Dilation Of Brachial Artery Research Articles

Vascular responses during handgrip exercise in healthy postmenopausal females and older males

Introduction: Aerobic exercise interventions improve peripheral endothelial function in healthy older males. However, this effect is not always observed in healthy postmenopausal females and possible mechanisms underlying this sex-related difference remain unknown. Greater vascular shear stress during acute exercise is a key stimulus mediating longer-term improvements in vascular function. It remains unknown if postmenopausal females display a reduced endothelial sensitivity to exercise-induced shear stress relative to males of similar age. Objective and hypothesis: The objective of this study is to test the hypothesis that healthy postmenopausal females exhibit a lower endothelial sensitivity to exercise-induced shear stress relative to males. Methods: Fourteen healthy postmenopausal females (67 ± 8 years) not under hormone replacement therapy and 9 males of similar age (65 ± 7 years) performed handgrip exercise for 4 minutes at 20%, 40%, 60%, and 80% of their maximal voluntary contraction. Each exercise bout was separated by a 10-min recovery period. Brachial artery diameter and blood velocity were continuously measured using high-resolution ultrasound and analyzed using edge-detection software. Endothelial sensitivity to shear rate was quantified as the slope of the linear regression between brachial artery dilation (% change from baseline) and shear stress and compared between groups with an independent t-test. Workload, vascular conductance, diameter dilation, and shear stress were analyzed with mixed-effects models. Results: Males exercised at greater workloads relative to females across all exercise bouts (M: 17 ± 11 vs. F: 9 ± 5 kg, p<0.01). Forearm vascular conductance was greater in males throughout each exercise intensity (M: 2.23 ± 1.70 vs. F: 1.03 ± 0.51 ml/min/mmHg, p=0.02). Despite these differences, arterial dilation (M: 5.32 ± 5.55 vs. F: 5.20 ± 4.80%, p=0.96) and shear stress (M: 142 ± 80 vs. F: 171 ± 86 s−1, p=0.27) did not differ between groups across exercise intensities. Endothelial sensitivity to exercise-induced shear stress did not differ between males (0.02 ± 0.05%/s−1) and females (0.03 ± 0.01%/s−1, p=0.67). Conclusion: These data suggest that a reduced endothelial sensitivity to exercise-induced shear stress may not explain why aerobic exercise interventions do not consistently improve peripheral endothelial function in healthy postmenopausal females. Montreal Heart Institute Foundation. This is the full abstract presented at the American Physiology Summit 2024 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.

Estrogen stimulates fetal vascular endothelial growth factor expression and microvascularization.

We recently showed that the ratio of capillaries to myofibers in skeletal muscle, which accounts for 80% of insulin-directed glucose uptake and metabolism, was reduced in baboon fetuses in which estrogen was suppressed by maternal letrozole administration. Since vascular endothelial growth factor (VEGF) promotes angiogenesis, the present study determined the impact of estrogen deprivation on fetal skeletal muscle VEGF expression, capillary development, and long-term vascular and metabolic function in 4- to 8-year-old adult offspring. Maternal baboons were untreated or treated with letrozole or letrozole plus estradiol on days 100-164 of gestation (term = 184 days). Skeletal muscle VEGF protein expression was suppressed by 45% (P < 0.05) and correlated (P = 0.01) with a 47% reduction (P < 0.05) in the number of capillaries per myofiber area in fetuses of baboons in which serum estradiol levels were suppressed 95% (P < 0.01) by letrozole administration. The reduction in fetal skeletal muscle microvascularization was associated with a 52% decline (P = 0.02) in acetylcholine-induced brachial artery dilation and a 23% increase (P = 0.01) in mean arterial blood pressure in adult progeny of letrozole-treated baboons, which was restored to normal by letrozole plus estradiol. The present study indicates that estrogen upregulates skeletal muscle VEGF expression and systemic microvessel development within the fetus as an essential programming event critical for ontogenesis of systemic vascular function and insulin sensitivity/glucose homeostasis after birth in primate offspring.

Individuals with Post-COVID Conditions Exhibit Delayed Vasodilatory Response following Brachial Artery Occlusion in the Absence of Endothelial Dysfunction and Arterial Stiffness

