Aspirin Resistance Is Associated with Glycemic Control, the Dose of Aspirin, and Obesity in Type 2 Diabetes Mellitus

Ertuğrul, Derun Taner; Tutal, Emre; Yıldız, Mehmet; Akın, Okhan; Yalçın, Ahmet Arif; Ure, Oznur Sari; Yilmaz, Hamiyet; Yavuz, Bünyamin; Deveci, Onur Sinan; Ata, Naim; Küçükazman, Metin

doi:10.1210/jc.2009-2392

Cited by 59 publications

(42 citation statements)

References 16 publications

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“…In most of these studies, an association between aspirin resistance and elevated HbA1c and increased fasting serum glucose levels was reported in diabetic patients [33,34,35]. The present study also found that fasting serum glucose level was a risk factor for aspirin resistance.…”

Section: Discussionsupporting

confidence: 81%

Frequency, Risk Factors, Prognosis, and Genetic Polymorphism of the Cyclooxygenase-1 Gene for Aspirin Resistance in Elderly Chinese Patients with Cardiovascular Disease

Fan¹,

Cao

Li³

et al. 2012

Gerontology

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Background: Cardiovascular disease (CVD) is an important cause of mortality in elderly patients worldwide. Aspirin resistance has been well reported in CVD. Objective: The frequency, risk factors, prognosis, and genetic polymorphism of the cyclooxygenase-1 (COX-1) gene for aspirin resistance have not been reported in elderly patients with CVD. We therefore undertook this study to evaluate these associations among elderly Chinese patients with CVD. Methods: Four hundred thirty-one elderly Chinese patients with CVD receiving daily aspirin therapy (≥75 mg) over 1 month were enrolled. Platelet aggregation was measured by light transmission aggregometry (LTA) and thromboelastography platelet mapping assay (TEG) using arachidonic acid (AA) as a stimulus. The median follow-up was 1.8 years. Results: After the median follow-up, aspirin-resistant patients were at an increased risk of the composite endpoint compared to nonresistant patients by LTA_AA + TEG_AA (23.7 vs. 9.2%, p = 0.025). Additionally, Cox proportional hazards regression modeling demonstrated that aspirin resistance and cerebrovascular disease were associated with major adverse long-term outcomes (HR for aspirin resistance = 2.31, 95% CI 1.11-4.81, p = 0.026). The variant G-allele of COX-1 rs1330344 (-1676 A/G) significantly increased the risk of aspirin resistance defined by LTA_AA + TEG_AA (OR = 1.82, 95% CI 1.13- 2.92, p = 0.01). Conclusions: Aspirin resistance, evaluated by LTA_AA + TEG_AA, is associated with an increased risk of adverse clinical events in elderly Chinese patients with CVD. The variant G-allele of COX-1 rs1330344 is significantly associated with aspirin resistance defined by LTA_AA + TEG_AA.

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Section: Discussionsupporting

confidence: 81%

Frequency, Risk Factors, Prognosis, and Genetic Polymorphism of the Cyclooxygenase-1 Gene for Aspirin Resistance in Elderly Chinese Patients with Cardiovascular Disease

Fan¹,

Cao

Li³

et al. 2012

Gerontology

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“…statins). [33,51,53] Indeed, 21-44% of patients [54][55][56][57][58] with diabetes display reduced laboratory responses (e.g. reduced TXA 2 production and platelet sensitivity) to antiplatelet therapies.…”

Section: Aspirin: Antiplatelet Effects and Pharmacokineticsmentioning

confidence: 99%

Aspirin in the prevention of cardiovascular events in patients with diabetes

Bell

2016

Postgraduate Medicine

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Diabetes imparts a substantial increased risk for cardiovascular disease-related mortality and morbidity. Because of this, current medical guidelines recommend prophylactic treatment with once-daily, low-dose aspirin (acetylsalicylic acid) for primary and secondary prevention of cardiovascular (CV) events in high-risk patients. However, only modest reductions in CV events and mortality have been observed with once-daily aspirin treatment in patients with diabetes, including patients with a previous CV event, perhaps because of disparity between aspirin pharmacokinetics and diabetes-related platelet abnormalities. Once-daily aspirin irreversibly inactivates platelets for only a short duration (acetylsalicylic acid half-life, approximately 15-20 minutes), after which time newly generated, active platelets enter the circulation and weaken aspirin's effect. Platelets from patients with diabetes are more reactive and are turned over more rapidly than platelets from normal individuals; the short inhibitory window provided by once-daily aspirin may therefore be insufficient to provide 24-h protection against CV events. Alternative conventional aspirin regimens (e.g. higher daily dose, twice-daily dosing, combination with clopidogrel) and newer formulations (e.g. 24-h, extended-release) have been proposed to overcome the apparent limited efficacy of conventional aspirin in patients with diabetes; however, tolerability concerns and limited clinical efficacy data need to be taken into account when considering the use of such regimens. ARTICLE HISTORY

