CARAMEL Observational Study

NCT07695376 | Recruiting

• 1 other identifier: PI2025166 (PS)
• Study Type: observational
• Target: 3,000
• Locations: 5 countries
• Sites: 6

Brief Summary

CARAMEL is a project funded by the European Commission under the Horizon Europe programme. Its aim is to develop a personalized prevention approach based on state-of-the-art artificial intelligence models for cardiovascular risk stratification in women aged 40-60 years. These models are trained using large amounts of multi-source data and complemented by digital self-assessment and self-management tools. The CARAMEL consortium brings together a diverse group of 25 organizations, including technology companies and research centers, clinical institutions, as well as experts in ethics, law, and communication. The CARAMEL-OS study is an observational study aimed at prospectively completing the proposed personalized cardiovascular risk stratification model for women aged 40-60 years that will be developed during the earlier phases of the overall CARAMEL project (https://www.caramel-project.eu/). The study has a purely observational design, and patient stratification will not entail any clinical intervention. The data collected will be used to complete the design of the personalized stratification model, as well as to develop and validate the performance of the predictive models in an independent prospective cohort, distinct from the retrospective cohort initially used. The performance of the models developed using retrospective data will be assessed in terms of accuracy, discrimination, calibration, and other relevant metrics. In addition, the study will enable the development of new predictive models with short-term prediction horizons, incorporating additional variables that are not available retrospectively. The study population will be recruited in four European Union countries: Croatia, Spain (Andalusia and The Basque Country - Gipuzkoa), Greece and Lithuania; and in Colombia. A prospective cohort of 3,000 women aged 40-60 will be recruited, with each partner contributing 500 participants.

Conditions

Women (Between 30 to 60 Years Old); Cardiovascular Disease Risk Factor; Perimenopause; Menopause; Cardiovascular (CV) Risk; Artificial Intelligence (Al)

Keywords

Women-specific risk factors; Cardiovascular (CV) Risk; Perimenopause; Menopause; Prediction models; Patient reported outcomes (PROM)

Outcome Measures

Primary Outcomes (4)

• Incidence of hypertension

  Incidence of hypertension will be assessed by measuring blood pressure during the baseline and final study visits, as well as by reviewing the diagnosis of hypertension recorded in the electronic health records. Participants enrolled during a self-monitoring month will be asked to measure their blood pressure twice daily throughout 1 month.

  From enrollment to program completion, spanning 21-24 months depending on the enrollment date.

• Incidence of dyslipidaemia

  Incidence of dyslipidaemia will be assessed through blood tests measuring HDL cholesterol, LDL cholesterol, total cholesterol, and triglyceride levels at the baseline and final study visits, as well as by reviewing diagnoses of dyslipidaemia recorded in the electronic health records.

  From enrollment to program completion, lasting 21-24 months depending on the enrollment date.

• Incidence of diabetes mellitus

  Incidence of diabetes mellitus will be assessed through blood tests measuring glomerular filtration rate, albumin-to-creatinine ratio, glucose and glycated hemoglobin levels at the baseline and final study visits, as well as by reviewing diagnoses of diabetes mellitus recorded in the electronic health records.

  From enrollment to program completion, lasting 21-24 months depending on the enrollment date.

• Incidence of cardiovascular disease

  The incidence of cardiovascular disease will be assessed through the diagnosis of the following conditions: myocardial infarction, chronic coronary syndrome, peripheral arterial disease, and stroke. This information will be collected through a structured medical history interview and by reviewing the electronic health records. These data will be collected during the baseline visit and the final visit.

  From enrollment to program completion, spanning 21-24 months depending on the enrollment date.

Secondary Outcomes (1)

• Mortality of cardiovascular events.

  From enrollment to program completion, spanning 21-24 months depending on the enrollment date.

Study Arms (1)

3,000 women aged 40-60 recruited in four European Union countries and Colombia.

