4182Sex specific patterns in the onset and manifestation of coronary atherosclerotic plaque; insights from the multi-center CCTA CONFIRM registry
Authors: Van Rosendael A R , Lin F Y , Gransar H , Van Den Hoogen I J , Gianni U , Al Hussein Alawamlh O , Lu Y , Pena J M , Al'aref S J , Berman D S , Min J K , Shaw L J , Bax J J 
Published: October 2019

Abstract

Background
Pathobiologic data support varied atherosclerotic plaque characteristics which uniquely define risk in women as compared to men (i.e., plaque erosion versus rupture). The advent of noninvasive coronary computed tomographic angiography (CCTA) allows for further exploration as to a sex-specific signature of atherosclerotic plaque features unique to women and different from that of men. In this analysis, we compared sex differences in the age of onset of coronary atherosclerosis and varied plaque findings between women and men.

Methods
From the multicenter CONFIRM registry, the Leiden CCTA score (based on segmental plaque extent, location, severity, and composition) was calculated in women and men without prior CAD, with imputation for missing plaque data. First, women and men were matched on the Leiden CCTA score to allow assessment of differences in atherosclerotic profile. Second, the earliest age of women and men to display a median Leiden CCTA score >0, >2, >6, >8 was evaluated. Third, the prognostic value of previously established thresholds of the Leiden CCTA score was examined for all-cause mortality with Cox-proportional hazard analysis, and specifically a sex interaction.

Results
In total, 11,678 women (age 58.5±12.4 years) and 13,272 men (age 55.6±12.5 years) were included. Of the patient subset matched on Leiden CCTA score (10,266 women, score 4.1±6.0 and 10,266 men, Leiden score 4.1±6.0, P=0.589), women were characterized by less obstructive CAD (≥50% stenosis) (17.5% vs 19.1%, P=0.003), more frequent non-obstructive left main plaque (10.1% vs 8.9%, P=0.004) and a lower number of segments with non-calcified or mixed plaque, but an equal number of calcified plaques. The earliest age when women and men have a median Leiden CCTA score above 0, 2, 4, 6, or 8 was consistently 14 to 16 years later for women. A visual representation of the CAD development delay is shown in Figure 1. Adjusted for age, the hazard ratio for death (827 events) for a score 6–20, and >20 (compared with 0–6) was 1.95 (95% CI 1.56–2.42), and 3.44 (95% CI 2.40–4.93) for women, respectively, and 1.63 (95% CI 1.31–2.03), 2.22 (95% CI 1.64–3.00) for men, respectively (P-interaction 0.006). Despite the low number of events, women <50 years with a score >20 were at 12.8 (95% CI 3.58–45.73) times increased risk.

Conclusion
There is an approximate 15-year delay in onset of coronary atherosclerosis for women compared to men. The burden of atherosclerotic plaque is associated with a higher relative hazard for death among women than men. The pattern of more nonobstructive CAD, especially in the left main coronary artery, but also less non-calcified plaque supports a sex-specific plaque signature which may uniquely define risk among women as compared to men.

Acknowledgement/Funding
The research reported in this manuscript was funded, in part, by the National Institute of Health (Bethesda, MD, USA) under award number R01 HL115150.