U-shaped association between variability of remnant cholesterol and risk of cardiac conduction block

CAO Liuliu; LI Man; WU Zhaohui; ZHENG Weiguo; WANG Baohua; ZHANG Li; ZHAO Maolin; LI Peng; ZHAO Haiyan; CHEN Shuohua; WU Shouling; SUN Lixia

doi:10.16016/j.2097-0927.202510061

您当前的位置：

首页 >

文章列表页 >

U-shaped association between variability of remnant cholesterol and risk of cardiac conduction block

Think Tank for Public Health | 更新时间：2026-02-04

- U-shaped association between variability of remnant cholesterol and risk of cardiac conduction block
- Journal of Army Medical University Vol. 48, Issue 2, Pages: 216-228(2026)
- 作者机构：
  
  1.华北理工大学附属医院：，急诊科，河北唐山
  5.华北理工大学附属医院：，重症医学科，河北唐山
  2.华北理工大学研究生院，河北唐山
  3.暨南大学第一附属医院重症医学科，广东广州
  4.山西医科大学研究生院，山西太原
  6.开滦总医院心血管内科，河北唐山
- 作者简介：
  
  WU Shouling，E-mail：drwusl@163.com
  SUN Lixia，E-mail：13323151999@189.cn
- 基金信息：
  
  the Project of the Key Research and Development Program of Hebei Province(19277791D)
- DOI：10.16016/j.2097-0927.202510061
  CLC： R181.37;R344.81;R541.76
- Received：21 October 2025，
  
  Revised：2026-01-05，
  
  Accepted：05 January 2026，
  
  Published：30 January 2026
- 稿件说明：
移动端阅览
曹柳柳，李曼，武朝辉，等.残余胆固醇的变异性与心脏传导阻滞风险的U型关联［J］.陆军军医大学学报，2026，48（02）：216-228.DOI：10.16016/j.2097-0927.202510061.

CAO L L，LI M，WU Z H，et al.U-shaped association between variability of remnant cholesterol and risk of cardiac conduction block［J］.J Army Med Univ，2026，48（02）：216-228.DOI：10.16016/j.2097-0927.202510061.
曹柳柳，李曼，武朝辉，等.残余胆固醇的变异性与心脏传导阻滞风险的U型关联［J］.陆军军医大学学报，2026，48（02）：216-228.DOI：10.16016/j.2097-0927.202510061. DOI：

CAO L L，LI M，WU Z H，et al.U-shaped association between variability of remnant cholesterol and risk of cardiac conduction block［J］.J Army Med Univ，2026，48（02）：216-228.DOI：10.16016/j.2097-0927.202510061. DOI：

摘要

目的

本研究基于开滦队列，探讨长期随访期间残余胆固醇（remnant cholesterol，RC）的变异性与心脏传导阻滞（cardiac conduction block，CCB）的关联。

方法

采用回顾性队列研究，以连续参加2006、2008、2010年度体检的开滦研究人群作为研究队列，根据纳入和排除标准，最终入选39 299例观察对象，计算随访期间RC的变异性，RC的变异性通过标准差（standard deviation，SD）、平均真实变异性（average real variability，ARV）、变异系数（coefficient of variation，CV）、独立于均值的变异（variation independent of mean，VIM）测量。以RC的变异性四分位进行分组，将观察对象分成4组，每2年进行1次随访，以发生CCB、死亡或随访结束（2019年12月31日）为随访终点，采用Kaplan-Meier法计算不同分组发生终点事件的累积发病率，并用Log-Rank检验比较各组终点事件累积发生率的差异。用Cox比例风险模型及限制性立方样条曲线（restricted cubic spline， RCS）分析RC的变异性与CCB及其亚型的关联。

结果

39 299例观察对象在平均随访7.43年后，发生CCB者共916人。以CCB为结局事件，校正混杂因素后，以RC-SD四分位分组，与RC-SD最低发病密度组（Q2）相比，Q1组发生CCB的

值为1.344（95%

： 1.110~1.626，

=0.002），Q3、Q4组发生CCB的

值分别1.068（95%

： 0.878~1.299，

=0.509）、1.311（95%

： 1.089~1.

