Roles of remnant cholesterol in the risk factor, occurrence and in-hospital outcomes of stroke

Author Identifier

Zhiyuan Wu

Date of Award


Document Type

Thesis - ECU Access Only


Edith Cowan University

Degree Name

Doctor of Philosophy (Joint-ECU host)


School of Medical and Health Sciences

First Supervisor

Wei Wang

Second Supervisor

Lois Balmer

Third Supervisor

Xiuhua Goo



Stroke is the leading cause of death and disability with high incidence and recurrence rates and has caused severe social burden worldwide. Data from epidemiological studies demonstrate that there were more than 101 million stroke cases globally in 2019, with ischemic stroke accounting for 62.4%. Of note, the global lifetime risk of stroke is 24.9%, while the lifetime risk of stroke in China is up to 39.3%. Independent of low-density lipoprotein (LDL) cholesterol, the atherogenic effect of remnant cholesterol is gradually recognized in the residual risk of cardiovascular disease. However, evidence on the association between remnant cholesterol level and stroke occurrence and its pivotal risk factor, arterial stiffness, in the Chinese population is relatively limited. Moreover, the causal association between remnant cholesterol and stroke and its subtypes is unclear. The association of remnant cholesterol level with in-hospital outcomes in stroke patients has not been reported. Therefore, this study combined multiple sources of data to systematically investigate the effects of remnant cholesterol on different aspects of stroke considering the data availability restriction.


To integrate a population-based study and Mendelian randomization design to investigate the association of remnant cholesterol with arterial stiffness, stroke occurrence, and in-hospital outcomes to provide evidence and a novel lipid biomarker for the primary and secondary prevention of stroke.


This study was based on the Beijing Health Management Cohort (BHMC), China Health and Nutrition Survey (CHNS), and China Health and Retirement Longitudinal Study (CHARLS) databases. A multi-trajectory model, logistic regression model, and marginal effect model were used to investigate the effects of remnant cholesterol on the outcome. Based on the two-sample Mendelian randomization design, univariable and multivariable Mendelian randomization methods were used to explore the causal association of remnant cholesterol with stroke. The association between remnant cholesterol level at admission and in-hospital outcomes (mRS score at discharge, bleeding event, and death during hospitalization) of stroke was investigated using data from inpatients from Shanghai Huashan Hospital.


Study I: Association of remnant cholesterol with arterial stiffness (precursor of

This study compiled data from 3186 participants across five biennial surveys of the BHMC from 2010 to 2019. Three clusters following distinct arteriosclerosis and atherosclerosis progression patterns by brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) were identified: stable baPWV/stable ABI (Group 1: 56.6%), increasing baPWV/stable ABI (Group 2: 36.4%), and increasing baPWV/decreasing ABI (Group 3: 7.0%). The median (P25-P75) age was 65.0 (57.0,75.0) years; 2445 (76.7%) were male; 829 (26.0%) with hypertension; and 337 (10.6%) with diabetes. The median level of remnant cholesterol was 23.35 mg/dL at 18 baseline. The proportion of the concordant remnant cholesterol group was 23.5%, while 40.1% had discordantly low remnant cholesterol and 36.4% had discordantly high remnant cholesterol.

The remnant cholesterol (medians: 22.6 vs 24.4 vs 26.9 mg/dL, p < 0.001) was significantly distributed in the three groups. Remnant cholesterol was weakly correlated with LDL cholesterol ( =0.061, P < 0.05) but moderately correlated with triglycerides ( =0.792, P < 0.001) and high-density lipoprotein (HDL) cholesterol ( =- 0.461, P < 0.001) after adjusting for age and sex. In the multivariable-adjusted ordinal logistics analyses, remnant cholesterol was significantly associated with adverse arterial stiffness progression (OR: 1.20; 95% CI: 1.13-1.28, per 10 mg/dL). For the discordance analyses, the discordant low remnant cholesterol group was associated with decreased risk compared to the concordant group (OR: 0.73; 95% CI: 0.60-0.89). People with a high remnant cholesterol level were at an increased risk of progressive arterial stiffness, even with optimal LDL cholesterol. . . .



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