CONTEXT:Nonalcoholic fatty liver disease (NAFLD) with advanced liver fibrosis is associated with cardiovascular disease (CVD). OBJECTIVE:This work aimed to examine if markers of vascular injury mediate the link between liver fibrosis noninvasive tests (LFNITs) and CVD events, and to compare the incremental predictive value of LFNITs over established CVD risk scores. METHODS:Consecutively recruited individuals (n = 1692) with or without clinically overt coronary artery disease (CAD) from the Athens Cardiometabolic Cohort, were analyzed. Fibrosis-4 index (FIB-4), NAFLD Fibrosis score (NFS), and BARD score were evaluated for direct and indirect associations with indices of subclinical arterial injury including carotid maximal wall thickness (maxWT) and pulse wave velocity (PWV) and with a composite of major adverse cardiovascular events (MACE) that consisted of cardiac death, acute myocardial infarction, or coronary revascularization (39-month median follow-up). RESULTS:FIB-4 was the only LFNIT that was consistently associated with multiple markers of vascular injury, irrespective of CAD presence and after controlling for traditional risk factors, surrogates of insulin resistance, or obesity (adjusted P < .05 for all). FIB-4 was also independently associated with CAD presence (adjusted odds ratio [OR] 6.55; 3.48-12.3; P < .001). Increased FIB-4 greater than 2.67 was incrementally associated with an increased risk for MACE (OR [95% CI] 2.00 [1.12-3.55], ΔAUC [95% CI] 0.014 [0.002-0.026]). These associations were mediated by maxWT rather than PWV. Only FIB-4 (>3.25) was independently and incrementally associated with all-cause mortality (adjusted P < 0.05). CONCLUSION:In a cardiometabolically diverse population, the incremental associations of LFNITs with CVD outcomes were mediated by atherosclerotic burden rather than arterial stiffening. FIB-4 consistently demonstrated associations with all study end points. These findings provide mechanistic insights and support the clinical applicability of FIB-4 in CVD prevention.

OBJECTIVE:High-intensity resistance exercise may temporarily induce vascular dysfunction mediated by pro-oxidant and pro-inflammatory pathways. In the present study, we aimed to evaluate the possible protective effect of the antioxidant N-acetyl cysteine (NAC) on vascular function after a bout of high-intensity resistance exercise. METHODS:In this randomized, crossover, placebo-controlled study, ten healthy male volunteers (mean age 24.2 ± 2.1 years) who exercised regularly were randomly allocated to a daily oral administration of NAC or placebo during an 8-day recovery after an acute intense eccentric exercise protocol. Pulse wave velocity (PWV) and flow-mediated dilation (FMD) measurements were performed pre- and post-exercise in both study arms. RESULTS:Muscle exercise induced a significant decrease in FMD in the placebo arm (p = 0.017) during the first 48 h after exercise, recovering thereafter. In contrast, in the NAC arm, FMD did not decrease significantly. By linear mixed-model analysis, a higher increase in CD4 cells levels correlated with preserved FMD (p = 0.046) only in the placebo arm (p = 0.811 in the NAC arm). PWV did not present significant fluctuations before and after exercise in either arm (p > 0.05). CONCLUSION:A bout of eccentric exercise induced endothelial dysfunction, which was attenuated by NAC, indicating that oxidative stress may be implicated in vivo in this setting.

