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Discordant High Remnant Cholesterol With LDL-C Increases the Risk of Stroke: A Chinese Prospective Cohort Study
Minghui Han1,2,3, Keyong Huang2,3, Chong Shen1,4
1Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, China (M.H., C.S., H.H., D.G.).
Insights
Higher remnant cholesterol (RC) increases stroke and ischemic stroke (IS) risk, independent of LDL-C levels. Discordantly high RC, not LDL-C, is linked to elevated stroke and IS risks, suggesting RC lowering for residual IS risk reduction.
Area of Science:
- Cardiovascular Epidemiology
- Lipid Metabolism
- Cerebrovascular Disease
Background:
- Previous research on remnant cholesterol (RC) and low-density lipoprotein cholesterol (LDL-C) effects on stroke often overlooks their combined influence.
- Understanding the interplay between RC and LDL-C is crucial for accurate cardiovascular risk assessment.
Purpose of the Study:
- To investigate the associations of remnant cholesterol (RC) and discordant high RC with LDL-C in relation to stroke, ischemic stroke (IS), and hemorrhagic stroke.
- To clarify the independent and combined effects of RC and LDL-C on cerebrovascular events.
Main Methods:
- A prospective cohort study utilizing data from the China-PAR project (n=98,967).
- Remnant cholesterol (RC) calculated as non-HDL-C minus LDL-C; discordant categories defined by established cut-points.
- Cox proportional hazards models employed to estimate hazard ratios and 95% confidence intervals for incident stroke.
Main Results:
- Higher RC levels were significantly associated with increased risks of overall stroke and IS, but not hemorrhagic stroke (per SD increase: aHR 1.06 [1.02-1.10] for stroke, 1.09 [1.04-1.13] for IS).
- Individuals with low LDL-C but high RC exhibited significantly higher risks of stroke (aHR 1.15 [1.02-1.30]) and IS (aHR 1.19 [1.03-1.38]) compared to those with low levels of both.
- Conversely, high LDL-C with low RC did not show a significant increase in stroke or IS risk.
Conclusions:
- Elevated remnant cholesterol (RC) is an independent risk factor for stroke and ischemic stroke (IS).
- Discordantly high RC, irrespective of LDL-C levels, confers a greater risk for stroke and IS.
- Interventions aimed at reducing RC may be beneficial in mitigating residual ischemic stroke risk.
Background:
Previous studies focusing on assessing the effects of remnant cholesterol (RC) and low-density lipoprotein cholesterol (LDL-C) on stroke may not consider their mutual influence. We aimed to explore the associations of RC and discordant high RC with LDL-C with stroke, ischemic stroke (IS), and hemorrhagic stroke.
Methods:
This prospective cohort study was conducted based on 3 cohorts of the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) project. RC was calculated as non-high-density lipoprotein cholesterol minus LDL-C estimated by Martin/Hopkins equations. Concordant/discordant categories for RC versus LDL-C were determined based on cut-points of 130 mg/dL for LDL-C and equivalent percentile (32.50 mg/dL) for RC. Cox models were used to estimate adjusted hazard ratios and 95% CIs for incident stroke.
Results:
Among 113 448 participants recruited at baseline, a total of 98 967 participants were eligible for the final analysis (mean age of 51.44 years; 40.45% were men). During 728 776.87 person-years of follow-up, 2859 stroke cases, 1811 IS cases, and 849 hemorrhagic stroke cases were observed. RC was positively associated with stroke and IS, but not hemorrhagic stroke, with adjusted hazard ratios (95% CIs) of 1.06 (1.02-1.10), 1.09 (1.04-1.13), and 0.95 (0.88-1.03) for per SD increase in RC. Compared with low LDL-C/low RC group, low LDL-C/high RC group had higher risks of stroke (adjusted hazard ratio, 1.15 [95% CI, 1.02-1.30]) and IS (1.19, 1.03-1.38), while high LDL-C/low RC group had no increased risk of stroke (1.07 [0.95-1.20]) and IS (1.09 [0.94-1.25]).
Conclusions:
Higher RC was associated with increased risks of stroke and IS but not hemorrhagic stroke. Discordantly high RC, not discordantly high LDL-C, conferred higher risks of stroke and IS. Our findings support further lowering RC by interventions to reduce residual IS risk.
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