Prognostic significance of the wall to lumen ratio of retinal arterioles evaluated by adaptive optics.

OBJECTIVE: Microvascular structural alterations may be considered an important form of hypertension-mediated organ damage. An increased media-to-lumen ratio of subcutaneous small arteries evaluated with locally invasive techniques (micromyography) predicts the development of cardiovascular (CV) events. However, it is not known whether retinal arteriole structural alterations evaluated with a noninvasive approach (Adaptive Optics) may have a prognostic significance. DESIGN AND METHODS: Two-hundred and thirty-seven subjects (mean age 58.7 ± 16.1 years, age range 13-89 years; 116 males) were included in the study: 65 normotensive subjects (27.4 %) and 172 patients with essential hypertension or primary aldosteronism (72.6 %). All subjects underwent a non-invasive evaluation of retinal arteriolar wall-to-lumen ratio (WLR) by Adaptive Optics. Subjects were re-evaluated after an average follow-up time of 4.55 years in order to assess the occurrence of clinical events (non CV and/or CV death or events). RESULTS: Fifty-four events occurred in the study population:26 were cardio-cerebrovascular events (ischemic or hemorragic stroke, atrial fibrillation, heart failure, coronary artery disease, peripheral artery disease, cardiac valvular disease) while the remaining were deaths for any cause, or neoplastic diseases. Subjects with events were older and had a WLR of retinal arterioles significantly greater than those without events. The event-free survival was significantly worse in those with a baseline WLR above the median value of the population (0.28) according to Kaplan-Mayer survival curves and multivariate analysis (Cox's proportional hazard model). The evidence was confirmed after restricting the analysis to CV events. CONCLUSIONS: Structural alterations of retinal arterioles evaluated by Adaptive Optics may predict total and CV events.

Impact of renal failure and high-platelet reactivity on major cardiovascular ischemic events among patients with acute coronary syndrome receiving dual antiplatelet therapy with ticagrelor.

BACKGROUND: No study has so far evaluated the impact of chronic kidney disease (CKD) on high-on treatment platelet reactivity (HRPR) with ticagrelor and their prognostic consequences, that were therefore the aim of the present study. METHODS: Patients on dual antiplatelet therapy with ASA+ticagrelor (90mg/twice a day) after percutaneous coronary revascularization for ACS were scheduled for platelet function assessment 30-90 days post-discharge. The primary study endpoint was defined as the occurrence of major cardiovascular events (a composite of cardiovascular death, recurrent acute coronary syndrome (MI), target vessel revascularization) at the longest available follow-up. RESULTS: We included 396 patients, that were divided according to CKD (eGFR

Perioperative management of P2Y12 inhibitors in patients undergoing cardiac surgery within 1 year of PCI.

AIMS: To evaluate the impact of perioperative P2Y12 receptor inhibitor therapy among patients undergoing cardiac surgery within 1 year of percutaneous coronary intervention (PCI). METHODS AND RESULTS: Patients undergoing cardiac surgery in the year post-PCI at three tertiary care centres between 2011 and 2018 were stratified into those who had received at least one dose of P2Y12 inhibitor prior to surgery (within 5 days for clopidogrel or prasugrel, or within 3 days for ticagrelor) and those who had not. The outcomes of interest were major adverse cardiac and cerebrovascular events (MACCEs) and bleeding. Among 20 279 PCI patients, 359 (1.8%) underwent cardiac surgery in the ensuing year, 76.3% of whom received coronary artery bypass grafts. Overall, 33 (9.2%) MACCEs and 85 (23.7%) bleeding events occurred within 30 days post-cardiac surgery. Perioperative P2Y12 inhibition (N = 133, 37%) was not associated with the risk of MACCEs or bleeding, despite numerically lower rates of myocardial infarction or stent thrombosis (0.0% vs. 2.6%; P = 0.089). Patients who continued the P2Y12 inhibitor until the day of surgery (N = 60, 17%) had significantly higher bleeding risk [adjusted odds ratio 2.93, 95% confidence interval 1.53-5.59)]. Predictors of MACCEs included a time interval from PCI to cardiac surgery of ≤30 days and reduced ejection fraction, whereas urgent/emergent surgery predicted bleeding. Chronic kidney disease and myocardial infarction as indication for PCI predicted both MACCEs and bleeding. CONCLUSION: Among patients undergoing cardiac surgery in the year after PCI, the perioperative risk of ischaemic and bleeding events might be influenced by P2Y12 inhibitor therapy in addition to other risk parameters, including the timing and urgency of the procedure.

Impact of Sex on the Functional Assessment of Intermediate Coronary Lesions by Instantaneous Wave-Free Ratio.

