Proteína C reactiva, aspectos cardiovasculares de una proteína de fase aguda: una actualización para el médico / C-reactive protein, cardiovascular issues of an acute-phase protein: an update for the clinician

Resumen La inflamación es un factor patogénico importante para el desarrollo de la enfermedad cardiovascular aterosclerótica. Actualmente, el biomarcador utilizado con mayor frecuencia que refleja la inflamación sistémica es la proteína C reactiva (PCR), una proteína de fase aguda producida principalmente por los hepatocitos bajo la influencia de la interleucina 6, la interleucina 1 beta y el factor de necrosis tumoral. La evidencia proveniente de estudios epidemiológicos ha demostrado una fuerte asociación entre las concentraciones elevadas de PCR en suero o plasma y la incidencia de un primer evento cardiovascular (incluido infarto agudo de miocardio, accidente vascular cerebral isquémico y muerte cardíaca súbita) en la población general, así como la recurrencia de eventos cardiovasculares adversos en los pacientes con enfermedad establecida. El valor aditivo que la medición de la PCR otorga a los factores de riesgo tradicionales se refleja en novedosas calculadoras de riesgo cardiovascular y en los actuales regímenes de intervención, que ya consideran a la PCR como objetivo terapéutico. Sin embargo, las variaciones en los niveles de PCR, que dependen del sexo, la etnia, el estado hormonal y algunas peculiaridades de los ensayos de medición, deben tenerse en cuenta al decidir implementar la PCR como un biomarcador útil en el estudio y el tratamiento de la enfermedad cardiovascular aterosclerótica. Esta revisión pretende ofrecer una visión actualizada de la importancia de medir la PCR como biomarcador de riesgo cardiovascular más allá de los factores tradicionales que estiman el riesgo de enfermedad aterosclerótica.

Abstract Inflammation is an important pathogenic factor for the development of atherosclerotic cardiovascular disease. Currently, the most frequently used biomarker reflecting systemic inflammation is C-reactive protein (CRP), an acute-phase protein produced primarily by hepatocytes under the influence of interleukin-6, interleukin-1 beta, and tumor necrosis factor. Growing evidence from epidemiological studies has shown a robust association between elevated serum or plasma CRP concentrations and the incidence of a first cardiovascular adverse event (including acute myocardial infarction, ischemic stroke, and sudden cardiac death) in the general population, as well as recurrence of major adverse cardiovascular events among patients with established disease. The additive value that CRP measurement gives to traditional risk factors is reflected in novel cardiovascular risk calculators and in current intervention regimens, which already consider CRP as a target therapeutic. However, the variations in CRP levels, that depend on sex, ethnicity, hormonal status, and some peculiarities of the measurement assays, must be taken into consideration when deciding to implement CRP as a useful biomarker in the study and treatment of atherosclerotic cardiovascular disease. This review aims to offer an updated vision of the importance of measuring CRP levels as a biomarker of cardiovascular risk beyond the traditional factors that estimate the risk of atherosclerotic disease.

Electrocardiographic Findings Among Asymptomatic Adults With Haemophilia

Abstract Background: People with haemophilia (PwH) are living longer. Therefore, they can develop atherosclerotic cardiovascular disease (ASCVD). Electrocardiogram (ECG) alterations may be a sign of initial ASCVD before the occurrence of symptoms. Objective: To describe the prevalence of resting ECG alterations among PwH adults asymptomatic for ASCVD. Methods: PwH aged ≥ 30 years without previous ASCVD events were considered for the analysis. Resting ECG traces were analysed according to international reference values and the Brazilian Longitudinal Adult Health Study (ELSA-Brasil) results for asymptomatic Brazilian men. Based on the established normal values and using the QT index, we further described the altered ECGs as minor or major changes, according to the Minnesota Code. Differences between prevalences were evaluated by Pearson's χ2 test. Differences between medians were evaluated by the Mann-Whitney U test. A p-value < 0.05 was accepted as statistically significant. Results: A total of 64 PwH were included in the study. Median age was 44 years (interquartile range 35-52). Most patients had haemophilia A (81%) and 47% were severe. The prevalence of obesity, systemic arterial hypertension (SAH), diabetes mellitus (DM), and dyslipidaemia were 16%, 56%, 14%, and 72%, respectively. All the PwH had sinus rhythm, except for one, who had an implanted pacemaker due to idiopathic third-degree atrioventricular block. Altered ECGs were found in 25% and 30% of PwH, according to established criteria and ELSA-Brasil criteria, respectively. Major changes were found in eight (13%) PwH according to the Minnesota Code, including two ECGs with ischaemia-like wall inactivity. Conclusions: The prevalence of altered ECG varied from 25% to 30% among asymptomatic PwH.

The clinical diagnosis of Parkinson's disease / O diagnóstico clínico da doença de Parkinson

Abstract After more than 200 years since its initial description, the clinical diagnosis of Parkinson's disease (PD) remains an often-challenging endeavor, with broad implications that are fundamental for clinical management. Despite major developments in understanding it's pathogenesis, pathological landmarks, non-motor features and potential paraclinical clues, the most accepted diagnostic criteria remain solidly based on a combination of clinical signs. Here, we review this process, discussing its history, clinical criteria, differential diagnoses, ancillary diagnostic testing, and the role of non-motor and pre-motor signs and symptoms.

