Pentraxin 3 (PTX3) plasma levels and carotid intima media thickness progression in the general population

Background and aimPentraxin 3 (PTX3) is an essential component of the humoral arm of innate immunity and, like C-reactive protein, is independently associated with the risk of developing vascular events. Aim of this study was to investigate, in two large population-based surveys, the Bruneck Study and the PLIC Study, whether PTX3 plasma levels predict the progression of common carotid artery intima–media thickness (CCA-IMT), a surrogate marker of atherosclerosis, in the general population during 5 or 6 years of follow-up.ResultsIn the Bruneck Study, PTX3 plasma levels did not predict a faster progression of CCA-IMT either in the carotid artery or in the femoral artery. This finding was confirmed in the PLIC Study where subjects within the highest tertile of PTX3 did not show an increased progression of CCA-IMT. PTX3 plasma levels were also not associated with the fastest maximum IMT progression.In summary, in more than 2400 subjects from the general population, PTX3 plasma level is neither an independent predictor of progression of subclinical atherosclerosis in different arterial territories, including carotid and femoral arteries nor of incident cardiovascular events.ConclusionThese findings support the relevance of investigating the predictive value of PTX3 plasma levels only in specific settings, like overt CVD, heart failure or acute myocardial infarction.     

Genetic variation in PTX3 and plasma levels associated with hepatocellular carcinoma in patients with HCV

Hepatitis C virus (HCV) is the main cause of chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC) worldwide. The risk to develop HCC increases with the severity of liver inflammation and fibrosis. Long pentraxin 3 (PTX3) is a soluble pattern‐recognition receptor produced by phagocytes and nonimmune cells at sites of inflammation or injury. The aim of the present study was to determine the association of PTX3 polymorphisms and its plasma levels with HCC occurrence among patients with HCV. Samples from 524 patients with chronic hepatitis C were evaluated in this study. Two polymorphisms (rs1840680 and rs2305619) in the PTX3 gene were determined by real‐time PCR. PTX3 plasma levels were measured by Enzyme‐linked Immunosorbent Assay (ELISA). Our data show a significant association between PTX3 polymorphisms and HCC occurrence in univariate and multivariate analysis (P = 0.024). Patients with HCC had higher PTX3 plasma levels compared to individuals with mild or severe fibrosis (P < 0.0001 and P = 0.002, respectively). In addition, PTX3 rs2305619 polymorphism and plasma levels were correlated with Child‐Pugh scores B and C in HCC individuals. PTX3 seems to be a risk factor for HCC occurrence in chronic hepatitis C. This is the first study that evaluates PTX3 in the context of hepatitis C.     

Circulating levels of pentraxin-3 (PTX3) in patients with liver cirrhosis

BackgroundDespite the circulating levels of PTX3 were related to the severity of various diseases, there are no studies investigating its role in patients with liver cirrhosis. We aimed to study PTX3 levels in patients with liver cirrhosis.Material and methodsA prospective cohort study included 130 patients hospitalized for acute decompensation of liver cirrhosis, 29 stable cirrhotic outpatients and 32 healthy controls evaluated in a tertiary hospital in Southern Brasil.ResultsThe median PTX3 level was significantly higher in stable cirrhotic patients compared to controls (2.6 vs. 1.1 ng/mL; p < 0.001), hospitalized cirrhotic patients compared to controls (3.8 vs. 1.1 ng/mL; p < 0.001), and hospitalized cirrhotic patients compared to stable cirrhotic patients (3.8 vs. 2.6 ng/ mL; p = 0.001). A positive correlation was found between PTX3 and serum creatinine (r = 0.220; p = 0.012), Chronic Liver Failure -Sequential Organ Failure Assessment score (CLIF-SOFA) (r = 0.220; p = 0.010), MELD (r = 0.279; p = 0.001) and Child-Pugh score (r = 0.224; p = 0.010). Significantly higher levels of PTX3 were observed in patients on admission with ACLF (8.9 vs. 3.1 ng/mL; p < 0.001) and MELD score ≥ 20 (6.6 vs. 3.4 ng/mL; p = 0.002). Death within 90 days occurred in 30.8% of patients and was associated with higher levels of PTX3 (5.3 vs. 3.4 ng/mL; p = 0.009). The probability of Kaplan-Meier survival was 77.0% in patients with PTX-3 < 5.3 ng mL (upper tercile) and 53.5% in those with PTX3 ≥ 5.3 ng/mL (p = 0.002).ConclusionThese results indicate the potential for use of PTX3 as an inflammatory biomarker for the prognosis of patients with hepatic cirrhosis.     

