| Title: | U-Shaped Lipid-CVD Links in Older Adults Reversed LDL-C and HDL-C Associations and Goldilocks Zone |
| Journal: | JACC Advances |
| Published: | 22 Jan 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41576597/ |
| DOI: | https://doi.org/10.1016/j.jacadv.2025.102544 |
Publication 18507
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Abstract
BACKGROUND: Guidelines and consensus statements lack consistent management targets and ranges for low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in older adults.</p>
OBJECTIVES: The objectives of the study were to investigate the relationships of LDL-C and HDL-C with cardiovascular disease (CVD) risk in older adults and to identify optimal target ranges for their management.</p>
METHODS: This study included 217,442 U.K. Biobank participants aged ≥60 years, free of CVD and cancer at baseline. Multivariable Cox regression models and restricted cubic splines were employed to estimate HRs and 95% CIs for the associations of LDL-C and HDL-C levels with CVD outcome.</p>
RESULTS: During follow-up, 26,756 CVDs and 2,726 CVD deaths occurred. LDL-C exhibited U-shaped relationships with both incident CVD and CVD mortality (minimal risk: 3.600-4.204 mmol/L). HDL-C showed an L-shaped association with incident CVD but a U-shaped association with CVD mortality (minimal risk: 1.421-1.699 mmol/L). Compared with the reference LDL-C group, the Q1 group had a 39% higher incident CVD risk (HR: 1.39; 95% CI: 1.32-1.47) and 27% higher CVD mortality risk (HR: 1.27; 95% CI: 1.08-1.48). Conversely, compared with the reference HDL-C group, the Q6 group was associated with a lower incident CVD (HR: 0.90; 95% CI: 0.84-0.97) and higher CVD mortality risk (HR: 1.24; 95% CI: 1.01-1.51). Notably, the CVD risk rose progressively with joint LDL-C and HDL-C risk tiers.</p>
CONCLUSIONS: U/L-shaped associations of LDL-C and HDL-C with CVD risk in older adults underscore the importance of maintaining lipids within an optimal range. This distinct "Goldilocks zone" is associated with minimized risk and highlights current guideline limitations.</p>
13 Authors
- Xiaoxin Ye
- Shengyan Du
- Shimin Chen
- Yueting Shi
- Wenchang Wang
- Yanhao Wan
- Jianhua Wang
- Jing Zeng
- Chunjiang Pan
- Shanshan Yang
- Miao Liu
- Shengshu Wang
- Yao He
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