Download Hypertension and Outcomes Following Myocardial Infarction

Hypertension and Outcomes Following Myocardial Infarction
Effect of Antecedent Hypertension and Follow-Up Blood
Pressure on Outcomes After High-Risk
Myocardial Infarction
Jens J. Thune, James Signorovitch, Lars Kober, Eric J. Velazquez, John J.V. McMurray,
Robert M. Califf, Aldo P. Maggioni, Jean L. Rouleau, Jonathan Howlett,
Steven Zelenkofske, Marc A. Pfeffer, Scott D. Solomon
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Abstract—The influence of blood pressure on outcomes after high-risk myocardial infarction is not well characterized. We
studied the relationship between blood pressure and the risk of cardiovascular events in 14 703 patients with heart
failure, left ventricular systolic dysfunction, or both after acute myocardial infarction in the Valsartan in Myocardial
Infarction Trial. We assessed the relationship between antecedent hypertension and outcomes and the association
between elevated (systolic: ⬎140 mm Hg) or low blood pressure (systolic: ⬍100 mm Hg) in 2 of 3 follow-up visits
during the first 6 months and subsequent cardiovascular events over a median 24.7 months of follow-up. Antecedent
hypertension independently increased the risk of heart failure (hazard ratio [HR]: 1.19; 95% CI: 1.08 to 1.32), stroke
(HR: 1.27; 95% CI: 1.02 to 1.58), cardiovascular death (HR: 1.11; 95% CI: 1.01 to 1.22), and the composite of death,
myocardial infarction, heart failure, stroke, or cardiac arrest (HR: 1.13; 95% CI: 1.06 to 1.21). While low blood pressure
in the postmyocardial infarction period was associated with increased risk of adverse events, patients with elevated
blood pressure (n⫽1226) were at significantly higher risk of stroke (adjusted HR: 1.64; 95% CI: 1.17 to 2.29) and
combined cardiovascular events (adjusted HR: 1.14; 95% CI: 1.00 to 1.31). Six months after a high-risk myocardial
infarction, elevated systolic blood pressure, a potentially modifiable risk factor, is associated with an increased risk of
subsequent stroke and cardiovascular events. Whether aggressive antihypertensive treatment can reduce this risk
remains unknown. (Hypertension. 2008;51:48-54.)
Key Words: myocardial infarction 䡲 heart failure, congestive 䡲 hypertension 䡲 hypotension 䡲 mortality
H
ypertension is an established risk factor for progression of cardiovascular disease,1 and antihypertensive
treatment has been associated with reduced risk of myocardial infarction (MI), heart failure (HF), stroke, and
cardiovascular death.2,3 While hypertension before MI is
associated with greater left ventricular (LV) dilation4,5 and
a higher risk of subsequent HF, stroke, and death,6 –12 a
drop in blood pressure after MI is common.13,14 Thus, the
influence of post-MI blood pressure on cardiovascular
outcomes may be complex, particularly in patients with
large infarctions. To better understand the relationship
between blood pressure and risk in the post-MI patient, we
performed a posthoc analysis of data from the VALsartan In
Acute myocardial INfarction Trial (VALIANT) to assess the
effect of antecedent hypertension and post-MI systolic blood pressure on subsequent adverse cardiovascular
outcomes.
Methods
Patients
VALIANT enrolled 14 703 patients with LV dysfunction (LV ejection
fraction: ⬍35%), HF, or both who had systolic blood pressure
⬎100 mm Hg between 12 hours and 10 days after an acute MI. Patients
were randomly assigned to receive valsartan (160 mg twice daily),
captopril (50 mg 3 times a day), or both (80 mg of valsartan twice daily
and 50 mg of captopril 3 times a day).15,16 All of the patients gave
written informed consent, and the research protocol was approved by the
appropriate institutional review boards.
Assessment of Hypertension and Follow-Up
Blood Pressure
Information on antecedent hypertension and other baseline data were
assessed at the randomization visit. Patients who reported a diagnosis
of hypertension before randomization were considered to have
hypertension antecedent to their MI. Blood pressure was recorded at
each follow-up visit, with the second visit on discharge or day 14,
whichever came first, and subsequent visits scheduled at 1, 3, 6, 9,
Received May 11, 2007; first decision June 6, 2007; revision accepted October 23, 2007.
