Risk of cardiovascular death in patients with hepatocellular carcinoma based on the Fine-Gray model

Yu-Liang Zhang; Zi-Rong Liu; Zhi Liu; Yi Bai; Hao Chi; Da-Peng Chen; Ya-Min Zhang; Zi-Lin Cui

doi:10.4251/wjgo.v16.i3.844

Risk of cardiovascular death in patients with hepatocellular carcinoma based on the Fine-Gray model

World J Gastrointest Oncol. 2024 Mar 15;16(3):844-856. doi: 10.4251/wjgo.v16.i3.844.

Authors

Yu-Liang Zhang¹, Zi-Rong Liu², Zhi Liu², Yi Bai², Hao Chi¹, Da-Peng Chen¹, Ya-Min Zhang², Zi-Lin Cui³

Affiliations

¹ First Central Clinical College, Tianjin Medical University, Tianjin 300070, China.
² Department of Hepatobiliary Surgery, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China.
³ Department of Hepatobiliary Surgery, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China. 13602184643@163.com.

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most common types of cancers worldwide, ranking fifth among men and seventh among women, resulting in more than 7 million deaths annually. With the development of medical technology, the 5-year survival rate of HCC patients can be increased to 70%. However, HCC patients are often at increased risk of cardiovascular disease (CVD) death due to exposure to potentially cardiotoxic treatments compared with non-HCC patients. Moreover, CVD and cancer have become major disease burdens worldwide. Thus, further research is needed to lessen the risk of CVD death in HCC patient survivors.

Aim: To determine the independent risk factors for CVD death in HCC patients and predict cardiovascular mortality (CVM) in HCC patients.

Methods: This study was conducted on the basis of the Surveillance, Epidemiology, and End Results database and included HCC patients with a diagnosis period from 2010 to 2015. The independent risk factors were identified using the Fine-Gray model. A nomograph was constructed to predict the CVM in HCC patients. The nomograph performance was measured using Harrell's concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and area under the ROC curve (AUC) value. Moreover, the net benefit was estimated via decision curve analysis (DCA).

Results: The study included 21545 HCC patients, of whom 619 died of CVD. Age (< 60) [1.981 (1.573-2.496), P < 0.001], marital status (married) [unmarried: 1.370 (1.076-1.745), P = 0.011], alpha fetoprotein (normal) [0.778 (0.640-0.946), P = 0.012], tumor size (≤ 2 cm) [(2, 5] cm: 1.420 (1.060-1.903), P = 0.019; > 5 cm: 2.090 (1.543-2.830), P < 0.001], surgery (no) [0.376 (0.297-0.476), P < 0.001], and chemotherapy(none/unknown) [0.578 (0.472-0.709), P < 0.001] were independent risk factors for CVD death in HCC patients. The discrimination and calibration of the nomograph were better. The C-index values for the training and validation sets were 0.736 and 0.665, respectively. The AUC values of the ROC curves at 2, 4, and 6 years were 0.702, 0.725, 0.740 in the training set and 0.697, 0.710, 0.744 in the validation set, respectively. The calibration curves showed that the predicted probabilities of the CVM prediction model in the training set vs the validation set were largely consistent with the actual probabilities. DCA demonstrated that the prediction model has a high net benefit.

Conclusion: Risk factors for CVD death in HCC patients were investigated for the first time. The nomograph served as an important reference tool for relevant clinical management decisions.

Keywords: Cardiovascular disease deaths; Fine-Gray model; Hepatocellular carcinoma; Nomograph; Predict; Risk factor.