Biomarker panel in sleep apnea patients after an acute coronary event.

BACKGROUND: Acute coronary syndrome (ACS) is a major cause of death and closely related with obstructive sleep apnea (OSA). Our hypothesis is that several cardiovascular-related biomarkers could have a differential prognostic value for ACS severity in patients with OSA, and could also help (individually or combined) in the detection of OSA in patients after a coronary event. METHODS: Up to 361 consecutive individuals admitted due to ACS were included in the study. All of them were evaluated for ACS severity (Killip score, number of diseased vessels, ejection fraction) and further classified as OSA or non-OSA. Medical records were registered and eleven blood biomarkers were measured, including heart-type fatty acid-binding globulin, N-terminal pro-brain natriuretic peptide, matrix metalloproteinase-9 (MMP9), placental growth factor (PlGF) and high-sensitivity C-reactive protein. Odds ratios of every biomarker for ACS severity-related parameters were calculated and adjusted for age, gender, body-mass index (BMI), hypertension, diabetes, smoking and drinking. The use of clinical measures and biomarkers for the diagnosis of OSA in ACS patients was evaluated both alone and combined using ROC curves. RESULTS: Several biomarkers showed a significant association with ACS severity, which remained after adjusting for OSA and other potentially confounding variables. The mathematical combination of age, BMI, PlGF and MMP9 showed an area under the ROC curve (AUC) for OSA identification of 0.741, which was greater than any individual parameter or combination assessed: AUC(BMI):0.687, AUC(age):0.576, AUC(PlGF):0.584, AUC(MMP9):0.555. CONCLUSIONS: The usefulness of biomarkers in the assessment of ACS severity was independent of OSA and the other variables evaluated. In patients admitted after a coronary event, the combination of clinical measures and biomarkers showed a significant discriminating power for the detection of OSA. CLINICAL TRIAL REGISTRATION: NCT01335087 (clinicaltrials.gov).

Cell Death Biomarkers and Obstructive Sleep Apnea: Implications in the Acute Coronary Syndrome.

Study Objectives: Nucleosomes and cell-free double-stranded DNA (dsDNA) have been suggested as promising biomarkers in cell death-related diseases, such as acute coronary syndrome (ACS). Currently, the impact of obstructive sleep apnea (OSA) in patients with ACS is unclear. Our aim was to evaluate the relationship between OSA, dsDNA, and nucleosomes and to assess their potential implication in the development of ACS. Methods: Up to 549 patients were included in the study and divided into four groups (145 ACS; 290 ACS + OSA; 62 OSA; 52 controls). All patients underwent a sleep study, and serum concentrations of dsDNA and nucleosomes were measured. Results: Nucleosome and dsDNA levels were higher in patients with OSA than in controls (nucleosomes: 1.47 ± 0.88 arbitary units [AU] vs. 1.00 ± 0.33 AU; p < .001, dsDNA: 315.6 ± 78.0 ng/mL vs. 282.6 ± 55.4 ng/mL; p = .007). In addition, both biomarker levels were higher in patients with ACS than in non-ACS, independently of the presence of OSA. Conclusions: Both nucleosomes and dsDNA are increased in patients with OSA and might be related with the high cardiovascular risk seen in these patients. The extensive cell lysis during a myocardial infarction seems to be the major contributor to the high biomarker levels, and OSA does not seem to be implicated in such elevation when this acute event occurs. Clinical trial registration: NCT01335087 (clinicaltrials.gov).

Hemolysis index to detect degree of hydroxocobalamin interference with common laboratory tests.