Background: Post-COVID Conditions (PCC) is a disorder in which individuals who contract the SARS-CoV-2 virus experience prolonged symptoms such as fatigue beyond 4 weeks after initial infection. Preliminary data suggest that individuals who are acutely infected display increased arterial stiffness and endothelial dysfunction, as well as autonomic dysfunction. However, it is not well understood if individuals with PCC continue to experience these dysfunctions beyond acute infection. Therefore, this study aimed to investigate whether vascular and autonomic function are impaired in individuals with PCC compared to individuals without PCC. Methods: Individuals previously infected with the SARS-CoV-2 virus at least 4 weeks prior to participation in the study had vascular and autonomic function assessed at baseline. Individuals experiencing PCC symptoms were classified as symptomatic (SYM, n=12) and individuals without PCC symptoms were classified as asymptomatic (ASYM, n=9). Participants were matched for age (30-55 years) and date since SARS-CoV-2 infection (ranging from 1-12 months). Arterial stiffness (carotid-femoral pulse wave velocity, cfPWV via tonometry), common carotid artery b-stiffness (via ultrasonography and tonometry), and endothelial function (brachial artery flow-mediated dilation, baFMD via ultrasonography) were assessed. Time-to-peak vasodilation (TTP) was assessed from baFMD as the time after cuff release until peak brachial artery dilation. Autonomic function was assessed with spontaneous cardiovagal baroreflex sensitivity (BRS) via sequence technique. Results: At baseline, there were no differences between groups in cfPWV (SYM: 6.2 ± 0.7 m/s, ASYM: 6.3 ± 1.1 m/s; p=0.90), baFMD (SYM: 7.3 ± 6.1%, ASYM: 7.7 ± 5.6%; p=0.87), brachial artery baseline diameter (SYM: 3.4 ± 0.6 mm, ASYM: 3.2 ± 0.4 mm; p=0.37) and common carotid b-stiffness index (SYM: 9.2 ± 2.1U, ASYM: 8.2 ± 2.5U; p=0.360). Despite no differences in baFMD% between groups, the SYM group had a significantly higher baseline baFMD TTP compared with the ASYM group (SYM: 61.6 ± 23.1 s, ASYM: 36.8 ± 14.3 s; p=0.010). There were no significant differences in cardiovagal BRS (SYM: 10.9 ± 6.8 ms/mmHg, ASYM: 11.8 ± 2.6 ms/mmHg; p=0.80). Conclusions: While arterial stiffness, endothelial function and baroreflex function did not differ between groups, individuals with PCC did present with delayed peak brachial artery vasodilation in response to shear stress. These data suggest any possible effects on vascular and autonomic function from acute SARS-CoV2 infection appear to be resolved beyond 4 weeks in those who experience prolonged symptoms. However, the delayed vasodilatory response may indicate some level endothelial dysfunction that persists in individuals with PCC. Funded by: Russell B. Day and Florence D. Day Chair in Liberal Arts and Sciences fund. This is the full abstract presented at the American Physiology Summit 2024 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.

Endogenous Acetylcholine Contributes to Flow-Mediated Dilation in Humans

Background &amp; Objective. Flow-mediated dilation (FMD) is a crucial function of the vascular endothelium wherein intraluminal shear stress stimulates endothelium-dependent vasodilation mediated primarily by nitric oxide. Brachial artery FMD (baFMD) is widely evaluated in clinical research as an index of endothelial function, and impaired baFMD is an independent predictor of cardiovascular risk. Despite the physiological and clinical relevance of FMD, the mechanisms by which shear stress is transduced to endothelium-dependent vasodilation (i.e., upstream of nitric oxide production) remain unclear. baFMD corresponds closely with sensitivity to the endothelium-dependent vasodilator acetylcholine (ACh), and preclinical models suggest ACh is released from endothelial cells in response to shear stress. Therefore, the present study tested the hypothesis that activation of muscarinic ACh receptors facilitates baFMD in humans. Methods. baFMD was evaluated using Doppler ultrasound in healthy participants (n=11; 5F/6M; 23±2 y; means ± SE) under control conditions and following local inhibition of muscarinic ACh receptors via intra-arterial atropine infused proximal to the measurement site. baFMD was assessed in response to transient and sustained shear stimuli in separate trials: 1) reactive hyperemia following 5 min of arterial cuff occlusion (RH-FMD) and 2) steady-state rhythmic handgrip exercise at graded intensities (10, 15, 20, &amp; 25% maximal voluntary contraction, MVC) to produce step increases in shear rate (EX-FMD). Blockade effcacy was confirmed via a dose-response to intra-arterial ACh infusion pre and post atropine. Results. Baseline brachial artery diameter and forearm blood flow were similar in all trials (all P&gt;0.05). Atropine reduced peak brachial artery dilation following cuff release (RH-FMD, Δ diameter, atropine: 4.6±0.8 vs. control: 6.5±0.8%, P=0.04) and increased the shear stimulus (shear rate area under the curve, SRAUC: atropine, 29±3 vs. control: 21±3 s−1×103, P=0.01) such that the percent change in brachial diameter was diminished by 35±16% when normalized to SRAUC (baFMD:SRAUC ratio, atropine: 1.7±0.3 vs. control: 3.9±1.0, P=0.02). Similarly, in the EX-FMD trial, atropine reduced brachial artery diameter at all exercise intensities (25% MVC, percent change in diameter: atropine, 10.8±1.4 vs. control, 15.5±1.7%, P=0.04) despite a greater shear stimulus (shear rate: atropine, 10.9±1.1 vs. control, 9.3±0.9 s−1×102, P=0.01). Thus, atropine reduced the slope describing the relationship between brachial artery vasodilation (percent change) and the change in shear rate by 38±8% across all exercise intensities (slope, atropine: 1.3±0.1 vs. control: 2.4±0.4% Δ×s×10−2, P=0.007). As expected, atropine reduced brachial artery vasodilation in response to upstream infusion of ACh (1.5 μg ACh/dl forearm volume/min, Δ diameter, atropine: 2±1 vs. control: 23±4%, P=0.001). Conclusions. The results suggest endogenous ACh facilitates baFMD in response to both transient and sustained shear stimuli, which highlights a novel physiological role of endogenous ACh in vascular regulation in humans and provides insight regarding the basic mechanisms of flow-mediated vasodilation. NIH R01 HL119337 and F31 HL142240. This is the full abstract presented at the American Physiology Summit 2024 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.

