Relationships between cardiorespiratory fitness, hippocampal volume, and episodic memory in a population at risk for Alzheimer’s disease

Introduction: Cardiorespiratory fitness (CRF) has been shown to be related to brain health in older adults. In individuals at risk for developing Alzheimer\u27s disease (AD), CRF may be a modifiable risk factor that could attenuate anticipated declines in brain volume and episodic memory. The objective of this study was to determine the association between CRF and both hippocampal volume and episodic memory in a cohort of cognitively healthy older adults with familial and/or genetic risk for Alzheimer\u27s disease (AD). Methods: Eighty‐six enrollees from the Wisconsin Registry for Alzheimer\u27s Prevention participated in this study. Participants performed a graded maximal exercise test, underwent a T‐1 anatomical magnetic resonance imaging scan, and completed the Rey Auditory Verbal Learning Test (RAVLT). Results: There were no significant relationships between CRF and HV or RAVLT memory scores for the entire sample. When the sample was explored on the basis of gender, CRF was significantly associated with hippocampal volume for women. For men, significant positive associations were observed between CRF and RAVLT memory scores. Summary: These results suggest that CRF may be protective against both hippocampal volume and episodic memory decline in older adults at risk for AD, but that the relationships may be gender specific

A Prospective Randomized Controlled Trial of the Effects of Vitamin D Supplementation on Cardiovascular Disease Risk

Vitamin D (VitD) supplementation has been advocated for cardiovascular risk reduction; however, supporting data are sparse. The objective of this study was to determine whether VitD supplementation reduces cardiovascular risk. Subjects in this prospective, randomized, double-blind, placebo-controlled trial of post-menopausal women with serum 25-hydroxyvitamin D concentrations >10 and <60 ng/mL were randomized to Vitamin D3 2500 IU or placebo, daily for 4 months. Primary endpoints were changes in brachial artery flow-mediated vasodilation (FMD), carotid-femoral pulse wave velocity (PWV), and aortic augmentation index (AIx). The 114 subjects were mean (standard deviation) 63.9 (3.0) years old with a 25-hydroxyvitamin D level of 31.3 (10.6) ng/mL. Low VitD (<30 ng/mL) was present in 47% and was associated with higher body-mass index, systolic blood pressure, glucose, CRP, and lower FMD (all p<0.05). After 4 months, 25-hydroxyvitamin D levels increased by 15.7 (9.3) ng/mL on vitamin D3 vs. −0.2 (6.1) ng/mL on placebo (p<0.001). There were no significant differences between groups in changes in FMD (0.3 [3.4] vs. 0.3 [2.6] %, p = 0.77), PWV (0.00 [1.06] vs. 0.05 [0.92] m/s, p = 0.65), AIx (2.7 [6.3] vs. 0.9 [5.6] %, p = 0.10), or CRP (0.3 [1.9] vs. 0.3 [4.2] mg/L, p = 0.97). Multivariable models showed no significant interactions between treatment group and low VitD status (<30 ng/mL) for changes in FMD (p = 0.65), PWV (p = 0.93), AIx (p = 0.97), or CRP (p = 0.26).In conclusion, VitD supplementation did not improve endothelial function, arterial stiffness, or inflammation. These observations do not support use of VitD supplementation to reduce cardiovascular disease risk

Biomechanics models predict increasing smooth muscle tone as a novel therapeutic target for central arterial dysfunction in hypertension.

INTRODUCTION: Vasodilation can paradoxically increase arterial stiffness in older, hypertensive adults. This study modeled increasing smooth muscle tone as a therapeutic strategy to improve central arterial dysfunction in hypertension using participant-specific simulations. METHODS: Participant-specific models of the carotid artery were parameterized from vascular ultrasound measures of nitroglycerin-induced vasodilation in 18 hypertensive veterans. The acute changes in carotid artery mechanics were simulated for changes of ±2, ±4, and ±6% in smooth muscle tone and ±5, ±10, and ±15 mmHg in mean arterial pressure (MAP). The chronic carotid artery adaptations were simulated based on the hypothesis that the carotid artery will remodel wall-cross sectional area to maintain mechanical homeostasis. RESULTS: A 6% increase in smooth muscle tone acutely decreased carotid pulse wave velocity from 6.89 ± 1.24 m/s to 5.83 ± 1.73 m/s, and a 15 mmHg decrease in MAP decreased carotid pulse wave velocity to 6.17 ± 1.23 m/s. A 6% increase in smooth muscle tone acutely decreased wall stress from 76.2 ± 12.3 to 64.2 ± 10.4 kPa, and a 15 mmHg decrease in MAP decreased wall stress to 60.6 ± 10.7 kPa. A 6% increase in smooth muscle tone chronically decreased wall cross-sectional area from 18.3 ± 5.4 to 15.2 ± 4.9 mm 2, and a 15 mmHg decrease in MAP decreased wall cross-sectional area to 14.3 ± 4.6 mm 2 . CONCLUSION: In participant-specific simulation, increasing smooth muscle tone can have a stronger or equivalent effect on carotid artery mechanics compared with decreasing blood pressure. Increasing central arterial smooth muscle tone may be a novel therapeutic target to improve central arterial dysfunction in older, hypertensive adults and should be a focus of future research

Treatment of Obstructive Sleep Apnea in Young and Middle-Aged Adults: Effects of Positive Airway Pressure and Compliance on Arterial Stiffness, Endothelial Function, and Cardiac Hemodynamics.

