Flow-mediated Vasodilation Research Articles

Frequency and Clinical Impact of Family History of Coronary Artery Disease in Patients with Vasospastic Angina.

Family history (FH) of coronary artery disease (CAD) [FH-CAD] is a well-known risk factor for atherosclerotic CAD. However, FH-CAD frequency in patients with vasospastic angina (VSA) remains unknown, and the clinical characteristics and prognosis of VSA patients with FH-CAD are unclear. Therefore, this study compared FH-CAD frequency between patients with atherosclerotic CAD and those with VSA and examined the clinical characteristics and prognosis of VSA patients with FH-CAD. Coronary angiography and spasm provocation tests (SPT) were used to investigate chest pain of coronary artery origin in patients classified into atherosclerotic CAD (362 cases), VSA (221 cases; positive for SPT) and non-VSA (73 cases; negative for SPT) groups, with FH-CAD being defined. In the VSA group, flow-mediated vasodilation (FMD) and nitroglycerin-independent vasodilation (NID) via brachial artery echocardiography and clinical symptoms in the groups with and without FH-CAD were checked, with Kaplan-Meier curves revealing major adverse cardiovascular events (cardiac death and rehospitalisation for cardiovascular disease) between the two groups. The atherosclerotic CAD group had a significantly lower FH-CAD frequency (12%, p = 0.029) than the VSA (19%) and non-VSA groups (19%). FH-CAD was more common in females in the VSA and non-VSA groups than in the atherosclerotic CAD group (p < 0.001). Nonpharmacological treatment for CAD in FH-CAD was more common in the atherosclerotic CAD group (p = 0.017). In the VSA group, FH-CAD tended to be more common in females (p = 0.052). Although no differences in FMD of the brachial artery were observed between the groups, the FH-CAD (+) group had significantly higher NID than the FH-CAD (-) group (p = 0.023). Kaplan-Meier's analysis revealed a similar prognosis between the two groups, and other clinical characteristics did not differ. Patients with VSA have a higher FH-CAD frequency than those with atherosclerotic CAD, especially in females. Although FH-CAD may affect vascular function in patients with VSA, its effect on the severity and prognosis of VSA appears to be minimal. FH-CAD and its confirmation may assist in CAD diagnosis, especially in female patients.

Longer-term mixed nut consumption improves brain vascular function and memory: A randomized, controlled crossover trial in older adults

Nut consumption may reduce age-related cognitive decline, but underlying mechanisms are unclear. To investigate in older adults longer-term effects of mixed nut consumption on brain vascular function, which may underlie improvements in cognitive performance. Twenty-eight healthy individuals (age [mean±SD]: 65±3 years; BMI: 27.9±2.3kg/m2) were included in a randomized, single-blinded, cross-over trial with a 16-week intervention (60g/d mixed nuts: walnuts, pistachio, cashew, and hazelnuts) and control period (no nuts), separated by 8 weeks of washout. Participants followed the Dutch food-based dietary guidelines. At the end of each period, cerebral blood flow (CBF), a marker of brain vascular function, was quantified using arterial spin labeling magnetic resonance imaging. Effects on endothelial function, arterial stiffness, and the retinal microvasculature were also assessed. Cognitive performance was measured using the Cambridge Neuropsychological Test Automated Battery. Body weight remained stable during the study. As compared to the control period, the mixed nut intervention resulted in a higher regional CBF in the right frontal and parietal lobes (treatment effect: 5.0±6.5mL/100g/min; P<0.001), left frontal lobe (5.4±7.1mL/100g/min; P<0.001), and bilateral prefrontal cortex (5.6±6.6mL/100g/min; P<0.001). Carotid artery reactivity (0.7PP; 95%CI: 0.2 to 1.2; P=0.007), brachial flow-mediated vasodilation (1.6PP; 95%CI: 1.0 to 2.2; P<0.001) and retinal arteriolar calibers were higher (2μm; 95%CI: 0 to 3; P=0.037), and carotid-to-femoral pulse wave velocity lower (-0.6m/s; 95%CI:-1.1 to-0.1; P=0.032). Further, visuospatial memory (-4 errors [16%]; 95%CI:-8 to 0; P=0.045) and verbal memory (+1 correct [16%]; 0 to 2; P=0.035) improved, but executive function and psychomotor speed did not change. Longer-term mixed nut consumption as part of a healthy diet beneficially affected brain vascular function, which may relate to the observed beneficial effects on memory in older adults. Moreover, different characteristics of the peripheral vascular tree also improved.

A Critical Review on Vasoactive Nutrients for the Management of Endothelial Dysfunction and Arterial Stiffness in Individuals under Cardiovascular Risk.