BACKGROUND: Cyanokit® (hydroxocobalamin OHCo) is the recommended treatment for cyanide poisoning. OHCo is a red chromophore and may cause interference with some biochemical measurements. In this study, we assessed the possible interference of Cyanokit on several cooximetric and plasma biochemistry tests and then determined the possible mathematical correction for some analytes. We studied the possibility of detecting and evaluating the degree of interference with the hemolysis index (HI) provided by our autoanalyzer because it is not possible to measure the OHCo concentration in conventional laboratories. METHODS: Several pools of plasma samples spiked with increasing concentrations of OHCo were prepared. Each one was compared to the pool without interferent. Interference was considered when the bias was more than 10%. An interferograph was developed for those analytes with significant interference. The correlation between interference agent concentration and HI was calculated by Spearman correlation coefficient. We used multiple regression analysis to determine the mathematical correction for amylase, creatinine, and lactate. RESULTS: We detected significant interference in the amylase, carboxyhemoglobin, creatinine, creatine kinase, bilirubin, lactate, and total protein measurement. The HI was positively correlated with OHCo concentration. Corresponding equations for estimating lactate and creatinine concentrations were obtained. CONCLUSIONS: OHCo interferes with many laboratory assays in an unpredictable way making some results invalid and confounding clinical decision making. We can detect and evaluate the degree of interference with the HI. We can still estimate real creatinine and lactate levels using the regression equation obtained in this study.

Impact of Obstructive Sleep Apnea on the Levels of Placental Growth Factor (PlGF) and Their Value for Predicting Short-Term Adverse Outcomes in Patients with Acute Coronary Syndrome.

BACKGROUND: Placental growth factor (PlGF) induces angiogenesis and promotes tissue repair, and plasma PlGF levels change markedly during acute myocardial infarction (AMI). Currently, the impact of obstructive sleep apnea (OSA) in patients with AMI is a subject of debate. Our objective was to evaluate the relationships between PlGF levels and both the severity of acute coronary syndrome (ACS) and short-term outcomes after ACS in patients with and without OSA. METHODS: A total of 538 consecutive patients (312 OSA patients and 226 controls) admitted for ACS were included in this study. All patients underwent polygraphy in the first 72 hours after hospital admission. The severity of disease and short-term prognoses were evaluated during the hospitalization period. Plasma PlGF levels were measured using an electrochemiluminescence immunoassay. RESULTS: Patients with OSA were significantly older and more frequently hypertensive and had higher BMIs than those without OSA. After adjusting for age, smoking status, BMI and hypertension, PlGF levels were significantly elevated in patients with OSA compared with patients without OSA (19.9 pg/mL, interquartile range: 16.6-24.5 pg/mL; 18.5 pg/mL, interquartile range: 14.7-22.7 pg/mL; p<0.001), and a higher apnea-hypopnea index (AHI) was associated with higher PlGF concentrations (p<0.003). Patients with higher levels of PlGF had also an increased odds ratio for the presence of 3 or more diseased vessels and for a Killip score>1, even after adjustment. CONCLUSIONS: The results of this study show that in patients with ACS, elevated plasma levels of PlGF are associated with the presence of OSA and with adverse outcomes during short-term follow-up. TRIAL REGISTRATION: ClinicalTrials.gov NCT01335087.

xCELLigence system for real-time label-free monitoring of growth and viability of cell lines from hematological malignancies.

The xCELLigence system is a new technological approach that allows the real-time cell analysis of adherent tumor cells. To date, xCELLigence has not been able to monitor the growth or cytotoxicity of nonadherent cells derived from hematological malignancies. The basis of its technology relies on the use of culture plates with gold microelectrodes located in their base. We have adapted the methodology described by others to xCELLigence, based on the pre-coating of the cell culture surface with specific substrates, some of which are known to facilitate cell adhesion in the extracellular matrix. Pre-coating of the culture plates with fibronectin, compared to laminin, collagen, or gelatin, significantly induced the adhesion of most of the leukemia/lymphoma cells assayed (Jurkat, L1236, KMH2, and K562). With a fibronectin substrate, nonadherent cells deposited in a monolayer configuration, and consequently, the cell growth and viability were robustly monitored. We further demonstrate the feasibility of xCELLigence for the real-time monitoring of the cytotoxic properties of several antineoplastic agents. In order to validate this technology, the data obtained through real-time cell analysis was compared with that obtained from using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. This provides an excellent label-free tool for the screening of drug efficacy in nonadherent cells and discriminates optimal time points for further molecular analysis of cellular events associated with treatments, reducing both time and costs.