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- Geriatrics and Gerontology
- Aging
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.