Vanessa Pfetsch1, Veronika Sanin1, Andrea Jaensch2, Dhayana Dallmeier3, Ute Mons4, Hermann Brenner4, Wolfgang Koenig5,6,7, Dietrich Rothenbacher2,4. 1. Deutsches Herzzentrum München, Technische Universität München, Lazarettstr. 36, 80636, Munich, Germany. 2. Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany. 3. AGAPLESION Bethesda Clinic, Geriatric Center Ulm/Alb-Donau, Research Unit on Aging, Ulm University, Ulm, Germany. 4. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. 5. Deutsches Herzzentrum München, Technische Universität München, Lazarettstr. 36, 80636, Munich, Germany. koenig@dhm.mhn.de. 6. Department of Internal Medicine II - Cardiology, University of Ulm Medical Centre, Ulm, Germany. koenig@dhm.mhn.de. 7. DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany. koenig@dhm.mhn.de.
Abstract
PURPOSE: sST2 (soluble suppression of tumorigenicity 2), a member of the interleukin-1 family, has been suggested to play a role in cardiac remodeling and inflammatory signaling. We assessed the association between sST2 in patients with stable coronary heart disease (CHD) with multiple cardiovascular outcomes and total mortality, simultaneously controlling for a large number of potential confounders. METHODS: Plasma concentrations of sST2 (ELISA, Critical Diagnostics) were measured at baseline in a cohort of 1081 patients. The Cox-proportional hazards model was used to determine the prognostic value of sST2 on a combined cardiovascular disease (CVD) endpoint, on cardiovascular death, and on total mortality after adjustment for covariates. RESULTS: The median sST2 level was 28.9 ng/mL (IQR 23.8, 35.1) (mean age at baseline 58.9 years, 84.6% male). sST2 concentration was positively correlated with inflammatory markers and emerging risk factors, e.g., cystatin C, N-terminal probrainnatriuretic peptide (NT-proBNP), high-sensitivity (hs)-Troponin T and I, mid-regional pro-atrial natriuretic peptide (MR-proANP), and growth differentiation factor 15 (GDF-15). Results after short- and long-term (4.5 and 12.3 years, respectively) follow-up (FU) displayed no statistically significant association with the combined endpoint of non-fatal and fatal CVD events when the top quartile (Q4) of sST2 concentration was compared to the bottom quartile (Q1). A relationship during long-term FU was seen with CVD mortality even after multivariable adjustments including clinical risk variables (HR 1.65; 95% CI 1.02-2.86), but not in a fully adjusted model whereas, in contrast, it was still highly significant after short-term FU (HR (5.97 (95%CI 1.32-27.06)). In addition, the sST2 concentration was still strongly associated with total mortality in the fully adjusted model including clinical variables and cystatin C based estimated glomerular filtration rate, NT-proBNP, hsCRP and hs-TnI comparing Q4 vs Q1 during long-term FU (HR of 1.48 (95% CI 1.03-2.13)) and short-term FU (HR 3.06 (95% CI 1.29-7.24)). CONCLUSIONS: Elevated levels of sST2 concentration in stable CHD patients may independently predict short- and long-term risk for fatal CVD events and total mortality but not non-fatal CVD events.
PURPOSE: sST2 (soluble suppression of tumorigenicity 2), a member of the interleukin-1 family, has been suggested to play a role in cardiac remodeling and inflammatory signaling. We assessed the association between sST2 in patients with stable coronary heart disease (CHD) with multiple cardiovascular outcomes and total mortality, simultaneously controlling for a large number of potential confounders. METHODS: Plasma concentrations of sST2 (ELISA, Critical Diagnostics) were measured at baseline in a cohort of 1081 patients. The Cox-proportional hazards model was used to determine the prognostic value of sST2 on a combined cardiovascular disease (CVD) endpoint, on cardiovascular death, and on total mortality after adjustment for covariates. RESULTS: The median sST2 level was 28.9 ng/mL (IQR 23.8, 35.1) (mean age at baseline 58.9 years, 84.6% male). sST2 concentration was positively correlated with inflammatory markers and emerging risk factors, e.g., cystatin C, N-terminal probrainnatriuretic peptide (NT-proBNP), high-sensitivity (hs)-Troponin T and I, mid-regional pro-atrial natriuretic peptide (MR-proANP), and growth differentiation factor 15 (GDF-15). Results after short- and long-term (4.5 and 12.3 years, respectively) follow-up (FU) displayed no statistically significant association with the combined endpoint of non-fatal and fatal CVD events when the top quartile (Q4) of sST2 concentration was compared to the bottom quartile (Q1). A relationship during long-term FU was seen with CVD mortality even after multivariable adjustments including clinical risk variables (HR 1.65; 95% CI 1.02-2.86), but not in a fully adjusted model whereas, in contrast, it was still highly significant after short-term FU (HR (5.97 (95%CI 1.32-27.06)). In addition, the sST2 concentration was still strongly associated with total mortality in the fully adjusted model including clinical variables and cystatin C based estimated glomerular filtration rate, NT-proBNP, hsCRP and hs-TnI comparing Q4 vs Q1 during long-term FU (HR of 1.48 (95% CI 1.03-2.13)) and short-term FU (HR 3.06 (95% CI 1.29-7.24)). CONCLUSIONS: Elevated levels of sST2 concentration in stable CHD patients may independently predict short- and long-term risk for fatal CVD events and total mortality but not non-fatal CVD events.
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