Abstract 3289: Biochemical Markers of Myocardial Collagen Network Remodeling Discriminate Between Systolic and Diastolic Heart Failure in Hypertensive Patients
Aims: It is still uncertain whether clinical systolic heart failure (SHF) and diastolic heart failure (DHF) correspond to different molecular phenotypes. To support the distinction between SHF and DHF, biochemical markers of myocardial collagen accumulation (procollagen type I carboxy-terminal peptide or PICP) and disruption (matrix metalloproteinase-1 or MMP-1) were measured in blood from hypertensive patients with chronic HF.
Methods and Results: 105 hypertensive patients with DHF and 66 with SHF were included. PICP, MMP-1 and the amino-terminal pro-brain natriuretic peptide (NT-proBNP) were analysed. MMP-1, MMP-1 to tissue inhibitor of metalloproteinases-1 (TIMP-1) ratio and NT-proBNP levels were higher (P<0.001) in SHF patients than in DHF patients. No differences between the two groups were observed for PICP. The ROC curve analysis identified the cutoff values of 16.25 ng/mL MMP-1 and 1525 pg/mL of NT-proBNP for the distinction between DHF and SHF. SHF was associated not just with an increased NT-proBNP (RR=4.36; 95% CI=2.24–8.48) but also with elevated MMP-1 (RR=5.40; 95% CI=2.76–10.59). MMP-1 correlated inversely with the ejection fraction (r=−0.350; P<0.001), and directly with parameters assessing left ventricular (LV) dilatation such as LV end-diastolic and -systolic diameters (r=0.274 and r=0.303, respectively; P<0.01), LV end-diastolic and -systolic volumes (r=0.371 and r=0.364, respectively; P<0.01), and LV end-diastolic volume index (r=0.362; P<0.01) in all patients, suggesting that MMP-1 may be involved in the development of systolic dysfunction in SHF patients. On the other hand, MMP-1 was directly correlated with circumferential end-systolic wall stress (r=0.323; P<0.001), suggesting that mechanical stress may play role in MMP-1 over-expression. These associations were independent from confounding factors.
Conclusions: These findings show that SHF and DHF of hypertensive origin differ in plasma MMP-1 and support the pathophysiological discrimination into SHF and DHF regarding collagen network remodeling. Large-scale longitudinal studies are needed to validate the clinical use of MMP-1 as a biochemical marker of collagen network disruption or as target for therapy or an indicator of therapeutic success.