬍ 120 mm Hg was
sufficiently lower than the values of 72 and 75 mm Hg in the
systolic groups ⬍ 130 and ⬍ 140 mm Hg, respectively, to explain the higher event rates.
It also could be argued that the increased events in patients
with systolic blood pressures ⬍ 120 mm Hg might be a form of
reverse causality, whereby the low blood pressures were actually due to existing heart disease, but this seems unlikely. The
event rate (per 1000 patient years) in the present analysis for
the primary end point in the patients with systolic blood pres-
sures ⬍ 120 mm Hg was 16.8, which clearly is not higher than
the rate of 18.7 for the same end point in ACCORD patients
randomized to ⬍ 120 mm Hg and who achieved that goal by
planned treatment titration.10
Effects on Stroke
In ACCORD, stroke rates were significantly lower in those
with a systolic blood pressure ⬍ 120 mm Hg than in those
with a level ⬍ 140 mm Hg.10 Likewise, in the present analysis we found stroke rates to be lowest at levels ⬍ 120 mm
Hg. It is tempting to argue that the offsetting outcomes we
observed at levels ⬍ 120 mm Hg— higher coronary rates
but lower stroke rates— could provide clinicians and patients with a context for deciding how aggressively to treat
hypertension. Unfortunately, our data show that cardiac risk
versus stroke risk does not seem to be an even trade. According to the data in Figures 3 and 4, achieving systolic
blood pressure ⬍ 120 mm Hg reduces stroke events (per
1000 patient years) by 2.9 but increases clinical coronary
events by 5.7. So, theoretically, it would cost approximately
2 coronary events to prevent 1 stroke.
Weber et al
Blood Pressure and Cardiovascular Outcomes
507
Figure 4 Event rates (per 1000 patient years) for major clinical outcomes in patients in ACCOMPLISH categorized according to their
achieved systolic blood pressures. The P values for differences between adjacent groups are shown only if they are significant, but are
shown for all comparisons between the ⬎ 140 mm Hg group and each of the other groups. The definitions of clinical coronary events
and increased serum creatinine are given in the “Materials and Methods” section.
Kidney Function
The clinical event that had the tightest connection to treatment blood pressures was elevation in serum creatinine,
defined as a sustained increase of at least 50% from baseline. Because 90% of patients at baseline were already
taking blockers of the renin-angiotensin system,12 drugs
known to increase creatinine,17 the increases during the trial
could not be attributed to initiating the trial’s angiotensinconverting enzyme inhibitor. Rather, changes in this index
of renal function seem to be meaningful, especially because
it has been reported that preventing increases of 50% or
greater in creatinine predicts a slower progression of nephropathy and an increased time to dialysis.18
Specifically, we found that on-treatment systolic blood
pressures from 130 to 139 mm Hg, compared with ⬎ 140
mm Hg, were associated with significantly lower adverse
renal effects. However, there was actually a worsening in
kidney function at levels ⬍ 130 mm Hg, with yet a further
deterioration at levels ⬍ 120 mm Hg. This sharp J-shaped
relationship defines a narrow range between 130 and 140
mm Hg as optimal for preserving kidney function. This
observation clarifies a previous meta-analysis that demonstrated reduced worsening of kidney function at systolic
blood pressures ⬍ 140 mm Hg,19 although other data suggested that even lower blood pressure values could be beneficial in patients with substantial proteinuria.20 Of note,
recent findings from a large patient cohort with stage 3
chronic kidney disease indicated that systolic blood pressures between 130 and 139 mm Hg were associated with
optimal protection against progression to end-stage renal
disease,21 coinciding closely with the present observations.
Study Limitations
The primary and some secondary end points reported differ
from those in the original ACCOMPLISH report but were
selected to be similar to those reported from other trials.
Although analysis of the effects of achieved blood pressures
on outcomes in ACCOMPLISH was prespecified, the decision to base our analysis on descending 10 mm Hg systolic
ranges starting at 140 mm Hg was made post hoc. In fact,
the only prospective comparison of different systolic blood
pressure targets was ACCORD, which compared events at
508
levels ⬍ 120 mm Hg with those at ⬍ 140 mm Hg.10 The
present report included calculations of the outcomes effects
of systolic blood pressures of ⬍ 130 mm Hg, ⬍ 120 mm Hg,
and ⬍ 140 mm Hg. This could represent a useful contribution because systolic pressures of approximately 130 mm
Hg might confer optimal cardiovascular protection.
CONCLUSIONS
This study demonstrates that cardiovascular outcomes in highrisk patients are effectively reduced at systolic blood pressures ⬍ 140 mm Hg. Pressures ⬍ 130 mm Hg provide similar
benefits, but there are increased cardiac events ⬍ 120 mm Hg.
The exceptions to these generalizations are stroke, which is
lowest at ⬍ 120 mm Hg, and adverse renal changes, which are
lowest at ⬍ 140 mm Hg but increase significantly in the lower
blood pressure ranges.
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Conflict of Interest: MAW consults for Boehringer-Ingelheim, Daiichi
Sankyo, Forest Pharmaceuticals, and Takeda Pharmaceuticals, and provides speaking services for Daiichi Sankyo, Forest, and Takeda. GLB
consults for Takeda, Abbott, Relapsya, Medtronic, Daiichi-Sankyo, and
Novartis, and has grants from Forest and Takeda. AH, TH, and DZ are
employees of Novartis. MRW consults for Amgen, Novartis, Pfizer, Daiichi-Sankyo, and MSD. BD consults for Novartis, Boehringer-Ingelheim,
Bayer, and Vicore Pharma; owns stock in Mintage Scientific AB; and
speaks for Novartis, MSD, Boehringer Ingelheim, Pfizer, Krka, Bayer, and
Vicore. EJV is a consultant to Novartis. BP is a consultant to Novartis. KJ
consults for Boehringer-Ingelheim, Forest, Novartis, XOMA, Pfizer, and
InVasc Therapeutics; speaks for Daiichi Sankyo, and receives research
support from the National Heart, Lung, and Blood Institute, National
Institutes of Health, National Institute of Diabetes and Digestive and
Kidney Diseases, and Novartis.