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Showing 401–420 of 2058 publications.
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Stewart, S.; Chan, Yih Kai; Playford, David A.; Strange, G. A.Background Although mild pulmonary hypertension is known to be associated with increased mortality, its impact on premature mortality is largely unknown. Methods We studied the distribution of estimated right ventricular systolic pressure (eRVSP) among a total of 154956 adults with no evidence of left heart disease investigated with echocardiography. We then examined individually linked mortality, premature mortality and associated life-years lost (LYL) according to eRVSP levels. Results The cohort comprised 70826 men and 84130 women (aged 61.317.7 and 61.418.4 years, respectively). Overall, 85173 (55.0%), 49276 (31.8%), 13060 (8.4%) and 7447 (4.8%) cases had eRVSP levels indicative of no (<30.0 mmHg), mild (30.0-39.9 mmHg), moderate (40.0-49.9 mmHg) or severe (?50.0 mmHg) pulmonary hypertension, respectively. During a median (interquartile range) 5.7 (3.2-8.9) years of follow-up, 38456/154986 (24.8%) individuals died. Compared with eRVSP <30.0 mmHg, age and sex-adjusted hazard ratios for all-cause and cardiovascular-related mortality were 1.90 (95% CI 1.84-1.96) and 1.85 (95% CI 1.74-1.97), respectively, for eRVSP 35.0-39.9 mmHg. Overall, 6256 (54%) men and 7524 (55%) women died prematurely. As a proportion of all deaths, premature mortality rose from 46.7% to 79.2% among those with eRVSP <30.0 versus ?60.0 mmHg with a mean of 5.1-11.4 LYL each time. However, due to more individuals affected overall, eRVSP 30.0-39.9 mmHg accounted for 58% and 53% of total LYL among men (40606/70019 LYL) and women (47333/88568 LYL), respectively. Conclusions These data confirm that elevated eRVSP levels indicative of mild pulmonary hypertension are associated with increased risk of death. Moreover, this results in a substantive component of premature mortality/LYL that requires more proactive clinical surveillance and management. 2022 European Respiratory Society. All rights reserved.
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Passam, Freda H.; Chen, Gang; Chen, Vivien Mun Yee; Qi, Miao; Krilis., Steven Anthony; Giannakopoulos, BillLittle is known about the physiological role of beta-2-glycoprotein I (?2GPI) despite it being the major auto-antigen in the antiphospholipid syndrome. A systematic study of the role of ?2GPI in thrombus formation in vivo has not been performed to date. Herein, we report that ?2GPI deficient (?/?) mice have enhanced thrombus formation compared to wild type (WT) mice in a laser-induced arteriole and venule model of thrombosis. Furthermore, neutrophil accumulation and elastase activity was enhanced in thrombi of ?2GPI ?/? compared with WT mice. The antithrombotic function of ?2GPI is dependent on its fifth domain (domain V); intravenous administration of the ?2GPI domain deletion mutant lacking domain V (human recombinant domain I-IV) had no effect on platelet and fibrin thrombus size in ?2GPI ?/? or WT mice. On the contrary, intravenous administration of human recombinant domain V significantly inhibited platelet and fibrin thrombus size in both ?2GPI ?/? mice and WT mice. These findings reveal a major role for ?2GPI as a natural anticoagulant and implicate domain V of ?2GPI as a potential antithrombotic therapy. 2021 Elsevier Ltd
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Schnabel, Renate B.; Wallenhorst, Christopher; Engler, Daniel; Blankenberg, Stefan S.; Pfeiffer, Norbert; Spruenker, Ngoc Anh; Buettner, Matthias; Michal, Matthias; Lackner, Karl Johannes; Mzel, Tomas F.; Wild, Philipp Sebastian; Martinez, Carlos; Freedman, Ben BenObjective Little is known on optimal screening population for detecting new atrial fibrillation (AF) in the community. We describe characteristics and estimate cost-effectiveness for a single timepoint electrocardiographic screening. Methods We performed a 12-lead ECG in the German population-based Gutenberg Health Study between 2007 and 2012 (n=15 010), mean age 5511 years, 51% men and collected more than 120 clinical and biomarker variables, including N-terminal pro B-type natriuretic peptide (Nt-proBNP), risk factors, disease symptoms and echocardiographic variables. Results Of 15 010 individuals, 466 (3.1%) had AF. New AF was found in 32 individuals, 0.2% of the total sample, 0.5% of individuals aged 6574 years and predominantly men (86%). The classical risk factor burden was high in individuals with new AF. The median estimated stroke risk was 2.2%/year, while risk of developing heart failure was 21% over 10 years. In the 6574 year age group, the cost per quality-adjusted life-year gained resulting from a single timepoint screening was 30 361. In simulations, the costs were highly sensitive to AF detection rates, proportion of treatment and type of oral anticoagulant. Prescreening by Nt-proBNP measurements was not cost-effective in the current setting. Conclusions In our middle-aged population cohort, we identified 0.2% new AF by single timepoint screening. There was a significant estimated risk of stroke and heart failure in these individuals. Cost-effectiveness for screening may be reached in individuals aged 65 years and older. The simple age cut-off is not improved by using Nt-proBNP as a biomarker to guide a screening programme. Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.
