Hepatitis C virus clearance by direct-acting antivirals agents improves endothelial dysfunction and subclinical atherosclerosis: HEPCAR study

INTRODUCTION: Hepatitis C virus (HCV) infection has been related to increased cardiovascular (CV) risk. The aim of this study was to analyze the impact of sustained virological response (SVR) on endothelial dysfunction and subclinical atherosclerosis in patients with hepatitis C virus treated with direct-acting antiviral agents. METHODS: A total of 114 patients were prospectively recruited and underwent CV risk assessment including (i) endothelial dysfunction determined through laser Doppler flowmetry and (ii) subclinical atherosclerosis, elucidated by the ankle-brachial index (ABI). Atherogenic lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides); markers of oxidative stress (oxidized low-density lipoprotein antibodies [OLAbs]), soluble markers of adhesion (vascular cell adhesion molecule [VCAM], e-selectin, and soluble markers of angiogenesis; and vascular endothelial growth factor, endothelial [EMPs] and platelet [PMPs] apoptotic microparticles, and cell-free DNA [cfDNA]) were measured. All determinations were performed at baseline, 12 weeks (SVR time), and 1 year after treatment. RESULTS: In patients with endothelial dysfunction, area of hyperemia improved after virus clearance (P 5 0.013) and was related to significant decrease in VCAM, e-selectin (P < 0.001), and cfDNA (P 5 0.017) and to increased OLAb levels (P 5 0.001). In patients with subclinical atherosclerosis at baseline, a significantly improved ABI was seen after HCV clearance (P < 0.001). Levels of both EMPs and PMPs also decreased after SVR and at follow-up (P 5 0.006 and P 5 0.002, respectively). DISCUSSION: HCV clearance improved not only liver function but also endothelial dysfunction and subclinical atherosclerosis promoted by decrease in levels of VCAM, e-selectin, cfDNA, and PMPs and EMPs.Instituto de Salud Carlos III Project GLD17/00203Spanish Government (Juan de la Cierva fellowship) FJC1-2014-2167

Obstructive Sleep Apnoea Syndrome, Endothelial Function and Markers of Endothelialization. Changes after CPAP

Study objectives This study tries to assess the endothelial function in vivo using flow-mediated dilatation (FMD) and several biomarkers of endothelium formation/restoration and damage in patients with obstructive sleep apnoea (OSA) syndrome at baseline and after three months with CPAP therapy. Design Observational study, before and after CPAP therapy. Setting and Patients We studied 30 patients with apnoea/hypopnoea index (AHI) >15/h that were compared with themselves after three months of CPAP therapy. FMD was assessed non-invasively in vivo using the Laser-Doppler flowmetry. Circulating cell-free DNA (cf-DNA) and microparticles (MPs) were measured as markers of endothelial damage and the vascular endothelial growth factor (VEGF) was determined as a marker of endothelial restoration process. Measurements and results After three month with CPAP, FMD significantly increased (1072.26 ± 483.21 vs. 1604.38 ± 915.69 PU, p< 0.005) cf-DNA and MPs significantly decreased (187.93 ± 115.81vs. 121.28 ± 78.98 pg/ml, p<0.01, and 69.60 ± 62.60 vs. 39.82 ± 22.14 U/μL, p<0.05, respectively) and VEGF levels increased (585.02 ± 246.06 vs. 641.11 ± 212.69 pg/ml, p<0.05). These changes were higher in patients with more severe disease. There was a relationship between markers of damage (r = -0.53, p<0.005) but not between markers of damage and restoration, thus suggesting that both types of markers should be measured together. Conclusions CPAP therapy improves FMD. This improvement may be related to an increase of endothelial restoration process and a decrease of endothelial damage

Relationship between the endothelial dysfunction and the expression of the β1-subunit of BK channels in a non-hypertensive sleep apnea group