From the Brigham and Women’s Hospital (J.J.T., J.S., M.A.P, S.D.S.), Boston, Mass; Rigshospitalet (L.K.), Copenhagen, Denmark; Duke Clinical
Research Institute (E.J.V., R.M.C.), Duke University Medical Center, Durham, NC; Western Infirmary (J.J.V.M.), Glasgow, Scotland; ANMCO Research
Center (A.P.M.), Florence, Italy; Montreal Heart Institute (J.L.R.), Montreal, Quebec, Canada; Queen Elizabeth II Health Sciences Centre (J.H.), Halifax,
Nova Scotia, Canada; and Novartis Pharmaceuticals (S.Z.), East Hanover, NJ.
Correspondence to Scott D. Solomon, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail
[email protected]
© 2007 American Heart Association, Inc.
Hypertension is available at http://hyper.ahajournals.org
DOI: 10.1161/HYPERTENSIONAHA.107.093682
48
Thune et al
Table 1.
Pre-MI and Post-MI Hypertension and Outcomes
49
Baseline Demographics
Demographics
No Antecedent Hypertension (n⫽6126)
Age, mean⫾SD, y*
Antecedent Hypertension (n⫽8575)
62.9⫾12.4
Male, n (%)*
66.2⫾11.2
4790 (78.2)
5342 (62.3)
White
5802 (94.7)
7944 (92.6)
Black
92 (1.5)
315 (3.7)
Asian
75 (1.2)
66 (0.8)
Other
157 (2.6)
250 (2.9)
Systolic*
114 (107, 123)
124 (112, 140)
Diastolic*
70 (61, 78)
75 (68, 80)
28.5⫾5.7
Race, n (%)*
Baseline BP, median (25th, 75th), mm Hg
2
BMI, mean⫾SD, kg/m *
27.0⫾4.6
eGFR, mean⫾SD, mL/min per 1.73 m2*
74.0⫾20.6
67.5⫾21.4
LVEF, mean⫾SD, %
35.5⫾10.3
35.7⫾10.3
Evidence or history of HF, n (%)*
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4642 (75.8)
6984 (81.4)
I
1912 (33.3)
2051 (26.5)
II
2563 (44.6)
3293 (42.5)
III
1087 (18.9)
2016 (26.0)
IV
184 (3.2)
384 (5.0)
Anterio, n (%)*
3642 (61.9)
4750 (57.8)
Q-wave type, n (%)*
4233 (71.6)
5209 (63.0)
Max CK (U/L), median (25th, 75th)*
1379 (608, 2902)
NYHA class, n (%)*
Qualifying MI
941 (472, 2012)
History, n (%)
MI*
Unstable angina*
Stable angina*
1372 (22.4)
2732 (31.9)
904 (14.8)
2225 (25.9)
1768 (28.9)
4072 (47.5)
HF*
527 (8.6)
1646 (19.2)
Stroke*
217 (3.5)
678 (7.9)
PVD*
384 (6.3)
853 (9.9)
Diabetes*
945 (15.4)
2455 (28.6)
Atrial fibrillation*
277 (4.5)
682 (8.0)
ACE inhibitor*
2173 (35.5)
3643 (42.5)
␤-Blocker*
Concomitant medication, n (%)
4292 (70.1)
6057 (70.7)
Calcium-channel blocker*
322 (5.3)
939 (11.0)
K-sparing diuretic†
500 (8.2)
830 (9.7)
2811 (45.9)
4587 (53.5)
Other diuretic*
BP indicates blood pressure; LVEF, LV ejection fraction; PVD, peripheral vascular disease; ACE, angiotensin-converting enzyme.
*P⬍0.001.
†P⬍0.01.
and 12 months after randomization and every 4 months thereafter.
Because blood pressure was assessed primarily for safety, no
recommendations for blood pressure measuring or number of times
to measure blood pressures at each visit were provided, although if
⬎1 blood pressure result was measured, investigators were asked to
report the lowest. No specific instructions were given to investigators
on how to treat blood pressure.
