Women’s health: an imAging-based cardiovascular risK-rEdUction Program (WAKE UP) study. Rationale and design.

Leticia Fernandez ^1* Samantha Wasniewski ¹ Rafaella Kfouri ¹ Sofia Capdevilla ¹ Isabel Rivera ¹ Elena Virosta ¹ Carolina Ortiz ² Pablo Diez-Villanueva ³ Antonio Adeba ⁴ Alberto Cordero ⁵ Marta Ruiza Lera ⁶ David Alonso ⁷ Rocio Tarifa ⁸ Alessia Ferrarini ^8,9 Josué Pagán ^10,11 José Ayala ⁹ Jorge Solis ¹² Malissa Wood ¹³ Blanca Miranda ¹⁴ Luis Padial ¹⁵

• ¹ HM Madrid Hospital, Madrid, Spain
• ² Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain
• ³ Fundación Biomédica, Hospital de La Princesa, Madrid, Catalonia, Spain
• ⁴ University Hospital of Cabueñes, Gijón, Spain
• ⁵ Hospital General Universitario de Alicante, Alicante, Spain
• ⁶ Marqués de Valdecilla University Hospital, Santander, Cantabria, Spain
• ⁷ Hospital de León, León, Spain
• ⁸ Spanish National Centre for Cardiovascular Research, Madrid, Catalonia, Spain
• ⁹ Escuela Técnica Superior de Ingeniería de Telecomunicación, Universidad Politécnica de Madrid., Madrid, Madrid, Spain
• ¹⁰ Universidade Politecnica, Maputo, Mozambique
• ¹¹ Universidad Politecnica, Madrid, Spain
• ¹² Fundación Investigación Biomédica Hospital 12 de Octubre, Madrid, Catalonia, Spain
• ¹³ Mass General Weight Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
• ¹⁴ Spanish Society of Cardiology, madrid, Spain
• ¹⁵ Toledo University Hospital, Toledo, Spain

Background: Cardiovascular (CV) disease is the leading cause of death in women. Although 80% of CV disease events can be prevented, mortality is projected to increase, particularly in young women. Objectives: To promote CV health in women and encourage appropriate lifestyle changes by increasing awareness through vascular ultrasound imaging. Methods: WAKE UP is a prospective case-control study in a target population of 720 asymptomatic women, aged 40-70 years with ≥1 major CV risk factor (RF). Participants will attend a baseline visit and follow-up visits at 6 and 12-months. Each visit will include the assessment of traditional and non-traditional risk factors (age, blood pressure, weight, smoking, diet, physical activity, psychosocial aspects, reproductive factors, family lifestyle), CV risk scores [Fuster-BEWAT Score (FBS) and SCORE], perception of CV disease risk, blood sampling of hormones, lipids, glycemic metabolism, inflammation parameters and omics. At baseline visit, women will be randomized to undergo 2D/3D/strain vascular ultrasound (360 with imaging vs 360 age- and RF-matched controls without imaging). Main outcomes will include changes from baseline to follow-up in overall knowledge, attitudes, and FBS. Conclusions: WAKE UP trial aims to raise awareness about women´s CV disease and promote lifestyle changes. Imaging can play a key role by revealing the presence of atherosclerotic plaques in a directly relatable way and thus, larger effects are anticipated in women with plaques. WAKE UP can significantly impact CV prevention by involving innovative actions addressing a major public health need and by fostering complementary and synergistic actions.