BackgroundThe cardiovascular effects of positive airway pressure (PAP) therapy in obstructive sleep apnea (OSA) patients are not clear because of confounding by comorbid conditions.Methods and resultsProspective interventional study of PAP therapy and withdrawal. Apnea Hypopnea Index (AHI; events/hour of sleep) was determined from polysomnography. Central aortic blood pressures (BPs), Aortic Augmentation Index (AAIx), and central (PWVc-f) and peripheral pulse wave (PWVc-r) velocities were determined by applanation tonometry. Echocardiography and brachial artery reactivity testing were performed at baseline, after 4 and 12 weeks of PAP therapy, and 1 week after PAP withdrawal. The 84 participants were mean (SD) 41.1 (7.6) years old and had 39.8 (24.5) AHI events/hour. After 4 weeks post-PAP initiation and sustained after 12 weeks, subjects experienced decreases in central systolic BP (P=0.008), diastolic BP, mean BP, AAIx, and PWVc-r, and brachial artery dilation (all P&lt;0.001), as well as improvements in left ventricular diastolic function and systemic and pulmonary vascular resistance. In adjusted models, PAP use (hours/night) predicted reductions in diastolic BP (β=-0.65 [SE, 0.32] mm Hg/hour; P=0.045), AAIx (β=-0.53 [0.27] %/hour; P=0.049) and PWVc-r (β=-0.13 [0.05] m·s(-1)/hour; P=0.007), and improved brachial artery flow-mediated dilation (β=0.31 [0.14] %/hour use; P=0.015). After 1 week of PAP withdrawal, brachial diameter, diastolic BP, mean BP, AAIx, and heart rate increased (P≤0.05).ConclusionsPAP therapy reduces arterial tone and improves endothelial and diastolic function in young to middle-aged adults. This positive effect is observed after 4 weeks and depends on hours of use, but reverts quickly with PAP withdrawal.Clinical trial registrationURL: https://clinicaltrials.gov/. Unique identifier: NCT01317329

Cardiovascular consequences of correction of the anemia of renal failure with erythropoietin

Cardiovascular consequences of correction of the anemia of renal failure with erythropoietin. The purpose of this study was to define the physiologic responses of the heart and peripheral circulation to chronic anemia using noninvasive measurements while eliminating confounding biochemical, pharmacologic and physiologic variables. Stable chronic hemodialysis patients were studied at the University Hospital based chronic dialysis unit and echocardiography laboratory before and after therapy with human recombinant erythropoietin (rHuEPO). Subjects included maintenance hemodialysis patients free of left ventricular regional wall motion abnormalities discernible by echocardiography, rhythm disturbance, significant valvular or ischemic heart disease. Two-dimensional echocardiograms and simultaneous targeted M-mode echocardiograms, phonocardiograms and externally acquired subclavian artery pulse tracings were used to measure whole blood viscosity, arterial blood gases and ionized calcium, complete blood count, electrolytes, creatinine, blood urea nitrogen (BUN), and inorganic phosphate. All measurements were made immediately post-dialysis before and after therapy with rHuEPO. The interval between pre- and post-rHuEPO studies was 8.3 ± 2.3 months. We found that post-dialysis hematocrit rose from 24.7 ± 0.9 to 36.4 ± 0.9%, hemoglobin from 83 ± 3 to 121 ± 3 g/liter and whole blood viscosity from 2.87 ± 0.11 to 3.71 ± 0.18 centipoise (all, P < 0.001 after therapy with rHuEPO). The remaining biochemical measurements did not change. Heart rate fell from 83 ± 3 to 77 ± 3 beats/min (P = 0.013). Left ventricular preload and afterload were not statistically different before and after rHuEPO. Total vascular resistance rose from 1313 ± 84 to 1568 ± 129 dynes · sec · cm-5, P = 0.029. Cardiac output and cardiac index fell by 12 and 15% (P = 0.024 and 0.030), respectively. Left ventricular contractility assessed using load and heart rate independent indices fell after therapy with rHuEPO (P = 0.003) in the nine patients in whom it was measured. In conclusion, correction of the anemia of chronic renal failure in maintenance hemodialysis patients with rHuEPO reduces measurements of global left ventricular systolic function by decreasing the heart rate and contractile state without significantly altering chamber loading conditions. The net effect is a decrease in the hyperdynamic circulatory state that typically characterizes chronic anemia

Exercise increases arterial stiffness independent of blood pressure in older Veterans.

BACKGROUND: Exercise-induced changes in arterial function could contribute to a hypertensive response to exercise (HRE) in older individuals. We performed the present analysis to define the acute arterial stiffness response to exercise in ambulatory older adults. METHODS: Thirty-nine Veterans (&gt;60 years old), without known cardiovascular disease, participated in this study, including 19 Veterans who were hypertensive (70.8 ± 6.8 years, 53% women) and 20 Veterans who were normotensive (72.0 ± 9.3 years, 40% women). Arterial stiffness parameters were measured locally with carotid artery ultrasound and regionally with carotid-femoral pulse wave velocity (cfPWV) before and during the 10 min after participants performed a Balke maximal exercise treadmill stress test. RESULTS: The arterial stiffness response to exercise was similar for control and hypertensive participants. At 6 min postexercise, cfPWV was significantly increased (Δ1.5 ± 1.9 m/s, P  = 0.004) despite mean blood pressure (BP) having returned to its baseline value (Δ1 ± 8 mmHg, P  = 0.79). Arterial mechanics modeling also showed BP-independent increases in arterial stiffness with exercise ( P  &lt; 0.05). Postexercise cfPWV was correlated with postexercise SBP ( r  = 0.50, P  = 0.004) while baseline cfPWV ( r  = 0.13, P  = 1.00), and postexercise total peripheral resistance ( r  = -0.18, P  = 1.00) were not. CONCLUSION: In older Veterans, exercise increases arterial stiffness independently of BP and the arterial stiffness increase with exercise is associated with increased postexercise SBP. BP-independent increases in arterial stiffness with exercise could contribute to a HRE in older adults