A clinical consensus statement published in the European Heart Journal highlighted the need to close persistent sex-based gaps in the diagnosis and treatment of cardiovascular (CV) disease. Led by Julia Grapsa, MD, from the Mass General Brigham Heart and Vascular Institute in Boston and developed by experts from scientific societies affiliated with the European Society of Cardiology, the document focused on the role of Women’s Heart Centers (WHCs), the barriers that have limited their expansion, and the need to establish additional centers across Europe.

The authors noted that broader initiatives also supported the need for action. “Broader initiatives, such as the Lancet Regional Health-Europe Commission on Inequalities and Disparities in CV Health, highlighted the structural factors underlying CV inequalities affecting women,” they wrote. The authors argued that WHCs could serve as an effective strategy to address these disparities and improve equity in CV care.

Sex Differences

CV disease is the leading cause of death among women and is responsible for approximately 30% of global mortality. Despite this burden, CV conditions continue to be underdiagnosed and undertreated in women, and only recently has research begun to focus more extensively on sex-related differences in CV health.

“Greater awareness among healthcare professionals and the public is essential for early recognition and appropriate management,” the authors wrote.

In an interview with Univadis Italy,part of the Medscape Professional Network, Gianluca Ruffin, MD, head of the Cardiology Unit at Humanitas San Pio X in Milan, Italy, said, “CV disease is the leading cause of death in both women and men, but scientific evidence confirms substantial sex-related differences in biology, symptoms, and prognosis.”

According to Ruffin, these differences extend across the entire disease continuum, from risk factors and clinical presentation to treatment outcomes.

• Classic risk factors: CV risk factors affect both sexes but often have different implications for women. For example, diabetes in women may diminish the natural CV protective effects of estrogen. Smoking is associated with a substantially higher CV risk in women, particularly when combined with oral contraceptive use. In addition, a history of hypertensive disorders of pregnancy, preeclampsia, gestational diabetes, or early menopause may be sex-specific risk factors for future CV disease.
• Symptom presentation: The clinical presentation also differs between women and men. Although men more commonly experience classic crushing chest pain that may radiate to the arm, women often present with symptoms that may be overlooked. These include pain or tightness in the neck, jaw, throat, or back; unexplained shortness of breath; sudden fatigue; nausea; vomiting; and dizziness.
• Development of diseases: The age at onset also differs. Men tend to develop CV disease earlier in life, often around age 50, while the risk in women rises sharply after menopause, likely because of the loss of estrogen’s protective effects.
• Pathophysiology: Sex-related differences extend to disease mechanisms. In ischemic heart disease, women are more likely to experience coronary microvascular and endothelial dysfunction than obstructive disease of the major coronary arteries, which is more commonly seen in men. Women are also more likely than men to develop heart failure with a preserved ejection fraction.
• Prognosis: Myocardial infarction is associated with higher case fatality rates and greater early mortality in women, partly because diagnosis may be delayed when symptoms are less readily recognized.

Specialized Centers

The consensus statement outlined an ideal model in which WHCs would act as specialized referral centers within a coordinated hub-and-spoke network. Rather than replacing general cardiology services or primary and community care, these centers would provide advanced expertise for patients with the most complex conditions, helping ensure that women receive the most appropriate CV care.

The experts outlined ten key recommendations for establishing WHCs.

• Adopt a hub-and-spoke model of care.
• Integrate sex-specific CV care across all levels of the healthcare system, from primary care to specialized centers.
• Establish clear governance and leadership structures.
• Prioritize education and training.
• Strengthening prevention efforts and public awareness.
• Standardize diagnostic and referral pathways.
• Ensure equitable access to interventional care.
• Leverage telemedicine and digital health technologies.
• Promote inclusive research and data generation.
• Implement quality assurance and continuous quality improvement.

“Preliminary data and follow-up results from the first operational pilot centers, including North American programs and data from the Monzino Women’s Heart Center in Italy, indicate clear improvements across several areas,” Ruffin said.

He cited improvements in diagnostic appropriateness through diagnostic review, better prevention and control of CV risk factors, and improved outcomes accompanied by fewer hospitalizations.

“WHCs currently represent the most robust tool for dismantling disparities in care,” he added.

Team Approach

One message appears clearly in the consensus statement: Women’s CV health requires an approach that extends beyond the boundaries of a single specialty.

Primary care physicians remain central to this model because they serve as the first line of defense, identifying sex-specific risk factors and ensuring long-term follow-up.

The document also highlighted several interdisciplinary specialties that should be represented within WHCs.

Cardio-obstetrics focuses on preventing, detecting, and managing CV disease during pregnancy and the postpartum period, while also ensuring early identification and long-term assessment of CV risk among women with adverse pregnancy outcomes.

Cardio-oncology addresses women’s differing susceptibility to cardiotoxic effects associated with certain cancer therapies and the influence of hormonal changes across their lifespan.

Cardio-rheumatology aims to improve the early diagnosis and management of CV involvement in women with autoimmune rheumatic diseases, which are conditions that disproportionately affect women.

The consensus statement also recommends including specialists trained in transgender medicine to support individuals undergoing gender transition and mental health professionals to improve the recognition and management of anxiety, depression, and stress among women with CV disease. These conditions are substantially more common in women than in men and can significantly influence prognosis.

Gender Medicine

Ruffin noted that gender specific medicine is reshaping modern cardiology.

“The classic approach based solely on coronary angiography in clinical settings involving ischemia with nonobstructive coronary lesions or myocardial infarction with nonobstructive coronary lesions is insufficient. Today there is increasing emphasis on additional assessments, including evaluation of the coronary microcirculation and vascular reactivity,” he said.

He also highlighted changes in the interpretation of pregnancy-related CV risk.

“Obstetric complications such as preeclampsia and gestational diabetes should no longer be viewed as isolated events. They should be considered biological stress tests that show women at increased future CV risk,” he said.

Another important development is the growing effort to address the historical underrepresentation of women in clinical trials, which is essential for understanding the efficacy and safety of therapies in women.

Gender-specific medicine extends far beyond cardiology and increasingly influences nearly every area of healthcare.

In Italy, discussion on the topic began almost 30 years ago through initiatives supported by the Ministries of Equal Opportunities and Health, together with contributions from the Italian Medicines Agency, Italy’s National Agency for Regional Health Services, and the Italian National Institute of Health.

The Center of Excellence for Gender Medicine, established in 2017 as the first center of its kind in Europe, together with the Italian Research Center for Gender Health and Medicine and the Italian Group for Health and Gender, created the Italian Network for Gender Medicine.

The network was established to advance scientific research, promote education for physicians and healthcare professionals, and increase public awareness. This includes collaboration between universities and scientific societies, including the Italian Society of General Practice and Primary Care.

On June 13, 2019, Italy’s Ministry of Health formally approved the “Plan for the Implementation and Dissemination of Gender Medicine Nationwide. The initiative aims to apply a gender-based approach across the four areas specified in Law 3/2018: prevention, diagnosis, treatment, and rehabilitation pathways; research and innovation; education and training; and communication.”

Ruffin reported having no relevant conflicts of interest. 

This story was translated from Univadis Italy.