Enhanced Response of Blood Monocytes to In Vitro Lipopolysaccharide-Challenge in Patients With Recurrent Unstable Angina

Background—C-reactive protein (CRP) plasma levels have been associated with short- and long-term occurrence of coronary events. We investigated whether circulating inflammatory cell responsiveness to low-grade stimuli could contribute to the reported association between CRP and coronary events.Methods and Results—We studied 32 patients with unstable angina who were followed for 24 months and were free of symptoms for 6 months (group 1): 19 patients had persistently high CRP levels (>0.3 mg/dL) (group 1A); 13 patients had normal CRP levels (group 1B). During the follow-up, 12 (63%) group 1A but no group 1B patients developed an infarction or recurrence of unstable angina (P<0.001). Eighteen patients with chronic stable angina (group 2) and 18 healthy subjects (group 3) were studied as controls. Interleukin (IL)-6 production (median, range) by peripheral blood mononuclear cells after 4 hours of in vitro stimulation with 1 ng/mL lipopolysaccharide (LPS) was significantly higher in group 1A (4526 pg/mL, 3042 to 10 583 pg/mL) than in group 1B (1752 pg/mL, 75 to 3981 pg/mL), group 2 (707 pg/mL, 41 to 3275 pg/mL), and group 3 (488 pg/mL, 92 to 3503 pg/mL) (allP<0.001). No significant differences were observed among the other groups. IL-6 production after LPS-challenge was correlated with baseline CRP levels (r=0.42,P=0.005).Conclusions—Mononuclear cells of patients with recurrent phases of instability exhibit an enhanced production of IL-6 in response to low-dose of LPS, correlated with baseline CRP levels, 6 months after the last acute event. This persisting enhanced acute-phase responsiveness may help explain the association between CRP and acute coronary events

Unusual CD4+CD28nullT Lymphocytes and Recurrence of Acute Coronary Events

ObjectivesWe hypothesized that the expansion of unusual T lymphocytes, CD4+CD28nullT cells, might represent a key pathogenetic mechanism of recurrent instability.BackgroundClinical presentation of acute coronary syndromes (ACS) is variable. Some patients have recurrent episodes of instability, despite optimal treatment, whereas others have a single acute event in their life. The CD4+CD28nullT cells, with a functional profile that favors vascular injury, have recently been found both in peripheral blood and in unstable coronary plaques of patients with ACS.MethodsPeripheral blood T cells from 120 consecutive unstable angina (UA) patients were analyzed for the distribution of T-cell subsets by flow cytometry. Patients were subgrouped according to the occurrence of prior (during the 24 months before the study enrollment) and subsequent (during the 24 months of follow-up) acute coronary events. For 51 patients, the index event was the first ever (G1); 30 patients had prior events (G2); and 39 patients had further events at follow-up (death, myocardial infarction, or UA) or both before and after the index event (G3).ResultsThe CD4+CD28nullT-cell frequency was higher in G3 than in G2 and G1 (median 9.5% [range 2.4% to 48.0%] vs. 5.1% [range 0.4% to 27.8%] and 2.3% [range 0.2% to 22.8%], respectively; p < 0.001). The expansion of these unusual T lymphocytes was higher in patients with elevated C-reactive protein levels, and it was reduced by statin therapy. On multivariate logistic regression analysis, CD4+CD28nullT-cell frequency was an independent predictor of future acute coronary events (odds ratio 3.01, 95% confidence interval 1.1 to 8.25; p = 0.023).ConclusionsA perturbation of T-cell repertoire is strongly associated with the recurrence of acute coronary events, conceivably playing a key pathogenetic role

Impact of diabetes mellitus on prediction of clinical outcome after coronary revascularization by ¹⁸F-FDG SPECT in patients with ischemic left ventricular dysfunction

