Association between Abdominal CT Measurements of Body Composition before Deceased Donor Liver Transplant with Posttransplant Outcomes.

Background Pre-liver transplant (LT) sarcopenia is associated with poor survival. Methods exist for measuring body composition with use of CT scans; however, it is unclear which components best predict post-LT outcomes. Purpose To quantify the association between abdominal CT-based body composition measurements and post-LT mortality in a large North American cohort. Materials and Methods This was a retrospective cohort of adult first-time deceased-donor LT recipients from 2009 to 2018 who underwent pre-LT abdominal CT scans, including at the L3 vertebral level, at Johns Hopkins Hospital. Measurements included sarcopenia (skeletal muscle index [SMI] <50 in men and <39 in women), sarcopenic obesity, myosteatosis (skeletal muscle CT attenuation <41 mean HU for body mass index [BMI] <25 and <33 mean HU for BMI ≥25), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio. Covariates in the adjusted models were selected with use of least absolute shrinkage and selection operator regression with lambda chosen by means of 10-fold cross-validation. Cox proportional hazards models were used to quantify associations with post-LT mortality. Model discrimination was quantified using the Harrell C-statistic. Results A total of 454 recipients (median age, 57 years [IQR, 50-62 years]; 294 men) were evaluated. In the adjusted model, pre-LT sarcopenia was associated with a higher hazard ratio (HR) of post-LT mortality (HR, 1.6 [95% CI: 1.1, 2.4]; C-statistic, 0.64; P = .02). SMI was significantly negatively associated with survival after adjustment for covariates. There was no evidence that myosteatosis was associated with mortality (HR, 1.3 [95% CI: 0.86, 2.1]; C-statistic, 0.64; P = .21). There was no evidence that BMI (HR, 1.2 [95% CI: 0.95, 1.4]), VAT (HR, 1.0 [95% CI: 0.98, 1.1]), SAT (HR, 1.0 [95% CI: 0.97, 1.0]), and VAT/SAT ratio (HR, 1.1 [95% CI: 0.90, 1.4]) were associated with mortality (P = .15-.77). Conclusions Sarcopenia, as assessed on routine pre-liver transplant (LT) abdominal CT scans, was the only factor significantly associated with post-LT mortality. © RSNA, 2022 See also the editorial by Ruehm in this issue.

Postembolization Persistence of Pulmonary Arteriovenous Malformations: A Retrospective Comparison of Coils and Amplatzer and Micro Vascular Plugs Using Propensity Score Weighting.

BACKGROUND. Endovascular embolization of pulmonary arteriovenous malformations (PAVMs) was historically performed with embolic coils. The Amplatzer Vascular Plug device (AVP) was introduced for this purpose in 2007 and the Micro Vascular Plug device (MVP) in 2013. OBJECTIVE. The purpose of this study was to compare coils, AVPs, and MVPs in terms of risk of persistence after PAVM embolization by use of propensity score weighting to account for biases in device selection. METHODS. This retrospective study included 112 patients (78 women and girls, 34 men and boys; mean age, 45 years) who underwent embolization of 393 PAVMs with a single device type (coil, MVP, or AVP) from January 2003 to January 2020. Persistence was defined as less than 70% reduction in PAVM sac size or contrast enhancement of the sac on follow-up pulmonary CTA. A Cox proportional hazards regression model was used to assess associations between embolic device selection and PAVM persistence. Inverse propensity score weighting was used to account for differences in embolic device selection based on patient and PAVM characteristics. RESULTS. The median postembolization follow-up period was 1.5 years (IQR, 0.3-5.6 years). Persistence was found in 10% (41/393) of PAVMs, including 16% (34/207) of those treated with coils, 8% (7/88) of those treated with AVPs, and 0% (0/98) of those treated with MVPs. Variables associated with embolization device (p < .25) were age, sex, pediatric versus adult status, smoking status, PAVM complexity, PAVM laterality, number of feeding arteries, and feeding artery diameter. The Cox regression model incorporated inverse propensity score weighting to account for the differences between treatment groups in these variables and incorporated feeding artery diameter because of imbalance remaining after weighting. With coils as the referent, MVPs had a hazard ratio for persistence of less than 0.01 (95% CI, < 0.01 to < 0.01; p < .001), and AVPs had a hazard ratio of 0.37 (95% CI, 0.16-0.90; p = .03). CONCLUSION. The risk of persistence after PAVM embolization was significantly lower for MVPs alone than for coils or AVPs alone. In addition, the risk of persistence was lower for AVPs than for coils. CLINICAL IMPACT. The findings support the clinical use of MVPs as the preferred device for PAVM embolization over coils and polytetrafluoroethylene-covered plugs.

