Risk Factors For Aspirin Resistance Research Articles

Aspirin Resistance in Children with Congenital Heart Disease and Its Relationship with Laboratory and Clinical Parameters

Background: Patients with congenital heart disease (CHD) are more prone to thromboembolism. Aspirin is the most commonly used medication around the world to prevent thrombosis in cardiovascular diseases. Objectives: This study aimed to define the frequency of aspirin resistance in pediatric patients with CHD and to evaluate the correlation of clinical and laboratory parameters with aspirin resistance. Methods: The study population consisted of 103 patients using aspirin, including 53 cases of cyanotic CHD and 50 cases of non-cyanotic CHD. Platelet aggregation was measured by the AggreGuide A-100 ADP Assay. Results: The prevalence of aspirin resistance was 36.9% in children with CHD. Although aspirin resistance in cyanotic CHD patients (41.5%) was higher than in non-cyanotic patients (32%), the difference was not statistically significant (P = 0.414). There was no significant association between aspirin responsiveness or resistance and the patient’s sex, age, duration of aspirin use, and concomitant medication use. Comparison of the laboratory data of aspirin-responsive and -resistant patients showed no significant difference between these groups, except for albumin (P = 0.032) and serum fibrinogen (P = 0.0001) levels. The fibrinogen level and thromboembolism history were independent risk factors for aspirin resistance. Also, there was a significant correlation between platelet aggregation in peripheral blood smears and aspirin resistance (P = 0.0001). Conclusions: Our findings suggest that measurement of the serum fibrinogen level and platelet aggregation in blood smears may be the first step to predict aspirin resistance.

A Narrative Review of Aspirin Resistance in VTE Prophylaxis for Orthopaedic Surgery.

Total hip arthroplasties (THA) and total knee arthroplasties (TKA) confer one of the highest risks for developing venous thromboembolism (VTE) and pharmacological prophylaxis is imperative to help mitigate the risks. Aspirin is the most cost-effective medication for VTE prophylaxis, and its use post-THA/TKA has grown in popularity. Aspirin resistance is categorised as clinical or laboratory resistance with obesity, advancing age, diabetes mellitus, dyslipidaemia and inflammatory diseases identified as risk factors for aspirin resistance. Treatment failure due to aspirin resistance has been reported in cardiovascular and cerebrovascular disease leading to increased rates of mortality and re-embolisation. However, aspirin resistance in patients undergoing a THA/TKA has not been described, nor has there been investigation into the incidence rates or clinical outcomes. The aim of this narrative review is to appraise the concept of aspirin resistance in the context of aspirin use for VTE prophylaxis after THA/TKA surgeries. This is important to investigate as the risk factors for aspirin resistance, including obesity, advancing age, diabetes mellitus, dyslipidaemia and inflammatory diseases, are also risk factors for THA/TKA and risk factors for VTE. The presence of aspirin resistance in patients undergoing orthopaedic surgery may place patients at greater risk of thrombotic events if aspirin is prescribed for VTE prophylaxis. This could further increase the risk of complications associated with VTE and potential long-term consequences such as post-thrombotic syndrome. Future research is required to explore and quantify the rates of aspirin resistance and the clinical outcomes in orthopaedic patients; especially in those patients with these overlapping risk factors for THA/TKA, VTE and aspirin resistance.

Long Non-Coding RNA H19 Positively Associates With Aspirin Resistance in the Patients of Cerebral Ischemic Stroke.

