Download Prognostic value of heart rate and systemic systolic blood pressure

Systemic Blood Pressure and Heart Rate as Prognostic Indicators
in Pulmonary Arterial Hypertension
Malcolm M. Bersohn, MD, PhD;1 Shelley Shapiro, MD, PhD;1 Dave P. Miller, MS;2 Michelle P. Turner, MS;2 Glenna L. Traiger, RN, MSN;1 Adaani E. Frost, MD3
1
VA Greater Los Angeles Healthcare System and David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 2ICON Clinical Research, San Francisco, CA, USA; 3Baylor College of Medicine, Houston, TX, USA
Introduction
• Vital sign measurements such as resting
heart rate and systemic systolic blood
pressure (SBP) can predict survival in
patients with congestive heart failure due
to left ventricular systolic dysfunction.1,2
The extent to which these vital sign
measurements alone serve as useful
prognostic indicators in patients with
pulmonary arterial hypertension (PAH)
is being explored.3
• We hypothesized that, similar to patients
with left ventricular dysfunction, a high
or increasing resting heart rate and/or low
or decreasing SBP would portend a worse
prognosis in patients with PAH.
• The Registry to EValuate Early And Longterm PAH Disease Management (REVEAL)
is a large (54-center), ongoing, prospective,
US-based observational study designed to
provide current information about the
demographics, course, and management
of approximately 3500 patients with PAH.
Patients have been enrolled and will be
followed for ≥5 years from the time of
enrollment.4
Results
• At the first vital sign follow-up, SBP data were available for 2521 patients,
heart rate data were available for 2497 patients, and SBP/heart rate ratio data
were available for 2478 patients.
• From enrollment to the first vital sign follow-up, data for changes in SBP were
available for 2415 patients, change in heart rate data for 2367 patients, and
change in SBP/heart rate ratio data for 2345 patients.
• A sensitivity analysis was performed excluding those patients with PCWP
>15 mm Hg, thus limiting analysis to those patients with traditional
hemodynamic criteria of PCWP ≤15 mm Hg, and it did not have an
effect upon the results. That implies that patients with PAH and mildly
elevated PCWP are not different from other patients with PAH.
Table 1. Survival and Freedom From Hospitalization 1 Year After the
First Vital Sign Follow-up by Quintiles of Vital Signs and of Changes
in Vital Signs
Quintiles
• To test the hypothesis that an increasing
resting heart rate and a decreasing resting
SBP between enrollment and the first
vital sign follow-up visit are significant
independent predictors of the time to first
all-cause hospitalization and all-cause
mortality 1 year after the first vital sign
follow-up in patients with PAH enrolled
in REVEAL.
Study Design
• Included in this analysis were consecutively
enrolled newly or previously diagnosed
patients with Group 1 PAH and aged ≥19
at enrollment with documentation of:
–– Mean pulmonary artery pressure of
>25 mm Hg at rest or >30 mm Hg
with exercise
–– Pulmonary capillary wedge pressure
(PCWP) ≤18 mm Hg at rest or left
ventricular end-diastolic pressure
(LVEDP) ≤18 mm Hg
–– Pulmonary vascular resistance (PVR)
≥240 dynes·sec·cm–5
• Patients were divided into quintiles according
to the value of heart rate, SBP, and the ratio
SBP/heart rate at the first vital sign follow-up
visit and according to the changes in each
variable between enrollment and the first vital
sign follow-up visit, which occurred after a
median of 3 months after enrollment.
