When Glanzmann thrombasthenia encounters antithrombin defi ciency: how do we balance the risk and benefi t of antithrombotic therapy?

Glanzmann’s thrombasthenia(GT)is an inherited autosomal recessive bleeding disorder,resulting from mutations in the ITGA2B and ITGB3 genes,that lead to a defect in the platelet membrane integrinαIIbβ3.[1]As integrinαIIbβ3 plays an important role in thrombus formation,the clinical manifestation of GT includes bleeding(mostly mucocutaneous)and purpura.For this reason,patients with GT are typically thought to be unlikely to suffer from thromboembolic incidents.Antithrombin is an anticoagulant that inhibits thrombin and is activated factor X and other serine proteases in the coagulation cascade.[2]Antithrombin deficiency is an autosomal dominant hereditary disease with an approximate prevalence of 1/500 in the overall population.[3]In contrast to the hemorrhagic tendency of GT,patients with antithrombin deficiency are at increased risk of thromboembolism,especially in the venous system.Herein,we describe a rare case of GT and antithrombin deficiency coexisting in a single patient.Rivaroxaban was used for the treatment of pulmonary embolism(PE)and deep vein thrombosis(DVT).

Risk factors for cardiovascular disease in the Chinese population:recent progress and implications

Cardiovascular disease(CVD)is the leading cause of death in both urban and rural areas of China.The current evidence regarding CVD risk factors was primarily established in Western countries,with limited generalizability to the Chinese population.In China,a growing number of population-based prospective cohort studies have emerged that have yielded substantial research data on CVD risk factors in the past five years.The research studies have covered biological risk factors(e.g.,blood lipids,blood pressure,blood glucose,adiposity),lifestyle risk factors(e.g.,smoking,alcohol,diet,physical activity),environmental risk factors(e.g.,ambient and indoor air pollution),and risk prediction.This study aimed to systematically review the research progress on CVD risk factors in the Chinese population in the past five years.Prospective studies in China have identified biological,lifestyle,and environmental risk factors for CVD and its main subtypes,along with some protective factors unique to the Chinese(e.g.,spicy food and green tea).This review aimed to provide high-quality evidence for achieving the Outline of Healthy China 2030,developing disease prevention guidelines and measures,and deepening efforts for popularization of health knowledge.

An extended analysis of cardiovascular benefits of indoor air filtration intervention among elderly:a randomized crossover trial(Beijing indoor air purifier study,BIAPSY)

Objective Evidence on potential cardiovascular benefits of personal-level intervention among the elderly exposed to high levels of particulate matter(PM)remains limited.We aimed to assess improvements in surrogate markers of cardiovascular injury in vulnerable populations at risks by using indoor air filtration units.Methods We conducted a randomized crossover trial for 2 separate 2-week air filtration interventions in 20 households of patients with stable chronic obstructive pulmonary disease and their partners in the winter of 2013,with concurrent measurements of indoor PM.The changes in biomarkers indicative of cardiac injury,atherosclerosis progression and systemic inflammation following intervention were evaluated using linear mixed-effect models.Results In the analysis,average levels of indoor PM with aerodynamic diameters<2.5µm(PM2.5)decreased significantly by 59.2%(from 59.6 to 24.3µg/m3,P<0.001)during the active air filtration.The reduction was accompanied by improvements in levels of high-sensitivity cardiac troponin I by−84.6%(95%confidence interval[CI]:−90.7 to−78.6),growth differentiation factor-15 by−48.1%(95%CI:−31.2 to−25.6),osteoprotegerin by−65.4%(95%CI:−56.5 to−18.7),interleukin-4 by−46.6%(95%CI:−62.3 to−31.0)and myeloperoxidase by−60.3%(95%CI:−83.7 to−3.0),respectively.Conclusion Indoor air filtration intervention may provide potential cardiovascular benefits in vulnerable populations at risks.

