Dietary Intake and Arterial Stiffness in Children and Adolescents: A Systematic Review.

Arterial stiffness is a risk factor for cardiovascular disease that is affected by diet. However, research understanding how these dietary risk factors are related to arterial stiffness during childhood is limited. The purpose of this review was to determine whether various dietary factors were associated with arterial stiffness in the pediatric population. Five databases were systematically searched. Intervention studies, cross-sectional and cohort studies were included that investigated nutrient or food intake and outcomes of arterial stiffness, primarily measured by pulse wave velocity (PWV) and augmentation index (AIx), in the pediatric population (aged 0-18 years). A final 19 studies (six intervention and 13 observational) were included. Only two intervention studies, including a vitamin D and omega-3 supplementation trial, found protective effects on PWV and AIx in adolescents. Findings from observational studies were overall inconsistent and varied. There was limited evidence to indicate a protective effect of a healthy dietary pattern on arterial stiffness and an adverse effect of total fat intake, sodium intake and fast-food consumption. Overall, results indicated that some dietary factors may be associated with arterial stiffness in pediatric populations; however, inconsistencies were observed across all study designs. Further longitudinal and intervention studies are warranted to confirm the potential associations found in this review.

Long-Term Effects of Sevelamer on Vascular Calcification, Arterial Stiffness, and Calcification Propensity in Patients Receiving Peritoneal Dialysis: The Randomized Pilot SERENE (Sevelamer on Vascular Calcification, Arterial Stiffness) Trial.

RATIONALE & OBJECTIVE: There is a concern regarding increased risk of vascular calcification with the use of calcium-based phosphorus binders. This study aimed to compare the effects of sevelamer used as a second-line, low-dose therapy with calcium-based phosphorus binders with those of sevelamer used as a first-line, high-dose therapy on coronary artery and heart valve calcification, aortic pulse wave velocity (PWV), and calcification propensity over 2 years in patients with hyperphosphatemia receiving peritoneal dialysis (PD). STUDY DESIGN: A 2-year-long prospective, multicenter, open-label, randomized pilot study. SETTING & PARTICIPANTS: Prevalent patients with hyperphosphatemia receiving PD from 2 university-affiliated hospitals in Hong Kong. INTERVENTIONS: The patients were randomized to receive sevelamer either as a first-line therapy at a high dose of 800 mg thrice daily (can titrate up to 1,200 mg thrice daily as required) or a second-line therapy at a low dose of 400 mg thrice daily with calcium carbonate to achieve a serum phosphorus target of ≤5.5 mg/dL. OUTCOMES: The primary endpoints were changes in coronary artery calcium score and aortic PWV over 104 weeks. The secondary endpoints were changes in heart valve calcium scores, calcification propensity measure, and biochemical parameters of chronic kidney disease-mineral bone disease over 104 weeks. RESULTS: Among 60 prevalent patients receiving PD, with a mean age of 53 ± 10 years and with 57% men, changes in the coronary artery calcium score (median [interquartile range], 225 [79-525] vs 223 [56-1,212], respectively; P = 0.21), aortic PWV (mean ± standard error, 0.3 ± 0.1 vs 0.8 ± 0.2 m/s, respectively; P = 0.31), heart valve calcium score, maturation or transformation time, serum calcium levels, and phosphorus levels over 104 weeks were similar for the second-line, low-dose and first-line, high-dose sevelamer groups. Alkaline phosphatase and intact parathyroid hormone levels increased and low-density lipoprotein cholesterol decreased in both the groups, with no significant between-group differences. LIMITATIONS: The sample size was small, and the dropout rates were relatively high. CONCLUSIONS: Low-dose sevelamer used as a second-line therapy for hyperphosphatemia in combination with a calcium-based phosphorus binder had similar effects on vascular calcification, valvular calcification, and arterial stiffness compared with high-dose sevelamer used as a first-line therapy. This approach may be considered in resource-constrained countries to minimize calcium loading. FUNDING: The study was supported by a competitive grant from SK Yee Medical Foundation. T50 assays and other biochemical assays were funded by a research grant from Sanofi Renal Corporation. TRIAL REGISTRATION: NCT00745589.

Effects of chronic dietary grape seed extract supplementation on aortic stiffness and hemodynamic responses in obese/overweight males during submaximal exercise.