The study population will be recruited in five sites belonging to four European Union countries: Croatia, Spain (Andalusia and The Basque Country - Gipuzkoa), Greece and Lithuania; and one South America country that is Colombia. A prospective cohort of 3,000 women aged 40-60 will be recruited, with each partner contributing 500 participants.

Eligibility Criteria

• Age: 40 Years - 60 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The study population will be recruited in four European Union countries: Croatia, Spain (Andalusia and The Basque Country - Gipuzkoa), Greece and Lithuania; and in Colombia. A prospective cohort of 3,000 women aged 40-60 will be recruited, with each partner contributing 500 participants. Eligible women may be invited to participate by their regular healthcare provider or may express their interest independently. To maximize representativeness, information about the study will be disseminated via multiple communication channels, including social media platforms (e.g., LinkedIn, Facebook, Bluesky, X). Women who express interest will be contacted by the CARAMEL research team, and detailed study documentation will be provided.

You may qualify if:

• Women 40 to 60 years of age, at recruitment.
• Ability to understand and complete the required informed consent for the study.
• Women who are covered by the corresponding healthcare system operating at each clinical site.

You may not qualify if:

• Severe comorbidity with less than 24 months life expectancy.
• Lack of basic digital skills to use or carry a smartphone and wearable devices.

Sponsors & Collaborators

• Biogipuzkoa Health Research Institute: lead
• Keralty SAS: collaborator
• Particle Summary: collaborator
• iBreve Limited: collaborator
• Magdalena Clinic: collaborator
• Andaluz Health Service: collaborator
• Asociación Centro de Investigación Cooperativa en Biociencias: collaborator
• Fundación Centro de Tecnologías de Interacción Visual y Comunicaciones Vicomtech: collaborator
• AE. Fundación Pública Andaluza para la gestión de la investigación en salud de Sevilla: collaborator
• Viesoji Istaiga Vilniaus Universiteto Ligonine Santaros Klinikos: collaborator
• Ulma Medical Technologies S Coop: collaborator
• Smartnanosenose Innovation: collaborator
• ETHNIKO KAI KAPODISTRIAKO PANEPISTIMIO ATHINON: collaborator

Study Sites (6)

Keralty SAS

Bogotá, Colombia

NOT YET RECRUITING

Magdalena - Klinika Za Kardiovaskularne Bolesti Medicinskog Fakultetasveucilista J.J. Strossmayera U Osijeku Ustanova

Krapinske Toplice, Croatia

NOT YET RECRUITING

Ethniko Kai Kapodistriako Panepistimio Athinon

Athens, Greece

RECRUITING

Viesoji Istaiga Vilniaus Universiteto Ligonine Santaros Klinikos

Vilnius, Lithuania

NOT YET RECRUITING

Biogipuzkoa Health Research Institute

San Sebastián, Spain

RECRUITING

Fundacion Para La Gestion de La Investigacion En Salud de Sevilla

Seville, Spain

RECRUITING

Related Publications (38)

• Mazzolai L, Teixido-Tura G, Lanzi S, Boc V, Bossone E, Brodmann M, Bura-Riviere A, De Backer J, Deglise S, Della Corte A, Heiss C, Kaluzna-Oleksy M, Kurpas D, McEniery CM, Mirault T, Pasquet AA, Pitcher A, Schaubroeck HAI, Schlager O, Sirnes PA, Sprynger MG, Stabile E, Steinbach F, Thielmann M, van Kimmenade RRJ, Venermo M, Rodriguez-Palomares JF; ESC Scientific Document Group. 2024 ESC Guidelines for the management of peripheral arterial and aortic diseases. Eur Heart J. 2024 Sep 29;45(36):3538-3700. doi: 10.1093/eurheartj/ehae179. No abstract available.

