Aortic pressure augmentation predicts adverse cardiovascular events in patients with established coronary artery disease

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ages of the arterial wall caused by the deleterious high frequency components present in the pulse waveform. In conclusion, our results suggest that smooth muscle modulates energy dissipation. This apparent disadvantage could positively contribute to maintain the cushioning exerted by the arterial wall. The energy dissipation improvement by ramipril in HT could be partially related to smooth muscle relaxation induced by angiotensin converting enzyme inhibition. Key Words: Arterial Wall Viscosity, Buffering Function, Carotid Artery

P-4 DIFFERENTIAL IMPACT OF BLOOD PRESSURE AND ATHEROGENIC LIPOPROTEINS ON ARTERIAL STRUCTURE AND FUNCTION: THE BOGALUSA HEART STUDY Wei Chen, Shengxu Li, Sathanur R Srinivasan, Gerald S Berenson. Department of Epidemiology, Tulane University Helth Sciences Center, New Orleans, LA. Arterial wall structure and function, important determinants of cardiovascular (CV) disease, are influenced by CV risk factors, especially high levels of blood pressure and the atherogenic lipoproteins measured as non-HDL cholesterol (total cholesterol minus HDL cholesterol). However, the differential impact of these two major risk factors on arterial wall thickness and stiffness in healthy, asymptomatic individuals is not clear. This aspect was examined in 951 black and white adults, ages 23-43 years, enrolled in the Bogalusa Heart Study. Carotid artery intimamedia thickness (IMT) (the mean of the maximum IMT readings of 3 right and 3 left far walls of common, bulb and internal segments) was measured by B-mode ultrasound and aorta-femoral pulse wave velocity (PWV) by echo-Doppler. Blacks vs whites had greater values of IMT (0.83 mm vs 0.80 mm, P⬍0.01) and PWV (5.4 m/sec vs 5.2 m/sec, P⬍0.01). PWV was associated with carotid IMT in both blacks (age-, sex- and body mass index-adjusted partial correlation coefficient, r⫽0.178, P⬍0.01) and whites (r⫽0.134, P⬍0.01). The influences of systolic blood pressure and non-HDL cholesterol on carotid IMT and PWV did not differ significantly between blacks and whites. Therefore, the impact of systolic blood pressure and non-HDL cholesterol was examine in a multivariate regression model for the total sample, adjusting for race, sex, age, body mass index, insulin, glucose and smoking. The association of systolic blood pressure with PWV (standardized regression coefficient, b⫽0.249, P⬍0.01) was stronger than the association with carotid IMT (b⫽0.127, P⬍0.01). Non-HDL cholesterol was significantly associated with carotid IMT (b⫽0.210, P⬍0.01), but not with PWV (b⫽0.042, P⫽0.17). These results indicate that atherogenic lipoproteins and blood pressure may play different roles in the development of overall arterial wall stiffness and segmental atherosclerosis. Ultrasound measurements provide a valuable assessment of CV risk. Key Words: Arterial Stiffness, Atherosclerosis, Cardiovascular Risk Factors

P-5 SMALL ARTERY COMPLIANCE IS REDUCED IN SLEEP APNEA Marilou I Ching, Bong Hee Sung, Michael F Wilson, Sandra A Block, Daniel I Rifkin. Cardiology and Neurology, State University of New York at Buffalo, Buffalo, NY. Although there is a strong link between sleep apnea and hypertension (HTN), the mechanism of HTN in sleep apnea continuous to be under investigation. Because decreased arterial compliance is associated with HTN, we sought to examine whether small artery elasticity index (SAEI) and large artery elasticity index (LAEI) are different in the sleep apnea cohort compared to their controls. Diagnosis of sleep apnea was based on overnight polysomnogram while sleep apnea was ruled out in the control

