Medicalteknika.jp

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, Howard J. Willens, Abstract—Pulse pressure (PP), a marker of arterial stiffness, predicts cardiovascular risk. We aimed to determine whether
augmentation pressure (AP) derived from the aortic pressure waveform predicts major adverse cardiovascular events
(MACE) and death independently of PP in patients with established coronary artery disease (CAD). We prospectively
followed-up 297 males undergoing coronary angiography for 1186Ϯ424 days. Ascending aortic pressure tracings
obtained during catheterization were used to calculate AP (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 and AIx can predict the
risk of MACE (unstable angina, acute myocardial infarction, coronary revascularization, stroke, or death) and death
using Cox regression. All models evaluating AP included PP to assess whether AP adds to the information already
provided by PP. Both AP and AIx significantly predicted MACE. The hazard ratio (HR) per 10 mm Hg increase in AP
was 1.20 (95% confidence interval [CI], 1.08 to 1.34; PϽ0.001); the HR for each 10% increase in AIx was 1.28 (95%
CI, 1.11 to 1.48; Pϭ0.004). After adjusting for other univariate predictors of MACE, age, and other potential
confounders, AP remained a significant predictor of MACE (HR per 10 mm Hg increaseϭ1.19; 95% CI, 1.06 to 1.34;
Pϭ0.002), as did AIx (adjusted HR, 1.28; 95% CI, 1.09 to 1.50; Pϭ0.003). AP was a significant predictor of death (HR
per 10 mm Hg increaseϭ1.18; 95% CI, 1.02 to 1.39; Pϭ0.03). Higher AIx was associated with a trend toward increased
mortality (HRϭ1.22; 95% CI, 0.98 to 1.52; Pϭ0.056). Aortic AP predicts adverse outcomes in patients with CAD
independently of PP and other risk markers. (Hypertension. 2005;45:980-985.)
Key Words: arterial stiffness Ⅲ cardiovascular events Ⅲ coronary angiography
Ⅲ coronary artery disease Ⅲ prospective study Increasedarterialstiffnesshasbeenshowntocorrelatewith augmentation index (AIx). AIx has been shown to be predic- coronary risk factors.1–4 In addition, measures of arterial tive for the presence of CAD5–7 and has been shown to predict stiffness correlate with the presence of angiographic coronary adverse outcomes in patients with end-stage renal disease.11 artery disease (CAD).5–7 An increased pulse pressure (PP), However, whether central pressure augmentation can predict which has been associated with increased arterial stiffness, is adverse outcomes independently of PP and angiographic an adverse cardiovascular risk predictor.8–10 The pressure severity of CAD in patients with established coronary disease waveform of the proximal aorta is affected by arterial stiffness and likely to be more informative than the pulse In this study, we aimed to determine whether AP and AIx can predict the incidence of major adverse cardiovascular The central aortic pressure wave is composed of a forward- events (MACEs) or all-cause mortality in patients with traveling wave generated by left ventricular ejection and a later-arriving reflected wave from the periphery.1–4 As aorticand arterial stiffness increase, transmission velocity of both forward and reflected waves increase, which causes the Study Population
reflected wave to arrive earlier in the central aorta and We studied a cohort of 420 male veterans undergoing clinically augment pressure in late systole. Therefore, augmentation of indicated coronary angiography at the Miami Veterans Administra-tion Medical Center between October 1998 and February 2000. The the central aortic pressure wave is a manifestation of wave study was approved by the Hospital’s Institutional Review Board and reflection. This can be expressed in absolute terms as the written informed consent was obtained from all patients. For this augmented pressure (AP), or as a percentage of PP as the study, only subjects with coronary artery stenosis on angiography of Received January 18, 2005; first decision February 3, 2005; revision accepted March 14, 2005.
From the University of Miami School of Medicine (J.A.C., J.P.Z., S.C., A.V., A.S., H.J.W., G.P., A.J.M.), Diabetes Research Institute (A.J.M.), and Veterans Affairs Medical Center (S.C., A.S., H.J.W.), Miami, Fla.
Correspondence to Julio A. Chirinos, MD, 111-A, V.A. Medical Center, 1201 NW 16th Street, Miami, FL 33125. E-mail jchirinos@med.miami.edu 2005 American Heart Association, Inc.
