Low-Density-Lipoprotein Cholesterol and Mortality Outcomes Among Healthy Older Adults: A Post Hoc Analysis of ASPREE Trial

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, Mark R. Nelson

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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, cardiovascular disease (CVD), cancer, and combined non-CVD/noncancer conditions in a cohort of individuals aged ≥65 years from the ASPirin in Reducing Events in the Elderly trial (NCT01038583). At baseline, participants had no diagnosed dementia, physical disability, or CVD, and were not taking lipid-lowering agents. Outcome analyses were performed using multivariable Cox models. Results: We analyzed 12 334 participants (mean age: 75.2 years). Over a median 7-year follow-up, 1 250 died. Restricted cubic splines found a U-shaped relation for LDL-c and all-cause mortality, cancer mortality, and noncancer/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. Similar trends were observed in analyses modeling LDL-c by quartiles. When modeling LDL-c as a continuous variable, the risk of all-cause mortality, cancer mortality, and noncancer/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/noncancer mortality risks were only significant in males but not females (pinteraction < .05). Conclusions: There were U-shaped relationships between LDL-c and all-cause mortality, cancer mortality, and noncancer/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.

Original languageEnglish
Article numberglad268
Number of pages8
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume79
Issue number4
DOIs
Publication statusPublished - Apr 2024

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