Association of plasma fatty acid-binding protein 3 with estimated glomerular filtration rate in patients with type 2 diabetes mellitus.

Background: Fatty acid-binding protein 3 (FABP3) located in renal mesangial and distal tubular cells, and had been shown to be a sensitive marker of renal injury, potentially be a mediator in pathogenesis of chronic kidney disease (CKD). Our previous study revealed that plasma FABP1 and FABP2 were independently associated with CKD, however, little is known about the relationship between plasma FABP3 level and CKD. The aim of this study was therefore to evaluate the plasma levels of FABP3 at different stages of estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 334 subjects with T2DM who enrolled in a disease management program were included in this study and stratified according to eGFR. Plasma FABP3 concentrations were measured by an enzyme-linked immunosorbent assay. Results: FABP3 levels increased in parallel with the eGFR level. Increasing concentrations of FABP3 were independently and significantly associated with eGFR stage G2-G4. Age- and sex-adjusted FABP3 levels were positively associated with uric acid, urinary albumin-to-creatinine ratio, FABP1, FABP2, and fatty liver index, but negatively associated with eGFR and hemoglobin. Conclusion: Our results indicate that circulating FABP3 in patients with T2DM is associated with eGFR, which suggests that increased plasma FABP3 may be involved in the pathogenesis of CKD.

The differential diagnostic value of selected cardiovascular biomarkers in Takotsubo syndrome.

INTRODUCTION: Takotsubo syndrome (TTS) is clinically indistinguishable from an acute coronary syndrome (ACS). In the absence of valid markers for differential diagnosis, coronary angiography has been indispensable. METHODS: In our study, we evaluated the serum levels of sST-2, GDF-15, suPAR and H-FABP in 92 patients with the suspicion of TTS (51 TTS and 41 ACS patients) and 40 gender matched controls (no coronary artery disease or signs of heart failure) at baseline. RESULTS: H-FABP was significantly higher in ACS patients compared to TTS patients. Even in in propensity score matching for left ventricular ejection fraction, sex and cardiovascular risk factors, differences in the plasma levels of H-FABP in the matched cohort of TTS vs ACS remained statistically significant. Whereas, sST-2 was significantly elevated in TTS patients. H-FABP was superior for prediction of an ACS with even higher accuracy than hs troponin in differential diagnosis (AUC 0.797, p ≤ 0.0001); the optimal cut off for discrimination towards a TTS was calculated as 2.93 ng/ml (sensitivity 70.0%, specificity 82.4%, PPV 75.7%, NPV 77.4%). sST-2 seemed most appropriate for identification of a TTS (AUC 0.653, p = 0.012). The optimal cut off for differential diagnosis was 11018.06 pg/ml (sensitivity 82.0%, specificity 51.2%, PPV 69.4%, NPV 71.9 %). CONCLUSION: H-FABP and sST-2 are the most promising markers with better accuracy than preexisting biomarkers in differential diagnosis in our study and therefore, could be crucial for the guidance of treatment in patients with high bleeding risk, advanced renal failure or multimorbidity.

Determination of 97.5th and 99th percentile upper reference limits for heart-type fatty acid-binding protein (H-FABP) in a US population.

BACKGROUND: Heart-type fatty acid binding protein (H-FABP), a low molecular weight protein found primarily in myocardial tissue, has been identified as a potential biomarker in the detection of acute coronary syndrome and acute kidney injury. To further investigate clinical utility, we sought to establish an upper reference limit (URL) of H-FABP within a healthy U.S. METHODS: Serum samples of healthy donors were acquired from the AACC Universal Sample Bank. We analyzed 355 samples for H-FABP concentration using the Randox Laboratories immunoturbidimetric assay on the Roche Cobas 8000 series analyzer. RESULTS: The final sample population consisted of individuals aged 18-74 y, with 170 males and 185 females. The distribution of the population exhibited a strong positive skew, affecting outlier analysis and URL determination. The 97.5th-percentile URL was found to be 7.4 ng/ml (95% CI: 6.3-9.2), while the 99th-percentile URL was 12.1 ng/ml (8.6-14.9). CONCLUSION: As the URL for H-FABP is highly affected by population distribution and outlier removal, final determination for an assay cutoff should be made in the context of clinical utility, either as a standalone assay or in conjunction with other biomarkers, and the desired clinical sensitivity and specificity.