Study objectives Vascular damage must be diagnosed early in patients with hypertension. In this regard, endothelial dysfunction (ED) is an early sign of vascular disease and a predictor of cardiovascular diseases. In obstructive sleep apnea (OSA), intermittent hypoxia triggers ED, but mechanisms are not clear. In this context, it has been described that BK channels regulates arterial tone and that chronic and intermittent hypoxia downregulates the expression of the BK channel β1-subunit facilitating vasoconstriction. Thus, we investigated the relationship among hypoxemia, ED, and mRNA expression of the β1-subunit in patients with severe OSA. We aimed to assess (1) ED in non-hypertensive patients with OSA using laser-Doppler flowmetry, (2) BK β1-subunit mRNA expression, and (3) the impact of continuous positive airway pressure (CPAP) treatment on ED and β1-subunit regulation. Methods OSA patients underwent 24-hour blood pressure monitoring to exclude hypertension. Laser-Doppler flowmetry was performed to assess ED, and β1-subunit mRNA expression was evaluated using a blood test of peripheral blood leukocytes at baseline and after 3 months of CPAP treatment. Results In normotensive patients with OSA, endothelial function correlated with the severity of OSA. CPAP improved endothelial function in normotensive OSA patients and the speed of the arterial response was significantly correlated with β1-subunit mRNA expression. β1-subunit mRNA expression at baseline correlated inversely with its change after CPAP. Conclusions Sleep apnea is related to ED in normotensive patients with OSA. CPAP therapy improves endothelial function and regulates β1-subunit mRNA expression

Maternal Body-Mass Index and Cord Blood Circulating Endothelial Colony-Forming Cells

Objective Endothelial colony-forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that are particularly abundant in umbilical cord blood. We sought to determine whether ECFC abundance in cord blood is associated with maternal body-mass index (BMI) in nonpathologic pregnancies. Study design We measured the level of ECFCs in the cord blood of neonates (n = 27) born from non-obese healthy mothers with nonpathologic pregnancies and examined whether ECFC abundance correlated with maternal BMI. We also examined the effect of maternal BMI on ECFC phenotype and function using angiogenic and vasculogenic assays. Results We observed variation in ECFC abundance among subjects and found a positive correlation between prepregnancy maternal BMI and ECFC content (r = 0.51, P = .007), which was independent of other obstetric factors. Despite this variation, ECFC phenotype and functionality were deemed normal and highly similar between subjects with maternal BMI <25 kg/m2 and BMI between 25-30 kg/m2, including the ability to form vascular networks in vivo. Conclusions This study underlines the need to consider maternal BMI as a potential confounding factor for cord blood levels of ECFCs in future comparative studies between healthy and pathologic pregnancies.National Institutes of Health (R00EB009096)Consejería de Salud de la Junta de Andalucía, Sistema Andaluz de Salud (SAS111241)Instituto de Salud Carlos III FIS (PI10/02473

PostCOVID effect on endothelial function in hypertensive patients: A new research opportunity

SARS-CoV-2 is causing devastation both in human lives and economic resources. When the world seems to start overcoming the pandemics scourge, the threat of long-term complications of COVID-19 is rising. Reports show that some of these long-term effects may contribute to the main cause of morbimortality worldwide: the vascular diseases. Given the evidence of damage in the endothelial cells due to SARS-CoV-2 and that endothelial dysfunction precedes the development of arteriosclerosis, the authors propose to measure endothelial function around 6–12 months after acute disease in hypertensive patients, especially if they have other cardiovascular risk factors or overt vascular disease. The methods the authors propose are cost-effective and can be made available to any hypertension unit. These methods could be the “in vivo” assessment of endothelial function by flow mediated vasodilatation after ischemia by Laser-Doppler flowmetry and the measurement of plasma free circulating DNA and microparticles of endothelial origin.Consejería de Salud , Junta de Andalucí

Pancreas fat content, insulin homeostasis and circulating endothelial microparticles in male essential hypertensive patients

Thepancreasfatcontenthasbeenpoorlyinvestigatedinessentialhypertension.Theauthorsaimtorelatepancreasandliverfatcontentwithparametersmeasuringinsulinresistance, beta-cell function and also with markers of endothelial dysfunction andplateletorendothelialcelldestruction.Theauthorsstudiedagroupof40malehyper-tensivepatientswithwell-controlledbloodpressure,maintainingastableweight,andhavingnotchangedtheirmedicationduringthelastyear.Pancreasfatcontentwascor-relatedwithHOMA-IR(r=.616,p<.001),HOMA-S(r=−.439,p<.005),betacellfunctionparameter(r=.457,p<.005),andQUICKI(r=.412,p<.01),whereasliverfatwasnotpatientsinthehighestquartileofpancreasfatcontenthadmorecirculatingendothelialmicroparticlesthanpatientsintheotherquartiles(median129[94.3–200]vs.60.9[49.4–88.8],p=.002).However,patientsinthehighestquartileofthepancreasfat content distribution did not differ from the lowest in hyperemic response afterischemianorcirculatingplateletmicroparticlescount.Liverfatcontentwasnotrelatedto any of the parameters studied. In a multivariate stepwise binary logistic regres-sionanalysis(WaldMethod)circulatingendothelialmicroparticlesremainsignificantlyassociatedwithpancreasfatcontentafteradjustingforconfoundingfactors,suchastobacco,diabetesmellitus,hypercholesterolemia,ormetabolicsyndrome.Ourresultsreflectthatinessentialhypertension,pancreasfatcontentissuperiortoliverfattostudybeta-cellfunctionalityandinsulinresistance.Moreover,theauthorsdescribedforthefirsttimethatpancreasfatcontentisrelatedtoendothelialcelldestruction.Furtherstudiesareneededtoconfirmthispoint.Instituto de Salud Carlos III PI13/0191

