Lower Extremity Arterial Disease in Patients with Type 2 Diabetes: Prevalence and Associated Factors at the Libreville University Hospital Center

Introduction: Lower extremity arterial disease in diabetic patients has distinct characteristics. Objectives: To study the hospital frequency of lower extremity arterial disease and identify associated factors in diabetic patients at the Libreville University Hospital Center (CHUL). Materials and Methods: This was a cross-sectional study conducted from July 1, 2023, to January 31, 2024, in the endocrinology department of the CHUL. All patients with type 2 diabetes over the age of 18 admitted to this department, regardless of the reason for hospitalization, who provided informed consent, were included. Socio-demographic data and cardiovascular risk factors were recorded. Personal and family cardiovascular history and functional symptoms were investigated. The physical examination included measuring blood pressure, heart rate, and the ankle-brachial index in all patients. Results: A total of 219 patients were included, of whom 75 had lower extremity arterial disease, representing a prevalence of 34.24%. It was compensated in 28 cases (37.33%) and decompensated in 39 patients (52%). In eight cases (10.67%), there was critical chronic ischemia. Cardiovascular risk factors associated with diabetes were physical inactivity (89.5%), hypertension (55.25%), overweight (49.77%), obesity (22.84%), and smoking (10.04%). In multivariate analysis, only hypertension (OR = 2.09;95% CI: 1.05 - 4.17;p = 0.035) and LDL cholesterol (OR = 2.75;95% CI: 1.10 - 6.85;p = 0.03) were significantly associated with lower extremity arterial disease in diabetics at the University Hospital of Libreville. Conclusion: Lower extremity arterial disease is common in diabetic patients at the University Hospital of Libreville. It is often asymptomatic, thus requiring systematic screening.[-rId11-]

PREVALENCE AND RISK FACTORS OF PERIPHERAL ARTERIAL DISEASE IN DIABETIC PATIENTS OVER 50 YEARS OLD IN CHINA

Objective To investigate the prevalence of peripheral arterial disease (PAD) in China type 2 diabetic patients and to demonstrate the relationships between putative risk factors and PAD. Methods In total 1 397 type 2 diabetic patients aged 50 years and older were enrolled and determined ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) in 15 Class III Grade A hospitals in 7 major cities of China. Results Mean patient age was 63.7±8.2 years and mean duration of diabetes mellitus was 9.39±7.4 years. Two hundreds and seventy-two (19.47%) patients were diagnosed as PAD by ABI <0.9, 122 (18.37%) in male and 150 (20.46%) in female. PAD patients had a significantly longer duration of diabetes mellitus, higher hemoglobin Alc, and a significantly lower mean body mass index than non-PAD ones. Aging, smoking, and systolic blood pressure were found to be positively related with the prevalence of PAD. In terms of lipid profiles, no variable was found to relate with PAD. Notably, baPWV showed as the same significant guiding index for PAD, almost matched with ABI. Conclusions PAD is a common complication in China type 2 diabetic patients. Therefore, PAD screening and treatment should be emphasized for diabetic patients with high risk factors.

Association between Free Triiodothyronine Levels and Peripheral Arterial Disease in Euthyroid Participants

This current cross-sectional study investigates the relationship between thyroid hormones and peripheral artery disease （PAD） among euthyroid Chinese population aged 40 years and above. Serum free triiodothyronine （FT3）, free thyroxin （FT4）, thyroid-stimulating hormone （TSH）, and thyroid antibodies were measured.

