Relationship Between Cumulative Exposure of Lactate Dehydrogenase Concentrations and Major Adverse Cardiac and Cerebrovascular Events in Hypertensive Patients: A Retrospective Cohort Study from Northwest China

Hui Wang, 1– 5, Nanfang Li, 1– 5, Mulalibieke Heizhati, 1– 5 Qing Zhu, 1– 5 Ling Yao, 1– 5 Huimin Ma, 1– 5 Qixin Wang, 1– 5 Xiaohong Liu, 1– 5 Bahejiamali Nuerbolati, 1– 5 Jing Hong1– 5 1Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 2Xinjiang Hypertension Institute, Urumqi, Xinjiang, People’s Republic of China; 3NHC Key Laboratory of Hypertension Clinical Research, Urumqi, Xinjiang, People’s Republic of China; 4Key Laboratory of Xinjiang Uygur Autonomous Region “Hypertension Research Laboratory”, Urumqi, Xinjiang, People’s Republic of China; 5Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases, Urumqi, Xinjiang, People’s Republic of ChinaThese authors contributed equally to this workCorrespondence: Nanfang Li, Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Urumqi, Xinjiang, People’s Republic of China, Tel +86 8564818, Email lnanfang2016@sina. comBackground: As of 2023, cardiovascular disease (CVD) affects 626 million people globally, imposing a heavy burden on both society and families. Despite advances in antihypertensive therapy, residual risk persists, underscoring the need for potential biomarkers to optimize risk stratification. Lactate dehydrogenase (LDH), traditionally a marker of tissue injury, may reflect metabolic or inflammatory stress associated with vascular damage. This study investigates the association between annual cumulative LDH exposure and incident major adverse cardiac and cerebrovascular events (MACCE) in hypertensive patients, providing insights for prevention strategies. Methods: In this retrospective cohort study, we included hypertensive patients treated at a large tertiary hospital in Urumqi, China, from January 2011 to April 2025. Kaplan-Meier curves visualized survival differences, and Cox proportional hazards models assessed the association between annual LDHAUC and MACCE risk. Stratified and sensitivity analyses evaluated robustness, while C-statistics compared the predictive performance of annual LDHAUC versus single-timepoint LDH. Results: During a median follow-up period of 47 months, a total of 879 new MACCE were recorded. The research results showed that whether the annual LDHAUC was used as a continuous variable or a categorical variable, an increase in annual LDHAUC would increase the risk of MACCE (HR=1. 012, 95% CI, 1. 007– 1. 017; HR=1. 431, 95% CI, 1. 185– 1. 727). Moreover, the predictive value of annual LDHAUC for MACCE is superior to that of a single LDH measurement. Conclusion: In hypertensive patients, elevated annual LDHAUC levels is associated with an elevated risk MACCE. Keywords: hypertension, lactate dehydrogenase, major adverse cardiac and cerebrovascular events