Breakfast skipping suppresses vascular endothelial function of the brachial artery after lunch.

Breakfast skipping has been suggested to be associated with cardiovascular diseases. However, whether breakfast skipping affects vascular endothelial function (VEF), a marker of cardiovascular diseases, remains unclear. This study aimed to investigate the impact of breakfast consumption (Eating trial) and skipping (Skipping trial) on brachial artery (BA) VEF in healthy breakfast eaters. A total of nine healthy individuals (four females and five males) either had breakfast between 8:30 and 9:00 or skipped it and had lunch between 12:00 and 12:30, followed by a 3-h rest period until 15:30. For BA VEF evaluation, flow-mediated dilation (FMD) was measured using ultrasound before and after breakfast and lunch. FMD was calculated as the percentage change in BA diameter normalized to the shear rate area under the curve (FMD/SRAUC). Blood glucose, plasma insulin, and plasma free fatty acid levels in capillaries were measured before and after breakfast and lunch. At 15:30, the Eating trial, but not the Skipping trial, significantly increased FMD/SRAUC from baseline (p = 0.006). The Skipping trial showed significantly lower changes in FMD/SRAUC from 8:30 than the Eating trial at 15:30 (p < 0.001). We found a significant inverse correlation between changes in FMD/SRAUC between 8:30 and 15:30 and peak glucose levels after lunch (r = -0.882, p < 0.001) and with an incremental area under the curve for glucose between 8:30 and 15:30 (r = -0.668, p < 0.001). These results suggest that a single bout of breakfast skipping can suppress BA VEF in the afternoon due to postlunch hyperglycemia.

Current topic of vascular function in hypertension in 2023-2024.

Noninvasive tests of vascular function are useful for assessing the severity of atherosclerosis and risk of cardiovascular events, understanding the pathophysiology of cardiometabolic disorders, and investigating the effects of therapeutic interventions on cardiovascular morbidity and mortality, all of which can provide additional information for the management of patients with cardiovascular risk factors or a history of cardiovascular disease. In 2023-2024, many excellent articles on vascular function were published in Hypertension Research and other major cardiovascular and hypertension journals, and we summarize the emerging evidence on vascular function in this review. We hope that this review will be helpful for the management of patients with cardiovascular risk factors in clinical practice and for future basic and clinical research on vascular function.

Microvascular effects of a mixed meal tolerance test: a model validation study.

PURPOSE: Endothelial dysfunction is a pathophysiological change preceding many cardiovascular events. Measuring improvements of endothelial function is challenging when function is already optimal, which may be remediated using a physiological challenge. This study aimed to determine whether imaging assessments can detect microvascular effects of a mixed meal tolerance test (MMTT). METHODS: Twenty healthy volunteers (age ≥45 and ≤70 years) underwent two MMTTs at the beginning (Day 1) and end (Day 84) of a twelve-week period. Imaging methods included laser speckle contrast imaging (LSCI) combined with post-occlusive reactive hyperaemia (PORH) and local thermal hyperaemia (LTH) challenges, passive leg movement ultrasonography (PLM), and sidestream dark field microscopy (SDFM). Measurements were conducted pre-MMTT and at 5 timepoints post-MMTT for PLM and SDFM and 3 timepoints post-MMTT for PORH and LTH. RESULTS: No consistent effects of the MMTT were detected on LSCI LTH, PLM and SDFM endpoints. LSCI PORH maximum perfusion was significantly suppressed 46, 136, and 300 min post-MMTT administration on Day 1, while residual perfusion decreased significantly 46 and 136 min post-MMTT on Day 1. However, when repeated on Day 84, PORH endpoints were not significantly affected by the MMTT. CONCLUSION: SDFM, PLM and LSCI LTH endpoints displayed high intra-subject variability and did not detect consistent effects of MMTT. LSCI PORH endpoints displayed the lowest intra-subject variability of all assessed endpoints and were affected by the MMTT on Day 1, but not on Day 84. Further standardization of methods or more robust challenges to affect vascular endpoints may be needed.

Differences in cardiovascular risk factors associated with sex and gender identity, but not gender expression, in young, healthy cisgender adults.

