Coronary Artery Disease (CAD) remains one of the most significant health problems worldwide, and in the case of women, its diagnosis, risk assessment, and management are often particularly difficult. Recent studies, including analyses conducted within the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE), have identified new critical factors that highlight significant differences between the sexes in the origin and prognosis of coronary pathology.
Sex Differences in the Context of Coronary Plaque Volume
Traditionally, CAD risk assessment has largely relied on cholesterol levels and plaque volume, which are often viewed simply as factors causing stenosis. However, new data shows that women possess a different profile regarding plaque formation and its associated risk prognosis.
The study evaluated male and female patients with stable chest pain of specific duration, none of whom had a previously diagnosed coronary artery disease. Of these, 4,267 were analyzed: 2,199 women and 2,068 men. Using Coronary Computed Tomography Angiography (CCTA), researchers measured both the total volume of plaques and the Plaque Burden (PB)—the percentage of plaque relative to the total volume of the vessel.
Significant findings:
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Plaque prevalence is rarer in women than in men (55% vs. 75%), and at the same time, women had a lower total volume of “high-risk” plaque (the scale of local occlusion).
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However, the incidence of Major Adverse Cardiovascular Events (MACE) (death, heart attack, or hospitalization due to unstable pain) was not significantly lower in women compared to men (2.3% vs. 3.4%).
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These results indicate that female patients are not at low risk, even if their total plaque volume is smaller. This is one of the key messages of the PROMISE study.
Sex Differentiation in Rising Risk Dynamics
The study also indicates that the risk of adverse events begins at a much lower PB than in men.
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In women, the risk begins to rise at approximately 20% PB.
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In men, the most common risk threshold begins at approximately 28% PB. Furthermore, as PB increases, the risk rises more rapidly in women than in men. This means that for the same reason, even the slightest change in plaque configuration or shape in women can lead to far more serious consequences.
Why is This Difference Important?
The article “Why heart disease in women may be missed on scans” draws attention to the fact that the cardiovascular physiological nature of women and men differs; women’s arteries are often smaller, and the female body reveals unusual reactions not only to hormones but also to microvascular function and inflammatory processes.
Additionally, heart disease in women is often not caused by obstructive stenosis (a severely blocked artery). Unfortunately, according to modern guidelines, such a “non-obstructive” substrate can easily be overlooked based on primary risk assessment methods, because traditional coronary disease diagnostics are focused exclusively on the degree of obstructive damage. In women, even small-sized plaques can cause microvascular failure, inflammation, and other physiological disorders that are not fully explained by cholesterol dosage or stenosis. This is supported by evidence that traditional models—often developed through leading studies conducted on men—do not fully reflect the biological and clinical reality of women.
Clinical and Public Significance
These discoveries hold important messages for the global heart health community:
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Sex-Specific Interpretation Studies, including the PROMISE analysis, clearly indicate that the standard “one size fits all” approach—which has been so actively taught in various educational institutions to determine which level of plaque is considered high-risk—is simply shameful (inadequate).
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Early Interventions and Treatment Therefore, early diagnosis and broad preventive measures in women are part of an approach that may require more aggressive management. This includes:
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Rigorous monitoring of risk factors;
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Use of CCTA or other imaging methods;
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Lifestyle changes and medicinal prophylaxis much earlier than standard practice provides for.
The information presented in this article indicates that the management of heart disease in women must be adapted according to sex, involving a more comprehensive and dynamic assessment of plaque data and more aggressive preventive strategies when vascular markers are present that may not be reflected by traditional risk models.
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