Vascular conditioning prevents adverse left ventricular remodelling after acute myocardial infarction: a randomised remote conditioning study

Aims: Remote ischemic conditioning (RIC) alleviates ischemia–reperfusion injury via several pathways, including micro-RNAs (miRs) expression and oxidative stress modulation. We investigated the effects of RIC on endothelial glycocalyx, arterial stiffness, LV remodelling, and the underlying mediators within the vasculature as a target for protection. Methods and results: We block-randomised 270 patients within 48 h of STEMI post-PCI to either one or two cycles of bilateral brachial cuff inflation, and a control group without RIC. We measured: (a) the perfusion boundary region (PBR) of the sublingual arterial microvessels to assess glycocalyx integrity; (b) the carotid-femoral pulse wave velocity (PWV); (c) miR-144,-150,-21,-208, nitrate-nitrite (NOx) and malondialdehyde (MDA) plasma levels at baseline (T0) and 40 min after RIC onset (T3); and (d) LV volumes at baseline and after one year. Compared to baseline, there was a greater PBR and PWV decrease, miR-144 and NOx levels increase (p  15% (odds-ratio of 3.75, p = 0.029). MiR-144 and PWV changes post-RIC were interrelated and associated with LVESV reduction at follow-up (r = 0.40 and 0.37, p < 0.05), in the single-cycle RIC. Conclusion: RIC evokes “vascular conditioning” likely by upregulation of cardio-protective microRNAs, NOx production, and oxidative stress reduction, facilitating reverse LV remodelling

Pulse wave analysis using the Mobil-O-Graph, Arteriograph and Complior device: a comparative study

Purpose: Pulse wave velocity (PWV) is a marker of arterial stiffness with major prognostic value. We compared Arteriograph and Complior devices with the Mobil-O-Graph for assessment of PWV and central systolic blood pressure (cSBP). Materials and Methods: We studied 316 consecutive subjects (age: 55 ± 14 years). For each individual, we measured PWV and cSBP with Arteriograph, Complior and Mobil-O-Graph and compared the readings. Differences in values among three devices were calculated for each measurement. We used Bland-Altman analysis, intraclass correlation coefficient (ICC) and coefficient of variation (CV). Results: Bland-Altman analysis indicated a mean difference for PWV: i.0.5 m/s (limits of agreement -1.4–2.4) between Complior and Mobil-O-Graph, ii.0.6 m/s (limits of agreement -1.4–2.6) between Arteriograph and Mobil-O-Graph. cSBP mean difference was 3.8 mmHg between Complior and Mobil-O-Graph (limits of agreement -12.5–20.1) and 9.2 mmHg between Arteriograph and Mobil-O-Graph (limits of agreement -7.6–26). ICC for PWV was 0.86 between Arteriograph and Mobil-O-Graph, 0.87 between Complior and Mobil-O-Graph and for cSBP 0.92 and 0.91 respectively. CV for PWV was 9.5% between Arteriograph and Mobil-O-Graph, 8.8% between Complior and Mobil-O-Graph. Respective values for cSBP were 6.8% and 5.1%. Conclusion: Our study shows acceptable agreement among the three devices regarding pulse wave analysis markers though Mobil-O-Graph appears to underestimate the values of these markers. Further studies are needed to explore the agreement between the 3 devices in various clinical settings and patient populations. © 2019, © 2019 Informa UK Limited, trading as Taylor &amp; Francis Group

Early detection of left ventricular dysfunction in first-degree relatives of diabetic patients by myocardial deformation imaging: The role of endothelial glycocalyx damage

Background First-degree relatives of type-2 diabetes patients (FDR) present insulin resistance. We investigated whether FDR and dysglycaemic subjects demonstrate abnormal endothelial glycocalyx and LV deformation during postprandial hyperglycemia. Methods We studied 40 FDR with normal oral glucose test (OGTT), 40 subjects with abnormal OGTT (dysglycaemic) and 20 subjects with normal OGTT without parental history of diabetes (normoglycaemic). At 0 and 120 min of OGTT we measured: a) LV longitudinal strain (LS) of subendocardial, mid-myocardial and subepicardial layers, global LS (GLS), peak twisting (pTw), untwisting velocity (pUtwVel), by speckle tracking echocardiography b) perfused boundary region (PBR) of the sublingual arterial microvessels; high PBR values represent reduced glycocalyx thickness. Insulin resistance was evaluated using insulin sensitivity index (ISI). Results ISI was related with baseline PBR, GLS and pTw in all subjects (p &lt; 0.05). Compared to normoglycaemics, FDR and dysglycaemics had higher PBR, lower ISI, GLS (− 18.4 ± 2.6 and − 16.8 ± 2.0 vs. − 19.2 ± 2.4%), subendocardial LS (− 19.0 ± 4.2 and − 17.9 ± 3.0 vs. − 20.1 ± 3.4%), pTw (14.4 ± 4.4 and 15.6 ± 6.4 vs. 16.9 ± 6.5 deg) and pUtwVel (p &lt; 0.05 for all comparisons). A GLS &lt; − 18% identified FDR with LV dysfunction (p = 0.016). Post-OGTT, GLS and the subendocardial LS decreased while pTw and pUtwVel increased in FDR and dysglycaemics (p &lt; 0.05) indicating prevalence of the motion of the subepicardial over a dysfunctioning subendocardial myocardial helix. Increased PBR was related with impaired deformation markers at baseline and 120 min of OGTT (p &lt; 0.05). Conclusion First-degree relatives and dysglycaemics have reduced glycocalyx thickness related with impaired LV longitudinal, twisting-untwisting function. Postprandial hyperglycemia when combined with insulin resistance causes LV longitudinal dysfunction leading to increased LV twisting. © 2017 Elsevier B.V

