Objective: This study analyzed the correlation between serum parameters (vaspin, GDF-15, and APN) and the severity of disease in patients with coronary artery disease with chronic heart failure. Methods: One hundred three patients with coronary heart disease with chronic heart failure treated by cardiovascular medicine in our hospital from June 2014 to April 2017 were selected as the observation group, and 32 healthy subjects were selected as the control group. According to the number of observed coronary artery lesion branches in patients with coronary heart disease, individuals were divided into the single-vessel lesion group (32 cases), double-vessel lesion group (34 cases), or multiple-vessel lesion group (35 cases). The severity of coronary artery disease was assessed by Gensini score. Patients in the observation group were divided into three groups: those with a score of less than 30 (29 patients), those with a score of 30 to 80 (38 patients), and those with a score greater than 80 (36 patients). The level of other risk factors related to coronary heart disease with chronic heart failure in the observation and control groups were recorded (including creatinine, cardiac troponin, high-density lipoprotein [HDL], and low-density lipoprotein [LDL]), observing the serum levels of vaspin, GDF-15, and APN in patients with coronary heart disease and analyzing the correlation between these serum levels and the severity of coronary artery disease. Results: The HDL level in the observation group was significantly lower than that in the control group, and the levels of Cr, cTnl, and LDL in the observation group were significantly higher than those in the control group (P < 0.05). The serum vaspin and APN levels in the observation group were significantly lower than those of the control group, and a higher number of coronary artery lesion branches correlated with lower the serum vaspin and APN levels. The serum vaspin and APN levels in the Gensini high-score group were significantly lower than those in the Gensini low-score group, with statistical significance (P < 0.05). The serum GDF-15 level in the observation group was significantly higher than that in the control group, and the greater the number of coronary artery lesion branches, the higher the level. The serum GDF-15 level in the Gensini high-score group was significantly higher than that in the Gensini low-score group, with statistical significance (P < 0.05). Pearson correlation analysis showed that serum vaspin and APN levels were negatively correlated with Gensini scores, and that serum GDF- 15 levels were positively correlated with Gensini scores. Conclusion: Compared with healthy subjects, patients with coronary heart disease with chronic heart failure displayed significantly lower levels of vaspin and APN, and a significantly higher level of GDF-15; these results significantly correlated with the severity of coronary artery disease.