Reference change values and determinants of variability of NT-proANP and GDF15 in stable chronic heart failure

Abstract

Biovariability, reference change values (RCV), and index of individuality (IOI) have not been previously described for NT-proANP or GDF15. Also, the relation of changes of these markers to other clinical variables or biomarkers is unknown. In 41 patients with stable chronic systolic dysfunction, NT-proANP and GDF15 were measured alongside with clinical variables/markers comprising NT-proBNP, hsTnT, and hsCRP at four sampling intervals (2 weeks, 1-, 2-, 3-month intervals). At 2 weeks, 1-, 2-, and 3-month-follow-up, individual NT-proANP variations were 27.1, 22.5, 28.9, 15.6%, respectively, corresponding to RCVs of 53.2, 62.4, 80.2, and 43.2%, respectively. For GDF15, the respective individual variations were 6.8, 4.1, 5.5, 6.8%, corresponding to RCVs of 18.8, 11.5, 15.3 and 18.8%. Neither changes of NT-proANP or GDF15 correlated with changes in any of the clinical variables or biomarkers examined except for GDF15 with renal function. Baseline hormonal levels and clinical variables did not consistently influence the extent of change. The IOI was 0.19-0.35 according to interval for NT-proANP and 0.06-0.09 for GDF 15. In patients with CHF preselected for clinical stability changes of NT-proANP at intermediate follow-up do not correlate with changes in other variables; changes of GDF15 inversely correlate with renal function. The extent of change in both markers is not related to baseline hormonal levels or other baseline variables. RCVs are high for NT-proANP and low for GDF15, while inter-individual variation is high in GDF15 and intermediate in NT-proANP.

Growth Differentiation Factor 15, Its 12-Month Relative Change, and Risk of Cardiovascular Events and Total Mortality in Patients with Stable Coronary Heart Disease: 10-Year Follow-up of the KAROLA Study

“…Cox-proportional hazards models evaluated the association of 12-month relative change of ln GDF-15 (continuous and categorical) with a secondary CVE and total mortality during the subsequent 9 years of follow-up. Categorical analysis shows an upper category including those with a 12-month relative change Ն20%, a reference group including those with a relative change Ͻ20% but ϾϪ20%, and a lower category for those with a relative change ՅϪ20% (14 ). We adjusted initially for baseline levels of ln GDF-15, age and sex (Model 1), followed by additional adjustment for well-established cardiovascular risk factors (Model 2), and further adjustment for biomarkers representing specific pathogenetic pathways: ln NT-proBNP, ln hs-CRP, and ln hs-cTnT (Model 3).…”

Change in Growth Differentiation Factor 15 Concentrations over Time Independently Predicts Mortality in Community-Dwelling Elderly Individuals

“…This change criterion was chosen because it approximated a normal distribution to a greater extent than other relative or absolute change criteria (Shapiro-Wilk W-test statistic ϭ 0.95). Second, we defined different change patterns considering published data on the biological variability of GDF-15 (17 ): decreasing, change in GDF-15 concentrations ՅϪ20%; increasing, change in GDF-15 concentrations Ն40%; or unchanged, change in GDF-15 concentrations between Ϫ19% and 39%. Independent predictors of changes were identified by multiple linear regression analysis and multivariable regression analysis, as appropriate.…”

Serial Measurement of Growth-Differentiation Factor-15 in Heart Failure

“…It is notable that the intraindividual biological variation of GDF-15 in patients with clinically stable chronic HF is lower compared with the intraindividual biological variation of the natriuretic peptides, 36,37 which may facilitate interpretation of temporal changes in GDF-15 in HF. Previous studies using echocardiography or repeat measurements of BNP found no evidence for a progressive worsening of cardiac function in patients from the Val-HeFT trial over the course of 12 months; in fact, slight improvements in LVEF and decreases in left ventricular internal diastolic dimension corrected for body surface area and BNP have been reported.…”