POSTERS: Arterial Structure and Compliance

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group based on sleep questionnaire. The mean respiratory disturbance index in those with SA was 38⫾29/hour with mean sleep efficiency of 68⫾11% and mean oxygen saturation nadir of 83⫾9%. Study group consisted of 16 newly diagnosed subjects with sleep apnea and 16 age and blood pressure matched controls. All were non-smokers. BP, HR, SAEI and LAEI were measured non-invasively using the HDI/Pulse Wave CR-2000 machine. With the patient supine, BP cuff was applied to the left arm. Radial pulse was palpated and arterial pulse sensor was placed on the right radial pulse. Three readings were obtained from radial artery pulse pressure waveform to ascertain reproducibility of the data. The two groups were analyzed using unpaired t-test. There were no differences in the sleep apnea group vs control with regards to age (mean⫾SD) (52⫾10 vs 52⫾11 yrs), gender (female⫽6, male⫽10 in each group) and BP (SBP⫽129⫾16 mmHg, DBP⫽75⫾11 mmHg vs SBP⫽129⫾11 mmHg, DBP⫽75⫾12 mmHg, p⫽ns). Subjects with sleep apnea were found to be significantly different in weight (233⫾56 vs.188⫾19 lbs, p⬍0.006), body mass index (34.4⫾7 vs. 27⫾2 kg/m2, ⬍0.001), HR (78⫾17 vs 61⫾7 bpm, p⬍0.002) and SAEI (5.6⫾2.3 vs 7.4⫾2.7, p⬍0.05). LAEI was similar between the two groups. All group analysis further revealed that subjects with sleep apnea were found to have lower SAEI independent of weight or body mass index. In conclusion, increased heart rate in the sleep apnea cohort may reflect heightened sympathetic activity and the reduced small artery elasticity index may be indicative of increased small artery stiffness. These taken together in addition to the increased body weight in subjects with sleep apnea may contribute to hypertension. Key Words: Arterial Compliance, Hypertension, Sleep Apnea

P-6 AORTIC PRESSURE AUGMENTATION PREDICTS ADVERSE CARDIOVASCULAR EVENTS IN PATIENTS WITH ESTABLISHED CORONARY ARTERY DISEASE Julio A Chirinos, Juan P Zambrano, Simon Chakko, Anila Veerani, Alan Schob, Guido Perez, Armando J Mendez. Medicine, University of Miami, Miami, FL; Medicine, Diabetes Research Institute, Miami, FL. Background: Pulse pressure (PP), a marker of arterial stiffness, is a cardiovascular risk predictor. Prospective studies have not evaluated other markers of arterial stiffness as predictors of major adverse cardiovascular events (MACE) in patients with established coronary artery disease (CAD). We aimed to determine whether the aortic augmentation pressure (AP, derived from the aortic pressure waveform) predicts MACE and death independently of the PP. Methods: We prospectively followed 297 males undergoing coronary angiography at the Miami VA Medical Center for 1186⫾424 days. We analyzed ascending aortic pressure tracings obtained during catheterization. Augmented pressure (AP) was defined as the difference between the second and the first systolic peak. Augmentation index (AIx) was defined as AP as a percentage of PP. We evaluated whether AP (adjusted for PP) and AIx can predict the risk of MACE (unstable angina, acute myocardial infarction, coronary revascularization, stroke or death), and all-cause mortality. We used Cox regression; AIx and AP were adjusted for mean aortic pressure, ejection fraction and heart rate in all models. Results: During the follow-up, 43.1% of patients had MACE and 19.5% died. Both the AP (adjusted for PP) and AIx significantly predicted the risk of MACE. The Hazard ratio (HR) per 10 mmHg increase in AP was 1.20 (95%CI⫽1.08-1.34; p⬍0.001); the HR for each 10% in AIx was 1.28 (95%CI⫽1.11-1.48; p⫽0.004). After adjusting for other univariate predictors, the PP-adjusted AP remained a significant predictor of MACE (adjusted HR⫽1.19; 95%CI⫽1.07-1.33; p⫽ 0.001), as did the AIx (adjusted HR⫽1.27; 95%CI⫽1.10-1.48; p⫽0.001). AP was a significant predictor of death (HR per 10 mmHg increase⫽1.18; 95%CI⫽1.02-1.39; p⫽0.03). Higher AIx was associated with a trend towards increased all-cause mortality (HR⫽1.22; 95%CI⫽0.98-1.52; p⫽0.056). Conclusions: Central AP predicts MACE and death in patients with established CAD independently of pulse pressure and other risk markers.