Pathophysiological conditions such as endothelial dysfunction and arterial stiffness, characterized by low nitric oxide bioavailability, deficient endothelium-dependent vasodilation and heart effort, predispose individuals to atherosclerotic lesions and cardiac events. Nitrate (NO3-), L-arginine, L-citrulline and potassium (K+) can mitigate arterial dysfunction and stiffness by intensifying NO bioavailability. Dietary compounds such as L-arginine, L-citrulline, NO3- and K+ exert vasoactive effects as demonstrated in clinical interventions by noninvasive flow-mediated vasodilation (FMD) and pulse-wave velocity (PWV) prognostic techniques. Daily L-arginine intakes ranging from 4.5 to 21 g lead to increased FMD and reduced PWV responses. Isolated L-citrulline intake of at least 5.6 g has a better effect compared to watermelon extract, which is only effective on endothelial function when supplemented for longer than 6 weeks and contains at least 6 g of L-citrulline. NO3- supplementation employing beetroot at doses greater than 370 mg promotes hemodynamic effects through the NO3--NO2-/NO pathway, a well-documented effect. A potassium intake of 1.5 g/day can restore endothelial function and arterial mobility, where decreased vascular tone takes place via ATPase pump/hyperpolarization and natriuresis, leading to muscle relaxation and NO release. These dietary interventions, alone or synergically, can ameliorate endothelial dysfunction and should be considered as adjuvant therapies in cardiovascular diseases.

The Association of Remnant Cholesterol with Endothelial Dysfunction and Subclinical Atherosclerosis in a Check-Up Population in China.

Vascular endothelial function and atherosclerosis are known to be important risk factors for cardiovascular disease. However, it remains unknown whether remnant cholesterol (RC) correlates with vascular endothelial function and atherosclerosis as represented by flow-mediated vasodilation (FMD) and brachial-ankle pulse wave velocity (baPWV). Therefore, in this study, we aimed to investigate this in the general population. In this study, we examined 13,237 subjects who have undergone blood lipid, FMD, and baPWV measurements. Participants were divided into four groups based on RC quartiles. Multivariable linear regression models were used to calculate odds ratios for FMD and baPWV according to the RC levels. A significant negative relationship was found between RC and FMD (β=-0.14, p=0.014), whereas RC was positively associated with baPWV (β=21.42, p＜0.001), especially in the male and without chronic disease medication populations. The population was divided into three groups according to their lipids: dyslipidemia group, nondyslipidemia but RC increased group (RC ＞0.78 mmol/L), and nondyslipidemia and RC normal group (RC ≤ 0.78 mmol/L). The FMD of the three groups was 7.09%±3.36%, 7.39%±3.38%, and 7.57%±3.54%, respectively. The baPWV of the three groups was 1445.26±261.56 cm/s, 1425.04±265.24 cm/s, and 1382.73±267.75 cm/s. Significant differences were noted between the groups. The findings indicated that a higher RC was an independent predictive factor for participants with endothelial function and atherosclerosis. It is important to use RC as a risk management indicator of vascular function, especially for those with normal conventional lipid parameters but increased RC.

PREVALENCE OF SUBCLINICAL ATHEROSCLEROSIS IN YOUNG HYPERTENSIVES

Objective: Evaluate the structure and arterial function in young hypertensive patients and determine the prevalence increase of EIM and atherosclerotic plaques: degree, location, total burden and its relation with pulse wave velocity. Design and method: An observational study was carried out transversally, at a population between 20 and 50 years old. The arterial evaluation has been done with a transductor lineal of 10MHZ ultrasound scanner. Measurement of endothelial function was performed by flow-mediated vasodilatation in the humeral artery. Continuous variables are presented as medium and standard deviation percentages. The comparation of variables between groups were carried on with T students. To compare the distribution of categorical variables, Chi square was operated. Pearson's correlation coefficient was used for the relation between VOP and other continuous numerical variables. A P&lt;0.05 was considered significant. Results: Between September of 2020 and December of 2021, 150 patients were studied, 35 of which were comprehended from 20 to 50 years of age inclusive. The age was 43,3 years (from 25 to 50 years), 19 were male (59%) and 13 were female (39%). The body mass index was 29.9 +- 4.86 (21-39.4) with a prevalence of overweight of 22% (7 patients) and obesity of 47% (15 patients). 14 patients (44%) dyslipidemia, 1 patient (3%) Diabetes mellitus, 2 patients (6,3%) hypothyroidism, 2 patients (6.3%) cerebral vascular accident and 2 patients (6.3%) active smoking. Among all patients, 87,5% of them (28 patients) presented in at least one arterial territory EIM equal or higher to percentile 75. Atherosclerotic plaque was observed in 12 patients (37,5%) Endothelial function was decreased in 16 patients (50%) and pulse wave velocity was abnormal in 4 patients (12.5%). Cardiovascular risk was estimated in 10 years according to Framingham; 84.3% (27 patients) showed a low risk and plaque in 42% (8 patients). The 15.6% (5 patients) showed intermediate risk and plaque in 80% (4 patients). Conclusions: The prevalence of subclinical atherosclerosis in young hypertensive patients with low and moderate risk is high, has very poor correlation with risk scores, and has a clear correlation with alterations in arterial function.