579，

=0.004）。以RC-ARV、RC-CV、RC-VIM四分位分组均得出类似的结论。RCS曲线表明，RC-SD与CCB之间呈U型关联（

overall

0.05，

nonlinearity

0.05）。敏感性分析、分层分析进一步验证了此结论。

结论

RC的变异性与CCB呈U型关联，该研究为预防CCB的发生提供了新的方向。对策　我国血脂管理策略应从追求“低水平稳定”，向兼顾“指标长期平稳性” 转型升级。即将 “维持血脂在适宜区间的生理性波动” 这一新理念，系统整合至国家心脑血管疾病防治规划、基层公共卫生服务项目及全民健康教育体系，以此推动慢性病管理迈向更加精准、科学的新阶段。

Abstract

Objective

To investigates the association between the variability of remnant cholesterol (RC) during long-term follow-up and cardiac conduction block (CCB) based on the Kailuan cohort.

Methods

A retrospective study was conducted on the research cohort in the Kailuan study population who consecutively participated in the physical examinations of 2006

2008

and 2010. Based on the inclusion and exclusion criteria

39 299 subjects were ultimately enrolled in the study. The variability of RC during the follow-up period was calculated

with the variability assessed through standard deviation (SD)

average real variability (ARV)

coefficient of variation (CV)

and variability independent of the mean (VIM). The participants were divided into 4 groups based on the interquartile range of RC variability

and followed up every 2 years. The endpoints were defined as the occurrence of CCB

death

or the termination of follow-up (December 31

2019). Kaplan-Meier test and Log-Rank test were carried out respectively calculate and compare the cumulative incidence rate of endpoint events across groups. Cox proportional hazards model and restricted cubic spline (RCS) analysis were performed to analyze the association between the variability of RC and CCB and its subtypes.

Results

After an average follow-up of 7.43 years in 39 299 participants

916 patients developed CCB. After adjusting for confounding factors

using CCB as the outcome event

and were dividing the participan

ts into groups based on the RC-SD quartiles

the hazard ratios (

) for CCB occurrence were 1.344 in the Q1 group (95%

: 1.110~1.626

=0.002)

1.068 (95%

: 0.878 to 1.299

=0.509) in the Q3 group and 1.311 (95%

: 1.089~1.579

=0.004) in the Q4 group

when compared to the group of lowest incidence density (the Q2 group). Similar results were obtained for the quartiles of RC-ARV

RC-CV

and RC-VIN grouping. RCS analysis revealed a U-shaped association between RC-SD and CCB (

overall

0.05

nonlinearity

0.05). Sensitivity and stratified analyses further validated this finding.

Conclusion

There exists a U-shaped association between the variability of RC and the risk of CCB. This finding provides a new direction for preventing the occurrence of CCB. Countermeasures　China’s blood lipid management strategy should undergo a paradigm shift from pursuing “low-level stability” toward integrating “long-term stability of biomarker levels” This entails systematically incorporating the new concept of “maintaining physiological fluctuations of blood lipids within an optimal range” into the national prevention and treatment plans for cardiovascular and cerebrovascular diseases

primary public health service programs

and the public health education system. Such a transition will propel chronic disease management into a more precise and scientific new stage.

关键词

Keywords

references

POWER D A ， LAMPERT J ， CAMAJ A ， et al . Cardiovascular complications of interatrial conduction block： JACC state-of-the-art review ［J］. J Am Coll Cardiol ， 2022 ， 79 （ 12 ）： 1199 - 1211 . DOI： 10.1016/j.jacc.2022.01.030 http://dx.doi.org/10.1016/j.jacc.2022.01.030 .

