期刊
JOURNAL OF THE AMERICAN HEART ASSOCIATION
卷 7, 期 5, 页码 -出版社
WILEY
DOI: 10.1161/JAHA.118.008522
关键词
ADP; collagen; epinephrine; myocardial infarction; P2RY12 receptor thrombosis; platelet aggregation; platelet function; platelet reactivity; risk prediction; stroke
资金
- National Heart, Lung, and Blood Institute (NHLBI) [NO1-HL 25195, R01-HL-48157, HHSN268201500001I]
- NHLBI Intramural Research Program funding
- Paavo Nurmi Foundation
Background-Platelet function is associated with adverse events in patients with cardiovascular disease (CVD). Methods and Results-We examined associations of baseline platelet function with incident CVD events in the community-based FHS (Framingham Heart Study). Participants free of prevalent CVD and without recent aspirin treatment with available data in the Framingham Offspring cohort (1991-1995) and Omni cohort (1994-1998) were included. Platelet function was measured with light transmission aggregometry using collagen (1.9 mu g/mL), ADP (0.05-15 mu mol/L), and epinephrine (0.01-15 mu mol/L). We used proportional hazards models to analyze incident outcomes (myocardial infarction/stroke, CVD, and CVD mortality) with respect to platelet measures. The study sample included 2831 participants (average age, 54.3years; 57% women). During follow-up (median, 20.4years), we observed 191 composite incident myocardial infarction or stroke events, 432 incident CVD cases, and 117 CVD deaths. Hyperreactivity to ADP and platelet aggregation at ADP concentration of 1.0 mu mol/L were significantly associated with incident myocardial infarction/stroke in a multivariable model (hazard ratio, 1.68 [95% confidence interval, 1.13-2.50] [P=0.011] for hyperreactivity across ADP doses; and hazard ratio, 1.16 [95% confidence interval, 1.02-1.33] [P=0.029] for highest quartile of ADP response at 1.0 mu mol/L versus others). No association was observed for collagen lag time or any epinephrine measures with incident myocardial infarction or stroke. Conclusions-Intrinsic hyperreactivity to low-dose ADP in our community-based sample, who were free of CVD and any antiplatelet therapy, is associated with future arterial thrombosis during a 20-year follow-up. These findings reinforce ADP activation inhibition as a critical treatment paradigm and encourage further study of ADP inhibitor-refractive populations.
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