Despite advances in cardiology, women continue to face significant disparities in the prevention, diagnosis, and treatment of ischemic heart disease—a condition caused by reduced blood flow to cardiac tissue and the leading cause of cardiovascular death worldwide. A study published in the European Heart Journal as a scientific position paper from the “Working Group on Coronary Pathophysiology and Microcirculation” and associations (ACVC and EAPCI) of the European Society of Cardiology (ESC) highlights how sex and gender differences play a decisive role in cardiovascular risk, pathophysiology, and prognosis in ischemic heart disease. It underscores the need to systematically integrate this perspective into clinical practice and research.
Far from being a simple variation of the male model, ischemic heart disease in women shows distinct characteristics across the entire disease continuum, from risk factors to clinical outcomes. “For decades, coronary artery disease has been studied and treated from a predominantly androcentric perspective, contributing to the underdiagnosis and suboptimal treatment of many women,” explains Dr. Teresa Padró, head of the Cardiovascular Disease Biomarkers Research Group at the Institut de Recerca Sant Pau (IR Sant Pau) and researcher at the Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), and corresponding author of the study.
In women, classic cardiovascular risk factors such as smoking, diabetes mellitus, and hypertension have a greater relative impact than in men. This profile is further shaped by female-specific risk factors, including pregnancy-related complications (preeclampsia, gestational hypertension, preterm delivery, or fetal growth restriction) and early menopause, all associated with an increased later risk of ischemic heart disease. A potentially unfavorable effect of hormone replacement therapy is also noted when initiated in older women or many years after menopause onset.
From an anatomical and functional perspective, women’s coronary circulation has relevant particularities, such as smaller vessel caliber and a more diffuse pattern of atherosclerotic disease. In addition, women more frequently present with non-obstructive coronary artery disease, microvascular dysfunction, and coronary spasm, all of which can cause myocardial ischemia even in the absence of significant stenosis. “Understanding this pathophysiology is key to explaining why many women present clear symptoms of ischemia without evident obstructive lesions on conventional angiography,” notes Dr. Padró.
The way ischemic heart disease manifests in women directly contributes to healthcare disparities. Compared with the typical chest pain seen in men, women more often present less specific symptoms, such as dyspnea, fatigue, or general discomfort, which lowers initial clinical suspicion and delays diagnosis. This issue is compounded by a historical bias in symptom interpretation, based on predominantly male patterns.
Differences also extend to the diagnostic setting. Women tend to have lower coronary flow reserve, while fractional flow reserve may be higher for the same degree of stenosis, reflecting the contribution of microvascular dysfunction to ischemia. Moreover, some traditional diagnostic tests perform less effectively in women, whereas functional imaging techniques and microcirculation-specific tests help detect ischemia in the absence of obstructive disease. When these factors are not considered, there is a real risk of underdiagnosis. “If these differences are not correctly interpreted, ischemic heart disease in women may go unnoticed or be inadequately treated,” Dr. Padró warns.
Regarding treatment, significant inequalities persist. Women are less likely to receive evidence-based therapies and invasive procedures, and they show higher rates of treatment discontinuation, partly due to adverse effects. These differences, combined with distinct risk profiles and clinical characteristics, result in worse clinical outcomes, especially after acute coronary syndrome, with higher mortality in women—particularly at younger ages—even after adjusting for baseline characteristics, treatments, and time to care.
One of the main limitations identified is the underrepresentation of women in randomized clinical trials, which affects the robustness of available evidence. Many studies are not designed to analyze sex and gender differences, making it difficult to identify variations in treatment efficacy, safety, or adverse effects in women and limiting the applicability of findings to clinical practice.
This lack of specific evidence perpetuates disparities in the management of ischemic heart disease and hinders progress toward a more personalized approach to medicine. To address this, it is essential to increase women’s participation in clinical trials and to design studies that explicitly incorporate a sex- and gender-based perspective from the outset.
The study also emphasizes the need to enhance awareness and training among healthcare professionals, optimize diagnostic strategies, and promote organizational and health policy changes to ensure more equitable cardiovascular care. “Systematically integrating a sex- and gender-based perspective into research and clinical practice is essential to improving women’s cardiovascular health,” Dr. Padró concludes.
This approach aligns with the research conducted at IR Sant Pau, where cardiology research prioritizes the pathophysiological mechanisms of cardiovascular disease and their clinical application, with increasing attention to sex and gender differences. The participation of IR Sant Pau researchers in internationally recognized work such as this reinforces the institution’s commitment to rigorous, translational cardiovascular research aimed at improving health outcomes.
