Novel biomarkers with potential for cardiovascular risk reclassification

Precise estimation of the absolute risk for CVD events is necessary when making treatment recommendations for patients. A number of multivariate risk models have been developed for estimation of cardiovascular risk in asymptomatic individuals based upon assessment of multiple variables. Due to the inherent limitation of risk models, several novel risk markers including serum biomarkers have been studied in an attempt to improve the cardiovascular risk prediction above and beyond the established risk factors. In this review, we discuss the role of underappreciated biomarkers such as red cell distribution width (RDW), cystatin C (cysC), and homocysteine (Hcy) as well as imaging biomarkers in cardiovascular risk reclassification, and highlight their utility as additional source of information in patients with intermediate risk.     

BMI and waist circumference in predicting cardiovascular risk factor clustering in Chinese adolescents

Objective: To derive the optimal BMI and waist circumference (WC) cut‐off values to predict clustering of cardiovascular risk factors in Hong Kong Chinese adolescents. Research Methods and Procedures: A total of 2102 Hong Kong Chinese 12 to 19 years of age were recruited. Participants were considered to have clustering of risk factors if at least three of the following risk factors were present: 1) high‐density lipoprotein cholesterol (HDL‐C) ≤1.03 mM, 2) low‐density lipoprotein cholesterol (LDL‐C) ≥2.6 mM, 3) triglyceride (TG) ≥1.24 mM, 4) fasting plasma glucose (FPG) ≥6.1 mM, and 5) age‐, sex‐, and height‐adjusted systolic or diastolic blood pressure (BP) ≥ 90th percentile. Receiver operating characteristics (ROC) curves were generated to identify the optimal age‐adjusted BMI and WC cut‐off values to predict clustering of risk factors in boys and girls separately. These age‐adjusted BMI and WC cut‐offs were transformed to percentile values. Cole's lambda‐mu‐sigma (LMS) method was used to obtain smoothed age‐specific BMI and WC at these percentile values. Results: The areas under ROC curves for BMI in girls and boys were 0.85 [95% confidence interval (CI), 0.77 to 0.92] and 0.76 (95% CI, 0.66 to 0.85), respectively. The respective areas under ROC curves for WC in girls and boys were 0.82 (95% CI, 0.74 to 0.91) and 0.78 (95% CI, 0.68 to 0.87). The optimal BMI thresholds were at the 78th percentile for girls and the 72nd percentile for boys. The respective values for WC were at the 77th percentile for girls and the 76th percentile for boys. The sensitivities and specificities of these cut‐off values ranged from 72% to 80%. Discussion: Age‐ and sex‐specific BMI and WC cut‐off values can be used to identify adolescents with clustering of cardiovascular risk factors.     

Whole blood glutathione peroxidase and erythrocyte superoxide dismutase activities, serum trace elements (Se, Cu, Zn) and cardiovascular risk factors in subjects from the city of Ponta Delgada, Island of San Miguel, The Azores Archipelago, Portugal

Activities of whole blood glutathione peroxidase (GSH-Px) and erythrocyte superoxide dismutase (SOD) and serum levels of selenium (Se), copper (Cu) and zinc (Zn) were measured in 118 apparently healthy subjects aged 20-60 years from the city of Ponta Delgada, Island of San Miguel, The Azores Archipelago, Portugal. Data were analysed by age/gender, lipid profile and blood pressure as cardiovascular risk factors searching for their relevance when assessing reference values for antioxidant biomarkers. GSH-Px was in the same range, but SOD was significantly lower than in other Portuguese populations. Neither activity differed with gender. GSH-Px activity increased with age, namely in normolipidemic men versus the hyperlipidemic group in which a decrease was observed. This suggests a progressive impairment of GSH-Px with age caused by an enhanced production of oxidant species in hyperlipidemia. GSH-Px was 30% lower in male hypertensives versus normotensives. SOD activity did not relate to age or blood pressure but was 17% higher in the hyperlipidemic men versus the normolipidemic group, suggesting a better antioxidant protection by SOD than by GSH-Px in hyperlipidemia and hypertension. Se was higher in men versus women, particularly in the older subjects, and partly related to hyperlipidemia. Zn levels showed a similar dependency on gender, not related to age or lipid profile. Cu levels were much higher in women than in men in all age or lipid profile classes and decreased in hyperlipidemia. They were lowered with age in both genders, particularly in normolipidemic women. The present research therefore suggests that hyperlipidemia and hypertension do affect antioxidant status and should be considered when assessing antioxidant biomarkers in blood.     

