Target remnant cholesterol to reduce residual risk of stroke
August 2024
In this prospective cohort study, high remnant cholesterol with controlled low-density lipoprotein
cholesterol conferred higher risk of stroke, specifically ischemic stroke. These findings support
targeting remnant cholesterol to reduce the high residual risk of ischemic stroke.
Han M, Huang K, Shen C, et al. Discordant high remnant cholesterol with LDL-C increases the risk of
stroke: A Chinese Prospective Cohort Study. Stroke 2024;55:2066-74.
STUDY SUMMARY
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Objective |
To explore the associations of remnant cholesterol and discordant high remnant cholesterol with low-density lipoprotein cholesterol (LDL-C) with stroke, ischemic stroke, and hemorrhagic stroke. |
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Study design |
Prospective cohort study using discordance analysis |
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Study population |
A total of 113,448 subjects were enrolled in three cohorts of the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) project, of whom 98,967 (mean age 51.4 years, 40.5% male) were eligible for the final analysis. |
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Main study variables |
Incident stroke, ischemic stroke and hemorrhagic stroke Remnant cholesterol, calculated as non-high-density lipoprotein cholesterol minus LDL-C. |
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Methods |
Concordant/discordant categories for remnant cholesterol versus LDL-C were based on cut-points of 130 mg/dL for LDL-C and the equivalent percentile (32.5 mg/dL) for remnant cholesterol. Cox models were used to estimate adjusted hazard ratios and 95% confidence intervals (Cis) for incident stroke. |
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Results |
During 728,776 person-years of follow-up, there were 2859 strokes, including 1811 cases of ischemic stroke and 849 cases of hemorrhagic stroke. Overall, remnant cholesterol was positively associated with stroke (adjusted Hazard ratio 1.06, 95% CI 1.02-1.10), and ischemic stroke (adjusted Hazard ratio 1.09, 95% CI 1.04-1.13), but not hemorrhagic stroke (adjusted Hazard ratio 0.95, 95% CI 0.88–1.03). Compared with subjects with low LDL-C/low remnant cholesterol levels (reference group), those with low LDL-C and high remnant cholesterol were at higher risk of stroke and ischemic stroke, whereas there was no increase in risk among subjects with high LDL–-C/ low remnant cholesterol levels (Table 1). Table 1. Risk of stroke and ischemic stroke according to remnant cholesterol/LDL-C category
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Author conclusions |
Higher remnant cholesterol was associated with increased risks of stroke and ischemic stroke but not hemorrhagic stroke. Discordantly high remnant cholesterol, not discordantly high LDL–C, conferred higher risks of stroke and ischemic stroke. Our findings support further lowering remnant cholesterol by interventions to reduce residual ischemic stroke risk. |
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Comment
Previous studies have shown associations between high remnant cholesterol concentration and risk of ischemic heart disease and ischemic stroke (1,2). Data from over 100,000 people in the Copenhagen General Population Study showed that step-wise higher remnant cholesterol concentrations were associated with step-wise higher ischemic stroke risk (3). However, whether these findings are applicable to other ethnicities, especially Chinese individuals who have lower LDLC levels but higher stroke incidence than Western populations, is uncertain (4). This large prospective cohort study provides important insights into this question, showing that remnant cholesterol was positively associated with risk for stroke, specifically ischemic stroke, but not hemorrhagic stroke in the Chinese population.
The study also answers another question relating to the residual risk of stroke among Chinese individuals with controlled LDL-C levels. Discordance analyses showed that individuals with high remnant cholesterol and LDL-C levels <130 mg/dL were at higher risk of stroke and ischemic stroke (by 15% and 19%, respectively) than those with low levels of each lipid parameter. In contrast, risk was not significantly elevated among individuals with LDL-C levels >130 mg/dL and low remnant cholesterol concentration (Table 1). These findings align with results from the Kailuan Prospective Cohort Study, a community study in 96,769 individuals (median age 51.6 years, 79% male), in which discordance analysis showed that a discordant elevated remnant cholesterol level with controlled LDL-C concentration was associated with higher risk of cardiovascular disease, myocardial infarction and stroke (5).
The strengths of the current study are the large sample size, long follow-up duration, and adequate number of cases of stroke and stroke subtypes. The authors do, however, note that remnant cholesterol was calculated, with the possibility of misclassification of individuals with low LDL-C levels. In conclusion, these findings support high remnant cholesterol concentration as a contributor to the residual risk of ischemic stroke in the Chinese population and provide a rationale for therapeutic targeting to reduce this risk.
References
- Langsted A, Madsen CM, Nordestgaard BG. Contribution of remnant cholesterol to cardiovascular risk. J Intern Med 2020;288:116-27.
- Varbo A, Benn M, Tybjærg-Hansen A, et al. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol 2013;61:427-36.
- Varbo A, Nordestgaard BG. Remnant cholesterol and risk of ischemic stroke in 112,512 individuals from the general population. Ann Neurol 2019;85:550-9.
- Tsai C-F, Thomas B, Sudlow CLM. Epidemiology of stroke and its subtypes in Chinese vs white populations: a systematic review. Neurology 2013;81:264–272.
- Zhang Y, Wu S, Tian X, et al. Discordance between remnant cholesterol and low-density lipoprotein cholesterol predicts cardiovascular disease: the Kailuan Prospective Cohort Study. Hellenic J Cardiol 2024;doi: 10.1016/j.hjc.2024.05.002.
Key words: ischemic stroke; Chinese population; residual risk; discordance analysis