Hypertension is available at http://www.hypertensionaha.org
DOI: 10.1161/01.HYP.0000165025.16381.44
980
Chirinos et al
Pressure Augmentation and Cardiovascular Risk
981
and reflected wave, which occurred in 27.9% of cases), an augmen-tation pressure of zero was assigned. To assess the reproducibility ofmanual calculation of the AIx, 12 consecutive beats were analyzed in15 patients. The average coefficient of variation in these analyseswas 8.8%.
Because arterial elasticity is not constant but instead depends on its distending pressure, the mean arterial pressure (MAP) wasincorporated into all models including AP or AIx, so that anticipatedeffects of distending pressure can be differentiated from real differ-ences in the elasticity of the arterial wall.13 Similarly, AIx reflects theinteraction between ventricular ejection and the properties of the Figure 1. Representation of a central aortic pressure waveform
arteries,6,14 and it can be affected by changes in left ventricular and calculation of the augmentation pressure and pulse pres- systolic function. Heart rate can also influence pulse wave velocity sure. The augmentation index is the augmentation pressure and central pressure augmentation.14–16 Therefore, the EF and heart expression as a proportion of the pulse pressure.
rate (RR interval preceding the cardiac cycle in which the AP wascalculated) were included in all models evaluating AP or AIx. In Ͼ10% were included and those with more than mild valvular heart addition, PP was included in all models evaluating AP. By means of adding AP to models already containing PP, one can estimate hazard A full demographic and clinical characterization was performed at ratios (HRs) for different levels of AP after adjustment for PP and, study entry. Data recorded included age, ethnicity, height, weight, importantly, test whether the addition of AP to a model already peripheral blood pressure, ejection fraction (EF) (measured byventriculography at the time of coronary angiography or echocardi- Baseline Characteristics of Study Subjects
ography within 1 month of the date of cardiac catheterization),current smoking, previous myocardial infarction, history of periph- eral vascular disease, congestive heart failure, diabetes mellitus,stroke, or revascularization procedures (coronary artery bypass surgery or percutaneous coronary intervention), and family history of CAD. The indication for cardiac catheterization and the medications that patients were receiving at that time were also recorded. Brachialblood pressure values were based on a single cuff pressure taken in the recumbent position the morning before cardiac catheterization.
Angiographic Studies
Coronary angiography was performed and images of the coronary
tree were obtained in routine standardized projections. The number of coronary vascular territories with at least one 50% or greater diameter stenosis before percutaneous or surgical coronary revascu-larization was used as an index of CAD severity (0-vessel, 1-vessel, 2-vessel, or 3-vessel disease). Left main lesions were categorized as Laboratory Analysis
Peripheral blood samples were collected just before the cardiac catheterization. Blood was allowed to clot for 30 minutes at room Aortic diastolic blood pressure, mm Hg (IQR) temperature and serum collected after centrifugation. Serum sampleswere stored in aliquots at Ϫ80°C until analyzed. Total cholesterol and triglycerides (Roche Diagnostics) and high-sensitivity C-reactive protein (Dade-Behring) levels were determined. High- density lipoprotein lipids were measured after precipitation ofapolipoprotein B– containing lipoproteins.12 Very-low-density li- poprotein and low-density lipoprotein cholesterol were estimated by Pulse Waveform Analysis
Central aortic pressure was recorded invasively via a low- compliance fluid-filled catheter positioned in the ascending aorta.
The system was inspected for the presence of bubbles or clots before pressure recordings. Only waveforms that were technically adequate on visual inspection were included in the analysis; waveform analysis was performed manually. The analyzer of the pressurewaveforms was blinded to the outcome and all clinical and labora- tory variables. Similarly, the assessment of outcomes during follow-up was blinded to variables derived from waveform analysis.