Animal exercise studies in cardiovascular research:Current knowledge and optimal design--A position paper of the Committee on Cardiac Rehabilitation,Chinese Medical Doctors’Association

Growing evidence has demonstrated exercise as an effective way to promote cardiovascular health and protect against cardiovascular diseases However,the underlying mechanisms of the beneficial effects of exercise have yet to be elucidated.Animal exercise studies are widely used to investigate the key mechanisms of exercise-induced cardiovascular protection.However,standardized procedures and well-established evaluation indicators for animal exercise models are needed to guide researchers in carrying out effective,high-quality animal studies using exercise to prevent and treat cardiovascular diseases.In our review,we present the commonly used animal exercise models in cardiovascular research and propose a set of standard procedures for exercise training,emphasizing the appropriate measurements and analysis in these chronic exercise models.We also provide recommendations for optimal design of animal exercise studies in cardiovascular research,including the choice of exercise models,control of exercise protocols,exercise at different stages of disease,and other considerations,such as age,sex,and genetic background.We hope that this position paper will promote basic research on exercise-induced cardiovascular protection and pave the way for successful translation of exercise studies from bench to bedside in the prevention and treatment of cardiovascular diseases.

Exercise training attenuates angiotensinⅡ-induced cardiac fibrosis by reducing POU2F1 expression

Background:Exercise training protects against heart failure.However,the mechanism underlying the protective effect of exercise training on angiotensinⅡ(AngⅡ)-induced cardiac fibrosis remains unclear.Methods:An exercise model involving C57BL/6N mice and 6 weeks of treadmill training was used.AngⅡ(1.44 mg/kg/day)was administered to induce cardiac fibrosis.RNA sequencing and bioinformatic analysis were used to identify the key factors mediating the effects of exercise training on cardiac fibrosis.Primary adult mouse cardiac fibroblasts(CFs)were used in vitro.Adeno-associated virus serotype 9 was used to overexpress POU domain,class 2,transcription factor 1(POU2F1)in vivo.Results:Exercise training attenuated AngⅡ-induced cardiac fibrosis and reversed 39 gene expression changes.The transcription factor regulating the largest number of these genes was POU2F1.Compared to controls,POU2F1 was shown to be signififcantly upregulated by AngⅡ,which is itself reduced by exercise training.In vivo,POU2F1 overexpression nullified the benefits of exercise training on cardiac fibrosis.In CFs,POU2F1 promoted cardiac fibrosis.CCAAT enhancer-binding proteinβ(C/EBPβ)was predicted to be the transcription factor of POU2F1and verified using a dual-luciferase reporter assay.In vivo,exercise training activated AMP-activated protein kinase(AMPK)and alleviated the increase in C/EBPβinduced by AngⅡ.In CFs,AMPK agonist inhibited the increase in C/EBPβand POU2F1 induced by Ang II,whereas AMPK inhibitor reversed this effect.Conclusion:Exercise training attenuates AngⅡ-induced cardiac fibrosis by reducing POU2F1.Exercise training inhibits POU2F1 by activating AMPK,which is followed by the downregulation of C/EBPβ,the transcription factor of POU2F1.

Perspectives of genetic management strategy for inherited cardiovascular diseases in China

Inherited cardiovascular diseases(CVDs)threaten human health and pose an enormous economic burden worldwide.Genetic alteration is a major risk factor for many CVDs.These disorders are usually controlled by a pair of alleles,affecting offspring according to the Mendelian principle,regardless of isolated primary damage or secondary injury from other syndromes or deficiency.To date,there are hundreds of inherited CVDs.With advances in nextgeneration sequencing(NGS)technologies,rapid and accurate molecular diagnosis of patients with inherited CVDs is clinically practical.Besides,great improvements have been made in recent years,and targeted therapy and assist devices have been used in clinical practice.Yet there is still no totally efficient strategy for dealing with inherited CVDs.Accordingly.

