Regulatory role of peroxynitrite in advanced glycation end products mediated diabetic cardiovascular complications

The Advanced Glycation End Products(AGE)binding with its receptor can increase reactive oxygen species(ROS)generation through specific signaling mediators.The effect of superoxide(O2-)and O2-mediated ROS and reactive nitrogen species depends on their concentration and location of formation.Nitric oxide(NO)has anti-inflammatory and anticoagulant properties and a vasodilation effect,but NO can be deactivated by reacting with O_(2)^(-).This reaction between NO and O2-produces the potent oxidant ONOO−.Therefore,ONOO-'s regulatory role in AGEs in diabetic cardiovascular complications must considered as a regulator of cardiovascular complications in diabetes.

Advanced glycation end products:Key mediator and therapeutic target of cardiovascular complications in diabetes

The incidence of type 2 diabetes mellitus is growing in epidemic proportions and has become one of the most critical public health concerns.Cardiovascular complications associated with diabetes are the leading cause of morbidity and mortality.The cardiovascular diseases that accompany diabetes include angina,myocardial infarction,stroke,peripheral artery disease,and congestive heart failure.Among the various risk factors generated secondary to hyperglycemic situations,advanced glycation end products(AGEs)are one of the important targets for future diagnosis and prevention of diabetes.In the last decade,AGEs have drawn a lot of attention due to their involvement in diabetic pathophysiology.AGEs can be derived exogenously and endogenously through various pathways.These are a nonhomogeneous,chemically diverse group of compounds formed nonenzymatically by condensation between carbonyl groups of reducing sugars and free amino groups of protein,lipids,and nucleic acid.AGEs mediate their pathological effects at the cellular and extracellular levels by multiple pathways.At the cellular level,they activate signaling cascades via the receptor for AGEs and initiate a complex series of intracellular signaling resulting in reactive oxygen species generation,inflammation,cellular proliferation,and fibrosis that may possibly exacerbate the damaging effects on cardiac functions in diabetics.AGEs also cause covalent modifications and cross-linking of serum and extracellular matrix proteins;altering their structure,stability,and functions.Early diagnosis of diabetes may prevent its progression to complications and decrease its associated comorbidities.In the present review,we recapitulate the role of AGEs as a crucial mediator of hyperglycemia-mediated detrimental effects in diabetes-associated complications.Furthermore,this review presents an overview of future perspectives for new therapeutic interventions to ameliorate cardiovascular complications in diabetes.

Cardiovascular complications following medical termination of pregnancy: An updated review

BACKGROUND Around 1 million cases of medical termination of pregnancy(MTP)take place yearly in the United States of America with around 2 percent of this population developing complications.The cardiovascular(CVD)complications occurring post MTP or after stillbirth is not very well described.AIM To help the reader better understand,prepare,and manage these complications by reviewing various cardiac comorbidities seen after MTP.METHODS We performed a literature search in PubMed,Medline,RCA,and google scholar,using the search terms“abortions”or“medical/legal termination of pregnancy”and“cardiac complications”or“cardiovascular complications”.RESULTS The most common complications described in the literature following MTP were infective endocarditis(IE)(n=16),takotsubo cardiomyopathy(TTC)(n=7),arrhythmias(n=5),and sudden coronary artery dissection(SCAD)(n=4).The most common valve involved in IE was the tricuspid valve in 69%(n=10).The most observed causative organism was group B Streptococcus in 81%(n=12).The most common type of TTC was apical type in 57%(n=4).Out of five patients de veloping arrhythmia,bradycardia was the most common and was seen in 60%(3/5)of the patients.All four cases of SCAD-P type presented as acute coronary syndrome 10-14 d post termination of pregnancy with predominant involvement of the right coronary artery.Mortality was only reported following IE in 6.25%.Clinical recovery was reported consistently after optimal medical management following all these complications.CONCLUSION In conclusion,the occurrence of CVD complications following pregnancy termination is infrequently documented in the existing literature.In this review,the most common CVD complication following MTP was noted to be IE and TTC.