Patients who completed ⱖ2 visits after discharge and 1 visit
between 4 and 8 months and were free of clinical events were
considered for the analyses as 6-month event-free survivors. Patients
with a systolic blood pressure ⬎140 mm Hg on 2 of the visits at 1,
3, and 6 months were considered to have an elevated blood pressure.
Patients with a systolic blood pressure ⬍100 mm Hg on 2 of the
visits at 1, 3, and 6 months were considered to have low blood
pressure. The remaining patients were considered to have normal
blood pressure. The same cutoffs were used for all of the patients
irrespective of comorbidities, such as diabetes or renal impairment.
Statistical Analysis
All of the major cardiovascular end points, including death, MI,
stroke, resuscitated cardiac arrest, and hospitalization for HF, were
adjudicated by an independent clinical events committee, and deaths
50
Hypertension
January 2008
Table 2.
Effect of History of Hypertension on Outcomes
Events/1000 Patient Years
Outcomes (No. of Events)
No History of
Hypertension
History of
Hypertension
HR
(95% CI)
Adjusted HR
(95% CI)*
All-cause mortality (2878)
77
115
1.47 (1.36 to 1.59)
1.08 (0.99 to 1.18)
CV death (2484)
65
100
1.52 (1.40 to 1.62)
1.11 (1.01 to 1.22)
Fatal and nonfatal stroke (463)
12
20
1.70 (1.39 to 2.07)
1.27 (1.02 to 1.58)
Fatal and nonfatal MI (1740)
53
75
1.36 (1.24 to 1.50)
1.02 (0.91 to 1.14)
Sudden death/resuscitated
cardiac arrest (1073)
29
43
1.42 (1.26 to 1.62)
1.09 (0.94 to 1.25)
65
118
1.72 (1.58 to 1.88)
1.19 (1.08 to 1.32)
146
235
1.53 (1.44 to 1.66)
1.13 (1.06 to 1.21)
HF (2388)
CV death, MI, HF, stroke, or
sudden death or resuscitated
cardiac arrest (4833)
CV indicates cardiovascular.
*Adjusted for age, sex, BMI, eGFR, previous MI, previous HF, previous stroke, baseline diabetes, peripheral vascular
disease, and NYHA class.
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were classified as cardiovascular or noncardiovascular. Only the first
occurrence of each nonfatal event was adjudicated and used for
analyses. End points were counted from the time of randomization
for analyses of antecedent hypertension (median follow-up: 750
days; range: 0 to 1432 days; total: 29 242 patient years) and from
time of the 6-month visit for analyses of post-MI systolic blood
pressure (median follow-up: 605 days; range: 0 to 1251 days; total:
17 751 patient years). Baseline variables were compared using the
Wilcoxon nonparametric test. The relationships between hypertension before and blood pressure 1 to 6 months after MI and
cardiovascular outcomes were assessed by univariate and multivariable (adjusted for age, sex, body mass index [BMI], estimated
glomerular filtration rate [eGFR], previous MI, previous HF, previous stroke, baseline diabetes, peripheral vascular disease, randomization arm [intention-to-treat], and New York Heart Association
[NYHA] class) proportional hazards regression of time to first event.
In addition, analyses of the association between post-MI blood
pressure and outcomes were adjusted for antecedent hypertension,
and we assessed for statistical interaction.
Supportive analyses of the nature of the relationship between the
average systolic blood pressure across the 1-, 3-, and 6-month visits
as a continuous variable and subsequent outcomes were performed
by allowing for increasingly complex relationships (linear, quadratic,
cubic, and splined) and reporting the simplest relationship that
significantly improved model fit compared with the preceding one,
adjusting for baseline covariates. To further test the robustness of our
analyses, we performed a Cox analysis with high or low systolic
blood pressure as a time-dependent variable censored 30 days before
first event.