Increased levels of serum pentraxin 3, a novel cardiovascular biomarker,in patients with inflammatory rheumatic disease

Objective

Pentraxin 3 (PTX3), a key component of innate immunity, is a strong marker of disease severity in coronary artery disease (CAD). The aim of this study was to compare levels of serum PTX3 in CAD patients with and without inflammatory rheumatic disease (IRD) and in healthy controls.

Methods

We examined 69 patients with IRD (CAD/IRD group) and 53 patients without IRD (CAD/non‐IRD) referred to coronary artery bypass grafting, and 30 healthy controls.

Results

The mean ± SD serum PTX3 level in the CAD/IRD group was 1.96 ± 0.98 ng/ml; this was statistically significantly higher than that of the CAD/non‐IRD (1.41 ± 0.74 ng/ml) and healthy control (1.21 ± 0.59 ng/ml) groups. In contrast to most other IRDs, serum PTX3 levels were relatively low in patients with systemic lupus erythematosus (SLE) and other systemic connective tissue diseases. In sex‐ and age‐adjusted analysis, IRD, acute coronary syndromes, and low alcohol intake were associated with higher serum PTX3 levels.

Conclusion

CAD patients with IRD had higher mean serum PTX3 levels than patients without IRD and healthy controls. In addition, acute coronary syndromes and low alcohol intake independently predicted higher serum PTX3 levels. Higher serum PTX3 levels in IRD may be related to the higher cardiovascular risk of IRD patients. Circulating PTX3 could likely be used as a biomarker for severity of cardiovascular disease in IRDs; its importance, however, might be limited in SLE and related disorders.     

Correlation between soluble receptor for advanced glycation end products levels and coronary artery disease in postmenopausal nondiabetic women

BACKGROUNDThe established cardiovascular risk factors cannot explain the overall risk of coronary artery disease (CAD), especially in women. Therefore, there is a growing need for the assessment of novel biomarkers to identify women at risk. The receptor for advanced glycation end products (RAGE) and its interaction with the advanced glycation end product (AGE) ligand have been associated with atherogenesis. The soluble fraction of RAGE (sRAGE) antagonizes RAGE signaling and exerts an antiatherogenic effect.AIMThe study aim was to explore the association between plasma levels of sRAGE and CAD in nondiabetic postmenopausal women.METHODSThis case-control study included 110 nondiabetic postmenopausal women who were enrolled in two groups. Group I included 55 angiographically proven CAD subjects with > 50% stenosis in at least one of the major coronary arteries and Group II included 55 healthy control women who did not have CAD or had < 50% stenosis of the coronary arteries. Stenosis was confirmed by invasive angiography. Plasma sRAGE was determined by an enzyme-linked immunosorbent assay.RESULTSWe observed significantly lower plasma sRAGE concentrations in subjects with CAD vs healthy controls (P < 0.05). Univariate and multivariate logistic regression analysis also revealed a significant correlation between plasma sRAGE levels and CAD (P = 0.01). Multivariate odds ratios for CAD revealed that subjects with sRAGE concentrations below 225 pg/mL (lowest quartile) had a 6-fold increase in CAD prevalence independent of other risk factors.CONCLUSIONOur findings indicated that low sRAGE levels were independently associated with CAD in nondiabetic postmenopausal women. Risk assessment of CAD in postmenopausal women can be improved by including sRAGE along with other risk factors.     

Elevated concentrations of pentraxin 3 are associated with coronary plaque vulnerability

Background

Inflammation is a critical contributing factor to the development and progression of atherosclerosis. Pentraxin 3 (PTX3) is produced abundantly in atherosclerotic lesions while C-reactive protein (CRP) is mainly produced in the liver. In this study, we investigated whether plasma levels of PTX3 might be a sensitive marker both for the severity of coronary artery disease and vulnerable plaques. Next, we determined whether assays for inflammatory molecules can be used to monitor the therapeutic effects of telmisartan on stabilization of vulnerable atherosclerotic plaques.

