Artery Flow-mediated Dilation Research Articles

The benefits and risks of menopause hormone therapy for the cardiovascular system in postmenopausal women: a systematic review and meta-analysis

BackgroundMenopause hormone therapy (MHT), as an effective method to alleviate the menopause-related symptoms of women, its benefits, risks, and potential influencing factors for the cardiovascular system of postmenopausal women are not very clear.ObjectivesTo evaluate cardiovascular benefits and risks of MHT in postmenopausal women, and analyze the underlying factors that affect both.Search strategyThe EMBASE, MEDLINE, and CENTRAL databases were searched from 1975 to July 2022.Selection criteriaRandomized Clinical Trials (RCTs) that met pre-specified inclusion criteria were included.Data collection and analysisTwo reviewers extracted data independently. A meta-analysis of random effects was used to analyze data.Main resultsThis systematic review identified 33 RCTs using MHT involving 44,639 postmenopausal women with a mean age of 60.3 (range 48 to 72 years). There was no significant difference between MHT and placebo (or no treatment) in all-cause death (RR = 0.96, 95%CI 0.85 to 1.09, I2 = 14%) and cardiovascular events (RR = 0.97, 95%CI 0.82 to 1.14, I2 = 38%) in the overall population of postmenopausal women. However, MHT would increase the risk of stroke (RR = 1.23, 95%CI 1.08 to 1.41,I2 = 0%) and venous thromboembolism (RR = 1.86, 95%CI 1.39 to 2.50, I2 = 24%). Compared with placebo, MHT could improve flow-mediated arterial dilation (FMD) (SMD = 1.46, 95%CI 0.86 to 2.07, I2 = 90%), but it did not improve nitroglycerin-mediated arterial dilation (NMD) (SMD = 0.27, 95%CI − 0.08 to 0.62, I2 = 76%). Compared with women started MHT more than 10 years after menopause, women started MHT within 10 years after menopause had lower frequency of all-cause death (P = 0.02) and cardiovascular events (P = 0.002), and more significant improvement in FMD (P = 0.0003). Compared to mono-estrogen therapy, the combination therapy of estrogen and progesterone would not alter the outcomes of endpoint event. (all-cause death P = 0.52, cardiovascular events P = 0.90, stroke P = 0.85, venous thromboembolism P = 0.33, FMD P = 0.46, NMD P = 0.27).ConclusionsMHT improves flow-mediated arterial dilation (FMD) but fails to lower the risk of all-cause death and cardiovascular events, and increases the risk of stroke and venous thrombosis in postmenopausal women. Early acceptance of MHT not only reduces the risk of all-cause death and cardiovascular events but also further improves FMD, although the risk of stroke and venous thrombosis is not reduced. There is no difference in the outcome of cardiovascular system endpoints between mono-estrogen therapy and combination therapy of estrogen and progesterone.

Power-Doppler Ultrasonic Imaging of Peripheral Perfusion in Diabetic Mice.

We explored the capabilities of power-Doppler ultrasonic (PD-US) imaging without contrast enhancement for monitoring changes in muscle perfusion over time. Ischemic recovery was observed in healthy and type II diabetic male and female mice with and without exercise. In separate studies, perfusion was measured during and after 5-min ischemic periods and during four-week recovery periods following irreversible femoral ligation. A goal was to assess how well PD-US estimates tracked the diabetic-related changes in endothelial function that influenced perfusion. The average perfusion recovery time following femoral ligation increased 47% in diabetic males and 74% in diabetic females compared with non-diabetic mice. Flow-mediated dilation in conduit arteries and the reactive hyperemia index in resistive vessels each declined by one half in sedentary diabetic mice compared with sedentary non-diabetic mice. We found that exercise reduced the loss of endothelial function from diabetes in both sexes. The reproducibility of perfusion measurements was limited primarily by our ability to select the same region in muscle and to effectively filter tissue clutter. PD-US measurements can precisely follow site-specific changes in skeletal muscle perfusion related to diabetes over time, which fills the need for techniques capable of regularly monitoring atherosclerotic changes leading to ischemic vascular pathologies.

Impairment of Endothelial Function by Aerosol From Marijuana Leaf Vaporizers.

