Cardiovascular disease (CV) is classified as collection of diseases that involve the heart or blood vessels (arteries and veins). This is one of the leading causes of mortality in amongst old persons and is more pronounced in patients with chronic kidney disease and diabetes mellitus. The high rate of mortality is associated with the development of atherosclerosis which is a condition in which fatty materials deposited along the arterial walls. This fatty material causes thickening and hardening (forms calcium deposits) that may eventually block the arteries1.
Arterial stiffening is the main cause of an increasing systolic pressure experienced by aging people and also in patients with arterial hypertension1. This is due to the degeneration of the arterial wall caused by the increased systolic pressure as a result of increasing amplitude of the aortic pressure wave1,2. Arterial stiffening has been linked as a marker for several cardiovascular diseases such as cardiac failure, stroke, kidney dysfunction and death3,4,5.
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Aging is associated with changes in the structure and function of the wall vessel due to an increased arterial stiffness which causes the reduction in its elasticity or ability to swell. The effect of this is an increased systolic blood pressure causing an elevated workload in the left ventricle and a reduction in diastolic pressure thereby predicting cardiovascular dysfuction2,6.
Arterial stiffness is usually expressed in terms of the visco-elasticity of the arterial wall using quantitative terms like Distensiblity and compliance7,8. Hamilton et al9 defines arterial compliance as a change in volume or cross-sectional area of a vessel for a given change in pressure. In terms of the arterial system, compliance refers to change in the arterial diameter caused by the ejection of blood from the left ventricle. Distensibility is defined in close association with compliance in relation to the initial diameter of the artery. Even though these terms are intertwined, they differ in their meanings10.
As described in Fig 1 below, it is worth noting that with aging, the arteries tends to thicken, stiffen, dilate and increase in length1 and has been linked to loss of elasticity in the aorta and in major arteries11.
Figure 1: A comparison detailing the differences in aorta distensibility and compliance between elastic vessels and vessels that have lost its elasticity as a result of increased arterial stiffness characterized by increased systolic pressure and decreased diastolic pressure12.
ROLES OF THE EXTRACELLULAR MATRIX IN ARTERIAL STIFFNESS
The human heart is composed of the cardiac muscle which plays an important role in the circulation of blood through the several tissues in the body. Blood from the veins are received by the heart through the atrium and pump into the ventricles by the contraction of the atrium. The left ventricle has the thickest walls of the heart because it needs to pump blood out of the heart to the body and the lungs. This is where the blood has the highest pressure13. The surge of blood causes the walls of the aorta to expand and the muscle stretches to accommodate the pressure.
Bramwell and Hill14 makes a remarkable statement which says " The amount of energy expended by the heart is proportional to the pressure developed; hence the amount of energy which the heart has to expend per beat, other things being equal, varies with the elasticity of the arterial system."
The human aortic wall consists of extracellular matrix (ECM) which majorly comprises of fibrous proteins such as collagen, elastin and also smooth muscle cells. This ensures wall resilience and maintains tensile strength15. There is a higher content percentage for elastin as compared with collagen in the aorta which confers the elastic nature of the vessel16 which enables it maintains tension of the arterial wall17. At normal physiological pressure, a well defined layer consisting of elastin, collagen and the smooth muscle cells is formed and the close alignment i.e. the arrangement of the thick and finer elastin, collagen fibers and the smooth muscle cells results in the visco-elastic characteristics and the dynamic features the aorta possess18,19.
Figure 2: This is a schematic representation giving a summary of the locations at which arterial stiffness could be elevated by changes in various components of the arteries3.
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Changes in the arterial wall due to arterial stiffness could include deposition of lipid, elevated proliferation of the smooth muscle cells and also a change in the ratio of elastin to collagen content( as shown in Fig 2). The reduction of elastin usually results in the increase in collagenous fibres5 which is stimulated by increased blood pressure19. The latter is known to affect the elastic character of the arterial wall20. In a bid for early detection of arterial stiffness of these vessels, the function and structure of the large artery is non-invasively examined21. The large arteries have been found to have a buffering function in the changing pressure phases which sometimes causes injury and are prone to developing atherosclerosis which increases cardiovascular risk22.