Methods and results

We measured PTX3 concentrations in the peripheral and coronary sinus plasma of 40 patients with angina pectoris (AP) and 20 control subjects. Next, in 28 patients with AP, we determined the correlation between levels of inflammatory molecules and the computed tomography (CT) density of plaques as a quantitative index of plaque vulnerability. There was no significant difference in peripheral plasma PTX3 concentrations between patients with AP and control subjects, while coronary sinus plasma PTX3 concentrations were significantly higher in AP patients than control subjects. The concentrations of PTX3 in coronary sinus and peripheral plasma correlated with Gensini scores as an index of severity of coronary atherosclerosis. Interestingly, there was a significantly negative correlation between plasma PTX3 concentrations and CT density (r = −0.67, p < 0.01). On the other hand, CT density did not correlate with the peripheral plasma concentrations of monocyte chemoattractant protein-1 (MCP-1) or high-sensitivity CRP (hsCRP). Furthermore, telmisartan treatment for 6 months decreased plasma concentrations of PTX3 but not those of MCP-1 or hsCRP in 12 patients with essential hypertension. Multivariate regression analysis revealed that changes in PTX3 levels were independent of blood pressure changes.

Conclusions

PTX3 is likely more specific than hsCRP as an indicator of coronary plaque vulnerability that could lead to plaque rupture.     

Lp-PLA2、PTX3对冠心病患者PCI术后支架内再狭窄的预测价值

目的 探讨脂蛋白相关性磷脂酶A2(Lp-PLA2)、正五聚蛋白-3(PTX3)对冠状动脉粥样硬化性心脏病（CHD）患者经皮冠状动脉介入（PCI）术后支架内再狭窄（ISR）的预测价值。方法 选取因冠状动脉严重狭窄行PCI治疗的CHD患者379例。根据术后6个月复查是否发生ISR,分为ISR组（n=53)、非ISR组(n=326)。收集两组一般临床资料,监测两组术后1 d的Lp-PLA2和PTX3水平。采用Logistic逐步回归分析ISR发生的危险因素。术后6个月复查外弹力膜横截面积（EEM-CSA）、斑块面积（PLA）、最小管腔面积（MLA）,内膜面积（IPA）及Gensini积分。分析Lp-PLA2和PTX3与Gensini积分、EEM-CSA、MLA、PLA、IPA的相关性。采用ROC曲线评估Lp-PLA2和PTX3预测ISR的最佳截断值与AUC。结果 (1)ISR组STEMI(P<0.05)、吸烟史（P<0.01）、糖尿病（P<0.01）、LDL-C(P<0.05)、支架串联（P<0.05）、应用分叉术式（P<0.01）、支架置入时长（P<...     

Circulating miR-214 is associated with the severity of coronary artery disease

Objective To study whether miR-214 is regulated in coronary artery disease (CAD) patients and whether placental growth factor (PLGF) is a possible target for miR-214 in atherosclerosis. Methods Circulating miR-214 was measured by quantitative PCR using RNA isolated from 40 patients with CAD, including 12 with stable angina pectoris, 16 with unstable angina pectoris and 12 with acute myocardial infarction, and 15 controls without CAD. Plasma level of PLGF was measured by ELISA. Results The miR-214 level was significantly lower in CAD patients compared with that in controls (P < 0.01). Compared to controls, patients with unstable angina pectoris (UAP, 38.6±9.1 pg/mL) and acute myocardial infarction (AMI, 46.3±13.4 pg/mL) had significantly higher level of plasma PLGF, but not those with stable angina pectoris (SAP; P = 0.012, UAP vs. Control; P = 0.005, AMI vs. Control). In patients with AMI, the plasma level of miR-214 was positively correlated to that of PLGF. Conclusions The results suggest that miR-214 is a beneficial microRNA for CAD patients. Loss of its protection may lead to increased PLGF levels and worsening atherosclerosis. Circulating miR-214 is a promising biomarker for alerting severe CAD.     

PTX3 in small‐vessel vasculitides: An independent indicator of disease activity produced at sites of inflammation

Objective

To verify whether the prototypical long pentraxin PTX3 represents an indicator of the activity of small‐vessel vasculitis.

