thromboxane-b2 and Atrial-Fibrillation

We evaluated the short-term safety and efficacy of aspirin-plus-clopidogrel as antithrombotic therapy in nonvalvular atrial fibrillation (AF).. Thirty patients (11 women, 45 to 75 years of age) with non-high-risk permanent (n = 12) or persistent AF awaiting cardioversion (n = 18) underwent transesophageal echocardiography to exclude left heart thrombi and were then randomly assigned to receive warfarin (international normalized ratio, 2 to 3 for 3 weeks) or aspirin (100 mg/d alone for 1 week)-plus-clopidogrel (75 mg/d added to aspirin for 3 weeks). Bleeding time and serum thromboxane B2 were measured at entry and at 3 weeks. Bleeding time, not affected by warfarin, was prolonged by 71% by aspirin (P <.05) and further, by 144%, by adding clopidogrel (P <.01 vs aspirin alone; +319%, P <.01, vs baseline). Thromboxane B2, not affected by warfarin, was reduced by aspirin (-98%, P <.01) but not further by clopidogrel. No thrombi or dense spontaneous echo-contrast were found at the 3-week transesophageal echocardiography. Seven of 9 patients receiving warfarin and 7 of 9 patients receiving aspirin-plus-clopidogrel, undergoing electrical cardioversion, achieved sinus rhythm. No thromboembolic or hemorrhagic events occurred in both arms throughout the 3-week treatment and a further 3-month follow-up.. Aspirin-plus-clopidogrel and warfarin were equally safe and effective in preventing thromboembolism in this small group of patients with non-high-risk AF.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Bleeding Time; Clopidogrel; Drug Therapy, Combination; Echocardiography, Transesophageal; Electric Countershock; Female; Humans; International Normalized Ratio; Male; Middle Aged; Pilot Projects; Platelet Aggregation Inhibitors; Thromboembolism; Thromboxane B2; Ticlopidine; Warfarin

Soluble proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to be predictive of cardiovascular events (CVEs) in patients who are at high cardiovascular risk. No data on the effect of PCSK9 levels in patients with atrial fibrillation (AF) are available.. This study investigated the association between PCSK9 and CVEs in AF as well as the relationship between PCSK9 and urinary 11-dehydro-thromboxane B. We conducted a prospective, single-center cohort study, including 907 patients with AF treated with vitamin K antagonists (3,865 patient-years), to assess CVEs, including fatal and nonfatal myocardial infarction, ischemic stroke, and cardiovascular death. At admission, plasma PCSK9 and urinary 11-dh-TxB. The mean age of patients was 73.5 ± 8.2 years, and 43.0% were women. At follow-up, 179 CVEs (4.6%/year) occurred: 43 (15.3%), 49 (15.5%), and 87 (28.0%) in the first, second, and third tertiles of PCSK9, respectively (log-rank test p = 0.009). Patients with CVEs had higher median PCSK9 compared with those without (1,500 pg/ml [IQR: 1,000 to 2,300 pg/ml] vs. 1,200 pg/ml [IQR: 827 to 1,807 pg/ml], respectively; p < 0.001). Multivariable Cox regression analysis showed that the third versus the first tertile of PCSK9 (hazard ratio: 1.640; 95% confidence interval: 1.117 to 2.407; p = 0.012), female sex, age, diabetes, smoking, heart failure, previous cerebrovascular and cardiac events, digoxin use, and total cholesterol to high-density lipoprotein cholesterol ratio were associated with CVEs. In 682 patients not treated with antiplatelet therapy, circulating PCSK9 and 11-dh-TxB. Plasma PCSK9 levels are associated with an increased risk of CVEs in patients with AF. The direct correlation between PCSK9 and 11-dh-TxB

Topics: Aged; Atrial Fibrillation; Cardiovascular Diseases; Female; Humans; Incidence; Male; Predictive Value of Tests; Proprotein Convertase 9; Prospective Studies; Risk Assessment; Thromboxane B2