EPSTEIN A E ， DIMARCO J P ， ELLENBOGEN K A ， et al . ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities： executive summary ［J］. Heart Rhythm ， 2008 ， 5 （ 6 ）： 934 - 955 . DOI： 10.1016/j.hrthm.2008.04.015 http://dx.doi.org/10.1016/j.hrthm.2008.04.015 .

SHAN R Q ， NING Y ， MA Y ， et al . Prevalence and risk factors of atrioventricular block among 15 million Chinese health examination participants in 2018： a nation-wide cross-sectional study ［J］. BMC Cardiovasc Disord ， 2021 ， 21 （ 1 ）： 289 . DOI： 10.1186/s12872-021-02105-3 http://dx.doi.org/10.1186/s12872-021-02105-3 .

ARO A L ， ANTTONEN O ， KEROLA T ， et al . Prognostic significance of prolonged PR interval in the general population ［J］. Eur Heart J ， 2014 ， 35 （ 2 ）： 123 - 129 . DOI： 10.1093/eurheartj/eht176 http://dx.doi.org/10.1093/eurheartj/eht176 .

Correction to： 2018 ACC/AHA/HRS Guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay： A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society ［J/OL］. Circulation ， 2019 ， 140 （ 8 ）： e506 - e508 . DOI： 10.1161/CIR.0000000000000721 http://dx.doi.org/10.1161/CIR.0000000000000721 .

CINCA J ， MENDEZ A ， PUIG T ， et al . Differential clinical characteristics and prognosis of intraventricular conduction defects in patients with chronic heart failure ［J］. Eur J Heart Fail ， 2013 ， 15 （ 8 ）： 877 - 884 . DOI： 10.1093/eurjhf/hft042 http://dx.doi.org/10.1093/eurjhf/hft042 .

YANG X M ， CHEN S H ， SONG H C ， et al . Association between cardiac conduction block and cardiovascular disease and all-cause mortality： The Kailuan study ［J］. Int J Cardiol ， 2024 ， 399 ： 131666 . DOI： 10.1016/j.ijcard.2023.131666 http://dx.doi.org/10.1016/j.ijcard.2023.131666 .

VARBO A ， BENN M ， TYBJÆRG-HANSEN A ， et al . Remnant cholesterol as a causal risk factor for ischemic heart disease ［J］. J Am Coll Cardiol ， 2013 ， 61 （ 4 ）： 427 - 436 . DOI： 10.1016/j.jacc.2012.08.1026 http://dx.doi.org/10.1016/j.jacc.2012.08.1026 .

OUYANG X L ， TANG X X ， PENG L ， et al . Remnant cholesterol and new-onset atrial fibrillation： The atherosclerosis risk in communities study ［J］. Heart Rhythm ， 2025 ， 22 （ 9 ）： 2233 - 2242 . DOI： 10.1016/j.hrthm. 2024. 10.030 http://dx.doi.org/10.1016/j.hrthm.2024.10.030 .

FU L Y ， TAI S ， SUN J X ， et al . Remnant cholesterol and its visit-to-visit variability predict cardiovascular outcomes in patients with type 2 diabetes： findings from the ACCORD cohort ［J］. Diabetes Care ， 2022 ， 45 （ 9 ）： 2136 - 2143 . DOI： 10.2337/dc21-2511 http://dx.doi.org/10.2337/dc21-2511 .

ZHANG Y J ， XU Q ， TIAN X ， et al . Longitudinal changes in remnant cholesterol and the risk of cardiovascular disease ［J］. Cardiovasc Diabetol ， 2025 ， 24 （ 1 ）： 1 . DOI： 10.1186/s12933-024-02556-w http://dx.doi.org/10.1186/s12933-024-02556-w .

