Combined role of the Lewis antigenic system, Chlamydia pneumoniae, and C-reactive protein in unstable angina

AbstractObjectivesThe goal of this study was to assess the prognostic role of the Lewis antigenic system, Chlamydia pneumoniae(CP) seropositivity (CP+), and C-reactive protein (CRP) levels in unstable angina (UA).BackgroundThe role of CP infection in acute coronary syndromes is contradictory. The Lewis antigenic system, a genetically determined blood group system associated with infections and several disorders, including ischemic heart disease, might influence the susceptibility to CP infection, inflammatory response, and risk of cardiac ischemic events.MethodsThe CRP levels, Lewis antigens, and CP+ were measured in 54 patients with Braunwald’s class IIIB UA. All patients were followed up for one year, and the occurrence of new coronary events (coronary death, myocardial infarction, and recurrence of instability) were recorded.ResultsTwenty-five coronary events occurred during follow-up. At univariate analysis CRP >3 mg/l (CRP+) (p = 0.0056), Lewis antigen b (Leb+) (p = 0.028), and the combination of Leb+ and CP+ (p = 0.006) and of CRP+ and Leb+ (p = 0.003) were associated with new coronary events, while CP+ alone was not. At multivariate analysis, CRP+ (p = 0.008) and combined Leb+CP+ (p = 0.03) were independent predictors of worse outcome. The event rate was 64% in CRP+ patients, 67% in Leb+CP+ patients, and 86% in CRP+Leb+CP+ patients. Combined Leb+CP+, but not Leb+ and CP+ alone, was related to CRP levels (p = 0.03). Among CP+ patients, CRP levels were higher in Leb+ than Leb- (p = 0.028).ConclusionsOur data demonstrate that in UA the Lewis antigenic system plays an important role, probably determining individual susceptibility to the detrimental effects of CP infection and by determining an enhanced inflammatory response

Relation Between Platelet Response to Exercise and Coronary Angiographic Findings in Patients With Effort Angina

Background— Platelet reactivity is increased by exercise in patients with obstructive coronary artery disease (CAD) but not in patients with syndrome X. In this study, we prospectively investigated whether the platelet response to exercise might help distinguish, among patients with angina, those with obstructive CAD from those with normal coronary arteries (NCAs). Methods and Results— Venous blood samples were collected before and 5 minutes after exercise from 194 consecutive patients with stable angina. Platelet reactivity was measured by the platelet function analyzer (PFA)-100 system as the time for flowing whole blood to occlude a collagen-adenosine diphosphate ring (closure time). Coronary angiography showed CAD in 163 patients (84%) and NCA in 31 patients (16%). Baseline closure time was shorter in NCA patients (78.0±16 versus 95.5±23 seconds, P <0.0001). With exercise, closure time decreased in CAD patients (−15.5 seconds; 95% confidence limits [CL], −13.0 to −18.0 seconds; P <0.0001), but increased in NCA patients (12.5 seconds; 95% CL, 7.4 to 17.7 seconds; P =0.0004). An increase in closure time with exercise ≥10 seconds had 100% specificity and positive predictive value for NCAs. Similarly, a decrease ≥10 seconds had 100% specificity and positive predictive value for CAD. A closure time change (increase or decrease) ≥10 seconds allowed a correct classification of 55% of all patients. Conclusions— Among patients with stable angina, the response of platelet reactivity to exercise was predictive of normal or stenosed coronary arteries at angiography. Specifically, an increase in closure time with exercise ≥10 seconds was invariably associated with the presence of NCA

Large, sustained cardiac lipid peroxidation and reduced antioxidant capacity in the coronary circulation after brief episodes of myocardial ischemia

AbstractOBJECTIVESWe sought to investigate whether a brief episode of myocardial ischemia produces a detectable cardiac oxidative stress in patients undergoing elective coronary angioplasty (PTCA).BACKGROUNDAlthough cardiac oxidative stress has been clearly demonstrated in experimental models of ischemia-reperfusion, its presence in patients after transient myocardial ischemia is still unclear.METHODSIn order to evaluate oxidative stress in ischemic cardiac regions, plasma conjugated dienes (CD), lipid hydroperoxides (ROOHs) and total antioxidant capacity (TRAP), independent indexes of oxidative stress, were measured in the aorta and great cardiac vein (GCV) before (t0), 1, (t1), 5 (t5) and 15 min (t15) after first balloon inflation in 15 patients undergoing PTCA on left anterior descending coronary artery (Group 1); six patients with right coronary artery stenosis (Group 2), which is not drained by the GCV, were studied as controls.RESULTSIn Group 1 at baseline, CD and ROOHs levels were higher in GCV than in aorta (p < 0.01 for both), and TRAP levels were lower (p < 0.01). Aortic levels of CD, ROOHs and TRAP did not change at any time after t0; venous levels of CD and ROOHs levels markedly increased at t1, at t5and remained elevated at t15(p < 0.01 for all comparisons vs. t0); venous levels of TRAP decreased at t1and t5(p < 0.01 vs. t0) and returned to normal at t15. In Group 2, CD, ROOHs and TRAP levels were similar in the aorta and GCV and did not change throughout the study.CONCLUSIONSShort episodes of myocardial ischemia during PTCA induce a sustained oxidative stress, which is detectable in the venous effluent of reperfused myocardium

Nebivolol and its 4-keto derivative increase nitric oxide in endothelial cells by reducing its oxidative inactivation

