Greater Aortic Stiffness Research Articles

Blood Pressure Variability, Arterial Stiffness, and Arterial Remodeling.

Greater very short- to midterm blood pressure variability (BPV) has been associated with an increased cardiovascular disease risk, especially stroke. However, this link remains incompletely understood. We hypothesized that increased arterial stiffness and maladaptive carotid arterial remodeling may underlie this association. We, therefore, investigated the association between very short- to midterm systolic BPV, aortic and carotid stiffness and carotid arterial remodeling using cross-sectional data from The Maastricht Study (aged 60±8 years; 53% men). Aortic (carotid-femoral pulse wave velocity, n=1671) and carotid stiffness (ultrasonography, n=1690) were assessed. A composite index of systolic BPV was derived by standardizing and averaging systolic within-visit, 24-hour, and 7-day BPV. We performed linear regression analyses with adjustment for age, sex, glucose metabolism status, mean arterial pressure, and cardiovascular risk factors. A 1-SD greater systolic BPV was statistically significantly associated with 0.10 m/s (95% CI, 0.01-0.20) greater carotid-femoral pulse wave velocity, but not with carotid distensibility (-0.033×10-3/kPa [-0.255 to 0.190]). In addition, a 1-SD greater systolic BPV was statistically significantly associated with greater carotid circumferential wall tension (0.84 dyne/cm [0.51-1.17]), circumferential wall stress (0.79 kPa [0.031-1.27]), and intima-media thickness (8.6 µm [1.0-16.3]). These results are indicative of maladaptive carotid remodeling, as circumferential wall tension and stress were not normalized despite greater intima-media thickness. In conclusion, greater very short- to midterm BPV is associated with greater aortic stiffness and maladaptive carotid arterial remodeling, but not with carotid stiffness. These findings may explain, at least partially, the increased BPV-associated cardiovascular disease risk, in particular stroke.

SEX DIFFERENCES IN THORACIC AORTIC ANEURYSM GROWTH: ROLE OF AORTIC STIFFNESS

Thoracic Aortic Aneurysm (TAA) is a deadly disease, affecting adults of all ages. Presently, the only parameter available for risk prediction is TAA size. However, many individuals suffer an aortic dissection with aneurysms that are smaller than guideline-based cutoffs for repair. Further, women with thoracic aortic aneurysms (TAAs) have faster aneurysm growth and greater risk of acute aortic syndromes and death than men. Since the stiffness of the aorta reflects the health of its wall, we hypothesized that aortic stiffness would be independently associated with TAA growth, and that sex would significantly modify this association. One hundred and thirty unoperated TAA subjects were recruited. Maximal aneurysm size at the oldest and latest imaging studies was measured; aneurysm growth rate was calculated as mm/year. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV) using applanation tonometry. Unadjusted and multivariable linear regression analyses assessed the association of cfPWV with TAA growth. Models were adjusted for age, sex, body size, aneurysm etiology and location, baseline aneurys size, follow-up time, mean arterial pressure, history of hypertension, diabetes and smoking, and concordant/ discordant nature of the imaging modality. We also tested the interaction term sex*cfPWV in the prediction of TAA growth. Seventy four percent of subjects were men. Mean±SD age, baseline aneurysm size and follow-up time were 62.9±11.8 years, 45.3±4.0 mm and 3.3±3.0 years, respectively, and not different by sex. cfPWV was 9.8±4.3 m/s in women and 9.5±3.2 m/s in men (P=0.70). TAA growth rate was 1.0±1.0 mm/year in women and 0.4±0.6 mm/year in men (P=0.006). Unadjusted regression results are depicted in the Figure. In multivariable linear regression, cfPWV was independently associated with TAA growth (β±SE for 1 m/s increase in cfPWV: 0.06±0.02, P=0.02). Other independent predictors of faster aneurysm growth were female sex and longer follow-up time (P<0.05 for each), but not baseline aneurysm size (P=0.28). The sex*cfPWV interaction term was significant (P<0.0001), thus sex-specific models were performed. cfPWV was independently associated with faster aneurysm growth in women (β±SE: 0.21±0.09, P=0.03), but not in men (β±SE: -0.001±0.024, P=0.94). Among TAA patients, higher aortic stiffness is independently associated with faster aneurysm growth, and findings are specific to women. Our findings highlight poorer aortic wall health, reflected by greater aortic stiffness, as a potential mechanism for TAA expansion, especially in women. Aortic stiffness assessment may represent a future target for TAA-related risk stratification, monitoring and therapeutics aimed at containing TAA growth.