Resumo Passados mais de 200 anos desde a sua descrição inicial, o diagnóstico clínico da doença de Parkinson (DP) continua a ser um processo muitas vezes desafiante, com amplas implicações que são fundamentais para o manejo clínico. Apesar dos grandes desenvolvimentos na compreensão da sua patogénese, marcadores patológicos, características não motoras e potenciais pistas paraclínicas, os critérios diagnósticos mais aceitos permanecem solidamente baseados numa combinação de sinais clínicos motores. Aqui, revisamos esse processo, discutindo sua história, critérios clínicos, diagnósticos diferenciais, testes diagnósticos complementares e o papel dos sinais e sintomas não motores e pré-motores.

Research progress of immune regulation and targeted therapy in the inflammatory response of atherosclerotic plaque / 临床神经病学杂志

Stroke has a high morbidity,disability and mortality.Early identification and intervention of carotid atherosclerotic plaque can prevent the occurrence of stroke.Studies have shown that atherosclerotic plaques are closely related to immune-mediated inflammation,and targeted inflammation therapy is expected to become a new method for the treatment of atherosclerotic plaques.This article systematically reviewed the role of immune regulatory mechanisms of different cells in the inflammatory response of atherosclerotic plaques,as well as potential targeted anti-inflammatory drugs,in order to provide reference for the clinical treatment of atherosclerosis related diseases.

Correlation between platelet to lymphocyte ratio,neutrophil to lymphocyte ratio and carotid atherosclerotic plaque in patients with type 2 diabetes mellitus / 新乡医学院学报

Objective To explore the correlation between platelet to lymphocyte ratio(PLR),neutrophil to lymphocyte ratio(NLR)and carotid atherosclerotic(CAS)plaque in patients with type 2 diabetes(T2DM),and the predictive value of PLR and NLR for T2DM complicated with CAS plaque.Methods A total of 369 T2DM patients admitted to the Department of Endocrinology,the Third Affiliated Hospital of Xinxiang Medical University from September 2019 to November 2021 were se-lected as research subjects.The clinical data such as gender,age,course of disease,body mass index(BMI),systolic blood pressure(SBP),diastolic blood pressure(DBP),personal history,and history of past illness of patients were collected by searching the electronic medical record system.Neutrophil(NC)count,lymphocyte count(LC)and platelet(PLT)count were detected by fully automated blood routine analyzer,and PLR,NLR were calculated;the levels of fasting blood glucose(FBG),total cholesterol(TC),triglycerides(TG),high-density lipoprotein-cholesterol(HDL-C)and low-density lipoprotein-cholesterol(LDL-C)were detected by biochemical analyzer;the level of glycosylated hemoglobin(HbA1c)were detected by high-performance liquid chromatography.The T2DM patients were divided into T2DM uncomplicated with CAS plaque group(n=94)and T2DM complicated with GAS plaque group(n=275)based on whether they complicated with CAS plaque or not;the general clinical data,blood indicators,and PLR,NLR of patients were compared between the two groups.The T2DM patients were divided into non plaque group(group A,n=94),1 plaque group(group B,n=79),2 plaque group(group C,n=89),and 3 or more plaques group(group D,n=107)based on the number of CAS plaques;the indicators with statistical differences between T2DM uncomplicated with CAS plaque group and T2DM complicated with CAS plaque group of patients were compared among the four groups.According to the PLR quartile,the patients were divided into P1 group(PLR≤94.87,n=93),P2 group(94.87＜PLR≤117.30,n=91),P3 group(117.30＜PLR ≤ 148.53,n=93),and P4 group(PLR＞148.53,n=92),and the detection rate of CAS plaques of patients was compared among the four groups;according to the NLR quartile,the patients were divided into N1 group(NLR≤1.59,n=92),N2 group(1.59＜NLR≤1.93,n=92),N3 group(1.93＜NLR≤2.50,n=93),and N4 group(NLR＞2.50,n=92),and the detection rate of CAS plaque of patients was compared among the four groups.The risk factors of T2DM complicated with CAS plaque was analysed by multivariate logistic regression analysis,and the predictive efficacy of PLR and NLR for T2DM complicated with CAS plaque were evaluated by receiver operating characteristic(ROC)curve.Results The age,course of T2DM,proportion of patients combined with hyper-tension,SBP,PLR,and NLR of patients in the T2DM complicated with CAS plaque group were significantly higher than those in the T2DM uncomplicated with CAS plaque group,while LC and TG levels were significantly lower than those in the T2DM uncomplicated with CAS plaque group(P＜0.05);there was no significant difference in gender,proportion of patients com-bined with hyperlipidemia,proportion of smoking history,proportion of drinking history,and the levels of DBP,BMI,NC,PLT,TC,HDL-C,LDL-C,FBG,HbA1c between the T2DM uncomplicated with CAS plaque group and T2DM complicated with CAS plaque group(P＞0.05).The age,proportion of patients combined with hypertension,course of T2DM,SBP,PLR,and NLR of patients in group B,group C,and group D were significantly higher than that in group A,while LC level was significantly lower than that in group A(P＜0.05).The TG level of patients in group D was significantly lower than those in group A(P＜0.05);there was no statistically significant difference in TG level of patients among group A,group B,and group C(P＞0.05).The age,proportion of patients combined with hypertension,and course of T2DM of patients in group C and group D were significantly higher than those in group B,while the SBP of patients in group D was significantly higher than that in group B(P＜0.05);there was no statistically significant difference in SBP of patients between group C and group B(P＞0.05).The age,proportion of patients combined with hypertension,course of T2DM,and SBP of patients in group D were significantly higher than those in group C(P＜0.05).There was no statistically significant difference in the levels of LC,TG,and PLR of patients among group B,group C,and group D(P＞0.05).The NLR of patients in group D was significantly higher than that in group B(P＜0.05);there was no statistically significant difference in NLR of patients between group C and group B(P＞0.05),and there was no statistically significant difference in NLR of patients between group D and group C(P＞0.05).The detection rate of CAS plaques of patients in P1 group,P2 group,P3 group,and P4 group showed a significant increase trend(x2=30.610,P=0.000);and the detection rate of CAS plaques of patients in N1 group,N2 group,N3 group,and N4 group showed a significant increase trend(x2=35.170,P=0.000).Multivariate logistic regression analysis showed that age,PLR,and NLR were independent risk factors for T2DM complicated with CAS plaque(odds ratio=1.107,1.017,1.940;P＜0.05).The opti-mal cutoff value of PLR in predicting T2DM complicated with CAS plaque was 119.95,with an area under the curve of 0.680,a sensitivity of 54.7％,and a specificity of 76.3％;the optimal cutoff value of NLR in predicting T2DM complicated with CAS plaque was 1.97,with an area under the curve of 0.698,a sensitivity of 56.5％,and a specificity of 79.6％.Conclusion PLR and NLR are associated with T2DM complicated with CAS plaque,which are independent risk factors for T2DM compli-cated with CAS plaque,and have certain predictive value for T2DM complicated with CAS plaque.

