Predictors of high on-aspirin platelet reactivity in elderly patients with coronary artery disease

Abstract

ObjectivesPrevious studies have illustrated the link between high on-aspirin platelet reactivity (HAPR) with increasing thrombotic risks. The aim of our study was to investigate relative risk factors of HAPR in elderly patients with coronary artery disease.MethodsElderly, hospitalized coronary artery disease patients on regular aspirin treatment were enrolled from January 2014 to September 2016. Medical records of each patient were collected, including demographic information, cardiovascular risk factors, concomitant drugs and routine biological parameters. Arachidonic acid (AA, 0.5 mg/mL) and adenosine diphosphate (ADP, 5 µmol/L) induced platelet aggregation were measured via light transmission assay (LTA) to evaluate antiplatelet responses, referred as LTA–AA and LTA–ADP.ResultsA total of 275 elderly patients were included, with mean age of 77.2±8.1 years, and males accounted for 81.8%. HAPR was defined as LTA–AA in the upper quartile of the enrolled population. HAPR patients tended to have lower renal function (P=0.052). Higher serum uric acid (SUA) level, as well as lower platelet count, hemoglobin and hematocrit were observed in HAPR patients, with a higher proportion of diuretics use (P<0.05). Multivariate analysis revealed that SUA (OR: 1.004, 95% CI: 1.000–1.007, P=0.048), platelet count (OR: 0.994, 95% CI: 0.989–1.000, P=0.045), hematocrit (OR: 0.921, 95% CI: 0.864–0.981, P=0.011) and concomitant P2Y12 receptor inhibitors use (OR: 1.965, 95% CI: 1.075–3.592, P=0.028) were correlated with HAPR. Spearman’s correlation analysis demonstrated an inverse association of LTA–AA with hematocrit (r=−0.234, P<0.001), hemoglobin (r=−0.209, P<0.001) and estimated glomerular filtration rate (r=−0.132, P=0.031).ConclusionSUA, platelet count, hematocrit and P2Y12 receptor inhibitors use were independently correlated with HAPR. These parameters might provide novel therapeutic targets for optimizing antiplatelet therapy.

Factors Influencing Aspirin Hyporesponsiveness in Elderly Chinese Patients

“…After multivariate adjustment, the results demonstrated the level of UA was independently and positively associated with aspirin hyporesponsiveness (OR: 1.003, 95% CI: 1.000–1.006, p=0.038), suggesting that increased UA level increases the risk of aspirin hyporesponsiveness. This is consistent with a previous study showing that the level of UA was an independent predictor of aspirin hyporesponsiveness (OR: 1.004, 95% CI: 1.000–1.007, p=0.048) [5]. A possible explanation is that the elevation of UA level promoted formation of a proinflammatory and prothrombotic state, with an increase in non-platelet-derived thromboxane A2 synthesis, leading to increased platelet aggregation and aspirin hyporesponsiveness [23].…”

“…In this study, the ratio of diuretics use was higher in the aspirin hyporesponsive group (Ara-Q4) than in the aspirin non-hyporesponsive group (Ara-Q1-3) (5/72, 6.94% vs. 3/220, 1.36%, p=0.036), which is consistent with a previous study [5]. A possible mechanism is that diuretics use decreased the glomerular filtration rate [29], resulting in accumulation of harmful substances and increase of non-platelet-derived thromboxane A2 synthesis, which could lead to aspirin hyporesponsiveness.…”

“…To date, there is still no consensus on the definition of aspirin hyporesponsiveness, mainly because various methods are used to evaluate aspirin responsiveness, and there is no universally accepted cut-off value of each method used to define aspirin hyporesponsiveness [5,11,12]. In this study, LTA was used to assess aspirin responsiveness and Ara located in the upper quartile after taking aspirin (Ara-Q4) were defined as aspirin hyporesponsiveness [5].…”

“…To evaluate aspirin responsiveness (before and after taking aspirin), 0.50 mg/mL arachidonic acid-induced platelet aggregation rate (Ara) was measured by light transmission assay (LTA) using LBY-NJ4 platelet aggregometer (PRECIL, Beijing, China), as described previously [5].…”

“…Patients with Ara in the upper quartile after taking aspirin (Ara-Q4) were defined as the aspirin hyporesponsive group, whereas patients with Ara below the upper quartile after taking aspirin (Ara-Q1-3) were defined as the aspirin non-hyporesponsive group [5].…”