Role of advanced oxidation protein products and Thiol ratio in patients with acute coronary syndromes

ObjectivesTo identify systemically detectable vascular inflammation associated to redox system unbalance, advanced oxidation protein products (AOPP), formed by HClO reaction with proteins, Thiol levels, and their ratio (AOPP/Thiol ratio) were measured in patients with acute coronary syndromes (ACS).Design and methodsWe evaluated AOPP/Thiol ratio together with CRP and IL-1β in 18 acute myocardial infarction (AMI) and in 16 unstable angina (UA) patients at admission, and in 16 control subjects (CTR); the measurements were repeated at 1 and at 6 months.ResultsAt admission, AMI and UA patients displayed higher AOPP/Thiol ratio and CRP and IL-1β compared to CTR subjects. A correlation between AOPP/Thiols and IL-1β in AMI was found. At follow-up, in UA only, AOPP/Thiol ratio and IL-1β levels still remained high.ConclusionsThe AOPP/Thiol ratio seems to affect the inflammatory process in ACS, and may represent a reliable marker of oxidative unbalance in this setting of patients.     

Lymphocytic enzymes and lipid peroxidation in patients with metabolic syndrome

ObjectivesMetabolic syndrome (MetS) is considered a state of chronic inflammation. This study aimed to ascertain selected parameters of purinergic and cholinergic systems related to glucose metabolism and inflammation, as well as _γ-glutamyltransferase (GGT) and N-acetyl-b-glucosaminidase (NAG) activities and lipoperoxidation in lymphocytes of patients with MetS.Design and methodsThe adenosine deaminase (ADA), dipeptidyl peptidase IV (DPP-IV), acetylcholinesterase (AChE), GGT and NAG activities, as well as thiobarbituric acid reactive substances (TBARS) levels were investigated in lymphocytes of patients with MetS (n = 38) and healthy volunteers (n = 41). We also evaluated the insulin levels, anthropometric measurements and routine biochemical analyses.ResultsADA (p < 0.05), DPP-IV and AChE (p < 0.0001) activities were higher in patients with MetS when compared to the control group. Furthermore, we observed correlations between ADA and DPP-IV activities (p = 0.0002; r = 0.5945), TBARS levels and ADA (p = 0.0021; r = 0.5172) and DPP-IV activities (p = 0.0022; r = 0.5010).ConclusionsOur findings showed that MetS might cause tissue distress that disturbed lymphocytic ADA, DPP-IV and AChE activities in response to inflammatory stimuli. These alterations evidence clinical abnormalities, since these enzymatic systems are able to regulate several aspects of adipose tissue function and inflammatory state of MetS and could be used successfully both for preventing and for halting the progression of MetS.     

Soluble klotho as an effective biomarker to characterize inflammatory states

Background & AimsSoluble α-Klotho (s-Klotho) is a circulating protein with pleiotropic effects that mainly induce protective effects. Our study investigates the associations between s-Klotho and several established inflammatory biomarkers, with the aim of examining whether s-Klotho levels are representative of inflammatory states.MethodsA total of 11,128 eligible participants from NHANES 2007–2016 were included in our study. Levels of four inflammatory biomarkers, uric acid (UA), C-reactive protein (CRP), white blood cell (WBC) count, and mean platelet volume (MPV), were examined for their relationship with s-Klotho levels. Sub-analyses sorted the total population by gender and into four quartiles. Linear regression models were used to evaluate the strengths of associations.ResultsAll four inflammatory biomarkers were significantly associated with s-Klotho levels. UA, CRP, and WBC count showed an inverse association, while MPV showed a direct one. Of the four markers, UA was most strongly correlated with s-Klotho levels (β coefficient: −28.89 in unadjusted model, p<.001), and this relationship was stronger in women than in men (β coefficient of UA in men: −22.01, p<.001; in women: −31.54, p<.001). In addition, all four biomarkers manifested stronger associations with s-Klotho in higher quartiles, and the highest absolute values of β coefficients appeared in Q4 vs. Q1.Conclusions-Klotho is significantly associated with well-recognized inflammatory biomarkers. A decrease in s-Klotho levels implies a general inflammatory status; therefore, s-Klotho serves as a potential biomarker that is inversely correlated with inflammatory conditions. Further applications in clinical practice will provide us with a better understanding of its role.

