Sex-Specific Computed Tomography Coronary Plaque Characterization and Risk of Myocardial Infarction

Abstract

Objectives: This study was designed to investigate whether coronary computed tomography angiography assessments of coronary plaque might explain differences in the prognosis of men and women presenting with chest pain.

Background: Important sex differences exist in coronary artery disease. Women presenting with chest pain have different risk factors, symptoms, prevalence of coronary artery disease and prognosis compared to men.

Methods: Within a multicenter randomized controlled trial, we explored sex differences in stenosis, adverse plaque characteristics (positive remodeling, low-attenuation plaque, spotty calcification, or napkin ring sign) and quantitative assessment of total, calcified, noncalcified and low-attenuation plaque burden.

Results: Of the 1,769 participants who underwent coronary computed tomography angiography, 772 (43%) were female. Women were more likely to have normal coronary arteries and less likely to have adverse plaque characteristics (p < 0.001 for all). They had lower total, calcified, noncalcified, and low-attenuation plaque burdens (p < 0.001 for all) and were less likely to have a low-attenuation plaque burden >4% (41% vs. 59%; p < 0.001). Over a median follow-up of 4.7 years, myocardial infarction (MI) occurred in 11 women (1.4%) and 30 men (3%). In those who had MI, women had similar total, noncalcified, and low-attenuation plaque burdens as men, but men had higher calcified plaque burden. Low-attenuation plaque burden predicted MI (hazard ratio: 1.60; 95% confidence interval: 1.10 to 2.34; p = 0.015), independent of calcium score, obstructive disease, cardiovascular risk score, and sex.

Conclusions: Women presenting with stable chest pain have less atherosclerotic plaque of all subtypes compared to men and a lower risk of subsequent MI. However, quantitative low-attenuation plaque is as strong a predictor of subsequent MI in women as in men. (Scottish Computed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590).

Keywords: computed tomography; computed tomography coronary angiography; coronary artery disease; quantitative plaque analysis; sex.

Conflict of interest statement

Funding Support and Author Disclosures Drs. Dey, Slomka, and Berman and Mr. Cadet may receive software royalties from Cedars-Sinai Medical Center; and Drs. Dey, Slomka, and Berman have a patent. This trial was funded by The Chief Scientist Office of the Scottish Government Health and Social Care Directorates (CZH/4/588), with supplementary awards from Edinburgh and Lothian’s Health Foundation Trust and the Heart Diseases Research Fund. Drs. Williams, Mills, Newby, and Dweck are supported by the British Heart Foundation (FS/ICRF/20/26002, CH/09/002, FS/11/014, FS/16/14/32023, RG/20/10/34966, RE/18/5/34216, RG/16/10/32375, FS/14/78/31020). Dr. Williams was supported by The Chief Scientist Office of the Scottish Government Health (PCL/17/04). Dr. Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr. van Beek is supported by Scottish Imaging Network: A Platform of Scientific Excellence (SINAPSE). Dr. Adamson is supported by a National Heart Foundation of New Zealand Senior Fellowship (1844). Dr. Dweck is supported by the Sir Jules Thorn Biomedical Research Award 2015 (15/JTA). The Royal Bank of Scotland supported the provision of 320-multidetector CT for NHS Lothian and the University of Edinburgh. The Edinburgh Imaging facility QMRI (Edinburgh) is supported by the National Health Service Research Scotland (NRS) through National Health Service Lothian Health Board. The Clinical Research Facility Glasgow and Clinical Research Facility Tayside are supported by National Health Service Research Scotland (NRS). Ms. McElhinney and Dr. Dey are supported by National Institute of Health/National Heart, Lung, and Blood Institute grants (1R01HL148787-01A1 and 1R01HL151266). Mr. Cadet is supported by the Miriam and Sheldon G. Adelson Medical Research Foundation. All other authors have no reported that they have norelationships relevant to the contents of this paper to disclose.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

FIGURE 1. Low-Attenuation Plaque on CCTA

Female (58 years of age) with typical chest pain, family history of coronary artery disease and abnormal exercise tolerance test. Coronary computed tomography angiography (CCTA) showed obstructive disease in the left anterior descending (LAD) artery (arrows), confirmed at invasive coronary angiography and treated with a stent. Two years later she experienced a non-ST elevation myocardial infarction. (A) A curved planar reformation with diffuse noncalcified plaque (red) and calcified plaque (yellow). Three-dimensional reformats of the proximal (B) and mid-distal LAD (C) show non calcified (red), low-attenuation (orange), and calcified (yellow) plaque, and coronary lumen (blue).

FIGURE 2. Quantitative Plaque Burden in Women and Men

Sex-based difference in plaque burden in patients who did or did not have a fatal or nonfatal myocardial infarction.

FIGURE 3. Predictive Ability of Low-Attenuation Plaque in Women and Men

Receiver operating curve (ROC) showing ability of low-attenuation plaque to predict fatal or nonfatal myocardial infarction for men (green) and women (red). AUC = area under the curve.

FIGURE 4. Myocardial Infarction and Low-Attenuation Plaque in Women and Men

Cumulative incidence plots of fatal or nonfatal myocardial infarction in women and men showing the difference in events between those with (red) and without (green) low-attenuation plaque above 4%.

CENTRAL ILLUSTRATION. Low-Attenuation Plaque Is an Important Predictor of Events in Both Women and Men

(A,B) Images from a 58-year-old woman with nonobstructive disease, but a heavy burden of low-attenuation plaque. Two years later she suffered a non-ST-segment elevation myocardial infarction. (C) Results of the multivariable model where low-attenuation plaque burden was a predictor of subsequent fatal or non-fatal myocardial infarction, independent of gender, presence of obstructive disease on CCTA and cardiovascular risk score. (D) The percentage of women or men who suffered myocardial infarction that had a low-attenuation plaque burden (LAP) above or below 4%. CCTA = coronary computed tomography angiography.