Background: Sex differences exist in cardiovascular disease risk factors including elevated blood pressure and arterial stiffness, and decreased endothelial function in males compared to females. Feminine gender expression may be associated with elevated risk of acute coronary syndrome. However, no study has investigated the associations between sex, gender identity, and gender expression and cardiovascular disease risk factors in young adults. Methods: One hundred and thirty participants (22 ± 3 years) underwent assessments of hemodynamics, arterial stiffness [pulse wave velocity (PWV)], and brachial artery endothelial function (flow-mediated dilation; %FMD). Participants completed a questionnaire capturing sex category (50 male/80 female), gender identity category (49 men/79 women/2 non-binary), and aspects of gender expression assessed by the Bem Sex Role Inventory-30 (39 androgynous/33 feminine/29 masculine/29 undifferentiated). Sex/gender identity category groups were compared using unpaired t-tests and gender expression groups compared using one-way ANOVAs. Results: Resting systolic and mean arterial pressure (p < 0.01) were elevated in males vs. females. Central PWV was elevated in males [median (interquartile range): 6.4 (1.8) vs. 5.8 (2.2) m/s, p = 0.02]; however, leg and arm PWV were not different between sexes. %FMD was elevated in males vs. females, after accounting for a larger baseline artery diameter in males (8.8 ± 3.3% vs. 7.2 ± 3.1%, p = 0.02); since the majority of participants were cisgender, the same results were found examining gender identity (men vs. women). There were no differences across gender expression groups (p > 0.05). Conclusions: Sex/gender identity category, but not gender expression, influence cardiovascular risk factors (blood pressure, arterial stiffness, endothelial function) in cisgender adults; further research is needed in gender-diverse populations.

Vascular endothelial function and its response to moderate-intensity aerobic exercise in trained and untrained healthy young men.

30 min of moderate-intensity aerobic exercise per day is recommended, but the response and adaptation of endothelial function (EF) to this exercise remains controversial. The purpose of this study was to determine the changes in EF in endurance trained and untrained individuals before and after this exercise and to compare the differences between trained and untrained individuals. Twelve endurance-trained male college athletes (trained group) and 12 untrained male college students (untrained group) performed a 30-min run at an intensity of 60% VO2max. Brachial artery flow-mediated dilation (FMD) was measured before exercise, 30 min and 60 min after exercise, and the following morning. Resting diameter and maximum diameter showed large time effects (p < 0.001, η2 = 0.533; p < 0.001, η2 = 0.502). Resting diameters at 30 and 60 min after exercise were higher than before exercise in both the untrained and trained groups (p < 0.05), and maximum diameters at 30 min after exercise were higher than before exercise in both the untrained and trained groups (p < 0.01). Resting diameter and maximum diameter also exhibited some group effects (p = 0.055, η2 = 0.157; p = 0.041, η2 = 0.176). Resting diameters and maximum diameters were higher in the trained group than in the untrained group before exercise (p < 0.05). FMD (%) showed no time, group, or time-group interaction effects. 30 min of moderate-intensity aerobic exercise can increase resting and maximal arterial diameters in both trained and untrained young men, but has no effect on FMD. Long-term endurance training has the potential to increase resting and maximal arterial diameters in young men, but not necessarily FMD.

Association between endothelial function and skin advanced glycation end-products (AGEs) accumulation in a sample of predominantly young and healthy adults.

BACKGROUND: In populations with chronic disease, skin autofluorescence (SAF), a measure of long-term fluorescent advanced glycation end-products (AGEs) accumulation in body tissues, has been associated with vascular endothelial function, measured using flow-mediated dilation (FMD). The primary aim of this study was to quantify the relationship between endothelial function and tissue accumulation of AGEs in adults from the general population to determine whether SAF could be used as a marker to predict early impairment of the endothelium. METHODS: A cross-sectional study was conducted with 125 participants (median age: 28.5 y, IQR: 24.4-36.0; 54% women). Endothelial function was measured by fasting FMD. Skin AGEs were measured as SAF using an AGE Reader. Participant anthropometry, blood pressure, and blood biomarkers were also measured. Associations were evaluated using multivariable regression analysis and were adjusted for significant covariates. RESULTS: FMD was inversely correlated with SAF (ρ = -0.50, P < 0.001) and chronological age (ρ = -0.51, P < 0.001). In the multivariable analysis, SAF, chronological age, and male sex were independently associated with reduced FMD (B [95% CI]; -2.60 [-4.40, -0.80]; -0.10 [-0.16, -0.03]; 1.40 [0.14, 2.67], respectively), with the multivariable model adjusted R2 = 0.31, P < 0.001. CONCLUSIONS: Higher skin AGE levels, as measured by SAF, were associated with lower FMD values, in a predominantly young, healthy population. Additionally, older age and male participants exhibited significantly lower FMD values, corresponding with compromised endothelial function. These results suggest that SAF, a simple and inexpensive marker, could be used to predict endothelial impairment before the emergence of any structural artery pathophysiology or classic cardiovascular disease risk markers. TRIAL REGISTRATION: The study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000821897) and concurrently entered into the WHO International Clinical Trials Registry Platform under the same ID number.

