HOUSTON – In all, 53% of 142 young men with type 2 diabetes were resistant to the anticlotting effects of aspirin in a retrospective analysis, suggesting that they may need higher-than-usual doses of prophylactic aspirin to prevent heart attacks and strokes.
The study shows that aspirin resistance is common in men with type 2 diabetes, even in those with good glycemic control, Dr. Subhashini Yaturu and her associates reported in a poster presentation at the annual meeting of the Endocrine Society.
The investigators combined test results and information that had been gathered at one institution for a previous study with supplemental analyses of urine samples in order to measure concentrations of 11-dehydro-thromboxane beta-2 (11-DH-TXB2), a major urinary metabolite of thromboxane that is formed during blood clotting. High urinary levels of 11-DH-TXB2, measured using an enzyme immunoassay kit, indicate resistance to aspirin. Aspirin resistance was defined as a urine level of at least 1,500 pg 11-DH-TXB2 per mg of creatinine.
The men had a mean age of 49 years and a mean body mass index of 34 kg/m2. They’d had diabetes for a mean of 8 years; 88% of them had hypertension, and 23% had a history of coronary artery disease.
The investigators had hypothesized that aspirin resistance might be associated with high insulin levels and inflammatory markers. They found that 11-DH-TXB2 per creatinine levels correlated with a history of coronary artery disease, abdominal fat content, and interleukin-6 levels. Levels were highest in patients with a longer duration of diabetes and increased urinary microalbumin levels, an indicator of early kidney disease in diabetes, said Dr. Yaturu, section chief of the endocrinology and metabolism department at the Albany (N.Y.) Stratton Veterans Affairs Medical Center.
Although high blood pressure and greater abdominal-fat distribution conventionally are associated with increased risk of cardiovascular disease, these were not associated with aspirin resistance in this study. Patients with or without aspirin resistance did not differ significantly in age, BMI, history of hypertension, or waist-to-hip ratio. They also did not differ significantly in biochemical parameters such as creatinine, thyroid function tests, lipid parameters, or glycosylated hemoglobin (HbA1C) measurements.
Patients with aspirin resistance had a mean HbA1c of 8.1%, compared with 7.7% in those without aspirin resistance.
Knowing that aspirin resistance is so common is important clinically because it may allow for additional measures. Giving patients higher medication doses or additional prophylactic therapy might be considered to prevent heart attacks and strokes, Dr. Yaturu said.
Identifying patients with aspirin resistance isn’t easy, however, given the lack of correlation with obvious clinical markers, she said in an interview. The measures used in the study are still a research tool. But if aspirin resistance is identified in a patient, consider doubling the standard low dose of aspirin, she suggested.
Cardiovascular risk in patients with type 2 diabetes is equivalent to that of patients without diabetes who have had a coronary event, she noted. The American Diabetes Association recommends enteric-coated aspirin at a dosage of 81-325 mg/day for the prevention of cardiovascular events in high-risk patients with diabetes, including those older than 40 years or patients with risk factors other than diabetes, such as hypertension, smoking, dyslipidemia, albuminuria, or a family history of cardiovascular disease.
Causes of aspirin resistance include concurrent use of NSAIDs that may compete with aspirin at the cyclooxygenase-1 receptor site; polymorphisms in the COX1 gene; poor glucose control; body weight; and conditions associated with a high turnover of platelets, she said.
Dr. Yaturu reported having no financial disclosures.