Abstract Aims The aim of the study was to assess the association of P‐selectin with outcomes in heart failure with preserved ejection fraction (HFpEF). Methods and results This is a prospective, observational study of 130 HFpEF patients who underwent clinical profiling, blood sampling, 6 min walk testing, Minnesota Living with Heart Failure Questionnaire evaluation, echocardiography, cardiovascular magnetic resonance imaging, calculation of the Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) risk scores, and blinded plasma P‐selectin measurement. Patients were followed up for the endpoint of all‐cause mortality. The HFpEF subgroup with higher P‐selectin levels [overall median 26 372, inter‐quartile range (19 360–34 889) pg/mL] was associated with lower age, higher heart rate, less prevalent atrial fibrillation, more frequent current smoking status, and lower right ventricular end‐diastolic volumes. During follow‐up (median 1428 days), there were 38 deaths. Following maximal sensitivity and specificity receiver operating characteristic curve analysis, P‐selectin levels above 35 506 pg/mL were associated with greater risk of all‐cause mortality [hazard ratio (HR) 2.700; 95% confidence interval (CI) 1.416–5.146; log‐rank P = 0.002]. Following multivariable Cox proportional hazards regression analysis and when added to MAGGIC scores, only P‐selectin (adjusted HR 1.707; 95% CI 1.099–2.650; P
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