The Initial Screening Of Heart Failure Related To Serum Markers And Related Research, And Ventricular Remodeling

ObjectiveIn previous studies, we found six proteins that were seldom studied were upregulated in end-stage failing human myocardium through genomics and proteomics screening. These proteins were, namely, DPT, LTBP-2, MLZE, MMP-10, IGF-IIR and TSC-22. In this study, we evaluated the consistency of serum levels of these markers with heart failure (HF) stages, and assessed the feasibility of these markers for screening healthy population for high risk population of heart failure.MethodsAccording to ACC/AHA heart failure stages,286 subjects were enrolled and divided into three groups:healthy control group (n=100), pre-HF group (n=90) and end-stage HF group (n=96). Clinical data were collected and serum levels of these markers and amino-terminal pro-brain natriuretic peptide (NT-proBNP) were measured.ResultsSerum levels of these markers and NT-proBNP were consistent with heart failure stages. (all P<0.01) Serum DPT, LTBP-2, MLZE and MMP-10 were significantly elevated in pre-HF group compared with healthy control group (all P<0.05). Similar elevation were not observed in levels of NT-proBNP, IGF-IIR and TSC-22 (all P>0.05). Receiver operating characteristic curve analysis further demonstrated the superiority of DPT, LTBP-2, MLZE and MMP-10 over NT-proBNP in screening for high risk population of HF.ConclusionSerum levels of DPT, LTBP-2, MLZE, MMP-10, IGF-IIR and TSC-22 were consistent with HF stages. Although further research is needed, there is some part for DPT, LTBP-2, MLZE and MMP-10 in screening community population for pre-HF people. ObjectiveBiomarkers could provide important information about diagnosis, risk stratification and prognosis of cardiovascular diseases, and could be potential therapeutic target. Previously, we found serum levels of DPT, LTBP-2, MLZE, MMP-10, IGF-IIR and TSC-22 were consistent with heart failure stages. Growth differentiation factor-15 (GDF-15) and follistatin like-1 (FSTL-1) are emerging as independent prognostic biomarkers in patients with cardiovascular disease. All markers above are upregulated in failing myocardium, therefore we hypothesized that serum levels of these markers were associated with the extent of left ventricular (LV) remodeling.MethodsTo relate levels of markers to indices of LV remodeling and function, serum levels of these markers and amino-terminal pro-brain natriuretic peptide (NT-proBNP) were measured in 156 patients with diagnosed valvular or coronary heart disease. The left ventricular remodeling was assessed by echocardiography, measuring left ventricular end-diastolic diameter (LVEDD), left ventricular mass index (LVMI) and relative LV wall thickness (RWT).ResultsSerum levels of DPT, LTBP-2, MLZE, MMP-10, IGF-IIR and TSC-22 were not related to LV remodeling indices (All P>0.05). Levels of FSTL-1 were related to LVEDD (r=0.444, P<0.001), LVMI (r=0.438, P<0.001), RWT (r=-0.244, P=0.003) and ejection fraction (r=-0.236, P=0.004). Levels of GDF-15 were related to LVEDD (r=0.431, P<0.001), LVMI (r=0.428, P<0.001), RWT (r=-0.254, P=0.002) and ejection fraction(r=-0.307.P<0.001). The positive association between LVMI and FSTL-1 or GDF-15 remained significant in a multivariate regression model adjusted for age, sex, conventional cardiovascular risk factors and established biomarkers, including NT-proBNP and hs-CRP (standardizedβ=0.371, P=0.002 for FSTL-1; standardizedβ= 1.446, P<0.001for GDF-15). Receiver operating characteristic curve analysis further illustrated that FSTL-1 and GDF-15 were strong markers of LV hypertrophy (area under the curve 0.707,95% CI 0.596 to 0.812, P=0.001 for FSTL-1; area under the curve, 0.737,95% CI 0.624 to 0.850, P=0.001 for GDF-15). Serum levels of FSTL-1 were related to increasing NYHA levels (P=0.008 for trend).ConclusionSerum levels of DPT, LTBP-2, MLZE, MMP-10, IGF-IIR and TSC-22 were not related to LV remodeling. Serum FSTL-1 and GDF-15 level was independently associated with LVMI in patients with valvular and coronary heart disease, demonstrating that FSTL-1 and GDF-15 are involved in LV remodeling and could be applied as cardiovascular biomarkers.