Key messages

• Soluble α-Klotho (s-Klotho) levels are significantly associated with the inflammatory markers uric acid, C-reactive protein, white blood cell count, and mean platelet volume.
• S-Klotho is involved in inflammatory processes and plays a protective role.
• S-Klotho may serve as an inverse indicator of inflammation.

     

妊娠相关蛋白-A及C反应蛋白对不稳定型心绞痛的诊断意义

目的探讨妊娠相关蛋白-A(PAPP-A)和C-反应蛋白(CRP)对不稳定型心绞痛(UA)的诊断意义。方法分别采用双抗体夹心酶联免疫吸附法和双抗体放射免疫法检测23例UA患者、21例稳定型心绞痛(SAP)患者和18名健康对照者的血浆PAPP-A和CRP浓度。结果UA组CRP和PAPP-A浓度明显高于SAP组和健康对照组(P<0.05)。SAP组和健康对照组CRP和PAPP-A浓度比较无明显差异性(P>0.05)。结论PAPP-A和CRP是UA的炎性标记物,可能是预测冠心病的危险程度的重要指标。     

Soluble CD40 ligand, soluble P-selectin and von Willebrand factor levels in subjects with prediabetes: the impact of metabolic syndrome

ObjectivesThe data regarding circulating levels of markers of platelet activation and endothelial function in people with prediabetes are scant. The aim of the present study was to search blood levels of soluble CD40 ligand (sCD40L), soluble P-selectin (sP-sel) and von Willebrand Factor (vWF) in subjects with prediabetes, along with the effects of the metabolic syndrome (MetS) on these markers.Design and methodsA total of 77 prediabetic individuals and 81 age, sex and body mass index matched healthy subjects with normal glucose tolerance (NGT) were prospectively analyzed. Anthropometric parameters, fasting plasma glucose, blood d lipid profiles and insulin resistance indexes were determined. Plasma sCD40L, sP-sel and vWF levels were measured by ELISA.ResultssCD40L, sP-sel and vWF levels in the prediabetic group were similar to those in the controls. However, prediabetic subjects with the MetS had significantly higher level of sCD40L compared to those without MetS. Moreover, sCD40L level correlated significantly with waist circumference, systolic blood pressure and HDL-cholesterol level in the patient group.ConclusionThese data imply that MetS may contribute, at least in part, to the mechanism of platelet activation and endothelial dysfunction in people with prediabetes.     

Immunonutrition before and during radiochemotherapy: improvement of inflammatory parameters in head and neck cancer patients

Purpose

Inflammatory, angiogenic and oxidative stress markers have been explored in head and neck squamous cell carcinoma (HNSCC) patients before and during radiochemotherapy. Furthermore, the effects of an oral supplementation containing amino acids, ω-3 fatty acids, ribonucleic acids, vitamins, and antioxidants on biological markers and acute toxicities were investigated.

Methods

Thirty-one patients with non-metastatic stage III or IV HNSCC treated with concomitant radiochemotherapy were recruited. A nutritional support (Oral Impact?) was given during 5?days before each cycle of chemotherapy. Biological samples were collected at baseline, after 5?days of oral supplementation and before the last cycle of chemotherapy. Acute phase proteins levels, proteomic cytokines determination and urinary isoprostanes levels were used as inflammatory and oxidative stress biomarkers. Toxicities were followed up during radiochemotherapy.

Results

At baseline, median levels of inflammatory (CRP 9.8?mg/l [0.8–130.1], IL-6 4.2?pg/ml [0.7–126.5]), pro-angiogenic (VEGF 229.5?pg/ml [13.1–595.9]) and pro-oxidative stress (urinary isoprostanes 118 pmol/mmol creatinine [51–299]) markers were increased. Decrease in CRP (p?=?0.002) and α-1 acid glycoprotein (p?=?0.020) levels were observed after 5?days of oral supplementation. During radiochemotherapy, no significant variation of inflammatory markers was reported, and a low incidence of severe acute mucositis was noted.