DEVELOPMENT AND MECHANISM OF ARTERIAL STIFFNESS
The circulatory system as described by windkassel theory13 views the mechanism of circulation of blood to comprise of a central elastic reservoir (the large arteries) into which blood is pumped by heart and also engages in the distribution of blood through the peripheral arteries which are non-elastic conduit to the tissues. The large arteries is quite elastic due to its high elastin to collagen ratio present in their walls, thus arterial stiffness sets in as a result of degeneration of elastin fibre over a period of time24. The effect of ageing on the aorta and the carotid artery (proximal arteries) which are mainly elastic arteries differs from radial and femoral arteries (Distal arteries) which are mainly muscular arteries in that the proximal arteries stiffens with increase in age while the distal arteries show little change with increase in age5. With increase in age and progressive arterial stiffening, the regular orderly structure of the elastic arteries is lost as a result of thinning and fragmentation.
AORTIC STIFFENINGArterial stiffening and ageing has a strong influence on the structure of the left ventricle25 which is responsible for pumping out blood from the heart to all parts of the body13 thereby increasing the complications such as myocyte hypertrophy, decrease in coronary perfusion and others as shown in fig 3.
â†“ Central aortic DBP
â†‘ Central aortic SBP
â†‘ LV afterload
â†“ Coronary perfusion
FIGURE 3: Pathophysiological pathways showing the development of diastolic dysfunction through various deviations in the systolic and diastolic blood pressures as a result of aortic stiffness23.
During the release of blood from the left ventricle during systole, an arterial pulse wave emanates which moves towards other arteries in the body7. If the movement of the pulse wave is impeded by high resistance arterioles, this results in the wave being reflected back to the heart. As a result of uneven elasticity in the arterioles caused by elevated collagen production, the wave form is distorted thereby creating irregular pressure waves with different velocity7. There is a constant reciprocal action between the incident pressure wave and the reflected pressure wave which sums up to the actual pressure wave along the arteries7,26.The faster pressure waves reach the peripheral circulation earlier and are reflected back earlier during systole instead of during diastole thereby increasing the systolic blood pressure and the left ventricular workload13,26,27. The elevated rate of the pressure wave velocity in conjunction with the increase in systolic blood pressure and decrease in diastolic blood pressure alters the heart-vessel coupling thereby increasing the risk of cardiovascular disesases26, 28. The orderly arrangement of the micro-vessels plays such an important and supportive role in this process as it determines the extent of vascular resistance (VR) so also is the number of small arterioles, their branching pattern and the angle of their branching7, 29.
CAUSES OF ARTERIAL STIFFNESS
The increasing prevalence and linked risk of arterial stiffness has stimulated a huge investigation into understanding the cellular, genetic and molecular causes and also the resulting functional dysfunction or physiological abnormalities of this disease5, 30.
In principle, arterial stiffness is caused majorly by high blood pressure and age22. Increased stiffness could occur in close relation to changes in extracellular matrix i.e. elastin to collagen ratio and thickening of the arterial wall and other collaborating factors (as shown in fig 4) such as oxidative stress causing endothelial dysfunction22, 31.
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Figure 4: This schematic representation shows some cardiovascular risk factors contributing to elevated arterial stiffness and some of its effect10.
Arterial stiffening has been linked to several factors known to influence the risk of cardiovascular diseases such as smoking, physical activity, diet and alcohol consumption, age, hypertension, gender, endothelial dysfunction and diabetes mellitus32.
Smoking has been tagged as the most avoidable cause of cardiovascular diseases in the world33, 34. Chronic smoking as been linked with elevated arterial stiffness35, 36 and had been shown to increase just after smoking one cigarette36.