Q1
≤102
≤70
Q2-4
103-130
Q5
Survival
Freedom from
hospitalization
Figure 5. One-year Freedom From Hospitalization by Resting
Heart Rate at First Follow-up
100
95
90
85
80
∆ SBP
∆ Heart
Rate
≤1.2
≤-12
≤-10
≤-0.2
71-95
1.2-1.7
-12 to 11
>130
>95
> 1.7
>11
>10
>0.2
2521
2497
2478
2415
2367
2345
Q1
83 ± 2
92 ± 1
80 ± 2
85 ± 2
90 ± 1
84 ± 2
Q2-4
91 ± 1
90 ± 1
91 ± 1
91 ± 1
90 ± 1
90 ± 1
Q5
91 ± 1
84 ± 2
93 ± 1
88 ± 2
86 ± 2
91 ± 1
Hazard ratio
1.9
1.5
2.1
1.3
1.2
1.3
P value
<0.001
<0.001
<0.0001
0.006
0.09
0.01
Q1
62 ± 2
74 ± 2
60 ± 2
66 ± 2
70 ± 2
70 ± 2
N
Q2-4
72 ± 1
70 ± 1
72 ± 1
72 ± 1
70 ± 1
69 ± 1
Q5
73 ± 2
66 ± 2
75 ± 2
71 ± 2
69 ± 2
74 ± 2
6-minute walk test
distance (m), mean ± SD
Hazard ratio
1.4
1.3
1.6
1.1
1.1
1.1
P value
<0.001
<0.001
<0.001
0.06
0.35
0.11
Mean pulmonary artery
pressure (mm Hg),
mean ± SD
-10 to 10 -0.2 to 0.2
• Patients in the highest quintile of resting heart rate (Q5: >95 bpm)
had significantly lower survival at 12 months (84% ± 2%) than those
in the other quintiles (Q1: 92% ± 1%, Q2-4: 90% ± 1%); hazard
ratio = 1.5, Wald chi-square P < 0.001.
Figure 3. One-year Survival by Resting SBP/Heart Rate at
First Follow-up
• Patients in the highest quintile of resting heart rate (Q5: >95 bpm) had
a lower freedom from hospitalization at 12 months (66% ± 2%) than
those in the other quintiles (Q1: 74% ± 2%, Q2-4: 70% ± 1%;);
hazard ratio = 1.3, Wald chi-square P < 0.001.
Figure 6. Freedom From Hospitalization by Resting SBP/Heart
Rate at First Follow-up
Figure 1. One-year Survival by Resting SBP at First Follow-up
Table 2. Traditional PAH Risk Factors Across Quintiles According to
Resting SBP, Heart Rate, and SBP/Heart Rate at First Follow-up
SBP/Heart Rate
(mm Hg/bpm)
≤1.2
>1.2–1.7
>1.7
2478
Q1
Q2–4
Q5
SBP (mm Hg)
≤102
>102–≤130
>130
2521
360 ± 125
373 ± 123
347 ± 123
Heart Rate
(bpm)
≤70
>70–≤95
>95
2497
381 ± 120
366 ± 123
350 ± 129
Q1
Q2–4
Q5
51 ± 14
49 ± 14
47 ± 14
47 ± 15
49 ± 14
51 ± 15
51 ± 14
50 ± 14
46 ± 14
349 ± 133
372 ± 120
368 ± 124
SD, standard deviation.
Results are mean ± SE; P value from Wald chi-square test comparing the worst quintile to the
remaining quintiles. ∆ indicates first follow-up value - enrollment value.
• Patients in the lowest quintile of resting SBP (Q1: ≤102 mm Hg) and the
highest quintile of resting heart rate (Q5: >95 bpm) had significantly lower
survival at 12 months and freedom from hospitalization at 12 months than
those in the other quintiles.
• Patients in the lowest quintile of resting SBP/heart rate (Q1: ≤1.2) had
significantly lower survival at 12 months and freedom from hospitalization
at 12 months than those in the other quintiles.
• All of the vital sign parameters were better predictors of survival than freedom
from hospitalization.
• There were no significant differences among quintiles in freedom from hospitalization
based on change in SBP/heart rate from enrollment to first follow-up; hazard ratio =
1.1, Wald chi-square P = 0.11.
• Changes in SBP or heart rate from enrollment to first follow-up were not significant
predictors of hospitalization.
Q1
Q2–4
Q5
• Evaluation of other traditional prognostic indicators in PAH showed similarity across
quintiles stratified according to the vital sign parameters.