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Ye, Xiaofei; Zhang, Wei; Chen, Yi; Miao, Chaoying; Huang, Qifang; Sheng, Changsheng; Shao, Shuai; Wang, Dian; Xu, Shaokun; Lei, Lei; Zhang, Di; Chen, Yilin; Hu, Leixiao; Xia, Jiahui; Cheng, Yibang; Wang, Ying; Guo, Qianhui; Li, Yan; Lowres, Nicole; Freedman, Ben Ben; Wang, JiguangBACKGROUND Alcohol consumption is a known modifiable risk factor for atrial fibrillation. The association, however, might differ according to gender. We investigated gender-specific associations between alcohol consumption and incident atrial fibrillation in an elderly Chinese population. METHODS Our study participants were elderly residents (? 65 years) recruited from five community health centers in the urban area of Shanghai (n = 6,618). Alcohol intake was classified as never drinkers and current light-to-moderate (< 40 g/day) and heavy drinkers (? 40 g/day). Atrial fibrillation was detected by a 30-s single-lead electrocardiography (ECG, AliveCor Heart Monitor) and further evaluated with a regular 12-lead ECG. RESULTS During a median of 2.1 years (interquartile range: 2.0?2.2) follow-up, the incidence rate of atrial fibrillation was 1.10% in all study participants. It was slightly but non-significantly higher in men (n = 2849) than women (n = 3769, 1.30% vs. 0.96%, P = 0.19) and in current drinkers (n = 793) than never drinkers (n = 5825, 1.64% vs. 1.03%, P = 0.12). In both unadjusted and adjusted analyses, there was interaction between sex and current alcohol intake in relation to the incidence of atrial fibrillation (P < 0.0001). After adjustment for confounding factors, current drinkers had a significantly higher incidence rate of atrial fibrillation than never drinkers in women (12.96% [7/54] vs. 0.78% [29/3715], adjusted odds ratio [OR] = 10.25, 95% confidence interval [CI]: 3.54?29.67, P < 0.0001), but not in men (0.81% [6/739] vs. 1.47% [31/2110], OR = 0.62, 95% CI: 0.25?1.51, P = 0.29). CONCLUSIONS Our study showed a significant association between alcohol intake and the incidence of atrial fibrillation in elderly Chinese women, but not men. 2022 JGC All rights reserved;
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Snir, Afik D.; Ng, Martin K.C.; Strange, G. A.; Playford, David A.; Stewart, S.; Celermajer, David S.BACKGROUND: The prevalence and outcomes of the different subtypes of severe low-gradient aortic stenosis (AS) in routine clinical cardiology practice have not been well characterized. METHODS AND RESULTS: Data were derived from the National Echocardiography Database of Australia. Of 192 060 adults (aged 62.817.8 [meanSD] years) with native aortic valve profiling between 2000 and 2019, 12 013 (6.3%) had severe AS. Of these, 5601 patients (47%) had high-gradient and 6412 patients (53%) had low-gradient severe AS. The stroke volume index was docu-mented in 2741 (42.7%) patients with low gradient; 1750 patients (64%) with low flow, low gradient (LFLG); and 991 patients with normal flow, low gradient. Of the patients with LFLG, 1570 (89.7%) had left ventricular ejection fraction recorded; 959 (61%) had paradoxical LFLG (preserved left ventricular ejection fraction), and 611 (39%) had classical LFLG (reduced left ventricular ejection fraction). All-cause and cardiovascular-related mortality were assessed in the 8162 patients with classifiable severe AS subtype during a meanSD follow-up of 8845 months. Actual 1-year and 5-year all-cause mortality rates varied across these groups and were 15.8% and 49.2% among patients with high-gradient severe AS, 11.6% and 53.6% in patients with normal-flow, low-gradient severe AS, 16.9% and 58.8% in patients with paradoxical LFLG severe AS, and 30.5% and 72.9% in patients with classical LFLG severe AS. Compared with patients with high-gradient severe AS, the 5-year age-adjusted and sex-adjusted mortality risk hazard ratios were 0.94 (95% CI, 0.851.03) in patients with normal-flow, low-gradient severe AS; 1.01 (95% CI, 0.921.12) in patients with paradoxical LFLG severe AS; and 1.65 (95% CI, 1.481.84) in patients with classical LFLG severe AS. CONCLUSIONS: Approximately half of those patients with echocardiographic features of severe AS in routine clinical practice have low-gradient hemodynamics, which is associated with long-term mortality comparable with or worse than high-gradient severe AS. The poorest survival was associated with classical LFLG severe AS. 2021 The Authors.