Effect of statins combined with PCSK9 inhibitors on coronary atheromatous plaque assessed by intravascular imaging: a Meta-analysis / 中国基层医药

Objective:To evaluate the effect of statins combined with PCSK9 inhibitors on coronary artery atherosclerotic plaque, as well as to verify the lipid-lowering effect of the combined therapy.Methods:A computerized search of PubMed, Embase, Web of Science, Cochrane Library, Wanfang, and CNKI databases was conducted to retrieve published literature from inception to December 20, 2022. The English search terms utilized included "PCSK9 inhibitors," "Alirocumab," "Evolocumab," "plaque," "IVUS," and "OCT." The corresponding Chinese search terms were "PCSK9 inhibitors," "plateau," "intravascular ultrasound," and "optical coherence tomography." The literature that examined the effect of statins alone or in combination with PCSK9 inhibitors on coronary atherosclerotic plaques using intravascular ultrasound or optical coherence tomography was identified. The collected data were subsequently processed using Review Manager (Revman) version 5.4.Results:In the final analysis, nine studies involving 1912 patients were included. The analysis results revealed that compared with statins alone, statins combined with PCSK9 inhibitors significantly reduced the percentage of atherosclerotic volume ( MD: -2.08 mm 3, 95% CI: -2.94 to -1.23 mm 3, P < 0.001), accelerated the regression of atherosclerotic volume ( MD: -1.13 mm 3, 95% CI: -1.49 to -0.77 mm 3, P < 0.001), slightly, but not significantly, reduced the overall atherosclerotic volume ( MD: -6.42 mm 3, 95% CI: -14.34-1.51 mm 3, P = 0.110). Nevertheless, the combined therapy contributed to a significant reduction in atherosclerotic volume ( MD: -5.16 mm 3, 95% CI: -7.09 to -3.23 mm 3, P < 0.001) and significantly increased the fiber cap thickness of thin cap plaques ( MD: 8.46 μm, 95% CI: 5.13-11.79 μm, P < 0.001). Additionally, this combined therapy significantly lowered blood lipid levels. Conclusion:The combination of statins and PCSK9 inhibitors can significantly improve the characteristics and phenotype of atherosclerotic plaques and significantly reduce blood lipid levels. For patients with high cardiovascular risk, it is recommended to initiate treatment with statins combined with PCSK9 inhibitors as soon as possible and maintain it for a long time to ensure more benefits.

Efficacy analysis of the acute endovascular treatment in patients with symptomatic severe anterior intracranial atherosclerotic stenosis / 中国脑血管病杂志