Marijuana leaf vaporizers, which heat plant material and sublimate Δ-9-tetrahydrocannabinol without combustion, are popular alternatives to smoking cannabis that are generally perceived to be less harmful. We have shown that smoke from tobacco and marijuana, as well as aerosol from e-cigarettes and heated tobacco products, impair vascular endothelial function in rats measured as arterial flow-mediated dilation (FMD). We exposed 8 rats per group to aerosol generated by 2 vaporizer systems (Volcano and handheld Yocan) using marijuana with varying Δ-9-tetrahydrocannabinol levels, in a single pulsatile exposure session of 2 s/min over 5 minutes, and measured changes in FMD. To model secondhand exposure, we exposed rats for 1 minute to diluted aerosol approximating release of uninhaled Volcano aerosol into typical residential rooms. Exposure to aerosol from marijuana with and without cannabinoids impaired FMD by ≈50%. FMD was similarly impaired by aerosols from Yocan (237 °C), and from Volcano at both its standard temperature (185 °C) and the minimum sublimation temperature of Δ-9-tetrahydrocannabinol (157 °C), although the low-temperature aerosol condition did not effectively deliver Δ-9-tetrahydrocannabinol to the circulation. Modeled secondhand exposure based on diluted Volcano aerosol also impaired FMD. FMD was not affected in rats exposed to clean air or water vapor passed through the Volcano system. Acute direct exposure and modeled secondhand exposure to marijuana leaf vaporizer aerosol, regardless of cannabinoid concentration or aerosol generation temperature, impair endothelial function in rats comparably to marijuana smoke. Our findings indicate that use of leaf vaporizers is unlikely to reduce the vascular risk burden of smoking marijuana.

Long-Term Adverse Effects of Neck Radiotherapy in Childhood on the Carotid Arteries in Survivors of Hodgkin Lymphoma.

Survivors of Hodgkin lymphoma are recognized to have an increased risk of stroke and carotid artery disease owing to neck irradiation (RT). However, it remains unclear whether the vascular modifications induced by the treatment of Hodgkin lymphoma during childhood persist over the long term. Our matched study involved 79 survivors of Hodgkin lymphoma in childhood who received neck RT and 57 healthy controls. Parameters of arterial stiffness (AS), intima-media thickness (IMT), and flow-mediated dilation (FMD) of carotid arteries were assessed using ultrasound. Our patient cohort demonstrated a significant increase in AS compared to controls (p < 0.05), though no such disparity was observed for FMD (p = 0.111). Neck RT intensified AS (B = 0.037, p = 0.000), while anthracyclines attenuated it (B = -0.803, p = 0.000). Multivariate analysis revealed a positive correlation between neck RT (p < 0.001) and AS. However, we found no significant association between neck RT and FMD (p = 0.277). We identified a substantial positive correlation between the dose of neck RT and AS. Vascular changes in survivors of childhood Hodgkin lymphoma after neck RT seem to be long-term. Therefore, these patients may have an increased risk of stroke. We suggest refinement of international guidelines according to our results.

Arterial Stiffness as a Surrogate Marker of Cardiovascular Disease and Atherosclerosis in Patients with Arthritides and Connective Tissue Diseases: A Literature Review.

The increased cardiovascular (CV) risk among patients with autoimmune rheumatic diseases, such as arthritides and connective tissue diseases, has been extensively documented. From a pathophysiological standpoint, systemic inflammation in the context of the disease can lead to endothelial dysfunction, accelerated atherosclerosis, and structural changes in vessel walls, which, in turn, are associated with exaggerated CV morbidity and mortality. In addition to these abnormalities, the increased prevalence of traditional CV risk factors, such as obesity, dyslipidemia, arterial hypertension, and impaired glucose metabolism, can further worsen the status of and overall prognosis for CV in rheumatic patients. However, data on appropriate CV screening methods for patients with systemic autoimmune diseases are scarce, and traditional algorithms may lead to an underestimation of the true CV risk. The reason for this is that these calculations were developed for the general population and thus do not take into account the effect of the inflammatory burden, as well as other chronic-disease-associated CV risk factors. In recent years, different research groups, including ours, have examined the value of different CV surrogate markers, including carotid sonography, carotid-femoral pulse wave velocity, and flow-mediated arterial dilation, in the assessment of CV risk in healthy and rheumatic populations. In particular, arterial stiffness has been thoroughly examined in a number of studies, showing high diagnostic and predictive value for the occurrence of CV events. To this end, the present narrative review showcases a series of studies examining aortic and peripheral arterial stiffness as surrogates of all-cause CV disease and atherosclerosis in patients with rheumatoid and psoriatic arthritis, as well as in systemic lupus erythematosus and systemic sclerosis. Moreover, we discuss the associations of arterial stiffness with clinical, laboratory, and disease-specific parameters.