An evaluation of the arterial occlusions in peripheral arterial disease by 64-detector multi-slice CT angiography: DSA correlation

Objective: Evaluation of peripheral arterial disease with 64-detector multi-slice CT angiography (MDCT- A) and comparison of the results with the results of digital subtraction angiography (DSA), a standard reference. Materials and Method: The written informed consent of the patients and ethics committee approval were obtained. The retrospective study group consisted of 28 patients with a diagnosis of peripheral arterial disease. Using 64-MDCT-A, the arterial tree of the lower extremity was evaluated for the presence of steno-occlusive lesions that might have led to luminal stenosis. The diagnostic reliability of 64-MDCT- A was calculated and compared with that of DSA. Findings: In the segment-based analysis, the sensitivity, specificity, and reliability rates of 64-MDCT angiography in determining significant stenoses were 97.7%, 97%, and 97.3%, respectively. The Kappa co-efficiency for compatibility between 64-MDCT-A and DSA methods in grading stenosis was calculated as 0.896

Peripheral arterial disease:leading us back to the heart

Peripheral arterial disease remains an afterthought among many clinicians, including specialists in cardiovascular diseases. In this issue, Sim et al.1……

Risk factors and ankle brachial indexes in cerebral infarction combined with peripheral arterial disease

BACKGROUND: Ankle brachial index (ABI) is widely involved in researches and clinical application of peripheral vascular injury of patients with diabetes mellitus (DM); however, the application in cerebral infarction (CI) is rare. OBJECTIVE: To investigate the possible risk factor of cerebral infarction plus peripheral arterial disease (PAD), compare metabolic characteristics of patients who having CI plus PAD or only having CI, and understand the significance of ABI on screening and diagnosing CI plus PAD of lower limb. DESIGN: Contrast observation based on CI patients. SETTING: Department of Neurology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region. PARTICIPANTS: A total of 124 CI patients were selected from Department of Neurology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region from July 2005 to April 2006, including 72 males and 52 females aged from 45 to 88 years. All patients met the diagnostic criteria of cerebrovascular disease established by National Academic Conference of Cerebrovascular Diseases in 1995 and determined as cerebral infarction with MRI or CT examination. All patients provided informed consent. There were 46 cases (37.2%) with CI plus PAD and 78 cases (62.8%) only with CI. METHODS: Blood pressure of bilateral ankles and upper extremities was measured at plain clinostatism with DINAMAP blood pressure monitor (GE Company). The ratio between average systolic pressure of lateral ankle and average systolic pressure of both upper extremities was regarded as ABI. The normal ABI was equal to or more than 0.9. If ABI < 0.9 occurred at one side, patients were diagnosed as PAD. On the second morning after hospitalization, blood was collected to measure fasting blood glucose (FBG), 2-hour postprandial blood glucose (PBG2h), glycosylated hemoglobin (HbA1c), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Among them, blood glucose, lipid and other biochemical markers were measured with enzyme chemistry assay and HbA1c was measured with HbA1c meter based on high liquid phase. Measurement data and enumeration data were compared with t test and Chi-square test, and multiple factors were dealt with Logistic regression analysis and multivariate linear regression analysis. MAIN OUTCOME MEASURES: Results of correlation between ABI and metabolic markers with multivariate linear regression analysis; risk factors of CI plus PAD with Logistic regression analysis; comparisons of metabolic markers between PAD and non-PAD patients. RESULTS: All 124 patients with acute CI were involved in the final analysis. ① Comparisons of metabolic markers: Levels of serum LDL-C and uric acid (UA) were higher of PAD patients than those of non-PAD patients (t =2.051 9, 3.339 1, P < 0.05); however, there were no significant differences among other metabolic markers (P > 0.05). ② Results of multivariate linear regression analysis: PBG2h, LDL-C and UA were obvious correlation with ABI of posterior tibial artery of lower limb and dorsal pedis artery (partial regression coefficient = -0.231 to -1.010, P < 0.05). ③ Risk factors of CI plus PAD with Logistic regression analysis: Age, smoking history, sum of CI focus (≥3) and LDL-C were independent risk factor of CI plus PAD (OR =1.524-5.422, P < 0.05-0.01). CONCLUSION: ① Levels of serum LDL-C and UA of patients with CI plus PAD are high. ② ABI of lower limbs is correlation with PBG2h, LDL-C and UA. In addition, measuring ABI is beneficial for early diagnosing PAD of lower limbs of patients who have poorly controlled blood glucose, abnormal lipid and poor renal function. ③ Age, LDL-C and sum of CI focus (≥3) are independent risk factors of CI plus PAD. It is of significance for screening non-PAD patients to evaluate risk degrees and prognosis and select therapeutic methods based on ABI measurement.