Objective Observing the feasibility of acute endovascular treatment for patients with symptomatic anterior intracranial atherosclerotic severe stenosis.Method From Jun 2019 to Jun 2023,30 symptomatic anterior intracranial atherosclerotic severe stenosis cases were retrospectively collected in the Guangdong Hospital of Traditional Chinese Medicine to evaluate the risk stratification score and explore the safety and effectiveness of acute(≤72.0h)endovascular treatment.Endovascular treatment includes balloon dilation+self-expanding stent placement,balloon-mounted stent placement,and balloon dilation.From the clinical experience,the risk stratification score was based on the ABCD3-I score for transient ischemic attacks(TIA)and additional evaluation of cerebral watershed infarction to identify the risk of stroke progression or recurrence in acute stage of symptomatic intracranial artery stenosis.The score of 0-3 was defined as low-risk,4-7 as medium risk,and 8-13 as high-risk.The successful revascularization of blood flow is determined based on the residual stenosis≤50％and the extended thrombolysis in cerebral infarction(eTICI)＞2c.The information of patient receiving endovascular treatment was recorded,including age,sex,risk factors of cerebrovascular disease(hypertension,diabetes,hyperlipidemia,hyperhomocysteinemia,drinking history,smoking history),onset data(time from onset to endovascular treatment,symptoms,progression),diseased vessels,risk stratification score,National Institutes of Health Stroke Scale(NIHSS)score before and 90 days after surgery,modified Rankin scale(mRS)score 90 days after surgery,intraoperative cerebrovascular events(intracranial hemorrhage,occlusion of responsible vessels),and postoperative cerebrovascular events 90 days after surgery(intracranial hemorrhage,cerebral infarction,TIA and in-stent restenosis)and deaths.Results Among 30 patients with symptomatic anterior intracranial atherosclerotic severe stenosis,3 patients were excluded from the time interval between onset and endovascular treatment＞72.0 hours,1 patient needed long-term anticoagulant drugs due to other diseases,1 patient lost follow-up,3 patients coexisted with other cardiogenic cerebral embolism diseases,4 patients with non-atherosclerotic arterial stenosis,and 7 patients refused emergency endovascular treatment.11 patients were finally included.(1)All 11 patients were successfully treated with endovascular treatment,and 7 were males;age ranged from 52 to 76 years old,with a median age of 64 years old;there were 9 cases with hypertension,3 cases diabetes,7 cases hyperlipidemia,2 cases hyperhomocysteinemia(only 9cases performed the examination),2cases smoking history,1 case drinking history;time from onset to endovascular treatment is 4.0-72.0 h,with a median time of 12.0 h;there were 3 and 8 cases of infarction in the left and right hemispheres,respectively,with 4,3,and 2 cases accompanied with anterior-posterior watershed,medial watershed,and anlerior-medial-posterior watershed infarctions,and 1 case accompanied by posterior-medial,anterior-medial watershed infarctions.(2)Among the 1 1 patients,the risk stratification score was 10-13 points,with a median score of 11 points;preoperative NIHSS score ranged 0-11 points,with a median score of 7 points.(3)Among the 1 1 patients,10 lesions located in the middle cerebral artery and 1 in the C7 segment of the internal carotid artery;the preoperative stenosis rate was 70％to 99％,with a median stenosis rate of 86％;preoperative eTICI grading was 2a in 7 cases and 2b50 in 4 cases(with slow distal blood flow);9 cases received balloon dilation and self-expanding stent placement,1 case received balloon-mounted stent placement,and 1 case received balloon dilation treatment;the postoperative stenosis rate is 10％to 20％,with a median stenosis rate of 15％;there were 3 cases with postoperative eTICI grade 2c and 8 cases with grade 3.(4)Among the 11 patients,one experienced intracranial hemorrhage on the first day after surgery and one had a new cerebral infarction on the third day after surgery.Eight patients were followed up by imaging 90days after surgery,demonstrating 2 cases of in-stent restenosis;90 days post-surgery,NIHSS score was 0-20 points,with a median score of 2 points;after 90 days of surgery,the mRS score was 0-4 points,with a median score of 1 point.There were 8 patients with mRS score ≤ 2 and no death events occurred.Conclusions Preliminary analysis shows that acute endovascular treatment for symptomatic anterior intracranial atherosclerotic severe stenosis has certain effectiveness,but the safety needs to be further validated.The screening of high-risk patients using risk stratification scores still requires further exploration through large sample and multicenter studies.

Analysis of the Impact of Different Low-density Lipoprotein Cholesterol Levels on the Progression of Intermediate Coronary Stenosis Based on Quantitative Flow Ratio Quantification / 中国循环杂志

Objectives:This study aims to investigate the impact of different Low-Density Lipoprotein cholesterol(LDL-C)levels on progression of intermediate coronary stenosis,and the associated risk factors leading to the progression of such lesions. Methods:Data were collected on 219 consecutive patients admitted at the Fuwai Central China Vascular Hospital from January 2020 to February 2021,underwent angiographic examinations and diagnosed with intermediate coronary stenosis,with at least one follow-up angiography after 11 months.Offline quantitative flow ratio(QFR)analysis was performed on these cases.Patients were divided into two groups:LDL-C controlled group(LDL-C<1.8 mmol/L,148 patients with 191 vessels)and LDL-C uncontrolled group(LDL-C≥1.8 mmol/L,71 patients with 98 vessels).Coronary artery QFR and anatomical indicators such as minimal lumen diameter,minimal lumen area,percentage diameter stenosis,percentage area stenosis were compared within and between the groups.Further analysis was performed to identify influencing factors leading to changes in coronary physiological parameters derived from QFR. Results:Within the LDL-C controlled group,there was no significant difference in the QFR values of the vessels compared to baseline(P>0.05),whereas in the LDL-C uncontrolled group(P<0.05),a notable decline in QFR was observed.Patients in the LDL-C controlled group had lower rates of maximum diameter and area stenosis and higher minimum lumen diameter and area(all P<0.05).Through multifactorial Logistic regression analysis,it was found that a body mass index＞28 kg/m2,LDL-C≥1.8 mmol/L,and a history of myocardial infarction were independent risk factors leading to the decline in QFR(all P<0.05). Conclusions:It was found that patients in the LDL-C controlled group had higher coronary artery QFR,minimum lumen diameter and area,lower rates of maximum diameter and area stenosis.

