Complementary Roles for Biomarkers of Biomechanical Strain ST2 and N-Terminal Prohormone B-Type Natriuretic Peptide in Patients With ST-Elevation Myocardial Infarction

Sabatine, Marc S.; Morrow, David A.; Higgins, Luke J.; MacGillivray, Catherine; Guo, Wei; Bode, C; Rifai, Nader; Cannon, Christopher P.; Gerszten, Robert E.; Lee, Richard T.

doi:10.1161/circulationaha.107.728022

Cited by 300 publications

(289 citation statements)

References 24 publications

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“…Data from a retrospective study by Hirsch et al showed an association between aortic stiffness and LV end‐systolic volume in patients with chronic infarcts 8. A rise in NT‐proBNP concentration is a sensitive indicator of increasing myocardial wall stress and a strong predictor of outcome after acute STEMI 6, 22. Our study group has recently shown an association between high aortic PWV and NT‐proBNP levels in the subacute and chronic phase after STEMI 2, 3.…”

Section: Discussionmentioning

confidence: 50%

Prognostic Value of Aortic Stiffness in Patients After ST‐Elevation Myocardial Infarction

Feistritzer

Klug

Reinstadler

et al. 2017

JAHA

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BackgroundHigh aortic stiffness has been shown to be a strong predictor of morbidity and mortality in the general population and several patient cohorts. However, in patients after ST‐elevation myocardial infarction, the prognostic value of high aortic stiffness is unknown so far.Methods and ResultsThis prospective observational study included 160 consecutive patients with first acute ST‐elevation myocardial infarction. Aortic pulse wave velocity (PWV) was measured 2 (interquartile range 2‐4 days) days after infarction using cardiac magnetic resonance imaging. The primary end point was defined as a composite end point of major adverse cardiac and cerebrovascular events (MACCE) comprising death, nonfatal myocardial reinfarction, new congestive heart failure, and stroke. During a median follow‐up of 1.2 years (interquartile range 1.0‐3.1 years), 19 (12%) MACCE events occurred. Kaplan‐Meier analysis showed a significantly lower MACCE‐free survival in patients with high PWV (PWV >7.3 m/s, log‐rank P=0.003). Multivariable Cox regression analysis revealed PWV >7.3 m/s to be an independent predictor of MACCE after adjustment for age, sex, mean blood pressure, N‐terminal pro–brain natriuretic peptide levels, presence of multivessel disease, and left ventricular stroke volume (hazard ratios ≥3.5; 95% confidence interval 1.4‐13.3; all P≤0.018). In reclassification analysis the addition of PWV to a risk model comprising major clinical prognostic parameters led to a net reclassification improvement of 0.11 (95% confidence interval 0.06‐0.17; P<0.001).ConclusionsIncreased aortic stiffness is an independent predictor of MACCE after acute ST‐elevation myocardial infarction. Moreover, the assessment of aortic stiffness in addition to classical risk factors significantly improved early risk stratification.

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Section: Discussionmentioning

confidence: 50%

Prognostic Value of Aortic Stiffness in Patients After ST‐Elevation Myocardial Infarction

Feistritzer

Klug

Reinstadler

et al. 2017

JAHA

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“…Circulating sST2 was previously identified as a prognostic marker in heart failure and myocardial infarction 7, 8, 9, 24. Together with other cardiac biomarkers such as troponin25 and B‐type natriuretic peptide (BNP),26, 27 our data highlight overlapping injury responses that occur following both cerebrovascular and cardiovascular injury.…”

Section: Discussionmentioning

confidence: 56%

“…Previous studies have identified sST2 as a prognostic biomarker in cardiovascular disease 7, 8, 9. In order to exclude the possibility that the association between sST2 and outcome was related to underlying cardiovascular disease, we developed sequential multivariable models that included cardiovascular disease risk factors.…”

Section: Resultsmentioning

confidence: 99%

“…A soluble form (sST2) is secreted into the circulation and functions as a decoy receptor for IL‐33, inhibiting its signaling 6. Circulating levels of sST2 are associated with adverse outcome and mortality in patients with chronic heart failure (CHF) and myocardial infarction (MI) 7, 8, 9. Recently, higher sST2 has been associated with an elevated risk of incident stroke 10…”

Section: Introductionmentioning

confidence: 99%

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Soluble ST2 predicts outcome and hemorrhagic transformation after acute stroke

