Arterial stiffness and its relationship to cardiovascular disease risk

¶ … Measuring Arterial Stiffness

Arterial Stiffness

Intermittent blood flow converts to steady blood flow due to arteries cushioning the pulsation. The expanding and contracting of the aorta promote steady forward flow of blood. Figure 1 show the design and muscle type of the arterial wall.

Figure 1 (Arnett, 2001)

When arterial stiffness becomes increased, the pressure of the systolic and diastolic readings increases. As we age, our blood pressure gets higher in regards to the systolic blood pressure (SBP), the diastolic blood pressure (DBP), and the pulse pressure (PP). High blood pressure can lead to or cause a heart attack or stroke. Stiffening of the arteries in addition to build up of calcium and plaque are some of the major causes of cardiovascular disease.

Predictions made by the World Health Organization declare that cardiovascular disease by 2010 will be a global health problem of major coincidence and in regards to the developing world could become a leading killer. Stephanie DeLoach and Raymond Townsend (2008), University of Pennsylvania Renal Division, in the American Society of Nephrology journal article, "Vascular Stiffness: Its Measurement and Significance for Epidemiologic and Outcome Studies" state, "Arterial stiffness is recognized increasingly as an important component in the determination of cardiovascular risk, particularly in chronic kidney disease." Other diseases and their associations with cardiovascular disease and arterial stiffening are starting to become known. Chronic inflammatory diseases might be associated with arterial stiffness, possibly as a manifestation of premature atherosclerosis. (Journal.Shouxi.net, 2010) Coronary artery disease (CAD) represents a major cause of death and complications in people with spinal cord injuries.

Atherosclerosis defined basically as a progressive vascular disease which can begin at an early age and progresses at variable rates. Lifestyle changes and therapies that reduce arterial stiffness are presented, including weight loss, exercise, salt reduction, alcohol consumption, and neuroendocrine-directed therapies, such as targeting the renin-angiotensin aldosterone system, natriuretic peptides, insulin modulators, and novel therapies targeting advanced glycation end products. (Zieman, Melenovsky. & Kass, 2005)

Gender differences also have affect on the stiffening of the arteries. Pregnancy and age are two factors in women that cause arterial stiffening. A normal cardiovascular response to pregnancy is seen as an increased heart rate, lower brachial blood pressures primarily due to vaso-dilation of peripheral vessels and the expansion of blood volume during pregnancy. (AtCor Medical, 2010) Nagaia, Earley, Kemper, Bacal, and Metter (1998) conducted studies proving arterial stiffening progresses with age in women but the use of estrogen replacement therapy can reduce the stiffness. Other factors such as height, weight, and alcohol consumption also play a part in the stiffening of arteries and depending on the gender the effects vary. The augmentation index (AI) is higher in women than it is in men.

Area Under Curve (AUC) and Incremental Area Under Curve (IAUC)

Incremental area under the curve (IAUC) is calculated by subtraction of the area under the curve (AUC) at baseline from the total AUC with negative values being set at zero. Bailey, Jacobsen, LeCheminant, Kirk, and Donnelly in the article, "The Effect of Analysis Method in Determining Change in Post Exercise Oxygen Consumption" declare, "The use of total area under the curve instead of incremental or positive incremental area under the curve may be a more sensitive method of detecting change in post-exercise oxygen consumption."

AUC, in the smooth and continuous form, contains a curve function F (X) that can be shown as the integral show: =badXXFAUC. Keh-Dong Shiang, in the article, "The SAS® Calculations of Areas Under the Curve (AUC) for Multiple Metabolic Readings," describes AUC as, "In biomedical studies, the computation of Area Under the Curve (AUC) is a convenient way to combine multiple readings, such as some metabolic values (glucose and insulin) or blood (serum or plasma) concentration within a specific time interval.

Pulse Wave Velocity (PWV)

Pulse Wave Velocity is defined by website, www.medifacts.com, (2010)

The measurement of pulse wave velocity The measurement of pulse wave velocity (PWV) is generally accepted as the most simple, non-invasive, robust, and reproducible method to determine arterial stiffness. PWV is a well-established technique for obtaining a measure of arterial stiffness between any two locations in the arterial tree. The velocity of the blood pressure pulse along an artery is dependent on the stiffness of the artery. Serial measurement of pulse wave velocity in a section of artery will indicate the magnitude of change in arterial stiffness. Most commonly, pulse wave velocity is measured between the carotid and femoral peripheral artery sites in order to provide a measure of aortic stiffness.