HDL cholesterol levels and endothelial glycocalyx integrity in treated hypertensive patients

Endothelial dysfunction indicates target organ damage in hypertensive patients. The integrity of endothelial glycocalyx (EG) plays a vital role in vascular permeability, inflammation and elasticity, and finally to cardiovascular disease. The authors aimed to investigate the role of increased HDL cholesterol (HDL-C) levels, which usually are considered protective against cardiovascular disease, in EG integrity in older hypertensive patients. The authors studied 120 treated hypertensive patients older than 50 years were divided regarding HDL-C tertiles in group HDLH (HDL-C ≥ 71 mg/dL, upper HDL-C tertile) and group HDLL (HDL-C &amp;lt; 71 mg/dL, two lower HDL-C tertiles). Increased perfusion boundary region (PBR) of the sublingual arterial microvessels (ranging from 5 to 9 µm) using Sideview Darkfield imaging (Microscan, Glycocheck) was measured as a non-invasive accurate index of reduced EG thickness. PBR 5-9 was significantly decreased in group HDLH (P = 0.04). In the whole population, HDL-C was inversely but moderately related to PBR 5-9 (r = −0.22, P = 0.01). In a multiple linear regression analysis model, using age, BMI, smoking habit, HDL-C, LDL-C, and office SBP, as independent variables, the authors found that BMI (β = 0.25, P = 0.006) independently predicted PBR 5-9 in the whole population. In older hypertensive patients, HDL-C ranging between 71 and 101 mg/dL might moderately protect EG and subsequently endothelial function. Future studies in several groups of low- or high-risk hypertensives are needed in order to evaluate the beneficial role of extremely elevated HDL-C regarding cardiovascular risk evaluation as well as endothelial glycocalyx as a novel index of target organ damage in essential hypertension. ©2018 Wiley Periodicals, Inc

Similarities in Coronary Function and Myocardial Deformation Between Psoriasis and Coronary Artery Disease: The Role of Oxidative Stress and Inflammation

Background: Psoriasis has been associated with increased risk for coronary artery disease (CAD). We investigated the presence of vascular and subclinical left ventricular (LV) dysfunction in patients with psoriasis compared with patients with CAD. Methods: We compared 59 patients with psoriasis without evidence of CAD (psoriasis area and severity index [PASI], 11.5 ± 8) with 59 patients with angiographically documented CAD and 40 controls. We measured (1) the carotid-femoral pulse wave velocity (PWVc) and central augmentation index (CAI), (2) coronary flow reserve (CFR) by Doppler echocardiography, (3) flow-mediated dilation (FMD) of the brachial artery and carotid intima media thickness (IMT), (4) LV global longitudinal strain (GLS) and GLS rate (GLSR) using speckle tracking echocardiography, and (5) malondialdehyde (MDA) and interleukin-6 (IL-6) levels. Results: Patients with psoriasis had higher PWVc, CAI, IMT, MDA, and IL-6 levels and lower FMD, CFR, GLS, and GLSR than did controls (. P&lt;0.05), but they had values of these markers that were similar to those of patients with CAD (. P &gt; 0.05) after adjustment for atherosclerotic risk factors: (PWVc [m/s], 10.4 ± 1.8 vs 8.6 ± 1.5 vs 10.3 ± 2, respectively; CFR, 2.4 ± 0.1 vs 3.4 ± 0.6 vs 2.6 ± 0.6, respectively; GLS [%],-16.2 ± 4 vs-21.9 ± 1.6 vs-16.6 ± 4.5, respectively; GLSR [L/sec],-0.85 ± 0.2 vs-1.2 ± 0.12 vs-0.9 ± 0.4, respectively; MDA [nM/L], 1.68 vs 1.76 vs 1.01, respectively; IL-6 [pg/mL], 2.26 vs 2.2 vs 1.7, respectively; P &lt; 0.05 for all comparisons). PASI was related to IMT (. r= 0.67; P &lt; 0.01). Decreased GLS was associated with increased MDA, IL-6, PWVc, CAI, and reduced CFR (. P &lt; 0.05). Conclusions: Psoriasis and CAD present similar vascular and LV myocardial dysfunction, possibly because of similar underlying inflammatory and oxidative stress processes. Vascular dysfunction in psoriasis is linked to abnormal LV myocardial deformation. © 2015 Canadian Cardiovascular Society

