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Aortic stiffening, assessed by carotid-femoral pulse wave velocity, is associated with CKD. Transmission of excessive flow pulsatility into the low-impedance renal microvasculature may mediate this association. However, direct analyses of macrovascular–microvascular relations in the kidney are limited. Using arterial tonometry, iohexol clearance, and magnetic resonance imaging, we related arterial stiffness, GFR, urinary albumin excretion, and potential mediators, including renal artery pulsatility index, renal vascular resistance, and arterial volume in the cortex, in 367 older adults (ages 72–92 years) participating in the Age, Gene/Environment Susceptibility-Reykjavik Study. In a model adjusted for age, sex, heart rate, and body size, aortic stiffness was related to GFR (Slope of regression B=−2.28±0.85 ml/min per SD, P=0.008) but not urine albumin (P=0.09). After accounting for pulsatility index, the relation between aortic stiffness and GFR was no longer significant (P=0.10). Mediation analysis showed that 34% of the relation between aortic stiffness and GFR was mediated by pulsatility index (95% confidence interval of indirect effect, −1.35 to −0.29). An additional 20% or 36% of the relation was mediated by lower arterial volume in the cortex or higher renal vascular resistance, respectively, when offered as mediators downstream from higher pulsatility index (95% confidence interval of indirect effect including arterial volume in the cortex, −2.22 to −0.40; 95% confidence interval of indirect effect including renal vascular resistance, −2.51 to −0.76). These analyses provide the first evidence that aortic stiffness may contribute to lower GFR by transferring excessive flow pulsatility into the susceptible renal microvasculature, leading to dynamic constriction or vessel loss.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a potentially powerful tool for analysis of kidney structure and function. The ability to measure functional and hypofunctional tissues could provide important information in groups at risk for chronic kidney disease (CKD), such as the elderly.Observational study with a cross-sectional design.493 volunteers (aged 72-94 years; 278 women; mean estimated glomerular filtration rate [eGFR], 67±15mL/min/1.73m(2); 40% with CKD) in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study.DCE-MRI kidney segmentation data.eGFR, urine albumin-creatinine ratio (ACR), and risk factors for and complications of CKD.After adjustment for age, sex, and height, eGFR was related to kidney volume (ΔR²=0.19; P0.001), cortex volume (ΔR²=0.14; P0.001), medulla volume (ΔR²=0.18; P0.001), and volume percentages of fibrosis (ΔR²=0.03; P0.001) and fat (ΔR²=0.01; P=0.03). In similarly adjusted models, log(ACR) was related to kidney volume (ΔR²=0.02; P0.001) and fibrosis volume percentage (ΔR²=0.03; P0.001). Using multivariable regression models adjusted for eGFR, ACR, age, sex, and height, kidney volume was related positively to body mass index (B=29.9±2.1[SE]mL; P0.001), smoking (B=19.7±7.7mL; P=0.01), and diabetes mellitus (B=14.8±7.1mL; P=0.04) and negatively to hematocrit (B=-4.4±2.1mL; P=0.04 [model R²=0.72; P0.001]); relations were per 1-SD greater value of the variable. Fibrosis volume percentage was associated positively with body mass index (B=0.28±0.03; P0.001), cardiac output (B=0.15±0.03; P0.001), and heart rate (B=0.08±0.03; P=0.01) and negatively with hematocrit (B=-0.07±0.3; P=0.02) and augmentation index (B=-0.06±0.03; P=0.04 [model R²=0.49; P0.001]); again, relations are per 1-SD greater value of the variable.Automatic segmentations were not validated by histology. The limited age range prevented meaningful interpretation of age effects on measured data or the automatic segmentation procedure.Kidney volume, cortex volume, and hypofunctional volume fraction assessed by DCE-MRI may provide information about CKD risk and prognosis beyond that provided by eGFR and urine ACR.

Background— Left ventricular (LV) contraction displaces the aortic annulus and produces a force that stretches the ascending aorta. We hypothesized that aortic stiffening increases this previously ignored component of LV load and may contribute to hypertrophy. Conversely, aortic stretch-related work represents stored energy that may facilitate early diastolic filling. Methods and Results— We performed MRI of the aorta and LV in 347 participants (72–91 years old, 189 women) in the Age, Gene/Environment Susceptibility-Reykjavik Study to examine relations of aortic stretch with LV structure and function. Aortic stiffness was evaluated as the product of Young’s modulus and aortic wall thickness. Force was computed from Young’s modulus and longitudinal aortic strain; work was the integrated product of force and annulus displacement during systole. LV mass and dynamic volume were measured using the area–length method. Filling was assessed from time-resolved LV volume curves. In multivariable models that adjusted for age, sex, height, weight, end-diastolic LV volume, augmentation index, end-systolic pressure, and cardiovascular disease risk factors, higher aortic stiffness was associated with increased LV mass (β=3.0±0.8% per SD, P P =0.8). Greater stretch-related aortic work was associated with enhanced early filling in men (β=4.0±0.8 mL/SD; P P =0.6). Conclusions— Higher aortic stiffness was associated with higher LV mass, independently of pressure. Higher stretch-related work was associated with greater early diastolic filling in men only. Impaired diastolic recovery of energy stored by systolic proximal aortic stretch may contribute to increased susceptibility to diastolic dysfunction in women.

Background Accurate assessment of mechanical properties of the proximal aorta is a requisite first step for elucidating the pathophysiology of isolated systolic hypertension. During systole, substantial proximal aortic axial displacement produces longitudinal strain, which we hypothesize causes variable underestimation of ascending aortic circumferential strain compared to values in the longitudinally constrained descending aorta. Methods and Results To assess effects of longitudinal strain, we performed magnetic resonance imaging in 375 participants (72 to 94 years old, 204 women) in the Age, Gene/Environment Susceptibility‐Reykjavik Study and measured aortic circumferential and longitudinal strain. Circumferential ascending aortic area strain uncorrected for longitudinal strain was comparable in women and men (mean [95% CI], 8.3 [7.8, 8.9] versus 7.9 [7.4, 8.5]%, respectively, P =0.3). However, longitudinal strain was greater in women (8.5±2.5 versus 7.0±2.5%, P P =0.010). Observed circumferential descending aortic strain, which did not require correction (women: 14.0 [13.2, 14.8], men: 12.4 [11.6, 13.2]%, P =0.005), was larger than uncorrected ( P P =0.12) circumferential ascending aortic strain. Carotid‐femoral pulse wave velocity did not correlate with uncorrected ascending aortic strain ( R =−0.04, P =0.5), but was inversely related to longitudinally corrected ascending and observed descending aortic strain ( R =−0.15, P =0.004; R =−0.36, P Conclusions Longitudinal strain creates substantial and variable errors in circumferential ascending aortic area strain measurements, particularly in women, and should be considered to avoid misclassification of ascending aortic stiffness.

Background-—Accurate assessment of mechanical properties of the proximal aorta is a requisite first step for elucidating the pathophysiology of isolated systolic hypertension. During systole, substantial proximal aortic axial displacement produces longitudinal strain, which we hypothesize causes variable underestimation of ascending aortic circumferential strain compared to values in the longitudinally constrained descending aorta.

High pulse pressure, a major cardiovascular risk factor, has been attributed to medial elastic fiber degeneration and aortic dilation, which transfers hemodynamic load to stiffer collagen. However, recent studies suggest higher pulse pressure is instead associated with smaller aortic diameter. Thus, we sought to elucidate relations of pulse pressure with aortic stiffness and aortic and cardiac dimensions. We used magnetic resonance imaging to examine relationships of pulse pressure with lumen area and wall stiffness and thickness in the thoracic aorta and left ventricular structure in 526 participants (72–94 years of age, 295 women) in the community-based Age, Gene/Environment Susceptibility-Reykjavik Study. In a multivariable model that adjusted for age, sex, height, weight, and standard vascular risk factors, central pulse pressure had a negative relationship with aortic lumen area (all effects expressed as mm Hg/SD; B=−8.1±1.2; P P P P =0.015). Higher pulse pressure in older people is associated with smaller aortic lumen area and greater aortic wall stiffness and thickness and left ventricular volume. Relationships of larger ventricular volume and smaller aortic lumen with higher pulse pressure suggest mismatch in hemodynamic load accommodation by the heart and aorta in older people.

Aortic stiffness increases with age and vascular risk factor exposure and is associated with increased risk for structural and functional abnormalities in the brain. High ambient flow and low impedance are thought to sensitize the cerebral microcirculation to harmful effects of excessive pressure and flow pulsatility. However, haemodynamic mechanisms contributing to structural brain lesions and cognitive impairment in the presence of high aortic stiffness remain unclear. We hypothesized that disproportionate stiffening of the proximal aorta as compared with the carotid arteries reduces wave reflection at this important interface and thereby facilitates transmission of excessive pulsatile energy into the cerebral microcirculation, leading to microvascular damage and impaired function. To assess this hypothesis, we evaluated carotid pressure and flow, carotid–femoral pulse wave velocity, brain magnetic resonance images and cognitive scores in participants in the community-based Age, Gene/Environment Susceptibility – Reykjavik study who had no history of stroke, transient ischaemic attack or dementia (n = 668, 378 females, 69–93 years of age). Aortic characteristic impedance was assessed in a random subset (n = 422) and the reflection coefficient at the aorta–carotid interface was computed. Carotid flow pulsatility index was negatively related to the aorta–carotid reflection coefficient (R = −0.66, P