Conclusions

Stage III or IV HNSCC patients are characterised by a pro-inflammatory, pro-angiogenic and pro-oxidative status. Nutritional support could improve this inflammatory state and could prevent severe acute mucositis.     

The Rho kinase signaling pathway participates in tubular mitochondrial oxidative injury and apoptosis in uric acid nephropathy

IntroductionOxidative stress is a pathologic feature of hyperuricemia that is highly prevalent and that contributes to kidney tubular interstitial fibrosis. Rho-kinase is closely related to mitochondrial-induced oxidative stress. Herein, we designed a study to explore the expression and role of Rho-kinase in hyperuricemia nephropathy. The secondary objective was to investigate whether the Rho-kinase signaling pathway regulates hyperuricemic tubular oxidative injury and apoptosis via the mitochondrial pathway in addition to the mechanisms that are involved.Materials and methodsHK-2 cells were divided into the following five groups: normal; uric acid (UA); UA+Fasudil; UA+ROCK1 si-RNA; and UA+sc-siRNA. Rho-kinase activity, mitochondrial oxidative injury, and apoptosis-related protein levels were measured in each group. A t-test was used to analyze the difference between groups.ResultsMyosin phosphatase target subunit 1 (MYPT1) overexpression was shown in HK-2 cells, which was caused by UA. High concentrations of UA also up-regulated Rho-kinase expression and mitochondrial and apoptosis-related protein expression, while treatment with fasudil and ROCK1 si-RNA significantly attenuated these responses.ConclusionThe Rho-kinase signaling pathway participates in tubular mitochondrial oxidative injury and apoptosis via regulating mitochondrial dyneins/biogenic genes in UA nephropathy, which suggests that the mitochondrial pathway might be a potential therapeutic target for hyperuricemia nephropathy.     

血清尿酸和C反应蛋白与老年女性脑梗死后疲劳发生的相关性分析

目的研究血尿酸(UA)及C反应蛋白(CRP)水平与老年女性脑梗死后疲劳(PSF)发生的相关性。方法回顾性选取本院2018年5月-2019年8月收治住院的老年女性脑梗死患者313例,依据是否发生PSF分为PSF组101例和对照组212例。比较两组一般临床资料,检测患者血清UA、CRP、Hcy水平,采用Barthel指数(ADL)评价患者日常生活能力。Logistic回归分析PSF发生的独立危险因素。Spearman相关分析对血清UA、CRP与ADL评分进行相关分析。结果相较于对照组,PSF组患者血清UA、CRP、Hcy水平明显增高(P<0.01)。血清UA与ADL评分呈负相关(r=-0.132,P=0.020);CRP与ADL评分呈负相关(r=-0.127,P=0.025)。结论除了血清Hcy,血清UA、CRP水平与老年女性PSF发生亦密切相关,血清UA、CRP升高是其独立危险因素之一,是影响患者预后的危险因素。     

Aldosterone,C-Reactive Protein,and Plasma B-Type Natriuretic Peptide Are Associated With the Development of Metabolic Syndrome and Longitudinal Changes in Metabolic Syndrome Components: Findings from the Jackson Heart Study

OBJECTIVE

Several pathomechanisms are implicated in the pathogenesis of metabolic syndrome (MetS), most of which have not been investigated in African Americans (AAs). We examined the contribution of a selected panel of biomarkers to the development of MetS in Jackson Heart Study (JHS) participants in this investigation.

RESEARCH DESIGN AND METHODS

We evaluated 3,019 JHS participants (mean age, 54 years; 64% women) with measurements for seven biomarkers representing inflammation (high-sensitivity C-reactive protein [CRP]), adiposity (leptin), natriuretic pathway (B-natriuretic peptide [BNP]), adrenal pathway (cortisol and aldosterone), and endothelial function (endothelin and homocysteine). We related the biomarker panel to the development of MetS on follow-up and to longitudinal changes in MetS components.

