Modest Blood Pressure Increase with Age in Adults with Down’s Syndrome

In contrast to the general population, where systolic blood pressure (SBP) rises with age and diastolic blood pressure (DBP) declines after middle age, increasing pulse pressure (PP) as a marker of arterial stiffness, adults with Down’s syndrome (DS) exhibit minimal age-related increases in SBP and PP despite risk factors such as obesity. Analysis of electronic health records (TriNetX) from 20,831 U.S. adults with DS (median age 34 years; median BMI 29.5 kg/m²) revealed marginal increases in median SBP and PP with age and BMI, while DBP remained stable (≤2 mm Hg variation across age groups). Men showed slightly higher SBP, DBP, and PP, though sex differences were minimal. Despite short stature—a known hypertension risk factor in the general population—individuals with DS maintained normal SBP and PP across all ages, suggesting a unique cardiovascular phenotype. Blunted sympathetic activity, analogous to mechanisms observed in monogenic obesity (e.g., *MC4R* mutations), may protect against arterial stiffening, potentially explaining reduced atherosclerosis risk in DS. These findings underscore the need for tailored clinical management and highlight DS as a model for understanding hypertension mechanisms, particularly interactions with coexisting conditions like obstructive sleep apnea.  

In contrast to the general population, where systolic blood pressure (SBP) rises with age and diastolic blood pressure (DBP) declines after middle age, increasing pulse pressure (PP) as a marker of arterial stiffness, adults with Down’s syndrome (DS) exhibit minimal age-related increases in SBP and PP despite risk factors such as obesity. Analysis of electronic health records (TriNetX) from 20,831 U.S. adults with DS (median age 34 years; median BMI 29.5 kg/m²) revealed marginal increases in median SBP and PP with age and BMI, while DBP remained stable (≤2 mm Hg variation across age groups). Men showed slightly higher SBP, DBP, and PP, though sex differences were minimal. Despite short stature—a known hypertension risk factor in the general population—individuals with DS maintained normal SBP and PP across all ages, suggesting a unique cardiovascular phenotype. Blunted sympathetic activity, analogous to mechanisms observed in monogenic obesity (e.g., *MC4R* mutations), may protect against arterial stiffening, potentially explaining reduced atherosclerosis risk in DS. These findings underscore the need for tailored clinical management and highlight DS as a model for understanding hypertension mechanisms, particularly interactions with coexisting conditions like obstructive sleep apnea.