Diastolic dysfunction, frailty and prognosis in elderly patients with acute coronary syndromes.

Background To investigate the relationship between 1-year outcome and diastolic dysfunction (DD) and frailty and/or physical performance (PP) in older adults admitted to hospital for acute coronary syndrome (ACS). Methods and results Older (age ≥ 70 years) hospitalized for ACS and receiving coronary artery angiography ± percutaneous coronary intervention were included. Before discharge a complete transthoracic echocardiogram (TTE) was performed with the assessment of DD, following the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging algorithm. Seven different scales of frailty and PP were assessed. The relationship between DD and tests of frailty and PP was investigated, as well as the association with the 1-year occurrence of all-cause death or re-hospitalization. Overall, 329 patients were included in the analysis. Patients were stratified in two groups: DD grade 0-1 versus 2-3. Those with undetermined degree of DD have been excluded by the analysis (n = 106). Mean age of the groups was 77 ± 5 vs 79 ± 6 years, respectively. Scales of frailty and/or PP were significantly poor in patients with DD grade 2-3 compared to the others. After multivariate Cox regression (considering age, female sex, haemoglobin, albumin, clinical presentation, LVEF and SPPB) DD (degree 2-3 vs. 0-1) emerged as an independent predictor of the composite endpoint (HR 1.69, 95%CI 1.04-2.75, p = 0.033). This was mainly driven by 1-year re-hospitalization (HR 2.01, 95%CI 1.22-3.27, p < 0.001). Conclusions In older ACS patients the assessment of DD is related to parameters of frailty and PP and it is an independent predictor of 1-year outcome.

Ticagrelor Increases SIRT1 and HES1 mRNA Levels in Peripheral Blood Cells from Patients with Stable Coronary Artery Disease and Chronic Obstructive Pulmonary Disease.

Ticagrelor is a powerful P2Y12 inhibitor with pleiotropic effects in the cardiovascular system. Consistently, we have reported that in patients with stable coronary artery disease (CAD) and concomitant chronic obstructive pulmonary disease (COPD) who underwent percutaneous coronary intervention (PCI), 1-month treatment with ticagrelor was superior in improving biological markers of endothelial function, compared with clopidogrel. The objective of this study was to investigate the mechanisms underlying these beneficial effects of ticagrelor by conducting molecular analyses of RNA isolated from peripheral blood cells of these patients. We determined mRNAs levels of markers of inflammation and oxidative stress, such as RORγt (T helper 17 cells marker), FoxP3 (regulatory T cells marker), NLRP3, ICAM1, SIRT1, Notch ligands JAG1 and DLL4, and HES1, a Notch target gene. We found that 1-month treatment with ticagrelor, but not clopidogrel, led to increased levels of SIRT1 and HES1 mRNAs. In patients treated with ticagrelor or clopidogrel, we observed a negative correlation among changes in both SIRT1 and HES1 mRNA and serum levels of Epidermal Growth Factor (EGF), a marker of endothelial dysfunction found to be reduced by ticagrelor treatment in our previous study. In conclusion, we report that in stable CAD/COPD patients ticagrelor positively regulates HES1 and SIRT1, two genes playing a protective role in the context of inflammation and oxidative stress. Our observations confirm and expand previous studies showing that the beneficial effects of ticagrelor in stable CAD/COPD patients may be, at least in part, mediated by its capacity to reduce systemic inflammation and oxidative stress.

Pain biomarkers.

The value of biomarkers in aiding early diagnosis of disease and predicting response to pharmacologic interventions is well known. The idea that biomarkers may also be used to identify and quantify pain has been investigated in preclinical and clinical studies. Findings from a preclinical study show that inflammatory pain and neuropathic pain have different biomarkers. Further investigations provided mixed results, on the one hand, cystatin C levels in cerebrospinal fluid appear to be a predictive marker for postherpetic neuralgia in patients with varicella-zoster virus, and a pain marker in women experiencing labour pain, but is not correlated with pain duration or intensity. Investigations into potential biomarkers for chest pain showed that cardiac markers used to aid in diagnosis and prognosis of cardiac disease correlate with tissue damage rather than with pain. Further studies are needed to gain insights into biomarkers for pain to enhance pain management practices.