COMMENTARY
Peripheral Vascular Disease Is Associated With Increased Pulse Wave Velocity and Augmentation Index: Clinical Implications George S. Chrysant, MD From the INTEGRIS Baptist Medical Center, Oklahoma City, OK
Several epidemiologic studies have shown that blood pressure (BP) changes with the advancement of age from the predominantly diastolic BP (DBP) in the young to the predominantly systolic BP (SBP) in the elderly. This change is due to the replacement of elastic fibers with collagen fibers in the large arteries of the body resulting in the stiffening of these vessels and the loss of compliance and elastic recoil. These changes lead to increases in SBP, pulse pressure (PP), pulse wave velocity (PWV), and augmentation index (AIx) in older patients.1
PATHOPHYSIOLOGY OF THE ATHEROSCLEROTIC PROCESS The large arteries in young individuals possess two functions: (1) to act as conduits that transfer blood to vital organs and tissues of the body, and (2) to act as cushions to smooth out the pulsatile action of blood flow produced by the intermittent contraction of the heart into a continuous and steady blood flow.2 As people age, these functions of the large arteries are modified as a consequence of the atherosclerotic process and the stiffening of the large arteries. In young persons, the elastic aorta expands during systole and absorbs part of the stroke volume. During diastole, it recoils back and sends the retained blood volume distally, thus converting the intermittent blood flow into a continuous steady flow. In older persons, the elasticity and compliance of the aorta is lost and most of the stroke volume is transmitted distally during systole with limited blood flow during diastole. The direct result of this function is an increase in SBP, a decrease in DBP, and a widening of PP. In addition, the morphology of the pulse wave curve also changes (Figure). In young individuals, the reflected wave is slower and returns to the aortic root early in diastole, augmenting the DBP, which helps the perfusion of the coronary arteries, whereas in the older person it is faster and returns late in systole, thus augmenting the aortic SBP and increases the left ventricular outflow pressure and is responsible for the development of left ventricular hypertrophy (LVH). In addition, because of the arterial stiffness, PWV is increased in older individuals compared with younger individuals (Figure). The augmentation of the central aortic SBP leads to an increase in AIx. Therefore, PP, PWV, and AIx are all increased in older individuals and Address for correspondence: George S. Chrysant, MD, INTEGRIS Baptist Medical Center, Oklahoma City, OK E-mail: [email protected] DOI: 10.1111/jch.12407
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are considered significant surrogate diagnostic characteristics of severe atherosclerosis.1,2 These findings are also present in patients with peripheral arterial disease (PAD).
PAD AS AN INDEX OF ATHEROSCLEROSIS PAD is a common condition in older persons, is considered a marker of severe atherosclerosis, and is associated with an increased risk of cardiovascular events.3–5 In fact, the mortality rate associated with PAD is higher than the mortality rate associated with myocardial infarction.6 Both asymptomatic and symptomatic patients carry a significantly higher mortality rate compared with persons without PAD. The mechanisms through which PAD increases the risk for cardiovascular disease (CVD) complications are not well defined. Some of the explanations are attributable to its association with severe generalized atherosclerosis, systemic inflammation, and oxidative stress, which is known to destabilize atherosclerotic plaques. In addition, the changes in systemic hemodynamics, such as the increases in SBP, PP, PWV, and AIx, are all associated with a high incidence of CVD complications.1,7–9 In addition, increased central aortic SBP and the development of LVH and PP are also associated with increased cardiovascular morbidity and mortality,10 and the wide PP has been associated with increased cardiovascular morbidity and mortality, as was demonstrated by the Strong Heart Study.10,11 In this issue of the Journal, Catalano and colleagues12 report their data on the association between AIx with PAD. They studied 97 patients with PAD (ankle-brachial pressure index ≤0.90) and 97 control patients. In the patients with PAD, there was a significant positive association between AIx and SBP (P=.0008), PP (P=.02), and MBP (P=.009) and a negative association between AIx and heart rate (HR; P=.0001). Although increased SBP, PP, and AIx are associated with systemic atherosclerosis and PAD, the negative association of AIx with HR has no association with PAD. The reflected wave returns slower to the aortic root in patients with lower HR and augments the central aortic SBP and AIx, whereas the opposite is seen with faster HR. For this reason, it is customary to index the AIx to HR 75 beats per minute for comparison with other patients and it could have been very useful in this case. In addition, the lasting effects of b-blockers should not be discarded in this case, because it is noted that the patients with PAD had slower HRs than the control patients (68 vs 71). It is unknown why no significant association between age and AIx was found in the PAD group, since atherosclerosis and high SBP are high in