Background and purposeAspirin is a novel anti-platelet drug that is intensively recommended for the prevention and treatment of cerebral ischemic stroke. However, the existence of aspirin resistance weakens the effects of aspirin and usually induces the recurrence of ischemic stroke. While the mechanism underlying aspirin resistance is still unclear. Long non-coding RNA H19 (H19) is closely associated with the onset and prognosis of cerebral ischemic stroke. Since the relationship between H19 and aspirin resistance have never been reported, herein, we aimed to evaluate the H19 expression in aspirin-resistant ischemic stroke patients and subsequently, ascertain the ability of H19 to diagnose aspirin resistance.MethodsWe included 150 patients with acute cerebral ischemic stroke who were followed up for one year to determine stroke recurrence. Levels of 11-dehydro thromboxane B2 (11dhTXB2) in urine were tested to evaluate the status of aspirin resistance, and those of H19 and 8-iso-prostaglandin-2α in plasma were assessed. The relationship between 11dhTXB2 or and 8-iso-prostaglandin-2α and H19, and the receiver operating characteristic curve of H19, the association of H19 and aspirin resistance with the recurrence of stoke were statistically analyzed.ResultsPlasma H19 was significantly up-regulated in patients with aspirin resistance (p=0.0203), and the H19 levels were positively associated with urine 11dhTXB2/creatinine (R=0.04364, p=0.0106) and positively associated with the level of 8-iso-PGF2α (R=0.04561, p=0.0089). The ROC curves indicated that H19 can sensitively and specifically diagnose aspirin resistance (area under the curve, 0.8005; 95% CI, 0.7301–0.8710; p < 0.0001; specificity, 75.86207%; sensitivity, 73.84615%.). H19 is an independent risk factor for aspirin resistance (OR=1.129, p=0.0321), and aspirin resistance and H19 are closely related with ischemic stroke recurrence.ConclusionsH19 is closely associated with aspirin resistance, and H19 probably induces aspirin resistance through increasing the production of 8-iso-prostaglandin-2α. Besides which, H19 may serve as a serological marker for diagnosing aspirin resistance with high specificity and sensitivity, and the test of H19 could give clues to the recurrence of ischemic stroke.

Associations of MDR1, TBXA2R, PLA2G7, and PEAR1 genetic polymorphisms with the platelet activity in Chinese ischemic stroke patients receiving aspirin therapy.

Aspirin resistance has an incidence of 5%-65% in patients with ischemic stroke, who receive the standard dose of aspirin, but the platelet function is inadequately inhibited, thereby leading to thrombotic events. Numerous evidence shows that thromboxane A2 receptor (TXA2 receptor, encoded by TBXA2R), lipoprotein-associated phospholipase A2 (Lp-PLA2, encoded by PLA2G7) and platelet endothelial aggregation receptor-1 (PEAR1, encoded by PEAR1) are crucial in regulating platelet activation, and P-glycoprotein (P-gp, encoded by MDR1) influences the absorption of aspirin in the intestine. In this study we examined the correlation between MDR1, TBXA2R, PLA2G7, PEAR1 genetic polymorphisms and platelet activity in Chinese ischemic stroke patients receiving aspirin therapy. A total of 283 ischemic stroke patients receiving 100 mg aspirin for 7 d were genotyped for polymorphisms in MDR1 C3435T, TBXA2R (rs1131882), PLA2G7 (rs1051931, rs7756935), and PEAR1 (rs12566888, rs12041331). The platelet aggregation response was measured using an automatic platelet aggregation analyzer and a commercially available TXB2 ELISA kit. Thirty-three patients (11.66%) were insensitive to aspirin treatment. MDR1 3435TT genotype carriers, whose arachidonic acid (AA) or adenosine diphosphate (ADP)-induced platelet aggregation was lower than that of CC+CT genotype carriers, were less likely to suffer from aspirin resistance (odds ratio=0.421, 95% CI: 0.233-0.759). The TBXA2R rs1131882 CC genotype, which was found more frequently in the aspirin-insensitive group (81.8% vs 62.4%) than in the sensitive group, was identified as a risk factor for aspirin resistance (odds ratio=2.712, 95% CI: 1.080-6.810) with a higher level of AA-induced platelet aggregation. Due to the combined effects of PLA2G7 rs1051931 and rs7756935, carriers of the AA-CC haplotype had a higher level of ADP-induced platelet aggregation, and were at considerably higher risk of aspirin resistance than noncarriers (odds ratio=8.233, 95% CI: 1.590-42.638). A considerable portion (11.66%) of Chinese ischemic stroke patients are insensitive to aspirin treatment, which may be correlated with the MDR1 C3435T, TBXA2R (rs1131882), and PLA2G7 (rs1051931-rs7756935) polymorphisms.

