Dataset Information

Association of plasma high-density lipoprotein cholesterol level with risk of incident dementia: a cohort study of healthy older adults.

ABSTRACT:

Background

Recent studies have reported associations between high plasma high-density lipoprotein cholesterol (HDL-C) levels and risk of all-cause mortality, age-related macular degeneration, sepsis and fractures, but associations with dementia risk remain unclear. To determine whether high plasma HDL-C levels are associated with increased incident dementia risk in initially-healthy older people.

Methods

We conducted a post-hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial; a double-blind, randomized, placebo-controlled trial of daily low-dose aspirin in healthy older people. ASPREE recruited 16,703 participants aged ≥70 years (from Australia) and 2411 participants aged ≥65 years (from the US) between 2010 and 2014. Participants had no diagnosed cardiovascular disease, dementia, physical disability, or life-threatening illness at enrolment and were cognitively healthy (3MS score ≥78). All-cause dementia was a primary trial endpoint, and determined by DSM-IV criteria. Cox regression was used to examine hazard ratios between HDL-C categories <40 mg/dL, 40-60 mg/dL (reference category), 60-80 mg/dL, and >80 mg/dL and dementia. Restricted cubic spline curves were used to determine nonlinear associations. Data analysis was performed from October 2022 to January 2023.

Findings

Of the 18,668 participants, 850 (4.6%) cases of incident dementia were recorded over 6.3 (SD 1.8) years. Participants with high HDL-C (>80 mg/dL) had a 27% higher risk of dementia (HR 1.27, 95% CI 1.03, 1.58). Age stratified analyses demonstrated that the risk of incident dementia was higher in participants ≥75 years compared to participants <75 years (HR 1.42, 95% CI 1.10, 1.83 vs HR 1.02, 95% CI 0.68, 1.51). Associations remained significant after adjusting for covariates including age, sex, country of enrolment, daily exercise, education, alcohol consumption, weight change over time, non-HDL-C, HDL-C-PRS, and APOE genotype.

Interpretation

In a population of initially-healthy older adults aged ≥75 years, high HDL-C levels were associated with increased risk of all-cause dementia.

Funding

National Institutes of Health, USA; National Health and Medical Research Council Australia; Monash University (Melbourne, VIC, Australia); and the Victorian Cancer Agency (Australia).

SUBMITTER: Hussain SM

PROVIDER: S-EPMC10920036 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

Association of plasma high-density lipoprotein cholesterol level with risk of incident dementia: a cohort study of healthy older adults.

Hussain Sultana Monira SM Robb Catherine C Tonkin Andrew M AM Lacaze Paul P Chong Trevor T-J TT Beilin Lawrence J LJ Yu Chenglong C Watts Gerald F GF Ryan Joanne J Ernst Michael E ME Zhou Zhen Z Neumann Johannes T JT McNeil John J JJ

The Lancet regional health. Western Pacific 20231129

<h4>Background</h4>Recent studies have reported associations between high plasma high-density lipoprotein cholesterol (HDL-C) levels and risk of all-cause mortality, age-related macular degeneration, sepsis and fractures, but associations with dementia risk remain unclear. To determine whether high plasma HDL-C levels are associated with increased incident dementia risk in initially-healthy older people.<h4>Methods</h4>We conducted a post-hoc analysis of the Aspirin in Reducing Events in the Eld ...[more]

