Elevated serum neopterin predicts future adverse cardiac events in patients with chronic stable angina pectoris

Avanzas, Pablo; Arroyo-Espliguero, Ramón; Quiles, Juan; Roy, Debashis; Kaski, Juan Carlos

doi:10.1093/eurheartj/ehi111

Cited by 126 publications

(101 citation statements)

References 33 publications

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“…Previous clinical studies have demonstrated that neopterin is associated with atherosclerotic plaque instability in coronary artery disease (CAD) [6][7][8][9][10][11][12][13][14][15][16][17] . Circulating levels of neopterin have been reported to be higher in patients with acute coronary syndrome (ACS) than in control subjects and in patients with stable angina pectoris (SAP) 6,7) .…”

Section: Neopterin and Plaque Instability In Coronary Arteriesmentioning

confidence: 99%

“…These findings suggest that neopterin is an important biomarker of plaque instability in both coronary and carotid atherosclerotic lesions. [6][7][8][9][10][11][12][13][14][15][16][17][18] . In this review, we focus on the relationship between neopterin and plaque instability in coronary and carotid arteries, and also introduce the results of our recent studies.…”

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confidence: 99%

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Neopterin and Atherosclerotic Plaque Instability in Coronary and Carotid Arteries

Sugioka

Naruko

Matsumura

et al. 2010

JAT

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Inflammation plays a key role in atherosclerosis and plaque vulnerability, and monocyte/macrophage activation contributes to these processes. Neopterin, a by-product of the guanosine triphosphate pathway, is produced by activated macrophages on stimulation with interferon-released from T lymphocytes, and is an activation marker for monocytes/macrophages. Coronary angiographic studies have shown a relationship between increased circulating levels of neopterin and the presence of complex coronary lesions in patients with unstable angina pectoris (UAP). Furthermore, in an immunohistochemical study performed using coronary atherectomy specimens, a significantly higher prevalence of neopterin-positive macrophages was found in culprit lesions in patients with UAP than in those with stable angina pectoris (SAP). We recently clarified that the presence of complex carotid plaques detected by carotid ultrasound was related to increased circulating levels of neopterin, and immunohistochemical localization of neopterin was observed in complex carotid lesions obtained from carotid endarterectomy in patients with SAP. These findings suggest that neopterin is an important biomarker of plaque instability in both coronary and carotid atherosclerotic lesions. [6][7][8][9][10][11][12][13][14][15][16][17][18] . In this review, we focus on the relationship between neopterin and plaque instability in coronary and carotid arteries, and also introduce the results of our recent studies.

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Section: Neopterin and Plaque Instability In Coronary Arteriesmentioning

confidence: 99%

mentioning

confidence: 99%

Neopterin and Atherosclerotic Plaque Instability in Coronary and Carotid Arteries

Sugioka

Naruko

Matsumura

et al. 2010

JAT

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“…Likewise, in patients with cardiovascular, neurodegenerative and autoimmune disorders, rather close associations have been described between the concentrations of total homocysteine and immune activation and inflammation markers: for example, neopterin (7,8) and C-reactive protein (9), which themselves are significant predictors of cardiovascular risk (10)(11)(12). Neopterin concentrations serve as a reliable immune response marker because a great amount of neopterin is released by monocyte-derived macrophages and dendritic cells upon stimulation with Th1-type cytokine interferon-γ (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Early Increase of Plasma Homocysteine in Sepsis Patients with Poor Outcome

Ploder

Kurz

Spittler

et al. 2010

Mol Med

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Moderate hyperhomocysteinemia is a well-established coronary risk factor that develops when dietary supply with folate and/or vitamin B 12 is inadequate. Recently, stimulated peripheral blood mononuclear cells were shown to produce homocysteine. Thus, the stimulated immune system may contribute to moderate hyperhomocysteinemia during certain diseases. Because multiple trauma and sepsis are accompanied by often strong inflammatory responses, we investigated whether hyperhomocysteinemia may develop in patients. Total homocysteine and cysteine concentrations were measured in 83 plasma specimens from 18 patients (14 men, 4 women; 15 posttrauma with sepsis and 3 with sepsis alone) every third day of follow-up. Finally results were compared with concentrations of cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6, the immune activation marker neopterin and the extent of tryptophan degradation as indicated by the kynurenine-to-tryptophan ratio (kyn/trp). Compared with baseline, average total homocysteine (P < 0.05, d 4-d 10) and cysteine (P < 0.05, d 7-d 13) concentrations increased during follow-up of patients. However, only the increase of homocysteine was related to the survival status: total homocysteine was significantly higher in nonsurvivors (P < 0.05, d 4 and d 10) than in survivors, whereas cysteine concentrations increased in both subgroups. Homocysteine correlated with kyn/trp but not with neopterin concentrations. Increase of total homocysteine is common in patients after trauma with unfavorable outcome. Because all patients received standardized enteral nutrition after the end of hypodynamic shock, inconsistent vitamin supply is unlikely to be the reason for hyperhomocysteinemia in some of the patients; rather, it is associated with a stronger proinflammatory response. Certainly, the number of patients in our study is still small and results can only be regarded as preliminary.

