Association Between Systemic Immune Inflammation Level and Poor Prognosis Across Different Glucose Metabolism Status in Coronary Artery Disease Patients

Xiayan Xu,1– 3,* Yun Xie,2– 4,* Xia Gu,5– 7,* Yang Zhou,2,3 Yu Kang,2,3,8 Jin Liu,2,3 Wenguang Lai,2– 4 Hongyu Lu,2,3 Shiqun Chen,2,3 Jun-yan Xu,2,3,9 Feng Lin,10 Yong Liu1– 3 1School of Medicine, South China University of Technology, Guangzhou, 510006, People’s Republic of China; 2Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 4School of Biology and Biological Engineering South China University of Technology, Guangzhou, 510006, People’s Republic of China; 5Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, People’s Republic of China; 6The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, Heilongjiang, 150086, People’s Republic of China; 7Cardiovascular Imaging Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, People’s Republic of China; 8Shantou University Medical College, Shantou, 515041, People’s Republic of China; 9Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, College of Emergency and Trauma, Hainan Medical University, Haikou, 571199, People’s Republic of China; 10Shenzhen People’s Hospital, Shenzhen, 518020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng Lin, Shenzhen People’s Hospital, Shenzhen, 518020, People’s Republic of China, Email linfeng3085@163.com Yong Liu, South China University of Technology, No. 382, Waihuan East Road, University City, Panyu District, Guangzhou, Guangdong Province, People’s Republic of China, Tel +86 2083827812-10528, Fax +86 2083851483, Email liuyong@gdph.org.cnBackground: Blood glucose levels significantly affect the clinical prognosis of patients with coronary artery disease (CAD), and systemic immune inflammation is a common risk factor for both CAD and diabetes. However, the relationship between immune inflammation levels and poor prognosis in patients with CAD with different glucose metabolic statuses remains unclear.Methods: Between January 2007 and December 2020, we recruited 84,645 patients with CAD. The systemic immune inflammation index (SII) was used to comprehensively reflect the immune and inflammatory levels of patients and was calculated using the following formula: neutrophils × platelets/lymphocytes. The patients were classified into nine groups according to their glucose metabolism status (diabetes mellitus [DM], pre-diabetes mellitus [pre-DM], and normal glucose regulation [NGR]). Cox regression models and competing risk Fine and Gray models were used to investigate the association between SII and clinical outcomes.Results: During the follow-up period, 12,578 patients died, including 5857 cardiovascular-related and 1251 cancer-related deaths. The risk of all-cause and cause-specific mortality increased with increasing SII tertiles in CAD patients with NGR, pre-DM, and DM. When considering glucose metabolism status, the multivariate cox regression revealed that CAD patients with DM and SII-H levels had the highest risk of all-cause mortality (1.69 [1.56– 1.83]), cardiovascular mortality (2.29 [2.02– 2.59]), and cancer mortality (1.29 [1.01– 1.66]). Moreover, incorporating the SII into traditional risk factor models significantly improved the C-index for predicting all-cause and cardiovascular mortality.Conclusion: Systemic immune inflammation levels on admission were correlated with a higher risk of all-cause and cause-specific mortality in patients with CAD, particularly in those with DM.Keywords: systemic immune inflammation index, coronary artery disease, type 2 diabetes, prognosis, mortality