Genetic counseling and testing for hereditary hemorrhagic telangiectasia.

Genetic counseling is an important means of identifying a patient's genetic risk of hereditary hemorrhagic telangiectasia (HHT) and assisting patients in making informed decisions about their health. With an increase in understanding of the genetic mechanisms underlying HHT over the last decade, genetic counseling is increasingly being incorporated into the care of patients affected by HHT. In addition to refining the diagnosis of symptomatic patients, genetic testing can help to distinguish asymptomatic, at-risk patients from those who are unaffected by HHT. The purpose of this review article is to summarize the current knowledge regarding the role of genetic counseling and genetic testing in identifying and managing HHT in at-risk populations. This article also reviews the guidelines, outcomes, risks, and challenges of genetic counseling and testing for HHT in various patient populations, and provides an algorithm for the use of genetic counseling in symptomatic and asymptomatic patients.

An international, multicenter study of intravenous bevacizumab for bleeding in hereditary hemorrhagic telangiectasia: the InHIBIT-Bleed study.

Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is a rare multisystem vascular disorder causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Bevacizumab, an anti-vascular endothelial growth factor antibody, may be effective to treat bleeding in HHT. This international, multicenter, retrospective study evaluated the use of systemic bevacizumab to treat HHT-associated bleeding and anemia at 12 HHT treatment centers. Hemoglobin, epistaxis severity score, red cell units transfused, and intravenous iron infusions before and after treatment were evaluated using paired means testing and mixed-effects linear models. 238 HHT patients received bevacizumab for a median of 12 (range, 1-96) months. Compared with pretreatment, bevacizumab increased mean hemoglobin by 3.2 g/dL (95% CI, 2.9-3.5 g/dL) [mean hemoglobin 8.6 (8.5, 8.8) g/dL versus 11.8 (11.5, 12.1) g/dL, p<0.0001)] and decreased the epistaxis severity score (ESS) by 3.4 (3.2-3.7) points [mean ESS 6.8 (6.6-7.1) versus 3.4 (3.2-3.7), P<0.0001] during the first year of treatment. Compared with 6 months pretreatment, RBC units transfused decreased by 82% [median of 6.0 (IQR 0.0-13.0) units versus 0 (IQR, 0.0-1.0) units, P<0.0001] and iron infusions decreased by 70% [median of 6.0 (1.0-18.0) infusions versus 1.0 (0.0-4.0) infusions, P<0.0001] during the first 6 months of bevacizumab treatment. Outcomes were similar regardless of underlying pathogenic mutation. Following initial induction infusions, continuous/scheduled bevacizumab maintenance achieved higher hemoglobin and lower ESS than intermittent/as needed maintenance but with more drug exposure. Bevacizumab was well tolerated: hypertension, fatigue, and proteinuria were the most common adverse events. Venous thromboembolism occurred in 2% of patients. In conclusion, systemic bevacizumab was safe and effective to manage chronic bleeding and anemia in HHT.

Clinical and molecular characterization of patients with hereditary hemorrhagic telangiectasia: Experience from an HHT Center of Excellence.

In this retrospective single-center study, we evaluated whether/how pathogenic/likely pathogenic variants of three hereditary hemorrhagic telangiectasia (HHT)-associated genes (ENG, ACVRL1, and SMAD4) are associated with specific clinical presentations of HHT. We also characterized the morphological features of pulmonary arteriovenous malformations (AVMs) in patients with these variants. Pathogenic or likely pathogenic variants were detected in 64 patients. Using nonparametric statistical tests, we compared the type and prevalence of specific HHT diagnostic features associated with these three variants. Pathogenic variants in these genes resulted in gene-specific HHT clinical presentations. Epistaxis was present in 93%, 94%, and 100% of patients with ENG, ACVRL1, and SMAD4 variants, respectively (p = 0.79). Pulmonary AVMs were more common in patients with the ENG variant (p = 0.034) compared with other subgroups. ACVRL1 variant was associated with the lowest frequency of pulmonary AVMs (p = 0.034) but the highest frequency of hepatic AVMs (p = 0.015). Patients with the ACVRL1 variant did not have significantly more pancreatic AVMs compared with the other groups (p = 0.72). ENG, ACVRL1, and SMAD4 pathogenic or likely pathogenic variants are associated with gene-specific HHT presentations, which is consistent with results from other HHT centers.

Prevalence of and Factors Associated with Arterial Aneurysms in Patients with Hereditary Hemorrhagic Telangiectasia: 17-Year Retrospective Series of 418 Patients.

PURPOSE: To estimate the prevalence of and identify characteristics associated with the presence of aneurysms in a cohort of patients with hereditary hemorrhagic telangiectasia (HHT). MATERIALS AND METHODS: In the study institution's HHT database, 418 patients with a definite HHT diagnosis were identified based on the clinical Curaçao criteria and/or an HHT-associated genetic mutation. Regression modeling was used to evaluate the association between arterial aneurysms and older age, male sex, smoking, alcohol consumption, hypertension, hyperlipidemia, genetic mutations, the presence of arteriovenous malformations (AVMs) unrelated to the aneurysms, and HHT-related genetic mutations. RESULTS: Forty-three (10.3%) patients had at least 1 aneurysm. Sixteen (3.8%) patients had multiple aneurysms. Of the variables analyzed, older age (odds ratio [OR] = 1.02; 95% confidence interval [CI]: 1.0-1.1), the presence of anatomically and flow-unrelated AVMs (OR = 3.2; 95% CI: 1.3-8.0), and the presence of activin A receptor type II-like 1 (ACVRL1) mutation (OR = 4.0; 95% CI: 1.5-10) were associated with the presence of at least 1 aneurysm. CONCLUSIONS: In this cohort of patients with HHT, the prevalence of intracranial and visceral arterial aneurysms was estimated to be 10.3%. Older age, the presence of unrelated AVMs, and the presence of the ACVRL1 mutation were associated with the presence of arterial aneurysms. Further study is required to assess the clinical importance and risk of rupture of aneurysms in patients with HHT.

Interventional Radiology Obesity Therapeutics: Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel.

The Society of Interventional Radiology Foundation commissioned a Research Consensus Panel to establish a research agenda on "Obesity Therapeutics" in interventional radiology (IR). The meeting convened a multidisciplinary group of physicians and scientists with expertise in obesity therapeutics. The meeting was intended to review current evidence on obesity therapies, familiarize attendees with the regulatory evaluation process, and identify research deficiencies in IR bariatric interventions, with the goal of prioritizing future high-quality research that would move the field forward. The panelists agreed that a weight loss of >8%-10% from baseline at 6-12 months is a desirable therapeutic endpoint for future IR weight loss therapies. The final consensus on the highest priority research was to design a blinded randomized controlled trial of IR weight loss interventions versus sham control arms, with patients receiving behavioral therapy.

o-Vanillin Derived Schiff Bases and Their Organotin(IV) Compounds: Synthesis, Structural Characterisation, In-Silico Studies and Cytotoxicity.

Six new organotin(IV) compounds of Schiff bases derived from S-R-dithiocarbazate [R = benzyl (B), 2- or 4-methylbenzyl (2M and 4M, respectively)] condensed with 2-hydroxy-3-methoxybenzaldehyde (oVa) were synthesised and characterised by elemental analysis, various spectroscopic techniques including infrared, UV-vis, multinuclear (¹H, 13C, 119Sn) NMR and mass spectrometry, and single crystal X-ray diffraction. The organotin(IV) compounds were synthesised from the reaction of Ph2SnCl2 or Me2SnCl2 with the Schiff bases (S2MoVaH/S4MoVaH/SBoVaH) to form a total of six new organotin(IV) compounds that had a general formula of [R2Sn(L)] (where L = Schiff base; R = Ph or Me). The molecular geometries of Me2Sn(S2MoVa), Me2Sn(S4MoVa) and Me2Sn(SBoVa) were established by X-ray crystallography and verified using density functional theory calculations. Interestingly, each experimental structure contained two independent but chemically similar molecules in the crystallographic asymmetric unit. The coordination geometry for each molecule was defined by thiolate-sulphur, phenoxide-oxygen and imine-nitrogen atoms derived from a dinegative, tridentate dithiocarbazate ligand with the remaining positions occupied by the methyl-carbon atoms of the organo groups. In each case, the resulting five-coordinate C2NOS geometry was almost exactly intermediate between ideal trigonal-bipyramidal and square-pyramidal geometries. The cytotoxic activities of the Schiff bases and organotin(IV) compounds were investigated against EJ-28 and RT-112 (bladder), HT29 (colon), U87 and SJ-G2 (glioblastoma), MCF-7 (breast) A2780 (ovarian), H460 (lung), A431 (skin), DU145 (prostate), BE2-C (neuroblastoma) and MIA (pancreatic) cancer cell lines and one normal breast cell line (MCF-10A). Diphenyltin(IV) compounds exhibited greater potency than either the Schiff bases or the respective dimethyltin(IV) compounds. Mechanistic studies on the action of these compounds against bladder cancer cells revealed that they induced the production of reactive oxygen species (ROS). The bladder cancer cells were apoptotic after 24 h post-treatment with the diphenyltin(IV) compounds. The interactions of the organotin(IV) compounds with calf thymus DNA (CT-DNA) were experimentally explored using UV-vis absorption spectroscopy. This study revealed that the organotin(IV) compounds have strong DNA binding affinity, verified via molecular docking simulations, which suggests that these organotin(IV) compounds interact with DNA via groove-binding interactions.