THORACIC AORTIC ANEURYSM GROWTH IN PATIENTS WITH BICUSPID AORTIC VALVES: ROLE OF AORTIC STIFFNESS AND PULSATILE HEMODYNAMICS

Bicuspid aortic valve (BAV) is the most common congenital cardiac abnormality, and the second most common etiology for thoracic aortic aneurysm (TAA) formation. Among BAV patients, risk of aortic dissection is increased 8-fold, and 25-year risk of aortic surgery is 25%. However, there are no clinical predictors of aneurysm growth for risk stratification. Since the health of the aortic wall is directly reflected in its stiffness, which increases pulsatile hemodynamic load due to impairment of the aorta’s pressure buffering function, we evaluated whether measures of aortic stiffness and hemodynamic load are associated with TAA growth in patients with BAV. Twenty nine participants with TAA due to BAV who had serial imaging were recruited. Aneurysm size was measured systematically by an imaging cardiologist blinded to hemodynamics, and growth rate was calculated in mm/year. Central arterial hemodynamics were non-invasively determined with validated methods that integrate arterial tonometry with echocardiography, yielding measures of aortic stiffness (aortic pulse wave velocity, aPWV), steady (systemic vascular resistance) and pulsatile hemodynamic load [aortic characteristic impedance (Zc), proximal aortic (PAC) and total arterial (TAC) compliances, central systolic (cSBP) and pulse pressures, forward (Pf) and reflected pressure wave amplitudes]. Spearman correlation coefficients were calculated between TAA growth rate and brachial blood pressure, as well as the aforementioned central hemodynamic measures. Multivariable linear regression adjusted for potential confounders (Table 1 legend) assessed the independent associations of hemodynamic variables with TAA growth. Sixty six percent of participants were men. Mean±standard deviation (SD) age, baseline aneurysm size and follow-up time were 57.2±8.3 years, 46.9±3.6 mm and 2.9±3.3 years, respectively. There were significant correlations between several measures of aortic stiffness and pulsatile arterial load with TAA growth (Table1, top). There were no significant correlations between brachial blood pressure parameters or steady hemodynamic load with TAA growth (P>0.05 for each). In multivariable linear regression, measures of aortic stiffness (aPWV) and pulsatile hemodynamic load (Zc, PAC, TAC) remained independently associated with aneurysm growth (Table 1, bottom). Other hemodynamic measures were not independently associated with TAA growth. In patients with TAA due to BAV, greater aortic stiffness and central pulsatile hemodynamic load are associated with faster aneurysm growth; while brachial blood pressure and steady hemodynamic load are not. Our findings suggest that evaluating aortic stiffness and pulsatile arterial load could be useful for risk stratification of subjects with TAA due to BAV, and may provide a therapeutic target for this disease.

Higher Aortic Stiffness Is Associated With Lower Global Cerebrovascular Reserve Among Older Humans.

Greater aortic stiffness and pulse pressure are associated with cerebrovascular remodeling, reduced white matter microstructure, and cognitive performance with aging in humans. However, it is unclear whether aortic stiffness and pulse pressure are associated with reduced basal global cerebral blood flow (CBF) and cerebrovascular reserve among older adults. Global CBF was quantified in 205 adults (range, 19-87 years; mean±SE: 30.6±1.3 years) using quantitative [15O]water brain positron emission tomography imaging. In a subset of older adults (n=24; 70.0±2.0 years), aortic stiffness (carotid femoral pulse wave velocity) and cerebrovascular reserve (change in global CBF after intravenous infusion of acetazolamide) were assessed. In the entire cohort, global CBF was lower in older compared with young adults (36.5±1.1 versus 50.5±0.7 mL/min per 100 mL; P<0.001). Global CBF was higher in young women compared with young men (51.0±0.30 versus 47.4±0.03 mL/min per 100 mL; P<0.001) but did not differ between older women and men (P=0.63). In older adults, greater carotid femoral pulse wave velocity was associated with lower cerebrovascular reserve (r=-0.68; P=0.001 adjusted for age, sex, and mean arterial pressure) but not global CBF (r=0.13; P=0.60). Brachial pulse pressure was not associated with lower cerebrovascular reserve (r=-0.37; P=0.159) when adjusted for age and sex. These data indicate that the age-related increases in aortic stiffness may contribute, in part, to the brain's impaired ability to augment blood flow in response to a stimulus with aging in humans.

Impairment of elastic properties of the aorta in bicuspid aortic valve: relationship between biomolecular and aortic strain patterns.

