Myocardial inflammation in COVID-19 has been documented. Its pathogenesis is not fully elucidated, but the two main theories foresee a direct role of ACE2 receptor and a hyperimmune response, which ...may also lead to isolated presentation of COVID-19-mediated myocarditis. The frequency and prognostic impact of COVID-19-mediated myocarditis is unknown. This review aims to summarise current evidence on this topic. We performed a systematic review of MEDLINE and Cochrane Library (1/12/19–30/09/20). We also searched clinicaltrials.gov for unpublished studies testing therapies with potential implication for COVID-19-mediated cardiovascular complication. Eligible studies had laboratory confirmed COVID-19 and a clinical and/or histological diagnosis of myocarditis by ESC or WHO/ISFC criteria. Reports of 38 cases were included (26 male patients, 24 aged < 50 years). The first histologically proven case was a virus-negative lymphocytic myocarditis; however, biopsy evidence of myocarditis secondary to SARS-CoV-2 cardiotropism has been recently demonstrated. Histological data was found in 12 cases (8 EMB and 4 autopsies) and CMR was the main imaging modality to confirm a diagnosis of myocarditis (25 patients). There was a substantial variability in biventricular systolic function during the acute episode and in therapeutic regimen used. Five patients died in hospital. Cause-effect relationship between SARS-CoV-2 infection and myocarditis is difficult to demonstrate. However, current evidence demonstrates myocardial inflammation with or without direct cardiomyocyte damage, suggesting different pathophysiology mechanisms responsible of COVID-mediated myocarditis. Established clinical approaches should be pursued until future evidence support different actions. Large multicentre registries are advisable to elucidate further.
Background
Accurate and reproducible diagnostic techniques are essential to detect left-sided cardiac thrombi either in the left ventricle (LV) or in the left atrial appendage (LAA) and to guide the ...onset and duration of antithrombotic treatment while minimizing the risk for thromboembolic and hemorrhagic events.
Methods
We conducted a systematic review and meta-analysis aiming to compare the diagnostic performance of transthoracic echocardiography (TTE) vs. cardiac magnetic resonance (CMR) for the detection of LV thrombi, and transesophageal echocardiography (TEE) vs. computed tomography (CT) for the detection of LAA thrombi.
Results
Six studies were included in the first meta-analysis (TTE vs. CMR for LV thrombosis). Pooled sensitivity and specificity values were 62% 95% confidence interval (CI), 37–81% and 97% (95% CI, 94–99%). The shape of the hierarchical summary receiver operating characteristic (HSROC) curve and the area under the curve (AUC) of 0.96 suggested a high accuracy. Ten studies were included in the second meta-analysis (CT versus TEE for LAA thrombosis). The pooled values of sensitivity and specificity were 97% (95% CI, 77–100%) and 94% (95% CI, 87–98%). The pooled diagnostic odds ratio (DOR) was 500 (95% CI, 52–4810), and the pooled likelihood ratios (LR + and LR−) were 17% (95% CI, 7–40%) and 3% (95% CI, 0–28%). The shape of the HSROC curve and 0.99 AUC suggested a high accuracy of CT vs. TEE.
Conclusions
TTE is a fair alternative to DE-CMR for the identification of LV thrombi, while CT has a good accuracy compared to TEE for the detection of LAA thrombosis.
PROSPERO registration
CRD42020185842.
Abstract 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.
This study examined the effects of orange juice (OJ) supplemented with vitamin D3 (2000 IU) and probiotics (
Shirota and
GG, 10
cfu/mL) on cardiometabolic risk factors in overweight and obese adults ...following a Westernized-type diet. Fifty-three high-risk individuals were randomly assigned to one of two groups. Over 8 weeks, one group consumed a vitamin D3 and probiotic-enriched OJ and the other regular OJ (control). Diets remained unchanged and were documented through food diaries. Measures of metabolic and inflammatory markers and blood pressure were measured at the start and end of the study. Post-intervention, the enriched OJ group showed the following significant metabolic improvements (without changes in triglycerides, inflammation, or central blood pressure): reduced fasting insulin, peripheral blood pressure, body weight (-1.4 kg 95% CI: -2.4, -0.4), energy (-270 kcal 95% CI: -553.2, -13.7), macronutrient (dietary fat -238 kcal 95% CI: -11.9, -1.0; carbohydrates -155 kcal 95% CI: -282.4, -27.3; sugars -16.1 g 95% CI: -11.9, -1.0) intake, and better lipid profiles (total cholesterol -10.3 mg/dL 95% CI: -21.4, 0.9; LDL-C -7 mg/dL 95% CI: -13.5, -0.5). The enriched OJ led to weight loss, less energy/macronutrient consumption, improved lipid profiles, and increased insulin sensitivity after 8 weeks in those following a Westernized diet, thus indicating potential benefits for cardiometabolic risk. This study was a part of FunJuice-T2EDK-01922, which was funded by the EU Regional Development Fund and Greek National Resources.