Nitrate-rich beetroot juice supplementation in midlife and older adults with renal dysfunction increases vascular endothelial function and changes the circulating milieu to improve endothelial cell nitric oxide production and oxidative stress

BACKGROUND: Midlife and older (ML/O) adults with mild-to-moderate renal dysfunction (MRD) are at increased risk for cardiovascular disease (CVD). A key antecedent to CVD in ML/O adults with MRD is vascular endothelial dysfunction, mediated by declines in nitric oxide (NO) bioavailability due to excess reactive oxygen species (ROS)-related oxidative stress. We have shown that targeting the nitrate-nitrite-NO pathway with sodium nitrite in heathy ML/O adults improves endothelial function and changes the circulating milieu to lower endothelial cell (EC) ROS bioactivity. However, if nitrate-rich beetroot juice (N-BRJ) is effective for improving endothelial function in ML/O men and women with MRD is unknown. HYPOTHESES: We tested the hypotheses that chronic N-BRJ in ML/O men and women with MRD would: 1) improve endothelial function and 2) induce changes to the circulating milieu to increase EC NO production and lower EC ROS bioactivity. We also assessed possible sex differences in the effcacy of N-BRJ for improving endothelial function. METHODS: Twenty-six ML/O men and women with MRD (estimated glomerular filtration rate [eGFR; CKD-EPI]: 40-89 mL/min/1.73m2) underwent three months of supplementation with N-BRJ (70 mL with 6.45 mmol nitrate/day) (n=13, 7 women; age: 65±2 years; eGFR: 69.2±3.3 mL/min/1.73m2) or nitrate-depleted BRJ (placebo, PBO) (n=13, 7 women; age: 68±2 years; eGFR: 79.8±3.1 mL/min/1.73m2) in a randomized, placebo-controlled, parallel-group design clinical trial. Endothelial function was assessed by brachial artery flow-mediated dilation (FMDBA). Smooth muscle sensitivity to NO was assessed by brachial artery dilation to sublingual nitroglycerin. Human aortic ECs (HAECs) in culture were exposed to 10% subject serum (n=10[6-7 women]/group) collected before and after N-BRJ and PBO supplementation. Acetylcholine-stimulated NO production (DAR-4M-AM) and whole-cell ROS bioactivity (CellROX) were assessed in HAECs using immunofluorescence. Results: N-BRJ supplementation increased FMDBA by 28% (pre: 4.6±0.7%, post: 5.9±0.8%; p=0.03). FMDBA did not change with PBO (pre: 4.6±0.9%, post: 4.7±0.8%; p&gt;0.05). Traditional CVD risk factors (i.e., blood pressure, cholesterol) and smooth muscle sensitivity to NO were unchanged in both groups (p&gt;0.05). Preliminary assessments suggest greater improvements in endothelial function with N-BRJ in women (Δ=post-pre intervention; ΔFMDBA=1.6±0.4) compared to men (ΔFMDBA=0.9±1.0). Compared to pre-intervention, NO production was (trending) 7% higher (p=0.05) and ROS bioactivity was 25% lower (p=0.02) in HAECs exposed to serum collected post N-BRJ. Serum from PBO had no effects (p&gt;0.05). CONCLUSION: N-BRJ supplementation in ML/O adults with MRD holds promise for improving endothelial function, in part by inducing changes to the circulating milieu that increase NO production and decrease oxidative stress in ECs. The effects on endothelial function may be greater in women compared to men. Targeting the nitrate-nitrite-NO pathway with N-BRJ may be an effective strategy for improving endothelial function in ML/O adults with renal dysfunction to possibly reduce CVD risk. K01DK115524 (MJR); R01AG013038 (DRS); F32HL167552 (KOM); NIH/NCATS CTSA UL1TR002535. This is the full abstract presented at the American Physiology Summit 2024 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.

P142 Effect of Atorvastatin on vascular endothelial function in early Systemic Sclerosis: An open label Randomized Controlled trial

Abstract Background/Aims Systemic Sclerosis (SSc) is driven by early endothelial dysfunction, leading to loss of endothelium-dependent vasodilatation. This predisposes to increased stiffness of large arteries. Prospective studies have found a conflicting role of statins in improving vascular function in established SSc. We undertook this study to explore if statins influence endothelium dependent vasodilation in early SSc Methods In this single center open label randomized controlled trial between July 2021 to January 2022, SSc patients (ACR-EULAR 2013) between 18-65 years, with duration &amp;lt; 3 years from the first non-Raynaud’s symptom were included. Those with complicated Raynaud’s, overlap syndromes and cardiovascular comorbidities were excluded. Participants were randomized into statin (atorvastatin 40 mg/day/A40) or no -statin arm. Both groups received stable doses of immunosuppression, during the study period. The primary outcome of flow-mediated dilation (FMD %) of brachial artery, measured by single assessor and secondary outcomes of common carotid intima medial thickness (CIMT), modified Rodnan Skin score (mRSS), Raynaud’s visual analogue scale (RayVAS:0-10), hs CRP, von Willebrand factor and oxidized low-density lipoproteins were measured at baseline and 16 weeks. All patients provided written informed consent; study protocol was approved by IEC(JIP/IEC/2020/026). Considering a change in FMD of 1% between arms as clinically meaningful, sample size was calculated to be 144. Analysis was performed using SPSS v.19.CTRI registration no: REF/2020/07/03495 Results Total 71 eligible patients were randomized into statin(n = 36) and no-statin(n = 35) arms. Baseline parameters were comparable between arms. Baseline mRSS was 14.25. On per-protocol analysis of statin (n = 28) and no-statin (n = 32) arms, there was no significant difference in FMD either at baseline or at 16 weeks (table 1). At week 16, basal brachial artery diameter increased (p = 0.008) in statin arm. Ray VAS scores improved in the statin arm,not achieving significance(p = 0.15). An increase in mRSS from 14 to 16 was noted in no-statin arm , whereas it remained stable in the statin arm (14.5). Secondary endpoints were not met. No adverse events were noted. Conclusion In early SSc, atorvastatin 40 mg/day, added to background immunosuppression, failed to improve endothelial function, assessed using brachial FMD, at 16 weeks. Stabilization of skin tightening was noted in the statin arm. Disclosure A.C. Das: None. M.M. Thabah: None. C. Mariaselvam: None. R. Vijayan: None. A. Anantharaj: None. V. Negi: None.

