Effect of Triglyceride-Glucose Indices and Circulating PCSK9-Associated Cardiovascular Risk in STEMI Patients with Primary Percutaneous Coronary Artery Disease: A Prospective Cohort Study

Xiaoxiao Zhao,1,* Li Song,1,* Jiannan Li,1 Jinying Zhou,1 Nan Li,1 Shaodi Yan,2 Runzhen Chen,1 Ying Wang,1 Chen Liu,1 Peng Zhou,1 Zhaoxue Sheng,1 Yi Chen,1 Hanjun Zhao,1 Hongbing Yan2 1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongbing Yan, Fuwai Hospital, Chinese Academy of Medical Sciences, 12 Langshan Road, Shenzhen, 518000, People’s Republic of China, Tel +86-13701339287, Email hbyanfuwai2018@163.com Hanjun Zhao, Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, No. 167, Beijing, 100037, People’s Republic of China, Tel +86-15210020808, Email 15210020808@163.comBackground and Aims: This study aimed to determine whether convertase subtilisin/kexin type 9 (PCSK9)-associated cardiovascular risk is modulated by triglyceride-glucose (TyG) in ST-segment elevation myocardial infarction (STEMI) patients with primary percutaneous coronary disease (PCI).Methods: A total of 1541 patients with STEMI (aged ≥ 18 years) undergoing primary PCI were consecutively enrolled between March 2017 and March 2019.Outcomes: When stratifying the overall population according to TyG indices less than or greater than the median (TyG median = 9.07) as well as according to quartiles of PCSK9 levels, higher TyG index levels were significantly associated with all-cause mortality only when TyG levels were 9.07 or higher (ie, relative to quartile 1 [Q1], the adjusted HR for all-cause mortality was 3.20 [95% CI, 0.54– 18.80] for Q2, p = 0.199; 7.89 [95% CI, 1.56– 40.89] for Q3, p = 0.013; and 5.61 [95% CI, 1.04– 30.30] for Q4, p = 0.045. During a median follow-up period of 1.96 years, the HR for all-cause mortality was higher in the subset of patients with TyG ≥median and PCSK9 ≥median (p for trend = 0.023) among those with type 2 diabetes mellitus (T2DM). However, there were no statistically significant differences among the subgroups. Among T2DM patients with a TyG index greater than the median, the Kaplan-Meier curve showed that patients with the highest PCSK9 levels had an increased risk of all-cause mortality (log-rank p = 0.017) and cardiac-cause mortality (log-rank p = 0.037) compared with lower PCSK9 quartile levels.Conclusion: Elevated PCSK9 levels are related to all-cause mortality and cardiac-related mortality when TyG levels are greater than the median, but not when levels are less than the median. This suggests a potential benefit of lowering circulating PCSK9 levels in STEMI patients with insulin resistance.Keywords: triglyceride glucose index, proprotein convertase subtilisin/kexin type 9, mortality, type 2 diabetes, ST-segment elevation myocardial infarction, primary percutaneous coronary intervention