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Rubenis, Imants; Tran, Derek L.; Bullock, Andrew M.; Wijesekera, Vishva A.; Baker, David William; d'Udekem, Yves A.; Du Plessis, Karin; Katz, Darren J.; Lowy, Michael P.; Zentner, Dominica; Celermajer, David S.; Cordina, Rachael LouiseIntroduction: It is unknown if the Fontan circulation has an impact on sexual health in men. This study assessed self-reported sexual health and fertility in men with a Fontan circulation. Aims: In this prospective, cross-sectional study, Australian men ?18 years enrolled in the Fontan Registry of Australia and New Zealand were invited to complete the International Index of Erectile Function (IIEF), alongside questions assessing fertility. These data were compared to historical, age-matched controls. Results: Of 227 eligible men, 54 completed the survey; of those 37 were sexually active and included in the final analysis. Mean age was 28 3 years, age at Fontan was 5 3 years. Fontan type was extra-cardiac conduit in 15 (41%), lateral tunnel in 12 (32%), and atriopulmonary connection (APC) in 10 (27%). Ventricular function was normal in 24 (83%), and all were New York Heart Association Class I (23 patients, 79%) and II (six patients, 21%). Nine participants (24%) had erectile dysfunction (IIEF-EF score ?25). The severity was mild (IIEF 2224) in six (16%), mildmoderate (IIEF 1721) in two (5%), and moderate (IIEF 1116) in one (3%). Baseline characteristics and current medication usage were similar in those with and without erectile dysfunction. Compared with historical control values, erectile function was not significantly impaired in the Fontan population (p =0.76). Men with a Fontan circulation had decreased levels of sexual desire and overall satisfaction (p < 0.001). There was no correlation between the presence of erectile dysfunction and any assessed parameter. Eleven (30%) of the cohort reported a pregnancy with a prior partner. Conclusion: In our cohort, overall erectile function was comparable between men with a Fontan circulation and historical controls, however sexual desire and overall satisfaction were reduced. There was no correlation between study parameters and the presence of erectile dysfunction. The proportion of the cohort who had a prior pregnancy was congruent with population data. 2021 Rubenis, Tran, Bullock, Wijesekera, Baker, d'Udekem, du Plessis, Katz, Lowy, Zentner, Celermajer and Cordina.
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Zhao, Yunduo Charles; Vatankhah, Pooya; Goh, Tiffany; Michelis, Rhys; Kyanian, Kiarash; Zhang, Yingqi; Li, Zhiyong; Ju, Lining ArnoldDisturbed blood flow has been increasingly recognized for its critical role in platelet aggregation and thrombosis. Microfluidics with hump shaped contractions have been developed to mimic microvascular stenosis and recapitulate the prothrombotic effect of flow disturbance. However the physical determinants of microfluidic hemodynamics are not completely defined. Here, we report a refined computational fluid dynamics (CFD) simulation approach to map the shear rate (?) and wall shear stress (?) distribution in the stenotic region at high accuracy. Using ultra-fine meshing with sensitivity verification, our CFD results show that the stenosis level (S) is dominant over the bulk shear rate (?<inf>0</inf>) and contraction angle (?) in determining ? and ? distribution at stenosis. In contrast, ? plays a significant role in governing the shear rate gradient (??) distribution whileit exhibits subtle effects on the peak ?. To investigate the viscosity effect, we employ a Generalized Power-Law model to simulate blood flow as a non-Newtonian fluid, showing negligible difference in the ? distribution when compared with Newtonian simulation with water medium. Together, our refined CFD method represents a comprehensive approach to examine microfluidic hemodynamics in three dimensions and guide microfabrication designs. Combining this with hematological experiments promises to advance understandings of the rheological effect in thrombosis and platelet mechanobiology. 2021, The Author(s).