Nuclear imaging using 18F-FDG is an established method for the noninvasive assessment of myocardial viability. Data on the value of 18F-FDG imaging in patients with diabetes mellitus are scarce. The aim of this study was to assess whether, in patients with diabetes mellitus and ischemic left ventricular (LV) dysfunction, 18/F-FDG imaging can predict improvement of LV function and heart failure symptoms after coronary revascularization. Methods: A total of 130 consecutive patients with ischemic LV dysfunction who were already scheduled for surgical revascularization were studied; 34 of the patients had diabetes mellitus. All patients underwent radionuclide ventriculography to assess left ventricular ejection fraction (LVEF), resting 2-dimensional echocardiography to identify dysfunctional myocardial tissue, and dual-isotope 18F-FDG/99m/Tc- tetrofosmin SPECT after oral administration of acipimox. Nine to 12 mo after coronary revascularization, radionuclide ventriculography and echocardiography were repeated. An improvement in LVEF by at least5% was considered significant. Results: 18F-FDG SPECT demonstrated that 610 (50%) of 1,212 dysfunctional segments were viable. Patients with and without diabetes mellitus had a comparable number of dysfunctional but viable segments per patient. Also, the number of patients with a substantial amount of dysfunctional but viable myocardium (≥ viable segments) was comparable between the groups with and without diabetes mellitus. The presence of substantial viability on 18F-FDG SPECT was predictive of improvement in LVEF and heart failure symptoms postoperatively (sensitivity and specificity of 82% and 89%, respectively, in patients with diabetes and 83% and 93%, respectively, in patients without diabetes; not statistically significant). Conclusion: 18F-FDG SPECT is practical for routine assessment of myocardial viability in patients with ischemic LV dysfunction with or without diabetes mellitus. Patients with substantial myocardial viability on 18F-FDG SPECT have a high probability of improvement of LV function and symptoms after coronary revascularization, irrespective of the absence or presence of diabetes mellitus.</p

Impact of diabetes mellitus on prediction of clinical outcome after coronary revascularization by ¹⁸F-FDG SPECT in patients with ischemic left ventricular dysfunction

Nuclear imaging using 18F-FDG is an established method for the noninvasive assessment of myocardial viability. Data on the value of 18F-FDG imaging in patients with diabetes mellitus are scarce. The aim of this study was to assess whether, in patients with diabetes mellitus and ischemic left ventricular (LV) dysfunction, 18/F-FDG imaging can predict improvement of LV function and heart failure symptoms after coronary revascularization. Methods: A total of 130 consecutive patients with ischemic LV dysfunction who were already scheduled for surgical revascularization were studied; 34 of the patients had diabetes mellitus. All patients underwent radionuclide ventriculography to assess left ventricular ejection fraction (LVEF), resting 2-dimensional echocardiography to identify dysfunctional myocardial tissue, and dual-isotope 18F-FDG/99m/Tc- tetrofosmin SPECT after oral administration of acipimox. Nine to 12 mo after coronary revascularization, radionuclide ventriculography and echocardiography were repeated. An improvement in LVEF by at least5% was considered significant. Results: 18F-FDG SPECT demonstrated that 610 (50%) of 1,212 dysfunctional segments were viable. Patients with and without diabetes mellitus had a comparable number of dysfunctional but viable segments per patient. Also, the number of patients with a substantial amount of dysfunctional but viable myocardium (≥ viable segments) was comparable between the groups with and without diabetes mellitus. The presence of substantial viability on 18F-FDG SPECT was predictive of improvement in LVEF and heart failure symptoms postoperatively (sensitivity and specificity of 82% and 89%, respectively, in patients with diabetes and 83% and 93%, respectively, in patients without diabetes; not statistically significant). Conclusion: 18F-FDG SPECT is practical for routine assessment of myocardial viability in patients with ischemic LV dysfunction with or without diabetes mellitus. Patients with substantial myocardial viability on 18F-FDG SPECT have a high probability of improvement of LV function and symptoms after coronary revascularization, irrespective of the absence or presence of diabetes mellitus.</p

Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) scientific statement on the simplification of the drug regimen for secondary cardiovascular prevention

: The issue of suboptimal drug regimen adherence in secondary cardiovascular prevention presents a significant barrier to improving patient outcomes. To address this, the utilization of drug combinations, specifically single pill combinations (SPCs) and polypills, was proposed as a strategy to simplify treatment regimens. This approach aims to enhance treatment accessibility, affordability, and adherence, thereby reducing healthcare costs and improving patient health. The document is an Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) scientific statement on simplifying drug regimens for secondary cardiovascular prevention. It discusses the underuse of treatments despite available, effective, and accessible options, highlighting a significant gap in secondary prevention across different socio-economic statuses and countries. The statement explores barriers to implementing evidence-based treatments, including patient, healthcare provider, and system-related challenges. The paper also reviews international guidelines, the role of SPCs and polypills in clinical practice, and their economic impact, advocating for their use in secondary prevention to improve patient outcomes and adherence

Why do patients with ischemic cardiomyopathy and a substantial amount of viable myocardium not always recover in function after revascularization?

In patients with ischemic cardiomyopathy and a substantial amount of dysfunctional but viable myocardium, myocardial revascularization may improve left ventricular ejection fraction. The aim of this study was to evaluate why not all patients with a substantial amount of viable tissue recover in function after revascularization