Aging is strictly associated with an increased incidence of cardiovascular events (CVEs) in the general population. Mechanisms underlying the risk of CVEs are still unclear. Platelet activation contributes to the onset of cardiovascular complications. The incidence of atrial fibrillation (AF) increases with age, and the natural history of AF is often complicated by CVEs. We prospectively investigated the relationship between age, urinary thromboxane (Tx) B2, which reflects platelet activation, and CVEs in 833 AF patients. Median TxB2 level was 120 [66-200] ng/mg of urinary creatinine. At multivariable linear regression analysis, age (B: 0.097, p=0.005) and previous MI/CHD (B: 0.069, p=0.047) were associated with log-TxB2 levels. When we divided our population into age classes (i.e. < 60, 60-69, 70-79, ≥ 80 years), we found a significant difference in TxB2 levels across classes (p=0.005), with a significant elevation at 74.6 years. During a mean follow-up of 40.9 months, 128 CVEs occurred; the rate of CVEs significantly increased with age classes (Log-rank test, p < 0.001). TxB2 levels were higher in patients with, compared to those without, CVEs in patients aged 70-79 (p < 0.001) and ≥ 80 (p = 0.020) years. In conclusion, TxB2 levels enhance by increasing age, suggesting that platelet activation contributes to CVEs in elderly patients with AF.

Topics: Age Factors; Aged; Aged, 80 and over; Anthropometry; Atrial Fibrillation; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Multivariate Analysis; Platelet Activation; Prospective Studies; Regression Analysis; Risk; Thromboxane B2

Experimental studies demonstrated that glutathione peroxidase 3 (GPx3), an antioxidant enzyme that catabolizes hydrogen peroxide, protects against thrombosis. Little is known about its role in cardiovascular disease.. A prospective cohort study was conducted in 909 atrial fibrillation patients. Serum activities of GPx3, superoxide dismutase (SOD), and catalase were measured at baseline to assess the risk of cardiovascular events during a mean follow-up of 43.4 months (3291 person-years). Serum Nox2 and urinary excretion of 11-deydro-thromboxane B2 were also measured. During follow-up 160 cardiovascular events occurred (4.9%/year). Significantly lower values of GPx3 (P<0.001) and SOD (P=0.037) were detected in patients with, compared to those without, cardiovascular events. A lower survival rate was observed in patients with GPx3 (P<0.001) and SOD (P=0.010) activities below the median, as compared to those above. In a fully adjusted Cox regression model, GPx3 was the only antioxidant enzyme predictor of cardiovascular events (hazard ratio 0.647, 95% confidence interval 0.524-0.798, P<0.001). GPx3 was inversely associated with urinary 11-dehydro-thromboxane B2 (B -0.337, P<0.001) and serum Nox2 (B: -0.423, P<0.001). GPx3 activity progressively decreased with decades of age (P<0.001), with a progressive reduction in people aged ≥70 years.. This study provides evidence that a low antioxidant status, as depicted by reduced levels of GPx3, increases the risk of cardiovascular events in patients with atrial fibrillation. The age-related decline of GPx3 may represent a mechanism for the enhanced cardiovascular risk in the elderly population.

Topics: Aged; Aged, 80 and over; Aging; Atrial Fibrillation; Cardiovascular Diseases; Catalase; Cohort Studies; Female; Follow-Up Studies; Glutathione Peroxidase; Humans; Ischemic Attack, Transient; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; NADPH Oxidase 2; Prognosis; Proportional Hazards Models; Prospective Studies; Stroke; Superoxide Dismutase; Thromboxane B2

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, 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.. 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.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers; Diet, Mediterranean; Female; Follow-Up Studies; Humans; Italy; Linear Models; Male; Middle Aged; Multivariate Analysis; Olive Oil; Patient Compliance; Platelet Activation; Platelet Aggregation Inhibitors; Prospective Studies; Surveys and Questionnaires; Thromboxane A2; Thromboxane B2; Warfarin; Wine