Impact of Resting Heart Rate on All-cause Mortality in Ultra-high Risk Atherosclerotic Cardiovascular Disease Patients / 中国循环杂志

Objectives:To investigate the impact of resting heart rate on the risk of all-cause mortality in ultra-high risk atherosclerotic cardiovascular disease(ASCVD)patients. Methods:A total of 3 645 patients with ultra-high risk ASCVD(as defined in the 2023 Chinese Lipid Management Guidelines)were screened from the 2006 to 2020 Kailuan Study cohort,and after excluding 602 patients with missing resting heart rate,3 043 patients were included in the final analysis.Patients were divided into＜68 beats/min group(n=744),68-74 beats/min group(n=786),75-80 beats/min group(n=760),and≥81 beats/min group(n=753)according to the resting heart rate.Cox proportional regression model was used to estimate the hazard ratios(HRs)and 95%CI for all-cause mortality associated with the different resting heart rate groups and every 10 beats/min increase of resting heart rate.The dose-effect relationship of resting heart rate level and all-cause mortality was assessed by a restricted cubic spline regression model.The Kaplan-Meier method was applied to calculate the cumulative all-cause mortality in different groups,and the differences were compared using log-rank test. Results:The median follow-up time was 5.81(3.46,9.64)years,there were 772(25.37%)all-cause deaths during follow up.After adjusting major confounding factors,the results showed that compared with＜68 beats/min group,the risk of all-cause mortality in 75-80 beats/min group and≥81 beats/min group increased by 24%(HR=1.24,95%CI:1.01-1.52,P=0.047)and 47%(HR=1.47,95%CI:1.20-1.81,P＜0.001),respectively;the risk of all-cause mortality in 68-74 beats/min group was similar(HR=1.06,95%CI:0.86-1.31,P=0.625).In addition,an increase of 10 beats/min in resting heart rate was associated with a 13%increase in the risk of all-cause mortality(HR=1.13,95%CI:1.07-1.19,P＜0.001).In stratified analyses,it was found that for every 10 beats/min increase in resting heart rate,women faced a higher risk of all-cause mortality than men,and patients＜65 years old faced a higher risk of all-cause mortality than patients≥65 years old.The restricted cubic spline analysis also showed that resting heart rate was linearly associated with the risk of all-cause mortality(Poverall＜0.001,Pnon-linear=0.933),and the risk increased significantly with resting heart rate＞70 beats/min. Conclusions:Increased resting heart rate is linearly associated with increased risk of all-cause mortality in patients with ultra-high risk ASCVD.The appropriate intervention cut-off point of resting heart rate for ultra-high risk ASCVD patients may be＞75 beats/min.

Synthesis and biological evaluation of 68Ga-NOTA-CD44: a novel tracer targeting atherosclerotic plaques / 中华核医学与分子影像杂志

Objective:To construct 68Ga-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-CD44 as a novel atherosclerosis tracer targeting hyaluronic acid (HA), and evaluate its biological property and molecular imaging features. Methods:Low molecular weight (LMW) recombinant human CD44 protein was selected, and the C-terminal of the protein was modified by sulfonation and coupled to the bifunctional ligand NOTA to synthesize a novel molecular probe 68Ga-NOTA-CD44 targeting HA. The biological properties of the probe, such as labeling rate and in vitro stability, were studied. Three atherosclerotic plaque model mice and three normal C57BL/6 mice were studied by 68Ga-NOTA-CD44 microPET/CT imaging and pathological examination. Results:68Ga-NOTA-CD44 tracer was synthesized and purified with the radiochemical purity above 99%, and the specific activity was up to 62.22 MBq/nmol. lts stability was good in PBS, and the radiochemical purity was over 90% after incubation for 3 h. After intravenous injection, the probe was metabolized mainly by the kidneys, and its metabolic level decreased successively in the liver, lungs and blood. MicroPET/CT imaging results of atherosclerotic model mice suggested that the uptake in the plaque of abdominal aorta was higher at 60 min after injection, with SUV max and target/background ratio (TBR) max of 1.14±0.02 and 4.95±0.93, and the probe had certain atherosclerotic plaque eroded targeting, which was consistent with the pathological result. Conclusions:As a novel probe, 68Ga-NOTA-CD44 is simple to prepare and has a high labeling rate. It has good physicochemical properties and in vivo biological properties, and can display atherosclerotic eroded plaques sensitively. 68Ga-NOTA-CD44 has a promising prospect to be a new molecular probe for early noninvasive recognition of atherosclerotic eroded plaques.

Correlation of circulating ceramides and residual cholesterol with intracranial atherosclerotic stenosis in elderly stroke patients / 中华老年心脑血管病杂志

Objective To investigate the correlation of ceramides(Cer),triglyceride-glucose(TyG)index,residual cholesterol(RC)and intracranial atherosclerotic stenosis(ICAS)in elderly with ischemic stroke(IS).Methods A total of 209 elderly IS patients admitted in the Affiliated Hospi-tal of Xuzhou Medical University from January to December 2022 were recruited,and according to intracranial artery stenosis,they were divided into stenosis group(n=122)and non-stenosis group(n=87).TyG index and RC levels were calculated after testing different types of Cer.Spearman correlation analysis and logistic regression analysis were used.Results Compared with the non-stenosis group,the stenosis group had significantly larger proportions of higher levels of LP(a),HbA1c,TyG index,RC and Cer16∶0,Cer18∶0,Cer24∶1,Cer16∶0/Cer24∶0,Cer24∶1/24∶0 and Cer18∶0/24∶0,and lower Cer24∶ 0 level(P＜0.05,P＜0.01).The levels of Cer16∶0,Cer18∶0,Cer24∶1,Cer16∶0/24∶0,Cer18∶0/24∶0,Cer24∶1/24∶0,LP(a),HbA1c,TyG index and RC were positively correlated with(r=0.290,0.343,0.383,0.436,0.434,0.481,0.166,0.248,0.140,0.204,P＜0.05,P＜0.01),and Cer24∶0 was negatively with ICAS(r=-0.247,P＜0.01).Cer18∶0,Cer24∶1,Cer16∶0/Cer24∶0,Cer18∶0/Cer24∶0 and RC were important influencing factors for ICAS(P＜0.05,P＜0.01).Conclusion The levels of Cer,TyG index and RC are higher in elderly IS patients,and these indicators might be the risk factors for ICAS.

