Statin therapy and inflammation in patients with diabetes treated with high dose aspirin.

BACKGROUND: Statin and aspirin form the therapeutic cornerstone in patients with coronary artery disease (CAD) and diabetes. Little is known about relationship of statins with blood thrombogenicity and inflammation in these patients. METHODS: Two hundred nine consecutive patients with diabetes and suspected CAD undergoing elective cardiac catheterization were divided in groups based on statin treatment in the Multi-Analyte, Thrombogenic, and Genetic Markers Atherosclerosis study. Urinary 11-dehydrothromboxane B2 (11-dh-TxB2), lipid profile and oxLDL/ß2GPI were measured by AspirinWorks™ ELISA assay, vertical density gradient ultracentrifugation and immunoassay respectively. Thrombelastography, and ADP- and collagen-induced light transmittance aggregometry assessed thrombogenicity. CAD was classified as none/minor [<20% diameter stenosis (DS)], moderate (20-75% DS), or severe (>75% DS). RESULTS: Severe, moderate, and no CAD was observed in 66, 19, and 15% of patients respectively. Patients on statins had significantly lower 11-dh-TxB2, collagen-induced aggregation, total cholesterol, total LDL, LDL3, oxidized-LDL, Apo B100, and ApoB100/A1 ratio (p<0.01 for all). Statin therapy demonstrated a lower proportion of patients with high urinary 11-dh-TxB2 (>1500pg 11-dh-TxB2/mg creatinine) (25 vs. 57%, p=0.01). CONCLUSION: Statins along with aspirin, confers additional anti-inflammatory and antithrombotic effect in diabetics with CAD. Urinary 11-dh-TxB2 may be a useful biomarker for personalizing statin therapy.

Comparison between urinary 11-dehydrothromboxane B2 detection and platelet Light Transmission Aggregometry (LTA) assays for evaluating aspirin response in elderly patients with coronary artery disease.

Aspirin is widely used in the primary and secondary prevention of cardiovascular diseases. The aim of our study was to compare between two established methods of aspirin response, urinary 11-dehydrothromboxane B2 (11dhTXB2) and platelet Light Transmission Aggregometry (LTA) assays in elderly Chinese patients with coronary artery disease (CAD), and to investigate the clinical significance of both methods in predicting cardiovascular events. Urinary 11dhTxB2 assay and arachidonic acid-induced (AA, 0.5mg/ml) platelet aggregation by Light Transmission Aggregometry (LTAAA) assay were measured to evaluate aspirin responses. High-on aspirin platelet reactivity (HAPR) was defined as urinary 11dhTxB2>1500pg/mg or AA-induced platelet aggregation≥15.22%-the upper quartile of our enrolled population. The two tests showed a poor correlation for aspirin inhibition (r=0.063) and a poor agreement in classifying HAPR (kappa=0.053). With a mean follow-up time of 12months, cardiovascular events occurred more frequently in HAPR patients who were diagnosed by LTA assay as compared with no-HAPR patients (22.5% versus 10.6%, P=0.039, OR=2.45, 95% CI=1.06-5.63). However, the HAPR status, as determined by urinary 11dTXB2 measurement, did not show a significant correlation with outcomes.

Correlation between the level of the urinary 11-dehydrothromboxane B2 and the clinical efficacy of aspirin in patients with type 2 diabete and coronary artery disease / 北京大学学报(医学版)

Objective:To elucidate the correlation between urinary 11-dehydro-thromboxane B2 ( 11 dhTxB2 ) and clinical efficacy of aspirin treatment in patients with type 2 diabete and coronary artery disease ( CAD) . Methods:In this prospective cohort study, 169 aged patients with type 2 diabete accom-panying CAD in Peking University First Hospital were enrolled. The level of urinary 11dhTxB2 was detec-ted using enzyme-linked immuno-sorbent assay. Low aspirin response or high on aspirin platelet reactivity (HAPR) was defined as urinary 11dhTxB2>1 500 ng/g. All the included patients were divided into two groups based on the results, HAPR group and No-HAPR group. Results:Baseline urinary 11dhTxB2 of the patients with type 2 diabete accompanying CAD was ( 3 687 ± 3 052 ) ng/g, while the urinary 11dhTxB2 was (1 954 ± 859) ng/g in patients after 100 mg/d aspirin treatment (P<0. 001). Preva-lence of HAPR in patients with type 2 diabete accompanying CAD were 32 . 5%. Within a mean follow-up time of 12 months, the outcomes occurred more frequently in HAPR group than in No-HAPR group ( P<0 . 05 ) . Conclusion:Urinary 11 dhTxB2 can be recognized as an effective indicator in evaluating aspirin clinical efficacy of patients with type 2 diabete accompanying CAD.

Statin therapy and thromboxane generation in patients with coronary artery disease treated with high-dose aspirin.

