Elevated Concentration of Interferon-Inducible Protein of 10 kD (IP-10) Is Associated With Coronary Atherosclerosis.

Several studies have shown that various chemokines are more highly expressed in atherosclerotic plaques than in normal vessel walls. In the present study, we investigated the relationship between coronary atherosclerosis and noteworthy chemokines, including interferon-inducible protein of 10 kD (IP-10); monocyte chemoattractant protein 1 (MCP-1); regulated on activation, normal T-cell expressed and secreted (RANTES); and high-sensitivity C-reactive protein (hsCRP), an established marker of atherosclerotic disease. We studied 28 patients who underwent coronary angiography because of suspected coronary artery disease (CAD). CAD was defined as stenosis of more than 50% of the vessel diameter on coronary angiograms. Blood samples were obtained both from the aorta and the coronary sinus (CS) just before coronary angiography. Relative to CAD (-) patients, those who were CAD (+) tended to have higher plasma concentrations of IP-10 in the aorta, as well as significantly higher transcoronary concentration gradients of circulating IP-10. There were no significant differences between the two groups in aortic plasma concentrations or transcoronary concentration gradients of MCP-1, RANTES, and hsCRP. Furthermore, both the aortic plasma concentrations and transcoronary concentration gradients of IP-10 correlated with the Gensini score (r = 0.58 and r = 0.63, respectively, P < 0.01), while the plasma MCP-1, RANTES, and serum hsCRP concentrations did not. This study suggests that IP-10 is a good surrogate marker of coronary atherosclerosis.

Congenital long QT syndrome with compound mutations in the KCNH2 gene.

Congenital long QT syndrome is a genetic disorder encompassing a family of mutations that can lead to aberrant ventricular electrical activity. We report on two brothers with long QT syndrome caused by compound mutations in the KCNH2 gene inherited from parents who had no prolonged QT interval on electrocardiography. The proband had syncope, and his elder brother suffered from ventricular fibrillation. Genetic testing revealed that both brothers had multiple mutations in the KCNH2 gene, including a missense mutation of C1474T (exon 6) as well as a frameshift/nonsense mutation, resulting from the insertion of 25 nucleotides, which caused an altered amino acid sequence beginning at codon 302 and a premature termination codon (i.e., TAG) at codon 339 (exon 4). Family genetic screening found that their father had the same frameshift mutation, and their mother and sister had the same missense mutation, in the KCNH2 gene. However, these other family members were asymptomatic, with normal QT intervals on electrocardiography. These results suggest that compound mutations in the KCNH2 gene inherited independently from the parents made the phenotypes of their sons more severe.

Pentraxin 3 is a local inflammatory marker in atrial fibrillation.

Increasing evidence indicates that inflammation contributes to the pathogenesis of atrial fibrillation (AF). Pentraxin 3 (PTX3) is produced abundantly in local inflammatory lesions while C-reactive protein (CRP) is produced mainly in the liver. In this study, we investigated whether a local level of PTX3 might be a sensitive marker for the local inflammation of AF. Blood from the periphery and left atrial appendage (LAA) was sampled from 23 patients with AF undergoing pulmonary vein isolation, and from 10 control subjects with Wolff-Parkinson-White syndrome. We measured peripheral and LAA plasma concentrations of CRP, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and PTX3. Plasma PTX3 concentrations in both locations were higher in patients with AF than in control subjects. PTX3 concentrations were significantly higher in the LAA than the periphery in patients with AF (3.7 ± 1.4 vs 3.3 ± 1.2 ng/ml, P < 0.01), but not in control subjects (2.4 ± 0.5 vs 2.4 ± 0.5 ng/ml, not significant). Patients and controls showed no significant differences in CRP, IL-6, or TNF-α concentrations between the periphery and LAA. Interestingly, there was a significant positive correlation between LAA plasma concentrations of PTX3 and left atrial volume (r = 0.55, P < 0.01). These data demonstrate that local PTX3 production in the left atrium might reflect the local inflammation of AF.