The Mechanisms of PCSK9 Inhibitor Reducing Lipoprotein(a) / 生物化学与生物物理进展

Lipoprotein(a) (Lp(a)) is a complex circulating lipoprotein, and increasing evidence has demonstrated its role as a risk factor for atherosclerotic cardiovascular disease and as a possible therapeutic target. Proprotein converting enzyme proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor significantly decreases the circulating level of Lp(a) and reduces the risk of cardiovascular events. Based on the research results in recent years, this review will systematically summarize the relevant mechanisms of PCSK9 inhibitor reducing Lp(a) synthesis and promoting its degradation. The mechanisms are influenced by whether statins used in combination and baseline levels of Lp(a). PCSK9 inhibitors decrease Lp(a) levels mainly by reducing Lp(a) synthesis. However, the importance of low-density lipoprotein receptor (LDLR) mediated enhancing Lp(a) degradation gradually increases when the LDL level decreases. Meanwhile, many other receptor pathways may also exist, including very low-density lipoprotein (VLDL) receptor, LDL receptor-related protein 1, CD36, toll-like receptor 2, scavenger receptor B1 and plasminogen receptor. At present, further studies are still needed to explore the mechanisms by which PCSK9 inhibitors reduce Lp(a) level, such as inhibition of Lp(a) synthesis and intracellular assembly, and LDLR-mediated Lp(a) degradation. In addition, whether the reduction of Lp(a) level by PCSK9 inhibitor is related to age, gender and race and whether the dose-effect relationship of reducing Lp(a) is influenced by background lipid level, all of which require in-depth exploration. In short, the cellular and molecular mechanisms underlying the regulation of Lp(a) synthesis and degradation is not completely clear. It is worth carrying out relevant research to provide a theoretical basis for better clinical application of such drugs.

Pathological Characteristics and Classification of Unstable Coronary Atheroscle-rotic Plaques / 法医学杂志

Important forensic diagnostic indicators of sudden death in coronary atherosclerotic heart dis-ease,such as acute or chronic myocardial ischemic changes,sometimes make it difficult to locate the ischemic site due to the short death process,the lack of tissue reaction time.In some cases,the de-ceased died of sudden death on the first-episode,resulting in difficulty for medical examiners to make an accurate diagnosis.However,clinical studies on coronary instability plaque revealed the key role of coronary spasm and thrombosis caused by their lesions in sudden coronary death process.This paper mainly summarizes the pathological characteristics of unstable coronary plaque based on clinical medi-cal research,including plaque rupture,plaque erosion and calcified nodules,as well as the influencing factors leading to plaque instability,and briefly describes the research progress and technique of the atherosclerotic plaques,in order to improve the study on the mechanism of sudden coronary death and improve the accuracy of the forensic diagnosis of sudden coronary death by diagnosing different patho-logic states of coronary atherosclerotic plaques.

Uso de Índices Aterogênicos como Métodos de Avaliação das Doenças Ateroscleróticas Clínicas / Use of Atherogenic Indices as Assessment Methods of Clinical Atherosclerotic Diseases

Resumo Fundamento A busca por métodos clinicamente úteis de avaliação de doenças ateroscleróticas, com boa acurácia, de baixo custo, sem invasividade e de fácil manejo, há anos vem sendo estimulada. Dessa forma, os índices aterogênicos avaliados deste estudo podem se encaixar nesta demanda crescente. Objetivos Avaliar o potencial dos índices aterogênicos como métodos de avaliação de pacientes portadores de aterosclerose clínica. Métodos Estudo transversal de centro único, por meio do qual foram avaliados os índices de Castelli I e II, índice aterogênico plasmático (IAP), índice de combinação de lipoproteínas e a variação do índice de perfusão periférica entre 90 e 120 segundos após um estímulo vasodilatador endotélio-dependente (ΔIPP90-120) na predição de aterosclerose. A significância estatística foi estabelecida em p < 0,05. Resultados A amostra foi composta por 298 indivíduos com idade média de 63,0 ± 16,1 anos, dos quais 57,4% eram mulheres. Comparações pareadas da análise curva ROC dos índices que alcançaram área sob a curva (ASC) > 0,6 mostram que ΔIPP90-120 e IAP foram superiores aos demais índices, sem diferenças observadas entre si (diferença entre ASC = 0,056; IC95% -0,003-0,115). Ademais, tanto a ΔIPP90-120 [odds ratio (OR) 9,58; IC95% 4,71-19,46] quanto o IAP (OR 5,35; IC95% 2,30-12,45) foram preditores independentes de aterosclerose clínica. Conclusões O IAP e ΔIPP90-120 apresentaram melhor acurácia para discriminar aterosclerose clínica. Além disso, foram preditores independentes de aterosclerose clínica, evidenciando uma possibilidade promissora para o desenvolvimento de estratégias preventivas e de controle para doenças cardiovasculares. Tratam-se, portanto, de marcadores adequados para estudos multicêntricos do ponto de vista de praticidade, custo e validade externa.