Whole blood glutathione peroxidase and erythrocyte superoxide dismutase activities,serum trace elements (Se,Cu, Zn) and cardiovascular risk factors in subjects from the city of Ponta Delgada,Island of San Miguel,The Azores Archipelago,Portugal

Activities of whole blood glutathione peroxidase (GSH-Px) and erythrocyte superoxide dismutase (SOD) and serum levels of selenium (Se), copper (Cu) and zinc (Zn) were measured in 118 apparently healthy subjects aged 20–60 years from the city of Ponta Delgada, Island of San Miguel, The Azores Archipelago, Portugal. Data were analysed by age/gender, lipid profile and blood pressure as cardiovascular risk factors searching for their relevance when assessing reference values for antioxidant biomarkers. GSH-Px was in the same range, but SOD was significantly lower than in other Portuguese populations. Neither activity differed with gender. GSH-Px activity increased with age, namely in normolipidemic men versus the hyperlipidemic group in which a decrease was observed. This suggests a progressive impairment of GSH-Px with age caused by an enhanced production of oxidant species in hyperlipidemia. GSH-Px was 30% lower in male hypertensives versus normotensives. SOD activity did not relate to age or blood pressure but was 17% higher in the hyperlipidemic men versus the normolipidemic group, suggesting a better antioxidant protection by SOD than by GSH-Px in hyperlipidemia and hypertension. Se was higher in men versus women, particularly in the older subjects, and partly related to hyperlipidemia. Zn levels showed a similar dependency on gender, not related to age or lipid profile. Cu levels were much higher in women than in men in all age or lipid profile classes and decreased in hyperlipidemia. They were lowered with age in both genders, particularly in normolipidemic women. The present research therefore suggests that hyperlipidemia and hypertension do affect antioxidant status and should be considered when assessing antioxidant biomarkers in blood.     

Associations of religious and existential variables with psychosocial factors and biomarkers of cardiovascular risk in bereavement

Bereavement increases in prevalence as people age and is associated with multiple psychological and health risks, including cardiovascular risk. Religious and existential variables may play an important role in the health impacts of bereavement. Theorized pathways linking religious and existential variables with health have suggested these associations are due to intermediary psychosocial variables, but have not been tested in bereavement. This research empirically tested these pathways in a bereaved population. In N = 73 adults within 1 year of bereavement (mean age = 64.36), this study examined associations between (1) religious and existential characteristics (religious and spiritual struggles, intrinsic religiosity, and existential quest) and intermediary psychosocial variables (depression, loneliness, and difficulties in emotion regulation), and between (2) intermediary psychosocial variables and bereavement-relevant health outcomes (self-reported health, change in health since last year, grief severity, and cardiovascular biomarkers). Cardiovascular biomarkers (heart rate, heart rate variability, and blood pressure) were collected before, during, and after a laboratory grief recall emotion elicitation. Anticipated associations between self-reported religious and existential characteristics and intermediary variables, and between intermediary variables and self-reported bereavement-relevant outcomes, were consistently observed. However, associations between intermediary variables and cardiovascular biomarkers were largely unobserved. This study examined the role of religious and existential variables in whole-person health after bereavement and is among the first to include biomarkers of cardiovascular risk. Results suggest that although religious and existential variables are associated with important bereavement-related outcomes, these associations may be “skin-deep,” and extensions to cardiovascular functioning should be re-examined.     