With a study based statistics presented by Doll et al 37 showing death was 60% higher in smokers and 80% higher in chronic smokers and has also shown smokers to be twice at higher risk of stroke or other cardiovascular diseases when compared to non-smokers. It is therefore appropriate to suggest smoking cessation to a smoker as a measure of prevention of cardiovascular disease33. As result of smoking cessation, there is a possibility of a 50% reduction in the susceptibility of patients suffering from myocardial infarction to sudden cardiac arrest or death33, 37. However the rate and duration of recovery of the arterial system when a smoker quits is still debateable with quotes ranging from 3-20 years37.
The exercise or physical activity has an advantageous effect in reducing the risk to cardiovascular diseases by a mediated influence on the possible risk factors such as blood pressure, lipid profile and glucose-insulin metabolism38, 39. Exercise has been proven to reduce vascular stiffness among young people and could also have a significant use in older adult with high risk cardiovascular complications40. Several epidemiological studies have shown a lower incidence of cardiovascular disease in men and women that engages in physical activity as compared to their sedentary peers39, 40. It is been supposed that the mechanical distension that occurs during physical activity causes a stretching and breaking of the cross-linkages formed by the glycated collagen fibres thereby improving arterial compliance 40,41.
Diet and alcohol consumption
Heavy consumption of alcohol increases the risk of cardiovascular diseases42 and its effect is more devastating in heavy alcoholic with irregular diets43. Consumption of alcohol outside of meals has been shown to increase risk of myocardial infarction and other cardiovascular disases43 because often time, heavy drinkers tend to eat less or eat unhealthily which aids the complications associated with arterial stiffening. It should be noted that a moderate consumption of alcohol has been shown to have a cardio-protective effect as compared to heavy drinkers and non-drinkers who have a higher risk of cardiovascular diseases which is represented by a J-shaped association42, 44 or a U-shaped association 44. Therefore, moderate drinkers may have reduced cardiovascular risk through the effects on anti-inflammatory pathways45. Wine drinkers are better protected from blood pressure raising effect of alcohol consumption because of the presence of polyphenolic flavonoids which exerts an anti-oxidising and vasodilating effect on the arteries43.
Arterial stiffness has a large influence on the arterial pressure, arterial pulse shape and impedance to the left ventricular output which in turn lays an effect on the total cardiac output46. An increase in the systolic blood pressure and pulse wave velocity is observed as a result arterial stiffness which could be associated with advancing age47. Advancing in age is accompanied by several alterations in the structure of the arterial walls47with tends to stiffen with advancing age48. The most observed changes that are manifested are thickening of the wall and a reduction in the elastic ability of the large artery. Elastic arteries like the aorta and the carotid artery become stiffer with advancing age leading to an elevated thickening of the walls49. The production and accumulation of advanced glycation end products (AGE) in the arterial wall contributes immensely to the alteration in the physical properties of the arterial wall47,49,50. There is also the occurrence of calcium deposition in the arterial wall which elevates with increasing age mostly after the age of 50yrs thereby contributing to the loss of distensibility51. There is therefore a large contribution of advancing age in the development and increase in the risk of cardiovascular diseases based on the aging effect on the arterial structure and functions47. Aging increases an individual's exposure to some age-related risk factors and this account for the increased occurrence and severity of cardiovascular diseases in older persons52.
High risk of cardiovascular diseases has been linked to be the main cause of mortality in subject suffering from diabetes53. Elevated arterial stiffness has been associated as a marker predicting the development of cardiovascular diseases in diabetics as an increase in the stiffness of the carotid artery and aorta is observed in diabetes54. There has been a linked association between increase in cardiovascular risk and hyperinsulinemia and insulin resistance55. Hyperinsulinemia increases atherosclerosis and thrombosis through the alteration of some complex processes in the arterial wall. The Helsinki policemen study56 shows a relationship between high plasma insulin and increased risk of cardiovascular heat diseases which are independent of other associated risk factors.
Type 1 diabetics have been established to have stiffer arteries when compared to non-diabetics of the same age and this accelerated stiffening occurs before any form of micro or macro vascular disease is seen57.