Aspirin and statin therapy are mainstay treatments in patients with coronary artery disease (CAD). The relation between statin therapy, in vivo thromboxane (Tx) generation; a marker of inflammation, and blood thrombogenicity has never been explored. Urinary 11-dehydro (dh) TxB2 was determined in patients with suspected CAD on 325 mg daily aspirin therapy prior to undergoing cardiac catheterisation (n=281). Thrombogenicity was estimated by thrombelastographic measurement of thrombin-induced platelet-fibrin clot strength (TIP-FCS) and lipids/lipoproteins were determined by vertical density gradient ultracentrifugation/ELISA. The influence of statin therapy and dose was analysed by the atorvastatin equivalent dose (5-10 mg, 20-40 mg, or 80 mg daily). Statin therapy (n=186) was associated with a dose-dependent reduction in urinary 11-dh TxB2 (p=0.046) that was independent of LDL and apo B100 levels but was strongly related to TIP-FCS (p=0.006). By multivariate analysis, no statin therapy (n=95) and female gender were independently associated with high urinary 11-dh TxB2 [OR=2.95 (0.1.57-5.50, p=0.0007); OR=2.25 (1.24-4.05, p=0.007)], respectively. In aspirin-treated patients, statin therapy was independently and inversely associated with inflammation in a dose-dependent manner. Elevated 11-dh TxB2 was associated with a prothrombotic state indicated by high TIP-FCS. Our data suggest that measurement of urinary 11-dTxB2 may be a useful method to optimise statin dosing in order to reduce thrombotic risk.

Acetylsalicylic acid therapy: influence of metformin use and other variables on urinary 11-dehydrothromboxane B2 levels.

BACKGROUND: The effect of acetylsalicylic acid (ASA) may be measured through the analysis of urinary concentrations of 11-dehydrothromboxane B2 (11-dhTXB2), a metabolite of thromboxane A2, which is a potent platelet aggregant agent. It has been suggested that metformin (an oral antidiabetic drug) could improve oxidative stress and control platelet activation in type 2 diabetic patients, potentially reducing cardiovascular risk. We determined the concentrations of urinary 11-dhTXB2 in type 2 diabetic patients taking ASA and its concentrations with metformin use and several other clinical variables (hypertension, age, gender, smoking, body mass index, insulin and statin use), considering a reduction of at least 75% in the concentrations of this marker as a target, compared to results before ASA intake. METHODS: Urinary concentrations of 11-dhTXB2 of 81 type 2 diabetic patients were measured before and at 15 days taking 100 mg of aspirin daily. RESULTS: Most patients who presented a reduction of 11-dhTXB2 above 75% were under metformin use. This reduction was achieved in 51.5% of patients taking this drug, against 20.0% in the patients who were not (p=0.027). The analysis of the other variables did not show a significant difference. The use of metformin appears to play a role in the reduction of 11-dhTXB2 concentrations in type 2 diabetic patients. CONCLUSION: According to previous reports, hyperglycemia control seems to be a determinant factor for the success of ASA therapy, given the influence of metformin in the reduction of 11-dhTXB2 concentrations.

Comparison of aspirin response measured by urinary 11-dehydrothromboxane B2 and VerifyNow aspirin assay in patients with ischemic stroke.

BACKGROUND: We looked for the prevalence of aspirin nonresponders, compared the results of 2 tests assessing aspirin responses-measurement of urinary 11-dehydrothromboxane B2 (dTXB2) and VerifyNow Aspirin assay-in patients with ischemic stroke, and examined the relationship of aspirin nonresponse and the outcomes of the patients. METHODS: One hundred one patients with ischemic stroke were prospectively included. Aspirin response was assessed by urinary dTXB2 measurement and VerifyNow Aspirin assay. The Spearman correlation coefficients and kappa statistics were calculated to assess correlation and agreement between the 2 tests. The measured outcome was the occurrence of cardiovascular events and death. RESULTS: Prevalence of aspirin nonresponders was 40% and 6%, if they were measured by urinary dTXB2 and VerifyNow Aspirin assay, respectively. Poor correlation in the results between the 2 tests was found (r = .135, P = .190). The degree of agreement between the 2 tests in relation to resistance status was weak (kappa = .032, P = .590). With a mean follow-up time of 17 months, the outcomes occurred significantly higher in aspirin nonresponders who were diagnosed by urinary dTXB2 measurement as compared with patients with aspirin response (18% versus 2%, odds ratio 8.8, 95% confidence interval 1.18-65.4, P = .037). CONCLUSIONS: Our research confirmed poor correlation and lack of agreement between the 2 tests. Only aspirin nonresponders who were diagnosed by dTXB2 measurement were related to having cardiovascular events and death. Further research is still needed to identify the best method of diagnosis of aspirin nonresponders.