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POSTERS: Arterial Structure and Compliance

Further studies are needed to determine the prognostic value of central pressure augmentation in other populations, further understand the mechanisms affecting it, and define its role as a therapeutic target. Key Words: Aaugmentation Index, Cardiovascular Events, Coronary Artery Disease

P-7 PULSE WAVE VELOCITY IN NORMOTENSIVE HEALTHY SOUTHERN US YOUTH R. Thomas Collins II, Bruce S. Alpert. Pediatrics, University of Tennessee Health Science Center, Memphis, TN. Pulse wave velocity (PWV), an established index of arterial compliance, has been shown in adults to be strongly associated with the presence and extent of atherosclerosis. PWV is the strongest predictor of CV mortality. We sought in a pilot study to establish normal values of brachial-ankle PWV (baPWV) in a group of 48 normotensive, healthy youths with BMI ⬍ 75% for age. The group consisted of 26 African-American (AA) and 22 Caucasian (C) subjects ages 12-18 yrs from a metropolitan area in the southern US. Measurements were performed using a previously validated protocol with the Colin Medical Instruments VP-1000 Vascular Profiling System. Each subject’s baPWV was defined as the average of two consecutive measurements obtained supine after at least five minutes of rest. All data are reported as mean ⫹/- SD. The baPWV of our subjects was 10.4 ⫹/- 1.45 m/s. The mean age was 15.1 yrs. A study by Avolio, et al.1 of PWV measurements in age-matched (mean 15.5 yrs), normotensive, healthy Chinese subjects has found PWV values of 6.32 ⫹/- 0.62 m/s. Our subjects’ values were markedly higher than those youth, p⬍0.0001 (95% CI 3.62 to 4.52). When the US subjects were separated by ethnicity the mean PWV of AA subjects tended to be higher (10.7 ⫹/1.3 m/s [SD] vs. 10.0 ⫹/- 1.5 m/s) than C, though not yet statistically significant (p⬃ 0.1). PWV in the composite US group was significantly higher when compared with the Chinese group. This marked difference suggests that in a normotensive, healthy population where the incidence of coronary artery disease, type 2 diabetes, hypertension, and obesity are much higher in adulthood, vascular changes commensurate with those diseases are already occurring and demonstrable early in life. In addition, although not yet statistically significant, the difference in AA and C measurements suggests that there may be a racial difference in PWV. To define whether a difference exists between AA and C during teenage years we are currently performing a larger study to include 75 normal weight (BMI ⬍ 75% for age) subjects per ethnic group, the number of subjects required by a power analysis to achieve statistical significance. Additionally, we are performing another study to include 50 overweight (BMI ⬎ 95% for age) subjects per ethnic group to determine the effect of overweight on PWV. 1. Circulation. 1985 Feb;71(2):202-210. Key Words: Arterial Compliance, Pediatric, Pulse Wave Velocity

P-8 AORTIC MECHANICAL PROPERTIES DETERIORATE FASTER WITH AGING AT THE ASCENDING THAN AT THE DESCENDING AORTA Daniel A Duprez, Cory Swingen, Ron Sih, Tony Lefebvre, Daniel R Kaiser, Michael Jerosch-Harold. Cardiovascular Division, University of Minnesota, Minneapolis, MN; Advanced Imaging Research Center, Oregon Health and Science University, Portland, OR. Background: The elasticity of the aorta is a major contributor to pulse pressure amplitude. Aortic stiffness increases with advancing age. It is unknown how age affects the mechanical properties at different segments of the aorta.