Fatty Acid-Binding Protein 3 and CXC-Chemokine Ligand 16 are Associated with Unfavorable Outcome in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with activation of the inflammatory cascade contributing to unfavorable outcome and secondary complications, such as delayed cerebral ischemia (DCI). Both fatty acid-binding protein 3 (FABP3) and CXC-chemokine ligand 16 (CXCL-16) have been linked to vascular inflammation and cellular death. The authors aimed to assess the 30-day prognostic value of serum levels of FABP3 and CXCL-16 and explore their associations with DCI in aSAH patients. METHODS: A total of 60 patients with aSAH were prospectively enrolled. Sampling for markers was done at 24 hours after the index event. FABP3 and CXCL-16 serum concentrations were determined by MilliPlex multiplex immunoassay method. The primary endpoint was unfavorable outcome at Day 30 based on the modified Rankin Scale. RESULTS: Both FABP3 and CXCL-16 levels were significantly elevated in patients with unfavorable outcome compared to those with favorable outcome after aSAH (FABP3: 2133 pg/mL, IQR: 1053-4567 vs. 3773, 3295-13116; p<0.003 and CXCL-16: 384 pg/mL, 313-502 vs. 498, 456-62, p<0.001). The area under the curve (AUC) for serum CXCL-16 levels as a predictor of unfavorable outcome at Day 30 was 0.747 (95% CI =0.622-0.871; p<0.001). Based on binary logistic regression analysis, serum CXCL-16 with a cut-off level >446.7 ng/L independently predicted Day 30 unfavorable outcome with a sensitivity of 81% and a specificity of 62%. Neither CXCL-16 nor FABP3 showed a significant correlation with DCI. CONCLUSION: Early FABP3 and CXCL-16 levels are significantly associated with poor 30-day outcome in patients with aSAH.

Changes of Certain Metabolic and Cardiovascular Markers Fructosamine, H-FABP and Lipoprotein (a) in Patients with Hypothyroidism.

BACKGROUND: Disorders of thyroid gland are common in general population, and it's the most common affecting the endocrine system after diabetes mellitus. Thyroid function regulates a wide range of metabolic parameters, as well as affects some cardiovascular disease risk factors. Fructosamine is produced by a reaction between albumin (protein) and glucose; it is used to monitor patients with diabetes for short-term glycemic changes. H-FABP is present in the cytoplasm of cardiac myocytes, and delivers fatty acids into these cells. It has been shown to increase in myocardial injury. Lipoprotein LP(a) is consist of a special apolipoprotein called apoprotein (a), and it's recognized as a cardiovascular disease independent risk factor. OBJECTIVE: To study whether certain metabolic and cardiovascular markers (fructosamine, H-FABP and lipoprotein (a) are changed in hypothyroid patients. METHODS: The current study included 280 overt hypothyroid, 272 with subclinical hypothyroidism compared with 270 healthy individuals of matched age and gender. For all subjects serum (TSH, T4, T3, FBS, HbA1c, fructosamine, triglycerides, cholesterol, lipoprotein (a), and Heart-type Fatty Acid-Binding Protein (H-FABP)) was measured. RESULTS: Serum fructosamine level significantly elevated (p value <0.05) in patient with hypothyroidism when compared with control group, and no significant change between subclinical and control groups. There is no significant change in serum H-FABP between study subjects. There is significant increase in lipoprotein (a) in patient with hypothyroidism and those with subclinical group when compared with control group. CONCLUSION: Serum fructosamine and level is significantly changed in patients with overt hypothyroidism when compared with euthyroid subjects. Also, we conclude that hypothyroidism increase risk of cardiovascular diseases by changing non-traditional marker such as lipoprotein (a), and no effect on H-FABP concentration.

Electrochemical immunosensor development based on core-shell high-crystalline graphitic carbon nitride@carbon dots and Cd0.5Zn0.5S/d-Ti3C2Tx MXene composite for heart-type fatty acid-binding protein detection.

