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(Circulation. 2004;109:2850-2856.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

Relations of Plasma Matrix Metalloproteinase-9 to Clinical Cardiovascular Risk Factors and Echocardiographic Left Ventricular Measures

The Framingham Heart Study

Johan Sundström, MD, PhD; Jane C. Evans, DSc; Emelia J. Benjamin, MD, ScM; Daniel Levy, MD; Martin G. Larson, ScD; Douglas B. Sawyer, MD, PhD; Deborah A. Siwik, PhD; Wilson S. Colucci, MD, PhD; Patrice Sutherland, BS; Peter W.F. Wilson, MD; Ramachandran S. Vasan, MD

From the Framingham Heart Study (J.S., J.C.E., E.J.B., D.L., M.G.L., P.S., P.W.F.W., R.S.V.), Framingham, Mass; the National Heart, Lung, and Blood Institute (D.L.); and the Department of Preventive Medicine (E.J.B., D.L., R.S.V.), Cardiology Section (E.J.B., D.B.S., W.S.C., R.S.V.), and the Myocardial Biology Unit (D.B.S., D.A.S., W.S.C.), Boston University School of Medicine, Boston, Mass.

Correspondence to Ramachandran S. Vasan, MD, The Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702–5803. E-mail vasan{at}bu.edu

Received October 24, 2003; de novo received December 11, 2003; revision received February 20, 2004; accepted February 25, 2004.

Background— Plasma levels of matrix metalloproteinase-9 (MMP-9), a key determinant of extracellular matrix degradation, are increased in heart failure and in acute coronary syndromes. We investigated cross-sectional relations of plasma MMP-9 to vascular risk factors and echocardiographic left ventricular (LV) measurements.

Methods and Results— We studied 699 Framingham Study participants (mean age, 57 years; 58% women), free of heart failure and previous myocardial infarction, who underwent routine echocardiography. We examined sex-specific distributions of LV internal dimensions (LVEDD) and wall thickness (LVWT) and sampled persons with both LVEDD and LVWT below the sex-specific median (referent, n=299), with increased LVEDD (LVEDD 90th percentile, n=204) and increased LVWT (LVWT 90th percentile, n=221) in a 3:2:2 ratio. Plasma MMP-9 was detectable in 138 persons (20%). In multivariable models, increasing heart rate (OR per SD, 1.41; 95% CI, 1.17 to 1.71) and antihypertensive treatment (OR, 1.63; 95% CI, 1.06 to 2.50) were key clinical correlates of detectable plasma MMP-9. In multivariable-adjusted models, detectable plasma MMP-9 was associated with increased LVEDD (OR, 2.84; 95% CI, 1.13 to 7.11), increased LVWT (OR, 2.54; 95% CI, 1.00 to 6.46), and higher LV mass (P=0.06) in men but not in women (OR for increased LVEDD, 1.37; 95% CI, 0.54 to 3.46; for increased LVWT, 0.99; 95% CI, 0.39 to 2.52; P=0.59 for LV mass).

Conclusions— In our community-based sample, detectable plasma MMP-9 levels were associated with increased LV diastolic dimensions and increased wall thickness in men. These observations indicate that plasma MMP-9 level may be a marker for cardiac extracellular matrix degradation, a process involved in LV remodeling.

Key Words: heart failure • hypertrophy • metalloproteinases • remodeling • echocardiography

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