Establishing a predictive model for aspirin resistance in elderly Chinese patients with chronic cardiovascular disease.

BackgroundResistance to anti-platelet therapy is detrimental to patients. Our aim was to establish a predictive model for aspirin resistance to identify high-risk patients and to propose appropriate intervention.MethodsElderly patients (n = 1130) with stable chronic coronary heart disease who were taking aspirin (75 mg) for > 2 months were included. Details of their basic characteristics, laboratory test results, and medications were collected. Logistic regression analysis was performed to establish a predictive model for aspirin resistance. Risk score was finally established according to coefficient B and type of variables in logistic regression. The Hosmer–Lemeshow (HL) test and receiver operating characteristic curves were performed to respectively test the calibration and discrimination of the model.ResultsSeven risk factors were included in our risk score. They were serum creatinine (> 110 μmol/L, score of 1); fasting blood glucose (> 7.0 mmol/L, score of 1); hyperlipidemia (score of 1); number of coronary arteries (2 branches, score of 2; ≥ 3 branches, score of 4); body mass index (20–25 kg/m2, score of 2; > 25 kg/m2, score of 4); percutaneous coronary intervention (score of 2); and smoking (score of 3). The HL test showed P ≥ 0.05 and area under the receiver operating characteristic curve ≥ 0.70.ConclusionsWe explored and quantified the risk factors for aspirin resistance. Our predictive model showed good calibration and discriminative power and therefore a good foundation for the further study of patients undergoing anti-platelet therapy.

Antiplatelet drug resistance is associated with early neurological deterioration in acute minor ischemic stroke in the Chinese population.

To evaluate the prevalence and risk factors of antiplatelet drug resistance and its association with early neurological deterioration (END) and recurrent ischemic stroke (RIS) in patients with acute minor stroke. Antiplatelet drug resistance was assessed by platelet aggregation assay in 426 patients with minor stroke who were receiving combined treatment of aspirin and clopidogrel. All patients were followed up for 90days. The primary endpoint of the study was END within 10days after admission. The secondary endpoints included RIS, myocardial infarction and death during 90days of treatment. The safety endpoints were intracerebral or extracranial hemorrhagic events. Cox proportional hazard regression analysis was performed to determine the risk factors for the primary endpoint and secondary endpoints. Among the 426 patients, 24.4% exhibited aspirin resistance, 35.9% exhibited clopidogrel resistance, and 19.2% displayed concomitant aspirin and clopidogrel resistance. In multivariate analysis, diabetes mellitus and high level of low density lipoprotein-cholesterol were independent risk factors for aspirin resistance, while diabetes mellitus was the only independent risk factor for clopidogrel resistance. END was observed in 93 (21.8%) patients. Diabetes mellitus, high fasting blood glucose level, and concomitant aspirin and clopidogrel resistance were independent risk factors for END. RIS was observed in 40 (9.4%) patients. Diabetes mellitus, hypertension, and concomitant aspirin and clopidogrel resistance were independent risk factors for RIS. Antiplatelet drug resistance is common in acute minor ischemic stroke patients and is associated with END and RIS after acute minor ischemic stroke in the Chinese population. http://www.chictr.org/ . Unique Identifier: ChiCTR-OCH-14004724.

Establishing a predictive model for aspirin resistance in aging male with coronary heart disease

Objective To quantify the risk factors for aspirin resistance so as to increase the prognosis for risk of coronary heart disease, and to establish a predictive model for aspirin resistance in order to guide the clinical anti-platelet therapy. Methods A total of 938 elderly male patients with stable coronary heart disease (CHD) receiving oral aspirin therapy (>75 mg/d) over 2 months were included in this study. Their clinical data were collected. Logistic regression analysis was performed to establish a predictive model and risk score for aspirin resistance. Hosmer Lemeshow (H-L) test and an area under the receiver operating characteristic (ROC) curve (the area under the ROC curve) were performed to test the calibration and discrimination of the model. Results Seven risk factors were included in the predictive model, including serum creatinine (>110 μmol/L: score of 1), fasting blood glucose (>7.0 mmol/L: score of 1), hyperlipidemia (score of 1), number of coronary arteries in lesion (2 branches: score of 2, ≥3 branches: score of 4), body mass index〔(20-25) kg/m2: score of 2, >25 kg/m2: score of 4〕, percutaneous coronary intervention (score of 2), smoking (score of 3). H-L test showed P≥0.05 and the area under the ROC curve>0.70 in this model. Conclusions the risk factors for aspirin resistance, and establishing a valid predictive model for aspirin resistance, could provide an important reference for anti-platelet therapy in CHD patients. Key words: Aspirin; Coronary disease; Proportional hazards models