Proteomic analysis of traumatic brain injury: the search for biomarkers

Although there are a number of causes of traumatic brain injury (TBI), the armed conflict in Iraq and Afghanistan has brought this disorder to the attention of the global community. A biomarker that would enable army medics to rapidly diagnose the severity of TBI on the battle-field would be a huge asset. Unfortunately, the study of TBI has not historically attracted the proteomic research community’s interest as other disorders have, such as cancer. On the positive side, however, many of the analytical and technological challenges that were overcome in the development of biofluid proteomic methods are now being applied to the study of TBI. In this review, we discuss and highlight select examples of discovery-driven proteomic studies focused on finding effective biomarkers for TBI.     

Impact of cardiovascular risk factors on oxidative stress and DNA damage in a high risk Mediterranean population

Abstract

The impact of classic cardiovascular risk factors on oxidative stress status in a high-risk cardiovascular Mediterranean population of 527 subjects was estimated. Oxidative stress markers (malondialdehyde, 8-oxo-7′8′-dihydro-2′-deoxyguanosine, oxidized/reduced glutathione ratio) together with the activity of antioxidant enzyme triad (superoxide dismutase, catalase, glutathione peroxidase) were analysed in circulating mononuclear blood cells. Malondialdehyde, oxidized glutathione and the ratio of oxidized to reduced glutathione were significantly higher while catalase and glutathione peroxidase activities were significantly lower in high cardiovascular risk participants than in controls. Statistically significant differences were obtained after additional multivariate control for sex, age, obesity, diabetes, lipids and medications. Among the main cardiovascular risk factors, hypertension was the strongest determinant of oxidative stress in high risk subjects studied at a primary prevention stage.     

Progress in the search for circulating biomarkers of nonalcoholic fatty liver disease

Abstract

Context: The definitive standard for the diagnosis of nonalcoholic fatty liver disease (NAFLD) is clinico-pathological correlation, but frequently the only laboratory abnormality is an elevation of serum aminotransferases.

Objective: This has resulted in the search for more specific laboratory biomarkers.

Methods: The literature was searched for novel plasma/serum markers of NAFLD.

Results: Studies reviewed here included histologically-confirmed patients presenting some stage of NAFLD and monitored one or more novel serum/plasma biomarkers.

Conclusion: The most promising application of some of these novel biomarkers for the detection and quantification of NAFLD and particularly NASH appears to be in the combination of several into diagnostic panels.     

Proteomics‐based discovery of biomarkers for paediatric acute lymphoblastic leukaemia: challenges and opportunities

There are important breakthroughs in the treatment of paediatric acute lymphoblastic leukaemia (ALL) since 1950, by which the prognosis of the child majority suffered from ALL has been improved. However, there are urgent needs to have disease‐specific biomarkers to monitor the therapeutic efficacy and predict the patient prognosis. The present study overviewed proteomics‐based research on paediatric ALL to discuss important advances to combat cancer cells and search novel and real protein biomarkers of resistance or sensitivity to drugs which target the signalling networks. We highlighted the importance and significance of a proper phospho‐quantitative design and strategy for paediatric ALL between relapse and remission, when human body fluids from cerebrospinal, peripheral blood, or bone‐marrow were applied. The present article also assessed the schedule for the analysis of body fluids from patients at different states, importance of proteomics‐based tools to discover ALL‐specific and sensitive biomarkers, to stimulate paediatric ALL research via proteomics to ‘build’ the reference map of the signalling networks from leukemic cells at relapse, and to monitor significant clinical therapies for ALL‐relapse.     

Proteomics approaches in cervical cancer: focus on the discovery of biomarkers for diagnosis and drug treatment monitoring

Introduction: The HPV virus accounts for the majority of cervical cancer cases. Although a diagnostic tool (Pap Test) is widely available, cervical cancer incidence still remains high worldwide, and especially in developing countries, attributed to a large extent to suboptimal sensitivities of the Pap test and unavailability of the test in developing countries.

Areas covered: Proteomics approaches have been used in order to understand the HPV virus correlation to cervical cancer pathology, as well as to discover putative biomarkers for early cervical cancer diagnosis and drug mode of action.

