Stiffening of the human aorta is associated with a number of factors, particularly aging, sedentary lifestyle and cardiovascular disease. The physiological consequences of aortic stiffening can be severe, including increased cardiac afterload, reduced coronary perfusion and isolated systolic hypertension. Moreover, aortic wave velocity, an accepted metric of central arterial stiffening, has been reported to be the single best predictor of cardiovascular risk among ten variables studied. However, widespread clinical assessment of aortic stiffness and related therapeutic interventions has been impeded by the lack of a robust, noninvasive measurement method. All techniques currently employed to noninvasively assess central arterial stiffness suffer significant methodological weaknesses, which limit their accuracy and/or pertinance to the elastic aorta. The applicant has recently proposed a novel and rapid means to determine aortic stiffness using magnetic resonance (MR) methodology. The technique employs a one-dimensional time-of-flight sequence to measure flow wave velocity (WV) in the thoracic aorta with an acquisition time of one cardiac cycle. Extensive testing, in both compliant tubes and in vivo, has established the validity of the proposed MR method, thereby laying the groundwork for larger-scale studies of aortic stiffness in clinically relevant subject cohorts. In this project, we will correlate aortic WV with age in a cross-sectional MR study of 280 adult men and women, representing seven decades of age. Screening criteria will be imposed in order to exclude persons with cardiovascular disease. In addition to a normal, sedentary cohort (112 subjects) we will also recruit endurance-trained athletes (56 subjects) and patients with isolated systolic hypertension (112 subjects). These groups respectively represent normal, successful and accelerated arterial aging, which we hypothesize will be differentiated on the basis of absolute WV and rate of increase of WV with age. We further hypothesize that in the hypertensive group, systolic blood pressure may be a strong predictor of WV. All enrolled participants will undergo a health and fitness assessment within the Virginia Commonwealth University General Clinical Research Center, in order to permit correlation of measured wave velocity with key clinical indicators (blood pressure, maximum oxygen consumption, plasma lipoprotein, glucose and insulin levels). Secondary statistical analysis will introduce such clinical indicators as covariables, by which the WV versus age regressions will be adjusted. Tertiary analysis will seek the combination of all variables that yields the best predictive model of WV. Lastly, the potential value of WV alone, as well as the ratio of WV to peak blood velocity, as a predictor of cardiovascular risk will be explored using Framingham risk scores as a correlate.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL069962-03
Application #
6728199
Study Section
Special Emphasis Panel (ZRG1-CCVS (01))
Program Officer
Desvigne-Nickens, Patrice
Project Start
2002-04-01
Project End
2005-09-30
Budget Start
2004-04-01
Budget End
2005-09-30
Support Year
3
Fiscal Year
2004
Total Cost
$292,043
Indirect Cost
Name
Virginia Commonwealth University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
Arena, R; Arrowood, J A; Fei, D et al. (2010) The influence of sex on the relationship between heart rate recovery and other cardiovascular risk factors in apparently healthy subjects. Scand J Med Sci Sports 20:291-7
Arena, Ross; Arrowood, James A; Fei, Ding-Yu et al. (2009) Maximal aerobic capacity and the oxygen uptake efficiency slope as predictors of large artery stiffness in apparently healthy subjects. J Cardiopulm Rehabil Prev 29:248-54
Arena, Ross; Arrowood, James A; Fei, Ding-Yu et al. (2008) Association of hypertensive diastolic blood pressure with dyslipidemia during exercise in apparently healthy subjects. J Cardiopulm Rehabil Prev 28:38-42
Kraft, Kenneth A; Arena, Ross; Arrowood, James A et al. (2007) High aerobic capacity does not attenuate aortic stiffness in hypertensive subjects. Am Heart J 154:976-82
Arena, Ross; Fei, Ding-Yu; Arrowood, James A et al. (2007) Influence on aerobic fitness on aortic stiffness in apparently healthy Caucasian and African-American subjects. Int J Cardiol 122:202-6
Kraft, Kenneth A; Fei, Ding-Yu; Shao, Xianzhi et al. (2006) Improved aortic stiffness assessment in the elderly using a one-dimensional fluid displacement MR method. J Magn Reson Imaging 24:603-10
Arena, Ross; Arrowood, James A; Fei, Ding-Yu et al. (2006) The relationship between C-reactive protein and other cardiovascular risk factors in men and women. J Cardiopulm Rehabil 26:323-7; quiz 328-9
Fei, Ding-Yu; Arena, Ross; Arrowood, James A et al. (2005) Relationship between arterial stiffness and heart rate recovery in apparently healthy adults. Vasc Health Risk Manag 1:85-9
Shao, Xianzhi; Fei, Ding-Yu; Kraft, Kenneth A (2004) Rapid measurement of pulse wave velocity via multisite flow displacement. Magn Reson Med 52:1351-7
Shao, Xianzhi; Fei, Ding-Yu; Kraft, Kenneth A (2004) Computer-assisted evaluation of aortic stiffness using data acquired via magnetic resonance. Comput Med Imaging Graph 28:353-61