The merging point of the incident and the reflected wave (inflectionpoint) was identified on the aortic pressure waveform. The first and second systolic peaks (P and P ) of the aortic pressure waveform were analyzed (Figure 1). AP was calculated as the difference between the second and first systolic peaks (P ϪP ). AIx was defined as AP expressed as a percentage of PP. When the inflection point CRP, C-reactive protein; IQR, interquartile range; LDL, low-density lipopro- could not be identified (because of superimposition of the incident 982
Hypertension
Univariate Predictors of Major Adverse
Cardiovascular Events (n؍297)
Figure 2. Augmentation pressure and augmentation index as
containing PP significantly improves the predictive ability of the predictors of major adverse cardiovascular outcomes. Hazard model (ie, whether AP adds significant prognostic information to ratios and 95% confidence intervals for each 10-mm Hg that already provided by PP). Finally, given that age and height affect increase in augmentation pressure (adjusted for pulse pressure)or 10% increase in augmentation index (AIx). Both augmentation wave reflections, these variables were included among the potential pressure and AIx were adjusted for mean aortic pressure, heart confounders in multivariate analyses.
rate, and ejection fraction in all models. Model 2 also includedunivariate predictors of major adverse cardiovascular events Definitions of Events and Follow-Up
shown in Table 2. Model 3 included variables in model 2, age, Events were documented by patient interview and review of elec- height, and other potential confounders (angiotensin-converting tronic hospital records. The primary combined endpoint was the first enzyme inhibitor, ␤-blocker, statin use, high-density lipoprotein occurrence of any of the following MACEs: death from any cause, cholesterol, and low-density lipoprotein cholesterol).
myocardial infarction, unstable angina, revascularization with eitherpercutaneous coronary intervention or coronary artery bypass graft were lost to follow-up and 1 patient died 1 day after cardiac surgery (if these procedures were not a direct result of the angio- catheterization and was excluded from the analysis. The final graphic findings during the index cardiac catheterization), andstroke. The secondary endpoint was death from any cause. The analysis was performed with data from 297 patients. The diagnosis of myocardial infarction was performed by the presence of baseline characteristics of our patient population are shown in suggestive symptoms, with either electrocardiographic evidence (new Q waves in 2 or more leads) or cardiac marker evidence ofinfarction, according to the standard Thrombolysis In Myocardial Predictors of MACE
Infarction (TIMI) and American College of Cardiology definition.
The mean follow-up among patients who did not have a Unstable angina was defined as ischemic discomfort at rest for atleast 10 minutes prompting rehospitalization, combined with one of MACE was 1186Ϯ424 days. During the follow-up period, the following: ST-segment or T-wave changes, cardiac marker 43.1% of patients had a MACE. Univariate predictors of elevations that were above the upper limit of normal but did not meet the criteria for myocardial infarction, or a second episode ofischemic chest discomfort lasting Ͼ10 minutes and that was distinct Augmentation Pressure and MACE
from the episode that had prompted hospitalization.
Absolute augmentation pressure significantly predictedMACE (Figure 2). There was a 20% increase in the risk of Statistical Analysis
MACE for every 10 mm Hg increase in augmentation pres- Normally distributed continuous variables are expressed asmeanϮstandard deviation. Non-normally distributed continuous sure (95% confidence interval [CI], 8% to 34%; PϽ0.001).
variables are expressed as median (interquartile range). Proportions This indicates that AP added significant prognostic informa- are expressed as counts and percentages. Univariate and multivariate tion to that already provided by PP. After adjusting for survival analyses were performed with Cox regression. Analyses univariate predictors of MACE (Table 2), AP significantly were performed separately for MACE and all-cause mortality.
predicted MACE (adjusted HR per 10 mm Hg in- Multivariate analysis was performed incorporating all univariate creaseϭ1.19; 95% CI, 1.07 to 1.33; Pϭ0.001). After also predictors of the outcome and other potential confounders. Allprobability values are 2-tailed. Values of PϽ0.05 were considered adjusting for age, height, and other potential confounders statistically significant. All analyses were performed with the statis- (angiotensin-converting enzyme inhibitor, ␤-blocker, statin tical package NCSS for Windows (Kaysville, Utah).
use, high-density lipoprotein cholesterol, and low-densitylipoprotein cholesterol), AP remained a significant predictor of MACE (adjusted HR per 10 mm Hg increaseϭ1.19; 95% Among the 420 patients who signed the informed consent, 360 had CAD. Nine patients were excluded from this studysecondary to significant valvular disease. Out of the 351 AIx as a Predictor of MACE
remaining patients, acceptable pressure waveforms on visual AIx significantly predicted the risk of MACE (Figure 2).
inspection were available in 312 subjects. Fourteen patients There was a 28% increase in the risk of MACE for every 10% Chirinos et al
Pressure Augmentation and Cardiovascular Risk
983
Univariate Predictors of All-Cause Mortality (n؍297)
AP and Death
AP was a significant predictor of death. For every 10-mm Hg
increase in AP, there was an 18% increase in the risk of death (95% CI, 2% to 39%; Pϭ0.03). When adjusted for univariate predictors of death (Table 3), an increased AP was associated with a trend toward increased mortality (HR for 10 mm Hg increase: 1.16; 95% CI, 0.99 to 1.35; Pϭ0.06).