Acute myocardial infarction (AMI) is a significant health problem owing to its high mortality rate. Heart-type fatty acid-binding protein (h-FABP) is an important biomarker in the diagnosis of AMI. In this work, an electrochemical h-FABP immunosensor was developed based on Cd0.5Zn0.5S/d-Ti3C2Tx MXene (MXene: Transition metal carbide or nitride) composite as signal amplificator and core-shell high-crystalline graphitic carbon nitride@carbon dots (hc-g-C3N4@CDs) as electrochemical sensor platform. Firstly, a facile calcination technique was applied to the preparation of hc-g-C3N4@CDs and immobilization of primary antibody was performed on hc-g-C3N4@CDs surface. Then, the conjugation of the second antibody to Cd0.5Zn0.5S/d-Ti3C2Tx MXene was carried out by strong π-π and electrostatic interactions. The prepared electrochemical h-FABP immunosensor was characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), x-ray diffraction (XRD) method, Fourier-transform infrared spectroscopy (FTIR), x-ray photoelectron spectroscopy (XPS), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The prepared electrochemical h-FABP immunosensor indicated a good sensitivity with detection limit (LOD) of 3.30 fg mL-1 in the potential range +0.1 to +0.5 V. Lastly, low-cost, satisfactory stable, and environmentally friendly immunosensor was presented for the diagnosis of acute myocardial infarction.

Elevated plasma fatty acid-binding protein 3 is related to prolonged corrected QT interval and reduced ejection fraction in patients with stable angina.

Background: Higher concentrations of plasma fatty acid-binding protein 3 (FABP3) play a role in the development of cardiovascular events, cerebrovascular deaths, and acute heart failure. However, little is known about the relationship between plasma FABP3 level and prolonged QT interval and reduced ejection fraction (EF). This study aimed to investigate the relationship between plasma FABP3 level and prolonged corrected QT (QTc) interval and reduced EF in patients with stable angina. Inflammatory cytokine and adipocytokine levels were also measured to investigate their associations with plasma FABP3. Methods: We evaluated 249 consecutive patients with stable angina. Circulating levels of FABP3 were measured by ELISA. In addition, 12-lead ECG and echocardiography recordings were obtained from each patient. Results: Multiple regression analysis showed that high-density lipoprotein cholesterol, high sensitivity C-reactive protein (hs-CRP), white blood cell (WBC) count, visfatin, adiponectin, FABP4, heart rate, QTc interval, left atrial diameter, left ventricular mass index, end-systolic volume, end-systolic volume index, fractional shortening, and EF were independently associated with FABP3 (all p<0.05). Patients with an abnormal QTc interval had a higher median plasma FABP3 level than those with a borderline and normal QTc interval. With increasing FABP3 tertiles, the patients had higher frequencies of abnormal QTc interval, left ventricular systolic dysfunction, and all-cause mortality, incrementally lower EF, higher WBC count, and higher levels of hs-CRP, visfatin, adiponectin, and FABP4. Conclusion: This study indicates that plasma FABP3 may act as a surrogate parameter of prolonged QTc interval and reduced EF in patients with stable angina, partially through the effects of inflammation or cardiomyocyte injury. Further studies are required to elucidate whether plasma FABP3 plays a role in the pathogenesis of QTc prolongation and reduced EF.

Prognostic value of serum heart-type fatty acid-binding protein in patients with sepsis: A protocol for systematic review and meta-analysis.

BACKGROUND: Sepsis is commonly acute and critical illness with high morbidity and high mortality, and requires timely diagnosis and treatment. Septic patients had elevated serum H-FABP levels, which may correlate with disease severity and mortality. However, previous studies showed that the association between H-FABP and mortality during the sepsis remains unclear. Thus, we performed a study to analyze this relationship. METHODS: The electronic databases such as Cochrane Library, PubMed, Embase, Web of Science, Cochrane Clinical Trials Database, Wanfang Database, and China National knowledge Infrastructure (CNKI) were systematically searched to determine the qualified clinical trials. The study language is limited to English or Chinese. The 2 authors used Cochrane Risk of Bias Tool v.2.0 to independently check the quality of papers and extract relevant data. Comprehensive analysis of data extracted in the research using appropriate statistical methods. RESULTS: Evaluation of the relationship between the prognosis of patients with sepsis and serum H-FABP is the result of this study. CONCLUSION: The analysis results of this study can infer that H-FABP may be an independent risk factor for the prognosis of patients with sepsis. It is also helpful for clinical workers to make early evaluation and early treatment of patients with sepsis. ETHICS AND DISSEMINATION: The conclusions of this meta-analysis study are based on the published evidence. Therefore, moral recognition is unnecessary. OSF REGISTRATION NUMBER: DOI: 10.17605/ OSF.IO / 2V4HN.(https://osf.io/2v4hn/).

