Download Reflection in the Arterial System and the Risk of Coronary Heart

AJH
2002; 15:405– 409
Reflection in the Arterial System
and the Risk of Coronary Heart Disease
Tomoshige Hayashi, Yasunori Nakayama, Kei Tsumura,
Kiyomichi Yoshimaru, and Hiroyasu Ueda
Background: Although it was reported that the augmentation index and inflection time are closely related to
reflection in the arterial system and large artery function,
it is not known whether these indices of the ascending
aortic pressure waveform increase the risk of coronary
heart disease (CHD). The purpose of this study was to
evaluate whether the aortic reflection of the ascending
aortic pressure waveform is related to an increased risk of
CHD.
Methods: We enrolled 190 men and women who had
chest pain, normal contractions, no local asynergy, and no
history of myocardial infarction. We measured the ascending aortic pressure using a fluid-filled system. The inflection time was defined as the time interval from initiation of
a systolic pressure waveform to the inflection point. We
investigated the association between the inflection time
and augmentation index of the ascending aorta and the risk
of CHD.
A
Results: Both the inflection time and augmentation
index were associated with an increased risk of CHD. The
crude prevalence rates of CHD were 66.0% for the shortest
quartile and 10.6% for the longest quartile of the inflection
time, and 17.0% for the lowest quartile and 40.4% for the
highest quartile of the augmentation index. The multipleadjusted odds ratio of CHD was 30.8 (95% confidence
interval [CI] 7.43–128.05) for the shortest quartile of the
inflection time compared with the longest quartile and was
3.82 (95% CI 1.26 –11.59) for the highest quartile of the
augmentation index compared with the lowest quartile.
Conclusions: The augmentation index and inflection time were associated with an increased risk of CHD.
Am J Hypertens 2002;15:405– 409 © 2002 American
Journal of Hypertension, Ltd.
Key Words: Risk factors, inflection time, coronary
disease, stenosis, aorta.
lthough previous clinical studies on risk factors
have greatly contributed to the understanding and
prevention of coronary heart disease (CHD),1– 8
some risk factors remain a challenge. The major risks
studied extensively include smoking, hypertension, high
serum cholesterol, low levels of high-density lipoprotein
cholesterol, type 2 diabetes, and aging.1–5 Although high
systolic hypertension, high diastolic hypertension, and
high pulse pressure are potent risk factors,6 – 8 the effects of
the reflection of the ascending aortic pressure waveform
on the occurrence of CHD have not been reported. The
fact that the analysis of reflection waveform is detected by
high fidelity measurements of arterial pressure waveform
makes it impractical in clinical settings. Therefore, we
measured inflection point using a fluid-filled recording
system and examined whether the inflection time is correctly defined.9 To quantify the artery reflection, we used
the augmentation index and inflection time.9 The augmentation index and inflection time using a fluid-filled recording system were reliable and unchanged by repeated measurements.
Previous investigators demonstrated that the ascending
aortic pressure waveform was divided by the augmentation index and that both inflection time and augmentation
index were related to the impedance spectral pattern.8 –11
Thus, the impedance spectra represent larger reflections as
the augmentation index becomes larger. In contrast, the
impedance spectra reveal smaller and more diffuse reflections as the augmentation index gets smaller. Both the
inflection time and augmentation index are closely related
to reflection in the arterial system and large artery function. These indices are promising tools for understanding
the arterial system using a fluid-filled recording system.
We hypothesized that the inflection time and large artery
Received January 2, 2002. First Decision January 8, 2002.
Accepted January 8, 2002.
ment of Internal Medicine (HU), Osaka City University Medical School,
Osaka, Japan.
Address correspondence and reprint requests to Dr. Yasunori Nakayama, Department of Cardiology, Ishikiriseiki Hospital, 18-28, Yayoi,
Higashiosaka-City, Osaka, 579-8026, Japan; e-mail: ahiru-nakayama@
par.odn.ne.jp
From the Department of Cardiology, Ishikiriseiki Hospital (TH, YN,
KY) and Department of Preventive Medicine and Environmental Health
(TH), Second Department of Internal Medicine (KT), and First Depart© 2002 by the American Journal of Hypertension, Ltd.
Published by Elsevier Science Inc.