Matrix Gla Protein and Nitric Oxide Synthase-3 Genetic Variants in Chronic Kidney Disease and Their Relation with Cardiovascular Risk.

Chronic kidney disease (CKD) is defined by gradual deterioration of renal parenchyma and decline of functioning nephrons. The risk of cardiovascular events is drastically increased in patients with CKD. This complicated link of CKD and cardiovascular disease (CVD) is not well understood till date. We aim to study the influence of genetic variants of matrix Gla protein (MGP) gene rs1800801, rs1800802, and rs4236 and nitric oxide synthase-3 (NOS3) gene rs1799983 and rs2070744 on the risk of CKD and its associated cardiovascular comorbidity in South Indian Tamils. One hundred and eighty-five CKD patients and 185 controls were recruited in this research. Flow-mediated dilatation (FMD) of brachial artery was measured ultrasonically. Circulating levels of MGP and nitric oxide (NO) were measured by ELISA. Genotyping was done by real-time PCR. We observed a significant difference in the distribution of TT and CT genotypes of NOS3 (rs2070744), indicating an increase in the risk of CKD. NO level was significantly decreased in CKD cases than controls. We also found a significant difference in the distribution of TTA and CCG haplotypes of MGP polymorphisms (1-rs4236; 2-rs1800801; 3-rs1800802) between the groups, indicating an increase in the risk of CKD. CT genotype of MGP (rs4236) and CT genotype of NOS3 (rs2070744) variants were found to be associated with decreased FMD, indicating endothelial dysfunction, the harbinger of CVD. We conclude that genetic variants of MGP and NOS3 enhance the risk of CKD and its associated cardiovascular comorbidity in South Indian Tamils.

412 Flow mediated dilatation of brachial artery to evaluate endothelial dysfunction in gestational diabetes mellitus

412 Flow mediated dilatation of brachial artery to evaluate endothelial dysfunction in gestational diabetes mellitus

The pathological reactions of brachial artery during and their significance in treatment of patients with chronic obstructive pulmonary disease

Background. The purpose of this study was to analyse the pathological reactions of brachial artery (BA) during test with reactive hyperemia (RH) for endothelial function (EF) estimation and their applicable significance in treatment of patients with chronic obstructive pulmonary disease (COPD). Material and methods. There were investigated 61 patients, mean age 47,7±5,11 years with moderate to severe forms of COPD (by GOLD criterion). Endothelial dysfunction (ED) estimation was performed non-invasive, using probe with RH with brachycephalic arteries Duplex with high resolution 8,0-10,0 MHz („Logiq S8” „General Electric”, SUA) by David S. Celermajer proposed method. ED was considered when EF index was less than 10%. Results. The analysis of obtained data revealed considerable decreasing of EF: mean EF index was 7,14±11,22%, between -15,0% and 29,4%. In 10 patients after RH test was noted pathological reaction of BA: instead of awaited endothelialdependent BA dilatation, there were observed spastic and negative reactions (in limits between 0% and −15,0%). In parallel there were visualized in a. carotis solitary and binary atherosclerotic plagues with 20-40% of vascular stenosis without any clinical manifestations. The levels of total cholesterol and LDL-C also were elevated: 7,5±2,0 mm/l и 4,7±1,8 mm/l, respectively. In all 10 patients with pathological BA reactions do not reduced mean and systolic pulmonary artery pressure after 5 weeks of treatment with perindopril (mean dose 2,9±1,5 mg once daily) or valsartan (mean dose 54,5±15,4 mg once daily). Conclusions. Thus, BA pathological reaction during RH test for ED estimation may be used like a criterion predictor of efficacity of treatment with perindopril or valsartan and for prognosis of survival in patients with severe forms of COPD.

Does Exercise Testing with Arm Crank Ergometer Substitute for Cycle Ergometer to Evaluate Exercise Capacity?