Results
Antecedent Hypertension
At the time of enrollment, 8575 patients (58.3%) reported
antecedent hypertension, and 7609 (88.7%) of these reported
receiving medical treatment for hypertension (no information
on 2 patients). Patients with antecedent hypertension were
older, more often female, had higher blood pressure at
baseline, higher BMI, lower eGFR, lower peak creatinine
kinase, higher prevalence of previous cardiac disease and risk
factors, and were more likely to receive antihypertensive
medication (Table 1). Patients with antecedent hypertension
had higher average systolic blood pressures across the
follow-up visits at 1, 3, and 6 months compared with patients
who did not report antecedent hypertension (difference in
medians: 9 mm Hg; P⬍0.0001). Antecedent hypertension
was associated with a statistically significant increased risk of
stroke, HF hospitalization, cardiovascular death, and a combined cardiovascular outcome of cardiovascular death, MI,
HF hospitalization, stroke, or sudden death or resuscitated
cardiac arrest in multivariable analyses (Table 2). Antecedent
hypertension did not affect the risk of developing renal
impairment (P⫽0.3) or hyperkaliemia (P⫽0.4).
Post-MI Blood Pressure
Of the 10 532 patients who had not experienced a cardiovascular event by the 6-month follow-up visit and had adequate
follow-up information, 1522 (14.5%) had elevated systolic
blood pressure, and 602 (5.7%) had low blood pressure 1 to
6 months post-MI. Patients with elevated systolic blood
pressure post-MI were older, more often female, had lower
eGFR, lower peak creatinine kinase, and had a higher
prevalence of cardiovascular risk factors and previous HF
(Table 3). Patients with elevated systolic blood pressure were
more likely to receive the target dose of the study drug
compared with patients with normal systolic blood pressure.
Compared with patients with normal systolic blood pressure,
patients with elevated systolic blood pressure were at significantly higher risk of stroke and a combined cardiovascular
outcome of cardiovascular death, MI, HF hospitalization,
stroke, or sudden death or resuscitated cardiac arrest (Table
4). Adding information about LV ejection fraction to the
model (n⫽8220) did not substantially change these results.
Elevated systolic blood pressure was most associated with the
adverse cardiovascular outcome in patients who received a
statin (P for interaction⫽0.0001) and in patients not using
long-lasting nitrates (P for interaction⫽0.001).
Patients with low systolic blood pressure between 1 and 6
months after MI were at a higher risk of HF, cardiovascular
death, all-cause death, and the combined cardiovascular
outcome. Patients with low systolic blood pressure were more
likely to experience renal impairment (adjusted hazard ratio
[HR]: 1.43; 95% CI: 1.01 to 2.04; P⫽0.047). Adding information about LV ejection fraction to the model attenuated the
Thune et al
Table 3.
Pre-MI and Post-MI Hypertension and Outcomes
Demographics of 6-Month Event-Free Survivors
Demographics
Age, mean⫾SD, y
Male, n (%)
Low BP (n⫽602)
Normal BP (n⫽8408)
59.6⫾12.5*
63.6⫾11.7
487 (80.8)*
6178 (73.5)
Elevated BP (n⫽1522)
68.8⫾9.9*
827 (54.3)*
Race, n (%)‡
White
558 (92.7)
7912 (94.1)
1431 (94.0)
Black
10 (1.7)
181 (2.2)
56 (3.7)
Asian
13 (2.2)
89 (1.1)
4 (0.3)
Other
21 (3.5)
226 (2.7)
