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In industrialized populations, systolic blood pressure (SBP) typically increases with age while diastolic BP (DBP) increases in childhood, adolescence, and young adulthood, plateaus in middle age, and declines after age 60 years.1 Such accruing differences may manifest as isolated systolic hypertension, resulting in increasing pulse pressure (PP), a surrogate for arterial stiffness.1 Highlighting the clinical relevance of PP, the Framingham Study demonstrated that PP, rather than SBP or DBP, is the best predictor of cardiovascular events in people over 60 years of age. Cardiovascular disease and hypertension have traditionally been cast as uncommon in adults with Down’s syndrome (DS), despite their tendency to higher weight, limited moderate-to-vigorous physical activity, and evidence of inflammation. UK Clinical Practice Research Datalink data support this lower risk.2 We leveraged the TriNetX electronic health record research network and longitudinal models (Supplementary Appendix) to assess relations of SBP, DBP, and PP with age in 5-year intervals, sex, race, and BMI.

In industrialized populations, systolic blood pressure (SBP) typically increases with age while diastolic BP (DBP) increases in childhood, adolescence, and young adulthood, plateaus in middle age, and declines after age 60 years.1 Such accruing differences may manifest as isolated systolic hypertension, resulting in increasing pulse pressure (PP), a surrogate for arterial stiffness.1 Highlighting the clinical relevance of PP, the Framingham Study demonstrated that PP, rather than SBP or DBP, is the best predictor of cardiovascular events in people over 60 years of age. Cardiovascular disease and hypertension have traditionally been cast as uncommon in adults with Down’s syndrome (DS), despite their tendency to higher weight, limited moderate-to-vigorous physical activity, and evidence of inflammation. UK Clinical Practice Research Datalink data support this lower risk.2 We leveraged the TriNetX electronic health record research network and longitudinal models (Supplementary Appendix) to assess relations of SBP, DBP, and PP with age in 5-year intervals, sex, race, and BMI. BP data were available for 20,831 adults aged ≥20 years [49% male; first encounter median (IQR) age: 34years (23-48) and BMI: 29.5kg/m2 (25-35)]. Demographics approximated the limited available estimates for adults with DS (Supplementary Table). SBP increased marginally with advancing age while DBP did not differ by >2mmHg for any age group compared with 20-24.9y (see Figure). Similarly, PP was slightly higher with advancing age. SBP, DBP, and PP were slightly higher in male patients and positively associated with BMI.

for adults with DS (Supplementary Table). SBP increased marginally with advancing age while DBP did not differ by >2mmHg for any age group compared with 20-24.9y (see Figure). Similarly, PP was slightly higher with advancing age. SBP, DBP, and PP were slightly higher in male patients and positively associated with BMI. Providing further compelling evidence for a unique CV phenotype in DS, SBP and PP were normal across the lifespan, despite the fact that short stature is typical among persons with DS. In contrast, in the general population, shorter stature is associated with higher SBP and CVD.3 The mechanisms underlying these observations are unclear. Blunted sympathetic activity and responsiveness are present in persons with DS during exercise and may offer protection against arterial stiffening;4 this mechanism appears operative in adults with monogenic MC4R-related obesity in whom hypertension risk is reduced and sympathetic activity dampened.5 Given that stiffness in large arteries promotes atherosclerosis, the current findings may explain the apparent protection from atheroma in persons with DS. Better understanding of the cardiovascular phenotype of DS is critical to plan screening in patients with DS and management practices. Indeed, while ischemic heart disease rates may be lower in DS, intersections with common DS-related comorbidities such as obstructive sleep apnea and dementia remain undefined. Further, findings in DS patients potentially provide insight into hypertension development in the general population.

and management practices. Indeed, while ischemic heart disease rates may be lower in DS, intersections with common DS-related comorbidities such as obstructive sleep apnea and dementia remain undefined. Further, findings in DS patients potentially provide insight into hypertension development in the general population. Our data confirm SBP and PP increases with increasing BMI, but only increases modestly with age,1 and unexpectedly, shows a minimal sex-effect in a large dataset with demographics comparable to estimates for the US adult population with DS.