Using the upper limbs to test cardiopulmonary exercise can be a useful option in the case of individuals who are unable to pedal a bicycle due to lower limb injury or disability. We evaluated whether exercise testing with the upper limbs can be used equivalently to that of the lower limbs in assessing exercise capacity. Nine collegiate rowers and eight collegiate cyclists underwent incremental exercise testing with an arm crank ergometer (ACE) and cycle ergometer (CE). Heart rate (HR) and oxygen uptake (VO2) were monitored throughout the tests. Segmental muscle mass and flow-mediated dilation of brachial artery were measured to assess the training status of the upper limbs. The muscle mass of the brachium, upper limb, and trunk were greater in the rowers than in the cyclists (p &lt; 0.05). The correlations between HR and VO2 was significantly different depending on exercise modalities, ACE and CE, in both groups (p &lt; 0.001). The estimated maximal VO2 using the correlation formula and age-predicted maximal HR was significantly lower in the exercise testing group with ACE than in the group with CE in rowers and cyclists (41.7 ± 7.3 vs. 52.6 ± 8.6 mL/kg/min, p = 0.010 and 35.5 ± 14.2 vs. 50.4 ± 13.4 mL/kg/min, p = 0.011, respectively). The results suggested that exercise capacity assessed by exercise testing with ACE is underestimated, regardless of the training status of the upper limbs. Further research is needed to verify factors which affect the correlations between HR and VO2 during upper- and lower-limb exercise.

Abstract 16485: Treatment With PCSK9 Inhibitors Influence miRNAs Expression and Changes of Arterial Wall Properties

Background and aim: MicroRNAs (miRNAs) are involved in the synthesis of proprotein convertase subtilisin-kexin type 9(PCSK9), which is one of regulators of low-density lipoprotein cholesterol (LDL-C) metabolism. There is no data on whether changes in the expression of miRNAs involved in PCSK9 metabolism, could be related to arterial wall properties changes. The aim was to verify whether PCSK9 inhibitors (PCSK9i) treatment and the changes in the expression of miRNAs are associated with arterial wall properties in post-myocardial infarction (MI) patients with insufficiently regulated LDL-C levels and increased Lp(a) levels. Methods: Seventy-six participants after MI were enrolled and randomized to a placebo group or PCSK9i group. The treatment group received subcutaneous alirocumab 150 mg or evolokumab 140 mg, every 2 weeks. Blood for biochemical and genetic analysis was taken and ultrasound measurements of flow-mediated dilation of brachial artery (FMD), carotid intima-media thickness (c-IMT) and pulse wave velocity (PWV) were performed. All measurements were measured initially and after 6 months of treatment. Results: FMD improved from 10.9±6.3 to 14.4±5.7% in the PCSK9i group and 10.8±6.8 to 11.2±4.6% in the placebo group (p&lt;0.001, p=0.584). PWV changed from 5.8±1.4 to 5.5±1.6 m/s (p=0.024) in the PCSK9i group and in the placebo group from 5.6±1.5 to 5.5±1.1 m/s (p=0.879), with better improvement in the treated group (p=0.007). c-IMT decreased in the PCSK9i group (from 0.65±0.10 to 0.63±0.10 mm; p=0.017), with no change in the placebo group (from 0.64±0.09 to 0.63±0.09 mm; p=0.482). The expression of miR-191-5p and miR-483-5p increased in the PCSK9i group (p=0.028, p=0.020; respectively). The expression of miR-191-5p significantly decreased in the placebo group (p&lt; 0.001). A decrease in c-IMT was associated with a decrease in the expression of miR-224-5p (r=0.303; p=0.019), miR-337-3p (r=0.329; p=0.010) and miR-483-5p (r=0.367; p=0.004). Conclusions: Our results suggest that changes in selected miRNAs were associated with changes in the morphological properties of the arterial vessel wall. We have shown that the increase in miR-483-5p expression can be a good indicator of the regression of morphological atherosclerotic changes.

Predictors of functional and morphological arterial wall properties in coronary artery disease patients with increased lipoprotein (a) levels before and after treatment with proprotein convertase subtilisin-kexin type 9 inhibitors

BackgroundIn addition to proatherogenic properties, lipoprotein (a) (Lp(a)) has also pro-inflammatory, antifibrinolytic and prothrombogenic features. The aim of the current study was to identify the predictors of functional and morphological properties of the arterial wall in patients after myocardial infarction and increased Lp(a) levels at the beginning and after treatment with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors.MethodsSeventy-six post-myocardial infarction patients with high Lp(a) levels were included in the study. Ultrasound measurements of flow-mediated dilation of brachial artery (FMD), carotid intima-media thickness (c-IMT) and pulse wave velocity (PWV) were performed initially and after 6 months of treatment. At the same time points lipids, Lp(a), inflammatory and hemostasis markers were measured in blood samples.ResultsIn linear regression model FMD significantly correlated with age at first myocardial infarction (β = 0.689; p = 0.022), high-sensitivity C-reactive protein (β = -1.200; p = 0.009), vascular cell adhesion protein 1 (VCAM-1) (β = -0.992; p = 0.006), overall coagulation potential (β = 1.428; p = 0.014) and overall hemostasis potential (β = -1.473; p = 0.008). c-IMT significantly correlated with age at first myocardial infarction (β = 0.574; p = 0.033) and Lp(a) (β = 0.524; p = 0.040). PWV significantly correlated with systolic blood pressure (β = 0.332; p = 0.002), tumor necrosis factor alpha (β = 0.406; p = 0.002), interleukin-8 (β = -0.315; p = 0.015) and plasminogen activator inhibitor 1 (β = 0.229; p = 0.031). After treatment FMD reached statistical significance only in univariant analysis with systolic blood pressure (r = -0.286; p = 0.004) and VCAM-1 (r = -0.229; p = 0.024). PWV and c-IMT correlated with age (r = 0.334; p = 0.001 and r = 0.486; p < 0.0001, respectively) and systolic blood pressure (r = 0.556; p < 0.0001 and r = 0.233; p = 0.021, respectively).ConclusionsOur results suggest that age, systolic blood pressure, Lp(a) levels and other biochemical markers associated with Lp(a) are predictors of functional and morphological properties of the arterial vessel wall in post-myocardial patients with high Lp(a) levels initially. However, after 6 months of treatment with PCSK9 inhibitors only age and systolic blood pressure seem to be predictors of these properties.Trial registrationThe protocol for this study was registered with clinicaltrials.gov on November, 3 2020 under registration number NCT04613167.Graphical

Normalization of Flow-mediated Dilation to Brachial Artery Material Property: A Feasibility Study.