Expert commentary: The present review summarizes the latest in vitro and in vivo proteomic studies for the discovery of putative cervical cancer biomarkers and the evaluation of available drugs and treatments.     

Proteomics studies in inner ear disorders: pathophysiology and biomarkers

Although proteomics has been exploited in a wide range of diseases for identification of biomarkers and pathophysiological mechanisms, there are still biomedical disciplines such as otology where proteomics platforms are underused due to technical challenges and/or complex features of the disease. Thus, in the past few years, healthcare and scientific agencies have advocated the development and adoption of proteomic technologies in otological research. However, few studies have been conducted and limited literature is available in this area. Here, we present the state of the art of proteomics in otology, discussing the substantial evidence from recent experimental models and clinical studies in inner-ear conditions. We also delineate a series of critical issues including minute size of the inner ear, delicacy and poor accessibility of tissue that researchers face while undertaking otology proteomics research. Furthermore, we provide perspective to enhance the impact and lead to the clinical implementation of these proteomics-based strategies.     

血浆游离DNA检测在心血管系统疾病诊断中的应用

心血管疾病发病率和病死率居高不下,寻求敏感性高的生物学指标帮助早期诊断和改善预后意义重大.血浆游离DNA(cell-free DNA,cfDNA)是一类存在于血浆、尿液及其他体液中游离于细胞之外的双链DNA片段.血浆cfDNA水平在心血管疾病的早期明显升高,提示其可能是心血管疾病的潜在生物标志物.为了更深入理解cfDN...     

Clinical significance of circulating microRNAs as diagnostic biomarkers for coronary artery disease

Coronary artery disease (CAD) is one of the biggest threats to human life. Circulating microRNAs (miRNAs) have been reported to be linked to the pathogenesis of CAD, indicating the possible role in CAD diagnosis. The present study aimed to explore the expression profile of plasma miRNAs and estimate their value in diagnosis for CAD. 67 Non‐CAD control subjects and 88 CAD patients were enrolled. We conducted careful evaluation by RT‐PCR analysis, Spearman rank correlation coefficients analysis, Receiver Operating Characteristic (ROC) curves analysis and so on. The plasma levels of six miRNAs known to be related to CAD were measured and three of them showed obvious expression change. Circulating miR‐29a‐3p, miR‐574‐3p and miR‐574‐5p were all significantly increased. ROC analysis revealed the probability of the three miRNAs as biomarkers with AUCs (areas under the ROC curve) of 0.830, 0.792 and 0.789, respectively. They were significantly correlated with each other in CAD patients, suggesting the possibility of joint diagnosis. The combined AUC was 0.915, much higher than each single miRNA. Therefore, our study revealed three promising biomarkers for early diagnosis of CAD. The combination of these miRNAs may act more effectively than individual ones for CAD diagnosis.     

Identification of circulating biomarkers of Crohn's disease and spondyloarthritis using Fourier transform infrared spectroscopy

Crohn's disease (CD) and spondyloarthritis (SpA) are two inflammatory diseases sharing many common features (genetic polymorphism, armamentarium). Both diseases lack diagnostic markers of certainty. While the diagnosis of CD is made by a combination of clinical, and biological criteria, the diagnosis of SpA may take several years to be confirmed. Based on the hypothesis that CD and SpA alter the biochemical profile of plasma, the objective of this study was to evaluate the analytical capability of Fourier transform infrared spectroscopy (FTIR) in identifying spectral biomarkers. Plasma from 104 patients was analyzed. After data processing of the spectra by Extended Multiplicative Signal Correction and linear discriminant analysis, we demonstrated that it was possible to distinguish CD and SpA from controls with an accuracy of 97% and 85% respectively. Spectral differences were mainly associated with proteins and lipids. This study showed that FTIR analysis is efficient to identify plasma biosignatures specific to CD or SpA.     