Tongxinluo promotes endothelium-dependent arteriogenesis to attenuate diabetic peripheral arterial disease

BACKGROUND Peripheral arterial disease(PAD)has become one of the leading causes of disability and death in diabetic patients.Restoring blood supply to the hindlimbs,especially by promoting arteriogenesis,is currently the most effective strategy,in which endothelial cells play an important role.Tongxinluo(TXL)has been widely used for the treatment of cardio-cerebrovascular diseases and extended for diabetes-related vascular disease.AIM To investigate the effect of TXL on diabetic PAD and its underlying mechanisms.METHODS An animal model of diabetic PAD was established by ligating the femoral artery of db/db mice.Laser Doppler imaging and micro-computed tomography(micro-CT)were performed to assess the recovery of blood flow and arteriogenesis.Endothelial cell function related to arteriogenesis and cellular pyroptosis was assessed using histopathology,Western blot analysis,enzyme-linked immunosorbent assay and real-time polymerase chain reaction assays.In vitro,human vascular endothelial cells(HUVECs)and human vascular smooth muscle cells(VSMCs)were pretreated with TXL for 4 h,followed by incubation in high glucose and hypoxia conditions to induce cell injury.Then,indicators of HUVEC pyroptosis and function,HUVECVSMC interactions and the migration of VSMCs were measured.RESULTS Laser Doppler imaging and micro-CT showed that TXL restored blood flow to the hindlimbs and enhanced arteriogenesis.TXL also inhibited endothelial cell pyroptosis via the reactive oxygen species/nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3/Caspase-1/GSDMD signaling pathway.In addition,TXL restored endothelial cell functions,including maintaining the balance of vasodilation,acting as a barrier to reduce inflammation,and enhancing endothelial-smooth muscle cell interactions through the Jagged-1/Notch-1/ephrin-B2 signaling pathway.Similar results were observed in vitro.CONCLUSION TXL has a pro-arteriogenic effect in the treatment of diabetic PAD,and the mechanism may be related to the inhibition of endothelial cell pyroptosis,restoration of endothelial cell function and promotion of endothelial cell-smooth muscle cell interactions.

A Case of Muscle Contraction-Induced Ischemic Limb Hyperemia in a Patient with Peripheral Arterial Disease during Incremental Repeat Isometric Knee Extensor Workloads

Background: To determine whether muscle contraction-induced leg blood flow (LBF) during exercise may be altered in a patient with an ischemic limb due to peripheral arterial disease (PAD) compared with the non-PAD limb. Case Presentation: A 66-year-old male patient with intermittent claudication due to PAD in the right leg (ankle brachial pressure index, 0.69) showed complete obstruction in both common iliac arteries including internal/external segments with collaterals above the femoral artery and popliteal artery with collaterals, and in the healthy left non-PAD-leg (1.06). He attempted unilateral repeat isometric knee extensions at a target contraction rhythm with each leg at incremental contraction intensities (5%, 10%, and 30% of maximum voluntary contraction [MVC] for 3 min at each intensity). Blood velocity/flow (Doppler ultrasound) in the femoral artery, blood pressure, and leg vascular conductance (LVC) were measured. Isometric thigh MVC strength pre-exercise was similar between the PAD-leg (48.0 kg) and non-PAD-leg (48.7 kg). Pre-exercise LBF (ml/min) was also similar between the PAD-leg (316) and non-PAD-leg (327). Blood pressure increases were similar during exercise. Average exercising LBF in ml/min in the last 1 min at each intensity was higher in the PAD-leg than the non-PAD-leg: 1087 vs. 471 at 5%, 2097 vs. 712 at 10%, and 2656 vs. 1517 at 30% MVC with a close positive linear relationship between LBF and %MVC in the non-PAD-leg (r = 0.999, P < 0.01), in agreement with previous findings, but less significant in the PAD-leg (r = 0.879, P = NS), indicating intense vasodilation (increasing LVC) in the PAD-leg compared with the non-PAD-leg. Conclusion: Knee extensor exercising LBF in the femoral artery was dissimilar between the PAD-leg and non-PAD-leg at the same exercise intensity, even though pre-exercising LBF was the same. Further research on the time-course in hemodynamics during leg exercise in PAD might potentially provide insight for the cardiovascular adjustment in severity of arteriosclerosis, stenosis and/or collaterals reserve.