RESULTS

There were 278 (22.9%) of 1,215 participants without MetS at baseline who had development of new-onset MetS at follow-up. The incidence of MetS was significantly associated with serum aldosterone (P = 0.004), CRP (P = 0.03), and BNP (P for trend = 0.005). The multivariable-adjusted odds ratios (95% CI) per SD increment of log biomarker were as follows: 1.25 (1.07–1.45) for aldosterone, 1.20 (1.02–1.43) for CRP, and 1.54 (1.07–2.23) and 1.91 (1.31–2.80) for low and high BNP quartiles, respectively. Aldosterone was positively associated with change in all MetS risk components, except low HDL cholesterol and waist circumference. CRP concentration was significantly and directly associated with change in systolic blood pressure (SBP) and waist circumference but inversely associated with HDL cholesterol. For BNP, we observed a U-shape relation with SBP and triglycerides.

CONCLUSIONS

Our analysis confirms that, in AAs, higher circulating aldosterone and CRP concentrations predict incident MetS. The nonlinear U-shape relation of BNP with MetS and its components has not been reported before and thus warrants replication.The main components of metabolic syndrome (MetS) include dyslipidemia (low HDL cholesterol [HDL-C] and high triglycerides levels), impaired glucose homeostasis (high fasting plasma glucose), high blood pressure (BP), and abdominal obesity. Findings from several cross-sectional and longitudinal studies have shown that MetS is associated with higher concentrations of circulating inflammatory markers (1,2) and neurohormonal activation (3,4). The elevation of these biomarkers often precedes the development of risk factors such as type 2 diabetes (5), insulin resistance (IR) (6,7), and hypertension (7,8). Few studies, however, have examined the conjoint and relative contributions of multiple biomarkers to the development of MetS, and none have been conducted in African Americans (AAs) to our knowledge. Recently, Ingelsson et al. (9) evaluated a comprehensive panel of eight biomarkers representing inflammation, hemostasis, neurohormonal activation, and endothelial dysfunction for their association with the incidence of MetS and its risk factors in Framingham. Ingelsson et al. found that higher circulating plasminogen activator inhibitor-I and aldosterone levels were each associated with the development of MetS and with longitudinal changes of MetS components in whites. Because ethnic differences exist in levels of visceral adiposity, IR, and circulating levels of novel biomarkers (such as C-reactive protein [CRP], adiponectin, and plasma homocysteine), we investigated the individual and conjoint association of selected circulating biomarkers with the incidence of MetS and with longitudinal tracking of MetS components among AAs in the Jackson Heart Study (JHS). We evaluated a panel of seven biomarkers representing inflammation (CRP), adiposity (leptin), adrenal pathway (cortisol and aldosterone), natriuretic pathway (B-type natriuretic peptide [BNP]), and endothelial function (endothelin, ET-1, and homocysteine). Although IR is not a key component of MetS, we used it as a covariate in secondary analysis because it frequently accompanies MetS (10,11) and to avoid confounding of any potential association by IR.     

中性粒细胞淋巴细胞比率在衡量肥胖病人炎症状态的初步探讨

目的 观察中性粒细胞淋巴细胞比率(neutrophil-lymphocyte ratio,NLR)作为炎症标志物在患有肥 胖和代谢综合征的病人中的诊断价值。方法 根据肥胖程度和代谢综合征的发展状态选取253个受试对象,根 据WHO推荐诊断标准,BMI<25 kg/m²,25 kg/m²2,BMI>30分别为健康组、超重组和肥胖组,比较各组间的代谢和炎症标志物,并进行相 关分析。结果 各组间白细胞计数和C反应蛋白(CRP)有显著差异(P<0.01),随着肥胖程度的发展, 淋巴细胞和中性粒细胞计数显著增加,NLR在各组间无显著性差异(P<0.05)。白细胞总数、中性 粒细胞、淋巴细胞和CRP与身高体重指数(BMI)呈显著相关性,但是NLR和BMI无显著相关性。结论 对评价肥 胖伴代谢综合征病人的炎症状态,NLR不是一个好的衡量炎症指标,白细胞计数和CRP是比较有用的衡量炎症 指标。     

