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Circulating vascular cell adhesion molecule-1 is associated with cerebral blood flow dysregulation, mobility impairment, and falls in older adults.

ABSTRACT: 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 people. 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 aged ?65 years in the Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly (MOBILIZE) Boston Study. Falls were recorded prospectively for 1 year on daily calendars. sVCAM-1 was measured by ELISA assay and beat-to-beat blood flow velocity in the middle cerebral artery during rest and in response to changes in end-tidal CO2 was measured by transcranial Doppler ultrasound. sVCAM-1 concentration was 1094±340 ng/mL in normotensives, 1195±438 ng/mL in controlled hypertensives, and 1250±445 ng/mL in uncontrolled hypertensives (P=0.008). The mean resting blood flow velocity and cerebral vasomotor range were, respectively, 41.0±10.3 cm/s and 1.3±0.4 cm/s per millimeter of mercury. Elevated sVCAM-1 levels indicative of endothelial dysfunction were associated with reduced resting blood flow velocity (P=0.017) and cerebral vasomotor range (P=0.0048). Elevated sVCAM-1 levels were associated with slower gait speed (<0.8 m/s; odds ratio, 3.01; 95% confidence interval, 1.56-5.83; P=0.0011) and an increased odds of injurious falls (odds ratio, 2.4; 95% confidence interval, 1.4-4.2; P=0.0028). An elevated sVCAM-1 level may be a marker of cerebral blood flow dysregulation because of endothelial damage from hypertension. It may also signal the presence of cerebral microvascular disease and its clinical consequences, including slow gait speed and falls.

SUBMITTER: Tchalla AE

PROVIDER: S-EPMC4807019 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Circulating vascular cell adhesion molecule-1 is associated with cerebral blood flow dysregulation, mobility impairment, and falls in older adults.

Tchalla Achille E AE Wellenius Gregory A GA Travison Thomas G TG Gagnon Margaret M Iloputaife Ikechukwu I Dantoine Thierry T Sorond Farzaneh A FA Lipsitz Lewis A LA

Hypertension (Dallas, Tex. : 1979) 20150608 2

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 people. 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 aged ≥6 ...[more]

PMID: 26056332

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Project description:BackgroundTo determine the association between amyloid-beta (Aβ) plaque deposition and changes in global cognition, executive functions, information processing speed, and falls risk over a 12-month period in older adults with a primary clinical diagnosis of subcortical ischemic vascular cognitive impairment (SIVCI).MethodsThis is a secondary analysis of data acquired from a subset of participants (N = 22) who were enrolled in a randomized controlled trial of aerobic exercise (NCT01027858). The subset of individuals completed an 11C Pittsburgh compound B (PIB) scan. Cognitive function and falls risk were assessed at baseline, 6-months, and 12-months. Global cognition, executive functions, and information processing speed were measured using: 1) ADAS-Cog; 2) Trail Making Test; 3) Digit Span Test; 4) Stroop Test, and 5) Digit Symbol Substitution Test. Falls risk was measured using the Physiological Profile Assessment. Hierarchical multiple linear regression analyses determined the unique contribution of Aβ on changes in cognitive function and falls risk at 12-months after controlling for experimental group (i.e. aerobic exercise training or usual care control) and baseline performance. To correct for multiple comparisons, we applied the Benjamini-Hochberg procedure to obtain a false discovery rate corrected threshold using alpha = 0.05.ResultsHigher PIB retention was significantly associated with greater decrements in set shifting (Trail Making Test, adjusted R2 = 35.3%, p = 0.002), attention and conflict resolution (Stroop Test, adjusted R2 = 33.4%, p = 0.01), and information processing speed (Digit Symbol Substitution Test, adjusted R2 = 24.4%, p = 0.001) over a 12-month period. Additionally, higher PIB retention was significantly associated with increased falls risk (Physiological Profile Assessment, adjusted R2 = 49.1%, p = 0.04). PIB retention was not significantly associated with change in ADAS-Cog and Verbal Digit Span Test (p > 0.05).ConclusionsSymptoms associated with SIVCI may be amplified by secondary Aβ pathology.Trial registrationClinicalTrials.gov, NCT01027858 , December 7, 2009.

Project description:ImportanceAccumulating evidence links inflammation and atrial fibrillation (AF).ObjectiveTo assess whether markers of systemic and atrial inflammation are associated with incident AF in the general population.Design, setting, and participantsThe Bruneck Study is a prospective, population-based cohort study with a 20-year follow-up (n = 909). The population included a random sample of the general community aged 40 to 79 years. Levels of 13 inflammation markers were measured at baseline in 1990. Findings were replicated in a case-control sample nested within the prospective Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study (n = 1770). Data analysis was performed from February to May 2016.ExposuresLevels of 13 inflammation markers.Main outcomes and measuresIncident AF over a 20-year follow-up period in the Bruneck Study.ResultsOf the 909 participants included in the Bruneck Study, mean [SD] age was 58.8 (11.4) years and 448 (49.3%) were women. Among the 880 participants free of prevalent AF (n = 29) at baseline, 117 developed AF during the 20-year follow-up period (incidence rate, 8.2; 95% CI, 6.8-9.6 per 1000 person-years). The levels of soluble vascular cell adhesion molecule 1 (VCAM-1) and osteoprotegerin were significantly associated with incident AF (hazard ratio [HR], 1.49; 95% CI, 1.26-1.78; and 1.46; 95% CI, 1.25-1.69, respectively; P < .001 with Bonferroni correction for both), but osteoprotegerin lost significance after age and sex adjustment (HR, 1.05; 95% CI, 0.87-1.27; P > .99 with Bonferroni correction). Matrix metalloproteinase 9, metalloproteinase inhibitor 1, monocyte chemoattractant protein-1, P-selectin, fibrinogen, receptor activator of nuclear factor-κB ligand, high-sensitivity C-reactive protein, adiponectin, leptin, soluble intercellular adhesion molecule 1, and E-selectin all fell short of significance (after Bonferroni correction in unadjusted and age- and sex-adjusted analyses). The HR for a 1-SD higher soluble VCAM-1 level was 1.34 (95% CI, 1.11-1.62; Bonferroni-corrected P = .03) in a multivariable model. The association was of a dose-response type, at least as strong as that obtained for N-terminal pro-B-type natriuretic peptide (multivariable HR for a 1-SD higher N-terminal pro-B-type natriuretic peptide level, 1.15; 95% CI, 1.04-1.26), internally consistent in various subgroups, and successfully replicated in the SAPHIR Study (age- and sex-adjusted, and multivariable odds ratios for a 1-SD higher soluble VCAM-1 level, 1.91; 95% CI, 1.24-2.96, P = .003; and 2.59; 95% CI, 1.45-4.60; P = .001).Conclusions and relevanceLevels of soluble VCAM-1, but not other inflammation markers, are significantly associated with new-onset AF in the general community. Future studies should address whether soluble VCAM-1 is capable of improving AF risk classification beyond the information provided by standard risk scores.

Dataset Information

Circulating vascular cell adhesion molecule-1 is associated with cerebral blood flow dysregulation, mobility impairment, and falls in older adults.

Publications

Circulating vascular cell adhesion molecule-1 is associated with cerebral blood flow dysregulation, mobility impairment, and falls in older adults.

Similar Datasets

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