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Reply to. "monitoring antivitamin K anticoagulants in antiphospholipid syndrome. a challenge in quality"
No full textN/
Anti Xa oral anticoagulants inhibit in vivo platelet activation by modulating glycoprotein VI shedding
No full textAnti Xa non-vitamin K oral anticoagulants (anti Xa NOACs) seem to possess antiplatelet effect in vitro, but it is unclear if this occurs also in vivo. Aim of the study was to compare the effect on platelet activation of two anti Xa NOACs, namely apixaban and rivaroxaban, to warfarin, and to investigate the potential underlying mechanism by evaluating soluble glycoprotein GPVI (sGPVI), a protein involved in platelet activation. We performed a cross-sectional including AF patients treated with warfarin (n=30), or apixaban 10mg/day (n=40), or rivaroxaban 20mg/day (n=40). Patients were balanced for sex, age and cardiovascular risk factors. Platelet activation by urinary excretion of 11-dehydro-thromboxane (Tx) B2 and soluble GPVI (sGPVI) were analysed at baseline and after 3 months of treatment. Baseline TxB2 value was 155.2±42.7ng/mg creatinine. The 3 months-variation of urinary excretion of TxB2 was -6.5% with warfarin (p=0.197), -29% with apixaban (p<0.001) and -31% with rivaroxaban (p<0.001). Use of anti Xa NOACs was independently associated to the variation of urinary TxB2 (B: -0.469, p<0.001), after adjustment for clinical characteristics; sGPVI was significantly lower in patients treated with NOACs at 3 months (p<0.001), while only a trend for the warfarin group (p=0.116) was observed. The variation of sGPVI was correlated with that of TxB2 in the NOACs group (Rs: 0.527, p<0.001). In 15 patients (5 per each group) platelet recruitment was significantly lowered at 3 months by NOACs (p<0.001), but not by warfarin. The study provides evidence that anti Xa NOACs significantly inhibit urinary TxB2 excretion compared to warfarin, suggesting that NOACs possess antiplatelet propert
Antiphospholipid syndrome and anticoagulation quality: A clinical challenge
No full textBACKGROUND AND AIMS:
Antiphospholipid Syndrome (APS) is often complicated by ischemic vascular events. Vitamin K Antagonists (VKAs) reduce the risk of recurrent thrombosis. Quality of VKAs treatment, as assessed by the Time in Therapeutic Range (TTR), has never been investigated in APS patients.
METHODS:
We performed a prospective observational study including 30 APS and 30 Atrial Fibrillation (AF) patients balanced by age and gender. All patients were treated with VKAs (INR target 2.5), and TTR was calculated.
RESULTS:
Median TTR of APS was 53.5% vs. 68% of AF patients (p = 0.001). A multivariable linear regression analysis confirmed that the presence of APS (vs. AF) was independently associated with a worse TTR (B: -14.067, 95% Confidence Interval -25.868/-2.266, p = 0.020). The weekly dosage of VKAs was significantly higher in APS than AF patients.
CONCLUSIONS:
APS patients disclose a lower quality of anticoagulation compared to those with AF, requiring higher doses of VKAs. The efficacy of non-vitamin K oral anticoagulants in this high-risk patients should be tested
Cancer and atrial fibrillation: Epidemiology, mechanisms, and anticoagulation treatment
No full textCancer patients are at an increased risk of developing atrial fibrillation (AF) and thrombosis. However, the management of anticoagulation in patients with both diseases may be challenging, and data on these patients are lacking. We summarize the current evidence on the incidence and prevalence of cancer in AF and vice versa and provide some practical considerations on the management of oral anticoagulation in specific clinical situations. Low-molecular weight heparins are not approved for thromboprophylaxis in AF, and management of warfarin can be difficult. The use of direct oral anticoagulants may be particularly attractive for their rapid onset/offset action and lower bleeding risk
Vitamin E serum levels and bleeding risk in patients receiving oral anticoagulant therapy. A retrospective cohort study
No full textBACKGROUND:
Hemorrhagic risk assessment is a crucial issue in patients with nonvalvular atrial fibrillation (NVAF) who are receiving oral anticoagulant therapy (OAT). Our aim was to analyze the relationship between vitamin E, which possesses anticoagulant properties, and bleeding events in NVAF patients.