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Li, Jialin; Lowres, Nicole; Koo, Tebbin (Fung); Gallagher, Robyn D.Aim: The aim of this study is to determine health professionals' experiences communicating with Chinese immigrants and identify potential education barriers. Background: Health professionals caring for Chinese immigrants often encounter communication barriers, leading to uncertainty of quality of care. Design: This study is a quantitative and qualitative systematic review. Data sources: MEDLINE, Scopus, CINAHL, PubMed and Google Scholar were searched, limited to 1980 to October 2020. Review methods: Articles were included if they reported results about health professional communication with Chinese patients. Quality was appraised using Consolidated Criteria for Reporting Qualitative Research guidelines and thematic synthesis conducted. Results: Of 1363 articles, seven studies were included. These described providerpatient communication in primary care, oncology and palliative settings only. Three core themes were identified: (1) family-centred health communication where family controls providerpatient information exchange; (2) mismatch of providerpatient health beliefs and knowledge on diet, nutrition, traditional medicine, place for death and disease prevention and (3) mismatch of language and resources as skilled providers proficient in specific dialects are limited; communication resources are perceived as infrequently available and content is insufficient. Conclusion: Studies describing health professionals' experiences communicating with Chinese immigrants are limited. Key barriers identified included cultural and language disparities and communication resources are inadequate to support health professionals' needs. 2021 John Wiley & Sons Australia, Ltd.
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Hall, Luke; Guo, Chaouri; Tandy, Sarah; Broadhouse, Kathryn M.; Dona, Anthony C.; Malle, Ernst; Bartels, Emil Daniel; Christoffersen, Christina Nadia; Grieve, Stuart M.; Figtree, Gemma A.; Hawkins, Clare L.; Davies, Michael J.Despite improvements in revascularization after a myocardial infarction, coronary disease remains a major contributor to global mortality. Neutrophil infiltration and activation contributes to tissue damage, via the release of myeloperoxidase (MPO) and formation of the damaging oxidant hypochlorous acid. We hypothesized that elevation of thiocyanate ions (SCN?), a competitive MPO substrate, would modulate tissue damage. Oral dosing of rats with SCN?, before acute ischemiareperfusion injury (30min occlusion, 24h or 4week recovery), significantly reduced the infarct size as a percentage of the total reperfused area (54% versus 74%), and increased the salvageable area (46% versus 26%) as determined by MRI imaging. No difference was observed in fractional shortening, but supplementation resulted in both left-ventricle end diastolic and left-ventricle end systolic areas returning to control levels, as determined by echocardiography. Supplementation also decreased antibody recognition of HOCl-damaged myocardial proteins. SCN? supplementation did not modulate serum markers of damage/inflammation (ANP, BNP, galectin-3, CRP), but returned metabolomic abnormalities (reductions in histidine, creatine and leucine by 0.83-, 0.84- and 0.89-fold, respectively), determined by NMR, to control levels. These data indicate that elevated levels of the MPO substrate SCN?, which can be readily modulated by dietary means, can protect against acute ischemiareperfusion injury. 2021, The Author(s).
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Schumann, Tina; Kig, Jg; von Loeffelholz, Christian; Vatner, Daniel F.; Zhang, Dongyang Yan; Perry, Rachel J.; Bernier, Michel; Chami, Jason; Henke, Christine; Kurzbach, Anica; El-Agroudy, Nermeen N.; Willmes, Diana Maria; Pesta, Dominik Hans; de Cabo, Rafael C.; OSullivan, John F.; Simon, Eric; Shulman, Gerald I.; Hamilton, Bradford S.; Birkenfeld, Andreas L.Genome-wide association studies have identified SLC16A13 as a novel susceptibility gene for type 2 diabetes. The SLC16A13 gene encodes SLC16A13/MCT13, a member of the solute carrier 16 family of monocarboxylate transporters. Despite its potential importance to diabetes development, the physiological function of SLC16A13 is unknown. Here, we validate Slc16a13 as a lactate transporter expressed at the plasma membrane and report on the effect of Slc16a13 deletion in a mouse model. We show that Slc16a13 increases mitochondrial respiration in the liver, leading to reduced hepatic lipid accumulation and increased hepatic insulin sensitivity in high-fat diet fed Slc16a13 knockout mice. We propose a mechanism for improved hepatic insulin sensitivity in the context of Slc16a13 deficiency in which reduced intrahepatocellular lactate availability drives increased AMPK activation and increased mitochondrial respiration, while reducing hepatic lipid content. Slc16a13 deficiency thereby attenuates hepatic diacylglycerol-PKC? mediated insulin resistance in obese mice. Together, these data suggest that SLC16A13 is a potential target for the treatment of type 2 diabetes and non-alcoholic fatty liver disease. 2021, The Author(s).