Effects of telmisartan on inflammatory cytokines and coronary plaque component as assessed on integrated backscatter intravascular ultrasound in hypertensive patients.

BACKGROUND: Telmisartan has unique pleiotropic effects in addition to renin-angiotensin system (RAS)-inhibition effects. The aim of this study was to evaluate the effects of telmisartan on the coronary plaque component and local inflammatory cytokines. METHODS AND RESULTS: A total of 50 patients with hypertension were randomized to 2 groups: the telmisartan group (additional treatment with telmisartan 80mg/day, n=25) or the control group (additional treatment with other anti-hypertensive drugs except RAS blockers, n=25) for 6 months. Tissue characteristics of target coronary plaque were analyzed using integrated backscatter intravascular ultrasound (IB-IVUS) before and after treatment. Plasma levels of inflammatory cytokines sampled in the coronary sinus (CS) and peripheral vein were also measured. Significant increases in fibrous volume (51.2±10.4 to 58.3±7.7%, P=0.03) and reductions in lipid volume (38.4±12.4 to 32.8±9.7%, P=0.03) were observed on IB in the telmisartan group, while there were no significant changes in the plaque component in the control group. CS levels of inflammatory cytokines (matrix metalloproteinase [MMP]3, tumor necrosis factor-α, high-sensitivity C-reactive protein and MMP9) were lower after than before treatment in the only telmisartan group (7.7±6.1 to 5.5±4.9ng/ml, 3.1±1.9 to 2.3±2.0pg/ml, 5.6±6.0 to 2.2±2.4mg/L, 36.1±39.3 to 19.9±27.5ng/ml, P=0.02, P=0.03, P=0.04, P=0.07, respectively). CONCLUSIONS: Decreased local inflammatory response and plaque stabilization on IB imaging were observed after 6 months of telmisartan treatment. These findings might be associated with local anti-inflammatory and anti-arteriosclerotic effects of telmisartan.

Eosinophilic myocarditis due to Churg-Strauss syndrome with markedly elevated eosinophil cationic protein.

A 67-year-old woman with asthma visited our hospital with increasing dyspnea and new-onset paresthesia and purpura in her legs. Physical examination showed a wheeze, pretibial edema, and surrounding purpura. Chest X-rays showed cardiac decompensation and an electrocardiogram revealed a new ST-T change. Laboratory data showed leukocytosis, hypereosinophilia (10,450/µL), troponin T(+), elevated BNP, and markedly elevated eosinophil cationic protein (ECP) (> 150 ng/mL). Echocardiography revealed diffuse left ventricular hypokinesis (ejection fraction 30%) with increased wall thickness. Coronary angiography was normal. Cardiac magnetic resonance imaging implied diffuse myocardial edema and subendocardial late gadolinium enhancement. Skin biopsy of purpura showed superfi cial perivascular dermatitis with remarkable eosinophilic infiltrations. No evidence of drug allergies, parasitic infection, or myeloproliferative disorder was detected. Based on these findings, a diagnosis of eosinophilic myocarditis due to Churg-Strauss syndrome was considered. She was administered prednisolone at a dose of 1 mg/kg, cyclophosphamide, and diuretics. Several markers of eosinophilic myocarditis and heart failure gradually improved, including ECP. She was discharged 30 days later with no cardiac event. Eosinophilic myocarditis is characterized by predominantly eosinophilic infi ltration. Eosinophilic granule proteins, such as ECP and major basic protein, play important roles in the pathogenesis of eosinophilic myocarditis. We experienced a rare case of eosinophilic myocarditis due to Churg-Strauss syndrome. Markedly elevated ECP played an important role in the early diagnosis and subsequent reduction in ECP served as a marker of monitoring. In an asthmatic patient with dyspnea, hypereosinophilia, and vasculitis, Churg-Strauss syndrome with eosinophilic myocarditis should be considered.

Two cases of acute myocardial infarction during combined chemotherapy in young patients with testicular cancer.

