Pharmacogenetic and clinical predictors of response to clopidogrel plus aspirin after acute coronary syndrome in Egyptians.

OBJECTIVES: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduces the risk for recurrent cardiovascular events after acute coronary syndrome (ACS). However, there is significant variation in response to DAPT that may be influenced by both genetic and nongenetic factors. This study aimed to assess the effect of genetic polymorphisms in PON-1, PEAR-1, P2Y12, CES1, and CYP2C19, along with clinical, demographic, and social factors, on variation in response to DAPT in Egyptians. PARTICIPANTS AND METHODS: This study included 230 Egyptians treated with clopidogrel 75 mg/day and aspirin 81 mg/day for at least 12 months following their first ACS. Simple and multivariable logistic regression analyses were carried out to identify factors associated with major adverse cardiovascular events (MACE), defined as the occurrence of recurrent ACS, ischemic stroke, stent-related revascularization, or death, in clopidogrel-treated participants. RESULTS: Using multivariable logistic regression analysis, the CYP2C19*2 polymorphism was the only genetic predictor of MACE [odds ratio (OR): 2.23, 95% confidence interval (CI): 1.15-4.33, P=0.01]. In addition, proton pump inhibitor use (OR: 4.77, 95% CI: 1.47-15.54, P=0.009) and diabetes (OR: 1.83, 95% CI: 1.03-3.26, P=0.03) were associated with higher cardiovascular risk, whereas statin use was associated with lower risk (OR: 0.43, 95% CI: 0.25-0.76, P=0.003). The contribution of these four genetic and nongenetic factors explained 19% of the variability in risk for MACE in Egyptians treated with DAPT. CONCLUSION: These results highlight that CYP2C19*2, along with diabetes, and use of proton pump inhibitor and statin are important factors jointly associated with variability in clinical response to DAPT following ACS in Egyptians.

Role of advanced glycation end product receptors in the pathogenesis of diabetic retinopathy.

PROBLEM: Advanced glycation end products (AGEs) and the interaction with their receptors (RAGE) play an important role in the pathogenesis of diabetic retinopathy (DR). Our study investigated whether serum soluble (s) RAGE (sRAGE) could serve as a prognostic tool for identifying the susceptibility to DR. Moreover, we examined the association between soluble forms of vascular cell adhesion molecules (sVCAM-1), nitric oxide (NO) and sRAGE levels in serum and the severity of DR. METHODS: Circulating levels of sRAGE, sVCAM-1, and NO were examined in 37 type 2 diabetic patient and 20 age-matched healthy nondiabetic subjects using ELISA. The diabetic subjects were categorized as patients without retinopathy, patients with nonproliferative DR (NPDR), and patients with proliferative DR (PDR). RESULTS: Serum sRAGE levels were significantly lower in patients with NPDR and PDR than in healthy controls and in those without retinopathy (1331.13 ± 126.13, 934.87 ± 66.27 vs. 1712.69 ± 167.3, 1833.1 ± 153.06 pg/ml, respectively, P<.05). Serum sVCAM-1 and NO were significantly higher in diabetic patients (1310.215 ± 54.712 vs. 616.55 ± 12.9 ng/ml and 96.432 ± 0.864 vs. 28.78 ± 5.88 µmol/l, respectively, P<.05) and were positively associated with the severity of DR. CONCLUSIONS: The results indicate that sRAGE is an endogenous protection factor against the occurrence of accelerated DR.