  PMID: 39210722 BACKGROUND

• Vrints C, Andreotti F, Koskinas KC, Rossello X, Adamo M, Ainslie J, Banning AP, Budaj A, Buechel RR, Chiariello GA, Chieffo A, Christodorescu RM, Deaton C, Doenst T, Jones HW, Kunadian V, Mehilli J, Milojevic M, Piek JJ, Pugliese F, Rubboli A, Semb AG, Senior R, Ten Berg JM, Van Belle E, Van Craenenbroeck EM, Vidal-Perez R, Winther S; ESC Scientific Document Group. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J. 2024 Sep 29;45(36):3415-3537. doi: 10.1093/eurheartj/ehae177. No abstract available.

  PMID: 39210710 BACKGROUND

• Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol. 2018 Oct 30;72(18):2231-2264. doi: 10.1016/j.jacc.2018.08.1038. Epub 2018 Aug 25. No abstract available.

  PMID: 30153967 BACKGROUND

• American Diabetes Association Professional Practice Committee. 1. Improving Care and Promoting Health in Populations: Standards of Care in Diabetes-2025. Diabetes Care. 2025 Jan 1;48(1 Suppl 1):S14-S26. doi: 10.2337/dc25-S001.

  PMID: 39651974 BACKGROUND

• Cherla A, Kyriopoulos I, Pearcy P, Tsangalidou Z, Hajrulahovic H, Theodorakis P, Andersson CE, Mehra MR, Mossialos E. Trends in avoidable mortality from cardiovascular diseases in the European Union, 1995-2020: a retrospective secondary data analysis. Lancet Reg Health Eur. 2024 Sep 27;47:101079. doi: 10.1016/j.lanepe.2024.101079. eCollection 2024 Dec.

  PMID: 39397877 BACKGROUND

• McCarthy CP, Bruno RM, McEvoy JW, Touyz RM. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension: what is new in pharmacotherapy? Eur Heart J Cardiovasc Pharmacother. 2025 Feb 8;11(1):7-9. doi: 10.1093/ehjcvp/pvae084. No abstract available.

  PMID: 39439212 BACKGROUND

• Rajput D, Wang WJ, Chen CC. Evaluation of a decided sample size in machine learning applications. BMC Bioinformatics. 2023 Feb 14;24(1):48. doi: 10.1186/s12859-023-05156-9.

  PMID: 36788550 BACKGROUND

• Kouz K, Monge Garcia MI, Cerutti E, Lisanti I, Draisci G, Frassanito L, Sander M, Ali Akbari A, Frey UH, Grundmann CD, Davies SJ, Donati A, Ripolles-Melchor J, Garcia-Lopez D, Vojnar B, Gayat E, Noll E, Bramlage P, Saugel B. Intraoperative hypotension when using hypotension prediction index software during major noncardiac surgery: a European multicentre prospective observational registry (EU HYPROTECT). BJA Open. 2023 May 4;6:100140. doi: 10.1016/j.bjao.2023.100140. eCollection 2023 Jun.

  PMID: 37588176 BACKGROUND

• Lopez-Lopez JP, Garcia-Pena AA, Martinez-Bello D, Gonzalez AM, Perez-Mayorga M, Munoz Velandia OM, Ruiz-Uribe G, Campo A, Rangarajan S, Yusuf S, Lopez-Jaramillo P. External validation and comparison of six cardiovascular risk prediction models in the Prospective Urban Rural Epidemiology (PURE)-Colombia study. Eur J Prev Cardiol. 2025 May 12;32(7):564-572. doi: 10.1093/eurjpc/zwae242.

  PMID: 39041366 BACKGROUND

• SCORE2-Diabetes Working Group and the ESC Cardiovascular Risk Collaboration. SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe. Eur Heart J. 2023 Jul 21;44(28):2544-2556. doi: 10.1093/eurheartj/ehad260.

  PMID: 37247330 BACKGROUND

• Goldenholz DM, Sun H, Ganglberger W, Westover MB. Sample Size Analysis for Machine Learning Clinical Validation Studies. Biomedicines. 2023 Feb 23;11(3):685. doi: 10.3390/biomedicines11030685.