Patients with nonvalvular atrial fibrillation (AF) show high residual cardiovascular (CV) risk despite oral anticoagulants. Urinary 11-dehydro-thromboxane B2 (TxB2) is associated with an increased risk of CV events (CVEs), but its predictive value in patients with anticoagulated AF is unknown.. A prospective single-center cohort study, including 837 patients with AF, was conducted. Mean time of follow-up was 30.0 months, yielding 2,062 person-years of observation. Urinary 11-dehydro-TxB2 was measured at baseline. The primary end point was the occurrence of a CVE including fatal/nonfatal myocardial infarction and ischemic stroke, transient ischemic attack, cardiac revascularization, and CV death.. Mean age of patients was 73.1 years, and 43.6% were women. Median 11-dehydro-TxB2 levels were 100 (interquartile range 50-187) ng/mg of urinary creatinine. Overall, the anticoagulation control was adequate (63.9% of mean time in therapeutic range). A CVE occurred in 99 (11.8%) patients, and 55 were CV deaths. At baseline, 11-dehydro-TxB2 levels were higher in patients with a CVE compared with those without (186 [107-400] vs 98 [52-170], P < .001). An increased rate of CVEs (log-rank test, P < .001) and CV deaths (P < .001) was observed across tertiles of 11-dehydro-TxB2. Cardiovascular events were associated with age (hazard ratios [HR] 1.72 per 1 SD, 95% CI 1.33-2.21, P < .001), diabetes mellitus (HR 1.89, 95% CI 1.20-2.96, P = .005), heart failure (HR 1.60, 95% CI 1.01-2.54, P = .044), history of stroke/transient ischemic attack (HR 1.96, 95% CI 1.25-3.06, P = .003), and 11-dehydro-TxB2 (HR 1.64 per 1 SD, 95% CI 1.42-1.89, P < .001).. Urinary 11-dehydro-TxB2 levels are associated with a residual risk of CVEs and CV mortality in patients with AF despite anticoagulant treatment.

Topics: Aged; Atrial Fibrillation; Biomarkers; Death, Sudden, Cardiac; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Incidence; Italy; Male; Myocardial Infarction; Prospective Studies; Risk Assessment; Stroke; Survival Rate; Thromboxane B2; Time Factors

Both platelet activation and lipid peroxidation are potential sources of vasoactive eicosanoids that can be produced via the cyclooxygenase pathway, ie, thromboxane (TX) A2, or by free radical-catalyzed peroxidation of arachidonic acid, ie, isoprostanes. We investigated the biosynthesis of TXA2 and F2-isoprostanes, as reflected by the urinary excretion of 11-dehydro-TXB2 and 8-epi-prostaglandin (PG) F2 alpha respectively, in 62 consecutive patients (30 men, 32 women; mean age, 67 +/- 14 years) with acute ischemic stroke.. At least two consecutive 6-hour urine samples were obtained during the first 72 hours after onset of symptoms. Urinary eicosanoids were measured by previously described radioimmunoassays.. Repeated periods of enhanced thromboxane biosynthesis were found in 52% of patients. Urinary 11-dehydro-TXB2 averaged 221 +/- 207 (mean +/- SD; n = 197; range, 13 to 967) pmol/mmol creatinine in 30 patients treated with cyclooxygenase inhibitors (mostly aspirin) at the time of study versus 392 +/- 392 (n = 186; range, 26 to 2533) in 32 untreated patients (P < .001). The corresponding values for 8-epi-PGF2 alpha excretion were 74 +/- 42 (range, 14 to 206) and 83 +/- 65 (range, 24 to 570) pmol/mmol creatinine (P > .05). The correlation between the two metabolites was moderate in both untreated patients (r = .41, P < .001) and patients with cyclooxygenase inhibitors (r = .31, P < .001). In a multiple regression analysis, increased thromboxane production was independently associated with severity of stroke on admission, atrial fibrillation, and treatment with cyclooxygenase-inhibiting drugs.. We conclude that during the first few days after an acute ischemic stroke (1) platelet activation occurs repeatedly in a cyclooxygenase-dependent fashion; (2) platelet activation is not associated with concurrent changes in isoprostane biosynthesis; (3) platelet activation is independently associated with stroke severity and atrial fibrillation; and (4) isoprostane biosynthesis is largely independent of platelet cyclooxygenase activity.