Arterial stiffness indirectly measured by the PWV and has influences including: radius of artery, thickness of wall, and density and blood. Measurement sites (Figure 3) are picked and the travel velocity of pressure wave in relations to the stiffness is determined.

Figure 2 (Arnett, 2001)

Figure 3 (ScanMed Website)

Pulse wave velocity (PWV) can determine the onset of cardiovascular disease.PWV increases with stiffness and is defined by the Moens-Korteweg equation, PWV=(Eh/2R), where E. is Young's modulus of the arterial wall, h is wall thickness, R is arterial radius at the end of diastole, and is blood density (Oliver & Webb, 2003)

The ultrasound-based pulse wave imaging (PWI) is used to calculate the PWV. The PWI shows excellent results, repeatability, and non-invasiveness in experiments conducted using it. The following techniques are examples of PWI and ultrasound and their descriptions from the Gale Encyclopedia of Medicine:

Doppler ultrasound that in which measurement and a visual record are made of the shift in frequency of a continuous ultrasonic wave proportional to the blood-flow velocity in underlying vessels; used in diagnosis of extra cranial occlusive vascular disease. It is also used in detection of the fetal heartbeat or of the velocity of movement of a structure, such as the beating heart.

Color flow Doppler ultrasound a form of pulse wave Doppler in which the energy of the returning echoes is displayed as an assigned color; by convention echoes representing flow towards the transducer are seen as shades of red, and those representing flow away from the transducer are seen as shades of blue. The color display is usually superimposed on the B-mode image, thus allowing simultaneous visualization of anatomy and flow dynamics.

Continuous wave Doppler ultrasound

A technique in which the transducer emits and receives the ultrasound beam continuously, enabling the measurement of high velocity blood flow, such as occurs through heart valve stenoses.

Duplex Doppler ultrasound

A form of image display in which both spectral and color flow images are seen simultaneously. This facilitates accurate anatomical location of the blood flow under investigation.

Doppler ultrasound flow meter

A device for measuring blood flow that transmits sound at a frequency of several megahertz downstream along the flowing blood. Some of the sound waves are reflected by the moving red blood cells back toward the transducer. The difference in pitch between the transmitted and reflected sounds is produced as an audible tone and is proportional to the velocity of blood flow. The flow meter can be incorporated into a stethoscope so that qualitative and quantitative measurements of the flow of blood through arteries and veins can be obtained. The Doppler flow meter is capable of recording very rapid pulsatile changes in flow as well as steady flow.

pulse wave Doppler ultrasound a technique in which the transducer emits ultrasound in pulses. Blood flow velocities so measured are limited to around the physiologic range (up to approximately 1.5 meters/second) but the depth from which the returning echoes originate can be accurately determined.

spectral Doppler ultrasound a form of ultrasound image display in which the spectrum of flow velocities is represented graphically on the Y-axis and time on the X-axis; both pulse wave and continuous wave Doppler are displayed in this way.

Pulse Wave Analysis (PWA)

Since ancient time, the arterial pulse interpretation has been extremely important in medical examinations. Marey and Mahomed during the last century, introduced graphical methods for the recording clinical pulse. (O'Rouke & Gallagher, 1996) The introduction of the sphygmomanometer over 100 years ago ceased Mahmoud's pulse analysis and now it is gaining ground due to limitations of the sphygmomanometer to measure only brachial pulse. Pressure pulse wave analysis allows for accurate and logical therapies impossible in past tomes.

Medifacts (2010) defines the Pulse Wave Analysis as:

The arterial pressure waveform has 2 components -- the first is the forward traveling wave when the left ventricle contracts and the second is the reflected wave returning from the periphery. In the case of stiff arteries, PWV rises and the reflected wave arrives back at the central arteries earlier, which leads to augmentation of the central aortic pressure further increasing left ventricular work. This phenomenon can be quantified through the augmentation index (AIx) which is defined as the difference between the second and first systolic peaks. These changes in pulse pressure cannot be appreciated by the measurement of simple brachial BP.

Pulse wave analysis (PWA) measures augmentation index (AI) and PWV representing a non-invasive technique that is simple and reproducible.

One form of PWA is the applanation tonometry technique. When evaluating completions rates involved with PWA, radial tonometry had a 66% and carotid tonometry had a 99%. The radial tonometry was determined to be easier on the patient.