  PMID: 36979665 BACKGROUND

• Powell-Wiley TM, Baumer Y, Baah FO, Baez AS, Farmer N, Mahlobo CT, Pita MA, Potharaju KA, Tamura K, Wallen GR. Social Determinants of Cardiovascular Disease. Circ Res. 2022 Mar 4;130(5):782-799. doi: 10.1161/CIRCRESAHA.121.319811. Epub 2022 Mar 3.

  PMID: 35239404 BACKGROUND

• NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021 Sep 11;398(10304):957-980. doi: 10.1016/S0140-6736(21)01330-1. Epub 2021 Aug 24.

  PMID: 34450083 BACKGROUND

• SCORE2 working group and ESC Cardiovascular risk collaboration. SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. Eur Heart J. 2021 Jul 1;42(25):2439-2454. doi: 10.1093/eurheartj/ehab309.

  PMID: 34120177 BACKGROUND

• Liu W, Laranjo L, Klimis H, Chiang J, Yue J, Marschner S, Quiroz JC, Jorm L, Chow CK. Machine-learning versus traditional approaches for atherosclerotic cardiovascular risk prognostication in primary prevention cohorts: a systematic review and meta-analysis. Eur Heart J Qual Care Clin Outcomes. 2023 Jun 21;9(4):310-322. doi: 10.1093/ehjqcco/qcad017.

  PMID: 36869800 BACKGROUND

• Ballena-Caicedo J, Zuzunaga-Montoya FE, Loayza-Castro JA, Vasquez-Romero LEM, Tapia-Limonchi R, De Carrillo CIG, Vera-Ponce VJ. Global prevalence of dyslipidemias in the general adult population: a systematic review and meta-analysis. J Health Popul Nutr. 2025 Aug 26;44(1):308. doi: 10.1186/s41043-025-01054-3.

  PMID: 40859400 BACKGROUND

• Hanley JA, McNeil BJ. A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology. 1983 Sep;148(3):839-43. doi: 10.1148/radiology.148.3.6878708.

  PMID: 6878708 BACKGROUND

• Diabetes Atlas. Country [Internet]. 2025 [cited 2025 Nov 1]. Available from: https://diabetesatlas.org/data-by-location/country/

  BACKGROUND

• Evolución de la prevalencia de la diabetes mellitus en España (1999-2014) - ClinicalKey [Internet]. 2018 [cited 2025 Nov 1]. Available from: https://www.clinicalkey.es/#!/content/playContent/1-s2.0-S253001641830171X?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS253001641830171X%3Fshowall%3Dtrue&referrer=

  BACKGROUND

• Banegas JR, Sanchez-Martinez M, Gijon-Conde T, Lopez-Garcia E, Graciani A, Guallar-Castillon P, Garcia-Puig J, Rodriguez-Artalejo F. Numerical values and impact of hypertension in Spain. Rev Esp Cardiol (Engl Ed). 2024 Sep;77(9):767-778. doi: 10.1016/j.rec.2024.03.011. Epub 2024 May 1. English, Spanish.

  PMID: 38701882 BACKGROUND

• Samplingbook package - RDocumentation [Internet]. 2025 [cited 2025 Nov 1]. Available from: https://www.rdocumentation.org/packages/samplingbook/versions/1.2.4

  BACKGROUND

• Front matter. In: Sample size tables for clinical studies [Internet]. Chichester: John Wiley & Sons, Ltd; 2008 [cited 2025 Nov 1]. p. i-viii. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/9781444300710.fmatter

  BACKGROUND

• James G, Witten D, Hastie T, Tibshirani R. An introduction to statistical learning: with applications in R [Internet]. New York (NY): Springer US; 2021 [cited 2025 Nov 1]. (Springer Texts in Statistics). Available from: https://link.springer.com/10.1007/978-1-0716-1418-1

  BACKGROUND

• Gholamy A, Kreinovich V, Kosheleva O. Why 70/30 or 80/20 relation between training and testing sets: a pedagogical explanation [Internet]. Departmental Technical Reports (CS); 2018 [cited 2025 Nov 1]. Available from: https://www.scirp.org/reference/referencespapers?referenceid=3324183

  BACKGROUND

• Hotter GJ. [Severe forms of tuberculosis observed during the past year (author's transl)]. Prax Klin Pneumol. 1979 Apr;33 Suppl 1:582-6. German.

