Long-Term Cardiovascular and Noncardiovascular Mortality After Acute Coronary Syndrome: A Nationwide Competing-Risks Analysis of 1.56 Million Patients

Jing Yang; Peng Yin; Mingxuan Li; Yuanchao Gao; Dingcheng Xiang; Maigeng Zhou; Yong Huo

doi:10.1016/j.jacc.2025.12.064

Long-Term Cardiovascular and Noncardiovascular Mortality After Acute Coronary Syndrome: A Nationwide Competing-Risks Analysis of 1.56 Million Patients

J Am Coll Cardiol. 2026 Feb 6:S0735-1097(25)10597-4. doi: 10.1016/j.jacc.2025.12.064. Online ahead of print.

Authors

Jing Yang¹, Peng Yin², Mingxuan Li³, Yuanchao Gao³, Dingcheng Xiang⁴, Maigeng Zhou⁵, Yong Huo⁶

Affiliations

¹ Department of Cardiology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
² National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
³ Department of Medicine, China Heart House, Suzhou, China.
⁴ Department of Cardiology, General Hospital of Southern Theatre Command of PLA, Guangzhou, China. Electronic address: dcxiang@foxmail.com.
⁵ National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. Electronic address: zhoumaigeng@ncncd.chinacdc.cn.
⁶ Department of Cardiology, Peking University First Hospital, Beijing, China. Electronic address: huoyong@263.net.cn.

PMID: 41706064
DOI: 10.1016/j.jacc.2025.12.064

Abstract

Background: Long-term mortality rates among postdischarge acute coronary syndrome (ACS) patients remain substantial. The temporal evolution and cause-specific drivers of this residual risk remain incomplete.

Objectives: This study aimed to comprehensively investigate the cumulative incidence of cardiovascular (CV) and non-CV mortality after ACS discharge using a competing-risks framework.

Methods: In this multicenter cohort study, we analyzed data from the China Cardiovascular Association Database-Chest Pain Center. Mortality outcomes were ascertained through linkage with the Chinese Center for Disease Control and Prevention Cause of Death Reporting System via national mortality surveillance. Eligible patients were aged 18 years or older with a discharge diagnosis of ACS between January 2018 and December 2021. The primary outcome was all-cause mortality. Causes of death were categorized as CV or non-CV, which were analyzed as competing events. Cumulative incidence and landmark analysis at 12 months were conducted to evaluate temporal mortality patterns. Multivariate competing risks regression (Fine and Gray model) was used to identify predictors associated with the cause-specific mortality. Subgroup analyses were conducted across age, sex, and ACS subtypes.

Results: Of 1,562,956 eligible patients, 1,074,289 (68.7%) were men, and the mean age was 63.8 ± 12.3 years. The competing risks analysis revealed that CV death was the primary driver of mortality at 1-month discharge (1.24% vs 0.26% for non-CV); yet, non-CV mortality showed a higher relative growth than CV mortality after 12-month discharge. Ischemic heart disease (68.5%) was the predominant CV death, whereas non-CV death was dominated by malignancy (38.3%) and chronic pulmonary disease (15.8%). Age ≥65 years (subdistribution HR [sHR]: 3.78; 95% CI: 3.72-3.849), chronic kidney disease (sHR: 2.07; 95% CI: 2.03-2.11), and chronic heart failure (sHR: 1.99; 95% CI: 1.96-2.02) were leading predictors of death. Lipid-lowering therapy was associated with lower risks of all-cause, CV, and non-CV death.

Conclusions: This national study demonstrates a transition in post-ACS mortality from CV to non-CV causes over time, with malignancy emerging as the leading cause of late-term death. These findings necessitate moving beyond traditional secondary prevention toward integrated survivorship care that addresses the full spectrum of competing risks.

Keywords: acute coronary syndrome; cause of death; chest pain center; mortality rates.