AIx and Death
Higher AIx (adjusted for EF, HR, and mean arterial blood pressure) was associated with a trend toward increased mortality (HRϭ1.22; 95% CI, 0.98 to 1.52; Pϭ0.056). When adjusted for univariate predictors of death, the adjusted HR per 10% increase in AIx was 1.01; the correlation did notreach statistical significance (P Aortic Pressures and Death
Aortic diastolic blood pressure inversely correlated with therisk of death (HR per 10-mm Hg increaseϭ0.74; 95% CI, increase in AIx (95% CI, 11% to 48%; PϽ0.001). After 0.60 to 0.93; Pϭ0.01). When adjusted for EF and MAP, PP adjusting for univariate predictors of MACE (Table 2), AIx predicted mortality (adjusted HR per 10-mm Hg increase in remained a significant predictor of MACE (adjusted HR per PPϭ1.17; 95% CI, 1.03 to 1.32; Pϭ0.01). Brachial PP did 10% increaseϭ1.27; 95% CI, 1.10 to 1.48; Pϭ0.001). After also adjusting for age, height, other potential confounders(angiotensin-converting enzyme inhibitor, ␤-blocker, statin Discussion
use, high-density lipoprotein cholesterol, and low-density We investigated whether AP, a marker of aortic stiffness and lipoprotein cholesterol), the correlation between AIx and wave reflection from the periphery, predicts adverse cardio- MACE persisted (adjusted HRϭ1.28; 95% CI, 1.09 to 1.50; vascular outcomes in patients with established CAD. We found a significant independent correlation between AP(adjusted for PP) and the risk of MACE. This indicates that Aortic Pressures and MACE
AP added significant prognostic information to that already Interestingly, centrally measured diastolic blood pressure was provided by PP and other risk markers and potential con- a predictor of MACE; for every 10 mm Hg increase in aortic founders. Similar results were obtained when AIx a single diastolic blood pressure, the HR was 0.83 (95% CI, 0.71 to composite term was analyzed. AP predicted all-cause mortal- 0.96; Pϭ0.01), indicating that lower aortic diastolic blood ity; when additional adjustments were performed, including pressure values were associated with a higher risk of MACE age and other predictors of death, a trend for increased death in our population. As expected, aortic diastolic blood pressure with increased AP persisted. A trend toward prediction of closely correlated with mean aortic blood pressure (rϭ0.71; death was found when AIx was adjusted for heart rate, EF, PϽ0.0001); therefore, we did not include aortic diastolic and MAP, but not when further adjustment was performed for blood pressure in the models described (which included the other predictors of mortality. These results raise the possibil- MAP) to avoid problems with colinearity. To test whether AP ity that AIx, although practical as a single composite value, or AIx predict MACE independently of aortic diastolic blood might not contain all the prognostic information contained in pressure, both aortic systolic blood pressure and aortic both values (AP and PP) expressed separately. Our study has diastolic blood pressure were entered in the model and mean not proven this concept, which needs to be tested in other aortic blood pressure was withdrawn (aortic systolic and populations and confirmed by means of prospective diastolic pressures did not closely correlate in our popula- tion). In these models, the adjusted HR for each 10% increase Although peripheral PP is the most commonly measured in AIx was 1.33 (95%CI: 1.14 to 1.55; Pϭ0.0002); the marker of arterial stiffness, the information contained within adjusted HR for each 10-mm Hg increase in AP was 1.23 the waveform of the proximal aorta is of particular interest (95%CIϭ1.10 to 1.37; Pϭ0.0002).
