Structural vs. load-dependent stiffness among individuals with Down syndrome: same, same, but different?

INTRODUCTION: Individuals with Down syndrome (DS) exhibit muscle hypotonia and joint laxity partially attributed to alterations in collagen. They also have low resting blood pressure and demonstrate blunted blood pressure responses to sympathoexcitatory stimuli compared to individuals without DS. Arterial stiffness, a key determinant of cardiovascular health, occurs via a combination of two mechanisms: (1) load-dependent stiffening resulting from elevated blood pressure, and (2) structural stiffening driven by vascular remodeling (e.g., changes in collagen and/or elastin). The present study aimed to characterize both structural and load-dependent components of carotid artery stiffness in apparently healthy individuals with DS. METHODS: Supine measures of B-mode carotid ultrasound and brachial blood pressure were assessed in individuals with DS (DS; n=23; M/F 13/10; 24±5 yrs; 30.0±6.3 kg/m 2 ) and age-matched controls without DS (CONT; n=24; M/F 13/11; 25±4 yrs; 26.5±4.5 kg/m 2 ). Total arterial stiffness was quantified using Peterson’s elastic modulus (PEM). Echo-tracking derived measures of arterial function included: β-stiffness, carotid intima–media thickness (cIMT), and arterial compliance. One-point (carotid) pulse wave velocity (PWV) was estimated based on the Bramwell-Hill equation. Using a participant-specific exponential model with a non-linear stiffness parameter, structural stiffness was derived by standardizing PEM to 120/80 mmHg, and load-dependent stiffness was calculated as the difference between total and structural stiffness. RESULTS: Individuals with DS exhibited lower PEM and reduced structural stiffness compared to individuals without DS (PEM Structural; CONT: 269±65 vs. DS: 228±48 mmHg, p=0.019). Echo-tracking carotid indices of arterial stiffness were also lower in the DS group (β-stiffness; CONT: 5.3±1.2 vs. DS: 4.5±1, p=0.026). However, groups did not differ in load-dependent stiffness (PEM Load: CONT: −42±37 vs. DS: −46±25 mmHg, p=0.626; PWV Load: CONT: −0.47±0.40 vs. DS: −0.59±0.35 m/s, p=0.266), or in resting blood pressure (Systolic blood pressure; CONT: 113±10 vs. DS: 108±11 mmHg, p=0.113). Despite being shorter in stature, individuals with DS demonstrated larger maximum systolic carotid diameters (CONT: 6.86±0.78 vs. DS: 7.34±0.57 mm, p=0.018) and greater mean diameters overall (p=0.043). The DS cohort also had increased carotid intima-media thickness (cIMT; CONT: 0.42±0.05 mm vs. DS: 0.50±0.11 mm, p=0.004) and arterial compliance (CONT: 1.03±0.2 vs. DS: 1.49±0.5 mm2/kPa, p< 0.001). DISCUSSION: These findings demonstrate lower structural carotid stiffness in individuals with DS, which may reflect altered collagen function. Attenuated structural stiffness is likely the main contributor to reduced standard carotid stiffness (e.g., β-stiffness). The DS group exhibited similar load-dependent stiffness vs. controls, despite reduced structural and echo-derived stiffness, and may be partially explained by similar resting blood pressure. The larger carotid diameters, increased cIMT, and arterial compliance among individuals with DS indicate structural-functional mismatches that may reflect unique collagen and/or vascular remodeling patterns specific to this group with DS. Collectively, these data highlight the need for deeper investigation into arterial stiffness phenotypes in DS, particularly regarding collagen pathology and its implications on cardiovascular physiology and risk in this population. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.