Oxidative stress parameters and keap 1 variants in T2DM: Association with T2DM,diabetic neuropathy,diabetic retinopathy,and obesity

IntroductionChronic hyperglycemia activates the inflammatory pathways and oxidative stress mechanisms with consequent damage to nerve tissue and retina. The Keap1‐Nrf2 pathway acts as one of the most important antioxidant pathways of the organism. Variants of Keap1 could affect susceptibility to diabetes and its complications.MethodsIn a case‐control study, 400 individuals included type 2 diabetes mellitus (T2DM) patients without complication, with neuropathy, with retinopathy, and healthy individuals were investigated. The levels of glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured using chemical methods. Using the PCR‐RFLP method, the Keap1 (rs11085735) variants were identified.ResultsNeuropathic patients had significantly lower levels of GSH, GPx, and TAC and higher levels of total oxidative status (TOS), MDA, and oxidative stress index (OSI) compared to T2DM patients without complication and controls. Lower levels of GSH and GPx and a higher level of MDA were observed in patients with retinopathy compared with controls. Obesity was associated with significantly lower GPx activity and higher TOS. A significantly higher Keap1 AA genotype was found in patients with neuropathy than T2DM without complication and controls. The presence of Keap1 AA genotype correlated with lower GPx activity compared to CC genotype.ConclusionsOur study suggests the role of reduced antioxidant system and Keap1 variants in the pathogenesis of T2DM and its complications of neuropathy and retinopathy and also obesity in enhanced oxidative stress. Monitoring oxidative stress parameters in diabetic patients, especially those with complication and their treatment with antioxidants is suggested.     

Altered nitric oxide/cGMP platelet signaling pathway in platelets from patients with acute coronary syndromes

This study was aimed at evaluating whether the nitric oxide (NO)/cyclic GMP (cGMP) signaling pathway is altered in platelets from patients with an acute coronary syndrome (unstable angina and acute myocardial infarction). We investigated 10 patients with unstable angina (UA), 14 with acute myocardial infarction (AMI) and 14 age and sex-matched healthy subjects. The serum markers of platelet activation (sP-selectin), inflammation (TNF-α and erythrocyte sedimentation rate), thrombotic state (fibrinogen) and plaque disruption were significantly higher in both UA and AMI patients compared to the healthy controls. In their platelets we assessed the cGMP levels in basal conditions and after stimulation with sodium nitroprusside (SNP), and performed Western blot analysis of homogenates to measure the expression of soluble guanylate cyclase isoforms. Basal levels of cGMP (pmol/10¹⁰ platelets) were significantly higher in platelets from UA patients (1,097 ± 111; p < 0.0001) and AMI (1,122 ± 77; p < 0.0001) compared to those collected from healthy controls (497 ± 80). The platelets of AMI patients exhibited a lack of cGMP increase after SNP stimulation in comparison with UA patients. The phosphorylation of upstream (Akt1 protein kinase α and endothelial NO synthase) and downstream (vasodilator-stimulated phosphoprotein, VASP) signaling proteins of the NO/cGMP pathway was investigated: serine phosphorylation in Akt1, eNOS and VASP was enhanced in platelets from UA and AMI patients when compared to controls. Furthermore, in AMI patients the inhibitors of guanylate cyclase and cGMP-dependent protein kinase did not revert the VASP phosphorylation. These data suggest that platelets from AMI patients are more resistant to SNP stimulation, not only as cGMP production, but also in terms of VASP activation. From these ex vivo results we hypothesize that the increased inflammatory state which often accompanies patients with cardiovascular diseases might promote a platelet preactivation resulting in their reduced sensitivity to NO.     

