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

Ye, X; Du, S; Chen, S; Shi, Y; Wang, W; Wan, Y; Wang, J; Zeng, J; Pan, C; Yang, S; Liu, M; Wang, S; He, Y

doi:10.1016/j.jacadv.2025.102544

Prevention & lipids

U-Shaped Lipid-CVD Links in Older Adults: Reversed Low Density Lipoprotein Cholesterol (LDL-C) and High Density Lipoprotein Cholesterol (HDL-C) Associations and Goldilocks Zone

JACC AdvPublished 22 Jan 2026Multivariable Cox regression models and restricted cubic splines

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Authors' conclusion

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.

Study context

Population: U.K. Biobank participants aged ≥60 years, free of cardiovascular disease (CVD) and cancer at baseline
Participants: 217,442 U.K. Biobank participants

Comparison: Associations of LDL-C and HDL-C levels with CVD outcome
Outcome: CVD events during follow-up

Methodological detailsU.K. Biobank

U.K. Biobank

Main finding

As reported in the abstract

CVDs

26,756

CVD deaths

2,726

Further findings

Outcome	← Lower risk ←→ Higher risk →	HR (95% CI)
Incident CVD and CVD mortality, LDL-C Q1LDL-C Q1vs reference LDL-C groupIncident CVD, 39% higher	0.512	1.39 (1.32–1.47)
Incident CVD and CVD mortality, LDL-C Q1LDL-C Q1vs reference LDL-C groupCVD mortality, 27% higher	0.512	1.27 (1.08–1.48)
Incident CVD and CVD mortality, HDL-C Q6HDL-C Q6vs reference HDL-C groupIncident CVD, lower	0.512	0.90 (0.84–0.97)
Incident CVD and CVD mortality, HDL-C Q6HDL-C Q6vs reference HDL-C groupCVD mortality, higher	0.512	1.24 (1.01–1.51)
	0.512Hazard ratio (log scale)

LDL-C and incident CVD and CVD mortality (shape)

U-shaped relationships; minimal risk: 3.600-4.204 mmol/L

HDL-C and incident CVD and CVD mortality (shape)

L-shaped with incident CVD; U-shaped with CVD mortality; minimal risk: 1.421-1.699 mmol/L

Joint LDL-C and HDL-C risk tiers

CVD risk rose progressively with joint LDL-C and HDL-C risk tiers

Original publication

U-Shaped Lipid-CVD Links in Older Adults: Reversed LDL-C and HDL-C Associations and Goldilocks Zone. JACC Adv. Published 22 January 2026. doi:10.1016/j.jacadv.2025.102544

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