Method for estimating pulsatile wall shear stress from one‐dimensional velocity waveforms

Wall shear stress (WSS)-a key regulator of endothelial function-is commonly estimated in vivo using simplified mathematical models based on Poiseuille's flow, assuming a quasi-steady parabolic velocity distribution, despite evidence that more rapidly time-varying, pulsatile blood flow during each cardiac cycle modulates flow-mediated dilation (FMD) in large arteries of healthy subjects. More exact and accurate models based on the well-established Womersley solution for rapidly changing blood flow have not been adopted clinically, potentially because the Womersley solution relies on the local pressure gradient, which is difficult to measure non-invasively. We have developed an open-source method for automatic reconstruction of unsteady, Womersley-derived velocity profiles, and WSS in conduit arteries. The proposed method (available online at https://doi.org/10.5281/zenodo.7576408) requires only the time-averaged diameter of the vessel and time-varying velocity data available from non-invasive imaging such as Doppler ultrasound. Validation of the method with subject-specific computational fluid dynamics and application to synthetic velocity waveforms in the common carotid, brachial, and femoral arteries reveals that the Poiseuille solution underestimates peak WSS 38.5%-55.1% during the acceleration and deceleration phases of systole and underestimates or neglects retrograde WSS. Following evidence that oscillatory shear significantly augments vasodilator production, it is plausible that mischaracterization of the shear stimulus by assuming parabolic flow leads to systematic underestimates of important biological effects of time-varying blood velocity in conduit arteries.

Novel Surrogate Markers of Cardiovascular Risk in the Setting of Autoimmune Rheumatic Diseases: Current Data and Implications for the Future.

Patients suffering from rheumatologic diseases are known to have an increased risk for cardiovascular disease (CVD). Although the pathological mechanisms behind this excess risk have been increasingly better understood, there still seems to be a general lack of consensus in early detection and treatment of endothelial dysfunction and CVD risk in patients suffering from rheumatologic diseases and in particular in those who haven't yet shown symptoms of CVD. Traditional CVD prediction scores, such as Systematic Coronary Risk Evaluation (SCORE), Framingham, or PROCAM Score have been proposed as valid assessment tools of CVD risk in the general population. However, these risk calculators developed for the general population do not factor in the effect of the inflammatory burden, as well as other factors that can increase CVD risk in patients with rheumatic diseases, such as glucocorticoid therapy, abnormal lipoprotein function, endothelial dysfunction or accelerated atherosclerosis. Thus, their sole use could lead to underestimation of CVD risk in patients with rheumatic diseases. Therefore, there is a need for new biomarkers which will allow a valid and early assessment of CVD risk. In recent years, different research groups, including ours, have examined the value of different CVD risk factors such as carotid sonography, carotid-femoral pulse wave velocity, flow-mediated arterial dilation and others in the assessment of CVD risk. Moreover, various novel CVD laboratory markers have been examined in the setting of autoimmune diseases, such as Paraoxonase activity, Endocan and Osteoprotegerin. Dyslipidemia in rheumatoid arthritis (RA) is for instance better quantified by lipoproteins and apolipoproteins than by cholesterol levels; screening as well as pre-emptive carotid sonography hold promise to identify patients earlier, when prophylaxis is more likely to be effective. The early detection of subtle changes indicating CVD in asymptomatic patients has been facilitated through improved imaging methods; the inclusion of artificial intelligence (AI) shows promising results in more recent studies. Even though the pathophysiology of coronary artery disease in patients with autoimmune rheumatic diseases has been examined in multiple studies, as we continuously gain an increased understanding of this comorbidity, particularly in subclinical cases we still seem to fail in the stratification of who really is at risk—and who is not. A the time being, a multipronged and personalized approach of screening patients for traditional CVD risk factors, integrating modern imaging and further CV diagnostic tools and optimizing treatment seems to be a solid approach. There is promising research on novel biomarkers, likewise, methods using artificial intelligence in imaging provide encouraging data indicating possibilities of risk stratification that might become gold standard in the near future. The present review concentrates on showcasing the newest findings concerning CVD risk in patients with rheumatologic diseases and aims to evaluate screening methods in order to optimize CVD risk evaluation and thus avoiding underdiagnosis and undertreatment, as well as highlighting which patient groups are most at risk.

Sympathetic-mediated blunting of forearm vasodilation is similar between young men and women

