Association between homocysteine levels and hyperlipidemia prevalence as well as all-cause mortality of hyperlipidemia patients in the US population: results from NHANES database

Abstract

Objective: Several studies have investigated the correlation between blood lipids and homocysteine, but no clear conclusions have been defined yet. Therefore, we utilized data from National Health and Nutrition Examination Survey (NHANES) to explore the correlation between serum homocysteine (Hcy) levels and hyperlipidemia, which is determined by the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). We believe this study can provide a scientific basis for the prevention and treatment of lipid abnormalities.

Methods: The data used in this study were sourced from NHANES 1999-2006, linked with National Death Index mortality data from January 1999 to December 2019. We employed logistic regression to assess the associations between Hcy levels and the presence of hyperlipidemia. Additionally, survival analysis using Kaplan-Meier estimate and Cox proportional hazards regression model was conducted to evaluate the associations between Hcy levels and all-cause mortality in the hyperlipidemia population.

Results: (1) A total of 13,661 subjects were included in the study. There were statistically significant differences in Hcy levels across different groups based on gender, age, race, marital status, education level, hypertension status, diabetes status, and Body Mass Index (BMI) (P < 0.05). (2) In the overall population, hyperhomocysteinemia (HHcy) was associated with an increased risk of high-TC hyperlipidemia (P < 0.05). Subgroup analysis by gender showed that HHcy in females was associated with an increased risk of dyslipidemia (OR = 1.30, 95% CI: 1.07-1.59, P < 0.05) and high-LDL-C hyperlipidemia (OR = 1.30, 95% CI: 1.00-1.68, P < 0.05). In addition, subgroup analysis by age revealed that HHcy in middle-aged people was associated with an increased risk of high-TC hyperlipidemia (OR = 1.21, 95% CI: 1.03-1.41, P < 0.05) and high-LDL-C hyperlipidemia (OR = 1.23, 95% CI: 1.06-1.43, P < 0.05). (3) HHcy was consistently associated with an increased mortality risk in the hyperlipidemia population (HR = 1.49, 95% CI: 1.35-1.65, P < 0.05).

Conclusion: There was positive correlation between Hcy levels and the presence of hyperlipidemia. In the overall population, HHcy was associated with an increased risk of high-TC hyperlipidemia. Among females, HHcy is linked to an increased risk of dyslipidemia and high-LDL-C hyperlipidemia. In middle-aged people, HHcy was associated with an elevated risk of high-TC hyperlipidemia and high-LDL-C hyperlipidemia. In addition, HHcy increased the all-cause mortality rate in hyperlipidemia patients.

Keywords: Kaplan-Meier estimate; NHANES; cox proportional hazards analysis; homocysteine; hyperlipidemia.

Figure 1

Flowchart depicting the participants selection.

Figure 2

Data distribution before (blue plots) and after (red plots) multiple imputation. Coordinate 0 of horizontal axis indicated the raw data without imputation; coordinate 1-5 indicated the results of 5 imputations.

Figure 3

Univariate Kaplan-Meier curves. The red plot indicated the survival curve of subjects with normal Hcy, while the blue plot indicated the survival curve of subjects with HHcy.

Figure 4

Forest plot for multivariate Cox regression analysis.