Peripheral Arterial Disease among Patient Undergoing Maintenance Hemodialysis in Dakar (Senegal)

Background: Peripheral arterial disease (PAD) is common in patients with chronic kidney disease (CKD). It is a surrogate marker of generalized atherosclerosis. In sub-Saharan Africa, PAD remains understudied in CKD. Ankle-brachial index (ABI) is a non-invasive and cost-effective tool to diagnose PAD. Objectives: Our aim was to determine the prevalence and associated risk factors for PAD in hemodialysis patients. Patients and Methods: We conducted a cross-sectional study from July 1 to December 31, 2012 in the department of Nephrology of the University Hospital Aristide le Dantec of Dakar. All consenting patients, aged above 18 years, on hemodialysis for at least 6 months were included. ABI measurements were performed using a handled pulse doppler. PAD was defined as an ABI of <0.9 or the history of surgical revascularization and/or amputation due to vascular disease. The patients were divided into two groups according to the presence or not of PAD. Standard blood tests and anthropometrical parameters were recorded. Results: A total of 53 patients with a mean age of 49.15 ± 15.18 were included. The sex ratio was 0.70. Hypertension (83.01%), low HDL-cholesterol (26.41%) and cigarette smoking (20.75%) were the main cardiovascular risk factors. Prevalence of PAD was 47.16%. Among patients with PAD, 52% had no suggestive symptoms. Lower pre-dialysis (p = 0.0384) and post-dialysis (p = 0.0447) diastolic blood pressure (BP) were significantly associated with PAD. The conventional risk factors (tobacco consumption, diabetes, alcohol consumption, dyslipidemia, hypertension, age), iPTH and CRP levels were not correlated with PAD. Conclusion: PAD is common among patients undergoing maintenance hemodialysis in Senegal. Early diagnosis and management of PAD should be routinely performed in CKD patients.

Long-Term Prognosis and Predictive Risk Factors for Polyvascular Disease in Patients with Peripheral Arterial Disease

Background: The aim of the current study was to assess fifteen-year life expectancy, cardiovascular events, fate of the limb, and risk factors with or without polyvascular disease in patients with Peripheral Arterial Disease (PAD). Methods: We conducted a prospective cohort study in 1019 PAD patients. The endpoints were Cardiovascular or Cerebrovascular Death (CCVD), All-Cause Death (ACD), Major Adverse Cardiovascular Events (MACE), and Cardiovascular and/or Limb Events (CVLE). Results: The patients who died were 539 (52.9%) during follow-up periods. The rate of CCVD was 50.5% (n = 272). In multiple regression analysis, the number of affected arteries had correlations with estimated Glomerular Filtration Rate (eGFR), HDL-cholesterol, Ankle Brachial Pressure Index (ABI), and diabetes (p < 0.05). In multiple logistic analysis, PAD with Cerebrovascular Disease (CVD) was correlated with older age, ABI, eGFR, and atrial fibrillation (p < 0.05);PAD with Coronary Heart Disease (CHD) was correlated with younger age, eGFR, HDL-cholesterol, LDL- cholesterol, and diabetes (p < 0.05);and triple vascular disease (PAD with CVD and CHD) was correlated with ABI, eGFR, HDL-cholesterol, and diabetes (p < 0.05). The number of affected arteries had significant correlations with CCVD, ACD, MACE, and CVLE (p < 0.05). In Cox multivariate analyses, age, Critical Limb Ischemia (CLI), eGFR, albumin, C-Reactive Protein (CRP), Body Mass Index (BMI), CVD, and CHD were related to CCVD (p < 0.05);age, albumin, eGFR, CRP, BMI, CLI, and CVD were associated with ACD (p < 0.05);age, albumin, eGFR, CRP, CLI, CHD, and diabetes were associated with MACE (p < 0.05);age, ABI, albumin, eGFR, CRP, CLI, CHD, and diabetes were related to CVLE (p < 0.05). Statins improved all outcomes (p < 0.05). Conclusions: Polyvascular disease was independently associated with fifteen-year mortality, cardiovascular events, and the fate of the limb with diverse risk factors in PAD patients.