Establishing a predictive model for aspirin resistance in elderly Chinese patients with chronic coronary heart disease

Objective: Resistance to anti-platelet therapy is detrimental to patients. Our aim was to establish a predictive model for aspirin resistance to identify high-risk patients and to propose appropriate intervention. Methods: Elderly patients (n=1130) with stable chronic coronary heart disease who were taking aspirin (75 mg) for >2 months were included. Details of their basic characteristics, laboratory test results, and medication were collected. Logistic regression analysis was performed to establish a predictive model for aspirin resistance. Risk score was finally established according to the coefficient B and type of variables in logistic regression. The Hosmer-Lemeshow (HL) test and a receiver operating characteristic curve were performed to respectively test the calibration and discrimination of the model. Results: Seven risk factors were included in our risk score. They were serum creatinine (>110 mol/L: score of 1); fasting blood glucose (>7.0 mmol/L: score of 1); hyperlipidaemia (score of 1); number of diseased coronary arteries (2 branches: score of 2; ≥3 branches: score of 4); body mass index (20-25 kg/m2: score of 2; >25 kg/m2: score of 4); percutaneous coronary intervention (score of 2); and smoking (score of 3). HL test showed P≥0.05 and area under the receiver operating characteristic curve ≥0.70. Conclusion: We explored and quantified the risk factors for aspirin resistance. Our predictive model showed good calibration and discriminative power. So it would be a good foundation for the further study of patients undergoing anti-platelet therapy.

High prevalence of aspirin resistance in elderly patients with cardiovascular disease (CVD) and hyperhomocysteinaemia

Although aspirin resistance is well reported in CVD, little is known about aspirin response in elderly patients with hyperhomocysteinaemia. The aim of the present study was to explore the prevalence of aspirin resistance in elderly patients with CVD and hyperhomocysteinaemia. A total of 370 elderly patients with CVD were recruited. The study included 216 patients with hyperhomocysteinaemia and 154 patients with normohomocysteinaemia receiving daily aspirin therapy (≥75mg) over 1 month. The effect of aspirin was assessed using by light transmission aggregometry (LTA). Aspirin resistance was defined as ≥20% arachidonic acid induced aggregation according to LTA. Aspirin resistance was defined in 48 (13.0%) of 370 patients. The prevalence of aspirin resistance was higher in hyperhomocysteinaemic patients than normohomocysteinaemic patients (16.7% vs. 7.8%, odds ratio (OR)=2.367; 95% confidence interval (CI)=1.188–4.715, p=0.012). In the multivariate logistic regression analysis, hyperhomocysteinaemia (OR=2.406, 95% CI=1.201–4.820, p=0.013) was a significant risk factor for aspirin resistance. A significant number of CVD patients with hyperhomocysteinemia are resistant to aspirin therapy. Hyperhomocysteinemia is a significant risk factor for aspirin resistance in elderly patients with CVD.

Non-HDL cholesterol is an independent risk factor for aspirin resistance in obese patients with type 2 diabetes