Frequency of the Cardiovascular Complications during the Chronic Renal Insufficiency with the Service of Nephrology of the National Hospital Donka

Introduction: Cardiovascular disease has become a major concern for the nephrologist as it is the leading cause of morbidity and mortality in patients with chronic kidney disease, and affects all stages of the disease, including the earliest stages of the disease. The goal of this work was to determine the frequency of cardiovascular complications during chronic kidney failure. Patients and methods: This was a six-month, descriptive cross-sectional study from March 01 to August 31, 2018. It covered all patients with chronic kidney disease hospitalized in the ward during the study period. Included were all chronic kidney failure patients with at least one cardiac and/or vascular complication diagnosed either on clinical examination, and/or paraclinical examination (Electrocardiogram or cardiac ultrasound, vessel echodoppler, scan). Results: During the study period, 84 out of 378 patients or 22.22% had at least one cardiovascular complication. Cardiovascular complications were hypertrophy of the left ventricle with 49/84 (44 at Electrocardiogram and 5 at cardiac echodoppler), valvulopathy with 33.33%, stroke with 50% of cases, obliterating arterial disease of the lower limbs 25%, hypokinetic dilated cardiomyopathy with 9/36 cases and pericarditis with 2/36. Conclusion: Cardiovascular complications affect both sexes and all ages. They were dominated by enlarged left ventricle, valvulopathy and dilated cardiomyopathy.

Association between preoperative high sensitive troponin I levels and cardiovascular events after hip fracture surgery in the elderly

Objective Cardiovascular complications contribute to postoperative morbidity and mortality in elderly hip fracture patients. Limited data are available regarding which preoperative risk factors predict cardiovascular course following hip fracture surgery （HFS）. We used high sensitive troponin I （hs-TnI） assays and clinical parameters to identify preoperative risk factors associated with major adverse cardiac events （MACE） in elderly hip frac^u＇e patients. Method From August 2014 to November 2016, 575 patients with hip fracture were enrolled in a retrospective, single-center registry. A total of 262 of these patients underwent HFS and hs-TnI assays. MACE was defined as postoperative all-cause deaths, heart failure （HF）, new-onset atrial fibrillation （AF）, myocardial infarction （MI） and cardiovascular re-hospitalization that occurred within 90 days postoperative. Results Of 262 HFS patients, MACE developed following HFS in 65 （24.8%）. Patients with MACE were older and had higher rates of renal insufficiency, coronary artery disease, prior HF, low left ventricular ejection fraction and use of beta blockers; higher levels of hs-Tnl and N-terminal pro-brain natriuretic peptide （NT-proBNP） and higher revised cardiac risk index. A preoperative hs-TnI≥ 6.5 ng/L was associated with high risk of postoperative HF, new-onset AF and MACE. In multivariable analysis, pre-operative independent predictors for MACE were age 〉 80 years [adjusted hazard ratio （HR）： 1.79, 95% confident interval （CI）： 1.03-3.13, P = 0.04], left ventricular ejection fraction （LVEF） 〈 50% （adjusted HR： 3.17, 95% CI： 1.47-5.82, P 〈 0.01） and hs-TnI 〉 6.5 ng/L （adjusted HR： 3.75, 95% CI： 2.09~5.17, P 〈 0.01）. Conclusion In elderly patients with hip fracture who undergo HFS, a preoperative assessment of hs-TnI may help the risk refinement of cardiovascular complications.

Diabetes, sleep apnea, obesity and cardiovascular disease: Why not address them together?

Obesity, sleep apnea, diabetes and cardiovascular diseases are some of the most common diseases encountered by the worldwide population, with high social and economic burdens. Significant emphasis has been placed on obtaining blood pressure, body mass index, and placing importance on screening for signs and symptoms pointing towards cardiovascular disease. Symptoms related to sleep, or screening for sleep apnea has been overlooked by cardiac, diabetic, pulmonary and general medicine clinics despite recommendations for screening by several societies. In recent years, there is mounting data where obesity and obstructive sleep apnea sit at the epicenter and its control can lead to improvement and prevention of diabetes and cardiovascular complications. This editorial raises questions as to why obstructive sleep apnea screening should be included as yet another vital sign during patient initial inpatient or outpatient visit.

