Search

Aim To evaluate the clinical relevance of antiphospholipid antibodies (aPL) in patients with lower extremity peripheral artery disease (PAD). Data sources EMBASE and MEDLINE databases were searched from inception to March 2020 for clinical studies reporting on the association between of aPL [IgG/IgM anticardiolipin (aCL) and lupus anticoagulant (LA)] and PAD. Methods We determined the pooled prevalence (PP) of patients positive for aPL in PAD or the PP of PAD in patients positive for aPL; we employed Peto's odds ratio with random effect for the meta-analysis. Results Twenty-one studies comprising 6,057 patients were evaluated: in patients with PAD, the PP of IgG aCL was 12% vs 4.1% in those without, IgM aCL was 13.2% vs 2.1%, and LA 13.3% vs 3.3%, respectively. The PP of patients with LA was greater in critical limb ischemia than in the control group (19.3% vs 4.2%). Also, the PP of patients with LA was greater in the failed than in the successful revascularisation group (35.8% vs 15.8%). The PP of post-procedural revascularisation failures was similar in the groups given or not given oral anticoagulation (59.2% vs 61.9%). Conclusion All the aPL related to PAD regardless of diagnostic definition used, whereas LA related also to critical limb ischaemia and failed revascularisation. Data expressed as percentage of participants positive for aPL limit the interpretation of these relationships.

Mastocytosis is a rare disease characterized by clonal proliferation of mast cells (MCs) in different organs. Clinical manifestations of mastocytosis are mostly due to release of mediators from MCs and, in many cases, such as urticaria, flushing, angioedema, and anaphylaxis, are an expression of the biological effects of mediators on endothelial cells. Chronic secretion of mediators in patients with mastocytosis can lead to alteration of endothelial function.We sought to investigate endothelial function in patients with mastocytosis using a noninvasive technique of flow-mediated dilation (FMD).Twenty-five adult patients with indolent and advanced forms of mastocytosis and 20 healthy control subjects were enrolled in the study. Ultrasound assessment of FMD was performed by measuring changes in the diameter of the brachial artery after 5 minutes of arterial occlusion. Changes in FMD were correlated with clinical parameters and serum tryptase levels.Patients with mastocytosis had lower FMD compared with healthy control subjects (P .001). Advanced and smoldering forms showed a lower FMD compared with indolent forms (P .001). FMD inversely correlated with age and serum tryptase levels and directly with median arterial pressure and recurrent flushing episodes. No correlation was found between FMD and osteoporosis, recurrent anaphylaxis, presence of skin lesions, and long-term antihistamine treatment.Endothelial dysfunction, as demonstrated by FMD reduction, is detectable in patients with mastocytosis and is more severe in patients with high tryptase levels and advanced disease. Endothelial function appears to be negatively influenced by MC proliferation rather than by the severity of mediator-related symptoms.

Community-acquired pneumonia (CAP) is complicated by cardiovascular events as myocardial infarction and stroke but the underlying mechanism is still unclear. We hypothesized that endothelial dysfunction may be implicated and that endotoxemia may have a role.Fifty patients with CAP and 50 controls were enrolled. At admission and at discharge, flow-mediated dilation (FMD), serum levels of endotoxins and oxidative stress, as assessed by serum levels of nitrite/nitrate (NOx) and isoprostanes, were studied.At admission, a significant difference between patients with CAP and controls was observed for FMD (2.1±0.3 vs 4.0±0.3%, p0.001), serum endotoxins (157.8±7.6 vs 33.1±4.8pg/ml), serum isoprostanes (341±14 vs 286±10 pM, p=0.009) and NOx (24.3±1.1 vs 29.7±2.2μM). Simple linear correlation analysis showed that serum endotoxins significantly correlated with Pneumonia Severity Index score (Rs=0.386, p=0.006). Compared to baseline, at discharge CAP patients showed a significant increase of FMD and NOx (from 2.1±0.3 to 4.6±0.4%, p0.001 and from 24.3±1.1 to 31.1±1.5μM, p0.001, respectively) and a significant decrease of serum endotoxins and isoprostanes (from 157.8±7.6 to 55.5±2.3pg/ml, p0.001, and from 341±14 to 312±14 pM, p0.001, respectively). Conversely, no changes for FMD, NOx, serum endotoxins and isoprostanes were observed in controls between baseline and discharge. Changes of FMD significantly correlated with changes of serum endotoxins (Rs=-0.315; p=0.001).The study provides the first evidence that CAP is characterized by impaired FMD with a mechanism potentially involving endotoxin production and oxidative stress.