31 (2.0)
BP at randomization, median (25th, 75th)
Systolic
110 (104, 118)*
120 (110, 130)
135 (120, 150)*
Diastolic
70 (60, 73)*
70 (65, 80)
80 (70, 82)*
Systolic
95 (92, 99)*
121 (113, 130)
151 (146, 160)*
Diastolic
62 (59, 67)*
73 (68, 80)
Average BP at 1 to 6 mo, median (25th, 75th)
Antecedent hypertension at baseline, n (%)
179 (29.7)*
4568 (54.3)
84 (78, 90)*
1229 (80.7)*
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BMI, mean⫾SD, kg/m2
26.8⫾4.1*
27.9⫾5.0
eGFR, mean⫾SD, mL/min/1.73 m2
75.3⫾20.7†
73.1⫾20.6
65.4⫾20.8*
LVEF, mean⫾SD, %
34.5⫾10.2†
36.3⫾10.2
37.7⫾11.0†
Evidence or history of HF, n (%)
434 (72.1)†
6368 (75.7)
28.6⫾5.3*
1272 (83.6)*
NYHA class at 6 mo, n (%)‡
I
332 (56.2)
4295 (51.6)
674 (44.8)
II
205 (34.7)
3326 (40.0)
652 (43.4)
III
51 (8.6)
662 (8.0)
171 (11.4)
IV
3 (0.5)
36 (0.4)
6 (0.4)
Qualifying MI
Anterior, n (%)
411 (70.9)*
4854 (59.8)
786 (53.7)*
Q-wave, n (%)
456 (78.4)*
5710 (70.1)
845 (57.4)*
1191 (561, 2538)
748 (414, 1468)*
Max CK, median (25th, 75th)
1878 (756, 3754)*
History, n (%)
MI
142 (23.6)
2073 (24.7)
382 (25.1)
Unstable angina
100 (16.6)
1691 (20.1)
323 (21.2)
Stable angina
690 (45.3)*
164 (27.2)*
3090 (36.8)
Previous HF
48 (8.0)*
967 (11.5)
234 (15.4)†
Stroke
23 (3.8)
403 (4.8)
104 (6.8)†
PVD
39 (6.5)
601 (7.1)
128 (8.4)
Diabetes
74 (12.3)*
1666 (19.8)
419 (27.5)*
Atrial fibrillation
30 (5.0)
419 (5.0)
109 (7.2)†
413 (68.6)†
6185 (73.6)
1117 (73.4)
Medications at 6 mo, n (%)
␤ -Blocker
Calcium-channel blocker
28 (4.7)†
745 (8.9)
357 (23.5)*
K-sparing diuretic
64 (10.6)
745 (8.9)
159 (10.4)
Other diuretic
197 (32.7)†
3163 (37.6)
743 (48.8)*
Statin
355 (59.0)†
4396 (52.3)
690 (45.3)*
Drug titration level at 6 mo, n (%)‡
30 (5.3)
312 (3.9)
76 (5.4)
1 to 3
0 (no study drug)
419 (74.0)
2903 (36.3)
174 (12.4)
4 (target dose)
117 (20.7)
4777 (59.8)
1155 (82.2)
BP indicates blood pressure; LVEF, LV ejection fraction; PVD, peripheral vascular disease.
*P⬍0.001 vs normal.
†P⬍0.01 vs normal.
‡P⬍0.001 for difference between categorical variables.
51
52
Table 4.
Hypertension
January 2008
Risk Associated With Blood Pressure Status 6 Months Post-MI
Events/1000 Patient Years,
Follow-Up BP
Low BP Compared
With Normal
High BP Compared
With Normal
Outcome
(No. of Events)
Low
(n⫽602)
Normal
(n⫽8408)
High
(n⫽1522)
HR
(95% CI)
Adjusted HR
(95% CI)*
HR (95% CI)
Adjusted HR
(95% CI)*
All-cause
mortality (936)
63
51
68
1.23 (0.95 to 1.58)
1.46 (1.11 to 1.91)
1.33 (1.13 to 1.57)
1.04 (0.87 to 1.24)
CV death (720)
48
39
52
1.24 (0.93 to 1.66)
1.48 (1.09 to 2.01)
1.33 (1.10 to 1.61)
1.02 (0.83 to 1.24)
Fatal and nonfatal
stroke (198)
6
10
22
0.60 (0.26 to 1.35)
0.81 (0.35 to 1.85)
2.19 (1.60 to 2.99)
1.64 (1.17 to 2.29)
Fatal and nonfatal
MI (509)
23
29
41
0.80 (0.52 to 1.21)
1.05 (0.69 to 1.61)
1.40 (1.13 to 1.75)
1.13 (0.89 to 1.43)
Sudden
death/resuscitated
cardiac arrest (364)
24
20
27
1.24 (0.82 to 1.87)
1.38 (0.90 to 2.13)
1.39 (1.06 to 1.80)
1.17 (0.88 to 1.54)
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HF (704)
42
39
61
1.06 (0.77 to 1.45)
1.49 (1.07 to 2.09)
1.53 (1.27 to 1.84)
1.07 (0.88 to 1.30)
CV death, MI, HF,
stroke, or sudden
death/resuscitated
cardiac arrest (1591)
92
91
137
1.03 (0.83 to 1.27)
1.32 (1.06 to 1.66)
1.50 (1.33 to 1.70)
1.14 (1.00 to 1.31)
BP indicates blood pressure; CV, cardiovascular; HF, hospitalization for heart failure.
