| Title: | Low and Decreasing Cholesterol Levels and Risk of All-Cause and Cause-Specific Mortality: A Prospective and Longitudinal Cohort Study |
| Journal: | Engineering |
| Published: | 1 Jul 2025 |
| DOI: | https://doi.org/10.1016/j.eng.2025.06.032 |
Publication 16513
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
This prospective study aimed to investigate the associations of untreated cholesterol levels and their longitudinal changes, especially low levels, with all-cause and cause-specific mortality in different populations. Participants were drawn from two Chinese cohorts and the UK Biobank, excluding those with lipid-lowering medications, coronary heart disease (CHD), stroke, cancer, clinically diagnosed chronic obstructive pulmonary disease, low body mass index (< 18.5 kg∙m-2) at baseline, and deaths within the first two years to minimize reverse causality. Individual cholesterol changes were assessed in a subset who attended the resurvey after over four years. Mortality data were linked to registries, and risks were estimated using Cox proportional hazards models. A total of 163 115 Chinese and 317 305 UK adults were included (mean age, 49-61 years), with 43%, 81%, and 44% males in Dongfeng-Tongji, Kailuan, and UK Biobank cohorts, respectively. During a median follow-up of 9.7-12.9 years, 9553 and 15 760 deaths were documented in the Chinese cohorts and UK Biobank, respectively. After multivariate adjustments, nonlinear relationships were observed between total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) levels and mortality. In both populations, high cholesterol was primarily associated with CHD mortality, while low cholesterol associated with all-cause and cancer mortality (P nonlinear ≤ 0.0161). The optimal levels for all-cause mortality risk in Chinese adults (TC: 200 mg∙dL-1; LDL-C: 130 mg∙dL-1; non-HDL-C: 155 mg∙dL-1) were lower than those in the UK Biobank but consistent with guideline recommendation. Additionally, decreasing cholesterol levels over four years were associated with higher all-cause and cancer mortality in the Chinese cohorts (P nonlinear ≤ 0.0100). Participants with low TC, LDL-C, or non-HDL-C levels at both baseline and resurvey experienced elevated all-cause mortality risks in both populations, as did those with low/medium baseline levels and > 20% reductions over time in Chinese adults. In conclusion, higher TC, LDL-C, and non-HDL-C levels are associated with elevated CHD mortality. Importantly, low and/or longitudinally decreasing cholesterol levels are robustly associated with increased all-cause and cancer mortality, potentially serving as markers of premature death. Regular cholesterol monitoring, with attention to both high and low levels, is recommended to inform guideline updates and clinical strategies.</p>
21 Authors
- Qin Jiang
- Jiachen Wu
- Yu Yuan
- Xingjie Hao
- Pinpin Long
- Kang Liu
- Shihe Liu
- Rong Peng
- Kuai Yu
- Rui Zeng
- Shuohua Chen
- Handong Yang
- Xiulou Li
- Xiaomin Zhang
- Meian He
- Lin Wang
- Xiang Cheng
- An Pan
- Shouling Wu
- Chaolong Wang
- Tangchun Wu
1 Application
| Application ID | Title |
|---|---|
| 88159 | Fine-mapping, genetic correlation and genetic risk prediction for complex traits in different populations |
Enabling scientific discoveries that improve human health