The two patients were males aged over 30 years. To treat testicular tumors, combination chemotherapy with bleomycin, etoposide, and cisplatin (BEP) had been employed. In case 1, during the 4th course of BEP therapy, thoracic pain suddenly appeared. Emergency coronary angiography revealed thrombus formation. Under a diagnosis of thrombus-related acute myocardial infarction, thrombus aspiration was conducted, and stent implantation was performed because mild stenosis and residual thrombus were observed. In case 2, during the 2nd course of BEP therapy, thoracic pain suddenly appeared. Emergency coronary angiography revealed thrombus formation. Intracoronary infusion of pro-urokinase was performed, and additional balloon dilatation was conducted because mild stenosis and residual thrombus were observed. In both cases, the courses were favorable, and the levels of coagulation markers on admission were high. When selecting combination chemotherapy in patients with coronary risk factors, such as obesity and smoking, despite a young age, as demonstrated in these two patients, it may be important to consider combination therapy with anticoagulants or switching to anticancer drugs that do not show vascular toxicity. .

Observation of short-term atorvastatin-induced changes in coronary arterial plaque properties using integrated backscatter intravascular ultrasound in a patient.

Integrated backscatter intravascular ultrasound (IB-IVUS) capable of assessing plaque properties has recently become clinically applicable. We observed short-term atorvastatin-induced changes in coronary arterial plaque properties using IB-IVUS. The patient was a 57-year-old man who underwent coronary angiography when admitted to our hospital for cerebrovascular surgery, and lesions were observed in 2 branches: 99% and 90% stenoses in the proximal anterior descending branch (LAD) and middle region of the circumflex, respectively. Stenting was performed for the LAD on November 4, 2009 and for the circumflex on December 9. Oral atorvastatin administration at 10 mg/day was initiated on November 5 because the LDL-cholesterol level was high (160 mg/dl). A region about 5 mm in length proximal to the stent placed in the LAD was analyzed using IB-IVUS. Atorvastatin lowered the LDL cholesterol level from 160 to 79 mg/dl. On IB image analysis, although the period was as short as about 1 month, a marked decrease in the fatty component (44% â†’ 26%) and an increase in the fibrous component (53% â†’ 66%) were observed in the plaque. It was suggested that atorvastatin changes the tissue properties of coronary arterial plaques from a very early phase. It might be associated with the stabilization of coronary plaque.

Ezetimibe ameliorates metabolic disorders and microalbuminuria in patients with hypercholesterolemia.

AIM: Ezetimibe, an inhibitor of Niemann-Pick C1-like 1 protein, has been shown to reduce the intestinal absorption of cholesterol. We investigated whether it also has beneficial effects on metabolic disorder and/or renal insufficiency in patients with hypercholesterolemia. METHODS: Ezetimibe was administered to 38 Japanese patients with hypercholesterolemia to obtain appropriate low-density lipoprotein cholesterol (LDL-chol) levels. Age- and sex-matched patients with hypercholesterolemia (n=38) were the controls. We evaluated the effects of ezetimibe before and 4 to 8 weeks after ezetimibe treatment. RESULTS: Ezetimibe significantly decreased LDL-chol levels and metabolic syndrome-related factors, including body weight, waist circumference, blood pressure; homeostasis model assessment insulin resistance (HOMA-IR), and urinary albumin excretion, were significantly reduced. In addition, it decreased the level of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-alpha, the urinary excretion of 8-hydroxy-2'-deoxyguanosine, a parameter of oxidative stress, and increased the urinary excretion of nitrate and nitrite (NOx). In the controls we observed no such changes. Excepting the decrease in the serum TNF-alpha level, the effects of ezetimibe were not correlated with decreased LDL-chol levels. CONCLUSION: Ezetimibe ameliorated the status of metabolic syndrome and microalbuminuria, reduced inflammation and oxidative stress, and increased nitric oxide bioavailability in a LDL-chol reduction-dependent and -independent manner.