METHODS AND RESULTS:
In this retrospective observational study we analyzed baseline serum cholesterol-adjusted vitamin E (vit E/chol) levels in 566 consecutive patients (59% males, mean age 73.6 years) receiving OAT followed up for a mean time of 22 months. Mean time in therapeutic INR range (TTR) was 64%. The overall incidence rate of any bleeding event was 9.2/100 person-years. Compared to patients who did not bleed, those who experienced bleeding events (n=92, 73 minor and 15 major bleedings and 4 cerebral hemorrhages according to International Society on Thrombosis and Haemostasis [ISTH] ) classification) showed a significant difference for history of coronary heart disease (P=0.039), HAS-BLED score (P=0.002), and vit E/chol levels (P<0.001). Higher vit E/chol serum levels were found in patients who bled compared to those who did not (5.27 ± 1.93 versus 4.48 ± 1.97 μmol/cholesterol; P<0.001), with a progressive increase from minor (5.16 ± 1.91 μmol/mmol cholesterol, P=0.006) to major bleedings (5.72 ± 2.0 μmol/mmol cholesterol, P=0.008). A Cox proportional hazard model demonstrated that serum vit E/chol quartiles (global P=0.0189) and HAS-BLED scores (P=0.005) predicted bleeding events.
CONCLUSIONS:
In a NVAF population being treated with warfarin, serum vitamin E predicted hemorrhagic events. Further study is necessary to see if the relationship between serum levels of vitamin E and bleeding is still maintained with the use of new anticoagulants
Mediterranean diet reduces Thromboxane A2 production in atrial fibrillation patients
No full textBACKGROUND & AIMS:
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).
METHODS:
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.
RESULTS:
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, p < 0.001). 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.
CONCLUSIONS:
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
Extra virgin olive oil blunt post-prandial oxidative stress via NOX2 down-regulation.
No full textObjective: Olive oil protects against cardiovascular disease but the underlying mechanism is still unclear.
We speculated that olive oil could inhibit oxidative stress, which is believed to be implicated in the
atherosclerotic process.
Methods and results: Post-prandial oxidative stress and endothelial dysfunction were investigated in
twenty-five healthy subjects who were randomly allocated in a cross-over design to a Mediterranean diet
added with or without extra virgin olive oil (EVOO, 10 g) (first study, n 1⁄4 25) or Mediterranean diet with
EVOO (10 g) or corn oil (10 g) (second study, n 1⁄4 25). Oxidative stress biomarkers including platelet
reactive oxidant species (ROS) and 8-iso-PGF2a-III, activity of NOX2, the catalytic sub-unit of NADPH
oxidase, as assessed in platelets and serum, serum vitamin E and endothelial dysfunction, were measured
before and 2 h after lunch.
In the first study a significant increase of platelet ROS, 8-iso-PGF2a-III, NOX2 activity, sE-selectin,
sVCAM1 and a decrease of serum vitamin E were detected in controls but not when EVOO was
included in the Mediterranean diet; oxidative stress and endothelial dysfunction increase were also
observed in the second study in subjects given corn oil. A significant correlation was found between
NOX2 activity and platelet oxidative stress. In vitro study demonstrated that EVOO but not corn oil
significantly decreased platelet and PMNs oxidative stress and NOX2 activity.
