Women develop coronary atherosclerosis more than a decade later than men

Sex and age-specific interactions of coronary atherosclerotic plaque onset and prognosis from coronary computed tomography

Literature - Van Rosendael SE, Bax AM, Lin FY, et al. - Eur Heart J Cardiovasc Imaging. 2023 May 11:jead094 [Online ahead of print]. doi: 10.1093/ehjci/jead094


Women develop coronary atherosclerosis and experience ACS later in life compared with men [1-3]. It remains unclear whether coronary plaque development has a later onset in women, whether the magnitudes of risk are similar between sexes and whether treatment should be different in women vs. men. Atherosclerotic assessment with coronary computed tomography angiography (CCTA) can be used to determine the ‘atherosclerotic plaque burden’, and determine intensity of treatment.

Aim of the study

The authors examined sex- and age-specific interaction in atherosclerotic onset and risk for MACE in stable patients undergoing a CCTA.



In this study, 24950 patients from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: an InteRnational Multicenter) registry were included. The CONFIRM registry consisted of a large, multi-center, international, observational cohort, of which prospectivelydata were collected from patients who underwent clinically indicated CCTA [4]. In this study, patients with known CAD were excluded. The Leiden CCTA score, which integrates coronary plaque presence, extent, severity, composition and location into a single score, was calculated. A total of 11678 women and 13272 men were followed for a median period of 3.7 years.


The primary outcome was the difference in CCTA score between women and men for similar age. Secondary outcomes were differences in MACE, defined as all-cause mortality and MI.

Main results

Leiden CCTA risk score

  • An age-dependent increase of the Leiden CCTA score was detected in both women and men, but atherosclerotic onset (score >0) occurred 12 years later in women compared with men (64-68 years in women vs. 52-56 years in men; P<0.001).
  • The Leiden CCTA score was lower in women vs. men, irrespective of age category.
  • The Leiden CCTA score was associated with MACE (score 6–20, HR: 2.29 [95%CI: 1.69-3.10]; score >20, HR: 6.71 [95%CI: 4.36-10.32] in women; and score 6–20, HR: 1.64 [95%CI: 1.29-2.08]; score >20, HR: 2.38 [95%CI: 1.73-3.29] in men).
  • The prognostic value for MACE of the Leiden CCTA score was higher in post-menopausal women compared with men (score 6–20, HR: 2.21 [95%CI: 1.57-3.11]; score >20, HR: 6.11 [95%CI: 3.84-9.70] in post-menopausal women; and score 6–20, HR: 1.57 [95%CI: 1.19-2.09]; score >20, HR: 2.25 [95%CI: 1.58-3.22] in men).
  • There was no difference in MACE risk between pre-menopausal women and men (score 6–20, HR: 2.34 [95%CI: 1.10-4.99]; score >20, HR: 2.28 [95%CI: 0.30-17.56] in pre-menopausal women; and score 6–20, HR: 2.32 [95%CI: 1.45-3.74]; score >20, HR: 3.33 [95%CI: 1.38-8.08] in men).

CAD and atherosclerotic plaque characteristics

  • A larger proportion of women had no CAD on CCTA compared with men (58.1% in women vs. 41.9% in men; P<0.001).
  • When CAD was present, this was more frequently non-obstructive in women vs. men (62.5% in women vs. 55.6% in men; P<0.001)
  • Women had fewer coronary segments with atherosclerosis compared with men (1.5 ± 2.3 in women vs. 2.6 ± 3.1 in men; P<0.001). In line with this, less sections were identified in women vs. men with non-calcified plaque (0.3 ± 0.9 vs. 0.5 ± 1.1; P<0.001), partially calcified plaque (0.5 ± 1.3 vs. 1.0 ± 1.9; P<0.001), calcified plaque (0.7 ± 1.5 vs. 1.1 ± 2.0; P<0.001), obstructive lesions (0.4 ± 1.0 vs. 0.7 ± 1.5; P=0.03) and non-obstructive lesions (1.0 ± 1.8 vs. 1.7 ± 2.4; P<0.001).
  • Women had fewer proximal sections with plaque compared with men (0.7 ± 1.1 in women vs. 1.1 ± 1.3 in men; P<0.001). Moreover, plaque in the left main artery occurred more frequently in men than in women (16.9% in men vs. 9.0% in women; P<0.001).


In this large registry with patients undergoing a CCTA, coronary atherosclerosis developed 12 years later in women compared with men. A lower Leiden CCTA score was detected in women vs. men across all age categories. The Leiden CCTA score was associated with MACE in both sexes, but the risk for all-cause mortality and MI was higher in post-menopausal women with a Leiden CCTA score >20 compared with men. “[This] may have therapeutic implications for initiation of the most intensive preventive medical therapies even in the absence of prior coronary events [in this patient group]”, said the authors.


1. Steingart RM, Packer M, Hamm P, et al. Sex differences in the management of coronary artery disease. Survival and ventricular enlargement investigators. N Eng J Med. 1991;325:226-230.

2. Canto JG, Rogers WJ, Goldberg RJ, et al. Association of age and sex with myocardial infarction symptom presentation and in-hospital mortality. JAMA. 2012;307:813-822.

3. Hochman JS, Tamis JE, Thompson TD, et al. Sex, clinical presentation, and outcome in patients with acute coronary syndromes. Global use of strategies to open occluded coronary arteries in acute coronary syndromes IIb investigators. N Eng J Med. 1999;341:226-232.

4. Min JK, Dunning A, Lin FY, et al. Rationale and design of the CONFIRM (COronary CT angiography EvaluatioN for clinical outcomes: an InteRnational multicenter) registry. J Cardiovasc Comput Tomogr. 2011;5:84–92.

Find this article online at Eur Heart J Cardiovasc Imaging.

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