Bicuspid aortic valve (BAV) is associated with aortic wall alterations. We aimed to detect any correlation between aortic elasticity and genetic and biomolecular patterns of elastin. Forty-nine BAV patients (mean age: 38 ± 17.05) were prospectively enrolled. A blood sample was drawn for analysis of a single nucleotide polymorphism of elastin gene (ELN rs2071307) responsible for misfolding of elastin, and for the amount of elastin soluble fragments (ESF) in the plasma. Aortic dimensions and elastic properties were determined by echocardiography, aortic stiffness (AS) by M-mode analysis, and longitudinal strain (LS) of the ascending aorta (AA) by speckle-tracking echocardiography; values of aortic strain were compared with 45 age-matched subjects (mean age: 33 ± 9.67) with tricuspid aortic valve (TAV). BAV patients had greater aortic dimensions [Valsalva sinus (P = 0.004), sinotubular junction (P = 0.013), AA (P < 0.001)] and stiffness (P = 0.002) but lower LS (P = 0.04) than those with TAV. Results from comparisons of mutated genotype patients (AA, n = 10) with heterozygous (GA, n = 21) and wild-types ones (GG, n = 16) revealed that the presence of mutation was associated with increased ESF (P = 0.010 GG vs. GA; P = 0.035 GA vs. AA), larger AA (P = 0.019 GG vs. GA; P = 0.001 GG vs. AA), and lower LS (P = 0.032 GG vs. AA). Patients with a dilated AA showed greater ESF (P < 0.001), greater AS (P = 0.007), and lower LS of the AA (P = 0.002) than those with a normal AA. The same parameters were not significantly different comparing patients with moderate or severe aortic valve disease and patients with less than moderate valve disease. Our results show a close correlation between genetic and biomolecular patterns of elastin and mechanical properties of the aorta in patients with BAV.

ARTERIAL STIFFNESS IS ASSOCIATED WITH LOWER CEREBRAL BLOOD PERFUSION IN OLDER ADULTS

Arterial stiffness is an emerging risk factor for Alzheimer's disease and related dementias, partly through its novel associations with both cerebrovascular disease and β-amyloid deposition. Initial reports suggest that greater aortic stiffness may be related to lower cerebral perfusion in the brain. This study included participants from a randomized controlled clinical trial of exercise who received brain MRIs and cognitive testing before and after 6 months of aerobic training or stretching exercise. MRI included multi-phase pseudo-continuous arterial spin labeling to define cerebral blood flow in the whole brain gray matter (CBFgm). A subset of participants received baseline (n=17) and/or post-intervention (n=22) measures of central arterial stiffness using the AtCor SphygmoCor XCEL to obtain carotid-femoral pulse wave velocity (cfPWV). General linear models were used to assess associations between cfPWV and (global and voxel wise) cerebral blood flow with and without adjustment for age, gender, education, intracranial volume and APOE-4 status. Participants in this sample had a mean(SD) age of 67(9) years [range 51–89], 60% women, 19% were APOE-ε4 positive and all had at least an 12th grade education. Baseline cfPWV was negatively correlated with CBFgm (figure), showed regional specificity, and remained significant adjustment for covariates (beta = -4.3(1.8), p=0.04). Baseline and post intervention measures of cfPWV were highly correlated (rho=0.62, P<0.01) and showed similar negative associations with global CBFgm; however, change in cfPWV was not associated with changes global CBFgm (p=0.35). Correlations between global CBF and arterial stiffness by gender.