Clinical analysis of 35 cases of peripheral arterial disease

Objective To analyse the current condition in diagnosis and treatment of peripheral arterial disease (PAD). Methods:35 cases of PAD hospitalized between July 2007 and May 2008 were collected and studied.Results:14 of them had the concomitant type 2,diabetes mellitus (shortly as DM) and 18 cases with ulcers or gangrene in the lower limb,up to 14 were found with DM.5 died of pulmonary infection and 1 died of multiple system organ failure (MSOF).Conclu- sion:DM was an important risk factor of PAD.PAD tended to start in younger age in those with DM and its local lesion was frequently more severe and often less effective in revasculation treatment.Death during hospitalization was mainly due to related complications from cerebral vascular problems but not DM.

Carbon dioxide-angiography for patients with peripheral arterial disease at risk of contrast-induced nephropathy

Patients with peripheral arterial disease(PAD)and critical limb ischemia are at risk for limb amputation and require urgent management to restore blood flow.Patients with PAD often have several comorbidities,including chronic kidney disease,diabetes mellitus,and hypertension.Diagnostic and interventional angiography using iodinated contrast agents provides excellent image resolution but can be associated with contrast-induced nephropathy(CIN).The use of carbon dioxide(CO2)as a contrast agent reduces the volume of iodine contrast required for angiography and reduces the incidence of CIN.However,CO2 angiography has been underutilized due to concerns regarding safety and image quality.Modern CO2 delivery systems with advanced digital subtraction angiography techniques and hybrid angiography have improved imaging accuracy and reduced the incidence of CIN.Awareness of the need for optimal imaging conditions,contraindications,and potential complications have improved the safety of CO2 angiography.This review aims to highlight current technological advances in the delivery of CO2 in vascular angiography for patients with PAD and critical limb ischemia,which result in limb preservation while preventing kidney damage.

Prevalence and related risk factors of peripheral arterial disease in elderly patients with type 2 diabetes in Wuhan, Central China

Background The investigations of prevalence and risk factors of peripheral arterial disease （PAD） in type 2 diabetic patients have been carried out in many countries and regions, except for Central China. In this study, we determined the prevalence of PAD in type 2 diabetic patients and the related factors that gave rise to increasing of the risk of PAD development in Wuhan, China. Methods The study enrolled 2010 patients aged 60 years and older who were regularly visiting the Central Hospital of Wuhan that is a public hospital from 2005 to 2010, where all residents of the city were offered the medical services. PAD was defined as an ankle-brachial index 〈0.90 in either leg. To evaluate the role of various risk factors in PAD development, uniformed interviews, clinical examinations and laboratory investigation of all of participants were performed in this study. The correlation between potential risk factors and PAD was analyzed. Results In Wuhan, the prevalence rate of PAD was 24.1% in elderly diabetic patients. Totally, 291 patients with PAD had at least one weak but not absent dorsalis pedis pulse in both feet, while 541 patients without PAD showed this way. At least one absent dorsalis pedis pulse was found in 192 patients with PAD as well as 10 patients without PAD. The results of multivariate regression analysis suggested that the age, smoking history, hypertension, diabetic neuropathy and macroangiopathy gave rise to significant increase of PAD development in type 2 diabetic diseases. Conclusions The prevalence of PAD in elderly patients with type 2 diabetes in Wuhan was close to the prevalence that was reported in other regions of China and other Asian countries. Control of the related risk factors and early diagnosis of PAD may play a role in PAD prevention and improving prognosis.