Sex differences in coronary physiology and in the pathogenesis of coronary artery disease (CAD) have been previously described. Contrasting data have been reported, so far, about the impact of sex on the assessment of the functional significance of intermediate coronary stenoses by fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR). The present study aimed at assessing the sex differences in the results of iFR in a cohort of patients undergoing coronary angiography. METHODS: We included patients undergoing coronary angiography and the functional assessment of intermediate (40 to 70%) coronary lesions in 2 centers. iFR measurement was performed by pressure-recording guidewire and automatically calculated at the core laboratory using the manufacturers' dedicated software. Quantitative parameters of the coronary lesions were calculated by an automatic edge-detection system. Minimal luminal diameter (MLD), reference diameter (RD), percent diameter stenosis, and length of the lesion were measured. Positive iFR was considered for values < 0.90. RESULTS: We included 325 patients undergoing coronary angiography and iFR evaluation of 371 intermediate coronary stenoses, including 20.6% of women. Females were older, displayed lower body weight and hemoglobin, lower rate of active smoking (p < 0.001) and previous PCI (p = 0.04), lower platelet count (p = 0.001) and creatinine (p = 0.02). Systolic blood pressure and heart rate at admission were more elevated in women (p = 0.001 and p = 0.05, respectively). At angiography, multivessel coronary artery disease was more uncommon (p = 0.001) and proximal lesions were more frequently assessed by iFR (p = 0.04). Mean values of iFR did not differ with sex and neither the percentage of positive iFR (19.1% vs 18.8%, p = 0.99, adjusted OR[95%CI] = 0.51[0.18-1.48], p = 0.22). CONCLUSION: Among patients undergoing functional assessment of intermediate coronary lesions by instantaneous wave-free ratio, no impact of sex was observed on the absolute values or the rate of positivity of iFR.

Impact of target vessel choice on outcomes following percutaneous coronary intervention in patients with a prior coronary artery bypass graft.

OBJECTIVES: To evaluate and compare characteristics and clinical outcomes of percutaneous coronary intervention (PCI) among target vessel types in patients with a prior coronary artery bypass graft (CABG) surgery. BACKGROUND: Patients with a prior CABG often require repeat revascularization with PCI. Graft PCI has been associated with worse outcomes compared to native vessel PCI, yet the optimal PCI strategy in prior CABG patients remains unknown. METHODS: We stratified prior CABG patients who underwent PCI at a tertiary-care center between 2009 and 2017 by target vessel type: native vessel, venous graft, and arterial graft. The primary outcome of major adverse cardiac events (MACE) was a composite of all-cause death, myocardial infarction, stent thrombosis, or target vessel revascularization up to 1 year post-PCI. RESULTS: Prior CABG patients (n = 3983) represented 19.5% of all PCI interventions during the study period. PCI was most frequently performed on native vessels (n = 2928, 73.5%) followed by venous (n = 883, 22.2%) and arterial grafts (n = 172, 4.3%). Procedural success and complications were similar among the groups; however, slow- and no-reflow phenomenon was more common in venous graft PCI compared to native vessel PCI (OR 4.78; 95% CI 2.56-8.95; p < 0.001). At 1 year, there were no significant differences in MACE or in its individual components. CONCLUSIONS: Target vessel choice did not appear to affect MACE at 1 year in a large cohort of patients with prior CABG undergoing PCI. Whether PCI of surgical grafts versus native arteries truly results in similar outcomes warrants further investigation in randomized controlled trials.

Microvascular Structural Alterations in Cancer Patients Treated With Antiangiogenic Drugs.

Objective: Antiangiogenic therapies (tyrosine kinase inhibitors-TKI and direct anti-VEGF monoclonal antibodies) are being increasingly used in the treatment of solid tumors; hypertension represents a common side effect of these agents. Several mechanisms are involved in the development of hypertension, including microvascular rarefaction and other microvascular alterations. Therefore, the aim of our study was to evaluate whether TKI and direct anti-VEGF agents may affect the structure of retinal arterioles or capillary density. Design and Methods: We investigated 20 patients with a diagnosis of cancer who underwent a treatment with either a TKI or an anti-VEGF antibody. Patients were submitted to ambulatory monitoring blood pressure for blood pressure evaluation. Basal and total capillary density were assessed by capillaroscopy whereas, retinal arteriole morphology was measured by Adaptive Optics. Patients were evaluated before starting the antiangiogenic therapy (T0) and re-evaluated after 3 (T3) and 6 (T6) months after treatment. Fourteen patients completed the study. Results: Systolic and diastolic blood pressure values were similar in all patients at T3 and T6 compared to T0. However, during the study antihypertensive treatment was optimized (increased dose and/or addition of drugs) in 57% of patients (n = 8). No differences were observed in retinal arteriole structural parameters and in large artery stiffness. Basal capillary density was reduced by antiangiogenic drugs after 3 or 6 months. Conclusions: Our data suggest that an increase of antihypertensive treatment is necessary in patients treated with a TKI or a direct VEGF inhibitor, confirming pro-hypertensive effects of these drugs. However, under adequate blood pressure control, microvascular structure seem to be partially preserved, since a worsening of basal capillary density but no changes in retinal arteriole morphology were observed.

