Sex differences in coronary atherosclerosis progression and major adverse cardiac events in patients with suspected coronary artery disease

doi:10.1016/j.jcct.2017.07.002

Journal of Cardiovascular Computed Tomography

Volume 11, Issue 5, September–October 2017, Pages 367-372

https://doi.org/10.1016/j.jcct.2017.07.002 Get rights and content

Highlights

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Coronary atherosclerosis keep progressing in both men and women.
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Compared with women, men harbored significantly higher coronary atherosclerosis progression.
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Coronary atherosclerosis progression was a significant predictor of MACE.

Abstract

Background

Little is known about the influence of coronary atherosclerosis progression on the risk of major adverse cardiac events (MACE). Similarly, differences between men and women regarding atherosclerosis progression are poorly understood. The purpose of this study was to investigate the progression of coronary atherosclerosis by coronary CT angiography (coronary CTA) in men and women, and to evaluate its prognostic value regarding MACE.

Methods

This study included 1046 patients with suspected coronary artery disease (CAD) who underwent serial coronary CTA because of new or worsening symptoms or because follow-up coronary CTA had been recommended by attending physicians. Coronary atherosclerosis was semi-quantitatively assessed as follows: three-vessel plaque score (TVPS), severe proximal plaque score (SPPS), segment stenosis score (SSS), segment involvement score (SIS), and coronary artery calcium score (CACS). Patients were followed-up regarding the occurrence of MACE, defined as cardiac death, coronary revascularization, nonfatal myocardial infarction and hospitalization due to unstable angina. Follow-up information was gathered by clinical visits or telephone contacts.

Results

Follow-up was achieved in 953 (91.1%) patients (63.8% male; mean age, 53.9 ± 9.7 years) with a mean interval of 4.9 ± 1.1 years. MACE occurred in 132 (13.9%) patients. The average interscan time was 2.1 years. Compared with women, men had significantly higher progression of SPPS, SSS and SIS (6.6% vs. 3.5%, 28.0% vs. 18.3%, 26.6% vs. 16.8%, respectively, all P < 0.005). There was a strong association between the progression of SPPS as well as SSS and MACE, both for men (SPPS, HR:2.17, P < 0.001; SSS, HR:1.28, P = 0.023) and women (SPPS, HR:2.75, P < 0.001; SSS, HR:1.19, P = 0.027).

Conclusions

Progression of coronary atherosclerosis as determined by coronary CTA is higher in men than women, it is associated with the risk of future MACE.

Introduction

Sex differences regarding the prognosis of coronary artery disease (CAD) are well documented,1, 2 and women both with symptoms and with nonobstructive CAD were found more likely to experience major adverse cardiac events (MACE).³ The occurrence of MACE may be associated with the progression of coronary atherosclerosis.⁴ Intravascular ultrasound and optical coherence tomography can be used to evaluate coronary atherosclerosis progression, but both are invasive, costly and not free from complications. Coronary CT angiography (coronary CTA) is a high-resolution cardiovascular imaging technology that permits the evaluation of luminal stenosis, coronary plaque amount and distribution, as well as plaque progression. Previous studies have demonstrated that plaque progression detected by serial coronary CTA was an independent predictor of acute coronary syndromes.⁵ However, sex differences in coronary atherosclerosis progression and their association with cardiac events in patients with suspected CAD are still unclear. In our study, we investigating sex differences in coronary atherosclerosis progression as determined by coronary CTA and we analyzed the association between the atherosclerosis progression and MACE stratified by sex.

Section snippets

Patients

The study was approved by the local institutional review board, and the requirement to obtain informed consent was waived. We retrospectively enrolled 1046 patients with suspected CAD who underwent serial coronary CTA because of new or worsening symptoms or because follow-up coronary CTA had been recommended by attending physicians from September 2009 to January 2015. Exclusion criteria included the following: 1) patients who underwent coronary revascularization (percutaneous coronary

Patient demographics

Of the 1046 patients, 953 (91.1%) patients were followed up and 53 (8.9%) were lost to followe up. Of the follow up patients, 608 (63.8%) were men and 345 (36.2%) were women. Women were significantly older than men (mean 57.5 ± 8.6 vs. 51.9 ± 9.8 years, P < 0.001). Clinical characteristics of patients by sex are presented in Table 1. Men had a significantly higher BMI and higher proportion of smoking and history of CAD compared with women (26.3 ± 3.0 vs. 25.1 ± 3.5 kg/m², 18.8% vs. 4.3%, and

Discussion

Our study demonstrated that sex disparities exist in coronary atherosclerosis progression and that men display significantly greater progression compared with women. Coronary atherosclerosis progression as determined by coronary CTA was significantly associated with the incidence of MACE in both men and women. Statistically significant differences for the risk of MACE were not found between men and women in this study. These findings illustrate that coronary CTA features may be incremental to

Funding

This work had been supported by the key special Grant of Chinese Government (2016YFC1300400 and 2007BAI05B02), and National Natural Science Foundation of China (81371548, 81571672 and 81171343) and a Taishan Scholar Projection.

Conflict of interest

The authors have no conflicts of interest to disclose.

Disclosures

None.

Acknowledgments

None.

References (12)

K. MacIntyre et al.
Gender and survival: a population-based study of 201,114 men and women following a first acute myocardial infarction
J Am Coll Cardiol
(2001)
J.K. Min et al.
Age- and sex-related differences in all-cause mortality risk based on coronary computed tomography angiography findings results from the International Multicenter ONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: an International Multicenter Registry) of 23,854 patients without known coronary artery disease
J Am Coll Cardiol
(2011)
T.L. Sedlak et al.
Sex differences in clinical outcomes in patients with stable angina and no obstructive coronary artery disease
Am Heart J
(2013)
S. Motoyama et al.
Plaque characterization by coronary computed tomography angiography and the likelihood of acute coronary events in mid-term follow-up
J Am Coll Cardiol
(2015)
H. Gu et al.
Difference of coronary stenosis severity between systolic and diastolic phases in quantitative CT angiography
J Cardiovasc Comput Tomogr
(2017)
J.K. Min et al.
Prognostic value of multidetector coronary computed tomographic angiography for prediction of all-cause mortality
J Am Coll Cardiol
(2007)

There are more references available in the full text version of this article.

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Research paperSex differences in coronary atherosclerosis progression and major adverse cardiac events in patients with suspected coronary artery disease

Highlights

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Patients

Patient demographics

Discussion

Funding

Conflict of interest

Disclosures

Acknowledgments

J Am Coll Cardiol

J Am Coll Cardiol

Am Heart J

J Am Coll Cardiol

J Cardiovasc Comput Tomogr

J Am Coll Cardiol

Research paper
Sex differences in coronary atherosclerosis progression and major adverse cardiac events in patients with suspected coronary artery disease