Low-density-lipoprotein cholesterol and mortality outcomes among healthy older adults: A post-hoc analysis of ASPREE trial
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(Published version)
Date
2024
Authors
Zhou, Z.
Tonkin, A.M.
Curtis, A.J.
Murray, A.
Zhu, C.
Reid, C.M.
Williamson, J.D.
Ryan, J.
McNeil, J.J.
Beilin, L.J.
Editors
Fielding, R.A.
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Journal article
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The journals of gerontology. Series A, Biological sciences and medical sciences, 2024; 79(4):glad268-1-glad268-8
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Zhen Zhou, Andrew M.Tonkin, Andrea J. Curtis, Anne Murray, Chao Zhu, Christopher M. Reid, Jeff D.Williamson, Joanne Ryan, John J. McNeil, Lawrence J. Beilin, Michael E. Ernst, Nigel Stocks, Paul Lacaze, Raj C. Shah, Robyn L.Woods, Rory Wolfe, Seana Gall, Sophia Zoungas, Suzanne G. Orchard, and Mark R. Nelson
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Abstract
Background: The prognostic implication of cholesterol levels in older adults remains uncertain. This study aimed to examine the relationship between low-density-lipoprotein-cholesterol (LDL-c) and mortality outcomes in older individuals. Methods: This post-hoc analysis examined the associations of LDL-c levels with mortality risks from all-cause, CVD, cancer, and combined non-CVD/non-cancer conditions in a cohort of individuals aged ≥65 years from the ASPREE trial (NCT01038583). At baseline, participants had no diagnosed dementia, physical disability, or cardiovascular disease (CVD), and were not taking lipid-lowering agents. Outcome analyses were performed using multivariable Cox models. Results: We analysed 12,334 participants (mean age:75.2 years). Over a median 7-year follow-up, 1250 died. Restricted cubic splines found a U-shaped relation for LDL-c and all-cause mortality, cancer mortality, and non-cancer/non-CVE mortality (nadir: 3.3-3.4 mmol/L); the risk of CVD mortality was similar at LDL-c below 3.3 mmol/L and increased above 3.3 mmol/L. The similar trends were observed in analyses modelling LDL-c by quartiles. When modelling LDL-c as a continuous variable, the risk of all-cause mortality, cancer mortality, and non-cancer/non-CVD mortality was decreased by 9%, 16% and 18% respectively per 1-mmol/L higher LDL-c, and the risk of CVD mortality was increased by 19% per 1-mmol/L higher LDL-c. Reduced all-cause and non-CVD/non-cancer mortality risks were only significant in males but not females (Pinteraction <0.05). Conclusions: There were U-shaped relationships between LDL-c and all-cause mortality, cancer mortality, and non-cancer/non-CVD mortality in healthy older adults. Higher LDL-c levels were associated with an increased risk of CVD mortality. Future studies are warranted to confirm our results.
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© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.