because the blood pressure profile at this site determines left After adjusting for EF and MAP, there was a trend for an ventricular load and coronary blood flow.13 AP results form increased risk of MACE with increasing aortic PP (HR per the pressure wave generated by the left ventricle, conducted 10 mm Hg increase in PP: 1.084; 95% CI, 0.997 to 1.178; by large arteries, and reflected at peripheral impedance small Pϭ0.057). Brachial PP did not predict MACE in our arteries and arterioles (and conducted back by large arteries to the proximal aorta). Therefore, central pressure augmentationis affected by large-artery stiffness as well as the tone of Predictors of All-Cause Mortality
impedance vessels, which, in turn, is influenced by the tone of During the follow-up period, 19.5% of patients died. Univar- arterial smooth muscle. It has been shown that nitric oxide iate predictors of death are shown in Table 3.
contributes to the functional regulation of stiffness.17–19 By 984
Hypertension
affecting the timing and magnitude of wave reflection, which subjects with isolated systolic hypertension were increased arterial stiffness has the potential to directly impair treated with chlorthalidone and atenolol (versus placebo) in a coronary blood flow in patients with CAD.20–22 Interestingly, stepwise manner;36 in this trial, a decrease of 5 mm Hg in high carotid AIx has been shown to be an independent diastolic blood pressure was associated with an increase in predictor of cardiac ischemic threshold during exercise in the risk of major adverse cardiovascular events (HRϭ1.11; patients with CAD.22 Therefore, AP is determined by the 95% CI, 1.05–1.16). Our findings are also consistent with a cumulative and integrated influence of various structural, recent preliminary from the large International Verapamil hemodynamic, and metabolic stimuli and can ultimately SR/trandolapril (INVEST) Study.37 Whether the correlation impair coronary blood flow. Arterial stiffness might be not of diastolic blood pressure with adverse outcomes in patients only a risk marker but also a therapeutic target for patients at with CAD is related to increased arterial stiffness, comorbid risk for CAD, as well as for patients with established CAD.
conditions, or a combination of both remains unclear. The Importantly, noninvasive recordings of radial arterial pressure association of diastolic blood pressure and the risk of MACE waveforms using radial tonometry and a generalized transfer in our population and the way it relates to arterial stiffness function now allow for determinations of central pressure and comorbid conditions is the focus of a separate analysis.
Our study is in agreement with previous studies that have Perspectives
shown that measures of arterial stiffness predict adverse Several studies indicate that markers of arterial stiffness are cardiovascular outcomes in different populations,11,25–33 such reliable predictors of cardiovascular events in the wide as patients with end-stage renal disease,11,25,26 hyperten- spectrum of atherosclerosis progression. Measures of arterial sion,27–29 diabetes mellitus,30 and patients older than 70 stiffness can identify nonhypertensive subjects at risk for years,31 all of which are populations at high risk for CAD.
hypertension, identify hypertensive, diabetic, and elderly Adding to this line of evidence, we have shown that increased subjects who are at increased risk for vascular events and AP predicted adverse cardiovascular outcomes in patients death, predict mortality in patients with established renal with established CAD independently of age, the angiographic disease, and predict adverse cardiovascular outcomes in severity of CAD, and other risk markers. It should be noted, patients with established angiographic coronary artery dis- however, that changes in AP may be partially independent of ease. The technology to noninvasively evaluate arterial stiff- changes in arterial stiffness. The factors that determine ness and wave reflections is available and suitable for clinical central pressure augmentation are diverse, complex, and use. Further studies are needed to further quantify the extent incompletely understood. Central pressure augmentation to which measures of arterial stiffness can improve risk likely represents a composite marker of disease-related ad- stratification and, most importantly, to determine whether its verse changes in hemodynamics that vary throughout differ- reduction is capable of independently predicting clinical ent sections of the arterial tree and deserve further mechanis- benefit of therapeutic interventions in different populations.
Our study has limitations. We did not test the frequency– Acknowledgments
amplitude performance of the catheterization laboratory am- This work was funded by support from the American Heart Asso- plifiers, which might affect the accuracy of measurements of ciation, grant in aid (grant 9950534N to A.J.M.), and The Retirement augmentation pressure. In addition, left ventricular dysfunc- tion is a poor prognostic indicator that tends to decreasepressure augmentation. Although we performed adjustments References
for EF in all models, these adjustments might not account for 1. O’Rourke MF, Staessen JA, Vlachopoulos C, Duprez D, Plante GE.
changes on the pattern of ventricular ejection. We should note Clinical Applications of Arterial Stiffness; Definitions and ReferenceValues. Am J Hypertens. 2002;15:426 – 444.
that these limitations would be expected to obscure the 2. Nichols WW, Singh BM. Augmentation index as a measure of peripheral predictive ability of AP rather than to underlie the correlation vascular disease state. Curr Opin Cardiol. 2002;17:543–551.
between pressure augmentation and outcomes. Finally, sta- 3. Izzo JL Jr. Arterial stiffness and the systolic hypertension syndrome. Curr tistical modeling for medication use might not incorporate the 4. McVeigh GE. Pulse Waveform Analysis and Arterial Wall Properties.
effect of individual agents prescribed in different doses.