马来酸罗格列酮对合并糖尿病的冠心病患者部分炎症指标的影响

目的观察应用马来酸罗格列酮对合并糖尿病的冠心病患者体内部分炎症因子水平的影响。方法30例合并有2型糖尿病的冠心病患者在原有治疗的基础上加用马来酸罗格列酮治疗,治疗前及治疗3个月后分别检测空腹血糖(FPG)、血胰岛素(FIns)、糖化血红蛋白(HbA1c),C反应蛋白(CRP),肿瘤坏死因子a(TNFa)和可溶性白介素2受体(SIL-2R),比较各指标的变化。结果马来酸罗格列酮治疗3个月后患者的CRP、TNFa、SIL-2R出现显著下降(P<0.01),FPG、FIns、HbA1c亦显著下降(P<0.01;P<0.05),胰岛素敏感性指数则明显上升(P<0.05)。结论在合并2型糖尿病的冠心病患者中应用马来酸罗格列酮治疗,不仅可以改善其糖代谢,还可降低患者体内部分炎症因子的水平,可能对冠心病患者的预后有益。     

高敏C-反应蛋白、同型半胱氨酸、D-二聚体在冠心病病情严重程度评估中的应用

目的探讨高敏c-反应蛋白（hs—cRP）、同型半胱氨酸（Hcy）、D一二聚体（D—D）与冠心痛（CHD）病情严重程度的相关性。方法选取冠心痛患者164例，其中急性心梗（AMI）7l例，不稳定性心绞痛（UA）58例，稳定性心绞痛（SA）35例，并对uA患者进行Braunwald分级，对AMI患者进行KiUip分级．另选健康体检者40例为对照；对以上所有受试者采用免疫散射比浊法检测hs—CRP的含量，采用循环酶法检测Hcy，采用增强免疫比浊法检测血浆D—D，并进行统计学分析。结果冠心病患者hs—CRP、Hey、D—D均显著高于正常对照组（P〈0．01），且AMI组〉uA组〉SA组；hs—CRP、Hey、D—D与疾病严重程度存在良好的相关性：随着Braunwald分级增高，uA患者hs—CRP、Hey、D—D逐渐升高，Hey、D—D三级问每两者之间的的差异均有统计学意义（P〈0．05）；随着KiUip分级增高。AMI患者血清hs—CRP、Hey、D—D也逐渐逐渐升高，Hey、D—D三级间每两者之间的的差异均有统计学意义（P〈0．05）；AMI组和uA组的hs—cI蹬、Hcy、D—D明显高于sA组（P〈0．05）。结论hs—cRP、Hcy、D—D与冠心病的严重程度存在良好的相关性，常规检测hs—CRP、Hcy、D—D时冠心病的辅助诊断及其病情严重程度的评估有一定的临床意义，并能早期预测急性冠脉综合症（hCS）危急事件的发生。     

Postsurgical inflammatory response is not associated with increased serum cystatin C values

ObjectivesCystatin C is used both as a glomerular filtration (GFR) marker and a cardiovascular risk marker. There are several studies showing an association between cystatin C and inflammatory markers and it has been suggested that the inflammatory response in itself could result in elevated cystatin C levels. The aim of this study was to evaluate if an induced inflammatory response has an effect on cystatin C levels in humans.Materials and methodsCRP and cystatin C were analyzed in serum samples from orthopedic surgery patients (n = 29). The patients were sampled prior to surgery and four and thirty days after surgery.ResultsThe surgery induced a pronounced CRP elevation on day four, median 137.3 (interquartile range 104.1–178.2) mg/L compared to 1.94 (1.20–8.70) mg/L before surgery, P < 0.001, but no significant difference in cystatin C levels before and four and thirty days after surgery could be seen.ConclusionsThe orthopedic surgery-induced inflammatory response does not cause changes in cystatin C levels.     