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Parvaneh, Maria; Witting, Paul Kenneth; Ku, Jacqueline M.; Moradi, Tala; Eroglu, Elif I.; Freedman, Ben Ben; Sutherland, G. T.; McCorkindale, Andrew N.; Guennewig, Boris; Choowong, Phannaphat; Bell-Anderson, Kim S.; Cooney, Gregory J.; Thomas, Shane R.; Eberhard, JoergThe treatment of periodontitis has numerous positive effects on established chronic health conditions, including cardiovascular disease and diabetes. However, ethical considerations do limit the establishment of human trials to investigate whether periodontitis promotes the early stages of chronic conditions. Therefore, the aim of this study was to investigate whether periodontitis induces endothelial dysfunction in hyperlipidemic apolipoprotein E gene-deficient (ApoE-/-) mice. Forty-five 8-week-old ApoE-/- mice were challenged by oral lavage with Porphyromonas gingivalis and Streptococcus gordonii for 4weeks. A subgroup of animals (n = 1517/group) was placed in a metabolic chamber immediately before euthanasia at 4weeks to measure VO<inf>2</inf>/CO<inf>2</inf> concentrations and voluntary locomotion. In infected and control animals alveolar bone levels were measured by x-ray imaging and endothelial function was determined by measuring endothelial-dependent vasorelaxation of aortic rings. The mRNA expression levels of serum amyloid A and tumor necrosis factor were determined in liver tissues by qRT PCR and protein concentrations in serum by ELISA. Caecal contents were analysed by sequencing to determine changes to the gut microbiota to investigate linkages between microbiome and systemic changes. The results showed that oral lavage of P. gingivalis and S. gordonii for 4weeks, initiated periodontitis in ApoE-/- mice, similar to the human situation. The oral inflammation was accompanied by a significant increase in mRNA expression of pro-inflammatory mediators serum amyloid A1 and tumor necrosis factor in the liver. Mice with periodontitis also exhibited impaired endothelial-dependent vasorelaxation responses to acetylcholine. This systemic response was connected to increased energy expenditure, locomotion and respiratory quotient. No differences were detected in caecal microbiota between the infected and control animals. Overall, this is the first report that provide evidence that periodontitis induces endothelial dysfunction in mice. Other systemic responses observed in response to the local reaction need further investigation. The study suggests that early prevention of periodontitis may help limit the early stages of endothelial dysfunction that is linked to atherogenesis in humans. 2021, The Author(s).
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Strange, G. A.; Scalia, Gregory M.; Playford, David A.; Simon, StewartBackground: We aimed to address the paucity of information describing the treatable burden of disease associated with severe aortic stenosis (AS) within Australias ageing population. Methods: A contemporary model of the population prevalence of symptomatic, severe AS and treatment pathways in Europe and North America was applied to the 2019 Australian population aged ? 55 years (7million people) on an age-specific basis. Applying Australian-specific data, these estimates were used to further calculate the total number of associated deaths and incident cases of severe AS per annum. Results: Based on an overall point prevalence of 1.48 % among those aged ? 55 years, we estimate that a minimum of 97,000 Australians are living with severe AS. With a 2-fold increased risk of mortality without undergoing aortic valve replacement (AVR), more than half of these individuals (?56,000) will die within 5-years. From a clinical management perspective, among those with concurrent symptoms (68.3 %, 66,500 [95 % CI 59,00074,000] cases) more than half (58.4 %, 38,800 [95 % CI 35,700 ? 42,000] cases) would be potentially considered for surgical AVR (SAVR) - comprising 2,400, 5,400 and 31,000 cases assessed as high-, medium- or low peri-operative mortality risk, respectively. A further 17,000/27,700 (41.6 % [95 % CI 11,600 ? 22,600]) of such individuals would be potentially considered to a transthoracic AVR (TAVR). During the subsequent 5-year period (20202024), each year, we estimate an additional 9,300 Australians aged ? 60 years will subsequently develop severe AS (6,300 of whom will experience concurrent symptoms). Of these symptomatic cases, an estimated 3,700 and 1,600 cases/annum, will be potentially suitable for SAVR and TAVR, respectively. Conclusions: These data suggest there is likely to be a substantive burden of individuals living with severe AS in Australia. Many of these cases may not have been diagnosed and/or received appropriate treatment (based on the evidence-based application of SAVR and TAVR) to reduce their high-risk of subsequent mortality. 2021, The Author(s).
