Evaluation of Vascular Function in Hemodialysis Patients: Small Artery Elasticity Index (SAE) Correlates with Pulse Wave Velocity (PWV) Summer 2011 Medical Scholars Program Allison M. Dubner, John J. White, Gaston K. Kapuku, David M. Pollock, Jennifer S. Pollock, and William D. Paulson Department of Nephrology, Summer Medical Scholar Program, Georgia Health Sciences University, Augusta, GA Introduction Arteriosclerosis is a major cause of cardiovascular disease and mortality in end-stage renal disease (ESRD) [1,2]. Arteriosclerosis is characterized by arterial stiffening, with high arterial systolic and pulse pressures [1-6]. These changes follow from the loss of dampening function of arteries, which causes an increase in pulse wave velocity. In a normal vascular circuit, arterial pulse waves are reflected back from the periphery and branch points, and these reflected waves augment diastolic pressure, thereby enhancing coronary perfusion. However, pulse waves travel more quickly in a stiff artery. Thus, reflected waves may return during systole, thereby augmenting systolic pressure and reducing diastolic pressure. This helps explain enhanced cardiovascular mortality in ESRD [7-10]. Thus, measurement of pulse wave velocity (PWV) is considered the gold standard for evaluating arterial stiffness and vascular function. A second method of measuring vascular health is flow mediated dilatation (FMD). FMD measures reactive dilatation of the brachial artery following release of nitric oxide. Stiff arteries generally demonstrate poor dilatation in response to nitric oxide [11,12]. This technique can be used to detect vascular dysfunction, but requires a highly trained sonographer and is difficult to perform. Although PWV and FMD can be used to evaluate cardiovascular disease in ESRD, these tests may not be fast and easy enough for widespread use. Measurement of arterial elasticity may meet this need since the test is quick and requires no significant training to perform. Additionally, small artery elasticity index (SAE) has been shown to correlate with clinical outcomes in both ESRD and non-ESRD patients [13,14]. In this project, we compared these three tests of vascular function to determine the relation between SAE and the two established measures of vascular function: PWV and FMD. Small Artery Elasticity Index (SAE) The HDI/PulseWave CR-2000 System (Hypertension Diagnostics, Inc.) was used to measure SAE. A noninvasive tonometer was applied to the skin above the radial artery at the wrist. The tonometer provided a pulse contour analysis of radial artery waveforms and calculated SAE. Twenty-five stable hemodialysis patients of were studied. Subjects were evaluated for vascular function with 3 methods: PWV, FMD and SAE. In addition, arterial blood pressure and heart rate were measured. Pulse Wave Velocity (PWV) Carotid-femoral pulse wave velocity was measured noninvasively with applanation tonometry (SphygmoCor Pulse Wave Velocity Vx System). In this method, a probe was applied over the carotid and femoral arteries to detect the arterial pressure wave. The timing of pulse wave arrivals was used to calculate PWV, which is high in stiff arteries. Flow Mediated Dilatation (FMD) A blood pressure cuff was inflated for 4 minutes (causing ischemia) and then suddenly released, causing an increase in blood flow and reactive release of nitric oxide, an arterial vasodilator. The diameter of the brachial artery was measured by ultrasound before and after occlusion of the brachial artery, and percentage increase in arterial diameter was computed. • • • • Measurements in this cohort of ESRD patients were generally consistent with arterial stiffness and dysfunction (high systolic and pulse pressures, high PWV, low SAE, and low FMD). Lower SAE was associated with higher PWV. There was no correlation between SAE and FMD Over 70% of SAE variation is explained by its association with PWV, pulse pressure, body mass index, and mean arterial pressure. Discussion Results • • • • • • Figure 1: Lower SAE was associated with higher PWV. Simple Regression Analysis SAE negatively correlated with PWV (R2 = 0.29, P = 0.009) SAE did not correlate with FMD (P = 0.81) SAE negatively correlated with mean arterial pressure (R2 = 0.242, P = 0.013). SAE negatively correlated with systolic pressure (R2 = 0.191, P = 0.029) SAE positively correlated with body mass index (R2 = 0.337, P = 0.002) • • • Multiple