OP.1C.01] HIGH SALT DIET INCREASES AORTIC STIFFNESS AND PRESSURE PULSE AMPLIFICATION IN RAT

Objective: High salt consumption is associated with increased blood pressure and vascular changes in humans. This association is confounded by other lifestyle factors that could equally influence cardiovascular function. This study examines effects of high salt diet on aortic function in a controlled animal study. Design and method: Sprague-Dawley rats were fed either high salt (8% sodium chloride, n = 6) or normal chow (0.26% sodium chloride, n = 5) from weaning. Body weight (BW), nose-to-rump length, tail-cuff systolic blood pressure (SBP), water and food intake, and urine output were measured. At 14 to 17 weeks, rats were anaesthetised and thoracic and abdominal aortic pressure (invasive solid-state catheters) recorded over a physiological mean arterial pressure (MAP) range (60 to 150 mmHg, induced via intra-venous infusion of phenylephrine and sodium nitroprusside, 30 μg/kg/min). Aortic pulse wave velocity (aPWV) and thoracic to abdominal aortic pulse pressure amplification (PPA) were calculated. Left ventricular (LV) and kidney mass were recorded post-mortem. Results Results: High salt diet rats had lower BW (average across all age: 451 ± 57 g, control 498 ± 68 g, p = 0.03), body mass index (0.79 ± 0.08 g/cm2, control 0.82 ± 0.10 g/cm2, p < 0.001) and kidney mass (kidney/BW 0.50 ± 0.09%, control 0.39 ± 0.05%, p = 0.01) without LV hypertrophy (LV/BW 0.24 ± 0.04%, control 0.22 ± 0.03%, p = 0.16). Food intake was similar (high salt 20 ± 3 g/day, control 19 ± 5 g/day, p = 0.36). High salt diet rats drank more (65 ± 10 ml/day, control 22 ± 6 ml/day, p < 0.001) with correspondingly higher urine output (55 ± 9 ml/day, control 15 ± 6 ml/day p < 0.001); conscious SBP was greater (125 ± 12 mmHg, control 117 ± 13 mmHg, p < 0.05). High salt diet resulted in higher aPWV (high salt aPWV across MAP range 60 to 150 mmHg, 4.3 ± 0.2 to 5.4 ± 0.2 m/s, control 3.6 ± 0.3 to 3.9 ± 1.1 m/s, p < 0.001 at each 5 mmHg MAP interval). PPA was greater in high salt diet rats (high salt PPA across MAP range 60 to 150 mmHg, 0.78 ± 0.04 to 1.53 ± 0.27, control 0.62 ± 0.14 to 1.25 ± 0.17, p < 0.001 at each 5 mmHg MAP interval). Conclusions: A high salt diet induced moderately higher arterial blood pressure, greater aortic stiffness and higher PPA, indicating marked changes in transmission characteristics of the aorta, including altered stiffness gradient across the aorta and changed peripheral wave reflection characteristics.

Effects of Arterial Stiffness on Brain Integrity in Young Adults From the Framingham Heart Study.

Previous work from the Framingham Heart Study suggests that brain changes because of arterial aging may begin in young adulthood and that such changes precede cognitive deficits. The objective of this study was to determine the association of arterial stiffness with measures of white matter and gray matter (GM) integrity in young adults. One thousand nine hundred three participants from the Framingham Heart Study Third Generation (mean age, 46±8.7 years) had complete tonometry measurements and brain magnetic resonance imaging (T1-weighted and diffusion tensor imaging). Tonometry measures included carotid-femoral pulse wave velocity, augmentation index, carotid-brachial pressure amplification, and central pulse pressure. Fractional anisotropy and GM density images were computed from diffusion tensor imaging and T1 images. Registration to a common anatomic template enabled voxel-based linear regressions relating measures of fractional anisotropy and GM to tonometry measures, adjusting for relevant covariables. Higher carotid-femoral pulse wave velocity was associated with lower regional fractional anisotropy, including the corpus callosum and the corona radiata (8.7 and 8.6 cc, respectively, P<0.001), as well as lower GM density in the thalamus region (0.9 cc, P<0.001). Analyses did not reveal significant associations between other tonometry measures and fractional anisotropy or GM. Among young healthy adults, higher aortic stiffness was associated with measures of reduced white matter and GM integrity in areas implicated in cognitive decline and Alzheimer's disease. Greater aortic stiffness may result in subclinical vascular brain injury at ages much younger than previously described.

Central arterial stiffness in COPD

Introduction: Increased arterial stiffness is a marker of cardiovascular disease and suggested to beassociated with impaired lung function in chronic obstructive pulmonary disease (COPD). However, whether patients with mild COPD have increased arterial stiffness and what factors are linked to is still not explicitly studied. We hypothesised that patients with mild COPD would have increased arterial stiffness than controls independent of lung function. Methods: As part of the ARCADE study, 70 patients with mild COPD and 150 controls free from lung disease were examined. Aortic pulse wave velocity (PWV), spirometry, body composition, blood pressure (BP), heart rate (HR) and C-reactive protein (CRP) were determined. Results: Patients and controls were similar in age, body composition and gender. However, patients had greater aortic PWV 9.4 (1.96) m/s, systolic BP 147 (18) mmHg, HR 72 (12) bpm and CRP* 3.1 (1.7) mg/l compared with controls PWV 8.4 (1.8) m/s, BP 140 (18) mmHg, HR 67 (10) bpm and CRP* 1.7 (1.6) mg/l, all p<0.001. Aortic PWV was related to HR in patients (r=0.39) and controls (r=0.26), all p<0.001. A stepwise regression analysis adjusted for age and MAP showed heart rate was only predictor of increased aortic PWV (Adjusted R2=33%, p<0.001) where waist circumference and HR in the controls (Adjusted R2=37%, p<0.001). Conclusion: Increased heart rate accelerates atherosclerosis process and vascular dysfunction and ultimately leads to increased incidence rate of coronary artery disease. Understanding the relationship between increased heart rate and greater aortic stiffness would allow for cardioprotective effect of lowering heart rate.