Abstract Background The search for clinically useful methods to assess atherosclerotic diseases (ASCVD) with good accuracy, low cost, non-invasiveness, and easy handling has been stimulated for years. Thus, the atherogenic indices evaluated in this study may fit this growing demand. Objectives To assess the potential of atherogenic indices to evaluate patients with clinical atherosclerosis. Methods Single-center cross-sectional study, through which the Castelli I and II indices, the atherogenic index of plasma (AIP), the lipoprotein combine index, and the variation in the peripheral perfusion index between 90 and 120 seconds after an endothelium-dependent (ΔPI90-120) vasodilator stimulus were evaluated in the prediction of atherosclerosis. Statistical significance was set at p < 0.05. Results The sample consisted of 298 individuals with an average age of 63.0±16.1 years, of which 57.4% were women. Paired comparisons of the ROC curve analysis of the indices that reached the area under the curve (AUC) > 0.6 show that ΔPI90-120 and AIP were superior to other indices, and no differences were observed between them (difference between AUC = 0.056; 95%CI -0.003-0.115). Furthermore, both the ΔPI90-120 [odds ratio (OR) 9.58; 95%CI 4.71-19.46)] and AIP (OR 5.35; 95%CI 2.30-12.45) were independent predictors of clinical atherosclerosis. Conclusions The AIP and ΔPI90-120 represented better accuracy in discriminating clinical ASCVD. Moreover, they were independent predictors of clinical ASCVD, evidencing a promising possibility for developing preventive and control strategies for cardiovascular diseases. Therefore, they are markers for multicenter studies from the point of view of practicality, low cost, and external validity.

Hallazgos por ecografía Doppler arterial oftálmica en pacientes con enfermedad renal crónica avanzada / Ophthalmic Arterial Doppler Ultrasound Findings in Patients with Advanced Chronic Kidney Disease

Objetivo: Determinar los hallazgos por ecografía Doppler arterial oftálmica en pacientes con enfermedad renal crónica avanzada. Métodos: Se efectuó un estudio observacional descriptivo y transversal con 212 órbitas de 106 pacientes con enfermedad renal crónica avanzada (estadios 4 y 5 en tratamiento dialítico). Por interrogatorio y examen físico se identificaron los factores de riesgo aterosclerótico. Además, se realizó ultrasonido orbitario y Doppler carotídeo, y solo en caso de resultar normales, se procedió a evaluar mediante ecografía Doppler las arterias oftálmicas. Resultados: Predominaron los pacientes mayores de 50 años, el sexo masculino, el color mestizo de piel y los normopesos; mientras que la hipertensión arterial, el tabaquismo y la diabetes mellitus tipo 2 fueron los factores de riesgo aterosclerótico mayoritarios. En todos los enfermos renales crónicos se demostró un incremento de la velocidad del flujo y de la resistencia vascular a nivel de las arterias oftálmicas, en tanto los casos con hipertensión arterial y diabetes mellitus tipo 2, así como los hipertensos exclusivos, mostraron los valores hemodinámicos más elevados. Conclusiones: La evaluación de las arterias oftálmicas mediante ecografía Doppler permite hacer un estudio y seguimiento más integral de los pacientes con enfermedad renal crónica avanzada(AU)

Objective: To determine ophthalmic arterial Doppler ultrasound findings in patients with advanced chronic kidney disease. Methods: A descriptive and cross-sectional observational study was carried out with 212 orbits of 106 patients with advanced chronic kidney disease (stages 4 and 5 in dialysis treatment). Atherosclerotic risk factors were identified by interrogation and physical examination. In addition, orbital ultrasound and carotid Doppler were performed, and only if they were normal, the ophthalmic arteries were evaluated by Doppler ultrasound. Results: Patients older than 50 years, male sex, mestizo skin color and normal weight predominated, while arterial hypertension, smoking and type 2 diabetes mellitus were the main atherosclerotic risk factors. An increase in flow velocity and vascular resistance at the level of the ophthalmic arteries was demonstrated in all chronic renal patients, while cases with arterial hypertension and type 2 diabetes mellitus, as well as exclusive hypertensives, showed the highest hemodynamic values. Conclusions: The evaluation of the ophthalmic arteries by Doppler ultrasound allows a more comprehensive study and follow-up of patients with advanced chronic kidney disease(AU)

Limitaciones de los puntajes de riesgo cardiovascular en prevención primaria. ¿Una oportunidad para los moduladores de riesgo? / Limitations of cardiovascular risk scores in primary prevention. An opportunity for risk modulators?

RESUMEN Introducción : Los puntajes de riesgo cardiovascular tienen limitaciones relacionadas con la calibración, la discriminación y la baja sensibilidad. Se han identificado diferentes "moduladores de riesgo" que permiten mejorar la estratificación del riesgo cardiovascular: placa aterosclerótica carotídea (PAC), puntaje de calcio arterial coronario (pCAC) y lipoproteína(a) [Lp(a)]. Objetivos : 1) determinar la prevalencia de los moduladores de riesgo citados en una población en prevención primaria; 2) determinar la concordancia entre los 2 métodos de detección de aterosclerosis subclínica; 3) establecer qué proporción de pacientes deberían recibir estatinas inicialmente, según su puntaje de riesgo, y posteriormente con el conocimiento de los moduladores de riesgo. Material y métodos : Se incluyeron individuos de 18 a 79 años, que asistieron para una evaluación de riesgo cardiovascular y que no estaban recibiendo tratamiento hipolipemiante. Se calculó el puntaje de riesgo (ASCVD Risk Estimator) en cada paciente. Se evaluó la presencia de PAC, el pCAC y el nivel plasmático de Lp(a). Resultados : Se incluyeron 348 pacientes (edad media 55,6 ± 12,2 años, 45,4% hombres). En la población total, 29,8%, 36,8% y 53,2% de los pacientes mostraron un valor de Lp(a) ≥ 50 mg/dL, PAC o un pCAC > 0, respectivamente. La prevalencia de PAC y pCAC fue progresivamente mayor según la categoría de riesgo cardiovascular; sin embargo, la proporción de sujetos de bajo riesgo que tenían moduladores de riesgo fue considerable (Lp(a) ≥ 50 mg/dl: 25,7%; PAC: 22%; pCAC > 0: 33%). En los 60 individuos menores de 45 años la prevalencia de pCAC > 0 y PAC fue de 18,3% y 10%, respectivamente. La concordancia entre los dos métodos para determinar la presencia de ateromatosis subclínica fue discreta (kappa 0,33). La indicación del tratamiento con estatinas aumentó un 31,6% luego de evaluar la presencia de moduladores. Conclusión : La presencia de moduladores de riesgo fue frecuente en esta población en prevención primaria, incluso en sujetos de bajo riesgo o menores de 45 años. La detección de moduladores de riesgo podría mejorar la estratificación inicial y llevar a reconsiderar el tratamiento con estatinas.

