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

Xiaoxin Ye1, Shengyan Du1, Shimin Chen1

  • 1Medical School of Chinese People's Liberation Army, Beijing, China; Institute of Geriatrics, Beijing Key Laboratory of Geriatric Comorbidity, National Clinical Research Center for Geriatrics Diseases, Second Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.

JACC. Advances
|January 23, 2026
PubMed

Insights

Maintaining optimal cholesterol levels is crucial for older adults to minimize cardiovascular disease (CVD) risk. This study identifies specific low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) ranges associated with the lowest CVD risk.

Area of Science:

  • Cardiology
  • Geriatric Medicine
  • Public Health

Background:

  • Current guidelines lack consistent lipid management targets for older adults.
  • Existing recommendations do not adequately address specific low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) ranges for this demographic.
  • This gap necessitates research into optimal lipid management strategies for elderly populations.

Purpose of the Study:

  • To investigate the associations between LDL-C and HDL-C levels and cardiovascular disease (CVD) risk in individuals aged 60 and older.
  • To identify optimal target ranges for LDL-C and HDL-C management in older adults to reduce CVD risk.
  • To inform evidence-based guidelines for lipid management in geriatric populations.

Main Methods:

  • Utilized data from 217,442 U.K. Biobank participants aged 60 years and above, excluding those with pre-existing CVD or cancer.
  • Employed multivariable Cox regression models and restricted cubic splines to analyze the relationship between lipid levels and CVD outcomes.
  • Estimated hazard ratios (HRs) and 95% confidence intervals (CIs) to quantify CVD risk associated with varying LDL-C and HDL-C concentrations.

Main Results:

  • LDL-C demonstrated a U-shaped association with both incident CVD and CVD mortality, with minimal risk observed between 3.600-4.204 mmol/L.
  • HDL-C showed an L-shaped association with incident CVD but a U-shaped association with CVD mortality, with minimal mortality risk between 1.421-1.699 mmol/L.
  • Higher LDL-C (Q1) and lower HDL-C (Q6) were associated with increased CVD risk and mortality, with combined lipid levels further modifying risk.

Conclusions:

  • The U/L-shaped relationships of LDL-C and HDL-C with CVD risk in older adults highlight the need for precise lipid management.
  • A specific "Goldilocks zone" for lipid levels is associated with minimized CVD risk in this age group.
  • Findings indicate limitations in current guidelines and emphasize the importance of individualized lipid targets for older adults.
Abstract

Keywords:
CVD morbidityCVD mortalitycohort studyhigh-density lipoprotein cholesterollow-density lipoprotein cholesterololder adults

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