Depression emerges as a risk factor for cardiovascular disease, and it is thought that successful antidepressant treatment may reduce such a risk. Therefore, antidepressant treatment embodies a ...potential preventive measure to reduce cardiovascular events in patients with depression. Accumulating evidence indicates that antidepressants have off-target effects on vascular dysfunction and in the early stages of atherosclerosis, which form the basis for cardiovascular disease (CVD) pathogenesis. In this context, we performed a thorough review of the evidence pertaining to the effects of different classes of antidepressant medications on hemodynamic and early atherosclerosis markers. The preclinical and clinical evidence reviewed revealed a preponderance of studies assessing selective serotonin reuptake inhibitors (SSRI), whereas other classes of antidepressants are less well-studied. Sufficient evidence supports a beneficial effect of SSRIs on vascular inflammation, endothelial function, arterial stiffening, and possibly delaying carotid atherosclerosis. In clinical studies, dissecting the hypothesized direct beneficial antidepressant effect of SSRIs on endothelial health from the global improvement upon remission of depression has proven to be difficult. However, preclinical studies armed with appropriate control groups provide evidence of molecular mechanisms linked to endothelial function that are indeed modulated by antidepressants. This suggests at least a partial direct action on vascular integrity. Further research on endothelial markers should focus on the effect of antidepressants on treatment responders versus non-responders in order to better ascertain the possible beneficial vascular effects of antidepressants, irrespective of the underlying course of depression.
Remnant cholesterol (RC) is an emerging factor contributing to residual risk for the development of atherosclerotic cardiovascular disease (ASCVD). We aimed to investigate the association of RC with ...ASCVD in high ASCVD risk patients.
RC was calculated in 906 participants (178 low/moderate-risk and 728 high-risk) consecutively recruited from a vascular registry. Subclinical carotid atherosclerosis was assessed by B-mode carotid ultrasonography. Maximal carotid wall thickness (maxWT) and carotid atherosclerotic burden (n ≥ 2 atherosclerotic plaques) were set as the vascular outcomes. An independent cohort of 87 consecutively recruited high-risk patients who were followed for their lipid profile for 3 months was also analyzed.
RC was increased in the high-risk group as compared to controls (26 ± 17 vs. 21 ± 11 mg/dl, respectively, p < 0.001). Increased RC levels were independently associated with increased maxWT and carotid atherosclerotic burden (p < 0.05), after adjustment for traditional cardiovascular risk factors (TRF) and ASCVD. RC levels were associated with the presence of flow-limiting ASCVD and coronary artery disease (CAD) (p < 0.05), after adjustment for TRFs. These associations remained significant in those not receiving hypolipidemic treatment and in treated individuals achieving LDL-C<100 mg/dl. In the prospective cohort, there was no significant interaction between change in RC levels and hypolipidemic status, as contrasted to LDL-C levels (p < 0.001).
In a high-risk population, RC was associated with subclinical and clinically overt ASCVD, particularly in patients with the most adverse lipid phenotype (untreated) or in treated patients with a low LDL-related risk profile. These findings support a residual pro-atherosclerotic role of RC in high-risk patients.