Commentary
FIGURE. The configuration of the arterial waveforms in younger (left) and older (right) persons is shown. The arterial waveforms are composite waves (top heavy line) composed of a forward wave (dashed line) and a backward reflective wave (dotted line). The vertical line represents the closure of the aortic value. The top solid line indicates the peak systolic blood pressure (SBP) in the younger and older person together with the augmentation pressure. The reflected wave in the younger person returns to the aortic root early in diastole augmenting diastolic blood pressure, which helps the perfusion of coronary arteries, whereas in the older person it returns to the aortic root late in systole, augmenting the SBP and increasing the left ventricular outflow pressure. Due to the arterial stiffness, pulse wave velocity (PWW) is increased in the older person (12 m/s) compared with the younger person (8 m/s). Adapted with permission from Franklin.9
older persons. It should be noted that SBP was higher in the PAD group compared with the control group, where a positive association between AIx and age was found. Findings similar to those reported in this study have been previously published by other investigators as well as by the same investigators using data from the same patient groups where an association between PAD and PWV was shown.13 What then are the clinical implications from the findings of this study? If an association between PAD and AIx, PP, and PWV is accepted, clinicians can extrapolate the presence of PAD in their patients with the presence of these findings, which have been associated with high cardiovascular morbidity and mortality and take the appropriate measures for a more targeted approach to treatment of their patients. From a practical standpoint, however, it is a lot easier for a busy clinician to measure the ankle-brachial pressure index than using applanation tonometry to measure augmentation pressure, AIx, and PWV. References 1. Chrysant SG, Chrysant GS. The age-related hemodynamic changes of blood pressure and their impact on the incidence of cardiovascular disease and stroke: new evidence. J Clin Hypertens (Greenwich). 2014;16:87–90. 2. O’Rourke M. Mechanical principles of arterial disease. Hypertension. 1995;26:2–9.
3. Criqui MH, Langer RD, Froneck A, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med. 1992;326:381–386. 4. Aronow WS, Ahmed MI, Ekundayo OJ, et al. A propensity-matched study of the association of peripheral arterial disease with cardiovascular outcomes in community-dwelling older adults. Am J Cardiol. 2009;103:130–135. 5. McDermott MM, Liu K, Criqui MH, et al. Ankle-brachial index and subclinical cardiac and carotid disease. The multi-ethnic study on atherosclerosis. Am J Epidemiol. 2005;162:33–41. 6. Caro J, Migliaccio-Walle K, Ishak KJ, Proskorovsky I. The morbidity and mortality following a diagnosis of peripheral arterial disease: long-term follow-up of a large database. BMC Cardiovasc Disord. 2005;5:14–21. 7. Khaleghi M, Kullo IJ. Aortic augmentation index is associated with ankle-brachial index: a community-based study. Atherosclerosis. 2007;195:248–253. 8. Brewer LC, Chai HS, Bailey KR, Kullo IJ. Measures of arterial stiffness and wave reflection are associated with walking distance in patients with peripheral arterial disease. Atherosclerosis. 2007;191:384–390. 9. Mosimann K, Jacomella V, Thalhammer C, et al. Severity of peripheral arterial disease is associated with aortic pressure augmentation and subendocardial viability ratio. J Clin Hypertens (Greenwich). 2012;14:855–860. 10. Roman MJ, Devereux RB, Kizer JR, et al. Central pressure more strongly relates to vascular disease outcome than does brachial pressure. The Strong Heart Study. Hypertension. 2007;50:197–203. 11. Palmieri V, Devereux RB, Hollywood J, et al. Association of pulse pressure with cardiovascular outcome is independent of left ventricular hypertrophy and systolic dysfunction: the Strong Heart Study. Am J Hypertens. 2006;19:601–607. 12. Catalano M, Scandale G, Carzaniga G, et al. Aortic augmentation index in patients with peripheral arterial disease. J Clin Hypertens (Greenwich). 2014;16:782–787. 13. Catalano M, Scandale G, Carzaniga G, et al. Increased aortic stiffness and related factors in patients with peripheral arterial disease. J Clin Hypertens (Greenwich). 2013;15:712–716. The Journal of Clinical Hypertension
Vol 16 | No 11 | November 2014
789