An analysis of patients receiving emergency CAG without PCI and the value of GRACE score in predicting PCI possibilities in NSTE-ACS patients

Background There are patients who underwent emergency coronary angiography （CAG） but did not receive percutaneous coronary intervention （PCI）. The aim of this study was to analyze these reasons. Methods This is a single-center retrospective study. We recruited 201 consecutive patients who received emergency CAG but did not receive PCI. To investigate the value of the Global Registry of Acute Coronary Events （GRACE） score in predicting PC1 possibilities in non-ST segment elevation acute coronary syndrome （NSTE-ACS） pa- tients, we recruited 80 consecutive patients who presented with NSTE-ACS and received emergency CAG as well as emergency PC1. Re- sults Among the 201 patients who received emergency CAG but did not receive PCI, 26% patients had final diagnosis other than coronary heart disease. In the patients with significant coronary artery stenosis, 23 patients （11.5%） were recommended to coronary artery bypass grafting （CABG）, one patient （0.5%） refused PCI; 13 patients （6.5%） with significant thrombus burden were treated with glycoprotein IIb/IIIa receptor antagonist; 74 patients （36.8%） were treated with drug therapy because no severe stenosis （〉 70%） was present in the crime vessel. Moreover, 80 of the 201 patients were presented with NSTE-ACS （excluding those patients with final diagnosis other than coronary heart disease, excluding those patients planned for CABG treatment）, referred as non PCI NSTE-ACS. When comparing their GRACE scores with 80 consecutive patients presented with NSTE-ACS who received emergency CAG as well as emergency PCI （referred as PCI NSTE-ACS）, we found that PCI NSTE-ACS patients had significantly higher GRACE scores compared with non PCI NSTE-ACS patients. We then used Receiver Operator Characteristic Curve （ROC） to test whether the GRACE score is good at evaluating the possibilities of PCI in NSTE-ACS patients. The area under the curve was 0.854 ~ 0.030 （P 〈 0.001）, indicating good predictive value. Furthermore, we analyzed results derived from ROC statistics, and found that a GRACE score of 125.5, as a cut-off, has high sensitivity and specificity in evaluating PCI possibilities in NSTE-ACS patients. Conclusions Our findings indicate that the GRACE score has predictive value in determining whether NSTE-ACS patients would receive PCI.

Visfatin Protects Rat Pancreatic β-cells against IFN-γ-Induced Apoptosis through AMPK and ERK1/2 Signaling Pathways

Objective Interferon-γ （IFN-γ） plays an important role in apoptosis and was shown to increase the riskof diabetes. Visfatin, an adipokine, has anti-diabetic, anti-tumor, and regulating inflammatoryproperties. In this study we investigated the effect of visfatin on IFN-γ-induced apoptosis in ratpancreatic β-cells.Methods The RINm5F （rat insulinoma cell line） cells exposed to IFN-γ were treated with or withoutvisfatin. The viability and apoptosis of the cells were assessed by using MTT and flow cytometry. Theexpressions of mRNA and protein were detected by using real-time PCR and western blot analysis.Results The exposure of RINm5F cells to IFN-γ for 48 h led to increased apoptosis percentage of thecells. Visfatin pretreatment significantly increased the cell viability and reduced the cell apoptosisinduced by IFN-γ. IFN-γ-induced increase in expression of p53 mRNA and cytochrome c protein,decrease in mRNA and protein levels of anti-apoptotic protein Bcl-2 were attenuated by visfatinpretreatment. Visfatin also increased AMPK and ERK1/2 phosphorylation and the anti-apoptotic actionof visfatin was attenuated by the AMPK and ERK1/2 inhibitor.Conclusion These results suggested that visfatin protected pancreatic islet cells against IFN-γ-inducedapoptosis via mitochondria-dependent apoptotic pathway. The anti-apoptotic action of visfatin ismediated by activation of AMPK and ERK1/2 signaling molecules.

