Background
Novel biomarkers representing different pathobiological pathways and their role in patients with acute myocardial infarction (AMI) were studied.
Methods
We retrospectively analysed serum ...levels of soluble suppression of tumorigenicity (sST2), growth‐differentiation factor‐15 (GDF‐15), soluble urokinase plasminogen activator receptor (suPAR), heart‐type fatty acid‐binding protein (H‐FABP) and plasma fetuin A in blood of patients with AMI (STEMI, n = 61; NSTEMI, n = 57) compared to controls with excluded coronary artery disease (n = 76). Furthermore, detailed correlation analysis was performed.
Results
Compared with controls, in patients with STEMI and NSTEMI higher levels expressed as median of sST2 in pg/mL (STEMI: 13210·9, NSTEMI: 11989·1, control: 5248; P < 0·001), GDF‐15 in pg/mL (STEMI: 818·8, NSTEMI 677·5, control 548·6; P < 0·001), suPAR in pg/mL (STEMI: 3461·1, NSTEMI: 3466·7, control: 2463·6; P < 0·001), H‐FABP in ng/mL (STEMI: 5·8, NSTEMI: 5·4, control: 0·0; P < 0·001) and lower plasma fetuin A levels in μg/mL (STEMI: 95, NSTEMI: 54, control: 116·6; P < 0·001) were detected. Correlation analysis found clinical and biochemical parameters such as ejection fraction, length of hospital stay, creatine kinase, NT‐proBNP and hs Troponin T levels as well as inflammatory markers (CRP, leucocytes) to be significantly correlated with novel biomarkers.
Conclusion
Plasma levels of novel biomarkers were significantly elevated (sST2, GDF‐15, H‐FABP, suPAR) or inversely downregulated (fetuin A) in patients with AMI compared to a control group with excluded coronary artery disease. Significant correlations with various clinical parameters and standard biochemical markers were found.
Background
Soluble ST2 (sST2) has been introduced as a novel biomarker in patients suffering from heart failure for risk stratification. In this study, we sought to investigate whether sST2 is useful ...for risk stratification and prediction of mortality in patients undergoing transcatheter aortic valve implantation (TAVI).
Materials and methods
A total of 274 patients undergoing TAVI were included in this study (149 female; age 81 ± 1 years; EUROSCORE 25 ± 1; STS score 3·8 ± 0·2). Plasma samples were obtained preinterventional and analysed for sST2. Patients were followed up 1 month and 1 year after TAVI.
Results
In a Cox regression analysis, sST2 plasma concentration was associated with increased mortality (changes per pg/mL sST2 concentration; HR 1·00006 95% (1·00004–1·00009); P < 0·001). A cut‐off by means of the Youden Index was calculated (10 070·27 pg/mL), and patients were retrospectively divided into two cohorts, in those above (31·3%) and those below (68·7%) this value. These two groups were then compared regarding mortality both after 30 days and 1 year: whereas 1‐month mortality did not differ (7·0% vs. 10·3%, OR 1·50 95% CI (0·60–3·79; P = 0·46)), patients with a sST2 concentration above the cut‐off of 10 070·27 pg/mL showed a significantly worse outcome after 1 year (49·2% vs. 23·2%; OR 3·21 95% CI (1·70–6·04); P < 0·001). After correction for confounders in a multivariate Cox regression analysis, sST2 (1·0002 95% CI (1·0001–1·0003); P = 0·001) concentration remained associated with mortality.
Conclusions
sST2 levels were associated with 1‐year mortality after TAVI. Based on these results, we assume that sST2 might help to identify patients at high risk for death in whom conservative treatment should be considered.
Background In current guidelines, intraaortic balloon pumping (IABP) is considered a class 1 indication in cardiogenic shock complicating acute myocardial infarction. However, evidence is mainly ...based on retrospective or prospective registries with a lack of randomized clinical trials. Therefore, IABP is currently only used in 20% to 40% of cardiogenic shock cases. The hypothesis of this trial is that IABP in addition to early revascularization by either percutaneous coronary intervention or coronary artery bypass grafting will improve clinical outcome of patients in cardiogenic shock. Study Design The IABP-SHOCK II study is a 600-patient, prospective, multicenter, randomized, open-label, controlled trial. The study is designed to compare the efficacy and safety of IABP versus optimal medical therapy on the background of early revascularization by either percutaneous coronary intervention or coronary artery bypass grafting. Patients will be randomized in a 1:1 fashion to 1 of the 2 treatments. The primary efficacy end point of IABP-SHOCK II is 30-day all-cause mortality. Secondary outcome measures, such as hemodynamic, laboratory, and clinical parameters, will serve as surrogate end points for prognosis. Furthermore, an intermediate and long-term follow-up at 6 and 12 months will be performed. Safety will be assessed, by the GUSTO bleeding definition, peripheral ischemic complications, sepsis, and stroke. Conclusions The IABP-SHOCK II trial addresses important questions regarding the efficacy and safety of IABP in addition to early revascularization in patients with cardiogenic shock complicating myocardial infarction.
