Novel Biomarkers and Their Role in the Diagnosis and Prognosis of Acute Coronary Syndrome.

The burden of cardiovascular diseases and the critical role of acute coronary syndrome (ACS) in their progression underscore the need for effective diagnostic and prognostic tools. Biomarkers have emerged as crucial instruments for ACS diagnosis, risk stratification, and prognosis assessment. Among these, high-sensitivity troponin (hs-cTn) has revolutionized ACS diagnosis due to its superior sensitivity and negative predictive value. However, challenges regarding specificity, standardization, and interpretation persist. Beyond troponins, various biomarkers reflecting myocardial injury, neurohormonal activation, inflammation, thrombosis, and other pathways are being explored to refine ACS management. This review article comprehensively explores the landscape of clinically used biomarkers intricately involved in the pathophysiology, diagnosis, and prognosis of ACS (i.e., troponins, creatine kinase MB (CK-MB), B-type natriuretic peptides (BNP), copeptin, C-reactive protein (CRP), interleukin-6 (IL-6), d-dimers, fibrinogen), especially focusing on the prognostic role of natriuretic peptides and of inflammatory indices. Research data on novel biomarkers (i.e., endocan, galectin, soluble suppression of tumorigenicity (sST2), microRNAs (miRNAs), soluble oxidized low-density lipoprotein receptor-1 (sLOX-1), F2 isoprostanes, and growth differentiation factor 15 (GDF-15)) are further analyzed, aiming to shed light on the multiplicity of pathophysiologic mechanisms implicated in the evolution of ACS. By elucidating the complex interplay of these biomarkers in ACS pathophysiology, diagnosis, and outcomes, this review aims to enhance our understanding of the evolving trajectory and advancements in ACS management. However, further research is necessary to establish the clinical utility and integration of these biomarkers into routine practice to improve patient outcomes.

Association of Soluble Suppression of Tumorigenesis-2 (ST2) with Endothelial Function in Patients with Ischemic Heart Failure.

Soluble suppression of tumorigenesis-2 (sST2) has been introduced as a marker associated with heart failure (HF) pathophysiology and status. Endothelial dysfunction is a component underlying HF pathophysiology. Therefore, we examined the association of arterial wall properties with sST2 levels in patients with HF of ischemic etiology. We enrolled 143 patients with stable HF of ischemic etiology and reduced left ventricular ejection fraction (LVEF) and 77 control subjects. Flow-mediated dilation (FMD) was used to evaluate endothelial function and pulse wave velocity (PWV) to assess arterial stiffness. Although there was no significant difference in baseline demographic characteristics, levels of sST2 were increased in HF compared to the control (15.8 (11.0, 21.8) ng/mL vs. 12.5 (10.4, 16.3) ng/mL; p < 0.001). In the HF group, there was a positive correlation of sST2 levels with age (rho = 0.22; p = 0.007) while there was no association of LVEF with sST2 (rho = -0.119; p = 0.17) nor with PWV (rho = 0.1; p = 0.23). Interestingly, sST2 was increased in NYHA III [20.0 (12.3, 25.7) ng/mL] compared to patients with NYHA II (15.0 (10.4, 18.2) ng/mL; p = 0.003) and inversely associated with FMD (rho = -0.44; p < 0.001) even after adjustment for possible confounders. In patients with chronic HF of ischemic etiology, sST2 levels are increased and are associated with functional capacity. There is an inverse association between FMD and sST2 levels, highlighting the interplay between the dysfunctional endothelium and HF pathophysiologic mechanisms.

Osteoprotegerin and Osteopontin Serum Levels are Associated with Vascular Function and Inflammation in Coronary Artery Disease Patients.