Prognostic value of coronary artery calcium score in patients with stable an-gina pectoris after percutaneous coronary intervention

Objectives To evaluate the prognostic value of the coronary artery calcium （CAC） score in patients with stable angina pectoris （SAP） who underwent percutaneous coronary intervention （PCI）. Methods A total of 334 consecutive patients with SAP who underwent first PCI following multi-slice computer tomography （MSCT） were enrolled from our institution between January 2007 and June 2012. The CAC score was calculated according to the standard Agatston calcium scoring algorithm. Complex PCI was defined as use of high pressure bal-loon, kissing balloon and/or rotablator. Procedure-related complications included dissection, occlusion, perforation, no/slow flow and emer-gency coronary artery bypass grafting. Main adverse cardiac events （MACE） were defined as a combined end point of death, non-fatal myo-cardial infarction, target lesion revascularization and rehospitalization for cardiac ischemic events. Results Patients with a CAC score〉300 （n=145） had significantly higher PCI complexity （13.1%vs. 5.8%, P=0.017） and rate of procedure-related complications （17.2%vs. 7.4%, P=0.005） than patients with a CAC score≤300 （n=189）. After a median follow-up of 22.5 months （4-72 months）, patients with a CAC score≤300 differ greatly than those patients with CAC score＆gt;300 in cumulative non-events survival rates （88.9 vs. 79.0%, Log rank 4.577, P=0.032）. After adjusted for other factors, the risk of MACE was significantly higher [hazard ratio （HR）：4.3, 95%confidence inter-val （95%CI）：2.4-8.2, P=0.038] in patients with a CAC score〉300 compared to patients with a lower CAC score. Conclusions The CAC score is an independent predictor for MACE in SAP patients who underwent PCI and indicates complexity of PCI and proce-dure-related complications.

Comparison of intraosseous access and central venous catheterization in Chinese adult emergency patients: A prospective, multicenter, and randomized study

BACKGROUND: It is challenging to establish peripheral intravenous access in adult critically patients. This study aims to compare the success rate of the first attempt, procedure time, operator satisfaction with the used devices, pain score, and complications between intraosseous(IO) access and central venous catheterization(CVC) in critically ill Chinese patients.METHODS: In this prospective clustered randomized controlled trial, eight hospitals were randomly divided into either the IO group or the CVC group. Patients who needed emergency vascular access were included. From April 1, 2017 to December 31, 2018, each center included 12 patients. We recorded the data mentioned above.RESULTS: A total of 96 patients were enrolled in the study. There were no statistically significant differences between the two groups regarding sex, age, body mass index, or operator satisfaction with the used devices. The success rates of the first attempt and the procedure time were statistically significant between the IO group and the CVC group(91.7% vs. 50.0%, P<0.001;52.0 seconds vs. 900.0 seconds, P<0.001). During the study, 32 patients were conscious. There was no statistically significant difference between the two groups regarding the pain score associated with insertion. There were statistically significant differences between the two groups regarding the pain score associated with IO or CVC infusion(1.5 vs. 0.0, P=0.044). Complications were not observed in the two groups.CONCLUSIONS: IO access is a safe, rapid, and effective technique for gaining vascular access in critically ill adults with inaccessible peripheral veins in the emergency departments.

Association between serum cartilage oligomeric matrix protein and coronary artery calcification in maintenance hemodialysis patients

Background Coronary artery calcification(CAC)is common in end-stage renal disease(ESRD)patients,and the extent of CAC is closely related to cardiovascular outcomes in ESRD patients.Cartilage oligomeric matrix protein(COMP),as a component of the vascular matrix,has been found to be an inhibitor of arterial calcification in basic studies.However,there is no clinical research on the correlation between COMP and CAC in maintenance hemodialysis(MHD)patients.The aim of this study was to explore the relationship between serum COMP levels and CAC and cardiovascular events in MHD patients.Methods Serum COMP levels were compared between 54 MHD patients and 66 healthy people.MHD patients were then divided into three groups according to the tertiles of the concentration of COMP level and were followed up for major adverse cardiac events(MACEs),which were defined as a combined end point of new onset angina pectoris,nonfatal myocardial infarction,heart failure,coronary artery revascularization,hospitalization due to angina pectoris and all-cause deaths.The CAC score was calculated based on computed tomography scans.Results The serum COMP level in MHD patients was significantly higher than that in the general population[984.23(248.43-1902.61)ng/mL vs.219.01(97.26-821.92)ng/mL,P<0.01].Serum COMP levels were positively correlated with CAC(r=0.313,P=0.021)and serum parathyroid hormone in MHD patients(r=0.359,P<0.01).Linear regression suggested that after adjusting for age,fasting blood glucose(Glu)and glycosylated hemoglobin(HbAlc),CAC score was an independent predictor in the final model for COMP level(β=0.424,t=3.130,P<0.01).The receiver operating characteristic(ROC)curve showed that COMP≥994 mg/mL had 68.0%sensitivity and 72.4%specificity for the prediction of severe CAC[area under the curve(AUC):0.674,P=0.030,95%CI:0.526-0.882].After a median follow-up of 16 months(8-24 months),there was no difference in the incidence rate of MACEs between the upper,middle and lower serum COMP groups.Conclusions Our study found that MHD patients have higher levels of circulating COMP than controls.The serum COMP level is positively correlated with CAC score and could be used as a biomarker of severe CAC in MHD patients.However,there is no obvious correlation between serum COMP levels and the incidence of cardiovascular events.