Type 2 diabetics have a 2-4 fold increased risk of cardiovascular morbidity as compared to non-diabetics with matching age and this is usually accompanied by hypertension58. There is the condition of premature stiffening of the arterial wall and an increase in pulse pressure usually typical for type 2 diabetes. This has been found to be a good predictor of cardiovascular morbidity and renal dysfunction59.
Although several statistics show that cardiovascular heart disease as a leading cause of mortality in adults60, its incidence in men and women differs. Cardiovascular diseases has a lower incidence in women at all ages when compare to men of matched ages but this tends to increase inexplicably in women after menopause due to a decline in the secretion of the ovarian sex steroids mainly oestrogen 61.
In elderly people usually aging over the 5th decade, there is a close relationship between hypertension and arterial stiffness62. The Framingham study shows link that elevated increase in arterial stiffness could result in an accelerated hypertensive condition in aging persons when untreated. Aging persons with untreated hypertension are more prone to exhibit an age related increase in systolic BP and decrease in diastolic BP when compared to age matches which are non-hypertensive63,64. Increase in arterial stiffness in hypertensive elderly persons results in cardiovascular complications such as atherogenesis, increase in left ventricular afterload and myocardial infarction. This therefore serves as a predictor of cardiovascular risk in hypertensive subjects65.
The endothelium is made up of thin layers of cells which line the blood vessels in the body which includes the arteries and serve as a barrier between the blood and the tissues66. The structure of the extracellular matrix in association with the endothelial cell function influences the stiffening of the arterial wall67. The vascular endothelium plays an important role in cardiovascular functions such as anti-thrombotic function, inhibition of smooth muscle cell proliferation and migration68.
The endothelial cells produce vaso-active substances such as Nitric oxide (NO) which play important roles in regulating cardiovascular disorders such as septic shock caused by the overproduction of NO while a reduction in the NO function is one of the causes of many cardiovascular disorders such as hypertension66,69.
Dysfunction of the endothelial is considered as the early phase in the development of the cardiovascular disease and is characterized by inactive vasodilatation which is dependent on endothelium NO66.
Impaired bioavailability of NO damages the relaxation of the smooth muscle and thus enhances the stiffening of the arteries70. Arterial stiffness has a bi-directional effect on endothelial dysfunction in that it could by itself weaken endothelial function and disturbs NO bio-availability70,71. This further accelerates the stiffness of the large arteries.
The effect of metabolic syndrome has been associated with hypertension and type 2 diabetes and therefore its association with increased pulse wave velocity rate established with aging is expected72. In young persons, metabolic syndrome was closely linked with carotid distensibilty which is ultrasonically estimated. The metabolic syndrome is characterized by a wide range of cardiovascular risk factors such as dyslipidemia, high blood pressure, diabetes and obesity73. Dyslipidemia has also be closely linked with higher central pulse pressure and elevated AIx73,74.
It could also be suggested that inflammation may be involved in arterial stiffening because there seem to be a relationship between pulse wave reflection, pulse pressure and pulse wave velocity to the level of inflammation in healthy persons75. C-reactive protein which is a marker of systemic inflammation is independently linked to pulse wave velocity which is a marker of arterial stiffness76. In subjects with renal insufficiency ranging from low to moderate reduction of creatinine clearance to complete renal dysfunction, elevated arterial stiffness is a typical noticeable characteristics77.
NON-INVASIVE METHODS FOR THE ASSESSMENT OF ARTERIAL STIFFNESS
It has been observed for a long time that the properties of the arterial pulse changes with age and the assessment of the arterial pulse has been incorporated into the clinical examination of patients with cardiovascular risk78.
Arterial elasticity has been assessed through several methodologies, some of which have been more widely applicable clinically than others. This could be divided into methods which are Non-invasive and Invasive78. The Non-invasive methods of assessment can be classified into three groups namely; 1) Measurement of the pulse wave velocity, 2) relating change in diameter (or area) of an artery to distending pressure, and 3) assessing arterial pressure waveforms79. Important indices which are commonly measured such as compliance, elastic modulus (elasticity), distensibility and vascular impedance are defined in table 1.