BackgroundThe in-vivo regulation of vascular conductance (VC) is a continuous balance between endothelial vasodilation and sympathetic vasoconstriction. Although women may report blunted sympathetic vasoconstriction along with higher endothelial vasodilation than men, it is currently unknown whether the interaction between vasoconstriction and vasodilation leads to different regulation of VC between sexes. This study assessed sex differences in sympathetic-mediated blunting of endothelial vasodilation after a brief period of ischemia and whether any restriction of vasodilation blunts tissue blood flow (BF) and re-oxygenation.Methods13 young women and 12 young men underwent two 5-min forearm circulatory occlusions followed by reperfusion, one in basal conditions and the other during cold pressor test-induced sympathetic activation (SYMP). Brachial artery diameter and BF, mean arterial pressure, total peripheral resistance (TPR), and thenar eminence oxygenation were collected. Percent changes normalized to baseline values of forearm VC, brachial artery BF and flow-mediated dilation (FMD), TPR, and hand oxygenation after circulatory reperfusion were calculated.ResultsTPR increased during SYMP in men (p = 0.019) but not in women (p = 0.967). Women showed a greater brachial artery FMD than men (p = 0.004) at rest, but sex differences disappeared after normalization to shear rate and baseline diameter (p > 0.11). The percent increases from baseline of peak and average forearm VC after circulatory reperfusion did not differ between sexes in basal conditions (p > 0.98) or during SYMP (p > 0.97), and were restrained by SYMP similarly in both sexes (p < 0.003) without impairing the hand re-oxygenation (p > 0.08) or average hyperemic response (p > 0.09).ConclusionsAlthough women may report blunted sympathetic vasoconstriction than men when assessed separately, the similar sympathetic-mediated restriction of vasodilation suggests a similar dynamic regulation of VC between sexes. SYMP-mediated restrictions of the normal forearm vasodilation do not impair the average hyperemic response and hand re-oxygenation in both sexes.

Anti-Inflammatory, Antioxidant, and Anti-Atherosclerotic Effects of Natural Supplements on Patients with FMF-Related AA Amyloidosis: A Non-Randomized 24-Week Open-Label Interventional Study.

We aimed to evaluate the effect of a combination of natural products on parameters related to inflammation, endothelial dysfunction, and oxidative stress in a cohort of familial Mediterranean fever (FMF) patients with Serum Amyloid A amyloidosis, in a non-randomized, 24-week open-label interventional study. Morinda citrifolia (anti-atherosclerotic-AAL), omega-3 (anti-inflammatory-AIC), and extract with Alaskan blueberry (antioxidant-AOL) were given to patients with FMF-related biopsy-proven AA amyloidosis. Patients were >18 years and had proteinuria (>3500 mg/day) but a normal estimated glomerular filtration rate (eGFR). Arterial flow-mediated dilatation (FMD), carotid intima media thickness (CIMT), and serum biomarkers asymmetric dimethylarginine (ADMA), high sensitivity C-reactive protein (hs-CRP), pentraxin (PTX3), malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and glutathione peroxidase (GSH-Px) were studied at baseline and after 24 weeks of treatment. A total of 67 FMF-related amyloidosis patients (52 male (77.6%); median age 36 years (range 21–66)) were enrolled. At the end of a 24-week treatment period with AAL, AIC, and AOL combination therapy, ADMA, MDA, PTX3, hsCRP, cholesterol, and proteinuria were significantly decreased compared to baseline, while CuZn-SOD, GSH-Px, and FMD levels were significantly increased. Changes in inflammatory markers PTX3, and hsCRP were negatively correlated with FMD change, and positively correlated with decreases in proteinuria, ADMA, MDA, cholesterol, and CIMT. Treatment with AAL, AIC and AOL combination for 24 weeks were significantly associated with reduction in inflammatory markers, improved endothelial functions, and oxidative state. Efficient control of these three mechanisms can have long term cardiovascular and renal benefits for patients with AA amyloidosis.

Conduit Artery and Forearm Microvascular Reactivity in Black and White Females: Examining the Role of Greater Superwoman Schema Endorsement

Among females in the United States, Black females suffer from the highest rates of hypertension, stroke, coronary artery disease, heart failure, and total cardiovascular disease (CVD) mortality. Importantly, vascular dysfunction precedes overt CVD and predicts CVD risk. In this regard, a recent study reported that upper limb microvascular but not macrovascular function was blunted in Black relative to White women. However, this is not always a consistent finding and such investigations have not incorporated psychosocial measures, which are known to contribute to race/ethnicity‐related disparities in cardiovascular health. Given the strong relationship between psychosocial stress and health, Woods‐Giscombe, et al. recently developed the Giscombe Superwoman Schema Questionnaire (G‐SWS‐Q), which operationalizes the Superwoman Schema (SWS) Conceptual Framework to quantify psychological stress processes specifically associated with being a Black woman. Accordingly, we tested the hypothesis that Black females would have blunted post‐occlusive upper limb microvascular and macrovascular vasodilation relative to White females and that greater SWS endorsement by Black females would be associated with blunted vascular responses.METHODSSeven Black (age: 22 ± 1 yr; BMI: 27.5 ± 1.6 kg/m2) and 6 White (age: 23 ± 1 yr; BMI: 25.9 ± 1.3 kg/m2) females participated. Post‐occlusive brachial artery flow‐mediated dilation (FMD) and forearm reactive hyperemia were assessed via well‐established procedures. Briefly, brachial artery diameter and blood velocity were measured continuously and recorded via Doppler ultrasound and a video capture system throughout a 2 min baseline, 5 min suprasystolic forearm cuff occlusion, and 3 min recovery. Offline analysis was performed via a continuous edge detection and blood velocity tracking software. Black participants also completed the G‐SWS‐Q, which is a 35‐item instrument designed to measure the cognitive, affective, and behavioral underpinnings associated with being a “Strong Black Woman” in the United States.RESULTSBrachial artery FMD was lower in Black relative to White females (3.99 ± 1.15 vs. 7.34 ± 1.10%; p = 0.03); however, after correcting for post‐occlusive shear rate AUC via ANCOVA, group differences in FMD were less apparent (p = 0.07). Post‐occlusive peak blood velocity and blood flow AUC were not different between groups (p = 0.43 and p = 0.42, respectively). A moderate negative correlation was observed between overall SWS and FMD (r = ‐0.58, p = 0.09). Among the SWS subscales, a strong negative correlation was observed between “Obligation to Present an Image of Strength” and FMD (r = ‐0.70, p = 0.04), whereas “Intense Motivation to Succeed” was moderately negatively correlated with FMD (r = ‐0.64, p = 0.06).CONCLUSIONThese preliminary data indicate that 1) upper limb macrovascular but not microvascular function may be blunted in young Black females and 2) stronger SWS endorsement may be associated with blunted vascular reactivity. Therefore, blunted conduit artery endothelial function in Black females may be partially attributable to greater SWS internalization.

