Relations of plasma matrix metalloproteinase-9 to clinical cardiovascular risk factors and echocardiographic left ventricular measures - The Framingham Heart Study

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Abstract
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 greater than or equal to 90th percentile, n = 204) and increased LVWT ( LVWT greater than or equal to 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.