TABLE 1: This shows a descriptive details about the indices of arterial stiffness commonly measured in the assesment of cardiovascular risk78.
There are 3 methods commonly used to determine arterial stiffness namely; 1) Pulse wave velocity (PWV), 2) Pulse pressure (PP), 3) pressure waveform analysis (Augmentation index)5.
Pulse wave velocity (PWV)
The pulse wave velocity is described as the speed at which the forward pressure wave is transmitted from the aorta through the vascular tree78. It is generally accepted that the measurement of PWV is non-invasive, simple, robust and a high degree of reproducible method which could be used in the determination of arterial stiffness80. This means of assessment involves measuring the time taken for the arterial waveform to pass between two points at a specific distance apart (as shown in fig 5) and relating them to the R wave of a simultaneously recorded ECG. The commonly used method to measure pulse wave velocity is the Foot-to-foot method78,80. The foot of the wave is usually taken to be the end of diastole which is when the steep rise of the waveform starts.
Fig 5: This shows the assessment of pulse wave velocity calculated from the distance between two points (âˆ†x) divided by the time taken for the pulse to travel between these two points (âˆ†t)14.
In cardiovascular diseases, the carotid-femoral PWV is a strong predictor for aortic stiffness usually observed with advancing age. Pulse wave velocity can be measured in different ways which could involve the arterial pulse wave reading taken at a proximal artery like the carotid and another at a distal artery like the femoral79. Pulse wave velocity is increased by distending pressure so therefore, the blood pressure should be taken into consideration in the use of PWV as a marker of cardiovascular risk or in the reduction of BP as a means of treatment in hypertensive79.
Pulse wave velocity increases with the stiffness of the arteries. Pulse wave velocity could be defined by the Moens-Korteweg equation:
Where Einc is Young's modulus in dynes/cm2, h is wall thickness in cm (assuming a homogeneous material of wall), r is radius (cm), and Ï is the density of blood (grams/cm3).
Einc describes the elastic properties of the arterial wall in terms of the change in length as a ratio of the force required to produce the elongation. The differential component composition i.e. collagen, elastin and muscle in the wall of the arteries contributes to the non-linear relationship observed between elastic modulus and distending pressure12.
In recent times, pulse wave velocity has replaced the earlier predictive factors (systolic and pulse pressure) as a better predictor of outcome which are independent of all measures of arterial blood pressure81,82.
Pulse pressure (PP) has been shown as a predictor of cardiovascular disease in healthy individuals, patients with treated and untreated hypertension, diabetics (Type 1 and Type 2)83,84. Pulse pressure arises as a result of cardiac contraction which occurs at intervals and also the characteristics of the arterial circulation11.
The measurement of pulse pressure serves a better and simple substitute in the measurement of arterial stiffness. Pulse pressure is simply calculated by subtracting the Diastolic blood pressure (DBP) from the systolic blood pressure (SBP) which is determined to a large extent by arterial stiffness and cardiac stroke volume9,11.
Pulse pressure = SBP - DBP
Pulse pressure as a predictor indicates the degree or extent of buffering dysfunction of the large arteries thereby showing predictive values for cardiovascular risk11,81,83. There is a linear increase in systolic blood pressure (SBP) and diastolic blood pressure associated with aging. This attains its peak at about the age of 60 years after which a decline in the DBP is observed due to stiffening of the arteries thus resulting in the increase in pulse pressure63,85.
Pulse pressure is quite easily measured using a standard sphygmomanometer which is highly available but has a setback in that its assessment is error-prone.
The assessment of arterial stiffness through pulse pressure could either be by measuring the central pulse pressure or by measuring the brachial artery. Some reports buttresses that fact that pulse pressure is more accurate when measured centrally86 because of its strong links with endothelial function when compared to pulse pressure taken at the brachial artery87. The brachial blood pressure is largely influenced by the pulse wave amplification which emanates from the aorta to the peripheral arteries which results in a difference in the measured values for the peripheral systolic blood and pulse pressure as compared to that measured from the central end peripheral arteries88. Pulse wave amplification is particularly noticeable in young people but tends to decrease with advancing age89.
