Diabetes and Platelet Response to Low-Dose Aspirin

Abstract

Context: Previous studies have suggested less cardioprotective benefit of aspirin in adults with diabetes, raising concerns about "aspirin resistance" and potentially reduced effectiveness for prevention of cardiovascular disease (CVD).

Objective: To examine differences in platelet response to aspirin by diabetes status.

Design, setting, participants: We examined platelet response before and after aspirin (81 mg/day for 14 days) in 2113 adults (175 with diabetes, 1,938 without diabetes), in the Genetic Study of Aspirin Responsiveness cohort, who had family history of early-onset CVD.

Main outcome measures: In vivo platelet activation (urinary thromboxane B2), in vitro platelet aggregation to agonists (arachidonic acid, adenosine diphosphate, collagen), and platelet function analyzer-100 closure time.

Results: Although adults with diabetes had higher in vivo platelet activation before aspirin, the reduction in in vivo platelet activation after aspirin was similar in those with vs without diabetes. Likewise, the reduction in multiple in vitro platelet measures was similar after aspirin by diabetes status. In regression analyses adjusted for age, sex, race, BMI, smoking, platelet counts, and fibrinogen levels, in vivo platelet activation remained higher in adults with vs without diabetes after aspirin (P = 0.04), but this difference was attenuated after additional adjustment for preaspirin levels (P = 0.10). No differences by diabetes status were noted for any of the in vitro platelet measures after aspirin in fully adjusted models that also accounted for preaspirin levels.

Conclusions: In vitro platelet response to aspirin does not differ by diabetes status, suggesting no intrinsic differences in platelet response to aspirin. Instead, factors extrinsic to platelet function should be investigated to give further insights into aspirin use for primary prevention in diabetes.

Figure 1.

Urinary TXB2 levels were higher in adults with vs without diabetes before aspirin [median (IQR) 182 (114 to 305) vs 138 (84 to 231) ng/mmol creatinine, P < 0.0001] and remained higher after aspirin [41.7 (27.9 to 69.7) vs 32.5 (20.7 to 52.3) ng/mmol creatinine, P = 0.0002].

Figure 2.

(A) In vitro whole blood platelet aggregation to collagen 1 μg/mL was similar in adults with vs without diabetes both before aspirin (mean ± SD 19.5 ± 6.1 Ω vs 19.6 ±5.8 Ω, P = 0.94) and after aspirin (mean ± SD 6.7 ± 5.3 Ω vs 6.2 ± 5.3 Ω, P = 0.31). (B) In vitro whole blood platelet aggregation to collagen 5 μg/mL was similar in adults with vs without diabetes both before aspirin (mean ± SD 26.1 ± 6.7 vs 26.2 ± 6.8, Ω, P = 0.77) and after aspirin (mean ± SD 23.9 ± 7.5 vs 23.7 ± 6.9, Ω, P = 0.67). (C) In vitro whole blood platelet aggregation to ADP 10 μM was similar in adults with vs without diabetes both before aspirin (mean ± SD 12.8 ± 5.9 vs 12.6 ± 5.6 Ω, P = 0.59) and after aspirin (mean ± SD 12.8 ± 6.4 vs 12.3 ± 5.9 Ω, P = 0.24).

Figure 3.

(A) In vitro PRP platelet aggregation to collagen 1 μg/mL was similar in adults with vs without diabetes both before aspirin (73.8% vs 73.9%, P = 1) and after aspirin (68.4% vs 66.6%, P = 0.63). (B) In vitro PRP platelet aggregation to collagen 5 μg/mL was similar in adults with vs without diabetes before aspirin (mean ± SD 81.4% ± 17.3% vs 81.8% ± 19%, P = 0.83) and after aspirin (mean ± SD 29.6% ± 23.2% vs 30.3% ± 22%, P = 0.70). (C) In vitro PRP platelet aggregation to ADP 2 μM was similar in adults with vs without diabetes before aspirin (mean ± SD: 41.3% ± 27.7% vs 42.9% ± 27.2%, P = 0.47) and after aspirin (mean ± SD 33.2% ± 17.8% vs 34.7% ± 17.6%, P = 0.28). (D) In vitro PRP platelet aggregation to ADP 10 μM was lower in adults with vs without diabetes before aspirin (mean ± SD: 75.0% ± 17.4% vs 78.1% ± 15.6%, P = 0.02) and remained slightly lower after aspirin (mean ± SD 65.2% ± 16.2% vs 67.7% ± 13.1%, P = 0.05).

Figure 4.

The PFA-100 CT was higher in adults with vs without diabetes before aspirin (mean ± SD 129.1 ± 31.3 vs 122.3 ± 29 seconds, P = 0.003) but similar after aspirin (mean ± SD 262.2 ± 59.9 vs 257.9 ± 63.8 seconds, P = 0.43).