ENDOTHELIAL FUNCTIONAL STATUS IN PATIENTS WITH HYPERTENSION AND TYPE 2 DIABETES MELLITUS AFTER COVID-19

Objective: Aim of the study was to estimate endothelial functional status in patients with hypertension and type 2 diabetes mellitus (T2DM) who underwent Covid-19. Design and method: 56 patients with hypertension and T2DM after coronavirus infection (Group I) and 56 patients with hypertension and T2DM without any history of Covid-19 (Group II) were enrolled in this study. Group I patients aged 43-75 years, mean age 62.4±12.5 years; male = 46% and Group II patients aged 42-77 years, mean age 63.6±13.7 years; male = 43%. Endothelial functional status was assessed by flow-mediated vasodilation of brachial artery (FMD). All statistical analysis were performed by SPSS 26.0 software. Results: FMD of brachial artery was significantly decreased in patients with hypertension and T2DM after Covid-19 than those patients without Covid-19 (P&lt;0.01). There were a correlation between Covid-19 and reduced FMD in Group I (r = 0.7, CI 95%, P = 0.032). When we assessed systolic function of the left ventricle, there were a positive correlation between reduced FMD and low ejection fraction (r = 0.6, CI 95%, P = 0.028), however this correlation were more pronounced in Group I (P = 0.001). Multivariate analysis revealed that reduced flow-mediated vasodilation of brachial artery was independent predictor of poor systolic function of patients with hypertension and T2DM especially in those after Covid-19 (odds ratio [OR] 1.52, P = 0.026). When we separately analyzed between men and women there were not any statistical significant changes between male and female (P&gt;0.05). Conclusions: Patients with hypertension and type 2 diabetes mellitus after Covid-19 had impaired FMD of brachial artery. Even though, there were positive correlation between flow-mediated vasodilation of brachial artery and reduced ejection fraction, patients with hypertension and T2DM after Covid-19 had strong correlation of it. In hypertensive patients with type 2 diabetes mellitus who have undergone Covid-19, FMD independently associated with poor left ventricular systolic function.

(297) Evaluation of Endothelial Function and Metabolic Profile in Patients with Prostate Cancer Undergoing Androgen Deprivation Therapy

Abstract Introduction Androgen deprivation therapy (ADT) has been the cornerstone of prostate cancer treatment. ADT delays cancer progression, alleviates cancer-related symptoms, and is associated with survival gains. Despite these established benefits, the therapy comes with known side effects, such as increased cardiovascular adverse events and metabolic changes. Despite the well-established association between the level of circulating testosterone and endothelial integrity, the direct effects of ADT on endothelial function remain controversial. Objective The aim of the present study was to investigate the impact of ADT on endothelial function, through the analysis of vascular parameters of the brachial artery, and the measurement of serum inflammatory markers. It was also our goal to evaluate early impact of ADT on anthropometric and metabolic parameters Methods We prospectively evaluated men with moderate to high-risk prostate cancer treated with ADT from January to July 2022 at our institution. Patients with decompensated diabetes mellitus (HbA1c &amp;gt;9%), active smokers or smokers who have ceased for less than 5 years and those with confirmed diagnosis of peripheral artery disease, coronary artery disease, angina, congestive heart failure, myocardial infarction, coronary revascularization or stroke, were excluded. Brachial artery assessment included vascular diameter and flow-mediated (endothelium-dependent) vasodilation (FMD) using high-resolution B-mode ultrasound. Our metabolic and inflammatory profile included serum measurement of total cholesterol and fractions, triglycerides, fasting glucose, glycated hemoglobin, basal insulin, C-reactive protein, and bioimpedance assessment of body fat distribution. All measurements were performed at baseline and after 3 months of ADT initiation with goserelin acetate 10.80mg. Results A total of 14 men with mean age of 67.9 ± 6.9 years were included. The prevalence of diabetes in the present cohort was 21.4%. FMD demonstrated a slight increase following ADT, which did not reach statistical significance after 3 months (median 2.2% vs. 5.0%; p = 0.8224 – Figure 1). Baseline brachial artery diameter significantly decreased with ADT compared to baseline (median diameter 0.43cm vs 0.40cm; p = 0.006). With regard to the metabolic profile, ADT significantly increased insulin resistance: fasting insulin levels (mean 9.67 ± 6.09 vs 13.19 ± 7.47; p = 0.002), glycated hemoglobin (mean 5.79% ± 0.47 vs 6.22% ± 0.75; p = 0.009) and homeostatic model assessment insulin resistance increased significantly after 3 months (p = 0.006). Low-density lipoprotein cholesterol (mean 112.00 ± 27.35 vs 128.90 ± 29.00; p = 0.01) and triglycerides (mean 145.40 ± 78.52 vs 168.20 ± 105.80; p = 0.03) concentrations were higher after 3 months of ADT. No significant differences were found in body fat distribution. Conclusions Although the present study has not demonstrated a significant change in brachial artery FMD, we verified an important and surprisingly early worsening of the metabolic profile with ADT, especially increased insulin resistance and dyslipidemia, which represent well-established risk factors for cardiovascular events. Disclosure No

(357) Nocturnal Penile Tumescence Test in Patients with Erectile Dysfunction Associates With Penile and Systemic Vascular Disease