Abstract Purpose Diabetes mellitus represents an increasing problem for patients and health care systems worldwide. We sought to investigate the effect of diabetes and its associated comorbidities on ...long-term survival and quality of life following an admission to a medical intensive care unit (ICU). Methods A total of 6662 consecutive patients admitted to ICU between 2004 and 2009 were included (patients with diabetes n = 796, non-diabetic patients n = 5866). The primary endpoint of the study was death of any cause. Data on mortality was collected upon review of medical records or phone interviews. Moreover, a questionnaire was sent to 500 randomly selected patients addressing Health related Quality of Life (HrQoL) after ICU treatment. Results Overall mortality did not differ significantly between diabetic and non-diabetic patients after ICU treatment (mean follow-up time: 490 days). For a subgroup of patients already exhibiting comorbidities associated with diabetes, the mortality rate was significantly higher (p = 0.022). Regarding quality of life, no differences were found between groups. Conclusions Diabetes was not associated with increased mortality or reduced quality of life in a general population of medical ICU patients. However, once comorbidities associated with diabetes occurred, the survival rate of patients with comorbidities associated with hyperglycemia was significantly reduced.
Early detection of atherosclerosis, i.e., in occupational health screening programs could reduce the rate of cardiovascular events in the working population. Changes of the augmentation index (AIX) ...correlate with changes of the arterial stiffness induced by aging, atherosclerosis, or arterial hypertension and have a prognostic value for cardiovascular events. Their diagnostic yield should be increased by normalizing the AIX to age, in terms of a calculating the vascular age (VA). In this pilot study, 30 patients (mean age 65.3 ± 8.8 years, 21 male) with suspected coronary heart disease underwent a duplex ultrasound of the carotid arteries and a measurement of the ankle brachial index in addition to the coronary angiography. The AIX was recorded with a portable device (Vascular Explorer), and the VA was calculated. Atherosclerosis was found in 24 patients. They were older than the patients without atherosclerosis, but there was no age dependency found for the distribution pattern or severity of atherosclerosis. In patients with findings of atherosclerosis, the calculated VA was higher than the chronological age, and these differences were significant in patients below 65 years of age. Comparing patients in higher blood pressure classes with patients in lower classes, significantly higher AIX, VA, and differences to the chronological age were found. The VA, deduced from the noninvasively obtained AIX, is a promising candidate for screening programs for atherosclerosis, i.e., in occupational health screening programs.
VEGF-, phosphoinositide 3-kinase (PI3K)- and protein kinase C (PKC)-regulated signaling in cardiac and vascular differentiation was investigated in mouse ES cells and in ES cell-derived Flk-1⁺ ...cardiovascular progenitor cells. Inhibition of PI3K by wortmannin and LY294002, disruption of PI3K catalytic subunits p110α and p110δ using short hairpin RNA (shRNA), or inhibition of p110α with compound 15e and of p110δ with IC-87114 impaired cardiac and vascular differentiation. By contrast, TGX-221, an inhibitor of p110β, and shRNA knockdown of p110β were without significant effects. Antagonists of the PKC family, i.e. bisindolylmaleimide-1 (BIM-1), GÖ 6976 (targeting PKCα/βII) and rottlerin (targeting PKCδ) abolished vasculogenesis, but not cardiomyogenesis. Inhibition of Akt blunted cardiac as well as vascular differentiation. VEGF induced phosphorylation of PKCα/βII and PKCδ but not PKCζ. This was abolished by PI3K inhibitors and the VEGFR-2 antagonist SU5614. Furthermore, phosphorylation of Akt and phosphoinositide-dependent kinase-1 (PDK1) was blunted upon inhibition of PI3K, but not upon inhibition of PKC by BIM-1, suggesting that activation of Akt and PDK1 by VEGF required PI3K but not PKC. In summary, we demonstrate that PI3K catalytic subunits p110α and p110δ are central to cardiovasculogenesis of ES cells. Akt downstream of PI3K is involved in both cardiomyogenesis and vasculogenesis, whereas PKC is involved only in vasculogenesis.