XIA X ， CHEN S H ， TIAN X ， et al . Association of triglyceride-glucose index and its related parameters with atherosclerotic cardiovascular disease： evidence from a 15-year follow-up of Kailuan cohort ［J］. Cardiovasc Diabetol ， 2024 ， 23 （ 1 ）： 208 . DOI： 10.1186/s12933-024-02290-3 http://dx.doi.org/10.1186/s12933-024-02290-3 .

NORDESTGAARD A T ， PRADHAN A D ， EVERETT B M ， et al . Expanding the triglyceride range in clinical trials： therapeutic opportunities ［J］. Eur Heart J ， 2025 ， 46 （ 19 ）： 1835 - 1848 . DOI： 10.1093/eurheartj/ehaf074 http://dx.doi.org/10.1093/eurheartj/ehaf074 .

WU S L ， HUANG Z R ， YANG X C ， et al . Prevalence of ideal cardiovascular health and its relationship with the 4-year cardiovascular events in a northern Chinese industrial city ［J］. Circ Cardiovasc Qual Outcomes ， 2012 ， 5 （ 4 ）： 487 - 493 . DOI： 10.1161/CIRCOUTCOMES.111.963694 http://dx.doi.org/10.1161/CIRCOUTCOMES.111.963694 .

CHOBANIAN A V ， BAKRIS G L ， BLACK H R ， et al . Seventh report of the joint national committee on prevention， detection， evaluation， and treatment of high blood pressure ［J］. Hypertension ， 2003 ， 42 （ 6 ）： 1206 - 1252 . DOI： 10.1161/01.HYP.0000107251.49515.c2 http://dx.doi.org/10.1161/01.HYP.0000107251.49515.c2 .

SATTAR N ， RAWSHANI A ， FRANZÉN S ， et al . Age at diagnosis of type 2 diabetes mellitus and associations with cardiovascular and mortality risks ［J］. Circulation ， 2019 ， 139 （ 19 ）： 2228 - 2237 . DOI： 10.1161/CIRCULATIONAHA. 118.037885 http://dx.doi.org/10.1161/CIRCULATIONAHA.118.037885 .

ZOU Q P ， SU C ， DU W W ， et al . Longitudinal association between physical activity， blood lipids， and risk of dyslipidemia among Chinese adults： findings from the China health and nutrition surveys in 2009 and 2015 ［J］. Nutrients ， 2023 ， 15 （ 2 ）： 341 . DOI： 10.3390/nu15020341 http://dx.doi.org/10.3390/nu15020341 .

LEVEY A S ， STEVENS L A ， SCHMID C H ， et al . A new equation to estimate glomerular filtration rate ［J］. Ann Intern Med ， 2009 ， 150 （ 9 ）： 604 - 612 . DOI： 10.7326/0003-4819-150-9-200905050-00006 http://dx.doi.org/10.7326/0003-4819-150-9-200905050-00006 .

LI W J ， HUANG Z G ， FANG W ， et al . Remnant cholesterol variability and incident ischemic stroke in the general population ［J］. Stroke ， 2022 ， 53 （ 6 ）： 1934 - 1941 . DOI： 10.1161/STROKEAHA.121.037756 http://dx.doi.org/10.1161/STROKEAHA.121.037756 .

CHEN Z T ， GUO D C ， GAO J W ， et al . Low remnant cholesterol and the subsequent risk of new-onset atrial fibrillation： a prospective cohort study ［J］. Heart Rhythm ， 2024 ， 21 （ 8 ）： 1258 - 1266 . DOI： 10.1016/j.hrthm. 2024. 05.044 http://dx.doi.org/10.1016/j.hrthm.2024.05.044 .

LI L K ， WANG C S ， YE Z B ， et al . Association between remnant cholesterol and risk of incident atrial fibrillation： population-based evidence from a large-scale prospective cohort study ［J］. J Am Heart Assoc ， 2024 ， 13 （ 10 ）： e033840 . DOI： 10.1161/JAHA.123.033840 http://dx.doi.org/10.1161/JAHA.123.033840 .

