Objective To investigate the expression level and clinical significance of WW domain-containing E3 ubiquitin protein ligase 1(WWP1)and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)in patients with heart failure with preserved ejection fraction(HFpEF).Methods A total of 153 patients with HFpEF admitted to Fengfeng General Hospital of North China Medical and Health Group from January 2021 to September 2022 were collected as the observation group.According to the New York Heart Association(NYHA)cardiac function grading of patients,they were grouped into cardiac function grading Ⅰ～Ⅱ group(n=64)and cardiac function grading Ⅲ～Ⅳ group(n=89),while 148 healthy volunteers were collected as the control group.The correlation between serum WWP1 and NLRP3 levels and cardiac function indexes of patients was explored by Pearson analysis.The diagnostic value of serum WWP1 and NLRP3 levels on the severity of heart failure in HFpEF patients was analyzed by the receiver operating characteristic(ROC)curve.Results Compared with the control group,the expression levels of WWP1(1.68±0.35 vs 1.04±0.19)and NLRP3(6.72±1.26 ng/ml vs 4.57±0.84 ng/ml)in the observation group were significantly increased,and the differences were statistically significant(t=19.623,17.359,all P<0.05).Compared with grade Ⅰ to Ⅱ groups,WWP1(1.87±0.39 vs 1.42±0.32)and NLRP3(7.53±1.40 ng/ml vs 5.59±1.18 ng/ml)expression levels in grade Ⅲ to Ⅳ groups were significantly increased and the differences were statistically significant(t=7.744,9.017,all P<0.05).The differences of heart rate,left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDD),left ventricular end-diastolic diameter(LVEDD),left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDD),left ventricular end-diastolic posterior wall thickness(LVPWT),left ventricular ejection fraction(LVPWT),left ventricular ejection fraction(LVEF),peak mitral early diastolic velocity(E)/peak late diastolic velocity(A)and the incidence of atrial fibrillation between the cardiac function grade Ⅰ to Ⅱ groups and the grade Ⅲ to Ⅳ groups were significant(t/χ2=2.757～7.069,all P<0.05).Serum WWP1 level in HFpEF patients was positively correlated with LAD,LVEDD and LVPWT(r=0.547,0.471,0.536,all P<0.05),and negatively correlated with LVEF and E/A(r=-0.485,-0.417,all P<0.05).Serum NLRP3 level was positively correlated with LAD,LVEDD and LVPWT(r=0.534,0.494,0.520,all P<0.05),and negatively correlated with LVEF and E/A(r=-0.462,-0.523,all P<0.05).ROC results showed that the area under the curve(AUC)of serum WWP1 and NLRP3 levels alone for diagnosing the severity of heart failure in HFpEF patients was 0.825 and 0.855,respectively,and the AUC(0.924)diagnosed by the combination of the two was significantly greater than that diagnosed by the serum WWP1 alone and the AUC diagnosed by the NLRP3 alone(Z=3.600,P<0.001;Z=3.053,P=0.002).Conclusion The levels of serum WWP1 and NLRP3 were increased in patients with HFpEF,which were closely related to the cardiac function of patients.Serum WWP1 and NLRP3 have certain diagnostic value for the severity of heart failure in patients with HFpEF.