Cardiovascular disease is the leading cause of death in women, yet risk is systematically underestimated and preventive interventions are often initiated too late. Women are disproportionately affected by obesity, diabetes, and smoking, but they also derive greater cardioprotective benefit from physical activity, reaching near-maximal protection at approximately half the exercise dose required in men. FEM-HEART targets a critical pre-clinical window by testing whether a personalized app-based intervention and a supervised face-to-face lifestyle program, both integrating tailored exercise, nutrition, and stress reduction, can improve early cardiovascular risk profiles in high-risk women during the peri- and postmenopausal transition.

In this prospective randomized controlled trial embedded in routine preventive care at SVS Gesundheitszentrum, 605 women will be randomized to a digital arm, a supervised intervention arm, or an untreated control group. The study will evaluate whether digital and supervised delivery formats differ in their ability to modify early cardiovascular trajectories before overt disease onset.

By targeting this modifiable pre-clinical phase, FEM-HEART shifts cardiovascular prevention from reactive care to proactive, sex-specific risk reduction and lays the foundation for scalable, woman-centered prevention strategies.

Inclusion Criteria:Eligible participants will be women aged >35 years in the perimenopausal transition or within 5 years after menopause and 35 years and in the perimenopausal transition (A) or within five years after menopause and younger than 65 years (B). In addition, all must meet at least two of three predefined risk profiles: (i) established cardiovascular risk factors, such as hypertension, dyslipidemia, overweight, or smoking; (ii) female-specific and hormone-related factors, such as pregnancy-associated complications or early menarche; and (iii) elevated psychosocial stress, assessed by validated questionnaires and physiological proxies.

Exclusion Criteria: include high levels of physical activity, hormone replacement therapy, and major comorbidities such as diabetes, moderate-to-severe kidney or liver disease, malignant tumors, musculoskeletal or neurological conditions limiting mobility, congenital heart defects, prior cardiac events, or a history of thrombosis.

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