Relation of Central Arterial Stiffness to Incident Heart Failure in the Community.

BackgroundArterial stiffness, pressure pulsatility, and wave reflection are associated with cardiovascular disease. Left ventricular function is coupled to proximal aortic properties, but the association of central aortic stiffness and hemodynamics with incident clinical heart failure (HF) is not well described.Methods and ResultsFramingham Study participants without clinical HF (n=2539, mean age 64 years, 56% women) underwent applanation tonometry to measure carotid‐femoral pulse wave velocity (CFPWV), central pulse pressure, forward wave amplitude, and augmentation index. CFPWV was inverse‐transformed to reduce heteroscedasticity and multiplied by −1 to restore effect direction (iCFPWV). Over 10.1 (range 0.04–12.9) years, 170 HF events developed. In multivariable‐adjusted analyses, iCFPWV was associated with incident HF in a continuous, graded fashion (hazards ratio [HR] per SD unit [SDU] 1.29, 95% confidence interval [CI] 1.02–1.64, P=0.037). iCFPWV was associated with HF with reduced ejection fraction (HR=1.69/SDU, 95% CI 1.19–2.42, P=0.0037) in age‐ and sex‐adjusted models, which was attenuated in multivariable‐adjusted models (P=0.065). Central pulse pressure and forward wave amplitude were associated with HF in age‐ and sex‐adjusted models (per SDU, HR=1.20, 95% CI 1.06–1.37, P=0.006, and HR=1.15, 95% CI 1.01–1.31, P=0.036, respectively), but not in multivariable‐adjusted models (both P≥0.28). Augmentation index was not associated with HF risk (P≥0.19 in all models).ConclusionsIn our prospective investigation of a large community‐based sample of middle‐aged to elderly individuals, greater aortic stiffness (reflected by higher iCFPWV) was associated with increased risk of HF. Future studies may investigate the impact of modifying aortic stiffness in reducing the community burden of HF.

Aortic Stiffness and Kidney Disease in an Elderly Population

Background/Aims: The causes of chronic kidney disease (CKD) in older people are not well understood. Aortic stiffness increases with age and results in the transmission of increased pulsatility into the kidney microvasculature, potentially contributing to CKD in older populations. Methods: We utilized data from the Age, Gene/Environment, Susceptibility-Reykjavik Study, a community-based prospective cohort study of cardiovascular disease (CVD) in Iceland. The relationship of carotid pulse pressure (CPP) and carotid-femoral pulse wave velocity (CFPWV) with estimated glomerular filtration rate (eGFR) based on creatinine and cystatin C and urine albumin-creatinine ratio (ACR) was assessed using linear regression, adjusting for demographics and CVD risk factors. Results: 940 participants (mean (SD) age 75.8 (4.7) years, mean (SD) CFPWV 12.9 (4.2) m/s, mean (SD) CPP 69 (21) mm Hg, mean (SD) eGFR 68 (16) ml/min/1.73 m², and median (IQR) ACR 3 (2-6) mg/g) were included in this study. At CPP greater than 85 mm Hg, a higher CPP was associated with a lower eGFR in unadjusted analyses but not after adjustment. CPP was significantly associated with a higher ACR in fully adjusted models (β (95% CI) = 0.14 (0.03, 0.24) ln mg/g per SD). Higher CFPWV was associated with lower eGFR and higher ACR in unadjusted analyses but not after adjustment. Conclusion: Greater aortic stiffness may be associated with modestly higher levels of albuminuria in the elderly. The association between aortic stiffness and lower eGFR may be confounded by age and CVD risk factors.

Increased aortic stiffness predicts future development and progression of peripheral neuropathy in patients with type 2 diabetes: the Rio de Janeiro Type 2 Diabetes Cohort Study.

