A portion of the arterial pressure wave travelling towards the extremities is reflected back from peripheral impedance points. In healthy individuals, the reflected wave returns to the aorta during diastole. With age and in the presence of vascular disease, arterial compliance decreases, and the arteries become stiff, thereby reducing the transit time for the incident and reflected waves. Consequently, the reflected wave arrives at the aorta during systole of the same cardiac cycle augmenting the central blood pressures. This augmentation of central pressure can be quantified by augmentation index (AIx), defined as the percentage of the central pulse pressure attributed to the reflected pulse wave.
AIx has been shown to be associated with cardiovascular risk [
146 patients recruited from the Cardiology Clinic at Tufts Medical Center in Boston were enrolled in the study. Subjects were instructed to fast overnight and to refrain from smoking, caffeine, or alcohol on the day of testing. Vasoactive medicines were withheld for a period of 12 hours prior to testing.
40 consecutive patients undergoing clinically indicated nonemergent left heart catheterization were retrospectively identified for inclusion into this study. As part of the standard catheterization protocol, blood pressures were measured within the femoral artery, ascending aorta, and the left ventricle using a 6-French end hole fluid-filled catheter and a pressure manometer prior to injection of any contrast agent. Pressures within the ascending aorta were considered as the central blood pressure (CBP) in the study.
The presence or absence of the following cardiovascular risk factors was assessed in all the subjects from both substudies: male gender, hypertension (systolic blood pressure >140 mmHg, diastolic blood pressure >90 mmHg, or being on an antihypertensive medication), hyperlipidemia (serum cholesterol >220 mg/dL or taking lipid-lowering medication), diabetes mellitus (fasting blood glucose >140 mg/dL or on oral hypoglycemics or insulin), family history of CAD (first-or second-degree relatives with premature CAD), postmenopausal women, and smoking (having smoked at least five times per day within last month). CAD was defined as the presence of ischemia or infarction on single-photon emission-computed tomographic (SPECT) nuclear myocardial perfusion imaging or >50% stenosis of an epicardial coronary artery by angiography.
Patients with moderate to severe heart failure (NYHA class III-IV, LVEF < 35), hemodynamic instability, peripheral arterial disease (Ankle-brachial Index <0.9), and finger deformities were excluded from the study. This study was approved by the Institutional Review Board at Tufts Medical Center. A written informed consent was obtained from all subjects.
Prior to collecting vascular measures, all study subjects rested in a quiet dark room for a period of 10 minutes. Post-acclimatization, the vascular data was recorded by PAT (EndoPAT2000, Itamar Medical Ltd, Caesarea, Israel) for a period of 5 minutes with the patient in supine position. The procedure for obtaining AIx is essentially the same as described in previous reports [
Data were entered into MS-Excel and analyzed with SPSS (SPSS Inc., Chicago, Ill, USA). Data are expressed as mean ± SEM. A priori significance was set at
186 subjects (129 men, 57 women) with an average age of 59 ± 1 years were enrolled. 61% of women were postmenopausal, and 35% were on hormone replacement therapy. 55% patients had CAD, 52% patients had hypertension, 24% were diabetic, 58% had hypercholesterolemia, 44% were smokers, and 35% had family history of CAD. Detailed characteristics of the study population are described in Table
Study population characteristics.
Total population | Number of cardiac risk factors | ||||
---|---|---|---|---|---|
<3 | 3–5 | >5 | |||
Age, yrs | 59 ± 1 | 54 ± 1*† | 60 ± 1 | 61 ± 1 | .0001 |
Females, | 57 (36) | 18 (51)*† | 28 (41) | 11 (13) | .01 |
Menopause, | 35 (61) | 12 (67)* | 14 (50) | 9 (81)‡* | .01 |
Heart rate, beats per minute | 68 ± 1 | 70 ± 1*† | 66 ± 1 | 64 ± 2 | .04 |
Mean arterial pressure, mmHg | 103 ± 1 | 99 ± 2*† | 103 ± 1 | 106 ± 1 | .009 |
Systolic blood pressure, mmHg | 128 ± 1 | 124 ± 2 | 129 ± 2 | 127 ± 2 | .18 |
Diastolic blood pressure, mmHg | 76 ± 1 | 78 ± 1 | 76 ± 1 | 71 ± 1*‡ | .006 |
Pulse pressure, mmHg | 51 ± 1 | 45 ± 1*† | 52 ± 1 | 56 ± 2 | .008 |
Height, inches | 67.8 ± 0.5 | 65 ± 1*† | 68 ± 0.5 | 70 ± 0.3 | .01 |
Weight, pounds | 192.9 ± 2.8 | 183 ± 6† | 191 ± 3† | 209 ± 4 | .02 |
Body mass index, kg/m2 | 29.7 ± 0.4 | 29.5 ± 1 | 29.4 ± 1.8 | 30.7 ± 0.6*‡ | .06 |
Total cholesterol, mg/dL | 174 ± 3 | 194 ± 5*† | 168 ± 4 | 155 ± 6.3 | .03 |
HDL cholesterol, mg/dL | 42 ± 9 | 50 ± 2*† | 39 ± 2 | 36 ± 9 | .03 |
LDL cholesterol, mg/dL | 103 ± 3 | 116 ± 7*† | 99 ± 5 | 92 ± 5 | .04 |
Triglycerides, mg/dL | 158 ± 10 | 131 ± 11 | 170 ± 19 | 152 ± 15 | .290 |
Hypertension, | 96 (52) | 6 (17) | 31 (46)†‡ | 59 (71)*‡ | .03 |
Diabetes mellitus, | 44 (24) | 0 (0) | 9 (14)‡† | 35 (42)*‡ | .0001 |
Hypercholesterolemia, | 109 (58) | 2 (6) | 37 (54)‡† | 70 (84)*‡ | .0001 |
Smoke, | 82 (44) | 7 (20) | 27 (40) | 48 (58) | .201 |
Family history, | 65 (35) | 5 (14) | 23 (34)‡† | 37 (45)‡ | .001 |
Coronary artery disease, | 102 (55) | 7 (11) | 53 (68)‡† | 42 (95)‡ | .001 |
Augmentation index, (%) | −4.86 ± 1.4 | −5.15 ± 2.09† | −3.60 ± 1.69 | 5.65 ± 2.55 | .02 |
‡Significantly different from cohort with <3 CRFs.
