Do ANGPTL-4 and galectin-3 reflect the severity of coronary artery disease?

BACKGROUND: Coronary artery disease (CAD) is one of the leading causes of mortality and morbidity worldwide. We thereby sought to investigate whether the biomarkers, angiopoietin-like 4 (ANGPTL-4) and galectin-3, reflect the severity of CAD. METHODS: Patients were screened based on inclusion/exclusion criteria and written informed consent was obtained from the patients. Serum ANGPTL-4 and galectin-3 was quantified using enzyme-linked immunosorbent assay (ELISA) and correlated with the Global Registry of Acute Coronary Events (GRACE) and GENSINI score using Spearman's rank correlation coefficient and multivariate analysis. RESULTS: A total of 226 patients consisting of ST-segment elevation myocardial infarction (STEMI), non-STEMI/unstable angina (USA), chronic stable angina (CSA) and normal controls (NCs) participated in the study. ANGPTL-4 and galectin-3 were significantly higher in CAD than the NC group. ANGPTL-4 showed significant negative correlation with GRACE score in acute coronary syndrome (ACS) ( r = -0.211, p = 0.03) patients. ANGPTL-4 showed significant positive correlation with serum creatinine ( r = 0.304, p = 0.056) and body mass index (BMI) ( r = 0.424, p = 0.009) in CSA patients. A modest positive correlation was observed between the serum galectin-3 levels and GRACE score ( r = 0.187, p = 0.055) in ACS patients. However, on multivariate analysis the positive correlation relationship between ANGPTL-4 and galectin-3 with the severity of CAD was not sustained. CONCLUSION: In conclusion, ANGPTL-4 and galectin-3 do not appear to have a promising role for assessing the severity of CAD. Nevertheless these biomarkers do warrant further exploration in improving the management of CAD.

Effect of tolvaptan on acute heart failure with hyponatremia--a randomized, double blind, controlled clinical trial.

OBJECTIVES: To assess the efficacy of tolvaptan in acute heart failure with hyponatremia using a randomized double-blinded placebo-controlled study design. BACKGROUND: Tolvaptan is a selective vasopressin receptor 2 antagonist. There are no published clinical trials on the utility of tolvaptan in acute heart failure with hyponatremia in the Indian population. METHODS: After screening and informed consent, 51 HF patients with hyponatremia were randomized using computer-generated randomization sequence to receive placebo or 15mg of tolvaptan for 5 days along with conventional medical therapy. The patient's perception of dyspnea using Likert score and the plasma sodium was measured at baseline and for the next 4 days. RESULTS: There was a mean improvement in sodium concentration by 5mEq/L (p=0.001) in patients receiving tolvaptan, whereas no significant improvement was seen in the placebo group (p=0.33). Significant improvement in Likert score was observed in both the groups (p=0.001), even though there was no difference between both the groups. Dry mouth and thirst were the most commonly occurring adverse effects observed in both the groups. There were no significant hemodynamic changes with tolvaptan therapy. CONCLUSION: Tolvaptan at a dose of 15mg is effective in reversing hyponatremia in acute heart failure and may be a suitable option in these patients.

GDF 15--A Novel Biomarker in the Offing for Heart Failure.

BACKGROUND: Several diagnostic and prognostic biomarkers are being explored in heart failure. GDF-15 belongs to the transforming growth factor ß (TGF-ß) cytokine family that is highly up regulated in inflammatory conditions. We undertook this systematic review to summarize the current evidence on the utility of GDF-15 as a biomarker in heart failure. DESIGN AND METHODS: Multiple electronic databases for studies that reported the association between GDF- 15 and heart failure were searched using different electronic databases such as MEDLINE, Science Direct, Springer Link, Scopus, Cochrane Reviews, and Google Scholar using pre-defined inclusion- exclusion criteria. RESULTS: Twenty one original studies were identified that included data from 20,920 study participants. GDF 15 was found to be a strong prognosticator of all-cause mortality in heart failure patients. Several studies found the benefit of using GDF-15 as a component of a multi-biomarker strategy in prognosticating patients with heart failure. CONCLUSION: More studies are warranted to elucidate the molecular pathways involving GDF-15 and to see how knowledge about GDF-15 can be used to make therapeutic decisions in the clinic.

Value of pentraxin-3 and galectin-3 in acute coronary syndrome: a short-term prospective cohort study.