0895-7061/02/$22.00
PII S0895-7061(02)02260-4
406
REFLECTION AND CORONARY HEART DISEASE
function would be associated with coronary artery conditions. Therefore, we investigated the effects of large artery
function, using the inflection time and augmentation index, in relation to the risk of CHD.
Methods
Study Subjects
The study group consisted of 190 consecutive patients
who were admitted to Ishikiriseiki Hospital, Osaka, Japan,
because of a CHD diagnosis using cardiac catheterization.
They were eligible for entry into the study if they had
normal contractions, no local asynergy shown by left
ventriculography, and no history of myocardial infarction
to approximately fix cardiac function. We enrolled 1021
men ranging in age from 35 to 78 years between January
1990 and March 1999 in whom cardiac catheterizations
were done for the first time. Of these, 831 were excluded
from this study because of acute myocardial infarction, the
presence of local asynergy shown by left ventriculography, chronic renal failure, severe valvular disease, post
cardiac surgery, cardiomyopathy, arterial fibrillation,
pacemaker implantation, sick sinus syndrome, or aortic
dissection. The protocol was in accordance with the Institutional Guidelines for Human Research, and each individual provided a written statement of informed consent to
the diagnostic and therapeutic procedures required for
examination, which stated that the results of the examination could be used for the study.
Measurement of Hemodynamic Variables
Hemodynamic measurements were made with the patient
in the supine position. Aortic pressure was measured using
a fluid-filled system (5F pigtail catheter) at the ascending
aorta. A hard copy was made of the pressure tracing using
a chart recorder (Nihon Koden, Surgical Monitoring System, Tokyo, Japan) at a paper speed of 100 mm/sec. We
compared tracings of systolic, diastolic, mean, and pulse
pressures in patients with and without CHD. Ascending
aortic pressure at the inflection point dividing into an early
and late systolic phase was used as inflection pressure.8 –11
We used the inflection time as the time interval between
onset of a systolic pressure waveform and the inflection
point.8 –11
To examine whether inflection time measured by a
fluid-filled recording system is correctly defined and truly
reliable, we compared the values of inflection time measured by interobserver with those by intraobserver. There
was a closely linear correlation between the inter- and
intraobserver in this study population (Yinter ⫽ 0.96Xintra
⫹ 1.4, R ⫽ 0.93). The inflection time defined by a fluidfilled recording system was reliable and unchanged by
repeated measurements.
Measurement of Angiographic Variables
Cardiac catheterization was performed according to a standard technique. Optimal views of the target lesions from
AJH–May 2002–VOL. 15, NO. 5
all technically suitable angiograms were analyzed, and
measurements were made of the maximal narrowing of the
target lesion, as well as a noninvolved segment. Angiographic measurements were calibrated using a guiding
catheter as the reference dimension. The absolute values
for the minimal lumen diameter (MLD) and the reference
lumen diameter were measured at end-diastole. Coronary
heart disease was defined as MLD stenosis ⬎50% on the
angiogram, and non-CHD was defined as MLD stenosis
ⱕ50% on the angiogram.
Statistical Analysis
Values were expressed as mean ⫾ one standard deviation.
Categoric variables were compared using the ␹2 test. Differences in the mean values between the two groups were
compared using an unpaired t test. A P value of ⬍ .05 was
considered significant. Multiple logistic regression analysis was used to evaluate the simultaneous effects of the
augmentation index or inflection time, age, body mass
index, smoking habits (current smokers or nonsmokers),
hypertension (yes or no), type 2 diabetes (yes or no),
hypercholesterolemia (yes or no), calcium channel blockers (yes or no), ␤-blockers (yes or no), angiotensin converting enzyme (ACE) inhibitors (yes or no), nitrates (yes
or no), parental history of CHD, and sex. The linear trends
in the risks were evaluated by entering indicators for each
categoric level of exposure using the median value for
each category. We calculated the 95% confidence interval
(CI) for each odds ratio (OR) and all P values were two
tailed. Statistical analyses were performed using the SPSS
10.0 software package (SPSS Inc., Chicago, IL).
