Abstract MP100: Arterial Stiffness and Pressure Amplification Associated with Markers of Cerebral Microvascular Disease: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Priya Palta ◽  
Jingkai Wei ◽  
Michelle Meyer ◽  
Melinda C Power ◽  
Jennifer A Deal ◽  
...  

Introduction: Small vessel disease is associated with decreased cognitive function, possibly differential by race. Age-related central arterial stiffening increases pulsatility resulting in hypoperfusion, microvascular damage and remodeling in the brain, potentially impairing cognition. We examined if arterial stiffness and pressure amplification are associated with lacunar infarcts and greater volumes of white matter hyperintensities (WMH) in a sample of Caucasian and African American (AA) older adults. Methods: We analyzed a cross-sectional sample of ARIC participants aged 67-90 years (n=1486) from visit 5 (2011-2013), with brain magnetic resonance imaging (MRI). The Omron VP-1000 Plus was used to measure aortic stiffness (carotid-femoral pulse wave velocity [cfPWV]) and pressure amplification measures (pulse pressure amplification [PPA], central pulse pressure [cPP], and estimated central systolic blood pressure [cSBP]). Aortic stiffness and pressure amplification were dichotomized at race-specific 25th percentile cut points. Brain MRI using 3D-1.5T equipment quantified the presence of lacunar infarcts and volumes of WMH following a standardized protocol. Logistic regression, adjusted for age, sex, education, ApoE4, heart rate, smoking and body mass index, was used to quantify the odds of lacunar infarcts in participants with high vs. low cfPWV, cPP, cSBP, and low vs. high PPA. Linear regression models, additionally adjusted for intracranial volume, estimated the difference in log-transformed volumes of WMH among participants with high vs. low cfPWV, cPP, cSBP, and low vs. high PPA. Probability sampling weights for an MRI were included to allow for generalizability to the full visit 5 cohort. Results: Among the 1486 participants with a brain MRI (mean age: 76, 41% male, 26% AA), measures of aortic stiffness and pressure amplification were associated with lacunar infarcts in Caucasians, but not in AAs. Caucasian participants with a high cfPWV had greater odds of lacunar infarcts (Odds Ratio [OR] =2.02, 95% confidence interval [CI]: 1.23, 2.20). Caucasians with high cSBP had higher odds of lacunar infarcts (OR=1.72, 95% CI: 1.10, 2.69). In Caucasians, high cfPWV was associated with a 21% (95% CI: 6, 38) greater volume of WMH as compared to a low cfPWV; high cSBP was associated with a 28% (95% CI: 14, 45) greater volume of WMH compared to a low cSBP. In AAs, high cfPWV was associated with a 32% (95% CI: 7, 62) greater volume of WMH as compared to low cfPWV. Cerebral microvascular imaging markers did not differ quantitatively with measures of PPA and cPP. Conclusions: Central arterial stiffening and pressure amplification are plausible microvascular contributors to cognitive aging, providing new information on modifiable pathways for previously observed associations between cardiovascular disease risk factors and the rates of cognitive decline and dementia among older adults.

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Uwe Raaz ◽  
Isabel N Schellinger ◽  
Lars Maegdefessel ◽  
Joshua M Spin ◽  
Gerd Hasenfuss ◽  
...  