ABSTRACT Background : Cardiovascular risk scores have limitations related to calibration, discrimination, and low sensitivity. Different "risk modulators" have been identified to improve cardiovascular risk stratification: carotid atherosclerotic plaque (CAP), coronary artery calcium (CAC) score and lipoprotein(a) [Lp(a)]. Objectives : The aims of this study were: 1) to determine the prevalence of risk modulators mentioned in a primary prevention population; 2) determine the concordance between the 2 methods of detecting subclinical atherosclerosis; and 3) establish which proportion of patients should receive statins according to the initial risk stratification and after being recategorized by screening for risk modulators. Methods : Individuals aged 18 to 79 years who consulted for cardiovascular risk assessment and who were not receiving lipid-lowering treatment were included. The risk score was calculated in each patient using ASCVD Risk Estimator. The presence of CAP, CAC score and Lp(a) level were evaluated. Results : The cohort was made up of 348 patients; mean age was 55.6 ± 12.2 years and 45.4% were men. In the total population, 29.8%, 36.8%, and 53.2% of patients showed Lp(a) value ≥50 mg/dL, CAP, or a CAC score >0, respectively. The prevalence of CAP and CAC score was progressively higher according to the cardiovascular risk category; however, the proportion of low-risk subjects who had risk modulators was considerable (Lp(a) ≥50 mg/dl: 25.7%; CAP: 22%; CAC score >0: 33%). In the 60 subjects <45 years, the prevalence of CAC score >0 and CAP was 18.3% and 10%, respectively. The agreement between the two methods for quantifying subclinical atheromatosis was fair (kappa= 0.33). The indication for statin treatment increased by 31.6% after evaluating the presence of modulators. Conclusion : The presence of risk modulators was common in this population in primary prevention, even in low-risk subjects or < 45 years. Detection of risk modulators could improve initial stratification and lead to reconsideration of statin treatment.

m 6A RNA Methylation Decreases Atherosclerotic Vulnerable Plaque Through Inducing T Cells

ABSTRACT Introduction: Knockdown of fat mass and obesity-associated gene (FTO) can induce N6-methyladenosine (m 6A) ribonucleic acid (RNA) methylation. The objective of this study was to explore the effect of m 6A RNA methylation on atherosclerotic vulnerable plaque by FTO knockdown. Methods: A total of 50 New Zealand white rabbits were randomly divided into pure high-fat group, sham operation group, vulnerable plaque group, empty load group, and FTO knockdown group (10 rabbits/group). Results: Flow cytometry showed that helper T (Th) cells in the FTO knockdown group accounted for a significantly higher proportion of lymphocytes than in the vulnerable plaque group and empty load group (P<0.05). Th cells were screened by cell flow. The level of m 6A RNA methylation in the FTO knockdown group was significantly higher than in the vulnerable plaque group and empty load group (P<0.05). The levels of total cholesterol, triglyceride, and low-density lipoprotein C were higher at the 12th week than at the 1st week, but the high-density lipoprotein C level was lower at the 12th week than at the 1st week. At the 12th week, the interleukin-7 level was significantly lower in the adeno-associated virus-9 (AVV9)-FTO short hairpin RNA group than in the control and AVV9-green fluorescent protein groups (P<0.001). Conclusion: After successfully establishing a vascular parkinsonism rabbit model, m 6A RNA methylation can decrease Th cells and vulnerable atherosclerotic plaques.

Gender differences with carotid atherosclerotic plaque： a metabolomic study based on UPLC-MS / 中风与神经疾病杂志

@#Objective The purpose of this study is to explore the differences of urine metabolites in carotid atherosclerotic plaque patients of different sexes， explore the different pathogenesis of carotid atherosclerotic plaque in men and women， and try to explain the biological differences caused by gender. Methods Urine of 28 men and 14 women with carotid atherosclerotic plaque were collected and analyzed by ultraperformance liquid chromatography mass spectrometry （UPLC-MS）. Perform metabolomics data analysis based on the Metaboanalysis website to identify differential metabolites between male and female patients. In order to further understand the function of metabolites， biological function and pathway enrichment analysis were conducted on metabolites. Results There were significant differences in the expression of 34 metabolites in the urine of patients with carotid atherosclerotic plaque of different sexes. The functions of these metabolites are mainly enriched in histidine metabolism，β-Alanine metabolism， arginine biosynthesis，pantothenate and coenzyme A biosynthesis，and glutathione metabolism pathways. Conclusion There are significant differences in urine metabolic profiles between male and female patients with carotid atherosclerotic plaque.