Diabetic peripheral neuropathy (DPN) is a chronic microvascular complication that is strongly associated with poor glycaemic control and also with a worse prognosis. We aimed to evaluate the predictors of the development and progression of DPN in a cohort of high-risk patients with type 2 diabetes. In a prospective study, 477 patients with type 2 diabetes were clinically assessed for the presence of DPN at baseline and after a median follow-up of 6.2 years (range 2-10 years). Clinical laboratory data were obtained at study entry and throughout the follow-up. Aortic stiffness was assessed by the carotid-femoral pulse wave velocity (cf-PWV) at baseline. Multivariate Poisson regression analysis was used to examine independent predictors of the development/progression of DPN. At baseline, 135 patients (28%) had DPN, and during follow-up 97 patients (20%) had either a new development or a worsening of DPN. Patients who showed a development or progression of DPN were taller and had a longer duration of diabetes, a greater prevalence of other microvascular complications and hypertension, greater aortic stiffness and poorer glycaemic control than patients who did not have new or progressive neuropathy. After adjustments for the baseline prevalence of DPN, the patient's age and sex, and the time interval between DPN assessments; an increased aortic stiffness (cf-PWV >10 m/s) were predictive of new/progressive DPN (incidence rate ratio 2.04, 95% CI 1.28, 3.23; p = 0.002). Other independent predictors were the mean first-year HbA1c level (p = 0.05), nephropathy (p = 0.006), arterial hypertension (p = 0.06) and height (p = 0.03). Increased aortic stiffness at baseline predicts the future development or progression of peripheral neuropathy, independent of diabetic metabolic control, suggesting a physiopathological link between macrovascular and microvascular abnormalities in type 2 diabetes.

Abstract 572: Relationship of Aortic Stiffness Measured by Cardiac MRI with Left Ventricular Geometry and Function

Background: The association of aortic stiffness parameters measured by MRI with cardiac structure and function remains poorly explored. We investigated how central aortic stiffness assessed by MRI relates to Left ventricular (LV) structure and function in broad rage aged subjects free for cardiovascular disease. Methods: 79 asymptomatic subjects (37 men, age range: 20 - 78 years) were studied. Ascending aortic distensibility (AAD) and aortic pulse wave velocity (PWV) was measured by phase contrast (PC) cine MRI at the level of the pulmonary artery bifurcation. LV mass and LV volume indexed to body surface area, LV ejection fraction (LVEF) and LV mass volume ratio (M/V ratio) were determined by cine MRI. LV circumferential strain (Ecc), longitudinal strain (Ell) and LV torsion were determined from tagged MRI. Central pressures were used to calculate AAD. Linear regression analysis was used to evaluate the association between arterial measures and LV measures. Distributions of AAD and PWV were skewed, so they were logarithmically transformed (logAAD and logPWV) for regression models. Results: Lower AAD and higher PWV, both indicating greater aortic stiffness, was associated with less/worse myocardial systolic function parameters; Ecc, Ell, and M/V ratio. After adjustment for age, gender and hypertension, only AAD was associated with LV deformation while PWV was not (Table). Conclusion: Our observations indicate that the association of increased aortic stiffness with LV dysfunction because of aging and hypertension may be captured by PWV but the association with decreased distensibility could be because of common atherosclerosis risk factors in healthy population.

Reduced cardiac baroreflex sensitivity is associated with greater aortic stiffness in middle-aged/older humans: Beneficial effect of habitual aerobic exercise

Reduced cardiac baroreflex sensitivity is associated with greater aortic stiffness in middle-aged/older humans: Beneficial effect of habitual aerobic exercise

Diet induced obesity promotes aortic stiffness by impairing elastin functionality (LB695)

Cardiovascular diseases (CVD) are the leading cause of mortality in the United States. Obesity is a primary risk factor for CVD resulting in greater large elastic artery stiffness. Importantly, stiffening of the aorta is an independent predictor of CV events and is a novel therapeutic target for attenuating CVD risk with obesity. The purpose was to determine if a high fat diet promotes aortic stiffening in mice that would result in a significant increase in aortic pulse wave velocity (aPWV) and intrinsic mechanical stiffness. Mice were randomly assigned into two groups receiving either a low fat (LF, 10% kcal fat) or high fat (HF, 60% kcal fat) diet. HF mice had greater aortic stiffness as assessed by aPWV (401 ± 26 vs. 304 ± 17 cm/s, P &lt; 0.05) and in vitro aortic mechanical stiffening. Specifically, the elastic modulus of the elastin region was decreased in HF compared with LF mice (398 ± 6 vs. 615 ± 42 kPa, P &lt; 0.05), whereas the collagen elastic modulus showed no difference between groups (3707 ± 694 vs. 3732 ± 403 kPa, P&lt;0.05). Collectively, these data suggest that the decrease in aortic elastic modulus of the elastin region is due to loss of functionality of the elastin protein fiber. These results support the notion that high fat diets promote aortic stiffening thus increasing CVD risk.