Hypertension. 2003;41:1010 –1011.
Careful analysis of the frequency–amplitude performance 5. Hayashi T, Nakayama Y, Tsumura K, Yoshimaru K, Ueda H. Reflection of the entire measurement system is recommended for those in the arterial system and the risk of coronary heart disease. Am J who wish to undertake similar work. This can be achieved Hypertens. 2002;15:405– 409.
6. Weber T, Auer J, O’Rourke MF, Kvas E, Lassnig E, Berent R, Eber B.
with the use of electrical pressure generators capable of Arterial stiffness, wave reflections, and the risk of coronary artery generating pressure waves in a liquid system at different disease. Circulation. 2004;109:184 –189.
frequencies, as performed by Smulyen et al,34 or using the 7. Imanishi R, Seto S, Toda G, Yoshida M, Ohtsuru A, Koide Y, Baba T, “pop-test” method as previously described.
Yano K. High brachial-ankle pulse wave velocity is an independent predictor of the presence of coronary artery disease in men. Hypertens The inverse association of centrally measured diastolic blood pressure with the risk of MACE in our population 8. Madhavan S, Ooi WL, Cohen H, Alderman MH. Relation of pulse deserves further mention. We found that lower aortic diastolic pressure and blood pressure reduction to the incidence of myocardial blood pressure were associated with a higher risk of MACE infarction. Hypertension. 1994;23:395– 401.
9. Fang J, Madhavan S, Cohen H, Alderman MH. Measures of blood and death. These findings are consistent with those from the pressure and myocardial infarction in treated hypertensive patients.
Systolic Hypertension in the Elderly Program (SHEP) trial, in J Hypertens. 1995;13:413– 419.
Chirinos et al
Pressure Augmentation and Cardiovascular Risk
985
10. Benetos A, Safar M, Rudnichi A, Smulyan H, Richard JL, Ducimetieere 23. O’Rourke MF, Pauca A, Jiang XJ. Pulse wave analysis. Br J Clin P, Guize L. Pulse pressure: a predictor of long-term cardiovascular Pharmacol. 2001;51:507–522.
mortality in a french male population. Hypertension. 1997;30: 24. O’Rourke MF, Pauca AL. Augmentation of the aortic and central arterial pressure waveform. Blood Press Monit. 2004;9:179 –185.
11. London GM, Blacher J, Pannier B, Guerin AP, Marchais SJ, Safar ME.
25. Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar ME, London GM.
Arterial wave reflections and survival in end-stage renal failure. Hyper- Impact of Aortic Stiffness on Survival in End-Stage Renal Disease.
tension. 2001;38:434 – 438.
Circulation. 1999;99:2434 –2439.
12. Grauholt AM, Grande P, Horby-Petersen J, Jensen J, Rostgaard M, 26. Blacher J, Pannier B, Guerin AP, Marchais SJ, Safar ME, London GM.
Meinertz H. High-density lipoprotein cholesterol assay by magnesium Carotid Arterial Stiffness as a Predictor of Cardiovascularand All-CauseMortality in End-Stage Renal Disease. Hypertension. 1998;32:570 –574.
dextransulphate precipitation. Scand J Clin Lab Invest. 1986;46:715–721.
27. Boutouyrie P, Tropeano AI, Asmar R, Gautier I, Benetos A, Lacolley P, 13. Oliver JJ, Webb DJ. Noninvasive Assessment of Arterial Stiffness and Laurent S. Aortic stiffness is an independent predictor of all-cause and Risk of Atherosclerotic Events. Arterioscler Thromb Vasc Biol. 2003;23: cardiovascular mortality in hypertensive patients. Hypertension. 2001;37: 14. Lantelme P, Mestre C, Lievre M, Gressard A, Milon H. Heart rate: an 28. Laurent S, Katsahian S, Fassot C, Tropeano AI, Gautier I, Laloux B, important confounder of pulse wave velocity assessment. Hypertension.