The effect of curcumin supplementation on endothelial function and blood pressure in patients with metabolic disorders: A meta-analysis of meta-analyses.

Several interventional studies have revealed the beneficial impact of curcumin supplementation on blood pressure and endothelial function, but the findings are conflicting. Therefore, this study was conducted to investigate the effects of curcumin supplementation on blood pressure and endothelial function. A meta-analyses of randomized clinical trials were performed by searching PubMed, Embase, Scopus, and Web of Science were searched up to March 31, 2024. Random effects models were used to calculate weighted mean differences (WMD). Pooled estimates of 10 studies revealed that curcumin decreased diastolic blood pressure (DBP) [WMD = -0.94, 95 % CI: -1.59, -0.30; p = 0.004], pulse wave velocity (PWV) [WMD = -45.60, 95 % CI: -88.16, -3.04; p = 0.03, I2 = 0.0 %, p = 0.59], and vascular cell adhesion molecule-1 (VCAM-1) [WMD = -39.19; 95 % CI: -66.15, -12.23, p =0.004; I2=73.0 %, p = 0.005] significantly, and increased flow-mediated dilation (FMD) [WMD = 1.64, 95 % CI: 1.06, 2.22; p < 0.001, I2 = 0.0 %, p = 0.61. However, curcumin did not significantly change systolic blood pressure (SBP) [WMD = -0.64, 95 % CI: -1.96, 0.67; p =0.34, I2 = 83.5 %, p <0.001], and Intercellular Adhesion Molecule 1 (ICAM1) [WMD = -17.05; 95 % CI: -80.79, 46.70, p =0.601; I2=94.1 %, p < 0.001]. These results suggest that curcumin has a beneficial effect on DBP, PWV, VCAM-1 and FMD levels and may be an effective adjunctive therapy for improving blood pressure and endothelial function.

[Clinical efficacy and safety of Picamilon in patients with progressive chronic cerebral ischemia]. / Klinicheskaya effektivnost' i bezopasnost' primeneniya preparata Pikamilon u patsientov s khronicheskoi ishemiei golovnogo mozga.

OBJECTIVE: To study the efficacy and safety of the drug Picamilon with various therapy regimens in patients with stage II chronic cerebral ischemia (CCI). MATERIAL AND METHODS: An open cohort clinical study involved 50 patients diagnosed with stage II CCI aged 51 to 69 years (average age 62.2±8.98 years). Patients received Picamilon first parenterally 200 mg (100 mg/ml, 2 ml) intravenously for 10 days, then orally in 50 mg tablets 3 times a day for 60 days. The total duration of therapy in the group was 70 days. The study included 3 visits (before treatment, after completion of the course, 1.5 months after completion of treatment). The dynamics of cognitive status according to the Montreal Cognitive Assessment Scale, vegetative disorders according to the A.M. Vane scale, neurological disorders according to the A.I. Fedin scale, and sleep quality according to the Ya. I. Levin scale were compared. The state of cerebral blood flow and endothelium was studied before and after treatment: dopplerography of cranial vessels, assessment of the level of methylated forms of arginine (ADMA, MMA, SDMA) and their ratios. The registration of adverse events against the background of therapy and the tolerability of treatment by patients was also carried out. RESULTS: Against the background of Picamilon treatment, a significant positive dynamics of the MoCA scale results was observed in the general sample of patients, increasing in the delayed period (20.9, 24.6 and 25.9, p<0.0001 and p=0.0006); sleep normalization was observed in 55% of patients by Visit 2 and in 81% of patients by Visit 3 (p<0.0001 and p=0.0025). Improvement of neurological functions is noted in 84% of patients, the score on the Fedin A.I. scale significantly decreases after treatment from 17.4±9.34 to 8.06±6.84 (p<0.0001) and to 5.31±5.71 in the delayed period (p=0.0002). Normalization of vegetative status was observed in 38% of patients with stage II CCI, and in 60% of cases there was a decrease in the severity of vegetative dystonia syndrome (p=0.0001). Picamilon therapy has high efficacy in assessing clinical outcomes (100%), good tolerability in 98% of patients and is characterized by a favorable safety profile (in 92% of patients). Picamilon significantly affects the parameters of cerebral hemodynamics: increases the linear velocity of blood flow, reduces the thickness of the intima-media complex and the resistance index. It affects markers of NO metabolism and endothelial function: significantly reduces elevated levels of ADMA and ADMA/MMA and (ADMA+SDMA)/MMA ratios. CONCLUSION: The use of Picamilon is effective in patients with stage II CCI in the form of step therapy contributes to a significant regression of neurological deficit, cognitive impairment, improvement of sleep quality and autonomic function; improves vascular endothelial function, reduces the risk of cardiovascular complications. Picamilon is a pathogenetic therapy agent that prevents the progression of CCI.