BAI M H ， LIAO J Q ， WANG Y ， et al . Remnant cholesterol and all-cause mortality risk： findings from the National Health and Nutrition Examination Survey， 2003-2015 ［J］. Front Endocrinol ， 2024 ， 15 ： 1417228 . DOI： 10.3389/fendo.2024.1417228 http://dx.doi.org/10.3389/fendo.2024.1417228 .

ZHAO L ， ZHAO X M ， TIAN P C ， et al . Predictive value of remnant cholesterol level for all-cause mortality in heart failure patients ［J］. Front Cardiovasc Med ， 2023 ， 10 ： 1063562 . DOI： 10.3389/fcvm.2023.1063562 http://dx.doi.org/10.3389/fcvm.2023.1063562 .

HISSA B ， OAKES P W ， PONTES B ， et al . Cholesterol depletion impairs contractile machinery in neonatal rat cardiomyocytes ［J］. Sci Rep ， 2017 ， 7 ： 43764 . DOI： 10.1038/srep43764 http://dx.doi.org/10.1038/srep43764 .

LIU P P ， WANG Y X ， ZHANG X F ， et al . Obesity and cardiac conduction block disease in China ［J］. JAMA Netw Open ， 2023 ， 6 （ 11 ）： e2342831 . DOI： 10.1001/jamanetworkopen.2023.42831 http://dx.doi.org/10.1001/jamanetworkopen.2023.42831 .

LI N ， CUI L F ， TSE G ， et al . The combination of hyperuricemia and elevated high-sensitivity C-reactive protein increased the risk of cardiac conduction block ［J］. J Inflamm Res ， 2024 ， 17 ： 3725 - 3736 . DOI： 10.2147/JIR.S458032 http://dx.doi.org/10.2147/JIR.S458032 .

CASTAÑER O ， PINTÓ X ， SUBIRANA I ， et al . Remnant cholesterol， not LDL cholesterol， is associated with incident cardiovascular disease ［J］. J Am Coll Cardiol ， 2020 ， 76 （ 23 ）： 2712 - 2724 . DOI： 10.1016/j.jacc.2020.10.008 http://dx.doi.org/10.1016/j.jacc.2020.10.008 .

YANG X R ， ZHAO S H ， WANG S H ， et al . Systemic inflammation indicators and risk of incident arrhythmias in 478， 524 individuals： evidence from the UK Biobank cohort ［J］. BMC Med ， 2023 ， 21 （ 1 ）： 76 . DOI： 10.1186/s12916-023-02770-5 http://dx.doi.org/10.1186/s12916-023-02770-5 .

LAZZERINI P E ， ACAMPA M ， CUPELLI M ， et al . Unravelling atrioventricular block risk in inflammatory diseases： systemic inflammation acutely delays atrioventricular conduction via a cytokine-mediated inhibition of Connexin43 expression ［J］. J Am Heart Assoc ， 2021 ， 10 （ 21 ）： e022095 . DOI： 10.1161/JAHA.121.022095 http://dx.doi.org/10.1161/JAHA.121.022095 .

WANG J Q ， JIN R ， JIN X H ， et al . Separate and joint associations of remnant cholesterol accumulation and variability with carotid atherosclerosis： a prospective cohort study ［J］. J Am Heart Assoc ， 2023 ， 12 （ 14 ）： e029352 . DOI： 10.1161/JAHA.122.029352 http://dx.doi.org/10.1161/JAHA.122.029352 .

曹柳柳，李曼，武朝辉，等 . 残余胆固醇炎症指数的变异性与卒中风险存在剂量反应关系：来自中国开滦队列的证据［J］. 陆军军医大学学报， 2025 ， 47 （ 22 ）： 2847 - 2857 . DOI： 10.16016/j.2097-0927.202509035 http://dx.doi.org/10.16016/j.2097-0927.202509035 .