Role of Circulating Cell-free DNA Levels in Patients With Severe Preeclampsia and HELLP Syndrome

BACKGROUND Increased plasma levels of circulating cell-free DNA (c-f DNA) have been recently described in diseases related to ischemia and/or hypoxia. Preeclampsia (PCL) is a hypertensive disorder of pregnancy, of unknown origin, where a defective placentation resulting in placental ischemia plays an important role. HELLP syndrome (haemolysis, elevated liver enzymes, and low platelet count) is the most serious form of PCL. The origin of the disease is unknown, and there are no markers to help us to make an early diagnosis of disease or to predict patients who are at risk of suffering serious complications. METHODS We measured circulating c-f DNA levels in a group of control pregnant women (n = 20), patients with mild PCL (n = 9), patients with severe PCL (n = 24), and patients with HELLP syndrome (n = 8). RESULTS Values of circulating c-f DNA were 333.59±64.3ng/ml in control subjects; 635.11±111.7ng/ml in patients with mild PCL; 1,264.63±127.1ng/ml in patients with severe PCL, and 1,595.95±269.8ng/ml in patients with HELPP syndrome. (P 950ng/ml had a sensitivity and specificity for detecting severe PCL and/or HELLLP syndrome of 0.71 and 0.93, respectively. CONCLUSIONS As far as we know, this is the first report of increased c-f DNA levels in HELLP syndrome. In this preliminary report, we have observed a gradual and strong relation between c-f DNA levels and range of severity of PCL, with it the highest in patients with HELLP syndrome. Further studies are needed for evaluating the utility of this technique in hypertensive disorders of pregnancy and, particularly, in HELLP syndrome.Instituto de Salud Carlos III PI10/02473Consejería de Salud de la Junta de Andalucía, Sistema Andaluz de Salud SAS11124

Olive oil polyphenols decrease blood pressure and improve endothelial function in young women with mild hypertension

Background: Olive oil polyphenols have been associated with several cardiovascular health benefits. This study aims to examine the influence of a polyphenol-rich olive oil on blood pressure (BP) and endothelial function in 24 young women with high-normal BP or stage 1 essential hypertension. Methods: We conducted a double-blind, randomized, crossover dietary-intervention study. After a run-in period of 4 months (baseline values), two diets were used, one with polyphenol-rich olive oil (∼30 mg/day), the other with polyphenol-free olive oil. Each dietary period lasted 2 months with a 4-week washout between diets. Systolic and diastolic BP, serum or plasma biomarkers of endothelial function, oxidative stress, and inflammation, and ischemia-induced hyperemia in the forearm were measured. Results: When compared to baseline values, only the polyphenol-rich olive oil diet led to a significant (P < 0.01) decrease of 7.91 mm Hg in systolic and 6.65 mm Hg of diastolic BP. A similar finding was found for serum asymmetric dimethylarginine (ADMA) (-0.09 ± 0.01 µmol/l, P < 0.01), oxidized low-density lipoprotein (ox-LDL) (-28.2 ± 28.5 µg/l, P < 0.01), and plasma C-reactive protein (CRP) (-1.9 ± 1.3 mg/l, P < 0.001). The polyphenol-rich olive oil diet also elicited an increase in plasma nitrites/nitrates (+4.7 ± 6.6 µmol/l, P < 0.001) and hyperemic area after ischemia (+345 ± 386 perfusion units (PU)/sec, P < 0.001). Conclusions: We concluded that the consumption of a diet containing polyphenol-rich olive oil can decrease BP and improve endothelial function in young women with high-normal BP or stage 1 essential hypertension.Instituto de Salud Carlos III (RD06/0014/0035