Elevated serum uric acid is associated with vascular inflammation but not coronary artery calcification in the healthy octogenarians: the Brazilian study on healthy aging.

BACKGROUND: There is a limited data on the association between serum uric acid (SUA) and cardiovascular disease (CVD) among the very elderly population. AIMS: We evaluated the association of SUA, highly sensitive C-reactive protein (hs-CRP, a marker of vascular and systemic inflammation), and coronary artery calcification (CAC, a marker of subclinical CVD) in a cohort of Brazilian octogenarians (≥80 years) free from known clinical CVD. METHODS: 208 individuals were included and evaluated for an association between increasing tertiles of SUA, elevated hs-CRP (>3 mg/dL), the presence and burden of CAC (CAC > 0 and CAC > 400). RESULTS: The median hs-CRP was 1.9 (IQR = 1.0-3.4) mg/L and mean SUA was 5.3 (±1.4) mg/dL. The overall prevalence of elevated hs-CRP (>3 mg/dL) was 31 %. A significant increase in the prevalence of hs-CRP was noted across the higher SUA tertiles (p < 0.001) with 3.4 times the odds of having elevated hs-CRP in the highest SUA tertile (3.40; CI = 1.27-9.08). No association was noted with either the CAC presence and/or CAC burden (CAC > 0 or CAC > 400) across the increasing SUA tertiles. DISCUSSION: In the healthy octogenarians, higher SUA levels are associated with vascular inflammation (hs-CRP) but not with coronary atherosclerosis (CAC); markers for the subclinical CVD.

Association Between Gut Hormones and Weight Change After Bariatric Arterial Embolization: Results from the BEAT Obesity Trial.

PURPOSE: To evaluate associations of ghrelin, glucagon-like peptide 1 (GLP-1), and peptide YY 3-36 (PYY3-36) with weight change after bariatric arterial embolization (BAE). MATERIALS AND METHODS: Subgroup analysis of data collected during the BEAT Obesity Trial involving 7 participants with BMI > 40 who were embolized with 300- to 500-µm Embosphere Microspheres. Three participants were characterized as "responders" (top tertile of weight loss at each visit) and 4 as "non-responders" (bottom tertile of weight loss at each visit). Mean ± standard deviation participant age was 44 ± 11 years, and 6 of 7 participants were women. Participants were evaluated at baseline, 2 weeks, and 1, 3, 6, and 12 months after BAE. After fasting, participants consumed a mixed meal test at each visit; blood samples were collected at 0, 15, 30, 60, 120, 180, and 240 min. Study outcome measures were changes in weight from baseline and plasma serum hormone levels. RESULTS: Percentage change in ghrelin decreased significantly in non-responders at 60 and 120 min at 1 and 12 months (estimated difference between 60 vs. 0 min at 1 month: 69% [95% CI - 126%, - 13%]; estimated difference between 120 vs. 0 min at 12 months: - 131% (95% CI - 239%, - 23%]). Responders had significantly lower ghrelin and greater weight loss than non-responders at 6 and 12 months. GLP-1 and PYY3-36 levels did not differ between groups. CONCLUSION: Participants with consistent weight loss throughout follow-up had lower ghrelin than non-responders, supporting decreased ghrelin as a mechanism underlying BAE-induced weight loss. LEVEL OF EVIDENCE I: High-quality randomized trial or prospective study; testing of previously developed diagnostic criteria on consecutive patients; sensible costs and alternatives; values obtained from many studies with multiway sensitivity analyses; systematic review of Level I RCTs and Level I studies.