A case of applying left bundle branch pacing combined with atrioventricular node ablation to treat atrial fibrillation-induced heart failure

The core treatment of rapid arrhythmiainduced heart failure(HF)is to control the ventricular rate to an optimized lower level,which is usually achieved with various anti-arrhythmic drugs.However,arrhythmias may not respond well to pharmaceutical treatment for various reasons.Iatrogenic atrioventricular(AV)node ablation needs to be performed under these extreme conditions to lower the patient’s heart rate.

Interleukin-13 promotes cellular senescence through inducing mitochondrial dysfunction in IgG4-related sialadenitis

Immunoglobulin G4-related sialadenitis(IgG4-RS)is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully understood.The aim of this study was to explore the role and mechanism of interleukin-13(IL-13)in the cellular senescence during the progress of IgG4-RS.We found that the expression of IL-13 and IL-13 receptorα1(IL-13Rα1)as well as the number of senescent cells were significantly higher in the submandibular glands(SMGs)of IgG4-RS patients.IL-13 directly induced senescence as shown by the elevated activity of senescence-associatedβ-galactosidase(SA-β-gal),the decreased cell proliferation,and the upregulation of senescence markers(p53 and p16)and senescence-associated secretory phenotype(SASP)factors(IL-1βand IL-6)in SMG-C6 cells.Mechanistically,IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6(p-STAT6)and mitochondrial-reactive oxygen species(mt ROS),while decreased the mitochondrial membrane potential,ATP level,and the expression and activity of superoxide dismutase 2(SOD2).Notably,the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger Mito TEMPO.Moreover,IL-13 increased the interaction between p-STAT6 and c AMP-response element binding protein(CREB)-binding protein(CBP)and decreased the transcriptional activity of CREB on SOD2.Taken together,our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6–CREB–SOD2-dependent pathway in IgG4-RS.

Aging in China: perspectives on public health

In line with the worldwide trend in population aging,China has stepped into an aging society since 2000.The outstanding features of aging,including a large proportion of the older population,rapid growth,dramatic expansion of the oldest-old,and uneven aging distribution,have put China in a unique position.Besides,older population is expanding in parallel with the escalating burden of disease,high prevalence of disability,and low social involvement.However,China is not prepared to solve these problems in terms of the economy,awareness,geriatric care system,geriatric team,social security,or age-friendly environment.From the perspective of public health,we summarized the major challenges and proposed the following policy recommendations:(1)strengthening the top-level design and building a"government-leading,multi-sectoral-cooperating,and society-participating"pattern;(2)enhancing health services by implementing the"comprehensive health"strategy;(3)developing home and community care,coordinately enhance institutional care,promote integration of medical and care systems,and establish a multidimensional tailored care system;(4)optimizing geriatric the supporting system,included the construction of geriatric team and the long-term care insurance system;and(5)establishing a physical and socially age-friendly environment.

