Differences in Plaque Characteristics and Myocardial Mass: Implications for Physiological Significance

Abstract

Background: The mechanism of the fractional flow reserve (FFR) difference according to sex has not been clearly understood.

Objectives: This study sought to evaluate sex differences in coronary stenosis, plaque characteristics, and left ventricular (LV) mass and their implications for physiological significance.

Methods: This was a post hoc analysis of a pooled population of multicenter, international prospective cohorts. Patients (166 women and 489 men) underwent coronary computed tomography angiography (CCTA) within 90 days before invasive FFR measurements were included. The minimal lumen area, percent of plaque burden, whole vessel plaque volume by composition, high-risk plaque characteristics, and LV mass were analyzed from CCTA images.

Results: Among 1,188 vessels analyzed, the FFR value was higher in women than that in men (0.85 ± 0.13 vs 0.82 ± 0.14; P = 0.001) despite a similar percentage of diameter stenosis between the sexes (45.9% ± 18.9% vs 46.1% ± 17.7%; P = 0.920). The composition of fibrofatty plaque + necrotic core (13.1% ± 16.9% vs 21.2% ± 19.9%; P < 0.001) and frequencies of low attenuation plaque (12.7% vs 24.5%; P < 0.001) and positive remodeling (33.8% vs 45.5%; P = 0.001) were lower in women than in men. Vessel, plaque, and lumen volumes were significantly smaller in women than that in men (all P < 0.001); however, no sex difference was observed in any of these parameters after adjustment for LV mass (all P > 0.10). Sex was not an independent predictor of the FFR value after adjustment for stenosis severity, plaque characteristics, and LV mass.

Conclusions: Higher FFR values for the same stenosis severity in women can be explained by fewer high-risk plaque characteristics and smaller myocardial mass in women than that in men. (CCTA-FFR Registry for Risk Prediction; NCT04037163).

Keywords: CAD, coronary artery disease; CCTA, coronary computed tomography angiography; FFNC, fibrofatty + necrotic core; FFR, fractional flow reserve; LV, left ventricle; MLA, minimal lumen area; coronary artery disease; fractional flow reserve; myocardial mass; plaque; sex.

Conflict of interest statement

This study was supported in part by an unrestricted research grant from St. Jude Medical (Abbott Vascular). The company had no role in study design, conduct, data analysis, or manuscript preparation. Dr Lee gas received a research grant from St. Jude Medical (Abbott Vascular) and Philips Volcano. Dr Doh has received a research grant from Philips Volcano. Dr Chen has been a consultant for Microport and Boston Scientific International; and has received a grant from the National Natural Scientific Foundation of China. Dr Koo has received an institutional research grant from St. Jude Medical (Abbott Vascular) and Philips Volcano. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

© 2022 The Authors.

Figures

Graphical abstract

Figure 1

Distributions of CCTA Parameters (A) Distributions of minimal lumen area (MLA), (B) percentage of plaque burden at the MLA site, (C) whole vessel plaque volume, and (D) fractional flow reserve (FFR). Bars indicate the frequencies among vessels. CCTA = coronary computed tomography angiography.

Figure 2

Vessel, Plaque, and Lumen Volume After Adjustment for LV Mass In whole vessel analysis, (A, C, E) vessel, plaque, and lumen volumes were significantly smaller in women than those in men. However, after adjustment for left ventricular (LV) mass, there were no differences in any of (B, D, F) vessel, plaque, and lumen volumes between women and men. Box-and-whisker plots indicate the median (center line of the box), 25% and 75% ranges (box edges), and 10% and 90% ranges (whiskers).

Figure 3

Comparison of Plaque Composition According to Sex The (A) absolute volume and (B) percentage of each plaque composition are plotted according to sex.

Central Illustration

Sex Differences in Coronary Computed Tomography Angiography Parameters and Fractional Flow Reserve Despite similar luminal narrowing and plaque burden between women and men, the composition of lipid-rich plaque and frequencies of qualitative high-risk plaque characteristics were lower in women, indicating more favorable plaque characteristics in women. The fractional flow reserve (FFR) value was higher in women than in men despite similar stenosis severity; however, sex was not an independent factor that affected the FFR value after adjusting for plaque characteristics and the left ventricular (LV) mass. CCTA = coronary computed tomography angiography; LAP = low attenuation plaque; PR = positive remodeling.