Obesity is associated with impaired platelet-inhibitory effect of acetylsalicylic acid in nondiabetic subjects

Tamminen, Marjo; Lassila, Riitta; Westerbacka, Jukka; Vehkavaara, Satu; Yki‐Järvinen, Hannele

doi:10.1038/sj.ijo.0802312

Cited by 72 publications

(53 citation statements)

References 36 publications

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“…Age, 4,24 sex, 4,9 cigarette smoking, 25,26 diabetes, 27,28 obesity, 29,30 and cholesterol 31,32 are reported to modify platelet responsiveness to ASA. We quantified the contribution of these cardiac risk factors to variability in platelet ASA response phenotypes and found that the total variance attributable to these factors was small.…”

Section: Discussionmentioning

confidence: 99%

Heritability of Platelet Responsiveness to Aspirin in Activation Pathways Directly and Indirectly Related to Cyclooxygenase-1

et al. 2007

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Background-The inability of aspirin (acetylsalicylic acid [ASA]) to adequately suppress platelet function is associated with future risk of myocardial infarction, stroke, and cardiovascular death. Genetic variation is a proposed but unproved mechanism for insufficient ASA responsiveness. Methods and Results-We examined platelet ASA responsiveness in 1880 asymptomatic subjects (mean age, 44Ϯ13 years; 58% women) recruited from 309 white and 208 black families with premature coronary heart disease. Ex vivo platelet function was determined before and after ingestion of ASA (81 mg/d for 2 weeks) with the use of a panel of measures that assessed platelet activation in pathways directly and indirectly related to cyclooxygenase-1, the enzyme inhibited by ASA. The proportion of phenotypic variance related to CHD risk factor covariates was determined by multivariable regression. Heritability of phenotypes was determined with the use of variance components models unadjusted and adjusted for covariates. ASA inhibited arachidonic acid-induced aggregation and thromboxane B 2 production by Ն99% (PϽ0.0001). Inhibition of urinary thromboxane excretion and platelet activation in pathways indirectly related to cyclooxygenase-1 was less pronounced and more variable (inhibition of 0% to 100%). Measured covariates contributed modestly to variability in ASA response phenotypes (r 2 ϭ0.001 to 0.133). Phenotypes indirectly related to cyclooxygenase-1 were strongly and consistently heritable across races (h 2 ϭ0.266 to 0.762; PϽ0.01), but direct cyclooxygenase-1 phenotypes were not. Conclusions-Heritable factors contribute prominently to variability in residual platelet function after ASA exposure.These data suggest a genetic basis for the adequacy of platelet suppression by ASA and potentially for differences in the clinical efficacy of ASA.

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Section: Discussionmentioning

confidence: 99%

Heritability of Platelet Responsiveness to Aspirin in Activation Pathways Directly and Indirectly Related to Cyclooxygenase-1

et al. 2007

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“…Obesity is associated with a modest yet significant increase in baseline platelet reactivity. After the addition of low-dose (50-81 mg) aspirin, platelets in obese patients have more incomplete inhibition of aggregation to arachidonic acid 46,47 and higher levels of thromboxane B2. 47 These changes remained significant after accounting for potentially confounding variables including hypertension, fasting blood sugar, and hyperlipidemia.…”

Section: Obesitymentioning

confidence: 99%

Aspirin Resistance: Current Status and Role of Tailored Therapy

Grinstein

Cannon

2012

Clinical Cardiology

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Aspirin is integral in the primary and secondary prevention of coronary artery disease and acute coronary syndrome. Given the high clinical importance of aspirin in the management of coronary artery disease, much attention has been directed towards the concept of “aspirin resistance.” Unfortunately, the term aspirin resistance is ill‐defined in the literature, leading to a large variance in the reported prevalence of this phenomenon. In this review, the current understanding of aspirin resistance is discussed. Commonly used functional and diagnostic tests of platelet function, including their strengths and weakness, are reviewed. We next discuss several proposed mechanisms of aspirin resistance and special high‐risk groups at risk for aspirin treatment failure. We then discuss optimal dosing and diagnostic strategies for those populations at risk for aspirin resistance with a focus on tailored aspirin therapy for high‐risk groups. Finally, future topics of interest in the field of aspirin resistance are considered. Clin. Cardiol. 2012 doi: 10.1002/clc.22031Jonathan Grinstein has no funding, financial relationships, or conflicts of interest to disclose. Christopher P. Cannon receives research grants/support from the following companies: Accumetrics, AstraZeneca, Essentialis, GlaxoSmithKline, Merck, Regeneron, Sanofi, and Takeda. He is also on the advisory board (but funds donated to charity) for Alnylam, Bristol‐Myers Squibb, and Pfizer. He is a Clinical Advisor, equity in Automedics Medical Systems.

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“…This difference, however, was statistically marginal. Several reports suggested that older and obese patients are more prone to the development of aspirin resistance (21,22). One can suggest that ASA antiplatelet effect is more pronounced in younger patients with lower BMI or that the optimal dose of ASA is BMI-dependent.…”

Section: Commentsmentioning

confidence: 99%

Safety of ultrasound-guided transrectal extended prostate biopsy in patients receiving low-dose aspirin

et al. 2010

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Purpose: To determine whether the peri-procedural administration of low-dose aspirin increases the risk of bleeding complications for patients undergoing extended prostate biopsies. Materials and Methods: From February 2007 to September 2008, 530 men undergoing extended needle biopsies were divided in two groups; those receiving aspirin and those not receiving aspirin. The morbidity of the procedure, with emphasis on hemorrhagic complications, was assessed prospectively using two standardized questionnaires. Results: There were no significant differences between the two groups regarding the mean number of biopsy cores (12.9 ± 1.6 vs. 13.1 ± 1.2 cores, p = 0.09). No major biopsy-related complications were noted. Statistical analysis did not demonstrate significant differences in the rate of hematuria (64.5% vs. 60.6%, p = 0.46), rectal bleeding (33.6% vs. 25.9%, p = 0.09) or hemospermia (90.1% vs. 86.9%, p = 0.45). The mean duration of hematuria and rectal bleeding was significantly greater in the aspirin group compared to the control group (4.45 ± 2.7 vs. 2.4 ± 2.6, p = < 0.001 and 3.3 ± 1.3 vs. 1.9 ± 0.7, p < 0.001). Multivariate logistic regression analysis revealed that only younger patients (mean age 60.1 ± 5.8 years) with a lower body mass index (< 25 kg/m 2 ) receiving aspirin were at a higher risk (odds ratio = 3.46, p = 0.047) for developing hematuria and rectal bleeding after the procedure. Conclusions: The continuing use of low-dose aspirin in patients undergoing extended prostatic biopsy is a relatively safe option since it does not increase the morbidity of the procedure.

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Obesity is associated with impaired platelet-inhibitory effect of acetylsalicylic acid in nondiabetic subjects

Cited by 72 publications

References 36 publications

Heritability of Platelet Responsiveness to Aspirin in Activation Pathways Directly and Indirectly Related to Cyclooxygenase-1

Heritability of Platelet Responsiveness to Aspirin in Activation Pathways Directly and Indirectly Related to Cyclooxygenase-1

Aspirin Resistance: Current Status and Role of Tailored Therapy

Safety of ultrasound-guided transrectal extended prostate biopsy in patients receiving low-dose aspirin

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