Low hemoglobin predicts high-platelet reactivity and major cardiovascular ischemic events at long-term follow-up among ACS patients receiving dual antiplatelet therapy with ticagrelor.

BACKGROUND: Reduced levels of hemoglobin (Hb) represent an established marker of impaired outcomes and increased cardiovascular risk in patients with coronary artery disease, challenging the management of dual antiplatelet therapy (DAPT). However, while anemia has emerged as an independent predictor of suboptimal platelet inhibition in patients receiving clopidogrel, no study has so far evaluated the impact of Hb levels on high-on treatment platelet reactivity (HRPR) with ticagrelor and their prognostic consequences, that were the aim of the present study. METHODS: Patients on DAPT with ASA + Ticagrelor (90 mg/twice a day) after percutaneous coronary revascularization for ACS were scheduled for platelet function assessment 30-90 days post-discharge. Aggregation tests were performed by multiple electrode aggregometry. Suboptimal platelet inhibition (HRPR-high residual platelet reactivity was defined if above the lower limit of normality (417 AU*min). The primary study endpoint was defined as the occurrence of major cardiovascular events (a composite of cardiovascular death, recurrent acute coronary syndrome [MI], target vessel revascularization) at longest available follow-up. RESULTS: We included 397 patients that were divided according to tertiles values of Hb (< 12.7, 12-7-14.09, ≥14.1 g/dl). Patients with lower Hb were older and displayed a more severe cardiovascular risk profile. Mean levels of platelet reactivity were enhanced in patients with lower Hb after stimulation with TRAP peptide (TRAP test, p = .03) and ADP (p = .02). Elevated platelet reactivity (HRPR) on Ticagrelor was more frequent among patients with reduced Hb (16.4% vs. 12% vs. 5.4%, p = .005, adjusted OR [95%CI] = 1.71[0.996;3.01], p = .056). At a mean follow-up of 820.9 ± 553.4 days, 21.4% of the patients experienced the primary composite endpoint, with a higher rate of events in patients with lower Hb (27.6% vs. 22.6% vs. 13.5%, p = .006, adjusted HR [95%CI] = 1.51[1.12; 2.03], p = .006), mainly driven by a higher rate of recurrent ACS. After correction for baseline differences lower Hb tertiles but not HRPR emerged as independent predictor of MACE (adjusted HR [95%CI] = 0.98[0.50; 1.92], p = .95). CONCLUSIONS: In the present study, we demonstrated that among patients on DAPT with ASA and ticagrelor after PCI for ACS, lower Hb levels are independently associated with a higher rate of HRPR and an increased rate of major ischemic events, and especially for recurrent ACS, although with no impact on survival. Neutral prognostic effect of HRPR was observed across Hb tertiles.

Impact of Age on the Functional Evaluation of Intermediate Coronary Stenoses With Instantaneous Wave-Free Ratio and Fractional Flow Reserve.

The optimal strategy for assessing the ischemic significance of intermediate coronary stenoses with adenosine-induced fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) is still debated. Few studies have previously assessed the impact of age on FFR and iFR, which was the aim of our study. Patients undergoing FFR and iFR evaluation for intermediate (40%-70%) coronary lesions were included and divided according to age. Fractional flow reserve was performed by intracoronary boluses of adenosine (60-1440 µg). Instantaneous wave-free ratio was automatically calculated. Among 148 patients undergoing FFR measurement of 166 lesions, 45.3% were ≥70 years. Elderly patients had higher minimal lumen diameter (P = .03). We also observed a linear relationship between iFR and FFR independently of age. Fractional flow reserve values were higher in the elderly patients, whereas iFR was not related to age. A total of 33 lesions had a positive iFR with no difference for age (17.3% vs 22%, P = .56), while FFR <0.80 was more infrequent in the elderly patients (17.1% vs 34.8%, P = .02). In intermediate coronary stenoses, iFR and FFR correlation is unaffected by age. Fractional flow reserve is higher in the elderly patients, whereas iFR is less affected by age. Future large-scale studies are needed to define whether iFR should be the preferred choice in elderly patients.

Association of lower vitamin D levels with inflammation and leucocytes parameters in patients with and without diabetes mellitus undergoing coronary angiography.