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Objective: This study aimed to examine aortic stiffness at the ascending and descending aorta in a group of young vs old normotensive subjects. Methods: Cine MRI was performed in 10 young vs 10 old normotensive subjects to evaluate aortic cross-sectional area (mm2), compliance (CC, mm2.mmHg僒1) and distensibility (DC, 10僒3mmHg僒1) in the ascending (Asc) and descending (Desc) aorta. Results: The results are summarized in Table 1 as mean ⫾ SD. Parameter

Young

Old

P-value

Age (yrs) SBP (mmHg) DBP (mmHg) PP (mmHg) Asc DiastArea mm2 Desc Diast Area mm2 Asc CC mm2.mmHg⫺1 Desc CC mm2.mmHg⫺1 Asc DC 10⫺3mmHg⫺1 Desc DC 10⫺3mmHg⫺1

25 ⫾ 2 117 ⫾ 9 70 ⫾ 15 47 ⫾ 11 435.9 ⫾ 110.6 269.7 ⫾ 45.1 4.3 ⫾ 1.2 2.3 ⫾ 0.5 10.5 ⫾ 3.4 8.5 ⫾ 1.7

56 ⫾ 6 126 ⫾ 14 81 ⫾ 5 45 ⫾ 12 733.7 ⫾ 190.5 355.0 ⫾ 77.0 2.0 ⫾ 1.1 1.6 ⫾ 0.7 2.9 ⫾ 1.9 5.0 ⫾ 2.6

P P P P P P P P P P

⬍ ⫽ ⫽ ⫽ ⬍ ⬍ ⬍ ⬍ ⬍ ⬍

0.0001 0.10 0.04 0.74 0.001 0.01 0.001 0.03 0.0001 0.003

Conclusion: Changes in aortic mechancial properties associated with aging are more pronounced in the ascending aorta than in the descending aorta. The increase in cross-sectional area, and decrease in CC and DC were greater in the ascending than the descending aorta with age. Regional measurement of aortic mechanical properties may provide an earlier detection of subclinical atherosclerosis and vascular aging. Key Words: Aortic cross-sectional compliance and distensibility, Aortic Stiffness, Vascular Aging

P-9 EXERCISE BLOOD PRESSURE RESPONSE IS INVERSELY RELATED TO LARGE ARTERY, BUT NOT TO SMALL ARTERY ELASTICITY Daniel A Duprez, Natalia Florea, Lynn Hoke, Brenda Killpatrick, Jay N Cohn. Cardiovascular Division, University of Minnesota, Minneapolis, MN. Background: An exaggerated blood pressure (BP) response to exercise is predictive of risk for new onset of hypertension in normotensive men and women. These findings may reflect pathophysiological features in the preclinical stage of hypertension. However it is unknown if this response is related to decreased large and/or small artery elasticity. Objective: This study aimed to examine the relationship between exercise systolic blood pressure response and large and small artery elasticity in a population attending a primary cardiovascular prevention programm. Methods: A total number of 529 patients (mean age 51.2 ⫾ 0.5 years; 65 % male, 35 % female; mean systolic BP 127.4 ⫾ 0.8 mm Hg and diastolic BP 82.6 ⫾ 1.4 mm Hg performed a treadmill exercise test for 3 minutes at 5 MET (metabolic equivalent) workload. BP was measured before and at 3 min exercise and the BP response was considered as the rise in systolic BP. Large (C1) and small (C2) artery elasticity index was measured by pulse wave analysis registered at the radial artery using the CV Profilor. Results: Mean large artery elasticity index was 16.65 ⫾ 0.25 ml/mm Hg x 10 and small artery elasticity index was 6.68 ⫾ 0.14 ml/mmHg x 100. Mean exercise systolic BP increase was 22.3 ⫾ 0.7 mm Hg . There was an inverse correlation between large artery elasticity index and the SBP response to exercise, r ⫽ - 0.32, P ⫽ 0.015, while there was no significant correlation with the small artery elasticity index. Conclusion: In a primary cardiovascular prevention population, the exercise blood pressure response is inversely related to large artery, but not to small artery elasticity index. These findings suggest that a reduction in large artery elasticity could impair pressure buffering during