Association between low density lipoprotein cholesterol and all-cause mortality: results from the NHANES 1999-2014

Abstract

The association between low density lipoprotein cholesterol (LDL-C) and all-cause mortality has been examined in many studies. However, inconsistent results and limitations still exist. We used the 1999-2014 National Health and Nutrition Examination Survey (NHANES) data with 19,034 people to assess the association between LDL-C level and all-cause mortality. All participants were followed up until 2015 except those younger than 18 years old, after excluding those who died within three years of follow-up, a total of 1619 deaths among 19,034 people were included in the analysis. In the age-adjusted model (model 1), it was found that the lowest LDL-C group had a higher risk of all-cause mortality (HR 1.708 [1.432-2.037]) than LDL-C 100-129 mg/dL as a reference group. The crude-adjusted model (model 2) suggests that people with the lowest level of LDL-C had 1.600 (95% CI [1.325-1.932]) times the odds compared with the reference group, after adjusting for age, sex, race, marital status, education level, smoking status, body mass index (BMI). In the fully-adjusted model (model 3), people with the lowest level of LDL-C had 1.373 (95% CI [1.130-1.668]) times the odds compared with the reference group, after additionally adjusting for hypertension, diabetes, cardiovascular disease, cancer based on model 2. The results from restricted cubic spine (RCS) curve showed that when the LDL-C concentration (130 mg/dL) was used as the reference, there is a U-shaped relationship between LDL-C level and all-cause mortality. In conclusion, we found that low level of LDL-C is associated with higher risk of all-cause mortality. The observed association persisted after adjusting for potential confounders. Further studies are warranted to determine the causal relationship between LDL-C level and all-cause mortality.

Figure 1

Multivariate analysis of low-density lipoprotein cholesterol (LDL-C) level and covariates associated with all-cause mortality in the NHANES Study, 1999–2014. (A) Age-adjusted model (model 1), adjusted for age (continuous). (B) Crude-adjusted model (model 2), adjusted for age (continuous), sex, race, marital status, education level, smoking status, BMI (continuous). (C) Fully-adjusted model (model 3), adjusted for age (continuous), sex, race, marital status, education level, smoking status, BMI (continuous), hypertension, diabetes, cardiovascular disease, cancer.

Figure 2

Spline plot of low-density lipoprotein cholesterol (LDL-C) level and all-cause mortality rate. The adjusted odd ratios and 95% confidence intervals (CIs) were calculated with logistic regression models after adjusting for age (continuous), sex, race, marital status, education level, smoking status, BMI (continuous), hypertension, diabetes, cardiovascular disease, cancer.