BACKGROUND: Diabetes mellitus has been associated with a chronic low-grade inflammation and a higher risk of cardiovascular and infectious disease, that could be prevented by the effects of vitamin D. We aimed at evaluating the impact of vitamin D levels on the biomarkers of acute-phase response, inflammation and glucose metabolism in a large cohort of diabetic patients with cardiovascular disease. MATERIALS AND METHODS: Consecutive patients undergoing coronary angiography were included. Diabetes mellitus was defined as previous diagnosis, specific treatment administration (oral drug or insulin), fasting glycaemia >6.99 mmol/L or HbA1c >48 mmol/L. Glucose parameters, white blood cells, Neutrophil-to-Lymphocyte Ratio (NLR), Monocyte-to-Lymphocyte Ratio (MLR), C-reactive protein (CRP) and vitamin D were measured at admission. Vitamin D levels were measured by chemiluminescence immunoassay kit LIAISON® Vitamin D assay (Diasorin Inc). RESULTS: We included 1472 diabetic patients and 2499 non-diabetic patients that were divided according to vitamin D tertiles. Among diabetic patients, lower levels of vitamin D were associated with female gender (P = .02), obesity (P = .004), active smoking and acute presentation (P < .001) and with a more atherogenic metabolic profile. The levels of white blood cells, leucocytes subfamilies, and inflammatory parameters significantly correlated with vitamin D levels in both patients with and without diabetes (diabetic: P = .012 for WBC, P = .004 for NLR and P < .001 for MLR and C-reactive protein, non-diabetic: P < .001 for WBC; NLR, MLR and C-reactive protein, respectively). Among diabetic patients, results were confirmed at multivariate analysis with no significant interaction according to glycaemic control. CONCLUSION: The present study demonstrates that, among patients with cardiovascular disease, vitamin D deficiency is associated with metabolic dysregulation and with an elevation of cellular and humoural inflammatory parameters, especially among diabetics, although not being dependent from glycaemic control.

Impact of the Polymorphism rs5751876 of the Purinergic Receptor ADORA2A on Periprocedural Myocardial Infarction in Patients Undergoing Percutaneous Coronary Intervention.

AIM: Periprocedural myocardial infarction (PMI), a severe complication of Percutaneous Coronary Intervention (PCI) procedures, has a negative prognostic effect, both at short and long-term follow-up. So far, adenosine's role in preventing PMI has shown contrasting results. A genetic variant of ADORA2A receptor, 1976 C＞T, has been suggested as a potential determinant of the interindividual response to adenosine, thus conditioning its potential benefits on PMI. In our study, we investigated whether the ADORA2A 1976 C＞T polymorphism is associated with PMI occurrence in patients undergoing coronary stenting. METHODS: The study included consecutive patients undergoing PCI at the Azienda Ospedaliera-Universitaria "Maggiore della Carità," Novara, Italy, between January 2010 and January 2016. Their genetic status was assessed using polymerase chain reaction (PCR) and restriction-fragment-length-polymorphism technique. Myonecrosis biomarkers were measured at intervals from 6 to 48 hours. PMI was defined as CKMB increased 3 times over the Upper Limit of Normal (ULN), or 50% of pre-PCI value; periprocedural myonecrosis was defined as troponin I increased 3 times over the ULN or by 50% of the baseline value. RESULTS: We included 1,104 patients undergoing PCI, 863 (78.2%) of whom carried the ADORA2A T-allele. No difference was found for the main demographic, clinical features, or biochemistry parameters. However, C-carriers had lower statin therapy use (p=0.008) and lower HDL-cholesterol levels (p=0.01). Homozygous C/C patients had more frequent multivessel disease (p=0.03), longer lesions (p=0.01) and Type C lesions (p=0.01), thus requiring more complex procedures. After correction for baseline confounding factors at multivariate analysis, there was no difference in myocardial necrosis according to the ADORA2A genotype (p=0.40). In contrast, PMI tended to increase in the homozygous C/C population (p=0.06), but this trend was attenuated at multivariate analysis after correction for baseline confounding factors (C/C: OR[95%CI]=1.52 [0.88-2.6], p=0.14). CONCLUSIONS: Our study showed that the polymorphism rs5751876 of the ADORA2A receptor is associated with a higher prevalence of complex coronary lesions and multivessel disease. However, it does not significantly influence the occurrence of periprocedural MI or myonecrosis.

Prognostic factors and predictors of outcome in patients with COVID-19 and related pneumonia: a retrospective cohort study.

