Stress and depression may affect cardiovascular (CV) health through biological, psychological, and social pathways, with sex and gender influencing vulnerability. During the 127th National Congress of the Italian Society of Internal Medicine (SIMI), held on October 2-4, 2026, Valeria Raparelli, MD, PhD, associate professor, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy, emphasized the importance of considering these factors when assessing CV risk.

Raparelli stressed that comprehensive patient care requires attention to psychological and social circumstances alongside physical health. Hippocrates recognized the influence of lifestyle and customs on health and the importance of considering the body and mind together, she noted. This principle remains relevant today, particularly in societies where daily life exposes individuals to substantial physical and psychological stress.

“As a physician working in today’s healthcare system, I am grateful to SIMI for the opportunity to discuss such an important and timely topic: the need to assess CV risk more broadly, taking a sex- and gender-specific approach,” Raparelli said.

As a member of the international, multidisciplinary Gender Outcomes International Group: to Further Well-being Development (GOING-FWD) research network, which is dedicated to integrating sex and gender dimensions into the study, prevention, and treatment of noncommunicable chronic diseases, Raparelli has worked to clarify the distinction between sex and gender, which are often used interchangeably despite referring to different concepts.

Gender is a non-biological variable that can be assessed and incorporated into research and clinical practice by collecting information across four main domains: identity, relationships, roles, and institutional factors. The latter encompasses how resources and opportunities are distributed according to gender within a particular culture or country.

Speaking to Univadis Italy, part of the Medscape Professional Network, Raparelli said, “Within the GOING-FWD network, we assessed CV risk datasets from several countries and found that the influence of gender varies by country and can have different associations with health outcomes. We cannot pretend to live in a bubble; our environment influences us.”

Sex and gender influence health throughout life. Research that focuses exclusively on the biological differences between men and women may overlook the contribution of gender to health outcomes. In line with this approach, SIMI published an article in 2022 outlining a roadmap for incorporating sex and gender considerations into clinical research.

CV Health Reflects Biology and Social Context

Gender is particularly relevant to CV disease, which remains one of the leading causes of death in both sexes but disproportionately affects women. In addition to biological and traditional CV risk factors, such as smoking and high blood pressure, women may face social and cultural factors that further increase their vulnerability.

Stress is another important contributor to CV disease. Stressors activate the corticolimbic system and other physiologic pathways, potentially contributing to disease development. The risk for adverse effects from excessive stress may be greater among women and individuals exposed to gender-related psychosocial and cultural factors, including low income and low educational attainment. These factors are also associated with depression, which affects 6% of the Italian population and is more prevalent among women. Women may be particularly vulnerable during certain life stages, including the postpartum and postmenopausal periods.

International data indicate that depression affects approximately 20% of individuals with CV disease. Raparelli noted that depression and CV disease share several pathophysiologic mechanisms.

“Oxidative stress, inflammation, alterations in cardiometabolic compensation, and hyperactivation of the sympathetic nervous system are some of the pathophysiological mechanisms shared by depression and CV disease. They create a bidirectional relationship that can reinforce itself in a vicious cycle,” she said.

The key message is that the brain, heart, and CV system are interconnected with biological, sex- and gender-specific, behavioral, psychological, and social factors that interact to influence CV health.

From Guidelines to Clinical Practice

Mental health should be an integral part of CV care. Clinical guidelines increasingly recognize the contribution of psychological and social factors to CV risk.

The European Society of Cardiology (ESC) guidelines on CV disease prevention, published in 2021, recognized psychosocial factors and mental disorders as risk modifiers. The 2024 guidelines on hypertension also included psychosocial and cultural factors, as well as stress, among the risk modifiers.

In 2025, the ESC consensus statement on mental and CV health reinforced this message, emphasizing the importance of screening patients for conditions that may affect their prognosis. Screening can be performed using simple, rapid tools such as the Patient Health Questionnaire-2. Raparelli emphasized that such tools can and should be used routinely in outpatient clinics.

However, a significant gap remains despite growing evidence on the role of sex and gender in CV health, and specific recommendations addressing these factors are still lacking. This highlights the gap between increasing awareness of the issue and its translation into practical clinical guidelines.

The collection of data on sex and gender, including sexual orientation and gender identity, remains uncommon in clinical practice. Misunderstandings regarding these concepts persist among both clinicians and patients, although progress is being made.

“The situation has improved since the Italian National Institute of Health established the National Observatory on Gender Medicine,” said Raparelli. Recently, she represented SIMI at a meeting of Italian scientific societies, where participants voted on recommendations to integrate sex and gender considerations across medical disciplines.

“These are small but important steps. We must remember that paradigm shifts of this magnitude take time,” she added, emphasizing the need to incorporate mental health screening tools into routine clinical practice and adopt a sex- and gender-specific approach to research.

Raparelli reported having no relevant conflicts of interest.

This story was translated from Univadis Italy.