Impact of type 2 diabetes on the plasma levels of vascular endothelial growth factor and its soluble receptors type 1 and type 2 in patients with peripheral arterial disease

Objective： Type 2 diabetes coexistent with lower extremity artery disease （peripheral arterial disease （PAD）） can be observed in numerous patients. The mechanism compensating for ischemia and contributing to healing is angiogenesis-the process of forming new blood vessels. The purpose of this study was to assess the likely impact of type 2 diabetes on the plasma levels of proangiogenic factor （vascular endothelial growth factor A （VEGF-A）） and angiogenesis inhibitors （soluble VEGF receptors type 1 and type 2 （sVEGFR-1 and sVEGFR-2）） in patients with PAD. Methods： Among 46 patients with PAD under pharmacological therapy （non-invasive）, we identified, based on medical history, a subgroup with coexistent type 2 diabetes （PAD-DM2＋, n=15） and without diabetes （PAD-DM2-, n=31）. The control group consisted of 30 healthy subjects. Plasma levels of VEGF-A, sVEGFR-1, and sVEGFR-2 were measured using the enzyme-linked immunosorbent assay （ELISA） method. Results： The subgroups of PAD-DM2＋ and PAD-DM2- revealed significantly higher concentrations of VEGF-A （P=-0.000007 and P=0.0000001, respectively） and significantly lower sVEGFR-2 levels （P=-0.02 and P=-0.00001, respectively）, when compared with the control group. Patients with PAD and coexistent diabetes tended to have a lower level of VEGF-A and higher levels of sVEGFR-1 and sVEGFR-2 comparable with non-diabetic patients. Conclusions： The coexistence of type 2 diabetes and PAD is demonstrated by a tendency to a lower plasma level of proangiogenic factor （VEGF-A） and higher levels of anglogenesis inhibitors （sVEGFR-1 and sVEGFR-2） at the same time. Regardless of the coexistence of type 2 diabetes, hypoxia appears to be a crucial factor stimulating the processes of angiogenesis in PAD patients comparable with healthy individuals, whereas hyperglycemia may have a negative impact on angiogenesis in lower limbs.

Bioengineering strategies for the treatment of peripheral arterial disease

Peripheral arterial disease(PAD)is a progressive atherosclerotic disorder characterized by narrowing and occlusion of arteries supplying the lower extremities.Approximately 200 million people worldwide are affected by PAD.The current standard of operative care is open or endovascular revascularization in which blood flow restoration is the goal.However,many patients are not appropriate candidates for these treatments and are subject to continuous ischemia of their lower limbs.Current research in the therapy of PAD involves developing modalities that induce angiogenesis,but the results of simple cell transplantation or growth factor delivery have been found to be relatively poor mainly due to difficulties in stem cell retention and survival and rapid diffusion and enzymolysis of growth factors following injection of these agents in the affected tissues.Biomaterials,including hydrogels,have the capability to protect stem cells during injection and to support cell survival.Hydrogels can also provide a sustained release of growth factors at the injection site.This review will focus on biomaterial systems currently being investigated as carriers for cell and growth factor delivery,and will also discuss biomaterials as a potential stand-alone method for the treatment of PAD.Finally,the challenges of development and use of biomaterials systems for PAD treatment will be reviewed.