  PMID: 461350 BACKGROUND

• Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA, Graham IM, Halliday A, Landmesser U, Mihaylova B, Pedersen TR, Riccardi G, Richter DJ, Sabatine MS, Taskinen MR, Tokgozoglu L, Wiklund O; ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020 Jan 1;41(1):111-188. doi: 10.1093/eurheartj/ehz455. No abstract available.

  PMID: 31504418 BACKGROUND

• Homepage | Globorisk [Internet]. [cited September 14, 2025]. Available at: https://www.globorisk.org/

  BACKGROUND

• WHO updates Cardiovascular Risk Charts [Internet]. [cited September 14, 2025]. Available at: https://www.who.int/news/item/02-09-2019-who-updates-cardiovascular-risk-charts

  BACKGROUND

• DANE - Vital statistics: births and deaths [Internet]. [cited September 14, 2025]. Available at: https://www.dane.gov.co/index.php/estadisticas-por-tema?id=34&phpMyAdmin=3om27vamm65hhkhrtgc8rrn2g4

  BACKGROUND

• Ashina M, Mitsikostas DD, Amin FM, Kokturk P, Schankin CJ, Sahin G, Pozo-Rosich P, Dorman PJ, Nezadal T, Poole AC, Martins IP, Sumelahti ML, Ramirez Campos V, Ahn AH, Lyras L, Tassorelli C. Real-world effectiveness of fremanezumab for the preventive treatment of migraine: Interim analysis of the pan-European, prospective, observational, phase 4 PEARL study. Cephalalgia. 2023 Nov;43(11):3331024231214987. doi: 10.1177/03331024231214987.

  PMID: 37987641 BACKGROUND

• Savulescu C, Krizova P, Valentiner-Branth P, Ladhani S, Rinta-Kokko H, Levy C, Mereckiene J, Knol M, Winje BA, Ciruela P, de Miguel S, Guevara M, MacDonald L, Kozakova J, Slotved HC, Fry NK, Pekka Nuorti J, Danis K, Corcoran M, van der Ende A, Vestrheim DF, Munoz-Almagro C, Sanz JC, Castilla J, Smith A, Colzani E, Pastore Celentano L, Hanquet G; SpIDnet VE study group. Effectiveness of 10 and 13-valent pneumococcal conjugate vaccines against invasive pneumococcal disease in European children: SpIDnet observational multicentre study. Vaccine. 2022 Jun 23;40(29):3963-3974. doi: 10.1016/j.vaccine.2022.05.011. Epub 2022 May 28.

  PMID: 35637067 BACKGROUND

• Balki I, Amirabadi A, Levman J, Martel AL, Emersic Z, Meden B, Garcia-Pedrero A, Ramirez SC, Kong D, Moody AR, Tyrrell PN. Sample-Size Determination Methodologies for Machine Learning in Medical Imaging Research: A Systematic Review. Can Assoc Radiol J. 2019 Nov;70(4):344-353. doi: 10.1016/j.carj.2019.06.002. Epub 2019 Sep 12.

  PMID: 31522841 BACKGROUND

• Bell KJL, White S, Hassan O, Zhu L, Scott AM, Clark J, Glasziou P. Evaluation of the Incremental Value of a Coronary Artery Calcium Score Beyond Traditional Cardiovascular Risk Assessment: A Systematic Review and Meta-analysis. JAMA Intern Med. 2022 Jun 1;182(6):634-642. doi: 10.1001/jamainternmed.2022.1262.