PMID: 38456089

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Project description:ImportanceIncreased levels of high-density lipoprotein cholesterol (HDL-C) have been associated with osteoporosis. Preclinical studies have reported that HDL-C reduces bone mineral density by reducing osteoblast number and function. However, the clinical significance of these findings is unclear.ObjectiveTo determine whether higher HDL-C levels are predictive of an increased fracture risk in healthy older adults.Design, setting, and participantsThis cohort study is a post hoc analysis of data from the Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial and the ASPREE-Fracture substudy. ASPREE was a double-blind, randomized, placebo-controlled primary prevention trial of aspirin that recruited participants between 2010 and 2014. These comprised community-based older adults (16 703 Australians aged ≥70 years, 2411 US participants ≥65 years) without evident cardiovascular disease, dementia, physical disability, and life-limiting chronic illness. The ASPREE-Fracture substudy collected data on fractures reported postrandomization from Australian participants. Cox regression was used to calculate hazard ratio (HR) and 95% CI. Data analysis for this study was performed from April to August 2022.ExposurePlasma HDL-C.Main outcomes and measuresFractures included were confirmed by medical imaging and included both traumatic and minimal trauma fractures. Fractures were adjudicated by an expert review panel.ResultsOf the 16 262 participants who had a plasma HDL-C measurement at baseline (8945 female participants [55%] and 7319 male [45%]), 1659 experienced at least 1 fracture over a median (IQR) of 4.0 years (0.02-7.0 years). In a fully adjusted model, each 1-SD increment in HDL-C level was associated with a 14% higher risk of fractures (HR, 1.14; 95% CI, 1.08-1.20). The results remained similar when these analyses were stratified by sex. Sensitivity and stratified analyses demonstrated that these associations persisted when the analyses were repeated to include only (1) minimal trauma fractures, (2) participants not taking osteoporosis medications, (3) participants who were never smokers and reported that they did not drink alcohol, and (4) participants who walked outside for less than 30 minutes per day and reported no participation in moderate/vigorous physical activity and to examine only (5) statin use. No association was observed between non-HDL-C levels and fractures.Conclusions and relevanceThis study suggests that higher levels of HDL-C are associated with an increased fracture risk. This association was independent of common risk factors for fractures.

Project description:BackgroundThe ratio of non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) (NHHR) served as a novel comprehensive lipid indicator. This study aimed to explore the association between NHHR and the incidence of cardiometabolic multimorbidity (CMM).MethodsThis study included 8191 individuals from the China Health and Retirement Longitudinal Study (CHARLS) database. We used multivariable cox proportional hazards regression, logistic regression, and restricted cubic splines (RCS) analysis to evaluate the association between NHHR and CMM. Subgroup analyses and interaction tests were also performed.ResultsThe incidences of CMM among participants in quartiles (Q) 1-4 of NHHR were 7.03%, 8.3%, 10.06%, and 16.55%, respectively. The NHHR was significantly higher in individuals with CMM compared to those without CMM (P < 0.001). When assessed as a continuous variable, NHHR was independently associated with the risk of CMM, as demonstrated by both multivariable cox proportional hazards regression analysis (HR = 1.05, 95% CI = 1.02-1.07, P < 0.001) and logistic regression analysis (OR = 1.09, 95% CI = 1.04-1.15, P < 0.001). Compared to individuals in the lowest quartiles of the NHHR (Q1), the risk of CMM in the highest quartiles (Q4) was increased by 1.25-fold according to multivariable cox proportional hazards regression analysis (HR = 2.25, 95% CI = 1.73-2.93, P < 0.001) and by 1.48-fold according to logistic regression analysis (OR = 2.48, 95% CI = 1.86-3.31, P < 0.001). This association was consistent across nearly all subgroups. RCS analysis revealed a significant nonlinear association between NHHR and CMM. Additionally, the predictive ability of NHHR for CMM was 0.613, which was superior to that of both HDL-C and non-HDL-C (P < 0.05). Furthermore, the composite variable comprising NHHR and other traditional risk factors exhibited the highest predictive value (C statistic = 0.679).ConclusionA higher NHHR was closely associated with an increased risk of CMM. Further studies on NHHR could be beneficial for preventing and treating CMM.

Dataset Information

Association of plasma high-density lipoprotein cholesterol level with risk of incident dementia: a cohort study of healthy older adults.

Background

Methods

Findings

Interpretation

Funding

Publications

Association of plasma high-density lipoprotein cholesterol level with risk of incident dementia: a cohort study of healthy older adults.

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