Estrogen Promotes Microvascularization in the Fetus and Thus Vascular Function and Insulin Sensitivity in Offspring.

We have shown that normal weight offspring born to estrogen-deprived baboons exhibited insulin resistance, although liver and adipose function and insulin receptor and glucose transporter expression were unaltered. The blood microvessels have an important role in insulin action by delivering insulin and glucose to target cells. Although little is known about the regulation of microvessel development during fetal life, estrogen promotes capillary proliferation and vascular function in the adult. Therefore, we tested the hypothesis that estrogen promotes fetal microvessel development and thus vascular function and insulin sensitivity in offspring. Capillary/myofiber ratio was decreased 75% (P < 0.05) in skeletal muscle, a major insulin target tissue, of fetal baboons in which estradiol levels were depleted by administration of aromatase inhibitor letrozole. This was sustained after birth, resulting in a 50% reduction (P < 0.01) in microvessel expansion; 65% decrease (P < 0.01) in arterial flow-mediated dilation, indicative of vascular endothelial dysfunction; and 35% increase (P < 0.01) in blood pressure in offspring from estrogen-deprived baboons, changes prevented by letrozole and estradiol administration. Along with vascular dysfunction, peak insulin and glucose levels during a glucose tolerance test were greater (P < 0.05 to P < 0.01) and the homeostasis model of insulin resistance 2-fold higher (P < 0.01) in offspring of letrozole-treated than untreated animals, indicative of insulin resistance. This study makes the novel discovery that estrogen promotes microvascularization in the fetus and thus normal vascular development and function required for eliciting insulin sensitivity in offspring and that placental hormonal secretions, independent from improper fetal growth, are an important determinant of risk of developing insulin resistance.

Early Inactivation of Membrane Estrogen Receptor Alpha (ERα) Recapitulates the Endothelial Dysfunction of Aged Mouse Resistance Arteries.

Flow-mediated dilation (FMD) of resistance arteries is essential for tissue perfusion but it decreases with ageing. As estrogen receptor alpha (Erα encoded by Esr1), and more precisely membrane ERα, plays an important role in FMD in young mice in a ligand-independent fashion, we evaluated its influence on this arteriolar function in ageing. We first confirmed that in young (6-month-old) mice, FMD of mesenteric resistance arteries was reduced in Esr1−/− (lacking ERα) and C451A-ERα (lacking membrane ERα). In old (24-month-old) mice, FMD was reduced in WT mice compared to young mice, whereas it was not further decreased in Esr1−/− and C451A-ERα mice. Markers of oxidative stress were similarly increased in old WT and C451A-ERα mice. Reduction in oxidative stress with superoxide dismutase plus catalase or Mito-tempo, which reduces mitochondrial superoxide restored FMD to a normal control level in young C451A-ERα mice as well as in old WT mice and old C451A-ERα mice. Estradiol-mediated dilation was absent in old WT mice. We conclude that oxidative stress is a key event in the decline of FMD, and that an early defect in membrane ERα recapitulates phenotypically and functionally ageing of these resistance arteries. The loss of this function could take part in vascular ageing.

Persistent Endothelial Dysfunction in Coronavirus Disease-2019 Survivors Late After Recovery.

