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Arterial Stiffness: If You Don’t Measure It, You Can’t Manage It

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Central Artery Stiffness, Baroreflex Sensitivity, and Brain White Matter Integrity in Older Adults

Central artery stiffness is associated with greater risk of white matter (WM) lesions and cognitive impairment in older adults, yet the pathophysiological mechanisms remain unclear.  Stiffening of central elastic arteries impairs cardiovagal baroreflex, a neurogenic mechanism of short-term blood pressure regulation, and may increase the risk of cerebral hypoperfusion in deep and periventricular WM areas.

Saxagliptin Prevents Increased Coronary Arterial Stiffness and Advanced Glycation End Product Expression in a Miniature Swine Model of Heart Failure with Preserved Ejection Fraction

Our lab recently reported coronary arterial dysfunction, a hallmark feature of heart failure (HF), and myocardial oxygen supply/demand imbalance in a mini-swine model of heart failure with preserved ejection fraction (HFpEF).  Accumulation of advanced glycation end products (AGEs) may play a role in this process by increasing vascular mechanical stiffness.  Dipeptidyl-peptidase 4 (DPP4) inhibitors have been shown to inhibit AGEs in diabetes, however, their impact on coronary fibrotic remodeling in HFpEF is unknown.  We hypothesized chronic treatment with the DPP4 inhibitor saxagliptin would prevent enhanced mechanical stiffness and AGEs accumulation in coronaries from HFpEF swine.

Cardio-Respiratory Interactions Immediately following Dynamic Leg Cycling: Influences of the Muscle Pump

Changes in cardiorespiratory coupling during the moments immediately following prolonged exercise are not well understood and the mode of recovery during the transition to post-exercise may be important.  Cardiorespiratory coupling influences the stresses put on the arterial system by oscillatory changes in cardiac output and systemic vascular resistance.  We hypothesized that the cessation of muscle pump activity and the unloading of the cardiopulmonary baroreceptors during inactive recovery would allow for exacerbated oscillations in neutrally-mediated cardiovascular function and arterial control resulting in an unstable cardiorespiratory environment.

Importance of Time Delay Estimation Methods for Aortic Pulse Wave Velocity Assessment with Phase-Contrast MRI

Pulse wave velocity (PWV) is a validated measure of arterial wall stiffness.  Assessments of PWV are highly dependent on pulse transit time estimations between 2 points.  No systematic assessments have been performed regarding the best method to assess pulse travel time using phase-contrast MRI.

Relationship of Common Carotid Artery Perivascular Adipose Tissue, Arterial Stiffness, and Intima-Medial Thickness, in Adult Humans

Most arteries in humans are directly surrounded by adipose tissue and it has been hypothesized that an excess of perivascular adipose tissue (PVAT) is involved in the pathogenesis of atherosclerosis and arterial stiffening.  There is a lack of research examining the relationships between PVAT with other measures of arterial health (i.e., stiffness and wall thickness).  The purpose of the current study was to examine relationships between the carotid PVAT measured through extra-medial thickness (EMT) ultrasonography and other measures of vascular health.

Longitudinal and Circumferential Strain of the Proximal Aorta

Proximal aortic stiffness increases with age and contributes to pathogenesis of wide pulse pressure and epidemic proportions of isolated systolic hypertension, which is difficult to control.  Elucidation of factors that contribute to abnormal mechanical properties of the proximal aorta may facilitate development of more effective interventions.  During systole there is substantial aortic long axis displacement and longitudinal strain, which we hypothesize causes overestimation of ascending aortic stiffness calculated from circumferential strain.

Effects of Acute Induced Inflammation on Pressure Waveforms: Does Age Matter? 

The Augmentation index (AIx) is a strong independent predictor of atherosclerosis.  Aging is characterized by increased AIx and low grade inflammation.  However, the effect of induced systemic inflammation on AIx is unclear.  

Sex Differences in Stiffness Parameters following Maximal Exercise

The sex differences found in cardiovascular disease risk and progression are well established.  These discrepancies are potentially attributed to the cardioprotective effect of estrogen or sex specific differences in fitness.  There may also be sex differences in the cardiovascular responses to exercise, which could underlie this disease risk.  We investigated arterial stiffness parameters at rest and following maximal exercise in untrained males and females.  

Correlations between Arterial Stiffness/Central Hemodynamics and Serum Cardiac Troponin T and Natriuretic Peptide Levels

Elevated serum levels of cardiac troponin T (cTnT) and N-terminal fragment of B-type natriuretic peptide (NT-proBNP), and also increased arterial stiffness/abnormal central hemodynamics are well-known risk factors for future cardiovascular events.  The present study was conducted to clarify which of the two - the serum level of cTnT or that of NT-proBNP - might be more closely associated with the arterial stiffness/central hemodynamics.