Abstract Introduction Erectile dysfunction (ED) is the most frequent male sexual dysfunction along with premature ejaculation. Moreover, its prevalence is increasing worldwide due to ageing of the population and spreading of risk factors like obesity, diabetes, hypercholesterolemia, hypertension, etc. Also, it represents an important cardiovascular risk marker because of its demonstrated tight association with cardiovascular disease (CVD). We dispose of many diagnostic tools to assess ED and a proper workup includes the anamnesis, a physical exploration, blood tests for hormonal and metabolic evaluation, and ED grading through validated questionnaires such as the International Index of Erectile Function (IIEF). One of the instrumental tests we may indicate is the nocturnal penile tumescence (NPT) test or “Rigiscan”. This test measures the spontaneous erections overnight and helps discriminating between organic and psychological ED. However, this is a highly specific but low sensitive test since a positive (normal) result can roll out an organic ED and suggest a psychological etiology while a negative result cannot confirm or exclude an organic condition. Objectives In this context the aim of this study is to investigate the predictive role of Rigiscan in discriminating patients with an organic ED and the presence of vascular disease in patients with ED. Methods We conducted a prospective study in patient 25 patient who underwent a Rigiscan test as part of ED assessment. Each patient had blood tests for hormonal and metabolic analysis, a measurement of the carotid intima-media thickness (cIMT), a brachial flow-mediated vasodilation test (FMD), and a penile color doppler ultrasound (PCDU) to assess penile hemodynamics. Results Our patients had a mean age of 47.9 ± 13.7 years, with a mean IIEF score of 9.0 ± 6.5. Among them 13 (54.2%) were active smokers, 5 (20.8%) were diabetics, 8 (32%) had dyslipidemia, and 4 (16.7%) had hypertension. Eleven patients (44%) had a normal Rigiscan while 14(56%) had a pathological result. We found that patient with a pathological Rigiscan presented with a cluster of impaired vascular function at different levels. In particular, they had statistically lower peak systolic velocity (PSV) in the PCDU (52.5 vs 80.2 cm/s p=0.014) and a higher prevalence of arterial insufficiency (42.9% vs 0.0% p=0.020). Moreover, in patients with negative Rigiscan, there was a higher cIMT (0.9 vs 0.7 mm) and lower response to FMD (7.7% vs 9.6%) with a more frequent diagnose of impaired FMD (63.6% vs 46.2%) but without reaching a statistically significance. Conclusion We can conclude that a negative Rigiscan is indicative of altered penile hemodynamics and may suggests the presence of systemic vascular disease. Therefore, while a positive Rigiscan excludes organic ED, a negative Rigiscan should be considered a cardiovascular risk marker and induce the clinician to address the cardiovascular risk in that patient. More studies with larger population are warranted to confirm and further investigated these findings. Disclosure No

Exercise reduced the concentration of an inflammatory makers without modulating the levels of epigenetic marker potentially involved in hypertension: a preliminary study

Abstract Epigenetic mechanisms such as histone acetylation status mediated by HAT and HDAC2 enzymes play a central role in the pathophysiology, etiology, and progression of hypertension. The anti-inflammatory effects of physical exercise may be related to the modulation of histone acetylation status, which may alter the epigenome, providing therapeutic benefits for hypertensive individuals. To investigate the effects of an exercise training protocol on epigenetic parameters (HAT activities and HDAC2 concentrations), inflammatory markers (interleukin (IL)-10, tumour necrosis factor (TNF)-α, and C-reactive protein (CRP)), and cardiopulmonary fitness parameters (VO2peak, ambulatory blood pressure, NOx, endothelin 1 (ET-1), flow-mediated dilation, high density lipoprotein (HDL), and triacylglycerol levels) in treated hypertensive patients. Nine hypertensive patients aged 30-59 years underwent 12 weeks of strength or aerobic exercise 3 times a week. Physical fitness, 24-h blood pressure (systolic and diastolic), flow-mediated vasodilation, blood lipid profile analysis, and biomarkers were assessed before and after the intervention. No alterations were found in epigenetic parameters since HAT activities and HDAC2 concentrations remained unchanged after the intervention. Significant increases were found in VO2peak (pre: 29.1±6.3 and post: 31.5±6.3, P=0.021) and HDL (pre: 41.4±9 and post: 46.8±9.5, P=0.003). Furthermore, a significant reduction was seen in 24-h systolic and diastolic blood pressure, respectively: (pre: 119.1±5.6 and post: 114.4±4.5, P=0.6; pre: 73.9±4.1 and post: 70.5±4.2, P=0.4) and in CRP (pre: 2.4±1.4; post: 1.2±0.7*, P=0.03). Lastly, no alterations were found in IL-10 and TNF-α. In treated hypertensive individuals undergoing 12 weeks of exercise training VO2peak, 24 h blood pressure, HDL, and CRP improved. However, changes were not found in concentrations and the activity of HDAC2 and HAT, respectively.

