Plazma asimetrik dimetilarjinin düzeyi stent restenozu için bir belirteç olabilir mi?

Günümüzde stentler, koroner arter hastalığında bir tedavi seçeneği olarak sıklıkla kullanılmaktadır. Stentler koroner arter hastaları için bir umut olmuş fakat kullanımları arttıkça başta restenoz olmak üzere bazı problemler ile karşılaşılmıştır. Düz kas hücresi ve matriksten oluşan neointima hiperplazisi stent içi restenozun başlıca nedenidir. Sağlam endotelden salınan nitrik oksit (NO) düz kas hücre proliferasyonunu önleyerek neointima hiperplazisini azaltır. Asimetrik dimetilarjinin (ADMA), endotelyal NO oluşumunda bir düzenleyicidir. Nitrik oksit sentetaz (NOS)’ ın yarışmacı inhibitörüdür. Bu çalışmanın amacı plazma ADMA düzeyinin stent restenozunda bir belirteç olup olamayacağını değerlendirmektir. Çalışmaya daha önce koroner stent uygulanmış ve herhangi bir nedenle koroner anjiyografi yapılan 91 hasta alındı. Kronik böbrek ve karaciğer yetmezliği, son 1 yıl içinde gelişen serebrovasküler olay, ciddi periferik arter hastalığı, kontrolsüz hipertansiyon (HT)’ u, klinik hipertiroidisi, erektil disfonksiyonu ve pulmoner hipertansiyonu olan hastalar ile kan glukozu kontrol altında olmayan diabet hastaları çalışma dışı bırakıldı. Tüm hastalarda ADMA plazmadan yüksek performanslı sıvı kromotografisi (HPLC) yöntemiyle çalışıldı. Çalışmaya alınan hastaların yaş ortalaması 58.9 ± 8.7 yıl olup, 72 (% 79.1)’ i erkekti. Çalışmaya alınan 91 hastanın toplam 144 stenti anjiyografik olarak değerlendirildi ve 46 (% 31.9)’ ında restenoz saptandı. Hasta bazında ise 35 (% 38.5) hastada restenoz tespit edildi. Restenoz gelişen ve gelişmeyen hastalar klinik ve laboratuvar özellikleri bakımından karşılaştırıldığında akut koroner sendrom (AKS) kliniği nedenli stent takılma öyküsü restenoz gelişen grupta anlamlı olarak daha yüksekti (p = 0.029). Laboratuvar parametrelerinden plazma ADMA düzeyi (p = 0.001), C-reaktif protein düzeyi (p = 0.01) ve beyaz küre sayısı (p = 0.044) restenoz gelişen grupta anlamlı derecelerde yüksek, sol ventrikül ejeksiyon fraksiyonu ise anlamlı derecede düşük idi (p = 0.023). Çoklu lineer regresyon analizinde plazma ADMA düzeyi (β = 0.281; p = 0.012) ve stent öncesi hastanın kliniği (β = 0.233; p = 0.037) restenozun bağımsız belirleyicileri olarak tespit edildi. Stent özellikleri ve uygulanma yöntemleri değerlendirildiğinde ise stent boyu (β = 0.238; p = 0.015) ve stent çapı (β = – 0.302; p = 0.001) restenoz gelişimi için bağımsız risk faktörleri olarak bulundu. Sonuç olarak, plazma ADMA düzeyi stent restenozu gelişiminin bağımsız bir belirleyicisidir. Nowadays stents are widely used for the treatment of coronary artery disease. During the wide spread usage of coronary stenting, stent restenosis was found to be the major problem related with this intervention. Neointimal hyperplasia composed of vascular smooth muscle cells and the matrix is the mainstay of stent restenosis. Nitric oxide secreted by intact endothelium inhibits vascular smooth muscle cell proliferation and prevents neointimal hyperplasia. Asymmetric dimethylarginine (ADMA) is a potent competitive inhibitor of nitric oxide synthase (NOS). The aim of this study was to examine whether plasma ADMA level is a predictor of stent restenosis or not. We recruited 91 patients with a history of coronary stenting who underwent coronary angiography due to various reasons. Subjects were eligible if they had no history of chronic kidney or liver disease, no history of cerebrovascular accident in the past year and were free of uncontrolled hypertension, clinical hyperthyroidism, erectile dysfunction, pulmonary hypertension and uncontrolled diabetes mellitus. Asymmetric dimethylarginine concentrations were measured by high performance liquid chromatography (HPLC). The mean age of the patients was 58.9 ± 8.7 years and 72 (79.1 %) of them were male. We assessed 144 stents of 91 patients with coronary angiography. Angiographic restenosis was found in 35 patients (38.5 %) and 46 of 144 stents (31.9 %). When clinical characteristics and laboratory findings considered, stenting history due to acute coronary syndrome (p = 0.029), plasma ADMA concentrations (p = 0.001), C-reactive protein concentrations (p = 0.01) and white blood cell count (p = 0.044) were higher and left ventricular ejection fraction (p = 0.023) lower in patients with restenosis. Plasma ADMA concentration (β = 0.281; p = 0.012) and clinical setting before stenting (β = 0.233; p = 0.037) were found to be the independent predictors of restenosis in multiple linear regression analysis. When we consider the properties of stent and the implantation procedure, we found the stent diameter (β = – 0.302; p = 0.001) and length (β = 0.238; p = 0.015) as the independent predictors of restenosis. In conclusion, plasma ADMA level is found to be an independent predictor of restenosis

Epicardial adipose tissue thickness and plasma homocysteine in patients with metabolic syndrome and normal coronary arteries

Background: Increased epicardial adipose tissue thickness and plasma homocysteine levels are associated with Metabolic Syndrome (MS) and coronary artery disease. The majority of patients with MS have subclinical or manifest coronary artery disease. The aim of this study was to evaluate the relationship between MS and plasma homocysteine levels and epicardial adipose tissue thickness in subjects without epicardial coronary artery disease. Methods: Patients who underwent coronary angiography due to angina or equivocal symptoms and/or abnormal stress test results and were found to have normal coronary arteries were evaluated for the presence of MS. The study group comprised 75 patients with normal coronary arteries and MS, and the control group included 75 age-gender matched subjects without coronary artery disease or MS. Results: Epicardial adipose tissue thickness (5.8 +/- 1.9 mm vs. 4.3 +/- 1.6 mm, p <0.001) and plasma homocysteine levels (21.6 +/- 6.1 mu mol/L vs. 15.1 +/- 5.8 mu mol/L, p <0.001) were significantly higher in the MS group. Body mass index, triglyceride level, weight, age and waist circumference were positively and HDL cholesterol level were negatively correlated with both epicardial adipose tissue thickness and plasma homocysteine level. Epicardial adipose tissue thickness had the strongest correlation with plasma homocysteine level (r = 0.584, p < 0.001). For each 1 mm increase in epicardial adipose tissue thickness, an increase of 3.51 mu mol/L (95% CI: 2.24-4.79) in plasma homocysteine level was expected. Conclusions: We observed a close relationship between MS and epicardial adipose tissue thickness and plasma homocysteine levels, even in the absence of overt coronary artery disease