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(Circulation. 2005;112:3722-3728.)
© 2005 American Heart Association, Inc.

Epidemiology

Cross-Sectional Relations of Peripheral Microvascular Function, Cardiovascular Disease Risk Factors, and Aortic Stiffness

The Framingham Heart Study

Gary F. Mitchell, MD; Joseph A. Vita, MD; Martin G. Larson, SD; Helen Parise, ScD; Michelle J. Keyes, MA; Elaine Warner, BS; Ramachandran S. Vasan, MD; Daniel Levy, MD; Emelia J. Benjamin, MD, ScM

From Cardiovascular Engineering, Inc (G.F.M., E.W.), Waltham, Mass; Department of Mathematics and Statistics (M.G.L., H.P.), Evans Department of Medicine (J.A.V., R.S.V., E.J.B.), Whitaker Cardiovascular Institute (J.A.V., R.S.V., E.J.B.), and Section of Preventive Medicine (R.S.V., D.L., E.J.B.), Boston University School of Medicine, Boston, Mass; the National Heart, Lung, and Blood Institute (D.L.), Bethesda, Md; and the NHLBI’s Framingham Study (M.G.L., M.J.K., R.S.V., D.L., E.J.B.), Framingham, Mass.

Correspondence to Gary F. Mitchell, MD, Cardiovascular Engineering, Inc, University Office Park, Bldg 2, 51 Sawyer Rd, Suite 100, Waltham, MA 02453. E-mail GaryFMitchell{at}mindspring.com

Received March 22, 2005; revision received August 23, 2005; accepted September 12, 2005.

Background— Aortic stiffness and small-artery structure and function share various risk factors; however, relations between these 2 measures of vascular function are complex and incompletely understood.

Methods and Results— We examined hyperemic forearm blood flow, an indicator of microvascular structure and function, and aortic stiffness in 2045 participants (1107 women, mean age 61±9 years) in the Framingham Heart Study offspring cohort. Using arterial tonometry, we evaluated 3 measures of aortic stiffness: brachial pulse pressure; carotid-femoral pulse wave velocity (CFPWV), which is related directly to aortic wall stiffness; and forward pressure wave amplitude (P_f), which is related directly to aortic wall stiffness and inversely to aortic diameter. Using high-resolution ultrasound and Doppler, we evaluated brachial artery diameter, blood flow, and forearm vascular resistance (FVR) at baseline and during reactive hyperemia after 5 minutes of forearm ischemia. In multivariable models that adjusted for cardiovascular disease risk factors, local brachial pulse pressure, CFPWV, and P_f, considered separately, were associated with increased baseline and hyperemic FVR (P<0.001). In models that further adjusted for mean arterial pressure, each measure of aortic stiffness was associated with reduced hyperemic flow (P<0.001). In risk factor–adjusted models that simultaneously considered CFPWV and P_f, both were associated with increased FVR at baseline (P<0.01) and during hyperemia (P<0.001).

Conclusions— Our findings indicate that abnormal aortic stiffness and increased pressure pulsatility are associated with blunted microvascular reactivity to ischemic stress that is in excess of changes attributable to conventional cardiovascular disease risk factors alone, including mean arterial pressure.

Key Words: endothelium • microcirculation • risk factors • epidemiology

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