Evaluation of a Multimarker Panel in Chronic Heart Failure
Chronic heart failure is a complex disease associated with various pathophysiological and biochemical disorders. We assessed the 10 years prognostic role of a multimarker panel of markers for myocyte stress (GDF-15), extra-cellular matrix remodeling (Galectin-3, mimecan, TIMP-1), inflammation (Galectin-3), myocyte injury (hs-TnT) and angiogenesis (endostatin, IBP-4, IGF-BP-7, sFlt-1 and PLGF) head-to-head with the biochemical gold-standard NT-proBNP.
Blood samples from 149 patients with heart failure were analysed. After 10 years of follow-up (median follow-up 104 months, IQR 43-117), data regarding rehospitalisation for chronic heart failure and all-cause-mortality were acquired.
Regarding Kaplan Meier analysis, all markers, dichotomized according to you denindex, were significant predictors for all-cause-mortality (each p<0.05) and for the combined end point of all-cause-mortality and rehospitalisation (each p<0,05). Including all markers in Cox Regression analysis, NT-pro-BNP, hs-TnT and IGF-BP7 were independent predictors for both end points (each p<0,05). Patients in whom all three markers were elevated had a significant worse long-time-prognosis than patients without elevated markers (risk of all-cause-mortality 90,5% vs. 25%, risk of all-cause-mortality or rehospitalisation 97,6% vs. 43,7%).
In a Cox regression model with clinical relevant parameters (ejection fraction<30%, age, serum creatinine, gender) and the multimarker panel (hs-TnT, NT-pro-BNP, IGF-BP7), all biomarkers remained independent significant predictors for both end points beside ejection fraction<30% and male gender (each p<0.05).
In a 10-years-follow-up, a combination of three biomarkers with different pathophysiological background (NT-pro-BNP, hs-TnT and IGF-BP7) increased the prognostic value and identified patients with a high risk of mortality and rehospitalisation. Especially IGF-BP7 seems to play an important role regarding prognostication in heart failure.
Heart failure is one of the major public health problems world wide. It can be defined as a pathologic state of systolic or diastolic dysfunction, which leads to a difference in oxygen supply and demand. Despite improvements in therapy, morbidity and mortality are still high. Due to ageing population, the prevalence of heart failure is on the rise. It also increases with a rising number of people suffering from cardiovascular comorbidities such as diabetes or arterial hypertension. In the last years, efforts were made to improve diagnosis and prognostication by identifying new biomarkers. Chronic heart failure is a complex disease with various pathophysiological and biochemical disorders that cannot be reflected by a single biomarker. The goal of the current study was to assess a multimarker panel of markers for myocyte stress (GDF-15), extra-cellular matrix remodeling (Galectin-3, mimecan, TIMP-1), inflammation (Galectin-3), myocyteinjury (hs-TnT) and angiogenesis (endostatin, IGF-BP4, IGF-BP7, sFlt-1 as antiangio genetic factors and PLGF as angio genetic factor) together with the biochemical gold-standard NT-proBNP. A 3 years follow-up of this panel was published in 2014. Herein, all markers except PLGF showed prognostic utility. The aim of the current study was to investigate the long-term prognostic role of these markers over a follow-up period of 10 years and to evaluate a simplified multimarker panel, which can identify patients with high risk of mortality or rehospitalisation.
Journal of Clinical chemistry and Laboratory Medicne