Obezite ve serum leptin seviyelerinin klopidogrel direnci üzerine etkisi

Objective: Clopidogrel inhibits platelet aggregation by blockade of platelet adenosine diphosphate (ADP) P2Y12 receptor. Leptin is the obesity gene product, and its serum level increases with obesity. Platelets have leptin receptors on their surfaces. Hyperleptinemia may induce ADP-mediated platelet aggregation. It has been proposed that clopidogrel effect could be diminished with high serum leptin levels. The aim of the present trial was to further investigate the relationship between serum leptin level and clopidogrel resistance.Methods: A total of 100 subjects who underwent percutaneous coronary intervention were enrolled. Two groups were organized according to presence of clopidogrel resistance, and serum leptin levels were compared. Threshold for clopidogrel resistance and hyperleptinemia were accepted as >=P2Y12 reaction unit (PRU) 240 and >=15 ng/mL leptin, respectively. Body mass index (BMI) of 30 kg/m2 or greater was considered obese.Results: A total of 37% of patients were considered clopidogrel-resistant. Comparison of groups revealed significantly higher clopidogrel resistance (p=0.017) and PRU levels (p=0.001) in hyperleptinemic patients. No significant difference in serum leptin levels (p=0.116) was found. Increased clopidogrel resistance was observed in patients with BMI >30 kg/m2 (p=0.015).Conclusion: Clopidogrel resistance is more common in obese and hyperleptinemic patients. Dosage should be individualized in these populations.

Özet

Amaç: Klopidogrel trombosit adenozin difosfat (ADP) P2Y12 reseptörlerini bloke ederek trombosit agregasyonunu inhibe eder. Leptin obezite geni ürünü olup, serum seviyesi obezite ile artar. Trombositler, yüzeylerinde leptin reseptörleri barındırırlar. Hiperleptinemi ADP aracılı trombosit agregasyonunu uyarabilir. Klopidogrel etkisinin yüksek serum leptin seviyeleri ile azalabileceği düşünülmektedir. Çalışmamızda serum leptin seviyeleri ile klopidogrel direnci arasındaki ilişkiyi araştırmayı amaçladık.Yöntemler: Çalışmaya perkütan koroner girişim uygulanmış 100 hasta alındı. Klopidogrel direnci bulunuşuna göre iki grup oluşturuldu ve serum leptin seviyeleri iki grup arasında karşılaştırıldı. Klopidogrel direnci ve hiperleptinemi için eşik değerler sırasıyla, >= PRU (P2Y12 reaction units) 240 ve >=15 ng/ml (leptin) olarak kabul edildi. Vücut kitle indeksinin (VKİ) 30 kg/m2 ve üstü oluşu obezite olarak değerlendirildi. Bulgular: Hastaların %37'sinde klopidogrel direnci olduğu bulundu. İki grubun karşılaştırılması klopidogrel direnci (p=0.017) ve PRU seviyelerinin (p=0.001) hiperleptinemik hastalarda anlamlı olarak daha yüksek olduğunu ortaya koydu. İki grup arasında serum leptin seviyelerine göre anlamlı fark yoktu (p=0.116). VKİ >30 olan hastalarda, daha fazla sayıda klopidogrel direnci gözlendi (p=0.015).Sonuç: Klopidogrel direnci obez ve hiperleptinemik hastalarda daha fazla görülür. Klopidogrel dozu bu hasta grubunda bireyselleştirilmelidir.

🔖

Cite This Article

ÖZDEMİR, E., GÖRMÜŞ, U., ÇİFTÇİ, C., USTA, E., KAHRAMAN, S., DOĞAN, A. (2022). Obezite ve serum leptin seviyelerinin klopidogrel direnci üzerine etkisi. Türk Kardiyoloji Derneği Arşivi, Cilt: 44 - Sayı: 7, 548–553. https://ajindex.com/articles/632470

📄 Full Text PDF Viewer

Open in New Tab ↗

↗New Tab

📄

PDF görüntüleyici hazırlanıyor...

References (10)

Steinhubl SR, Moliterno DJ. The role of the platelet in the pathogenesis of atherothrombosis. Am J Cardiovasc Drugs 2005;5:399-408.
Savi P, Beauverger P, Labouret C, Delfaud M, Salel V, Kaghad M, et al. Role of P2Y1 purinoceptor in ADP-induced platelet activation. FEBS Lett 1998;422:291-5.
Herbert JM, Savi P. P2Y12, a new platelet ADP receptor, tar- get of clopidogrel. Semin Vasc Med 2003;3:113-22.
Ma TK, Lam YY, Tan VP, Kiernan TJ, Yan BP. Impact of ge- netic and acquired alteration in cytochrome P450 system on pharmacologic and clinical response to clopidogrel. Pharma- col Ther 2010;125:249-59.
Bhatt DL, Bertrand ME, Berger PB, L'Allier PL, Moussa I, Moses JW, et al. Meta-analysis of randomized and registry comparisons of ticlopidine with clopidogrel after stenting. J Am Coll Cardiol 2002;39:9-14.
Gurbel PA, Bliden KP, Hiatt BL, O'Connor CM. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 2003;107:2908-13.
Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Alfonso F, Macaya C, Bass TA, et al. Variability in individual respon- siveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol 2007;49:1505-16.
Matetzky S, Shenkman B, Guetta V, Shechter M, Beinart R, Goldenberg I, et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004;109:3171- 5. Hochholzer W, Trenk D, Bestehorn HP, Fischer B, Valina CM, Ferenc M, et al. Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clin- ical outcome of elective coronary stent placement. J Am Coll Cardiol 2006;48:1742-50.
Ben-Dor I, Kleiman NS, Lev E. Assessment, mechanisms, and clinical implication of variability in platelet response to aspirin and clopidogrel therapy. Am J Cardiol 2009;104:227- 33. Vlachojannis GJ, Dimitropoulos G, Alexopoulos D. Clopido- grel resistance: current aspects and future directions. Hellenic J Cardiol 2011;52:236-45.
Gremmel T, Steiner S, Seidinger D, Koppensteiner R, Panzer S, Kopp CW. Comparison of methods to evaluate clopidogrel- mediated platelet inhibition after percutaneous intervention with stent implantation. Thromb Haemost 2009;101:333-9. van Werkum JW, van der Stelt CA, Seesing TH, Hackeng CM, ten Berg JM. A head-to-head comparison between the VerifyNow P2Y12 assay and light transmittance aggregome-