BackgroundCoronavirus disease 2019 (COVID-19) can result in an endothelial dysfunction in acute phase. However, information on the late vascular consequences of COVID-19 is limited.MethodsBrachial artery flow-mediated dilation (FMD) examination were performed, and inflammatory biomarkers were assessed in 86 survivors of COVID-19 for 327 days (IQR 318–337 days) after recovery. Comparisons were made with 28 age-matched and sex-matched healthy controls and 30 risk factor-matched patients.ResultsBrachial artery FMD was significantly lower in the survivors of COVID-19 than in the healthy controls and risk factor-matched controls [median (IQR) 7.7 (5.1–10.7)% for healthy controls, 6.9 (5.5–9.4)% for risk factor-matched controls, and 3.5(2.2–4.6)% for COVID-19, respectively, p < 0.001]. The FMD was lower in 25 patients with elevated tumor necrosis factor (TNF)-α [2.7(1.2–3.9)] than in 61 patients without elevated TNF-α [3.8(2.6–5.3), p = 0.012]. Furthermore, FMD was inversely correlated with serum concentration of TNF-α (r = −0.237, p = 0.007).ConclusionSurvivors of COVID-19 have a reduced brachial artery FMD, which is inversely correlated with increased serum concentration of TNF-α. Prospective studies on the association of endothelial dysfunction with long-term cardiovascular outcomes, especially the early onset of atherosclerosis, are warranted in survivors of COVID-19.

Physiological Adaptations to High-Intensity Interval Training Combined with Blood Flow Restriction in Masters Road Cyclists.

High-intensity interval training (HIIT) and blood flow restriction (BFR) training have been used to enhance athletic performance and cardiovascular health. Combining these training modalities might be an effective training modality for masters athletes who seek to enhance athletic performance and to reduce cardiovascular risks. Fifty masters road cyclists age 35-49 yr were randomly assigned to the continuous exercise training (n = 16), continuous plus HIIT (n = 17), and continuous plus BFR training combined with HIIT (BFRIT; n = 17) for 12 wk. Both HIIT and BFRIT were performed on a cycle ergometer twice a week. Maximal oxygen consumption (V̇O2max) increased in the HIIT and BFRIT groups (P < 0.05). This was accompanied by significant improvements in maximal cardiac output and stroke volume (P < 0.05). Forty-kilometer time trial performance improved in all three groups (P < 0.05). Peak power output increased in both HIIT and BFRIT groups (P < 0.05). Flow-mediated dilation in both brachial and popliteal arteries increased in all three groups (all P < 0.05). There were no significant changes in carotid intima-media thickness and arterial stiffness in any of the groups. Total lean mass, muscle cross-sectional area and thickness in rectus femoris and vastus lateralis, and peak torque of isokinetic knee extension increased only in the BFRIT group (all P < 0.05). Tissue saturation index decreased only in the BFRIT group (P < 0.05). Changes in 40-km time trial performance were associated with corresponding changes in V̇O2max (r = -0.312, P = 0.029) and peak isokinetic extensor torque (r = -0.432, P = 0.002). Including HIIT particularly with BFR in the routine continuous training may be more effective in enhancing performance and physiological functions in masters road cyclists.

Abstract P355: Comparable Impairment Of Vascular Endothelial Function By A Wide Range Of Electronic Nicotine Delivery Devices

Introduction: Electronic nicotine delivery systems (ENDS; i.e., vaping devices) such as e-cigarettes, heated tobacco products, and newer coil-less ultrasonic vaping devices are promoted as less harmful alternatives to combustible cigarettes. However, the cardiovascular health effects of these devices are understudied. We investigated whether exposure to aerosol from a wide range of ENDS devices with and without nicotine, including a new ultrasonic vaping device, impairs endothelial function. Hypothesis: ENDS aerosols irrespective of nicotine, flavors, and heating coil impair endothelial function comparably to smoke from cigarettes. Methods: We exposed 11 groups (n=8), of anaesthetized rats to aerosol from propylene glycol (PG), vegetable glycerin (VG), PG+VG without nicotine, a USONICIG Zip ultrasonic vaping device, previous generation e-cigarettes (tank style with freebase nicotine), 5% nicotine JUUL pods of three flavors (Virginia tobacco, Mango, and Menthol), and an IQOS heated tobacco product; with Marlboro Red cigarette smoke and clean air as controls, to a single session of 10 cycles of pulsatile 5s exposure over 5 minutes. Endothelial function was quantified as arterial flow-mediated dilation (FMD) using micro-ultrasound. Results: Aerosol/smoke from all conditions except air significantly impaired FMD (Figure: each colored line denotes one rat, black horizontal bars denote means). The extent of impairment ranged from 40%-67% although there were no significant differences between groups. Nicotine absorption into the blood varied widely from these undiluted aerosols (those containing nicotine), with IQOS being the highest, and USONICIG and previous generation e-cig being the lowest. Conclusions: A single session of exposure to aerosol from a wide range of ENDS, including multiple types of e-cigarettes, a heated tobacco product, and an ultrasonic vaping device, all impair endothelial vascular function comparably to combusted cigarettes. Key words: JUUL, IQOS, ultrasonic vaping device, e-liquids, flow-mediated dilation