The aim of the present study was to simultaneously assess several potential predictors of outcome (co-morbidity, previous and in-hospital treatment, radiologic Brixia score) in patients with COVID-19. This retrospective cohort study included 258 consecutive patients with confirmed COVID-19 admitted to a medical ward at Montichiari Hospital, Brescia, Italy from February 28th to April 30rd, 2020. Patients had SARS-CoV-2 related pneumonia with respiratory failure, and were treated with hydroxychloroquine and lopinavir plus ritonavir. In some patients, additional treatment with tocilizumab, dexamethasone and enoxaparin was adopted. Outcomes (death or recovery) were assessed at the end of the discharge period or at the end of the follow-up (August 2020). During hospitalization, 59 patients died, while 6 died after discharge. The following variables were demonstrated to be associated with a worse prognosis: Radiologic Brixia score higher than 8, presence at baseline of hypertension, diabetes, chronic obstructive pulmonary disease, heart disease, cancer, previous treatment with ACE-inhibitors or anti-platelet drugs. Anticoagulant treatment during hospital admission with enoxaparin at a dose higher than 4000 U once daily was associated with a better prognosis. In conclusion, our study demonstrates that some co-morbidities and cardiovascular risk factors may affect prognosis. The radiologic Brixia score may be a useful tool to stratify the risk of death at baseline. Anticoagulant treatment with enoxaparin might be associated to a clinical benefit in terms of survival in patients with COVID-19.

Impact of the rs73598374 polymorphism of the adenosine deaminase gene on platelet reactivity and long-term outcomes among patients with acute coronary syndrome treated with ticagrelor.

BACKGROUND: The positive interaction of ticagrelor with the metabolism of adenosine has been claimed for the large antithrombotic and antiischemic benefits of this antiplatelet agent in acute coronary syndromes (ACS). Adenosine catabolism is regulated by the activity of the adenosine deaminase enzyme (ADA), for which several polymorphisms have been identified. Therefore, the aim of our study was to explore the impact of the rs73598374 polymorphism of ADA gene on platelet reactivity in ACS patients treated with ticagrelor. METHODS: We included consecutive patients receiving ASA and ticagrelor after an ACS and coronary intervention. Platelet reactivity was evaluated by impedance aggregometry at 30-90 days post-discharge. The genetic analysis was carried out by PCR and RFLP. Clinical endpoints were mortality, cardiovascular death, recurrent myocardial infarction or coronary revascularization at the maximum available follow-up. RESULTS: Our population is represented by 464 patients, of whom 33.4% were A-heterozygotes and 6 homozygotes. A-allele carriers showed a greater prevalence of renal failure (p = 0.02) and a lower rate of previous coronary artery bypass graft (p = 0.03) and statin treatment (p = 0.02). No differences in the mean values of platelet reactivity or HRPR on ticagrelor were found according to the ADA genotype (11.3%vs13.9%, p = 0.45; adjusted OR[95% CI] = 1.17[0.64-2.14], p = 0.61). At follow up, patients carrying the A-allele showed a non-significantly lower incidence of ACS and repeated unplanned revascularization, although with no effect on mortality. CONCLUSIONS: In the present study the rs73598374 polymorphism of the ADA gene did not affect platelet reactivity or the long-term prognosis in patients with ACS receiving dual antiplatelet therapy with ASA and ticagrelor.

Higher neutrophil-to-lymphocyte ratio (NLR) increases the risk of suboptimal platelet inhibition and major cardiovascular ischemic events among ACS patients receiving dual antiplatelet therapy with ticagrelor.

BACKGROUND: Neutrophil to lymphocyte ratio (NLR) has emerged as a useful and easy-to-assess prognostic tool and biomarker of cardiovascular risk. However, few studies have evaluated its role on platelet inhibition among patients on dual antiplatelet therapy (DAPT), and especially in the settings of acute coronary syndromes (ACS). We aimed at assessing the impact of NLR on platelet reactivity and the risk of major ischemic events at long-term follow-up among ACS patients on DAPT with ticagrelor. METHODS: Patients on dual antiplatelet therapy with ASA + ticagrelor (90 mg/twice a day) after percutaneous coronary revascularization for ACS were scheduled for platelet function assessment 30-90 days post-discharge. Aggregation tests were performed by Multiple Electrode Aggregometry (MEA). Suboptimal platelet inhibition (HRPR-high residual platelet reactivity was defined if above the lower limit of normality (417 AU*min). The primary study endpoint was defined as the occurrence of major cardiovascular events (a composite of cardiovascular death, recurrent acute coronary syndrome, target vessel revascularization) at longest available follow-up. RESULTS: We included 397 patients, that were divided according to NLR tertiles. Patients with higher NLR were older (p < .001), less frequently smokers (p = .03), with higher rates of renal failure (p = .001), previous bypass surgery (p = .05) and use of statins (p = .03) and diuretics (p = .01). Higher white blood cells count and C-reactive protein (p < .001) and lower haemoglobin (p = .001) were associated with NLR. Mean platelet reactivity and the prevalence of high platelet reactivity (HRPR) on ticagrelor were significantly associated to higher NLR tertiles values (7% vs 12% vs 14.3%, p = .04), with a significant relationship between NLR and platelet reactivity being confirmed for all the different activating stimuli. At a mean follow-up of 939 ± 581.4 days, 21.2% of the patients experienced the primary composite endpoint, with a trend for a higher risk of events across NLR tertiles (15.4% vs 24.2% vs 24.4%, p = .09), that became statistically significant after correction for baseline confounders (adjusted HR[95%CI] = 1.13[1.008-1.26], p = .036). Moreover, NLR was significantly associated to overall mortality and recurrent ACS (adjusted p = .008, p = .06 and p = .02 respectively). CONCLUSIONS: In the present study we found that among ACS patients treated with ASA and ticagrelor after PCI, suboptimal platelet inhibition despite DAPT was significantly increased for higher values of Neutrophil-to-Lymphocyte Ratio. Moreover, mortality and the risk of recurrent major ischemic events at long-term were associated to NLR.