Circulating amyloid-beta 1–40 (Αb40) has pro-atherogenic properties and could serve as a biomarker in atherosclerotic cardiovascular disease (ASCVD). However, the association of Ab40 levels with morphological characteristics reflecting atherosclerotic plaque echolucency and composition is not available. Carotid atherosclerosis was assessed in consecutively recruited individuals without ASCVD (n = 342) by ultrasonography. The primary endpoint was grey scale median (GSM) of intima-media complex (IMC) and plaques, analysed using dedicated software. Vascular markers were assessed at two time-points (median follow-up 35.5 months). In n = 56 patients undergoing carotid endarterectomy, histological plaque features were analysed. Plasma Αb40 levels were measured at baseline. Ab40 was associated with lower IMC GSM and plaque GSM and higher plaque area at baseline after multivariable adjustment. Increased Ab40 levels were also longitudinally associated with decreasing or persistently low IMC and plaque GSM after multivariable adjustment (p < 0.05). In the histological analysis, Ab40 levels were associated with lower incidence of calcified plaques and plaques without high-risk features. Ab40 levels are associated with ultrasonographic and histological markers of carotid wall composition both in the non-stenotic arterial wall and in severely stenotic plaques. These findings support experimental evidence linking Ab40 with plaque vulnerability, possibly mediating its established association with major adverse cardiovascular events.

Hypertension is a chronic, multifactorial disease, leading to high cardiovascular morbidity and mortality globally. Despite the advantages of pharmaceutical treatments, natural products have gained scientific interest due to their emerging phytotherapeutic properties. Chios mastic is a natural Greek product, consisting of bioactive compounds which modify microRNAs’ (small, expression-regulating molecules) expression. In this study, we investigated the antihypertensive properties of Chios mastic through the assessment of miR-21 levels. Herein, plasma samples of 57 individuals with hypertension, recruited for the purposes of the HYPER-MASTIC study, were analyzed. This was a clinical trial with Chios mastic supplements in which the patients were divided into groups receiving high and low mastic doses and placebo supplements, respectively. miR-21 was significantly upregulated in patients compared to normotensive individuals. Mean changes in miR-21 levels were statistically significant, after adjusting for sex and age, between the placebo and low-dose group and between the low- and high-dose group. Post-intervention miR-21 levels were positively associated with night-time systolic blood pressure, pulse pressure, and central systolic mean arterial pressure and negatively associated with night-time pulse wave velocity in the low-dose group. Our findings suggest a potential implication of miR-21 in the association of Chios mastic with night-time blood pressure measurements.

Objective: Chios mastic is a natural nutritional supplement consisting of several bioactive compounds and it possesses antioxidant and anti-inflammatory activities. Preliminary recent evidence suggests an anti-hypertensive effect of mastic. HYPER-MASTIC is a double-blind, randomized and controlled clinical trial, with the aim of investigating the additional effect of a three-month supplementation with Chios mastic on arterial hypertension of Greek patients with well-managed cardiovascular risk factors. Design and method: Patients with well controlled hypertension are being consecutively recruited and randomly allocated into three groups of supplements: 1500mg of mastic, 2800 mg of mastic and placebo in this ongoing study. For the current analyses, the two mastic groups were merged. Blood pressure measurements, using both office and 24h blood pressure measurement, and blood tests were performed at baseline and at 3 months. Flow-mediated dilatation (FMD) at the level of the brachial artery was measured in all patients as a measure of endothelial function. Patients reported no recent history of acute myocardial infarction or stroke and no history of heart failure. Herein, the preliminary results of the study are presented. Results: At the time of analysis, twenty one patients [48% females, age: 62 (14)] were consecutively recruited and randomized, with available data at 3 months. Thirteen volunteers were allocated to mastic and eight to placebo. No difference was found regarding age, sex distribution, BMI levels, personal or family history of hyperlipidemia and hypertension, diabetes mellitus type 2 and coronary artery disease between the two groups. Patients in the mastic group reduced their night-time diastolic blood pressure compared to placebo [-5 (10) vs -2.5 (16.3) mmHg | p = 0.025, respectively]. No other differences from placebo were observed on the effect of mastic on BP parameters. FMD dropped with time in the placebo group, whereas in the mastic group it was preserved [-1.2 (2.7) vs -0.2 (0.8) | pinteraction = 0.010]. Conclusions: Chios mastic supplementation leads to improved night-time diastolic blood pressure and preserved endothelial function in patients with well-controlled hypertension, suggesting that it may incrementally exert anti-hypertensive and vasculoprotective properties over anti-hypertensive medication.

