Effect of Longitudinal Trajectories of Total Cholesterol on the Onset of a Stroke：a Prospective Cohort Study

doi:10.12114/j.issn.1007-9572.2020.00.073

Abstract

Abstract: Background　Total cholesterol（TC） at baseline is an influencing factor of the incidence of stroke，while no studies have been conducted on the effect of longitudinal trajectories of TC on the incidence of stroke at home and abroad.Objective　To explore the effect of longitudinal trajectories of TC on the incidence of stroke.Methods　A prospective cohort study was conducted based on KaiLuan research cohort.Cox regression model was used to analyze the effect of single TC measurement on the incidence of stroke among baseline subjects（n=95 943） with complete TC data and no previous history of stroke in 2006.According to TC levels，patients were divided into normal level group（TC≤5.2 mmol/L，n=59 065），marginal increase group（5.2 mmol/L<TC≤6.2 mmol/L，n=26 330），and hypercholesterolemia group（TC>6.2 mmol/L，n=10 548）.The patients（n=51 394） with complete TC data in 2008 and 2010 and no previous history of stroke before 2010 were taken as the observation population for repeated measurement.The follow-up period was（6.77±1.00）years，and the incidence of stroke was collected annually during the follow-up period.According to the longitudinal trajectories of TC，three different groups were determined：22 116（43.03%） patients in the low-stable group，24 441（47.56%） patients in the medium-stable group，and 4 837（9.41%） patients in the high-stable group.The Cox regression model was used to analyze the influence of longitudinal trajectories of TC on the incidence of stroke.Results　In the baseline observation group，Cox regression analysis showed that compared with the ideal level group，the HR values（95%CI） of stroke，ischemic stroke and hemorrhagic stroke in the hypercholesterolemia group were 1.13（1.03，1.23），1.21（1.11，1.33），and 0.80（0.65，0.99），respectively，after adjusting for gender and other influencing factors.During the follow-up period，the cumulative incidence of stroke and ischemic stroke increased with the increase of TC longitudinal trajectories（P<0.05）.Cox regression analysis showed after adjusting for gender and other influencing factors，the HR values（95%CI） of stroke in each group were 1.21（1.08，1.35） and 1.32（1.11，1.57），and of ischemic stroke were 1.25（1.09，1.43） and 1.34（1.05，1.72） when compared with that in the low-stable group.The HR values of hemorrhagic stroke were not statistically significant（P>0.05）.In addition，after adjusting for baseline TC levels in 2010，the HR values（95%CI） of stroke in each group were 1.21（1.07，1.37） and 1.33（1.05，1.67），and of ischemic stroke were 1.25（1.13，1.44） and 1.34（1.20，1.72） when compared with that in the low-stable group.The HR values of hemorrhagic stroke were not statistically significant（P>0.05）.The baseline TC levels in 2010 had no statistical significance on stroke and ischemic stroke（P>0.05）.Conclusion　A single increase in TC levels is the risk factor of the incidence of stroke and ischemic stroke，while it is a protective factor of the incidence of hemorrhagic stroke.The increased longitudinal trajectory of TC levels is a risk factor of the incidence of stroke and ischemic stroke，while it has no statistical correlation with the risk of the incidence of hemorrhagic stroke.

Key words: Stroke, Total cholesterol, Longitudinal trajectory, Root cause analysis, Prospective studies, Cohort studies

摘要： 背景　基线总胆固醇（TC）是新发脑卒中的影响因素，但目前国内外尚缺乏关于TC纵向轨迹对新发脑卒中影响的前瞻性队列研究。目的　探究TC纵向轨迹对新发脑卒中的影响。方法　采用前瞻性队列研究方法，基于开滦研究队列，选取2006年度TC资料完整且既往无脑卒中病史的基线观察人群（n=95 943），根据TC水平分为理想水平组（TC≤5.2 mmol/L，n=59 065）、边缘升高组（5.2 mmol/L<TC≤6.2 mmol/L，n=26 330）、高胆固醇血症组（TC>6.2 mmol/L，n=10 548），采用Cox比例风险回归模型分析单次TC测量值对新发脑卒中的影响。选取其中2008、2010年度TC资料完整且2010年度前无脑卒中病史者（n=51 394）作为重复测量观察人群，随访（6.77±1.00）年，每年收集1次新发脑卒中事件发生情况，依据TC纵向轨迹分为低-稳定组22 116例（43.03%）、中-稳定组24 441例（47.56%）、高-稳定组4 837例（9.41%），采用Cox比例风险回归模型分析TC纵向轨迹对新发脑卒中的影响。结果　在基线观察人群中，Cox比例风险回归分析结果显示，校正了性别等影响因素后，与理想水平组相比，高胆固醇血症组发生脑卒中、缺血性脑卒中、出血性脑卒中的HR（95%CI）分别为1.13（1.03，1.23）、1.21（1.11，1.33）、0.80（0.65，0.99）。随访期间，脑卒中、缺血性脑卒中累积发病率均随TC纵向轨迹的增高而增高（P<0.05）。Cox回归分析结果显示，校正性别等影响因素后，与低-稳定组相比，中-稳定组、高-稳定组发生脑卒中的HR（95%CI）分别为1.21（1.08，1.35）、1.32（1.11，1.57），发生缺血性脑卒中的HR（95%CI）分别为1.25（1.09，1.43）、1.34（1.05，1.72），发生出血性脑卒中的HR值均无统计学意义（P>0.05）。增加校正2010年度TC水平后，与低-稳定组相比，中-稳定组、高-稳定组发生脑卒中的HR（95%CI）分别为1.21（1.07，1.37）、1.33（1.05，1.67），发生缺血性脑卒中的HR（95%CI）分别为1.28（1.13，1.44）、1.44（1.20，1.72），发生出血性脑卒中的HR值均无统计学意义（P>0.05）。2010年度TC水平对脑卒中、缺血性脑卒中发病的影响均无统计学意义（P>0.05）。结论　单次TC测量值升高是新发脑卒中、缺血性脑卒中的危险因素，是新发出血性脑卒中的保护因素；TC纵向轨迹水平升高是新发脑卒中、缺血性脑卒中的危险因素，与新发出血性脑卒中的风险无统计学关联。

关键词: 脑卒中, 总胆固醇, 纵向轨迹, 影响因素分析, 前瞻性研究, 队列研究

HUANGFU Chunmei,SONG Yongjian,YUAN Jianxin, et al. Effect of Longitudinal Trajectories of Total Cholesterol on the Onset of a Stroke：a Prospective Cohort Study　[J]. Chinese General Practice, 2020, 23(13): 1654-1662. DOI: 10.12114/j.issn.1007-9572.2020.00.073.
皇甫春梅,宋永健,袁建新等. 总胆固醇纵向轨迹对新发脑卒中影响的前瞻性队列研究[J]. 中国全科医学, 2020, 23(13): 1654-1662. DOI: 10.12114/j.issn.1007-9572.2020.00.073.

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