Abstract-The prevalence of occlusive stroke is inversely correlated with potassium intake. We explored the hypothesis that a high potassium intake attenuates platelet reactivity, as expressed in ADP-evoked platelet aggregation. We studied healthy men (nϭ31) and women (nϭ42), blacks (nϭ33) and whites (nϭ40). In this cohort, we supplemented the habitual intake of 17 men and 21 women with 60 mmol KCl/70 kg body weight per day for 3 days and maintained 14 men and 21 women on their habitual intake. We then compared the change in ADP concentration causing 50% of the maximal initial rate (EC 50 ) of platelet aggregation in the potassium-supplemented versus control groups. Potassium supplementation attenuated platelet reactivity, expressed by an increase in EC 50 of platelet aggregation (Pϭ0.0005), which was primarily attributable to an increase in EC 50 in whites (Pϭ0.0004). Urinary potassium excretion was significantly lower in blacks than in whites under basal conditions and after potassium supplementation. We conclude that potassium supplementation diminishes platelet reactivity, a phenomenon that provides a link between platelet biology and occlusive stroke. Key Words: stroke Ⅲ cardiovascular disease Ⅲ atherosclerosis T he potential cardiovascular benefits of dietary potassium in the general population have been considered primarily from the perspectives that potassium may serve as a sodium substitute in the diet and that a high potassium intake enhances natriuresis. 1 Accordingly, the beneficial effect of a high dietary potassium intake on the cardiovascular system would presumably be mediated by the concomitant reduction in dietary sodium intake, coupled with enhanced sodium excretion, as well as other mechanisms that may ultimately lower blood pressure. 2 The question that follows is whether or not the cardiovascular effect of a high potassium intake may also be mediated through blood pressure-independent mechanisms, given that large-scale studies strongly suggest that dietary potassium intake is inversely correlated with occlusive stroke, a relationship that is independent of the effect of potassium intake on blood pressure. [3][4][5][6][7] Further, in the Systolic Hypertension in the Elderly Program (SHEP) within the treatment group, the risk for cardiovascular events, including stroke and myocardial infarction, was significantly higher in subjects with hypokalemia (serum potassium Ͻ3.5 mmol/L) associated with diuretic use. 8 Collectively, these findings suggest a link between systemic potassium homeostasis and atherosclerosis and thrombosis. 9,10 We note, however, that potassium is primarily an intracellular ion, so that dietary intake and diuretic use are likely to have an effect on intracellular potassium pool even without detectable changes in serum potassium.Because thromboembolic processes largely depend on platelet biology, we hypothesized that a high potassium intake would diminish platelet reactivity. This concept was explored in the present work. Materials and Methods SubjectsWe studied healthy men (...