*Adjusted for age, sex, BMI, eGFR, previous MI, previous HF, previous stroke, baseline diabetes, peripheral vascular disease, history of hypertension, and NYHA
class at 6 months.
relationship between low systolic blood pressure and the risk
of hospitalization for HF (adjusted HR: 1.35; 95% CI: 0.92 to
1.96; P⫽0.12) and combined cardiovascular events (adjusted
HR: 1.26; 95% CI: 0.98 to 1.61; P⫽0.07). There was no
interaction between antecedent hypertension and the effect of
elevated or low systolic blood pressure at 6 months (for all
end points P⬎0.2).
Assessing the relationship between the average systolic
blood pressure across the 1-, 3-, and 6-month visits as a
continuous variable and the risk of subsequent cardiovascular
events demonstrated a linear relationship between increasing
systolic blood pressure and stroke (P for linear term⫽0.003)
and a quadratic relationship between systolic blood pressure
and the risk of all-cause death (P for quadratic term⫽0.0003;
nadir: 135 mm Hg), cardiovascular death (P⫽0.002; nadir:
135 mm Hg), sudden death or resuscitated cardiac arrest
(P⫽0.02; nadir: 127 mm Hg), and combined cardiovascular
events (P⫽0.004; nadir: 131 mm Hg; Figure). The average
systolic blood pressure across the 1-, 3-, and 6-month visits
was not associated with the risk of recurrent MI (P for linear,
quadratic, cubic, or splined, all ⬎0.2), whereas the relationship with the risk of hospitalization for HF was complex (P
for cubic fit⫽0.002). A time-dependent Cox analysis also
demonstrated that both post-MI systolic blood pressure
⬎140 mm Hg (adjusted HR: 1.11; 95% CI: 1.01 to 1.21;
P⫽0.03) and systolic blood pressure ⬍100 mm Hg (adjusted
HR: 1.38; 95% CI: 1.21 to 1.59; P⬍0.0001) were significantly associated with the combined outcome. Classification
of patients based on diastolic blood pressure demonstrated
trends similar to those seen for systolic blood pressure, but
the relationships were not significant because of the lower
number of patients with consistent diastolic blood pressure
⬍60 mm Hg (n⫽301) or ⬎90 mm Hg (n⫽302).
Discussion
We observed that antecedent hypertension at the time of MI
is strongly associated with adverse cardiovascular outcomes
in patients with LV dysfunction, HF, or both receiving
contemporary therapy, including inhibitors of the renin-an-
Figure. Adjusted HR as a function of average blood pressure
across the 1-, 3-, and 6-month visits relative to hazard at
130 mm Hg. The red lines are 95% CI. For each end point, the
simplest model not significantly improved by a more complex
model is shown.
Thune et al
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giotensin system. Moreover, in this well-treated cohort, in
which nearly all of the patients, by design, received an
renin-angiotensin system inhibitor, 68% received a
␤-blocker, and 84% received ⱖ1 antihypertensive drug in
addition to study drug; ⬇15% of post-MI patients who
survived to 6 months had elevated systolic blood pressure on
2 of 3 visits, and these patients were at increased risk for
subsequent stroke and combined cardiovascular events compared with patients with normal blood pressure.
