Exploring the Causal Roles of Circulating Remnant Lipid Profile on Cardiovascular and Cerebrovascular Diseases: Mendelian Randomization Study

Si, Shucheng; Hou, Lei; Chen, Xiaolu; Li, Wenchao; Liu, Xinhui; Liu, Congcong; Li, Yunxia; Yuan, Tonghui; Wang, Bojie; Li, Hongkai; Xue, Fuzhong

doi:10.2188/jea.je20200305

Cited by 27 publications

(11 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to its atherogenic properties, RC can contribute to atherosclerosis in both the carotid artery [ 21 ] and arterioles in the brain. A Mendelian randomization study confirmed the causal relationship of remnant lipoprotein-associated genes and ischemic stroke [ 22 ]. Prospective cohort studies on symptomatic intracranial atherosclerotic stenosis and ischemic stroke indicated that RC causes cerebral hypoperfusion [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Association between remnant cholesterol and verbal learning and memory function in the elderly in the US

Xie¹,

Zhao²,

Gao³

et al. 2022

Lipids Health Dis

View full text Add to dashboard Cite

Background The relationship between remnant cholesterol (RC) and atherosclerotic cardiovascular risk has been given increasing attention in recent years. However, its association with verbal learning and memory performance has not been reported. Methods Data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 database. Participants aged ≥60 years with available fasting lipid data were included. Verbal learning and memory performance were evaluated using the Consortium to Establish a Registry for Alzheimer’s Disease Word List Memory Task (CERAD-WL) subtest. The CERAD total score was calculated as the mean of three immediate recalls and a delayed recall. RC was calculated as total cholesterol (TC) minus the sum of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Multivariate ordinal logistic regression was performed to evaluate the association between RC, as well as its derived marker, the TC/RC ratio, and age-stratified quartiles of the CERAD total score. Results A total of 1377 participants were analysed. On a continuous scale, per 1 mmol/L increase in RC and per 1 unit increase in the TC/RC ratio were associated with multivariable adjusted odds ratios (95% CI) of 0.74 (0.58–0.94) and 1.45 (1.13–1.87), respectively, for having a CERAD total score in a higher quartile. On a categorical scale, higher RC quartiles were associated with a CERAD total score in a lower quartile; in contrast, the higher TC/RC quartile was associated with a CERAD total score in a higher quartile (all P for trend < 0.05). Conclusions The current study suggests that lower RC levels and a higher TC/RC ratio are associated with better verbal learning and memory function, which indicates that lowering RC levels could be beneficial for preventing cognitive impairment in elderly individuals. Further research is needed to validate the causal roles of RC and the TC/RC ratio in cognition.

show abstract

Section: Discussionmentioning

confidence: 99%

Association between remnant cholesterol and verbal learning and memory function in the elderly in the US

Xie¹,

Zhao²,

Gao³

et al. 2022

Lipids Health Dis

View full text Add to dashboard Cite

show abstract

“…F-statistics were applied to quantify the strength of the selected instruments. In general, the Fstatistic > 10 would be considered strong as previous research [19].…”

Section: Genetic Instrumental Variables (Ivs)mentioning

confidence: 70%

Genetically predicted levels of circulating cytokines and risk of Alzheimer's and Parkinson's disease: evidence from complementary genetic methods

