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(Circulation. 2007;115:3079-3085.)
© 2007 American Heart Association, Inc.

Epidemiology

Associations of Plasma Natriuretic Peptide, Adrenomedullin, and Homocysteine Levels With Alterations in Arterial Stiffness

The Framingham Heart Study

Daniel Levy, MD; Shih-Jen Hwang, PhD; Atilla Kayalar, MD; Emelia J. Benjamin, MD, MSc; Ramachandran S. Vasan, MD; Helen Parise, ScD; Martin G. Larson, ScD; Thomas J. Wang, MD; Jacob Selhub, PhD; Paul F. Jacques, ScD; Joseph A. Vita, MD; Michelle J. Keyes, MA; Gary F. Mitchell, MD

From the NHLBI Framingham Heart Study, Framingham, Mass (D.L., S.-J.H., E.J.B., R.S.V., T.J.W., M.G.L., M.J.K.); the National Heart, Lung, and Blood Institute, Bethesda, Md (D.L., S.-J.H.); Department of Medicine, MetroWest Medical Center, Framingham, Mass (A.K.); Division of Cardiology, Massachusetts General Hospital, Boston, Mass (T.J.W.), Jean Mayer USDA Human Nutrition Research Center on Aging and Friedman School of Nutrition Science and Policy, Tufts University, Boston, Mass (J.S., P.F.J.); Departments of Mathematics and Statistics, Boston University, Boston, Mass (H.P., M.G.L.); Cardiology Section (D.L., E.J.B., R.S.V., J.A.V.) and Preventive Medicine and Epidemiology (E.J.B., R.S.V., M.G.L., D.L.), Boston University School of Medicine, Boston, Mass; and Cardiovascular Engineering, Inc, Waltham, Mass (G.F.M.).

Correspondence to Daniel Levy, MD, 73 Mt Wayte Ave, Ste 2, Framingham, MA 01702.

Received July 18, 2006; accepted April 3, 2007.

Background— Increased arterial stiffness and higher plasma natriuretic peptide and homocysteine levels are associated with elevated risk for cardiovascular disease. Little is known about the relations of natriuretic peptides and homocysteine to arterial wall stiffness in the community.

Methods and Results— We assessed the relations of plasma N-terminal atrial natriuretic peptide, B-type natriuretic peptide, adrenomedullin, and homocysteine concentrations to arterial stiffness in participants in the Framingham Heart Study. Central pulse pressure, forward pressure wave, reflected pressure wave, carotid-femoral pulse wave velocity, and carotid-radial pulse wave velocity were assessed by tonometry in 1962 participants (mean age, 61 years; 56% women) in the Framingham Heart Study. Central systolic and diastolic blood pressures were 123/75 mm Hg in men and 119/66 mm Hg in women. After adjustment for age and clinical covariates, N-terminal atrial natriuretic peptide and B-type natriuretic peptide were associated with carotid-femoral pulse wave velocity (men: partial correlation, 0.069, P=0.043 and r=0.115, P0.001, respectively; women: r=–0.063, P=0.037 and r=–0.062, P=0.040), and carotid-radial pulse wave velocity (men: r=–0.090, P=0.009 and r=–0.083, P0.015; women: r=–0.140, P0.001 and r=-0.104, P=0.001, respectively). In men, N-terminal atrial natriuretic peptide and B-type natriuretic peptide also were associated with forward and reflected wave and carotid pulse pressure. In men, adrenomedullin was associated with mean arterial pressure (r=0.089, P=0.009), and homocysteine was associated with carotid-femoral pulse wave velocity (r=0.072, P=0.036), forward pressure (r=0.079, P=0.02), and central pulse pressure (r=0.072, P=0.035). Interaction tests indicated sex differences in the relations of several biomarkers to measures of arterial stiffness.

Conclusions— Plasma natriuretic peptide, adrenomedullin, and homocysteine levels are associated with alterations in conduit vessel properties that differ in men and women.

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