Limited Efficacy of Aspirin in Patients with Peripheral Arterial Occlusive Disease

Antiplatelet drugs represent one of the basic options for management of patients with different atherosclerotic diseases. Aspirin is the oldest and most often prescribed antiplatelet drug. It seems that it is most effective in coronary patients with clinically unstable disease, less effective in prevention of cerebrovascular incidents, and its efficacy is uncertain in peripheral artery disease （PAD） patients. One of the first meta-analysis indicated that antiplatelet drugs also significantly reduce cardiovascular events in patients with PAD. However, latest meta-analysis of randomized control trials of aspirin therapy involving patients with diabetes and PAD demonstrated no benefit of aspirin in reducing cardiovascular events. Also in patients with preclinical PAD aspirin did not result in a significant reduction of vascular events. The new anti-platelet drugs prasugrel, ticagrelol, picotamide seem to be more effective than aspirin in PAD patients, particularly in diabetic patients with PAD. However, evidence based data are scanty. New studies on PAD patients are necessary to better define the role of anti-platelet agents in these patient and one of the promising ways of access to anti-platelet treatment would be personalized anti-platelet therapy.

Nε-carboxymethyl-lysine and inflammatory cytokines,markers and mediators of coronary artery disease progression in diabetes

This editorial refers to the article“Comparative analysis of Nε-carboxymethyllysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients”,published in the recent issue of the World Journal of Diabetes 2023 is based on glucose metabolism,advanced glycation end products(AGEs),inflammation and adiposity on diabetes and coronary artery disease(CAD).This study has included CAD patients who were stratified according to glycosylated hemoglobin higher than 6.5 and sex-matched.A higher prevalence of hypertension,dyslipidemia,and non-vegetarian diet were found in the diabetic group.These risk factors might influence body weight and adiposity and explain the increment of the left atrium.Although this data was not supported by the study.The diet can also explain the non-enzymatic reactions on lipids,proteins,or nucleic acids and consequently an increment of AGEs.These molecules can emit fluorescence.However,one of the non-fluorescent and most abundant AGEs is Nε-carboxymethyl-lysine(CML).Its association with coronary artery stenosis and severity in the diabetic group might suggest its role as a player in CAD progression.Thus,CML,after binding with its receptor(RAGE),can induce calcification cascade through reactive oxygen species and mitogen-activated protein kinase.Moreover,this interaction AGE-RAGE can cause activation of the transcription nuclear factor-kb and induce inflammatory cytokines.It might explain the relationship between CML and pro-inflammatory cytokines in diabetic and CAD patients.Although this is a population from one center,the determination of CML and inflammatory cytokines might improve the diagnosis of severe and progressive CAD.Future and comparative studies among glycosylated hemoglobin,CML,and other AGE levels according to diagnosis and prognosis value might modify the clinical practice.Although these molecules are irreversible,they can act through a specific receptor inducing a signal transduction that might be modulated by inhibitors,antibodies,or siRNA.Further mechanistic studies might improve the development of future preventive therapies for diabetic patients.

Inflammatory markers,oxidative stress,and mitochondrial dynamics:Repercussions on coronary artery disease in diabetes

Inflammatory markers and mediators that affect the development of cardiovascular diseases have been the focus of recent scientific work.Thus,the purpose of this editorial is to promote a critical debate about the article titled“Nε-carboxymethyl-lysine and inflammatory cytokines,markers,and mediators of coronary artery disease progression in diabetes”,published in the World Journal of Diabetes in 2024.This work directs us to reflect on the role of advanced glycation end products,which are pro-inflammatory products arising from the metabolism of fatty acids and sugars whose main marker in tissues is Nε-carboxymethyllysine(NML).Recent studies have linked high levels of pro-inflammatory agents with the development of coronary artery disease(CAD),especially tumor necrosis factor alpha,interleukins,and C-reactive protein.These inflammatory agents increase the production of reactive oxygen species(ROS),of which people with diabetes are known to have an increased production.The increase in ROS promotes lipid peroxidation,which causes damage to myocytes,promoting myocardial damage.Furthermore,oxidative stress induces the binding of NML to its receptor RAGE,which in turn activates the nuclear factor-kB,and consequently,inflammatory cytokines.These inflammatory cytokines induce endothelial dysfunction,with increased expression of adhesion molecules,changes in endothelial permeability and changes in the expression of nitric oxide.In this sense,the therapeutic use of monoclonal antibodies(inflammatory reducers such as statins and sodium-glucose transport inhibitors)has demonstrated positive results in the regression of atherogenic plaques and consequently CAD.On the other hand,many studies have demonstrated a relationship between mitochondrial dynamics,diabetes,and cardiovascular diseases.This link occurs since ROS have their origin in the imbalance in glucose metabolism that occurs in the mitochondrial matrix,and this imbalance can have its origin in inadequate diet as well as some pathologies.Photobiomodulation(PBM)has recently been considered a possible therapeutic agent for cardiovascular diseases due to its effects on mitochondrial dynamics and oxidative stress.In this sense,therapies such as PBM that act on pro-inflammatory mediators and mitochondrial modulation could benefit those with cardiovascular diseases.