Methods

Concentrations of PTX3, a pentraxin induced in endothelium by cytokines, were measured by enzyme‐linked immunosorbent assay in the sera of 43 patients with Churg‐Strauss syndrome, Wegener's granulomatosis, and microscopic polyangiitis. PTX3 was also measured in the sera of 28 patients with systemic lupus erythematosus (SLE), 22 with rheumatoid arthritis, and 16 with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias). Serum concentrations of C‐reactive protein (CRP) were measured by immunoturbidimetry. The cells involved in PTX3 production in vivo were identified in skin biopsy samples.

Results

Patients with active vasculitis had significantly higher concentrations of PTX3 than did those with quiescent disease (P < 0.001). PTX3 levels in the latter group were similar to those in healthy controls. PTX3 levels were higher in patients with untreated vasculitis and lower in patients who underwent immunosuppressive treatments (P < 0.005). In contrast, patients with active SLE had negligible levels of the pentraxin. PTX3 levels did not correlate with CRP levels in vasculitis patients. Endothelial cells produced PTX3 in active skin lesions.

Conclusion

PTX3 represents a novel acute‐phase reactant produced at sites of active vasculitis.

     

Adiponectin receptor 1 and small ubiquitin-like modifier 4 polymorphisms are associated with risk of coronary artery disease without diabetes

Background The genes encoding adiponectin receptor 1 (ADIPOR1) and small ubiquitin-like modifier 4 (SUMO4) have been linked to anti-atherogenic effects, but little is known about whether polymorphisms in the two genes, acting separately or interacting, affect risk of coronary artery disease (CAD) without diabetes. Methods We genotyped 200 CAD patients without diabetes and 200 controls without CAD or diabetes at three single-nucleotide polymorphisms (SNPs) in ADIPOR1 and one SNP in SUMO4, which were chosen based on previous studies. Potential associations were also explored between these SNPs and clinical characteristics of CAD without diabetes. Results Risk alleles at three SNPs in ADIPOR1 (rs7539542-G, rs7514221-C and rs3737884-G) and the G allele at SNP rs237025 in SUMO4 significantly increased risk of CAD without diabetes, with ORs ranging from 1.79 to 4.44. Carriers of any of these four risk alleles showed similar adverse clinical characteristics. Compared with individuals with a CC or GC genotype, those with a GG genotype at rs3737884 were at significantly higher risk of CAD that affected the left anterior descending coronary artery (OR: 6.77, P = 0.009), the right coronary artery (OR: 4.81, P = 0.028) or a relatively large number of vessels (P = 0.04). Individuals carrying a risk allele at one or more of the three SNPs in ADIPOR1 as well as a risk allele at the SNP in SUMO4 were at significantly higher risk of CAD without diabetes than individuals not carrying any risk alleles (OR: 5.82, 95% CI: 1.23?27.7, P = 0.013). Conclusions SNPs in ADIPOR1 and SUMO4 are associated with elevated risk of CAD without diabetes, and SNPs in the two genes may interact to jointly affect disease risk.     

Anatomic features of the left main coronary artery and factors associated with its bifurcation angle: a 3-dimensional quantitative coronary angiographic study

Objective : To assess the anatomic characteristics of the left main coronary artery (LM), and the relation between anatomic and clinical factors and the LM bifurcation angle (BA) using a novel, three dimensional quantitative coronary angiography (3D QCA) software. Background : Percutaneous intervention of the LM is a therapeutic option in selected patients with coronary artery disease (CAD). The anatomic features of the LM and its BA are determinants of procedural success and clinical outcome. However, those features and the factors that may affect the LM BA have not been fully described. Methods : The LM anatomy was evaluated from angiograms of 203 patients (age = 66 ± 11 years, 31% female) with and without LM CAD using 3D QCA analysis (IC‐PRO, Paieon, Israel). LM size as well as the proximal BA (between LM and LCX) and the distal BA (between left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX)) were measured in end‐diastole. Angiographic and clinical findings were also recorded. Results : 133/203 patients (65%) had no LM CAD. 3D QCA analysis demonstrated significant variability in the anatomy of the normal LM, including the LM branch vessels (LAD, LCX) diameter, and the LM BA. Among the 70 patients with LM CAD, 44 had distal LM disease. Importantly, patients with distal LM CAD had narrower proximal BA and a wider distal BA. Multivariate analysis (adjusted for clinical and anatomic variables) identified female sex (P = 0.02), trifurcation anatomy (P = 0.009), age > 75 years (P = 0.0009), and LM length > 12 mm (P = 0.001) as independent associates of the proximal BA. Independent associates of the distal BA were: trifurcation anatomy (P = 0.001), LM length > 12 mm (P < 0.0001), age > 75 years (P = 0.004), and a history of coronary bypass surgery (P = 0.04). Conclusions : The current study demonstrates significant variability in the anatomy of the LM. The LM BA differs between patients with and without distal LM CAD, and both anatomic and clinical factors may affect the LM BA. Our findings also emphasize the possible usefulness of 3D QCA in the assessment of the LM. © 2012 Wiley Periodicals, Inc.     

