Omapatrilat reduces pulse pressure and proximal aortic stiffness in patients with systolic hypertension. results of the conduit hemodynamics of omipatrilat international research study

2002 ◽  
Vol 11 (6) ◽  
pp. 57-58
Author(s):  
G.F. Mitchell ◽  
J.L. Izzo ◽  
Y. Lacourciere
Circulation ◽  
2002 ◽  
Vol 105 (25) ◽  
pp. 2955-2961 ◽  
Author(s):  
Gary F. Mitchell ◽  
Joseph L. Izzo ◽  
Yves Lacourcière ◽  
Jean-Pascal Ouellet ◽  
Joel Neutel ◽  
...  

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.


Hypertension ◽  
2005 ◽  
Vol 45 (4) ◽  
pp. 586-591 ◽  
Author(s):  
Jacobien C. Verhave ◽  
Pierre Fesler ◽  
Guilhem du Cailar ◽  
Jean Ribstein ◽  
Michel E. Safar ◽  
...  

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.


2019 ◽  
Vol 33 (1) ◽  
pp. 70-76
Author(s):  
Arturo Figueroa ◽  
Arun Maharaj ◽  
Sarah A Johnson ◽  
Stephen M Fischer ◽  
Bahram H Arjmandi ◽  
...  

Abstract Background Peripheral mean arterial pressure (MAP) responses to muscle metaboreflex activation using postexercise muscle ischemia (PEMI) in type 2 diabetes patients (T2D) are contradictory. Given that aortic pulse pressure (PP) and wave reflections are better indicators of cardiac load than peripheral MAP, we evaluated aortic blood pressure (BP) and wave amplitude during PEMI. METHODS Aortic BP and pressure wave amplitudes were measured at rest and during PEMI following isometric handgrip at 30% maximum voluntary contraction (MVC) in 16 T2D and 15 controls. Resting aortic stiffness (carotid-femoral pulse wave velocity, cfPWV) and fasting blood glucose (FBG) were measured. RESULTS Increases in aortic MAP (Δ26 ± 2 mmHg vs. Δ17 ± 2 mmHg), PP (Δ15 ± 2 mmHg vs. Δ10 ± 1 mmHg), augmentation index (AIx) (Δ8.2 ± 1.0% vs. Δ4.5 ± 1.3%), augmented pressure (AP) (Δ11 ± 1 mmHg vs. Δ5 ± 1 mmHg), forward (Pf) (Δ9 ± 1 mmHg vs. Δ5 ± 1 mmHg), and backward pressure waves (Pb) (Δ10 ± 1 mmHg vs. Δ5 ± 1 mmHg) responses to PEMI were greater in T2D than controls (P < 0.05). Aortic PP, but not MAP, response to PEMI was correlated to Pf (r = 0.63, P < 0.001) and Pb (r = 0.82, P < 0.001) responses and cfPWV (r = 0.37, P < 0.05). CONCLUSIONS Aortic BP and pressure wave responses to muscle metaboreflex activation are exaggerated in T2D. Aortic PP during PEMI was related to increased wave reflection, forward wave amplitude, and aortic stiffness in T2D patients.


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