Cardiac and Hemodynamic Manifestations of Hereditary Hemorrhagic Telangiectasia.

The autosomal dominant trait hereditary hemorrhagic telangiectasia (HHT) causes multiorgan dysplastic lesions of the vasculature that can activate multiple physiological cascades leading to a broad array of cardiovascular diseases. Up to 78% of patients with HHT develop hepatic arteriovenous malformations (AVMs), which cause a hyperdynamic circulatory state secondary to hepatic/portal shunting. This condition can eventually progress to high-output cardiac failure (HOCF) with continued peripheral tissue hypoxemia. Treatment for HOCF is often limited to supportive measures (diuretics and treatment of anemia); however, recent studies using systemic bevacizumab have shown promise by substantially reducing the cardiac index. In the context of liver AVMs and high cardiac output, the pulmonary vasculature can also experience high flow. Without adequate dilation of pulmonary vessels, post-capillary pulmonary hypertension can develop. Another form of pulmonary hypertension observed in HHT, pulmonary arterial hypertension, is caused by HHT-related mutations in ENG and ACVRL1 causing congestive arteriopathy. Post-capillary pathogenesis is addressed by reducing the high-output state, whereas the pre-capillary state is treated with supportive mechanisms (diuretics, oxygen) and agents targeting pulmonary vasoreactivity: endothelin-1 receptor antagonists and phosphodiesterase-5 inhibitors. If either form of pulmonary hypertension is left untreated or proves refractory and progresses, the common hemodynamic complication is right heart failure. Targeted right heart therapies involve similar strategies to those of pulmonary arterial hypertension, with several experimental approaches under study. In this review, we describe in detail the mechanisms of pathogenesis, diagnosis, and treatment of the hemodynamic complications and associated cardiovascular diseases that may arise in patients with HHT.

Coronary Calcium to Rule Out Obstructive Coronary Artery Disease in Patients With Acute Chest Pain.

OBJECTIVES: This study aimed to evaluate the ability of coronary artery calcium (CAC) as an initial diagnostic tool to rule out obstructive coronary artery disease (CAD) in a very large registry of patients presenting to the emergency department (ED) with acute chest pain (CP) who were at low to intermediate risk for acute coronary syndrome (ACS). BACKGROUND: It is not yet well established whether CAC can be used to rule out obstructive CAD in the ED setting. METHODS: We included patients from the Baptist Health South Florida Chest Pain Registry presenting to the ED with CP at low to intermediate risk for ACS (Thrombolysis In Myocardial Infarction risk score ≤2, normal/nondiagnostic electrocardiography, and troponin levels) who underwent CAC and coronary computed tomography angiography (CCTA) procedures for evaluation of ACS. To assess the diagnostic accuracy of CAC testing to diagnose obstructive CAD and identify the need for coronary revascularization during hospitalization, we estimated sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV). RESULTS: Our study included 5,192 patients (mean age: 53.5 ± 10.8 years; 46% male; 62% Hispanic). Overall, 2,902 patients (56%) had CAC = 0, of which 135 (4.6%) had CAD (114 [3.9%] nonobstructive and 21 [0.7%] obstructive). Among those with CAC >0, 23% had obstructive CAD. Sensitivity, specificity, PPV, and NPV of CAC testing to diagnose obstructive CAD were 96.2%, 62.4%, 22.4%, and 99.3%, respectively. The NPV for identifying those who needed revascularization was 99.6%. Among patients with CAC = 0, 11 patients (0.4%) underwent revascularization, and the number needed to test with CCTA to detect 1 patient who required revascularization was 264. CONCLUSIONS: In a large population presenting to ED with CP at low to intermediate risk, CAC = 0 was common. CAC = 0 ruled out obstructive CAD and revascularization in more than 99% of the patients, and <5% with CAC = 0 had any CAD. Integrating CAC testing very early in CP evaluation may be effective in appropriate triage of patients by identifying individuals who can safely defer additional testing and more invasive procedures.

Enhancing soluble phosphate concentration in sludge liquor by pressurised anaerobic digestion.

Recovery of phosphate from wastewater is challenging, with one of the best opportunities being recovery from sludge anaerobic digestion liquor, as struvite. However, this is limited by the proportion of total phosphorous which is soluble, due to in-digester metal ion precipitation. High-pressure anaerobic digestion may enable enhanced phosphate solubility (and hence recovery potential), without the use of added acid, due to an increased liquid phase CO2 concentration. This was tested at 2, 4, and 6 bar absolute (bara) vs a 1 bara control reactor, fed with activated sludge. Increased pressure significantly (p = 0.0008), increased the fraction of phosphate that was soluble, ranging from 52% at 1 bara, to 75% at 6 bara. Model based analysis indicated that the main reason for increased solubility was pH depression (down to 6.4 at 6 bara), rather than changes in ion pairing (with carbonates) or increases in ionic activity. However, biological performance was adversely impacted, with a substantial loss in VS and COD destruction (on the order of 5%-10% absolute). No organic acid accumulation was observed. Bacterial and archaeal communities were significantly impacted (p∼0.0003-0.0005), with a shift to specific organisms, including Bacteroidales Rikenellaceae within the bacteria, and a Deep Sea Euryarchaeotal Group at 2 bara, and Methanocellaceae within the archaea at 4 and 6 bara. The work indicates that high-pressure operation is a technically viable option to improve phosphate recovery, and produce a high-methane biogas product, but that the loss of overall conversion needs to be further addressed, possibly through two-stage digestion.

Influence of low pH on continuous anaerobic digestion of waste activated sludge.

The influence of low pH on single stage continuous anaerobic digestion was evaluated, with the goal of increasing soluble phosphorus (P) concentration to mitigate in-reactor P precipitation. This was performed at pH 5.0, 5.5, 6.0, 6.5 and 7.0 using 1 L stirred-tank mesophilic reactors fed with sewage waste activated sludge. Low pH (5.5) caused a significant (p < 0.01) increase in soluble P concentration up to 79% of the total P, while methane yield was reduced by 50%. Total volatile fatty acids and soluble chemical oxygen demand concentrations increased from 40 to 504 mg L-1 and 600 to 2017 mg L-1 respectively, as the pH was reduced from 7.0 to 5.5. Higher concentrations of propionic acid (370-430 mg L-1) were found at low pH (5.5). The reduction in methane yield was associated with a shift in microbial community and decreased destruction of particulate organics. Acidogens dominated at low pH (< 6.0), while methanogens decreased by 88% at pH 5.5 compared to neutral pH. Apart from the loss in methanogenic and hydrolytic capacity, chemical needs for acid dosing to maintain low pH conditions, and other negative impacts of chemical dosing were identified as key limitations.

Association Between Coronary Artery Disease and MicroRNA: Literature Review and Clinical Perspective.

BACKGROUND: Until recently, circulating micro-RNAs (miRNAs) have attracted major interest as novel biomarkers for the early diagnosis of coronary artery disease (CAD). This review article summarizes the available evidence on the correlation of micro-RNAs with both the clinical and subclinical coronary artery disease and highlights the necessity for exploring miRNAs as a potential diagnostic and prognostic biomarker of early CAD in an adult population. METHODS: A systematic literature analysis and retrieval online systems Public/Publisher MEDLINE/ Excerpta Medica Database /Medical Literature Analysis and Retrieval System Online,(PUBMED/EMBASE/MEDLINE) search were conducted for relevant information. Search was limited to the articles published in English language and conducted on humans, January 2000 onwards. We excluded studies of heart surgery, coronary artery bypass grafting (CABG), angioplasty and heart transplant. Eighteen studies met the inclusion criteria. RESULTS: Seven out of 18 studies were multivariate, i.e. adjusted for age, gender, body mass index (BMI), smoking, hypertension, diabetes, and blood lipid profiles, while the remaining twelve studies were univariate analysis. Different sources of miRNAs were used, i.e. plasma/serum, microparticles, whole blood, platelets, blood mononuclear intimal and endothelial progenitor cells were investigated. Fourteen out of 18 studies showed up-regulation of different miRNA in CAD patients and in vulnerable plaque disease. Four out of 18 studies showed both the up-regulation and down-regulation of miRNA in the population, while only three studies showed down-regulation of miRNA. Various sources and types of miRNA were used in each study. CONCLUSION: This review gives an extensive overview of up-regulation and down-regulation of miRNA in CAD and non-CAD patients. The pattern of miRNA regulation with respect to CAD/non-CAD study subjects varies across individual studies and different parameters, which could be the possible reason for this aberrancy. We suggest further trials be conducted in future for highlighting the role of miRNA in CAD, which may improve both the diagnostic and therapeutic approaches to stratifying CAD burden in the general population.