We investigated the effect of chronic grape seed extract (GSE) on blood pressure and aortic stiffness (AoS) among overweight and obese males. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), stroke volume (SV), cardiac output (Q), total vascular conductance (TVC), and AoS were measured during two submaximal cycling exercises (40% and 60% VO2max), after 7 consecutive days of GSE or placebo (PL) ingestion with one week washout period. Compared with PL, GSE supplementation significantly decreased MAP at rest (85 ± 3 mmHg vs. 82 ± 3 mmHg), 40% (102 ± 3 mmHg vs. 99 ± 3 mmHg), and 60% workloads (109 ± 3 mmHg vs. 107 ± 3 mmHg) (P = 0.001, ES = 0.2). AoS was significantly reduced (13.0 ± 1.9 AU vs. 10.2 ± 1.0 AU) at rest (P = 0.002, ES = 0.6). Q was decreased at rest and across all workloads, but there were no significant differences (7.5 ± 0.4 L/min vs. 7.1 ± 0.4 L/min; 20.4 ± 1.2 L/min vs. 19.6 ± 0.9 L/min; 26.3 ± 1.1 L/min vs. 25.5 ± 1.6 L/min, respectively). GSE had no effect on HR, TVC, and SV. Our study indicates that chronic supplementation with GSE reduces arterial pressure at rest and during exercise primarily via the substantial reduction in AoS. Thus, GSE can be a dietary supplement to treat augmented blood pressure responses in obese and overweight males at rest and during exercise.Trial registration: ClinicalTrials.gov identifier: NCT04465110.

Aging-induced microbleeds of the mouse thalamus compared to sensorimotor and memory defects.

The aim of this study is to investigate the relationship between aging and brain vasculature health. Three groups of mice, 3, 17-18, and 24 months, comparable to young adult, middle age, and old human were studied. Prussian blue histology and fast imaging with steady precession T2∗-weighted magnetic resonance imaging were used to quantify structural changes in the brain across age groups. The novel object recognition test was used to assess behavioral changes associated with anatomical changes. This study is the first to show that the thalamus is the most vulnerable brain region in the mouse model for aging-induced vascular damage. Magnetic resonance imaging data document the timeline of accumulation of thalamic damage. Histological data reveal that the majority of vascular damage accumulates in the ventroposterior nucleus and mediodorsal thalamic nucleus. Functional studies indicate that aging-induced vascular damage in the thalamus is associated with memory and sensorimotor deficits. This study points to the possibility that aging-associated vascular disease is a factor in irreversible brain damage as early as middle age.

Association of Low Serum l-Carnitine Levels with Aortic Stiffness in Patients with Non-Dialysis Chronic Kidney Disease.

l-carnitine (LC) is a co-factor in fatty acid metabolism; its role with respect to aortic stiffness (AS) associated with chronic kidney disease (CKD) was unclear. Our aim was to investigate associations between serum LC levels and AS in patients with non-dialysis CKD stage 3-5. The AS patients were those with carotid-femoral pulse wave velocities (cfPWV) >10 m/s; those with cfPWV ≤10 m/s were included as controls. Serum LC was measured by liquid chromatography and mass spectrometry. Of 136 CKD patients, the 44 (32.4%) with AS were older, exhibited higher rates of diabetes, and had elevated diastolic and systolic blood pressures (SBP), elevated fasting glucose levels and lower levels of serum LC compared to controls. Multivariable logistic regression revealed that serum LC (odds ratio [OR] = 0.949, 95% confidence interval [CI] 0.911-0.988, p = 0.011) and age (OR = 1.055, 95% CI 1.013-1.099, p = 0.009) were independent predictors of AS. Multivariable stepwise linear regression revealed significant positive (age and SBP) and negative (serum LC) correlations with cfPWV. The area under the curve of serum LC as a means to predict AS in CKD patients was 0.657 (95% CI 0.571-0.736, p = 0.0009). We concluded that low serum LC is a significant predictor of AS in patients diagnosed with CKD.

Music decreases aortic stiffness and wave reflections.