Results
Baseline Clinical Characteristics
The baseline clinical characteristics of the study group are
summarized in Table 1. Although the mean level of body
mass index; the distribution of sex; the presence of parental history of CHD, hypertension, type 2 diabetes, or
hypercholesterolemia; and the smoking status were similar
in the two groups, the mean age was higher in patients
with CHD than those without CHD. There were no significant differences in heart rate or ejection fraction between the two groups. Although systolic, diastolic, and
mean pressures in the ascending aorta were not different
between the two groups, the pulse pressure was higher in
patients with CHD than those without CHD (66.5 ⫾ 21.3
and 73.6 ⫾ 19.7 mm Hg, respectively; P ⫽ .029). The
augmentation index was significantly higher in patients
with CHD than in those without CHD (0.22 ⫾ 0.16 and
0.30 ⫾ 0.14, respectively; P ⫽ .001), and the inflection
time was significantly longer in patients with CHD than in
those without CHD (110.3 ⫾ 21.1 and 90.5 ⫾ 22.5,
respectively; P ⬍ .001).
Illustrated in Fig. 1 are the waveforms of ascending
aortic pressure in the cases of patient without CHD (left
panel) and patient with CHD (right panel). Although heart
AJH–May 2002–VOL. 15, NO. 5
REFLECTION AND CORONARY HEART DISEASE
407
Table 1. Baseline characteristics of study patients (n ⫽ 190)
Variables
Male sex (n)
Age (y)
Body mass index (kg/m2)
Hypertension
Type 2 diabetes
Hypercholesterolemia
Current smoker
Parental history of CHD
Heart rate (beats/min)
Ejection fraction (%)
Ascending aorta
Systolic pressure (mm Hg)
Diastolic pressure (mm Hg)
Mean pressure (mm Hg)
Pulse pressure (mm Hg)
Augmentation index
Inflection time (mm sec)
CHD (ⴚ)
78
57.8
23.5
47
34
61
63
20.0
68.8
75.5
139.7
73.2
100.2
66.5
0.22
110.3
CHD (ⴙ)
(60.9)
⫾ 11.4
⫾ 3.3
(36.7)
(26.6)
(47.7)
(49.2)
(15.6)
⫾ 13.3
⫾ 6.8
43
62.1
23.9
62
23
32
31
15.0
66.3
75.8
24.7
9.5
12.9
21.3
0.16
21.1
144.6
71.1
101.5
73.6
0.30
90.5
⫾
⫾
⫾
⫾
⫾
⫾
P
(69.4)
⫾ 9.8
⫾ 3.5
(48.4)
(37.1)
(51.6)
(50.0)
(24.2)
⫾ 11.7
⫾ 7.2
.258
.012
.387
.125
.137
.609
.920
.153
.230
.812
22.2
10.7
13.3
19.7
0.14
22.5
.183
.162
.517
.029
.001
⬍.001
⫾
⫾
⫾
⫾
⫾
⫾
CHD ⫽ coronary heart disease.
Values are mean ⫾ SD or No. (%) of patients.
rates are similar in the two cases, the inflection point is
much earlier in patients with CHD than in patients without
CHD. As a result, inflection time is shorter in patients with
CHD than in patients without CHD.
The Augmentation
Index and the Risk of CHD
To examine the association between the augmentation
index and the risk of CHD, all patients were classified into
quartiles of the augmentation index level. The augmenta-
tion index was associated with an increase in the risk of
CHD (Table 2). The crude prevalence rates of CHD were
17.0% for quartile 1, 25.0% for quartile 2, 47.9% for
quartile 3, and 40.4% for quartile 4 of augmentation index
levels. After adjustment for age, body mass index, smoking habits, hypertension, hypercholesterolemia, type 2 diabetes, calcium channel blockers, ␤-blockers, ACE inhibitors, nitrates, parental history of CHD, and sex, the OR of
CHD was 1.00 (reference) for quartile 1, 1.85 (95% CI
0.63–5.45) for quartile 2, 4.63 (95% CI 1.57–13.7) for
FIG. 1. Left) Without coronary heart disease; (right) with coronary heart disease. Schematic representation of augmentation index and
inflection time of ascending aortic artery in a representative case. Augmentation index is the ratio of inflection pressure to pulse pressure. The
inflection time was defined as the time interval between onset of a systolic pressure waveform and the inflection point.