Conclusion: The study provides the first evidence that post-prandial oxidative stress may be triggered by
NOX2 up-regulation. EVOO but not corn oil, is able to counteract such phenomenon suggesting that
addition of EVOO to a Mediterranean diet protects against post-prandial oxidative stress
Does mediterranean diet reduce cardiovascular events and oxidative stress in atrial fibrillation
No full textAtrial fibrillation (AF) is characterized by enhanced oxidative stress and is complicated by cardiovascular events (CVEs), which are only partially prevented by anticoagulant treatment. The Mediterranean diet (Med-Diet) has a positive effect on atherosclerotic progression. In a prospective cohort of 709 anticoagulated AF patients, adherence to Med-Diet was assessed to investigate whether Med-Diet may reduce CVEs by lowering oxidative stress. The cohort was divided into three groups according to the Med-Diet score: low (0-3 points), medium (4-6 points), and high (7-9 points) adherence. During a mean follow-up of 39.9 months (2604.8 patients/year), we registered 72 (2.8%/year) CVEs: 23.4% in the low-adherence group, 8.4% in the intermediate-adherence group, and 5.3% in the high-adherence group (p<0.001). There were no differences in time in the therapeutic range among groups. The Med-Diet score was inversely correlated with sNOX2-dp (soluble NOX2-derived peptide; Rs: -0.297, p<0.001) and F2-isoprostanes (F2-IsoP; Rs: -0.411, p<0.001). Median values of sNOX2-dp (p<0.001) and F2-IsoP progressively decreased across groups (p<0.001). A Cox regression analysis showed that the Med-Diet score (HR: 0.771, p=0.001), F2-IsoP (HR: 1.002, p=0.004), and heart failure (HR: 1.876, p=0.024) predicted CVEs. In conclusion, these findings raise the hypothesis that adherence to Med-Diet could be associated with a reduction of CVEs, through an antioxidant effect, as shown by a concomitant downregulation of Nox2 and decreased excretion of F2-IsoP
Response to "Digoxin or digoxin prescribed patient? Randomized trials are essential to discriminate the principal risk factor for the association of digoxin and increased mortality".
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Incidence of Myocardial Infarction and Vascular Death in Elderly Patients With Atrial Fibrillation Taking Anticoagulants Relation to Atherosclerotic Risk Factors
No full textBACKGROUND:
Recent findings suggest that patients with atrial fibrillation (AF), in addition to thromboembolic risk, are also at risk for myocardial infarction (MI). Our aim was to investigate predictors of MI and cardiovascular death in a cohort of anticoagulated AF patients.
METHODS:
We prospectively followed-up 1019 AF patients for a median of 33.7 months (3223 person/years). All patients were treated with oral vitamin K antagonists. Primary outcome was a composite endpoint of cardiovascular events (CVEs) including fatal/non-fatal MI, cardiac revascularization and cardiovascular death.
RESULTS:
Mean age was 73.2 years, 43.8% were female. At follow-up, 111 CVEs (3,43%/year) occurred: 47 fatal-nonfatal MI/revascularization and 64 cardiovascular deaths. In addition, 31 stroke/TIA (0.96%/year) were recorded. Patients experiencing CVEs were older (p<0.001), with a higher prevalence of metabolic syndrome (MetS, p=0.005), heart failure (HF, p=0.001), prior cardiac (p<0.001) and cerebrovascular events (p<0.001). On a Cox proportional hazard analysis, age (hazard ratio [HR] 1.083, 95% confidence interval [CI], 1.053-1.113, p<0.001), smoking (HR 2.158, 95% CI, 1.193-3.901, p=0.011), history of cerebrovascular (HR 1.704, 95% CI, 1.119-2.597, p=0.013), and cardiac events (HR 1.658, 95% CI, 1.105-2.489, p=0.015), MetS (HR 1.663, 95% CI, 1.107-2.499, p=0.014), HF (HR 1.584, 95% CI, 1.021-2.456, p=0.040), male sex (HR 1.499, 95% CI, 1.010-2.223, p=0.044) predicted CVEs.
CONCLUSIONS:
AF patients still experience a high rate of CVEs despite being on anticoagulant treatment. MetS is a common clinical feature in AF patients, which increases the risk of CVEs. A holistic approach is needed to reduce the risk of cardiovascular risk in patients with AF.
Clinical Trial Registration:
ClinicalTrials.gov NCT01882114
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