Arterial Mechanics at Rest and During Exercise in Adolescents and Young Adults After Arterial Switch Operation for Complete Transposition of the Great Arteries

We sought to determine the arterial mechanics at rest and during exercise in adolescents and young adults with complete transposition of the great arteries after arterial switch operation and their relations with neoaortic complications. Thirty patients (22 men) aged 16.2 ± 2.1 years and 22 controls (15 men) were studied. Central and peripheral arterial pulse wave velocities, carotid and radial augmentation indices, and central systolic blood pressure (cSBP) were determined by oscillometry and applanation tonometry, whereas arterial dimensions were measured by 2-dimensional echocardiography. Arterial strain, distensibility, and stiffness were determined at rest and during supine bicycle exercise testing. At rest, patients had significantly higher heart-carotid pulse wave velocity, carotid and radial augmentation indices, and cSBP than controls. At rest and during submaximal exercise, patients had significantly lower aortic strain and distensibility, greater aortic and carotid stiffness, and higher SBP than controls. Dilated aortic sinus found in 23 (76.7%) patients was associated with lower aortic distensibility, greater aortic stiffness, and higher cSBP at rest and lower aortic distensibility and strain at submaximal exercise. Significant aortic regurgitation found in 20% (6 of 30) of patients was associated with significantly higher neoaortic z scores. Multivariate analysis identified aortic stiffness at rest (β = 0.46, p = 0.003) and age at operation (β = 0.44, p = 0.004) as significant determinants of aortic sinus z scores. In conclusion, altered mechanics of the central arteries are present at rest and during exercise in adolescents and young adults after arterial switch operation. These findings may have important implications on progression of neoaortic root dilation, exercise recommendations, and medical therapy.

Exploring the Relationship Between Increased Arterial Stiffness and Myocardial Hypertrophy in Infants of Diabetic Mothers

We have previously shown that infants of diabetic mothers (IDM) have increased aortic stiffness in the first 6 months of life, and aortic stiffness is related to poor maternal glycemic control in pregnancy. Increased left ventricular (LV) posterior (LVPW) and interventricular septal (IVS) wall thickness is observed in IDM in late gestation and early infancy, predominantly in mothers with worse glycemic control. Although it is generally believed that the LV hypertrophy in IDM regresses after the first 3 months, we have recently shown that hypertrophy persists even in late infancy. In this study we sought to explore the relationship between aortic stiffness and LV hypertrophy in IDM. We hypothesized that LVPW and IVS wall thickness would be greater in infants with greater aortic stiffness.

Prevalence and Significance of Late Gadolinium Enhancement in Children and Adolescents With Hypertrophic Cardiomyopathy

s S97 BACKGROUND: We have previously shown that infants of diabetic mothers (IDM) have increased aortic stiffness in the first 6 months of life, and aortic stiffness is related to poor maternal glycemic control in pregnancy. Increased left ventricular (LV) posterior (LVPW) and interventricular septal (IVS) wall thickness is observed in IDM in late gestation and early infancy, predominantly in mothers with worse glycemic control. Although it is generally believed that the LV hypertrophy in IDM regresses after the first 3 months, we have recently shown that hypertrophy persists even in late infancy. In this study we sought to explore the relationship between aortic stiffness and LV hypertrophy in IDM. We hypothesized that LVPW and IVS wall thickness would be greater in infants with greater aortic stiffness. METHODS: Diabetic pregnancies were prospectively recruited in the mid trimester. Their infants were evaluated in infancy by echocardiography. LVPW and IVS wall thickness was measured by m mode and measurements were compared to normative data for the calculation of z scores based on body surface area. Aortic wall stiffness was assessed with echocardiography, using 2D and pulsed Doppler interrogation of the ascending aorta and distal arch. Aortic pulse wave velocity (PWV) was calculated as the distance from the ascending aorta to distal arch, divided by the time interval from the QRS to the onset of flow for the two interrogated sites (m/s). RESULTS: Twenty-one IDM were investigated at a median age of 7 weeks (range 2-48 weeks). Mean aortic PWV was 4.7 1.7m/s, and the mean IVS and LVPW z scores were 1.3 1.2 and LVPW 1.4 1.1, respectively. Although no relationship was observed between PWV and IVS, there was a weak but positive correlation between aortic PWV and LVPW z score (r1⁄40.50, p1⁄40.027). CONCLUSION: Our study suggests that a potential relationship exists between the degree of stiffness of the aorta and LV wall thickness. This could be due to a common prenatal exposure (hyperglycemia) or to a causal relationship (greater aortic stiffness leading to evolution or persistence of LV hypertrophy). Further studies are underway to determine the etiology of increased aortic stiffness and LV hypertrophy and the natural course of these changes. 025 PREVALENCE AND SIGNIFICANCE OF LATE GADOLINIUM ENHANCEMENT IN CHILDREN AND ADOLESCENTS WITH HYPERTROPHIC CARDIOMYOPATHY L Grosse-Wortmann, J Windram, D Andreea, S Yoo, L Mertens, D Wong, L Benson

