Sex differences in coronary plaque burden and plaque progression during 10-year serial coronary CT angiography follow-up

Sex-specific differences in coronary artery disease (CAD) have been observed with a delayed onset of CAD, a lower plaque burden and less obstructive CAD in women. It has been suggested that women have accelerated plaque development and increased cardiovascular disease risk after menopause. Understanding these sex differences in coronary atherosclerosis development is crucial for improved CAD risk assessment and prevention strategies.

This study investigated sex-based differences in coronary atherosclerotic burden and 10-year plaque progression in men and postmenopausal women.

Per-protocol, patients from a coronary CT angiography (CCTA) cohort were invited for repeat CCTA imaging. A total of 299 patients underwent follow-up imaging with a median scan interval of 10.2 [IQR 8.7-11.2] years. Patients who underwent coronary artery bypass grafting and vessels revascularized by percutaneous coronary intervention were excluded. Scans were analyzed using atherosclerosis imaging-quantitative CCTA analysis (AI-QCT). Baseline and follow-up measurements of total and compositional plaque volume were normalized to the analyzed total vessel length. The associations between sex, baseline and follow-up plaque characteristics were evaluated using multivariable regression adjusted for age, clinical risk factors, statin use, baseline plaque volumes and scanner settings. Plaque progression was assessed using propensity score matching, stratified by age and baseline plaque burden.

In total, 267 patients were included, 114 (43%) were women. The mean age was 57±7 years, women had higher high density lipoprotein (HDL) cholesterol levels (1.64 ± 0.54 mmol/l vs. 1.29 ± 0.48 mmol/l; p<0.001) and lower triglycerides (1.10 (0.09, 1.70) mmol/l vs. 1.50 (1.10, 2.40) mmol/l; p<0.001) . No difference in the prevalence of clinical risk factors (diabetes, hypertension, hypercholesterolemia, family history of CAD, smoking history) and medication use was observed (all p>0.05). At baseline, women had a lower median percent atheroma volume (PAV) (1.7%; IQR 0.4-4.2 vs. 3.1%; IQR 0.9-8.5; p=0.001), less non calcified percent atheroma volume (NCPAV) (1.3%; IQR, 0.3-2.8 vs. 2.7%; IQR 0.8-6.4; p=0.001) as well as less calcified percent atheroma volume (CPAV) (0.0%; IQR 0.0-1.2 vs 0.6%; IQR 0.0-2.4; p=0.014). In multivariate analysis, female sex was associated with less high risk plaque (HRP) (β = -0.667; p=0.034) and less low-attenuation plaque (LAP) (β = -0.798; p=0.044) after 10 year follow-up. After propensity score matching women had a significantly lower NCPAV progression (0.94% vs 1.66%; p=0.012, Figure 1) and overall PAV progression was higher in men (2.90% vs 4.24%; p=0.032, Figure 1).

Postmenopausal women demonstrated lower rates of noncalcified and total plaque progression with less HRP and LAP development. These results suggest that developing sex-specific risk assessment tools could enhance cardiovascular risk estimation.Figure 1