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Title: The effect of total cholesterol/high-density lipoprotein cholesterol ratio on mortality risk in the general population
Authors: Zhou, D
Liu, X
Lo, K 
Huang, Y
Feng, Y
Issue Date: 2022
Source: Frontiers in Endocrinology, 2022, v. 13, 1012383
Abstract: Background: The relationship between the total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratio and all−cause and cardiovascular mortality has not been elucidated. Herein, we intend to probe the effect of the TC/HDL-C ratio on all-cause and cardiovascular mortality in the general population.
Methods: From the 1999–2014 National Health and Nutrition Examination Surveys (NHANES), a total of 32,405 health participants aged ≥18 years were included. The TC/HDL-C levels were divided into five groups: Q1: <2.86, Q2: 2.86–3.46, Q3: 3.46–4.12, Q4: 4.12–5.07, Q5: >5.07. Multivariate Cox regression models were used to explore the relationship between the TC/HDL-C ratio and cardiovascular and all-cause mortality. Two−piecewise linear regression models and restricted cubic spline regression were used to explore nonlinear and irregularly shaped relationships. Kaplan–Meier survival curve and subgroup analyses were conducted.
Results: The population comprised 15,675 men and 16,730 women with a mean age of 43 years. During a median follow-up of 98 months (8.1 years), 2,859 mortality cases were recorded. The TC/HDL-C ratio and all-cause mortality showed a nonlinear association after adjusting for confounding variables in the restricted cubic spline analysis. Hazard ratios (HRs) of all-cause mortality were particularly positively related to the level of TC/HDL-C ratio in the higher range >5.07 and in the lower range <2.86 (HR 1.26; 95% CI 1.10, 1.45; HR 1.18; 95% CI 1.00, 1.38, respectively), although the HRs of cardiovascular disease mortality showed no difference among the five groups. In the two-piecewise linear regression model, a TC/HDL-C ratio range of ≥4.22 was positively correlated with cardiovascular mortality (HR 1.13; 95% CI 1.02, 1.25). In the subgroup analysis, a nonlinear association between TC/HDL-C and all-cause mortality was found in those aged <65 years, men, and the no lipid drug treatment population.
Conclusion: A nonlinear association between the TC/HDL-C ratio and all-cause mortality was found, indicating that a too-low or too-high TC/HDL-C ratio might increase all-cause mortality. However, for cardiovascular mortality, it does not seem so. The cutoff value was 4.22. The individuals had higher cardiovascular mortality with a TC/HDL-C ratio >4.22.
Keywords: Total cholesterol/high-density lipoprotein cholesterol ratio
All-cause mortality
Cardiovascular mortality
Nonlinear association
Prognostic capacity
Publisher: Frontiers Media S.A.
Journal: Frontiers in Endocrinology 
DOI: 10.3389/fendo.2022.1012383
Rights: © 2022 Zhou, Liu, Lo, Huang and Feng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
The following publication Zhou D, Liu X, Lo K, Huang Y and Feng Y (2022) The effect of total cholesterol/high-density lipoprotein cholesterol ratio on mortality risk in the general population. Front. Endocrinol. 13:1012383 is available at https://doi.org/10.3389/fendo.2022.1012383.
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