Topics: Acute Disease; Aged; Atrial Fibrillation; Brain Ischemia; Cerebrovascular Disorders; Cyclooxygenase Inhibitors; Dinoprost; Female; Humans; Lipid Peroxides; Male; Middle Aged; Platelet Activation; Reference Values; Thromboxane B2

Thromboxane A2 (TXA2) biosynthesis was studied in healthy subjects, patients with chronic cerebral infarction, patients under chronic aspirin treatment and patients with atrial fibrillation. Urinary 11-dehydro-TXB2, as a major metabolite of TXA2, was measured by radioimmunoassay. The extent of carotid atherosclerosis was determined by B-mode ultrasonography. The mean +/- SD urinary excretion in patients with cerebral infarction and distinct carotid-atherosclerotic lesions (1,725 +/- 239 ng/g creatinine, n = 6) was significantly higher (p less than 0.01) than in healthy subjects (911 +/- 239 ng/g creatinine, n = 44) and patients with cerebral infarction who had no distinct carotid lesion (1,050 +/- 191 ng/g creatinine, n = 6). The urinary excretion of healthy subjects was higher (p less than 0.01) in smokers (1,063 +/- 244 ng/g creatinine, n = 17) than in non-smokers (815 +/- 183 ng/g creatinine, n = 27). Aspirin largely suppressed 11-dehydro-TXB2 excretion (266 +/- 114 ng/g creatinine, n = 7). Three of 5 patients with atrial fibrillation showed very high values. Our results indicated that platelet activation occurs in the atherosclerotic lesions, and that urinary 11-dehydro-TXB2 is the appropriate analytic target for detecting platelet activation.

Topics: Adult; Aged; Arteriosclerosis; Aspirin; Atrial Fibrillation; Carotid Artery Diseases; Cerebral Infarction; Female; Humans; Male; Middle Aged; Platelet Activation; Thromboxane A2; Thromboxane B2

Thromboxane++ (TX), prostacyclin (PC) and platelet factor IV (PF) were assayed using radioimmune kits in 46 patients with cardiac fibrillation secondary to coronary heart disease and rheumatic fever. The study established elevated TX beta 2 levels, low concentrations of 6-ketoPGF1 alpha, enhanced activity of PF. Restoration of the sinus rhythm by electroimpulse treatment (EIT) brought about augmentation of the Tx-Pc-PF unbalance on day 2-3. This may give rise to "normalization" thromboembolism. On days 5-7 after EIT the intensity of platelet aggregation and PF secretion diminish. It is concluded that patients with sudden cardiac fibrillation in need of sinus rhythm correction will benefit from disaggregation and anti-coagulant therapy.

Topics: 6-Ketoprostaglandin F1 alpha; Atrial Fibrillation; Electric Countershock; Humans; Platelet Factor 4; Thromboembolism; Thromboxane B2; Time Factors

This study was performed to determine the relationship between plasma concentration of thromboxane B2 (TXB2), 6-keto-prostaglandin F1a and atrial thrombosis in patients with mitral stenosis (MS). By radioimmunoassay and pathological examination, peripheral plasma TXB2 level was remarkably higher in patients with MS and persistent atrial fibrillation (AF) than in patients with MS but without AF (P less than 0.01). Plasma TXB2 level was significantly higher in patients with than in those without atrial thrombosis (P less than 0.05). There was no significant difference in plasma 6-keto-PGF1 alpha, plasma prostanoids level in peripheral venous blood correlated closely with that in left atrial blood. Patients with high plasma TXB2 level had a greater incidence of microthrombosis.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Atrial Fibrillation; Female; Heart Diseases; Humans; Male; Middle Aged; Mitral Valve Stenosis; Rheumatic Heart Disease; Thrombosis; Thromboxane B2