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CC BY-NC-ND 4.0 · Thromb Haemost 2024; 124(07): 684-694
DOI: 10.1055/s-0043-1771188
Original Article: Atherosclerosis and Ischaemic Disease

Inverse Association of Lipoprotein(a) on Long-Term Bleeding Risk in Patients with Coronary Heart Disease: Insight from a Multicenter Cohort in Asia

Peizhi Wang   *
1   Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Deshan Yuan   *
1   Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Xueyan Zhao
2   Special Demand Medical Care Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Pei Zhu
1   Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Xiaogang Guo
3   Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
,
Lin Jiang
1   Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Na Xu
1   Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Zhifang Wang
4   Department of Cardiology, Xinxiang Central Hospital, Xinxiang, Henan Province, China
,
Ru Liu
1   Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Qingsheng Wang
5   Department of Cardiology, The First Hospital of Qinhuangdao, Qinhuangdao, Hebei Province, China
,
Yan Chen
1   Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Yongzhen Zhang
6   Department of Cardiology, Peking University Third Hospital, Beijing, China
,
Jingjing Xu
1   Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Zhenyu Liu 
7   Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Ying Song
1   Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Zheng Zhang
8   Department of Cardiology, The First Hospital of Lanzhou University, Lanzhou, Gansu Province, China
,
Yi Yao
1   Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Yingqing Feng
9   Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangzhou, Guangdong Province, China
,
Xiaofang Tang
1   Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Xiaozeng Wang
10   Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning Province, China
,
Runlin Gao
1   Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Yaling Han   **
10   Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning Province, China
,
Jinqing Yuan   **
1   Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
11   National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
› Author Affiliations Funding This work was supported by grants from the Ministry of Science and Technology of the People's Republic of China [2016YFC1301300 and 2016YFC1301301], National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences [Grant No. NCRC2020013], and the CAMS Innovation Fund for Medical Sciences (CIFMS) [2020-I2M-C&T-B-049]. The funding organizations had no role in the study's design and concept; the collection, management, analysis, and interpretation of the data; or the manuscript's preparation, review, or approval. National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Grant No. NCRC2020013. The CAMS Innovation Fund for Medical Sciences (CIFMS), 2020-I2M-C&T-B-049. The Ministry of Science and Technology of the People's Republic of China, 2016YFC1301300 and 2016YFC1301301. Fundamental Research Funds for the Central Universities, Grant No. 3332023128.
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Abstract

Background Lipoprotein(a), or Lp(a), has been recognized as a strong risk factor for atherosclerotic cardiovascular disease. However, the relationship between Lp(a) and bleeding remains indistinct, especially in the secondary prevention population of coronary artery disease (CAD). This investigation aimed to evaluate the association of Lp(a) with long-term bleeding among patients with CAD.

Methods Based on a prospective multicenter cohort of patients with CAD consecutively enrolled from January 2015 to May 2019 in China, the current analysis included 16,150 participants. Thus, according to Lp(a) quintiles, all subjects were divided into five groups. The primary endpoint was bleeding at 2-year follow-up, and the secondary endpoint was major bleeding at 2-year follow-up.

Results A total of 2,747 (17.0%) bleeding and 525 (3.3%) major bleeding were recorded during a median follow-up of 2.0 years. Kaplan–Meier survival analysis showed the highest bleeding incidence in Lp(a) quintile 1, compared with patients in Lp(a) quintiles 2 to 5 (p < 0.001), while the incidence of major bleeding seemed similar between the two groups. Moreover, restricted cubic spline analysis suggested that there was an L-shaped association between Lp(a) and 2-year bleeding after adjustment for potential confounding factors, whereas there was no significant association between Lp(a) and 2-year major bleeding.

Conclusion There was an inverse and L-shaped association of Lp(a) with bleeding at 2-year follow-up in patients with CAD. More attention and effort should be made to increase the clinician awareness of Lp(a)'s role, as a novel marker for bleeding risk to better guide shared-decision making in clinical practice.

Keywords

lipoprotein(a) - bleeding - inverse association - L-shaped association - prognosis

Authors' Contribution

P.W., D.Y., J.Y., and Y.H. contributed to the study design. P.Z., L.J., N.X., R.L., Y.C., J.X., Y.S., Y.Y., and X.T. participated in the collection, analysis, or interpretation of data. P.W. and D.Y. performed the statistical analysis and drafted the manuscript. J.Y., Y.H., R.G., X.W., Y.F., Z.Z., Z.L., Y.Z., Q.W., Z.W., X.G., and X.Z. critically revised the manuscript. All authors read and approved the final submitted version.


* These authors shared first co-authorship.


** These authors Han shared last co-authorship.


Supplementary Material



Publication History

Received: 07 December 2022

Accepted: 08 June 2023

Article published online:
24 July 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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