OBJECTIVE: Music has been related to cardiovascular health and used as adjunct therapy in patients with cardiovascular disease. Aortic stiffness and wave reflections are predictors of cardiovascular risk. We investigated the short-term effect of classical and rock music on arterial stiffness and wave reflections. METHODS: Twenty healthy individuals (22.5±2.5 years) were studied on three different occasions and listened to a 30-min music track compilation (classical, rock, or no music for the sham procedure). RESULTS: Both classical and rock music resulted in a decrease of carotid-femoral pulse wave velocity (PWV) immediately after the end of music listening (all p<0.01). Augmentation index (AIx) decreased with either classical or rock music in a more sustained way (nadir by 6.0% and 5.8%, respectively, at time zero post-music listening, all p<0.01). When music preference was taken into consideration, both classical and rock music had a more potent effect on PWV in classical aficionados (by 0.20 m/s, p=0.003 and 0.13 m/s, p=0.015, respectively), whereas there was no effect in rock aficionados (all p=NS). Regarding wave reflections, classical music led to a more potent response in classical aficionados (AIx decrease by 9.45%), whereas rock led to a more potent response to rock aficionados (by 10.7%, all p<0.01). CONCLUSIONS: Music, both classical and rock, decreases aortic stiffness and wave reflections. Effect on aortic stiffness lasts for as long as music is listened to, while classical music has a sustained effect on wave reflections. These findings may have important implications, extending the spectrum of lifestyle modifications that can ameliorate arterial function.

The effects of long-chain omega-3 fish oils and multivitamins on cognitive and cardiovascular function: a randomized, controlled clinical trial.

OBJECTIVE: Fish oils and multivitamins are two of the most commonly used dietary supplements. Fish oil use may reduce vascular risk factors associated with cognitive decline, thus providing benefits to both heart and brain health. Multivitamins may also have direct effects on brain function. The present study investigated the effects of fish oil, with and without the addition of a multivitamin, on cognitive and cardiovascular function. METHODS: In a randomized, placebo-controlled, double-blind fashion, 160 healthy adults aged 50-70 years were randomized to receive either 3 g of fish oil (240 mg eicosapentaenoic acid [EPA] + 240 mg docosahexaenoic acid [DHA]) with a multivitamin, 6 g of fish oil (480 mg EPA + 480 mg DHA) with a multivitamin, or 6 g of fish oil without a multivitamin or a placebo. Cognitive performance, brachial blood pressure, and aortic (central) blood pressure were measured at baseline, 6 weeks, and 16 weeks. RESULTS: Treatment allocation had no effect on the primary cognitive outcomes at endpoint. Absolute increases in the red blood cell omega-3/6 ratio were associated with improvements in spatial working memory. The group receiving 6 g fish oil without the multivitamin displayed a significant decrease in aortic pulse pressure and aortic augmentation pressure, two measures of aortic blood pressure and aortic stiffness. CONCLUSIONS: Fish oil decreased aortic pulse pressure and augmentation pressure. Reductions in aortic blood pressure were not accompanied by consistent improvements in cognition.

Active vitamin D and accelerated progression of aortic stiffness in hemodialysis patients: a longitudinal observational study.

BACKGROUND: We hypothesized that high-dose active vitamin D therapy in the form of alphacalcidol (α-calcidol), used to treat secondary hyperparathyroidism in chronic kidney disease, could lead to vascular calcification and accelerated progression of aortic stiffness. METHODS: We conducted an observational study in 85 patients on chronic hemodialysis, among which 70 were taking a weekly dose of α-calcidol of <2 µg and 15 were taking a weekly dose of ≥2 µg (pharmacological dose). Parathyroid hormone, 25-hydroxyvitamin D, fibroblast growth factor 23, and α-klotho were determined. Aortic stiffness was assessed by determination of carotid-femoral pulse wave velocity (cf-PWV) at baseline and after a mean follow-up of 1.2 years. A multivariable regression model was used to evaluate the impact of pharmacological dose of α-calcidol on the progression of aortic stiffness. RESULTS: At baseline, clinical, biological, and hemodynamic parameters were similar. At follow-up, cf-PWV increased more in patients with pharmacological dose of α-calcidol (0.583±2.291 m/s vs. 1.948±1.475 m/s; P = 0.04). After adjustment for changes in mean blood pressure and duration of follow-up, pharmacological dose of α-calcidol was associated with a higher rate of progression of cf-PWV (0.969 m/s; 95% confidence interval = 0.111-1.827; P = 0.03), and this association persisted after further adjustments for parameters of mineral metabolism. CONCLUSIONS: In this study, pharmacological dose of α-calcidol was associated with accelerated progression of aortic stiffness. This study suggest that the vascular safety of active vitamin D posology may need to be specifically addressed in the treatment of chronic kidney disease-related bone mineral disorder.