Inflammatory markers in relation to insulin resistance and the metabolic syndrome

Background Inflammation has repeatedly been demonstrated to be associated with the metabolic syndrome (MetS) and insulin resistance, but the relative importance of different aspects of the inflammatory process is largely unexplored. Design We measured circulating interleukins (IL‐1α, IL‐1β, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10); other cytokines (tumour necrosis factor‐α, interferon gamma and monocyte chemotactic protein‐1), cell adhesion molecules [vascular cell adhesion molecule‐1 (VCAM‐1), intercellular adhesion molecule‐1, E‐selectin, P‐selectin, l ‐selectin], and systemic inflammation markers [C‐reactive protein (CRP) and leukocyte count] in 943 70 year old participants (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. We related these biomarkers to MetS and the homeostasis model assessment insulin resistance index (HOMA‐IR). Results In a multivariable model including all inflammatory markers conjointly together with sex, log VCAM‐1 [odds ratio (OR), 1·45; 95% confidence interval (CI), 1·22–1·72 per 1 SD increase; P < 0·0001], log E‐selectin (OR, 1·33; 95% CI, 1·12–1·57 per 1SD increase; P = 0·001), and log CRP (OR, 1·41; 95% CI, 1·20–1·66 per 1‐SD increase; P < 0·0001) were independently associated with MetS. These biomarkers were also independently associated with HOMA‐IR. Conclusions Among 17 inflammatory biomarkers, most of them previously not examined in relation to MetS and insulin resistance, VCAM‐1, E‐selectin and CRP demonstrated the strongest associations with MetS and insulin resistance in our community based sample of the elderly. The relative importance of these biomarkers in predicting the development of MetS, insulin resistance and cardiovascular disease needs to be further examined in a longitudinal setting.     

Relationship between markers of activated coagulation, their correlation with inflammation, and association with coronary heart disease (NPHSII)

Summary.  Objective:  To determine whether activation of coagulation increases in parallel with inflammation and whether coagulation activation markers (CAMs) are independently associated with coronary heart disease (CHD), in the prospective study, NPHSII. Methods:  Surveillance of 2997 men between 50 and 63 years yielded 314 first CHD events during 36507 person-years of observation. The plasma levels of activated factor XII (FXIIa), the peptides released upon activation of factor X (FXpep) and factor IX (FIXpep), activated factor VII (FVIIa), prothrombin fragment 1 + 2 (F1 + 2) and fibrinopeptide A (FpA) served as indices of activity along the coagulation pathway. C reactive protein (CRP) provided a marker of inflammatory activity. Results:  While borderline or significant correlations were identified for each CAM with inflammation, as determined by CRP levels, these did not reach as high a numerical value as was shown for fibrinogen with CRP. FVIIa and FIXpep possessed independent associations with CHD: a one SD increase in adjusted FIXpep and FVIIa level was associated with a relative hazard of 1.20 (95% CI 1.00–1.43) and 0.70 (CI 0.58–0.86), respectively, using a group including all CHD events, compared with 'no-event'. Conclusions:  Inflammation has significant but minimal impact upon CAMs of the extrinsic coagulation pathway. Reduced FVIIa and increased FIXpep levels were found to be significant, independent, predictors of CHD.     

不稳定型心绞痛患者血清cTnI、CK-MB、CRP水平变化及与心肌微循环状态的关系

目的探讨不稳定型心绞痛(UA)患者血清心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶MB(CKMB)、C反应蛋白(CRP)水平变化及与心肌微循环状态的关系。方法选取2019年2月至2020年7月于南京中医药大学附属盐城市中医院和江苏省苏州市相城人民医院就诊住院的109例心绞痛患者和54例同期体检健康者为研究对象,根据WHO分级标准分为稳定型心绞痛(SA)组44例、UA组65例、健康组54例,采用夹心酶联免疫吸附法、免疫抑制法、乳胶增强免疫透射比浊法分别检测3组研究对象血清cTnI、CK-MB、CRP水平,并记录其阳性检出率。UA组行冠状动脉造影(CAG),根据入院时的Braunwald分级标准另分为Ⅰ级低危险组20例、Ⅱ级中危险组23例、Ⅲ级高危险组22例,对比各危险组患者血清cTnI、CK-MB、CRP水平及阳性检出率,并分析UA组患者血清cTnI、CK-MB、CRP水平与心肌微循环状态关系。结果 UA组、SA组与健康组的血清cTnI、CK-MB、CRP水平及其阳性检出率由高到低均呈UA组>SA组>健康组变化(P<0.05)。高危险组、中危险组与低危险组的cTnI、CK-MB、CRP水平及其阳性检出率、病变血管支数组间两两比较,差异均无统计学意义(P>0.05);高危险组、中危险组与低危险组CTFC值由高到低呈高危险组>中危险组>低危险组变化(P<0.05)。UA组中cTnI、CK-MB、CRP检测结果为阳性者发生血管病变的比例均明显高于结果为阴性者(P<0.05)。结论 UA患者血清CK-MB、CRP水平较SA患者及健康人群高,其血清水平上调可能预测心肌微循环状态不良,临床监测上述指标对其具有重要诊断及鉴别价值。     