Background: Accelerated arterial stiffening is a complication of diabetes mellitus and associated with the development of hypertension. Arterial stiffening results from extensive extracellular matrix remodeling (elastin breakdown, collagen accumulation). MicroRNA miR-29b directly regulates the expression of genes governing fibrosis (such as COL1A1, COL3A1) and elastin breakdown ( MMP2, MMP9 ). However, its impact on aortic stiffness is unclear. Objective: This study was designed to investigate the role of miR-29b as potential mediator of diabetic aortic stiffening. Methods and Results: Serial ex vivo mechanical testing of the thoracic aorta and volume-pressure recording (VPR) based tail-cuff blood pressure measurements revealed that aortic stiffening precedes blood (pulse) pressure elevations in diabetic db/db mice. Vascular stiffening was accompanied by increased elastin fragmentation and collagen deposition (EvG and Picrosirius Red staining). qRT-PCR, in-situ hybridization and immunohistochemistry revealed decreased expression of miR-29b and de-repression of target genes ( Col1A1, COL3A1, MMP2, MMP9 ) in db/db mice compared to controls. Investigating the mechanistic significance of miR-29b for arterial stiffening, forced downregulation of miR-29b (via systemic LNA-miR-29b inhibitor application) results in enhanced elastin fragmentation, increased medial collagen deposition, aortic stiffness and augmented pulse pressure. Conclusions: In conclusion this study identifies miR-29b as a regulator and potential therapeutic target of diabetic aortic stiffening.


Angiology ◽  
2015 ◽  
Vol 67 (4) ◽  
pp. 375-383 ◽  
Author(s):  
YH Gomez ◽  
Zahra Hudda ◽  
Noha Mahdi ◽  
Anais Hausvater ◽  
Lucie Opatrny ◽  
...  

2004 ◽  
Vol 22 (Suppl. 2) ◽  
pp. S299
Author(s):  
J. E. Sharman ◽  
C. M. McEniery ◽  
R. Campbell ◽  
P. Pusalkar ◽  
I. B. Wilkinson ◽  
...  

2019 ◽  
Vol 42 (3) ◽  
pp. 287-293
Author(s):  
Eleftherios Papakonstantinou ◽  
Maria Pikilidou ◽  
Panagiotis Georgianos ◽  
Maria Yavropoulou ◽  
Georgios Tsivgoulis ◽  
...  

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S927-S928
Author(s):  
Kevin J Sullivan ◽  
Michael Griswold ◽  
Timothy Hughes ◽  
Christina E Hugenschmidt ◽  
Samuel Lockhart ◽  
...  

Abstract Neuropathological markers including amyloid-beta (Aβ) have been implicated in mobility decline in older adults, but no studies have examined the relationship between these markers and longitudinal change in gait speed in a racially diverse community-based sample. In the multi-site prospective ARIC study, a subsample of participants (n=1,978, mean age=76.3, 28.5% black) underwent brain MRI at Visit 5 (2011-13). Of these, 343 participants (mean age=75.9, 42.6% black) completed PET scans using the tracer florbetapir to estimate global brain Aβ. We investigated the relationship between four neuropathological markers [white matter hyperintensities (WMH; log2cm3), infarcts (present/absent), brain atrophy (log2cm3), and global Aβ (log2SUVR)] with cross-sectional usual pace gait speed (cm/s) over 4 meters, and change in gait speed through Visits 6 (2016-17) and 7 (2018-19). Linear regression models were adjusted for age, site, sex, education, BMI, intracranial volume, and all race interactions. Cross-sectionally, slower gait was associated with higher WMH volume (β=-2.16, 95%CI: -2.92, -1.39), infarcts (β=-5.81, 95%CI: -7.86, -3.76), and brain atrophy (β=-16.39, 95%CI: -21.07, -11.71). Longitudinally, only higher WMH volume was statistically associated with gait speed decline (β=-0.14, 95%CI: -0.28, -0.01). Global Aβ was not statistically associated with gait speed cross-sectionally (β=-.269, 95%CI: -8.11, 7.57) or longitudinally (β=-1.16, 95%CI: -2.94, 0.62). There were no significant interactions with race. Detrimental relations of cerebral small vessel disease to mobility and mobility decline were observed across race in this diverse sample. The magnitude of the Aβ association with gait speed decline was high, although not statistically significant in the smaller PET subsample.


2007 ◽  
Vol 1 (S1) ◽  
pp. S24
Author(s):  
F.U.S. Mattace-Raso* ◽  
W.J. Bos ◽  
T.J.M. van der Cammen ◽  
B.E. Westerhof ◽  
R. Asmar ◽  
...  

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