Wolcott

Batra

Bevers

et al. 2017

Ann Clin Transl Neurol

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Objective ST2 is a member of the toll‐like receptor superfamily that can alter inflammatory signaling of helper T‐cells. We investigated whether soluble ST2 (sST2) could independently predict outcome and hemorrhagic transformation (HT) in the setting of stroke.MethodsWe measured sST2 in patients enrolled in the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) network biomarker study. 646 patients had plasma samples collected at the time of hospital admission and 210 patients had a second sample collected 48 h after stroke onset. Functional outcome was assessed using the modified Rankin Scale (mRS), with good and poor outcomes defined as mRS 0‐2 and 3‐6, respectively. HT was classified using ECASS criteria. The relationships between sST2, outcome, and HT were evaluated using multivariable logistic regression, Kaplan–Meier survival analysis and receiver operating characteristic curves.Results646 patients were included in the analysis (mean age 69 years; 44% women), with a median NIHSS of 5 [IQR: 2–12]. The median sST2 level on hospital admission was 35.0 ng/mL [IQR: 25.7–49.8 ng/mL] and at 48 h it was 37.4 ng/mL [IQR 27.9–55.6 ng/mL]. sST2 was independently associated with poor outcome (OR: 2.77, 95% CI: 1.54–5.06; P = 0.003) and mortality (OR: 3.56, 95% CI: 1.58–8.38, P = 0.001) after multivariable adjustment. Plasma sST2 was also associated with hemorrhagic transformation after adjustment for traditional risk factors (OR: 5.58, 95% CI: 1.40–37.44, P = 0.039).InterpretationSoluble ST2 may serve as a prognostic biomarker for outcome and hemorrhagic transformation in patients with acute stroke. ST2 may link neuroinflammation and secondary injury after stroke.

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“…The involvement of sST2 has been observed in a variety of pathological conditions characterized by: (1) intravascular inflammation [145,[148][149][150][151] (i.e. myocardial infarction [152][153][154], atherosclerotic vascular disease [155], sepsis and trauma [149,150]); and (2) an imbalance of Th1/Th2 immune response [141,156,157] (i.e. asthma and other allergic conditions [145,148,158,159]), both of which are also observed in patients with preeclampsia [23,25,132,160,161].…”

Section: Introductionmentioning

confidence: 99%

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

Stampalija

Chaiworapongsa

Romero

et al. 2013

The Journal of Maternal-Fetal & Neonatal Medicine

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Objectives: Angiogenic/anti-angiogenic factors have emerged as one of the promising biomarkers for the prediction of preeclampsia. Since not all patients with preeclampsia can be identified by these analytes, the search for additional biomarkers continues. The soluble form of ST2 (sST2), a protein capable of binding to interleukin (IL)-33 and thus contributing to a Th1-biased immune response, has been reported to be elevated in maternal plasma of women with preeclampsia. The aims of this study were to examine: (1) differences in maternal plasma concentrations of sST2 and IL-33 between women diagnosed with preeclampsia and those having uncomplicated pregnancies; (2) the relationship between sST2, umbilical and uterine artery Doppler velocimetry, and the severity of preeclampsia; and (3) the performance of sST2 and angiogenic/anti-angiogenic factors in identifying patients with preeclampsia at the time of diagnosis. Methods: This cross-sectional study included women with preeclampsia (n ¼ 106) and women with an uncomplicated pregnancy (n ¼ 131). Plasma concentrations of sST2, IL-33, soluble vascular endothelial growth factor receptor (sVEGFR)-1, soluble endoglin (sEng) and placental growth factor (PlGF) were determined by enzyme linked immune sorbent assay. Area under the receiver operating characteristic curve (AUC) for the identification of preeclampsia was examined for each analyte. Results: (1) Patients with preeclampsia had a higher mean plasma concentrations of sST2 than those with an uncomplicated pregnancy (p50.0001), while no significant difference in the mean plasma concentration of IL-33 between the two groups was observed; (2) the magnitude of this difference was greater in early-onset, compared to late-onset disease, and in severe compared to mild preeclampsia; (3) sST2 plasma concentrations did not correlate with the results of uterine or umbilical artery Doppler velocimetry (p ¼ 0.7 and p ¼ 1, respectively) among women with preeclampsia; (4) sST2 correlated positively with plasma concentrations of sVEGFR1-1 and sEng (Spearman's Rho ¼ 0.72 and 0.63; each p50.0001), and negatively with PlGF (Spearman's Rho ¼ À0.56, p50.0001); and (5) while the AUC achieved by sST2 and angiogenic/anti-angiogenic factors in identifying women with preeclampsia at the time of diagnosis were non-significantly different prior to term (537 weeks of gestation), thereafter the AUC achieved by sST2 was significantly less than that achieved by angiogenic/anti-angiogenic factors. Conclusions: Preeclampsia is associated with increased maternal plasma concentrations of sST2. The findings that sST2 concentrations do not correlate with uterine or umbilical artery Doppler velocimetry in women with preeclampsia suggest that elevated maternal plasma sST2 concentrations in preeclampsia are not related to the increased impedance to flow in the uteroplacental circulation. The performance of sST2 in identifying preeclampsia at the time of diagnosis prior to 37 weeks of gestation was comparable to that of angiogenic/anti-angiogenic f...

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Complementary Roles for Biomarkers of Biomechanical Strain ST2 and N-Terminal Prohormone B-Type Natriuretic Peptide in Patients With ST-Elevation Myocardial Infarction

Cited by 300 publications

References 24 publications

Prognostic Value of Aortic Stiffness in Patients After ST‐Elevation Myocardial Infarction

Prognostic Value of Aortic Stiffness in Patients After ST‐Elevation Myocardial Infarction

Soluble ST2 predicts outcome and hemorrhagic transformation after acute stroke

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

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