In this vein, it could be rightly said that the central blood pressure contributes to the early conditions observed in the development of cardiovascular diseases such as left ventricular hypertrophy and antherosclerosis to a very large extent90.
Pulse pressure has been shown in a number of studies as an important predictor of cardiovascular risk. Data obtained from the Framingham study further comments that the pulse pressure is a better predictor of cardiovascular diseases in hypertensive patients when compared to Diastolic and systolic pressure only63,78. Conversely, in young and middle-aged subjects (i.e. <50years), the diastolic pressure is still the best blood pressure index to adequately predict coronary heart disease63.
Pressure waveform analysis
Pulse wave analysis is a non-invasive method of measuring stiffening of the large artery91,92. A forward pressure wave which travels throughout the arterial tree is created by the contraction of the left ventricle. When the forward wave reaches points at which the arteries forms branches and regions with elevated arterial stiffness or high resistance arterioles, the wave is reflected causing the generation of a backward wave93. The reflected (backward) wave is superimposed on the forward wave generated by the contraction of the left ventricle resulting in the generation of an arterial waveform which varies across the arterial tree.
Aging is attributed with a clearly noticeable effect on pressure waveform94,95 which is close related to aortic stiffening as a causative factor. The stiffening of the arteries increases the velocity and amplitude of the reflected waves96. In the elastic vessels, the reflected wave tends to arrive back to the aorta during diastole thereby augments diastolic pressure and also improves coronary perfusion. This is seen to change as the arteries stiffen with aging51,96. Due to the stiffening of the arteries, the pulse wave velocity increases thus influencing the reflected wave returning to the aorta at an earlier phase of the cardiac cycle causing it to augment the systolic pressure instead of the diastolic pressure92,93. As a result, this reduces coronary perfusion and increases cardiac oxygen consumption causing the left ventricular afterload. The extent of the wave reflection is assessed more accurately by analyzing the central pressure waveform than the peripheral since the arterial waveform varies throughout the arterial tree88. Although the reflected waves originates predominantly at the major branches of the aorta, stiffness of the smaller arteries and arterioles has a considerable influence on the central pressure waveform88,89. Central pulse pressure augmentation may therefore provide a better marker of systemic arterial stiffness than single large artery measures, such as pulse wave velocity or aortic ultrasound90.
The augmentation index (AIx) is a non-invasive method of measuring systemic arterial stiffness which is calculated as the difference between the first and second systolic peaks expressed as a percentage of the central pulse pressure88 or the peripheral pulse pressure (as shown in Fig.6).
Figure 6: This shows the definition of peripheral and central augmentation index (pAI and cAI) and also the peripheral and central arterial waveforms showing Diastolic blood pressure (DBP), Change in peripheral systolic blood pressure (pSBP and pSBP2) and the central systolic blood pressure97.
The augmentation index is dependent on attributes such as the elasticity of the ascending aorta, the shape of the forward wave which is largely influenced by the left ventricular outflow as well as the timing of the reflected wave which is influenced by gender, height and vessel stiffness9,98.
Augmentation of the central and peripheral arterial pressure amplification has been regarded as important though unrelated in which the central arterial pressure is determined by characteristics of wave propagation in the aorta and by reflections from the head and lower body while the peripheral is characterised by the reflections from the upper limb. However, there is a close relation between the central augmentation index (cAI) and the peripheral augmentation index (pAI)97.
The AIx has been linked with the presence and degree of coronary artery disease99 while in cases of renal failure, patients with high AIx has been recognised as a predictor of being prone to cardiovascular mortality100.
However, there are problems associated with the assessment of arterial stiffness by measuring the AIx. The high heart rate recorded due to the arrival of the pulse wave reflection to the aorta at the earlier phase of the cardiac cycle influences the augmentation of the central systolic pressure by shifting the reflected wave into diastole which may limit the use of AIx as a measure of arterial stiffness88.