Variability in Cardiac Biomarkers during Hemodialysis: A Prospective Cohort Study.

BACKGROUND: The effect of hemodialysis on cardiac biomarkers is unclear. We sought to evaluate the degree and causes of intradialytic variability of high sensitivity troponin I (hs-TnI), galectin-3 (gal-3), and heart-type fatty acid binding protein (hFABP). METHODS: hs-TnI, gal-3, and hFABP were prospectively measured pre-dialysis and post-dialysis for 1 week every month for 6 months in 178 prevalent adult hemodialysis patients at a single center in Hamilton, Canada. The degree of change from pre-dialysis to post-dialysis for each cardiac biomarker was estimated with multilevel linear regression models. RESULTS: The median change in the concentration of hs-TnI during hemodialysis was -1 ng/L (interquartile range [IQR] -1 to 2 ng/L) while gal-3 and hFABP changed by -36.3 ng/mL (IQR -27.7 to -46.8 ng/mL) and -19.41 ng/mL (IQR -13.61 to -26.87 ng/mL), respectively. The median (IQR) percentage intradialytic changes for hs-TnI, gal-3, and hFABP were 2.6% (-4.4% to 12.5%), -59.8% (-54.7% to -64.8%) and -35.3% (-28.4% to -42.1%), respectively. Ultrafiltration was associated with an increase in concentration of hs-TnI, gal-3, and hFABP (mean 0.99 ng/L, 1.05 ng/mL, and 1.9 ng/mL per L ultrafiltration, respectively, P < 0.001). Both gal-3 and hFABP concentrations decreased in association with the volume of blood processed (P < 0.001) and with hemodialysis treatment time (P = 0.02 and P = 0.04) while hs-TnI concentration decreased only in association with hemodialysis treatment time (P < 0.001). CONCLUSIONS: Ultrafiltration volume and hemodialysis treatment time influenced hs-TnI, gal-3, and hFABP concentrations during hemodialysis and should be considered when interpreting their measurement.

Myokines in treatment-naïve patients with cancer-associated cachexia.

Cancer-associated cachexia is a complex metabolic syndrome characterized by weight loss and systemic inflammation. Muscle loss and fatty infiltration into muscle are associated with poor prognosis in cancer patients. Skeletal muscle secretes myokines, factors with autocrine, paracrine and/or endocrine action, which may be modified by or play a role in cachexia. This study examined myokine content in the plasma, skeletal muscle and tumor homogenates from treatment-naïve patients with gastric or colorectal stages I-IV cancer with cachexia (CC, N = 62), or not (weight stable cancer, WSC, N = 32). Myostatin, interleukin (IL) 15, follistatin-like protein 1 (FSTL-1), fatty acid binding protein 3 (FABP3), irisin and brain-derived neurotrophic factor (BDNF) protein content in samples was measured with Multiplex technology; body composition and muscle lipid infiltration were evaluated in computed tomography, and quantification of triacylglycerol (TAG) in the skeletal muscle. Cachectic patients presented lower muscle FSTL-1 expression (p = 0.047), higher FABP3 plasma content (p = 0.0301) and higher tumor tissue expression of FABP3 (p = 0.0182), IL-15 (p = 0.007) and irisin (p = 0.0110), compared to WSC. Neither muscle TAG content, nor muscle attenuation were different between weight stable and cachectic patients. Lumbar adipose tissue (AT) index, visceral AT index and subcutaneous AT index were lower in CC (p = 0.0149, p = 0.0455 and p = 0.0087, respectively), who also presented lower muscularity in the cohort (69.2% of patients; p = 0.0301), compared to WSC. The results indicate the myokine profile in skeletal muscle, plasma and tumor is impacted by cachexia. These findings show that myokines eventually affecting muscle wasting may not solely derive from the muscle itself (as the tumor also may contribute to the systemic scenario), and put forward new perspectives on cachexia treatment targeting myokines and associated receptors and pathways.

Acute kidney injury risk in orthopaedic trauma patients pre and post surgery using a biomarker algorithm and clinical risk score.

