An invasive but simple and accurate method for ascending aorta–femoral artery pulse wave velocity measurement

Abstract

Introduction. Pulse wave velocity (PWV) is an emerging predictor in the assessment of cardiovascular risk in diseased and healthy populations. We suggest a novel method for the accurate measurement of PWV. Method. PWV is calculated from pulse transit time using two separate pulse recordings over a known distance. 8F sheaths were placed in the right femoral arteries and routine coronary angiographies were performed with 5F diagnostic catheters. Ascending aorta pressures were measured with right diagnostic catheter tip in the ascending aorta and synchronous femoral artery pressures were measured with the sheath in the femoral artery. The distance between the two pressure sites was calculated as follows: total length of the right diagnostic catheter−length of the catheter outside the sheath−Sheath length. Results. We evaluated the PWV measured using the catheter method in 24 subjects. PWV correlated positively and independently with age (p = 0.004), coronary artery disease (p = 0.04), ascending aorta systolic pressure (p = 0.006), femoral artery systolic pressure (p = 0.008), ascending aorta pulse pressure (p = 0.003) and femoral artery pulse pressure (p = 0.04). In coronary artery disease patients, the mean PWV value was significantly higher than in patients with normal coronary arteries (12.61 ± 6.31 m/s vs 7.58 ± 2.26 m/s p = 0.04). Conclusion. We describe a novel and accurate but invasive method for measurement of PWV. Our results may serve as a reference for non-invasive assessment of aorta–femoral artery PWV.

Key Words::

• Aortic stiffness
• coronary artery disease
• hypertension
• pulse wave velocity

Introduction

In recent years, the assessment of aortic stiffness has emerged as a new potential cardiovascular risk predictor (1). Aortic stiffness reflects both aortic wall elasticity and the mechanical tension of aortic wall, and several studies show that aortic stiffness increases with hypertension (HT), diabetes mellitus (DM), atherosclerosis, cigarette smoking and age (2–4).

The correlation between pulse pressure and coronary artery disease (CAD) suggests that arterial stiffness is a risk factor for CAD (2–4). A French study of HT showed that there is a relationship with large artery stiffness (pulse wave velocity, PWV) and CAD (5). Indices of arterial stiffness including PWV have been found to be higher in patients with angiographic CAD than those without CAD (6–11).

In addition to the measurement of arterial stiffness, PWV has emerged as a potential predictor of subclinical organ damage caused by HT. Using invasive and non-invasive methods, PWV can be determined by assessing the aortic pulse transmission time between two known points on the aortic body (12).

In invasive experimental studies measuring PWV, two proximal and distal points located on the same line and the same artery is used (13). However, in the majority of non-invasive clinical studies, for measuring PWV, two palpable measuring points of the peripheral arteries on the body surface are used. Commonly, the following sites are used for measurement of aortic PWV, the carotid and femoral arteries; upper arm PWV, the carotid and brachial arteries, arm PWV, the carotid and radial arteries, leg PWV, the femoral and tibial arteries (13). However, these points are not exactly on the same line as the pulse on the transmission path. The most important problem regarding this method of measurement is limitation of its use. This study was undertaken in an effort to develop a new and simple method for measuring PWV in hypertensive patients and in patients with atherosclerotic cardiovascular disease, and to compare the measured PWV with clinical and hemodynamic parameters.

Material and methods

Twenty-four patients were scheduled for elective coronary angiography. The study protocol approved by Ankara Diskapi Yildirim Beyazit Education and Training Hospital Clinical Research Ethics Board, dated 02 April 2009, with decision No. 2009/08. The inclusion and exclusion criteria for the study are indicated in Table I.

Table I. The inclusion and exclusion criteria for study.

Criteria for inclusion	Exclusion criteria
Persons giving consent to the study	Patients with moderate or severe valve stenosis
Patients scheduled for elective coronary angiography	Patients with moderate or severe valve insufficiency
Patients between the ages of 18 and 80	Patients diagnosed with cardiomyopathy
	Patients with atrial fibrillation, atrial flutter, other tachyarrhythmia and bradyarrhythmias
	Patients with electrocardiographic bundle branch block
	Patients with early acute myocardial infarction or unstable angina pectoris
	Patients with congenital heart disease
	Patients with symptomatic heart failure
	Systemic diseases that involves aorta (Marfan's, Ehler Danlos, etc.)
	Patients with aortic aneurysm

Patient population

Patients with the complaint of stable angina pectoris and patients who had been scheduled for coronary angiography for diagnosed or suspected CAD were included in our study. Twenty-four consecutive patients were included in the study. Each patient was informed about the scope of the study and gave approval for participation. Electrocardiogram, echocardiographic examination and routine biochemistry tests were performed. After coronary angiography, patients were divided into two groups – the one with CAD and the other with normal coronary arteries.