Lack of impact of ipragliflozin on endothelial function in patients with type 2 diabetes: sub-analysis of the PROTECT study

BackgroundWe assessed the impact of 24 months of treatment with ipragliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on endothelial function in patients with type 2 diabetes as a sub-analysis of the PROTECT study.MethodsIn the PROTECT study, patients were randomized to receive either standard antihyperglycemic treatment (control group, n = 241 ) or add-on ipragliflozin treatment (ipragliflozin group, n = 241) in a 1:1 ratio. Among the 482 patients in the PROTECT study, flow-mediated vasodilation (FMD) was assessed in 32 patients in the control group and 26 patients in the ipragliflozin group before and after 24 months of treatment.ResultsHbA1c levels significantly decreased after 24 months of treatment compared to the baseline value in the ipragliflozin group, but not in the control group. However, there was no significant difference between the changes in HbA1c levels in the two groups (7.4 ± 0.8% vs. 7.0 ± 0.9% in the ipragliflozin group and 7.4 ± 0.7% vs. 7.3 ± 0.7% in the control group; P = 0.08). There was no significant difference between FMD values at baseline and after 24 months in both groups (5.2 ± 2.6% vs. 5.2 ± 2.6%, P = 0.98 in the ipragliflozin group; 5.4 ± 2.9% vs. 5.0 ± 3.2%, P = 0.34 in the control group). There was no significant difference in the estimated percentage change in FMD between the two groups (P = 0.77).ConclusionsOver a 24-month period, the addition of ipragliflozin to standard therapy in patients with type 2 diabetes did not change endothelial function assessed by FMD in the brachial artery.Trial registrationRegistration Number for Clinical Trial: jRCT1071220089 (https://jrct.niph.go.jp/en-latest-detail/jRCT1071220089).

Assessment of early vascular changes in adult females with polycystic ovary syndrome: correlation with insulin resistance

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in females in the reproductive period with estimated prevalence of 5% to 18% [1]. It contributes to the mortality and morbidity in patients with PCOS due to the increased risk of different metabolic and cardiovascular (CV) complications [2]. Despite the presence of obesity in 40-60% of cases [3], the disease may occur in non-obese women. The occurrence of metabolic disorders in non-obese PCOS patients, suggests that the syndrome itself may play a role in the development of metabolic and CV co-morbidities [4]. The identification of early stages of atherosclerosis in patients with PCOS might be useful in the development of new strategies to control modifiable CV risk factors [5]. Assessment of vascular endothelial function (ED) as an initial reversible step in atherosclerosis development, may serve as an integral index for CV risk factor burden [6]. In addition, carotid intima media thickness (CIMT) is a helpful marker for atherosclerosis and for the identification of increased risk of CV disease [7]. Our study assessed the early vascular changes in Egyptian women with PCOS both physically and functionally by looking at the CIMT using high resolution Doppler ultrasound and by measuring ED using brachial artery flow–mediated vasodilatation (FMD). Our results indicate that patients with PCOS have significant ED and premature atherosclerosis which is, to a great extent, independent of obesity and IR. This suggests that PCOS patients are at increased risk for premature CVD and may benefit from early detection and management.

Regular Consumption of Cocoa and Red Berries as a Strategy to Improve Cardiovascular Biomarkers via Modulation of Microbiota Metabolism in Healthy Aging Adults.

The aim of the present study was to analyze the effects of cocoa flavanols and red berry anthocyanins on cardiovascular biomarkers, such as homocysteine, angiotensin-converting enzyme (ACE), nitric oxide (NO), flow-mediated vasodilation (FMD), blood pressure and lipid profile. Additionally, we aimed to ascertain their possible interactions with microbiota related metabolites, such as secondary bile acids (SBA), short-chain fatty acids (SCFA) and trimethylamine N-oxide (TMAO). A randomized, parallel-group study, single-blind for the research team, was performed on 60 healthy volunteers between the ages of 45 and 85, who consumed 2.5 g/day of cocoa powder (9.59 mg/day of total flavanols), 5 g/day of a red berry mixture (13.9 mg/day of total anthocyanins) or 7.5 g/day of a combination of both for 12 weeks. The group that had consumed cocoa showed a significant reduction in TMAO (p = 0.03) and uric acid (p = 0.01) levels in serum, accompanied by an increase in FMD values (p = 0.03) and total polyphenols. corrected by creatinine (p = 0.03) after the intervention. These latter values negatively correlated with the TMAO concentration (R = -0.57, p = 0.02). Additionally, we observed an increase in carbohydrate fermentation in the groups that had consumed cocoa (p = 0.04) and red berries (p = 0.04) between the beginning and the end of the intervention. This increase in carbohydrate fermentation was correlated with lower levels of TC/HDL ratio (p = 0.01), systolic (p = 0.01) and diastolic blood pressure (p = 0.01). In conclusion, our study showed a positive modulation of microbiota metabolism after a regular intake of cocoa flavanols and red berry anthocyanins that led to an improvement in cardiovascular function, especially in the group that consumed cocoa.