Body Composition, Vascular Health, Cardiorespiratory Fitness, Lung Function, Muscle Architecture, and Physical Activity in People with Young Onset Dementia: A Case-Control Study.

BACKGROUND: Body composition, blood pressure, estimated maximal oxygen uptake (VO2max), lung function, physical activity, muscle architecture, and endothelial function had not previously been examined in people with young onset dementia. Therefore, the study measured these variables in a young onset dementia group, compared them to age-matched controls. METHODS: Estimated VO2max (via the Astrand-Rhyming test), body composition, blood pressure, lung function (via spirometry), muscle architecture (via ultrasonography) and endothelial function (via flow mediated dilation) were assessed. Physical activity was measured using ActiGraph accelerometers for 7 days. RESULTS: We recruited 33 participants (16 young onset dementia, 17 controls). The young onset dementia group had shorter fascicle lengths of the vastus lateralis, were sedentary for longer over a seven-day period, and completed less moderate-vigorous physical activity than controls (p=0.028, d=0.81; large effect, p=0.029, d=0.54; moderate effect, and p=0.014, d=0.97; large effect, respectively for pairwise comparisons). Pairwise comparisons suggest no differences at the p<0.05 level between young onset dementia and controls for estimated VO2max (despite a moderate effect size [d=0.66]), height, body mass, BMI, blood pressure, light physical activity, lung function, muscle thickness, pennation angle, or endothelial function. CONCLUSION: This study highlights differences between people with young onset dementia and controls, underscoring the need for multicomponent exercise interventions. Future interventions should target muscle architecture, increase moderate-vigorous physical activity, and reduce sedentariness, with the goal of improving quality of life and promoting functional independence.

Effects of excess sodium consumption on arterial function in C57BL/6 mice.

Excess sodium consumption contributes to arterial dysfunction in humans. The C57BL/6 strain of mice has been used to identify mechanisms by which arterial dysfunction occurs after excess sodium consumption. However, there are concerns that C57BL/6 mice have strain-specific resistance to high-sodium (HS) diet-induced hypertension. To address this concern, we performed a meta-analysis to determine if excess sodium consumption in C57BL/6 mice induces arterial dysfunction. Databases were searched for HS versus standard diet studies that measured arterial function [i.e., systolic blood pressure (BP), endothelium-dependent dilation (EDD), and central arterial stiffness] in C57BL/6 mice. A total of 39 studies were included, demonstrating that the HS condition resulted in higher systolic BP than control mice with a mean difference of 9.8 mmHg (95% confidence interval [CI] = [5.6, 14], P < 0.001). Subgroup analysis indicated that the systolic BP was higher in HS compared with the control condition when measured during night compared with daytime with telemetry (P < 0.001). We also identified that the difference in systolic BP between HS and control was ∼2.5-fold higher when administered through drinking water than through food (P < 0.001). A total of 12 studies were included, demonstrating that the HS condition resulted in lower EDD than control with a weighted mean difference of -12.0% (95% CI = [-20.0, -4.1], P = 0.003). It should be noted that there was considerable variability across studies with more than half of the studies showing no effect of the HS condition on systolic BP or EDD. In summary, excess sodium consumption elevates systolic BP and impairs EDD in C57BL/6 mice.NEW & NOTEWORTHY C57BL/6 mice are perceived as resistant to high-sodium diet-induced arterial dysfunction. This meta-analysis demonstrates that excess sodium consumption elevates blood pressure and impairs endothelium-dependent dilation in C57BL/6 mice. Nighttime measurements show more pronounced blood pressure elevation. In addition, sodium administration via drinking water, compared with food, induces a greater blood pressure elevation. These findings may be influenced by outlier studies, as the majority of studies showed no adverse effect of excess sodium consumption on arterial function.

