Association between matrix metalloproteinase‐9 and worsening heart failure events in patients with chronic heart failure

Abstract

AimsMatrix metalloproteinase (MMP) is up‐regulated during heart failure (HF) and influences ventricular remodeling. We hypothesized that disparity between MMP‐9 and tissue inhibitors of MMP‐1 (TIMP‐1) results in clinical manifestations and is related to prognostic risk in patients with chronic HF.Methods and resultsPlasma levels of MMP‐9, TIMP‐1, and brain natriuretic peptide (BNP) were measured in 173 patients with chronic HF. Combined endpoints of worsening HF events were assessed during follow‐up (median 109 months). MMP‐9 and TIMP‐1 levels and the MMP‐9/TIMP‐1 ratio increased with increasing severity of the New York Heart Association class (P for trend = 0.003, 0.011, and 0.005, respectively). Patients with HF events (n = 35) had significantly higher MMP‐9 than those without HF events (P = 0.004). Kaplan–Meier analysis demonstrated a higher probability of HF events with high MMP‐9 values (>23.2 ng/mL; P = 0.005). A multivariate Cox proportional hazard model showed that high MMP‐9 values were an independent predictor of HF events (hazard ratio, 3.73; 95% confidence interval (CI), 1.03–13.46; P = 0.043). In patients with lower BNP levels (≤210 pg/mL), the adjusted hazard ratio for HF events was 3.63 (95% CI, 1.20–11.02; P = 0.023) among patients with high MMP‐9 values compared with patients with low BNP and low MMP‐9 values.ConclusionsMMP‐9 and TIMP‐1 levels correlate with the severity of chronic HF. MMP‐9 is a strong predictor of HF events, suggesting that a disparity between MMP‐9 and TIMP‐1 levels and increased MMP‐9 levels may help predict HF events.

Association between Atrial Fibrillation and Aortic Aneurysms: A Population-Based Cohort Study

“…Elevated MMP-2, longer AF duration, and atrial extracellular matrix remodeling of AF further increased the risk of difficulties in restoring sinus rhythm in AF patients [29-31]. Active myocardial remodeling is accompanied by enhanced activation of MMP-2 and MMP-9 [32, 33]. In the present study, the use of medications was balanced before any comparisons were made.…”

Role of Gender Specifics in Myocardial Remodelling, Cardiovascular Complications Development and Efficacy of Pharmacotherapy in Heart Failure Patients After Cardiac Surgery

“…Как показано в ряде иссле- дований, TIMP-1 способен связываться с неактивной формой рro-MMP-9, образуя комплекс, в котором ТИМП-1 сохраняет свою способность ингибировать активность других активных MMП. Известно, что высокие значения ММП-9 и нарушение баланса ММП-9/ТИМП-1 являются независимым предикто-ром неблагоприятных событий у пациентов с ХСН [13]. Данный факт подтверждается и нашим исследо-ванием: у пациентов с СНсрФВ и неблагоприятным исходом после КХО отмечалась высокая экспрессия ММП-9 и умеренная ТИМП-1, что отражает их дис-баланс.…”

Specific biomarkers of myocardial inflammation and remodeling processes as predictors of mortality in high‐risk patients undergoing percutaneous mitral valve repair (MitraClip)

“…In particular, MMP‐2 and MMP‐9 levels are elevated in patients with LV volume overload, which contributes to myocardial collagen accumulation and subsequent cardiac dysfunction. Further, both MMPs have predictive value regarding cardiovascular events, including mortality . Myocardial remodeling processes are also closely associated with inflammation processes, and published data have shown that extensive inflammation magnifies these cardiac structural alterations and thus may accelerate the progression of heart failure (HF) .…”

“…[11][12][13] Increased cardiac collagen synthesis and impaired degradation in response to pressure and volume overload in patients with MR lead to an imbalance of collagen metabolism and contribute to collagen accumulation and consequently cardiac structural remodeling processes, myocardial stiffness, and fibrosis. [14][15][16] Matrix metalloproteinases (MMPs) are important regulators of ECM turnover and myocardial remodeling processes. [14][15][16] In particular, MMP-2 and MMP-9 levels are elevated in patients with LV volume overload, which contributes to myocardial collagen accumulation and subsequent cardiac dysfunction.…”