Buffering of Carotid Artery Pressure and Flow Pulsatility during Cognitive Engagement in Healthy Adults

The matching of vascular supply to neuronal metabolic demand during cognitive engagement is known as neurovascular coupling (NVC).  Excessive hemodynamic pulsatility may have a detrimental effect on neural function and affect NVC.  Arterial stiffness is a prominent determinant of pulsatility in the brain.

Effects of Systemic Niacin Infusion on Sympathetic Activity, Arterial Stiffness and Aortic Wave Reflection: A Pilot Study

Free fatty acids (FFA) may increase sympathetic activity and arterial stiffness.  Niacin decreases FFA, however, little is known regarding the direct effects of niacin on sympathetic activity and arterial stiffness.  We tested the hypothesis that niacin would decrease arterial stiffness,central aortic blood pressures, indices of aortic wave reflection, and muscle sympathetic nerve activity (MSNA).

Racial Differences in Circulating csRAGE and Alternatively Spliced esRAGE in Healthy Adolescents: Relation with Aortic Stiffness

Binding of ligands to the receptor for advanced glycation end products (RAGE) triggers pro-inflammatory/oxidant signaling in the vascular wall.  Increased circulating soluble forms of RAGE (sRAGE) are associated with decreased vascular risk and may be protective by acting as a decoy to prevent ligand binding to full-length RAGE.  Sheddases, such as matrix metalloproteinase-9 (MMP 9) proteolytically cleave cell surface receptors including RAGE, forming cleaved soluble RAGE (csRAGE).  However, sRAGE also includes endogenous secretory RAGE (esRAGE), an isoform of RAGE without receptor function derived from alternative splicing of RAGE pre-mRNA.  sRAGE is lower in African-American (AA) compared with Caucasian adults and is hypothesized to contribute to elevated arterial stiffening and vascular risk in AAs.  Indeed, we have previously demonstrated that sRAGE (1567±68.9 vs. 955±101.1 pg/mL, p<0.001) but not MMP9 is higher in Caucasian compared with AA adolescents and associated with lower carotid-femoral pulse wave velocity (CFPWV) (5.3±0.2 vs. 5.9±0.2 m/sec, p<0.05).

Effects of Acute Dietary Nitrate Supplementation on Aortic Wave Reflection in Young Adults

Evidence suggests that dietary nitrate supplementation (i.e. beetroot juice) decreases measures of peripheral blood pressure.  However, the effects of acute dietary nitrates on central aortic pressures are unclear.  Thus, the objective of this study was to investigate the effects of beetroot juice consumption on central aortic pressures and indices of aortic wave reflection.

Spironolactone as Add-On Therapy to Chlorthalidone Improves Endothelial Function, Arterial Stiffness and Insulin Resistance in European and African American Patients with Essential Hypertension – A Double-Blind Placebo-Controlled Randomized Study

Diuretics have been shown to have a neutral effect on cardiovascular (CV) biomarkers like arterial stiffness and endothelial function despite their blood pressure (BP) lowering effect.  Thiazide diuretics generally have harmful effects on glucose metabolism, however, the effect of mineralocorticoid receptor antagonists on insulin resistance in essential hypertension (eHTN) is only partially elucidated.  We hypothesized that chlorthalidone (CHT) in combination with spironolactone (SPL) results in better arterial compliance then CHT therapy alone through additional improvement of glucose metabolism parameters.

A Multi-Modality 4D system for Analysis of the Aortic Morphology and Function from MR or CT

Develop an integrated system for multi-modality 4D (3D+time) aortic data analysis including data construction, interactive pre-segmentation, accurate multi-surface segmentation and refinement, and quantitative index measurement.  Provide a graphical user interface (GUI) with intuitive data visualization and workflow control.  Test the capabilities of the system on MR and CT data.

Sex Differences in the Development of Abnormal Endothelium-Dependent Vasodilation in Aorta from Type 2 Diabetic Rats: Possible Role of Nitric Oxide

Little is known about the interaction between diabetes and sex in vasculature.  This study was designed to investigate whether there were sex differences in rat aortic endothelium- dependent vasodilation (EDV) in Zucker diabetic fatty (ZDF) rats, and the potential role of nitric oxide (NO).

