This study investigates the association between low-density lipoprotein cholesterol (LDL-C) levels and mortality in populations with different atherosclerotic cardiovascular disease (ASCVD) risk profiles in China. The ChinaHEART project, a prospective cohort study involving 3,789,025 participants aged 35 to 75 years from 31 provinces in mainland China, was used to explore these associations. Participants were categorized into low-risk, primary prevention, and secondary prevention cohorts based on their medical history and ASCVD risk. The primary endpoint was all-cause mortality, with secondary endpoints including cause-specific mortality. Data were collected from the National Mortality Surveillance System and Vital Registration. The association between LDL-C levels and mortality was assessed using Cox proportional hazard regression models with various adjusted variables. Key findings include: - A U-shaped association was observed between LDL-C levels and all-cause or cardiovascular disease (CVD) mortality in the low-risk and primary prevention cohorts. - A J-shaped association was found in the secondary prevention cohort. - The LDL-C levels corresponding to the lowest CVD mortality were 117.8 mg/dL in the low-risk group, 106.0 mg/dL in the primary prevention cohort, and 55.8 mg/dL in the secondary prevention cohort. - Individuals with diabetes had lower LDL-C concentrations associated with the lowest all-cause and CVD mortality compared to those without diabetes. The study suggests that lipid management strategies should be differentiated based on ASCVD risk levels and comorbidities, particularly for individuals with higher ASCVD risk and diabetes. These findings highlight the importance of intensive lipid control in reducing mortality risk across different ASCVD risk populations.This study investigates the association between low-density lipoprotein cholesterol (LDL-C) levels and mortality in populations with different atherosclerotic cardiovascular disease (ASCVD) risk profiles in China. The ChinaHEART project, a prospective cohort study involving 3,789,025 participants aged 35 to 75 years from 31 provinces in mainland China, was used to explore these associations. Participants were categorized into low-risk, primary prevention, and secondary prevention cohorts based on their medical history and ASCVD risk. The primary endpoint was all-cause mortality, with secondary endpoints including cause-specific mortality. Data were collected from the National Mortality Surveillance System and Vital Registration. The association between LDL-C levels and mortality was assessed using Cox proportional hazard regression models with various adjusted variables. Key findings include: - A U-shaped association was observed between LDL-C levels and all-cause or cardiovascular disease (CVD) mortality in the low-risk and primary prevention cohorts. - A J-shaped association was found in the secondary prevention cohort. - The LDL-C levels corresponding to the lowest CVD mortality were 117.8 mg/dL in the low-risk group, 106.0 mg/dL in the primary prevention cohort, and 55.8 mg/dL in the secondary prevention cohort. - Individuals with diabetes had lower LDL-C concentrations associated with the lowest all-cause and CVD mortality compared to those without diabetes. The study suggests that lipid management strategies should be differentiated based on ASCVD risk levels and comorbidities, particularly for individuals with higher ASCVD risk and diabetes. These findings highlight the importance of intensive lipid control in reducing mortality risk across different ASCVD risk populations.