J24924 possesses cardiovascular and renal protective effects on pristane-induced lupus through inhibition of RhoA/Rho kinase pathway in mice

OBJECTIVE To explore whether J24924could prevent the development of pristane-induced lupus in a mouse model,and whether it could protect renal and lower the cardiovascular risk.METHODS The effect of J24924 was assessed in female BALB/c mice intraperitoneal injected with 0.5 m L of pristane,and serum autoantibodies were tested every month,blood pressure wasmeasured every 2 months,while serum inflammatory markers,spleen pathologic characteristics,renal injury and vascular function were observed at 6 month.RESULTS J24924 could decrease serum autoantibodies and serum inflammatory markers in the SLE mice and improved the spleen pathologic characteristics,and at the same time improved the renal injury and decreased inflammatory responses in kidneys,reduced blood pressure and improved vascular endothelial function.Western blotting assays revealed that inhibition for the activation of NF-κB and Rho/ROCKs signaling pathways and the downstream signaling molecules might be the potential mechanisms of J24924.CONCLUSION Our findings suggestthat therapy of J24924 may be a strategy to prevent SLE and ameliorate associated kidney and cardiovascular complications.

Antihypertensive prescribing patterns in non-dialysis dependent chronic kidney disease:Findings from the Salford Kidney Study

BACKGROUND Hypertension is commonly observed in patients living with chronic kidney disease(CKD).Finding an optimal treatment regime remains challenging due to the complex bidirectional cause-and-effect relationship between hypertension and CKD.There remains variability in antihypertensive treatment practices.AIM To analyze data from the Salford Kidney Study database in relation to antihypertensive prescribing patterns amongst CKD patients.METHODS The Salford Kidney Study is an ongoing prospective study that has been recruiting CKD patients since 2002.All patients are followed up annually,and their medical records including the list of medications are updated until they reach study endpoints[starting on renal replacement therapy or reaching estimated glomerular filtration rate(eGFR)expressed as mL/min/1.73 m2≤10 mL/min/1.73 m2,or the last follow-up date,or data lock on December 31,2021,or death].Data on antihypertensive prescription practices in correspondence to baseline eGFR,urine albumin-creatinine ratio,primary CKD aetiology,and cardiovascular disease were evaluated.Associations between patients who were prescribed three or more antihypertensive agents and their clinical outcomes were studied by Cox regression analysis.Kaplan-Meier analysis demonstrated differences in survival probabilities.RESULTS Three thousand two hundred and thirty non-dialysis-dependent CKD patients with data collected between October 2002 and December 2019 were included.The median age was 65 years.A greater proportion of patients were taking three or more antihypertensive agents with advancing CKD stages(53%of eGFR≤15 mL/min/1.73 m2 vs 26%of eGFR≥60 mL/min/1.73 m2,P<0.001).An increased number of patients receiving more classes of antihypertensive agents was observed as the urine albumin-creatinine ratio category increased(category A3:62%vs category A1:40%,P<0.001),with the upward trends particularly noticeable in the number of individuals prescribed renin angiotensin system blockers.The prescription of three or more antihypertensive agents was associated with all-cause mortality,independent of blood pressure control(hazard ratio:1.15;95%confidence interval:1.04-1.27,P=0.006).Kaplan-Meier analysis illustrated significant differences in survival outcomes between patients with three or more and those with less than three antihypertensive agents prescribed(log-rank,P<0.001).CONCLUSION Antihypertensive prescribing patterns in the Salford Kidney Study based on CKD stage were consistent with expectations from the current United Kingdom National Institute of Health and Care Excellence guideline algorithm.Outcomes were poorer in patients with poor blood pressure control despite being on multiple antihypertensive agents.Continued research is required to bridge remaining variations in hypertension treatment practices worldwide.

Clinical correlates of hypotension in patients with acute organophosphorus poisoning

BACKGROUND:The aim of the present study is to describe the clinical correlates of hypotension and its associated outcomes in patients with acute organophosphorus poisoning(AOPP).METHODS:In this retrospective cohort study,we analyzed data pertaining to 871 patients with AOPP who were treated at two hospitals.Data from hypotensive and non-hypotensive patients were compared to identify clinical correlates of hypotension.We also evaluated the association between clinical parameters(including hypotension)and in-hospital mortality.RESULTS:The incidence of hypotension in AOPP patients was 16.4%.Hypotensive patients showed signifi cantly higher in-hospital mortality(1.1%vs.39.9%,P<0.001).Advanced age(odds ratio[OR]1.25,95%confi dence interval[CI]1.08–1.44),history of diabetes(OR 2.65,95%CI 1.14–5.96),and increased white blood cell count(OR 1.06,95%CI 1.03–1.09),plasma cholinesterase(OR 0.91,95%CI 0.84–0.94),plasma albumin(OR 0.88,95%CI 0.85–0.92),serum amylase(OR 1.01,95%CI 1.01–1.02),and blood pH(OR 0.64,95%CI 0.54–0.75)were signifi cantly associated with hypotension.After adjusting for potential confounders,hypotension was associated with increased in-hospital mortality(hazard ratio 8.77–37.06,depending on the controlled variables).CONCLUSIONS:Hypotension is a common complication of AOPP and is associated with increased in-hospital mortality.Advanced age,history of diabetes,and changes in laboratory parameters were associated with hypotension in AOPP patients.

Glucagon-like-1 receptor agonists and sodium/glucose cotransporter-2 inhibitors combination—are we exploiting their full potential in a real life setting?

BACKGROUND The sodium/glucose cotransporter-2 inhibitors(SGLT-2i)and glucagon-like-1 receptor agonists(GLP-1RA)are antidiabetic agents effective both in hemoglobin A1c(HbA1c)reduction(with a low risk of hypoglycemia)and cardiovascular event prevention.In patients with type 2 diabetes,the add-on value of combination therapy of GLP-1RA and an SGLT-2i seems promising.AIM To investigate whether the efficacy of GLP-1RA and SGLT-2i combination observed in randomized controlled trials translates into therapeutic benefits in the Croatian population during routine clinical practice and follow-up.METHODS We included 200 type 2 diabetes patients with poor glycemic control and analyzed the effects of treatment intensification with(1)GLP-1RA on top of SGLT-2i,(2)SGLT-2i on top of GLP-1RA compared to(3)simultaneous addition of both agents.The primary study endpoint was the proportion of participants with HbA1c<7.0%and/or 5%bodyweight reduction.Secondary outcomes included changes in fasting plasma glucose(FPG),prandial plasma glucose,lowdensity lipoprotein cholesterol,estimated glomerular filtration rate(eGFR),and cardiovascular(CV)incidents assessment over a follow-up period of 12 mo.RESULTS The majority of patients were over 65-years-old,had diabetes duration for more than 10 years.The initial body mass index was 39.41±5.49 kg/m2 and HbA1c 8.32±1.26%.Around half of the patients in all three groups achieved target HbA1c below 7%.A more pronounced decrease in the HbA1c seen with simultaneous SGLT-2i and GLP-1RA therapy was a result of higher baseline HbA1c and not the effect of initiating combination therapy.The number of patients achieving FPG below 7.0 mmol/L was significantly higher in the SGLT-2i group(P=0.021),and 5%weight loss was dominantly achieved in the simultaneous therapy group(P=0.044).A composite outcome(reduction of HbA1c below 7%(53 mmol/mol)with 5%weight loss)was achieved in 32.3%of total patients included in the study.Only 18.2%of patients attained composite outcome defined as HbA1c below 7%(53 mmol/mol)with 5%weight loss and low-density lipoprotein cholesterol<2.5 mmol/L.There were no significant differences between treatment groups.No differences were observed regarding CV incidents or eGFR according to treatment group over a follow-up period.CONCLUSION Combination therapy with GLP-1RA and SGLT-2i is effective in terms of metabolic control,although it remains to be determined whether simultaneous or sequential intensification is better.

Role of cardiac magnetic resonance imaging in the diagnosis and management of COVID-19 related myocarditis: Clinical and imaging considerations

There is a growing evidence of cardiovascular complications in coronavirusdisease 2019 (COVID-19) patients. As evidence accumulated of COVID-19 mediatedinflammatory effects on the myocardium, substantial attention has beendirected towards cardiovascular imaging modalities that facilitate this diagnosis.Cardiac magnetic resonance imaging (CMRI) is the gold standard for thedetection of structural and functional myocardial alterations and its role inidentifying patients with COVID-19 mediated cardiac injury is growing. Despiteits utility in the diagnosis of myocardial injury in this population, CMRI’s impacton patient management is still evolving. This review provides a framework for theuse of CMRI in diagnosis and management of COVID-19 patients from theperspective of a cardiologist. We review the role of CMRI in the management ofboth the acutely and remotely COVID-19 infected patient. We discuss patientselection for this imaging modality;T1, T2, and late gadolinium enhancementimaging techniques;and previously described CMRI findings in other cardiomyopathieswith potential implications in COVID-19 recovered patients.