CAO L L ， LI M ， WU Z H ， et al . Variability of remnant cholesterol inflammation index exhibits a dose-response relationship with stroke risk： Evidence from the Chinese Kailuan cohort ［J］. J Army Med Univ ， 2025 ， 47 （ 22 ）： 2847 - 2857 . DOI： 10.16016/j.2097-0927.202509035 http://dx.doi.org/10.16016/j.2097-0927.202509035 .

LEPPERT M H ， POISSON S N ， SCARBRO S ， et al . Association of traditional and nontraditional risk factors in the development of strokes among young adults by sex and age group： a retrospective case-control study ［J］. Circ Cardiovasc Qual Outcomes ， 2024 ， 17 （ 4 ）： e010307 . DOI： 10.1161/CIRCOUTCOMES.123.010307 http://dx.doi.org/10.1161/CIRCOUTCOMES.123.010307 .

ROSSI A ， MIKAIL N ， BENGS S ， et al . Heart-brain interactions in cardiac and brain diseases： why sex matters ［J］. Eur Heart J ， 2022 ， 43 （ 39 ）： 3971 - 3980 . DOI： 10.1093/eurheartj/ehac061 http://dx.doi.org/10.1093/eurheartj/ehac061 .

XU Y ， ARENAS I A ， ARMSTRONG S J ， et al . Estrogen modulation of left ventricular remodeling in the aged heart ［J］. Cardiovasc Res ， 2003 ， 57 （ 2 ）： 388 - 394 . DOI： 10.1016/s0008-6363（02）00705-8 http://dx.doi.org/10.1016/s0008-6363（02）00705-8 .

DU Z ， XING L Y ， LIN M ， et al . Prevalence of first-degree atrioventricular block and the associated risk factors： a cross-sectional study in rural Northeast China ［J］. BMC Cardiovasc Disord ， 2019 ， 19 （ 1 ）： 214 . DOI： 10.1186/s12872-019-1202-4 http://dx.doi.org/10.1186/s12872-019-1202-4 .

KEROLA T ， ERANTI A ， ARO A L ， et al . Risk factors associated with atrioventricular block ［J］. JAMA Netw Open ， 2019 ， 2 （ 5 ）： e194176 . DOI： 10.1001/jamanetworkopen. 2019.4176 http://dx.doi.org/10.1001/jamanetworkopen.2019.4176 .

ARO A L . First-degree atrioventricular block： risk marker or innocent finding？［J］. Heart ， 2016 ， 102 （ 9 ）： 655 - 656 . DOI： 10.1136/heartjnl-2015-309256 http://dx.doi.org/10.1136/heartjnl-2015-309256 .

CUSPIDI C ， CIULLA M ， ZANCHETTI A . Hypertensive myocardial fibrosis ［J］. Nephrol Dial Transplant ， 2006 ， 21 （ 1 ）： 20 - 23 . DOI： 10.1093/ndt/gfi237 http://dx.doi.org/10.1093/ndt/gfi237 .

Jr Salvador DB ， Gamba M R ， Gonzalez-Jaramillo N ， et al . Diabetes and myocardial fibrosis： a systematic review and meta-analysis ［J］. JACC Cardiovasc Imaging ， 2022 ， 15 （ 5 ）： 796 - 808 . DOI： 10.1016/j.jcmg.2021.12.008 http://dx.doi.org/10.1016/j.jcmg.2021.12.008 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Variability of remnant cholesterol inflammation index exhibits a dose-response relationship with stroke risk: Evidence from the Chinese Kailuan cohort

Related Author

CAO Liuliu

LI Man

WU Zhaohui

ZHAO Maolin

WANG Baohua

ZHANG Li

LI Peng

YANG Yongna

Related Institution

Department of Emergency

Department of Critical Care Medicine， Affiliated Hospital of North China University of Science and Technology

Department of Critical Care Medicine， the First Affiliated Hospital of Jinan University

Groduate School Shanxi Medical University

Department of Cardiovascular Medicine， Kailuan Hospital

⁰