Relationship between adenosine A2a receptor polymorphism rs5751876 and fractional flow reserve during percutaneous coronary intervention.

Fractional flow reserve (FFR) assessed during adenosine-induced maximal hyperemia has emerged as a useful tool for the guidance of percutaneous coronary interventions (PCI). However, interindividual variability in the response to adenosine has been claimed as a major limitation to the use of adenosine for the measurement of FFR, carrying the risk of underestimating the severity of coronary stenoses, with potential negative prognostic consequences. Genetic variants of the adenosine receptor A2a (ADORA2A gene), located in the coronary circulation, have been involved in the modulation of the hyperemic response to adenosine. However, no study has so far evaluated the impact of the single nucleotide polymorphism rs5751876 of ADORA2A on the measurement of FFR in patients undergoing percutaneous coronary intervention that was, therefore, the aim of our study. We included patients undergoing coronary angiography and FFR assessment for intermediate (40-70%) coronary lesions. FFR measurement was performed by pressure-recording guidewire (Prime Wire, Volcano), after induction of hyperemia with intracoronary boli of adenosine (from 60 to 1440 µg, with dose doubling at each step). Restriction fragment length polymorphism (RFLP) analysis was performed to assess the presence of rs5751876 C>T polymorphism of ADORA2a receptor. We included 204 patients undergoing FFR measurement of 231 coronary lesions. A total of 134 patients carried the polymorphism (T allele), of whom 41 (30.6%) in homozygosis (T/T).Main clinical and angiographic features did not differ according to ADORA2A genotype. The rs5751876 C>T polymorphism did not affect mean FFR values (p = 0.91), the percentage of positive FFR (p = 0.54) and the duration of maximal hyperemia. However, the time to recovery to baseline FFR values was more prolonged among the T-allele carriers as compared to wild-type patients (p = 0.04). Based on these results, in patients with intermediate coronary stenoses undergoing FFR assessment with adenosine, the polymorphism rs5751876 of ADORA2A does not affect the peak hyperemic response to adenosine and the results of FFR. However, a more prolonged effect of adenosine was observed in T-carriers.

Impact of gender on immature platelet count and its relationship with coronary artery disease.

The impact of platelet parameters on the cardiovascular risk is still debated. Gender differences in platelet volume indexes and turnover have been previously reported, potentially conditioning their role in the development of coronary artery disease (CAD). However, few studies have addressed, so far, the impact of gender on the immature platelet fraction (IPF) and count (IPC) and their relationship with CAD. We enrolled consecutive patients undergoing coronary angiography in a single centre. IPF and platelet indexes were measured at admission. Significant CAD was defined as the presence of at least one coronary stenosis more than 50%. A total of 2550 patients were included, 1835 (72%) were males, and 715 (28%) were females. Female patients were older (p < 0.001), with lower BMI (p = 0.002), lower prevalence of active smoking (p < 0.001), previous MI, previous PCI and CABG (p = 0.001, p = 0.001, p < 0.001), whilst a higher prevalence of renal failure (p = 0.02), acute presentation (p < 0.001) and CAD (p < 0.001). Platelet count was higher in females (p < 0.001), as well as the IPC levels (838.38 ± 562.05 vs 792.24 ± 535.66, p = 0.05) with no difference in the levels of immature platelet fraction (3.67 ± 2.68% vs 3.74 ± 2.6%, p = 0.55) or the prevalence of patients with IPF ≥ 3rd tertile (33.7% vs 35.2%, p = 0.26). At multivariate analysis, after correction for baseline confounders, gender did not emerge as an independent predictor of higher IPF (adjusted OR [95% CI] = 0.82 [0.64-1.06], p = 0.13). When dividing our patients according to the levels of IPF, in women we observed an inverse association between IPF ≥ 3rd tertile and coronary calcifications (p = 0.025) and a higher prevalence of restenosis (p = 0.003), but no difference in CAD (65.6% vs 66.9%, p = 0.71) or severe CAD (28.1% vs 24.7%, p = 0.31). In males, the IPF ≥ 3rd tertile related with a lower TIMI flow (p = 0.001). Males with lower IPF had a significantly higher percentage of CAD (87.7% vs 83.3%, p = 0.007; adjusted OR: 0.699 [95% CI] = [0.54-0.91], p = 0.008) but not for severe CAD (36.5% vs 39.9%, p = 0.134). The present study shows that among patients undergoing coronary angiography, gender is not associated to the levels of immature platelet fraction. Moreover, we found no association between IPF and the prevalence and extent of CAD in female gender, whereas in male gender the IPF was inversely related with the prevalence of CAD.