Differential effects of heat-not-burn and conventional cigarettes on coronary flow, myocardial and vascular function

We compared the effects of Heat-not-Burn cigarette (HNBC) to those of tobacco cigarette (Tcig), on myocardial, coronary and arterial function as well as on oxidative stress and platelet activation in 75 smokers. In the acute study, 50 smokers were randomised into smoking a single Tcig or a HNBC and after 60 min were crossed-over to the alternate smoking. For chronic phase, 50 smokers were switched to HNBC and were compared with an external group of 25 Tcig smokers before and after 1 month. Exhaled carbon monoxide (CO), pulse wave velocity (PWV), malondialdehyde (MDA) and thromboxane B2 (TxB2) were assessed in the acute and chronic study. Global longitudinal strain (GLS), myocardial work index (GWI), wasted myocardial work (GWW), coronary flow reserve (CFR), total arterial compliance (TAC) and flow-mediated dilation (FMD) were assessed in the chronic study. Acute HNBC smoking caused a smaller increase of PWV than Tcig (change 1.1 vs 0.54 m/s, p < 0.05) without change in CO and biomarkers in contrast to Tcig. Compared to Tcig, switching to HNBC for 1-month improved CO, FMD, CFR, TAC, GLS, GWW, MDA, TxB2 (differences 10.42 ppm, 4.3%, 0.98, 1.8 mL/mmHg, 2.35%, 19.72 mmHg%, 0.38 nmol/L and 45 pg/mL respectively, p < 0.05). HNBCs exert a less detrimental effect on vascular and cardiac function than tobacco cigarettes.Trial registration Registered on https://clinicaltrials.gov/ (NCT03452124, 02/03/2018).

The impact of standing desks on cardiometabolic and vascular health.

Sedentary behavior is associated with cardiovascular disease (CVD) and mortality, independent of physical activity. The biological mechanisms underlying these associations are largely unknown. We hypothesized that obese subjects with sedentary desk jobs, when assigned a sit-stand desk, will reduce daily sedentary time, and show improvement in arterial flow-mediated dilation (FMD), an early indicator of CVD. Overweight and obese subjects without known CVD were recruited at our institution and given an adjustable sit-stand desk at work. Activities were quantified with an accelerometer for 7 days at baseline and during the intervention. FMD of the brachial and superficial femoral arteries, fasting lipids, insulin and glucose labs, and anthropometrics were measured at baseline, and 12 and 24 weeks. Repeated one-way ANOVA tests were used to compare measurements over time. Fifteen participants were enrolled (93% female, mean age 40 ± 5 years, mean body mass index [BMI] 33 ± 5). Mean daily sedentary time at work decreased by 90 minutes from baseline (385 ± 49 minutes) to 12 weeks (297 ± 80 minutes, p = 0.002) and 24 weeks (295 ± 127 minutes, p = 0.015). Femoral FMD increased from baseline (4.9 ± 1.7%) to 12 weeks (6.4 ± 2.3%, p = 0.043) and further to 24 weeks (8.1 ± 3.2%, p = 0.009). Significant improvement in fasting triglycerides and insulin resistance occurred. There was no change in brachial FMD, exercise activity, step counts, weight, or BMI. A significant reduction in sedentary time during working hours was identified with utilization of a sit-stand desk and sustained over 24 weeks. Improvements in FMD, triglycerides, and insulin resistance provide insight into mechanisms of adverse health risks associated with sedentary behavior.

Effects of compression stockings on lower-limb venous and arterial system responses to prolonged sitting: A randomized cross-over trial.

Exposure to prolonged sitting increases blood pooling and the risk of lower-extremity vascular arterial and venous complications, including deep vein thrombosis. Compression garment stockings (CGS) may prevent pooling, thereby mitigating the associated vascular complications. Three aims were addressed: (i) does use of CGS help to prevent blood pooling; (ii) does blood pooling correlate with decreased stroke volume; and (iii) does use of CGS preserve leg arterial flow-mediated dilation and reactive hyperemia response. Twenty inactive participants (22 ± 4 years, 30% female, 22.1 ± 2.0 kg/m2) were randomized to sit for 3 hours with (CGS) and without use of CGS. Blood pooling was determined using medial gastrocnemius total hemoglobin. Stroke volume was estimated using finger photoplethysmography, respectively. Macrovascular and microvascular function were measured using popliteal artery flow-mediated dilation and reactive hyperemia, respectively. In response to 3 hours of sitting: (i) there was an interaction effect for total hemoglobin (p < 0.001); the condition without use of CGS increased 10.5% (95% CI: 6.7 to 14.3) and CGS increased 4.3% (95% CI: 0.1 to 7.7); (ii) blood pooling was negatively associated with stroke volume (r = -0.58, 95% CI: -0.68 to -0.45); (iii) reactive hyperemia and flow-mediated arterial dilation was impaired after prolonged sitting, and use of CGS was not associated with attenuation of this impairment. Use of CGS decreases blood pooling but does not preserve arterial macrovascular and microvascular responses to prolonged sitting. Further study is warranted to determine whether CGS has additive benefits when combined with sitting interruption strategies.