Regression Analysis SAE correlated with PWV, pulse pressure, body mass index, and mean arterial pressure (R2 = 0.701, all P <0.022) This study supports the utility of small artery elasticity index as a measure of arterial stiffness and vascular function in ESRD. In both simple and multiple regression analyses, SAE correlated with various vascular indicators, including PWV, systolic pressure, and mean arterial pressure. While SAE did not correlate with FMD, FMD did not correlate with any measures of vascular function (data not shown). This suggests that FMD may not be an optimal method of measuring vascular health in ESRD. An unexpected finding was the positive correlation between body mass index (BMI) and SAE. A previous study found the same relationship and suggested it might be due to the improved vascular function found at higher BMIs within the non-obese range [15]. References Table 1: Patient demographics and mean values for vascular testing. Values are consistent with arterial dysfunction: high systolic & pulse pressure, low SAE, high PWV, low FMD. Figure 2: Lower SAE was associated with higher systolic blood pressure. Patient characteristics (n = 25) Materials and Methods Summary Patient age (yrs) 46.68 Female (%) 8 African American (%) 92 Body mass index (kg/m2) 28.01 Diabetes Mellitus (%) 32 Cardiovascular disease (%) 52 Systolic blood pressure (mmHg) 144.12 Diastolic blood pressure (mmHg) 81.47 Mean arterial pressure (mmHg) 105.77 Pulse pressure (mmHg) 62.65 Small artery elasticity index (ml/mmHg x100) 5.69 Pulse wave velocity (m/s) 9.49 Flow mediated dilatation (%) 6.18 1. London GM, Marchais SJ, Guerin AP, et al. "Arterial structure and function in end-stage renal disease.” Nephrol Dial Transplant 17: 1713-1724, 2002. 2. Pannier B, Guerin AP, Marchais SJ, et al. "Arterial structure and function in end-stage renal disease.” Art Res 1: 79-88, 2007. 3. USRDS. United States Renal Data System; Annual Data Report, 2010. 4. Blacher J, Guerin AP, Pannier B, et al. "Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease.” Hypertension. 2001 Oct;38(4):938-42. 5. Briet M, Bozec E, Laurent S, et al. “Arterial stiffness and enlargement in mild-tomoderate chronic kidney disease.” Kidney Int 69: 350-357, 2006. 6. Ku YM, Kim YO, Kim JI, et al. “Ultrasonographic measurement of intima-media thickness of radial artery in predialysis ureaemic patients: comparison with histological examination.” Nephrol Dial Transplant 21: 715-720, 2006. 7. Glassock RJ, Pecoits-Filho R, Barberato SH. Left Ventricular Mass in Chronic Kidney Disease and ESRD. Clin J Am Soc Nephrol 4: S79–S91, 2009 8. Henrich WL. Optimal Cardiovascular Therapy for Patients with ESRD over the Next Several Years. Clin J Am Soc Nephrol 4: S106–S109, 2009 9. McCullough PA. “Coronary Artery Disease.” Clin J Am Soc Nephrol 2: 611-616, 2007. 10. Ritz E, Bommer J. “Cardiovascular Problems on Hemodialysis: Current Deficits and Potential Improvement.” Clin J Am Soc Nephrol 4: S71–S78, 2009. 11. Kapuku GK, Harshfield GA, Davis HC, Treiber FA. “Early markers of cardiovascular disease.” Vascul Pharmacol. 45(5):277-80, 2006. 12. Faulx MD, Wright AT, Hoit BD. “Detection of endothelial dysfunction with brachial artery ultrasound scanning.” Am Heart J. 145(6):943-51, 2003. 13. Kheda MF, Brenner LE, Patel MJ, Wynn JJ, White JJ, Prisant LM, Paulson WD. “Influence of arterial elasticity and vessel dilatation on arteriovenous fistula maturation: a prospective cohort study.” Nephrol Dial Transplant 25: 525–531, 2010. 14. Wilson AM, O'Neal D, Nelson CL, Prior DL, Best JD, Jenkins AJ. “Comparison of arterial assessments in low and high vascular disease risk groups.” Am J Hypertens. 17(4):28591, 2004. 15. Kals JP, Kampus M, Kals R, et al. "Arterial Elasticity Is Associated with Endothelial Vasodilatory Function and Asymmetric Dimethylarginine Level in Healthy Subjects." Scan J Clin Lab Inves 67.5: 536-44, 2007. Acknowledgements Figure 3: Higher SAE was associated with higher body mass index (BMI). I would like to thank Dr. White, Dr. Kapuku, and Dr. Paulson for all of the help they have given me on this project. I also appreciate all the hard work James Halbert has put into the study. Finally, I would like to thank the GHSU Dean’s Summer Research Fellowship Program for funding the research and giving me the opportunity to pursue my interests this summer.
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