Lower extremity vascular responses to preexercise intermittent passive stretch and treadmill exercise

Intermittent passive stretch induces local tissue hypoxia with subsequent increases in micro- and- macrovascular shear-rate, a powerful stimulus for nitric oxide generation in endothelial cells. Acute aerobic exercise stress has been associated with decreased endothelial function of the active limb. Whether intermittent passive stretch can reduce endothelial injury and improve endothelial function if performed before exercise has yet to be shown. This work investigated the impact of preexercise intermittent passive stretch on popliteal artery flow-mediated vasodilation (FMD) and the post occlusive reactive hyperemic (PORH) response within the gastrocnemius after aerobic exercise. We hypothesized that preexercise intermittent passive stretch of the calf muscles would prevent a decline in micro- and- macrovascular function after treadmill exercise. Sixteen healthy college-aged males and females participated in a single laboratory visit and underwent a PORH test with near-infrared spectrometry and FMD test to assess micro- and- macrovascular function. Participants were split into a PS group and a sham-control group performing minimal stretch. Intermittent passive calf stretching was performed by having participants place their foot in a splinting device for a 5-minute stretch, 5-minute relaxation period, repeated four times. Pre, post treatment, and post exercise time points were used in this investigation for analysis with a two-way repeated measures ANOVA and significance set at (P≤0.05). Following the treatment protocol, participants completed a VO 2 peak test to calculate 65% VO 2 peak and ran at this intensity for 30-minutes with post measurements taking place after a brief 10–20-minute recovery period. PORH with the NIRS revealed that microvascular responsiveness was preserved with the passive stretch group (pre: 0.053±0.009 %/s -1 ), (post: 0.051±0.013 %/s -1 ). There was a significant reduction (p=0.05) in the sham control group (pre: 0.072± 0.015 %/s -1 ), (post: 0.051±0.007 %/s -1 ) after treadmill exercise. Flow mediated vasodilation of the popliteal artery showed similar responses. In the passive stretch group, %FMD (pre: 7.58±0.88 %), (post: 6.40±1.21 %; p=0.27) and shear normalized FMD did not significantly decline after exercise (pre: 7.24 E-04 ±1.50 E-04 ), (post: 5.05 E-04 ±1.25 E-04 ; p=0.83). In the sham-control group %FMD (pre: 9.31±0.72 %), (post: 4.73±1.24 %; p&lt;0.001) and normalized FMD were significantly reduced (pre: 1.06 E-03 ± 1.58 E-04 ), (post: 5.06 E-04 ±1.97 E-04 ; p&lt;0.001). Passive stretch prior to acute exercise preserved popliteal artery endothelial function and gastrocnemius microvascular reperfusion. This vasoprotection was not shown in the sham-control group after acute exercise. Passive stretch is an easy low-cost method to maintain vascular function in the face of an acute exercise stress. Future work investigating adaptations to long term training when combined with preexercise stretch would be a valuable next step. University of Wisconsin- La Crosse Start up funds This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of monitoring exercise rehabilitation with target intensity on the patient with twice PCI: A case report.

As the core of cardiac rehabilitation (CR), early exercise rehabilitation is beneficial for patients with coronary heart disease (CHD), and center-based CR with target intensity is superior to home-based CR. However, there was no research to observe the effects of exercise rehabilitation on cardiopulmonary exercise capacity, oxygen uptake efficiency slope, endothelial function evaluated as flow-mediated vasodilation (FMD), and blood plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) in CHD patients undergone percutaneous coronary intervention (PCI) for 3 months. A 57-year-old woman had been identified with triple vessel disease and undergone twice PCI for complete revascularization, however, there was no improvement in Lp-PLA2, FMD, and related indicators of cardiopulmonary exercise testing. Coronary angiography showed an 85% stenosis in the middle left anterior descending artery, an 85% stenosis in the proximity of a thick first-diagonal branch, a long 75 to 85% stenosis in the middle left circumflex artery, and a 90 to 95% stenosis in the proximal. The case was diagnosed as CHD. The patient obtained optimal medical therapy comprising therapeutic lifestyle changes, and began monitoring exercise rehabilitation with target intensity 3 months after the second PCI in the CR center. There were changes in cardiopulmonary exercise capacity, oxygen uptake efficiency slope, FMD, and Lp-PLA2 in the patient with 3 apparent stenotic coronary arteries who was done PCI twice, without or with postoperative exercise rehabilitation, respectively. We proved that monitoring exercise rehabilitation training with target intensity could improve the prognosis of chronic coronary syndrome patients, and it was never too late to do regular exercise rehabilitation.

The efficacy of sodium ferulate combination therapy in coronary heart disease: A systematic review and meta-analysis

BackgroundSodium ferulate (SF), a derivative of ferulic acid, is one of the active constituents in medicinal plants thought to be useful in fighting cardiovascular diseases. However, there still lacks a systematic review of the efficacy and safety of SF in treating coronary heart disease (CHD). It is therefore the purpose of this study to comprehensively review all clinical randomized controlled trials (RCTs) of SF in CHD to assess its efficacy and safety. MethodsAll analysis is based on 8 databases as of February 2023, which includes 35 outcomes of RCTs that investigate the effect of SF combination therapy in CHD. The present study evaluates the quality and bias of selected literature by the Jadad scale and Cochrane Collaboration's tools, and also the quality of evidence by GRADE Profiler. Furthermore, it applies sensitivity analysis to assess the high heterogeneity impact of outcomes and conducted subgroup analysis to estimate the influence factors in these studies. The study protocol was set documented, and published beforehand in PROSPERO (Registration No.CRD42022348841). ResultsThe meta-analysis of 36 studies (with 3207 patients) shows that SF combined with conventional drugs has improved clinical effectiveness for patients with CHD [RR: 1.21 (95% CI 1.17,1.26); p < 0.00001]. Statistically significant results of meta-analyses are also seen in electrocardiography (ECG) efficacy, frequency of angina attacks, endothelium-dependent flow-mediated vasodilation (FMD), nitric oxide (NO), endothelin (ET), whole Blood low shear rate (LS), platelet aggregation test (PAgT), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL6), triglyceride (TG). Adverse events are reported in 6 RCTs. By GRADE approaches, 2 outcomes (clinical efficacy, CRP) indicate a moderate quality of evidence, 17 outcomes indicate low quality of evidence, with the other 16 very low-quality. ConclusionSF combination therapy has a better curative effect than conventional therapy. However, due to items with low-quality evidence demonstrated in the study, the presence of clinical heterogeneity, and imprecision in partial outcome measures, all these led to limitations in the evidence of this study. Thus, the conclusion needs to be further verified by more in-depth research.

Racial Differences in Mental Stress-Induced Transient Endothelial Dysfunction and Its Association With Cardiovascular Outcomes.

This study aimed to investigate differences in transient endothelial dysfunction (TED) with mental stress in Black and non-Black individuals with coronary heart disease (CHD), and their potential impact on cardiovascular outcomes. We examined 812 patients with stable CHD between June 2011 and March 2016 and followed through February 2020 at a university-affiliated hospital network. Flow-mediated vasodilation (FMD) was assessed before and 30 minutes after mental stress. TED was defined as a lower poststress FMD than prestress FMD. We compared prestress FMD, post-stress FMD, and TED between Black and non-Black participants. In both groups, we examined the association of TED with an adjudicated composite end point of cardiovascular death or nonfatal myocardial infarction (first and recurring events) after adjusting for demographic, clinical, and socioeconomic factors. Prestress FMD was lower in Black than non-Black participants (3.7 [2.8] versus 4.9 [3.8], p < .001) and significantly declined with mental stress in both groups. TED occurred more often in Black (76%) than non-Black patients (67%; multivariable-adjusted odds ratio = 1.6, 95% confidence interval = 1.5-1.7). Over a median (interquartile range) follow-up period of 75 (65-82) months, 142 (18%) patients experienced either cardiovascular death or nonfatal myocardial infarction. Black participants had a 41.9% higher risk of the study outcome than non-Black participants (95% confidence interval = 1.01-1.95). TED with mental stress explained 69% of this excess risk. Among CHD patients, Black individuals are more likely than non-Black individuals to develop endothelial dysfunction with mental stress, which in turn explains a substantial portion of their excess risk of adverse events.

Vascular and metabolic effects of ipragliflozin versus sitagliptin (IVS) in type 2 diabetes treated with sulphonylurea and metformin: IVS study.

In patients with type 2 diabetes who were inadequately controlled with metformin and sulphonylurea, we compared the glucose-lowering efficacy, cardiometabolic parameters and safety of two drugs, ipragliflozin, a sodium-glucose cotransporter-2 inhibitor, and sitagliptin, a dipeptidyl peptidase-4 inhibitor. MATERIALSANDMETHODS: Patients with 7.5%-9.0% glycated haemoglobin treated with metformin and sulphonylurea were randomly assigned to ipragliflozin (50 mg, n = 70) or sitagliptin (100 mg, n = 70) therapy for 24 weeks. Measures of glycaemic control, fatty liver indices, other metabolic parameters and subclinical atherosclerosis were compared by a paired t-test before and after 24 weeks of treatment. Mean glycated haemoglobin levels decreased from 8.5% to 7.5% in the ipragliflozin group and from 8.5% to 7.8% in the sitagliptin group, resulting in a 0.34% between-group difference (95% confidence interval, 0.10%-0.43%, p = .088). Fasting and postprandial 2-h glucose levels also showed a similar trend, with a greater reduction with ipragliflozin therapy. An increase of over 70% in ketone levels and a decrease in whole body and abdominal fat masses were observed with ipragliflozin treatment. Fatty liver indices also improved with ipragliflozin treatment. Despite no difference in carotid intima-media thickness and ankle-brachial index, ipragliflozin therapy improved flow-mediated vasodilation, reflecting endothelial function, while sitagliptin did not. The safety profile did not differ between the two groups. Ipragliflozin add-on therapy can be a viable option for better glycaemic control with multiple vascular and metabolic benefits in patients with type 2 diabetes who are inadequately controlled with metformin and sulphonylurea.