Insulin resistance and acute glucose changes determine arterial elastic properties and coronary flow reserve in dysglycaemic and first-degree relatives of diabetic patients

Background: Insulin resistance is linked to endothelial dysfunction. We investigated whether first-degree relatives of type-2 diabetes patients (FDR) present differences in vascular function at baseline and during postprandial hyperglycemia compared to dysglycaemic or normoglycaemic subjects. Methods: We studied 40 FDR with normal oral glucose test (OGTT), 40 subjects with abnormal OGTT (dysglycaemic) and 20 subjects with normal OGTT without parental history of diabetes (normoglycaemic) with similar clinical characteristics. Glucose, insulin, pulse wave velocity (PWV), central systolic blood pressure (cSBP) and augmentation index (AI) were measured at 0, 30, 60, 90 and 120min during OGTT. Coronary flow reserve (CFR) was assessed using Doppler echocardiography at 0 and 120min after OGTT. Insulin sensitivity was evaluated using Matsuda and insulin sensitivity index (ISI). Results: FDR and dysglycaemics had higher fasting insulin, reduced ISI, Matsuda index as well as reduced CFR (2.54±0.5 vs. 2.45±0.3 vs. 2.74±0.5), increased PWV, (8.9±1.1 vs. 10.3±2.4vs. 8.0±1.5m/sec), AI (23.8±13.6 vs. 26.5±14.4vs.17.7±14%) and cSBP than normoglycaemics (p&lt;0.05 for all comparisons). During OGTT, AI was similarly reduced in both normoglycaemic and FDR (p&lt;0.05) at peak insulin levels (60min) though FDR had 2-fold higher insulin than normoglycaemics. AI was increased in dysglycaemics after peak glucose levels, at 120min (p&lt;0.05). CFR was reduced by 10% and 15% at 120min in FDR and dysglycaemic respectively, while remained unchanged in normoglycaemics (p&lt;0.05). The percent reduction of CFR was related with the percent increase of glucose levels, ISI and Matsuda index(p&lt;0.05). Conclusion: First-degree relatives and dysglycaemic patients have impaired arterial and coronary microcirculatory function. Insulin resistance determines acute vascular responses during postprandial hyperglycemia. © 2015 Published by Elsevier Ireland Ltd

Differential effects of inhibition of interleukin 1 and 6 on myocardial, coronary and vascular function

Background: Anakinra, an interleukin-1 receptor antagonist and tocilizumab, an interleukin-6 receptor blocker, are used for the treatment of rheumatoid arthritis. We investigated the differential effects of anakinra and tocilizumab on myocardial and vascular function in an atherosclerosis model of patients with rheumatoid arthritis. Methods: 120 patients with rheumatoid arthritis were randomized to anakinra (n = 40), tocilizumab (n = 40) or prednisolone (n = 40) for 3 months. Primary outcome measure was the change of left ventricular longitudinal strain after 3 months of treatment. Additionally, we measured coronary flow reserve, flow-mediated dilatation of the brachial artery, carotid-femoral pulse wave velocity, malondialdehyde and protein carbonyls as oxidative stress markers and C-reactive protein blood levels at baseline and post-treatment. Results: At baseline, patients among the three treatment arms had similar age, sex, disease activity score and atherosclerotic risk factors. Compared with baseline, all patients had improved longitudinal strain (− 16% vs. − 17.8%), coronary flow reserve (2.56 vs. 2.9), malondialdehyde (2.0 vs. 1.5 µM/L), protein carbonyls (0.0132 vs. 0.0115 nmol/mg), and C-reactive protein post-treatment. In all patients, the percent decrease of malondialdehyde was correlated with percent increase of longitudinal strain (p &apos; 0.001). Compared with tocilizumab and prednisolone, anakinra treatment resulted in a greater improvement of longitudinal strain (18.7% vs. 9.7% vs. 6%) and coronary flow reserve (29% vs. 13% vs. 1%), while pulse wave velocity and brachial blood pressure were improved only after tocilizumab treatment (11 ± 3 vs. 10.3 ± 2 m/s p &apos; 0.05 for all comparisons). Conclusions: Anakinra is associated with an improvement in cardiac function and tocilizumab with improvement in vascular function. Clinical Trial Registration: URL: https://http://www.clinicaltrials.gov. Unique identifier: NCT03288584. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature