Sex Differences in Coronary Inflammation and Atherosclerosis Phenotypes in Response to Imaging Marker of Stress-Related Neural Activity

Neng Dai; Xianglin Tang; Xinyu Weng; Haidong Cai; Jianhui Zhuang; Guangjie Yang; Fan Zhou; Ping Wu; Bao Liu; Shaofeng Duan; Yongfu Yu; Weifeng Guo; Zhiguo Ju; Longjiang Zhang; Zhenguang Wang; Yuetao Wang; Bin Lu; Hongcheng Shi; Juying Qian; Junbo Ge

doi:10.1161/CIRCIMAGING.123.016057

Sex Differences in Coronary Inflammation and Atherosclerosis Phenotypes in Response to Imaging Marker of Stress-Related Neural Activity

Circ Cardiovasc Imaging. 2024 Feb;17(2):e016057. doi: 10.1161/CIRCIMAGING.123.016057. Epub 2024 Feb 20.

Authors

Neng Dai^{1

2}, Xianglin Tang^{1

2}, Xinyu Weng^{1

2}, Haidong Cai³, Jianhui Zhuang⁴, Guangjie Yang⁵, Fan Zhou⁶, Ping Wu^{7

8}, Bao Liu^{9

10

11}, Shaofeng Duan¹², Yongfu Yu¹³, Weifeng Guo^{14

15}, Zhiguo Ju¹⁶, Longjiang Zhang⁶, Zhenguang Wang⁵, Yuetao Wang^{9

10}, Bin Lu¹⁷, Hongcheng Shi¹⁸, Juying Qian^{1

2}, Junbo Ge^{1

2}

Affiliations

¹ Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, China (N.D., X.T., X.W., J.Q., J.G.).
² National Clinical Research Center for Interventional Medicine, Shanghai, China (N.D., X.T., X.W., J.Q., J.G.).
³ Department of Nuclear Medicine (H.C.), Shanghai Tenth People's Hospital, China.
⁴ Department of Cardiology (J.Z.), Shanghai Tenth People's Hospital, China.
⁵ Department of Nuclear Medicine, The Affiliated Hospital of Qingdao University, Shandong, China (G.Y., Z.W.).
⁶ Department of Radiology, Jinling Hospital, Medical School of Nanjing University, Jiangsu, China (F.Z., L.Z.).
⁷ Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, China (P.W.).
⁸ Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Shanxi Medical University, Taiyuan, China (P.W.).
⁹ Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China (B.L., Y.W.).
¹⁰ The Nuclear Medicine and Molecular Imaging Clinical Translation Institute of Soochow University, Changzhou, China (B.L., Y.W.).
¹¹ Department of Radiology, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (B.L.).
¹² GE Healthcare China, Shanghai, China (S.D.).
¹³ School of Public Health, and The Key Laboratory of Public Health Safety of Ministry of Education (Y.Y.), Fudan University, Shanghai, China.
¹⁴ Department of Radiology, Zhongshan Hospital (W.G.), Fudan University, Shanghai, China.
¹⁵ Shanghai Institute of Medical Imaging, China (W.G.).
¹⁶ College of Medical Imaging, Shanghai University of Medicine and Health Science, China (Z.J.).
¹⁷ State Key Laboratory of Cardiovascular Disease and National Center for Cardiovascular Diseases, Beijing, China (B.L.).
¹⁸ Department of Nuclear Medicine, Zhongshan Hospital (H.S.), Fudan University, Shanghai, China.

PMID: 38377235
DOI: 10.1161/CIRCIMAGING.123.016057

Abstract

Background: Sex-specific differences in coronary phenotypes in response to stress have not been elucidated. This study investigated the sex-specific differences in the coronary computed tomography angiography-assessed coronary response to mental stress.

Methods: This retrospective study included patients with coronary artery disease and without cancer who underwent resting ¹⁸F-fluorodexoyglucose positron emission tomography/computed tomography and coronary computed tomography angiography within 3 months. ¹⁸F-flourodeoxyglucose resting amygdalar uptake, an imaging biomarker of stress-related neural activity, coronary inflammation (fat attenuation index), and high-risk plaque characteristics were assessed by coronary computed tomography angiography. Their correlation and prognostic values were assessed according to sex.

Results: A total of 364 participants (27.7% women and 72.3% men) were enrolled. Among those with heightened stress-related neural activity, women were more likely to have a higher fat attenuation index (43.0% versus 24.0%; P=0.004), while men had a higher frequency of high-risk plaques (53.7% versus 39.3%; P=0.036). High amygdalar ¹⁸F-flourodeoxyglucose uptake (B-coefficient [SE], 3.62 [0.21]; P<0.001) was selected as the strongest predictor of fat attenuation index in a fully adjusted linear regression model in women, and the first-order interaction term consisting of sex and stress-related neural activity was significant (P<0.001). Those with enhanced imaging biomarkers of stress-related neural activity showed increased risk of major adverse cardiovascular event both in women (24.5% versus 5.1%; adjusted hazard ratio, 3.62 [95% CI, 1.14-17.14]; P=0.039) and men (17.2% versus 6.9%; adjusted hazard ratio, 2.72 [95% CI, 1.10-6.69]; P=0.030).

Conclusions: Imaging-assessed stress-related neural activity carried prognostic values irrespective of sex; however, a sex-specific mechanism linking psychological stress to coronary plaque phenotypes existed in the current hypothesis-generating study.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05545618.

Keywords: computed tomography angiography; coronary artery disease; female; inflammation; positron emission tomography computed tomography.

Publication types

Clinical Study
Research Support, Non-U.S. Gov't

MeSH terms

Atherosclerosis*
Biomarkers
Computed Tomography Angiography / methods
Coronary Angiography / methods
Coronary Artery Disease* / diagnostic imaging
Coronary Vessels
Female
Humans
Inflammation
Male
Phenotype
Plaque, Atherosclerotic*
Predictive Value of Tests
Retrospective Studies
Sex Characteristics

Substances

Biomarkers

Associated data

ClinicalTrials.gov/NCT05545618