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Kim, Taiyun; Tang, Owen; Vernon, Stephen Thomas; Kott, Katharine A.; Koay, Yen Chin; Park, John; James, David Ernest; Grieve, Stuart M.; Speed, Terence P.; Yang, Pengyi; Figtree, Gemma A.; OSullivan, John F.; Yang, Jean Yee HwaLiquid chromatography-mass spectrometry-based metabolomics studies are increasingly applied to large population cohorts, which run for several weeks or even years in data acquisition. This inevitably introduces unwanted intra- and inter-batch variations over time that can overshadow true biological signals and thus hinder potential biological discoveries. To date, normalisation approaches have struggled to mitigate the variability introduced by technical factors whilst preserving biological variance, especially for protracted acquisitions. Here, we propose a study design framework with an arrangement for embedding biological sample replicates to quantify variance within and between batches and a workflow that uses these replicates to remove unwanted variation in a hierarchical manner (hRUV). We use this design to produce a dataset of more than 1000 human plasma samples run over an extended period of time. We demonstrate significant improvement of hRUV over existing methods in preserving biological signals whilst removing unwanted variation for large scale metabolomics studies. Our tools not only provide a strategy for large scale data normalisation, but also provides guidance on the design strategy for large omics studies. 2021, The Author(s).
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Dutta, Shashwati; Li, Desmond K.; Wang, Andy Yi Yang; Ishak, Mark; Cook, Kristina M.; Farnham, M. M. J.; Dissanayake, Hasthi U.W.; Cistulli, Peter A.; Hunyor, Imre; Liu, Renping; Wilcox, Ian; Koay, Yen Chin; Yang, Jean Yee Hwa; Lal, Sean P.; OSullivan, John F.Aims: Sleep apnoea and congestive heart failure (CHF) commonly co-exist, but their interaction is unclear. Metabolomics may clarify their interaction and relationships to outcome. Methods and results: We assayed 372 circulating metabolites and lipids in 1919 and 1524 participants of the Framingham Heart Study (FHS) (mean age 5410years, 53% women) and Women's Health Initiative (WHI) (mean age 677years), respectively. We used linear and Cox regression to relate plasma concentrations of metabolites and lipids to echocardiographic parameters; CHF and its subtypes heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF); and sleep indices. Adenine dinucleotide phosphate (ADP) associated with left ventricular (LV) fractional shortening; phosphocreatine with LV wall thickness; lysosomal storage molecule sphingomyelin 18:2 with LV mass; and nicotine metabolite cotinine with time spent with an oxygen saturation less than 90% (?=2.3min, P=2.3נ10?5). Pro-hypertrophic metabolite hydroxyglutarate partly mediated the association between LV wall thickness and HFpEF. Central sleep apnoea was significantly associated with HFpEF (P=0.03) but not HFrEF (P=0.5). There were three significant metabolite canonical variates, one of which conferred protection from cardiovascular death [hazard ratio=0.3 (0.11, 0.81), P=0.02]. Conclusions: Energetic metabolites were associated with cardiac function; energy- and lipid-storage metabolites with LV wall thickness and mass; plasma levels of nicotine metabolite cotinine were associated with increased time spent with a sleep oxygen saturation less than 90%, a clinically significant marker of outcome, indicating a significant hazard for smokers who have sleep apnoea. 2021 Heart Research Institute. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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Kearney, Katherine L.; Zentner, Dominica; Cordina, Rachael LouisePurpose of the Review: The purpose of this review is to discuss the risk stratification and management of pregnancy in women with complex congenital heart disease. Recent Findings: Classifying congenital heart defects (CHD) including both anatomy and physiology is important for maternal risk stratification. Although most women with CHD can tolerate the physiological challenge of pregnancy, some may experience serious risks both to their health and that of their foetus. The WHO maternal risk classification model remains the best-validated risk measure. Ideally, women with CHD should have pre-conception assessment with a CHD cardiologist. General principles of management, such as need for expert centre delivery, a multidisciplinary team, epidural and mode of delivery are based on WHO risk in combination with expert assessment of status. Summary: CHD is increasingly prevalent in women of child-bearing age. Assessment by an adult CHD cardiologist, ideally pre-conception, is key in assessing and minimising risk to mother and foetus. 