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“…(34), akut miyokart enfarktüslü (MI) hastaları sağlıklı kontrol grubu ve KAP'lı hastalarla karşılaştırdığında neopterin düzeylerini akut MI'lı hastalarda yüksek bulmuşlardır. Kararlı anjina pektorisli 297 hastanın 1 yıllık takiplerinde neopterinin majör kardiyak olayların bağımsız prediktörü olduğu gösterilmiştir (7). Artmış neopterin düzeyleri ayrıca hipertansif ve tıkayıcı olmayan koroner arter hastalıklı bireylerde istenmeyen kardiyak olay gelişimi ile (35) ve koroner revaskülarizasyon yapılan hastalarda hastalığın hızlı seyri ile ilişkili bulunmuştur (36).…”

Section: Discussionunclassified

“…C-reaktif protein (CRP), koroner arter hastalığı risk faktörlerinden bağımsız olarak iskemik olaylar için güçlü bir belirteçtir (5,6). Benzer şekilde, inflamasyonla ilişkili bir belirteç olan neopterin de kararlı anjina pektorisli (KAP) hastalarda kardiyovasküler olayları öngördürücü bir piteridin bileşiğidir (7).…”

Section: Introductionunclassified

The relation between exercise- induced myocardial ischemia and high-sensitive C-reactive protein and neopterin levels

Başar¹,

Yaşar²,

Erden³

et al. 2010

Anadolu Kardiyol Derg

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ÖZETAmaç: Yüksek duyarlılıklı C-reaktif protein (hsCRP) ve neopterin, ateroskleroz gelişimi ile ilişkilidir. Bu çalışmada kararlı anjina pektorisli (KAP) hastalarda, egzersiz stres testi (EST) esnasında oluşan miyokart iskemisi ile hsCRP ve neopterin seviyeleri arasındaki ilişki ve EST ile hsCRP ve neopterin düzeylerinde meydana gelen değişimin tıkayıcı koroner lezyon varlığını öngörmedeki yeri araştırılmıştır. Yöntemler: Çalışmamız prospektif, gözlemsel olarak dizayn edildi. Çalışmaya KAP ile takip edilen 45 hasta alındı. Egzersiz stres testi pozitif grupta 23 (15 erkek, yaş ortalaması 54±10 yıl), EST-negatif grupta 22 hasta (14 erkek, yaş ortalaması 52±9 yıl) mevcuttu. Her hastadan EST'den 1 saat önce ve 30 dakika sonra alınan kan örneklerinde hsCRP ve neopterin düzeyleri belirlendi. Egzersiz stres testi pozitif olan hastalara koroner anjiyografi yapılarak tıkayıcı koroner lezyon varlığı ve Gensini skoru ile yaygınlığı değerlendirildi. Bulgular: Egzersiz stres testi öncesi hsCRP ve neopterin düzeyleri iki grup arasında benzer iken EST sonrası hsCRP düzeyleri, EST-pozitif grupta daha yüksek izlendi (p=0.03); neopterin düzeyleri açısından EST sonrasında iki grup arasında fark saptanmadı (p=0.4). Egzersiz stres testi, ESTpozitif olan grupta hem hsCRP, hem de neopterin düzeylerinde anlamlı artışa neden olurken (sırasıyla, 3.8±2.8 mg/L'den 4.3±3.1 mg/L'ye, p=0.001; 8.7±4.0 nmol/L'den 13.1±10.0 nmol/L'ye, p=0.001), egzersiz stres testi negatif olan grupta sadece neopterin düzeylerinde anlamlı artış izlendi (6.9±1.8 nmol/L'den 9.0±3.9 nmol/L'ye, p=0.001). Tıkayıcı koroner lezyon varlığı ve yaygınlığı ile herhangi bir noktada bakılan hsCRP ve neopterin düzeyleri arasında ise anlamlı ilişki izlenmedi. İstatistiksel analiz Ki-kare, eşleştirilmemiş t, Mann-Whitney U ve Wilcoxon rank testleri ile yapıldı. Testlerin öngördürücü değerini belirlemede lojistik regresyon analizi kullanıldı. Sonuç: Kararlı anjina pektorisli hastalarda tıkacı lezyonun varlığından bağımsız olarak pozitif egzersiz testi sonrasında oluşan hsCRP artışı, miyokardiyal iskemi sırasında oluşan immün aktivasyonun bir göstergesi olabilir. (Anadolu Kardiyol Derg 2010 Aralık 1; 10(6): 502-7) Anahtar kelimeler: Egzersiz stres test, kararlı anjina pektoris, hsC-reaktif protein, neopterin, tıkayıcı koroner lezyon, testlerin prediktif değeri ABSTRACT Objective: High sensitivity C-reactive protein (hsCRP) and neopterin are associated with atherosclerosis. We aimed to evaluate the association between hsCRP and neopterin, and myocardial ischemia during exercise stress test (EST) in patients with stable angina pectoris (SAP) and to assess the predictive value of these mediators in obstructive coronary artery disease. Methods: Forty-five patients with SAP were included in this prospective observational study. EST-positive group included 23 patients (15 males, mean age 54±10 years) and EST-negative group-22 patients (14 males, mean age 52±9 years). In each patient, blood samples were obtained 1 hour before and 30 minutes after EST. In EST-positive group, coronary ang...

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Elevated serum neopterin predicts future adverse cardiac events in patients with chronic stable angina pectoris

Abstract: Serum neopterin is an independent predictor of major adverse coronary events in patients with chronic stable angina pectoris. This marker of macrophage activation may be useful for risk stratification in patients with chronic stable angina.

Cited by 126 publications

References 33 publications

Neopterin and Atherosclerotic Plaque Instability in Coronary and Carotid Arteries

Neopterin and Atherosclerotic Plaque Instability in Coronary and Carotid Arteries

Early Increase of Plasma Homocysteine in Sepsis Patients with Poor Outcome

The relation between exercise- induced myocardial ischemia and high-sensitive C-reactive protein and neopterin levels

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