Application of mass spectrometry to the discovery of biomarkers for detection of prostate cancer

There has been an impressive emergence of mass spectrometry based technologies applied toward the study of proteins. Equally notable is the rapid adaptation of these technologies to biomedical approaches in the realm of clinical proteomics. Concerted efforts toward the elucidation of the proteomes of organ sites or specific disease state are proliferating and from these efforts come the promise of better diagnostics/prognostics and therapeutic intervention. Prostate cancer has been a focus of many such studies with the promise of improved care to patients via biomarkers derived from these proteomic approaches. The newer technologies provide higher analytical capabilities, employ automated liquid handling systems, fractionation techniques and bioinformatics tools for greater sensitivity and resolving power, more robust and higher throughput sample processing, and greater confidence in analytical results. In this prospects, we summarize the proteomic technologies applied to date in prostate cancer, along with their respective advantages and disadvantages. The development of newer proteomic strategies for use in future applications is also discussed.     

Plasma biomarkers for the identification of women at risk for early-onset preeclampsia

Background: To identify potential biomarkers in the 1st trimester of pregnancy for the identification of women destined to develop early onset preeclampsia (EOPE).

Methods: Blood samples were obtained from pregnant women at 11–13 weeks of gestation. Women were followed up until delivery. Five samples from EOPE complicated pregnancies and 5 from unaffected ones were analysed using 2-DE and MALDI-TOF-TOF MS/MS. The altered expression of selected proteins was verified by ELISA in an extended sample cohort.

Results: Twelve proteins were differentially expressed in the plasma of women who subsequently developed EOPE as compared to controls. Alpha-1-antitrypsin (A1AT), CD5 antigen-like molecule (CD5L) Keratin, type I cytoskeletal 9 (K1C9), Myeloid cell nuclear differentiation antigen (MNDA), Transferrin (TRFE) and Vitamin D-binding protein (VTDB) were up-regulated with fold changes 3.14, 2.18, 1.53, 1.53, 4.26 3.38 respectively, whereas Alpha-2-HS-glycoprotein (FETUA), Beta-2-glycoprotein 1 (APOH), Complement factor B (CFAB), Haptoglobin (HPT), Vitronectin (VTNC) and Zinc-alpha-2-glycoprotein (ZA2G) were down-regulated with fold changes -0.38, -0.76, -0.24, -0.47, -0.23, and -0.50 respectively. The down-regulation of APOH, VTNC and HPT was verified using ELISA.

Conclusions: The differentially expressed proteins represent potential biomarkers for the early screening for EOPE. Follow-up experiments however are necessary for evaluation.     

Application of proteomics for discovery of protein biomarkers.

Biomarkers of drug efficacy and toxicity are becoming a key need in the drug development process. Mass spectral-based proteomic technologies are ideally suited for the discovery of protein biomarkers in the absence of any prior knowledge of quantitative changes in protein levels. The success of any biomarker discovery effort will depend upon the quality of samples analysed, the ability to generate quantitative information on relative protein levels and the ability to readily interpret the data generated. This review will focus on the strengths and weaknesses of technologies currently utilised to address these issues.     

Endocrine organs of cardiovascular diseases: Gut microbiota

Gut microbiota (GM) is a collection of bacteria, fungi, archaea, viruses and protozoa, etc. They inhabit human intestines and play an essential role in human health and disease. Close information exchange between the intestinal microbes and the host performs a vital role in digestion, immune defence, nervous system regulation, especially metabolism, maintaining a delicate balance between itself and the human host. Studies have shown that the composition of GM and its metabolites are firmly related to the occurrence of various diseases. More and more researchers have demonstrated that the intestinal microbiota is a virtual ‘organ’ with endocrine function and the bioactive metabolites produced by it can affect the physiological role of the host. With deepening researches in recent years, clinical data indicated that the GM has a significant effect on the occurrence and development of cardiovascular diseases (CVD). This article systematically elaborated the relationship between metabolites of GM and its effects, the relationship between intestinal dysbacteriosis and cardiovascular risk factors, coronary heart disease, myocardial infarction, heart failure and hypertension and the possible pathogenic mechanisms. Regulating the GM is supposed to be a potential new therapeutic target for CVD.