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

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, nϭ299), with increased LVEDD (LVEDD Ն90th percentile, nϭ204) and increased LVWT (LVWT Ն90th percentile, nϭ221) 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 (Pϭ0.06) 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; Pϭ0.59 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.

Clinical and echocardiographic correlates of plasma procollagen type III amino-terminal peptide levels in the community

“…5,19,40 Diez et al showed that levels of type I carboxy-terminal pro-collagen peptide were associated with LV mass in hypertensive individuals, whereas plasma PIIINP was not. 5 Type I collagen is more abundant in the extracellular matrix than type III collagen, 4 although an increase in the proportion of type III collagen may be an early response to pressure overload.…”

“…We have previously reported age-adjusted associations of LV indices with plasma levels of matrix metalloproteinase-9 (MMP-9) in men 40 and TIMP-1 in both sexes. 19 The association of MMP-9 with echocardiographic features persists even after adjustment for baseline cardiovascular disease risk factors.…”

Identification of Factors Causing Sudden Coagulation in Patients with Acute Myocardial Infarction

“…MMP-9 was detected in 20% of the patients reported in the Framingham Heart Study [17]. The presence of this circulating biomarker reflects plaque inflammation, and its plasma concentration indicates the risk of future cardiovascular mortality in patients with CAD [18].…”

“…The presence of this circulating biomarker reflects plaque inflammation, and its plasma concentration indicates the risk of future cardiovascular mortality in patients with CAD [18]. However, none of these studies [17,18] demonstrated that MMP-9 is directly involved in the coagulation process.…”

Matrix Metalloproteinase-9 Level and Gene Polymorphism in Sleep DisorderedBreathingPatientswithorwithout CardiovascularDisorders

“…Matrix metalloproteinase-9 (MMP-9) is a proteolytic enzyme which contributes to extracellular matrix degradation and vascular remodeling (5). MMP-9 shows proteolytic activity on type IV collagen which forms a basement membrane under the endothelium of all blood vessels.…”