SARS-CoV-2 infection and diabetes:Pathophysiological mechanism of multi-system organ failure

Since the discovery of the coronavirus disease 2019 outbreak,a vast majority of studies have been carried out that confirmed the worst outcome of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in people with preexisting health conditions,including diabetes,obesity,hypertension,cancer,and cardiovascular diseases.Likewise,diabetes itself is one of the leading causes of global public health concerns that impose a heavy global burden on public health as well as socio-economic development.Both diabetes and SARS-CoV-2 infection have their independent ability to induce the pathogenesis and severity of multi-system organ failure,while the co-existence of these two culprits can accelerate the rate of disease progression and magnify the severity of the disease.However,the exact pathophysiology of multi-system organ failure in diabetic patients after SARS-CoV-2 infection is still obscure.This review summarized the organ-specific possible molecular mechanisms of SARS-CoV-2 and diabetesinduced pathophysiology of several diseases of multiple organs,including the lungs,heart,kidneys,brain,eyes,gastrointestinal system,and bones,and subsequent manifestation of multi-system organ failure.

MitochondrialtRNA^(leu(UUR)) Gene Mutation and the DecreasedActivity of Cytochrom e c Oxidase in Preeclam psia

To explore the roles of mitochondria tRNA leu(UUR) gene mutation at nucleotide 3243 and the activity of cytochrome c oxidase in pathogenesis of preeclampsia, 57 patients with preeclampsia and 60 normotension pregnancy women were screened for tRNA leu(UUR) nt3243 A→G mutation with the method of polymers chain reaction (PCR) and restriction fragment length polymorphism. Cytochrome c oxidase activity was determined by measuring the rate of cyanide sensitive oxidation of reduced cytochrome c using luminosity photographer. The results showed that cytochrome c oxidase activity was significantly lower in the preeclampsia group (0.30±0.39/min, n = 32) than that in the controls (0.73±0.54/min, n = 26, P <0.01). The mitochondria DNA mutation at position 3243 was not found in our series. The results suggested that the decreased activity of cytochrome c oxidase might impair the energy production, leading to the mitochondria dysfunction and placenta dysfunction in preeclampsia patients. Mitochondria dysfunction may be involved in the pathogenesis of preeclampsia. The mutation of mitochondria DNA may not be the common contributor of preeclampsia in our series.

Outcome and risk factors of early onset severe preeclampsia

Background Early onset severe preeclampsia is a specific type of severe preeclampsia, which causes high morbidity and mortality of both mothers and fetus. This study aimed to investigate the clinical definition, features, treatment, outcome and risk factors of early onset severe preeclampsia in Chinese women. Methods Four hundred and thirteen women with severe preeclampsia from June 2006 to June 2009 were divided into three groups according to the gestational age at the onset of preeclampsia as follows： group A （less than 32 weeks, 73 cases）, group B ,（between 32 and 34 weeks, 71 cases）, and group C （greater than 34 weeks, 269 cases）. The demographic characteristics of the subjects, complications, delivery modes and outcome of pregnancy were analyzed retrospectively. Results The systolic blood pressure at admission and the incidence of severe complications were significantly lower in group C than those in groups A and B, prolonged gestational weeks and days of hospitalization were significantly shorter in group C than those in groups A and B. Liver and kidney dysfunction, pleural and peritoneal effusion, placental abruption and postpartum hemorrhage were more likely to occur in group A compared with the other two groups. Twenty-four-hour urine protein levels at admission, intrauterine fetal death and days of hospitalization were risk factors that affected complications of severe preeclampsia. Gestational week at admission and delivery week were also risk factors that affected perinatal outcome. Conclusions Early onset severe preeclampsia should be defined as occurring before 34 weeks, and it is featured by more maternal complications and a worse perinatal prognosis compared with that defined as occurring after 34 weeks. Independent risk factors should be used to tailor the optimized individual treatment plan, to balance both maternal and neonatal safety.