Background: Female sexual dysfunction (FSD) has been suggested to be correlated with the burden of cardiovascular risk factors. Aim: We aimed to evaluate the possible association between functional indices of vascular function and FSD scores in apparently healthy postmenopausal women. Methods This cross-sectional study included 116 postmenopausal women who underwent assessment of endothelial function with measurement of flow-mediated dilation (FMD) of the branchial artery and arterial stiffness estimation with measurement of the carotid-femoral pulse wave velocity (PWV). We used the Greene Climacteric Scale to evaluate vasomotor symptomatology, the Female Sexual Function Index (FSFI) to evaluate FSD and the Beck Depression Inventory to evaluate mood disorder. Low sexual function was defined as an FSFI score <26.55. Outcomes: These included FSFI and low sexual function scores as well as measures of PWV and FMD. Results: Sexual function scores were associated with measures of blood pressure (normal vs low sexual function; systolic blood pressure: 120.2 +/- 15.0 mm Hg vs 113.4 +/- 14.6 mm Hg; analysis of covariance P = .026; diastolic blood pressure: 75.9 +/- 10.5 mm Hg vs 70.3 +/- 9.9 mm Hg; analysis of covariance P = .012; both adjusted for age, body mass index, current smoking, and PWV). Systolic blood pressure, but not diastolic blood pressure, was associated with FSFI (B = 0.249, P = .041) and PWV (B = 0.392, P < .001). PWV measures were associated with FSFI (B = -0.291, P = .047) and pulse pressure (B = 0.355, P = .017). FMD measures were also associated with FSFI (B = 0.427, P = .033). All models were adjusted for age, body mass index, current smoking, insulin resistance, vasomotor symptomatology, and Beck Depression Inventory. Clinical implications: Our findings demonstrate that lower scores of sexual function are associated with deteriorated vascular function mainly manifested as arterial stiffening, further contributing to systolic blood pressure changes. Strengths and limitations: The strength of this study is the carefully selected healthy sample of postmenopausal women, with simultaneous assessment of climacteric symptomatology and mood disorders. The limitations include the small sample size, the cross-sectional design, and the recruitment of consecutive outpatients of a university menopause clinic. Conclusion: Longitudinal studies and interventions to improve FSD should further assess the clinical relevance of these findings.

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a novel class of hypolipidemic drugs, providing an additional therapeutic option over conventional hypolipidemic treatments. Given the constantly lowering recommended LDL-C goals, low goal achievement rate and low compliance with treatment, new hypolipidemic drug classes may substantially contribute to residual risk reduction for atherosclerotic cardiovascular disease (ASCVD). This review aims to summarize contemporary evidence on the clinical role of PCSK9i in ASCVD prevention. PubMed and MEDLINE databases were searched for keywords in studies on PCSK9i and ASCVD. Approved PCSK9i are the monoclonal antibodies (Mabs), evolocumab and alirocumab, targeting PCSK9, and inclisiran, a small interfering RNA inhibiting PSCK9 synthesis. Overall, PCSK9i effectively reduced LDL-C and other atherogenic lipoproteins, including apolipoprotein B and lipoprotein( a) primarily. PSCK9i Mabs improved imaging markers reflecting coronary atherosclerotic plaque vulnerability and reduced ASCVD events in high-risk patients after short-term treatment ( < 3 years follow-up). They are currently indicated as a third-line treatment for secondary prevention and primary prevention in patients with familial hypercholesterolemia at high risk of not achieving their LDL-C goals. Patients with higher baseline ASCVD risk receive greater benefits from PCSK9i. Recent evidence suggests that evolocumab was effective and safe after long-term treatment. Ongoing trials investigate new therapeutic indications for PCSK9i while their cost-effectiveness is still being considered. PCSK9i is a novel hypolipidemic drug class currently indicated for reducing residual risk in secondary ASCVD prevention and high-risk patients.