Three-Dimensional Echocardiographic Assessment of the Longitudinal Tricuspid Valve Changes Associated With Tricuspid Regurgitation in Hypoplastic Left Heart Syndrome

s S97 BACKGROUND: We have previously shown that infants of diabetic mothers (IDM) have increased aortic stiffness in the first 6 months of life, and aortic stiffness is related to poor maternal glycemic control in pregnancy. Increased left ventricular (LV) posterior (LVPW) and interventricular septal (IVS) wall thickness is observed in IDM in late gestation and early infancy, predominantly in mothers with worse glycemic control. Although it is generally believed that the LV hypertrophy in IDM regresses after the first 3 months, we have recently shown that hypertrophy persists even in late infancy. In this study we sought to explore the relationship between aortic stiffness and LV hypertrophy in IDM. We hypothesized that LVPW and IVS wall thickness would be greater in infants with greater aortic stiffness. METHODS: Diabetic pregnancies were prospectively recruited in the mid trimester. Their infants were evaluated in infancy by echocardiography. LVPW and IVS wall thickness was measured by m mode and measurements were compared to normative data for the calculation of z scores based on body surface area. Aortic wall stiffness was assessed with echocardiography, using 2D and pulsed Doppler interrogation of the ascending aorta and distal arch. Aortic pulse wave velocity (PWV) was calculated as the distance from the ascending aorta to distal arch, divided by the time interval from the QRS to the onset of flow for the two interrogated sites (m/s). RESULTS: Twenty-one IDM were investigated at a median age of 7 weeks (range 2-48 weeks). Mean aortic PWV was 4.7 1.7m/s, and the mean IVS and LVPW z scores were 1.3 1.2 and LVPW 1.4 1.1, respectively. Although no relationship was observed between PWV and IVS, there was a weak but positive correlation between aortic PWV and LVPW z score (r1⁄40.50, p1⁄40.027). CONCLUSION: Our study suggests that a potential relationship exists between the degree of stiffness of the aorta and LV wall thickness. This could be due to a common prenatal exposure (hyperglycemia) or to a causal relationship (greater aortic stiffness leading to evolution or persistence of LV hypertrophy). Further studies are underway to determine the etiology of increased aortic stiffness and LV hypertrophy and the natural course of these changes. 025 PREVALENCE AND SIGNIFICANCE OF LATE GADOLINIUM ENHANCEMENT IN CHILDREN AND ADOLESCENTS WITH HYPERTROPHIC CARDIOMYOPATHY L Grosse-Wortmann, J Windram, D Andreea, S Yoo, L Mertens, D Wong, L Benson

Sex-Related Differences in Hypertension

Much of what we understand about the regulation of arterial pressure and extracellular fluid volume has been derived from studies in men. Although the responses that can be mounted against major physiological challenges to extracellular fluid volume (hemorrhage/dehydration) are essentially similar in men and women, there are marked sex-related differences in the regulation of renal and cardiovascular physiology. These possibly underpin the greater risk of renal and cardiovascular disease (CVD) in men and, conversely, confer the relative protection from these conditions in women, at least until menopause. In recent years, advances have been made in understanding the mechanistic bases for sex-related differences in CVD and these have been reviewed in detail.1–3 Therefore, the purpose of this report is to provide an update of findings in the past few years. Increasingly, studies are incorporating sex as a factor into their analyses. Although not all studies demonstrate a sex-specific interaction,4–7 many do, exemplifying the mantra, seek and ye shall find; this appears to be particularly true for sex-related differences in CVD. In recent years, evidence that women have smaller and stiffer hearts because of a greater collagen content has received a good deal of attention for the reason that it may explain some of the puzzling differences in clinical signs of CVD between men and women. Puntmann et al8 examined aortic stiffness by pulse wave velocity and ventricular deformation indices using MRI both at rest and during dobutamine challenge in elderly men and women. At rest, women had greater aortic stiffness and ventricular deformation than men. Moreover, sex-related differences were observed during stress because men had increased longitudinal and circumferential ventricular deformation during dobutamine challenge, whereas women only had an increase in circumferential deformation.8 These data suggest that differential loading of the aortic reservoir …