Abstract
BackgroundThe risk of stroke in individuals with very low low-density lipoprotein cholesterol (LDL-C) concentrations remains high. We sought to prioritize predictive risk factors for stroke in Chinese participants with LDL-C concentrations < 70 mg/dL using a survival conditional inference tree, a machine learning method.MethodsThe training dataset included 9327 individuals with LDL-C concentrations < 70 mg/dL who were free of cardiovascular diseases and did not use lipid-modifying drugs from the Kailuan I study (N = 101,510). We examined the validity of this algorithm in a second Chinese cohort of 1753 participants with LDL-C concentrations < 70 mg/dL from the Kailuan II study (N = 35,856).ResultsDuring a mean 8.5–9.0-year follow-up period, we identified 388 ischemic stroke cases and 145 hemorrhagic stroke cases in the training dataset and 20 ischemic stroke cases and 8 hemorrhagic stroke cases in the validation dataset. Of 15 examined predictors, poorly controlled blood pressure and very low LDL-C concentrations (≤ 40 mg/dL) were the top hierarchical predictors of both ischemic stroke risk and hemorrhagic stroke risk. The groups, characterized by the presence of 2–3 of aforementioned risk factors, were associated with a higher risk of ischemic stroke (hazard ratio (HR) 7.03; 95% confidence interval (CI) 5.01–9.85 in the training dataset; HR 4.68, 95%CI 1.58–13.9 in the validation dataset) and hemorrhagic stroke (HR 3.94, 95%CI 2.54–6.11 in the training dataset; HR 4.73, 95%CI 0.81–27.6 in the validation dataset), relative to the lowest risk groups (presence of 0–1 of these factors). There was a linear association between cumulative average LDL-C concentrations and stroke risk. LDL-C concentrations ≤ 40 mg/dL was significantly associated with increased risk of ischemic stroke (HR 2.07, 95%CI 1.53, 2.80) and hemorrhagic stroke (HR 2.70, 95%CI 1.70, 4.30) compared to LDL-C concentrations of 55–70 mg/dL, after adjustment for age, hypertension status, and other covariates.ConclusionIndividuals with extremely low LDL-C concentrations without previous lipid-modifying treatment could still be at high stroke risk.Trial registrationChinese Clinical Trial Register, ChiCTR-TNRC-11001489. Registered on 24-08-2011.
Highlights
The risk of stroke in individuals with very low low-density lipoprotein cholesterol (LDL-C) concentrations remains high
Identified were 388 ischemic stroke cases and 145 hemorrhagic stroke cases in the Kailuan I study with a mean of 9.0 years of follow-up and 20 ischemic stroke cases and 8 hemorrhagic stroke in the Kailuan II study with a mean of 8.5 years of follow-up
Participants (i) with poorly controlled blood pressure and LDL-C concentrations ≤33.2 mg/dL and (ii) with well-controlled blood pressure, aged > 64.9 years, and LDL-C concentrations ≤32.0 mg/dL had the highest ischemic stroke risk among the 9 sub-groups identified by the survival conditional inference tree (SCTREE) model (Fig. 1)
Summary
The risk of stroke in individuals with very low low-density lipoprotein cholesterol (LDL-C) concentrations remains high. The LDL-C concentration of 70 mg/dL was considered as an appropriate target goal for optimal lipid management in people who are at high risk of CVD [3,4,5]. It is of clinical significance to understand the factors related to the risk of cerebrovascular diseases in the population with low LDL-C concentrations. Whether other metabolic abnormalities (e.g., hypertension, diabetes mellitus, and obesity) contribute to the risk of stroke within the context of a low LDL-C concentration remains unclear. LDL-C concentrations and metabolic and lifestyle risk factors covary and may together have a synergistic or antagonistic effect on stroke-related outcomes
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