University of São Paulo Medical School (FMUSP) 

This project will investigate cardiometabolic risk factors and early markers of subclinical atherosclerosis in adults with classic CAH by integrating advanced imaging techniques (abdominal CT and pulse wave velocity) with sensitive biochemical markers of cardiovascular health, including in- vitro HDL functionality. By correlating these findings with cumulative glucocorticoid exposure, treatment adherence, and androgen control, we aim to identify predictors of cardiovascular disease across different treatment profiles. These insights will help shape safer therapeutic regimens, refine long-term management, and guide the development of tailored cardiovascular monitoring strategies.
To overcome existing gaps in Brazilian CAH care, the project incorporates innovative methodologies never applied to this population, including advanced HDL functionality analysis and pulse wave velocity (PWV). These tools detect subtle and early cardiovascular alterations that routine clinical markers often miss.
HDL functionality analysis is especially relevant: serum HDL levels do not reflect the true protective actions of the particle. In CAH, hormonal imbalance and prolonged glucocorticoid exposure may impair cholesterol efflux capacity, antioxidant and anti-inflammatory activity, and anti- aggregant/anti-apoptotic functions. The in-vitro assessment of these mechanisms using cultured mouse macrophages enables the detection of early metabolic and vascular abnormalities that precede dyslipidemia or clinical disease. This methodology has never before been performed in individuals with CAH, representing a novel contribution to the field.
Pulse wave velocity (PWV) provides a complementary perspective by assessing arterial stiffness, a reliable, non-invasive predictor of future cardiovascular events. Adults with CAH may experience accelerated vascular aging due to glucocorticoid therapy, altered body composition, or low-grade inflammation, even when routine tests appear normal. PWV therefore offers a deeper understanding of early vascular changes and supports precise risk stratification. 

Beyond its scientific contributions, the project responds to important public health needs. Limited access to specialized care and significant regional disparities persist across Brazil, while emerging therapies, such as modified-release hydrocortisone, CRF1 antagonists, and adrenal-targeted agents, remain inaccessible to many. By generating robust national evidence on cardiovascular outcomes, elucidating the consequences of chronic glucocorticoid exposure, and demonstrating the clinical benefits of physiologic glucocorticoid replacement, the study will provide crucial support for the inclusion of hydrocortisone in Brazil’s list of essential medications and reinforce ongoing discussions with the Ministry of Health regarding stable national distribution.
Furthermore, the findings of this project may strengthen the rationale for adopting more effective and accessible therapeutic options in the future, ultimately improving long-term outcomes for children and adults living with CAH across Brazil.
Finally, findings will be translated into educational materials, clearer clinical guidance, and self-management tools designed to empower patients, families and support clinicians. Results will be disseminated at national and international scientific meetings, increasing visibility for the Brazilian CAH experience, and community initiatives will be expanded to promote equitable, long-term care throughout Brazil.