# U-Shaped Lipid-CVD Links in Older Adults: Reversed LDL-C and HDL-C Associations and Goldilocks Zone

## TL;DR

This study finds that both high and low levels of LDL-C and HDL-C are linked to increased cardiovascular risk in older adults, suggesting an optimal 'Goldilocks zone' for lipid management.

## Contribution

The study identifies U- and L-shaped associations between lipid levels and CVD risk in older adults, revealing optimal target ranges not previously emphasized in guidelines.

## Key findings

- LDL-C has a U-shaped relationship with CVD risk, with minimal risk at 3.600-4.204 mmol/L.
- HDL-C shows an L-shaped association with incident CVD but a U-shaped association with CVD mortality.
- Joint LDL-C and HDL-C risk tiers show progressively higher CVD risk.

## Abstract

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.

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.

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.

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.

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.