Plasma matrix metalloproteinase-9 and left ventricular remodelling after acute myocardial infarction in man: a prospective cohort study

Abstract

Aim: To describe temporal profiles of plasma matrix metalloproteinases (MMP-2 and MMP-9), and their relationship with echocardiographic (Echo) parameters of left ventricular (LV) function and remodelling, after acute myocardial infarction (AMI) in man.

Methods and results: Plasma MMP-2 and MMP-9 were assayed at intervals (0-12, 12-24, 24-48, 48-72, 72-96, and > 96 h) in 91 patients with AMI (ST-elevation/non-ST-elevation 77/24; 73% male; 40% anterior site) and on a single occasion in 172 age- and sex-matched control subjects with stable coronary artery disease. Echo assessment of LV volumes, LV ejection fraction (LVEF), and wall motion index score were assessed before discharge and at follow-up (median 176, range 138-262 days) for patients and on a single occassion in controls. Plasma MMP-2 was similar at all times after AMI, elevated when compared with control (P = 0.005-0.001) and unrelated to LV function or volume during index admission or at follow-up. Maximal MMP-9 was seen at 0-12 h and was elevated when compared with control (P = 0.002) followed by fall to a plateau. Both maximal and plateau MMP-9 concentration correlated with white blood cell (WBC, P = 0.023 to < 0.001) and neutrophil count (P = 0.014 to < 0.001). Maximal MMP-9 had independent predictive value for lower LVEF (P = 0.004) during admission and for greater change in LV end-diastolic volume between admission and follow-up (R = 0.3, P = 0.016). In contrast, higher plateau levels of MMP-9 were associated with relative preservation of LV function (increasing LVEF, P = 0.002; decreasing WMIS, P = 0.009) and less change in end-systolic volume and end-diastolic volumes after discharge (P = 0.001 and 0.024, respectively).

Conclusion: Both MMP-9 and MMP-2 are elevated following AMI. The biphasic profile of plasma MMP-9 is related to LV remodelling and function following AMI in man. Higher early levels of MMP-9 associate with the extent of LV remodelling and circulating WBC levels. In contrast, higher plateau levels later after AMI are associated with relative preservation of LV function. Temporal profile, rather than absolute magnitude, of MMP-9 activity appears to be important for LV remodelling after AMI.

Figure 1

Temporal profiles of MMP-2 (upper) and MMP-9 (lower) post-AMI. Data are median with upper and lower quartiles and range. Asterisk indicates P < 0.05 anterior vs. inferior territory of AMI.

Figure 2

Upper panel: LVEF according to peak MMP-9 below or above the median value (113 ng/mL). Lower panel: LVEF according to plateau MMP-9 below or above the median value (36.4 ng/mL).

Figure 3

Relationship between peak MMP-9 (upper) and plateau MMP-9 (lower) and the change in LVEDV (ΔEDV).