Angiographic study

Coronary angiography recordings of all patients were performed with the Siemens Bicor Top Model (Germany, 1996) angiography device. Initially an 8F arterial sheath was placed in the right femoral artery and standard coronary angiography was performed by 5F diagnostic catheters. Immediately after right coronary angiography, the diagnostic catheter was withdrawn to the aortic root and the calibration was performed for the measurement of pressure while the zero reference point is at the level of heart. Then the connection between the catheter and the transducer was opened and pressure and ECG tracings were recorded with paper speed of 100 mm/s. Through a 5F right diagnostic catheter, the systolic and diastolic blood pressures in the ascending aorta and by the 8F arterial sheath through the femoral artery, systolic and diastolic blood pressures of femoral artery were recorded simultaneously (Figure 1). The aortic and femoral pulse pressure was calculated by subtracting diastolic blood pressure from systolic blood pressure in both regions. The distance between the two regions was identified through the right diagnostic catheter. Aortic PWV was calculated by dividing pulse transmission time by the distance between the two regions.

Figure 1. The pressure curves obtained from the ascending aorta (P1) and the femoral artery (P2) (t, transit time).

The presence of coronary lesions causing 30% or more stenosis was defined as CAD. Patients who had normal coronary arteries were included in the reference group.

Statistical methods

Data analysis was performed using SPSS for Windows 15.0 (Statistical Package for Social Science, SPSS inc., Chicago, IL, USA). Descriptive statistics was expressed as mean ± standard deviation. For the comparison of the averages of the two groups, we used a t-test. We assessed the linear relationship between the two variables with Pearson's (for normal distributed data) and Spearman's (for abnormal distributed data) correlation coefficient. For comparison of numerical data between groups, the one-way analysis of variance (ANOVA) test and for multiple comparisons the post hoc Tukey's HSD test were used. In the statistical analysis, a p < 0.05 was considered statistically significant.

Results

In eight of 24 patients, no angiographic evidence of atherosclerosis (plaque or stenosis) was found and these patients were enrolled in the normal coronary arteries group. Sixteen patients had at least one coronary artery lesion causing 30% or more stenosis and were included in the CAD group. With a simple catheter method, the aortic PWV was calculated in all patients. Our study groups included 19 men and five women with the mean age of 57.0 ± 10.8 years (range 40–76 years). Clinical features of the patient groups are summarized in Table II.

Table II. Clinical characteristics of patients.

	Male (n = 19, %79,2)	Female (n =5, %20,8)
Age (year)	56.7 ± 11.8	58.2 ± 7.0
Body mass index (kg/m^2)	28.1 ± 4.2	28.4 ± 3.7
HT (n, %)	10 (52.6)	4 (80.0)
DM (n, %)	3 (15.7)	2 (40.0)
Total cholesterol, (mg/dl)	192.6 ± 48.1	179.6 ± 49.4
LDL cholesterol, (mg/dl)	112.8 ± 36.6	100.6 ± 42.4
HDL cholesterol, (mg/dl)	46.6 ± 11.9	50.2 ± 14.5
Triglyceride,(mg/dl)	167.5 ± 90.2	142.2 ± 54.2
Smoking (n, %)	12 (63.1)	1 (20.0)
CAD in family (n, %)	7 (36.8)	2 (40.0)
Prior MI (n, %)	4 (21.0)	1 (20.0)

HT, hypertension; DM, diabetes mellitus; LDL, low-density lipoprotein; HDL, high-density lipoprotein; CAD, coronary artery disease; MI, myocardial infarction.

Aortic PWV and clinical parameters (age, gender, body weight, height, smoking, CAD, HT, DM, hyperlipidemia), hemodynamic parameters (systolic pressure in the ascending aorta, the aorta, diastolic pressure, pulse pressure in the ascending aorta, femoral artery systolic pressure, diastolic pressure in the femoral artery, femoral artery pulse pressure, heart rate) and plasma parameters [total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), fasting plasma glucose] were compared with Pearson's correlation analysis.

