CArdiometabolic riSk and Comorbidities in Adults with Down syndrome- Electronic Health Record Examination (CASCADE)

Despite their well-recognized increased risk of overweight and obesity, adults with Down syndrome (DS) have not traditionally been considered at increased risk for “cardiometabolic” conditions such as Type 2 diabetes (T2D) and atheromatous disease. Recent robust epidemiologic data from the UK Clinical Practice Research Datalink suggest adolescence and young adulthood are specific periods of vulnerability for T2D development in this population. Overweight and obesity are clear risk factors, but their intersection with both DS-related co-morbidities [obstructive sleep apnea (OSA), congenital heart defects (CHD), dementia, hypogonadism, cancer survivorship] and demographics [race/ethnicity, aging] recognized to confer increased cardiometabolic risk (CMR) remain undefined. An improved understanding of CMR as well as potentially cardioprotective factors in a large, diverse population of individuals with DS is crucial for defining screening practices and interventions that minimize patient burden while considering the relevance of both traditional T2D complications and the intersection of CMR with established DS- related co-morbidities. This study will leverage de-identified data from a large, Research diverse population of adults with DS captured in the TriNetX Network of multiple health care organizations to 1) describe the prevalence of T2D, dyslipidemia, hypertension, OSA as well quantify HbA1C and lipids (HDL, LDL, TC, TG) by 5-year intervals; 2) examine the relationships of T2D, atheromatous disease, and dyslipidemia with common co-occurring condition in adults with DS (history of CHD, overweight/obesity, OSA, psychiatric medication prescription, dementia, menopause, cancer survivorship) and demographics (age, sex, race/ethnicity), 3) explore microvascular complications in the subset of patients with diabetes and 4) quantify screening practices for co-occurring conditions in adults with DS. This large database effort performed in a diverse, national population of adults with DS will advance our understanding of the prevalence of CMR, vascular complications, and cardiovascular risk factors in DS, a critical step for developing screening guidelines and targeted interventions that minimize patient burden without compromising care. This work will serve as the foundation for a longitudinal study aimed at defining the relevance of T2D and CMR for individuals with DS and to develop interventions to optimize screening for co-occurring conditions. Project Number: 1R03HL181717-01 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: ANDREA KELLY | Institution: CHILDREN'S HOSP OF PHILADELPHIA, PHILADELPHIA, PA | Award Amount: $370,096 | Activity Code: R03 | Study Section: Special Emphasis Panel[ZRG1 IVBH-A (56)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R03HL18171701