Elevated remnant cholesterol and triglycerides are predictors of increased total mortality in a primary health care population of 327,347 patients

BACKGROUND: Hyperlipidemia is a well-established risk factor for cardiovascular disease and mortality. Recently, remnant cholesterol has been introduced as an important risk factor. This study explores the association between levels of remnant cholesterol, compared to the traditional lipid parameters (total cholesterol, low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) and triglycerides), and all-cause mortality in a population from general practice. Additionally, the impact of lipid-lowering treatment was evaluated.

METHODS: Observational cohort study based on the first lipid panel measurement from 327,347 patients from general practice in the Capital Region of Denmark between 2001 and 2018. LDL-C was calculated using the Friedewald equation. Patients with diagnoses or medical treatments that affected lipid levels were excluded. Cox proportional hazards models with restricted cubic splines were used to evaluate the association between all-cause mortality and lipid levels.

RESULTS: A total of 34,014 patients died during the study. In an analysis censoring individuals receiving lipid lowering treatment after the lipid measurement, remnant cholesterol increased all-cause mortality risk linearly, with a hazard ratio (HR) of 1.6 (95% CI: 1.4; 1.7) at 3 mmol/L compared to a reference level of 0.9 mmol/L. Total cholesterol showed a U-shaped relationship with all-cause mortality with a HR of 2.5 (95% CI: 2.3; 2.7) at 2.5 mmol/L and 1.7 (95% CI: 1.6; 1.9) at 9 mmol/L (reference level 5 mmol/L). LDL-C and non-HDL-C exhibited a very similar U-shaped pattern. HDL-C also showed a U-shaped curve with a HR of 1.7 (95% CI: 1.6; 1.9) at 0.5 mmol/L and 1.4 (95% CI: 1.3; 1.5) at 3.5 mmol/L (reference level 1 mmol/L). The mortality risk related to triglycerides increased with rising triglyceride level, with a HR of 1.5 (95% CI: 1.3; 1.6) at 4.5 mmol/L (reference level 2 mmol/L).

CONCLUSIONS: In this study, high levels of all the six lipids as well as low levels of total cholesterol, LDL-C, non-HDL-C and HDL-C were associated with higher all-cause mortality in a primary health care population. Further research is needed, to consider if the current lipid lowering guidelines are appropriate and if more focus on remnant cholesterol levels should be applied.