BACKGROUND: Acute coronary syndrome (ACS) continues to be a leading cause of morbidity and mortality worldwide. Galectin-3 and pentraxin-3 are two prognostic biomarkers that have been studied in heart failure (HF). However, there are limited data on these biomarkers in the ACS population. The objective of the study was to determine the variables that are most affected by high concentrations of pentraxin-3 and galectin-3, and the influence they have on outcomes of all-cause mortality in patients with ACS. METHODS: We included a total of 160 patients [ST elevation myocardial infarction (STEMI),n = 64; non STEMI/unstable angina (NSTEMI/UA), n = 38; and control subjects with chronic stable angina (CSA)/microvascular angina (MVA) n = 58]. Plasma pentraxin-3 and galectin-3 levels were assessed from these patients at the time of hospital admission. Major adverse cardiovascular events including all-cause mortality, rehospitalizations and coronary artery bypass graft surgery (CABG) were assessed at 6 months. RESULTS: The median concentration of pentraxin-3 and galectin-3 were significantly higher in STEMI than in NSTEMI patients (p < 0.005) or controls (p < 0.005). Greater numbers of deaths (4 versus 0) were observed in STEMI patients with higher levels of these biomarkers. In addition, ACS patients with high levels of pentraxin-3 and galectin-3 had lower left ventricular ejection fraction (LVEF) (p < 0.005), and a moderate correlation was observed between LVEF and pentraxin-3 levels (r = -0.45, p < 0.005). Patients with higher galectin-3 levels were also observed to have a lower estimated glomerular fraction rate (eGFR), and a moderate correlation was observed between them (r = -0.34, p < 0.005). CONCLUSION: Pentraxin-3 and galectin-3 hold much promise in the ACS population as prognostic biomarkers.

Riociguat: Something new in pulmonary hypertension therapeutics?

Pulmonary hypertension (PH) continues to be a disease that is associated with woeful outcomes. The search for an ideal drug molecule for PH led to the discovery of riociguat, which is a first-in-class drug molecule that activates soluble guanylate cyclase. We conducted a systematic literature search using databases such as PubMed, Science Direct, Springer, Cochrane Reviews and Google Scholar to gather evidence generated from published clinical trials on the efficacy, safety, pharmacokinetics and regulatory status of riociguat. CHEST-1 and the PATENT-1 were phase-3 pivotal clinical trials that showed that riociguat was able to significantly improve the 6-min walk distance with 16 weeks of therapy as compared with the placebo arm. The drug also showed improvement in secondary outcome measures such as improvement in the pulmonary vascular resistance, N-terminal pro-brain natriuretic peptide levels, World Health Organization functional class, time to clinical worsening and Borg dyspnea score. The drug had a modest safety profile, with hypotension being the most bothersome adverse effect. These findings led to various regulatory agencies around the world granting approval for riociguat for the treatment of pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH). The entry of a new class of drug for PAH and CTEPH therapy portends some hope for patients with a disease that is traditionally linked with a poor prognosis.

Evaluation of Endothelial and Platelet Derived Microparticles in Patients with Acute Coronary Syndrome.

BACKGROUND: Microparticles (MP) are a nuclear fragments of membrane released by the damaged cell during stress. Elevated levels of MP have been found in patients with acute coronary syndrome (ACS) owing to the damage in the endothelium. AIM: To determine if the levels of endothelial and platelet microparticles (EMP & PMP) in patients with ACS influenced the severity of the disease. MATERIALS AND METHODS: This was a prospective cohort study performed in 63 ACS patients (ST elevation myocardial infarction- STEMI-28, non ST elevation myocardial infarction -NSTEMI-35). After obtaining consent, blood samples were collected from the patients and processed by flow cytometry. RESULTS: The NSTEMI group had higher levels of EMP {792.11(327.59-1661.49) vs 300.35 (176.3-550.46), p=0.001} and PMP {218.87(86.65-439.77) vs 114.45(50.34-196.75), p= 0.007} as compared to the STEMI group. However, it was found that the EMP (r=-0.438, p=0.001) and PMP (r= -0.316, p=0.024) negatively correlated with Global Registry of Acute Coronary Events score (GRACE in-hospital score) for the entire cohort. CONCLUSION: The levels of microparticles are elevated in ACS patients and may reflect a protective effect in patients with acute coronary syndrome.