Background: Platelet activation occurs in an endothelium-dependent flow-mediated dilation (FMD) impairment environment. Although platelet activation plays a major role in the pathogenesis of atherothrombotic events, only few data exist regarding the predictors and modulators of platelet activity in healthy subjects.
Methods: To explore the long-term association between brachial artery FMD, platelet function, cardiovascular (CV) events (all-cause mortality, nonfatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary intervention) and non-CV events in healthy subjects, we prospectively assessed brachial FMD in 89 consecutive healthy subjects 64 (72%) men, mean age 51±11 years. Following overnight fasting for ≥ 12 hours FMD and endothelium-independent, nitroglycerin-mediated vasodilation (NTG) were assessed. Platelet aggregation was assessed by conventional aggregometry, and platelet adhesion and aggregation under flow conditions by cone-and-plate(let) technology (Impact-R).
Results: After a mean follow-up of 7±1 years there were 29 total adverse clinical events, of which 11 were CV end points. Subjects with CV events had significantly lower FMD compared to those without CV events (10.4±8.0% vs 17.5±9.7%, p=0.02), while NTG was similar in both groups. Furthermore, 73% with and 37% without CV events had FMD < the median (p=0.02). Additionally, subjects with the highest (FMD>16.8%) compared to the lowest baseline FMD tertile (FMD≤ 9.6%) had significantly the less CV events compared to the associated with low CV events (p<0.01) (Figure). ADP- and arachidonic acid-induced platelet aggregation were significantly higher in subjects with compared to those without CV events (p≤0.01). In addition, platelet adhesion which reflects platelet reactivity, as seen by surface coverage (SC) under flow conditions, was greater in those with than without CV events (14±8% vs 9±6%, p<0.05). Furthermore, more subjects without compared with CV events had SC < the median (62% vs 27%, p=0.02).
Conclusions: Brachial artery FMD and platelet function are associated with long-term CV events in subjects without heart disease.
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