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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Queiroz, Raphael Ferreira; Stanley, Christopher P.; Wolhuter, Kathryn; Kong, Stephanie M.Y.; Rajivan, Ragul; McKinnon, Naomi; Nguyen, Giang T.H.; Roveri, Antonella; Guttzeit, Sebastian; Eaton, Philip J.; Donald, William Alexander; Ursini, Fulvio; Winterbourn, Christine C.; Ayer, Anita; Stocker, RolandDuring systemic inflammation, indoleamine 2,3-dioxygenase 1 (IDO1) becomes expressed in endothelial cells where it uses hydrogen peroxide (H<inf>2</inf>O<inf>2</inf>) to oxidize L-tryptophan to the tricyclic hydroperoxide, cis-WOOH, that then relaxes arteries via oxidation of protein kinase G 1?. Here we show that arterial glutathione peroxidases and peroxiredoxins that rapidly eliminate H<inf>2</inf>O<inf>2</inf>, have little impact on relaxation of IDO1-expressing arteries, and that purified IDO1 forms cis-WOOH in the presence of peroxiredoxin 2. cis-WOOH oxidizes protein thiols in a selective and stereospecific manner. Compared with its epimer trans-WOOH and H<inf>2</inf>O<inf>2</inf>, cis-WOOH reacts slower with the major arterial forms of glutathione peroxidases and peroxiredoxins while it reacts more readily with its target, protein kinase G 1?. Our results indicate a paradigm of redox signaling by H<inf>2</inf>O<inf>2</inf> via its enzymatic conversion to an amino acid-derived hydroperoxide that escapes effective reductive inactivation to engage in selective oxidative activation of key target proteins. 2021, The Author(s).
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Chen, Hao; Chhor, Michael; Rayner, Benjamin Saul; McGrath, Kristine C.Y.; McClements, LanaBackground: A number of circulating biomarkers are currently utilized for the diagnosis of chronic heart failure with preserved ejection fraction (HFpEF). However, due to HFpEF heterogeneity, the accuracy of these biomarkers remains unclear. Aims: This study aimed to systematically determine the diagnostic accuracy of currently available biomarkers for chronic HFpEF. Methods: PubMed, Web of Science, MEDLINE and SCOPUS databases were searched systematically to identify studies assessing the diagnostic accuracy of biomarkers of chronic HFpEF with left ventricular ejection fraction (LVEF) ? 50%. All included studies were independently assessed for quality and relevant information was extracted. Random-effects models were used to estimate the pooled diagnostic accuracy of HFpEF biomarkers. Results: The search identified 6145 studies, of which 19 were included. Four biomarkers were available for meta-analysis. The pooled sensitivity of B-type natriuretic peptide (BNP) (0.787, 95% confidence interval [CI] 0.7190.842) was higher than that of N-terminal pro-BNP (NT-proBNP) (0.696, 95% CI 0.5990.779) in chronic HFpEF diagnosis. However, NT-proBNP showed improved specificity (0.882, 95% CI 0.7780.941) compared to BNP (\0.796, 95% CI 0.6720.882). Galectin-3 (Gal-3) exhibited a reliable diagnostic adequacy for HFpEF (sensitivity 0.760, 95% CI 0.6310.855; specificity 0.803, 95% CI 0.6670.893). However, suppression of tumorigenesis-2 (ST2) displayed limited diagnostic performance for chronic HFpEF diagnosis (sensitivity 0.636, 95% CI 0.4650.779; specificity 0.595, 95% CI 0.4270.743). Conclusion: NT-proBNP and BNP appear to be the most reliable biomarkers in chronic HFpEF with NT-proBNP showing higher specificity and BNP showing higher sensitivity. Although Gal-3 appears more reliable than ST2 in HFpEF diagnosis, the conclusions are limited as only three studies were included in this meta-analysis. 2021 Elsevier Masson SAS
