Objective To explore the relationship between the levels of serum adipocyte fatty acid binding protein （AFABP）， polyadenosine diphosphate ribose polymerase 1 （PARP1）， glucose-regulated protein 78 （GRP78）， and insulin-like growth factor binding protein-7 （IGFBP-7） in patients with chronic heart failure （CHF）， and the relationship between these levels and their clinical classification and prognosis. Methods A total of 259 patients with CHF who were admitted to our hospital from January 2023 to January 2025 （CHF group） and 259 healthy individuals with age- and gender-matching who underwent physical examinations during the same period （control group） were selected. According to the cardiac function classification of the New York Heart Association （NYHA）， CHF patients were divided into grade II （106 cases）， grade III （91 cases）， and grade IV （62 cases）. CHF patients were classified into three clinical subtypes based on left ventricular ejection fraction （LVEF）， namely the heart failure with preserved ejection fraction （HFpEF， LVEF ≥ 50%）， the heart failure with mildly reduced ejection fraction （HFmrEF， LVEF 41% - 49%）， and the heart failure with reduced ejection fraction （HFrEF， LVEF ≤ 40%）， with 114 cases， 91 cases， and 54 cases respectively. These subtypes are respectively referred to as the preservation group， the mild-reduction group， and the reduction group. After the treatment， a 6-month follow-up was carried out. During the follow-up period， 11 cases were lost to follow-up， while a total of 248 cases successfully completed the follow-up. Based on the occurrence of major adverse cardiac events （MACE， including cardiac death or rehospitalization due to heart failure）， the cases were divided into the poor prognosis group （64 cases） and the good prognosis group （184 cases）. The clinical data of all the research subjects were statistically analyzed， and the levels of serum AFABP， PARP1， GRP78， and IGFBP-7 in CHF patients with different cardiac function grades and clinical types were compared among the CHF group， the control group， the poor prognosis group， and the good prognosis group. Spearman correlation analysis was employed to examine the correlations between the levels of serum AFABP， PARP1， GRP78， and IGFBP-7 and the NYHA cardiac function classification and clinical typing. Multivariate logistic regression analysis was utilized to identify the risk factors for poor prognosis in patients with CHF. The predictive efficacy of the combined detection of serum AFABP， PARP1， GRP78， and IGFBP-7 levels for the poor prognosis of CHF patients was evaluated by the receiver operating characteristic curve （ROC）. Results The levels of serum AFABP， PARP1， GRP78， and IGFBP-7 in the CHF group were significantly higher than those in the control group （P < 0.05）. As the NYHA cardiac function classification deteriorated （from grade II to grade IV） and the LVEF decreased （from HFpEF to HFrEF）， the levels of each index exhibited a gradually increasing trend （P < 0.05）. Spearman analysis indicated that the levels of serum AFABP， PARP1， GRP78， and IGFBP-7 were positively correlated with the NYHA cardiac function classification （r = 0.652， 0.570， 0.631， 0.588， P < 0.05） and also positively correlated with the patient's clinical classification （r = 0.496， 0.768， 0.601， 0.608， P < 0.05）. There were statistically significant differences in the levels of serum AFABP， PARP1， GRP78， and IGFBP-7， as well as the proportion of cardiac function classification and clinical classification， between the poor-prognosis group and the good-prognosis group （P < 0.05）. The results of multivariate logistic regression analysis showed that a worse cardiac function classification （OR = 3.086， 95%CI： 1.376 - 6.921）， the HFrEF phenotype （OR = 3.647， 95%CI： 1.921 - 6.923）， a high AFABP level （OR = 2.675， 95% CI 1.248 - 5.734）， a high PARP1 level （OR = 2.713， 95%CI： 1.298 - 5.669）， a high GRP78 level （OR = 2.492， 95%CI： 1.113 - 5.576）， and a high IGFBP-7 level （OR = 2.237， 95%CI： 1.158 - 4.321） were all risk factors for poor prognosis in CHF patients （all P < 0.05）. After drawing the ROC curve， it was found that the combined detection of serum AFABP， PARP1， GRP78， and IGFBP-7 levels had an AUC value for the poor prognosis of CHF patients （0.936， 95%CI： 0.898 - 0.963）， which was higher than that of individual detection of each index （P < 0.05）. The sensitivity and specificity of the combined detection were 90.62% and 80.43%， respectively. Conclusions The levels of AFABP， PARP1， GRP78， and IGFBP-7 are highly expressed in the serum of patients with CHF. These levels are closely related to the cardiac function classification and clinical type of CHF patients. A worse cardiac function classification， the HFrEF phenotype， high levels of AFABP， PARP1， GRP78， and IGFBP-7 are all risk factors for the poor prognosis of CHF patients. The combined detection of AFABP， PARP1， GRP78， and IGFBP-7 has high predictive value for the poor prognosis of CHF patients and is expected to become a new biomarker combination for evaluating the condition and prognosis of CHF.