In clinical practice, the applanation method that uses a Millar transducer is employed to record pressures at the radial or the carotid artery and also a validated generalized transfer function based upon comparison with intra-arterial pressure is applied to generate the corresponding central waveform92,101. Therefore, in patients with diabetes, derivation of central waveforms by generalized transfer function may be unsuitable thereby making assessing arterial stiffness through the AIx unreliable in these patients102.
TREATMENT OF ARTERIAL STIFFNESS
Several pharmacological and non-pharmacological approaches has been used in the study of changes in arterial stiffness in a bid to find an intervention protocol13,80,103 . Examples of such approaches is summarised in table 2 below.
Moderate alcohol Consumption
Calcium channel Antagonists
Table 2: This shows some non-pharmacological and pharmacological intervention associated with the treatment of arterial stiffness80.
Moderate physical activity such as aerobic exercise has been linked to reduce the effect of arterial stiffness and cardiovascular risk burden and has also been recommended in the intervention or management of cardiovascular diseases104. Reduction in the arterial stiffness of the central and peripheral arteries has been observed after 30-60mins of both moderate and high intensity exercise in healthy young individuals105.
Dietary modification has various effects on arterial stiffness which is independent of body weight. Modifications could include changes in diet by Supplementing with n-3 polyunsaturated fatty acids found in fish oil which lowers the level of triglycerides and LDL concentration thereby improving the arterial compliance in subjects with dyslipidemia106. Also the administration of isoflavones which binds to the human estrogen receptors is shown to reduce pulse wave velocity in healthy individuals107. Similarly, anti-oxidative vitamins (C and E) have been reported to reduce pulse wave velocity as a consequence of reduced peripheral resistance but vitamin C shows no significant effect on carotid arterial stiffness108,109.
Sodium intake has the most potent effect on the arterial stiffness and a low-sodium diet has been shown to improve arterial compliance110.
Several non-invasive assessment methods of arterial stiffness such as pulse wave velocity, pulse wave reflection and blood pressure are improved by vasodilator drugs such as angiotensin receptor blockers, ACE-inhibitors, calcium channel blockers and nitrates acts in the muscular arteries and arterioles as smooth muscle cell relaxant thereby reducing the effect of arterial stiffness111,112. Vasodilator drugs causes a reduction in AIx and pulse wave thereby aiding the dilation of the resistance arteries and reducing peripheral resistance113,114.
Furthermore, they tend to lower distending pressure of the arteries therefore having a passive reduction effect on arterial stiffness. There is to a large extent a lowering of the central systolic and pulse pressure as a consequence of the effect of vasodilators on pulse wave reflection as compared to a slightly insignificant effect on the brachial systolic and pulse pressure. This effect could give a possible explanation for the brachial pressure independent effect noticed with the clinical trials of vasodilators such as in the HOPE trial115.
Drugs with effect on the vessel wall structure
Most drugs used in the treatment of hypertension (anti-hypertensive agents) acts by reducing the dynamic vaso-constrictive properties of arterial stiffness but with the inclusion of newer therapeutic drugs, the structure of the arterial wall can be modified. These new drugs acts through several mechanisms which include the inhibition of the formation of AGEs (Aminoguanidine and pyridoxamine), blocking of AGE receptors and non-enzymatic cleavage of the existing AGE cross-linkages of the arterial wall. Even though there are some unresolved safety issues regarding drugs such as aminoguanidine, clinical trials have shown to improve arterial stiffness in patents with diabetic nephropathy116.
Changes in arterial compliance and distensibility and its association with aging have been widely studied and such changes have been linked to a large extent to increased incidence of cardiovascular events 95,117. The assessment and treatment of arterial stiffness has no doubt improved the understanding of the clinical and non-clinical management of cardiovascular diseases. Furthermore, this has also assisted in the wide range of possible intervention approaches available and still increasing in numbers. Intervention methods include dietary and lifestyle modification as well as various pharmacological treatments that have proved beneficial in the reduction of arterial stiffness3,119. The present techniques available for the assessment of arterial stiffness are to a large extent accurate and reproducible but still subject to improvement.