Allopurinol improves endothelial function and reduces oxidant-inflammatory enzyme of myeloperoxidase in metabolic syndrome

OBJECTIVE: In this study, we tested in patients with metabolic syndrome whether allopurinol through decreasing oxidative stress improves endothelial function, and ameliorates inflammatory state represented by markers of myeloperoxidase, C-reactive protein (CRP) and fibrinogen. METHODS: In a randomized, double-blind fashion; subjects with metabolic syndrome were treated with allopurinol (n = 28) or placebo (n = 22) for one month. Before and after treatment, blood samples were collected and the flow-mediated dilation (FMD) and isosorbide dinitrate (ISDN)-mediated dilation of the brachial artery were performed. RESULTS: Baseline clinical characteristics of the allopurinol and placebo groups demonstrated no differences in terms of clinical characteristics, endothelial function and inflammatory markers. After the treatment with allopurinol, FMD was increased from 8.0 +/- 0.5 % to 11.8 +/- 0.6% (P < 0.01), but there were no change in the placebo group. In both groups, ISDN-mediated dilation is unaffected by the treatment. As a marker of oxidative stress, allopurinol significantly reduced malondialdehyde. Moreover, myeloperoxidase levels were reduced by the treatment with allopurinol (56.1 +/- 3.4 ng/ml vs. 44.4 +/- 2.4 ng/ml, P < 0.05) but there were no change in the placebo group. Surprisingly, neither CRP nor fibrinogen levels were affected by the treatment in both groups. CONCLUSION: Xanthine oxidoreductase inhibition by allopurinol in patients with metabolic syndrome reduces oxidative stress, improves endothelial function, ameliorates myeloperoxidase levels and does not have any effect on CRP and fibrinogen levels.     

血清VILIP-1、尿酸、CRP、NSE水平与脑梗死患者预后的关系研究

目的探讨血清视锥蛋白样蛋白-1(VILIP-1)、血尿酸(UA)、C反应蛋白(CRP)、神经元特异性烯醇化酶(NSE)的水平与脑梗死患者预后的关系。方法选取2018年11月至2019年4月该院收治的首次发病脑梗死患者90例为试验组,选取同期来该院体检的健康者90例为对照组。采用酶联免疫吸附试验(ELISA)测定血浆VILIP-1水平,酶法测定血清UA水平,免疫透射比浊法检测CRP水平,电化学发光法测定血清NSE水平。然后在患者接受治疗的第1天及第90天分别进行Rankin评分。结果试验组患者血清VILIP-1、UA、CRP、NSE水平均明显高于对照组(P<0.05);经统计学分析,随着脑卒中病情的加重及梗死面积的扩大,血清VILIP-1、UA、CRP、NSE水平升高(P<0.05);预后良好的患者血清VILIP-1、UA、CRP、NSE水平明显低于预后不良的患者(P<0.05);ROC曲线分析结果显示,VILIP-1的临界值、灵敏度和特异度分别为7.27μg/L、0.835、0.807,UA的临界值、灵敏度和特异度分别为326.42μmol/L、0.693、0.722,CRP的临界值、灵敏度和特异度分别为1.85mg/L、0.685、0.713,NSE的临界值、灵敏度和特异度分别为20.65ng/L、0.785、0.862,4项指标联合检测的曲线下面积最大,为0.922。结论血清VILIP-1、UA、CRP、NSE异常表达参与了急性脑梗死发病过程,且与患者脑损伤严重程度、预后密切相关,早期联合检测可作为预测急性脑梗死预后的重要标志物。