Endothelial reactivity (ER) is widely measured using flow-mediated dilation (FMD) of brachial artery. Conventional measurement of FMD is influenced by factors such as input shear stress, arterial transmural pressure, diameter and thereby arterial material properties (ε). Thus, for a reliable interpretation of FMD, it has to be normalized with respect to the above confounding factors. Normalization of FMD with shear stress at the time of measurement has been reported to reduce measurement variability. However, its widespread usage among the research community is limited. In this work, we examine the feasibility of normalizing the brachial FMD index (FMD%) to ε : extrema (εp), baseline (εb) and extrema change (∆ε) post-ischemia using its inter-day variability against FMD. In-vivo measurements were performed on 10 participants for 2 consecutive days and simultaneous pressure-diameter cycles were collected to estimate the material properties during reactive hyperemia (RH). The box-whisker plot reveals differences in the mean and deviation of FMD to FMD|εb. A significant value for repeatability (ICC ≥ 0.6) was obtained for normalized FMD (FMD|εb) for specific stiffness index (β), pressure-strain elastic modulus (Ep), and local pulse wave velocity (PWV) as compared to FMD. Hence, normalization of FMD% to arterial ε can potentially improve the measurement reliability of ER assessment.Clinical Relevance- This pilot study demonstrates the feasibility of brachial artery stiffness assessment during FMD and its potential use for normalizing the standard FMD measurement.

Metabolic Syndrome as a Cardiovascular Risk Factor: A Reality or Just a Multiplex of Risk Factors? A Study on Association Between Endothelial Dysfunction And Metabolic Syndrome as a Cardiovascular Risk Factor

Background:Metabolic syndrome is a constellation of various cardiovascular risk factors with a potential to double the risk of coronary artery disease. However, in real world scenario, this is just a combination of multiple CV risk factors and its separate existence is somehow regarded as a myth in endothelial function assessment. Endothelial dysfunction is regarded as a precursor and a surrogate marker of atherosclerosis and coronary artery disease. Therefore a study was designed to evaluate the role of metabolic syndrome as a cardiovascular risk factor by assessing endothelial function in subjects with it. Methods: One hundred subjects with various cardiovascular risk factors were selected and endothelial dysfunction was assessed by measuring flow-mediated dilation of brachial artery. The rates of endothelial dysfunction was compared between subjects with and without metabolic syndrome. Similarly the rates of metabolic syndrome was calculated in subjects with and without endothelial dys-function in this cohorts of cardiovascular risk factors. Results: Out of 100 subjects with cardiovascular risk factors, mean age 46.75 (9.95) years and mean number of risk factors 2.81 (1.17), similarly, there was no significant difference in the rates of metabolic syndrome among subjects with and without endothelial dysfunction (84.85% vs 79.10% respectively; p=0.67). Only age and hypertension were associated with endothelial dysfunction. Conclusion: The association between metabolic syndrome and endothelial dys-function was not significantly different than the association between multiplex of risk factors and endothelial dysfunction. Therefore its putative role as a separate cardiovascular risk factors, rather than just a multiplex still remains under scrutiny if not a myth. Further well-designed study should be conducted to establish the role of metabolic syndrome as a separate cardiovascular risk factor other than just a multiplex.

Multi-marker panel in patients with NSTEMI: pillars of pathogenesis and diagnostics

Aim. Assessment within the multi-marker panel applied to patients with NSTEMI of admission levels of the main markers of cardiovascular pathology in order to disentangle the pathogenetic interface and identify diagnostic predictors. Material and methods. The research was carried out on a group of 87 patients with NSTEMI, exposed to angioplasty, in which the admission values of 2 morphofunctional markers of endothelial dysfunction were determined, as well as the serum levels of 53 biochemical markers with reference to: inflammation, oxidative stress, endothelial dysfunction, cell injury, hemostasis disorder, myocardial and extracellular matrix (ECM) remodeling. The control group has consisted of 40 apparently healthy people. Results. The analysis of the multi-makrer panel revealed significant deviations of the majority of the explored markers compared to the control level. Endothelial dysfunction was marked by the increase of thickness of the medial-intima complex of the carotid artery and the decrease of the flow-mediated dilation of brachial artery in association with a 7694% raise of endothelial cell fragments (EF), phospholipase A2 (PhA2) and angiopoietin 2 (Ang 2). Among 16 markers of inflammation, the elevation of myeloperoxidase (MPO) by 156% is remarkable as a specific marker of NETosis. Activated oxidative stress is the result of the impairment of the antioxidant defense, and hemostasis disorder must be underlined by double increase of fibrin monomers (FM). From a pathogenetic point of view, the multiple increase (more than 8 times) of cardiac myosin-binding protein (cMyBP-C) is important and understandable, and the markers of myocardial and ECM remodeling basically demonstrated an activation of several types of metalloproteinases. Conclusion. From the spectrum of the multi-marker panel applied to patients with NSTEMI, markers with plausible diagnostic value due to inteligibly reflected pathogenetic mechanism are highlighted as: MPO, PhA2, Ang 2, EF, FM, and cMyBP-C.

