Although normative aging is accompanied by increases in arterial stiffness,the relationship between stiffness and cardiac structure and function is not known. The ultimate goals of this project are to determine how arterial stiffness properties influence myocardial structure and function and predict cardiovascular morbidity and mortality.Several sub-projects are described below.A.To determine whether arterial stiffness per se exerts an independent influence on left ventricular (LV) mass,we derived LV mass index (LVMI) from echocardiograms and arterial stiffness from pulse wave velocity (PWV) and applanation tonometry-derived augmentation index (AGI) in 133 normentensive BLSA subjects age 23-87 yrs. Age-associated increases were seen in LVMI (r=0.24), systolic blood pressure(SBP, r=0.31), PWV (r=0.66) and AGI (r=0.53).By multiple regression analysis, AGI (p=.004), SBP (p<.03) and male sex (p=.04) but not age or PWV were independent predictors of greater LVMI.B.To test whether the blunted LV emptying and LV ejection fraction(LVEF) response to exercise in older versus younger subjectscan be ameliorated by reducing central arterial stiffness,we performed maximal upright cycle exercise in 9 healthy subjects 64-82 years old and 8 subjects <40 years old before and after adminstering the vasodilator sodium nitroprusside (N) intravenously.N reduced LV end systolic volume (ESV) and increased LVEF at peak effort in these older subjects, eliminating age differences in these variables noted prior to N.C.We will test the hypothesis that several months of home-based aerobic exercise training can reduce arterial stiffness in an NIH-sponsored multicenter trial of 810 individuals 35-75 years old.D.We have recently completed a study examining the effect of age, sodium intake, body composition and physical activity on arterial stiffness and LV mass in 2 populations in Taiwan.(Cf Contract #N01-AG-02-2118)E.A multicenter study to determine whether arterial stiffness is an independent risk factor for cardiovascular events in elderly free-living persons is being developed by the Epidemiology Demography Biometry Program of the intramural NIA.F.A method for calculation of charteristic impedance of the arterial tree from non-invasive measurements of central arterial pressure and flow has recently been developed.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000270-06
Application #
5200291
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1995
Total Cost
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Mackey, Rachel H; Sutton-Tyrrell, Kim; Vaitkevicius, Peter V et al. (2002) Correlates of aortic stiffness in elderly individuals: a subgroup of the Cardiovascular Health Study. Am J Hypertens 15:16-23
Sutton-Tyrrell, K; Newman, A; Simonsick, E M et al. (2001) Aortic stiffness is associated with visceral adiposity in older adults enrolled in the study of health, aging, and body composition. Hypertension 38:429-33
Scuteri, A; Chen, C H; Yin, F C et al. (2001) Functional correlates of central arterial geometric phenotypes. Hypertension 38:1471-5
Vaitkevicius, P V; Lane, M; Spurgeon, H et al. (2001) A cross-link breaker has sustained effects on arterial and ventricular properties in older rhesus monkeys. Proc Natl Acad Sci U S A 98:1171-5
Kass, D A; Shapiro, E P; Kawaguchi, M et al. (2001) Improved arterial compliance by a novel advanced glycation end-product crosslink breaker. Circulation 104:1464-70
Scuteri, A; Bos, A J; Brant, L J et al. (2001) Hormone replacement therapy and longitudinal changes in blood pressure in postmenopausal women. Ann Intern Med 135:229-38
Scuteri, A; Lakatta, E G; Bos, A J et al. (2001) Effect of estrogen and progestin replacement on arterial stiffness indices in postmenopausal women. Aging (Milano) 13:122-30
Sutton-Tyrrell, K; Mackey, R H; Holubkov, R et al. (2001) Measurement variation of aortic pulse wave velocity in the elderly. Am J Hypertens 14:463-8