Correlation of neutrophil to lymphocyte ratio to severity of coronary artery disease and in-hospital clinical outcomes in patients with acute coronary syndrome: A prospective observational study

Objective:To explore correlation of neutrophil-to-lymphocyte ratio(NLR)to severity of coronary artery disease(CAD)and in-hospital clinical outcomes in patients with acute coronary syndrome(ACS).Methods:In this prospective and observational study,we recruited 500 patients with ACS.For all the eligible patients,demographic details were collected,and laboratory parameters were evaluated.The CAD severity was evaluated in terms of the number of involved vessels.The NLR was calculated based on neutrophils and lymphocytes and the correlation of various risk factors and severity and outcome of CAD was performed.Results:77.2%of Patients was male,and 52%of the patients aged between 55-70 years.Based on the type of ACS,396 out of 500 patients had ST-elevation myocardial infarction.An ascending trend in the white blood cell levels and NLR value was noted as the severity of the ACS increased and the highest white blood cell levels and NLR was noted among classⅣpatients.The mean NLR value among the non-survivors were higher compared to the survivors(9.52±5.72 vs.4.76±2.36;P<0.01).Receiver operating curve showed that the cut-off NLR value was 5.76 with a sensitivity of 75.0%and a specificity of 77.3%.Conclusions:The NLR can be used as an independent prognostic marker in ACS.An elevated NLR value serves as a reliable predictor for short-term complications,notably in-hospital mortality.

Transplantation of mobilized peripheral blood mononuclear cells for peripheral arterial occlusive disease of the lower extremity

Objectives To assess the clinical efficacy,safety,and feasibility of autologous transplantation of mobilized peripheral blood mononuclear cells(PBMNCs)for patients with peripheral arterial occlusive disease(PAOD)of the lower extremity.Methods A total of 152 patients with PAOD of the lower extremity were enrolled into this non-controlled observational study from November 2003 to March 2006.All patients received subcutaneous injections of recombinant human granulocyte colony-stimulating factor(G-CSF,450-600μg/day)for 5 days in order to mobilize stem/progenitor cells;their PBMNCs were collected and transplanted by multiple intramuscular injections into ischemic limbs.Patients were followed up for at least 12 weeks.Results At 12 weeks,primary manifestations,including lower limb pain and coldness,were significantly improved in 137(90.1%)of the patients;limb ulcers improved or healed in 46(86.8%)of the 53 patients,while 25 of the 48(47.9%)patients with limb gangrene remained steady or improved.Ankle-brachial index(ABI)improved in 33(22%)of the cases,and TcPO_(2) increased in 45(30%)of the cases.Angiography before treatment,and at 12 weeks after treatment,was performed in 10 of the patients and showed formation of new collateral vessels.No severe adverse effects or complications specifically related to cell transplantation were observed.Conclusion Autologous transplantation of G-CSF-mobilized PBMNCs might be a safe and effective treatment for lower limb ischemic disorder.