Platelet activation plays a major role in cardiovascular events (CVEs). Mediterranean diet (Med-Diet) reduces the incidence of stroke and myocardial infarction but it is still unclear if it affects platelet activation. Aim of the study was to evaluate the effect of Med-Diet on the urinary excretion of 11-dehydro-thromboxane (Tx) B2, a marker of in vivo platelet activation, in patients with atrial fibrillation (AF).Prospective observational cohort study including 801 non-valvular AF patients on chronic treatment with warfarin/acenocumarol referring to I Medical Clinic - Atherothrombosis Center of Sapienza University of Rome, Italy, from February 2008 to December 2013. Adherence to Med-Diet was evaluated by a short nine-items dietary questionnaire. Urinary excretion of 11-dehydro-TxB2 was measured in all patients.Mean follow-up was 33.9 (±19.8) months, yielding 2223 patient/year of observation. Mean age of patients was 73.3 (±8.9) years, 43.7% were female. Median value of urinary TxB2 was 105.5 [60.0-190.0] ng/mg creatinine. We found a significant inverse correlation between total Med-Diet score and 11-dehydro-TxB2 values (Rs: -0.356, p0.001). In a multivariable stepwise linear regression analysis, history of stroke/TIA (β = 0.146, p = 0.003), olive oil (β = -0.130, p = 0.007), wine (β = -0.102, p = 0.036) and antiplatelet drugs (β = -0.098, p = 0.045) were independently associated to 11-dehydro-TxB2. We found no differences in the rate of ischemic or bleeding events across tertiles of Med-Diet score during follow-up.Med-Diet adherence is inversely associated to urinary excretion of 11-dehydro-TxB2, suggesting that Med-Diet may favorably affect platelet function in AF patients. Clinical Trial Registration: ClinicalTrials.gov NCT01882114.

BACKGROUND Recent findings suggest that patients with atrial fibrillation (AF), in addition being at thromboembolic risk, are at risk of myocardial infarction (MI). Our aim was to investigate predictors of MI and cardiovascular death in a cohort of patients with AF who were taking anticoagulants. METHODS We prospectively followed up 1,019 patients with AF for a median of 33.7 months (3,223 person-years). All patients were treated with oral vitamin K antagonists. Primary outcome was a composite end point of cardiovascular events (CVEs) including fatal/nonfatal MI, cardiac revascularization, and cardiovascular death. RESULTS The mean age of the patients was 73.2 years, and 43.8' were women. At follow-up, 111 CVEs (3.43'/y) had occurred: 47 fatal-nonfatal MI/revascularization and 64 cardiovascular deaths. In addition, 31 stroke/transient ischemic attacks (0.96'/y) were recorded. Patients experiencing CVEs were older ( P P = .005), heart failure ( P = .001), and prior cardiac ( P P P P = .011), history of cerebrovascular (HR, 1.704; 95' CI, 1.119-2.597; P = .013) and cardiac (HR, 1.658; 95' CI, 1.105-2.489; P = .015) events, MetS (HR, 1.663; 95' CI, 1.107-2.499; P = .014), heart failure (HR, 1.584; 95' CI, 1.021-2.456; P = .040), and male sex (HR, 1.499; 95' CI, 1.010-2.223; P = .044) predicted CVEs. CONCLUSIONS Patients with AF still experience a high rate of CVEs despite receiving anticoagulant treatment. MetS is a common clinical feature in patients with AF, which increases the risk of CVEs. A holistic approach is needed to reduce the cardiovascular risk in patients with AF. TRIAL REGISTRY ClinicalTrials.gov ; No.: NCT01882114; URL: www.clinicaltrials.gov