Racial Differences of eNOS Expression Respond to C-reactive Protein

African Americans (AA) have higher rates of cardiovascular diseases (CVD) compared to Caucasians (CA).  Endothelial dysfunction is a common feature of CVD risk factors.  Previous studies suggest racial differences in endothelial function exist at the physiological level.  C-reactive protein (CRP), a risk marker for CVD, causes a reduction in eNOS expression and bioactivity in endothelial cells (ECs).  AA individuals have significant higher concentrations of CRP than Caucasian (CA) individuals.  The aim of this study was to investigate the racial differences of endothelial function under CRP stimulation at the cellular level.

Arterial Hemodynamics in Overweight Young Adult Males Following Maximal Exercise

Overweight (OV), defined by body mass index (BMI), is related to increased cardiovascular risk and greater aortic stiffening.  In contrast, enhanced cardiorespiratory fitness (CRF) is associated with reduced cardiovascular risk, and lower aortic stiffness.  It is unknown whether CRF is related to aortic stiffness in young OV adult males.  We hypothesized CRF would be inversely associated with aortic stiffness, and the post-exercise hemodynamic response would be impaired in OV males.

Relationship between Carotid Artery Stiffness and Altered Cerebrovascular Hemodynamics in South Asian Indian Older Adults

This study will investigate whether differences exist in common carotid artery (CCA) stiffness between South Asian (SA) and white Caucasian (CA) older adults, and its association with cerebrovascular hemodynamic properties.

The Temporal Relationship between Metabolically Healthy Obesity and Carotid Atherosclerosis in Men

There is conflicting evidence regarding the relationship between metabolically healthy obesity and the burden of carotid atherosclerosis, but whether metabolically healthy obesity is related to the progression of atherosclerosis remains unclear.

Reduced Cardiac Baroreflex Sensitivity Is Associated with Greater Aortic Stiffness in Middle-Aged/Older Humans: Beneficial Effect of Habitual Aerobic Exercise

Sedentary aging is characterized by reduced cardiac baroreflex sensitivity (BRS) and increased aortic stiffness, both independent predictors of higher cardiovascular disease (CVD) risk in middle-aged/older (MA/O) adults.  However, MA/O adults who perform habitual endurance exercise demonstrate lower CVD risk perhaps in part from reduced aortic stiffness and enhanced cardiac BRS.

A New Arterial Stiffness Index Permitting Isobaric Comparisons

Arterial stiffness is pressure-dependent and comparisons among individuals and between groups should be made under isobaric conditions.  Statistical methods are typically employed to adjust stiffness indices for pressure-dependence.  In this ongoing study, we employ our new stiffness index, CPI, which allows for explicit evaluation at a reference pressure and stroke volume, to investigate its change with age and disease.

Ultrasound Biomicroscopic Study of Arteries in Detection of Doxorubicin-induced Disorders

Ultrasound biomicroscopy (UBM) has been a valuable, non-invasive technique in monitoring cardiac function such as echocardiography.  However, UBM is not commonly used in vascular research, especially in small animals.  In addition, the use of doxorubicin (DOX), an anti-cancer drug, in treatment for malignancies is limited because of its cardiotoxicity.  Whether DOX causes vascular disorders is unknown.

Significant Basal and Stimulated Variations in Inflammatory Gene Expression Profiles in African American and Caucasian HUVECS

Biomarkers related to hypertensive disease onset and progression are differentially implicated in African Americans (AA) and Caucasians (Cau) and investigation of these biomarkers is needed to elucidate their significance.  Racial disparity studies are carried out solely in vivo making it difficult to focus on the cause(s) of endothelial dysfunction (EnDy) leading to vascular complications.

Aortic Hemodynamics following Discontinuation of Menopausal Hormone Therapy in Postmenopausal Women

Arterial stiffness and aortic hemodynamics are important determinants of cardiovascular disease risk.  Menopausal hormone therapy (MHT) reduces progression of cardiovascular disease in postmenopausal women due to its effects on the endothelium and smooth muscle of the central and peripheral vasculature.  However, it remains unclear whether these effects are sustained after MHT cessation.  We hypothesized that MHT administered early during the menopausal transition (less than three years from menopause) would not produce a sustained protective effect on aortic hemodynamics in women following discontinuation of MHT. 

Racial Differences in Vascular Function

Racial disparities are evident in regards to cardiovascular health and prevalence.  Currently, there have not yet been any studies investigating the differences in markers of vascular function between Hispanics (HS), Caucasians (CA), and African Americans (AA).  This study sought to assess the differences in vascular function at the endothelial cell level between these racial groups.