ObjectiveWe evaluated the prevalence of aspirin resistance and predictive factors for aspirin resistance in Korean type 2 diabetes patients. Approach and resultsA total of 1045 type 2 diabetes patients from 11 hospitals who were taking aspirin (100 mg/day for ≥2 weeks) and no other antiplatelet agents were studied to evaluate aspirin resistance. Aspirin resistance was measured in aspirin reaction units using VerifyNow®. Aspirin resistance was defined as ≥550 aspirin reaction units.Aspirin resistance was detected in 102 of the 1045 subjects (prevalence 9.8%). Aspirin resistance was associated with total cholesterol (P = 0.013), LDL-cholesterol (P = 0.028), and non-HDL cholesterol (P = 0.008) concentrations in univariate analysis. In multivariate logistic regression analysis, only non-HDL cholesterol was associated with aspirin resistance in obese (BMI >25 kg/m2) type 2 diabetes patients (adjusted odds ratio 3.55, 95% CI: 1.25–10.05, P = 0.017). ConclusionsThe prevalence of aspirin resistance in Korean type 2 diabetes patients is 9.8%. Non-HDL cholesterol is an independent risk factor for aspirin resistance, especially in obese type 2 diabetes patients.

GW24-e3522 Establishing of aspirin resistance incident prediction model for the old patients with chronic coronary heart disease

ObjectivesCoronary heart disease is one of the leading causes of mortality in women and men in the world. Aspirin use for the primary and secondary prevention of coronary heart disease...

Prevalence of and risk factors for aspirin resistance in elderly patients with coronary artery disease.

ObjectiveTo assess the prevalence of and related risk factors for aspirin resistance in elderly patients with coronary artery disease (CAD).MethodsTwo hundred and forty-six elderly patients (75.9 ± 7.4 years) with CAD who received daily aspirin therapy (≥ 75 mg) over one month were recruited. The effect of aspirin was assessed using light transmission aggregometry (LTA) and thrombelastography platelet mapping assay (TEG). Aspirin resistance was defined as ≥ 20% arachidonic acid (AA)-induced aggregation and ≥ 70% adenosine diphosphate (ADP)-induced aggregation in the LTA assay. An aspirin semi-responder was defined as meeting one (but not both) of the criteria described above. Based on the results of TEG, aspirin resistance was defined as ≥ 50% aggregation induced by AA.ResultsAs determined by LTA, 23 (9.3%) of the elderly CAD patients were resistant to aspirin therapy; 91 (37.0%) were semi-responders. As determined by TEG, 61 patients (24.8%) were aspirin resistant. Of the 61 patients who were aspirin resistant by TEG, 19 were aspirin resistant according to LTA results. Twenty-four of 91 semi-responders by LTA were aspirin resistant by TEG. Multivariate logistic regression analysis revealed that elevated fasting serum glucose level (Odds ratio: 1.517; 95% CI: 1.176–1.957; P = 0.001) was a significant risk factor for aspirin resistance as determined by TEG.ConclusionsA significant number of elderly patients with CAD are resistant to aspirin therapy. Fasting blood glucose level is closely associated with aspirin resistance in elderly CAD patients.

381 Prevalence and risk factors for aspirin resistance in patients with coronary artery disease

381 Prevalence and risk factors for aspirin resistance in patients with coronary artery disease

Prevalence and risk factors for aspirin resistance in older patients with cardiovascular disease

ObjectivesTo evaluate the prevalence and risk factors for aspirin resistance in older patients with cardiovascular disease (CVD).DesignCross-sectional analysis.SettingGeneral community.Participants454 patients aged 65 years or older with CVD.MeasurementsThe older patients received...

Prevalence and Risk Factors for Aspirin Resistance in Elderly Patients With Type 2 Diabetes

Aspirin resistance in patients with diabetes is recognized. However, the prevalence and related risk factors for aspirin resistance in elderly patients with Type 2 diabetes have not been reported, which is why we undertook this study. One hundred and forty elderly patients (age, 73.84 ± 8.02 years) with Type 2 diabetes receiving daily aspirin therapy (≥75 mg) over 1 month were recruited. Platelet aggregation was measured by light transmission aggregometry (LTA) and thrombelastography (TEG) platelet mapping assay. The definitions of aspirin resistance were 20% or greater arachidonic acid-induced and 70% or greater adenosine diphosphate-induced aggregation by LTA. Aspirin semiresponders were defined as meeting one (but not both) of these criteria. Aspirin resistance by TEG was defined as 50% or greater aggregation induced by arachidonic acid. By LTA, 6 (4.3%) patients with Type 2 diabetes were found to be resistant to aspirin therapy; 44 (31.4%) patients were semiresponders. By TEG, 31 patients (22.1%) were aspirin resistant. Of the 31 patients who were aspirin-resistant by TEG, 3 were aspirin-resistant by LTA. Eight of 44 semiresponders by LTA were aspirin-resistant by TEG. In the multivariate logistic regression analysis, being female (odds ratio: 5.54, 95% confidence interval: 1.17–27.47, p = 0.036) and homocysteine levels (odds ratio: 1.15, 95% confidence interval: 1.00–1.31, p = 0.043) were significant risk factors for aspirin resistance by TEG. The prevalence of aspirin resistance in elderly patients with Type 2 diabetes was considerably higher in female patients and in patients with higher serum levels of homocysteine.