  PMID: 35467692 BACKGROUND

• Refaee MA, Al-Absi HRH, Islam MT, Househ M, Shah Z, Rahman MS, Alam T. The Linkage Between Bone Densitometry and Cardiovascular Disease. Stud Health Technol Inform. 2022 Jan 14;289:244-247. doi: 10.3233/SHTI210905.

  PMID: 35062138 BACKGROUND

• Kuller L, Arnold A, Tracy R, Otvos J, Burke G, Psaty B, Siscovick D, Freedman DS, Kronmal R. Nuclear magnetic resonance spectroscopy of lipoproteins and risk of coronary heart disease in the cardiovascular health study. Arterioscler Thromb Vasc Biol. 2002 Jul 1;22(7):1175-80. doi: 10.1161/01.atv.0000022015.97341.3a.

  PMID: 12117734 BACKGROUND

• Georgiopoulos G, Mavraganis G, Delialis D, Georgiou S, Aivalioti E, Patras R, Petropoulos I, Dimopoulou MA, Angelidakis L, Sianis A, Bampatsias D, Dimoula A, Maneta E, Kosmopoulos M, Vardavas C, Stellos K, Stamatelopoulos K. Carotid ultrasonography improves residual risk stratification in guidelines-defined high cardiovascular risk patients. Eur J Prev Cardiol. 2022 Oct 18;29(13):1773-1784. doi: 10.1093/eurjpc/zwac095.

  PMID: 35580589 BACKGROUND

• Den Ruijter HM, Peters SA, Anderson TJ, Britton AR, Dekker JM, Eijkemans MJ, Engstrom G, Evans GW, de Graaf J, Grobbee DE, Hedblad B, Hofman A, Holewijn S, Ikeda A, Kavousi M, Kitagawa K, Kitamura A, Koffijberg H, Lonn EM, Lorenz MW, Mathiesen EB, Nijpels G, Okazaki S, O'Leary DH, Polak JF, Price JF, Robertson C, Rembold CM, Rosvall M, Rundek T, Salonen JT, Sitzer M, Stehouwer CD, Witteman JC, Moons KG, Bots ML. Common carotid intima-media thickness measurements in cardiovascular risk prediction: a meta-analysis. JAMA. 2012 Aug 22;308(8):796-803. doi: 10.1001/jama.2012.9630.

  PMID: 22910757 BACKGROUND

• Vogel B, Acevedo M, Appelman Y, Bairey Merz CN, Chieffo A, Figtree GA, Guerrero M, Kunadian V, Lam CSP, Maas AHEM, Mihailidou AS, Olszanecka A, Poole JE, Saldarriaga C, Saw J, Zuhlke L, Mehran R. The Lancet women and cardiovascular disease Commission: reducing the global burden by 2030. Lancet. 2021 Jun 19;397(10292):2385-2438. doi: 10.1016/S0140-6736(21)00684-X. Epub 2021 May 16.

  PMID: 34010613 BACKGROUND

Related Links

• CARAMEL project website, which provides general information, updates on the project's development, non-confidential results, information about the consortium members, among other relevant content.

Biospecimen

Retention: SAMPLES WITH DNA

A maximum of three 500 µL serum aliquots per participant will be retained. The number of aliquots retained will depend on the number of repeat measurements required for each participant, as these aliquots will consist solely of the remaining material from the study-related analyses. If participants have provided consent for sample retention in the signed informed consent form (ICF), the remaining samples will be stored at -80°C. The use of these samples will be pseudonymized and may extend beyond the scope of the present study for future scientific research projects related to cardiovascular health, metabolic diseases, and women's health.

Central Study Contacts

Primary Care - OSIs Research Unit

CONTACT

(+34)943006086; unidadinvestigaciongip@osakidetza.eus

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 24 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2026
• First Posted: July 10, 2026
• Study Start: March 16, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: July 10, 2026

Record last verified: 2026-07

Locations

CR (1); ES (2); GR (1); CO (1); LI (1)