The coincidence of low vitamin K status and high expression of growth differentiation factor 15 may indicate increased mortality risk in stable coronary heart disease patients

Author(s):  
Otto Mayer ◽  
Jan Bruthans ◽  
Jitka Seidlerová ◽  
Petra Karnosová ◽  
Markéta Mateřánková ◽  
...  
2017 ◽  
Vol 63 (1) ◽  
pp. 325-333 ◽  
Author(s):  
Emil Hagström ◽  
Claes Held ◽  
Ralph A H Stewart ◽  
Philip E Aylward ◽  
Andrzej Budaj ◽  
...  

Abstract BACKGROUND Higher growth differentiation factor 15 (GDF-15) concentrations are associated with cardiovascular (CV) and non-CV morbidity and mortality. However, information on associations between GDF-15 and the risk of specific CV and non-CV events in stable coronary heart disease (CHD) patients is limited. METHODS In 14 577 patients with stable CHD participating in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial (STABILITY), GDF-15 and other prognostic biomarkers (N-terminal pro–B-type natriuretic peptide, high-sensitivity troponin T, cystatin C, and high-sensitivity C-reactive protein) were measured. In adjusted Cox regression models, the associations between GDF-15 and the composite CV end point [CV death, myocardial infarction (MI), and stroke], as well as other CV and non-CV events, were assessed. RESULTS The median concentration (interquartile range) of GDF-15 at baseline was 1253 (915–1827) ng/L. The hazard ratio for the composite end point for the highest compared to the lowest quartile of GDF-15 was 1.8 (95% CI, 1.5–2.2); for CV death, 2.63 (1.9–3.6); for sudden death, 3.06 (1.9–4.8); for heart failure (HF) death, 4.3 (1.3–14); for cancer death, 2.5 (1.3–4.7); for hospitalization for HF, 5.8 (3.2–10); for MI 1.4 (95% CI, 1.1–1.9); and for stroke, 1.8 (95% CI, 1.1–2.8). After adjustment for other prognostic biomarkers, GDF-15 remained significantly associated with all outcomes except for MI. CONCLUSIONS In stable CHD, GDF-15 was independently associated with CV, non-CV, and cancer mortality, as well as with MI and stroke. When also adjusting for other prognostic biomarkers, the associations to all fatal and nonfatal events were maintained except for MI. Information on GDF-15, therefore, might be helpful when assessing the risk of adverse outcomes in patients with stable CHD. ClinicalTrials.gov Identifier: NCT00799903


2016 ◽  
Vol 62 (7) ◽  
pp. 982-992 ◽  
Author(s):  
Dhayana Dallmeier ◽  
Hermann Brenner ◽  
Ute Mons ◽  
Wolfgang Rottbauer ◽  
Wolfgang Koenig ◽  
...  

Abstract BACKGROUND This study considered whether baseline concentrations and 12-month changes of growth differentiation factor 15 (GDF-15) are associated with subsequent cardiovascular events (CVEs) and total mortality in patients with stable coronary heart disease. METHODS Baseline GDF-15 serum concentrations were measured in 1073 participants in a cardiac rehabilitation program (median follow-up 10 years). GDF-15 associations with subsequent CVE and total mortality were evaluated by Cox-proportional hazards models adjusting for well-established cardiovascular risk factors (Model 2), plus N-terminal probrain natriuretic peptide, high-sensitivity (hs) CRP, and hs cardiac troponin T (Model 3). RESULTS In our study population [84.7% men, mean age 59 years, median baseline GDF-15 1232 ng/L (interquartile range, 916, 1674)] we observed 190 CVE and 162 deaths. Compared to participants with GDF-15 <1200 ng/L, increased risk for death was found in participants with GDF-15 ≥1200 and ≤1800 ng/L [hazard ratio (HR) 1.68 (95% CI, 1.08–2.62)] and with GDF-15 >1800 ng/L [HR 1.73 (1.02–2.94)], even in Model 3. The 12-month relative median change was −16.7%. As compared to participants with 12-month relative changes between −20% and 20%, GDF-15 increments >20% were associated with: a) an HR of 1.84 (1.04–3.26) for CVE in Model 2, but found nonsignificant in Model 3; (b) an HR of 2.26 (1.32–3.86) for death even in Model 3. CONCLUSIONS GDF-15 at baseline is independently associated with subsequent CVE and 10-year total mortality. Twelve-month relative changes remained associated with subsequent CVE when adjusting for well-established cardiovascular risk factors, and with total mortality even after further adjustment for established cardiac biomarkers.


2009 ◽  
Vol 2 (3) ◽  
pp. 286-292 ◽  
Author(s):  
Tibor Kempf ◽  
Jan-Malte Sinning ◽  
Anja Quint ◽  
Christoph Bickel ◽  
Christoph Sinning ◽  
...  

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