Gender Differences in Platelet Reactivity in Diabetic Patients Receiving Dual Antiplatelet Therapy.

BACKGROUND: Increased comorbidities and a perceived high-bleeding risk often prevent the use of dual antiplatelet therapy (DAPT) in female patients. However, more aggressive antiplatelet treatment would certainly offer additional outcome benefits in coronary artery disease, especially among diabetic patients. The aim of the present study was to evaluate the gender differences in high-residual on treatment platelet reactivity (HRPR) among diabetic patients treated with DAPT. METHODS: Our population is represented by a consecutive cohort of diabetic patients treated with DAPT (ASA + clopidogrel, ticagrelor or dose-adjusted prasugrel) for an acute coronary syndrome or elective PCI, undergoing platelet reactivity assessment at 30-90 days post-discharge. Aggregation was assessed by multiple-electrode aggregometry and in diabetic patients naïve to antiplatelet therapy, by light transmission aggregometry, surface expression of P-selectin and plasma concentration of Thromboxane B2. RESULTS: We included 472 patients, 113 (23.9%) women. Female gender was associated with more advanced age, and increased comorbidities. Mean platelet reactivity did not differ according to gender. The rate of HRPR was similar in women as compared to men (for ASA: adjusted OR[95%CI] = 0.59[0.27-1.33], p = 0.21, for ADP-antagonists: adjusted OR[95%CI] = 1.24[0.25-1.80], p = 0.27), however, the benefits of the new ADP-antagonists on platelet reactivity were lower in women than in men (p interaction = 0.01). No impact of gender on platelet reactivity was confirmed among 50 diabetic patients naïve to antiplatelet therapy. CONCLUSIONS: Among diabetic patients receiving dual antiplatelet therapy gender does not affect platelet reactivity or high-on treatment platelet reactivity. However, the enhanced platelet inhibition provided by the new-ADP antagonists of new-ADP antagonists could be mitigated in women.

Impact of active smoking on the immature platelet fraction and its relationship with the extent of coronary artery disease.

INTRODUCTION: Smoking represents a major cardiovascular risk factor, due to the induction of oxidative stress and low-grade, continuous, inflammation that contribute to promote atherothrombosis. However, the mechanisms leading to increased platelet aggregability associated with smoking are only partially defined. A potential role has been hypothesized for immature platelets, a younger and potentially more reactive fraction, previously associated with the main determinants of coronary artery disease (CAD). Therefore, the aim of our study was to define the impact of smoking on the immature platelet fraction (IPF) and its relationship with prevalence and extent of coronary artery disease. METHODS: We enrolled a cohort of consecutive patients undergoing coronary angiography in a single centre. Significant CAD was defined as at least 1 vessel stenosis >50%, while severe CAD was defined as left main and/or three-vessel disease. IPF was measured at admission by routine blood cell count (Sysmex XE-2100). RESULTS: We included in our study 2553 patients who were divided according to smoking status (active smokers: 512; nonactive smokers: 2041). Smokers were younger, more frequent males, with lower rate of diabetes mellitus, previous PCI and previous CABG (P < .001, respectively) and were in treatment less often with ARB, BB, nitrates, statins, ASA, clopidogrel, CCB and diuretics (P < .001, respectively) as compared to nonactive smokers. Higher percentage of smokers was observed in patients with higher IPF values, and at multivariate analysis, active smoking resulted as an independent predictor of higher IPF (adjusted OR [95% CI] = 1.59[1.03-2.45], P = .035). Among smokers, higher IPF was associated with lower ejection fraction (P = .034), percentage of acute coronary syndrome (P = .002) and platelet count (P < .001) compared to ones with lower IPF. However, the IPF (according to quartiles values) was not associated with the prevalence and extent of CAD (82.5%, 80.4%, 86.1% and 80.9%, from 1st to 4th quartile, respectively, adjusted OR[95% CI] = 0.98[0.79-1.23], P = .89) and severe CAD (31%, 31.1%, 39.1% and 35.2%, from 1st to 4th quartile, respectively, adjusted OR[95% CI] = 1.03[0.86-1.23], P = .76). CONCLUSION: The present study shows an independent association between active smoking and the levels of immature platelet fraction in patients undergoing coronary angiography. However, among active smokers, IPF did not result as an independent predictor of CAD or severe CAD.