Endothelial dysfunction and the risk of heart failure in a community-based study: the Multi-Ethnic Study of Atherosclerosis.

AimsWe aimed to investigate the association between endothelial dysfunction, assessed by brachial flow‐mediated dilation (FMD), and the incidence of heart failure (HF) in the community‐based Multi‐Ethnic Study of Atherosclerosis.Methods and resultsBrachial artery FMD was measured in a nested case‐cohort sample including 3496 of 6814 Multi‐Ethnic Study of Atherosclerosis participants without prevalent cardiovascular disease (mean age 61 years, 50% women). Multivariable probability‐weighted Cox proportional hazards analysis was used to examine the association between FMD and incident HF. We also investigated the association between FMD and HF with reduced vs. preserved ejection fraction [HFrEF (left ventricular ejection fraction <45%) vs. HFpEF (left ventricular ejection fraction ≥45%)]. During follow‐up (median 12 years), 149 participants developed incident HF (incidence rate 3.7 events per 1000 person years). There were 56 HFrEF and 69 HFpEF events (incidence rates 1.4 and 1.7 events per 1000 person years, respectively). In multivariable models adjusted for established HF risk factors (age, sex, race/ethnicity, body mass index, systolic blood pressure, antihypertensive treatment, heart rate, diabetes mellitus, history of myocardial infarction, current smoker, and former smoker status), individuals in the highest quartile of FMD (reflecting better endothelial function) had a lower HF risk compared with individuals in the lowest quartile [hazard ratio 0.53, 95% confidence interval (CI) 0.31–0.95]. Lower risk according to higher FMD was particularly evident for HFrEF, but not for HFpEF (hazard ratio per standard deviation increase 0.79, 95% CI 0.64–0.97 vs. 0.99, 95% CI 0.78–1.26, respectively). Results remained similar after adjustment for baseline natriuretic peptide levels. The addition of FMD to established HF risk factors generally rendered no or only modest improvement in C‐statistics [C‐statistics for model with established HF risk factors: 0.774, and with the addition of FMD: 0.776 (delta C 0.002, 95% confidence interval −0.002 to 0.006)].ConclusionsEndothelial dysfunction was independently associated with HF in this community cohort, suggesting a pathophysiological contribution of endothelial function to the development of HF, in particular HFrEF. However, the value of FMD measurements for HF risk prediction seems limited.

Effect of direct renin inhibition on vascular function after long-term treatment with aliskiren in hypertensive and diabetic patients.

We tested the hypothesis that chronic treatment with the direct renin inhibitor aliskiren improves vascular function in resistance and conduit arteries of type two diabetic and hypertensive patients. Sixteen patients with mild essential hypertension and with a previous diagnosis of noninsulin-dependent diabetes mellitus were included in the study. Patients were then randomized to aliskiren (150 mg once daily, n = 9), or ramipril (5 mg once daily, n = 7). Each patient underwent a biopsy of the subcutaneous tissue and small arteries were dissected and mounted on a pressurized micromyograph to evaluate endothelium dependent vasorelaxation in response to acetylcholine ± N omega-nitro-L-arginine methyl ester hydrochloride in vessels precontracted with norepinephrine. Endothelial function has been quantified also in large conduit arteries by flow-mediated dilation. A similar office blood pressure-lowering effect was observed with the two drugs, although changes in DBP were not statistically significant in the ramipril group. Aliskiren significantly improved endothelium-dependent relaxation in subcutaneous resistance arteries, as well as increased flow-mediated dilation in conduit arteries, whereas the effects induced by ramipril did not reach statistical significance. Only aliskiren significantly increased the expression of p1177-endothelial nitric oxide synthase in the endothelium. Both aliskiren and ramipril had a negligible effect on markers of oxidative stress. Aliskiren restored endothelial function and induced a more prompt peripheral vasodilation in hypertensive and diabetic patients possibly through the increased production of nitric oxide via the enhanced expression and function of the active phosphorylated form of endothelial nitric oxide synthase.