The aortic PWV measured by our method showed a significant relationship with age. With advancing age, the aortic PWV (r = 0.33, p =0.004) was significantly increased. Under the age of 65 years, patients (mean) aortic PWV was 9.88 ±3.76 m/s, and in patients over 65 years of age the aortic PWV was 16.5 ±11.03 m/s. Aortic PWV was also significantly higher in patients with CAD (r = 0.17, p = 0.04). In patients with CAD the mean aortic PWV was 12.61 ± 6.31 m/s and in patients with normal coronary arteries the PWV value was 7.58 ± 2.26 m/s (p = 0.04). In addition, we observed a significant association between ascending aorta PWV and aortic systolic pressure (r = 0.30, p = 0.006) (Table III). The ascending aorta PWV in patients with mean systolic pressure over 140 mmHg was 14.17 ± 7.62 m/s, and in those below 140 mmHg, the mean PWV was 9.0 ± 3.32 m/s. Again, there was a significant relationship between the femoral artery systolic pressure and PWV (r = 0.27, p = 0.008). In patients with femoral artery systolic pressure over 140 mmHg, mean PWV was 14.15 ± 8.14 m/s, and in those below 140 mmHg, it was 9.33 ± 3.48 m/s. In addition, there was also a significant relationship between ascending aortic pulse pressure and PWV (r = 0.33, p = 0.003). In patients with ascending aorta pulse pressure over 60 mmHg, the mean PWV was 12.32 ± 6.84 m/s; in those below 60 mmHg, the mean PWV was 9.0 ± 3.27 m/s. Again, there was a significant relationship between the femoral aortic pulse pressure and aortic PWV (r = 0.16, p = 0.04). In patients with the femoral artery pulse pressure over 60 mmHg, the mean PWV was 12.58 ±7.10 m/s, and in those below 60 mmHg, it was 9.3 ± 3.69 m/s (Table IV).

Table III. Comparison of hemodynamic parameters in the groups with and without coronary artery disease (CAD).

Hemodynamic parameters	With CAD	Without CAD	p-value
Aortic pulse wave velocity (m/s)	12.61 ± 6.31	7.58 ± 2.26	0.04*
Ascending aorta systolic pressure (mmHg)	145.56 ± 27.99	129.75 ± 13.41	0.14
Diastolic pressure in the ascending aorta	75.81 ± 10.43	71.12 ± 11.14	0.32
Pulse pressure in the ascending aorta	69.75 ± 20.78	58.62 ± 13.28	0.18
Femoral artery systolic pressure	141.06 ± 30.0	115.25 ± 23.6	0.04*
Femoral artery diastolic pressure	70.75 ± 17.57	56.37 ± 18.95	0.07
Femoral artery pulse pressure	70.25 ± 25.41	58.87 ± 17.49	0.27

*p <0.05.

Table IV. Correlation analysis of aortic pulse wave velocity (PWV) with age, the presence of coronary artery disease (CAD) and hemodynamic parameters.

Parameters	r	p-value
Age	0.33	0.004*
Presence of coronary artery disease	0.17	0.04*
Heart rate	0.39	0.053
Systolic pressure in the ascending aorta	0.30	0.006*
Femoral artery systolic pressure	0.27	0.008*
Pulse pressure in the ascending aorta	0.33	0.003*
Femoral artery pulse pressure	0.16	0.04*
Diastolic pressure in the ascending aorta	0.24	0.25
Femoral artery diastolic pressure	0.33	0.11

*p <0,05.

Our study showed no significant correlation between aortic PWV and plasma parameters, hemodynamic parameters such as the diastolic pressure in the ascending aorta, femoral artery diastolic pressure or heart rate. The mean aortic PWV was higher in patients with DM, but it did not reach statistical significance. In non-diabetic patients, the mean PWV was 10.6 ±6.3 m/s, and in patients with diabetes, the PWV was 12.0 ± 2.6 m/s (p = 0.23). Furthermore, the average aortic PWV was numerically higher in patients with hyperlipidemia, but it did not reach statistical significance. The mean PWV in patients without hyperlipidemia was 9.8 ±4.2 m/s, while in patients with hyperlipidemia it was 10.6 ± 3.8 m/s (p = 0.68). In addition, statistically significant difference was not found between smokers and non-smokers regarding the mean aortic PWV.

Discussion

For the evaluation aortic stiffness, various invasive and non-invasive methods are being used. Non- invasive methods include pressure–diameter hysteresis curves, arterial diameter waveform, arterial pressure waveform, arterial wall thickness, viscoelastic parameters, arterial compliance and PWV measurements. In recent years, PWV has become a commonly used method for measuring aortic stiffness, and arterial stiffness assessment has increasingly been accepted as an important predictor of cardiovascular risk in various patient populations (13). Aortic PWV can be calculated by determining the transit time of the pulse in the aortic body over a known distance. Compared with common methods for cardiovascular risk prediction such as blood pressure measurement, it is more difficult for clinicians to measure PWV accurately. In addition, PWV measurements need specific equipments and trained personnel (13).