*Significantly different from cohort with 3–5 CRFs
†Significantly different from cohort with >5 CRFs.
A significant association was observed between PAT-AIx and age (
Patients with >5 cardiac risk factors had a significantly higher PAT-AIx compared to those with <3 CRFs (
PAT-AIx was significantly higher amongst CAD+ patients (1.01 ± 1.6%) as compared to CAD− patients (−5.46 ± 1.7%,
CAD− patients have significantly lower PAT-AIx values than CAD+ patients (
The classification performance of peripheral AIx, assessed by generating a receiver operated characteristic curve, revealed an AUC of 0.604 (
Prevalence of CAD in study patients divided into tertiles based on their PAT-AIx results. The highest number of CAD cases was found in the tertile with the highest PAT-AIx values (Tertile III). Tertile I, having the lowest PAT-AIx values, had the lowest number of CAD cases.
A positive correlation was noted between peripherally derived AIx and centrally measured blood pressures. PAT-AIx correlated with aortic systolic pressure (
Positive correlation between PAT-AIx and aortic systolic blood pressure (
Positive correlation between PAT-AIx and aortic pulse pressure (
Analysis focusing on effects of medications on peripheral augmentation index revealed a significant association between PAT-AIx with beta-blockers (
Our study was undertaken to evaluate the association of peripheral AIx and cardiovascular risk factors. Similar to what has been found with AIx derived from applanation tonometry [
PAT-AIx was associated with the cumulative CRFs burden in this study population. Patients with >5 CRFs had a significantly higher PAT-AIx as compared with those having only a few CRFs. Similarly, when the prevalence of CAD was assessed across tertiles of PAT-AIx, it was noted that patients in the highest tertile had a significantly higher prevalence of CAD as compared to those in the lower tertiles.
PAT-AIx was able to discern the presence or absence of CAD amongst a heterogeneous patient population with varying in cardiovascular risk. The classification performance of peripheral AIx was assessed by generating a receiver-operated characteristic curve which revealed an AUC of 0.604. However, after adjusting for traditional risk factors such as age, sex, heart rate, height, weight, hypertension, diabetes mellitus, hypercholesterolemia, smoking, and family history of premature coronary heart disease, AIx lost its statistical significance. Thus, PAT-derived AIx is not an independent predictor of CAD in this population.
The importance of assessing central blood pressure lies in the fact that traditionally measured brachial artery blood pressure is often a poor representation of actual central pressures. Due to pressure wave amplification, the brachial systolic pressure can be up to 20 mmHg higher than the aortic systolic pressure [
We do acknowledge certain limitations in this study. While it has been suggested that arterial stiffness and augmented pressure from wave reflections make the most significant contributions to the digital volume pulse inflection point, vascular correlates or PAT-AIx remain unexplored. CAD was defined on the basis of diagnosis with angiography and/or positive SPECT imaging. It is true that SPECT imaging results do not always correlate with severity of coronary artery stenosis. However, we chose stress testing because it provides physiologic information regarding ischemia and prior infarction. While SPECT imaging does not confer 100% sensitivity and specificity, this technique is a reliable, noninvasive assessment of myocardial ischemia/infarction. In Substudy 2, central pressures were obtained using conventional fluid-filled catheters, rather than high-fidelity pressure transducers. In addition, AIx was not obtained simultaneously during catheterization when actual central pressure values were obtained. Rather, PAT was performed at the bedside following cardiac catheterization.
PAT has been under investigation over recent years as a technique for assessment of vascular endothelial function. The present data suggest that this simple, noninvasive technique may also provide information regarding augmentation index. Our findings suggest that finger-derived AIx may be comparable to applanation tonometry for measurement of augmentation index and evaluation of cardiovascular risk. However, as observed by Haller et al. [
Funding for K. S. Heffernan provided by NIH T32 HL069770-06. The peripheral arterial tonometer (PAT) finger probes were provided by Itamar Medical, LTD, Caesarea, Israel.