Acute kidney injury (AKI) after major trauma is associated with increased mortality. The aim of this study was to assess if measurement of blood biomarkers in combination with clinical characteristics could be used to develop a tool to assist clinicians in identifying which orthopaedic trauma patients are at risk of AKI. This is a prospective study of 237 orthopaedic trauma patients who were consecutively scheduled for open reduction and internal fixation of their fracture between May 2012 and August 2013. Clinical characteristics were recorded, and 28 biomarkers were analysed in patient blood samples. Post operatively a combination of H-FABP, sTNFR1 and MK had the highest predictive ability to identify patients at risk of developing AKI (AUROC 0.885). Three clinical characteristics; age, dementia and hypertension were identified in the orthopaedic trauma patients as potential risks for the development of AKI. Combining biomarker data with clinical characteristics allowed us to develop a proactive AKI clinical tool, which grouped patients into four risk categories that were associated with a clinical management regime that impacted patient care, management, length of hospital stay, and efficient use of hospital resources.

Reaming of femoral fractures with different reaming irrigator aspirator systems shows distinct effects on cardiac function after experimental polytrauma.

Cardiac injuries are recorded after multiple trauma and are associated with a poor patient outcome. Reaming prior to locked intramedullary nailing is a frequently used technique to stabilize femoral diaphysis fractures. However, in polytraumatized patients, complications such as fat emboli and acute respiratory distress syndrome have been associated with reaming. The reaming irrigator aspirator (RIA) system provides concomitant irrigation and suction of the intramedullary contents, and should, therefore, reduce reaming-associated complications. The aim of the study was to investigate cardiac function after multiple trauma with regard to two different RIA devices (RIAI vs RIAII). 15 male pigs were included in the study. Pigs received either sham treatment or multiple trauma (chest trauma, femur fracture, liver laceration, and hemorrhagic shock), followed by intramedullary nailing after reaming with either the RIAI or RIAII system (RIAII: reduced diameter of the reamer, improved control of irrigation and suction). Cardiac function was assessed by transesophageal echocardiography and systemic inflammation as well as local cardiac damage examined. Pigs of both treatment groups showed impaired cardiac function, valvular insufficiency, and cardiac damage. Systemic inflammation and local cardiac alterations were observed which might contribute to early myocardial damage in vivo. Multiple trauma including long-bone fracture and subsequent intramedullary reaming induces cardiac dysfunction and valvular insufficiency, which might be linked to both mechanical cardiac injury and increased systemic inflammation. 6 hours after trauma there are less differences between RIAI and RIAII treatment with regard to post-traumatic cardiac consequences in multiple injured pigs, indicating no beneficial effect of RIAII over RIAI.

Heart-type fatty acid-binding protein: an overlooked cardiac biomarker.

Cardiac troponins (cTn) are currently the standard of care for the diagnosis of acute coronary syndromes (ACS) in patients presenting to the emergency department (ED) with chest pain (CP). However, their plasma kinetics necessitate a prolonged ED stay or overnight hospital admission, especially in those presenting early after CP onset. Moreover, ruling out ACS in low-risk patients requires prolonged ED observation or overnight hospital admission to allow serial measurements of c-Tn, adding cost. Heart-type fatty acid-binding protein (H-FABP) is a novel marker of myocardial injury with putative advantages over cTn. Being present in abundance in the myocellular cytoplasm, it is released rapidly (<1 h) after the onset of myocardial injury and could potentially play an important role in both earlier diagnosis of high-risk patients presenting early after CP onset, as well as in risk-stratifying low-risk patients rapidly. Like cTn, H-FABP also has a potential role as a prognostic marker in other conditions where the myocardial injury occurs, such as acute congestive heart failure (CHF) and acute pulmonary embolism (PE). This review provides an overview of the evidence examining the role of H-FABP in early diagnosis and risk stratification of patients with CP and in non-ACS conditions associated with myocardial injury. Key messages Heart-type fatty acid-binding protein is a biomarker that is elevated early in myocardial injury The routine use in the emergency department complements the use of troponins in ruling out acute coronary syndromes in patients presenting early with chest pain It also is useful in risk stratifying patients with other conditions such as heart failure and acute pulmonary embolism.

Serum Heart Type Fatty Acid Binding Protein Levels in Prediabetes-An Invaluable Cardiovascular Biomarker.