Correlation between single nucleotide polymorphisms in the 3 primer untranslated region of PTX3 and the risk of essential hypertension: A case–control study

The aim of this study was to investigate the correlation between single-nucleotide polymorphisms (SNPs) in the 3 primer of untranslated region (3’UTR) of the Pentraxin 3 (PTX3) gene and the risk of essential hypertension (EHT).PTX3 genotypes, rs2614, rs111451363, and rs73158510 locus, were found in 260 patients with EHT and 260 healthy controls. Quantitative real-time polymerase chain reaction was used to detect plasma hsa-miR-4766-5p levels. Enzyme-linked immunosorbent assay was used to detect plasma PTX3 levels. The dual-luciferase reporter assay was used to identify the binding site of hsa-miR-4766-5p to the PTX3.PTX3 rs2614 locus T allele was a high risk factor for EHT (odds ratio [OR] = 2.76, 95% confidence interval [CI]: 1.86–4.09, P < .01). Sex and diabetes history affected the correlation between PTX3 gene rs2614 locus SNP and EHT risk. The CCG haplotype was a protective factor for EHT (OR = 0.40, 95% CI: 0.28–0.57, P < .01), whereas the TCG haplotype was a risk factor for EHT (OR = 2.35, 95% CI: 1.51–3.66, P < .01). The plasma PTX3 level of patients with EHT was significantly higher than that of the control group, and the difference was statistically significant (P < .01). The area under the curve for EHT diagnosis in plasma PTX3 levels was 0.62 (95% CI: 0.57–0.66, P < .01). The plasma hsa-miR-4766-5p level in patients with EHT was significantly lower than that in the control group (P < .01). The area under the curve for the diagnosis of EHT according to the plasma hsa-miR-4766-5p level was 0.88 (95% CI: 0.85–0.91, P < .01). Plasma PTX3 levels were significantly negatively correlated with hsa-miR-4766-5p levels in patients with EHT and the control group (r = −0.87, −0.85, P < .01, P < .01). The PTX3 gene rs2614 locus C allele was the target gene of hsa-miR-4766-5p.The PTX3 rs2614 locus SNP is significantly associated with EHT risk.     

Correlation between serum osteoprotegerin and atherosclerotic vascular disorders in rheumatoid arthritis patients

Aim of the workThe aim of the present study was to investigate the association of serum osteoprotegerin (OPG) level with the presence of angiographically documented asymptomatic coronary artery disease (CAD) in patients with rheumatoid arthritis (RA) and to evaluate its relationship with plasma thrombomodulin (TM), as a marker of endothelial dysfunction and with carotid artery intima media thickness (IMT), as a marker of atherosclerosis.Patients and methodsThe study included 20 rheumatoid patients without CAD (negative results on exercise ECG stress test) and other 20 rheumatoid patients with CAD (positive results on exercise ECG stress test and confirmed by coronary angiography). In addition, 20 age and sex matched normal control subjects were studied. Serum OPG and plasma TM levels were measured and carotid artery IMT was determined.ResultsThe study revealed that serum OPG levels were significantly higher in rheumatoid patients with and without CAD than in controls (P < 0.001, P < 0.01; respectively) and were positively correlated with age, duration of disease, Disease active score 28(DAS28), Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and carotid IMT in rheumatoid patients with and without CAD. Serum OPG level was correlated significantly with plasma TM only in rheumatoid patients with CAD (P < 0.001).ConclusionOsteoprotegerin is a clinically important molecule independently associated with the presence of coronary artery disease and may be a good indicator of atherosclerotic vascular damage and macroangiopathy in asymptomatic rheumatoid patients. Hence, measurement of serum OPG merits further investigation as a simple test for improving early diagnosis of asymptomatic CAD in rheumatoid patients.     