Endothelial Function Is Preserved in Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy

Heart failure (HF) is associated with endothelial dysfunction. Vascular function per se plays an important role in cardiac function, whether it is a cause or consequence. However, there is no information on vascular function in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). The purpose of this study was to evaluate vascular function in patients with ATTRwt-CM. We measured flow-mediated vasodilation (FMD) as an index of endothelial function and nitroglycerine-induced vasodilation (NID) as an index of vascular smooth muscle function and brachial artery intima-media thickness (bIMT) and brachial-ankle pulse wave velocity (baPWV) as indices of arterial stiffness in 22 patients with ATTRwt-CM and in 22 one-by-one matched control patients using vascular function confounding factors. FMD was significantly greater in patients with ATTRwt-CM than in the controls (5.4 ± 3.4% versus 3.5 ± 2.4%, p = 0.038) and the N-terminal pro-brain natriuretic peptide (NT-proBNP) level was significantly greater in patients with ATTRwt-CM than in the controls (2202 ± 1478 versus 470 ± 677 pg/mL, p < 0.001). There were no significant differences in NID, bIMT or baPWV between the two groups. There was a significant relationship between NT-proBNP and FMD in patients with ATTRwt-CM (r = 0.485, p = 0.022). NT-proBNP showed no significant relationships with NID, bIMT or baPWV. Conclusions: Endothelial function was preserved in patients with ATTRwt-CM. Patients with ATTRwt-CM may have compensatory effects with respect to endothelial function through elevation of BNP.

Proteomics of high-density lipoprotein subfractions and subclinical atherosclerosis in type 1 diabetes mellitus: a case–control study

BackgroundSubclinical atherosclerosis is frequently observed in type 1 diabetes (T1D) although the mechanisms and markers involved in the evolution to established cardiovascular disease are not well known. High-density lipoprotein cholesterol in T1D is normal or even high, and changes in its functionality and proteomics are considered. Our aim was to evaluate the proteomics of HDL subfractions in T1D and control subjects and its association with clinical variables, subclinical atherosclerosis markers and HDL functionality.MethodsA total of 50 individuals with T1D and 30 matched controls were included. Carotid-femoral pulse wave velocity (PWV), flow-mediated vasodilation (FMD), cardiovascular autonomic neuropathy (CAN), and ten-year cardiovascular risk (ASCVDR) were determined. Proteomics (parallel reaction monitoring) was determined in isolated HDL2 and HDL3 that were also utilized to measure cholesterol efflux from macrophages.ResultsAmong 45 quantified proteins, 13 in HDL2 and 33 in HDL3 were differentially expressed in T1D and control subjects. Six proteins related to lipid metabolism, one to inflammatory acute phase, one to complement system and one to antioxidant response were more abundant in HDL2, while 14 lipid metabolism, three acute-phase, three antioxidants and one transport in HDL3 of T1D subjects. Three proteins (lipid metabolism, transport, and unknown function) were more abundant in HDL2; and ten (lipid metabolism, transport, protease inhibition), more abundant in HDL3 of controls. Individuals with T1D had higher PWV and ten-year ASCVDR, and lower FMD, Cholesterol efflux from macrophages was similar between T1D and controls. Proteins in HDL2 and HDL3, especially related to lipid metabolism, correlated with PWV, CAN, cholesterol efflux, HDLc, hypertension, glycemic control, ten-year ASCVDR, and statins use.ConclusionHDL proteomics can be predictive of subclinical atherosclerosis in type 1 diabetes. Proteins that are not involved in reverse cholesterol transport may be associated with the protective role of HDL.

Aerobic high-intensity interval exercise training in patients with angina and no obstructive coronary artery disease: feasibility and physiological effects.

Patients with chest pain and normal coronary angiogram [angina with normal coronary arteries (ANOCA)] constitute a therapeutic problem with considerable functional limitation and reduced quality of life. The aims of the current pilot study were to (i) explore if a structured aerobic high-intensity interval training (HIT) program for 12 weeks was feasible in patients with ANOCA, and (ii) to assess mechanisms related to symptoms in this population. Sixteen patients with ANOCA underwent a 3-month aerobic HIT program with one-to-one monitored exercise sessions on treadmill in a 4 min × 4 manner, three times a week. Four patients served as controls. Coronary flow velocity reserve (CFVR) transthoracic Doppler, flow-mediated vasodilation (FMD) and VO2max was measured at baseline and after 12 weeks. The average attendance to training sessions was 82.3% ± 10.1 (56-94). CFVR in the training group increased from 2.50 ± 0.48 to 3.04 ± 0.71 (P < 0.001) whereas FMD increased from 4.19 ± 2.42% to 8.28 ± 2.85% (P < 0.001). Improvement in CFVR correlated with the relative improvement in FMD (R = 0.45, P = 0.047). This was associated with an increase in VO2max from 28.75 ± 6.51 mL/kg/min to 31.93 ± 6.46 mL/kg/min (P < 0.001). A 3-month program of monitored HIT was feasible, with high adherence resulting in improved functional capacity in patients with ANOCA. CFVR improved and this improvement was associated with improved FMD. NCT02905630.