The frequency of aspirin resistance and its risk factors in patients with metabolic syndrome

Background Although different populations were examined for the incidence of aspirin resistance, the frequency and related risk factors for aspirin resistance in patients with metabolic syndrome have not been reported yet. This study aimed to determine the frequency of aspirin resistance and its risk factors in patients with metabolic syndrome. Methods We performed a cross-sectional study in 110 patients with metabolic syndrome. After one week of 100 mg/day aspirin, blood samples were obtained. Platelet function analyzer (PFA-100™) was used to determine the frequency of aspirin resistance. Endothelial functions, carotid intima media thickness, and the presence of plaques in the carotid arteries were evaluated for subclinical atherosclerosis and the levels of inflammatory markers were assessed as risk factors for aspirin resistance. The presence of subclinical atherosclerosis was defined as a maximum carotid intima media thickness of ≥ 0.9 mm and/or the presence of carotid atheroma. Results Aspirin resistance was detected in 21.9% of the patients. In the multivariate analysis, hs-CRP levels (odds ratio [95% CI] = 2.8 [1.3–5.9], p = 0.009), diastolic blood pressure, (0.9 [0.8–1.0], p = 0.007), and the presence of subclinical atherosclerosis (4.1 [1.4–12.2], p = 0.012) were statistically significant risk factors for aspirin resistance. Conclusions We concluded that the frequency of aspirin resistance confirmed in this cohort of patients with metabolic syndrome was higher in patients with a lower diastolic blood pressure, higher hs-CRP levels and atherosclerotic changes in their carotid arteries.

Prevalence and biologic profile of aspirin resistance in patients with angiographically proven coronary artery disease

Background Aspirin protects from cardiovascular events. However, a number of patients who take this drug suffer events, probably due to aspirin resistance. The role of certain biologic variables that may affect resistance is still uncertain. Aim To determine the prevalence of aspirin resistance in patients taking this drug and to test if resistance is related to haemostatic, inflammatory and lipidic variables. Methods Platelet function measured with PFA-100 was studied in 268 patients (185 men) with stable coronary disease who took aspirin (100 to 300 mg/day). Aspirin resistance was defined when epinephrine closure time < 174 s. Results of lipoprotein(a) are expressed in median (interquartile range). Results Aspirin resistance was found in 16% of cases. Patients with aspirin resistance had higher levels of Apolipoprotein B (109.27 ± 27.65 vs 100.92 ± 23.77 mg/dl; p < 0.05), lipoprotein(a) [20.37 (4.83–36.72) vs 10.02 (1.88–25.41); p < 0.01], Platelet Count (241.42 ± 75.35 vs 213.94 ± 56.74 mm 3; p < 0.05) and fibrinogen (388.93 ± 107.27 vs 354.33 ± 89.35 mg/dl; p < 0.05). We used the logistic regression analysis to detect the independent predictors of aspirin resistance. Lipoprotein(a) was found to be the only independent risk factor to identify aspirin resistance ( p < 0.05; OR: 1.302; CI 95%: 1.003–1.688). Conclusions Although the potential mechanisms of aspirin resistance still remains uncertain, we found that platelet responsiveness to aspirin is reduced in patients with high levels of Apolipoprotein B and lipoprotein(a). Our work demonstrate that lipoprotein(a) is an independent risk factor for aspirin resistance possibly due to the interaction of Apolipoprotein(a) with human platelets.