Autonomic reinnervation and functional regeneration in autologous transplanted submandibular glands in patients with severe keratoconjunctivitis sicca

Autologous submandibular gland（SMG） transplantation has been proved to ameliorate the discomforts in patients with severe keratoconjunctivitis sicca. The transplanted glands underwent a hypofunctional period and then restored secretion spontaneously.This study aims to investigate whether autonomic nerves reinnervate the grafts and contribute to the functional recovery, and further determine the origin of these nerves. Parts of the transplanted SMGs were collected from the epiphora patients, and a rabbit SMG transplantation model was established to fulfill the serial observation on the transplanted glands with time. The results showed that autonomic nerves distributed in the transplanted SMGs and parasympathetic ganglionic cells were observed in the stroma of the glands. Low-dense and unevenly distributed cholinergic axons, severe acinar atrophy and fibrosis were visible in the patients＇ glands 4–6 months post-transplantation, whereas the cholinergic axon density and acinar area were increased with time. The acinar area or the secretory flow rate of the transplanted glands was statistically correlated with the cholinergic axon density in the rabbit model, respectively. Meanwhile, large cholinergic nerve trunks were found to locate in the temporal fascia lower to the gland, and sympathetic plexus concomitant with the arteries was observed both in the adjacent fascia and in the stroma of the glands. In summary, the transplanted SMGs are reinnervated by autonomic nerves and the cholinergic nerves play a role in the morphological and functional restoration of the glands. Moreover, these autonomic nerves might originate from the auriculotemporal nerve and the sympathetic plexus around the supplying arteries.

Extracting and Measuring Uncertain Biomedical Knowledge from Scientific Statements

Purpose:Given the information overload of scientific literature,there is an increasing need for computable biomedical knowledge buried in free text.This study aimed to develop a novel approach to extracting and measuring uncertain biomedical knowledge from scientific statements.Design/methodology/approach:Taking cardiovascular research publications in China as a sample,we extracted subject-predicate-object triples(SPO triples)as knowledge units and unknown/hedging/conflicting uncertainties as the knowledge context.We introduced information entropy(IE)as potential metric to quantify the uncertainty of epistemic status of scientific knowledge represented at subject-object pairs(SO pairs)levels.Findings:The results indicated an extraordinary growth of cardiovascular publications in China while only a modest growth of the novel SPO triples.After evaluating the uncertainty of biomedical knowledge with IE,we identified the Top 10 SO pairs with highest IE,which implied the epistemic status pluralism.Visual presentation of the SO pairs overlaid with uncertainty provided a comprehensive overview of clusters of biomedical knowledge and contending topics in cardiovascular research.Research limitations:The current methods didn’t distinguish the specificity and probabilities of uncertainty cue words.The number of sentences surrounding a given triple may also influence the value of IE.Practical implications:Our approach identified major uncertain knowledge areas such as diagnostic biomarkers,genetic polymorphism and co-existing risk factors related to cardiovascular diseases in China.These areas are suggested to be prioritized;new hypotheses need to be verified,while disputes,conflicts,and contradictions need to be settled.Originality/value:We provided a novel approach by combining natural language processing and computational linguistics with informetric methods to extract and measure uncertain knowledge from scientific statements.

Pulmonary hypertension concurrent with pericardial effusion and superior vena cava syndrome: who is the initiator?

The diagnosis of pulmonary hypertension(PH) should be made by combining clinical manifestations and echocardiographic probability.[1] Following the confirmation of PH, the classification should begin with the more common groups [group 2(PH due to left heart disease) and group 3(PH due to lung diseases and/or hypoxia)], then group 4(chronic thromboembolic PH and other pulmonary artery obstructions) and finally group 1(pulmonary arterial hypertension) and group 5(PH with unclear and/or multifactorial mechanisms).[1] In this case, we demonstrate a rare scenario of obstruction-caused group 4 PH.