Circulating biomarkers of angiogenesis as indicators of left ventricular systolic dysfunction amongst patients with coronary artery disease

Background. Patients with coronary artery disease (CAD) and left ventricular systolic dysfunction (LVSD) are often asymptomatic. Angiogenesis is implicated in the physiology of vascular repair and cardiac remodelling, and is one of many pathophysiological processes implicated in heart failure. We hypothesized that plasma indices associated with angiogenesis [angiogenin, vascular endothelial growth factor (VEGF), and angiopoietin (Ang)‐1 and Ang‐2] would be abnormal in CAD patients with LVSD, being correlated with EF and wall motion abnormalities (wall motion score) independently of underlying CAD (coronary atheroma score). We also evaluated the specificity of angiogenic ‘biomarkers’ in their detection of LVSD [ejection fraction (EF) <40%] amongst CAD patients. Methods. Using a cross sectional approach, we measured angiogenin, VEGF, Ang‐1 and Ang‐2 by ELISA in 194 CAD patients (aged 34–81 years) undergoing elective coronary angiography. Results. Levels of angiogenin were inversely related with EF (r = ?0.17, P = 0.02) and positively with coronary atheroma scores (r = 0.15, P = 0.04, but not independently of EF). Other angiogenic markers were unrelated to objective measures of LVSD but VEGF (P = 0.008) and Ang‐2 (P = 0.015) were lower amongst those patients with heart failure. Angiogenin levels were related to wall motion scores (r = 0.16, P = 0.024). Conclusion. Heart failure has a modest impact on biomarkers of angiogenesis, in patients with CAD. Further research is warranted into the diagnostic and prognostic utility of biomarkers of angiogenesis, in this common cardiac condition.     

Serum paraoxonase-3 concentration is associated with insulin sensitivity in peripheral artery disease and with inflammation in coronary artery disease

ObjectiveThere are no data on the relationship between serum paraoxonase-3 (PON3) concentration and atherosclerosis in humans. Our aim was to investigate possible associations, using recently developed methods, in patients with peripheral artery disease (PAD) or coronary artery disease (CAD).MethodsWe studied 118 PAD and 72 CAD patients and 175 healthy volunteers. Serum PON3 was determined by in-house ELISA using polyclonal antibodies generated against a synthetic peptide with a sequence specific to PON3. Polymorphisms of the PON3 promoter were analysed by the Iplex Gold MassArray? method.ResultsThere was a significant increase in serum PON3 concentration in both groups of patients with respect to the control group. In PAD patients, we observed significant positive correlations between PON3, insulin levels and HOMA index. These associations were not observed in CAD. There were significant positive associations between serum PON3 and β-2-microglobulin, CCL2 and high-sensitivity C-reactive protein in CAD patients, but not in PAD. We did not find any significant differences in PON3 gene promoter polymorphisms and their haplotypes between patients and controls, indicating that associations were not genetically determined.ConclusionIn both atherosclerotic phenotypes, serum PON3 concentration was increased, but this was associated with decreased insulin sensitivity in PAD and with inflammation in CAD.     

Excess coronary heart disease in Familial Combined Hyperlipidemia, in relation to genetic factors and central obesity

AIM: To determine the prevalence of non-fatal coronary artery disease (CAD) in kindred with Familial Combined Hyperlipidemia (FCHL) in relation to various cardiovascular risk factors and DNA variation in the apo AI-CIII-AIV gene cluster. METHODS AND RESULTS: Data were collected from 18 Dutch FCHL probands, 202 living first and second degree relatives, and 175 spouses. Probands and first degree relatives showed dyslipidemia, increased plasma insulin and glucose concentrations, higher waist--hip ratio (WHR), and blood pressure, than spouses. The frequency of the minor alleles M2 and S2 was increased in probands and first degree relatives. The Odds Ratio for CAD was 5.3 in male FCHL relatives (P=0.005), and 5.1 in all FCHL relatives (P=0.001). First and second degree relatives had a markedly reduced CAD-free life-span (logrank vs. spouses: P<0.001 and P=0.03, respectively). The presence of the S2, but not M2, minor allele, showed a marked reduction in CAD-free life-span (logrank S2 present vs. S2 absent: P=0.035). CONCLUSION: Men with FCHL have a severely increased risk of CAD, that appears to be mediated through genetic relation to the proband as the strongest independent risk factor for CAD, followed by increased WHR.     