Vascular function in patients with advanced heart failure and continuous-flow or pulsatile ventricular assist devices.

BACKGROUND: A significant proportion of patients with heart failure (HF) progress to an advanced stage, which is associated with a substantial increase in morbidity and mortality. These patients may be eligible for advanced treatment strategies such as mechanical circulatory support with ventricular assist devices (VAD). Vascular dysfunction is a hallmark of heart failure pathophysiology and prognosis. However, whether and to what degree the hemodynamic benefits of VADs influence vascular function remain unknown. METHODS AND RESULTS: In this study, we evaluated endothelial vascular function with flow-mediated vasodilatation (FMD) and with flicker-light induced retinal vasodilatation (FID). 34 patients with a VAD (age 58 ± 10 years, 85% male, 74% ischemic heart disease, 26 continuous-flow (CF)-LVAD, and 8 pulsatile biventricular (bi)-VAD) were compared to 34 propensity-matched patients (mean age 62 ± 9 years, 68% male, 59% ischemic heart disease) with advanced HF (AdvHF). Endothelial function of larger arteries (FMD) was significantly better in patients after VAD implantation compared to matched AdvHF patients (7.2 ± 4.6% vs. 5.0 ± 3.2%, p = 0.03), whereas microvascular arteriolar function (FIDart) did not differ (0.99 ± 1.43% vs. 1.1 ± 1.7%, p = 0.78). The arterio-venous ratio (AVR) was higher in the VAD group (0.90 ± 0.06 vs 0.85 ± 0.09, p = 0.01), reflecting wider retinal arteriolar and narrower venular diameters. There was no difference in vascular function between patients with CF-LVAD and pulsatile Bi-VAD. CONCLUSION: In patients with advanced heart failure, VAD implantation was associated with better endothelial function at the level of large arteries, but not in the microcirculation.

Vascular endothelium: The interface for multiplex signal transduction.

As the innermost monolayer of the vasculature, endothelial cells (ECs) serve as the interface for multiplex signal transduction. Directly exposed to blood-borne factors, both endogenous and exogenous, ECs actively mediate vascular homeostasis and represent a therapeutic target against cardiometabolic diseases. ECs act as the first-line gateway between gut-derived substances and vasculature. Additionally, ECs convert blood flow-exerted hemodynamic forces into downstream biochemical signaling to modulate vascular pathophysiology. Besides, ECs can sense other forms of stimuli, like cell extrusion, thermal stimulation, photostimulation, radiation, magnetic field, noise, and gravity. Future efforts are still needed to deepen our understanding on endothelial biology.

Menstrual and oral contraceptive pill cycles minimally influence vascular function and associated cellular regulation in premenopausal females.

BACKGROUND: Historical exclusion of females in research has been, in part, due to the perceived influence of natural menstrual (NAT) and oral contraceptive pill (OCP) cycles on vascular outcomes. NAT and OCP cycle phases may influence brachial artery (BA) endothelial function, however, findings are mixed. Minimal research has examined arterial stiffness, smooth muscle and lower limb endothelial function. The purpose of this study was to investigate the influence of NAT and OCP cycles on cardiovascular outcomes and cellular regulation. METHODS: Forty-nine premenopausal females (n=17 NAT, n=17 2nd generation OCP, n=15 3rd generation OCP) participated in two randomized order visits in the low (LH: early follicular/placebo) and high (HH: mid-luteal/active) hormone cycle phases. BA and femoral artery (SFA) endothelial function [flow-mediated dilation (FMD) test], smooth muscle function (nitroglycerine-mediated dilation test) and carotid and peripheral (pulse wave velocity) arterial stiffness were assessed. Cultured female human endothelial cells were exposed to participant serum for 24h to examine endothelial nitric oxide synthase (eNOS) and estrogen receptor alpha (ERα) protein content. RESULTS: BA FMD was elevated in the HH versus LH phase, regardless of group (HH:7.7±3.5%, LH:7.0±3.3%, p=0.02); however, allometric scaling for baseline diameter resulted in no phase effect (HH:7.6±2.6%, LH:7.1±2.6%, p=0.052, d=0.35). SFA FMD, BA and SFA smooth muscle function, arterial stiffness, and eNOS and ERα protein content were unaffected. CONCLUSIONS: NAT and OCP phases examined have minimal influence on vascular outcomes and ERα-eNOS pathway, apart from a small effect on BA endothelial function partially explained by differences in baseline artery diameter.