BACKGROUND: Osteoprotegerin and osteopontin have recently emerged as key factors in both vascular remodelling and atherosclerosis progression. Interleukin-6 (IL-6) is an inflammatory cytokine with a key role in atherosclerosis. The relationship of osteoprotegerin, osteopontin, and IL-6 serum levels with endothelial function and arterial stiffness was evaluated in patients with coronary artery disease (CAD). METHODS: We enrolled 219 patients with stable CAD and 112 control subjects. Osteoprotegerin, osteopontin and IL-6 serum levels were measured using an ELISA assay. Endothelial function was evaluated by flow-mediated dilation (FMD) in the brachial artery and carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. RESULTS: There was no significant difference between control subjects and CAD patients according to age and sex. Compared with control subjects, CAD patients had significantly impaired FMD (p<0.001) and increased PWV (p=0.009). CAD patients also had significantly higher levels of osteoprotegerin (p<0.001), osteopontin (p<0.001) and IL-6 (p=0.03), compared with control subjects. Moreover, IL-6 levels were correlated with osteoprotegerin (r=0.17, p=0.01) and osteopontin (r=0.30, p<0.001) levels. FMD was correlated with osteoprotegerin levels independent of possible confounders [b coefficient= - 0.79, 95% CI (-1.54, -0.05), p=0.04]. CONCLUSION: CAD patients have increased osteoprotegerin, osteopontin and IL-6 levels. Moreover, there is a consistent association between osteoprotegerin and osteopontin serum levels, vascular function and inflammation in CAD patients. These findings suggest another possible mechanism linking osteoprotegerin and osteopontin serum levels with CAD progression through arterial wall stiffening and inflammation.

Cardiovascular effects of electronic cigarettes: A systematic review and meta-analysis.

AIMS: The electronic cigarette is marketed as a safe alternative to tobacco smoking, but electronic cigarette cardiovascular effects remain largely unknown. We systematically reviewed and meta-analysed published literature to investigate the cardiovascular effects and associated risk from electronic cigarette use. METHODS AND RESULTS: We searched PubMed from January 2000 to November 2017 for published studies assessing the cardiovascular effects of the electronic cigarette. Evidence suggests that the electronic cigarette negatively affects endothelial function, arterial stiffness and the long-term risk for coronary events, but these findings are from single study reports and have not been confirmed in additional studies. Conflicting evidence exists on the effects of the electronic cigarette on heart rate and blood pressure, which is mainly based on non-randomized clinical studies of moderate quality. The meta-analysis of 14 studies (N + 441 participants) suggested that despite the negative acute effects of the electronic cigarette on heart rate (pooled mean difference (MD) + 2.27, 95% confidence interval (CI): 1.64 to 2.89, p < 0.001), diastolic (pooled MD + 2.01 mmHg, 95% CI: 0.62 to 3.39, p + 0.004) and systolic blood pressure (pooled MD + 2.02 mmHg, 95% CI: 0.07 to 3.97, p + 0.042), benefits may be observed in terms of blood pressure regulation when switching from tobacco smoking to chronic electronic cigarette use (systolic blood pressure pooled MD + -7.00, 95% CI: -9.63 to -4.37, p < 0.001; diastolic blood pressure pooled MD + -3.65, 95% CI: -5.71 to -1.59, p + 0.001). CONCLUSIONS: The existing evidence on the cardiovascular effects of the electronic cigarette is concerning, with several unexplored issues. Unless supported by stronger evidence, the electronic cigarette should not be labelled as a cardiovascular safe product. Future studies should delineate whether electronic cigarette use is less hazardous to cardiovascular health than conventional cigarette smoking.

The association among biomarkers of renal and heart function in patients with heart failure: the role of NGAL.

AIM: The NGAL is a biomarker of renal injury associated with the progression of heart failure (HF). We examine the association of NGAL with galectin-3 in patients with chronic HF. METHODS: We consecutively enrolled 115 subjects with stable ischemic HF of reduced ejection fraction. Serum levels of galectin-3, b-type natriuretic peptide and NGAL were measured. RESULTS: NGAL levels were positively correlated with galectin-3 (rho = 0.26; p = 0.04) and b-type natriuretic peptide levels (rho = 0.30; p = 0.005) and inversely correlated with ejection fraction (rho = -0.31; p = 0.02) and creatinine clearance levels. The NGAL was independently associated with galectin-3 levels. CONCLUSION: A positive correlation between NGAL and galectin-3 in HF patients was found, revealing a potential association between renal injury and myocardial fibrosis and remodeling in HF.