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Mak, Hoiyin; OuYang, Qian; Tumanov, Sergey; Xu, Jiesi; Rong, Ping; Dong, Feitong; Lam, Sin Man; Wang, Xiaowei; Lukmantara, Ivan E.; Du, Ximing; Gao, Mingming; Brown, Andrew J.; Gong, Xin; Shui, Guanghou; Stocker, Roland; Huang, Xun; Chen, Shuai; Yang, HongyuanAGPATs (1-acylglycerol-3-phosphate O-acyltransferases) catalyze the acylation of lysophosphatidic acid to form phosphatidic acid (PA), a key step in the glycerol-3-phosphate pathway for the synthesis of phospholipids and triacylglycerols. AGPAT2 is the only AGPAT isoform whose loss-of-function mutations cause a severe form of human congenital generalized lipodystrophy. Paradoxically, AGPAT2 deficiency is known to dramatically increase the level of its product, PA. Here, we find that AGPAT2 deficiency impairs the biogenesis and growth of lipid droplets. We show that AGPAT2 deficiency compromises the stability of CDP-diacylglycerol (DAG) synthases (CDSs) and decreases CDS activity in both cell lines and mouse liver. Moreover, AGPAT2 and CDS1/2 can directly interact and form functional complexes, which promote the metabolism of PA along the CDP-DAG pathway of phospholipid synthesis. Our results provide key insights into the regulation of metabolic flux during lipid synthesis and suggest substrate channelling at a major branch point of the glycerol-3-phosphate pathway. 2021, The Author(s).
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Bortolussi, Giulia; Shi, Xiaoxia; Bloemendaal, Lysbeth Ten; Banerjee, Bhaswati; de Waart, Dirk Rudi; Baj, G.; Chen, Weiyu; Oude Elferink, Ronald P.J.; Beuers, U. H.W.; Paulusma, Coen C.; Stocker, Roland; Muro, Andr Fernando; Bosma, Piter JabikAccumulation of neurotoxic bilirubin due to a transient neonatal or persistent inherited deficiency of bilirubin glucuronidation activity can cause irreversible brain damage and death. Strategies to inhibit bilirubin production and prevent neurotoxicity in neonatal and adult settings seem promising. We evaluated the impact of Bvra deficiency in neonatal and aged mice, in a background of unconjugated hyperbilirubinemia, by abolishing bilirubin production. We also investigated the disposal of biliverdin during fetal development. In Ugt1?/? mice, Bvra deficiency appeared sufficient to prevent lethality and to normalize bilirubin level in adults. Although biliverdin accumulated in Bvra-deficient fetuses, both Bvra?/? and Bvra?/? Ugt1?/? pups were healthy and reached adulthood having normal liver, brain, and spleen histology, albeit with increased iron levels in the latter. During aging, both Bvra?/? and Bvra?/? Ugt1?/? mice presented normal levels of relevant hematological and metabolic parameters. Interestingly, the oxidative status in erythrocytes from 9-months-old Bvra?/? and Bvra?/? Ugt1?/? mice was significantly reduced. In addition, triglycerides levels in these 9-months-old Bvra?/? mice were significantly higher than WT controls, while Bvra?/? Ugt1?/? tested normal. The normal parameters observed in Bvra?/? Ugt1?/? mice fed chow diet indicate that Bvra inhibition to treat unconjugated hyperbilirubinemia seems safe and effective. 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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Khandkar, Chinmay; Vaidya, Kaivan; Galougahi, Keyvan Karimi; Patel, SanjayCoronary artery disease (CAD) and osteoporosis both cause significant morbidity and mortality. Recent interest in inflammation and the bone-vascular axis suggests a mechanistic link between the two conditions. This review and meta-analysis was conducted to examine the potential association between low bone mineral density (BMD) and CAD in adults. Two authors searched for studies that examined the association between low BMD and CAD. Risk of bias assessment was conducted using the modified Newcastle Ottawa score. Ten studies were selected from the 2258 unique records identified. Pooled analysis showed a significant association between low BMD and CAD (OR 1.65, 95%CI 1.372.39, p < 0.01). Subgroup analysis investigating males and females separately was not significant. The subgroup analyses looking for any differences across geographic locations and differences between coronary imaging modalities were also negative. Studies with adjusted ORs (n = 4) were also pooled (OR 3.01, 95%CI 0.919.99, p = 0.07). Low BMD is associated with CAD; however, it is unclear whether this result is confounded by common risk factors given the heterogeneity between study populations and methodologies. Further large-scale epidemiological studies are required. 2021
