关键词: 总胆固醇, 累积暴露值, 卒中, 影响因素分析, 前瞻性研究, 队列研究

Abstract: Background　Baseline total cholesterol（TC） is an influencing factor of new-onset stroke，but no studies have been conducted on the effect of cumulative total cholesterol exposure（cumTC） on new-onset stroke.Objective　To explore the effect of cumTC on new-onset stroke.Methods　Using prospective cohort study method，52 427 working and retired employees of Kailuan Group who had physical examination in 11 hospitals including KaiLuan General Hospital from 2006 to 2010 were selected as the study objects.The starting point of the follow-up was when the objects completed the physical examination in 2010，and the end point was when new-onset stroke or deaths happened or the end of the follow-up（2017-12-31）.Baseline data and the incidence of new-onset stroke in each group were observed after all objects were grouped according to the cumTC quartile.The cumulative incidence was calculated by Kaplan-Meier method and tested by Log-Rank method.Cox regression model was used to analyze the effect of different cumTC on new-onset stroke.The fitting degree of different models was compared by likelihood ratio test.Results　There were significant differences in age，male proportion，systolic blood pressure（SBP），diastolic blood pressure（DBP），BMI，cumTC，TC，high-density lipoprotein cholesterol（HDL-C），fasting blood glucose（FBG），stroke，ischemic stroke，smoking，drinking，hypertension and diabetes detection rates，taking lipid-lowering drugs proportion among groups with different levels of cumTC（P<0.05）.During a mean follow-up year of（6.89±0.72），there were 1 611 new cases of stroke（1 415 cases of ischemic stroke and 229 cases of hemorrhagic stroke）.The cumulative incidence of stroke was 2.53%（331/13 089），2.92%（384/13 148），4.18%（547/13 085） and 4.36%（571/13 105） in the first to the fourth quartile group，respectively，and the cumulative incidence of ischemic stroke was 2.17%（284/13 089），2.51%（330
/13 148），3.71%（485/13 085） and 3.99%（523/13 105），respectively.The difference was statistically significant by Log-Rank test（χ2=73.15，P<0.001；χ2=109.13，P<0.001）.Cox regression analysis showed that after adjusting age，gender，BMI，hypertension，diabetes，smoking，drinking，physical exercise，HR（95%CI） of stroke and ischemic stroke in the fourth quartile group were 1.27（1.10，1.48） and 1.37（1.16，1.60） and those in the third quartile group were 1.22（1.05，1.41） and 1.27（1.08，1.50） compared with that in the first quartile group of cumTC.Increasing the factors of baseline TC level and taking lipid-lowering drugs，after likelihood ratio test，the fitting degree of the model was not optimized（P>0.05）.After adjusting age，gender，BMI，hypertension，diabetes，smoking，drinking，physical exercise，HR（95%CI） of stroke and ischemic stroke in the group with cumulative exposure for more than 4 years were 1.20（1.02，1.40） and 1.28（1.08，1.50），compared with the group with cumulative exposure to hypercholesterolemia for 0 years.Increasing the factors of baseline TC level and taking lipid-lowering drugs，the cumulative exposure of hypercholesterolemia had no statistical correlation with the new-onset stroke，ischemic stroke and hemorrhagic stroke.After the likelihood ratio test，the fitting degree of the model was not optimized（P>0.05）.Conclusion　High cumTC is a risk factor of new-onset stroke and ischemic stroke.

Key words: Total cholesterol, Cumulative exposure, Stroke, Root cause analysis, Prospective studies, Cohort studies