408
REFLECTION AND CORONARY HEART DISEASE
AJH–May 2002–VOL. 15, NO. 5
Table 2. Odds ratio of coronary heart disease according to the augmentation index and inflection time
Augmentation index
Quartile 1 (⫺0.14–0.14)
Quartile 2 (0.15–0.26)
Quartile 3 (0.27–0.36)
Quartile 4 (0.37–0.74)
Wald, ␭2
P for trend
Continuous, per 0.1
Wald, ␭2
Inflection time (mm sec)
Quartile 1 (56–85)
Quartile 2 (86–102)
Quartile 3 (103–123)
Quartile 4 (124–208)
Wald, ␭2
P for trend
Continuous, per 10 mm
sec decreased
Wald, ␭2
Crude OR
(95% CI)
Multiple-Adjusted*
OR (95% CI)
17.0
25.0
47.9
40.4
1.00
1.63 (0.60–4.43)
4.48 (1.74–11.58)
3.31 (1.27–8.62)
12.2
.002
1.40 (1.13–1.72)
9.7
1.00
1.85 (0.63–5.45)
4.63 (1.57–13.7)
3.82 (1.26–11.59)
9.4
.007
1.38 (1.08–1.76)
6.6
66.0
42.6
12.2
10.6
16.2 (5.38–49.20)
6.22 (2.08–18.56)
1.17 (0.33–4.14)
1.00
37.9
⬍.001
30.8 (7.43–128.05)
6.77 (2.01–22.74)
1.04 (0.27–3.98)
1.00
34.1
⬍.001
1.59 (1.33–1.90)
26.5
1.71 (1.38–2.13)
23.2
n
Cases
(%)
47
48
48
47
8
12
23
19
47
47
49
47
31
20
6
5
OR ⫽ odds ratio; CI ⫽ confidence interval.
* Adjusted for age, body mass index, smoking habits, hypertension, type 2 diabetes, hypercholesterolemia, parental history of coronary
heart disease, calcium channel blockers (yes or no), ␤-blockers (yes or no), angiotensin converting enzyme inhibitors (yes or no), nitrates
(yes or no), and sex.
quartile 3, and 3.82 (95% CI 1.26 –11.59) for quartile 4 of
the augmentation index level (Wald ␭2 ⫽ 9.4, P for trend
⫽ .007). To further quantify the effect of the augmentation
index on CHD, we modeled the augmentation index as a
continuous variable. The multiple-adjusted OR of CHD
was increased by 38% when the augmentation index was
increased by 0.1 (OR 1.38; 95% CI 1.08 –1.76, Wald ␭2 ⫽
6.6).
for age, body mass index, smoking habits, hypertension,
type 2 diabetes, hypercholesterolemia, calcium channel
blockers, ␤-blockers, ACE inhibitors, nitrates, parental
history of CHD, and sex, the association was significant.
The inflection time had a stronger association with the risk
of CHD than the augmentation index.
The Inflection Time and the Risk of CHD
Index to Quantify Large Artery Function
To examine the association between the inflection time
and the risk of CHD, all patients were classified into
quartiles of inflection time. The analysis of inflection time
in ascending aorta is summarized in Table 2. The inflection time as it decreased was also associated with an
increase in the risk of CHD. The crude prevalence rates of
CHD were 66.0% for quartile 1, 42.6% for quartile 2,
12.2% for quartile 3, and 10.6% for quartile 4 of inflection
time. The multiple-adjusted OR of CHD was 30.8 (95% CI
7.43–128.05) for quartile 1, 6.77 (95% CI 2.01–22.74) for
quartile 2, 1.04 (95% CI 0.27–3.98) for quartile 3, and
1.00 (reference) for quartile 4 of inflection time (Wald ␭2
⫽ 34.1, P for trend ⬍ .001). When we modeled the
inflection time as a continuous variable, the multipleadjusted OR of CHD was increased by 71% when the
inflection time was decreased by 10 mm sec (OR 1.71;
95% CI 1.38 –2.13, Wald ␭2 ⫽ 23.2).
Because arteriosclerosis decreases the compliance of the
aortic artery and increases the characteristic impedance, it
causes the aortic arterial input impedance to be relatively
high. Although ascending aortic input impedance most
clearly demonstrates manifest arteriosclerosis,12,13 the fact
that the estimation of impedance necessitates high fidelity
measurements of instantaneous ascending aortic flow and
pressure makes it impractical in clinical settings. Instead
of measuring ascending aortic input impedance, we focused on more simple variables pertaining to the dynamic
mechanical properties of the arterial system. The augmentation index and inflection time are closely related to
reflection in the arterial system and large artery function.
