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Articles by T Kempf
Total Records ( 3 ) for T Kempf
  T Kempf , J. M Sinning , A Quint , C Bickel , C Sinning , P. S Wild , R Schnabel , E Lubos , H. J Rupprecht , T Munzel , H Drexler , S Blankenberg and K. C. Wollert

Background— Growth-differentiation factor-15 (GDF-15) is a stress-responsive transforming growth factor-β-related cytokine that has emerged as a prognostic biomarker in acute coronary syndrome trial populations. Its predictive role in stable coronary heart disease (CHD) has never been assessed.

Methods and Results— The circulating levels of GDF-15 were measured by immunoradiometric assay in patients with stable angina pectoris (n=1352) or acute coronary syndrome (n=877) who were followed up for a median of 3.6 years. Stable angina pectoris patients presenting with normal (<1200 ng/L), moderately elevated (1200 to 1800 ng/L), or markedly elevated (>1800 ng/L) GDF-15 levels had 3.6-year CHD mortality rates of 1.4%, 2.7%, and 15.0%, respectively (P<0.001). By backward stepwise Cox-regression analysis, which adjusted for age and gender, clinical variables, the number of diseased vessels, renal function, the levels of C-reactive protein, cardiac troponin I, and N-terminal pro-B-type natriuretic peptide, GDF-15 remained an independent predictor of CHD mortality (P<0.001). Addition of GDF-15 improved the prognostic accuracy of a clinical risk prediction model concerning CHD mortality (c-statistic, 0.84 versus 0.74; P=0.005). Analysis of the acute coronary syndrome part of the study population confirmed GDF-15 as an independent predictor of CHD mortality (P<0.001). The circulating levels of GDF-15 did not predict the future risk of nonfatal myocardial infarction in patients with stable angina pectoris or acute coronary syndrome.

Conclusion— This study identifies GDF-15 as a strong and independent predictor of CHD mortality across the broad spectrum of patients with stable and unstable CHD.

  K. M Eggers , T Kempf , B Lagerqvist , B Lindahl , S Olofsson , F Jantzen , T Peter , T Allhoff , A Siegbahn , P Venge , K. C Wollert and L. Wallentin

Background— Growth-differentiation factor-15 (GDF-15) has emerged as a prognostic biomarker in patients with non–ST-segment–elevation acute coronary syndrome. This study assessed the time course and the long-term prognostic relevance of GDF-15 levels measured repetitively in patients with non–ST-segment–elevation acute coronary syndrome during 6 months after the acute event.

Methods and Results— GDF-15 and other biomarkers were measured at randomization, after 6 weeks, and after 3 and 6 months in 950 patients with non–ST-segment–elevation acute coronary syndrome included in the FRagmin and Fast Revascularization during InStability in Coronary artery disease II study. Study end points were death, recurrent myocardial infarction, and their composite during 5-year follow-up. Median GDF-15 levels decreased slightly from 1357 ng/L at randomization to 1302 ng/L at 6 months (P<0.001). GDF-15 was consistently related to cardiovascular risk factors and biochemical markers of hemodynamic stress, renal dysfunction, and inflammation. Moreover, GDF-15 was independently related to the 5-year risk of the composite end point when measured at both 3 months (adjusted hazard ratio, 1.8 [1.0 to 3.0]) and 6 months (adjusted hazard ratio, 2.3 [1.3 to 4.1]). Serial measurements of GDF-15 at randomization and 6 months helped to identify patient cohorts at different levels of risk, with patients with persistently elevated GDF-15 levels >1800 ng/L having the highest rate of the composite end point.

Conclusions— GDF-15 is independently related to adverse events in non–ST-segment–elevation acute coronary syndrome both in the acute setting and for at least 6 months after clinical stabilization. Therefore, continued research on GDF-15 should be focused on the usefulness of GDF-15 for support of clinical management in acute and chronic ischemic heart disease.

  C Widera , R Horn Wichmann , T Kempf , K Bethmann , B Fiedler , S Sharma , R Lichtinghagen , H Leitolf , B Ivandic , H. A Katus , E Giannitsis and K. C. Wollert

Background: Follistatin-like 1 (FSTL1) is a 308–amino acid secreted glycoprotein. Tissue levels of FSTL1 are induced in animal models and patients with chronic inflammatory and cardiovascular disease. We hypothesized that FSTL1 can be measured in the human circulation and used as a biomarker in acute coronary syndrome (ACS).

Methods: We developed an immunoluminometric assay (ILMA), assessed the preanalytic characteristics of FSTL1, and determined circulating FSTL1 concentrations in 120 apparently healthy individuals and 216 patients with ACS.

Results: The assay had a limit of detection of 0.17 µg/L, limit of quantification of 1.02 µg/L, intraassay imprecision of ≤12.7%, and interassay imprecision of ≤15.4%. Selectivity was demonstrated with size-exclusion chromatography and lack of cross-reactivity with related proteins. The assay was not appreciably influenced by unrelated biological substances. FSTL1 in serum or whole blood was stable at room temperature for 48 h and was resistant to 4 freeze-thaw cycles. Measured FSTL1 concentrations in citrated plasma and heparin-treated plasma were 18% and 17% lower, respectively, than concentrations measured in serum. Apparently healthy individuals presented with a median FSTL1 serum concentration of 7.18 (range 1.06–18.49) µg/L. Serum FSTL1 concentrations were increased in ACS and related to the risk of all-cause mortality during follow-up.

Conclusions: The ILMA permits detection of FSTL1 in human serum and plasma. We expect that the favorable preanalytic characteristics of FSTL1 and the reference limits defined here for apparently healthy individuals will facilitate future studies of FSTL1 as a biomarker in various disease settings, including ACS.

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