Abstract 12463: Low-Density-Lipoprotein Cholesterol and Mortality Outcomes Among Healthy Older Adults Not Taking Lipid-Lowering Agents: A Cohort Study With 12,334 Participants

Abstract

Introduction: Clinical uncertainty remains about the relationship between cholesterol levels and risk of death in older persons. Hypothesis: Lower low-density lipoprotein (LDL) cholesterol level was associated with a decreased mortality risk from cardiovascular disease (CVD) and an increased mortality risk due to non-CVD causes in primary prevention older populations. Methods: We examined the relationship between LDL cholesterol levels and mortality outcomes in a cohort of older individuals aged ≥65 years enrolled into a clinical trial. At baseline, participants had no diagnosed dementia, physical disability or CVD events, and were not taking lipid-lowering agents. Multivariable Cox proportional-hazards models were used to examine associations of LDL cholesterol with all-cause, CVD, cancer, and combined non-CVD/non-cancer mortality. Restricted cubic splines were used to depict non-linear relationships. Results: Among 12,334 participants included in this analysis [mean (SD) age: 75.2 (4.6) years; 54% females], who were followed for a median of 6.9 (5.7-8.0) years, 1250 (10%) died (24% due to CVD, 43% cancer, and 33% non-CVD/non-cancer). There was a U-shaped relation linking LDL cholesterol and all-cause mortality (nadir: 3.3mmol/L) and a curvilinear relation for other mortality outcomes. Each 1-mmol/L higher LDL cholesterol was associated with a lower risk of all-cause mortality (HR=0.91, 95% CI 0.85-0.98), cancer mortality (0.83, 0.74-0.94) and non-CVD/non-cancer mortality (0.81, 0.71-0.93), but a higher risk of CVD mortality (1.19, 1.03-1.38). Reduced risks of all-cause and non-CVD/non-cancer mortality were only significant in males and but not females (P values for sex interaction <0.05). When deaths in the five years after baseline were excluded, the HRs for all-cause, cancer, non-CVD/non-cancer and CVD mortality were 1.03, 1.05, 0. 91 and 1.21 respectively (all P>0.10). Conclusions: Higher LDL cholesterol is associated with a greater risk of CVD mortality in older adults. Reduced risks for non-CVD mortality were likely driven by reverse causality, evidenced by the absence of associations after excluding deaths that occurred within the initial five years of follow-up.