Plasma PTX3 levels in sickle cell disease patients,during vaso occlusion and acute chest syndrome (data from Saudi population)

Background

Sickle cell disease (SCD) is a chronic, incurable hereditary disease. The vaso-occlusive crisis (VOC) is the most frequently occurring acute complication in sickle cell patients and accounts for the majority of SCD-related hospital admissions. Another major complication is the potentially fatal acute chest syndrome (ACS). The prototypic long pentraxin-3 (PTX3), an acute phase protein and a key component of innate immunity, is linked to ischemia-induced inflammation, a condition incriminated in SCD complications.

Aim

To investigate the expression of PTX3 in stable SCD and VOC patients and to assess its relation to the development and progression of ACS.

Subjects and methods

We conducted this study on 160 patients with confirmed SCD (20 stable SCD and 140 in VOC), and 10 healthy age- and sex-matched controls. Patients were diagnosed as SCD by high-performance liquid chromatography. PTX3 levels were assessed using enzyme-linked immunosorbant assay.

Results

In the stable state, all 20 SCD patients had PTX3 levels (range = 0.9–2.1 ng/ml; median = 1.1) comparable to those of healthy controls (range = 0.8–2.0 ng/ml; median = 1.0) (P > 0.05). During the VOC, plasma PTX3 significantly increased (range = 8.7–37.2 ng/ml; median = 22.3) (P < 0.01). Out of 140 VOC patients, 15 (10.7%) developed ACS and four required mechanical ventilation, of which two died. The median plasma level of PTX3 (22.3 ng/ml) was set as a cut-off value to stratify patients into low- and high-PTX3 expressers. Of the 140 VOC patients, 43 (30.7%) had PTX3 levels >22.3 ng/ml, of these, 13 patients developed ACS (13/43; 30.2%); of the remaining 97 patients who had PTX3 ≤22.3 ng/ml, only two patients (2/97; 2.1%) progressed to ACS, with a further increment in PTX3 in all of them. PTX3 levels were correlated with length of hospital stay in VOC patients and markers of lung injury in ACS patients.

Conclusion

PTX3 levels were higher in SCD patients in VOC, being associated with longer hospital stay. Higher initial PTX3 concentrations were related to the development of ACS with a further increase in PTX3 levels observed upon progression to ACS. Thus, PTX3 could be used as a subjective method to predict occurrence and severity of SCD acute complications.     

Interleukin-18: a strong predictor of the extent of coronary artery disease in patients with unstable angina

The aim of this study was to confirm that plasma interleukin (IL)-18 level is associated with the extent of coronary artery disease in unstable angina patients. Previous studies have shown that patients with unstable angina have significantly higher plasma IL-18 levels than healthy volunteers. However, the association between IL-18 and the extent of coronary artery atherosclerosis in patients with unstable angina remains unclear. Plasma concentrations of IL-18 and high-sensitivity C-reactive protein (hs-CRP) were measured in 166 consecutive patients admitted for coronary arteriography. One hundred and eighteen patients with unstable angina had coronary artery disease (coronary artery disease group; severity score: 2.32 ± 1.47; Gensini score: 31.3 ± 25.9), and 48 patients with coronary risk factors and without coronary artery lesions served as the risk control group. Plasma levels of IL-18 were higher in the coronary artery disease group than in the risk control group (P = 0.062). Additionally, plasma levels of IL-18 were significantly higher in 77 coronary artery disease patients with severity score ≥2 than in the risk control group (242.3 ± 110.6 vs 209.8 ± 120.3 pg/ml, P = 0.016). By univariate analysis, log-transformed plasma IL-18 concentration was positively correlated with coronary artery disease severity score (r = 0.244, P = 0.009). By multiple regression analyses, the association between coronary artery disease severity score and IL-18 remained significant (β = 0.733, P = 0.017) when controlling for age, diabetes mellitus and left ventricular ejection fraction. Additionally, coronary artery disease severity score was greater in the highest tertile (>246 pg/ml) of plasma IL-18 levels than in the middle (176–246 pg/ml) and the lowest (<176 pg/ml) tertiles (2.79 ± 1.52 vs 2.05 ± 1.08 vs 2.13 ± 1.66, P = 0.028). Of note, plasma hs-CRP level had no significant correlation with coronary artery severity. Plasma IL-18 level is associated with the extent of coronary artery disease in unstable angina patients, suggesting the link between IL-18 and coronary artery atherosclerosis in these patients.     