The role of intestinal dysbiosis in endothelial dysfunction evolution in patients with microvascular angina

Purpose. Evaluation of circulating levels of lipopolysaccharide and zonulin in conjunction with markers of endothelial dysfunction, inflammation, and oxidative stress in patients with microvascular angina (MА). Material and methods. The study was carried out in a group of 58 patients with MA hospitalized in the Institute of Cardiology. The determination of circulating levels of 20 biomarkers was carried out in cooperation with the laboratory investigation center of Sapienza University (Italy). All functional and biochemical markers were also determined in 48 apparently healthy people (control group) with the values of which the markers of MA patients were compared. Results. Endothelial dysfunction in patients with MA excelled by increasing the thickness of the intima-media complex of the carotid artery by 41%, as well as by reducing of flow-mediated brachial artery dilatation (FMD) by 31,6%. The presence of dysbiosis was manifested by an 80% increase in the serum content of lipopolysaccharides (LPS) and by doubling of zonulin (1,8±0,3 vs 3,6±0,7 ng/ml). Endothelial dysfunction and dysbiosis evolved in association with oxidative stress activation estimated by means of 6 markers and increased serum content of 6 important pro-inflammatory markers (hsCRP, IL-6, TNF-α, etc.) Conclusions. 1. In patients with MA, elevated circulating levels of LPS and zonulin more than twice compared to the control value were found, which indicates the presence of intestinal dysbiosis. 2. LPS and zonulin correlate robustly with morphofunctional and biochemical markers of endothelial dysfunction, as well as with markers of its main pathogenetic factors, - inflammation and oxidative stress.

The impact of age on the vascular response to acute sauna exposure

Passive heat exposure has been shown to be a promising method to improve endothelial health. Sauna usage specifically, has been linked to reduced risk of cardiovascular disease in young and middle-aged populations. Increases in blood flow and shear rates associated with heat exposure are often considered to have a major influence on the observed improved endothelial function following repeated heat exposure; however, the magnitude of these shear and flow responses may potentially vary with age or starting endothelial function. Purpose: The purpose of this study was to determine if the vascular response to acute sauna heating is similar between healthy young and middle-aged adults and if the response is related to baseline endothelial function. Methods: 10 young (24.9 ± 4.2 years, 6 male and 4 female) and 8 middle aged adults (55.6 ± 3.9 years 4 males and 4 females) underwent 40 min of sauna exposure at 80ºC. Esophageal temperature was recorded throughout the duration of the experiment. Brachial artery flow-mediated dilation (FMD) blood flow, artery diameter, shear rates and blood pressure were recorded at baseline and following heat exposure. Results: The increase in core temperature (Tc) followed similar trends in both the young and middle-aged adults (young ΔTc = 1.386 ± 0.52 ºC vs middle-Age Δ Tc = 1.637 ± 0.56 ºC). Heat-induced brachial artery dilation and brachial artery shear rate also increased similarly in both age groups (young Δ diameter = 0.048 ± 0.022 cm vs middle-age Δ diameter = 0.074 ± 0.036 cm, young Δ shear = 164.5± 106.8 sec- 1 vs middle-age Δ shear = 150.3 ± 56.29 sec -1 ). Heat induced dilation was strongly correlated to baseline endothelial function in the young (r = 0.86, P=0.006). This relationship was not observed in the brachial artery of middle-aged adults (r = 0.257, P=0.539). Systolic blood pressure (SBP) was significantly reduced following sauna in the middle-aged participants from 135.25 ± 17.50 mmHg to 122.38 ± 19.7 mmHg (P=0.017). There was a slight elevation in SBP following sauna in the young participants from 119.4 ± 6.38 mmHg to 123.1 ± 7.65 mmHg (P=0.017). Diastolic blood pressure (DBP) was significantly reduced in both age groups (P&lt;0.001) with middle age seeing greater reductions (P=0.05) from 80.63 ± 10.97 mmHg to 69.75 ± 8.41 mmHg vs the young 71.2 ± 8.24 mmHg to 66.9 ± 4.56 mmHg. Conclusion: Young and middle-aged adults have similar changes in shear rate and brachial artery dilation in response to acute sauna heating, but the middle-aged adults exhibit significantly greater decreases in SBP and DBP than young adults. In young adults, endothelial function is strongly correlated to heat induced dilation in the brachial artery. This relationship is not present in the middle age population suggesting that heat-induced dilation may rely on mechanisms other than endothelial function in middle-aged adults. 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.