Peripheral Vascular Disease Is Associated With Increased Pulse Wave Velocity and Augmentation Index: Clinical Implications George S. Chrysant, MD From the INTEGRIS Baptist Medical Center, Oklahoma City, OK
Several epidemiologic studies have shown that blood pressure (BP) changes with the advancement of age from the predominantly diastolic BP (DBP) in the young to the predominantly systolic BP (SBP) in the elderly. This change is due to the replacement of elastic fibers with collagen fibers in the large arteries of the body resulting in the stiffening of these vessels and the loss of compliance and elastic recoil. These changes lead to increases in SBP, pulse pressure (PP), pulse wave velocity (PWV), and augmentation index (AIx) in older patients.1
PATHOPHYSIOLOGY OF THE ATHEROSCLEROTIC PROCESS The large arteries in young individuals possess two functions: (1) to act as conduits that transfer blood to vital organs and tissues of the body, and (2) to act as cushions to smooth out the pulsatile action of blood flow produced by the intermittent contraction of the heart into a continuous and steady blood flow.2 As people age, these functions of the large arteries are modified as a consequence of the atherosclerotic process and the stiffening of the large arteries. In young persons, the elastic aorta expands during systole and absorbs part of the stroke volume. During diastole, it recoils back and sends the retained blood volume distally, thus converting the intermittent blood flow into a continuous steady flow. In older persons, the elasticity and compliance of the aorta is lost and most of the stroke volume is transmitted distally during systole with limited blood flow during diastole. The direct result of this function is an increase in SBP, a decrease in DBP, and a widening of PP. In addition, the morphology of the pulse wave curve also changes (Figure). In young individuals, the reflected wave is slower and returns to the aortic root early in diastole, augmenting the DBP, which helps the perfusion of the coronary arteries, whereas in the older person it is faster and returns late in systole, thus augmenting the aortic SBP and increases the left ventricular outflow pressure and is responsible for the development of left ventricular hypertrophy (LVH). In addition, because of the arterial stiffness, PWV is increased in older individuals compared with younger individuals (Figure). The augmentation of the central aortic SBP leads to an increase in AIx. Therefore, PP, PWV, and AIx are all increased in older individuals and Address for correspondence: George S. Chrysant, MD, INTEGRIS Baptist Medical Center, Oklahoma City, OK E-mail: [email protected] DOI: 10.1111/jch.12407
788
The Journal of Clinical Hypertension
Vol 16 | No 11 | November 2014
are considered significant surrogate diagnostic characteristics of severe atherosclerosis.1,2 These findings are also present in patients with peripheral arterial disease (PAD).
PAD AS AN INDEX OF ATHEROSCLEROSIS PAD is a common condition in older persons, is considered a marker of severe atherosclerosis, and is associated with an increased risk of cardiovascular events.3–5 In fact, the mortality rate associated with PAD is higher than the mortality rate associated with myocardial infarction.6 Both asymptomatic and symptomatic patients carry a significantly higher mortality rate compared with persons without PAD. The mechanisms through which PAD increases the risk for cardiovascular disease (CVD) complications are not well defined. Some of the explanations are attributable to its association with severe generalized atherosclerosis, systemic inflammation, and oxidative stress, which is known to destabilize atherosclerotic plaques. In addition, the changes in systemic hemodynamics, such as the increases in SBP, PP, PWV, and AIx, are all associated with a high incidence of CVD complications.1,7–9 In addition, increased central aortic SBP and the development of LVH and PP are also associated with increased cardiovascular morbidity and mortality,10 and the wide PP has been associated with increased cardiovascular morbidity and mortality, as was demonstrated by the Strong Heart Study.10,11 In this issue of the Journal, Catalano and colleagues12 report their data on the association between AIx with PAD. They studied 97 patients with PAD (ankle-brachial pressure index ≤0.90) and 97 control patients. In the patients with PAD, there was a significant positive association between AIx and SBP (P=.0008), PP (P=.02), and MBP (P=.009) and a negative association between AIx and heart rate (HR; P=.0001). Although increased SBP, PP, and AIx are associated with systemic atherosclerosis and PAD, the negative association of AIx with HR has no association with PAD. The reflected wave returns slower to the aortic root in patients with lower HR and augments the central aortic SBP and AIx, whereas the opposite is seen with faster HR. For this reason, it is customary to index the AIx to HR 75 beats per minute for comparison with other patients and it could have been very useful in this case. In addition, the lasting effects of b-blockers should not be discarded in this case, because it is noted that the patients with PAD had slower HRs than the control patients (68 vs 71). It is unknown why no significant association between age and AIx was found in the PAD group, since atherosclerosis and high SBP are high in