Effect of Thyroxin Treatment on Carotid Intima-Media Thickness (CIMT) Reduction in Patients with Subclinical Hypothyroidism (SCH): a Meta-Analysis of Clinical Trials.

AIM: Research shows that subclinical hypothyroidism (SCH) is related to an increased carotid intima-media thickness (CIMT), a surrogate marker of subclinical cardiovascular disease (CVD). It is controversial whether or not SCH should be treated to reduce CVD morbidity and mortality. This meta-analysis aimed to determine whether SCH is associated with an increase in CIMT as compared to Euthyroidism (EU) and whether thyroxin (T4) treatment in SCH can reverse the change in CIMT. METHODS: Two independent reviewers conducted an extensive database research up to December 2016. A total of 12 clinical trials discussed the effect of Thyroxin on CIMT values at pre- and post-treatment in subjects with SCH. RESULTS: CIMT was significantly higher among SCH (n=280) as compared to EU controls (n=263) at baseline; the pooled weighted mean difference (WMD) of CIMT was 0.44 mm [95% confidence interval (CI) 0.14, 0.74], p=0.004; I2=65%. After treatment with thyroxin in subjects with SCH (n=314), there was a statistically significant decrease in CIMT from pre- to post-treatment; the pooled WMD of CIMT decrease was [WMD －0.32; 95% CI (－0.47, －0.16), p=＜0.0001; I2=2%], and it was no longer different from EU controls [WMD 0.13 mm; 95% CI (－0.04, 0.30); p=0.14; I2=27%]. The total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) were higher in SCH as compared to EU controls and decreased significantly after treatment with thyroxin. CONCLUSION: This meta-analysis shows that thyroxin therapy in subjects with SCH significantly decreases CIMT and improves lipid profile, modifiable CVD risk factors. Thyroid hormone replacement in subjects with SCH may play a role in slowing down or preventing the progression of atherosclerosis.

Association of Subjective and Objective Sleep Duration as well as Sleep Quality with Non-Invasive Markers of Sub-Clinical Cardiovascular Disease (CVD): A Systematic Review.

AIM: Abnormal daily sleep duration and quality have been linked to hypertension, diabetes, stroke, and overall cardiovascular disease (CVD) morbidity& mortality. However, the relationship between daily sleep duration and quality with subclinical measures of CVD remains less well studied. This systematic review evaluated how daily sleep duration and quality affect burden of subclinical CVD in subjects free of symptomatic CVD. METHODS: Literature search was done via MEDLINE, EMBASE, Web of Science until June 2016 and 32 studies met the inclusion criteria. Sleep duration and quality were measured either via subjective methods, as self-reported questionnaires or Pittsburg Sleep Quality Index (PSQI) or via objective methods, as actigraphy or polysomnography or by both. Among subclinical CVD measures, coronary artery calcium (CAC) was measured by electron beam computed tomography, Carotid intima-media thickness (CIMT) measured by high-resolution B-mode ultrasound on carotid arteries, endothelial/microvascular function measured by flow mediated dilation (FMD) or peripheral arterial tone (PAT) or iontophoresis or nailfold capillaroscopy, and arterial stiffness measured by pulse wave velocity (PWV) or ankle brachial index (ABI). RESULTS: Subjective short sleep duration was associated with CAC and CIMT, but variably associated with endothelial dysfunction (ED) and arterial stiffness; however, subjective long sleep duration was associated with CAC, CIMT and arterial stiffness, but variably associated with ED. Objective short sleep duration was positively associated with CIMT and variably with CAC but not associated with ED. Objective long sleep duration was variably associated with CAC and CIMT but not associated with ED. Poor subjective sleep quality was significantly associated with ED and arterial stiffness but variably associated with CAC and CIMT. Poor objective sleep quality was significantly associated with CIMT, and ED but variably associated with CAC. CONCLUSIONS: Overall, our review provided mixed results, which is generally in line with published literature, with most of the studies showing a significant relationship with subclinical CVD, but only some studies failed to demonstrate such an association. Although such mechanistic relationship needs further evaluation in order to determine appropriate screening strategies in vulnerable populations, this review strongly suggested the existence of a relationship between abnormal sleep duration and quality with increased subclinical CVD burden.