Patients with coronary artery disease not amenable to traditional revascularization: Prevalence and 3‐year mortality

Objectives: To determine the contemporary prevalence of and mortality in patients with coronary artery disease (CAD) not amenable to revascularization. Background: A growing number of patients have severe CAD with ongoing angina despite optimal medical therapy which is not amenable to traditional revascularization. Limited data exist on contemporary prevalence and outcome for these patients. Methods: Clinical and angiographic data were reviewed for 493 consecutive patients undergoing coronary angiography and revascularization if indicated. Patients were categorized into six groups: (1) normal coronary arteries, (2) CAD <70%, (3) CAD >70% with complete revascularization by percutaneous intervention or coronary artery bypass grafting, (4) CAD >70% with partial revascularization, (5) CAD >70% treated medically, and (6) CAD >70% on optimal medical therapy with no revascularization option. All‐cause mortality at 3 years was determined. Results: Prevalence for groups 1–6 was 14.8, 19.5, 36.9, 12.8, 9.3, and 6.7%, respectively. Three‐year mortality increased with angiographic severity of CAD: 2.7, 6.3, 8.2, 12.7, 17.4, and 15.2%, respectively. Patients with incomplete revascularization (groups 4–6, n = 142) had higher mortality than completely revascularized patients (groups 1–3, n = 351): 14.8 vs. 6.6% (P = 0.004). Conclusions: In a contemporary series of patients undergoing coronary angiography, 28.8% (142/493) of patients had significant CAD and did not undergo complete revascularization, including 12.8% partially revascularized, 9.3% managed medically, and 6.7% with “no‐option.” These patients had higher mortality at 3 years (14.8 vs. 6.6%, P = 0.004) when compared with completely revascularized patients. © 2010 Wiley‐Liss, Inc.     

Decreased plasma urotensin Ⅱ levels inversely correlate with extent and severity of coronary artery disease

Objective To determine the plasma urolensin Ⅱ(UII) levels in various types of coronary heart disease and to clarify how the plasma UII levels correlate with the clinical presentation, extent and severity of coronary artery atherosclerosis (CAD). Methods: One hundred and three aged patients undergoing elective diagnostic coronary angiography for proven or clinical suspected coronary heart disease were enrolled in this study. The extent and severity of coronary artery disease were evaluated by vessel score and Gensini score, respectively. Plasma UII levels were measured by radioimmunoassay. Results: The plasma UII levels in the patients with modest to severe coronary stenosis (3.03±0.34 pg/ml, 1.83±0.67 pg/ml) were significantly lower than that in subjects with normal coronary artery (4.80±1.11 pg/ml, P<0.001). The plasma UII levels in patients with coronary heart disease were also significantly lower than that in patients with insignificant coronary stenosis (P < 0. 001). Compared to patients with stable angina pectoris, plasma UII levels in patients with acute coronary syndrome were significantly decreased (1.89±0.51 pg/ml vs 2.42±0.77 pg/ml, P < 0.001). Plasma UII levels were found to be negatively correlated with the severity of coronary artery stenosis (r = -0.488, P<0.001), as well as the vessel score (r = -0.408, P<0.05) in the patients with CAD. Conclusion: Significant inverse correlations exist between the plasma UII levels, and the extent and severity of coronary artery stenosis. These findings suggest that plasma UII contribute to the development and progression of coronary artery stenosis, and may be a novel marker to predict clinical types, as well as the extent and severity of coronary artery disease in the patients.