Determinants of Smoking Status in a Sample of Outpatients Afferent to a Tertiary Referral Hospital.

The identification of determinants of attempts to quit smoking and quitting smoking success is crucial for effective smoking prevention and/or cessation programs. Thus, here we have conducted a survey to determine the sociodemographic characteristics of tobacco use and the potential determinants of quitting smoking among a population of 140 subjects-101 smokers and 39 ex-smokers-referred to our clinic for respiratory diseases. Subject characteristics included demographic data, employment and education status, respiratory disease family history, smoking habits, life habits, diet, alcohol intake, and physical activity. In comparison with former smokers, active smokers were younger, lived with at least one smoking family member, and were more frequently exposed to passive smoke. They also displayed a higher coffee consumption, a higher frequency of in-between-meal snacks, and a lower chronic obstructive pulmonary disease (COPD) prevalence. In comparison with subjects who had never attempted to quit smoking, individuals who had attempted to quit smoking were younger, had a lower pack-year median, consumed a higher amount of coffee and alcohol, and conducted regular physical activity. Determinants of successful smoking cessation were older age, lower passive smoking exposure and daily coffee intake, and COPD diagnosis. Overall, our findings underscore the importance of health education in fostering successful smoking cessation in respiratory disease patients.

Case report of a sub-occluding thrombus in thoracic aorta: what is the origin?

BACKGROUND: Aortic thrombosis represents a consequence of atherosclerotic disease. In few cases, it can be secondary to large vessel or infective vasculitis. More rarely, aortic thrombosis is the manifestation of a primary malignant neoplasm of the aortic wall. Aortic angiosarcoma is a rare tumour, its clinical presentation is often non-specific and associated signs and symptoms may vary greatly. An early diagnosis is difficult to reach and the presence of metastatic disease is not uncommon at the time of diagnosis. The prognosis is poor overall. CASE SUMMARY: We report the case of a female patient who presented to her GP because of fatigue, hyporexia, weight-loss, and anaemia. An ultrasound of the abdomen showed two small pancreatic lesions, confirmed and described as benign cystic pancreatic lesions on computed tomography (CT) imaging; an incidental thrombus in the superior mesenteric artery was also found on CT imaging. The thoracic CT identified a large thrombotic lesion in the descending thoracic aorta with significant narrowing of the aortic lumen and confirmed the presence of an osteolytic bone lesion on the VIII right rib, in the absence of atherosclerotic disease. Signs of increased metabolic activity in the aortic lumen and in the VIII posterior right rib were shown at a subsequent positron emission tomography. A CT-guided biopsy of the bone lesion was performed and at histology the diagnosis of metastatic angiosarcoma of the aortic wall was made. DISCUSSION: Aortic angiosarcoma is a rare cause of aortic thrombosis, to be taken into consideration in a patient with thrombotic lesions of the aorta in the absence of atherosclerotic disease. The differential diagnosis is difficult because of clinical presentation and radiological features similar to those of inflammatory aortic disease. In our case, the final diagnosis of angiosarcoma was made only by a biopsy of a bone metastatic lesion.

Impact of long-term therapy with acetylsalicylic acid on immature platelet count: a single-centre cohort study.

: Acetylsalicylic acid (ASA) represents one of the most widely used pharmacological treatments for the prevention of atherothrombotic events. However, its use in low-risk patients is still debated, due to the complex balance between benefits and bleeding complications, therefore requiring new tools for the assessment of cardiovascular risk. Immature platelet count (IPC) has been suggested as a marker of platelet reactivity and turnover, thus potentially reflecting the progression of the chronic atherothrombotic vascular damage, which could be prevented by ASA. However, no study has evaluated, so far, the impact of long-term therapy with ASA on the IPC among patients undergoing coronary angiography, which was the aim of the present study. We included patients from a single centre. Significant coronary artery disease (CAD) was defined as at least one-vessel stenosis more than 50%. Immature platelet fraction (IPF) levels were measured by routine blood cells count (a Sysmex XE-2100) in patients naive or chronically treated with ASA at admission. Among 1475 patients, 464 (31.5%) were ASA-naive. Patients on long-term antiplatelet therapy were more often men (P < 0.001), with a higher prevalence of cardiovascular risk factors and CAD. The mean levels of IPC did not differ between ASA-naive and treated patents (8 ±â€Š5.3 vs. 7.8 ±â€Š4.9, P = 0.48). Similar results were obtained when considering IPC distribution across tertiles, as ASA therapy did not result as an independent predictor of IPC levels above the third tertile (≥8.6 × 10/ml) [adjusted odds ratio (95% confidence interval) = 0.96 (0.63-1.48), P = 0.87]. Results were confirmed in major higher risk subgroups of patients. The present study shows that among high-risk patients undergoing coronary angiography, the long-term therapy with ASA does not affect the levels of IPC.