Commentary
FIGURE. The configuration of the arterial waveforms in younger (left) and older (right) persons is shown. The arterial waveforms are composite waves (top heavy line) composed of a forward wave (dashed line) and a backward reflective wave (dotted line). The vertical line represents the closure of the aortic value. The top solid line indicates the peak systolic blood pressure (SBP) in the younger and older person together with the augmentation pressure. The reflected wave in the younger person returns to the aortic root early in diastole augmenting diastolic blood pressure, which helps the perfusion of coronary arteries, whereas in the older person it returns to the aortic root late in systole, augmenting the SBP and increasing the left ventricular outflow pressure. Due to the arterial stiffness, pulse wave velocity (PWW) is increased in the older person (12 m/s) compared with the younger person (8 m/s). Adapted with permission from Franklin.9
older persons. It should be noted that SBP was higher in the PAD group compared with the control group, where a positive association between AIx and age was found. Findings similar to those reported in this study have been previously published by other investigators as well as by the same investigators using data from the same patient groups where an association between PAD and PWV was shown.13 What then are the clinical implications from the findings of this study? If an association between PAD and AIx, PP, and PWV is accepted, clinicians can extrapolate the presence of PAD in their patients with the presence of these findings, which have been associated with high cardiovascular morbidity and mortality and take the appropriate measures for a more targeted approach to treatment of their patients. From a practical standpoint, however, it is a lot easier for a busy clinician to measure the ankle-brachial pressure index than using applanation tonometry to measure augmentation pressure, AIx, and PWV. References 1. Chrysant SG, Chrysant GS. The age-related hemodynamic changes of blood pressure and their impact on the incidence of cardiovascular disease and stroke: new evidence. J Clin Hypertens (Greenwich). 2014;16:87–90. 2. O’Rourke M. Mechanical principles of arterial disease. Hypertension. 1995;26:2–9.
3. Criqui MH, Langer RD, Froneck A, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med. 1992;326:381–386. 4. Aronow WS, Ahmed MI, Ekundayo OJ, et al. A propensity-matched study of the association of peripheral arterial disease with cardiovascular outcomes in community-dwelling older adults. Am J Cardiol. 2009;103:130–135. 5. McDermott MM, Liu K, Criqui MH, et al. Ankle-brachial index and subclinical cardiac and carotid disease. The multi-ethnic study on atherosclerosis. Am J Epidemiol. 2005;162:33–41. 6. Caro J, Migliaccio-Walle K, Ishak KJ, Proskorovsky I. The morbidity and mortality following a diagnosis of peripheral arterial disease: long-term follow-up of a large database. BMC Cardiovasc Disord. 2005;5:14–21. 7. Khaleghi M, Kullo IJ. Aortic augmentation index is associated with ankle-brachial index: a community-based study. Atherosclerosis. 2007;195:248–253. 8. Brewer LC, Chai HS, Bailey KR, Kullo IJ. Measures of arterial stiffness and wave reflection are associated with walking distance in patients with peripheral arterial disease. Atherosclerosis. 2007;191:384–390. 9. Mosimann K, Jacomella V, Thalhammer C, et al. Severity of peripheral arterial disease is associated with aortic pressure augmentation and subendocardial viability ratio. J Clin Hypertens (Greenwich). 2012;14:855–860. 10. Roman MJ, Devereux RB, Kizer JR, et al. Central pressure more strongly relates to vascular disease outcome than does brachial pressure. The Strong Heart Study. Hypertension. 2007;50:197–203. 11. Palmieri V, Devereux RB, Hollywood J, et al. Association of pulse pressure with cardiovascular outcome is independent of left ventricular hypertrophy and systolic dysfunction: the Strong Heart Study. Am J Hypertens. 2006;19:601–607. 12. Catalano M, Scandale G, Carzaniga G, et al. Aortic augmentation index in patients with peripheral arterial disease. J Clin Hypertens (Greenwich). 2014;16:782–787. 13. Catalano M, Scandale G, Carzaniga G, et al. Increased aortic stiffness and related factors in patients with peripheral arterial disease. J Clin Hypertens (Greenwich). 2013;15:712–716. The Journal of Clinical Hypertension
Vol 16 | No 11 | November 2014
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