Sex differences in cardiovascular disease and dysregulation in Down syndrome

Abstract

This meta-analysis, which consisted of a scoping review and retrospective medical record review, is focused on potential sex differences in cardiovascular diseases in patients with Down syndrome. We limited our review to peer-reviewed, primary articles in the English language, in the PubMed and Web of Science databases from 1965 to 2021. Guidelines for scoping reviews were followed throughout the process. Four categorical domains were identified and searched using additional keywords: 1) congenital heart disease, 2) baseline physiology and risk factors, 3) heart disease and hypertension, and 4) stroke and cerebrovascular disease. Articles were included if they reported male and female distinct data, participants with Down syndrome, and one of our keywords. The retrospective medical record review was completed using 75 participating health care organizations to identify the incidence of congenital and cardiovascular diseases and to quantify cardiovascular risk factors in male and female patients. Female patients with Down syndrome are at higher risk of hypertension, ischemic heart disease, and cerebrovascular disease. The risk of congenital heart disease is higher in males with Down syndrome at all ages included in our analyses. Some of the male-to-female sex differences in cardiovascular disease risk in the general patient population are not present, or reversed in the Down syndrome population. This information should be considered for future investigations and ongoing patient care.NEW & NOTEWORTHY In patients with Down syndrome (DS), CHD is the leading cause of death <20 yr old and cardiovascular disease is a leading cause of death in individuals >20 yr old. Men with DS live longer than women. It is unknown if sex differences are present in cardiovascular disease and dysregulation in DS across the lifespan. We observed higher risk of hypertension, ischemic heart disease, and cerebrovascular disease in females and a higher risk of CHD in males with DS.

Keywords: Down syndrome; Moyamoya; blood pressure; cardiovascular physiology; congenital heart disease; heart rate; trisomy 21.

Figure 1.

Diagram depicting the search terms included in the scoping literature search process. Searches of PubMed and Web of Science were completed in June 2021 to evaluate potential sex differences in 4 categorical domains. Image was created using a licensed version of BioRender.

Figure 2.

Results of the systematic literature search, indicating the number of papers retained for inclusion at each step. n₁ = search 1, n₂ = search 2. Following the initial search, publications were excluded that were 1) duplicates across the searches (i.e., detected in PubMed and Web of Science), 2) case studies or reviews, 3) duplicates across domain topics, and 4) did not statistically evaluate potential male/female differences or interactions. *For the Heart Disease and Hypertension domain, 1 additional publication was excluded (15), as it appeared to have the same data set as another publication in the domain. The final count for this domain was ultimately 4. Image was created using a licensed version of BioRender.