Boutouyrie P. Aortic stiffness is an independent predictor of fatal stroke in essential hypertension. Stroke. 2003;34:1203–1206.
15. Hayward CS, Avolio AP, O’Rourke MF, Lantelme P, Mestre C, Lievre 29. Boutouyrie P, Tropeano AI, Asmar R, Gautier I, Benetos A, Lacolley P, M, Gressard A, Milon H. Arterial pulse wave velocity and heart rate.
Laurent S. Aortic Stiffness Is an Independent Predictor of Primary Hypertension. 2002;40:8e–9e.
Coronary Events in Hypertensive Patients: A Longitudinal Study. Hyper- 16. Wilkinson IB, MacCallum H, Flint L, Cockcroft JR, Newby DE, Webb DJ. The influence of heart rate on augmentation index and central arterial 30. Cruickshank K, Riste L, Anderson SG, Wright JS, Dunn G, Gosling RG.
pressure in humans. J Physiol. 2000;525:263–270.
Aortic pulse-wave velocity and its relationship to mortality in diabetes 17. Kelly RP, Millasseau SC, Ritter JM, Chowienczyk PJ. Vasoactive drugs and glucose intolerance: an integrated index of vascular function? Cir- influence aortic augmentation index independently of pulse-wave culation. 2002;106:2085–2090.
velocity in healthy men. Hypertension. 2001;37:1429 –1433.
31. Meaume S, Benetos A, Henry OF, Rudnichi A, Safar ME. Aortic Pulse 18. Wilkinson IB, Qasem A, McEniery CM, Webb DJ, Avolio AP, Cockcroft Wave Velocity Predicts Cardiovascular Mortality in Subjects Ͼ70 Years JR. Nitric oxide regulates local arterial distensibility in vivo. Circulation.
of Age. Arterioscler Thromb Vasc Biol. 2001;21:2046 –2050.
32. Grey E, Bratteli C, Glasser SP, Alinder C, Finkelstein SM, Lindgren BR, 19. Stewart AD, Millasseau SC, Kearney MT, Ritter JM, Chowienczyk PJ.
Cohn JN. Reduced small artery but not large artery elasticity is an Effects of inhibition of basal nitric oxide synthesis on carotid-femoral independent risk marker for cardiovascular events. Am J Hypertens.
2003;16:265–269.
pulse wave velocity and augmentation index in humans. Hypertension.
33. Cohn JN, Quyyumi AA, Hollenberg NK, Jamerson KA. Surrogate markers for cardiovascular disease: functional markers. Circulation 2004; 20. Bogren HG, Mohiaddin RH, Klipstein RK, Firmin DN, Underwood RS, Rees SR, Longmore DB. The function of the aorta in ischemic heart 34. Smulyan H, Siddiqui DS, Carlson RJ, London GM, Safar ME. Clinical disease: a magnetic resonance and angiographic study of aortic com- utility of aortic pulses and pressures calculated from applanated radial- pliance and blood flow patterns. Am Heart J. 1989;118:234 –247.
artery pulses. Hypertension. 2003;42:150 –155.
21. Ohtsuka S, Kakihana M, Watanabe H, Sugishita Y. Chronically decreased 35. Nichols, W. W., and M. F. O’Rourke. McDonald’s Blood Flow in aortic distensibility causes deterioration of coronary perfusion during Arteries. Philadelphia, PA: Lea and Febiger; 1990:147.
increased left ventricular contraction. J Am Coll Cardiol. 1994;24: 36. Somes GW, Pahor M, Shorr Rim Cushman WC; Applegate WB: The role of diastolic blood pressure when treating isolated systolic hypertension.
22. Kingwell BA, Waddell TK, Medley TL, Cameron JD, Dart AM. Large Arch Int Med 1999;159, 17:2004 –2009.
artery stiffness predicts ischemic threshold in patients with coronary 37. Messerli FH, Kupfer S, Pepine CJ. J curve in hypertension and coronary artery disease. J Am Coll Cardiol. 2002;40:773–779.
artery disease. Am J Cardiol. 2005;95:160.

Source: http://www.medicalteknika.jp/app/download/5023953474/5+AIXao+vs+CAD.pdf?t=1339639309