The causative associations between glycemia and early alterations in renal and vascular function remain unclear. To examine the interplay among glycemia, renal function, and markers of subclinical atherosclerosis in apparently healthy subjects. Nondiabetic (30–60 years old) individuals ( n = 205) without chronic kidney disease or cardiovascular disease were consecutively recruited from a cardiovascular prevention clinic. All subjects underwent arterial stiffness assessment by measuring the carotid-femoral pulse wave velocity (cfPWV). Glomerular filtration rate (GFR) was estimated by CKD-EPI equation. Study procedures were identical in the two visits (median follow-up 66 months). We employed structural equation modeling (SEM) analysis to investigate the directionality of associations. Baseline fasting plasma glucose (FPG) was independently and inversely associated with GFR ( p = 0.008). GFR was significantly associated with cfPWV ( p < 0.001) at baseline. By SEM analysis decreasing baseline GFR directly correlated with increasing cfPWV ( p = 0.003) whereas FPG correlated with cfPWV indirectly through GFR (mediation) ( P = 0.032). FPG did not mediate the effect of GFR on cfPWV ( P = 0.768). SEM analysis of longitudinal data revealed bidirectional correlations between changes in FPG and GFR ( P < 0.001). Alterations in GFR were directly related to changes in cfPWV ( p < 0.001) whereas FPG only indirectly correlated with cfPWV through GFR changes ( P = 0.002). In apparently healthy nondiabetic subjects, the association between baseline or longitudinal glycemia levels and arterial stiffening was indirect, consistently mediated by renal function status. These findings provide the first clinical evidence supporting the directionality between kidney function and glycemia in nondiabetic subjects leading to vascular dysfunction. In apparently healthy nondiabetic subjects, without cardiovascular disease or chronic kidney disease, the association between baseline or longitudinal glycemia levels and arterial stiffening was indirect, consistently mediated by renal function status.

(1) Background: A considerable number of systematic reviews, with substantial heterogeneity regarding their methods and included populations, on the impact of COVID-19 on infected pregnant women and their neonates, has emerged. The aim was to describe the obstetric-perinatal and neonatal outcome of infected pregnant women and their newborns during the COVID-19 pandemic; (2) Methods: Three bibliographical databases were searched (last search: 10 September 2020). Quality assessment was performed using the AMSTAR-2 tool. Primary outcomes included mode of delivery, preterm delivery/labor, premature rupture of membranes (PROM/pPROM) and abortions/miscarriages. Outcomes were mainly presented as ranges. A separate analysis, including only moderate and high-quality systematic reviews, was also conducted. The protocol was registered with PROSPERO (CRD42020214447); (3) Results: Thirty-nine reviews were analyzed. Reported rates, regarding both preterm and term gestations, varied between 52.3 and 95.8% for cesarean sections; 4.2–44.7% for vaginal deliveries; 14.3–63.8% specifically for preterm deliveries and 22.7–32.2% for preterm labor; 5.3–12.7% for PROM and 6.4–16.1% for pPROM. Maternal anxiety for potential fetal infection contributed to abortion decisions, while SARS-CoV-2-related miscarriages could not be excluded. Maternal ICU admission and mechanical ventilation rates were 3–28.5% and 1.4–12%, respectively. Maternal mortality rate was <2%, while stillbirth, neonatal ICU admission and mortality rates were <2.5%, 3.1–76.9% and <3%, respectively. Neonatal PCR positivity rates ranged between 1.6% and 10%. After accounting for quality of studies, ranges of our primary outcomes remained almost unchanged, while among our secondary outcomes, maternal ICU admission (3–10%) and mechanical ventilation rates (1.4–5.5%) were found to be relatively lower; (4) Conclusions: Increased rates of cesarean sections and preterm birth rates were found, with iatrogenic reasons potentially involved. In cases of symptomatic women with confirmed infection, high maternal and neonatal ICU admission rates should raise some concerns. The probability of vertical transmission cannot be excluded. Further original studies on women from all trimesters are warranted.