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Long non-coding RNAs (lncRNAs) have emerged as critical regulators in human disease including atherosclerosis. However, the mechanisms involved in the post-transcriptional regulation of the ...expression of disease-associated lncRNAs are not fully understood. Gene expression studies revealed that Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) lncRNA expression was increased by >2-fold in peripheral blood mononuclear cells (PBMCs) derived from patients with coronary artery disease (CAD) or in carotid artery atherosclerotic plaques. We observed a linear association between NEAT1 lncRNA expression and prevalence of CAD which was independent of age, sex, cardiovascular traditional risk factors and renal function. NEAT1 expression was induced by TNF-α, while silencing of NEAT1 profoundly attenuated the TNF-α-induced vascular endothelial cell pro-inflammatory response as defined by the expression of CXCL8, CCL2, VCAM1 and ICAM1. Overexpression of the RNA editing enzyme adenosine deaminase acting on RNA-1 (ADAR1), but not of its editing-deficient mutant, upregulated NEAT1 levels. Conversely, silencing of ADAR1 suppressed the basal levels and the TNF-α-induced increase of NEAT1. NEAT1 lncRNA expression was strongly associated with ADAR1 in CAD and peripheral arterial vascular disease. RNA editing mapping studies revealed the presence of several inosines in close proximity to AU-rich elements within the AluSx3+/AluJo‐ double-stranded RNA complex. Silencing of the stabilizing RNA-binding protein AUF1 reduced NEAT1 levels while silencing of ADAR1 profoundly affected the binding capacity of AUF1 to NEAT1. Together, our findings propose a mechanism by which ADAR1-catalyzed A-to-I RNA editing controls NEAT1 lncRNA stability in ASCVD.
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•Expression of NEAT1 lncRNA is increased in human coronary artery disease (CAD) and in carotid artery atherosclerotic plaques.•NEAT1 lncRNA controls endothelial cell innate immune response to TNF-α.•Alu RNA editing events on NEAT1 lncRNA are located within close proximity to AUF1 binding sites.•ADAR1 controls NEAT1 stability by enabling the recruitment of AUF1 to NEAT1 lncRNA.
Background
Accumulating evidence suggests that endothelial dysfunction is implicated in the pathogenesis and severity of coronavirus disease 2019 (COVID‐19). In this context, vascular impairment in ...COVID‐19 might be associated with clinical manifestations and could refine risk stratification in these patients.
Methods
This systematic review aims to synthesize current evidence on the frequency and the prognostic value of vascular dysfunction during acute and post‐recovery COVID‐19. After systematically searching the MEDLINE, clinicaltrials.gov and the Cochrane Library from 1 December 2019 until 05 March 2022, we identified 24 eligible studies with laboratory confirmed COVID‐19 and a thorough examination of vascular function. Flow‐mediated dilation (FMD) was assessed in 5 and 12 studies in acute and post‐recovery phase respectively; pulse wave velocity (PWV) was the marker of interest in three studies in the acute and four studies in the post‐recovery phase.
Results
All studies except for one in the acute and in the post‐recovery phase showed positive association between vascular dysfunction and COVID‐19 infection. Endothelial dysfunction in two studies and increased arterial stiffness in three studies were related to inferior survival in COVID‐19.
Discussion
Overall, a detrimental effect of COVID‐19 on markers of endothelial function and arterial stiffness that could persist even for months after the resolution of the infection and provide prognostic value was congruent across published studies. Further research is warranted to elucidate clinical implications of this association.
In this study we used Mendelian randomization (MR) to investigate the potential causal association of lipoprotein (a) Lp(a) levels with pulse wave velocity (PWV).
Genetic variants associated with ...Lp(a) were retrieved from the UK Biobank GWAS (N = 290,497). A non- overlapping GWAS based on a European cohort (N = 7,000) was used to obtain genetic associations with PWV (outcome) and utilized two different measures for the same trait, brachial-ankle (baPWV) and carotid-femoral (cfPWV) PWV. We applied a two-sample MR using the inverse variance weighting method (IVW) and a series of sensitivity analyses for 170 SNPs that were selected as instrumental variables (IVs).
Our analyses do not support a causal association between Lp(a) and PWV for neither measurement β
(baPWV) = -.0005, p = .8 and β
(cfPWV) = -.006, p = .16. The above findings were consistent across sensitivity analyses including weighted median, mode-based estimation, MR-Egger regression and MR-PRESSO.
We did not find evidence indicating that Lp(a) is causally associated with PWV, the gold standard marker of arterial stiffness.
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