Lipoprotein(a) and Cardiovascular Outcomes in Patients With Coronary Artery Disease and Different Metabolic Phenotypes

Jing-Lu Jin; Hui-Wen Zhang; Hui-Hui Liu; Cheng-Gang Zhu; Yuan-Lin Guo; Na-Qiong Wu; Rui-Xia Xu; Qian Dong; Jian-Jun Li

doi:10.3389/fcvm.2022.870341

Lipoprotein(a) and Cardiovascular Outcomes in Patients With Coronary Artery Disease and Different Metabolic Phenotypes

Front Cardiovasc Med. 2022 May 20:9:870341. doi: 10.3389/fcvm.2022.870341. eCollection 2022.

Authors

Jing-Lu Jin^{1

2}, Hui-Wen Zhang¹, Hui-Hui Liu¹, Cheng-Gang Zhu¹, Yuan-Lin Guo¹, Na-Qiong Wu¹, Rui-Xia Xu¹, Qian Dong¹, Jian-Jun Li¹

Affiliations

¹ Key Laboratory of Cardiovascular Disease, Cardiometabolic Center, National Center for Cardiovascular Diseases, Fu Wai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
² Department of Endocrinology, Genetics, and Metabolism, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China.

Abstract

Background: The positive relationship between metabolic healthy obesity (MHO) and cardiovascular risk has been under debate in recent years. Previously, strong evidence supported the causal role of increased plasma lipoprotein(a) [Lp(a)] levels in cardiovascular disease (CVD). The current study aimed to investigate the different associations of Lp(a) and cardiovascular events (CVEs) in patients with coronary artery disease (CAD) and different metabolic phenotypes.

Methods: A total of 5,089 patients who were angiography-proven CAD were consecutively included and followed up for CVEs. Obesity was defined as a body mass index (BMI) ≥25 kg/m² according to Asia-specific BMI criteria. Patients were divided into four groups according to metabolic phenotypes, namely metabolically healthy/unhealthy non-obese and metabolically healthy/unhealthy obese [metabolically healthy non-obese (MHN), MHO, metabolically unhealthy non-obese (MUN), and metabolically unhealthy obesity (MUO)]. Comparisons of CAD severity and outcomes were performed among four groups. Cox regression analyses and cubic spline models were used to examine the relationship between Lp(a) and CVEs in patients with different metabolic phenotypes.

Results: During a median of 7.5 years' follow-up, 540 (10.6%) CVEs occurred. MUN and MUO populations had more severe coronary stenosis than MHN ones, while no significant difference in the Gensini score (GS) was observed between MHN and MHO. Patients with MUN and MUO presented a higher risk of CVEs than patients with MHN (hazard ratio [HR]: 1.414, 95% CI: 1.024-1.953-1.556 and HR: 1.747, 95% CI: 1.295-1.363, p < 0.05). In subgroup analysis, restricted cubic spline models showed that there was no association between Lp(a) and CVEs in patients in MHN and MHO, while the MUN and MUO groups presented increasing associations between Lp(a) and CVEs and such association was stronger in the MUO group. In Cox regression analysis, Lp(a) >50 mg/dl was associated with a 2.032- and 2.206-fold higher risk of subsequent CVEs in the MUO and MUN subgroups, respectively.

Conclusion: Among patients with angiography-proven stable CAD, Lp(a) had a more significant prognostic value in both MUO and MUN individuals regardless of obesity, suggesting the importance of screening for cardiovascular risk with Lp(a) in metabolically unhealthy patients.

Keywords: CAD; coronary severity; lipoprotein(a); metabolic phenotypes; outcome.