Higher Aortic Stiffness and Carotid Systolic and Pulse Pressure are Selectively Associated with Lower White Matter Integrity in the Genu and Frontal Cortex in Older Healthy Adults

Previous studies have demonstrated an association between higher aortic stiffness and central pulse pressure (PP) with lower brain white matter structural integrity (WMI) and neuropsychological functioning in older adults.  However, it is unknown if aortic stiffness and central PP are associated with lower WMI in select brain regions or if they relate to cognitive abilities that decline with age such as processing speed.

Dependency of Arterial Stiffness Indicators on Acute Blood Volume Changes

Increased arterial stiffness is associated with greater risk for cardiovascular disease. It is unknown if indicators of stiffness are dependent on acute changes in cardiovascular conditions (such as altered central blood volume).

Sex Differences in Hemodynamic Responses following Acute Inflammation: Wave Separation Analysis

Acute inflammation temporarily increases risk of cardiovascular events and alters hemodynamics.  However, it is unknown whether acute inflammation differentially affects blood pressure and pulse wave characteristics, including forward or reflected pressure waves, in males versus females.

Left Ventricular End-Systolic Elastance (Ecavi) Estimated with CAVI

Left ventricular end-systolic elastance (Ecavi) was estimated using the parameters measured for calculating cardio-ankle vascular index (CAVI).

The Implications of Poor Sleep Quality on Arterial Health in Persons with Multiple Sclerosis

Multiple sclerosis (MS) is a chronic, autoimmune disease that is associated with increased risk of cardiovascular disease (CVD) when compared to the general population.  Approximately 47% of patients with MS have reported poor sleep quality.  Evidence supports an association between poor sleep and increased CVD risk.  Augmentation index (AIx) is a marker of arterial health.  The purpose was to examine the association between sleep quality and arterial health in patients with MS.

Higher Central Augmentation Pressure/Index Is Associated with Tension-Type Headache but Not Migraine in Middle-Aged/Older Obese Humans

Obesity is associated with a five-fold increased risk of developing chronic daily headache, especially chronic migraine.  Migraine attacks are more frequent and more severe among obese migraineurs and they improve with weight loss; however, the underlying mechanisms are unknown.  Given that elevated aortic stiffness and central pulse pressure are associated with cerebral microvascular dysfunction/damage, we hypothesized that obese middle-aged/older adults with history of migraine would demonstrate higher aortic stiffness, central blood pressure (BP) and augmentation index (AI) /pressure (AP) compared with those without a history of migraine.

Changes in Cerebrovascular Pulsatility during Aerobic Exercise Are Unrelated to Brachial-Ankle Pulse Wave Velocity in Chronic Stroke

Arterial stiffness contributes to increased cerebral hemodynamic pulsatility and independently predicts negative outcomes post-stroke.  Exercise can contribute towards recovery after stroke, yet it is unclear whether arterial stiffness influences acute cerebrovascular responses to exercise.  One study in healthy young men showed high-intensity resistance exercise increased stiffness and pressure pulsatility up to 30 minutes post-exercise without affecting cerebral hemodynamics (1).  The influence during acute aerobic exercise, however, is unknown.

Creation of a Fixed Central Arterial-Venous Anastomosis on Arterial Stiffness and Central Haemodynamics: A Treatment for Hypertension Targeting the Physical Properties of the Arterial Vasculature

Current device based treatments for resistant hypertension target selective modification of the somatic, sympathetic, or parasympathetic nervous systems.  The influence of the respective nervous systems on vascular stiffness and haemodynamics is unclear, and there is little data on the effect of current devices nor pharmaco therapy on arterial stiffness often associated with resistant hypertension. 

Carotid Strain Does Not Explain Sex Differences in Blood Pressure

Women have a lower incidence of cardiovascular morbidity and mortality prior to menopause when compared to age-matched men.  Specifically, on the vascular level, carotid arterial stiffness increases with age in both sexes, but with greater changes in older postmenopausal women.  Arterial stiffness is a well-established predictor of future risk of CVD, and 2-dimensional ultrasound imaging of vascular deformation (Strain) using speckle tracking directly characterizes the elastic properties of the carotid arterial wall.  The purpose of this study was to determine if sex differences exist for strain in the common carotid artery.

Sex-Specific Differences in Cardiovascular Parameters in Spinal Cord Injured Individuals

Females represent 20% of the spinal cord injury (SCI) population, yet sex-specific differences in cardiovascular parameters have not been examined.  Given that SCI is associated with an increased risk of cardiovascular disease, establishing whether sex-specific differences in cardiovascular health exist is essential.

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