Some evidences suggest that the use of digoxin may be harmful inatrial fibrillation (AF) patients. The aim of the study was to investigate in a "real world" of AF patients receiving vitamin K antagonists (VKAs), the relationship between digoxin use and mortality.Prospective single-center observational study including 815 consecutive non-valvular AF patients treated with VKAs. Total mortality was the primary outcome of the study. We also performed a sub-analysis considering only cardiovascular (CV) deaths. Time in therapeutic range (TTR) was used for anticoagulation quality.Median follow-up was 33.2months (2460 person-years); 171 (21.0%) patients were taking digoxin. Compared to those without, patients on digoxin were older (p=0.007), with a clinical history of HF (p0.001) and at higher risk of thromboembolic events (p0.001). No difference in TTR between the two groups was registered (p=0.598). During the follow-up, 85 deaths occurred: 47 CV and 38 non-CV deaths; 35 deaths occurred in digoxin users (20.6%). A significant increased rate of total mortality was observed in digoxin-treated patients (p0.001). Multivariable analysis showed that digoxin was associated with total mortality (hazard ratio [HR]: 2.224, p0.001) and CV death (HR: 4.686, p0.001). A propensity score-matched analysis confirmed that digoxin was associated with total mortality (HR: 2.073, p=0.0263) and CV death (HR: 4.043, p=0.004).In AF patients on good anticoagulation control with VKAs, digoxin use was associated with a higher rate of total and CV mortality.

ReplyWe thank Dr Yildiz and Dr Soydinc for their interest and commentsonourrecentworkregardingtheassociationbetweentheuseofdigox-in and increased mortality in patients affected by atrial fibrillation (AF)[1].IntheirLettertotheEditor[2],Authorsraisemanyinterestingques-tions, suggesting that other factors, in addition to those reported in ourobservational study, may influence the incidence of cardiovascularoutcome in AF digoxin-treated patients.A crucialpointraisedby theAuthorsconcernsthe dosageof digoxinand blood concentrations, as these two factors contribute to the in-creasedriskofmortality[3].Digoxinserumlevelsabovethetherapeuticrangecanbefoundinapercentageofpatientsrangingfrom4to10%[4],and are known to be associated with cardiac toxicity and increasedmortality [5]. However, in a large cohort of 5100 patients in whichblood concentration of digoxin was measured, clinical toxicity attribut-ed to thepro-arrhythmic effectof digoxin havebeensuspected for only0.25% of total patients treated with digitalis [3].Renal dysfunction is another critical issue, which requires digoxintailoring to avoid toxicity; thus, 50%–70% of digitalis is excreted un-changed by the kidney [6].Noteworthy, in the large RIKS-HIA trial [7] including 1493 patientswith and 5540 without digoxin, the relative risk for death betweenpatients discharged with and without digoxin, after adjustment forpropensity score, was independent from baseline serum creatinine.Recent findings from the TREAT-AF study [8] confirmed that, in avery large cohort of 122,465 AF patients (353,168 person-years), theincreased mortality by digoxin was apparently independent from theestimated glomerular filtration rate (eGFR), the effect persisting alsoin the propensity-matched cohort.Inourpopulation,wefoundnodifferencesinrenalfunctionbetweenAF patients treated (n = 90, eGFR calculated by MDRD formula, 69.5[56.4–88.9] ml/min) or not (n = 426, eGFR 73.6 [59.5–87.3] ml/min,p = 0.601) with digoxin.Body mass composition did not apparently influence results fromour study, as at baseline no differences of body mass index (27.4 ±5.0 vs. 27.4 ± 4.7 kg/m