Laser Doppler Imaging (LDI)

Laser Doppler Imaging (LDI) has increased significance over previous single probe techniques. Blood flow is no longer measured at a single site but between an area and the LDI due to being non-contact cannot interfere with the final results. LDI is a 1mm laser beam that uses a mirror to scan in two dimensions. A small amount of light penetrates the skin; the depth depends on wavelength and absorption, of area scanned and interacts with cells and tissues. Speed and density of moving cells determine the signal sent to detector. Discovery Technology International defines the amount of tissue measured as:

we have estimated that for well-perfused tissue such as muscle, the mean sampling depth for our probes is in the region 0.5-1.0 mm with a concomitant sampling volume in the region 0.3-0.5 mm3. For cutaneous measurements, the sampling depth is likely to be in the range 1.0 -- 1.5 mm. These estimates have been obtained heuristically through many years of experience and are based on both in vitro observations and mathematical modeling of photon diffusion through 'imaginary tissues' using Monte-Carlo techniques.

Acetylcholine (Ach) and Sodium Nitroprusside (SNP)

Acetylcholine and also Sodium Nitroprusside injected in to the site to be scanned by the LDI caused vasodililation and allowed for scanning of the areas more accurately and studies prove the two injects are reproducible. One group of researchers used the following technique:

Drugs used: 2.5 ml of 1% acetylcholine chloride (Sigma Chemical Co., St. Louis, MO, U.S.A.) was introduced into the anodal chamber. 2.5 ml of 1% sodium nitroprusside (Sigma) was introduced into the cathodal chamber. The vehicle for both drugs was 0.5% sodium chloride solution. (Balmain et al., 2007)

Results

All statistical analyses were performed using SPSS 15.0 for Microsoft Windows. The data was checked for normality using the Shapiro-Wilk test, as the number of subjects was less than fifty. Those data that were not normally distributed were transformed and reassessed. A repeated measure ANOVA was used to determine significant differences between time points for repeated LDI, PWV and PWA measurements. A value of P (0.050 was used to define significance and a 95% confidence interval. The data presented in tables and graphs is displayed as mean ± SD (standard deviation), unless otherwise stated.

Outliers have been checked but not eliminated, although some of them are not within the range of 2 SD, they are not eliminated due to the consistency between all 4 visits as per subject.

Statistical results from studies

From Patti LDI ACH 2003 we can see the dramatic difference between using Area under Curve vs. Incremental Area under Curve. The values for AUC are almost always half the values gotten from the IAUC.

ACH AUC

SEM

Std Dev

0

6

12

18

ACH IAUC

SEM

Std Dev

0

6

12

79.54888

18

52.00063

Discussion

The difference of the arterial stiffness between males and females is evident more at earlier ages and tend to decrease with age. Women have a lower arterial stiffness due to hormones and hormone therapies. (Nagia, Early, Kemper, Bacal, & Metter, 1997) Still this study (Patty LDI ACH 2003) only tested a group of seven men and tested seventeen women. The sample population is low in the number of men and accuracy would need to be tested.

The extremely large means, standard deviations, and standard error of mean show large inconsistencies in the numbers and bring the topic of repeatability in to question.

In Patty LDI PWA 2003, these numbers correlate to proven studies where women had an augmentation index of approximately 22 and the men's range was approximately 8. (Yasmin & Brown, 1999)

Patty LDI PWA 2003

Patty LDI PWA 2003

The repeatability of Patty LDI PWA 2003 was exception well for the 18-week period and the gender differences were consistant with studies conducted and mentioned earlier in the paragraph.

All of the data, charts, and calculations in this study show the same repeatibility and results found in other studies.

Conclusion

Arterial stiffness and cardiovascular disease are directly or indirectly related to a vast number of disease and conditions. Arterial stiffening is caused by a vast number of conditions which vary with gender, age, and demographics. Cardiovascular disease could become the next major cause of death around the world if treatments are not produced they more accurately combat the stiffening of the arteries.

The techniques such as Laser Doppler Imaging and Pulse Wave Analysis indicate the future of research in regards to the stiffening of arteries is very bright. ANOVA combined with the Bland and Altman plots guarantee the results will be more accurate and repeatable saving wasted time and money as well as resources.

Treatment in the form of non-invasive procedures allows the test to be performed on the patient in a less stressful method and give a more relaxed result. This results in accurate results not bias by the subject being uncomfortable or in distress. With all the new techniques on the market today early detection of arterial stiffening can lead to decrease in the number of stroke and heart attack victims from cardiovascular disease and the hundreds of diseases like diabetes, spinal cord injuries, etc. that have links and are correlated with cardiovascular disease or the stiffening of arteries.