Zhang

Wang

Liu

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Background Alzheimer's disease (AD) and Parkinson's disease (PD) are the top two common neurodegenerative diseases. In recent years, the role of cytokines-related neuroinflammatory response in the pathogenesis of AD/PD has received increasing attention. This study aims to investigate the relationship between genetically determined cytokines and the risk of AD/PD.Methods Four systematic univariable Mendelian randomizations (MR) approaches were adopted to assess the causal effect of cytokines on AD/PD and their robustness, including inverse-variance weighted (IVW), weighted-median estimator (WME), robust adjusted profile score (RAPS), and wald ratio (WRO) methods. Furthermore, multivariate MR (MVMR) with Bayesian model averaging (MR-BMA) was performed to prioritize the cytokine combinations that may be on the AD/PD causal pathway. Besides, we used the standard IVW MVMR to re-estimate the causal effect and confidence interval of each cytokine in the top 10 models screened by MR-BMA. Bidirectional MR analysis was additionally performed to detect the causal directionality. Finally, results generated by univariate MR and MR-BMA methods were combined.Results Univariable MR (IVW) analysis indicated genetically determined higher levels of macrophage inflammatory protein-1 beta (MIP1b) were positively associated with both AD and PD [odds ratios (ORs) and 95% confidence intervals (95%CIs) were 1.05 (1.01–1.09) and 1.06 (1.02–1.10)]. Besides, Interleukin (IL) IL16 was positively associated with PD [OR (95%CI): 1.09 (1.01–1.18)]. However, IL2 receptor alpha (IL2ra) was negatively associated with AD [OR (95%CI): 0.92 (0.86–0.98)]. Particularly, MR-BMA analysis corroborated that MIP1b was the top priority risk factor for both AD and PD [posterior probability (marginal inclusion probability): 0.212 (0.190) and 0.509 (0.782)]. In addition, standard IVW MVMR detected that the genetical positive effect of MIP1b on both AD and PD was still significant. The relationship between MIP1b and PD was further replicated by FinnGen summary-level dataset. Finally, the results of bidirectional MR showed neither AD nor PD could modify the level of MIP1b.Conclusions Genetic predisposition to elevated circulating levels of MIP1b was associated with a higher risk of both AD and PD. In addition, MIP1b was screened as the most prioritized cytokine-related risk factor. Whether targeting MIP1b or its pathways could lower the AD/PD incidence requires future functional studies.

show abstract

“…Due to its atherogenic properties, RC can contribute to atherosclerosis in both the carotid artery [21] and arterioles in the brain. A Mendelian randomization study con rmed the causal relationship of remnant lipoprotein-associated genes and ischaemic stroke [22]. Prospective cohort studies on symptomatic intracranial atherosclerotic stenosis and ischaemic stroke indicated that RC causes cerebral hypoperfusion [23].…”

Section: Discussionmentioning

confidence: 99%

Association between Remnant Cholesterol and Verbal Learning and Memory Function in the Elderly in the US

Xie

Zhao

Gao

et al. 2022

Preprint

View full text Add to dashboard Cite

Background The relationship between remnant cholesterol (RC) and atherosclerotic cardiovascular risk has been given increasing attention in recent years. However, its association with verbal learning and memory performance has not been reported. Methods Data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 database. Participants aged ≥ 60 years with available fasting lipid data were included. Verbal learning and memory performance were evaluated using the Consortium to Establish a Registry for Alzheimer’s Disease Word List Memory Task (CERAD-WL) subtest. The CERAD total score was calculated as the mean of three immediate recalls and a delayed recall. RC was calculated as total cholesterol (TC) minus the sum of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Multivariate ordinal logistic regression was performed to evaluate the association between RC, as well as its derived marker, the TC/RC ratio, and age-stratified quartiles of the CERAD total score. Results A total of 1377 participants were analysed. On a continuous scale, a 1 mmol/L increase in RC and a 1 unit increase in the TC/RC ratio were associated with multivariable adjusted odds ratios (95% CI) of 0.74 (0.58–0.94) and 1.45 (1.13–1.87), respectively, for having a CERAD total score in a higher quartile. On a categorical scale, higher RC quartiles were associated with having a CERAD total score in a lower quartile; in contrast, the higher TC/RC quartile was associated with having a CERAD total score in a higher quartile, with all P for trend < 0.05. Conclusions The study suggests that lower RC levels and a higher TC/RC ratio are associated with better verbal learning and memory function, which indicates that lowering RC levels could be beneficial for preventing cognitive impairment in the elderly. Further research is needed to validate the causal roles of RC and the TC/RC ratio in cognition.

show abstract

Exploring the Causal Roles of Circulating Remnant Lipid Profile on Cardiovascular and Cerebrovascular Diseases: Mendelian Randomization Study

Abstract: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record.

Cited by 27 publications

References 42 publications

Association between remnant cholesterol and verbal learning and memory function in the elderly in the US

Association between remnant cholesterol and verbal learning and memory function in the elderly in the US

Genetically predicted levels of circulating cytokines and risk of Alzheimer's and Parkinson's disease: evidence from complementary genetic methods

Association between Remnant Cholesterol and Verbal Learning and Memory Function in the Elderly in the US

Contact Info

Product

Resources

About