The effect of hypertension on the risk of adverse CV
events has been well documented in patients without MI,17
and our results confirm previous findings that antecedent
hypertension increases the risk of HF, stroke, and death after
MI.6 – 8,18 –21 Other studies have also examined the relationship
between post-MI blood pressure and outcomes. A U-shaped
relationship between diastolic blood pressure and death from
coronary heart disease was observed in patients with a
previous MI from the Framingham Heart Study cohort,22
whereas a linear increase in the risk of reinfarction and
coronary heart disease death was seen with increasing systolic blood pressure.23 However, an analysis of the Coronary
Drug Project found no relation between diastolic or systolic
blood pressure after MI and adverse cardiovascular outcomes
when adjusting for other clinical variables.24 Low diastolic or
systolic blood pressure was associated with adverse outcome
early after MI in the Multiple Risk Factor Intervention Trial,
whereas high blood pressure was worse for long-term outcome.11 In 2677 community-based post-MI patients, the risk
of stroke was increased with higher diastolic and systolic
blood pressure after MI, whereas reinfarction and all-cause
death were associated with low diastolic blood pressure
only.25 Finally, the International Verapamil-Trandolapril
Study, in which a third of the patients had a previous MI, and
⬇5% had HF, noted a quadratic relationship between blood
pressure and the rate of death, MI, or stroke.26
Although decreased blood pressure after MI may be
associated with reduced LV function, and our data demonstrate higher morbidity and mortality in patients with low
blood pressure after MI, we and others have found that
elevated blood pressure in medium- and long-term survivors
of MI re-emerges as a potent risk factor for new cardiovascular events. Although a number of mechanisms may underlie
the increased risk associated with post-MI hypertension, we
have shown previously that patients with a previous history of
hypertension are at the greatest risk for adverse LV remodeling post-MI, which itself is associated with an increased
likelihood of adverse outcomes.4 Similarly, LV hypertrophy,
a consequence of hypertension, is itself an independent
predictor of both adverse remodeling and clinical outcomes
post-MI.5,9 Unfortunately, few data on patients with high-risk
MI are available from the large, randomized, placebocontrolled hypertension trials, which either specifically excluded patients with HF or included too few patients with a
previous MI to perform adequate subgroup analyses.27–30
Thus, whether aggressive blood pressure treatment in the
post-MI population would reduce the risk of stroke or other
cardiovascular events remains unknown.
Our finding that elevated blood pressure at follow-up was
associated with adverse cardiovascular outcome in high-risk,
Pre-MI and Post-MI Hypertension and Outcomes
53
post-MI patients contrasts with large studies of patients with
acute or stable HF. In these studies, increasing blood pressure
has generally been associated with improved prognosis, even
for patients with blood pressure in the normal and high
range.31–35 This finding may be explained in part by the fact
that 44% of the patients in VALIANT were in NYHA class 1
at the 6-month follow-up visit, and only 11% were in class 3
or 4. Thus, whereas cardiac function may be the main
determinant of outcome in the HF population, in post-MI
patients without overt HF, elevated blood pressure may be
more common and may reflect an increased risk of ischemic
events.
Some important limitations of this analysis should be
noted. Patients who survived to the 6-month follow-up visit
were not representative of the baseline cohort, and these
differences may reflect significant survivor bias, potentially
limiting the generalizability of our findings to early post-MI
patients. We cannot exclude the possibility that some patients
not considered hypertensive at 6 months might have lower
blood pressure secondary to worsening LV function. The
interpretation of the effect of diastolic blood pressure on
outcomes is complicated by the potential for increased pulse
pressure because of increased conduit vessel stiffness. Finally, because VALIANT was not a hypertension trial, there
was no strict definition of antecedent hypertension, and blood
pressure was measured during the trial in an ambulatory
setting with no strict protocol. Nevertheless, this limitation
likely attenuated the true relationship between post-MI hypertension and outcome.
Perspectives
Both low and elevated systolic blood pressure after a highrisk MI are associated with an increased risk for adverse
cardiovascular events. Elevated systolic blood pressure, a
potentially modifiable risk factor, is associated with a profound increase in the risk of stroke. Whether more aggressive
treatment of elevated blood pressure in patients with a
previous MI can reduce adverse outcomes remains unknown.
Source of Funding
VALIANT was sponsored by Novartis Pharmaceuticals.
Disclosures
E.J.V., J.J.V.M., R.M.C., J.H., M.A.P., and S.D.S. report having
received research funding from Novartis Pharmaceuticals. E.J.V.,
J.L.R., J.H., M.A.P., and S.D.S. report having served as consultants
for or having received honorariums from Novartis Pharmaceuticals.
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Hypertension. 2008;51:48-54; originally published online November 19, 2007;
doi: 10.1161/HYPERTENSIONAHA.107.093682
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