A nomogram based on endothelial function and conventional risk factors predicts coronary artery disease in hypertensives

BackgroundThere is currently a lack of a precise, concise, and practical clinical prediction model for predicting coronary artery disease (CAD) in patients with essential hypertension (EH). This study aimed to construct a nomogram to predict CAD in patients with EH based on flow-mediated dilation (FMD) of brachial artery and traditional risk factors.MethodsClinical data of 1752 patients with EH were retrospectively collected. High-resolution vascular ultrasound was used to detect FMD in all patients at the Fujian Hypertension Research Institute, China. Patients were divided into two groups, i.e. training group (n = 1204, from August 2000 to December 2013) and validation group (n = 548, from January 2014 to May 2016) according to the time of enrollment. Independent predictors of CAD were analyzed by multivariable logistic regression in the training group, and a nomogram was constructed accordingly. Finally, we evaluated the discrimination, calibration, and clinical applicability of the model using the area under curve (AUC) of receiver operating characteristic analysis, calibration curve combined with Hosmer-Lemeshow test, and decision curve, respectively.ResultsThere were 263 (21.8%) cases of EH combined with CAD in the training group. Multivariate logistic regression showed that FMD, age, duration of EH, waist circumference, and diabetes mellitus were independent influencing factors for CAD in EH patients. Smoking which was close to statistical significance (P = 0.062) was also included in the regression model to increase the accuracy. Ultimately, the nomogram for predicting CAD in EH patients was constructed according to above predictors after proper transformation. The AUC values of the training group and the validation group were 0.799 (95%CI 0.770–0.829) and 0.836 (95%CI 0.787–0.886), respectively. Calibration curve and Hosmer-Lemeshow test showed that the model had good calibration (training group: χ2 = 0.55, P = 0.759; validation group: χ2 = 1.62, P = 0.446). The decision curve also verified the clinical applicability of the nomogram.ConclusionThe nomogram based on FMD and traditional risk factors (age, duration of EH disease, smoking, waist circumference and diabetes mellitus) can predict CAD high-risk group among patients with EH.

High sodium intake differentially impacts brachial artery dilation when evaluated with reactive versus active hyperemia in salt resistant individuals.

This study sought to determine if high sodium (HS) intake in salt resistant (SR) individuals attenuates upper limb arterial dilation in response to reactive (occlusion) and active (exercise) hyperemia, two stimuli with varying vasodilatory mechanisms, and the role of oxidative stress in this response. Ten young, SR participants (9 males, 1 female) consumed a 7-day HS (6,900 mg/day) and a 7-day recommended sodium intake (RI: 2,300 mg/day) diet in a randomized order. On the last day of each diet, brachial artery (BA) function was evaluated via reactive (RH-FMD: 5 min of cuff occlusion) and active [handgrip (HG) exercise] hyperemia after consumption of both placebo (PL) and antioxidants (AO). The HS diet significantly elevated sodium excretion (P < 0.05), but mean arterial blood pressure was unchanged. During the PL condition, the HS diet significantly reduced RH-FMD when compared with RI diet (P = 0.01), but this reduction was significantly restored (P = 0.01) when supplemented with AO (HS + PL: 5.9 ± 3.4; HS + AO: 8.2 ± 2.7; RI + PL: 8.9 ± 4.7; RI + AO: 7.0 ± 2.1%). BA shear-to-dilation slopes, evaluated across all HG exercise workloads, were not significantly different across sodium intervention or AO supplementation. In SR individuals, HS intake impaired BA function when assessed via RH-FMD, but was restored with acute AO consumption suggesting oxidative stress as a contributor to this dysfunction. However, exercise-induced BA dilation was unaltered, potentially implicating an inability of HS intake to influence the mechanisms responsible for effectively maintaining skeletal muscle perfusion during exercise.NEW & NOTEWORTHY This study examined if high sodium (HS) intake in salt resistant (SR) individuals attenuates brachial artery (BA) flow-mediated dilation in response to reactive (occlusion) and active (exercise) hyperemia. In SR individuals, HS intake impaired reactive hyperemia-induced BA dilation, but not exercise-induced BA dilation. This finding suggests that although brachial artery nitric oxide bioavailability may be reduced following HS intake, the redundant mechanisms associated with adequate upper limb blood flow regulation during exercise are maintained.

Clinical value of flow-mediated dilatation of brachial artery in hypertensive disorders complicating pregnancy.

Hypertensive disorders complicating pregnancy (HDCP) are common pregnancy-related disorders. In this study, we aimed to study the clinical value of flow-mediated dilation (FMD) in HDCP and its association with endothelial dysfunction and HDCP-related factors. 160 HDCP patients and 120 healthy pregnancies were enrolled in the study. The expressions of endothelial function markers and FMD were determined. In addition, their correlations in HDCP patients were also analyzed using Pearson's correlation analysis. FMD value decreased gradually from normal pregnancy to severe PE. The levels of plasma nitric oxidase (NO) were significantly lower in the HDCP group than those in the control group, while the levels of plasma endothelin-1 (ET-1) were increased dramatically in the HDCP group. Moreover, the levels of placental growth factor (PLGF) in HDCP women were significantly lower, while the soluble FMS-like tyrosine kinase 1 (sFLt-1) levels were markedly higher than those in control. In addition, the FMD value was correlated with the levels of plasma NO, ET-1, PLGF and sFlt1. It was also found that lower levels of FMD correspond to endothelial dysfunction and abnormal concentrations of PLGF and sFlt-1. The FMD value was associated with endothelial function indicators and could be a strong and non-invasive measure to predict HDCP. The association between the FMD values and endothelial function indicators in HDCP could be helpful for the prediction of pregnant hypertension more accurately.