Arterial Stiffness, Wave Reflections, and the Risk of Coronary Artery Disease Thomas Weber, MD; Johann Auer, MD; Michael F. O’Rourke, MD; Erich Kvas, ScD; Elisabeth Lassnig, MD; Robert Berent, MD; Bernd Eber, MD Background—Increased arterial stiffness, determined invasively, has been shown to predict a higher risk of coronary atherosclerosis. However, invasive techniques are of limited value for screening and risk stratification in larger patient groups. Methods and Results—We prospectively enrolled 465 consecutive, symptomatic men undergoing coronary angiography for the assessment of suspected coronary artery disease. Arterial stiffness and wave reflections were quantified noninvasively using applanation tonometry of the radial artery with a validated transfer function to generate the corresponding ascending aortic pressure waveform. Augmented pressure (AP) was defined as the difference between the second and the first systolic peak, and augmentation index (AIx) was AP expressed as a percentage of the pulse pressure. In univariate analysis, a higher AIx was associated with an increased risk for coronary artery disease (OR, 4.06 for the difference between the first and the fourth quartile [1.72 to 9.57; P 0.01]). In multivariate analysis, after controlling for age, height, presence of hypertension, HDL cholesterol, and medications, the association with coronary artery disease risk remained significant (OR, 6.91; P 0.05). The results were exclusively driven by an increase in risk with premature vessel stiffening in the younger patient group (up to 60 years of age), with an unadjusted OR between AIx quartiles I and IV of 8.25 (P 0.01) and a multiple-adjusted OR between these quartiles of 16.81 (P 0.05). Conclusions—AIx and AP, noninvasively determined manifestations of arterial stiffening and increased wave reflections, are strong, independent risk markers for premature coronary artery disease. (Circulation. 2004;109:184-189.) Key Words: coronary disease waves arteries arteriosclerosis Pulse pressure, reflecting the pulsatile component of blood pressure and thus to some extent arterial stiffness,1 is a well-known risk factor for myocardial infarction,2,3 particularly in men.4 More accurate determinations of the elastic properties of the aorta and the large arteries, including angiographic measures,5 echocardiography,6 ultrasound measures of abdominal aortic and carotid arterial diameter,7 MRI,8 radionuclide angiography,9 and pulse wave velocity, 10,11 have shown associations with coronary atherosclerosis. The central aortic pressure wave is composed of a forward-traveling wave generated by left ventricular ejection and a later-arriving reflected wave from the periphery.12 As aortic and arterial stiffness increase, transmission velocity of both forward and reflected waves increase, which causes the reflected wave to arrive earlier in the central aorta and augment pressure in late systole. Therefore, augmentation of the central aortic pressure wave is a manifestation of early wave reflection and is the boost of pressure from the first systolic shoulder to the systolic pressure peak.13 This can be expressed in absolute terms (augmented pressure [AP]) or as a percentage of pulse pressure (augmentation index [AIx]). AIx, determined invasively, has been shown to be predictive for coronary artery disease (CAD).14 Because a noninvasive approach clearly would be of value for the examination of larger populations, we investigated the association between CAD and aortic AIx, assessed by noninvasive pulse waveform analysis (PWA).