Assessment of causal direction between thyroid function and cardiometabolic health:a Mendelian randomization study

BACKGROUND Growing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular metabolism.However,the causal relationship of thyroid function and cardiometabolic health remains partly unknown.METHODS The Mendelian randomization(MR)was used to test genetic,potentially causal relationships between instrumental variables and cardiometabolic traits.Genetic variants of free thyroxine(FT4)and thyrotropin(TSH)levels within the reference range were used as instrumental variables.Data for genetic associations with cardiometabolic diseases were acquired from the genome-wide association studies of the FinnGen,CARDIoGRAM and CARDIoGRAMplusC4D,CHARGE,and MEGASTROKE.This study was conducted using summary statistic data from large,previously described cohorts.Association between thyroid function and essential hypertension(EHTN),secondary hypertension(SHTN),hyperlipidemia(HPL),type 2 diabetes mellitus(T2DM),ischemic heart disease(IHD),myocardial infarction(MI),heart failure(HF),pulmonary heart disease(PHD),stroke,and non-rheumatic valve disease(NRVD)were examined.RESULTS Genetically predicted FT4 levels were associated with SHTN(odds ratio=0.48;95%CI=0.04−0.82,P=0.027),HPL(odds ratio=0.67;95%CI=0.18−0.88,P=0.023),T2DM(odds ratio=0.80;95%CI=0.42−0.86,P=0.005),IHD(odds ratio=0.85;95%CI=0.49−0.98,P=0.039),NRVD(odds ratio=0.75;95%CI=0.27−0.97,P=0.039).Additionally,genetically predicted TSH levels were associated with HF(odds ratio=0.82;95%CI=0.68−0.99,P=0.042),PHD(odds ratio=0.75;95%CI=0.32−0.82,P=0.006),stroke(odds ratio=0.95;95%CI=0.81−0.97,P=0.007).However,genetically predicted thyroid function traits were not associated with EHTN and MI.CONCLUSIONS Our study suggests FT4 and TSH are associated with cardiometabolic diseases,underscoring the importance of the pituitary-thyroid-cardiac axis in cardiometabolic health susceptibility.

Animal models of coronary heart disease

Cardiovascular disease,predominantly coronary heart disease and stroke,leads to high morbidity and mortality not only in developed worlds but also in underdeveloped regions.The dominant pathologic foundation for cardiovascular disease is atherosclerosis and,as to coronary heart disease,coronary atherosclerosis and resulting lumen stenosis,even total occlusions.In translational research,several animals,such as mice,rabbits and pigs,have been used as disease models of human atherosclerosis and related cardiovascular disorders.However,coronary lesions are either naturally rare or hard to be fast induced in these models,hence,coronary heart disease induction mostly relies on surgical or pharmaceutical interventions with no or limited primary coronary lesions,thus unrepresentative of human coronary heart disease progression and pathology.In this review,we describe the progress of animal models of coronary heart disease following either spontaneous or diet-accelerated coronary lesions.

Short-term exposure to ambient ozone associated with cardiac arrhythmias in healthy adults

Objective The exact biological mechanism whereby exposure to ambient ozone(O3)may contribute to clinical onset of cardiovascular events remains unclear.In this study,we aim to examine the impacts of O3 exposure on cardiac arrhythmias and potential pathways involved through autonomic dysfunction and myocardial injury.Methods Seventy-three non-smoking healthy adults were followed with 4 repeated measurements of 24-hour ambulatory arrhythmias,heart rate variability,ST-segment deviation,and blood pressure(BP)in Beijing,China,2014‒2016.Generalized additive mixed models coupled with distributed lag nonlinear models were constructed to evaluate the associations and potential interlinks between O3 exposure and outcome measurements.Results During the study period,24-hour average concentrations of ambient O3 were 47.4µg/m3(ranging from 1.0 to 165.9µg/m3).Increased risks of premature ventricular contraction and ventricular tachycardia were associated with interquartile range increases in O3 exposure during the last 5 days before each participant's clinic visit,with relative risks of 2.14(95%confidence interval[CI]:1.95 to 2.32)and 5.47(95%CI:3.51 to 7.43),respectively.Mediation analyses further showed that sympathetic activation,parasympathetic inhibition,and elevated BP levels,as well as heightened risks of ST-segment depression could mediate up to 47.74%of the risks of arrhythmias attributable to O3 exposure.Conclusion Our results suggest that short-term exposure to ambient O3 could prompt the genesis of arrhythmias partially through worsening autonomic function and myocardial burden.