Asperuloside as a Novel NRF2 Activator to Ameliorate Endothelial Dysfunction in High Fat Diet-Induced Obese Mice.

Aims: Current treatments are inadequate in alleviating obesity-associated vascular diseases. The development of effective therapies to ameliorate endothelial dysfunction and attenuate oxidative stress is of utmost importance. Asperuloside (ASP), a bioactive compound extracted from Eucommia species, exhibits antiobesity properties. However, the effects of ASP on vasculopathy have not been investigated. Therefore, the effects of ASP on vascular dysfunction and related mechanisms were elucidated. Results: ASP significantly reversed the impaired endothelium-dependent relaxations (EDRs) in obese mice and interleukin (IL)-1ß-treated aortas. ASP suppressed endothelial activation in obese mice aortas and IL-1ß-treated endothelial cells. ASP attenuated oxidative stress, scavenged mitochondrial reactive oxygen species (ROS), and upregulated heme oxygenase-1 (HO-1) expression in endothelium, independent of its anti-inflammatory properties. HO-1 knockdown diminished the protective effects of ASP against impaired EDRs, ROS overproduction, and endothelial activation. Endothelial cell-specific nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown eliminated the ASP-mediated vascular protective effects and endothelial HO-1 upregulation, emphasizing that ASP improves endothelial function by activating Nrf2/HO-1 signaling. ASP facilitated Nrf2 nuclear translocation and the direct binding of Nrf2 to antioxidant response element, thereby enhancing HO-1 transcription and scavenging ROS. The cellular thermal shift assay results provide the first experimental characterization of the direct binding of ASP to Nrf2. Conclusions: These findings demonstrate that ASP ameliorates obesity-associated endothelial dysfunction by activating Nrf2/HO-1 signaling and thereby maintaining redox hemostasis, suggesting its potential as a novel Nrf2-targeted therapeutic agent and dietary supplement for vasculopathy.

Increase of PCSK9 expression in diabetes promotes VEGFR2 ubiquitination to inhibit endothelial function and skin wound healing.

Diabetic foot ulcers (DFUs) are a serious vascular disease. Currently, no effective methods are available for treating DFUs. Pro-protein convertase subtilisin/kexin type 9 (PCSK9) regulates lipid levels to promote atherosclerosis. However, the role of PCSK9 in DFUs remains unclear. In this study, we found that the expression of PCSK9 in endothelial cells (ECs) increased significantly under high glucose (HG) stimulation and in diabetic plasma and vessels. Specifically, PCSK9 promotes the E3 ubiquitin-protein ligase NEDD4 binding to vascular endothelial growth factor receptor 2 (VEGFR2), which led to the ubiquitination of VEGFR2, resulting in its degradation and downregulation in ECs. Furthermore, PCSK9 suppresses the expression and activation of AKT, endothelial nitric oxide synthase (eNOS), and ERK1/2, leading to decreased nitric oxide (NO) production and increased superoxide anion (O2._) generation, which impairs vascular endothelial function and angiogenesis. Importantly, using evolocumab to limit the increase in PCSK9 expression blocked the HG-induced inhibition of NO production and the increase in O2._ production, as well as inhibited the phosphorylation and expression of AKT, eNOS, and ERK1/2. Moreover, evolocumab improved vascular endothelial function and angiogenesis, and promoted wound healing in diabetes. Our findings suggest that targeting PCSK9 is a novel therapeutic approach for treating DFUs.

Effects of Singing on Vascular Health in Older Adults with Coronary Artery Disease: A Randomized Trial.

