Association of Low-Density Lipoprotein With All-Cause and Cause-Specific Mortality Among Us Adults

Background: To determine the association between levels of low-density lipoprotein-cholesterol (LDL-C) and all-cause and cause-specific mortality among US adults based on a prospective cohort study. Methods: All participants were included from the National Health and Nutrition Examination Survey (NHANES) 1999-2014, a survey conducted by the Centers for Disease Control and Prevention (CDC). Among 10850 individuals, 1355 (12.5%) died after an average follow-up of 5.7 years. Baseline levels of LDL-C associated with risk of mortality were evaluated on a continuous scale (restricted cubic splines) and by a priori defined quantile categories with Cox regression models. Results: The association between levels of LDL-C and the risk of all-cause mortality was L shaped, with low levels associated with an increased mortality risk. The concentration of LDL-C associated with the lowest risk of all-cause mortality was 124 mg/dL (3.2mmol/L) in the overall population, and 134 mg/dL (3.4mmol/L) in individuals not receiving lipid lowering treatment. Compared with individuals with concentrations of LDL-C of 110-134 mg/dL (the 3rd quartile), the multivariable adjusted hazard ratio for all-cause mortality was 1.18 (95% confidence interval 1.01 to 1.38) for individuals with LDL-C concentrations of less than 89 mg/dL (the lowest quartile). In participants with coronary heart diseases, the conclusion was similar but the critical point was lower. Conclusions: In the general population, low levels of LDL-C were associated with an increased risk of all-cause mortality, and the lowest risk of all-cause mortality for LDL-C concentration was 124mg/dL (3.2mmol/L). The critical point was 92 mg/dL (1.04 mmol/L) in participants with coronary heart disease. Funding Information: None. Declaration of Interests: The authors have nothing to disclose regarding conflict of interest with respect to this manuscript. Ethics Approval Statement: The protocol was approved by the Institutional Review Board of the CDC and no new data was added.