Determinants of growth differentiation factor 15 in patients with stable and acute coronary artery disease. A prospective observational study

Abstract

BackgroundGrowth differentiation factor 15 (GDF-15) is a member of the transforming growth factor ß family and has been associated with inflammation, cancer, aging, diabetes mellitus (DM) and atherosclerosis. Determinants of GDF-15 have been investigated in several conditions. We aimed to investigate determinants of GDF-15 plasma levels in patients with angiographically proven coronary artery disease (CAD).MethodsFour hundred and seventy three consecutive patients with CAD were investigated between May 2009 and February 2011. Patients were separated into those with stable CAD (SCAD) and with ST-elevation and non-ST-elevation myocardial infarction (STEMI and NSTEMI). Blood samples for determination of GDF-15 were obtained before coronary angiography. Determinant of GDF-15 levels were analyzed by logistic regression analysis in unadjusted and adjusted models. Study endpoints were cardiovascular death (CV-death), myocardial infarction, unstable angina, unplanned revascularization, stent thrombosis and stroke assessed at a mean follow-up of 188 (177.2–243) days.ResultsOverall median and (25–27th percentile) GDF-15 level was 1212.8 pg/ml (833.2–1957 pg/ml). GDF-15 was significantly higher in STEMI compared to SCAD and NSTEMI groups (P < 0.0001). In a multivariate regression analysis advanced age, DM, acute hyperglycemia (AHG), CRP and chronic kidney disease (CKD) were independent predictors of elevated GDF-15 levels (P < 0.05). Receiver operating curve analysis of GDF-15 for prediction of CV-death showed an area under the curve of 0.852 with a confidence interval of 0.745-0.960, P < 0.0001. The estimated cut-off was 2094.6 pg/ml with a sensitivity of 76 % and specificity of 80 %.ConclusionIn patients with CAD undergoing PCI with stent implantation, GDF-15 is determined by advanced age, acute and chronic hyperglycemia, inflammation and CKD. GDF-15 is a valuable predictor of CV-death in a population of CAD patients after PCI.

Multibiomarker analysis in patients with acute myocardial infarction

“…We focused on newer generation biomarkers in patients suffering AMI and their incremental value for risk stratification. With respect to their prognostic value, the measurement of sST2 and GDF-15 levels after AMI may enhance standard tools already used in clinical practice and may be useful in detection of patients prone to longer hospitalization and at risk of developing new-onset or worsening heart failure [5][6][7][8][9][10]15,[17][18][19]. Patients with a longer duration of hospitalization showed increased levels of sST2 and GDF-15 compared with patients with an earlier discharge date, supporting the data by Barbarash et al [44] that sST2 is a sensitive indicator for an unfavourable hospitalization course.…”

“…Patients with a longer duration of hospitalization showed increased levels of sST2 and GDF-15 compared with patients with an earlier discharge date, supporting the data by Barbarash et al [44] that sST2 is a sensitive indicator for an unfavourable hospitalization course. With respect to their prognostic value, the measurement of sST2 and GDF-15 levels after AMI may enhance standard tools already used in clinical practice and may be useful in detection of patients prone to longer hospitalization and at risk of developing new-onset or worsening heart failure [5][6][7][8][9][10]15,[17][18][19]. Early and aggressive treatment in-hospital and close follow-ups in specialized outpatient clinics should be recommended in patients with elevated levels of these two novel biomarkers.…”

“…sST2 levels are markedly elevated after AMI and have been associated with adverse remodelling in AMI patients and new-onset or worsening heart failure after STEMI, recently also after NSTEMI with worse outcomes [5][6][7][8][9][10]. It has been evidenced as a prognostic marker for patients with NSTEMI and STEMI and associated with increased adverse events in large population trials (GUSTO-IV, ICTUS and FRISC II) [16][17][18][19]. Its prominent anti-apoptotic, antihypertrophic and antiinflammatory actions in cardiovascular disease suggest that GDF-15 may play a counter-regulatory role in the context of cardiovascular injury [11][12][13].…”

“…In patients, GDF-15 has been detected in the infarcted myocardium and in atherosclerotic plaques [14,15]. It has been evidenced as a prognostic marker for patients with NSTEMI and STEMI and associated with increased adverse events in large population trials (GUSTO-IV, ICTUS and FRISC II) [16][17][18][19]. Heart-type fatty acid-binding protein (H-FABP) is a low molecular weight protein, which is abundant in the cytoplasm of myocardial cells and released very early as myocardial cell membrane is damaged by ischaemia [20][21][22][23].…”

Plasma growth differentiation factor 15 predicts first-ever stroke in hypertensive patients

“…[6–11] GDF-15 is also a predictor of cardiovascular death in a population of coronary artery disease patients after percutaneous coronary intervention. [12] During pathological stresses, GDF-15 expression can be increased and the protein secreted into the plasma to exert protective effects. [7,8] In an experimental animal model of brain injury, GDF-15 expression is increased.…”