Conclusions
• Patients in the lowest quintile of resting SBP/heart rate (Q1: ≤1.2
mm Hg/bpm) had significantly lower survival at 12 months (80% ± 2%)
than those in the other quintiles (Q2-4: 91% ± 1%, Q5: 93% ± 1%);
hazard ratio = 2.1, Wald chi-square P < 0.001.
Figure 4. One-year Freedom From Hospitalization by Resting
SBP at First Follow-up
• Patients in the lowest quintile of resting SBP/heart rate (Q1: ≤1.2 mm
Hg/bpm) had significantly lower freedom from hospitalization at 12
months (60% ± 2%) than those in the other quintiles (Q2-4: 72% ±
1%, Q5: 75% ± 2%); hazard ratio = 1.6, Wald chi-square P < 0.001.
Figure 7. One-year Survival by Change in Resting SBP/Heart
Rate From Enrollment to First Follow-up
Statistical Analyses
• Data lock was January 14, 2010.
• Patients were included if they had at least
one vital sign recorded (SBP and/or heart
rate) at the first follow-up visit occurring
within 1 year of enrollment and if they had at
least 1 year of follow-up thereafter. A total of
2540 patients were included in the analysis.
• Vital sign parameters were divided into
quintiles to analyze survival and freedom
from hospitalization one year after the first
follow-up using Kaplan-Meier curves.
• The results for quintiles 2–4 were similar
and were combined in the final analysis.
Log-rank analysis with a Bonferroni
correction was used to assess differences
(Bonferroni adjusted alpha = 0.017).
• Hazard ratios were computed from
univariate Cox regression models
comparing patients in the worst quintile
for the parameter to all others.
Figure 8. One-year Freedom From Hospitalization by Change in Resting
SBP/Heart Rate at First Follow-up
∆ SBP/
Heart
Rate
N
Methods
Objective
SBP
Heart
Rate
SBP/
Heart
Rate
Figure 2. One-year Survival by Resting Heart Rate at First
Follow-up
• Current values of vital signs were more useful than changes in vital signs in predicting
mortality and hospitalization. The predictive value of vital signs at the first follow-up
visit was similar to the predictive value of enrollment vital signs, which we have
previously presented.3 Thus, the presence of hypotension and or tachycardia at any
time predicts a worse clinical outcome.
• High heart rate (>95 bpm), low SBP (≤102 mm Hg), and a ratio of SBP/heart rate
≤1.2 mm Hg/bpm identified high-risk groups of patients that had 50-100% increase
in mortality and 30-60% increase in hospitalization over 1 year among a large group
of adults with PAH. These simple vital sign parameters are useful by themselves
and as part of a more comprehensive predictive formula.5
• These data reflect the similarity to left ventricular dysfunction, where low SBP and
high heart rate are also predictive of poor outcome.
Acknowledgments
Funding for the REVEAL Registry and the development of this poster was provided
by Actelion Pharmaceuticals US, Inc. Editorial assistance was provided by Kathryn
Leonard of inScience Communications, a Wolters Kluwer business.
References
• Patients in the lowest quintile of resting SBP (Q1: ≤102 mm Hg) had
significantly lower survival at 12 months (83% ± 2%) than those in the
other quintiles (91% ± 1%); hazard ratio = 1.9, Wald chi-square P < 0.001.
• Patients in the lowest quintile of resting SBP (Q1: ≤102 mm Hg)
had significantly lower freedom from hospitalization at 12 months
(62% ± 2%) than those in the other quintiles (Q2-4: 72% ± 1%,
Q5: 73% ± 2%); hazard ratio = 1.4, Wald chi-square P < 0.001.
• Patients in the lowest quintile of change resting SBP/heart rate (Q1: ≤-0.2
mm Hg/bpm) had lower survival at 12 months (84% ± 2%) than those in
the other quintiles (Q2-4: 90% ± 1%, Q5: 91% ± 1%); hazard ratio = 1.3,
Wald chi-square P = 0 .01.
• Comparison with Figure 3 shows that the change in SBP/heart rate
was not as strong a predictor as the SBP/heart rate at first follow-up.
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