Background: The impact of singing on cardiovascular health has not been extensively studied. The aim of this study is to investigate the effect of singing on cardiovascular biomarkers in an aging population with coronary artery disease. Methods: Participants had three study visits separated by 2-7 days, according to a randomized, single-blind, cross-over, controlled design: (1) a 30-minute period of coached singing from an in-person music therapist, (2) a 30-minute period of singing along to an instructional video and (3) a 30-minute rest (control). Primary outcomes included macrovascular endothelial function assessed by brachial artery flow-mediated dilation and microvascular function assessed by peripheral arterial tonometry (Framingham reactive hyperemia index; fRHI). Heart rate variability was a secondary outcome. Results: Sixty-five subjects (mean age 67.7± 0.8, 40% women) completed the study. Compared to control, there was an increase in fRHI for the singing video intervention (estimate 0.54, SE 0.25, p=0.005) but not for the coaching intervention (estimate 0.11, SE 0.18, p=0.570). There was no change in macrovascular function with either intervention. The low frequency/high frequency (LF/HF) ratio increased by 2.80 (SE 1.03, p=0.008), and the LnHF power decreased by -0.90 ms2 (SE 0.29, p=0.003) with the video (during to pre-change). When assessing post- to pre- change, the coaching intervention showed a significant change of -0.62 ms2 (SE 0.29, p=0.036) in LnHF power. Conclusions: Singing along to an instructional video for 30 minutes improved microvascular, but not macrovascular, endothelial function, in older patients with CAD. HRV changes with singing are similar to that of exercise. Clinical trial registration: ClinicalTrials.gov, identifier: NCT04121741.

Association of Gestational Diabetes With Subclinical Cardiovascular Disease.

Background: Gestational diabetes mellitus (GDM) is associated with increased long-term risk of cardiovascular disease but the cardiovascular structural and functional changes that contribute to risk are not well understood. Objectives: The purpose of this study was to determine whether GDM is associated with adverse cardiac remodeling and endothelial dysfunction a decade after delivery, independent of type 2 diabetes. Methods: Women with deliveries between 2008 and 2009 were initially selected from a prospective clinical cohort. Pregnancy history was chart abstracted and a follow-up study visit was conducted at 8 to 10 years postpartum. Cardiac structure and function were assessed with echocardiography. Endothelial function was measured with peripheral arterial tonometry and glycocalyx analysis. Results: Among 254 women assessed at an average age of 38 years, 53 (21%) had prior GDM. At follow-up, women with GDM had more incident prediabetes or diabetes (58% vs 20% without GDM), more impairment in peripheral arterial tonometry (reactive hyperemia 1.58 vs 1.95; P = 0.01) and reduced perfusion, a marker of glycocalyx assessment (red blood cell filling 0.70 ± 0.04 vs 0.72 ± 0.05; P < 0.01). Despite adjustment for demographic and reproductive characteristics, women with GDM had great septal wall thickness by 8% (95% CI: 2.3%-14.7%) and worse diastology with higher E/E' by 11% (95% CI: 1.1%-21.5%). After additional adjustment for diabetes and prediabetes, several parameters remained significantly impaired. Conclusions: Having GDM within the past decade was associated with more adverse cardiac structure/function and vascular endothelial function. Some, but not all, risks may be mediated through the development of prediabetes or type 2 diabetes. Enhanced preventive efforts are needed to mitigate cardiovascular risk among women with GDM.

Perfusion and pulsatile pressure: their relationship with target organ damage in the African-PREDICT study.

BACKGROUND: Hypertension is the leading risk factor for subclinical target-organ damage (TOD) and cardiovascular disease (CVD). Little is known about the relationship between different pressure measures and subclinical TOD, especially in young populations. We compared the strength of associations of subclinical TOD markers with perfusion and pulsatile pressure in young adults. METHODS: A total of 1 187 young adults from the African-PREDICT study were included. Ambulatory mean arterial pressure (MAP) and pulse pressure (PP) was obtained. Markers of subclinical TOD were measured and included left ventricular mass index (LVMi), carotid intimamedia thickness (cIMT), carotidfemoral pulse wave velocity (cfPWV), central retinal arteriolar equivalent (CRAE) and albumin to creatinine ratio (ACR). RESULTS: Measures of sub-clinical TOD (cIMT, cfPWV and CRAE), associated stronger with perfusion pressure (all p < 0.001) than pulsatile pressure in unadjusted models. Stronger associations were found between cfPWV (adjusted R2 = 0.26), CRAE (adjusted R2 = 0.12) and perfusion pressure (all p ≤ 0.001) than pulsatile pressure independent of several non-modifiable and modifiable risk factors. CONCLUSIONS: In young, healthy adults, perfusion pressure is more strongly associated with subclinical TOD markers than pulsatile pressure. These findings contribute to the understanding of the development of early cardiovascular changes and may guide future intervention strategies.