Arterial pulse can be determined non-invasively by the use of a Doppler ultrasound probe over aortic body and carotid artery, subclavian artery or the femoral artery (12). Although the measurement of PWV can be done with a pulse wave Doppler ultrasound device, the distance measurement of this wave appears to be a big problem. The proposed measurement method for the determination of this distance generally does not measure the real distance. Also, the need for correction with respect to age, excess weight and breast size, spine and thorax abnormalities can create problems and cause incorrect results (14–16). Commonly, the pulse pressure is recorded by using a mechanical converter. Today, the most commonly used method for measuring PWV non-invasively is to record the carotid and femoral artery pulse simultaneously by using two separate probes (Complior device, Artech Medical) or sequential recording is made 舃舃with the help of a single probe and ECG recording (e.g. R wave) to determine carotid–femoral pulse transit time (Sphygmocor device, Atcor Medical). It has been shown that measurements of the pulse transition time obtained by both methods can be as accurate as those obtained by catheter methods (12). However, the most important problem with these methods is the inability to correctly measure the pulse transition distance. In our study, the pulse transition distance, which is the most important issue in non-invasive measurement of PWV, was simply and accurately determined with the help of the right diagnostic catheter during routine angiography without requiring any additional equipment. Thus, PWV was measured accurately and precisely. The accuracy of our PWV measurements has been proven by its significant correlation with hemodynamic parameters and CAD.

Both in normotensive and hypertensive subjects, the relationship between BP components and major cardiovascular events is known and well documented by previous studies (17). In patients over 50 years of age, compared with diastolic BP, brachial systolic BP and pulse pressure were more powerful in predicting myocardial infarction, congestive heart failure, stroke, end-stage renal failure and all-cause mortality (18). Increased systolic BP and pulse pressure in patients with advanced age, and degeneration and hyperplasia in the arterial wall, may result in increased elastic artery stiffness (18). We showed that there is a significant and independent correlation between the measured PWV with our method and the ascending aorta and femoral artery systolic pressure, and ascending aorta and femoral artery pulse pressures. Furthermore, there was no correlation between the ascending aorta and femoral artery diastolic pressures and our PWV measurements, which also supports that the values we measured are correct. Since an increase in the aortic stiffness increases PWV, which is then reflected during systole rather than diastole, the diastolic BP decreases in return. As a result, there is an increase in systolic BP and pulse pressure. When left ventricular afterload increases, there is deterioration and decrease in coronary perfusion. As a result, there is an inversely proportional relationship between diastolic BP and CAD (18).

In previous studies, a relationship between heart rate and presence of impaired aortic elastic parameters has been shown (19). In a recently published study, Yildiz and coworkers (20) showed a relationship between aortic distensibility and strain and the presence and severity of CAD. In addition, in patients with angina, there is a relationship between the number of diseased coronary arteries and subdiafragmatic aortic distensibility (21). The hypothesis put forward to explain this association is related to the vasa vasorum, which feed the aorta, and that originate from coronary arteries. For this reason, in the presence of CAD, abnormal nutrition and blood supply to aortic wall may damage the elastic properties of the aortic wall (22).

In the same study, there was a relationship between aortic elastic parameters obtained by applanation tonometry and the presence, prevalence and severity of CAD obtained by angiography supporting this hypothesis (22–24). In addition, it has been reported that, in patients with a moderate degree of CAD, the stiffness of the great arteries is a major determinant of exercise-induced myocardial ischemia (25). Moreover, in previous studies evaluating the relationship between PWV in CAD and non-CAD groups, it has been demonstrated that PWV was significantly higher in CAD patients. The independent and significant relationship between PWV and CAD in our study also supports this notion.

Recently, a relationship between the central hemodynamic parameters and heart rate has been described. In particular, the result of the CAFÉ (1) study showed that central pressures were lower in hypertensive patients on an atenolol-based as compared with an amlodipine-based treatment. This result raises the question of whether heart rate has any effect on study results. In our study, PWV was higher in patients with elevated heart rate but this finding did not reach statistical significance (p = 0.053). Larger-scale studies are needed to solve this question.

Furthermore, it has been reported in previous studies that diabetes increases aortic stiffness and has an unfavorable effect on aortic stiffness indices (3). However, it is not known by which mechanism diabetes may cause an increase in aortic rigidity. A plausible explanation could be that in patients with DM, accumulation of glycosides in arterial wall may result in stiffening of the arteries. In our study, however, the average aortic PWV in patients with diabetes was not increased compared with non-diabetic patients. We believe this may due to the small number of patients included, which is also the most important limitation of our study.

Limitations of the study

This study is a single-center, observational and non-randomized comparative study. A small number of patients was included in the study and the authors suggest confirmation of the findings and evaluation of the usefulness of PWV in risk stratification of patients in a larger cohort of CAD patients.

Conclusion

We describe a novel and accurate but invasive method for measurement of PWV in ascending aorta–femoral artery for the assessment of cardiovascular risk. Our results may serve as a reference for non-invasive assessment of aorta–femoral artery PWV.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.