These indices are simple to measure and make attractive
tools to understand the arterial system. We hypothesized
that reflection in the arterial system and large artery function would be related to coronary artery conditions. Therefore, we investigated the effects of reflection in the arterial
system and large artery function in relation to the risk of
CHD. Our results revealed that these indices were associated with an increased risk of CHD.
Discussion
The inflection time and augmentation index were associated with an increased risk of CHD. Even after adjustment
AJH–May 2002–VOL. 15, NO. 5
Clinical Implications Regarding the
Augmentation Index and Inflection Time
Although major risks include smoking, hypertension, high
serum cholesterol, low levels of high-density lipoprotein
cholesterol, diabetes mellitus, and aging,1–5 other risk factors for CHD remain a challenge in clinical settings. The
augmentation index and inflection time of the ascending
aortic pressure waveform can reveal the large artery function. Because large artery function is composed of compliance, characteristic impedance, and resistance, the inflection time and augmentation index of the ascending
aortic pressure waveform would enable us to choose the
best drugs for patients with hypertension and angina pectoris. This study contributes not only to the understanding
and prevention of CHD, but also to the understanding of
the arterial system.
REFLECTION AND CORONARY HEART DISEASE
5.
6.
7.
8.
9.
10.
References
11.
1.
2.
3.
4.
Doyle JT: Cigarette smoking and coronary heart disease: combined
experience of the Albany and Framingham studies. N Engl J Med
1988;266:796 –801.
Kannel WB: Smoking and hypertension as predictors of cardiovascular risk in population study. J Hypertens 1990;8:53–58.
Shah PK, Pasternak R: The role of lipids in restenosis following
angioplasty. Curr Opin Lipidemiol 1993;4:310 –313.
Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP,
Knoke JD, Jacobs DR Jr, Bangdiwala S, Tyroler HA: High-density
12.
13.
409
lipoprotein cholesterol and cardiovascular disease: four prospective
American studies. Circulation 1989;79:8 –15.
Kannel WB: Diabetes and cardiovascular risk factors: the Framingham study. Circulation 1979;59:8 –13.
Benetos A, Safar M, Rudnichi A, Smulyan H, Richard JL, Ducimetieere P, Guize L: Pulse pressure: a predictor of long-term cardiovascular mortality in a French male population. Hypertension
1997;30:1410 –1415.
Mitchell GF, Moye LA, Braunwald E, Rouleau JL, Bernstein V,
Geltman EM, Flaker GC, Pfeffer MA: Sphygmomanometrically
determined pulse pressure is a powerful independent predictor of
recurrent events after myocardial infarction in patients with impaired left ventricular function. Circulation 1997;96:4254 –4260.
Kelly RP, Hayward CS, Avolio AP, O’Rourke MF: Non-invasive
determination of age-related changes in the human arterial pulse.
Circulation 1989;80:1652–1659.
Nakayama Y, Nakanishi N, Hayashi T, Nagaya N, Sakamaki F,
Satoh N, Ohya H, Kyotani S: Pulmonary artery reflection for differentially diagnosing primary pulmonary hypertension and chronic
pulmonary thromboembolism. J Am Coll Cardiol 2001;38:214 –
218.
Murgo JP, Westerhof N, Giolma JP, Altobelli SA: Aortic input
impedance in normal man: relationship to pressure wave forms.
Circulation 1980;62:105–116.
Murgo JP, Westerhof N, Giolma JP, Altobelli SA: Effects of exercise on aortic input impedance and pressure wave forms in normal
humans. Circ Res 1981;48:334 –343.
Sunagawa K, Maughan WL, Sagawa K: Stroke volume effect of
changing arterial input impedance over selected frequency ranges.
Am J Physiol 1985;248:H477–H486.
Nakayama Y, Tsumura K, Yamashita N, Yoshimaru K, Hayashi T:
Pulsatility of ascending aortic pressure waveform is a powerful
predictor of restenosis after percutaneous transluminal coronary
angioplasty. Circulation 2000;101:470 –472.