Effects of smoking cessation on endothelial function as assessed by flow-mediated total dilation.

BACKGROUND: In assessing the effects of smoking cessation on endothelial function, low-flow-mediated constriction (L-FMC) may provide complementary information to flow-mediated dilation (FMD). However, the value of flow-mediated total dilation (FMTD), an index that incorporates L-FMC into FMD, remains underreported. We aimed to evaluate the effect of smoking cessation on endothelial function, as assessed by FMD and FMTD, and clarify its associated clinical factors. METHODS: We enrolled 118 consecutive current smokers without previous coronary artery disease (72.9% were men; age: 59 ± 11 years) who underwent smoking cessation treatment. The clinical variables %FMD, %L-FMC, and %FMTD were examined before and 20 weeks after treatment initiation. A multivariate linear regression model was used to investigate the effects of smoking cessation on %FMD and %FMTD and the interaction between smoking cessation and baseline clinical variables. RESULTS: After 20 weeks, 85 smokers (69.4% were men; age: 59 ± 12 years) ceased smoking (abstainers), whereas 33 smokers (81.8% were men; age: 58 ± 11 years) did not (continued smokers). The estimated group differences (abstainers - continued smokers) in changes in the %FMD and %FMTD were 0.77% (95% confidence interval [CI], -0.22-1.77%; p = 0.129) and 1.17% (95% CI, 0.16-2.18%; p = 0.024), respectively. Smoking cessation-associated improvement in %FMTD was greater in women than in men (5.41% [95% CI, 3.15-7.67%] versus 0.24% [95% CI, -0.81-1.28%]; p-value for interaction, < 0.001). Additionally, a greater %FMTD improvement was observed in patients who smoked fewer cigarettes per day (p-value for interaction, 0.042) and those who had a smaller resting baseline lumen diameter (Dbase) (p-value for interaction, 0.023). CONCLUSIONS: Smoking cessation was associated with an improvement in %FMTD. Sex, cigarettes smoked per day, and Dbase significantly affected this improvement. The FMTD may help in risk stratification after smoking cessation.

Relationship Between Endothelial Function, Vital Parameters, and Cognitive Performance in Community Dwellers with Subjective Cognitive Decline: An Observational Study with Six Months Follow Up.

Background: With advancing age, cognitive decline is frequently associated with endothelial dysfunction, but data on vascular performance prior to the onset of mild cognitive impairment (MCI) is scarce. Objective: To investigate the relationship between endothelial function, vital parameters and cognitive performance in older adults with subjective cognitive decline (SCD). Methods: Forty-five volunteers aged 65 years and older with SCD underwent comprehensive geriatric assessment-based prognosis evaluation by means of the Multidimensional Prognostic Index (MPI), full neuropsychological examination and peripheral arterial tonometry measurement by means of EndoPAT™2000 to evaluate endothelial flexibility and vital parameters. Six months after initial evaluation, participants were contacted by phone and a telephone-administered version of the MPI (TELE-MPI) was conducted. Results: Fifteen study participants scored below the cutoff score of 26 on the Montreal Cognitive Assessment, suggesting MCI (26.56±2.23). Nominal significant correlations were found between heart rate (HR) and trail making test (TMT) A (ß= -0.49, p = 0.03), between heart rate variability (HRV) and TMT B (ß= 0.78, p = 0.041), between power of low-frequency band (LF) HRV and Mini Nutritional Assessment-Short Form (ß= 0.007, p = 0.037) as well as between augmentation index (AI) and CogState Detection Test (ß= 0.002, p = 0.034). Conclusions: HR, HRV, and AI, but not endothelial flexibility are associated with cognitive performance in SCD and suspected MCI patients and may serve as clinical biomarkers in the early diagnosis of neurodegenerative disorders with advancing age.