Circulating Vascular Cell Adhesion Molecule-1 (sVCAM-1) Is Associated with Cerebral Blood Flow Dysregulation Mobility Impairment and Falls in Older Adults

摘要

Soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) is associated with hypertension, vascular inflammation, and systemic endothelial dysfunction. We evaluated whether elevated plasma sVCAM-1 is associated with impaired cerebrovascular function and mobility impairments in elderly. We studied the cross-sectional relationships between plasma sVCAM-1 level, gait speed, and cerebrovascular hemodynamics, and its longitudinal relationship with falls in 680 community-dwelling participants in the MOBILIZE Boston Study aged 65 and older. Falls were recorded prospectively for one year on daily calendars. sVCAM-1 was measured by ELISA assay and beat-to-beat blood flow velocity (BFV) in the middle cerebral artery during rest and in response to changes in end-tidal CO2 was measured by transcranial Doppler ultrasound.Soluble VCAM-1 concentration was 1094± 340 ng/mL in normotensives, 1195 ± 438ng/mL in controlled hypertensives and 1250 ± 445ng/mL in uncontrolled hypertensives (p=0.008). The mean resting BFV and cerebral vasomotor range (VMR) were respectively 41.0 ± 10.3 cm/s and 1.3 ± 0.4 cm/sec/mmHg. Elevated sVCAM -1 levels indicative of endothelial dysfunction were associated with reduced resting BFV (p=0.017) and cerebral VMR (p=0.0048). Elevated sVCAM-1 levels were associated with slower gait speed ((< 0.8 m/sec) OR = 3.01, 95 %CI (1.56 – 5.83), p=0.0011) and an increased odds of injurious falls (OR = 2.4, 95 %CI (1.4 – 4.2), p=0.0028).Elevated sVCAM-1 levels may be a marker of cerebral blood flow dysregulation due to endothelial damage from hypertension. It may also signal the presence of cerebral microvascular disease and its clinical consequences, including slow gait speed and falls.