AbstractObjectivesThe objective of the present study was to elucidate the vasodilator mechanisms of nebivolol, a high selective β1-receptor antagonist with antioxidant properties.BackgroundOxidative inactivation of nitric oxide (NO) is regarded as an important cause of its decreased biological activity.MethodsOxidative stress was induced through the binding of oxidized (ox)-low-density lipoprotein (LDL) to its specific endothelial receptor, called “lectin-like oxidized LDL receptor-1” (LOX-1), in bovine and human endothelial cells and in Chinese hamster ovary cells stably expressing bovine LOX-1 (BLOX-1-CHO cells). Reactive oxygen species (ROS), superoxide (O2·−), and NO were measured in cells by flow cytometry.ResultsNebivolol and its 4-keto derivative prevented in a dose-dependent manner the increase of ROS (p < 0.001) and O2·−(p < 0.001) in bovine aortic endothelial cells (BAECs), human umbilical vein endothelial cells (HUVECs), and BLOX-1-CHO cells stimulated with ox-LDL. Atenolol had no effect. The incubation of HUVECs and BAECs with ox-LDL reduced basal and bradykinin-induced NO and nitrite concentration (p from <0.001 to <0.01). Nebivolol and its 4-keto derivative prevented the reduction of basal and stimulated NO and nitrite concentration (p from <0.001 to <0.01) while atenolol had no effect. The preincubation of BAECs with blocking anti-LOX-1 monoclonal antibody (LOX-1 mAb) significantly counteracted the effect of ox-LDL on stimulated generation of NO (p < 0.001), but the effect was significantly lower than that of nebivolol and its 4-keto derivative alone (p < 0.01).ConclusionsIn conclusion, the findings of the present study indicate that nebivolol increases NO also by decreasing its oxidative inactivation

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

Electronic Cigarettes and Cardiovascular Risk: Caution Waiting for Evidence

Electronic cigarettes use is a growing trend in contemporary societies, with the propensity to compete with traditional tobacco smoking. Some preclinical studies demonstrated the toxic and detrimental effects of electronic cigarettes liquid components. Its impact on human health remains unknown and insufficiently studied. While some studies suggest that electronic cigarettes use might be associated with endothelial dysfunction, impaired platelet function and increased risk of adverse clinical events, other studies did not confirm these findings and epidemiological data mostly suggest that the use of electronic cigarettes appears to be safer than that of traditional tobacco cigarettes. This article provides an up-to-date overview of the current state of knowledge regarding electronic cigarettes and their impact on human health, with special emphasis on their effect on cardiovascular diseases

ORal anticoagulants In fraGile patients with percutAneous endoscopic gastrostoMy and atrIal fibrillation: the (ORIGAMI) study

BACKGROUND: Randomized trials support the safety and efficacy of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with nonvalvular atrial fibrillation, leading to increased use of these compounds. Crushed forms of DOACs have been shown to be reliable, but evidence supporting percutaneous endoscopic gastrostomy (PEG) delivery is lacking. PEG is a long-term option for enteral food and drug delivery in patients unable to maintain oral intake, bypassing the risks and disadvantages of parenteral nutrition.AIMS: The ORal anticoagulants In fraGile patients with percutAneous endoscopic gastrostoMy and atrIal fibrillation (ORIGAMI) study investigates the safety and efficacy of Edoxaban administered via PEG in patients with atrial fibrillation and a clinical indication for a long-term anticoagulation.DESIGN: In this prospective, single-centre observational study, 12 PEG-treated patients with indication to anticoagulation will receive edoxaban via PEG and will be followed up to 6 months. Plasma antifactor Xa activity and edoxaban concentrations will be assessed. Thromboembolic (ischaemic stroke, systemic embolism, venous thromboembolism) and bleeding events (Bleeding Academic Research Consortium and Thrombolysis in Myocardial Infarction) will be recorded at 1 and 6 months.PRELIMINARY CASES: A retrospective analysis of five atrial fibrillation cases undergoing PEG implantation at our Institution who received edoxaban via PEG showed plasma anti-FXa levels at a steady state of 146 ± 15 ng/ml, without major adverse event at a mean follow-up of 6 months.CONCLUSION: ORIGAMI prospectively investigates PEG-administration of edoxaban in PEG-treated patients requiring long-term anticoagulation. Our preliminary retrospective data support this route of DOAC administration. CLINICALTRIALS.GOV IDENTIFIER: NCT04271293

Parathyroid Retrospective Analysis of Neoplasms Incidence (pTRANI Study): An Italian Multicenter Study on Parathyroid Carcinoma and Atypical Parathyroid Tumour

Background: Parathyroid cancer (PC) is a rare sporadic or hereditary malignancy whose histologic features were redefined with the 2022 WHO classification. A total of 24 Italian institutions designed this multicenter study to specify PC incidence, describe its clinical, functional, and imaging characteristics and improve its differentiation from the atypical parathyroid tumour (APT). Methods: All relevant information was collected about PC and APT patients treated between 2009 and 2021. Results: Among 8361 parathyroidectomies, 351 patients (mean age 59.0 ± 14.5; F = 210, 59.8%) were divided into the APT (n = 226, 2.8%) and PC group (n = 125, 1.5%). PC showed significantly higher rates (p &lt; 0.05) of bone involvement, abdominal, and neurological symptoms than APT (48.8% vs. 35.0%, 17.6% vs. 7.1%, 13.6% vs. 5.3%, respectively). Ultrasound (US) diameter &gt;3 cm (30.9% vs. 19.3%, p = 0.049) was significantly more common in the PC. A significantly higher frequency of local recurrences was observed in the PC (8.0% vs. 2.7%, p = 0.022). Mortality due to consequences of cancer or uncontrolled hyperparathyroidism was 3.3%. Conclusions: Symptomatic hyperparathyroidism, high PTH and albumin-corrected serum calcium values, and a US diameter &gt;3 cm may be considered features differentiating PC from APT. 2022 WHO criteria did not impact the diagnosis