BACKGROUND: The pathophysiological effects of diabetes on the heart and the rest of the cardiovascular system begins much earlier in its precedent stage of prediabetes and one major underlying defect is insulin resistance. Heart-type fatty acid binding protein (H-FABP) is a recently studied molecule inherent to the cardiac myocytes found to rise in both coronary and non-coronary heart diseases. The utility of the molecule in prediabetes and its relationship with insulin resistance is being studied. OBJECTIVE: The aim of the study is to compare serum levels of H-FABP in prediabetics and controls and correlate them with Homeostatic model assessment - insulin resistance (HOMA-IR). METHODS: 50 prediabetic patients and 50 age, sex and BMI matched controls were employed in the case control study. Serum fasting and postprandial blood sugars, glycosylated hemoglobin (HbA1c), fasting insulin levels were measured in cases and controls. HOMA-IR index was calculated from fasting glucose and insulin values. Serum H-FABP was measured in both cases and controls using Immunoturbidimetric method with anti- H-FABP coated latex reagent kits. The values were compared between both the groups. RESULTS: The mean serum fasting insulin level among cases was 12.22mIU/ml and that of the control group was 5.37mIU/ml (p value <0.0001). HOMA- IR mean values were 3.31 ± 1.56 and 1.16 ± 0.44 in cases and controls respectively (p- <0.001). The mean serum levels of H-FABP among cases and controls were 6.38± 2.76ng/ml and 3.24 ± 2.47 ng/ml respectively (p <0.0001). The correlation between the two variables, HOMA-IR and H-FABP was also found to be strongly positive (r=0.675). Linear regression analysis showed that for 1 unit increase in HOMA-IR, H-FABP increased by 1.095 and for 1 unit increase in Fasting insulin, H-FABP increased by 0.038. CONCLUSION: Prediabetics have a higher risk of cardiovascular morbidity when compared to normoglycemics with insulin resistance being the single most important contributor. Serum H-FABP levels are elevated in prediabetes representing a marker of subclinical cardiovascular disease (CVD).

Evaluation of the cardioprotective effects of crystalloid del Nido cardioplegia solution via a rapid and accurate cardiac marker: heart-type fatty acid-binding protein

Background/aim: Our aim in this study was to compare the efficacy and safety of crystalloid del Nido solution and cold blood cardioplegia solution on clinical and laboratory parameters. Materials and methods: Sixty patients who underwent elective coronary bypass operation between July 2019 and January 2020 were included in our study. Patients were divided into 2 groups of 30 patients using del Nido solution (DNS) and cold blood cardioplegia solution (CBCS), which were given for cardiac arrest. Demographic data, preoperative, postoperative 0th h, 6th h and 4th day creatine kinase myocardial band (CK-MB) and troponin I values were compared with a specific cardiac enzyme heart-type fatty acid-binding protein (H-FABP). Results: We found that aortic cross clamp duration and cardiopulmonary bypass (CPB) time were shorter in patients using del Nido solution than cold blood cardioplegia solution (57.30 ± 23.57 min, 76.07 ± 27.18 min, P = 0.006) (95.07 ± 23.06 min, 114.13 ± 33.93, P = 0.014). Total cardioplegia solution volume was higher in the cold blood cardioplegia solution group (1426.67 ± 416.00 vs. 1200 ± 310.73 P = 0.02). Preoperative and postoperative levels of cardiac enzymes including CK-MB, troponin I and H-FABP were comparable in del Nido solution and cold blood cardioplegia solution groups. Conclusion: According to these results, when we compare both demographic data and CK-MB, troponin I and H-FABP levels, both cardioplegia solutions were comparable regarding safety and efficacy in terms of myocardial protection.

Dynamic Changes of Heart Failure Biomarkers in Response to Parabolic Flight.

BACKGROUND: we aimed at investigating the influence of weightlessness and hypergravity by means of parabolic flight on the levels of the heart failure biomarkers H-FABP, sST2, IL-33, GDF-15, suPAR and Fetuin-A. METHODS: 14 healthy volunteers (males: eight; mean age: 28.9) undergoing 31 short-term phases of weightlessness and hypergravity were included. At different time points (baseline, 1 h/24 h after parabolic flight), venous blood was drawn and analyzed by the use of ELISA. RESULTS: sST2 evidenced a significant decrease 24 h after parabolic flight (baseline vs. 24, p = 0.009; 1 h vs. 24 h, p = 0.004). A similar finding was observed for GDF-15 (baseline vs. 24 h, p = 0.002; 1 h vs. 24 h, p = 0.025). The suPAR showed a significant decrease 24 h after parabolic flight (baseline vs. 24 h, p = 0.1726; 1 h vs. 24 h, p = 0.009). Fetuin-A showed a significant increase at 1 h and 24 h after parabolic flight (baseline vs. 24 h, p = 0.007; 1 h vs. 24 h, p = 0.04). H-FABP and IL-33 showed no significant differences at all time points. CONCLUSION: Our results suggest a reduction in cardiac stress induced by exposure to gravitational changes. Moreover, our findings indicate an influence of gravitational changes on proliferative processes and calcium homeostasis.