Introduction. Obesity during adolescence is an increasing problem for both the individual and health care systems alike. In Western world countries, childhood adiposity has reached epidemic ...proportions. It is known that elevated levels of proinflammatory cytokines can be found in the plasma of obese patients. In this study, we sought to determine the relation between IL-12p40, IL-12p70, and Interleukin-16 (IL-16) in overweight adolescents. Materials and Methods. Seventy-nine male Caucasian adolescents aged 13–17 years were included in this study. Thirty-seven of them had a body mass index (BMI) above the 90th age-specific percentile. Il-12p40, IL-12p70, and IL-16 were measured from plasma using Luminex multiplex technology. Results. Both IL-12p40 and IL-16 concentrations were significantly increased in overweight subjects compared to normal weight controls (IL-12p40: 1086.6 pg/mL ± 31.7 pg/mL SEM versus 1228.6 pg/mL ± 43.5 pg/mL SEM; IL-16 494.0 pg/mL ± 29.4 pg/mL SEM versus 686.6 pg/mL ± 52.5 pg/mL SEM, P < 0.05 and P < 0.01 , resp.). No differences were found for IL-12p70. Conclusions. Based on these results, we believe that the increased levels of IL-12p40 and IL-16 are associated with an ongoing inflammatory response in obese individuals and could lead to the development of disease conditions related to obesity.
Background
Increased levels of endothelial cell microparticles (EMP) are known to reflect endothelial dysfunction (ED). In diabetes mellitus type 2 (T2DM), the expression of endothelin (ET)‐1 is ...increased. As treatment with an ET‐1 antagonist significantly inhibited atherosclerosis in animal models, we sought to investigate whether treatment with ET‐1 antagonists affects EMP levels in vitro and in vivo in patients with T2DM.
Materials and methods
In vitro study: Human umbilical vein endothelial cells (HUVEC) were stimulated with ET‐1 alone and ET‐1 in combination with a dual ET‐A and ET‐B endothelin receptor blocker. In vivo study: Patients with T2DM were randomized to treatment with the ET receptor antagonist bosentan or placebo. After 4 weeks, the patients were re‐examined and blood samples were obtained. EMP counts in supernatants and plasma samples were determined using flow cytometry.
Results
In vitro study: In supernatants of ET‐1‐stimulated HUVECs, the increased release of EMP was reduced significantly by co‐incubation with an ET‐1 receptor antagonist (e.g. CD31+/CD42b‐EMP decreased from 37·1% ± 2·8 to 31·5% ± 2·8 SEM, P = 0·0078). In vivo study: No changes in EMP levels in blood samples of patients with T2DM were found after 4 weeks of bosentan treatment (n = 36, P = ns).
Conclusions
Our in vitro results suggest that ET‐1 stimulates the release of EMP from HUVECs via a receptor‐dependent mechanism. Co‐incubation with an endothelin receptor blocker abolished ET‐1‐dependent EMP release. However, treatment with bosentan for 4 weeks failed to alter EMP levels in patients with T2DM. Other factors seem to have influenced EMP release in patients with T2DM independent of ET‐1 receptor‐mediated mechanisms.
Degenerative aortic stenosis (AS) is the most frequent form of acquired valvular heart disease. AS is known to entail endothelial dysfunction caused by increased mechanical shear stress leading to ...elevated circulatory levels of microparticles. Endothelial and platelet microparticles (EMP and PMP) are small vesicles that originate from activated cells and thrombocytes. We sought to evaluate whether transcatheter aortic valve implantation (TAVI) procedure would elicit effects on circulating EMP and PMP. 92 patients undergoing TAVI procedure for severe AS were included in this study. Samples were obtained at each visit before TAVI, 1 week post-procedure and at 1, 3 and after 6 months after TAVI and were evaluated using flow cytometry. A 12 month clinical follow-up was also performed. CD62E+ EMP concentration before TAVI was 21.11 % (±6.6 % SD) and declined to 20.99 % (±6.8 % SD) after 1 week, to 16.63 % (±5.4 % SD,
p
< 0.0001) after 1 month, to 17.08 % (±4.6 % SD,
p
< 0.0001) after 3 months and to 15.94 % (±5.4 % SD,
p
< 0.0001) after 6 months. CD31+/CD42b−, CD31+/Annexin+/− EMP remained unchanged. CD31+/CD41b+ PMP evidenced a slight, but statistically significant increase after TAVI and remained elevated during the entire follow-up. Apart from a procedure-related improvement in echocardiographic parameters, TAVI procedure led also to a decline in CD62E+ EMP. The reduction in pressure gradients with less hemodynamic shear stress seems also to have beneficially affected endothelial homeostasis.
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