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“…Other possible mechanisms leading to enhanced platelet reactivity under hyperglycemia include osmotic effect of glucose, increased activation of protein kinase C and decreased activation of nitric oxide (NO) - cyclic guanosine monophosphate (cGMP) - cGMP-dependent protein kinase pathway [15–17]. These assumptions are supported by clinical studies demonstrating relationship between HAPR and inadequate glycemic control, as well as in vitro studies showing enhanced platelet activation, assessed using flow cytometry, with increasing glucose concentrations despite incubation with ASA [6,7,18–23]. Alongside with poor glycemic control, HAPR in DM2 patients has been linked to high triglyceride, total cholesterol and low-density lipoprotein (LDL) concentrations, as well as low high-density lipoprotein (HDL) concentration [18,20,24].…”

Section: Introductionmentioning

confidence: 99%

Younger age, higher body mass index and lower adiponectin concentration predict higher serum thromboxane B2 level in aspirin-treated patients with type 2 diabetes: an observational study

Kapłon‐Cieślicka

Postuła

Rosiak

et al. 2014

Cardiovasc Diabetol

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BackgroundEvidence from the literature suggests diminished acetylsalicylic acid (ASA) treatment efficacy in type 2 diabetes (DM2). High on-aspirin platelet reactivity (HAPR) in DM2 has been linked to poor glycemic and lipid control. However, there are no consistent data on the association between HAPR and insulin resistance or adipose tissue metabolic activity. The aim of this study was to assess the relationship between laboratory response to ASA and metabolic control, insulin resistance and adipokines in DM2.MethodsA total of 186 DM2 patients treated with oral antidiabetic drugs and receiving 75 mg ASA daily were included in the analysis. Response to ASA was assessed by measuring serum thromboxane B2 (TXB2) concentration and expressed as quartiles of TXB2 level. The achievement of treatment targets in terms of glycemic and lipid control, insulin resistance parameters (including Homeostatic Model Assessment-Insulin Resistance, HOMA-IR, index), and serum concentrations of high-molecular weight (HMW) adiponectin, leptin and resistin, were evaluated in all patients. Univariate and multivariate logistic regression analyses were performed to determine the predictive factors of serum TXB2 concentration above the upper quartile and above the median.ResultsSignificant trends in age, body mass index (BMI), HOMA-IR, HMW adiponectin concentration, C-reactive protein concentration and the frequency of achieving target triglyceride levels were observed across increasing quartiles of TXB2. In a multivariate analysis, only younger age and higher BMI were independent predictors of TXB2 concentration above the upper quartile, while younger age and lower HMW adiponectin concentration were predictors of TXB2 concentration above the median.ConclusionsThese results suggest that in DM2, the most important predictor of HAPR is younger age. Younger DM2 patients may therefore require total daily ASA doses higher than 75 mg, preferably as a twice-daily regimen, to achieve full therapeutic effect. Higher BMI and lower HMW adiponectin concentration were also associated with less potent ASA effect. This is the first study to demonstrate an association of lower adiponectin concentration with higher serum TXB2 level in patients treated with ASA.

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Aspirin Resistance Is Associated with Glycemic Control, the Dose of Aspirin, and Obesity in Type 2 Diabetes Mellitus

Abstract: These data suggest that glycemic control, obesity, and the dose of aspirin have influence on AR in diabetic subjects. Further studies with larger groups are needed to clarify the role of glycemic control on AR.

Cited by 59 publications

References 16 publications

Frequency, Risk Factors, Prognosis, and Genetic Polymorphism of the Cyclooxygenase-1 Gene for Aspirin Resistance in Elderly Chinese Patients with Cardiovascular Disease

Frequency, Risk Factors, Prognosis, and Genetic Polymorphism of the Cyclooxygenase-1 Gene for Aspirin Resistance in Elderly Chinese Patients with Cardiovascular Disease

Aspirin in the prevention of cardiovascular events in patients with diabetes

Younger age, higher body mass index and lower adiponectin concentration predict higher serum thromboxane B2 level in aspirin-treated patients with type 2 diabetes: an observational study

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