Correlation between Heart fatty acid binding protein and severe COVID-19: A case-control study.

BACKGROUND: Heart-fatty acid binding protein (HFABP) has been recognized as a highly heart-specific marker. However, it is currently unknown that its HFABP is also closely related to the severity of COVID-19. METHODS: We retrospectively screened 46 patients who met our inclusion criteria within 4 weeks. They were tested for HFABP after the diagnosis of COVID-19, and monitored for HFABP during their hospital stay. We tracked the patients during their hospital stay to determine if they had severe COVID-19 or mild-to-severe transition features. We calculated the chi-square test values found for HFABP to predict the correlation between HFABP levels and the severity of the COVID-19. RESULTS: Of these 46 cases, 16 cases with confirmed COVID-19 were tested for HFABP> 7 ng / mL upon admission; among them, 14 cases were diagnosed with severe COVID-19 within the hospitalization. The Odds ratio of the measured HFABP elevation was 6.81(95% confidence interval [CI] 5.23-8.40), and 3 patients with severe COVID-19 progressed in 5 patients with mild HFABP> 7 ng/mL. CONCLUSION: These data indicate that the elevation of HFABP is closely related to the severity of COVID-19 in the patients, and the elevated HFABP may cause rapid development of patients with mild COVID-19 into severe COVID-19. But serum HFABP negative maybe make patients with mild COVID-19 safer, the current data show no effect on the all-cause mortality. TRIAL REGISTRATION: Our study has been registered with the Chinese Clinical Trial Registry, the registration number: ChiCTR2000029829.

Circulating miRNA-21 as a diagnostic biomarker in elderly patients with type 2 cardiorenal syndrome.

Circulating miRNAs have attracted attention as serum biomarkers for several diseases. In this study, we aimed to evaluate the diagnostic value of circulating miRNA-21 (miR-21) as a novel biomarker for elderly patients with type 2 cardiorenal syndrome (CRS-2). A total of 157 elderly patients with chronic heart failure (CHF) were recruited for the study. According to an estimated glomerular filtration rate (eGFR) cut-off of 60 ml/min/1.73 m2, 84 patients (53.5%) and 73 patients (46.5%) were assigned to the CRS group and the CHF group, respectively. Expression levels of serum miR-21 and biomarkers for CRS, such as kidney injury factor-1 (KIM-1), neutrophil gelatinase-related apolipoprotein (NGAL), cystatin C (Cys C), amino-terminal pro-B-type natriuretic peptide (NT-proBNP), N-acetyl-κ-D-glucosaminidase (NAG), and heart-type fatty acid-binding protein (H-FABP), were detected. Serum miR-21, KIM-1, NGAL, Cys C, NT-proBNP and H-FABP levels were significantly higher in the CRS group than in the CHF group (P < 0.01), whereas NAG expression was not significantly different between the two groups (P > 0.05). Cys C, H-FABP and eGFR correlated significantly with miR-21 expression, but correlations with miR-21 were not significant for NT-proBNP, NGAL, NAG and KIM-1. Moreover, multivariate logistic regression found that serum miR-21, increased serum Cys C, serum KIM-1, hyperlipidaemia and ejection fraction (EF) were independent influencing factors for CRS (P < 0.05). The AUC of miR-21 based on the receiver operating characteristic (ROC) curve was 0.749, with a sensitivity of 55.95% and a specificity of 84.93%. Furthermore, combining miR-21 with Cys C enhanced the AUC to 0.902, with a sensitivity of 88.1% and a specificity of 83.6% (P < 0.001). Our findings suggest that circulating miR-21 has medium diagnostic value in CRS-2. The combined assessment of miR-21 and Cys C has good clinical value in elderly patients with CRS-2.

Prognostic utility of heart-type fatty acid-binding protein in patients with stable coronary artery disease and impaired glucose metabolism: a cohort study.

BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is a novel marker of myocardial injury and has been reported to be associated with cardiovascular diseases (CVD) including patients with diabetes mellitus (DM). Unfortunately, its prognostic value in patients with CVD and impaired glucose metabolism (IGM) is unclear. The objective of this study was to investigate the prognostic value of H-FABP in CVD patients with IGM. METHODS: A total of 4594 patients with angiography-proven coronary artery disease (CAD) were enrolled and divided into subgroup according to glucose metabolism status (normal glucose regulation [NGR], pre-DM, and DM). Baseline levels of H-FABP were measured using latex immunoturbidimetric method. The cardiovascular events (CVE) were defined as cardiovascular death, myocardial infarction, stroke and coronary revascularization. Cox regression and Kaplan-Meier analysis were used to evaluate the relations of H-FABP and glucose metabolism status to CVEs. RESULTS: During the follow-up period with up to 7.1 years, 380 CVEs occurred. Patients with CVE had higher levels of H-FABP compared to those without CVE (p < 0.001). Interestingly, H-FABP levels were also elevated in DM and pre-DM groups compared with NGR group (p < 0.001), when combined glucose metabolism status with H-FABP stratification, patients in the highest tertile of H-FABP appeared to have higher risk of CVEs with pre-DM (adjusted hazard ratio [HR]: 1.855, 95% confidential intervals [CIs] 1.076-3.214; p = 0.033) and DM (adjusted HR: 2.560, 95% CIs 1.409-4.650; p = 0.002). The Kaplan-Meier curve indicated that DM patients with the highest H-FABP levels were associated with the greatest risk of CVEs (p < 0.05). CONCLUSIONS: Our data firstly showed that elevated H-FABP levels were associated with worse outcomes in CAD patients with pre-DM and DM, which provided the novel information that H-FABP might be a prognostic marker for clinical outcomes among patients with CAD and IGM.

Analysis of Novel Cardiovascular Biomarkers in Patients With Pulmonary Hypertension (PH).

BACKGROUND: Due to the non-specific clinical presentation of patients with pulmonary hypertension (PH), diagnosis is often delayed, consequently resulting in limited therapeutic success and an impaired prognosis. In this trial, we analysed the plasma concentrations of novel cardiovascular biomarkers that reflect different pathobiological pathways (sST2: soluble suppression of tumorigenicity 2, H-FABP: heart type fatty acid binding protein, suPAR: soluble urokinase plasminogen activator receptor and GDF-15: growth-differentiation factor-15) potentially involved in PH associated vascular and right ventricular remodelling. Thus, these markers could contribute to the development of a non-invasive approach for diagnosis and therapy surveillance of PH patients in the future. METHODS: In total, we enrolled 162 patients in this single-centre retrospective analysis consisting of 88 patients suffering from PH and 74 controls. The latter were admitted for elective coronary angiography and coronary artery disease was excluded. Plasma samples of all patients were obtained and analysed for sST2, H-FABP, GDF-15 and suPAR serum concentrations by means of enzyme-linked immunosorbent assay (ELISA) kits (DuoSet ELISA, DY523B, DY957, DY807, DGAL30, R&D Systems, Minneapolis, MN, USA) after obtaining informed consent. RESULTS: Compared with controls, all of the investigated biomarkers were significantly elevated in patients with pulmonary hypertension (H-FABP median 3.5 ng/ml vs. median 0.0 ng/ml, p < 0.001; sST2 median 6364.6 pg/ml vs. median 5015.9 pg/ml, p = 0.004; GDF-15 median 1829.3 pg/ml vs. median 514.1 pg/ml, p < 0.001; suPAR median 4878.7 pg/ml vs. median 2227.0 pg/ml, p < 0.001). Interestingly, we found a significant difference in the biomarker concentrations of H-FABP, GDF-15 and suPAR between the five groups of pulmonary hypertension. In fact, we found that H-FABP levels were primarily elevated in group 2 and 3 PH, whereas the concentrations of GDF-15 and suPAR were primarily associated with pulmonary hypertension due to left sided heart disease (group 2). CONCLUSIONS: While sST2 constitutes a general biomarker of pulmonary hypertension regardless of the subtype, H-FABP, GDF-15 and suPAR represent indicators of postcapillary PH. Thereby, they could constitute potential discriminators between pre- and postcapillary PH.