Association of Low-density Lipoprotein Cholesterol Levels with the Risk of Mortality and Cardiovascular Events: A Meta-analysis of Cohort Studies with 1,232,694 Participants

Background: Lowering elevated low-density lipoprotein cholesterol (LDL-C) is an important strategy to prevent cardiovascular disease (CVD), while some studies report low LDL-C increases all-cause mortality. Our study aimed to explore the appropriate low LDL-C level with the lower CVD risk but with no excess risk for all-cause mortality.

Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched until April 7, 2021. Twenty cohort studies with 1232,694 adults were obtained. Effect size index was evaluated using pooled relative risk (RR) with 95% confidence interval (CI). Heterogeneity was assessed using the Cochran's Q test and I2 statistic, and heterogeneity sources was investigated using meta-regression. Publication bias was assessed and sensitivity analysis was performed.

Results: The risks of all-cause mortality (RR: 1.34, 95%CI: 1.00-1.80), CVD death (RR: 1.79, 95%CI: 1.26-2.54), CHD death (RR: 2.03, 95%CI: 1.36-3.03) were higher in LDL-C ≥ 160 mg/dL than LDL-C of 70-129 mg/dL. Both LDL-C of 130-159 mg/dL and ≥ 160 mg/dL were associated with higher CVD risk than LDL-C of 70-129 mg/dL, with RR of 1.26 (95%CI: 1.08-1.47) and 1.70 (95%CI: 1.35-2.14), respectively. Compared to LDL-C of 70-129 mg/dL, no association was found between LDL < 70 mg/dL and all-cause mortality and CVD events.

Conclusion: Our results found LDL-C ≥ 130 mg/dL was associated with the higher risk of all-cause mortality and CVD risk, indicating that adults with high LDL-C should take interventions to regulate the LDL-C level lower than 130 mg/dL.